Severe Hypocalcemia Occurring During the Hospitalization of a Patient Affected by Permanent Post-Surgical Hypoparathyroidism with Multimorbidity: A Case Report.

BACKGROUND: Patients with permanent hypoparathyroidism experience an impaired quality of life, due to acute and chronic complications that may affect several organs, with an increased risk of hospitalisation and death. Adequate and continuous replacement therapy with calcium and calcitriol is necessary to avoid symptoms and long-term complications related to hypocalcemia. CASE PRESENTATION: A 63 years old male, affected by permanent post-surgical hypoparathyroidism, was hospitalized in the cardiology department because of a dehiscence of the subcutaneous housing of the double-chambered implantable cardioverter-defibrillator. Chronic replacement therapy for hypoparathyroidism was poorly controlled and, during hospitalization, severe hypocalcemia occurred together with electrocardiographic and echocardiogram life-threatening alterations. CONCLUSION: Constant and targeted long-term replacement therapy with calcium and particularly calcitriol is necessary to avoid major consequences on patients' health, especially during acute events and in the presence of other comorbidities.

Vitamin D Binding Protein (DBP), Free Calcidiol, and Total Calcitriol in Adults from Northern Greece.

Background: An ongoing debate has been raised on whether is better to use total or free calcidiol as a screening test in the population. Methods: In winter and summer, free calcidiol, total calcitriol, and vitamin D binding protein (DBP) concentrations were determined by immunoenzymatic assays in 326 adults (161 males, 165 females). These included 99 osteoporotic patients, 53 type 1 and 51 type 2 diabetics, and 123 athletic healthy persons, all from northern Greece. Results: In the whole sample, free calcidiol mean concentrations differed significantly (p < 0.001) between males (5.53 pg/ml) and females (4.68 pg/ml). Free calcidiol was significantly greater in the athletic healthy group (6.02 pg/ml) than in the three patient groups, and lowest in the osteoporosis group (3.69 pg/ml). Total calcitriol mean concentration did not differ significantly between genders in the whole sample (p = 0.896) or in the study groups, except for type 2 diabetics (males 38.33 pg/ml, females 54.52 pg/ml, p = 0.001). It was significantly less in the osteoporotics (34.61 pg/ml) than in the athletic healthy group (41.65 pg/ml, p = 0.037) and type 1 diabetics (43.73 pg/ml, p = 0.030), whereas it did not differ significantly between the other study groups. The DBP mean concentrations were not significantly different between genders in the whole sample and the study groups nor among the study groups (p = 0.467). Conclusion: Comparisons with our previously reported results of total calcidiol suggest the measurement of free calcidiol offers nothing more than that, and total calcitriol is not a sensitive measure for assessing vitamin D status.

The effect of an acute bout of exercise on circulating vitamin D metabolite concentrations: a randomised crossover study in healthy adults.

The effect of acute exercise on circulating concentrations of vitamin D metabolites is unclear. To address this knowledge gap, we examined the effect of a bout of treadmill-based exercise versus rest on circulating concentrations of 25(OH)D3, 25(OH)D2, 3-epi-25(OH)D3, 24,25(OH)2D3, 1,25(OH)2D3, and vitamin D2 and D3 in healthy men and women. Thirty-three healthy adults (14 females, 41 (15) years, body mass index 26.2 (3.7) kg/m2, V ̇ O 2 max ${{\dot{V}}_{{{{\mathrm{O}}}_{\mathrm{2}}}{\mathrm{max}}}}$ 36.2 (9.2) ml/kg/min; mean (SD)) completed two laboratory visits involving 60 min of moderate-intensity treadmill exercise (60% V ̇ O 2 max ${{\dot{V}}_{{{{\mathrm{O}}}_{\mathrm{2}}}{\mathrm{max}}}}$ ) versus 60 min of seated rest, both in an overnight fasted-state, as part of a randomised crossover design. Venous blood samples were drawn at baseline, immediately (0 h), 1 h and 24 h after the exercise or rest-period. There was a significant time × trial interaction effect for total circulating 25(OH)D (P = 0.0148), 25(OH)D3 (P = 0.0127) and 1,25(OH)2D3 (P = 0.0226). Immediately post-exercise, 25(OH)D, 25(OH)D3 and 1,25(OH)2D3 concentrations were significantly elevated compared to the control resting condition, and 1,25(OH) 2D3 remained significantly elevated 1 h later. Circulating albumin, vitamin D binding protein, calcium and parathyroid hormone were elevated immediately post-exercise. Thus, an acute bout of moderate intensity exercise transiently increases concentrations of circulating 25(OH)D and 1,25(OH)2D3 compared to resting conditions. KEY POINTS: Observational studies suggest that acute exercise might change circulating concentrations of vitamin D metabolites, but this has not been investigated using randomised crossover studies and using robust analytical procedures. In this study, we used a randomised crossover design to examine the effect of a bout of treadmill-based exercise (vs. rest) on circulating concentrations of a wide range of vitamin D metabolites in healthy humans. We show that an acute bout of moderate intensity exercise transiently increases concentrations of circulating 25(OH)D and 1,25(OH)2D3 compared to resting conditions. These findings indicate that regular exercise could lead to transient but regular windows of enhanced vitamin D biological action.

