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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. [ABSTRACT FROM AUTHOR]

Background: Vitamin D possesses an important role in the maintenance and health of broiler chickens. Herbal essential oils (EOs) have been proposed as a suitable alternative to chemical drugs in intensive production management systems for better performance of broilers with slight side effects and admirable therapeutic properties. Objectives: This experiment was conducted to investigate the effects of feeding cholecalciferol (VD) in combination of Satureja rechingeri EO (SREO) on growth performance, haematological indicators and immunological response of broilers. Methods: A total of 540 1‐day‐old mixed‐sex broiler chickens (Ross 308) were used in a completely randomized design with a 3 × 3 factorial arrangement of treatments. Experimental treatments included different concentrations of cholecalciferol (VD) (0, 2000 and 4000 IU/kg = 0, 0.05 and 0.1 mg/kg) and SREO (0, 200 and 400 mg/kg) on growth performance, haematological indicators and immunological responses of broiler chickens were investigated. Results: The results showed that the chicken fed diet supplemented with 0.1 mg/kg VD (VD0.1) in combination of 200 mg/kg SREO (SREO200) increased the feed intake during the overall and first 14‐day periods of the trial when compared with other dietary treatments. Interaction of VD0.1 × SREO200 led to more body weight gain (BWG) in the grower and finisher phases than all other feed treatment groups. The blood level of lymphocyte at day 42, heterophil at days 28 and 42 and heterophil/lymphocyte (H/L) ratio at 14 and 28 days of age were affected by VD0.1 + SREO200 in comparison with VD0 + SREO0 group. Feeding VD and/or SREO decreased triglyceride, cholesterol and low‐density lipoprotein concentrations at days 28 and 42 of the study, especially in VD0.1 + SREO200 treatment. Feeding VD0.1 + SREO200 also resulted in higher serum status of immunoglobulin M, lysozymes and phagocytic percentage among all treatments. Conclusion: Considering the outcomes, it is suggested that the combination of suitable concentration of VD and EO of the plant had favourable effects on the immune system and performance criteria of broiler chickens. [ABSTRACT FROM AUTHOR]

Adipose stem cells are considered one of the primary drivers of autologous fat graft biological activity and survival. We have previously demonstrated that hormonally active VD3 improved adipose stem cell viability in ex vivo and in vivo fat grafting models. In this study, we evaluated the inactive form of VD3 (cholecalciferol) on adipose stromal cell (ASC) phenotype during hypoxia and the subsequent effect on human fat graft retention in the xenograft model. Lipoaspirate collected from six human donors was used for ex vivo particle culture studies and isolated ASC studies. Adipose particles were treated with increasing doses of VD3 to determine impact on ASC survival. Expanded stromal cells were treated with VD3 during hypoxic culture and assessed for viability, apoptosis, mitochondrial activity, and nitric oxide (NO) release via caspase, DAF-FM, or TMRM. Finally, 40 Nu/J mice receiving bilateral dorsal human lipoaspirate were treated thrice weekly with (1) vehicle control, (2) 50 ng calcitriol, (3) 50 ng VD3, (4) 500 ng VD3, and (5) 5,000 ng VD3 for 12 weeks, n = 8 per group. Graft weight, volume, and architecture were analyzed. Adipose particles treated with dose-escalating VD3 had significantly increased ASC viability compared with control (P < 0.01). Under hypoxia, ASCs treated with 1 nM VD3 had significantly greater viability than untreated and pretreated cells (P < 0.01, P < 0.01) and significantly lower apoptosis-to-viability ratio (P < 0.01). ASCs pretreated with 1 nM VD3 had significantly lower NO release (P < 0.05) and lower mitochondrial polarization (P < 0.05) compared with controls. In vivo results showed mice receiving 5,000 ng VD3 had significantly greater graft weight (P < 0.05) and volume (P < 0.05) after 12 weeks of treatment compared with controls. Grafts had enhanced neovascularization, intact adipocyte architecture, and absence of oil cysts. VD3 is an over-the-counter nutritional supplement with a known safety profile in humans. Our xenograft model suggests administering VD3 at the time of surgery may significantly improve fat graft retention. [ABSTRACT FROM AUTHOR]

Meat products containing Vitamin D3 (VD3) are an innovative option that could contribute to reducing deficiencies in this micronutrient. Designing nanoemulsions that carry VD3 is the first step in developing functional meat products. Thereby, this study investigated the impact of food components on the nanoemulsion properties. A central composite design was used to study the effects of pea protein (PP, 0.5–2.5%), safflower oil (SO, 5–15%), and salt (0–0.5%) on the nanoemulsion stability (ζ-potential and particle size) and the VD3 retention. Also, the optimized nanoemulsion carrying VD3 was incorporated into a meat matrix to study its retention after cooking. The combination of food components in the optimized nanoemulsion were SO = 9.12%, PP = 1.54%, and salt content = 0.4%, resulting in the predicted values of ζ-potential, particle size, and VD3 retention of −37.76 mV, 485 nm, and 55.1%, respectively. The VD3 that was nanoencapsulated and included in a meat product remained more stable after cooking than the VD3 that was not encapsulated. If a meat product is formulated with 5 or 10% safflower oil, the stability of the nanoencapsulated VD3 is reduced. This research contributes to developing functional meat products carrying nanoencapsulated vitamin D3 in natural food-grade components. [ABSTRACT FROM AUTHOR]

Vitamin D3 (VD) is a secosteroid hormone and shows a pleiotropic effect in brain-related disorders where it regulates redox imbalance, inflammation, apoptosis, energy production, and growth factor synthesis. Vitamin D3's active metabolic form, 1,25-dihydroxy Vitamin D3 (1,25(OH)2D3 or calcitriol), is a known regulator of several genes involved in neuroplasticity, neuroprotection, neurotropism, and neuroinflammation. Multiple studies suggest that VD deficiency can be proposed as a risk factor for the development of several age-related neurological disorders. The evidence for low serum levels of 25-hydroxy Vitamin D3 (25(OH)D3 or calcidiol), the major circulating form of VD, is associated with an increased risk of Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), dementia, and cognitive impairment. Despite decades of evidence on low VD association with neurological disorders, the precise molecular mechanism behind its beneficial effect remains controversial. Here, we will be delving into the neurobiological importance of VD and discuss its benefits in different neuropsychiatric disorders. The focus will be on AD, PD, and HD as they share some common clinical, pathological, and epidemiological features. The central focus will be on the different attributes of VD in the aspect of its anti-oxidative, anti-inflammatory, anti-apoptotic, anti-cholinesterase activity, and psychotropic effect in different neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

BackgroundAimPatients and methodsResultsConclusionAlopecia areata (AA) is a common autoimmune T-cell mediated non-scarring, form of hair loss. It affects people of all ages and sexes.To compare the efficacy of intralesional vitamin D3 injection versus that of intralesional triamcinolone acetonide in the treatment of patchy alopecia areata.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.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.Intralesional vitamin D3 is a promising effective, simple, safe, and inexpensive, therapeutic modality for patchy AA. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Vitamin D3 is clinically used for the treatment of vitamin D3 deficiency or osteoporosis, partially because of its role in regulating phosphate (Pi) and calcium (Ca2+) homeostasis. The renal sodium-phosphate cotransporter 2a (Npt2a) plays an important role in Pi homeostasis; however, the role of vitamin D3 in hypophosphatemia has never been investigated. We administered vehicle or vitamin D3 to wild-type (WT) mice or hypophosphatemic Npt2a−/− mice. In contrast to WT mice, vitamin D3 treatment increased plasma Pi levels in Npt2a−/− mice, despite similar levels of reduced parathyroid hormone and increased fibroblast growth factor 23. Plasma Ca2+ was increased ~ twofold in both genotypes. Whereas WT mice were able to increase urinary Pi and Ca2+/creatinine ratios, in Npt2a−/− mice, Pi/creatinine was unchanged and Ca2+/creatinine drastically decreased, coinciding with the highest kidney Ca2+ content, highest plasma creatinine, and greatest amount of nephrocalcinosis. In Npt2a−/− mice, vitamin D3 treatment completely diminished Npt2c abundance, so that mice resembled Npt2a/c double knockout mice. Abundance of intestinal Npt2b and claudin-3 (tight junctions protein) were reduced in Npt2a−/− only, the latter might facilitate the increase in plasma Pi in Npt2a−/− mice. Npt2a might function as regulator between renal Ca2+ excretion and reabsorption in response to vitamin D3. [ABSTRACT FROM AUTHOR]

