젤라틴

BACKGROUND: The effects of sodium bicarbonate (NaHCO3) on anaerobic and aerobic capacity are commonly acknowledged as unclear due to the contrasting evidence thus, the present study analyzes the contribution of NaHCO3 to energy metabolism during exercise. METHODS: Following a search through five databases, 17 studies were found to meet the inclusion criteria. Meta-analyses of standardized mean differences (SMDs) were performed using a random-effects model to determine the effects of NaHCO3 supplementation on energy metabolism. Subgroup meta-analyses were conducted for the anaerobic-based exercise (assessed by changes in pH, bicarbonate ion [HCO3-], base excess [BE] and blood lactate [BLa]) vs. aerobic-based exercise (assessed by changes in oxygen uptake [VO2], carbon dioxide production [VCO2], partial pressure of oxygen [PO2] and partial pressure of carbon dioxide [PCO2]). RESULTS: The meta-analysis indicated that NaHCO3 ingestion improves pH (SMD = 1.38, 95% CI: 0.97 to 1.79, P < 0.001; I2 = 69%), HCO3- (SMD = 1.63, 95% CI: 1.10 to 2.17, P < 0.001; I2 = 80%), BE (SMD = 1.67, 95% CI: 1.16 to 2.19, P < 0.001, I2 = 77%), BLa (SMD = 0.72, 95% CI: 0.34 to 1.11, P < 0.001, I2 = 68%) and PCO2 (SMD = 0.51, 95% CI: 0.13 to 0.90, P = 0.009, I2 = 0%) but there were no differences between VO2, VCO2 and PO2 compared with the placebo condition. CONCLUSIONS: This meta-analysis has found that the anaerobic metabolism system (AnMS), especially the glycolytic but not the oxidative system during exercise is affected by ingestion of NaHCO3. The ideal way is to ingest it is in a gelatin capsule in the acute mode and to use a dose of 0.3 g•kg- 1 body mass of NaHCO3 90 min before the exercise in which energy is supplied by the glycolytic system.

BACKGROUND: Bacterial vaginosis (BV) is a very common cause of vaginitis that has been associated with a high incidence of obstetric and gynaecologic complications and increased risk of HIV-1 transmission. This has led to renewed research interest in its treatment. OBJECTIVES: To assess the effects of antimicrobial agents on BV in non-pregnant women. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), MEDLINE, EMBASE, LILACS, and African Healthline (December 2007); and proceedings of relevant international conferences (from 1981 to date). SELECTION CRITERIA: Randomised controlled trials comparing any two or more antimicrobial agents, or antimicrobial agents with placebo or no treatment, in women with clinical or Gram-stain criteria of BV. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial quality and extracted data from the original publications while the third author cross checked the data. MAIN RESULTS: Twenty-four trials involving 4422 participants were reviewed. Most examined symptomatic women only. Only seven trials analysed results by intention to treat; we re-analysed the remainder.Compared with placebo, clindamycin showed a lower rate of treatment failure (relative risk (RR) 0.25, 95% confidence interval (CI) 0.16 to 0.37). Clindamycin and metronidazole showed identical rates of treatment failure, irrespective of regimen type, at two and four-week follow up (RR 1.01, 95% CI 0.69 to 1.46; RR 0.91, 95% CI 0.70 to 1.18, respectively). Clindamycin tended to cause a lower rate of adverse events (RR 0.75, 95% CI 0.56 to 1.02); metallic taste, and nausea and vomiting were more common in the metronidazole group (RR 0.08, 95% CI 0.1 to 0.59; RR 0.23, 95% CI 0.10 to 0.51, respectively). Given intravaginally as gelatin tablets, lactobacillus was more effective than oral metronidazole (RR 0.20, 95% CI 0.05 to 0.08). Similarly, oral lactobacillus combined with metronidazole was more effective than metronidazole alone (RR 0.33, 95% CI 0.14 to 0.77). Clindamycin showed a lower rate of clinical failure than triple sulfonamide cream (RR 0.46, 95% CI 0.29 to 0.72). Hydrogen peroxide douche s

The objective of this study was to evaluate the potential applications of low-molecular-weight collagen peptides (LMWCPs), produced through enzymatic hydrolysis of fish skin-derived gelatin using a specific protease. LMWCP is enriched in Gly-X-Y tripeptide sequences, particularly Gly-Pro-Hyp (GPH). Preliminary human pharmacokinetic data showed that oral LMWCP markedly increased systemic exposure to GPH, yielding an approximately 54-fold higher area under the concentration-time curve from 0 to 2 h (3388 ± 1084 ng·h/mL) than general collagen. In a subsequent randomized, placebo-controlled trial, 114 women aged 20-50 years with thigh cellulite and self-reported hair thinning received either LMWCP (1000 mg/day) or placebo for 24 weeks. Efficacy endpoints included cellulite severity, dermal-subcutaneous border length, skin roughness, skin elasticity, and hair diameter. The LMWCP group demonstrated significant improvements in cellulite severity, dermal-subcutaneous border length, skin roughness, and skin elasticity at weeks 12 and 24 compared to the placebo group. Hair diameter also increased significantly at week 24, with a larger proportion of participants in the LMWCP group exhibiting measurable hair thickening. These findings indicate that LMWCP, characterized by high GPH content and enhanced systemic exposure resulting from targeted enzymatic hydrolysis, exerts beneficial effects on both skin and hair parameters. Daily intake of LMWCP for 24 weeks effectively reduces thigh cellulite and promotes hair thickness, supporting its potential as an orally administered functional ingredient for skin and hair health.

OBJECTIVE: To compare the efficacy of fibrin glue versus Gelfoam in cartilage tympanoplasty, focusing on graft uptake rates and short-term hearing outcomes. METHODS: In this double-blind, randomised clinical trial, forty-six patients with dry tympanic membrane perforations were randomly allocated to two groups: fibrin glue with cartilage graft (Group A) and Gelfoam with cartilage graft (Group B). A single surgeon carried out all surgeries. Graft integrity and air-bone gap (ABG) closure (≤15 dB) were evaluated three months post-surgery. RESULTS: Graft uptake rates were 91.3% in the fibrin group and 82.6% in the Gelfoam group (p > 0.05). However, ABG closure ≤15 dB was achieved in 87% of the fibrin group compared to 60.9% of the Gelfoam group (p = 0.044), indicating a significant improvement in early hearing outcomes. CONCLUSION: Fibrin glue tympanoplasty achieved comparable graft uptake rates to conventional Gelfoam tympanoplasty, while providing superior short-term hearing improvement. Both techniques demonstrated comparable graft integration, while fibrin glue was associated with superior early hearing recovery.

