L-Histidine

OBJECTIVE: The aim of this meta-analysis was to explore the effects of beta-alanine supplementation on Yo-Yo test performance. METHODS: Nine databases were searched to find relevant studies. A random-effects meta-analysis of standardized mean differences (SMD) was performed for data analysis. Subgroup meta-analyses were conducted to explore the effects of beta-alanine supplementation duration on Yo-Yo test performance, and the effects of beta-alanine supplementation on performance only in Yo-Yo level 2 test variants. RESULTS: Ten study groups were included in the meta-analysis. All studies included athletes as study participants. When considering all available studies, there was no significant difference between the placebo/control and beta-alanine groups (SMD: 0.68; 95% confidence interval [CI]: -0.30, 1.67). When considering only the studies that used supplementation protocols lasting between 6 and 12 weeks, there was a significant ergogenic effect of beta-alanine (SMD: 1.02; 95% CI: 0.01, 2.05). When considering only the studies that used the level 2 variants of the Yo-Yo test, there was a significant ergogenic effect of beta-alanine (SMD: 1.41; 95% CI: 0.35, 2.48). CONCLUSIONS: This meta-analysis found that beta-alanine is ergogenic for Yo-Yo test performance in athletes when the supplementation protocol lasts between 6 and 12 weeks and when using the level 2 variants of the Yo-Yo test.

Autism spectrum disorders (ASD) are an emerging health problem worldwide. So far, no definite cure for ASD exists. L-Carnosine is an amino acid containing β-alanine and L-histidine which has been proposed to have neuroprotective, antioxidant and anti-convulsive properties that may benefit affected children with this disorder. This review aimed to assess the effect of L-Carnosine in the management of ASD in children. We systematically reviewed randomised controlled trials (RCTs) which documented the effect of L-Carnosine in children with ASD. A literature search was performed in PubMed, Cochrane Library, Google Scholar, ClinicalTrials.gov, Clinical Trial Registry-India databases from inception to December 20, 2020. Articles were selected based on pre-set inclusion/exclusion criteria. The primary outcomes were changes in social, communication and behavioural responses and the secondary outcomes were improvement in sleep disorders, gastrointestinal problems, oxidative stress markers and adverse effects. Jadad scale was used to assess the quality of RCTs and modified Cochrane risk of bias tool was used to check the risk of bias of the included studies. The meta-analysis was reported based on the fixed-effects model. Four double-blinded, placebo-controlled, RCTs and one open label trial with a total of 215 participants were selected for the review. All the trials were methodological of high quality according to the Jadad scale. The modified Cochrane risk of bias tool showed a low to high risk of bias. Results from the meta-analysis of three studies showed no significant difference between L-Carnosine and placebo groups in the Gilliam autism rating scale (GARS) (MD = - 2.57; 95% CI - 10.30, 5.16, p = 0.52) and in its socialisation (MD = - 1.51; 95% CI - 6.16, 3.14, p = 0.53), behaviour (MD = - 0.48; 95% CI - 4.82, 3.87, p = 0.83) and communication (MD = - 3.94; 95% CI - 10.00, 2.11, p = 0.20) subscales as well as the childhood autism rating scale (CARS) (MD = - 0.88; 95% CI - 6.96, 5.20; p = 0.78). Current data do not support the use of L-Carnosine in the management of children with ASD due to a low number of studies and sample size available. Further studies are warr

BACKGROUND: Understanding the multifactorial nature of major depressive disorder (MDD) is crucial for tailoring treatments. However, the complex interplay of various factors underlying the development and progression of MDD poses significant challenges. Our previous study demonstrated improvements in cognitive functions in MDD patients undergoing treatment with selective serotonin reuptake inhibitors (SSRIs) supplemented with Lactobacillus plantarum 299v (LP299v). METHODS: To elucidate the biochemical mechanisms underlying cognitive functions improvements, we explored underlying metabolic changes. We employed multi-platform metabolomics, including LC-QTOF-MS and CE-TOF-MS profiling, alongside chiral LC-QqQ-MS analysis for amino acids. RESULTS: Supplementation of SSRI treatment with LP299v intensified the reduction of long-chain acylcarnitines, potentially indicating improved mitochondrial function. LP299v supplementation reduced N-acyl taurines more than four times compared to the placebo, suggesting a substantial impact on restoring biochemical balance. The LP299v-supplemented group showed increased levels of oxidized glycerophosphocholine (oxPC). Additionally, LP299v supplementation led to higher levels of sphingomyelins, L-histidine, D-valine, and p-cresol. LIMITATIONS: This exploratory study suggests potential metabolic pathways influenced by LP299v supplementation. However, the need for further research hinders the ability to draw definitive conclusions. CONCLUSIONS: Observed metabolic changes were linked to mitochondrial dysfunction, inflammation, oxidative stress, and gut microbiota disruption. Despite the subtle nature of this alterations, our research successfully detected these differences and connected them to the metabolic disruptions associated with MDD. Our findings emphasise the intricate relationship between metabolism, gut microbiota, and mental health prompting further research into the mechanisms of action of probiotics in MDD treatment.

