L-Methionine

The purpose of this study was to perform a meta-analysis comparing the biological efficiency of DL-methionine and L-methionine (DL-Met and L-Met) in broiler nutrition. This analysis was based on a dataset comprising experiment results published in peer-reviewed papers since 2007. All experiments investigated the response of broilers (aged 0-21 d) to different dietary concentrations of DL- and L-Met, achieved by supplementing crystalline Met. A graphical analysis was conducted on the database using ellipses coverage and nonparametric density techniques. Two methods of linear and nonlinear exponential meta-regression analysis were used to determine relative bioavailability based on average daily gain (ADG) and feed conversion ratio (FCR) responses to dietary Met sources. The analyses of ADG and FCR obtained from both linear and exponential models showed a relative difference between the tested methionine sources. The results showed that both ADG and FCR were improved in L-Met compared to DL-Met supplemented diets. Linear regression analysis revealed that DL-Met was 94.97% (for ADG) and 95.63% (for FCR) as efficacious as L-Met (P < 0.01). In contrast, the analysis of the fitted nonlinear exponential model showed that the biological efficiencies of DL-Met were 91.33% and 76.57% of the values for L-Met for ADG (P = 0.01) and FCR (P = 0.09), respectively. Based on the meta-analytical results, an equivalence of relative biological efficiency of DL-Met in comparison with L-Met for young broilers could not be confirmed.

In this article, we aimed to assess the efficacy of adjunctive administration of nutritional supplements to antidepressants by means of a systematic review and meta-analysis. The supplements included were inositol, vitamin D, folic acid, vitamin B12, S-adenosyl-L-methionine (SAMe), omega-3 polyunsaturated fatty acids (n-3 PUFA) and zinc. A structured database search (MEDLINE, EBSCO, CENTRAL, Web of Science) was performed using terms for the respective substances in conjunction with terms for depression and the mode of treatment ("add-on" OR "adjunctive" OR "augmentation"). Meta-analyses, randomized controlled trials (RCTs) and non-randomized comparative studies that investigated the supplements as an add-on in the treatment of clinically diagnosed MDD were included. Agents had to be added to an existing antidepressant regime (augmentation) or started simultaneously with the antidepressant (acceleration). For n-3 PUFAs, folic acid and zinc, new meta-analyses were performed as part of this work. Our meta-analyses of 10 articles on n-3 PUFAs and four on zinc support their efficacy. For folic acid, our meta-analysis does not support efficacy. For n-3 PUFAs, sensitivity analysis showed no difference between acceleration and augmentation designs, but significant differences between individuals with or without comorbidities. For the remaining substances, only a few RCTs were available. The preliminary data on inositol was negative, while one RCT for vitamin D demonstrated positive results. For vitamin B12 one and for SAMe two RCTs and a few open trials are available reporting positive and mixed results. To summarize, for most of the substances, the available data is not yet sufficient or inconclusive.

It has been well established that S-adenosyl-L-methionine (SAMe) is the principal methyl donor in methyltransferase reactions and that SAMe supplementation restores hepatic glutathione (GSH) deposits and attenuates liver injury. However, the effectiveness of SAMe therapy in chronic liver disease has not been adequately addressed. We searched globally recognized electronic databases, including PubMed, the Cochrane Database and EMBASE, to retrieve relevant randomized controlled trials (RCTs) of chronic liver disease published in the past 20 years. We then performed a systematic review and meta-analysis of the enrolled trials that met the inclusion criteria.The results showed that twelve RCTs from 11 studies, which examined 705 patients, were included in this research. For liver function, certain results obtained from data synthesis and independent comparisons demonstrated significant differences between the levels of total bilirubin (TBIL) and aspartate transaminase (AST). However, no studies identified significant differences regarding alanine transaminase (ALT) levels. An analysis of the adverse events and long-term prognosis also indicated no significant differences between the SAMe and the placebo groups. In a subgroup analysis of gravidas and children, several of the included data indicated that there was a significant difference in the pruritus score. Furthermore, the results regarding ursodeoxycholic acid (UDCA) and stronger neo-minophagen C (SNMC) indicated that both treatments were more effective than SAMe was in certain chronic liver diseases. These findings suggest that SAMe could be used as the basis of a medication regimen for liver function improvement because of its safety. However, SAMe also demonstrated limited clinical value in the treatment of certain chronic liver diseases.

BACKGROUND: There are at least three reasons to believe antidepressants might help in smoking cessation. Firstly, nicotine withdrawal may produce depressive symptoms or precipitate a major depressive episode and antidepressants may relieve these. Secondly, nicotine may have antidepressant effects that maintain smoking, and antidepressants may substitute for this effect. Finally, some antidepressants may have a specific effect on neural pathways (e.g. inhibiting monoamine oxidase) or receptors (e.g. blockade of nicotinic-cholinergic receptors) underlying nicotine addiction. OBJECTIVES: The aim of this review is to assess the effect and safety of antidepressant medications to aid long-term smoking cessation. The medications include bupropion; doxepin; fluoxetine; imipramine; lazabemide; moclobemide; nortriptyline; paroxetine; S-Adenosyl-L-Methionine (SAMe); selegiline; sertraline; St. John's wort; tryptophan; venlafaxine; and zimeledine. SEARCH METHODS: We searched the Cochrane Tobacco Addiction Group Specialised Register which includes reports of trials indexed in the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and PsycINFO, and other reviews and meeting abstracts, in July 2013. SELECTION CRITERIA: We considered randomized trials comparing antidepressant medications to placebo or an alternative pharmacotherapy for smoking cessation. We also included trials comparing different doses, using pharmacotherapy to prevent relapse or re-initiate smoking cessation or to help smokers reduce cigarette consumption. We excluded trials with less than six months follow-up. DATA COLLECTION AND ANALYSIS: We extracted data and assessed risk of bias using standard methodological procedures expected by the Cochrane Collaboration.The main outcome measure was abstinence from smoking after at least six months follow-up in patients smoking at baseline, expressed as a risk ratio (RR). We used the most rigorous definition of abstinence available in each trial, and biochemically validated rates if available. Where appropriate, we performed meta-analysis using a fixed-effect model. MAIN RESULTS: Twenty-four new trials were identified since the 2009 update, bri

PURPOSE: Athletes are at increased risk for functional constipation due to high-intensity training, irregular diets, and disrupted circadian rhythms. Soluble fibers, particularly konjac glucomannan (KGM), have shown potential in alleviating constipation, but clinical evidence, especially in athletes, is limited. This study aimed to assess the effects of an 8-week KGM intervention on gastrointestinal symptoms and gut microbiota in elite male Taekwondo athletes with functional constipation. METHODS: In this double-blind randomized controlled trial, we enrolled male elite Taekwondo athletes diagnosed with functional constipation according to Rome IV criteria. Participants were randomly assigned to receive either KGM supplementation (dietary intervention group, DG) or placebo (control group, CG) for 8 weeks. Primary outcomes included the Patient Assessment of Constipation Symptoms (PAC-SYM), Patient Assessment of Constipation Quality of Life (PAC-QoL), bowel movement frequency (BMF), Bristol Stool Scale, and the Bowel Function Index (BFI). Stool samples were collected for 16S rRNA gene sequencing to evaluate microbial composition and diversity. RESULTS: Compared to the placebo group, the KGM group exhibited significant improvements in PAC-SYM, PAC-QoL, BMF, and BFI scores (p < 0.05 for all). Microbial analysis revealed a marked increase in α-diversity and elevated relative abundances of Prevotella_9, Phascolarctobacterium, Lactobacillus, Bacteroides, and members of the Prevotellaceae family, alongside reduced levels of Alistipes and Desulfovibrio. Correlation analyses indicated a strong association between microbial shifts and symptom improvement. Functional predictions further suggested differential expression in microbial metabolic pathways, including upregulation of biotin biosynthesis I and nitrate reduction VI (assimilatory), and downregulation of L-methionine biosynthesis III (all p < 0.05). CONCLUSIONS: Konjac glucomannan significantly ameliorated gastrointestinal symptoms in elite athletes with functional constipation, potentially via modulation of the gut microbiota. © 2025. Springer-Verlag GmbH Germany, part of Springer Nature.

