Liver damage and metabolic dysfunctions, the defining features of non-alcoholic fatty liver disease (NAFLD), are marked by inflammation, oxidative stress, and excessive hepatic fat accumulation. The current therapeutic approaches for NAFLD are limited, necessitating exploring novel treatment strategies. Dioxopiperidinamide derivatives, particularly DOPA-33, have shown effective anti-inflammatory and antioxidant properties, potentially offering therapeutic benefits against NAFLD. This study investigated the combined potential of vitamin D3 (Vit D3) and DOPA-33 in treating NAFLD. The network pharmacology analysis identified key NAFLD targets modulated by Vit D3 and DOPA-33, emphasizing their potential mechanisms of action. In NAFLD-induced zebrafish models, Vit D3 and DOPA-33 significantly reduced hepatic lipid accumulation, oxidative stress, and apoptosis, demonstrating superior efficacy over individual treatments. The treatment also lowered reactive oxygen species (ROS) levels, decreased liver damage, and enhanced antioxidant defense mechanisms. Moreover, behavioral analyses showed improved locomotion and reduced weight gain in treated zebrafish. Biochemical analyses revealed lower triglycerides (TG) and glucose levels with improved oxidative markers. Furthermore, histological analyses indicated reduced hepatic steatosis and inflammation, with decreased expression of lipogenesis-related genes and inflammatory mediators. Finally, high-performance liquid chromatography (HPLC) confirmed a significant reduction in hepatic cholesterol levels, indicating the effectiveness of the combination therapy in addressing key NAFLD-related dyslipidemias. These findings suggest that Vit D3 + DOPA-33 targets pathways involved in lipid metabolism, inflammation, and oxidative stress by offering a promising therapeutic approach for NAFLD.

OBJECTIVE: The gut microbiota plays a key role in host health. An intake of omega-3 and vitamin D3 in a separate manner is vital for maintaining good health of gut microbiota and controlling some illness manifestations. The aim of this study is to investigate the potential change in biodiversity of the gut microbiome in healthy rats supplemented with vitamin D3, omega-3 alone and their combination and to reflect onto the triglyceride levels in serum and fecal samples.
RESULTS: Using the 16S rRNA gene Miseq Illumina NGS, and monitoring triglyceride levels in serum and fecal samples coupled with several clinical parameters, we examined the effect of orally taken combination of omega-3 and vitamin D3 alongside the separate intake of supplements on gut microbiota in 24 healthy white Wistar rats for six weeks. The study findings showed that combination treatment encouraged the growth of opportunistic Clostridia class during day 21 and 42 of treatment by 7.7 and 7.4 folds, respectively, exhibited incomplete absorption levels for both supplements when used concomitantly, demonstrated a damaging effect on the gut intestinal lining wall thickness (126 µm) when compared to control group (158  µm), increasing lumen diameter (400 µm), and showed higher triglyceride level in fecal samples.
CONCLUSIONS: These findings indicate that omega-3 and vitamin D3 supplements as combination intake reveal unfavorable effects, thus, it is advised to conduct further in-depth studies to clarify the presence or absence of any chemical interaction between both supplements\' molecules and to investigate based on human model to attain a superior perspective.

Vitamin D3 is a crucial fat-soluble pro-hormone essential for bolstering bone health and fortifying immune responses within the human body. Orodispersible films (ODFs) serve as a noteworthy formulation strategically designed to enhance the rapid dissolution of vitamin D, thereby facilitating efficient absorption in patients. This innovative approach not only streamlines the assimilation process but also plays a pivotal role in optimizing patient compliance and therapeutic outcomes. The judicious utilization of such advancements underscores a paradigm shift in clinical strategies aimed at harnessing the full potential of vitamin D for improved patient well-being. This study aims to examine the vitamin D3 ODF structure using spectroscopic techniques to analyze interactions with excipients like mannitol. Fourier-transform infrared spectroscopy (FTIR) and ultraviolet-visible (UV-Vis) spectroscopy were utilized to assess molecular composition, intermolecular bonding, and vitamin D3 stability. Understanding these interactions is essential for optimizing ODF formulation, ensuring stability, enhancing bioavailability, and facilitating efficient production. Furthermore, this study involves a translational approach to interpreting chemical properties to develop an administration protocol for ODFs, aiming to maximize absorption and minimize waste. In conclusion, understanding the characterized chemical properties is pivotal for translating them into effective self-administration modalities for Vitamin D films.