Talazoparib is a poly(ADP-ribose) polymerase inhibitor approved for the treatment of breast and prostate cancer. Commercialization of a soft gelatin capsule (SGC) formulation developed post-approval required a bioequivalence (BE) and food effect (FE) study to bridge SGC with the initial commercial hard capsule (HC) formulation. Study execution and meeting BE criteria are challenging due to high variability in Cmax, potentially higher Cmax for SGC based on dissolution data, and the need to perform BE/FE assessment at steady state in cancer patients. Model-informed drug development (MIDD) was used to facilitate an efficient/feasible study design. Semi-mechanistic pharmacokinetic (PK)/pharmacodynamic (PD) modeling and simulations showed that AUC, instead of Cmax, drove hematologic events, the main side effects of talazoparib. This supported a BE study powered for AUC equivalence only. Population PK simulation showed that following a 28-day treatment in the first period, 14 days in subsequent periods is sufficient for steady-state BE/FE assessments. Study results showed AUC met BE criteria while Cmax was 37% higher for SGC relative to HC, which was deemed not clinically significant based on the PK/PD model. FE on SGC formulation was consistent with FE on HC formulation reported previously. The safety profile of the two formulations was generally consistent with the known safety profile. The totality of data (AUC equivalence, lack of impact of Cmax on safety, observed safety data) supported bridging of the two formulations although Cmax failed to meet BE criteria. MIDD was critical in study design optimization and supported approval of the SGC formulation. Trial Registration: ClinicalTrials.gov Identifier: NCT04672460. © 2025 Pfizer Inc. CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.

PURPOSE: To evaluate and compare the clinical efficacy and biocompatibility of gelatin sponge and hydroxyapatite bioceramic in the repair of bone defects in apicectomy. METHODS: A total of 187 patients with periapical cysts treated from January 2020 to January 2024 were selected and randomly divided into two groups using a random number table method: gelatin sponge group(n=93) and hydroxyapatite ceramic (HA) group(n=94). Apicectomy was performed in both groups, gelatin sponge group was filled with gelatin sponge, HA group was repaired with hydroxyapatite bioceramics.Preoperative and two-week postoperative laboratory indicators were statistically analyzed and compared between the two groups. Additionally, the bone graft height, thickness and bone growth outcomes were compared six months after treatment. The postoperative healing and occurrence of adverse reactions were also compared between the two groups. RESULTS: The bone graft height, bone graft thickness and new bone density in HA group were significantly higher than those of the gelatin sponge group(P＜0.05). The levels of white blood cell count (WBC), neutrophil ratio (NEU), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and serum creatinine (SCR) in HA group were significantly lower than those of the gelatin sponge group(P＜0.05). The levels of alanine aminotransferase (ALT) and aspartate aminotransferase(AST) in HA group were significantly higher than those in the gelatin sponge group(P＜0.05). The effective rate of HA group was 100.00%, which was significantly higher than that of the gelatin sponge group (95.70%, P＜0.05). The incidence of adverse reactions in HA group was 4.26%, which was significantly lower than 12.90% in the gelatin sponge group (P＜0.05). CONCLUSIONS: Hydroxyapatite bioceramics shows better repairing effect and biocompatibility than gelatin sponges in bone defect repair after apicectomy. Hydroxyapatite bioceramics may be a more effective bone repair material, especially in promoting new bone formation and reducing postoperative complications.

OBJECTIVES: This study aimed to compare the effects of locally applied hyaluronic acid (HA) and injectable platelet-rich fibrin (I-PRF) on patient morbidity, oral health-related quality of life (OHRQoL), and healing of palatal donor sites, palatal tissue consistency, complete epithelization (CE), and color match (CM). MATERIALS AND METHODS: Sixty-seven patients undergoing free gingival grafting (FGG) were randomly assigned to three groups in an examiner-masked clinical trial. Test group 1 received a 0.8% HA gel-impregnated gelatin sponge, test group 2 received an I-PRF-impregnated sponge, and the control group received a sterile sponge. Pain and burning were assessed via a visual analog scale (VAS) on days 3, 7, 14, and 21. CM was evaluated on days 3, 7, 14, 21, 28, and at months 1 and 3. CE and Landry Wound Healing Index (WHI) were recorded on days 3, 7, 14, 21, and 28. RESULTS: Topical application of hyaluronic acid (HA) and injectable platelet-rich fibrin (I-PRF) significantly reduced postoperative discomfort and improved complete epithelization (CE) compared to the control group (p < 0.05). HA showed better outcomes than I-PRF in wound healing and morbidity, while I-PRF also significantly reduced postoperative pain (p < 0.05). Palatal tissue thickness at the 1st and 3rd months differed significantly among groups (p = 0.001), and OHRQoL scores decreased significantly from day 7 to day 14 in all groups (p < 0.05). CONCLUSION: The adjunctive use of HA or I-PRF with gelatin sponge is more effective in minimizing discomfort and enhancing healing at palatal donor sites than sponge use alone. CLINICAL RELEVANCE: Optimizing healing and minimizing patient discomfort at palatal donor sites are crucial for improving outcomes in free gingival grafting procedures. This study demonstrates that the adjunctive application of HA or I-PRF significantly enhances soft tissue healing and reduces postoperative morbidity. Particularly, HA was found to be more effective in promoting wound healing and comfort. These findings support the clinical use of HA or I-PRF as simple, biocompatible adjuncts to improve patient experience and surgical outcomes in periodontal procedures. CLINICA