A reliable nanotechnological sensing strategy, based on an S,N-co-doped graphene quantum dot (GQD) platform, has been developed to distinctly detect two key variants of vitamin D3, specifically the free (VD3) and the nanoencapsulated form (VD3Ms). For this purpose, food-grade vitamin D3 micelles were self-assembled using a low-energy procedure (droplet size: 49.6 nm, polydispersity index: 0.34, ζ-potential: −33 mV, encapsulation efficiency: 90 %) with an innovative surfactant mixture (Tween 60 and quillaja saponin). Herein, four fluorescent nanoprobes were also synthesized and thoroughly characterized: S,N-co-doped GQDs, α-cyclodextrin-GQDs, β-cyclodextrin-GQDs, and γ-cyclodextrin-GQDs. The goal was to achieve a selective dual sensing strategy for free VD3 and VD3Ms by exploiting their distinctive quenching behaviors. Thus, the four nanosensors allowed the individual sensing of both targets to be performed (except α-CD-GQD for VD3Ms), but S,N-GQDs were finally selected due to selectivity and sensitivity (quantum yield, QY= 0.76) criteria. This choice led to a photoinduced electron transfer (PET) mechanism associated with static quenching, where differentiation was evidenced through a displayed 13-nm hypsochromic (blue) shift when interacting with VD3Ms. The reliability of this dual approach was demonstrated through an extensive evaluation of analytical performance characteristics. The feasibility and accuracy were proven in commercial food preparations and nutritional supplements containing declared nanoencapsulated and raw VD3, whose results were validated by a paired Student's t-test comparison with a UV-Vis method. To the best of our knowledge, this represents the first non-destructive analytical approach addressing the groundbreaking foodomic trend to distinctly detect different bioactive forms of vitamin D3, while also preserving their native nanostructures as a chemical challenge, thus providing reliable information about their final stability and bioavailability. [ABSTRACT FROM AUTHOR]

Vitamin D3 plays a crucial role in female reproduction. As research progresses, the mechanisms of action of vitamin D3 on follicular development have been widely discussed. Firstly, key enzymes involved in the synthesis and metabolism of vitamin D3 have been discovered in the ovary, suggesting that vitamin D3 can be synthesized and metabolized locally within the ovary. Additionally, the detection of vitamin D3 receptors (VDR) in follicles suggests that vitamin D3 may exert its effects by binding specifically to these receptors during follicular development. Further research indicates that vitamin D3 promotes follicular growth by enhancing the development of granulosa cells (GCs) and oocytes. Currently, the mechanism of action of vitamin D3 in follicular development is becoming increasingly clear. Vitamin D3 promotes oocyte development by regulating molecules involved in meiotic arrest in oocytes. It also enhances granulosa cell proliferation by stimulating steroid hormone synthesis and cell cycle regulation. Additionally, vitamin D3 exerts anti-inflammatory effects by reducing oxidative stress and advanced glycation end-products (AGEs), mitigating the detrimental effects of inflammation on follicular development. These functions of vitamin D3 have clinical applications, such as in treating polycystic ovary syndrome (PCOS), improving female fertility, and enhancing outcomes in in vitro fertilization (IVF). This review summarizes the research progress on the role and mechanisms of vitamin D3 in follicular development and briefly summarizes its clinical applications. [ABSTRACT FROM AUTHOR]

BACKGROUND: Diabetic osteoporosis is gaining public attention. However, few studies have reported the effect of a high-glucose environment on the osteogenic differentiation of human umbilical cord mesenchymal stem cells and the corresponding therapeutic strategies. OBJECTIVE: To investigate whether vitamin D3 can restore the osteogenic differentiation potential of human umbilical cord mesenchymal stem cells in a high)glucose environment. METHODS: The viability of human umbilical cord mesenchymal stem cells was detected by CCK-8 assay to screen the appropriate vitamin D3 intervention concentration. Under the high-glucose environment, RT-qPCR, western blot assay, immunofluorescence, JC-1 mitochondrial membrane potential, alizarin red staining, and β-galactosidase staining were used to evaluate the osteogenic differentiation potential, intracellular reactive oxygen species accumulation, mitochondrial membrane potential alteration, and cell senescence of human umbilical cord mesenchymal stem cells after vitamin D3 intervention. The underlying mechanism was also discussed. RESULTS AND CONCLUSION: (1) Vitamin D3 significantly promoted the proliferation of human umbilical cord mesenchymal stem cells in the range of 0.1 μmol/L to 1 mmol/L. (2) High-glucose environment down-regulated the mRNA and protein level expressions of osteogenic-related genes α1-I collagen, alkaline phosphatase, Runt-associated transcription factor 2, and osteocalcin in human umbilical cord mesenchymal stem cells, which induced oxidative stress and cellular senescence. (3) Vitamin D3 at an intervention concentration of 10 μmol/L significantly restored the osteogenic phenotype of human umbilical cord mesenchymal stem cells under high-glucose conditions and attenuated intracellular oxidative stress and cellular senescence by activating the Nrf2/HO-1 signaling pathway. (4) These findings suggested that the osteogenic differentiation ability of human umbilical cord mesenchymal stem cells was reduced in the high-glucose environment, and vitamin D3 could partially improve their osteogenic differentiation ability and reduce cell damage. [ABSTRACT FROM AUTHOR]

Objective: Lipocalin-2 is an acute phase-associated adipokine that can serve as an inflammatory and biomarker indicator of cartilage deterioration in osteoarthritis. However, its role in the musculoskeletal system remains not fully understood. Hence, this study aimed to evaluate lipocalin-2 and its relationship with markers of inflammation (Interferon-gamma, ESR, and CRP), bone density (vitamin D3 and calcium), and the triglyceride-glucose index in new-onset arthritis patients in Mosul, Iraq. Methods: This study included 125 participants aged 20 to 65, divided into two groups. The Arthritis Patient Group comprised 70 participants (37 females and 33 males) attending the Bone Diseases Consultation Unit at the Ibn Sina Teaching Hospital in Mosul, Iraq. The Control Group comprised 31 females and 24 males. Ethical approval was obtained from the Iraqi Ministry of Health - Nineveh Health (No. 2022095). Commercial ELISA kits were used to measure serum lipocalin-2, Interferon-gamma, ESR, and CRP as inflammation markers, vitamin D3, and calcium as bone density markers. Moreover, the Triglyceride Glucose (TYG) Index was evaluated. Results: The findings revealed a significant increase in lipocalin-2 levels in males compared to females, with LCN-2 increasing with age. Arthritis patients showed a significant increase (72%) in lipocalin-2 levels. Inflammatory indicators (erythrocyte sedimentation rate, C-reactive protein, interferon-gamma) displayed significant increases (46%, 1200%, and 581%, respectively). Glucose (23%), triglycerides (71%), and TYG index (21%) also exhibited significant increases. Meanwhile, bone density indicators (vitamin D3 and calcium) found a significant decrease (53% and 20%, respectively) in arthritis patients. Linear correlation coefficient (R) analysis revealed a significant positive relationship between lipocalin-2 and indicators of inflammation, glucose, TG, and TYG index. Conclusion: This study's findings suggest that LCN-2 serum levels were higher in patients with new-onset arthritis than in controls in Mosul, and LCN-2 serum increased in males compared with females and getting older serum LCN-2 increased for the patients and control groups. Furthermore, a significant correlation was found between the Triglyceride Glucose Index, which measures metabolic disorders, and serum LCN-2 levels and inflammatory indicators in new-onset arthritis patients in Mosul, Iraq. [ABSTRACT FROM AUTHOR]

