Search Results (3,224)

Echinophora sibthorpiana Guss. (Apiaceae) is an aromatic plant of considerable ethnobotanical significance, traditionally employed as a flavouring and preservative agent in food and valued for its medicinal properties across the Eastern Mediterranean region, yet its non-volatile phytochemistry and biosafety profile remain insufficiently characterized. In the present study, the n-butanol fraction of the 80% methanolic extract of the aerial parts of E. sibthorpiana was fractionated using chromatographic methods and the structures of the isolated compounds were elucidated by 1D and 2D-NMR spectroscopy and HR-ESI-MS. The distribution of Echinophora metabolites isolated by our group across six species in Türkiye was assessed by LC-qTOF-MS. Antioxidant capacity was evaluated by CUPRAC, FRAP, and TEAC assays; DNA-protective activity by the pBR322 plasmid model; genotoxic and antigenotoxic potential in the Drosophila melanogaster wing SMART assay. Four secondary metabolites, known as vicenin-2 (1), rutin (2), isoquercitrin (3) and betulalbuside A (4), were isolated and reported from E. sibthorpiana for the first time. Notably, the C-glycoside flavone vicenin-2 and the acyclic monoterpene glucoside betulalbuside A also represent the first isolation of these compounds from the genus Echinophora. LC-qTOF-MS profiling identified widely distributed flavonoid constituents together with more restricted metabolites that may have chemotaxonomic relevance. The n-BuOH fraction and the flavonol glycosides rutin and isoquercitrin exhibited the highest antioxidant and DNA-protective activities. None of the tested samples displayed genotoxic activity, while all showed antigenotoxic effects against ethyl methanesulfonate-induced DNA damage, with total spot frequency inhibition ranging from 47% to 83%. Overall, these findings provide a first comprehensive characterization of the non-volatile phytochemistry and biosafety profile of E. sibthorpiana and support the further investigation of its constituents as safe antioxidant and chemopreventive agents with potential nutraceutical applications. Full article

Our earlier studies have revealed the beneficial impact of vitamin D3 (VD3) metabolites on the development of pulmonary fibrosis in a murine model of hypersensitivity pneumonitis (HP). Despite the discovery of the great antifibrotic potential of both the bioactive form of VD3, 1,25(OH)₂-VD3 and its direct precursor, 25(OH)-VD3, study designs based on the co-administration of VD3-metabolites and fibrosis-inducers do not reflect the clinical situation. Thus, the presented study aims to examine the effectiveness of therapeutic interventions based on the mentioned inhalations, initiated during the acute phase of HP at the first signs of pulmonary fibrosis. The research was performed using VD3-deficient mice with HP, while VD3-sufficient mice were used as the main control. The data were collected after 28 days of daily exposure of the mice to a fibrosis-inducer (an antigen of Pantoea agglomerans, a well-known etiological factor in HP), with 25(OH)-VD3 or 1,25(OH)₂-VD3 administered daily during the last 14 days of the experiment. The effect of the intervention was monitored by whole-body plethysmography, histological assessment, flow cytometry, RealTime-PCR, and ELISA. Treatment with VD3 metabolites initiated during the acute phase of HP alleviated the disease courses and restored respiratory function, thanks to inhibition of pathological extracellular matrix deposition, immune-cell infiltration of lung parenchyma, profibrotic cytokine production, and EMT progression. Despite the discovery of the beneficial features of the investigated VD3-based therapies, none of them caused full recovery in mice with HP. Nevertheless, after verification in additional animal models and a deeper understanding of the underlying molecular mechanisms, the identified beneficial features of the investigated metabolites have the potential to serve as a foundation for future therapies for HP fibrosis. Full article