Introduction: metabolic syndrome comprises a combination of diabetes, high blood pressure, and obesity, and metabolic associated fatty liver disease (MAFLD) is associated with it. Objective: to evaluate the effect of supplementation with S-adenosyl-L-methionine + N-acetylcysteine + thioctic acid + vitamin B6 (MetioNac®) for 3 months on lipidic and biochemical parameters in subjects with metabolic syndrome and at risk of MAFLD. The reduction in body weight and the oxidative stress markers malondialdehyde (MDA) and superoxide dismutase (SOD) were also evaluated. Methods: patients with metabolic syndrome, at risk of MAFLD (FIB-4 < 1.30), and with an indication for weight reduction were recruited (n = 15). Control group followed a semipersonalized Mediterranean diet (MD) for weight reduction, according to the recommendations of the Spanish Society for the Study of Obesity (SEEDO). Experimental group, in addition to the MD, took three capsules of MetioNac® supplement per day. Results: compared with the control group, subjects taking MetioNac® showed significant (p < 0.05) reductions in the levels of TG and VLDL-c, as well as in total cholesterol, LDL-c, and glucose levels. They also showed increased levels of HDL-c. Levels of AST and ALT decreased after the intervention with MetioNac®, but this decrease did not reach statistical significance. Weight loss was observed in both groups. Conclusion: supplementation with MetioNac® may be protective against hyperlipidemia, insulin resistance, and overweight among metabolic syndrome patients. Further studies on this issue are needed in a larger population. Publisher: Introducción: el síndrome metabólico se define como una combinación de diabetes, hipertensión arterial y obesidad, que se asocia con la enfermedad del hígado graso asociada a disfunción metabólica. Objetivo: evaluar el efecto de la suplementación con S-adenosil-L-metionina + N-acetilcisteína + ácido tióctico + vitamina B6 (MetioNac®) durante 3 meses sobre parámetros lipídicos y bioquímicos en sujetos con síndrome metabólico y en riesgo de enfermedad del hígado graso asociada a disfunción metabólica. También se evaluaron la reducción del peso corporal y los marc

OBJECTIVE: To evaluate the efficacy of dietary supplementation with a combination of antioxidants (lipoic acid, N-acetylcysteine, vitamin B6, and S-adenosyl-L-methionine) for the modulation of metabolic, endocrine, and clinical parameters in comparison with oral contraception in non-diabetic women newly diagnosed with polycystic ovary syndrome (PCOS). METHODS: This was a prospective, partially randomized, multicenter study in which non-diabetic women with PCOS were recruited under routine clinical practice conditions and distributed in three groups to receive the following regimen for 6 months: 1) antioxidant combination (MN group); 2) oral contraception (OC group); or 3) oral contraception and the antioxidant combination (MN + OC group). General recommendation of healthy diet and regular exercise was given to all patients. Metabolic, endocrine, clinical, and quality of life parameters were recorded at baseline and after 6 months of therapy. RESULTS: A total of 96 women with PCOS were included in the study. After 6 months of treatment, the homeostasis model assessment-estimated insulin resistance (HOMA-IR) level was reduced only in the MN group, with a significant mean reduction of -0.92 points. Androstenedione was significantly reduced in all groups. Clinical parameters that significantly improved in all groups were hirsutism, acne, irregular menstruation, and quality of life, with no statistical differences between the groups. CONCLUSIONS: This study showed that the antioxidant combination might be a suitable therapy for patients with PCOS when oral contraceptive is not indicated, because in all groups clinical parameters, irregular menstruation as well as androstenedione and quality of life were significantly improved with no statistical difference between groups.

OBJECTIVE: The aim: To evaluate the effectiveness of the use of the Deprilium® complex for the relief of subclinical symptoms of depression in patients with NCD. PATIENTS AND METHODS: Materials and methods: There were 140 patients involved in the study. To assess the subclinical symptoms, the Hamilton Depression Rating Scale (HAM-D) was used. In order to obtain additional information about the patient's condition, the Somatic Symptom Scale SSS-8 and the Quality of Life Scale (QOLS) were used. Patients were randomized by block randomization to an intervention group, which took Deprilium® complex, and a control group, which took placebo. RESULTS: Results: After 60 days a statistically significant difference was observed in all clinical indicators between the intervention group and the control group. The median value of the HAM-D scale differed between the groups by 6 points, significantly (p <0.000) lower results were observed in the intervention group, which participants were taking the Deprilium® complex. When comparing the indicators of the intervention group on the 1st and on the 60th day of the study, statistically significant changes (p <0.000) were observed in all three indicators. CONCLUSION: Conclusions: The received results confirm the available evidence for the properties of SAMe in depression and complement them with evidence of the ef-fectiveness of the Deprilium® complex that contains SAMe and L-methylfolate with methylcobalamin, which together produce pharmacological and clinical synergy to reduce the severity of subclinical depressive manifestations in patients with NCD. Further studies of the effectiveness of the use of the Deprilium® complex in patients with NCD are required.

AIM: To assess the safety and efficacy of Remaxol, solution for infusion, compared with parenteral form of S-adenosyl-L-methionine, in the treatment of patients with intrahepatic cholestasis syndrome accompanying chronic diffuse liver diseases of various etiology. MATERIALS AND METHODS: In a multicenter open-label comparative study of the safety and efficacy of Remaxol (inosine + meglumine + methionine + nicotinamide + succinic acid) 317 patients aged 18 to 65 years were randomized into 2 groups: patients of the experimental group (n=168) received intravenous Remaxol, solution for infusion, 400 ml, and patients of the control group (n=149) Heptral (S-adenosyl-L-methionine) 800 mg. The duration of treatment was 10 days. The primary efficacy endpoint was the proportion of patients who responded to therapy, as demonstrated by dynamics of laboratory parameters of liver functional status: decrease in gamma glutamyl transpeptidase level by 40%, and/or alkaline phosphatase level by 30%, and/or decrease total bilirubin level by 30% from baseline by the end of the treatment course. RESULTS: The proportion of responders was 51% in the Remaxol group vs. 44.9% in the Heptral group (p=0.303); the lower limit of the one-sided 95% confidence interval for the difference in the proportions of responders was -4.01%, which exceeds the non-inferiority margin pre-defined by the study protocol, thus, the non-inferiority hypothesis was proven, i.e. Remaxol at a dose of 400 ml/day demonstrates similar efficacy to Heptral at a dose of 800 mg/day in patients with intrahepatic cholestasis syndrome associated with chronic diffuse liver diseases. Similar positive trends in the levels of transaminases, total bilirubin and the severity of pruritus were revealed in both treatment groups. We did not reveal statistically significant between-group differences in the frequency of adverse events definitely related to the study treatment. CONCLUSION: Administration of Remaxol as a part of the pathogenetic therapy of patients with intrahepatic cholestasis syndrome who need hepatoprotection is justified. Publisher: Цель. Оценка безопасности и эффективности применения препарата Ремаксол раствор для ин

BACKGROUND: Currently, there is no approved medication for non-alcoholic fatty liver disease management. Pre-clinical and clinical studies showed that several bioactive molecules in plants or foods (i.e., curcumin complex, bergamot polyphenol fraction, artichoke leaf extract, black seed oil, concentrate fish oil, picroliv root, glutathione, S-adenosyl-L-methionine and other natural ingredients) have been associated with improved fatty liver disease. Starting from these evidences, our purpose was to evaluate the effects of a novel combination of abovementioned nutraceuticals as a treatment for adults with fatty liver disease. METHODS: A total of 140 participants with liver steatosis were enrolled in a randomized, double-blind, placebo controlled clinical trial. The intervention group received six softgel capsules daily of a nutraceutical (namely Livogen Plus®) containing a combination of natural bioactive components for 12 weeks. The control group received six softgel capsules daily of a placebo containing maltodextrin for 12 weeks. The primary outcome measure was the change in liver fat content (CAP score). CAP score, by transient elastography, serum glucose, lipids, transaminases, and cytokines were measured at baseline and after intervention. RESULTS: After adjustment for confounding variables (i.e., CAP score and triglyceride at baseline, and changes of serum γGT, and vegetable and animal proteins, cholesterol intake at the follow-up), we found a greater CAP score reduction in the nutraceutical group rather than placebo (- 34 ± 5 dB/m vs. - 20 ± 5 dB/m, respectively; p = 0.045). The CAP score reduction (%) was even greater in those with aged 60 or less, low baseline HDL-C, AST reduction as well as in men. CONCLUSION: Our results showed that a new combination of bioactive molecules as nutraceutical was safe and effective in reducing liver fat content over 12 weeks in individuals with hepatic steatosis. Trial registration ISRCTN, ISRCTN70887063. Registered 03 August 2021-retrospectively registered, https://doi.org/10.1186/ISRCTN70887063. © 2022. The Author(s).