This study involved fortifying pumpkin slices with calcium and vitamin D3 using vacuum impregnation (VI) pre‐treatment and assessing the quality characteristics of the resulting desserts/jams. Slices were subjected to immersion or VI pre‐treatments for 30, 60, and 90 min in a solution containing calcium oxide and vitamin D3. Calcium ions contributed to the hardness of desserts, with VI reducing processing time. The highest impregnated calcium (58.17 mg/100 g fw) and vitamin D3 contents (6.02 mg/100 g dm) were determined in slices pre‐treated by VI for 90 min. VI was more effective than immersion in terms of calcium and vitamin D3 transition into pumpkin tissues. Scanning electron microscope (SEM) images indicated that calcium oxide particles were noticeable in slices pre‐treated by VI. Immersing fruit slices for 90 min produced desserts with a textural hardness of 11.04 N, while VI pre‐treatment for the same duration increased their hardness value to 18.92 N. Desserts produced with VI‐pre‐treated slices exhibited superior texture and sensory attributes, with no adverse taste resulting from calcium oxide. In conclusion, VI pre‐treatment shows significant potential for the industrial production of desserts/jams with enhanced structural integrity for fruits. [ABSTRACT FROM AUTHOR]

Gravity in space can have a negative impact on the reproductive system. Given that the reproductive system is one of vitamin D's objectives, this study will use a simulated microgravity model to evaluate its impact on the rat reproductive system. Twenty-two male Wistar rats were allocated into four groups at random. Under microgravity circumstances, the rats were housed in both special and standard cages. Each group was then separated into two subgroups, one of which received vitamin D3 and the other did not. Blood was drawn twice to determine blood levels of vitamin D3, LH, FSH, and testosterone. Rat testes were isolated for histological analysis, as well as a piece of epididymis for sperm count and morphological examination. Microgravity had a detrimental effect on testicular tissue, resulting in lower serum levels of LH and testosterone (p-value < 0.001). Spermatogenesis was largely inhibited under microgravity. During microgravity conditions, however, vitamin D3 had a good effect on testicular structure, and the total number of sperm. Simulated microgravity affects the male reproductive system, compromising testicular morphology, sperm parameters, and hormonal balance. However, this study shows that vitamin D3 supplementation can act as a preventative strategy, minimizing the negative consequences of microgravity. The beneficial effect of vitamin D3 on testicular health and sperm quality implies that it may be useful in protecting male reproductive function in space-related situations. [ABSTRACT FROM AUTHOR]

Vitamin D3, an essential micronutrient, often requires supplementation via medicines or food supplements, which necessitate quality control (QC). This study presents the development of a method for detecting and quantifying seven impurities of vitamin D3 in oily drug products using supercritical fluid chromatography–mass spectrometry (SFC‐MS). Targeted impurities include two esters of vitamin D3 and five non‐esters including four that are isobaric to vitamin D3. Firstly, a screening study highlighted the Torus 1‐AA column and acetonitrile modifier as adequate for the separation, followed by optimization of the SFC conditions. Secondly, make‐up solvent composition and MS settings were optimized to reach high sensitivity. For both the separation and MS response, the screening design of experiments proved useful. Lastly, a fast saponification and liquid–liquid extraction method was developed, enabling efficient sample cleanup and impurities recovery from the complex oily matrix. The SFC‐MS method suitability was assessed in two validation studies. The first study employed the ICH Q2 guideline for impurity limit test to demonstrate method specificity and establish a limit of detection (LOD) and a limit of quantification (LOQ) at 0.2% and 0.5%, respectively, for ester impurities. The second study conducted a comprehensive quantitative assessment for three non‐ester impurities using a total error approach, determining method validity through accuracy profiles. The validated method exhibited reliable performance across impurity concentrations from 0.1% to 2.0%, with estimated LODs ranging from 2 to 7 ng/mL. This study further promotes SFC‐MS as a valuable, versatile, and green tool for routine pharmaceutical QC. [ABSTRACT FROM AUTHOR]

Vitamin D3 deficiency and insufficiency are becoming a common global issue for us, especially in the most industrially developed countries. The only acknowledged activity of vitamin D3 in vertebrates is to promote the absorption of calcium and, therefore, allow for the mineralization of bones. Accordingly, its deficiency is associated with diseases such as rickets. Other numerous vital functions associated with vitamin D3 are yet to be considered, and the function of vitamin D2 in plants is unknown. Thus, 100 years after its discovery, the importance of vitamin D still seems to be unacknowledged (except for rickets), with little attention given to its decrease throughout the world. In this review, I suggest that vitamin D deficiency and insufficiency may be linked to the westernized lifestyle in more developed countries. Furthermore, I suggest that, rather than the calcemic activity, the main function of vitamin D is, in general, that of strengthening living organisms. I conclude with the hypothesis that vitamin D deficiency may represent a marker for a greater risk of chronic inflammatory diseases and a shorter life expectancy. [ABSTRACT FROM AUTHOR]

Abstract 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

Objective: The purpose of this study was to investigate the effects of 8 weeks of high-intensity interval training (HIIT)and vitamin D3 supplementation on Chemokine (C-C motif) Ligand 5 (CCL-5) and C-C motif chemokine receptor 5(CCR5) in the white adipose tissue (WAT) of male rats with type 2 diabetes (T2DM).Materials and Methods: The experimental study involved 40 male Wistar rats divided into 5 groups (n=8). Thesegroups were healthy control (HC), diabetic control (DC), diabetic+HIIT (DHIIT), diabetic+vitamin D3 (DD3), anddiabetic+HIIT+vitamin D3 (DHIITD3). The rats completed 8 weeks of HIIT, consisting of 12 sessions lasting 1 minuteeach at an intensity of 90-95% of their maximum running speed. Additionally, the rats were administered a weekly doseof 10,000 IU/kg of vitamin D3 for 8 weeks.Results: The levels of CCL-5 (P

Dysmenorrhea is defined as “painful menstruation”. Two types of dysmenorrhea are known: primary, which occurs in the absence of any gynecological disease, and secondary, which is associated with an underlying pathology. Primary dysmenorrhea typically occurs approximately 6 months after menarche. Approximately 16% to 81% of women of childbearing age experience primary dysmenorrhea, with 2% to 29% reporting moderate to severe intensity. The treatment of primary dysmenorrhea focuses on pain relief. However, supplements such as Vitamin D3 and Zinc should be considered. Vitamin D3 inhibits prostaglandin synthesis, while zinc also inhibits its synthesis, thereby improving uterine microcirculation and reducing the intensity of uterine contractions. It is important to note that not only pharmacological treatment should be considered, but also lifestyle changes that promote maximum physical and emotional well-being to reduce the consumption of analgesics and achieve control or remission of the underlying pathology.

Abstract Vitamin D3 is clinically used for the treatment of vitamin D3 deficiency or osteoporosis, partially because of its role in regulating phosphate (Pi) and calcium (Ca2+) homeostasis. The renal sodium-phosphate cotransporter 2a (Npt2a) plays an important role in Pi homeostasis; however, the role of vitamin D3 in hypophosphatemia has never been investigated. We administered vehicle or vitamin D3 to wild-type (WT) mice or hypophosphatemic Npt2a−/− mice. In contrast to WT mice, vitamin D3 treatment increased plasma Pi levels in Npt2a−/− mice, despite similar levels of reduced parathyroid hormone and increased fibroblast growth factor 23. Plasma Ca2+ was increased ~ twofold in both genotypes. Whereas WT mice were able to increase urinary Pi and Ca2+/creatinine ratios, in Npt2a−/− mice, Pi/creatinine was unchanged and Ca2+/creatinine drastically decreased, coinciding with the highest kidney Ca2+ content, highest plasma creatinine, and greatest amount of nephrocalcinosis. In Npt2a−/− mice, vitamin D3 treatment completely diminished Npt2c abundance, so that mice resembled Npt2a/c double knockout mice. Abundance of intestinal Npt2b and claudin-3 (tight junctions protein) were reduced in Npt2a−/− only, the latter might facilitate the increase in plasma Pi in Npt2a−/− mice. Npt2a might function as regulator between renal Ca2+ excretion and reabsorption in response to vitamin D3.

