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Sulfate accumulation may reduce calcium (Ca) activity in solution. The objective of this study was to relate solution and foliar nutrients for greenhouse tomato (Lycopersicon esculentum Mill. cv ‘Trust’) receiving nutrient solutions enriched with 0.1, 5.2, 10.4, or 20.8 mM of sulfate. Solution components were expressed as crude or free concentrations, which were row-centered log ratioed (RCLR). As an expression for nutrient balance, RCLR adjusts any nutrient value to the geometric mean of all nutrient levels. Solution and foliar datasets were related to each other using canonical correlations. RCLR produced greatest redundancy between the two datasets (R2=0.640–0.654), and raw data, the smallest (R2=0.498–0.513). Canonical analysis of RCLR-transformed free concentrations indicated a dominant sulfate effect and significant secondary effects due to adjustment of the anion–cation balance in solution. Free sulfate concentration as RCLR explained 66% of the variation in foliar sulfur (S) and 71% of the variation in foliar Ca. The RCLR transformation should be further examined in relation with Ca imbalance and interactions in fruit crops. [ABSTRACT FROM AUTHOR]

Context: Our previous biological study demonstrated that Fructus Ligustri Lucidi (FLL), the fruit of Ligustrum lucidum Ait. (Oleaceae), could be used to maintain calcium balance and prevent age-related osteoporosis since it effectively decreased calcium loss and increased calcium retention in rats. Objective: This study investigates the combination effect of the Chinese herbal medicine FLL and a high calcium diet on calcium imbalance induced by ovariectomy in mice. Materials and methods: The ovariectomized (OVX) mice were orally treated with vehicle, FLL extract (700 mg/kg), milk powder (5 g/mice) fortified with calcium (1.0% Ca) and the combination of FLL with milk powder. After 6 weeks of treatment, urine, serum, and tibia were preserved for biochemical analysis and kidneys were taken for gene expression analysis. Results: The combination treatment of FLL and a high calcium diet significantly increased bone calcium content (6.80 ± 0.34 mg) by 22% ( p < 0.05) and decreased urine calcium excretion (0.099 ± 0.009 mg/mg) by 62% ( p < 0.01) as compared with those of the OVX group (bone Ca, 5.57 ± 0.31 mg; urine Ca/Cr, 0.261 ± 0.017 mg/mg). The mRNA expression of renal calcium-binding protein-9k (CaBP-9k) and calcium-sensing receptor (CaSR) in combination treatment group was significantly up-regulated and down-regulated, respectively, as compared with those of the OVX group. Conclusion: The beneficial effects of this combination therapy on calcium balance of OVX mice were, at least partially, attributed to its regulation on mRNA expression of CaBP-9k and CaSR in kidney. [ABSTRACT FROM AUTHOR]

A variety of genetic, mechano-response-related, endocrine-metabolic, and nutritional determinants impact bone health. Among the nutritional influences, protein intake and dietary acid load are two of the factors most controversially discussed. Although in the past high protein intake was often assumed to exert a primarily detrimental impact on bone mass and skeletal health, the majority of recent studies indicates the opposite and suggests a bone-anabolic influence. Studies examining the influence of alkalizing diets or alkalizing supplement provision on skeletal outcomes are less consistent, which raises doubts about the role of acid–base status in bone health. The present review critically evaluates relevant key issues such as acid–base terminology, influencing factors of intestinal calcium absorption, calcium balance, the endocrine-metabolic milieu related to metabolic acidosis, and some methodological aspects of dietary exposure and bone outcome examinations. It becomes apparent that for an adequate identification and characterization of either dietary acid load's or protein's impact on bone, the combined assessment of both nutritional influences is necessary. [ABSTRACT FROM PUBLISHER]

Skeletal abnormalities such as bone loss occur when there is an imbalance in bone matrix synthesis and bone resorption. This imbalance is also caused by hormonal changes and inflammation. Chia (Salvia hispanica L.) has a high nutritional value and is an excellent source of calcium. Evaluate the bioavailability of calcium from chia, and its effect on bone metabolism when consumed as part of a standard or high fat diet (HFD) in ovariectomized rats. The study was conducted with 80 female Wistar rats that received standard diet or HFD. 40 female mice were ovariectomized (OVX) and 40 were sham-operated (SHAM). After recovery from surgery the animals received chia as a source of 20% of the calcium recommendation, calcium bioavailability was measured using the calcium balance technique. Bone strength and bone morphometry were evaluated by weight, length and microtomography measurements. HFD increased serum calcium and decreased calcium retention. The addition of chia to HFD did not alter bone morphology. Ovariectomy led to lower percentage of bone volume, smaller trabecular thickness, higher trabecular separation and higher porosity, when ovariectomy was associated with HFD, the final weight, waist circumference, body mass index and adiposity were increased. Chia maintained bone health when offered as a source of 20% calcium, in a diet that met 100% of the mineral recommendation, regardless of the type of diet, in animals non-ovariectomized adults. [ABSTRACT FROM AUTHOR]

Vitamin D and calcium deficiency have been reported as one of the causes of preeclampsia. In this study, levels of vitamin D, calcium and phosphorus were evaluated in 51 normotensive pregnant women and 52 women with preeclampsia at the gestational age between 28 and 36 weeks in Tabriz. Logistic regression and general linear models were used for comparing levels and means of vitamin D, calcium and phosphorus between the two groups adjusting for education and Body Mass Index (BMI). The results showed that mean serum vitamin D (p = .73), calcium (p = .12) and phosphorus (p = .60) levels were not significantly different between the groups after adjusting for education and BMI. Based on this study, no relationship was observed between vitamin D deficiency and preeclampsia; however, it was seen that the hypocalcaemia could increase the risk of preeclampsia up to 8.5 times. Based on our results and the literature, it seems that further studies need to be done to provide more insights into this area.Impact statementWhat is already known on this subject? Preeclampsia is one of the three leading causes of maternal morbidity and mortality worldwide. Despite the importance of preeclampsia, the causes and methods of prevention of this disease are still unknown. Deficiency of vitamin D affects the calcium balance of mothers and fetuses and has also been reported as one of the causes of preeclampsia disease. Reducing serum calcium can lead to increased blood pressure in preeclamptic women. Changes in calcium metabolism during pregnancy could be one of the potential causes of preeclampsia. Although the association of vitamin D, calcium and phosphorus with preeclampsia have been discussed previously, the results are not consistent.What do the results of this study add? The results showed that mean serum vitamin D, calcium and phosphorus levels were not significantly different between the groups.What are the implications of these findings for clinical practice and/or future research? Based on this study, no relationship was observed between vitamin D deficiency and preeclampsia; however, it was seen that the hypocalcaemia could increase the risk of preeclampsia by up to 8.5 times. Based on our results and the literature, it seems that further studies need to be done to provide more insights into this area. [ABSTRACT FROM AUTHOR]