ALG-055009 is an oral thyroid hormone receptor beta (THR-β) agonist being evaluated for treating metabolic dysfunction-associated steatohepatitis (MASH). This study evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics of ALG-055009 and bioavailability/food effect. Part 1 was a single-ascending dose study in healthy participants randomized to ALG-055009 (0.1 to 4.0 mg) or placebo. Part 2 was a multiple-ascending dose study in participants with mild hyperlipidemia randomized to ALG-055009 (0.3 to 1.0 mg) or placebo once daily for 14 days. Part 3 was an open-label study to determine relative bioavailability and food effect of 0.6 mg ALG-055009 solution versus soft gelatin (softgel) capsule formulation. Among 78 participants, ALG-055009 was well tolerated, and most adverse events were mild or moderate with no clinically meaningful safety issues. Transient reductions in thyroid hormone levels were observed with no clinical manifestation of hypo/hyperthyroidism. Plasma ALG-055009 exposure increased in a dose-proportional manner with rapid absorption, low variability, accumulation ranging from 1.6-2.6-fold, and t1/2 of 20 h. Relative bioavailability of the softgel capsule was 86% versus solution, with no food effect. Dose-dependent decreases in atherogenic lipids and increases in sex hormone binding globulin were observed. These results support further development of ALG-055009 for patients with MASH. © 2025 Aligos Therapeutics, Inc. Clinical Pharmacology in Drug Development published by Wiley Periodicals LLC on behalf of American College of Clinical Pharmacology.

OBJECTIVES: To evaluate the efficacy and safety of a live-attenuated gelatin-free herpes zoster (HZ) vaccine in adults ≥40 years. METHODS: In a multicentre, randomized, double-blind, placebo-controlled phase 3 trial (2020-2021, Zhejiang and Jiangsu provinces), HZ-naïve adults stratified by age (40-49, 50-59, 60-69, and ≥70 years) were randomized 1:1 to receive a single dose of the HZ vaccine (≥4.3 lg PFU) or placebo and followed for 13 months. The primary endpoint was the incidence of HZ; safety outcomes included adverse events (AEs) and serious AEs. RESULTS: The trial included 25 000 participants. HZ incidence was 5.3 versus 12.6/1000 person-years in the vaccine and placebo groups, respectively, resulting in a vaccine efficacy of 57.6% (95% CI: 43.1-68.7%) overall. Per age stratum, vaccine efficacy was 37.4% (95%CI: -117.0% to 83.9%), 62.7% (39.6-77.7%), 64.4% (42.5-78.7%), and 18.63% (-80.4% to 64.0%) in the 40-49, 50-59, 60-69, and ≥70 age groups, respectively. Few postherpetic neuralgia cases occurred (n = 13), limiting vaccine efficacy assessment. Solicited AEs were mild/moderate (13.8% [1719/12 491] vaccine vs. 5.1% [634/12 499] placebo), with no vaccine-related serious AEs. Grade 3 reactions, such as fever, were rare (0.06%, [7/12 491]), and AE rates declined with age (22.0% [219/995] in 40-49 vs. 9.1% [136/1499] in ≥70). DISCUSSION: China's gelatin-free HZ vaccine is safe and moderately effective, particularly in adults aged 50-69 years, with an age-dependent safety profile.

AIM: To evaluate the clinical outcomes of collagen sponges (CSs) on wound healing following palatal graft harvesting and compare their efficacy with gelatine sponges (GSs). MATERIALS AND METHODS: Thirty-two participants who had undergone free gingival grafts or de-epithelialised gingival grafts were randomised into the CS group or the GS group. Wound healing rate was calculated as the percentage of the healed wound area divided by the initial wound area. Wound healing rate and complete epithelialisation were evaluated at 1, 2, 3 and 4 weeks. Postoperative pain was assessed on days 1, 3 and 7. Willingness to repeat graft harvesting, delayed bleeding and aesthetic outcomes were also recorded. RESULTS: CS group had higher wound healing rates than GS group at 1 and 2 weeks (24.44% ± 6.28% vs. 5.56% ± 2.19%, p < 0.01; 91.54% ± 3.20% vs. 75.56% ± 4.77%, p < 0.05). Complete epithelialisation was achieved within 2-3 weeks in CS group and within 2-4 weeks in GS group, but no significant difference was found. Postoperative pain in VAS was lower in the CS group on Day 1 compared with the GS group (1.6 ± 0.4 vs. 3.1 ± 0.5, p < 0.05). No significant difference could be detected in willingness to repeat graft harvesting, delayed bleeding and aesthetic outcomes. CONCLUSIONS: Compared with GS, CS seemed to offer improved early healing and reduced postoperative pain following palatal graft harvesting. TRIAL REGISTRATION: This trial was registered in the Chinese Clinical Trial Registry with the registration number ChiCTR2200057221 (https://www.chictr.org.cn/showproj.html?proj=154474) on March 4, 2022. © 2025 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Management of the complications occurring in the donor area after epithelialized gingival graft (EGG) harvesting still poses a challenge for clinicians. This study aimed to evaluate the influence of gelatin sponge (GS), cyanoacrylate (CY), and coconut oil (CO) combination in comparison with GS + CY in donor site management. Fifty EGG were harvested from the lateral palate in 50 patients, who were subsequently randomized to receive the GS + CY (control) or GS + CY + CO combination (test). Postoperative pain perception (PP), quantity of analgesics (QA), epithelization level (EL), color match (CM), sensation loss (SL), postoperative discomfort (PD), and delayed bleeding (DB) were evaluated. The GS + CY + CO group showed lower PP scores compared to the GS + CY (p < 0.05). The QA intake was similar in both groups. On day 14, the GS + CY + CO group achieved 80% full EL rate, which was higher than the GS + CY group (32%) (p = 0.002). CM scores were higher in the GS + CY + CO group at all follow-up periods (p < 0.001). Both groups reported similar SL, PD, and DB values (p > 0.05). GS + CY + CO combination is more effective in reducing pain compared to GS + CO in donor site management after EGG harvesting. Additionally, GS + CY + CO combination may accelerate epithelialization and improve color match compared to GS + CY alone.Clinical Trial Registration: ClinicalTrials.gov: NCT06583226. © 2025. The Author(s).