Abstract Background Of the 2 million children living with HIV globally, 90% live in sub-Saharan Africa. Despite antiretroviral therapy, longstanding HIV infection is associated with several chronic complications in children including growth failure, particularly stunting and delayed puberty. Vitamin D deficiency, which is highly prevalent among children living with HIV in sub-Saharan Africa, has further adverse impact on bone health. This trial aims to establish whether supplementation with vitamin D3 and calcium carbonate improves musculoskeletal health among peripubertal children living with HIV. This paper is an update to an already existing protocol that was previously published in Trials in 2022 and details changes in the trial outcomes. Methods/design We will conduct an individually randomised, double-blinded, placebo-controlled trial of weekly high-dose vitamin D3 (20,000 IU) plus daily calcium carbonate (500 mg) supplementation for 48 weeks. Eight hundred and forty children living with HIV aged 11–19 years taking ART for ≥ 6 months will be enrolled and followed up for 96 weeks. The primary outcome is DXA-measured total body less-head bone mineral density Z-score (TBLH-BMD) at 48 weeks and is an update to the previous primary outcome total body less-head bone mineral content adjusted for lean mass (TBLH-BMCLBM) Z-score. The primary outcome was updated to address the substantial differences in distributions of TBLH-BMCLBM Z-score between the two sites as a result of software differences of the DXA machines. Secondary outcomes are DXA-measured TBLH-BMD Z-score adjusted for height at 48 weeks a new secondary outcome, lumbar spine bone mineral apparent density Z-score, number of respiratory infections, lean muscle mass and grip-strength at 48 and 96 weeks, and TBLH-BMD Z-score at 96 weeks. Sub-studies will investigate the effect of the intervention on vitamin D3 pathway metabolites and markers of bone turnover, intestinal microbiota, and innate and acquired immune function. Discussion This is the largest trial to date of vitamin D supplementation in children living with HIV. Intervening to address deficits in bone accrual through childhood is critical for optimising adolescent and early adult bone health, and prevention of later adult osteoporotic fractures. Trial results will draw attention to the need to screen for and treat long-term comorbidities in children living with HIV in resource-limited settings. Trial registration Pan African Clinical Trials Registry PACTR20200989766029. Registered on September 3, 2020. URL of trial registry record: https://pactr.samrc.ac.za Trial status Participant follow-up completed; data analysis ongoing.

Abstract This study involved fortifying pumpkin slices with calcium and vitamin D3 using vacuum impregnation (VI) pre‐treatment and assessing the quality characteristics of the resulting desserts/jams. Slices were subjected to immersion or VI pre‐treatments for 30, 60, and 90 min in a solution containing calcium oxide and vitamin D3. Calcium ions contributed to the hardness of desserts, with VI reducing processing time. The highest impregnated calcium (58.17 mg/100 g fw) and vitamin D3 contents (6.02 mg/100 g dm) were determined in slices pre‐treated by VI for 90 min. VI was more effective than immersion in terms of calcium and vitamin D3 transition into pumpkin tissues. Scanning electron microscope (SEM) images indicated that calcium oxide particles were noticeable in slices pre‐treated by VI. Immersing fruit slices for 90 min produced desserts with a textural hardness of 11.04 N, while VI pre‐treatment for the same duration increased their hardness value to 18.92 N. Desserts produced with VI‐pre‐treated slices exhibited superior texture and sensory attributes, with no adverse taste resulting from calcium oxide. In conclusion, VI pre‐treatment shows significant potential for the industrial production of desserts/jams with enhanced structural integrity for fruits.

Abstract Vitamin D3 plays a crucial role in female reproduction. As research progresses, the mechanisms of action of vitamin D3 on follicular development have been widely discussed. Firstly, key enzymes involved in the synthesis and metabolism of vitamin D3 have been discovered in the ovary, suggesting that vitamin D3 can be synthesized and metabolized locally within the ovary. Additionally, the detection of vitamin D3 receptors (VDR) in follicles suggests that vitamin D3 may exert its effects by binding specifically to these receptors during follicular development. Further research indicates that vitamin D3 promotes follicular growth by enhancing the development of granulosa cells (GCs) and oocytes. Currently, the mechanism of action of vitamin D3 in follicular development is becoming increasingly clear. Vitamin D3 promotes oocyte development by regulating molecules involved in meiotic arrest in oocytes. It also enhances granulosa cell proliferation by stimulating steroid hormone synthesis and cell cycle regulation. Additionally, vitamin D3 exerts anti-inflammatory effects by reducing oxidative stress and advanced glycation end-products (AGEs), mitigating the detrimental effects of inflammation on follicular development. These functions of vitamin D3 have clinical applications, such as in treating polycystic ovary syndrome (PCOS), improving female fertility, and enhancing outcomes in in vitro fertilization (IVF). This review summarizes the research progress on the role and mechanisms of vitamin D3 in follicular development and briefly summarizes its clinical applications.

Introduction. COVID-19 is strongly linked to cardiovascular disease, with direct myocardial injury and systemic inflammation as common mechanisms. Pre-existing or infection-induced cardiovascular disease worsens the outcomes for COVID-19 patients. Materials and methods. To estimate the serum electrolytes (Na+, K+, Ca++, Zn) and vitamin D3, the study depended on ichroma ii device for Vitamin D3 and Chemistry Analyzer for electrolytes in patient samples. Results. A study was conducted on 192 individuals diagnosed with COVID-19, including 35 critical cases, 53 severe cases, 54 moderate cases, and 50 individuals in a control group. The age group with the highest prevalence of infection was between 50‒69 years, while the lowest prevalence was observed in those under 30 years. The study found significant decreases in calcium, potassium, sodium, zinc, and vitamin D3 levels among COVID-19 patients compared to the control group. Zinc and vitamin D3 levels showed a significant correlation with sex, with males experiencing a decline in zinc levels and females having lower vitamin D3 levels. The concentration of calcium, sodium, and zinc showed a negative correlation with age, with older patients having the lowest levels. COVID-19 patients with chronic cardiac issues and high blood pressure exhibited the lowest levels of these markers. The severity of the disease also had a detrimental impact on electrolyte levels, zinc, and vitamin D3, with critical cases showing the lowest levels. The complications such as heart failure were associated with lower levels of potassium, sodium, and zinc. Conclusion. In conclusion, the study revealed significant associations between COVID-19 and decreased electrolyte levels, zinc, and vitamin D3. Sex and age were found to be correlated with these markers. Patients with chronic cardiac issues and high blood pressure exhibited the lowest levels of these markers. The severity of the disease was also linked to lower electrolyte levels, zinc, and vitamin D3. Complications such as heart failure were associated with decreased levels of potassium, sodium, and zinc.

BACKGROUND: Osteonecrosis of the femoral head is a common and disabling disease, which is mainly characterized by microcirculation disorders and bone cell metabolism disorders. Luzhongjiangu decoction was developed by Shandong Academy of Chinese Medicine and used in the form of soup in the clinic, which has good efficacy in the treatment of osteonecrosis of the femoral head. However, its mechanism of action has not been clarified. OBJECTIVE: To study the effect mechanism of Luzhongjiangu decoction on intestinal flora in rats with osteonecrosis of the femoral head based on 16S rDNA sequencing technique. METHODS: The model of osteonecrosis of the femoral head was established in Wistar rats by intragastric administration of retinoic acid. The therapeutic effect of Luzhongjiangu decoction was evaluated by serum hormone, bone histopathology and serum hormone levels. 16s rDNA sequencing technique was used to detect the intestinal flora of rats in the blank control group, model group and middle-dose Luzhongjiangu decoction group. The corresponding library was constructed and OTU clustering and microbial community diversity and abundance analysis were carried out to determine the composition of intestinal flora and the changes of species and diversity among groups. RESULTS AND CONCLUSION: Luzhongjiangu decoction could significantly increase the expression of osteocalcin, osteopontin and other osteogenic related factors, alleviate the destruction of bone trabeculae, increase bone mineral density, and had a significant therapeutic effect on osteonecrosis of the femoral head, of which the middle dose group showed the most significant effect. The results of intestinal flora sequencing showed that Luzhongjiangu decoction improved the flora disorder of rats with osteonecrosis of the femoral head to some extent, and screened out different colonies such as Bacillus, Desulfurizans, Desulfurization, Isobacteria, Bifidobacterium and so on; it could up-regulate the abundance of beneficial bacteria such as Bifidobacterium, down-regulate the abundance of harmful bacteria such as Desulfovibrio, and improve the structure of intestinal flora. Functional prediction analysis indicated that Luzhongjiangu decoction could mainly affect amino acid metabolism and energy metabolism. Correlation analysis showed that the differential bacteria of Bifidobacterium and Intestinimonas in the middle dose group of Luzhongjiangu decoction were positively correlated with vitamin D3, estradiol and calcitonin, and negatively correlated with prostaglandin E2. In the model group, Escherichia-Shigella, Desulfovibrio, Globicatella and Streptococcus were positively correlated with prostaglandin E2 and negatively correlated with vitamin D3, estradiol and calcitonin. To conclude, Luzhongjiangu decoction may play a role in the treatment of osteonecrosis of the femoral head by regulating the structure of intestinal flora, up-regulating the abundance of beneficial bacteria and affecting the secretion of vitamin D3, estradiol, calcitonin and prostaglandin E2. [ABSTRACT FROM AUTHOR]