We investigated the dynamic expression of calcium transporters, TRPV5 and TRPV6, in placenta and bone to determine their role in maternal and fetal calcium balance during gestation. In placenta, TRPV5 was expressed predominantly in syncytiotrophoblasts of the labyrinthine zone, whereas TRPV6 was expressed in spongiotrophoblasts of the junction zone. In bone, the two transporters were found in osteoblasts, osteoclasts, cartilage and bone matrices. During the first half of gestation, TRPV5 and TRPV6 levels in bone were increased on pregnancy day (P) 0.5, then decreased on P3.5 followed by a slight increase on P6.5. During the second half of pregnancy, both the proteins and their mRNAs gradually increased from P9.5 to P15.5−P17.5 in both bone and placenta, followed at parturition by relatively high amounts in placenta, but markedly decreased amounts in bone. The expression pattern is likely related to the fetal and maternal calcium requirement during gestation, which may be regulated by estrogen and other hormones, because the fetal demand for calcium is greatest during the last few days of gestation for rats; maternal calcium metabolism is designed to meet the calcium needs of the fetus during this period. We found that TRPV5 and TRPV6 are involved in calcium transport in the placenta and bone, and therefore play a role in calcium homeostasis during embryonic and fetal development. [ABSTRACT FROM AUTHOR]

Citrate dialysate (CD) has been successfully used in conventional hemodialysis and continuous renal replacement therapy; however, no study has compared pre- and post-dilution online hemodiafiltration (oL-HDF). Therefore, we aimed to investigate the efficacy of citrate anticoagulation for oL-HDF and the metabolic changes and quality of life of patients on hemodialysis treated using both modes Eight dialysis patients were treated with CD containing 0.8 mmol of citric acid for 4 weeks in each phase. Visual clotting scores were investigated as the primary endpoints. Adequacy of dialysis, laboratory parameters, and quality of life were measured as secondary objectives. The mean clotting scores in the pre-dilution mode were significantly lower than those in the post-dilution mode and in all phases except the heparin-free phase (p < 0.001 in the baseline phase, p = 0.001 in phase 1, and p = 0.023 in phase 2). The values of Kt/V in both modalities were comparable except during the baseline phase, in which the values of pre-dilution were significantly greater than post-dilution (2.36 ± 0.52/week vs. 1.87 ± 0.33/week;95% CI −0.81 to −0.19, p = 0.002). The patient's quality of life regarding their physical activity level was significantly higher in the post-dilution mode than in the pre-dilution mode at baseline and in phase 1 (p = 0.014 and 0.004 at baseline and in phase 1, respectively). Metabolic changes did not differ between the two modes. Citrate dialysate decreased or prevented anticoagulation in both pre- and post-dilution modes of oL-HDF without significant side effects and had comparable adequacy of dialysis. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is an immune-mediated condition of the central nervous system (CNS). Intake of fruits and vegetables high in vitamins, minerals, fiber, and active molecules contributes to the body's overall health, immunity, and physiological function. This study sought to review the literature and investigate the relationship between fruits and vegetables consumption and MS odds. In the current systematic review and meta-analysis, a systematic search of original databases from inception to 21 Dec 2022 was conducted based on the PRISMA 2020 statement. Human observational studies examining the association between fruits or vegetables consumption and MS prevalence were included if they reported and provided effect size with 95% confidence intervals (CIs). The systematic review and meta-analysis included eight studies. Random effect model showed the protective effect of fruits (I2 = 81.0%, P for heterogeneity < 0.001; pooled OR = 0.52, 95%CI = 0.27, 0.97, P-value = 0.042) and vegetables consumption (I2 = 73.5%, P for heterogeneity = 0.002; pooled OR = 0.61, 95%CI = 0.38, 1.00, P-value = 0.050) on MS odds. According to a linear dose–response meta-analysis of four case–control studies, an increase of 100 grams of fruits per day reduced the odds of MS by 9% (I2 = 0.0%, P for heterogeneity = 0.77; pooled OR = 0.91, 95%CI = 0.83, 0.99, P-value = 0.021). Consumption of fruits and vegetables may be associated with a potential protective effect against MS. However, further confirmation is required through prospective longitudinal studies and randomized clinical trials. [ABSTRACT FROM AUTHOR]

Studies show a high prevalence of osteoporosis and fracture risk in kidney transplant candidates and recipients. However, little is known about the prevalence of osteoporosis among transplant recipients and candidates living with HIV. To determine the prevalence of osteopenia and osteoporosis and investigate the socio-demographic and nutritional factors associated with BMD in HIV-positive transplant candidates and recipients from an HIV-positive donor. In this cross-sectional study, 20 HIV- positive transplant recipients and 36 transplant candidates on haemodialysis (HD) and awaiting transplantation had BMD and body composition measured by dual-energy X-ray absorptiometry (DEXA). Vitamin D status was measured using serum 25-hydroxyvitamin D [25(OH)D]. Dietary Vitamin D and calcium intake was obtained from a single 24-hour recall. Participants were mainly black African (92.9%), male (55.4%) with a mean age of 43.8 ± 8.3 years. Serum 25(OH)D levels were low for the group as a whole, with a mean of 22.04 ± 12.74 ng/ml. Osteoporosis was more prevalent amongst transplant recipients (20.0%) than transplant candidates (13.9%). Conversely, osteopenia was present amongst transplant candidates (27.8%). T-scores strongly correlated positively, with lean mass and BMD of the spine (r = 0.707, p = 0.007), and moderately, with each side of the total hip BMD (r = 0.455, p = 0.007 and r = 0.420, p = 0.007). There was a significant positive association between dietary calcium and all BMD sites in transplant recipients only. The prevalence of osteoporosis was similar, and in some cases, lower than in transplant recipients elsewhere. Lean mass was positively associated with BMD, and in transplant recipients, dietary calcium intake was positively associated with BMD emphasising the role of diet and exercise in preserving BMD. [ABSTRACT FROM AUTHOR]