BACKGROUND: Lentil is considered a high protein source. However, it is low in sulphur amino acids (SAA) and their metabolic availability (MA) is further affected by antinutritional factors in lentils. The combination of lentils with grains such as rice can enhance the protein quality of a lentil-based meal but the MA of SAA in lentils must first be known. OBJECTIVES: The objectives of the current study were to assess the MA of methionine in lentils and to test the effects of consumption of complementing lentils with rice in young adults. METHODS: Five healthy young men [age <30 y, BMI <25 (in kg/m2)] were each studied at 8 or 10 intake amounts of methionine in random order; 4 daily intake amounts of l-methionine: 0.5, 1, 2, and 3 mg.kg-1.d-1 (reference diet), 3 daily intake amounts of methionine from lentils, and 3 daily intake amounts of the mixed meal of lentils + rice (test diets). The MA of methionine and the effects of complementation were assessed by comparing the indicator amino acid oxidation (IAAO) response to varying intakes of methionine in cooked Canadian lentils, and in rice + lentils combined, compared with the IAAO response to l-methionine intakes in the reference protein (crystalline AA mixture patterned after egg protein) using the slope ratio method. l-[1-13C] phenylalanine was used as the indicator. Data were analyzed using the procedure "MIXED" with subject as a random variable, and oxidation day as repeated measure. RESULTS: The MA of methionine from lentils was 69%. Complementation of cooked lentils with rice decreased the oxidation of l-[1-13C] phenylalanine by up to 16% (P < 0.05). CONCLUSIONS: The content and MA of methionine are low in lentils. However, combination of lentils with rice in a 1:1 ratio can improve the protein quality of lentil-based diets, resulting in increased protein synthesis in young healthy adults. This trial was registered at www.clinical trials.gov as NCT03110913. © The Author(s) 2022. Published by Oxford University Press on behalf of the American Society for Nutrition.

Different infant diets have strong effects on child development and may engender variations in fecal microbiota and metabolites. The objective of this study was to evaluate the effect of an infant formula containing sn-2 palmitate on fecal microbiota and metabolites in healthy term infants. The study involved three groups as indicated below. Investigational: the group fed a formula containing high sn-2 palmitate for 16 weeks. Control: the group fed a formula using a regular vegetable oil for 16 weeks. Breastfed: the group fed breast milk for 16 weeks. Fecal samples were collected at 8 weeks (n = 35, 37, and 35, respectively) and 16 weeks (n = 30, 32, and 30, respectively) for the control, investigational, and breastfed infants. Microbiota data were obtained using 16S rRNA sequencing. Short-chain fatty acid (SCFA) analysis was performed using GC-MS, and untargeted metabolomics was conducted using LC-MS. The effect of the formula containing sn-2 palmitate was different from that of the control formula on microbiota and metabolites. Sn-2 palmitate promoted the proliferation of Bifidobacterium and reduced the abundance of Escherichia-Shigella at 8 weeks. Furthermore, it increased α-diversity and enhanced acetate content in feces at both 8 and 16 weeks. In the investigational group infants, the abundance of DL-tryptophan, indole-3-acrylic acid, acetyl-β-methylcholine, L-methionine, and 2-hydroxyvaleric acid significantly increased at 8 weeks, while a notable increase in the abundance of 3-phenyllactic acid, palmitic acid, L-phenylalanine, and leucylproline was observed at 16 weeks. In addition, compared with that of the control infants, the intestinal microbiota and metabolites of sn-2 palmitate-supplemented infants were more similar to those of the breastfed infants. The study hopes to provide a scientific basis for the development of functional infant formulas in the future.

OBJECTIVE: To compare the effect of ursodesoxycholic acid (UDCA) with S-adenosyl-L-methionine (SAMe) plus UDCA in handling of cholestasis in neonates, and their influences on serum endotoxin, matrix metalloproteinase-9 (MMP-9) and interleukin 18 (IL-18). STUDY DESIGN: Randomised controlled trial. PLACE AND DURATION OF STUDY: Luzhou People's Hospital, China, from April 2019 to December 2020. METHODOLOGY: A total of 102 neonates with cholestasis were evenly divided into control group and observation group with random double-blind. The former treated with UDCA tablets, and the latter was treated with SAMe plus UDCA. Serum endotoxin, MMP-9 and IL-18 were compared between the two groups. RESULTS: Total effective rate of treatment in observation group was 92.16% (47 cases), which was higher than that in control group 70.59% (36 cases) (p=0.005). Levels of serum endotoxin, MMP-9 and IL-18 in observation group were respectively 11.12 ± 1.07 pg/mL, 646.72 ± 42.56 ng/mL and 2.51 ± 0.19 pg/mL, which was lower than those in control group (p<0.001, p =0.007 and p<0.001, respectively) after 10 days of treatment. CONCLUSION: Compared with UDCA alone, SAMe plus UDCA can more effectively improve the curative effect of neonatal cholestasis, and reduce serum endotoxin, MMP-9 and IL-18 levels. Key Words: Ursodesoxycholic acid (UDCA), Neonates, Cholestasis, Endotoxin, Matrix metalloproteinase-9 (MMP-9), Interleukin 18 (IL-18).

OBJECTIVE: To observe the effect of acupuncture combined with rehabilitation training on cognitive function and amino acid metabolism in children with cerebral palsy. METHODS: Twenty children with cerebral palsy (cerebral palsy group) were randomly divided into an acupuncture and rehabilitation group (11 cases) and a rehabilitation group (9 cases), and 10 healthy children were included as the normal group. The rehabilitation group was treated with rehabilitation training, 30 min each time; on the basis of rehabilitation training, the acupuncture and rehabilitation group was treated with acupuncture at Sishenzhen, Zhisanzhen, Naosanzhen, Niesanzhen, Dazhui (GV 14), Shenzhu (GV 12), Mingmen (GV 4), etc. The Sishenzhen (left and right points) and the ipsilateral Niesanzhen were respectively connected with a group of electrodes, intermittent wave, frequency of 2 Hz for 30 min. Both groups were treated once every other day, three times a week, totaling for 3 months. The Gesell developmental diagnostic scale (GESELL) was used to evaluate the developmental quotient (DQ) scores before and after treatment, and the blood samples of children with cerebral palsy before and after treatment and normal children were collected for amino acid metabolomics. RESULTS: Compared before treatment, the DQ scores of adaptation, fine motor and social in the acupuncture and rehabilitation group was increased after treatment (P<0.05), and the DQ score of fine motor in the rehabilitation group was increased after treatment (P<0.05). Compared with the normal group, the serum L-glutamate, L-ornithine, L-tyrosine, L-methionine and L-arginine in the cerebral palsy group were down-regulated, and L-histidine, L-citrulline, 5-hydroxylysine and L-glutamine were up-regulated before treatment. The functional pathways mapped by different metabolites between the cerebral palsy group and the normal group included arginine biosynthesis, arginine and proline metabolism, etc. Compared with the cerebral palsy group, the serum L-histidine was decreased, and L-citrulline showed decreasing trend in the acupuncture and rehabilitation group after treatment. CONCLUSION: Acupuncture combined with rehabilitation tr

Metastatic castration-resistant prostate cancer (mCRPC) is the most aggressive kind of prostate cancer (PCa). Because the traditional taxane-based therapy is ineffective, cabazitaxel (CBZ), a second-generation, semisynthetic taxane, has been developed. Despite it demonstrating efficacy in patients resistant to docetaxel and paclitaxel, two commonly used taxanes, and representing one of the second-line therapeutic options for patients with mCRPC, CBZ has limitations, including considerable side issues and reduced drug susceptibility that gradually emerge and constitute the primary cause of therapeutic failure. For the purposes of this study, the application of nature-derived adjuvants in chemotherapy is emerging as a promising area of research. S-Adenosyl-L-methionine (AdoMet) is a naturally occurring sulfur-containing nucleoside that serves as the major methyl donor for numerous methyltransferases, which is a key metabolite in the cell, participating in a broad range of essential biochemical processes. In the current research, we bring attention to the effectiveness of the combination of AdoMet and CBZ during treatment of mCRPC cells. Using mCRPC cell lines DU 145 and PC-3, we found that the combination of CBZ and AdoMet worked better than either agent alone in suppressing cancer cell growth. This synergistic effect may be mediated by increased production of reactive oxygen species (ROS) and a weakening of the cancer cells' antioxidant defenses, including reductions in glutathione, GPX4, and catalase. The resulting oxidative stress caused DNA damage and interference with mitotic spindle assembly, which induces cell cycle arrest and programmed cell death. These data indicate that AdoMet is capable of intensifying CBZ responsiveness in mCRPC cells, making the treatment more effective. © 2026 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.

