BACKGROUND: Our search for plant-derived ceramides from sustainable sources led to the discovery of ceramides and glucosylceramides in wine lees.
OBJECTIVE: This study evaluated the efficacy and safety of wine lees extract (WLE)-derived ceramides and glucosylceramides in enhancing skin barrier function.
METHODS: A randomized, double-blind, placebo-controlled study was conducted with 30 healthy Japanese subjects aged 20-64. Subjects were allocated to receive either the WLE-derived ceramides and glucosylceramides (test group) or placebo for 12 weeks. The primary outcome was transepidermal water loss (TEWL), and secondary outcomes included skin hydration, visual analog scale (VAS) of itching sensation, and the Japanese Skindex-29.
RESULTS: One participant withdrew for personal reasons, resulting in 29 subjects for data analysis (placebo n = 15; test n = 14). The test group showed a tendency of lower TEWL compared to the placebo after 8 weeks (p = 0.07). Furthermore, after 12 weeks of administration, the test group had significantly lower TEWL than the placebo (p = 0.04). On the other hand, no significant differences were observed in the secondary outcome parameters. No adverse events related to the supplements were reported.
CONCLUSIONS: Oral supplementation of WLE-derived ceramides and glucosylceramides is a prominent and safe approach to enhancing skin barrier function and health.
BACKGROUND: (UMIN000050422).

The fluorescent compound relmapirazin has been rationally designed for use in point-of-care measurement of glomerular filtration rate (GFR), with attributes including negligible protein binding, negligible metabolites in vivo, negligible tubular secretion, and excellent chemical and photo stability. Twenty-four nonclinical assays were performed in accordance with FDA requirements yielding negligible toxicology concerns. Here, a clinical study was performed to validate relmapirazin as a GFR tracer in patients by comparison to iohexol. This was evaluated in 120 adults at three clinical sites with eGFR values ranging from normal to Stage 4 chronic kidney disease. Relmapirazin and iohexol were administered intravenously in consecutive boluses to each subject and serial blood samples obtained over the subsequent 12 hours. Plasma concentrations were measured and the corresponding plasma GFR for each agent was determined using a standard two-compartment pharmacokinetic assessment. Urine from each subject was collected for the entire 12-hour study period to measure the amount of administered dose appearing in the urine. A near perfect linear regression correlation was observed between the GFRs measured by these two tracers (r2=0.99). Bland-Altman analysis confirmed agreement between these two measures of GFR (limits of agreement -7.0 to +5.6 mL/min; mean of -0.7 mL/min). The GFR determined by relmapirazin was independent of GFR stratification by chronic kidney disease stage, and importantly by race. The percent of the administered relmapirazin dose recovered in the urine was greater than or equal to that of iohexol with no reported severe adverse events. Thus, relmapirazin may be used as a GFR tracer agent in humans.

UNASSIGNED: To prove that the \"sports rehabilitation bed\" is a device aimed at improving the precision of stretching, which can help to reduce the difficulty of rehabilitation therapy, cut down the manpower input of rehabilitation therapy, and shorten the therapy duration as well.
UNASSIGNED: This was a clinical comparative study. Twenty patients who underwent stretching therapy in Sichuan Province Orthopedic Hospital from June 2020 to August 2020 were randomly selected to carry out a control study on both lower extremities. The experimental group was given sports rehabilitation bed to assist rehabilitation therapy, while the control group was given conventional bare-handed stretching rehabilitation therapy. The stretching angle, stretching value, and the effective rate of stretching therapy between the two groups to analyze the clinical value of the new sports rehabilitation therapy bed.
UNASSIGNED: The stretching angle in the experimental group when using the sports rehabilitation therapy bed for stretching was lower than the conventional bare-handed stretching in the control group (T<0, P=0.05), with a statistically significant difference; the stretching values of the experimental group were lower than those of the control group(P<0.01), with a statistically significant difference. Moreover, the response rate of stretching therapy in the experimental group was lower than that in the control group(P<0.05), with a statistically significant difference.
UNASSIGNED: Sports rehabilitation therapy beds can results in the advantages of effectively preventing iatrogenic injury in the process of stretching, and providing a more accurate and convenient stretching therapy method than the current commonly used bare-handed stretching for sports rehabilitation and intervention.