Using ultrafine silicate cement as the cementitious material, and admixtures such as expansion agent, rapid-setting agent and water reducer as additives, a new type of composite grouting material with high early strength and high toughness was obtained by modification with nano-Al₂O₃ (NA). The influence of NA content on the mechanical properties, flowability, bleeding behavior, setting time, volume shrinkage, and microstructure was investigated for composite grouting materials. The results show that, as the NA content increases, the flowability of the paste decreases, the bleeding rate reduces, and the setting time increases first and then decreases. Appropriate NA can effectively improve the mechanical strength of the composite grouting material. Especially at the condition of 3% NA, the composite grouting material reached the highest early compressive strength and toughness. Compared with the control group, the compressive strength of the specimen increases by 39.54% and 6.83% respectively at 1 d and 21 d, and the flexural strength increased by 55.41% at 1 d. XRD, FTIR, SEM and hydration heat analysis confirm that the NA can promote the early hydration heat of ultrafine cement, and shorten the induction period. Moreover, more C-A-H gel products will be generated by consuming Ca(OH)₂ with active NA, leading to an improvement in the matrix compactness. Such an outstanding mechanical property can be mainly attributed to the triple coupling mechanism of the hydration regulation, microstructure and filling effect of superfine cement by nano-Al₂O₃ in combination with multi-component admixtures. Full article

Background: This study aimed to compare a chemiluminescence immunoassay (CLIA; Siemens Atellica IM 1600) with an automated liquid chromatography–tandem mass spectrometry (LC–MS/MS) analyser (Thermo Scientific Cascadion SM) for serum 25-hydroxyvitamin D [25(OH)D] measurement in unselected outpatients, and its impact on clinical classification. Methods: 25(OH)D was measured on 1064 paired serum samples (828 women, 236 men; age 3–111 years); both platforms participated in the Vitamin D Standardisation Program (VDSP). Agreement was assessed by the Wilcoxon signed-rank test, Passing–Bablok regression, Bland–Altman analysis on log-transformed values, Breusch–Pagan testing for heteroscedasticity, consistency-based intraclass correlation coefficient (ICC), Lin’s concordance correlation coefficient, and Cohen’s kappa with McNemar’s test on six- and two-category clinical classifications. Results: Methods differed significantly ($p<2.2\times {10}^{-16}$). Passing–Bablok regression showed proportional bias (slope 1.33; 95% confidence interval [CI], 1.28–1.38; LC–MS/MS higher). Consistency ICC was 0.928 (95% CI, 0.919–0.936). Log-Bland–Altman bias was 35.5% (limits of agreement, $-18.3$% to $+124.5$%; heteroscedasticity, $p=5.18\times {10}^{-11}$). Cohen’s kappa was 0.32 unweighted and 0.72 weighted on six clinical categories, and 0.56 on a two-class scheme (McNemar $p<2.2\times {10}^{-16}$). In discordant pairs, CLIA classified deficiency 118-fold more often than LC–MS/MS. Conclusions: In our study, despite preserved rank ordering, a non-linear concentration-dependent bias and different limits of agreement caused systematic differences in the classification of vitamin D deficiency. Adoption of automated LC–MS/MS can substantially reclassify outpatients toward sufficiency, with implications for supplementation and laboratory harmonisation. Full article