BACKGROUND: The elimination of the causative agent and the facilitation of tissue regeneration are the fundamental objectives of periodontal therapy. Various adjunctive agents have been investigated to optimize treatment outcomes with surgical interventions. Periostin is a matricellular protein predominantly expressed in periodontal tissues, playing a key role in tissue remodeling, inflammation, and wound healing. The human placental extract has been used in periodontal surgery and compared with open flap debridement alone, with gingival crevicular fluid (GCF) periostin levels assessed to gauge periodontal wound healing. METHODS: Sixteen systemically healthy patients diagnosed with Stage III Grade C periodontitis were enrolled in the study. Participants were randomly assigned to either the test group (n = 8) or the control group (n = 8), with a total of nine males and seven females distributed across the groups. The test group underwent open flap debridement (OFD), followed by applying human placental extract gel absorbed into a gelatin sponge, while the control group received only OFD. Clinical parameters were assessed at baseline and 3 month post-treatment. GCF periostin levels were measured at baseline, 6 weeks, and 3 months. RESULTS: The test group demonstrated a mean probing pocket depth (PPD) reduction of 4.75 ± 1.28 mm, compared to 3.12 ± 1.12 mm in the control group, with the difference being statistically significant. The relative attachment level (RAL) gain was 4.37 ± 1.18 mm in the test group and 2.75 ± 0.70 mm in the control group; however, this difference was not statistically significant. At 3 months, the mean healing index score was 4.50 ± 0.53 in the test group and 3.62 ± 0.51 in the control group, with a statistically significant intergroup difference. The Plaque Index (PI), Gingival Index (GI), and Gingival Bleeding Index (BI) showed moderate reductions at 3 months; however, intergroup differences were not statistically significant, except for BI, where the difference at 3 months was -0.180. CONCLUSIONS: The adjunctive use of placental extract gel in surgical periodontal therapy demonstrated beneficial effects on healing outcomes. In addition,

Triple-negative breast cancer (TNBC) represents one of the most aggressive breast cancer subtypes, lacking effective targeted therapies and relying primarily on chemotherapy. In this study, we investigated the cytotoxic and molecular effects of doxorubicin (DOX) and methyl divanillate (DMV), alone or in combination, in three-dimensional spheroid models derived from MDA-MB-231 (claudin-low) and HCC70 (basal-like) TNBC cell lines. Combined DOX/DMV treatment significantly reduced spheroid viability and was associated with increased reactive oxygen species (ROS) accumulation and thiol depletion, thereby indicating redox imbalance and cytoskeletal disruption. Immunofluorescence further confirmed actin filament disorganization and nuclear instability under combined therapy. Integrated qPCR and proteomic analyses revealed lineage-dependent modulation of apoptotic signaling in MDA-MB-231 spheroids, DOX/DMV broadly suppressed apoptosis-associated proteins, whereas in HCC70 spheroids, the combination upregulated key intrinsic apoptotic regulators, including caspases and mitochondrial stress-related proteins. Furthermore, gene expression analysis, gelatin zymography, and proteomic profiling demonstrated that DOX and DMV modulated metalloproteinase (MMP) activity and cytoskeletal remodeling, with combination therapy promoting MMP9 suppression and widespread downregulation of actin cytoskeleton regulators in MDA-MB-231 spheroids, while inducing cytoskeletal reinforcement-associated profiles in HCC70 spheroids. Transgelin-2 expression also exhibited divergent patterns between the cell lines at both transcript and protein levels. Collectively, our findings indicate that DOX/DMV combination therapy exerts synergistic interaction, as determined by Combination Index analysis (CI = 0.3 for MDA-MB-231 spheroids and CI = 0.8 for HCC70 spheroids), resulting in enhanced cytotoxicity associated with oxidative stress, apoptotic pathway modulation, and cytoskeletal remodeling in a subtype-dependent manner. These results underscore the potential of DMV as a redox-modulating adjuvant to enhance chemotherapy efficacy in TNBC, while highlighting the importance of tumor subtype context in det

Ethanol and nicotine are among the most widely used drugs in the USA, and their combined use is associated with increased health risks. This study aimed to investigate the acute effects of ethanol alone and in combination with nicotine on risky choice in rats using a probability-discounting task. Sprague-Dawley rats chose between a smaller, certain reinforcer (one food pellet) and a larger, probabilistic reinforcer (two food pellets). In Experiment 1, effects of acute ethanol administration were assessed. In Experiment 2, acute nicotine was administered either alone or in combination with ethanol. Ethanol was delivered via oral 'Jell-O shots' and nicotine was delivered via subcutaneous injection. Ethanol (2.0 g/kg) and nicotine (0.3 mg/kg) each increased risky choice compared with vehicle controls. The highest combined dose of ethanol (2.0 g/kg) and nicotine (1.0 mg/kg) further increased risky choice compared with the same ethanol dose paired with a lower nicotine dose (0.3 mg/kg), although there was no evidence that the combination increased risky choice beyond either drug alone. These findings highlight drug interactions that may contribute to heightened risk-taking behaviors associated with comorbid use. Future studies should explore the influence of ethanol dose, concentration, vehicle, and administration route on risky choice to further characterize these effects. This study underscores the need for basic investigations to inform interventions targeting the combined use of ethanol and nicotine.

BACKGROUND: Resistance to docetaxel (DTX), a frontline chemotherapeutic agent for prostate cancer (PC), remains a major therapeutic challenge, often driven by impaired apoptosis and enhanced metastatic potential. Calebin A (CA), a natural polyphenol derived from turmeric, has demonstrated anticancer properties in various malignancies. This study investigated the individual and combined effects of CA and DTX on proliferation, apoptosis, cell cycle progression, migration, and gene expression in human PC3 prostate cancer cells. METHODS: PC3 cells were treated with varying concentrations of CA and DTX, alone or in combination. Cell viability was assessed using the MTT assay, and drug interactions were evaluated using the combination index (CI) analysis. Flow cytometry was employed to analyze apoptosis and cell cycle distribution. Gene expression of Bax, Bcl-2, MMP-2, and MMP-9 was quantified using qRT-PCR, while gelatin zymography and wound healing assays evaluated protease activity and migratory behavior, respectively. RESULTS: Both CA and DTX exhibited time- and dose-dependent cytotoxicity, with combination treatment producing synergistic effects (CI < 1). Co-treatment significantly increased apoptotic cell populations and induced marked sub-G1 and G2/M cell cycle arrest. The combination therapy upregulated the pro-apoptotic Bax/Bcl-2 ratio and downregulated MMP-2 expression, with modest reductions in MMP-2 and MMP-9 enzymatic activities. Furthermore, migratory capacity was significantly diminished under combinatorial treatment compared to monotherapies. CONCLUSION: CA enhances the antitumor efficacy of DTX by potentiating apoptosis, inhibiting migration, and modulating gene expression associated with metastasis and survival. These findings suggest CA as a promising adjuvant to overcome chemoresistance and improve therapeutic outcomes in prostate cancer. © 2025. The Author(s), under exclusive licence to Tehran University of Medical Sciences.