Deficits in N-methyl-d-aspartate receptor (NMDAR) signaling are implicated in the pathogenesis of schizophrenia. Luvadaxistat (TAK-831/NBI-1065844) is an investigational d-amino acid oxidase (DAAO) inhibitor that increases d-serine levels at NMDAR coagonist sites. INTERACT is a phase 2 randomized, placebo-controlled study that evaluated the efficacy and safety of three doses of luvadaxistat, covering a range of DAAO occupancy and d-serine levels, in patients with schizophrenia with persistent negative symptoms. The study included a 14-day, single-blinded placebo run-in period and a 12-week, double-blinded treatment period. The primary efficacy endpoint was the 12-week change from baseline in Positive and Negative Syndrome Scale-Negative Symptom Factor Score (PANSS NSFS). Secondary efficacy endpoints included the 12-week changes from baseline in Brief Assessment of Cognition in Schizophrenia (BACS) score and Schizophrenia Cognition Rating Scale (SCoRS) score. Safety endpoints included adverse event assessments. The full analysis set included all randomized patients (N = 256 [placebo, n = 87; luvadaxistat 50 mg, n = 58; 125 mg, n = 56; 500 mg, n = 55]); 228 patients completed the study. No significant improvements in PANSS NSFS were observed at any dose versus placebo at week 12. Improvements were observed with luvadaxistat 50 mg versus placebo in cognitive endpoints: BACS composite score (nominal one-sided p = 0.031) and SCoRS interviewer total score (nominal one-sided p = 0.011). Luvadaxistat did not significantly improve negative symptoms of schizophrenia. However, luvadaxistat 50 mg met the prespecified secondary endpoints for cognitive performance (BACS) and function (SCoRS), warranting further investigation in patients with cognitive impairment associated with schizophrenia. Luvadaxistat was well-tolerated in INTERACT, with no new safety signals observed. ClinicalTrials.gov: NCT03382639.

Stroke is a primary cause of noncommunicable disease-related death and disability worldwide. The most common form, ischemic stroke, is increasing in incidence resulting in a significant burden on patients and society. Urgent action is thus needed to address preventable risk factors and improve treatment methods. This review examines emerging technologies used in the management of ischemic stroke, including neuroimaging, regenerative medicine, biology, and nanomedicine, highlighting their benefits, clinical applications, and limitations. Additionally, we suggest strategies for technological development for the prevention, diagnosis, and treatment of ischemic stroke.

Nanoemulsions have carved their position in topical delivery owing to their peculiar features of forming a uniform film on the skin and conquering stratum corneum barrier and hence fostering dermal penetration and retention. The present work developed syringic acid nanoemulsion (SA-NE) by spontaneous emulsification as an anti-psoriatic remedy via the dermal route. SA-NE were prepared with either lauroglycol90, limonene or their combination (oil phase) and tween80 (surfactant) with variable concentrations. The physicochemical characteristics of SA-NE were assessed together with Ex-vivo skin deposition and dermal toxicity. The effectiveness of optimal formula in psoriatic animal model and psoriatic patients was investigated using PASI scoring and dermoscope examination. Results showed that, SA-NE containing mixture of lauroglycol 90, limonene and 10 % tween80 (F5), was selected as the optimal formula presenting stable nanoemulsion for 2-month period, showing droplet size of 177.6 ± 13.23 nm, polydispersity index of 0.16 ± 0.06, zeta potential of -21.23 ± 0.41 mV. High SA% in different skin strata and no dermal irritation was noticed with limonene-based SA-NE also it showed high in-vitro anti- inflammatory potential compared to the blank and control formulations. A preclinical study demonstrated that limonene-based SA-NE is effective in alleviating psoriasis-like skin lesions against imiquimod-induced psoriasis in rats. Clinically, promising anti-psoriatic potential was asserted as all patients receiving F5 experienced better clinical improvement and response to therapy, achieving ≥ 50 % reduction in PASI scores versus only 35 % responders in the Dermovate® cream group. Collectively, the practical feasibility of limonene-based SA-NE topical delivery can boost curative functionality in the treatment of psoriatic lesions.