Caffeine is probably the most frequently ingested pharmacologically active substance in the world. It is found in common beverages (coffee, tea, soft drinks), in products containing cocoa or chocolate, and in medications. Because of its wide consumption at different levels by most segments of the population, the public and the scientific community have expressed interest in the potential for caffeine to produce adverse effects on human health. The possibility that caffeine ingestion adversely affects human health was investigated based on reviews of (primarily) published human studies obtained through a comprehensive literature search. Based on the data reviewed, it is concluded that for the healthy adult population, moderate daily caffeine intake at a dose level up to 400 mg day[sup -1] (equivalent to 6 mg kg[sup -1] body weight day[sup -1] in a 65-kg person) is not associated with adverse effects such as general toxicity, cardiovascular effects, effects on bone status and calcium balance (with consumption of adequate calcium), changes in adult behaviour, increased incidence of cancer and effects on male fertility. The data also show that reproductive-aged women and children are 'at risk' subgroups who may require specific advice on moderating their caffeine intake. Based on available evidence, it is suggested that reproductive-aged women should consume ≥ 300 mg caffeine per day (equivalent to 4.6 mg kg[sup -1] bw day[sup -1] for a 65-kg person) while children should consume ≥ 2.S mg kg[sup -1] bw day[sup -1]. [ABSTRACT FROM AUTHOR]

Oxidative stress may play a crucial role in cardiac and vascular abnormalities in different types of cardiovascular diseases. In the present study, we explored the mechanism underlying oxidative stress-mediated cardiomyocyte apoptosis with a focus on the Akt-p53 signaling pathway. In vitro, cardiomyocyte was cultured with different concentrations of hydrogen peroxide. Then, cardiomyocyte viability, apoptosis rate and signaling pathway were analyzed through ELISA, immunofluorescence, qPCR and western blots. The results indicated that oxidative stress caused cardiomyocyte apoptosis in a dose-dependent manner. Mechanistically, oxidative stress inhibited cardiomyocyte glucose metabolism and promoted lactic acid accumulation. Besides, oxidative stress triggered calcium overload in cardiomyocyte. Finally, we found that oxidative stress inhibited the activity of Akt pathway while activated p53 signaling pathway. Genetic knockdown of p53 abolished oxidative stress-mediated cardiomyocyte injury and death through regulating the expressions and activities of caspase-3 and Bax. Altogether, our results illustrate that oxidative stress is associated with cardiomyocyte apoptosis through a mechanism involving dysregulated Akt/p53 signaling pathway. [ABSTRACT FROM AUTHOR]

Chronic kidney disease in the later stages poses many treatment challenges. Hyperphosphatemia is one that is well-known and is often linked to increased cardiovascular morbidity/mortality. Currently, a number of phosphate binders are available that act to conserve serum phosphate at normal or near normal levels. However, it is the overall profile of all binders that needs to be taken into account and the risks and the potential benefits associated with each agent must be balanced when selecting a particular phosphate binder. It is known that calcium-based binders, although effective phosphate binders, may lead to hypercalcemia and/or positive calcium balance and cardiovascular calcification. One, new non-calcium phosphate binder, recently approved in Europe, is colestilan. Colestilan possesses a range of properties that may afford further advantages over simply reducing serum phosphate. This review assesses the pharmacology and clinical data of colestilan used to treat hyperphosphatemia in chronic kidney disease stage 5 patients on dialysis. The article was written based on literature searches using PubMed to find articles published on phosphate binders or colestilan over the last 10 years. [ABSTRACT FROM AUTHOR]

Calcium oxalate (CaOx) crystals, ubiquitous in numerous plant families, have emerged as fascinating and complex structures with far-reaching implications in plant physiology, ecology, and human health. This paper encapsulates a comprehensive exploration of CaOx crystals, beginning with their formation and physiological role within plants, to their larger ecological implications, and finally, their impact on human society. Recent research has elucidated key genes involved in CaOx crystal formation, as well as the crystals' diverse physiological roles, including their function in calcium regulation, defense against herbivory, and potential contributions to carbon sequestration. We also highlight the ecological significance of CaOx crystals in nutrient cycling and plant-soil interactions, and the potential hazards posed by these crystals in human nutrition, particularly in the context of oxalate-rich diets and kidney stone formation. Despite significant advances, many aspects, particularly their ecological impacts and potential role in climate change mitigation, remain under-explored, necessitating future research. [ABSTRACT FROM AUTHOR]

Morphometric vertebral fractures (VFs) and osteopathy are prevalent and clinically significant complications of Cushing disease (CD). However whether they represent an early occurrence in the natural progression of the disease is an ongoing debate. This study aimed to assess the prevalence and determinants of VFs in patients newly diagnosed with CD. This cross-sectional case–control study recruited 75 newly diagnosed CD patients and compared them with a control group of individuals without pituitary disorders or secondary forms of osteoporosis. Demographic, clinical and biochemical data were collected. The VFs were assessed using preoperative lateral chest radiography. We found a significantly higher prevalence of VFs in the CD group than in the control group (58.7% vs. 14.5%; P < 0.001). Among the CD patients with VFs, 27 (61.4%) showed moderate/severe VFs. The CD patients with VFs had significantly higher preoperative 8 am serum cortisol (8ASC) levels than those without VFs (P < 0.001). The preoperative 4 pm adrenocorticotropic hormone (ACTH) levels (P = 0.031), preoperative 0 am ACTH levels (P = 0.021) and systolic blood pressure were slightly higher in CD patients with VFs than in those without VFs (P = 0.028). A binary multiple logistic analysis showed that 8ASC was an independent predictor of VF risk (P = 0.003). The optimal cut-off value of the preoperative serum 8ASC level for predicting VFs was 22.18 ng/mL. This is the first study reporting a high prevalence of radiologic VFs in recently diagnosed CD patients. VFs may represent an early manifestation of CD and may be related to cortisol levels. Therefore, VF assessment should be included in the workup during CD diagnosis. [ABSTRACT FROM AUTHOR]

Fructus Ligustri Lucidi (FLL), a commonly used herb of traditional Chinese medicine (TCM), is the fruit of Ligustrum lucidum Ait. (Oleaceae). The ethanol extract of FLL is a potential candidate for preventing and treating postmenopausal osteoporosis (PMOP) by nourishing the liver and kidneys. This study determines whether an ethanol extract of FLL has anti-osteoporotic effects in ovariectomized (OVX) mice and explores the underlying mechanism. The OVX model of eight-week-old C57BL/6J female mice was taken, and ovariectomy was used as PMOP. Mice were divided into five groups: sham-operated group (n = 10), OVX group (n = 10), OVX + E2 group (n = 10; 0.039 mg/kg), OVX + FLL group (n = 10; 2 g/kg) and OVX + FLL group (n = 10; 4 g/kg). Mice were treated by gavage with FLL or CMCNa once daily for 8 weeks. We harvested uteri, femur, and tibias from mice; bone mineral density (BMD) and bone microstructure were obtained by X-ray absorptiometry and micro-CT. Furthermore, the effect of FLL on the balance of osteoblast and adipocyte differentiation was investigated using bone marrow mesenchymal stem cells (BMMSCs). The results indicated that FLL did not affect OVX-induced estradiol reduction. Compared with OVX mice, FLL significantly increased BMD (63.54 vs. 61.96), Conn. D (86.46 vs. 57.00), and left tibial strength (13.91 vs. 11.27), decreased Tb. Sp (0.38 vs. 0.44) and body fat content (4.19% vs. 11.24%). FLL decreased osteoclast activity and enhanced RUNX2 expression; inhibited perilipin peroxisome proliferator-activated receptor gamma (PPARγ) expression and adipocyte differentiation from BMMSCs. FLL prevented additional bone loss and improved bone microstructure in OVX mice by modulating bone and fat balance, suggesting that FLL might be a therapeutic agent for PMOP. [ABSTRACT FROM AUTHOR]