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

In this study, we report a facile method to construct a bioactive (poly(phenylalanine)-b-poly(l-histidine)-b-poly(ethylene glycol) polypeptide nanoconstruct to co-load doxorubicin (DOX) and quercetin (QUR) (DQ-NV). The smart pH-sensitive nanovehicle was fabricated with precisely tailored drug-to-carrier ratio that resulted in accelerated, sequential drug release. As a result of ratiometric loading, QUR could significantly enhance the cytotoxic potential of DOX, induced marked cell apoptosis; change cell cycle patterns, inhibit the migratory capacity of sensitive and resistant cancer cells. In particular, pro-oxidant QUR from DQ-NV remarkably reduced the GSH/GSSG ratio, indicating high oxidative stress and damage to cellular components. DQ-NV induced tumor shrinkage more effectively than the single drugs in mice carrying subcutaneous SCC-7 xenografts. DQ-NV consistently induced high expression of caspase-3 and PARP and low expression of Ki67 and CD31 immunomarkers. In summary, we demonstrate the development of a robust polypeptide-based intracellular nanovehicle for synergistic delivery of DOX/QUR in cancer chemotherapy. STATEMENT OF SIGNIFICANCE: In this study, we report a facile method to construct bioactive and biodegradable polypeptide nanovehicles as an advanced platform technology for application in cancer therapy. We designed a robust (poly(phenylalanine)-b-poly(l-histidine)-b-poly(ethylene glycol) nanoconstruct to co-load doxorubicin (DOX) and quercetin (QUR) (DQ-NV). The conformational changes of the histidine block at tumor pH resulted in accelerated, sequential drug release. QUR could significantly enhance the cytotoxic potential of DOX, induce marked cell apoptosis, change cell cycle patterns, and inhibit the migratory capacity of sensitive and resistant cancer cells. DQ-NV induced tumor shrinkage more effectively than the single drugs and the 2-drug cocktail in tumor xenografts. In summary, we demonstrate the development of an intracellular nanovehicle for synergistic delivery of DOX/QUR in cancer chemotherapy.

Cationic peptides as a non-viral gene vector have become a hotspot of research because of their high transfection efficcacy and safety. Based on our previous study, we synthesized a cationic reduction-responsive vector based on disulfide cross-linked L-arginine, L-histidine and lipoic acid (LHRss) as the co-carrier of both doxorubicin (DOX) and the necrosis factor-related apoptosis-inducing ligand (pTRAIL). The LHRss/DOX/TRAIL construct has reduction-sensitive behavior and an enhanced endosomal escape ability to increase the cytotoxicity of DOX and the transfection efficiency. Further, the LHRss/DOX/TRAIL construct increased the accumulation of DOX and promoted the expression of pTRAIL, thus increasing cellular apoptosis by 83.7% in MCF-7/ADR cells. In addition, the in vivo biodistribution results showed that the LHRss/DOX/TRAIL construct could target tumors well. The in vivo anti-tumor effect study demonstrated that the LHRss/DOX/TRAIL construct inhibited tumor growth markedly, with a tumor inhibitory rate of 94.0%. The co-delivery system showed a significant synergistic anti-tumor effect. The LHRss/DOX/TRAIL construct may prove to be a promising co-delivery vector for the effective treatment of drug resistant breast cancer.

