It is crucial to regulate N-methyl-D-aspartate (NMDA) function bivalently depending on the central nervous system (CNS) conditions. CNS disorders with NMDA hyperfunction are involved in the pathogenesis of neurotoxic and/or neurodegenerative disorders with elevated D-serine, one of the NMDA receptor co-agonists. On the contrary, NMDA-enhancing agents have been demonstrated to improve psychotic symptoms and cognition in CNS disorders with NMDA hypofunction. Serine racemase (SR), the enzyme regulating both D- and L-serine levels through both racemization (catalysis from L-serine to D-serine) and β-elimination (degradation of both D- and L-serine), emerges as a promising target for bidirectional regulation of NMDA function. In this study, we explored using dimethyl malonate (DMM), a pro-drug of the SR inhibitor malonate, to modulate NMDA activity in C57BL/6J male mice via intravenous administration. Unexpectedly, 400 mg/kg DMM significantly elevated, rather than decreased (as a racemization inhibitor), D-serine levels in the cerebral cortex and plasma. This outcome prompted us to investigate the regulatory effects of dodecagalloyl-α-D-xylose (α12G), a synthesized tannic acid analog, on SR activity. Our findings showed that α12G enhanced the racemization activity of human SR by about 8-fold. The simulated and fluorescent assay of binding affinity suggested a noncooperative binding close to the catalytic residues, Lys56 and Ser84. Moreover, α12G treatment can improve behaviors associated with major CNS disorders with NMDA hypofunction including hyperactivity, prepulse inhibition deficit, and memory impairment in animal models of positive symptoms and cognitive impairment of psychosis. In sum, our findings suggested α12G is a potential therapeutic for treating CNS disorders with NMDA hypofunction.

Objective: This study aimed to determine whether liposomal delivery enhances the effects of a collagen tripeptide‐containing formulation on dermal structural and biomechanical parameters, as well as appearance‐related skin properties, compared with a nonliposomal formulation and placebo. Methods: In a randomized, double‐blind, placebo‐controlled trial, 75 healthy adults aged 25–65 years were assigned to receive placebo, a nonliposomal formulation containing collagen tripeptides, or a liposomal formulation containing collagen tripeptides (50 mL/day) for 8 weeks. Objective assessments of dermal collagen density, skin hydration, elasticity, wrinkle area, skin luminance, and tone evenness were performed at baseline and Weeks 2, 4, and 8 using standardized instrumental measurements. Results: Both collagen tripeptide‐containing formulation groups showed significant improvements in dermal collagen density, hydration, and elasticity compared with placebo ( p < 0.05). The liposomal formulation demonstrated an earlier onset and a greater magnitude of improvement across multiple parameters, with a statistically significant advantage in skin elasticity at Week 8 compared with the nonliposomal formulation ( p < 0.05). Notably, only the liposomal collagen tripeptide‐containing formulation group exhibited a significant reduction in wrinkle area at Week 8 relative to placebo ( p < 0.05). Both collagen tripeptide formulation groups also showed significant increases in skin luminance and tone evenness. Conclusion: Liposomal delivery significantly enhances the functional effects of a collagen tripeptide‐containing formulation on dermal structure and biomechanical performance, particularly dermal collagen density and skin elasticity, as well as optical skin properties including luminance and tone evenness. These findings support the application of liposomal formulations containing collagen tripeptides as an effective oral nutricosmetic strategy for improving visible signs of skin aging. Trial Registration: ClinicalTrials.gov identifier: NCT06771388

Objective: To compare the efficacy and safety of ultrasound-guided intra-articular hyaluronic acid injection versus supervised rehabilitation in patients with frozen-phase adhesive capsulitis. Design: Single-center, parallel-group, randomized controlled trial with 26-week follow-up. Subjects/Patients: Forty-six adults aged 40–70 years with clinically and radiologically confirmed frozen-phase adhesive capsulitis. Methods: Participants were randomly assigned to receive either three weekly ultrasound-guided intra-articular hyaluronic acid injections or supervised physical therapy twice weekly for six weeks. Outcomes assessed at baseline and at weeks 4, 6, 8, and 26 included the Shoulder Pain and Disability Index (SPADI) and shoulder range of motion. Results: Both groups achieved significant within-group improvements in SPADI and range of motion over 26 weeks (all p < 0.01 vs. baseline). No statistically significant between-group differences were observed in total SPADI or its pain and disability subscales at any follow-up time point (all p > 0.05). At week 26, the hyaluronic acid group’s mean total SPADI decreased from 43.0 ± 17.7 to 16.1 ± 12.8 (p < 0.01), while the rehabilitation group improved from 52.0 ± 18.4 to 23.2 ± 21.8 (p < 0.01). Pain subscores were reduced by 64.3% (hyaluronic acid) and 56.1% (rehabilitation); function subscores decreased by 60.9% and 54.8%, respectively (all p < 0.01). Both groups showed significant gains in active and passive flexion, abduction, and external rotation, without significant between-group differences (all p > 0.05). No treatment-related adverse events were observed. Conclusion: Ultrasound-guided hyaluronic acid injection and supervised rehabilitation produced comparable and clinically meaningful improvements in pain, function, and shoulder mobility in frozen-phase adhesive capsulitis.