Calcitriol alleviates noise-induced hearing loss by regulating the ATF3/DUSP1 signalling pathway.

BACKGROUND: Calcitriol (Cal) is the most active metabolite of vitamin D and has antioxidant and anti-inflammatory properties. The aim of this study was to investigate the role of Cal in noise-induced hearing loss (NIHL) to further elucidate the mechanism of noise-induced oxidative stress in the mouse cochlea. METHODS: C57BL/6 J mice were given six intraperitoneal injections of Cal (500 ng/kg/d). After 14 days of noise exposure, auditory brainstem response (ABR) thresholds, and the cochlear outer hair cell loss rate were analysed to evaluate auditory function. Real-time fluorescence quantitative PCR, immunofluorescence and western blotting were performed in vitro after the treatment of cochlear explants with 100 µM tert-butyl hydroperoxide (TBHP) for 2.5 h and HEI-OC1 cells with 250 µM TBHP for 1.5 h. RESULTS: In vivo experiments confirmed that Cal pretreatment mitigated NIHL and outer hair cell death. The in vitro results demonstrated that Cal significantly reduced TBHP-induced cochlear auditory nerve fibre degradation and spiral ganglion neuron damage. Moreover, treatment with Cal inhibited the expression of oxidative stress-related factors (3-NT and 4-HNE) and DNA damage-related factors (γ-H2A.X) and attenuated TBHP-induced apoptosis in cochlear explants and HEI-OC1 cells. A total of 1479 upregulated genes and 1443 downregulated genes were screened in cochlear tissue 1 h after noise exposure. The level of transcription factor 3 (ATF3) was significantly elevated in HEI-OC1 cells after TBHP stimulation. Gene Transcription Regulation Database （GTRD）and Cistrome database analyses revealed that the downstream target gene of ATF3 is dual specificity phosphatase 1 (DUSP1). Cistrome DB Toolkit database results showed that the transcription factor of DUSP1 was ATF3. In addition, the ChIP-PCR results indicated that ATF3 might be a direct transcription factor of DUSP1. CONCLUSION: The results of our study suggest that Cal attenuates NIHL and inhibits noise-induced apoptosis by regulating the ATF3/DUSP1 signalling pathway.

Effect of aluminum hydroxide on serum phosphate and fibroblast growth factor 23 concentrations in young adult cats with surgically induced chronic kidney disease.

OBJECTIVE: To describe serum fibroblast growth factor 23 (FGF-23) concentrations in young adult cats with remnant kidney model-induced chronic kidney disease (CKD) and to evaluate the effects of orally administered aluminum hydroxide (ALOH) on serum phosphate and FGF-23 concentrations in these cats. ANIMALS: 17 adult, purpose-bred cats with induced CKD and 13 healthy, age-matched cats. METHODS: A prospective, randomized study. Cats with induced CKD fed a wet renal diet received treatment with ALOH (90 mg/kg/d, PO) on days 0 to 42 and no treatment on days 43 to 84 (treatment group, n = 9) or no treatment on days 0 to 84 (control group, n = 8). Standard serum and urine biochemical analyses and several parameters reflective of calcium-phosphate balance, including serum parathyroid hormone and FGF-23 concentrations, were evaluated at baseline and various time points, including days 42 and 84. Age-matched, healthy, community-owned cats underwent similar evaluations at a single time point. Baseline data from CKD cats were compared to those of healthy cats. Longitudinal data from CKD cats were compared over time. RESULTS: Serum phosphate, total and ionized calcium, and FGF-23 concentrations were significantly higher in CKD cats at baseline relative to healthy cats (all P ≤ .009). Serum phosphate concentration did not change significantly over time in either CKD group; however, FGF-23 concentrations significantly increased over time in the control group (P < .02) but not the treatment group (P = .059). CLINICAL RELEVANCE: Aluminum hydroxide did not reduce serum phosphate or FGF-23 concentrations in this small study of cats with induced CKD chronically eating a phosphate-restricted diet.