Background/Objectives: Physical activity is widely recognized for its beneficial effects on bone density during adolescence, which could lead to enhanced bone density in later life, thus acting as a health-promoting activity with long-lasting implications. However, not all studies are conclusive regarding the type, intensity, duration, and frequency of the most effective physical activities. This study focuses on combat sports athletes and examines the relationship between their somatic build and heel bone parameters using ultrasound (USG) and their vitamin D3 levels. Methods: The study included 40 male athletes specializing in various combat sports. The measurements of body height, body mass, skinfold thickness, and bone widths at multiple sites were performed to estimate the somatic build. The USG parameters of the heel bone and the blood levels of vitamin D3 were also recorded. Statistical significance was determined using one-way ANOVA, with differences among sports disciplines also examined. Results: The study found significant differences in the body composition and USG bone parameters among athletes from different combat sports (p ≤ 0.05). The calcaneus stiffness index (SI) and speed of sound (SOS) were significantly higher in athletes with normal vitamin D3 levels compared to those with below-normal levels (p = 0.0015 and p = 0.001, respectively). These findings suggest that vitamin D3 may influence bone stiffness and density. Conclusions: The study underscores the importance of maintaining adequate vitamin D3 levels to support bone mineralization in athletes, particularly those training indoors with limited exposure to sunlight. It also highlights the potential of using USG as a non-invasive method to assess bone health, aiding in the optimization of training programs to prevent injuries and improve performance.

OBJECTIVE: Vitamin D supplementation in aging subjects manifests a positive effect on various health-related parameters. We performed a functionally-histological analysis of the adrenal cortex regarding the factors of vitamin D activity and corticosterone output after vitamin D3 application in a rat model of the andropause.
METHODS: Middle-aged Wistar rats were divided into sham operated (SO; n=8), orchidectomized (Orx; n=8) and vitamin D3-treated orchidectomized (Orx+vit. D; n=8) groups. Vitamin D3 (5 μg/kg b.m.) was administered subcutaneously for three weeks, while the SO and Orx groups received the vehicle alone. Set objectives were achieved using histochemistry/immunohistochemistry, stereology, ultrastructural and biochemical analyses.
RESULTS: Orchidectomy (Orx) decreased the adrenal cortex-related volume densities of vascular (p<0,0001), vitamin D receptor (VDR; p<0,0166), cytochrome P450 oxidase 2R1 (CYP 2R1; p<0,0001) and cytochrome P450 oxidase 24 (CYP 24; p<0,0001) depots, but increased the volume density of cytochrome P450 27B1 (CYP 27B1; p<0,0001) depots. In Orx+vit. D rats, increase of the adrenal cortex-related volume densities of collagen (p<0,0001), VDR (p<0,0001) and CYP 2R1 (p<0,0001) depots as well as the lipid-droplet diameter (p<0,0001) in adrenocortical outer zona fasciculata cells was observed, while a decrease of volume densities of the vascular (p<0,0001), CYP 27B1 (p<0,0001) and CYP 24 (p<0,0001) depots was registered, all versus Orx group. Plasma level of ACTH was decreased (p=0,0155) and serum concentrations of 25-hydroxyvitamin D3 and corticosterone were increased (p<0,0001 and p=0,0187, respectively), all after the same treatment.
CONCLUSIONS: Increased corticosterone output after vitamin D3 application to andropausal rats appears not to be related to increased availability of 25-hydroxyvitamin D3 and decreased degradation of 1,25-dihydroxyvitamin D3 in adrenal tissue, but rather involves the central regulatory mechanisms.

BACKGROUND: Vitamin D3, which originates from cholesterol, exerts its influence on immune cells and potentially cancer cells via the metabolite 1,25-dihydroxycholecalciferol (1,25(OH)2D3), impacting their proliferation, differentiation, and apoptosis. An umbrella review was conducted to evaluate the potential protective effect of vitamin D3 intake and serum levels on the incidence and mortality of cancer.
METHODS: A systematic search was conducted in MEDLINE, Cochrane Central Register of Controlled Trials, and EMBASE databases from their inception to October 1, 2023. We included meta-analyses of observational or randomized clinical trials that compared interventions (vitamin D3 intake) or blood levels in a healthy population, with cancer incidence or mortality as outcomes. The grading of evidence certainty followed established criteria, including strong, highly suggestive, suggestive, weak, or not significant.
RESULTS: A total of 71 systematic reviews were included. Strong evidence indicated that vitamin D3 supplementation reduced total cancer mortality (odds ratio [OR], 0.9 [95% CI, 0.87-0.92]; P < 0.01). In the context of site-specific cancers, there exists highly suggestive evidence pointing towards the potential prevention of head and neck, breast, colorectal, lung, and renal cell cancers through the intake of vitamin D3. Furthermore, strong evidence suggests that maintaining sufficient levels of vitamin D3 may effectively lower the risk of renal cell and thyroid cancer (OR = 0.76 [95%CI 0.64-0.88]).
CONCLUSIONS: There is significant evidence that vitamin D3 intake may reduce the incidence of some cancers. Routine assessments to ensure sufficient levels of vitamin D3 and administering supplements to address deficiencies may serve as crucial preventive measures for healthcare systems.