Heparin anticoagulation (HA) is commonly employed for membrane therapeutic plasma exchange (mTPE). However, for patients with increased bleeding risk, there were controversial opinions on the use of HA versus regional citrate anticoagulation (RCA) for mTPE. Our present study aimed to evaluate the efficacy and safety of HA vs. RCA for mTPE in patients with increased bleeding risk. Patients with increased bleeding risk who underwent mTPE between 2014 and 2021 in our center were screened. Observations of anticoagulation efficacy and safety were used as the study endpoints. A total of 108 patients with 368 mTPE sessions were included. Of the included patients, 38 and 70 received HA and RCA mTPE, respectively. There was no significant difference in the clotting of extracorporeal circuits between the HA and RCA groups (4.1% vs. 4.4%, p = 0.605). More bleeding episodes were observed in the HA group compared to the RCA group (16.4% vs. 4.4% mTPE sessions, p < 0.001). The frequency of postoperative transfusion within 24 h (11% vs. 3.4%, p = 0.007) was significantly different in the HA and RCA group. Anticoagulation strategy (HA vs. RCA; OR 5.659, 95%CI 2.266–14.129; p < 0.001), and mean arterial pressure (prior treatment, OR 1.052, 95%CI 1.019–1.086; p = 0.002) were independent risk factors of bleeding episodes. At the end of mTPE treatment, the incidence of metabolic alkalosis (16.7% vs. 54.1%, p = 0.027) and hypocalcemia (41.7% vs. 89.2%, p = 0.001) was significantly different in the HA (n = 5, 12 sessions) and RCA (n = 22, 74 sessions) groups, respectively. RCA is as effective as HA for mTPE. However, for patients with increased bleeding risk, RCA is associated with a lower risk of bleeding, compared with HA. With careful monitoring and timely adjustment, RCA most likely is a safe and effective anticoagulation option for mTPE in patients with increased bleeding risk. [ABSTRACT FROM AUTHOR]

Background: Hypophosphatemia and bone disease are common in HIV-positive (HIV+) patients on tenofovir disoproxil fumarate-containing antiretroviral therapy (TDF-containing ART). The underlying etiology is not completely understood. Objective: To examine the effects of treatment of calcium and vitamin D deficiency on phosphate metabolism and bone disease in HIV+ patients on tenofovir. Methods: This was an open-label, pilot study of calcium and phosphate metabolism, bone turnover, and bone density in 24 HIV+ patients on TDF, who were receiving a 1-year treatment for vitamin D and/or calcium deficiency according to a predefined protocol. Eight patients without calcium or vitamin D deficiency served as controls. Results: One-year treatment improved vitamin D levels, decreased serum parathyroid hormone (PTH), and improved calcium balance and bone mineral density. It did not affect the serum levels of PTH-related peptide (PTH-rp) or fibroblast growth factor 23 (FGF-23) nor did it raise serum phosphate levels or decrease renal phosphate loss. Conclusion: Treatment of calcium or vitamin D deficiency in HIV+ patients on ART including TDF has favorable effects on bone density, but it does not improve serum phosphate levels. Renal phosphate wasting in these patients is not caused by excess PTH, PTH-rp, or FGF-23 nor by vitamin D or calcium deficiency. [ABSTRACT FROM AUTHOR]

The aim of this study was to examine the effects of biological ageing on concentration of free calcium ions ([Ca2+]i) in platelets of type 2 diabetic patients, an issue not documented till now. Since diabetes platelets are surrounded by a hyperglycemic environment enriched in products of nonenzymatic glycation and oxidation of proteins (known as "advanced glycation end products" (AGEs)), we questioned on the individual effect of high glucose concentration, AGEs, and oxidative stress on platelet [Ca2+]i. To these purposes, we performed: (i) measurement of basal and thrombin-stimulated [Ca2+]i in platelets isolated from type 2 diabetic patients and from normal subjects of young (27 ± 7 years), mature (48 ± 12 years) and older (>60 years) age, and (ii) quantitation of [Ca2+]i when platelets of young healthy subjects were exposed to 25.5 mM glucose (vs. 11 mM glucose), 0.23-1.7 mM AGE-poly-L-lysine (vs. poly-L-lysine), 0.3-2.26 mM AGE-albumin (vs. albumin), and to 10 mM and 100 mM H2O2. Reactions of nonenzymatic glycation were conducted in vitro to prepare AGE-poly-L-lysine and AGE-albumin, and spectrofluorimetry was used to measure platelet free [Ca2+]i following Fura-2/AM cells loading. The results showed that: (i) in physiological conditions, [Ca2+]i was ∼10% increased in the platelets of the mature subjects, and ∼33% enhanced at the older group (vs. young), sustaining that biological ageing is associated with accumulation of free [Ca2+]i within the platelets cytoplasm; (ii) in type 2 diabetes, [Ca2+]i was ∼16% and ∼27% higher in the platelets of mature and older patients, respectively (vs. age-matched normals), demonstrating that ageing of diabetics is accompanied by alterations in calcium balance (vs. physiological ageing); (iii) thrombin (1U/ml) induced ∼39% increase of [Ca2+]i in platelets of matures and ∼29% at older normals, and ∼34% increase at the mature diabetics, ∼84% at the older diabetics (vs. no thrombin condition), indicating that under thrombin stimulation simultaneous insults of diabetes and advanced age produced a higher thrombin-evoked mobilization of Ca2+ from intracellular stores; (iv) the components of the diabetic milieu had various effects on platelet free [Ca2+]i: high enhancement (∼73%) in 25.5 mM glucose (vs. 11 mM glucose), a minor increase (∼15%) in 100 mM H2O2, and a decrease (by ∼56% and ∼132%) in 1.7 mM AGE- poly-L-lysine (vs. poly-L-lysine) and 2.26 mM AGE- albumin (vs. albumin), respectively. Thus, a complex of factors contribute to platelet free [Ca2+]i during biological ageing of diabetics: age, hyperglycemia and oxidative stress release Ca2+ from intracellular stores, while AGE products reduced the cytosolic free Ca2+. Thus, platelets [Ca2+]i level is the final result of the combined effects of ageing and of the components of the diabetic milieu. [ABSTRACT FROM AUTHOR]