The therapeutic potential of 1, 25-dihydroxy vitamin D3 on cisplatin-affected neurological functions is associated with the regulation of oxidative stress and inflammatory markers as well as levels of MMP2/9.

Calcitriol as a biologically active form of vitamin D3 has beneficial effects on all body systems. This vitamin has a potent neuroprotective effect via several independent mechanisms against brain insults induced by anticancer drugs. The present study was designed to examine the neuroprotective effects of calcitriol against neurotoxicity induced by cisplatin. Induction of neurotoxicity was done with cisplatin administration (5 mg/kg/week) for 5 successive weeks in male Wistar rats. The neuroprotective influence of calcitriol supplementation (100ng/kg/day for 5 weeks) was assessed through behavioral, electrophysiological, and molecular experiments. Cisplatin administration impaired spatial learning and memory and decreased prefrontal brain-derived neurotrophic factor (BDNF). Peripheral sensory neuropathy was induced through cisplatin administration. Cisplatin also reduced the amplitudes of the compound action potential of sensory nerves in electrophysiological studies. Cisplatin treatment elevated MDA levels and reduced anti-oxidant (SOD and GPx) enzymes. Pro-inflammatory cytokines (IL-1ß and TNF-α) and metalloproteinase-2 and 9 (MMP-2/9) were augmented through treatment with cisplatin. Learning and memory impairments along with BDNF changes caused by cisplatin were amended with calcitriol supplementation. Reduced sensory nerve conduction velocity in the cisplatin-treated group was improved by calcitriol. Calcitriol partially improved redox imbalance and diminished the pro-inflammatory cytokines and MMP-2/9 levels. Our findings showed that calcitriol supplementation can relieve cisplatin-induced peripheral neurotoxicity. Calcitriol can be regarded as a promising new neuroprotective agent.

Hypercalcemia Associated with Pregnancy and Lactation.

Hypercalcemia during pregnancy is a risk for adverse maternal and fetal consequences. Although primary hyperparathyroidism is by far the most common etiology of hypercalcemia in pregnancy, an array of other etiologies of hypercalcemia associated with pregnancy and lactation have been described. Parathyroidectomy continues to be the preferred treatment for primary hyperparathyroidism. Medical management options are limited.

Endocrine Shades of Silicone Fillers: A Case of Calcitriol-mediated Hypercalcemia.

Background: The inflammatory reaction of foreign body granulomas (FBG) may be so vast that it leads to severe systemic effects. Case report: A 42-year-old woman was referred to the ED with severe recurrent symptomatic hypercalcemia associated with worsening kidney function. She had presented multiple times with similar complaints. Severe hypercalcemia (13.8 mg/dL) was noted, with appropriately low PTH, elevated PTHrP, low 25-hydroxyvitamin D, and normal 1,25-dihydroxyvitamin D levels. She admitted having significant subcutaneous silicone filler injections in the hips six years prior. Admission workup revealed a normal 25-hydroxyvitamin D, but a marked elevation of 1,25-dihydroxyvitamin D (138 pg/mL). Whole-body PET-CT demonstrated moderate 2-18F-fluoro-2-deoxy-d-glucose (FDG) uptake within the subcutaneous adipose tissue of the lateral aspects of the gluteal regions. She was diagnosed with silicone filler injection-induced hypercalcemia, secondary to granulomatous inflammation. Her calcium level normalized a month after the initiation of prednisone. Discussion: FBG may occur years after filler injection. In rare cases, a significant granulomatous immune response leads to uncontrolled production of calcitriol. Pro-inflammatory cytokines can also upregulate PTHrP expression in macrophages, further contributing to hypercalcemia. Treatment focuses on general hypercalcemia management and FBG remission, most effectively achieved with anti-inflammatory corticosteroid doses. Nevertheless, further studies are needed to evaluate its long-term treatment efficacy. Conclusion: Granulomatous inflammation from silicone filler injection can cause hypercalcemia by uncontrolled production of calcitriol and increased PTHrP production by macrophages and giant cells.