BACKGROUND/AIM: To determine whether methionine restriction using recombinant methioninase (rMETase) enhances the efficacy of ultra-low-dose cisplatinum against lung cancer cells in vitro, and whether combining a methionine-restricted (MR) diet with low-dose cisplatinum can inhibit lung cancer growth in vivo with reduced toxicity. MATERIALS AND METHODS: Human A549 lung adenocarcinoma cells were treated with rMETase and cisplatinum in vitro. Cell viability was assessed after 72 hours using the WST-8 reagent. The IC50 value of rMETase was determined, and synergy was evaluated by combining rMETase at its IC50 with cisplatinum at its determined IC10-IC50. For in vivo analysis, A549 xenografts were established in nude mice and assigned to four groups: control: standard-dose cisplatinum [6 mg/kg, intraperitoneally (i.p.), weekly]; low-dose cisplatinum (3 mg/kg, i.p., weekly) + a methionine-restricted (MR) diet; or the MR diet alone. Treatments were administered for two weeks, with tumor size and body weight were monitored. RESULTS: For A549 lung-cancer cells the IC50 value of rMETase was 0.64 U/ml. Combination treatment with rMETase (IC50) and cisplatinum (IC10-IC50) synergistically reduced cell viability compared with either agent alone, even at the IC10 of cisplatinum. In vivo, A549 tumor eradication was observed only in the low-dose cisplatinum + MR diet group. Standard-dose cisplatinum alone and MR-alone showed delayed or limited efficacy. Body-weight loss was minimal in the low-dose cisplatinum + MR group compared with the standard-dose cisplatinum group, indicating reduced systemic toxicity. CONCLUSION: Methionine restriction enhances the efficacy of ultra-low-dose cisplatinum on lung cancer cells in vitro. Low-dose cisplatinum in combination with an MR diet prevented lung-cancer growth in nude mice. The present approach of cancer therapy may help reduce platinum-related toxicity and improve treatment outcomes, suggesting further investigation for clinical translation.

BACKGROUND/AIM: Methionine addiction is a fundamental and general hallmark of cancer termed the Hoffman effect. Methionine restriction using recombinant methioninase (rMETase) has shown synergistic efficacy with numerous types of chemotherapeutic agents against cancer cells and not normal cells. Methionine adenosyltransferase 2A (MAT2A) is a crucial enzyme converting methionine to S-adenosylmethionine (SAM). A MAT2A inhibitor, AG-270, has been proposed as a potential anti-cancer drug. The present study evaluated whether AG-270 is a cancer-specific agent by comparing its efficacy in combination with rMETase on cancer and normal cells. MATERIALS AND METHODS: The half-maximal inhibitory concentrations (IC50) of rMETase and AG-270 were determined on HCT116 human colon-cancer cells and Hs-27 human normal fibroblasts in vitro. The efficacy of rMETase combined with AG-270, at their respective IC50 values, on HCT116 and Hs-27 was also determined. Cell viability was evaluated using the WST-8 reagent. RESULTS: The IC50 values of rMETase were 0.35 U/ml for HCT116 and 1.14 U/ml for Hs-27. The IC50 values of AG-270 were 4.38 μM for HCT116 and 6.55 μM for Hs-27. The combination of rMETase and AG-270, at their respective IC50, had synergistic efficacy on both cancer and normal cells, reducing viability to approximately 20% in both cell lines (p<0.05). CONCLUSION: AG-270 showed lack of cancer specificity in combination with rMETase when tested on both cancer and normal cells. The present results contrast with numerous chemotherapy agents, which in combination with rMETase are synergistic on cancer cells but not on normal cells. The present findings suggest that MAT2A inhibition affects crucial metabolic pathways in normal as well as cancer cell types and thus AG-270 may not be suitable as a cancer-specific therapeutic strategy.

BACKGROUND/AIM: Lung cancer remains one of the leading causes of cancer-related mortality worldwide due to its high incidence and poor prognosis. Although targeted therapies and immunotherapies have advanced, survival outcomes remain unsatisfactory for lung-cancer patients. Recombinant methioninase (rMETase), which targets methionine addiction, a fundamental and general hallmark of cancer, has demonstrated synergistic efficacy with chemotherapeutic agents in numerous cancer types. We have previously shown synergy of rMETase and ivermectin against pancreatic-, colon-, and breast-cancer cells. The present study aimed to investigate the synergistic efficacy of rMETase in combination with cisplatinum and ivermectin on lung-cancer cells compared to normal fibroblasts. MATERIALS AND METHODS: The human lung-adenocarcinoma cell line A549 and normal human-fibroblast cell strain Hs27 were seeded in 96-well plates (1,000 cells/well) containing Dulbecco's Modified Eagle's medium and incubated for 24 h. The cells were then treated for 72 h with rMETase (0.0625-8 U/ml), cisplatinum (0.25-32 μM), or ivermectin (1-128 μM). Cell viability was assessed using the WST-8 assay, and the 30% inhibitory concentration (IC30) for each drug was calculated for both cell types. To evaluate synergy, both cell types were treated with each drug alone or in two-drug and three-drug combinations based on their respective IC30 values, and cell viability was measured. To assess the time-dependent effects of the triple-combination treatment, A549 lung-cancer cells and Hs27 fibroblasts were cultured under the same conditions and treated with the triple combination. Cell viability was then measured at 24, 48, 72, and 96 h after treatment initiation. RESULTS: The IC30 value of rMETase was 0.46 U/ml; cisplatinum was 0.33 μM; and ivermectin was 2.08 μM for A549 lung-cancer cells. For normal Hs27 fibroblasts the IC30 value for rMETase was 0.5 units/ml; for cisplatinum was 0.35 μM and for ivermectin was 6.4 μM. When these 3 agents were combined at their respective A549 IC30 concentrations, A549 cell viability was significantly reduced compared to monotherapy or dual combinations (p<0.05), indicating synerg

BACKGROUND/AIM: Methionine addiction is a metabolic hallmark of cancer. Recombinant methioninase (rMETase) targets methionine addiction and effectively depletes methionine. rMETase has shown synergy with chemotherapeutic agents on numerous types of cancer cells. Chloroquine (CQ), an anti-autophagy agent, has demonstrated anti-cancer efficacy in pre-clinical studies. The present study aimed to evaluate the cancer selectivity and synergistic efficacy of rMETase and CQ in a co-culture model of colon-cancer cells and normal fibroblasts. MATERIALS AND METHODS: HCT116 human colon-cancer cells and Hs-27 human normal fibroblasts were co-cultured in Dulbecco's Modified Eagle's Medium (DMEM) and treated with rMETase (0.1-0.5 U/ml) alone, CQ (10-60 μM) alone, or rMETase at various concentrations in combination with CQ (20 μM). Cell morphology and viability were monitored for six days using phase-contrast microscopy (Olympus IX71). The effects of each treatment on the cancer cells and normal fibroblasts were compared. RESULTS: rMETase treatment selectively reduced HCT116 viability in a dose-dependent manner while sparing normal fibroblasts. In contrast, high-concentrations of CQ decreased the viability of both cell types, with strong cytotoxicity at ≥40 μM. Combination treatment with rMETase and low-dose CQ (20 μM) produced greater selective efficacy against the cancer cells than rMETase alone, eliminating the cancer cells and without significant inhibition of fibroblast viability. CONCLUSION: rMETase has selective efficacy against cancer cells in the presence of normal cells, and its efficacy is significantly enhanced selectively on the cancer cells by CQ. The results of the present study suggest the potential for future clinical application of the combination of rMETase and CQ for cancer treatment.