The antipsychotic properties of haloperidol are primarily attributed to its ability to block dopamine D2 receptors. Histaminergic transmission modulates some of the behavioral effects of haloperidol. Hence, the present study investigated the contribution of central histaminergic transmission in the cataleptic and neuroleptic effect of haloperidol respectively, using bar test and conditioned avoidance response (CAR) in a two-way shuttle box. The studies revealed that haloperidol (0.50 or 1 mg/kg, i.p.) exhibited cataleptic behavior and inhibited conditioned avoidance response (CAR) in the doses 0.25 or 0.50 mg in rats. The rats, pretreated centrally (i.c.v.) with histamine precursor, L-histidine (1, 2.5 μg) or histamine neuronal inducer (H3 receptor antagonist), thioperamide (20, 50 μg/rat), showed an enhanced cataleptic effect with sub-maximal dose of haloperidol (0.5 mg/kg, i.p.). Similarly, the neuroleptic effect of haloperidol (0.25 mg/kg, i.p.) in CAR was also potentiated in the rats pretreated with L-histidine (2.5 μg) or thioperamide (50 μg/rat). Further, the cataleptic effect of haloperidol (1 mg/kg, i.p.) was attenuated in rats pretreated with the H1 receptor antagonist, chlorpheniramine (60, 80 μg/rat, i.c.v.) or H2 receptor antagonist, ranitidine (60 μg/rat, i.c.v.). However, the neuroleptic effect of haloperidol (0.5 mg/kg, i.p.) was completely reversed by pretreatment with ranitidine (60 μg/rat, i.c.v.), and partially attenuated by chlorpheniramine (80 μg/rat, i.c.v.). These findings suggest the possible involvement of histaminergic transmission in the cataleptic and neuroleptic effects of haloperidol probably via H1 or H2 receptor stimulation.

BACKGROUND: Sonodynamic therapy (SDT) is a promising methodology for cancer treatment. Lomefloxacin hydrochloride (LFLX) has been reported to have sonodymamic antitumor effects. MATERIALS AND METHODS: We synthesized LFLX derivatives conjugated with methoxy polyethylene glycol (PEGylated LFLXs) and investigated their ultrasonically induced antitumor effects. RESULTS: After ultrasound exposure at 2.0 MHz for 30 s, the survival rates of Sarcoma 180 cells in the presence of lower molecular weight PEGylated LFLXs (200 microM) were significantly lower than those of the control and the LFLX at 1.5 and 2.0 W/cm2. This enhancement was significantly inhibited by the addition of L-histidine, but not by D-mannitol or superoxide dismutase. There was no apparent cell damage in the presence of high molecular weight PEGylated LFLX even at 3.0 W/cm2. CONCLUSION: These findings indicate that the sonodynamic antitumor effects of lower molecular weight PEGylated LFLXs are better than those of LFLX.

Erratum in Rejuvenation Res. 2008 Oct;11(5):988. The addition of the neuropeptide carnosine (beta-alanyl-L-histidine) as a food additive to the basic protocol of Parkinson's disease treatment results in significant improvement of neurological symptoms, along with increase in red blood cell Cu/Zn-SOD and decrease in blood plasma protein carbonyls and lipid hydroperoxides, with no noticeable change in platelets MAO B activity. The combination of carnosine with basic therapy may be a useful way to increase efficiency of PD treatment.

The neuropeptide carnosine (beta-amyloid peptide aggregation has been demonstrated. Carnosine protection against peroxynitrite damage is particularly relevant, but until now there has been no evidence of any direct interaction with nitric oxide. In this study we examined the protection that carnosine provides against nitric oxide (NO)-induced cell death in primary rat astroglial cell cultures treated with lipopolysaccharide (LPS) and interferon gamma (INFgamma), a well-known neurotoxic proinflammatory condition. A correlation was found between cell protection and NO free-radical scavenging activity of carnosine. Moreover, by competitive spectrophotometric measurement and electrospray mass spectrometry analysis in cell-free experiments, we demonstrated a direct interaction of the dipeptide with NO. A comparison of carnosine with its homologues or derivatives (homocarnosine and carcinine) as well as with its amino acid constituents (L-histidine and beta-alanine) highlighted that only histidine showed significant scavenging activity. Therefore, carnosine shows direct NO-trapping ability and may be a valuable multifunctional molecule in the treatment of neurodegenerative disorders. (c) 2007 Wiley-Liss, Inc.