The "Sunshine Vitamin" and Its Antioxidant Benefits for Enhancing Muscle Function.

Pathological states marked by oxidative stress and systemic inflammation frequently compromise the functional capacity of muscular cells. This progressive decline in muscle mass and tone can significantly hamper the patient's motor abilities, impeding even the most basic physical tasks. Muscle dysfunction can lead to metabolic disorders and severe muscle wasting, which, in turn, can potentially progress to sarcopenia. The functionality of skeletal muscle is profoundly influenced by factors such as environmental, nutritional, physical, and genetic components. A well-balanced diet, rich in proteins and vitamins, alongside an active lifestyle, plays a crucial role in fortifying tissues and mitigating general weakness and pathological conditions. Vitamin D, exerting antioxidant effects, is essential for skeletal muscle. Epidemiological evidence underscores a global prevalence of vitamin D deficiency, which induces oxidative harm, mitochondrial dysfunction, reduced adenosine triphosphate production, and impaired muscle function. This review explores the intricate molecular mechanisms through which vitamin D modulates oxidative stress and its consequent effects on muscle function. The aim is to evaluate if vitamin D supplementation in conditions involving oxidative stress and inflammation could prevent decline and promote or maintain muscle function effectively.

A Health Technology Assessment Based on Chinese Guideline: Active Vitamin D and Its Analogs in the Treatment of Osteoporosis.

Objective: To quantitatively assess all dosage forms of three active vitamin D and its analogs, namely, calcitriol, alfacalcidol, and eldecalcitol, to provide a basis for the selection of active vitamin D and its analogs in hospitals. Methods: In this study, three active vitamin D and its analogs were evaluated by quantitative scoring in five dimensions, including pharmaceutical properties (28 points), efficacy (27 points), safety (25 points), economy (10 points), and other attributes (10 points). Results: The final scores of quantitative assessment for the selection of alfacalcidol soft capsules, calcitriol soft capsules I, calcitriol soft capsules II, alfacalcidol tablets, alfacalcidol capsules, alfacalcidol oral drops, calcitriol injection, and eldecalcitol soft capsules were 73.17, 72.06, 71.52, 71.29, 69.62, 68.86, 65.60, 64.05 points. Conclusion: Based on the scoring results, alfacalcidol soft capsules, calcitriol soft capsules I, calcitriol soft capsules II, alfacalcidol tablets can be entered into the medication list of medical institutions as strongly recommended drugs. This study offers guidance on selecting and using active vitamin D and its analogs in hospitals, with consideration for the patient's needs.

Vitamin D in Central Nervous System: Implications for Neurological Disorders.

Vitamin D, obtained from diet or synthesized internally as cholecalciferol and ergocalciferol, influences bodily functions through its most active metabolite and the vitamin D receptor. Recent research has uncovered multiple roles for vitamin D in the central nervous system, impacting neural development and maturation, regulating the dopaminergic system, and controlling the synthesis of neural growth factors. This review thoroughly examines these connections and investigates the consequences of vitamin D deficiency in neurological disorders, particularly neurodegenerative diseases. The potential benefits of vitamin D supplementation in alleviating symptoms of these diseases are evaluated alongside a discussion of the controversial findings from previous intervention studies. The importance of interpreting these results cautiously is emphasised. Furthermore, the article proposes that additional randomised and well-designed trials are essential for gaining a deeper understanding of the potential therapeutic advantages of vitamin D supplementation for neurological disorders. Ultimately, this review highlights the critical role of vitamin D in neurological well-being and highlights the need for further research to enhance our understanding of its function in the brain.

Structural diversification of vitamin D using microbial biotransformations.