We aimed to investigate the factors associated with vitamin D deficiency and changes in 25 (OH)D levels, as well as the impact of those changes on disease activity and renal function among SLE patients. This retrospective cohort study was based on the medical records of SLE patients hospitalized between 2010 and 2021. We collected relevant information from this patient population. Logistic regression analysis was employed to determine the factors associated with vitamin D deficiency and increased 25 (OH)D levels, and we calculated the odds ratios (ORs) and 95% confidence intervals (CIs) accordingly. At baseline, among the 1257 SLE patients, the median and interquartile range of 25 (OH)D levels were 14 (9, 20) ng/ml, with 953 (75.8%) patients exhibiting 25 (OH)D deficiency (< 20 ng/ml). The presence of 25 (OH)D deficiency was found to be associated with renal involvement and a high glucocorticoid (GC) maintenance dose. Among the 383 patients who were followed up for an average of 18 months, an increase of at least 100% in 25 (OH)D levels was positively associated with a decreased GC maintenance dose and vitamin D3 supplementation, with adjusted odds ratios(OR) (95% confidence interval [CI]) of 2.16 (1.02, 4.59) and 1300 (70, 22300), respectively. Furthermore, an increased level of 25 (OH)D was significantly associated with a decrease in the Disease Activity Index 2000 score and the urinary protein/creatinine ratio. Patients with SLE have low vitamin D levels, especially those with impaired kidney function. Increased 25 (OH)D levels can be achieved through supplementation with high doses of vitamin D3 and are associated with improvements in disease activity and the urinary protein/creatinine ratio. [ABSTRACT FROM AUTHOR]

Intestinal absorption of phosphate is bimodal, consisting of a transcellular pathway and a poorly characterized paracellular mode, even though the latter one contributes to the bulk of absorption under normal dietary conditions. Claudin-3 (Cldn3), a tight junction protein present along the whole intestine in mice, has been proposed to tighten the paracellular pathway for phosphate. The aim of this work was to characterize the phosphate-related phenotype of Cldn3-deficient mice. Cldn3-deficient mice and wildtype littermates were fed standard diet or challenged for 3 days with high dietary phosphate. Feces, urine, blood, intestinal segments and kidneys were collected. Measurements included fecal, urinary, and plasma concentrations of phosphate and calcium, plasma levels of phosphate-regulating hormones, evaluation of trans- and paracellular phosphate transport across jejunum and ileum, and analysis of intestinal phosphate and calcium permeabilities. Fecal and urinary excretion of phosphate as well as its plasma concentration was similar in both genotypes, under standard and high-phosphate diet. However, Cldn3-deficient mice challenged with high dietary phosphate had a reduced urinary calcium excretion and increased plasma levels of calcitriol. Intact FGF23 concentration was also similar in both groups, regardless of the dietary conditions. We found no differences either in intestinal phosphate transport (trans- or paracellular) and phosphate and calcium permeabilities between genotypes. The intestinal expression of claudin-7 remained unaltered in Cldn3-deficient mice. Our data do not provide evidence for a decisive role of Cldn3 for intestinal phosphate absorption and phosphate homeostasis. In addition, our data suggest a novel role of Cldn3 in regulating calcitriol levels. [ABSTRACT FROM AUTHOR]

The intestine is the principal digestive organ which is generally divided into three segments as the proximal intestine (PI), the mid intestine (MI), and the distal intestine (DI) in fish. In this study, the role of dietary vitamin D3 (VD3) in regulating the function and health of different intestinal segments was evaluated in grass carp (Ctenopharyngodon idella) fingerlings through the supplementation with the increasing levels of dietary VD3 (0, 500, 1000, 1500, 2000, and 2500 IU/kg). The results showed that VD3 supplementation (1000–2000 IU/kg) significantly enhanced the fish growth performance, and the correlation analysis suggested that this effect was positively correlated with intestinal somatic index (ISI) and intestinal length index (ILI) of MI and DI except PI. In support of this finding, dietary VD3 enhanced the activities of digestive and brush border enzymes in the fish mainly in MI and DI rather than PI. Furthermore, the intestinal microbiota analysis revealed that VD3 increased the abundance of intestinal flora at the genus level rather than the phylum level. Meanwhile, hematoxylin and eosin staining presented that VD3 supplementation reduced epithelial goblet cell hyperplasia and lamina propria edema compared with the VD3 deficiency group in the MI and DI. Further studies showed that feeding VD3 decreased malondialdehyde levels but increased total antioxidant capacity, glutathione levels, and total superoxidase activity in MI or DI but not PI, suggesting the antioxidant potential of VD3 in two intestinal segments. Moreover, in MI and DI but not PI, dietary VD3 suppressed pro-inflammatory cytokine (il1 β and tnf α ) but enhanced antimicrobial peptide (hepcidin and βdefensin) mRNA levels and increased the activities of immune-related enzymes (lysozyme and acid phosphatase), highlighting the ability to improve fish immunity. Corresponding to these effects, dietary VD3 was able to mediate NF-E2-related factor 2 (Nrf2) and NF-κB pathways in MI and DI. Finally, quadratic regression models based on weight gain (PWG), feed efficiency (PE), ISI, and ILI suggested that the appropriate VD3 requirements for grass carp fingerlings were 1233.70–1387.11 IU/kg. Taken together, our findings strengthened the potential of dietary VD3 in managing the functions and health of particular intestinal segments and provided valuable reference data for VD3 requirements of fingerling fish. [ABSTRACT FROM AUTHOR]

Abstract Background Limited studies are available on vitamin D supplementation in dogs. This study evaluates the effect of a commercial vitamin D3 supplement on serum 25-hydroxy vitamin D as well as selected biochemical and hematological parameters in healthy dogs. Eight intact male adult dogs with a mean body weight of 20 kg from mixed breeds were included in the study. After adaptation period, dogs received vitamin D3 supplement at the dose of 50 IU/kg body weight per day. Blood samples were collected on days 0, 14, 28 and 42 of supplementation. Food was used for analysis of vitamin D3 content. Results Significant increase in serum level of 25-hydroxy vitamin D3 was detected since day 14 of supplementation. Changes in serum 25-hydroxy vitamin D3 concentration during time showed an upward significance (p

Abstract Orthodontic tooth movement (OTM) is a critical process in dental alignment, driven by the application of calibrated orthodontic forces. This study delves into the intricate molecular and cellular mechanisms by which vitamin D3 influences OTM. Vitamin D3 is identified as a critical regulator in bone metabolism, enhancing osteoblast activity and bone formation while also modulating osteoclast quantity and RANKL expression, essential for the remodeling of the alveolar bone. The precise mechanisms through which vitamin D3 facilitates these processes are explored, highlighting its potential in accelerating bone remodeling and, consequently, tooth alignment. This comprehensive review underscores vitamin D3's anabolic impact on bone metabolism and its pivotal role in the synthesis and mineralization processes governed by osteoblasts. The findings illuminate vitamin D3's promise in augmenting orthodontic therapy, suggesting its utility in improving treatment efficiency and reducing duration. However, the need for further research into the optimal application of vitamin D3 in orthodontics is emphasized, particularly concerning dosage, timing, and delivery methods.