Background: Non-proliferative diabetic retinopathy (NPDR) is a common microvascular complication of type 2 diabetes mellitus (T2DM) associated with chronic inflammation, metabolic dysregulation, and multiple interacting systemic factors. This study evaluated the associations of inflammatory biomarkers, serum 25-hydroxyvitamin D [25(OH)D], electrolyte homeostasis, and lipid-derived indices with NPDR. Methods: In this cross-sectional study with prospective recruitment, 98 patients with T2DM were classified into NPDR (n = 55) and non-DR (n = 43) groups. Clinical characteristics, hematological inflammatory indices, serum interleukin-6 (IL-6), C-reactive protein (CRP), 25(OH)D, electrolyte concentrations, lipid profile, and derived biomarkers—including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune–inflammation index (SII), LDL-C/HDL-C ratio, and calculated serum osmolarity—were compared. Receiver operating characteristic (ROC) analysis and multivariable logistic regression were performed to assess discriminatory performance and independent associations with NPDR. Results: Patients with NPDR had significantly lower serum 25(OH)D concentrations than the non-DR group (16.6 ± 7.5 vs. 21.0 ± 5.2 ng/mL, p < 0.001). Serum IL-6 levels (4.2 ± 3.1 vs. 2.8 ± 1.4 pg/mL, p = 0.047), NLR (p = 0.043), LDL-C/HDL-C ratio (p = 0.031), and calculated serum osmolarity (p = 0.033) were significantly higher, whereas lymphocyte count and the lymphocyte-to-monocyte ratio were significantly lower. Among individual biomarkers, serum 25(OH)D showed the best discriminatory performance (AUC = 0.712). A multivariable model including insulin therapy, IL-6, serum 25(OH)D, and the LDL-C/HDL-C ratio demonstrated good discrimination (AUC = 0.813), with 81.8% sensitivity and 81.4% specificity. Bootstrap validation supported the stability of the model. Conclusions: NPDR was associated with lower serum 25(OH)D concentrations, systemic inflammation, and a less favorable LDL-C/HDL-C ratio. A multivariable model integrating inflammatory, metabolic, and nutritional biomarkers showed better discriminatory performance than individual biomarkers. The association between insulin therapy and NPDR likely reflects greater diabetes severity rather than a direct effect of insulin. These findings are exploratory, and prospective studies in larger independent cohorts are needed to determine whether these biomarkers improve risk stratification beyond established clinical factors. Full article

Background/Objectives: Boronic acid-based proteasome inhibitors (BABPIs) including Bortezomib, Ixazomib, and Delanzomib are clinically relevant anticancer agents whose mechanism of action depends on direct interaction between the boronic acid warhead and the threonine residue at the first position (Thr1), leading to the formation of covalent tetrahedral complex. Although the formation of this complex is well studied, the subsequent behavior of the boronic acid warhead, particularly the possible formation of monoanionic boronate species through deprotonation of one of the two boronic hydroxyl groups, remains unexplored. Therefore, the present study addresses whether the formation of Thr1-OH and a monoanionic boronate species is thermodynamically favorable and which of the two hydroxyl groups is more favorable for deprotonation. Methods: Density Functional Theory (DFT) calculations at the B3LYP/6-311+G(d,p) level, combined with the Polarizable Continuum Model (PCM), were used to study two competing deprotonation pathways for the inhibitors and for a simplified warhead model. To mimic the proteasome environment, reactions were modeled in different polar media—diethyl ether (ε = 4), methanol (ε = 33), and water (ε = 78). Results: Our DFT calculations confirmed that the covalent tetrahedral complex could convert into Thr1-OH and a monoanionic boronate species, representing the deprotonation of one of the boronic hydroxyl groups. Deprotonation via pathway 1 is more favorable than deprotonation via pathway 2 for all inhibitors, especially in polar solvents. Bortezomib demonstrated a strong preference for -OH₁ deprotonation with ∆∆G ≈ −7 kcal·mol⁻¹. In contrast, Ixazomib, Delanzomib, and the simplified warhead model showed smaller ∆∆G values (≈−2 kcal·mol⁻¹), within the method’s uncertainty (±2 kcal·mol⁻¹), suggesting both deprotonation modes under physiological conditions. Conclusions: These results provide comparative thermodynamic insight into the deprotonation behavior of BABPIs, suggesting that the two hydroxyl groups are not equivalent during deprotonation. This finding offers a physicochemical framework that may support the rational design of next-generation BABPIs. Full article