BACKGROUND/AIM: Pancreatic ductal adenocarcinoma (PDAC) is recalcitrant to conventional therapies. Recombinant methioninase (rMETase), rapamycin, and chloroquine target fundamental hallmarks of cancer. The present study examined the efficacy of each agent alone and in all combinations against PDAC cells compared to normal fibroblasts. MATERIALS AND METHODS: The 30% inhibitory concentration (IC30) of rMETase, rapamycin, and chloroquine on MiaPaCa-2 PDAC cells and Hs-27 normal human fibroblasts was determined with in vitro cell-viability assays using the WST-8 reagent. Combination treatment was performed at IC30 concentrations for MiaPaCa-2 cells to evaluate synergistic efficacy of all combinations of rMETase, rapamycin, and chloroquine on each cell type. RESULTS: rMETase alone led to significantly higher cytotoxicity against MiaPaCa-2 cells than Hs-27 fibroblasts (p<0.05). The triple combination of rMETase, rapamycin and chloroquine synergistically eradicated MiaPaCa-2 cells, reducing viability to 3.8% (p<0.05). In contrast, normal Hs-27 fibroblasts were not synergistically inhibited by the triple combination. CONCLUSION: The combination of rMETase, rapamycin and chloroquine had highly synergistic and selective efficacy against PDAC cells in vitro compared to normal cells, supporting its potential as a precision-targeted metabolic clinical therapy for pancreatic cancer.

BACKGROUND/AIM: Pancreatic cancer is a recalcitrant disease which often presents with few symptoms in the early stages and is frequently diagnosed with distant metastases, limiting treatment options and resulting in a poor prognosis. Recombinant methioninase (rMETase), which targets cancer-specific methionine addiction, has shown synergistic efficacy with numerous types of chemotherapy against all major cancer types. Ivermectin and chloroquine, anti-parasitic drugs, are showing promise against cancer. The present study investigates in vitro the potential synergy of rMETase combined with ivermectin and chloroquine, two agents with multiple anticancer mechanisms, as a novel treatment strategy for metastatic pancreatic cancer. MATERIALS AND METHODS: The human pancreatic-cancer cell line MiaPaCa-2 and normal human fibroblasts Hs27 were cultured in 96-well plates (1×103 cells/well) for 24 h. Cell viability was assessed using the WST-8 reagent following 72-h treatment with rMETase, ivermectin, or chloroquine to determine their 30% inhibitory concentration (IC30) values. To evaluate synergy, cells were treated with each drug alone or double or triple combinations at their respective IC30 concentrations. Additionally, to evaluate the optimal order of the combination therapy, MiaPaCa-2 cells were divided into four groups and sequentially treated for 72 h as follows: (1) untreated control; (2) the triple-drug combination therapy alone; (3) rMETase followed by the triple-drug combination therapy; (4) the triple-drug combination therapy followed by rMETase. RESULTS: The IC30 value of rMETase was 0.39 U/ml, ivermectin was 4.41 μM, and chloroquine was 3.29 μM on MiaPaCa-2 cells. The triple combination of these agents at their IC30 concentrations significantly inhibited MiaPaCa-2 cell growth compared to monotherapies or dual combinations, indicating a synergistic efficacy. In contrast, the same combination had minimal impact on Hs27 cells at the IC30 values determined for MiaPaCa-2. Regarding the treatment sequence, triple-drug combination therapy and triple-drug combination treatment followed by rMETase treatment significantly inhibited cell proliferation more than rMETase fo

BACKGROUND/AIM: Metastatic colon cancer is a recalcitrant disease. Previous studies have shown efficacy of Salmonella typhimurium A1-R (A1-R), recombinant methioninase (rMETase), and chloroquine (CQ) on cancer cells as they target fundamental hallmarks of cancer. The present study examined these agents alone and all combinations against colon-cancer cells compared to normal fibroblasts. MATERIALS AND METHODS: The in vitro cytotoxicity and synergy of A1-R, rMETase, and CQ were assessed on the HCT116 colon-cancer cell line and Hs-27 normal fibroblasts. Cell viability was measured using the WST-8 assay. IC30 and IC50 values were determined. Combination treatments were performed at IC30 concentrations to evaluate synergistic efficacy of all combinations of A1-R, rMETase, and CQ on each cell type. RESULTS: A1-R alone and rMETase alone showed significantly higher cytotoxicity on HCT116 cells than on Hs-27 fibroblasts. Combination of A1-R with either rMETase or CQ demonstrated selective cytotoxicity toward HCT116 cells compared to normal Hs-27 fibroblasts. The triple combination selectively eradicated the cancer cells. CONCLUSION: Tumor-targeting with A1-R combined with methionine restriction (rMETase) or autophagy inhibition (CQ) resulted in selective and synergistic cytotoxicity against colon-cancer cells compared to normal fibroblasts. The present findings support the clinical potential of the combination of A1-R, rMETase, and CQ for recalcitrant colon cancer.

BACKGROUND/AIM: Metastatic colon cancer is a recalcitrant disease with a 5-year survival rate of 15.7-26.0%, and more effective treatments are necessary. Methionine addiction is a fundamental and general hallmark of cancer. Targeting methionine addiction with recombinant methioninase (rMETase) is effective against colon-cancer cells. Combining the autophagy inhibitor chloroquine with rMETase has shown efficacy on breast cancer and osteosarcoma cells. The present study aimed to determine whether the combination of chloroquine and rMETase is selectively synergistic against colon-cancer cells in contrast to normal fibroblasts. MATERIALS AND METHODS: The present study used the human colon-cancer cell line HCT-116 and Hs27 normal human fibroblasts. Cells (1×103) were seeded in each well of 96-well plates and cultured in Dulbecco's modified Eagle's medium (DMEM) with 10% fetal bovine serum at 37°C in 5% CO2 for 24 h. Cells were then treated with rMETase at concentrations ranging from 0.0625 U/ml to 8 U/ml or chloroquine at concentrations ranging from 0.5 μM to 128 μM for 72 h. Drug-sensitivity curves were generated using a cell viability assay with the WST-8 reagent. The half-maximal inhibitory concentration (IC50) of rMETase and chloroquine against HCT-116 and Hs27 cells was calculated. Cell viability of cells treated with rMETase alone, chloroquine alone, and the combination of rMETase and chloroquine at IC50 concentrations was assessed. RESULTS: The IC50 concentrations of rMETase on HCT-116 and Hs27 were 0.61 μM and 0.67 μM, respectively. The IC50 concentrations of chloroquine on HCT-116 and Hs27 were 7.52 U/ml and 10.85 U/ml, respectively. Cell viability assays using these IC50 concentrations showed that the combination of rMETase and chloroquine had synergistic efficacy on HCT-116 cells, but not on Hs27 cells. CONCLUSION: The combination of chloroquine and rMETase had synergistic efficacy on colon-cancer cells, but not on normal fibroblasts. rMETase is used clinically as an oral supplement, and chloroquine is a drug approved for clinical use. Therefore, the combination of rMETase and chloroquine has the potential for safe clinical application.

BACKGROUND/AIM: The prognosis for advanced/metastatic colon cancer is poor, with low survival rates despite aggressive treatment. Recombinant methioninase (rMETase) targets the methionine addiction of cancer and works synergistically with many anticancer drugs. The present study aimed to determine the synergistic efficacy of the combination of rMETase, rapamycin (RAPA), and chloroquine (CQ) on human HCT116 colon cancer cells in vitro. MATERIALS AND METHODS: The half-maximal inhibitory concentrations (IC50) of rMETase, RAPA, and CQ were determined for the human HCT116 cell line in vitro. The synergy of rMETase combined with RAPA; rMETase combined with CQ; and rMETase combined with RAPA and CQ, at their respective IC50 values, was determined on HCT116 cells. Cell viability was measured with the WST-8 reagent. RESULTS: The IC50 value of rMETase was 0.48 U/ml; for RAPA 19.6 μM; and for CQ 16.5 μM on the HCT116 cell line. Synergy was observed with both the combination of rMETase and RAPA (p=0.02) and the combination of rMETase and CQ (p=0.03). The triple combination of rMETase, RAPA, plus CQ showed the strongest synergistic efficacy, eradicating HCT116 cells (p=0.01). CONCLUSION: The triple combination of rMETase, RAPA and CQ shows strong synergistic efficacy on the human HCT116 colon cancer cell line. The results of the present study suggest the potential for future clinical applications of this triple-combination treatment for advanced/metastatic colon cancer.