Vitamin D deficiencies are linked to multiple human diseases. Optimizing its synthesis, physicochemical properties, and delivery systems while minimizing side effects is of clinical relevance and is of great medical and industrial interest. Biotechnological techniques may render new modified forms of vitamin D that may exhibit improved absorption, stability, or targeted physiological effects. Novel modified vitamin D derivatives hold promise for developing future therapeutic approaches and addressing specific health concerns related to vitamin D deficiency or impaired metabolism, such as avoiding hypercalcemic effects. Identifying and engineering key enzymes and biosynthetic pathways involved, as well as developing efficient cultures, are therefore of outmost importance and subject of intense research. Moreover, we elaborate on the critical role that microbial bioconversions might play in the a la carte design, synthesis, and production of novel, more efficient, and safer forms of vitamin D and its analogs. In summary, the novelty of this work resides in the detailed description of the physiological, medical, biochemical, and epidemiological aspects of vitamin D supplementation and the steps towards the enhanced and simplified industrial production of this family of bioactives relying on microbial enzymes. KEY POINTS: • Liver or kidney pathologies may hamper vitamin D biosynthesis • Actinomycetes are able to carry out 1α- or 25-hydroxylation on vitamin D precursors.

Hypercalcemia Secondary to Calcitriol Production From Dual Combination Immunotherapy in Pulmonary Metastatic Melanoma.

Nivolumab and ipilimumab are immunotherapy agents recommended for the treatment of metastatic melanoma. A rare adverse effect of these agents is hypercalcemia. The mechanism of immunotherapy-mediated hypercalcemia is thought to be due to ectopic calcitriol production from activated macrophages, similar to sarcoidosis. We present a case of a 76-year-old female with metastatic melanoma who developed severe hypercalcemia after completing a cycle of combined nivolumab and ipilimumab therapy. After other common causes of hypercalcemia in malignancy were ruled out, the decision was made to aggressively treat her hypercalcemia while inpatient and hold immunotherapy at discharge. Since holding immunotherapy, she has not had a repeat occurrence of hypercalcemia. This case stresses the importance of including immunotherapy adverse effects in the differential diagnosis for hypercalcemia in malignancy.

Calcitriol in Sepsis-A Single-Centre Randomised Control Trial.

Background/Objectives: Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. Sepsis is a significant cause of hospital admission and the leading reason for admission to the ICU and is associated with high mortality. Vitamin D has shown promising immunomodulatory effects by upregulating the antimicrobial peptide, cathelicidin. However, previous studies analysing the use of calcitriol in sepsis have shown variable results and did not utilise APACHE II (Acute Physiology and Chronic Health Evaluation II) scores as endpoints. This study evaluates the efficacy of intramuscular calcitriol in patients admitted to the ICU with sepsis, focusing on its impact on APACHE II scores. The primary aim was to determine if intramuscular calcitriol improved APACHE II scores from day 1 to day 7 or discharge from the ICU, whichever was earlier. Secondary outcomes included 28-day mortality, ventilator days, vasopressor days, ICU stay length, adverse events, and hospital-acquired infections in ICU patients. Methods: This was a triple-blinded phase III randomised control trial. A total of 152 patients with suspected sepsis were block-randomised to receive either intramuscular calcitriol (300,000 IU) (n = 76) or a placebo (n = 76). The trial was registered with the Clinical Trials Registry-India (CTRI No: CTRI 2019/01/17066) following ethics committee approval and was not funded. Results: There was no significant difference in APACHE II scores between the calcitriol and placebo groups from day 1 to day 7 (p = 0.382). There were no significant changes in 28-day mortality (14.4% vs. 17%, p = 0.65), number of days on a ventilator (5 vs. 5, p = 0.84), number of days on vasopressors (3 vs. 3, p = 0.98), length of ICU stay (10 days vs. 11 days, p = 0.78), adverse events (27.6% vs. 19.7%, p = 0.25), and hospital-acquired infections (17.1% vs. 15.8%, p = 0.82). Conclusions: There was no effect of intramuscular calcitriol in patients admitted to the ICU with sepsis.

Vitamin D supplementation in primary hyperparathyroidism: effects on 1,25(OH)2 vitamin D and FGF23 levels.