Among the clinical and metabolic complications of progressive chronic kidney disease (CKD), CKD-mineral bone disorder (CKD-MBD) significantly contributes to morbidity and mortality. While overt and persistent hyperphosphatemia is typical of advanced CKD and requires treatment, other abnormalities of calcium/phosphate metabolism begin to occur since the early stages of the disease. We searched on the PubMed database, without restrictions for language or time range, for randomized clinical trials and meta-analyses investigating phosphate-lowering therapies. The various phosphate binders show different safety profiles and diverse effects on calcium/phosphate metabolism and vascular calcification. The in-depth knowledge of the characteristics of these drugs is crucial to ensure adequate treatment to CKD patients. A proper control of serum phosphate can be achieved using phosphate binders. These medications may induce side effects. Moreover, data on their impact on clinical outcomes are partly controversial or scarce, especially for the new generation drugs. Hyperphosphatemia favors cardiovascular disease and increases the risk for CKD progression. These effects are partially mediated by fibroblast growth factor 23 (FGF23), a phosphaturic hormone that raises to maintain normal serum phosphate. Since there are no data supporting the use of phosphate-lowering agents when phosphataemia is normal, a key role is played by reducing dietary phosphate intake with the aim to control serum phosphate and the compensatory FGF23 and parathyroid hormone (PTH) increase. Plain Language Summary: The progressive reduction in renal function, a condition known as chronic kidney disease (CKD), is characterized by several clinical and metabolic complications. Among them are the alterations of calcium and phosphorous metabolism that are part of the so-called CKD-MBD (chronic kidney disease-mineral bone disorder) and contribute to increase morbidity and mortality, especially due to vascular calcification. Persistent hyperphosphatemia is typical of advanced CKD but other abnormalities occur earlier to maintain normal serum calcium and phosphorus levels. These compensatory mechanisms are also involved in the pathophysiology of CKD-MBD and should be counteracted to improve clinical outcomes of CKD patients. Given the crucial role of hyperphosphatemia, numerous therapeutic strategies have been developed over time to help maintain phosphate serum levels within the normal range and prevent or treat CKD-MBD and its consequences. Phosphate binders act by binding dietary phosphate in the gastrointestinal lumen to prevent its absorption. According to their molecular structure, these drugs can be classified into calcium-based (calcium carbonate, calcium acetate), non-calcium-containing (sevelamer carbonate, sevelamer hydrochloride, lanthanum carbonate), aluminum-containing (aluminum hydroxide), and iron-based (sucroferric oxyhydroxide, ferric citrate) compounds. The various phosphate binders show different safety profiles and diverse effects on calcium/phosphate metabolism and vascular calcification. Despite the ability of hyperphosphatemia to favor CKD-MBD development and cardiovascular risk, there are no data supporting the use of phosphate-lowering agents when serum phosphate is normal also due to the potential adverse effects of long-term therapies. Accordingly, a key role is played by reducing dietary phosphate overload since the first stages of CKD. [ABSTRACT FROM AUTHOR]

Engineered nanomaterials induce hazardous effects at the cellular and molecular levels. We investigated different mechanisms underlying the neurotoxic potential of zinc oxide nanoparticles (ZnONPs) on cerebellar tissue and clarified the ameliorative role of Quercetin supplementation. Forty adult male albino rats were divided into control group (I), ZnONPs-exposed group (II), and ZnONPs and Quercetin group (III). Oxidative stress biomarkers (MDA & TOS), antioxidant biomarkers (SOD, GSH, GR, and TAC), serum interleukins (IL-1β, IL-6, IL-8), and tumor necrosis factor alpha (TNF-α) were measured. Serum micro-RNA (miRNA): miRNA-21-5p, miRNA-122-5p, miRNA-125b-5p, and miRNA-155-3p expression levels were quantified by real-time quantitative polymerase-chain reaction (RT-QPCR). Cerebellar tissue sections were stained with Hematoxylin & Eosin and Silver stains and examined microscopically. Expression levels of Calbindin D28k, GFAP, and BAX proteins in cerebellar tissue were detected by immunohistochemistry. Quercetin supplementation lowered oxidative stress biomarkers levels and ameliorated the antioxidant parameters that were decreased by ZnONPs. No significant differences in GR activity were detected between the study groups. ZnONPs significantly increased serum IL-1β, IL-6, IL-8, and TNF-α which were improved with Quercetin. Serum miRNA-21-5p, miRNA-122-5p, miRNA-125b-5p, and miRNA-155-p expression levels showed significant increase in ZnONPs group, while no significant difference was observed between Quercetin-treated group and control group. ZnONPs markedly impaired cerebellar tissue structure with decreased levels of calbindin D28k, increased BAX and GFAP expression. Quercetin supplementation ameliorated cerebellar tissue apoptosis, gliosis and improved calbindin levels. In conclusion: Quercetin supplementation ameliorated cerebellar neurotoxicity induced by ZnONPs at cellular and molecular basis by different studied mechanisms.Abbreviations: NPs: Nanoparticles, ROS: reactive oxygen species, ZnONPs: Zinc oxide nanoparticles, AgNPs: silver nanoparticles, BBB: blood–brain barrier, ncRNAs: Non-coding RNAs, miRNA: Micro RNA, DMSO: Dimethyl sulfoxide, LPO: lipid peroxidation, MDA: malondialdehyde, TBA: thiobarbituric acid, TOS: total oxidative status, ELISA: enzyme-linked immunosorbent assay, H2O2: hydrogen peroxide, SOD: superoxide dismutase, GR: glutathione reductase, TAC: total antioxidant capacity, IL-1: interleukin-1, TNF: tumor necrosis factor alpha, cDNA: complementary DNA, RT-QPCR: Real-time quantitative polymerase-chain reaction, ABC: Avidin biotin complex technique, DAB: 3′, 3-diaminobenzidine, SPSS: Statistical Package for Social Sciences, ANOVA: One way analysis of variance, Tukey's HSD: Tukey's Honestly Significant Difference, GFAP: glial fiberillar acitic protein, iNOS: Inducible nitric oxide synthase, NO: nitric oxide, HO-1: heme oxygenase-1, Nrf2: nuclear factor erythroid 2-related factor 2, NF-B: nuclear factor-B, SCI: spinal cord injury, CB: Calbindin [ABSTRACT FROM AUTHOR]