This systematic review and meta-analysis aimed to assess the efficacy and acceptability of S-adenosyl-L-methionine (SAMe) in treating depression. We conducted a comprehensive search of PubMed, Embase, Cochrane Library, and ClinialTrials.gov from inception to July 3, 2023, identifying randomized controlled trials comparing SAMe with placebo or antidepressants (ADs). We synthesized data on reduced depressive symptoms (efficacy) and overall dropout rates (acceptability) using a random-effects model for pairwise frequentist meta-analysis. Our analysis included 23 trials (N = 2183) classified into three categories: 11 trials comparing SAMe and placebo, 5 trials comparing SAMe plus ADs and placebo plus ADs, and 7 trials comparing SAMe and ADs. Differences between experimental and control interventions in reducing depressive symptoms were observed: i) SAMe demonstrated significantly superior efficacy compared to placebo (SMD = -0.58, 95% CI = -0.93 to -0.23, I2 = 68%); ii) in conjunction with ADs, SAMe did not show a significant difference from placebo (SMD = -0.22, 95%CI = -0.63 to 0.19, I2 = 76%); and iii) SAMe did not exhibit a significant difference from ADs alone (SMD = 0.06, 95%CI = -0.06 to 0.18, I2 = 49%). No significant differences in dropout rates were observed across the three comparison categories. Moderate-certainty evidence suggests that SAMe monotherapy may offer a moderate therapeutic benefit in alleviating depressive symptoms. Considering its favorable acceptability profile, SAMe monotherapy should be considered as a treatment option for patients with depression. However, uncertainties regarding its efficacy as an adjunct to AD and its comparative efficacy with ADs remain unresolved.

BACKGROUND: Major depressive disorder (MDD) is an intractable disease requiring long-term treatment. S-adenosyl-L-methionine (SAMe), a natural substance, has antidepressant effects, but the exact effect remains unclear. This study examines the evidence concerning the efficacy of SAMe as a monotherapy or in combination with antidepressants. METHODS: The PubMed, EMBASE, and Cochrane electronic databases were searched for meta-analyses of randomized controlled clinical trials (RCTs) until June 30, 2023. We performed a systematic review and meta-analysis of the enrolled trials that met the inclusion criteria, with the aim to compare the effects of SAMe to those of a placebo or active agents, or SAMe combined with other antidepressants in the treatment of MDD. RESULTS: Fourteen trials, with a total of 1522 subjects, were included in this review. The daily dose of SAMe varied from 200 to 3200 mg and the study duration ranged between 2 and 12 weeks. The results of SAMe versus placebo as a monotherapy, SAMe versus imipramine or escitalopram as a monotherapy, and SAMe versus placebo as an adjunctive therapy, showed no significant difference in depression with SAMe compared to the comparison treatment. CONCLUSIONS: SAMe may provide relief of depression symptoms similar to imipramine or escitalopram. However, the results of the comparisons should be interpreted with caution due to the small number of studies and the large range of SAMe doses that were used in the included trials. Therefore, we recommend that patients discuss treatment options with their doctor before taking SAMe.

Uncomplicated urinary tract infection (UTI) is the most common bacterial infection in women. Since 1948, the relationship between urinary pH and antibiotics (ABs) has been established. We aimed to search for the best urinary pH for each family of antibiotics and to assess whether pH changes bacterial susceptibility to them. We included in vitro research and in vivo studies including one or more bacterial species and tested the effect of one or more ABs at different pH values. We also included randomized controlled clinical trials (RCTs) in uncomplicated UTI (EAU guidelines 2019 definition), choosing the ABs based on urinary pH or using an antibiotic plus urinary pH modifiers (L-methionine, vitamin C…) vs. an antibiotic and a placebo. Quadas-2 tool was used as a quality assessment of the studies and PRISMA set of items for systematic reviews. Two authors independently screened and evaluated the papers, while two additional authors individually repeated the search. A fifth researcher acted as an arbiter, and another author collaborated as a hospital pharmaceutical consultant. Alkaline-friendly antibiotics are most fluoroquinolones, aminoglycosides, trimethoprim. Acidic-friendly antibiotics are fosfomycin, tetracycline, nitrofurantoin and some β-lactams. We suggest performing urine cultures with antibiogram tests, in both acidic and alkaline media, to define the bacterial susceptibility profile. There is insufficient in vivo evidence to support whether choosing an antibiotic based on a patient's urinary pH or adding urinary pH modifiers will lead to a higher cure rate.

Aggression in correctional and psychiatric settings is relatively common and has a negative effect on physical and mental health both among inmates/clients and staff, as well as organizational-level functioning. The aim of the present study was to critically review the evidence on the effectiveness of nutritional supplements in reducing aggression and violence to contribute to a better understanding of options available for managing aggressive behaviors in adults. The EMBASE, MEDLINE, PsycINFO, Cochrane Library, and PubMed databases were searched for effectiveness studies published in English anytime up until March 2020. Study quality was assessed using the Mixed Methods Appraisal Tool. Altogether, 14 studies met inclusion criteria; 2 investigated micronutrients, 10 examined macronutrients, while further 2 examined a combination of micro and macronutrients. Out of the 14 studies, 5 reported a beneficial effect of nutritional supplementation (omega-3 fatty acids, vitamins/minerals, S-adenosyl-l-methionine, or tryptophan). Five studies did not report a significant beneficial effect of nutritional supplementation (omega-3 fatty acids, folic acid, tryptophan, broad range supplement containing vitamins and fatty acids, and fatty acids in augmentation with valproic acid), while four studies reported mixed effects (on l-tryptophan, broad-range micronutrient formula, folic acid, and omega-3 fatty acids). The results overall indicated that research in this area is in its infancy: very few studies examined the same composition of nutritional supplementation and when they did so the results were contradictory. The methodological shortcoming of existing studies and directions for future research are discussed to facilitate high-quality research in this evolving area of nutritional psychiatry. © 2021 Wiley Periodicals LLC.

Posttreatment high-grade gliomas are usually monitored with contrast-enhanced MRI, but its diagnostic accuracy is limited as it cannot adequately distinguish between true tumor progression and treatment-related changes. According to recent Response Assessment in Neuro-Oncology recommendations, PET overcomes this limitation. However, it is currently unknown which tracer yields the best results. Therefore, a systematic review and metaanalysis were performed to compare the diagnostic accuracy of the different PET tracers in differentiating tumor progression from treatment-related changes in high-grade glioma patients. Methods: PubMed, Web of Science, and Embase were searched systematically. Study selection, data extraction, and quality assessment were performed independently by 2 authors. Metaanalysis was performed using a bivariate random-effects model when at least 5 studies were included. Results: The systematic review included 39 studies (11 tracers). 18F-FDG (12 studies, 171 lesions) showed a pooled sensitivity and specificity of 84% (95% confidence interval, 72%-92%) and 84% (95% confidence interval, 69%-93%), respectively. O-(2-18F-fluoroethyl)-l-tyrosine (18F-FET) (7 studies, 172 lesions) demonstrated a sensitivity of 90% (95% confidence interval, 81%-95%) and specificity of 85% (95% confidence interval, 71%-93%). For S-11C-methyl)-l-methionine (11C-MET) (8 studies, 151 lesions), sensitivity was 93% (95% confidence interval, 80%-98%) and specificity was 82% (95% confidence interval, 68%-91%). The numbers of included studies for the other tracers were too low to combine, but sensitivity and specificity ranged between 93%-100% and 0%-100%, respectively, for 18F-FLT; 85%-100% and 72%-100%, respectively, for 3,4-dihydroxy-6-18F-fluoro-l-phenylalanine (18F-FDOPA); and 100% and 70%-88%, respectively, for 11C-choline. Conclusion:18F-FET and 11C-MET, both amino-acid tracers, showed a comparably higher sensitivity than 18F-FDG in the differentiation between tumor progression and treatment-related changes in high-grade glioma patients. The evidence for other tracers is limited; thus, 18F-FET and 11C-MET are preferred when available. Our results support the incorporat

OBJECTIVE: Approximately 55-76% of Service members use dietary supplements for various reasons; although such use has become popular, decisions are often driven by information that is not evidence-based. This work evaluates whether current research on dietary ingredients for chronic musculoskeletal pain provides sufficient evidence to inform decisions for practice and self-care, specifically for Special Operations Forces personnel. METHODS: A steering committee convened to develop research questions and factors required for decision-making. Key databases were searched through August 2016. Eligible systematic reviews and randomized controlled trials were assessed for methodological quality. Meta-analysis was applied where feasible. Grading of Recommendations, Assessment, Development and Evaluation was used to determine confidence in the effect estimates. The committee used a decision table to make evidence-informed judgments across decision-making factors and recommendations for practice and self-care use. RESULTS: Nineteen dietary ingredients were assessed. No recommendations were given for boswellia, ginger, rose hip, or s-adenosyl-L-methionine (SAMe); specifically, although ginger can be obtained via food, no recommendation is provided for use as a supplement due to unclear research. Further, there were insufficient strong research on boswellia and SAMe and possible compliance issues (i.e., high number of capsules required daily) associated with rose hip. CONCLUSIONS: No recommendations were made when the evidence was low quality or trade-offs were so closely balanced that any recommendation would be too speculative. Research recommendations are provided to enhance the quality and body of evidence for the most promising ingredients. Clinicians and those with chronic pain can rely on evidence-based recommendations to inform their decisions. © 2019 American Academy of Pain Medicine.