PURPOSE: In patients with Primary Hyperparathyroidism (PHPT) vitamin D deficiency has been associated with more severe presentations. Our aim was to investigate the effects of Vitamin D supplementation on mineral homeostasis and related hormones in individuals with and without PHPT. METHODS: Individuals with and without PHPT (CTRL) received 14,000 IU/week of oral vitamin D3 for 12 weeks. At baseline and endpoint, blood samples were collected to measure 1,25(OH)2vitamin D (1,25(OH)2D), intact Fibroblast Growth Factor 23 (FGF23), 25OHD, Parathormone, and other biochemical markers. The 1,25(OH)2D measurement was performed using liquid chromatography and mass spectrometry (LC-MS/MS). RESULTS: 70 PHPT patients and 75 CTRL were included, and 55 PHPT and 64 CTRL completed the 12-week protocol. After the intervention, there were significant increases in the FGF23 levels (PHPT: 47.9 ± 27.1 to 76.3 ± 33.3; CTRL: 40.5 ± 13.9 to 59.8 ± 19.8 pg/mL, p < 0.001), and significant decreases in 1,25(OH)2D levels (PHPT: 94.8 ± 34.6 to 68.9 ± 25.3; CTRL: 68.7 ± 23.5 to 56.4 ± 20.7 pg/mL, p < 0.001). The reduction of 1,25(OH)2D was inversely associated with the increase of FGF23 in both the PHPT (r = -0.302, p = 0.028) and CTRL (r = -0.278, p = 0.027). No changes in plasmatic or uninary calcium concentrations were observed in both groups. CONCLUSION: The weekly administration of 14,000 IU of Vitamin D3 was safe and efficient to increase in 25OHD levels in both groups. However, a paradoxical decrease in 1,25(OH)2D levels measured by LC-MS/MS was associated with a significant increase in FGF23 levels in both groups. This phenomenon might represent a defense against hypercalcemia after vitamin D supplementation and paves the way for new studies in this regard.

Structure and the Anticancer Activity of Vitamin D Receptor Agonists.

Vitamin D is a group of seco-steroidal fat-soluble compounds. The two basic forms, vitamin D2 (ergocalciferol) and vitamin D3 (cholecalciferol), do not have biological activity. They are converted in the body by a two-step enzymatic hydroxylation into biologically active forms, 1α,25-dihydroxyvitamin D2 [ercalcitriol, 1,25(OH)2D2] and 1α,25-dihydroxyvitamin D3 [calcitriol, 1,25(OH)2D3], which act as classical steroid hormones. 1,25(OH)2D3 exerts most of its physiological functions by binding to the nuclear vitamin D receptor (VDR), which is present in most body tissues to provide support to a broad range of physiological processes. Vitamin D-liganded VDR controls the expression of many genes. High levels of 1,25(OH)2D3 cause an increase in calcium in the blood, which can lead to harmful hypercalcemia. Several analogs of 1,25(OH)2D3 and 1,25(OH)2D2 have been designed and synthesized with the aim of developing compounds that have a specific therapeutic function, for example, with potent anticancer activity and a reduced toxic calcemic effect. Particular structural modifications to vitamin D analogs have led to increased anticancer activity and reduced calcemic action with the prospect of extending work to provide future innovative therapies.

Temporal patterns of food consumption and their association with cardiovascular risk in rotating shift workers.

OBJECTIVE: We aimed to evaluate the association of temporal patterns of food consumption with cardiovascular disease (CVD) risk. METHODS: This cross-sectional study included male rotating shift workers in an iron ore extraction company. Data on food consumption was collected using a 24 h recall, applied by trained interviewers. The variables for temporal patterns of food consumption were: eating window, eating at night, number of meals and omission of breakfast. CVD-risk was measured by calculating the Framingham coronary heart disease risk score (FCRS), and classified as low risk or intermediate to high risk. Descriptive, univariate and multivariate logistic regression analyses examined the association between variables related to temporal patterns of food consumption and CVD-risk. RESULTS: The study assessed 208 workers, the majority with 20-34 years (45.1%), non-white (77.2%), and 5 years or more in shift work (76.0%). Most participants had a feeding window exceeding 12 h (63.9%), consumed meals until 10 p.m. (68.1%), had five or more meals per day (54.8%), and did not skip breakfast (86.5%). Regarding CVD-risk, 43.8% of the participants were classified with intermediate to high risk for CVD. In the multivariate model, a feeding window (OR: 2.32; 95%CI: 1.01-5.35), eating after 10 p.m. (OR: 3.31; 95%CI: 1.01-11.0), and skipping breakfast (OR: 2.58; 95%CI: 1.07-6.19) increased the likelihood of intermediate to high CVD-risk. Conversely, having five or more meals per day decreased the odds (OR: 0.27; 95%CI: 0.08-0.92). CONCLUSION: Eating window longer than 12 h, eating after 10 p.m., less than four meals a day and omission of breakfast, are associated with cardiovascular risk in shift workers.

Comparative effects of calcitriol and calcimimetic on bone health in renal insufficiency.