Colorectal cancer (CRC) is the third most common malignancy worldwide. 5-fluorouracil (5-FU) remains the first-line drug for treatment of the metastatic stage despite the limits of its efficacy. Here, we investigated the anti-tumor effect of two phytochemicals, baicalein and 6-(methylsulfinyl)hexyl isothiocyanate (6-MITC), on colorectal cancer cells (HCT-116 and RKO) and determined whether these individual agents, when used alone or in combination with 5-FU, could enhance treatment efficacy. The evaluations included assays that measure cell viability and proliferation (MTT), apoptosis, cell migration, cell cycle, gelatin zymography, and combination index analyses. In both cell lines, baicalein [HCT-116 cells; IC50 = 40.82 ± 7.77 μM (24 h) and 33.83 ± 1.99 μM (48 h), and RKO cells; IC50 = 55.84 ± 3.12 μM (24 h) and 45.11 ± 3.05 μM (48 h)] and 6-MITC [HCT-116 cells; IC50 = 24.66 ± 1.57 μM (24 h) and 8.28 ± 0.56 μM (48 h), and RKO cells; IC50 = 45.74 ± 1.63 μM (24 h) and 9.85 ± 1.42 (48 h) μM] suppressed cancer cell proliferation in a dose-dependent manner at 24 and 48 h, while 5-FU was cytotoxic only after 48 h [HCT-116 cells; IC50 18.43 ± 3.82, and RKO cells; IC50 = 30.57 ± 8.34 μM]. Compared with 5-FU treatment only, the combined treatments induced significant increases in the pre-G1 phase and decreases in the G1 and S phases in both cell lines. In HCT-116 cells, combined treatments induced significantly greater apoptosis compared to 5-FU alone. Single and combination treatments with baicalein or 6-MITC significantly lowered the migration of cells compared to 5-FU alone in both cell lines. In conclusion, our study showed that both baicalein and 6-MITC induced similar anti-tumor effects compared to 5-FU alone in both cell lines, however, the combined treatments were more efficient. © 2025. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

Iberdomide is a BCS III CELMoD™ agent currently under development for treatment of multiple myeloma. Five formulations were used during clinical development, starting with active ingredient in gelatin capsule (AIC), followed by subsequent formulations in gelatin (F1), HPMC capsules (F2 and F3), and finally the intended commercial form (ICF). A food effect study with the Phase I AIC formulation showed no food effect and two relative bioavailability studies bridging from AIC to formulation F1 and F2 showed similar systemic exposure. Modeling and simulation, based on in vitro dissolution, was used to bridge gaps in clinical data to demonstrate lack of a food effect across all formulations including ICF. First, a previously developed population pharmacokinetic (PK) model showed that formulation was not a covariate on iberdomide PK. Then a physiologically-based pharmacokinetic model (PBPK) informed by in vitro biorelevant dissolution was used to mechanistically describe iberdomide absorption. While minor differences between formulations were noted in their in vitro dissolution, PBPK modeling showed lack of a food effect across all five formulations. Sensitivity analysis using the PBPK model demonstrated that iberdomide permeability and total amount of drug released from formulation are the most sensitive parameters in defining the systemic exposure of iberdomide, in agreement with iberdomide's BCS III classification where drug release from drug product, and not solubility, is the rate-limiting step of dissolution. Based on the totality of evidence, which included clinical and in vitro data supplemented by modeling and simulation, no food effect is expected with the ICF. © 2025. The Author(s).

BACKGROUND: As traditional Chinese medicinal materials, E'jiao and cubilose are rich in various bioactive substances with good antioxidant, anti-inflammatory, and immune-regulating effects. AIM: To obtain the optimal ratio of synergistic effect between E'jiao and cubilose. METHODS: The antioxidant capacity of E'jiao and cubilose digestive fluid was evaluated in vitro, as well as the intracellular oxidation balance between HSF cells and 3D whole-skin model induced by H2O2. RESULTS: E'jiao, cubilose, and their different ratios of composites had better scavenging ability against free radicals such as DPPH (2,2-Diphenyl-1-picrylhydrazyl). Using HSF cells induced by H2O2 as an oxidative damage model, it was found that the combination of E'jiao and cubilose in a ratio of 2:3 significantly enhanced the activities of SOD, GSH-PX, and CAT enzymes compared to the separate treatments of E'jiao and cubilose, as well as other combination ratios. It effectively reduced the accumulation of reactive oxygen species caused by H2O2 in HSF (Human Skin Fibroblast) cells and protected the integrity of the cells. Further analysis using flow cytometry and a 3D full-thickness skin model revealed that the combination ratio of 2:3 increased the proportion of H2O2-treated cells in the S%+G2% phase from 19.1% + 7.4%-22.1% + 28.8%, helping oxidatively damaged cells partially recover their proliferative capacity. It also promoted the expression of collagen I and collagen IV in the 3D full-thickness skin model, with improvement rates reaching 168.00% and 123.68%, respectively. CONCLUSIONS: These findings indicate that the combination of E'jiao and cubilose in a ratio of 2:3 exhibits good synergistic effects, enhancing the ability of cells to resist oxidative damage, promoting cellular renewal and metabolism, and improving skin antiwrinkle capacity. © 2024 The Author(s). Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.