Background/Objectives: Maternal vitamin D deficiency has been associated with preeclampsia, but evidence regarding preconception partner-specific vitamin D biomarkers is limited. We evaluated associations between preconception maternal and paternal vitamin D biomarkers and the odds of preeclampsia. Methods: This secondary prospective cohort analysis used data from the Folic Acid and Zinc Supplementation Trial (FAZST), a multicenter study conducted in the United States between 2013 and 2017. Of the 2370 enrolled couples who were seeking infertility treatment, 1054 couples achieved a documented pregnancy. Because preeclampsia can only be ascertained among pregnancies progressing beyond 20 weeks of gestation, the primary analytic population was restricted to 826 pregnancies that reached ≥20 weeks, including 98 with preeclampsia and 728 without preeclampsia. Preconception serum total 25-hydroxyvitamin D (25(OH)D), vitamin D-binding globulin (VDBG), albumin, free 25(OH)D, and bioavailable 25(OH)D were assessed in both partners. Multivariable logistic regression models estimated adjusted odds ratios (aORs) and 95% confidence intervals (CIs). Results: In categorical analyses, maternal total 25(OH)D findings were consistent with a possible U-shaped pattern. Compared with concentrations of 30–< 50 ng/mL, concentrations ≤20 ng/mL were associated with higher odds of preeclampsia (aOR = 2.58, 95% CI: 1.13–5.88), as were concentrations ≥50 ng/mL (aOR = 5.45, 95% CI: 1.71–17.41). Similar categorical patterns were observed for maternal free 25(OH)D, with higher odds at concentrations ≤8.25 pg/mL (aOR = 2.23, 95% CI: 1.13–4.43) and ≥12.5 pg/mL (aOR = 4.71, 95% CI: 1.97–11.29), and for maternal bioavailable 25(OH)D concentrations ≤3.5 ng/mL (aOR = 2.61, 95% CI: 1.19–5.72) and ≥5.0 ng/mL (aOR = 5.38, 95% CI: 2.15–13.46). Lower paternal bioavailable 25(OH)D was associated with lower odds of preeclampsia in the fully adjusted model (aOR = 0.50, 95% CI: 0.28–0.89); however, this finding should be considered exploratory. Conclusions: Among pregnancies progressing to ≥20 weeks, lower and higher categories of maternal total, free, and bioavailable 25(OH)D were associated with the odds of preeclampsia relative to intermediate categories. These categorical findings are consistent with a possible U-shaped pattern but do not establish a nonlinear dose–response relationship. Paternal findings were limited and should be considered exploratory. Full article

Background/objective: Postpartum depression (PPD) is a significant public health issue affecting about 19% of mothers globally. It has well-documented impacts on maternal well-being, mother–infant relationships, and child developmental outcomes. At the same time, the level of vitamin D deficiency in women of reproductive age is very high (affecting 60–87 percent of pregnant women globally). The review aims to synthesize current evidence and highlight priority research areas to improve maternal mental health outcomes. Methods: A systematic literature search of PubMed, Scopus, and Google Scholar (2015–2026) was conducted, followed by narrative synthesis of mechanistic, observational, and interventional evidence. Results: Adequate vitamin D status may contribute to a reduced risk of postpartum depression through multiple interacting pathways, including serotonin synthesis and metabolism (via tryptophan hydroxylase 2 (TPH2) and monoamine oxidase-A (MAO-A) regulation), neuroplasticity via brain-derived neurotrophic factor (BDNF) signaling, and suppression of the pro-inflammatory cytokine cascade. Dose–response meta-analyses and large prospective cohort studies indicate consistent negative relationships between maternal vitamin D levels and postpartum depressive and anxiety symptoms with optimal serum 25-hydroxyvitamin D (25(OH)D) levels of 90–110 nmol/L. Conclusions: There is still limited evidence on the intervention; it is still methodologically diverse, and only a few randomized controlled trials have been carried out on specifically postpartum populations. Full article