The present study was designed to investigate the efficacy of post-conditioning (POC) in the diabetic heart with myopathy (DCM) against ischaemia-reperfusion (I/R) injury in an isolated rat heart model. Present work includes three groups of male Wistar rat viz., (i) normal, (ii) diabetes mellitus (DM) and (iii) DCM and each group was subdivided into normal perfusion, I/R, and POC. Isolated heart from the rats was analysed for tissue injury, contractile function, mitochondrial function, and oxidative stress. Results demonstrated that unlike in DM heart and normal heart, POC procedure failed to recover the DCM heart from I/R induced cardiac dysfunction (measured via cardiac hemodynamics and infarct size. POC was unsuccessful in preserving mitochondrial subsarcolemmal fraction during I/R when compared with DM and normal heart. To conclude, the development of myopathy in diabetic heart abolished the cardioprotective efficacy of POC and the underlying pathology was linked with the mitochondrial dysfunction. Early studies reported contradicting response of diabetic heart towards post-conditioning mediated cardioprotection. Deteriorated mitochondrial function underlines the failure of post-conditioning in DCM. Efficacy of cardioprotection depends on the varying pathology of different diabetes stages. [ABSTRACT FROM AUTHOR]

Pathology-supported genetic testing (PSGT) enables transitioning of risk stratification from the study population to the individual. We provide an overview of the translational research performed in postmenopausal breast cancer patients at increased risk of osteoporosis due to aromatase inhibitor therapy, as the indication for referral. Both tumor histopathology and blood biochemistry levels were assessed to identify actionable disease pathways using whole exome sequencing (WES). The causes and consequences of inadequate vitamin D levels as a modifiable risk factor for bone loss were highlighted in 116 patients with hormone receptor-positive breast cancer. Comparison of lifestyle factors and WES data between cases with vitamin D levels at extreme upper and lower ranges identified obesity as a major discriminating factor, with the lowest levels recorded during winter. Functional polymorphisms in the vitamin D receptor gene contributed independently to therapy-related osteoporosis risk. In a patient with invasive lobular carcinoma, genetic counseling facilitated investigation of the potential modifying effect of a rare CDH1 variant co-occurring with BRCA1 c.66dup (p.Glu23ArgfsTer18). Validation of PSGT as a three-pronged pharmacodiagnostics tool for generation of adaptive reports and data reinterpretation during follow-up represents a new paradigm in personalized medicine, exposing significant limitations to overcome. [ABSTRACT FROM AUTHOR]

Paget's disease of bone (PDB) is a focal bone disorder caused by a marked dysregulation of osteoblasts and osteoclasts in basic multicellular units, leading to abnormal and disorganized deposition of collagen fibers (the so-called 'woven bone'). Therefore, pagetic bones are increased in size, and at increased risk for bone pain, deformities, fractures, osteoarthritis, and, more rarely, neoplastic degeneration. In this review, we revise the available information concerning the pharmacological treatment of PDB. PDB progresses slowly within the affected skeletal sites and, if untreated, often leads to bone overgrowth, with bone pain, deformity, and a likely increased risk of complications. Thus, the primary goal of treatment is the restoration of a normal bone turnover, in order to relieve bone pain or other symptoms and possibly prevent the complications. PDB long remained a poorly treatable disorder until the discovery of antiresorptive agents such as calcitonin first and bisphosphonates (BPs) later. With the recent development of potent intravenous BPs like zoledronate, allowing a better control of disease activity over the long term with a single infusion, has contributed to a marked improvement of the clinical management of this invalidating disorder. [ABSTRACT FROM AUTHOR]

There are so many literatures about vegetarians being less prone to chronic, noninfectious diseases, which are, however, the main cause of the decline in quality of life and mortality in developed countries. However, according to various scientific sources, vegetarian and especially vegan diets often contain less saturated fats, protein, calcium, vitamins D and B12, or long-chain ω-3 PUFAs. One of the most common pathology associated with a predominantly plant diet is osteopenia and osteoporosis. An analysis of 13 studies has shown that vegetarians and vegans are at a higher risk of reducing of bone mineral density, thereby increasing the incidence of fractures. At the same time, plant-based diets are usually richer in many other micronutrients important for bone health: vitamins C and K, carotenoids, potassium, magnesium, manganese, copper, or silicon. Moreover, with the deepening of our knowledge about the role of nutrients in the body and the features of the nutritional status of the population, the quality of vegetarian and vegan diets also increases. They are less and less prone to micronutrient deficiencies. Recent studies show that BMD, as well as the risk of osteoporotic fractures, at least in vegetarians, equaled these indicators in omnivores. [ABSTRACT FROM AUTHOR]

The first reports of quail breeding describe it as a little explored activity and used mainly for ornamentation. However, characteristics such as rapid growth, productivity precocity and low production cost, made this activity spread globally. Although there are other quail species, the Japanese quail has become the most used in industry and in the field of scientific research.Great technological advances have occurred over the years in the nutrition and feeding of these birds. Therefore, this review was prepared aiming to present the evolution of studies on nutrition and food and may contribute to future research. The great evolution of meat and egg production rates observed in quail farming is due to advances in genetics, improvement of management techniques, ambience and nutrition, with the development of studies using different ingredients in feed, thus meeting the production needs. However, constant updates are needed in research, considering advances in science, the population's food habits and needs, in addition to economic, well-being and environmental issues, observing production goals and genetic characteristics for each stage of life, sex of birds and the quality of quail products. [ABSTRACT FROM AUTHOR]

Vitamin D deficiency is a global concern, linked to suboptimal musculoskeletal health and immune function, with status inadequacies owing to variations in UV dependent cutaneous synthesis and limited natural dietary sources. Endogenous biofortification, alongside traditional fortification and supplement usage is urgently needed to address this deficit. Evidence reviewed in the current article clearly demonstrates that feed modification and UV radiation, either independently or used in combination, effectively increases vitamin D content of primary produce or ingredients, albeit in the limited range of food vehicles tested to date (beef/pork/chicken/eggs/fish/bread/mushrooms). Fewer human trials have confirmed that consumption of these biofortified foods can increase circulating 25-hydroxyvitamin D [25(OH)D] concentrations (n = 10), which is of particular importance to avoid vitamin D status declining to nadir during wintertime. Meat is an unexplored yet plausible food vehicle for vitamin D biofortification, owing, at least in part, to its ubiquitous consumption pattern. Consumption of PUFA-enriched meat in human trials demonstrates efficacy (n = 4), lighting the way for exploration of vitamin D-biofortified meats to enhance consumer vitamin D status. Response to vitamin D-biofortified foods varies by food matrix, with vitamin D3-enriched animal-based foods observing the greatest effect in maintaining or elevating 25(OH)D concentrations. Generally, the efficacy of biofortification appears to vary dependent upon vitamer selected for animal feed supplementation (vitamin D2 or D3, or 25(OH)D), baseline participant status and the bioaccessibility from the food matrix. Further research in the form of robust human clinical trials are required to explore the contribution of biofortified foods to vitamin D status. [ABSTRACT FROM AUTHOR]