Triple-negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer, lacking targeted therapeutic options. Hydrogels, particularly gelatin methacrylate (GelMA), have emerged as promising materials for localized drug delivery due to their biocompatibility and tunable properties. This study investigates a dual-delivery system for enhancing the treatment efficacy of triple-negative breast cancer (TNBC) using a combination of extracellular vesicles (EVs) derived from Citrus limon L. and the chemotherapeutic drug doxorubicin (DOX). We fabricated 3D bioprinted GelMA scaffolds to achieve localized and controlled release of EVs and evaluated their synergistic effects with systemic DOX delivery on both primary and metastatic 3D TNBC models. The GelMA scaffolds, especially those with 95 % methacrylation, exhibited higher stiffness, which enhanced their sustained release. Following 48-h incubation, the combination of EVs and DOX significantly increased cytotoxicity in the primary 3D TNBC model, reducing cell viability to approximately 30 % compared to controls. This was notably more effective than treatments with DOX or EVs alone. During the extended 7-day incubation period, the combination treatment continued to show superior efficacy, with persistently high levels of ROS generation and further reduction in cell viability. In a metastatic 3D TNBC model, a significant sensitivity to the combined treatment was observed, which notably inhibited aggregate formation and migration. Importantly, EVs-embedded scaffolds promoted the proliferation of human fibroblasts, highlighting their non-toxic nature, while concurrently inhibiting TNBC cell growth. This approach provides a promising strategy to improve the treatment outcomes of TNBC by exploiting the synergistic effects of local EVs release and systemic chemotherapy.

One concern that has been considered potentially fatal is bacterial infection. In addition to the development of biocompatible antibacterial dressings, the screening and combination of new antibiotics effective against antibiotic resistance are crucial. In this study, designing hemostasis electrospun composite nanofibers containing chitosan (CS), polyvinyl pyrrolidone (PVP) and Gelatin (G) as the major components of hydrogel and natural nanofibrillated sodium alginate (SA)/polyvinyl alcohol (PVA) and ZnO nanoparticles (ZnONPs) combination as the nanofiller ingredient, has been investigated which demonstrated significant potential for accelerating wound healing. The hydrogels were developed for the delivery of the amikacin and cefepime antibiotics, along with zinc oxide nanoparticles that were applied to an electrospun layer. Amikacin is a highly effective aminoglycoside antibiotic, particularly for hospital-acquired infections, but its use is limited due to its toxicity. By utilizing it in low concentrations in the form of nanofibers and combining it with cefepime, which exhibits synergistic effects, enhanced efficacy against bacterial pathogens is achieved while potentially minimizing cytotoxicity compared to individual antibiotics. This dressing demonstrated efficient drug release, flexibility, and good swelling properties, indicating its suitable mechanical properties for therapeutic applications. After applying the biocompatible hydrogel to wounds, a significant acceleration in wound closure was observed within 14 days compared to the control group. Furthermore, the notable antibiotic and anti-inflammatory properties underscore its effectiveness in wound healing, making it a promising candidate for medical applications.

PURPOSE: This Phase III, multicenter, open-label, single-arm study evaluated the safety and immunogenicity of the measles-mumps-rubella (MMR) combined vaccine, JVC-001, as a second MMR vaccination. METHODS: Healthy Japanese children aged 5-6 years received a single dose of JVC-001 following a first measles, mumps, and rubella vaccination (measles-rubella bivalent and mumps monovalent vaccine [Hoshino or Torii strain] or JVC-001) or the MMR vaccine received between ages 1 to <4 years. Immunogenicity was evaluated using antibody titers before and after vaccination (Day 1/Day 43). The primary endpoint was the seroprotection rate of antibody titers against each virus; geometric mean titer (GMT) was also evaluated. Adverse events (AEs) and adverse drug reactions (ADRs) were monitored. RESULTS: One-hundred participants completed the study. The seroprotection rate of antibody titers against measles, rubella, and mumps virus (genotype D) were 100.0 % (95 % confidence interval [CI] 96.4 %, 100.0 %), 100.0 % (95 % CI 96.4 %, 100.0 %), and 100.0 % (95 % CI 96.3 %, 100.0 %), respectively. GMT (fold) increases (Day 1 to Day 43) were 16.0 to 55.7 for measles virus, 35.5 to 99.0 for rubella virus, and 25.7 to 89.5 for mumps virus (genotype D). Solicited ADRs occurred in 40.0 % of participants (injection site, 34.0 %; systemic, 13.0 %). CONCLUSIONS: The second MMR vaccination with JVC-001 demonstrated sufficient antibody coverage against all three viruses; the safety profile was tolerable. CLINICAL TRIAL REGISTRATION: jRCT2080225022.

PURPOSE: To investigate the safety of replacing doxorubicin with tirapazamine in conventional transarterial chemoembolization (TACE) in an Asian population with hepatocellular carcinoma (HCC), and to determine the optimal tirapazamine dose for phase II studies. MATERIALS AND METHODS: This was a phase I, 3 + 3 dose-escalation study for patients with unresectable early- and intermediate-stage HCC who received 5, 10, or 20 mg/m2 of intra-arterial (IA) tirapazamine followed by ethiodized oil/gelatin sponge-based embolization. Key eligibilities included HCCs no more than 10 cm in diameter, prior embolization allowed, Eastern Cooperative Oncology Group performance status of 0 or 1, Child-Pugh score of 5-7, and platelet count of ≥60,000 μL. Dose-limiting toxicity (DLT) was defined as any grade 3 nonhematological or grade 4 hematological toxicity, with the exception of transient elevation of aminotransferase levels after the procedure. RESULTS: Seventeen patients were enrolled, 59% of whom had progression from a prior HCC therapy and 35% of whom had progression or recurrence after TACE. All patients tolerated the tirapazamine TACE well without any DLT or serious adverse event. Using the modified Response Evaluation Criteria in Solid Tumors, the complete response (CR) rate was 47%, and the CR + partial response rate was 65%. The median duration of response was not reached. The median time to progression was 12.6 months (95% confidence interval, 5.1-not reached). The median overall survival was 29.3 months. The selected phase II dose was set at a fixed dose of 35 mg of IA tirapazamine. CONCLUSIONS: IA tirapazamine with transarterial embolization was well tolerated and showed promising efficacy signals in intermediate-stage HCC, justifying pursuit of a phase II study.