Rex rabbit fur is a high-value material in the textile industry; however, the integrated metabolomic and transcriptomic mechanisms underlying differences in fur traits between fur-type Rex rabbits and meat-type New Zealand White rabbits remain incompletely understood. In this study, 40 rabbits (20 per group) raised under identical feeding conditions were used to evaluate fur quality traits. Dorsal skin samples were collected for metabolomic and transcriptomic analyses. The results showed that Rex rabbits had significantly lower fibre length and fur thickness than New Zealand White rabbits (p < 0.01). Metabolomic analysis identified 267 DMs, mainly comprising lipids and organic acids. These metabolites were enriched in butanoate metabolism, steroid hormone biosynthesis, cysteine and methionine metabolism, and the citrate cycle. Key metabolites included histamine, L-arginine, creatine, and indoxyl. Transcriptomic analysis identified 895 DEGs, enriched in MAPK, cAMP, and HIF-1 signaling pathways, including keratin family genes (KRT34, KRT84, KRT82), FGFR4, EGF, BMP5, and DKK2. Integrated analysis identified 211 DEGs and 97 DMs co-enriched in 103 pathways, including HIF-1, cAMP, and AMPK signaling pathways. These findings reveal a gene-metabolite regulatory network involved in skin and hair follicle development, provide molecular markers for improving rabbit fur quality, and enhance understanding of the genetic and metabolic basis of mammalian hair follicle development.

This study evaluated the effects of supplementing methionine to a low-protein diet on nutrient digestibility, nitrogen (N) metabolism, growth performance, serum biochemical parameters, fur quality, and intestinal microbiota composition in blue foxes (Vulpes lagopus) during the fur-growing period. Fifty 17-week-old blue foxes were randomly allocated to five experimental groups (n = 10 per group). The control group received a diet containing 28% crude protein (CP), while the experimental groups were fed a 22% CP diet supplemented with 0%, 0.35%, 0.55%, or 0.75% methionine on a dry matter (DM) basis, designated as M0, M1, M2, and M3, respectively. Results demonstrated that the final body weight (FW), total weight gain (TW), and average daily gain (ADG) of the M3 group were comparable to the control group (p > 0.05). Methionine supplementation significantly enhanced fur quality and stimulated hair follicle development (p < 0.05). Although the reduction in dietary protein level led to decreased N intake and fecal N excretion, the M2 and M3 groups exhibited significantly higher N retention compared to the control, M0, and M1 groups (p < 0.05). Regarding nutrient digestibility, the M2 and M3 groups showed higher DM digestibility (p < 0.05), while the M3 group maintained organic matter (OM) digestibility comparable to the control group (p > 0.05). The highest CP digestibility was observed in the M3 group (p < 0.05). Additionally, ether extract (EE) digestibility was significantly improved in the methionine-supplemented groups (M1-M3) relative to the control (p < 0.05). Serum analysis revealed dose-dependent increases in total protein (TP), albumin (ALB), and high-density lipoprotein (HD

Several strains of Lysobacter have demonstrated keratin-degrading capabilities, positioning them as promising candidates for the degradation and utilization of wool waste. In our previous study, a novel strain, Lysobacter brunescens YQ20, exhibiting highly efficient keratin degradation capabilities, was isolated. In this study, transcriptomic and proteomic analyses were conducted to elucidate the underlying mechanisms of keratin degradation. Our findings revealed that several metabolic pathways, specifically, valine, leucine, and isoleucine biosynthesis; phenylalanine, tyrosine, and tryptophan biosynthesis; glycine, serine, and threonine metabolism; and histidine metabolism, were highly active during keratin degradation, thereby supporting the growth and metabolism of L. brunescens YQ20. Additionally, the upregulation of genes related to sulfur metabolism, cysteine and methionine metabolism, and glutathione metabolism pathways facilitated the cleavage of disulfide bonds in keratin. Moreover, keratinases identified among the differentially expressed genes and proteins (DEGs/DEPs) were classified into the S8, M14, and M28 families, whose synergistic activity contributed to the efficient hydrolysis of keratin. Collectively, these results provide valuable insights

4. Stem Cell Res Ther. 2025 Nov 24;16(1):692. doi: 10.1186/s13287-025-04806-4. The human umbilical cord-mesenchymal stem cell secretome regulates hair growth and cycle transition by promoting methylthioadenosine synthesis via the PI3K/AKT/mTOR pathway. Zhang Y(#)(1)(2)(3), Wang X(#)(1)(2)(3), Chen Q(1)(2)(3), Zhao S(1)(2)(3), Bu L(1)(2)(3), Wu S(1)(2)(3), Huang J(1)(2)(3), Xu X(1)(2)(3), Yang X(1)(2)(3), Miao Y(4), Zhang L(5)(6)(7), Zhang M(8)(9)(10). Author information: (1)Department of Histology and Embryology, School of Basic Medical Sciences, Southern Medical University, No. 1023-1063, Shatai South Road, Baiyun District, Guangzhou, 510515, People's Republic of China. (2)NMPA Key Laboratory for Safety Evaluation of Cosmetics, GDMPA Key Laboratory of Key Technologies for Cosmetics Safety and Efficacy Evaluation, Southern Medical University, No. 1023-1063, Shatai South Road, Baiyun District, Guangzhou, 510515, People's Republic of China. (3)Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering, Southern Medical University, No. 1023-1063, Shatai South Road, Baiyun District, Guangzhou, 510515, People's Republic of China. (4)Department of Plastic and Aesthetic Surgery, Nanfang Hospital of Southern Medical University Guangzhou, No. 1838, North Guangzhou Avenue, Baiyun District, Guangzhou, 510515, Guangdong Province, People's Republic of China. [email protected]. (5)Department of Histology and Embryology, School of Basic Medical Sciences, Southern Medical University, No. 1023-1063, Shatai South Road, Baiyun District, Guangzhou, 510515, People's Republic of China. [email protected]. (6)NMPA Key Laboratory for Safety Evaluation of Cosmetics, GDMPA Key Laboratory of Key Technologies for Cosmetics Safety and Efficacy Evaluation, Southern Medical University, No. 1023-1063, Shatai South Road, Baiyun District, Guangzhou, 510515, People's Republic of China. [email protected]. (7)Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering, Southern Medical University, No. 1023-1063, Shatai South Road, Baiyun District, Guangzhou, 510515, People's Republic of China. [email protected].

This study furnishes insights into how methionine mitigates heat-stress-induced impairments in hair follicle development in Rex rabbits at the cellular level. Dermal papilla cells from the dorsal skin of Rex rabbits were isolated, cultured in vitro, and divided into six groups, i.e., control (37 °C; 0 mM methionine), heat stress (45 °C; 0 mM methionine), and heat stress + methionine (45 °C; 15 mM, 30 mM, 45 mM, and 60 mM methionine), with six replicates per group. The heat stress groups were exposed to 45 °C, 5% CO2, and 95% humidity for 30 min, followed by recovery at 37 °C, repeated three times over three days. On the third day, samples were collected post-heat stress. The results show that methionine markedly fortified HSP70, MSRA, and SOD expression (p < 0.01); augmented proliferation (p < 0.01); ameliorated cell cycle progression; and lessened apoptosis (p < 0.05). Adding Wnt signaling pathway activators and inhibitors manifested that these effects were associated with diminished β-catenin phosphorylation and aggrandized expression of the Wnt10b, β-catenin (p < 0.001), and LEF/TCF nuclear transcription factors (p < 0.01). Thus, this study demonstrates that methionine regulates the growth and development of heat-stressed hair papilla cells via the Wnt signaling pathway, remitting heat-stress trauma.