The etiology of sex differences in the risk of asthma-COPD phenotype and COPD is still not completely understood. Genetic and environmental risk factors are commonly believed to play an important role. This study aims to identify sex-specific genetic markers associated with asthma-COPD phenotype and COPD using the Canadian Longitudinal Study on Aging (CLSA) Baseline Comprehensive and Genomic data. There were a total of 1,415 COPD cases. Out of them, 504 asthma-COPD phenotype cases were identified. 20,524 participants without a diagnosis of asthma and COPD served as controls. We performed genome-wide SNP-by-sex interaction analysis. SNPs with an interaction p-value < 10−5 were included in a sex-stratified multivariable logistic regression for asthma-COPD phenotype and COPD outcomes. 18 and 28 SNPs had a significant interaction term p-value < 10−5 with sex in the regression analyses of asthma-COPD phenotype and COPD outcomes, respectively. Sex-stratified multivariable analysis of asthma-COPD phenotype showed that 7 SNPs in/near SMYD3, FHIT, ZNF608, RIMBP2, ZNF133, BPIFB1, and S100B loci were significant in males. Sex-stratified multivariable analysis of COPD showed that 8 SNPs in/near MAGI1, COX18, OSTC, ELOVL5, C7orf72 FGF14, and NKAIN4 were significant in males, and 4 SNPs in/near genes CAMTA1, SATB2, PDE10A, and LINC00908 were significant in females. An SNP in the ZPBP gene was associated with COPD in both males and females. Identification of sex-specific loci associated with asthma-COPD phenotype and COPD may offer valuable evidence toward a better understanding of the sex-specific differences in the pathophysiology of the diseases. [ABSTRACT FROM AUTHOR]

Paracetamol (also known as acetaminophen or APAP) is an analgesic and antipyretic drug that is widely used all over the world. Boron is an element proven by many studies that it has indispensable effects on human health. In light of the information expressed about boron, we investigated whether there are any effects of boron on paracetamol-induced liver damage. We analyzed the 8-hydroxyguanosine (8-OHG), ALT, AST, glutathione (GSH), malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and nitric oxide (NO) levels in serum or erythrocyte and liver tissue. At the same time, TNF-α, IL-1β, IL-18 levels were examined in liver tissues to determine the effect of boron on inflammation caused by paracetamol in serum and liver tissue. In this study to determine the effect of ER stress-mediated apoptosis, signal transducers that lead the cell to ER stress-mediated apoptosis, IRE1, ATF6 and PERK, caspase 1, 3, 8, 9 and 12, which play a role in the apoptotic process, antiapoptotic factors bcl2, bcl-xL mRNA gene expressions were determined and the effect level of boron on ER stress-mediated apoptosis was determined by immunohistochemical methods. This study demonstrate that boric acid protects against paracetamol-induced liver damage in association with the augmentation of biomarkers of oxidative and nitrosative stress, inflammation and the ER stress / apoptosis axis in rats. [ABSTRACT FROM AUTHOR]

This study examined whether levetiracetam contributes to improvements in the axon-nerve damage in an experimental rat model. Forty-eight Wistar albino adult male rats weighing 250–300 gr were randomized into six groups having or not having sciatic nerve damages and receiving different (none, 300 and 600 mg/kg) levetiracetam doses, and control (non-levetiracetam). Functional gait analysis and tissue sample analysis with the aid of light microscopy and hematoxylin-eosin dye were evaluated between the groups. Additionally, scanning electron microscopy (SEM) was used for the detailed examination of sciatic nerves. S-100 (Schwann cell marker) immunoreactivities in sciatic nerve was detected by immunohistochemistry. Sciatic functional index of the injured rats receiving 300 mg/kg levetiracetam was −65.59 ± 29.48 and −47.13 ± 21.36 in the 2nd and 6th weeks, respectively (p < 0.001). Also, IMA and TOS levels were significantly higher in the control group compared to those receiving levetiracetam (p = 0.001 and p < 0.001, respectively). The most significant nerve regeneration was in the group injured and treated with LEV 600 mg/kg (p < 0.05). There was a significant improvement in the sciatic functional index, histopathological findings, and parameters showing tissue oxidant status in rats with sciatic nerve injury receiving levetiracetam treatment. Further investigations should be performed to evaluate the contribution of levetiracetam as a treatment modality in sciatic nerve injuries. [ABSTRACT FROM AUTHOR]

Simvastatin is a prodrug of the potent 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor. The main purpose of the current study is to assess the accurate function of simvastatin on osteoporosis of extremity bones in aging rats. Fifty 15-month-old SD rats were divided into five groups (four simvastatin groups and one control group). The rats in four simvastatin groups were fed with different doses of simvastatin (5, 10, 20, and 40 mg/kg/d, respectively) for 3 months, whereas the rats in control group were fed the equal physiological saline. Calcium (Ca), phosphorus (P), and the lipid spectrum in serum were measured. Biochemical markers of bone metabolism, osteocalcin (OC), and tartrate-resistant acid phosphatase (Trap-5b), were analyzed using ELISA. The content of adipocytes in bone marrow was analyzed by histological staining. Finally, the bone quality of the femur and tibia were evaluated using dual-energy X-ray absorptiometry (DEXA), peri-quantity CT (pQCT), and the 3-point bending biomechanical test. Simvastatin reduced serum triglycerides (TG), and 10 mg/kg/d of simvastatin significantly reduced the content of adipocytes in bone marrow compared to the control group. However, statistically significant differences between the simvastatin groups and the control group were not found in the CA, P, OC, Trap-5b, or the evaluation indexes of bone quality from DEXA, pQCT, and biomechanical tests. Simvastatin could not prevent osteoporosis of the extremity bones in aging rats. [ABSTRACT FROM AUTHOR]

This article informs that progressive, high-intensity resistance training is needed to maintain or increase bone density in adults. However, before researchers prescribe such programs for bone health, the risks versus benefits must be considered. Despite these limitations, the finding that calcium balance remained unchanged in the exercisers but decreased in the control subjects suggests that exercise may enhance calcium absorption. This finding provides insight into the mechanism of the effects of exercise on bone, and supports the notion that an adequate intake of calcium may be required to reap the bone-stimulating benefits of exercise.