Objectives: Intra-articular hyaluronic acid (HA) is a widely used treatment for knee osteoarthritis (OA), offering localized symptomatic relief with minimal systemic exposure. This post-market clinical follow-up (PMCF) study aimed to evaluate the safety and clinical performance of a high-purity sodium hyaluronate formulation in a real-world population with symptomatic knee OA. Methods: In this prospective, single-arm, open-label post-market follow-up study, 65 patients with radiographically confirmed knee OA received three weekly intra-articular injections of a high-purity sodium hyaluronate formulation (1.5%, 15 mg/mL). Patients were followed through Week 28. The primary outcome was safety, assessed by adverse event (AE) monitoring and vital signs. Secondary assessments included radiographic Kellgren–Lawrence (KL) grading as part of structural safety monitoring, resting knee pain, and patient satisfaction, both assessed using 100-mm visual analog scales (VAS). Results: No serious treatment-related adverse events (AEs) were reported. Mild, transient joint pain and swelling occurred in two participants (3.1%) and resolved without intervention. VAS pain scores improved significantly from baseline (41.5 ± 23.1 mm) to Week 6 (17.6 ± 19.6 mm, p < 0.001) and Week 28 (12.7 ± 17.3 mm, p < 0.001). Median KL grade remained stable (median 2, IQR 2–3) over the study period, with no acute or unexpected structural changes. At Week 28, 88.1% of participants reported being satisfied or very satisfied. Conclusions: Intra-articular injection of high-purity sodium hyaluronate was well tolerated and associated with significant pain reduction and high patient satisfaction, with no radiographic signs of acute or unexpected structural deterioration. These findings support the use of this high-purity HA formulation as a safe and effective option for symptomatic management of knee OA in real-world clinical practice. Trial registration: This study was registered at ClinicalTrials.gov (Identifier: NCT05881317; registered May 31, 2023). Key Points • High-purity intra-articular sodium hyaluronate was well tolerated, with only mild, self-resolving adverse events. • Significant and sustained reduction in knee pain was observed through 28 weeks of follow-up. • Radiographic Kellgren–Lawrence grades remained stable at both short-term and mid-term safety evaluations. • Most patients reported high satisfaction, supporting the formulation as a safe and effective real-world option for symptomatic knee osteoarthritis.

This study investigated the in vitro gastrointestinal protective effects of a multi-component food bioactive formulation composed of turmeric, manuka honey, sea buckthorn, black pepper, and chocolate chili extracts. The formulation was evaluated in peripheral blood mononuclear cells, gastric epithelial cells, and esophageal epithelial cells for its influence on lipopolysaccharide-induced cytokine secretion, mucin (MUC5B) production, and tight-junction protein (ZO-1) expression, as well as its antimicrobial activity against Helicobacter pylori. Compared with single ingredients or partial combinations, the complete formulation demonstrated synergistic activity by attenuating proinflammatory cytokine release, reinforcing epithelial barrier integrity, normalizing mucin secretion, and inhibiting H. pylori growth. These findings provide mechanistic evidence that multi-component food bioactive formulations can contribute to gastrointestinal protection through complementary anti-inflammatory and antimicrobial mechanisms, supporting their potential as functional strategies for maintaining gut health.

Objective: To evaluate the safety and clinical performance of a high-purity, non–cross-linked 1.0% sodium hyaluronate administered via intra-articular injection in patients with symptomatic knee osteoarthritis (OA). Design: This 30-week, single-center, open-label post-market clinical performance evaluation enrolled adults with radiographically confirmed knee OA. Participants received five weekly intra-articular injections of 1.0% sodium hyaluronate. Resting pain (VAS), Kellgren–Lawrence (KL) grade, and patient satisfaction were assessed through Week 30, and adverse events were monitored throughout. Results: Mean VAS pain scores decreased by 48.3% at Week 8 and 42.8% at Week 30 compared with baseline (both p < 0.001). KL grades were generally stable over time, with no clear radiographic worsening observed during follow-up. Approximately 90% of patients reported satisfaction with treatment, and no treatment-related serious adverse events occurred. Conclusions: Five weekly intra-articular injections of 1.0% sodium hyaluronate were well tolerated and were associated with reductions in resting pain and stable radiographic findings over 30 weeks, supporting its role as a well-tolerated viscosupplementation option in routine clinical care for knee OA.