BACKGROUND: Sepsis is associated with capillary leakage and vasodilatation and leads to hypotension and tissue hypoperfusion. Early plasma volume replacement is required to achieve haemodynamic stability (HDS) and maintain adequate tissue oxygenation. The right choice of fluids to be used for plasma volume replacement (colloid or crystalloid solutions) is still a matter of debate, and large trials investigating the use of colloid solutions containing gelatine are missing. This study aims to investigate the efficacy and safety of plasma volume replacement using either a combined gelatine-crystalloid regime (1:1 ratio) or a pure crystalloid regime. METHODS: This is a prospective, controlled, randomized, double-blind, international, multicentric phase IV study with two parallel groups that is planned to be conducted at European intensive care units (ICUs) in a population of patients with hypovolaemia in severe sepsis/septic shock. A total of 608 eligible patients will be randomly assigned to receive either a gelatine-crystalloid regime (Gelaspan® 4% and Sterofundin® ISO, B. Braun Melsungen AG, in a 1:1 ratio) or a pure crystalloid regime (Sterofundin® ISO) for plasma volume replacement. The primary outcome is defined as the time needed to achieve HDS. Plasma volume replacement will be target-controlled, i.e. fluids will only be administered to volume-responsive patients. Volume responsiveness will be assessed through passive leg raising or fluid challenges. The safety and efficacy of both regimens will be assessed daily for 28 days or until ICU discharge (whichever occurs first) as the secondary outcomes of this study. Follow-up visits/calls will be scheduled on day 28 and day 90. DISCUSSION: This study aims to generate evidence regarding which regimen-a gelatine-crystalloid regimen or a pure crystalloid regimen-is more effective in achieving HDS in critically ill patients with hypovolaemia. Study participants in both groups will benefit from the increased safety of target-controlled plasma volume replacement, which prevents fluid administration to already haemodynamically stable patients and reduces the risk of harmful fluid overload. TRIAL REGISTRATION: The Europ

PURPOSE: The aim of this study was to develop a tablet formulation of choline alfoscerate and to assess its bioequivalence by comparing its pharmacokinetic parameters with those of a commercially available soft gelatin capsule (Gliatilin®) in healthy Korean male volunteers. MATERIALS AND METHODS: Film-coated tablet formulation was optimized to control the hygroscopicity of choline alfoscerate. Bioequivalence study was performed under fasted condition with a randomized, single-dose, two-period crossover design. Subjects were orally treated with 1,200 mg of test or reference choline alfoscerate (400 mg × three doses) formulation. Blood samples were collected up to 12 hours the day before dosing to correct the baseline level of choline and 12 hours after dosing to obtain drug absorption profile. Pharmacokinetic parameters were determined after analyzing plasma concentration of choline by using LC-MS/MS. RESULTS: Hygroscopicity of choline alfoscerate was successfully controlled by adding suitable amount of Neusilin® (magnesium aluminometasilicate) in the film-coated tablet. Stability of the tablet formulation was also confirmed under the accelerated condition for 3 months. Bioequivalence study showed that the mean area under the plasma concentration-time curve from time 0 to infinity of test tablet and reference soft capsule was 3.428±2.170 and 3.305±1.803 µg⋅h/mL, respectively; the mean Cmax was 0.365±0.158 and 0.380±0.108 µg/mL, respectively; and the mean Tmax was 3.51±2.57 and 3.85±3.19 hours, respectively. The 90% CIs for geometric mean ratios of test to reference formulation for AUC0-t and Cmax were 84.51%-111.98% and 83.31%-104.10%, respectively, and satisfied the EMA regulatory criteria for bioequivalence. CONCLUSION: Pharmacokinetic parameters including the Cmax and AUC0-t determined after oral administration of the two formulations in healthy Korean male volunteers showed that the differences between the formulations (tablet vs soft capsule) were not significant for bioequivalence. Both formulations were well tolerated, with no serious adverse events reported.

OBJECTIVE: To explore the efficiency of single application of lobaplatin in tran-scatheter arterial chemoembolization (TACE) for patients with a primary hepatic carcinoma who were unable or unwilling to undergo surgery. METHODS: 173 patients with primary hepatic carcinoma diagnosed by imaging or pathology were randomly divided into experimental and control groups and respectively treated with lobaplatin and pirarubicin hydrochloride as chemotherapeutic drugs for TACE. The amount of iodipin was regulated according to the tumor number and size, and then gelatin sponge or polyvinyl alcohol particles were applied for embolisms. The efficiency of treatment in the two groups was compared with reference to survival time and therapeutic response. RESULTS: The experimental group (single lobaplatin as chemotherapy drug) was superior to control group (single pirarubicin hydrochloride as chemotherapy drug) in the aspects of survival time and therapeutic response, with statistical significance. CONCLUSIONS: Single lobaplatin can be as a chemotherapy drug in TACE and has better efficiency in the aspects of mean survival time and therapeutic response, deserving to be popularized in the clinic.

PURPOSE: To evaluate the safety and efficacy of transcatheter arterial chemoembolization used for the treatment of unresectable hepatocellular carcinoma (HCC) with an Asian cooperative prospective study between Japan and Korea. MATERIALS AND METHODS: Patients with unresectable HCC unsuitable for curative treatment or with no prior therapy for HCC were enrolled. The patients underwent transcatheter arterial chemoembolization with emulsion of Lipiodol and anthracycline agent, followed by embolization with gelatin sponge particles, which was repeated on an as-needed basis. The primary endpoint was 2-year survival rate, and the secondary endpoints were adverse events and response rate. RESULTS: The 2-year survival rate of 99 patients was 75.0% (95% confidence interval, 65.2%-82.8%). The median time-to-progression was 7.8 months, and the median overall survival period was 3.1 years. Of 99 patients, 42 (42%) achieved a complete response, and 31 (31%) had a partial response. The response rate was 73% using modified Response Evaluation Criteria in Solid Tumors. The grade 3-4 toxicities included increased alanine aminotransferase level in 36%, increased aspartate aminotransferase level in 35%, thrombocytopenia in 12%, and abdominal pain in 4% of patients. All other toxicities were generally transient. CONCLUSIONS: Asian transcatheter arterial chemoembolization demonstrated sufficient safety and reasonable efficacy as a standard treatment for unresectable HCC. These results could be useful as reference data for future trials of transcatheter arterial chemoembolization.