Objective: Vitamin D deficiency is a global concern, but its prevalence in critically ill patients in high-sunlight tropical regions is limited. This study evaluated the prevalence of vitamin D deficiency in intensive care unit (ICU) patients in southern Taiwan and identified which variables correlate with deficiency and in-hospital mortality. Methods: We prospectively enrolled 221 critically ill patients, categorizing them by serum 25(OH)D levels as follows: Group A (sufficient, ≥30 ng/mL), Group B (insufficient, 20.0–29.9 ng/mL), and Group C (deficient, ≤19.9 ng/mL). Clinical variables, laboratory parameters, and outcomes were analyzed. Results: Despite the tropical climate, 33.5% of patients were vitamin D-deficient, and 47.1% were insufficient. Group C patients were significantly younger than other groups (p = 0.049). Significant differences between Groups C and A were observed in ICU length of stay (p = 0.036) and total hospital stay (p = 0.004). Multivariable analysis confirmed that only younger age (OR 0.968, p = 0.008) and low albumin level (OR 0.171, p < 0.001) were independently associated with vitamin D deficiency. Only serum albumin (p = 0.001) and C-reactive protein (CRP) levels (p = 0.015) were significantly associated with in-hospital mortality. Conclusions: Vitamin D deficiency is highly prevalent among critically ill patients in southern Taiwan, challenging the assumption that tropical ultraviolet exposure is naturally protective. Younger age and hypoalbuminemia are independent predictors of vitamin D deficiency. However, vitamin D levels were not independently associated with in-hospital mortality, which was instead predicted by albumin and CRP levels. These findings highlight a high rate of hypovitaminosis D in ICU but do not support its role as an independent predictor of mortality. Full article

Phosphate accounts for about 0.6% of body weight at birth and about 1% of body weight in adults. This anion is essential for the performance of many essential human cellular processes, including energy metabolism and cell signaling; it is also a key component of the phospholipid bilayer and nucleic acids structure. In addition, phosphate is responsible for maintaining acid-base balance within the cells, functioning of the nervous system and preserving bone integrity. Normal serum phosphate levels change throughout life, varying from the neonatal period, through adolescence, and stabilizing at adult values by the end of puberty. Serum phosphate homeostasis is maintained through dietary intake, intra- and intercellular shifts, and excretion/absorption/reabsorption processes mediated by Fibroblast Growth Factor 23, parathyroid hormone, and 1,25-(OH)₂D₃. Within this homeostatic network, dietary sources and current population-based intake data highlight a widespread oversupply in modern diets that can influence chronic disease outcomes. Ultimately, alterations in serum phosphate concentrations lead to numerous pathological conditions, both congenital and acquired. These conditions may involve either hypo- or hyperphosphatemia, each characterized by a wide spectrum of clinical manifestations, some of which primarily affect the musculoskeletal system. Starting from this evidence, the primary purpose of this review is to examine the phosphate-related pathological conditions from biological-molecular and clinical perspectives, while also considering targeted nutritional and clinical strategies for managing phosphate balance. Algorithms for management and differential diagnosis are also considered, thus providing a recent overview of a medical field that is becoming increasingly important for clinicians. Full article

Background/Objectives: Date seeds contain a wide range of biologically active constituents and have been associated with multiple health benefits. Our study aimed to evaluate the utility of biphasic aqueous methanol/chloroform extraction for separating diverse metabolites from powdered Malakabi Ajwa date seeds and to identify the most effective chromatographic and spectroscopic techniques for their comprehensive profiling and structural characterization. Methods: Biphasic extraction generated organic, aqueous, and insoluble phases. Proper chromatography-mass spectrometry and spectroscopy analytical tools were then utilized to profile the metabolites in the aqueous and organic phases. Results and Conclusions: In the organic phase, fatty acids and their methyl esters were identified using GC-MS and confirmed by ¹H NMR, while the absence of an O–H band in the FT-IR spectrum, together with ¹H NMR data, supported the natural esterification of these fatty acids. In the aqueous phase, UV-Vis spectroscopy and LC-MS revealed anthocyanin pigments, and LC-MS additionally detected four amino acids. HPLC was used to quantify and validate the sugar composition, and ¹H 1D and 2D NMR spectra enabled the assignment of α- and β-glucopyranose, β-fructopyranose, and sucrose signals. ³¹P NMR indicated that orthophosphate monoesters were the predominant phosphorus-containing compounds in both organic and aqueous phases. Overall, our findings show how an integrated chromatographic and spectroscopic workflow provides a robust strategy for comprehensive metabolite profiling of natural products such as Malakabi Ajwa date seeds. Full article