Carnosine (beta-alanyl-l-histidine) has been characterized as a putative neurotransmitter. However, so far, understanding of the role of carnosine in the brain is very limited. The objective of this study was to examine the effects of carnosine on the development of pentylenetetrazol (PTZ) kindling seizures and protection against the PTZ kindled seizures in rats. Chemical kindling was elicited by repeated intraperitoneal injection of PTZ (35 mg/kg) once every 48 h until the occurrence of Stage 4-5 seizures, and the seizure activity of kindling was recorded for 30 min. In an acute PTZ challenge study, 60 mg/kg PTZ was used to induce kindled seizure. Injection of carnosine (200, 500 mg/kg, i.p.) significantly decreased seizure stage, and prolonged the latencies for myoclonic jerks, in a dose- and time-dependent manner. In the seizure development process, 500 mg/kg carnosine also significantly delayed the onset of PTZ kindled seizures. In addition, carnosine significantly reversed decreased histamine levels induced by PTZ kindled seizure in the hippocampus. These results indicate that carnosine can protect against PTZ-induced seizures in both the development of kindling and the challenge process in rats. The results suggest that carnosine might be an endogenous anticonvulsant factor in the brain and can be used as a new antiepileptic drug in future.

Interactions between carnosine (beta-alanyl-L-histidine), being plentiful in skeletal muscles and neuronal tissues, and captopril, a widely used angiotensin-converting enzyme (ACE) inhibitor, were examined concerning free radical scavenging activity and ACE activity in vitro. Not only captopril, but also carnosine, at concentrations less than those ordinarily found in muscles and neuronal tissues, significantly scavenged 2,2'-azinobis (3-ethylbenzothiazoline-6-sulphonate) (ABTS) radical cations, and inhibited ACE activity. Cupric ions reversed the ABTS scavenging activity of carnosine and captopril, whereas cupric ions strengthened the inhibitory action of carnosine on ACE activity. In contrast, cupric ions antagonized the inhibition of ACE activity induced by ethylenediaminetetraacetic acid, indicating that the inhibitory effect of carnosine on ACE activity is not related to the chelating action of carnosine. On the other hand, carnosine and captopril synergistically enhanced the free radical scavenging activity, but not the inhibitory effect on the ACE activity. These data suggest that carnosine in its concurrent use with captopril could act as a beneficial free radical scavenger, with less danger of overdose, in the inhibition of ACE activity.

Experiments were performed with 62 longitudinal strips of the uterine horns from 10 nonpregnant rats. The ability of continuously infused epinephrine in high concentration (10(-6) g/ml, 30 min) to suppress spontaneous contractions due to activation of beta-adrenoceptors progressively decreased, which was associated with receptor desensitization. Histidine in a concentration of 3 x 10(-11) g/ml had no effect, while in concentrations of 3 x 10(-8), 3 x 10(-7), and 3 x 10(-6) g/ml decreased the degree of desensitization. Our results indicate that histidine not only potentiates beta-adrenoceptor activation, but also prevents the development of desensitization. These data should be taken into account during therapy with beta-adrenoceptor agonists.

Even though their contents in the brain are high, the function of brain carnosine and its constituents has not been clarified. Both carnosine and anserine inhibited food intake in a dose dependent fashion when injected intracerebroventricularly. The constituents of carnosine, beta-alanine (beta-Ala) and l-histidine (His), also inhibited food intake, but their effects were weaker than carnosine itself. Co-administration with beta-Ala and His inhibited food intake similar to carnosine, but also altered other behaviors. Injection of carnosine induced hyperactivity and increased plasma corticosterone level, whereas beta-Ala plus His induced hypoactivity manifested as sleep-like behavior. This later effect seemed to be derived from beta-Ala, not His. These results suggest that central carnosine may act in the brain of chicks to regulate brain function and/or behavior in a manner different from its constituents.

Selenoneine is the major selenium compound in fish muscles, and fish appears to be an important source of selenium in the fish-eating population. Selenoneine has strong antioxidant activity and a detoxifying function against methylmercury (MeHg) toxicity. Dietary intake, bioaccumulation, and metabolism of selenoneine have not been characterized in humans. A nutritional survey was conducted in remote islands of the Kagoshima Prefecture in Japan. To evaluate the potential risks and benefits of fish consumption for health, we measured concentrations of selenoneine, total selenium, MeHg, inorganic mercury, and polyunsaturated fatty acid (LC-PUFA) in the blood of a fish-eating human population. The erythrocyte, leukocyte, and platelet residues following removal of serum (cellular fraction) contained 0.510 μg Se/g, 0.212 μg selenoneine Se/g, and 0.262 μg Se-containing proteins Se/g, whereas the serum contained 0.174 μg total Se/g. Selenoneine was highly concentrated in the cellular fraction in a manner that was dependent on subjects' frequency of fish consumption. Concentrations of selenoneine were closely correlated with concentrations of MeHg in the cellular fraction. Selenoneine is the major chemical form of selenium in the blood cells of this fish-eating human population and may be an important biomarker for selenium redox status.