Vitamin D has shown antimicrobial effects. This study aimed to explore the antiviral effects of vitamin D3 on saliva samples collected from patients with coronavirus disease-19 (COVID-19) and compare saliva and swab results to aid in policy development. Saliva and swab samples were collected from adult patients with a positive test for COVID-19 at the King Faisal Specialist Hospital and Research Centre, Jeddah. Patients who were immunocompromised and pregnant and aged < 18 years were excluded. Vitamin D3 compound (100, 300, 800, and 1,200 IU) was added to the first saliva sample in the laboratory (n = 20); the rest of the swab specimens were compared with the saliva samples via real-time polymerase chain reaction. Of the 257 patients, 236 (94.8%) had positive saliva sample test results, 7 (2.8%) had errors, and 6 (2.4%) had negative results. Of the 236 positive tests, 235 (99.6%) had a cycle threshold (Ct) indicating strong positive reactions, and only one (Ct = 28.86) was weak. Among the 236 positive results, 235 (99.6%) exhibited robust positive reactions, indicating a substantial positive sample size. Thus, saliva might be a dependable alternative testing tool when obtaining swab samples from patients is inconvenient or challenging.

Vitamin D encapsulation can significantly improve its bioavailability, stability, and solubility. Various biopolymers viz. whey protein isolate, carboxymethyl cellulose, alginate and gum arabic were studied for their potential to be used as wall material and gum arabic was selected for encapsulating vitamin D3 as it possesses lesser particle size, apparent viscosity and better stability in terms of zeta potential. Box Behnken design was employed for optimizing the process conditions for developing vitamin D3 nanoemulsion. Box Behnken design was constructed using ultrasonic amplitude, sonication time and vitamin D3/wall material percent as independent factors. The optimum conditions obtained were ultrasonic amplitude (80 %), sonication time (12 min) and vitamin D3/wall material percent (5). The designed nanoemulsion showed a particle size of 20.04 nm, zeta potential of -28.2 mV, and encapsulation efficiency of 71.9 %. Chemical interactions were observed in the developed nanoemulsion as demonstrated by Differential scanning calorimeter thermograms and Fourier transform infrared spectra of the nanoemulsion. The Korsmeyer-Peppas model was the most suitable for describing the release of vitamin D3 from the nanoemulsion. Fabricated nanoemulsion has the potential to be used in food and pharmaceutical industries.

Most patients with schizophrenia (SCZ) do not exhibit violent behaviors and are more likely to be victims rather than perpetrators of violent acts. However, a subgroup of forensic detainees with SCZ exhibit tendencies to engage in criminal violations. Although numerous models have been proposed, ranging from substance use, serotonin transporter gene, and cognitive dysfunction, the molecular underpinnings of violence in SCZ patients remains elusive. Lithium and clozapine have established anti-aggression properties and recent studies have linked low cholesterol levels and ultraviolet (UV) radiation with human aggression, while vitamin D3 reduces violent behaviors. A recent study found that vitamin D3, omega-3 fatty acids, magnesium, and zinc lower aggression in forensic population. In this review article, we take a closer look at aryl hydrocarbon receptor (AhR) and the dysfunctional lipidome in neuronal membranes, with emphasis on cholesterol and vitamin D3 depletion, as sources of aggressive behavior. We also discuss modalities to increase the fluidity of neuronal double layer via membrane lipid replacement (MLR) and natural or synthetic compounds. This article is part of the Special Issue on \"Personality Disorders\".

UNASSIGNED: Alopecia areata (AA) is a common autoimmune T-cell mediated non-scarring, form of hair loss. It affects people of all ages and sexes.
UNASSIGNED: To compare the efficacy of intralesional vitamin D3 injection versus that of intralesional triamcinolone acetonide in the treatment of patchy alopecia areata.
UNASSIGNED: This clinical study was carried on 40 adult patients with patchy alopecia areata, the patients were categorized into two groups. Group I involved 20 patients who received 1 ml of intralesional injection of vitamin D3 (cholecalciferol aqueous preparation 200 000 IU/2 ml) every 4 weeks for a maximum of three sessions. Group II involved 20 patients who received 1 ml of intralesional injection of triamcinolone acetonide 40 mg/mL every 4 weeks for a maximum of three sessions. Clinical and trichoscopic evaluations were done at the baseline, each session and for 3 months after the last session.
UNASSIGNED: There was no statistically significant difference between the two studied groups regarding the degree of clinical improvement (p = .8). A statistically significant reduction in AA specific trichoscopic signs was detected at the end of the sessions and after 3 months of follow-up in both groups, without any statistically significant difference between them. Also a statistically significant difference was found between both groups regarding the reported adverse effects with a significant better patient satisfaction encountered toward the intralesional vitamin D3 injection.
UNASSIGNED: Intralesional vitamin D3 is a promising effective, simple, safe, and inexpensive, therapeutic modality for patchy AA.