Background: Chronic low back pain (CLBP) is a leading cause of global disability, linked to elevated IL-6 and vitamin D deficiency or insufficiency. While interferential current (IFC) therapy and exercise therapy are established treatments, their combined effect with vitamin D supplementation on inflammatory biomarkers, pain, and functional disability remains underexplored. Objective: The aim of this study was to evaluate the combined effects of physiotherapy and vitamin D supplementation on pain, disability, IL-6 expression, and vitamin D levels in CLBP patients. Methods: This two-arm, parallel-group, randomized controlled trial enrolled 60 CLBP patients, randomized into Group A (physiotherapy alone: IFC therapy and exercise therapy; n = 30) or Group B (physiotherapy plus vitamin D supplementation; n = 30). Outcomes included pain intensity (11-point Numeric Pain Rating Scale (NPRS)), disability (Arabic Oswestry Disability Index (ODI), 0–100%), and serum IL-6 and 25-hydroxyvitamin D (both by ELISA; pg/mL and ng/mL, respectively), which were assessed at baseline and 6 weeks. All 60 participants enrolled had laboratory-confirmed vitamin D deficiency or insufficiency (serum 25(OH)D < 20 ng/mL) at screening. Independent samples t-tests compared continuous baseline characteristics and between-group differences in 6-week change scores; paired t-tests assessed within-group change from baseline to 6 weeks; the chi-square test compared the categorical variable of gender (α = 0.05). Results: Both groups showed significant improvements in NPRS and ODI at six weeks (p < 0.001). Group B demonstrated significant reductions in NPRS (−3.01 vs. −1.71) and ODI (21.83% vs. 16.33%). IL-6 decreased significantly only in Group B (18.24 pg/mL, p < 0.001), with no significant change in Group A (25.96 pg/mL, p = 0.626). Vitamin D levels increased significantly in Group B (31.68 ng/mL, p < 0.001) compared with Group A (19.68 ng/mL, p = 0.115), a between-group difference that was also statistically significant. Conclusions: Combining physiotherapy with vitamin D supplementation improves outcomes in the management of CLBP. This approach effectively reduces pain, functional disability, inflammation, and vitamin D deficiency or insufficiency, offering a comprehensive, evidence-based treatment strategy. Full article

The unique contributions of 2D Ti₃C₂ MXenes surface, electrical, and chemical features play a crucial role in determining toxic and flammable gas-sensing behavior. Specifically, its high electrical conductivity (metallic nature), layered nanosheet structure (nanosheets), and surface termination groups (–O, –F, and –OH) collectively contribute to excellent hydrogen (H₂) and ammonia (NH₃) gas-sensing behavior. This review systematically explores the impact of pristine and modified Ti₃C₂ MXene, including its interfaces with various metals and metal oxides for enhancing H₂ and NH₃ detection. Furthermore, the significance of room temperature operation and flexible gas sensing mechanisms is explored. Notably, integration of Ti₃C₂ MXene and sulfur nanosheets demonstrates rapid response and recovery times with detection limits at ppt level. Ti₃C₂ MXene-based interfaces also exhibit excellent long-term stability under various relative humidity conditions. The selective surface termination groups (–OH and –O) facilitate the formation of hydrogen bonds with NH₃ molecules for enhancing gas adsorption and sensing selectivity. In addition, the expansion of the interlayer spacing plays a vital role in improving the gas-sensing performance. Partial oxidation of Ti₃C₂ MXene into TiO₂ increases the interlayer distance, promoting faster diffusion of gas molecules and quicker sensor response. Overall, the intrinsic properties of Ti₃C₂ MXene and its composites significantly achieve high-performance room-temperature H₂ and NH₃ gas-sensing performance. Full article