Zhi Yang,1 Yao Song,1 Bangtao Chen,2 Fei Hao1 1Department of Dermatology, Third Affiliated Hospital of Chongqing Medical University, Chongqing, 401120, People’s Republic of China; 2Department of Dermatology, Chongqing University Three Gorges Hospital, School of Medicine, Chongqing University, Chongqing, 404100, People’s Republic of ChinaCorrespondence: Bangtao Chen; Fei Hao, Email medisci@163.com; haofei62@163.comObjective: To analyze the associations of the gut and circulating microbiota with circulating vitamin D3 (VD3), type I interferon (IFNI), systemic inflammation, and clinical profiles in chronic spontaneous urticaria (CSU) patients.Methods: A total of 36 CSU patients with VD3 insufficiency (VDI; serum 25(OH)VD3 < 30 ng/mL) and 36 sex-, age-, and body mass index–matched CSU patients with non-VDI were enrolled. Fecal and serum bacteria were identified through 16S rRNA sequencing, and serum 25(OH)VD3 and inflammation biomarkers were assessed using ELISA kits. IFNI response was determined by measuring the stimulatory activity of serum on IFNI-stimulated response element in HEK293 cells in vitro with luciferase assays.Results: Higher urticarial activity score over 7 days (UAS7), higher frequency of levocetirizine resistance, and more severe proinflammation but weaker IFNI response were observed in VDI than non-VDI patients (all P< 0.05). IFNI response was strongly positively associated with serum 25(OH)VD3 level in both groups (P< 0.001). Compared to non-VDI patients, abundance of the fecal genera Prevotella 9, Escherichia–Shigella, and Klebsiella was significantly increased, while Bacteroides, Faecalibacterium, and Agathobacter were remarkably reduced in VDI patients (all P< 0.05). Burkholderia–Caballeronia–Paraburkholderia (40.95%), Acinetobacter (3.05%), and Aquabacterium (2.37%) were the top three bacteria in sera from VDI patients. Both serum 25(OH)VD3 level and IFNI response were positively associated with fecal Bacteroides in the two groups (P< 0.05). In non-VDI patients, there were moderately positive associations between IFNI response and fecal Lachnoclostridium, unclassified_f__Lachnospiraceae, and Phascolarctobacterium and between serum 25(OH)VD3 level and fecal Lachnoclostridium (all P< 0.01). Circulating microbiota in VDI patients was closely related only to proinflammation and UAS7 (both P< 0.05).Conclusion: Changes in gut but not circulating microbiota composition are associated with serum 25(OH)VD3 insufficiency and impaired IFNI homeostasis, which points to greater disease severity (UAS7) and systemic proinflammation in CSU patients.Keywords: chronic spontaneous urticaria, microbiota, vitamin D3, type I interferon, inflammation

Mastitis-causing bacteria can establish persistent infections in the mammary glands of commercially important dairy animals despite the presence of strong specific humoral and cellular immune mechanisms. We investigated the effect of vitamin D3 in the diet at a set level, but in two different forms (i.e., unencapsulated and encapsulated by complex coacervation with sulfur-saturated bovine lactoferrin-alginate using microbial transglutaminase-catalyzed crosslinking) on the immune response in late-lactating dairy goats. Dairy goats (n = 18) were randomly assigned to three experimental groups (n = 6). Dairy goats were orally administered 0.35 mg of vitamin D3/day in the unencapsulated form and 0.35 mg of vitamin D3/day in the encapsulated powder form. Another group received the basal diet. The experimental period lasted 6 weeks. The blood serum concentrations of 25-hydroxyvitamin D3 [25-(OH)-D3], lactoferrin, immunoglobulin A (IgA), and interferon-gamma (INF-γ) were measured. There were major differences in these parameters between dietary groups. However, the delivery of vitamin D3 in the encapsulated powder form to dairy goats resulted in a marked increase in 25-(OH)-D3 concentration in serum, while the serum level of lactoferrin also increased. Alternatively, the serum levels of IgA and the immunomodulatory cytokine INF-γ were elevated following supplementation with the encapsulated vitamin D3. The observed effects suggest that the deliverable form of dietary vitamin D3 results in differences in the immune response in late-lactating dairy goats. [ABSTRACT FROM AUTHOR]

Mucosal-associated invariant T (MAIT) cells, a subset of Vα7.2+ T cells, are a crucial link between innate and adaptive immunity, responding to various stimuli through TCR-dependent and independent pathways. We investigated the responses of MAIT cells and Vα7.2+/CD161− T cells to different stimuli and evaluated the effects of Cyclosporin A (CsA) and Vitamin D3 (VitD). Peripheral blood mononuclear cells (PBMCs) from healthy donors were stimulated with various agents (PMA/Ionomycin, 5-OP-RU, 5-OP-RU/IL-12/IL-33) with or without CsA and VitD. Flow cytometric analysis assessed surface markers and intracellular cytokine production. Under steady-state conditions, MAIT cells displayed elevated expression of CCR6 and IL-13. They showed upregulated activation and exhaustion markers after activation, producing IFNγ, TNFα, and TNFα/GzB. CsA significantly inhibited MAIT cell activation and cytokine production. Conversely, Vα7.2+/CD161− T cells exhibited distinct responses, showing negligible responses to 5-OP-RU ligand but increased cytokine production upon PMA stimulation. Our study underscores the distinct nature of MAIT cells compared to Vα7.2+/CD161− T cells, which resemble conventional T cells. CsA emerges as a potent immunosuppressive agent, inhibiting proinflammatory cytokine production in MAIT cells. At the same time, VitD supports MAIT cell activation and IL-13 production, shedding light on potential therapeutic avenues for immune modulation. [ABSTRACT FROM AUTHOR]

The spontaneous healing of critical-sized bone defects is often limited, posing an increased risk of complications and suboptimal outcomes. Osteogenesis, a complex process central to bone formation, relies significantly on the pivotal role of osteoblasts. Despite the well-established osteogenic properties of vitamin D 3 (VD 3), its lipophilic nature confines administration to oral or muscle injection routes. Therefore, a strategic therapeutic approach involves designing a multifunctional carrier to enhance efficacy, potentially incorporating it into the delivery system. Here, we introduce an innovative sterosome-based delivery system, utilizing palmitic acid (PA) and VD 3 , aimed at promoting osteogenic differentiation and facilitating post-defect bone regeneration. The delivery system exhibited robust physical characteristics, including excellent stability, loading efficiency, sustained drug release and high cellular uptake efficiency. Furthermore, comprehensive investigations demonstrated outstanding biocompatibility and osteogenic potential in both 2D and 3D in vitro settings. A critical-sized calvarial defect model in mice recapitulated the notable osteogenic effects of the sterosomes in vivo. Collectively, our research proposes a clinically applicable strategy for bone healing, leveraging PA/VD 3 sterosomes as an efficient carrier to deliver VD 3 and enhance bone regenerative effects. [Display omitted] [ABSTRACT FROM AUTHOR]

Heparin-binding protein 17 (HBp17), first purified in 1991 from the conditioned medium of the human A431 squamous cell carcinoma (SCC) cell line, was later renamed fibroblast growth factor-binding protein 1 (FGFBP-1). HBp17/FGFBP-1 is specifically expressed and secreted by epithelial cells, and it reversibly binds to fibroblast growth factor (FGF)-1 and FGF-2, as well as FGFs-7, -10, and -22, indicating a crucial involvement in the transportation and function of these FGFs. Our laboratory has investigated and reported several studies to elucidate the function of HBp17/FGFBP-1 in SCC cells and its potential as a molecular therapeutic target. HBp17/FGFBP-1 transgene exoression in A431-4 cells, a clonal subline of A431 that lacks tumorigenicity and does not express HBp17/FGFBP-1, demonstrated a significantly enhanced proliferation in vitro compared with A431-4 cells, and it acquired tumorigenicity in the subcutis of nude mice. Knockout (KO) of the HBp17/FGFBP-1 by genome editing significantly suppressed tumor growth, cell motility, and tumorigenicity compared with control cells. A comprehensive analysis of expressed molecules in both cell types revealed that molecules that promote epithelial cell differentiation were highly expressed in HBp17/FGFBP-1 KO cells. Additionally, we reported that 1α,25(OH)2D3 or eldecalcitol (ED-71), which is an analog of 1α,25(OH)2D3, suppresses HBp17/FGFBP-1 expression and tumor growth in vitro and in vivo by inhibiting the nuclear factor kappa-light-chain-enhancer of activated B cells signaling pathway. Here, we discuss the prospects of molecular targeted therapy targeting HBp17/FGFBP-1 with 1α,25(OH)2D3 or ED71 in SCC and oral SCC. [ABSTRACT FROM AUTHOR]