We present a case of a male term neonate with lethargy, hypotonia, hypoventilation and severe encephalopathy. The infant had a history of two siblings who died in the neonatal period from unclear causes. The infant exhibited skin and hair abnormalities, including desquamation of the extremities, angular stomatitis, cheilitis, neonatal acne and thin, sparse hair. Additionally, the infant had a tall stature; long, slender fingers and toes; and facial dysmorphism characterised by a long, narrow face with increased interpalpebral distance. The condition deteriorated rapidly, and unfortunately, death occurred before a definitive diagnosis could be established. Tandem mass spectrometry suggested low methionine and clinical exome sequencing identified a nonsense mutation in the MTHFR gene. © BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.

AP collagen peptides (APCPs) are enzymatically decomposed collagen peptides that contain tri-peptides such as glycine-proline-hydroxyproline. We found that APCPs increased the proliferation of both human dermal papilla cells (hDPCs) and human outer root sheath cells (hORSCs). APCPs also stimulated the secretion of several growth factors, including IGFBP-6, PDGF-AB, PIGF and VEGF in hDPCs. Moreover, APCPs enhanced the phosphorylation of Akt(Ser473), GSK-3β(Ser9) and β-catenin(Ser675), indicating the activation of the GSK-3β/β-catenin signalling pathway. Ex vivo culture of human hair follicles (hHFs) tissue and in vivo patch assay revealed that APCPs promoted the elongation of hHFs and the induction of new hair shafts. In a mouse model, APCPs significantly promoted the transition from telogen to anagen phase and prolonged anagen phase, resulting in increased hair growth. APCPs also improved the thickness, amino acid content (cystine and methionine) and roughness of mouse hair. Taken together, these findings demonstrate that APCPs accelerate hair growth and contribute to overall hair health. Therefore, APCPs have the potential to be utilized as a food supplement and ingredient for preventing hair loss and maintaining hair health. © 2024 The Author(s). Experimental Dermatology published by John Wiley & Sons Ltd.

OBJECTIVE: To investigate the relationship between homocysteine (HCY) and androgenetic alopecia (AGA). METHODS: A case control study and two observational experiments on mice were conducted. In the first part, a total of 528 Chinese AGA patients and 500 age-matched healthy controls were included. Serum HCY levels of AGA and controls were compared. In the second part, eight mice were divided into two groups. Both groups of mice had their hair removed. AGA group received a DHT injection, and the other as control group. HCY levels in hair follicles (HFs) were detected by ELISA and compared. In the third part, twelve mice were divided into three groups and fed with different concentrations of methionine. After 4 weeks, serum HCY levels, parameters related to hair growth through observation and HE staining, and expression of immunohistochemistry (IHC) hair-growth-related markers Ki67, VEGF, IGF-1, Krt27, FGF9, and TGF-β1 were compared among the three groups. RESULTS: In the first part, HCY levels were higher in AGA than the controls of both genders. However, there was no difference in HCY levels between groups with varying severity. Rates of hyperhomocysteinemia was higher in AGA patients than the controls. Logistic regression analysis showed serum HCY levels was positively correlated with the incidence of AGA. In the second part, HCY of the HFs in the AGA group was significantly higher than that in the control group. The third part showed that the increase in serum HCY levels inhibited the growth of mice hair, with the less expressed stimulative markers Ki67, VEGF, IGF-1, Krt27, and FGF9, while there was no difference in the expression of inhibitory markers TGF-β1. CONCLUSION: There is a potential relationship between H

BACKGROUND/AIM: Hair-follicle keratinocytes contain high levels of cysteine, which is derived from methionine, rapidly proliferate, and form the hair shaft. The high proliferation rate of hair-follicle keratinocytes resembles that of aggressive cancer cells. In the present study, we determined the effect of a methionine-deficient diet on hair loss (alopecia) in mice with or without homocysteine supplementation. MATERIALS AND METHODS: Mice were fed a normal rodent diet (2020X, ENVIGO) (Group 1); a methionine-choline-deficient diet (TD.90262, ENVIGO) (Group 2); a methionine-choline-deficient diet with a 10 mg/kg/day supply of homocysteine administered by intra-peritoneal (i.p.) injection for 2 weeks (Group 3). In Group 2, mice were fed a methionine-choline-deficient diet for an additional 2 weeks but with 10 mg/kg/day of i.p. l-homocysteine and the mice were observed for two additional weeks. Subsequently, the mice were fed a standard diet that included methionine. Hair loss was monitored by photography. RESULTS: After 14 days, hair loss was observed in Group 2 mice on a methionine-restricted diet but not in Group 3 mice on the methionine-restricted diet which received i.p. homocysteine. In Group 2, at 2 weeks after methionine restriction, hair loss was not rescued by homocysteine supplementation. However, after restoration of methionine in the diet, hair growth resumed. Thus, after 2 weeks of methionine restriction, only methionine restored hair loss, not homocysteine. CONCLUSION: Hair maintenance requires methionine in the diet. Future experiments will determine the effects of methionine restriction on hair-follicle stem

The hair and skin of domestic cats or dogs account for 2% and 12-24% of their body weight, respectively, depending on breed and age. These connective tissues contain protein as the major constituent and provide the first line of defense against external pathogens and toxins. Maintenance of the skin and hair in smooth and elastic states requires special nutritional support, particularly an adequate provision of amino acids (AAs). Keratin (rich in cysteine, serine and glycine) is the major protein both in the epidermis of the skin and in the hair. Filaggrin [rich in some AAs (e.g., serine, glutamate, glutamine, glycine, arginine, and histidine)] is another physiologically important protein in the epidermis of the skin. Collagen and elastin (rich in glycine and proline plus 4-hydroxyproline) are the predominant proteins in the dermis and hypodermis of the skin. Taurine and 4-hydroxyproline are abundant free AAs in the skin of dogs and cats, and 4-hydroxyproline is also an abundant free AA in their hair. The epidermis of the skin synthesizes melanin (the pigment in the skin and hair) from tyrosine and produces trans-urocanate from histidine. Qualitative requirements for proteinogenic AAs are similar between cats and dogs but not identical. Both animal species require the same AAs to nourish the hair and skin but the amounts differ. Other factors (e.g., breeds, coat color, and age) may affect the requirements of cats or dogs for nutrients. The development of a healthy coat, especially a black coat, as well as healthy skin critically depends on AAs [particularly arginine, glycine, histidine, proline, 4-hydroxyproline, and serine, sulfur AAs (methionine, cysteine, and taurine), phenylalanine, and tyrosine] and creatine. Although there are a myriad of studies

Methods for targeting enzymes exhibiting anticancer properties, such as methionine γ-lyase (MGL), have not yet been sufficiently developed. Here, we present the data describing the physico-chemical properties and cytotoxic effect of fusion protein MGL-S3 - MGL from Clostridium sporogenes translationally fused to S3 domain of the viral growth factor of smallpox. MGL-S3 has methioninase activity comparable to native MGL. In solution, MGL-S3 protein primarily forms octamers, whereas native MGL, on the contrary, usually forms tetramers. MGL-S3 binds to the surface of the neuroblastoma SH-SY5Y and e

BACKGROUND: Oral supplementation with some amino acids (like methionine, taurine, and cysteine) could be useful in subjects with hair loss conditions such as androgenic alopecia (AGA or FAGA) or telogen effluvium (TE). Hydrolysed collagen (HC) oral supplementation has demonstrated to have beneficial effects on nail and skin health and could improve hair growth. A food supplement in tablet formulation containing hydrolysed fish-origin collagen (300 mg/dose), taurine, cysteine, methionine, iron, and selenium has been recently available. To date no controlled data are available regarding the clinical efficacy of this product as adjuvant to hair loss specific treatments in these clinical conditions. STUDY AIMS: To evaluate and compare the efficacy and tolerability of an oral supplementation based on HC and amino acids in subjects with hair loss due to AGA/FAGA or chronic TE in combination with drug treatments in comparison with drug treatments alone. METHODS AND SUBJECTS: In a prospective, 12-week, randomized, assessor-blinded controlled trial 83 subjects (mean age 41 ± 16 years; 26 men and 57 women) were enrolled in the study. Fifty-nine subjects suffered from