AIM OF THE STUDY: So-cheong-ryong-tang (SCRT) and Yeon-gyo-pae-dok-san (YPS) extracts are widely used in treatment of the common cold. The purpose of this study is to evaluate the efficacy of SCRT and YPS on the common cold. METHODS: Four hundred eighty participants with symptoms of the common cold within 48 h were recruited for this randomized, double-blind, placebo-controlled trial. SCRT extract and YPS extract were put in gelatin capsules and orally administered 3 times a day. The pattern of participants was determined according to the Questionnaire for Common Cold Pattern Identification (QCCPI), and the severity of illness was assessed by Wisconsin Upper Respiratory Symptom Survey-21 Korean version (WURSS-21-K) every 7 days. RESULTS: The test and control groups were not significantly different in gender, age, smoking history, and baseline score of WURSS-21-K at the time of enrollment. SCRT treatment significantly decreased the total WURSS-21-K score on the 6th and 7th day (p<0.05) of the enrollment compared with the placebo group. YPS treatment decreased the total WURSS-21-K score on the 5th and 6th day (p<0.05 vs. the placebo group) of the enrollment. In the patients with Wind-cold pattern cold, SCRT significantly decreased the total WURSS-21-K score from 4th to 8th day (p<0.05), and YPS significantly decreased the total WURSS-21-K score from 4th to 6th day (p<0.05). For the Wind-heat pattern cold, neither SCRT nor YPS group showed significant difference from the placebo group. SCRT and YPS did not significantly decrease the time to complete resolution of the cold symptoms. CONCLUSIONS: SCRT and YPS have beneficial, albeit limited, effects on common cold patients, especially those with the Wind-cold pattern cold. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

The aim of this study was to compare 6% hydroxyethyl starch 130/0.4 with 4% succinylated gelatin for priming the cardiopulmonary bypass circuit and as volume replacement in patients undergoing coronary artery bypass, in terms of postoperative bleeding, blood transfusion requirements, renal function, and outcome after surgery. Forty-five patients received 6% hydroxyethyl starch 130/0.4 (Voluven) and another 45 were given 4% succinylated gelatin (Gelofusine) as the priming solution for the cardiopulmonary bypass circuit as well as for volume replacement. Postoperative bleeding was quantified from the hourly chest drainage in the first 4 h and at 24 h postoperatively. The baseline characteristics of both groups were similar. In the hydroxyethyl starch group, the total amount of colloid used was 1.9 +/- 1.0 L, while the gelatin group had 2.0 +/- 0.7 L. There was no significant difference in hourly chest drainage between groups. Blood transfusion requirements, estimated glomerular filtration rate, extubation time, intensive care unit and hospital stay were similar in both groups. It was concluded that 6% hydroxyethyl starch 130/0.4 is a safe alternative colloid for priming the cardiopulmonary bypass circuit and volume replacement in patients undergoing coronary artery bypass surgery.

OBJECTIVE: To assess the efficacy and safety of a "mini-perc" technique of percutaneous nephrolithotomy using a 14-Fr peel-away sheath for the removal of pyelocaliceal stones, and to determine appropriate inclusion criteria. MATERIALS AND METHODS: From July 1999 to June 2002, the medical records and radiographic images of 72 patients who underwent the "mini-perc" technique of percutaneous nephrolithotomy with a 14-Fr peel-away sheath, were reviewed to determine clinical history, stone characteristics, immediate stone free rate, final stone free rate after additional procedures, complications, and hospital stay. We also analyzed the effect of the longest stone diameter, the cumulative longest diameter of stones, the cumulative stone burden, and the stone density on the immediate stone free rate using a Fisher exact test. RESULTS: The only major complication, arterial bleeding, occurred in a patient with Child A liver cirrhosis and was successfully treated by embolization with coils and a gelatin sponge. The immediate stone free rate was 80.6 %, which was significantly influenced by stone diameter but not stone density. The mean hospital stay after the procedure was 3.97 days. CONCLUSION: The "mini-perc" technique of percutaneous nephrolithotomy, which uses the 14-Fr peel-away sheath, is a safe and effective modality for treating renal calculi.

This randomized, controlled trial assessed the efficacy of transarterial Lipiodol (Lipiodol Ultrafluide, Laboratoire Guerbet, Aulnay-Sous-Bois, France) chemoembolization in patients with unresectable hepatocellular carcinoma. From March 1996 to October 1997, 80 out of 279 Asian patients with newly diagnosed unresectable hepatocellular carcinoma fulfilled the entry criteria and randomly were assigned to treatment with chemoembolization using a variable dose of an emulsion of cisplatin in Lipiodol and gelatin-sponge particles injected through the hepatic artery (chemoembolization group, 40 patients) or symptomatic treatment (control group, 40 patients). One patient assigned to the control group secondarily was excluded because of unrecognized systemic metastasis. Chemoembolization was repeated every 2 to 3 months unless there was evidence of contraindications or progressive disease. Survival was the main end point. The chemoembolization group received a total of 192 courses of chemoembolization with a median of 4.5 (range, 1-15) courses per patient. Chemoembolization resulted in a marked tumor response, and the actuarial survival was significantly better in the chemoembolization group (1 year, 57%; 2 years, 31%; 3 years, 26%) than in the control group (1 year, 32%; 2 years, 11%; 3 years, 3%; P =.002). When adjustments for baseline variables that were prognostic on univariate analysis were made with a multivariate Cox model, the survival benefit of chemoembolization remained significant (relative risk of death, 0.49; 95% CI, 0.29-0.81; P =.006). Although death from liver failure was more frequent in patients who received chemoembolization, the liver functions of the survivors were not significantly different. In conclusion, in Asian patients with unresectable hepatocellular carcinoma, transarterial Lipiodol chemoembolization significantly improves survival and is an effective form of treatment.