Background: Limited studies are available on vitamin D supplementation in dogs. This study evaluates the effect of a commercial vitamin D3 supplement on serum 25-hydroxy vitamin D as well as selected biochemical and hematological parameters in healthy dogs. Eight intact male adult dogs with a mean body weight of 20 kg from mixed breeds were included in the study. After adaptation period, dogs received vitamin D3 supplement at the dose of 50 IU/kg body weight per day. Blood samples were collected on days 0, 14, 28 and 42 of supplementation. Food was used for analysis of vitamin D3 content. Results: Significant increase in serum level of 25-hydroxy vitamin D3 was detected since day 14 of supplementation. Changes in serum 25-hydroxy vitamin D3 concentration during time showed an upward significance (p < 0.05). Vitamin D3 content of the food was 2900 IU/kg dry matter. Changes in serum phosphorus levels were upward significant. No dog showed calcium or phosphorus levels above the highest reference level. Liver and kidney parameters remained in the reference range during the experiment. A gradual significant increase was observed in hemoglobin and hematocrit which was started from day 14. Vitamin D3 supplementation had no significant effect on neutrophils, monocytes and lymphocytes percent during the study. Conclusions: Vitamin D3 supplementation at 50 IU/kg BW daily, increases serum levels of 25-hydroxy vitamin D in healthy dogs fed with a diet containing proper amount of this vitamin. It also increases hemoglobin and hematocrit levels in a time dependent manner without inducing adverse effects. [ABSTRACT FROM AUTHOR]

Since the beginning of the COVID-19 pandemic, vitamin D has attracted interest due to its immunomodulatory properties. Numerous studies show a correlation between vitamin D levels and COVID-19 cases and mortality. Therefore, we conducted a meta-analysis in order to assess the relationship between vitamin D3 supplementation and COVID-19 severity. We included 13 randomized clinical trials that contained the analyzed endpoints: length of COVID-19 hospitalization, number of intensive care unit (ICU) admissions, length of stay in the ICU, number of cases requiring any supplemental oxygenation, duration of any supplemental oxygenation, number of overall mortality and number of deaths associated with COVID-19. The relative risk with 95% confidence interval (CI) and the mean difference with 95% CI were calculated to compare the effect. A random effects model was used to calculate effect sizes. Our meta-analysis showed a positive effect of vitamin D3 supplementation on ICU admission (RR = 0.73; 95% CI [0.57; 0.95], p = 0.02, I2 = 19.6%) and mortality associated with COVID-19 among patients (RR = 0.56; 95% CI [0.34; 0.91]; p = 0.02; I2 = 0%). Vitamin D3 supplementation may potentially reduce the risk of ICU admission and death associated with COVID-19. [ABSTRACT FROM AUTHOR]

Compared with water‐soluble osteogenic drugs, fat‐soluble osteogenic drugs exhibit higher bioavailability and drug stability, making them valuable for enhancing the osseointegration of implants. However, existing drug‐loading coatings are primarily designed for water‐soluble drugs, limiting their effectiveness in loading and delivering fat‐soluble osteogenic drugs. This study employed alkali treatment, silanization, and oleic acid acylation to sequentially modify the surface of Ti alloy, aiming to fabricate surfaces capable of efficiently loading and delivering fat‐soluble osteogenic drugs. Results show that the hydrophilicity and loading capacity of fat‐soluble osteogenic drugs strongly depended on the duration of the acylation treatment. Furthermore, the drug release mechanism involved direct diffusion from the coating to the cells in contact, resulting in improved bioavailability, as opposed to diffusion into the surrounding medium and subsequent cellular uptake. In vitro experiments using vitamine D3 (VD3) as a model drug confirmed that the coating effectively promoted bone formation through the highly efficient delivery of VD3. Furthermore, in vivo experiments demonstrated that the VD3‐loaded lipophilic surface significantly enhanced osteogenic capability and improved the osseointegration of titanium implants. This study provides a promising strategy for loading fat‐soluble drugs onto Ti implants and direct experimental evidence demonstrating the significant value of fat‐soluble drugs in promoting implant osseointegration. [ABSTRACT FROM AUTHOR]

The inhalation of gasoline vapors (GV) is associated with developing various pathologies. Particularly, oil refinery and gas station workers are at a greater risk of developing lung cancer, kidney cancer, bladder cancer, and hematological disorders, including acute myeloid leukemia. Therefore, preventing the harmful effects of GV and alleviating their consequences appear to be important and timely issues. In this study, we investigated the potential of vitamin D3, turmeric powder, and their combination to ameliorate the toxicity of gasoline fumes in rats. Separate groups of animals fed with a standard rodent diet, with or without the supplementation of vitamin D3 (750 IU/kg body weight) and/or turmeric powder (0.5%, w/w, in food), were untreated or treated with GV (11.5 ± 1.3 cm3/h/m3/day) for 30, 60, or 90 days. Changes in the body weight were monitored weekly. Histological, biochemical, and hematological parameters were determined at the end of each treatment period. While the exposure of rats to GV resulted in a time-dependent reduction in body weight, supplementation with vitamin D3, but not with turmeric root powder or their combination, partially prevented weight loss. Macroscopical and histological analyses showed pronounced time-dependent changes in the organs and tissues of GV-treated rats. These included alveolar wall collapse in the lungs, the destruction of the lobular structure and hepatocytolysis in the liver, the shrinkage and fragmentation of glomeruli in the kidneys, and the disorganization of the lymphoid follicles in the spleen. However, co-treatment with the nutritional supplements tested, especially vitamin D3, noticeably alleviated the above conditions. This was accompanied by a significant improvement in the blood chemistry and hematological parameters. Collectively, our results demonstrate that the harmful effects of environmental exposure to GV can be reduced upon supplementation of vitamin D3. The fact that the protective activity of vitamin D3 alone was higher than that of turmeric root powder or the combined treatment suggests that combinations of these supplements may not always be more beneficial than each agent applied separately. [ABSTRACT FROM AUTHOR]

Simple Summary: Zilpaterol hydrochloride (ZH) is an additive used to enhance the growth performance and dressing carcass in ruminants. However, its use can lead to a reduction in meat quality, resulting in tougher meat. Meat tenderness is a crucial quality trait that affects consumer acceptability, satisfaction, and repeat purchase. Studies have shown that supplementing ruminants with vitamin D3 (D3) before slaughter can improve meat tenderness. It is believed that supplementing cattle treated with ZH with D3 can mitigate the negative effects of ZH and improve meat quality. In this study, we aimed to evaluate the combined effect of ZH and D3 on growth performance, energy efficiency, carcass traits, and meat quality of feedlot lambs. ZH supplementation improved growth, energy efficiency, and carcass quality but resulted in tougher meat. In contrast, supplementing lambs with D3 negatively affected dry matter intake and weight gain. However, D3 improved meat pH and color attributes but had no effect on reducing toughness. In addition, lambs fed both additives (ZH and D3) as well reduced their dry matter intake and weight gain. The inclusion of vitamin D did not reduce the toughness of the meat related to the use of zilpaterol. This study evaluated the impact of supplementing ZH in combination with D3 on the growth performance, energy efficiency, carcass traits, and meat quality of feedlot lambs. Thirty-two Dorper × Katahdin cross lambs (37.3 ± 5.72 kg) were utilized in a 29 d experiment in a completely randomized block design with a 2 × 2 factorial structure consisting of two levels of ZH for 26 d (0 and 0.20 mg/kg PV−1) and two levels of D3 for 7 d (0 and 1.5 × 106 IU/d−1). ZH improved (p ≤ 0.05) the average daily gain (ADG) and feed efficiency by 9.9% and 17.8%, respectively, as well as hot carcass weight (HCW) and dressing carcass by 4.3% and 2.6%, respectively. (p ≤ 0.03). However, ZH increased (p < 0.01) muscle pH and Warner–Bratzler shear force (WBSF) (2.5 and 23.0%, respectively). D3 supplementation negatively affected (p ≤ 0.02) dry matter intake (DMI) (last 7 d) and ADG by 15.7% and 18.1%. On the other hand, D3 improved the pH of the longissimus thoracis muscle by 1.7% (p = 0.03) without affecting WBSF. When D3 was supplemented in combination with ZH, it was observed that meat quality was improved by reducing muscle pH compared to lambs treated only with ZH. However, D3 did not improve the meat tenderness negatively affected by ZH supplementation. [ABSTRACT FROM AUTHOR]