Calcitriol and calcimimetics are used to treat hyperparathyroidism secondary to chronic kidney disease (CKD). Calcitriol administration and the subsequent increase in serum calcium concentration decrease parathyroid hormone (PTH) levels, which should reduce bone remodeling. We have previously reported that, when maintaining a given concentration of PTH, the addition of calcimimetics is associated with an increased bone cell activity. Whether calcitriol administration affects bone cell activity while PTH is maintained constant should be evaluated in an animal model of renal osteodystrophy. The aim of the present study was to compare in CKD PTH-clamped rats the bone effects of calcitriol and calcimimetic administration. The results show that the administration of calcitriol and calcimimetic at doses that induced a similar reduction in PTH secretion produced dissimilar effects on osteoblast activity in 5/6 nephrectomized (Nx) rats with secondary hyperparathyroidism and in Nx rats with clamped PTH. Remarkably, in both rat models, the administration of calcitriol decreased osteoblastic activity, whereas calcimimetic increased bone cell activity. In vitro, calcitriol supplementation inhibited nuclear translocation of ß-catenin and reduced proliferation, osteogenesis, and mineralization in mesenchymal stem cells differentiated into osteoblasts. In conclusion, besides the action of calcitriol and calcimimetics at parathyroid level, these treatments have specific effects on bone cells that are independent of the PTH level.

Vitamin D3 (Calcitriol) Monotherapy Decreases Tumor Growth, Increases Survival, and Correlates with Low Neutrophil-to-Lymphocyte Ratio in a Murine HPV-16-Related Cancer Model.

Vitamin D3 or calcitriol (VitD3) has been shown to have anticancer and anti-inflammatory activity in in vitro models and clinical studies. However, its effect on HPV-16-related cancer has been sparsely explored. In this study, we aimed to determine whether monotherapy or combination therapy with cisplatin (CP) reduces tumor growth and affects survival and systemic inflammation. Treatments were administered to C57BL/6 mice with HPV-16-related tumors (TC-1 cells) as follows: (1) placebo (100 µL vehicle, olive oil, orally administered daily); (2) VitD3 (3.75 µg/kg calcitriol orally administered daily); (3) CP (5 mg/kg intraperitoneally, every 7 days); and (4) VitD3+CP. Tumor growth was monitored for 25 days, survival for 60 days, and the neutrophil-to-lymphocyte ratio (NLR) was evaluated on days 1 (baseline), 7, and 14. VitD3+CP showed greater success in reducing tumor volume compared to CP monotherapy (p = 0.041), while no differences were observed between CP and VitD3 monotherapy (p = 0.671). Furthermore, VitD3+CP prolonged survival compared to CP (p = 0.036) and VitD3 (p = 0.007). Additionally, at day 14 the VitD3 and VitD3+CP groups showed significantly lower NLR values than the CP group (p < 0.05, for both comparisons). Vitamin D3 could be a promising adjuvant in the treatment of cervical cancer or solid tumors and deserves further investigation.

[Biosynthesis of calcifediol and calcitriol: a review].

VD3 is a crucial vitamin for human health, as it enhances calcium absorption in the intestines and prevent rickets. Calcifediol (25(OH)VD3) and calcitriol (1α,25(OH)2VD3) are two derivatives of vitamin D3 that play an important role in preventing and treating osteoporosis, as well as regulating human physiological functions. Currently, the production of calcifediol, and calcitriol primarily relies on chemical synthesis, which has disadvantages such as low product yield, numerous by-products, and environmental unfriendliness. Therefore, developing a green, safe, and environmentally friendly biocatalytic synthesis pathway is of utmost importance. This article mainly reviews the biocatalytic synthesis pathways of calcifediol, and calcitriol. The P450 enzymes, including P450 monooxygenases (cytochrome P450 monooxygenases, CYPs) and P450 peroxygenases (unspecific peroxygenases, UPOs), are crucial for the production of calcifediol and calcitriol. The catalytic mechanism of the extensively studied P450 monooxygenases, the selection of suitable redox partners, and the key residues involved in the enzyme's catalytic activity are analyzed. In addition, the review explores H2O2-driven UPOs, including their catalytic mechanism, strategies for high heterologous expression, and in situ regeneration of H2O2. UPOs are regarded as highly promising biocatalysts because they can facilitate reactions without the need for expensive cofactors and redox partners. This review offers insights into the engineering of P450 for the efficient production of vitamin D3 derivatives.