Background/Objectives: Vitamin D deficiency is commonly observed in patients with breast cancer and may affect disease course and treatment outcomes. The determinants of vitamin D status in this population remain incompletely understood, particularly with respect to lifestyle, psychosocial, and tumour-related factors. The aim of this study was to identify environmental and clinical factors associated with serum 25-hydroxyvitamin D [25(OH)D] concentrations in women with breast cancer, with particular emphasis on dietary patterns, psychological distress, sleep quality, and tumour molecular subtype. Methods: A cross-sectional observational study was conducted among 101 women with histopathologically confirmed invasive breast cancer, recruited at the St. John of Dukla Oncology Centre of the Lublin Region (COZL) in Lublin, Poland, between 2018 and 2019. Serum 25(OH)D concentrations were measured by electrochemiluminescence immunoassay (ECLIA; Roche Diagnostics) within 2–8 weeks after surgical treatment. Clinical and lifestyle data were collected using standardised questionnaires and medical records. Dietary patterns were assessed with the KomPAN questionnaire (pro-healthy diet index pHDI-10 and non-healthy diet index nHDI-14). Psychological distress was measured with the Distress Thermometer. Multiple linear regression with backward stepwise elimination was applied to identify factors independently associated with of 25(OH)D concentration. Results: Insufficient vitamin D status (25(OH)D < 30 ng/mL) was found in 56.4% of participants. The multivariable regression model was statistically significant (F(6,92) = 15.298; p < 0.001), explaining 49.9% of the variance in 25(OH)D concentrations. Factors independently associated with lower 25(OH)D included higher BMI (b = −0.715; p = 0.005), sleep disturbances (b = −6.257; p = 0.020), higher psychological distress score (b = −2.263; p < 0.001), and luminal B versus luminal A subtype (b = −5.909; p = 0.025). A higher pro healthy diet index (pHDI-10) was independently associated with higher 25(OH)D (b = 0.245; p = 0.040). Conclusions: Vitamin D status in patients with breast cancer is shaped by complex interactions among modifiable lifestyle factors and tumour characteristics. Targeted interventions addressing diet quality, psychological well-being, sleep health, and weight management may improve vitamin D status in this population. The association between molecular subtype and 25(OH)D concentrations warrants further prospective investigation. These findings should be interpreted with caution, as vitamin D supplementation and direct measures of sun exposure—both established determinants of 25(OH)D—could not be included as covariates and may account, at least in part, for the associations reported. Full article

Primary hyperparathyroidism (PHPT) and vitamin D deficiency (VD) are two frequent medical conditions in the Western world. Purely by dint of their prevalence, these conditions are commonly comorbid. Moreover, they can interact with one another: VD may stimulate PTH secretion, while PHPT may lead to unregulated vitamin D activation from 25-hydroxyvitamin D (25OHD) to 1,25-dihydroxyvitamin D (1,25OH2D), thereby lowering 25OHD levels and further exacerbating VD. Thus, a real conundrum arises: should the careful clinician replete VD in PHPT or not? On the one hand, both conditions could lead to bone mineral density (BMD) loss if untreated, ultimately resulting in osteoporosis and fragility fractures; on the other hand, vitamin D supplementation could lead to further worsening of hypercalcemia and its dreaded complications. To complicate matters, patients undergoing parathyroidectomy (PTX) after long-standing PHPT can also suffer from postoperative hungry-bone syndrome and symptomatic hypocalcemia, which may be further exacerbated by VD. This narrative review aims to summarize the relevant pathophysiological mechanisms underlying these two diseases and their complex interactions. The latest evidence regarding thresholds and targets for vitamin D supplementation in PHPT will be discussed, with a focus on the balance between benefits and risks. Full article