BACKGROUND: Intestinal development and function are critical to maintaining sustained broiler growth. The present study aimed to evaluate the effects of coated sodium butyrate (CSB) and vitamin D3 (VD3) on the intestinal immunity, barrier, oxidative stress and microflora in early‐stage broilers. In total, 192 one‐day‐old broilers were assigned to a 2 × 2 factorial design including two dietary supplements at two different levels, in which the main effects were VD3 (3000 or 5000 IU kg−1) and CSB (0 or 1 g kg−1). RESULTS: The results showed that CSB supplementation increased ileal goblet cells (GCs) numbers, villus height and decreased crypt depth in broilers. CSB increased ileal proliferating cell nuclear antigen expression and high‐level VD3 decreased cluster of differentiation 3 expression. CSB reduced serum d‐lactate, endotoxin (ET), adrenocorticotropic hormone, corticosterone and malondialdehyde (MDA) concentrations and increased total antioxidant capacity (T‐AOC) level. Meanwhile, high‐level VD3 decreased serum ET concentration. Furthermore, CSB increased ileal T‐AOC, lysozyme (LYZ) and transforming growth factor (TGF)‐β and decreased MDA, whereas high‐level VD3 decreased ileal MDA and increased secretory immunoglobulin A. CSB up‐regulated ileal claudin1, superoxide dismutase 1, TGF‐β and LYZ mRNA expression and down‐regulated interleukin‐1β mRNA expression. CSB combined with high‐level VD3 increased ileal Faecalibaculum abundance. Spearman correlation analysis showed that Faecalibaculum was related to the immune and barrier function. CONCLUSION: Dietary supplementation with CSB and high‐level VD3 improved early gut health in broilers by promoting intestinal development, enhancing antioxidant capacity, strengthening barrier function and enhancing the favorable composition of the gut bacterial flora. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

BACKGROUND: Vitamin D deficiency is common in postmenopausal women and is associated with low vitamin D intake, increased age, decreased absorption. Especially at advanced age, vitamin D deficiency may increase muscle weakness and disbalance resulting in increased risk of fracture. OBJECTIVES: This study aims to explore the correlation between 25(OH) vitamin D3 levels and quadriceps muscle strength in postmenopausal women. METHODS: We evaluated bilateral qadriceps muscle strength in postmenopausal women with isokinetic test. We evaluated the correlation of muscle power with measurements of parathormone, vitamin D, Calcium, creatinine, alanine transaminase, alkaline phosphatase, total creatine kinase. RESULTS: The mean vitamin D level of 95 participants included in the study was 18.24 ± 8.94 ng/ml. Vitamin D levels were found to be deficient (< 10 ng/ml) in 23 (24.1%), insufficient in 62 (65.26%) and normal in 10 (10.53%) of the 95 participants. A weak negative correlation was observed between participants' vitamin D levels and PT values (r = - 0.271, p = 0.012). A moderate negative correlation was found between ALP and vitamin D levels (r = - 0.317, p = 0.002). However, there was no significant correlation between vitamin D levels and the 60∘ and 90∘ flexion and extension peak torque values (All p values > 0.05). CONCLUSIONS: Vitamin D levels and muscle strength weren't statistically significant. Few studies are available in the related literature, highlighting the need for further research to achieve a clearer consensus. [ABSTRACT FROM AUTHOR]

Orthodontic tooth movement (OTM) is a critical process in dental alignment, driven by the application of calibrated orthodontic forces. This study delves into the intricate molecular and cellular mechanisms by which vitamin D3 influences OTM. Vitamin D3 is identified as a critical regulator in bone metabolism, enhancing osteoblast activity and bone formation while also modulating osteoclast quantity and RANKL expression, essential for the remodeling of the alveolar bone. The precise mechanisms through which vitamin D3 facilitates these processes are explored, highlighting its potential in accelerating bone remodeling and, consequently, tooth alignment. This comprehensive review underscores vitamin D3's anabolic impact on bone metabolism and its pivotal role in the synthesis and mineralization processes governed by osteoblasts. The findings illuminate vitamin D3's promise in augmenting orthodontic therapy, suggesting its utility in improving treatment efficiency and reducing duration. However, the need for further research into the optimal application of vitamin D3 in orthodontics is emphasized, particularly concerning dosage, timing, and delivery methods. [ABSTRACT FROM AUTHOR]

Background: Warts pose a considerable challenge in dermatology, necessitating effective therapeutic interventions. This prospective study aims to compare the efficacy and safety of intralesional administration of the measles, mumps, and rubella (MMR) vaccine with intralesional vitamin D3 in patients with multiple warts. Methods: Conducted at the Department of Dermatology, Government Medical College, Anantnag, this prospective study involved patients attending the Dermatology OPD with clinically diagnosed cutaneous warts, either multiple or single, based on predefined inclusion and exclusion criteria. A total of 200 patients were randomly selected, with 100 patients allocated to each group. Patients clinically diagnosed with cutaneous warts were divided into two groups: Group A received intralesional MMR, and Group B received intralesional vitamin D3. Results: In Group A, 43 cases (86%) exhibited a complete treatment response, 4 cases (8%) showed a partial response, and 3 cases (6%) had no response to treatment. Similarly, in Group B, 39 cases (78%) demonstrated a complete treatment response, 6 cases (12%) showed a partial response, and 5 cases (10%) had no response. The comparison between the two groups yielded a non-significant p-value of 0.578. Regarding distant wart clearance, Group A displayed a complete response in 39 cases (78%), while Group B showed a comparable response in 35 cases (70%). Partial response was observed in 14% of cases in Group A and 16% in Group B. Additionally, no response was recorded in 8% of cases in Group A and 14% in Group B. Both groups were comparable with respect to the clearance of distant warts with a non-significant p-value of 0.576. Furthermore, our findings affirm the favorable tolerability and safety profiles of both intralesional MMR vaccine and vitamin D3 immunotherapy, with no occurrences of serious adverse events documented. Conclusion: The study demonstrates that both treatments exhibit similar effectiveness and safety profiles, with MMR showing slightly better response rates. No serious adverse events were reported with either treatment. [ABSTRACT FROM AUTHOR]

The use of doxorubicin (Dox) in the treatment of breast cancer negatively affects the intestines and other tissues. Many studies have proven that probiotics and vitamin D3 have antitumor and intestinal tissue-protecting properties. To achieve effectiveness and minimize side effects, the current study aims to administer Dox together with probiotics (Lactobacillus acidophilus and Lactobacillus casei) and vitamin D3. Forty-two female BALB/c inbred mice were divided into six groups: Group 1 (Control), Group 2 (Dox), Group 3 (Dox and probiotics), Group 4 (Dox and vitamin D3), Group 5 (Dox, probiotics, and vitamin D3), and Group 6 (probiotics and vitamin D3). The 4T1 mouse carcinoma cell line was injected into the mammary fat pad of each mouse. Gene expression was examined using quantitative real-time PCR. The treated groups (except group 6) showed significantly reduced tumor volume and weight compared to the control group (P < 0.05, P < 0.01). Probiotics/vitamin D3 with Dox reduced chemotherapy toxicity and a combination of supplements had a significant protective effect against Dox (P < 0.05, 0.01, 0.001). The treated groups (except 6) had significantly higher expression of Bax/Caspase 3 genes and lower expression of Bcl-2 genes than the control group (P < 0.05, 0.01). Coadministration of Dox with probiotics and vitamin D3 showed promising results in reducing tumor size, protecting intestinal tissue and influencing gene expression, suggesting a strategy to enhance the effectiveness of breast cancer treatment while reducing side effects. [ABSTRACT FROM AUTHOR]