BACKGROUND: To assess the efficacy of a chitosan-based gel (ChitoCare) for the treatment of non-healing diabetic foot ulcers (DFUs).
METHODS: Forty-two patients with chronic DFUs were randomized to the ChitoCare or placebo gel for a 10-week treatment period and 4-week follow-up. The primary study end point was the rate of complete wound closure at week 10, presented as relative rate.
RESULTS: Thirty patients completed the 10-week treatment and 28 completed the 4-week follow-up. The ChitoCare arm achieved 16.7% complete wound closure at week 10 vs 4.2% in the placebo arm (p=0.297), 92.0% vs 37.0% median relative reduction in wound surface area from baseline at week 10 (p=0.008), and 4.62-fold higher likelihood of achieving 75% wound closure at week 10 (p=0.012). Based on the results of the Bates-Jensen Wound Assessment Tool, the wound state at week 10 and the relative improvement from the baseline were significantly better (median 20 vs 24 points, p=0.018, and median 29.8% vs 3.6%, p=0.010, respectively).
CONCLUSIONS: ChitoCare gel increased the rate of the DFU healing process. Several secondary end points significantly favored ChitoCare gel.
BACKGROUND: NCT04178525.

BACKGROUND: Diabetic foot ulcers (DFUs) are a common complication of diabetes, often leading to severe infections, amputations, and reduced quality of life. The current standard treatment protocols for DFUs have limitations in promoting efficient wound healing and preventing complications. A comprehensive treatment approach targeting multiple aspects of wound care may offer improved outcomes for patients with DFUs. The hypothesis of this study is that a comprehensive treatment protocol for DFUs will result in faster wound healing, reduced amputation rates, and improved overall patient outcomes compared to standard treatment protocols.
OBJECTIVE: To compare the efficacy and safety of a comprehensive treatment protocol for DFUs with those of the standard treatment protocol.
METHODS: This retrospective study included 62 patients with DFUs, enrolled between January 2022 and January 2024, randomly assigned to the experimental (n = 32) or control (n = 30) group. The experimental group received a comprehensive treatment comprising blood circulation improvement, debridement, vacuum sealing drainage, recombinant human epidermal growth factor and anti-inflammatory dressing, and skin grafting. The control group received standard treatment, which included wound cleaning and dressing, antibiotics administration, and surgical debridement or amputation, if necessary. Time taken to reduce the white blood cell count, number of dressing changes, wound healing rate and time, and amputation rate were assessed.
RESULTS: The experimental group exhibited significantly better outcomes than those of the control group in terms of the wound healing rate, wound healing time, and amputation rate. Additionally, the comprehensive treatment protocol was safe and well tolerated by the patients.
CONCLUSIONS: Comprehensive treatment for DFUs is more effective than standard treatment, promoting granulation tissue growth, shortening hospitalization time, reducing pain and amputation rate, improving wound healing, and enhancing quality of life.

Sleep disorders associated with lifestyle changes and unhealthy habits are major public health concerns. Our previous study showed that Bifidobacterium adolescentis SBT2786 has a potent sleep-promoting effect on fruit flies. Fruit flies share many similarities with mammals, making them suitable model organisms for studying sleep. Thus, in the present study, we conducted a randomized, double-blind, placebo-controlled clinical trial to test whether SBT2786 has sleep-enhancing effects in humans. In this study, 61 participants in the SBT2786 group and 65 participants in the placebo group were analyzed. The results showed that SBT2786 increased sleep time; however, it predominantly increased light sleep and did not improve subjective sleep quality. Interestingly, mood improvement was observed. A subgroup analysis was conducted on participants with high stress levels, and results showed that these participants experienced an increase in sleep duration and an improvement in sleepiness upon waking up and reported feeling well-rested during the day. We concluded that SBT2786 may improve sleep quality, particularly in individuals experiencing high levels of stress, and that SBT2786 can be used as a dietary supplement to improve sleep and mood.

Areca nut (AN), the fruit or seed of Areca catechu Linn, has many uses, including chewing and medicinal purposes. It has sparked worries about health due to the presence of alkaloids. Chewing AN may have a variety of negative consequences; however, the medicinal use of AN has no notable adverse effects. To completely understand and effectively use AN, researchers have investigated its chemical makeup or biological activity, analyzed the variations between different AN species and different periods, and improved extraction and processing procedures. Today, an increasing number of researchers are exploring the underlying reasons for AN variations, as well as the molecular mechanisms of biosynthesis of chemical components, to comprehend and change AN at the genetic level. This review presents an overview of the clinical study, pharmacology, and detection of the main bioactive components in AN, and the main factors influencing their content, delving into the omics applications in AN research. On the basis of the discussions and summaries, this review identifies current research gaps and proposes future directions for investigation.