Phytoestrogens, with a wide range of beneficial effects, prevent bone loss caused by oestrogen deficiency. The purpose of this study was to evaluate the effect of Medicago sativa ethanol extract compared to 17β-oestradiol on osteoporosis in ovariectomized mice. The study was carried out on female mice, divided into five groups: control mice (GI), Medicago sativa treated mice (0.75 g/kg BW/day) (GII), ovariectomized mice (GIII) and ovariectomized mice treated either with Medicago sativa (GIV) or with 17β-oestradiol (50 µg/Kg BW/day) (GV). Our results showed that Medicago sativa or 17β-oestradiol treatments significantly attenuated perturbations of mineral levels, histological changes and oxidative stress in the femurs of ovariectomized mice. Medicago sativa prevented bone loss induced by oestrogen deficiency, which could be attributed to its richness in kaempferol, syringic acid, naringenin and myrictin. Its effects were more beneficial or similar compared to 17β-oestradiol. [ABSTRACT FROM AUTHOR]

Objectives: Inadequate maternal dietary pattern has been associated to negative pregnancy and fetal outcomes. With this study, we aimed to evaluate the adequacy of diet in pregnant women that delivered prematurely and its possible correlations with bone status of preterm newborns. Study design: We prospectively enrolled women who delivered prematurely (-than 34 gestational weeks) and their newborns (Neonatal Intensive Care, University Hospital of Padova) from January 2017 to May 2018. Maternal nutritional status and diet supplementations were assessed using a validated questionnaire. The preterm newborns were evaluated with anthropometric measurements and bone status by Quantitative Ultrasound of the second metacarpal bone within 72 h from birth. Results: One hundred and eighty mothers and 202 preterm newborns were evaluated. The mothers assumed more calories, proteins, total lipids and simple sugars compared to the revised National Guidelines. The intake of calcium, phosphorus and Vitamin D was inadequate despite the use of multivitamin supplements. The mothers assumption of vitamin D and zinc positively correlated with bone status and mothers with very low intake of vitamin D during gestation (<7 mg/die) had preterm newborns with a worst bone status at birth compared to those with a better intake (>7 mg/die). Conclusions: Nutrition of pregnant women could be improved and maternal intakes of Vitamin D and zinc positively correlated with preterm newborn's bone status. [ABSTRACT FROM AUTHOR]

Publications of expressions of concern and retractions should be timely, accurate and comprehensive. We as sessed these characteristics for 292 publications by a research group about which we submitted concerns about publication integrity to 77 journals and 29 publishers between March 2013 and February 2020. By October 2020, 115 publications were corrected (3), had expressions of concern (18), or were retracted (94). The median (95% CI) time from submission of concerns to the first journal correction was 22.1 (18.2–26.9) months: this did not diminish by year of submission of concerns, varied between publishers, and was shorter for journals with higher impact factors. Eighty-four publications of original research were retracted. The median (range) proportion of concerns raised with the journal that were mentioned in the ensuing retraction notices was 9.5% (2–49). At least 75% of retraction notices included the suggested content for 7/9, 3/9 and 3/16 items in the Committee for Publication Ethics and Retraction Watch minimum and optimal recommended formats, respectively. Thus, assessment of concerns about publication integrity was delayed and incomplete. Adherence to recommended content of retraction notices was moderate at best. Strategies are needed to improve the efficiency, accuracy and transparency of processes for resolving concerns about publication integrity. [ABSTRACT FROM AUTHOR]

Macrophages serve an active role in the pathophysiology of chronic obstructive pulmonary disease (COPD). Erythromycin (EM) has been verified as an effective treatment for COPD. However, there are few studies on the effect of EM on the ultrastructure of macrophages exposed to cigarette smoke extract (CSE). In the present study, human macrophages were randomly divided into three groups: The control, CSE and the CSE+EM group, using electron microscopy, the effect of EM was evaluated by comparing the ultrastructural changes between these groups. The macrophages were additionally divided into a further four groups: The control, CSE, CSE+EM 24 h and CSE+EM 48 h groups. The generation of reactive oxygen species (ROS) in each group was evaluated by detecting fluorescence intensity. It was observed that the cellular ultrastructure of the CSE group exhibited abnormal changes, though this effect was reversed back to the level of the control in the CSE+EM group. Compared with the control group, the ROS expression level was significantly increased in the CSE group (P <.05); however, compared with the CSE group, the ROS concentration was decreased in the CSE+EM 24 h (P <.05) and CSE+EM 48 h groups (P <.05), though this was more apparent in the EM 48 h group. It was concluded that EM protects human macrophages against CSE. Moreover, it was hypothesized that EM may reduce the symptoms of patients with COPD by protecting the macrophage ultrastructure from the effects of CSE, resulting in the decreased generation of ROS, inhibiting autophagy and reducing endoplasmic reticulum stress. [ABSTRACT FROM AUTHOR]

Among the mechanisms underlying Parkinson's disease, many pathogenic mechanisms are suggested to be effective such as oxidative stress, mitochondrial dysfunction, disruption of the ubiquitin-proteasome system, and neuroinflammation. Calcium is very important for neuronal and glial cells, neurodegenerative disease mechanisms are closely related to disturbed calcium homeostasis. Recent studies strongly support the role of inflammation in nigrostriatal degeneration in PD. In recent years, Rifampicin, a macrocyclic antibiotic has been shown to have a protective effect on neurons. This study aims to evaluate the effects of rifampicin in the experimental PD model induced by rotenone in zebrafish focusing on the relationship between calcium-dependent mitochondrial dysfunction and inflammation. Adult zebrafish were exposed to rotenone and rifampicin for 3 weeks. Locomotor activity was determined as the total distance that the zebrafish traveled for 5 min. Neuroinflammation and PD-related gene expressions were determined by RT-PCR. Mitochondrial calcium levels were determined using inductively coupled plasma-optical emission spectrometry (ICP-OES). Gamma synuclein, Park 7, Sigma-1 receptor expressions were determined by Western Blot. Our results show that rifampicin may be effective in reducing neuroinflammation, which may be an effective strategy to reduce mitochondrial dysfunction due to impaired calcium homeostasis in PD. [ABSTRACT FROM AUTHOR]

Osteoporosis is an important public health problem worldwide. Although many factors relating to bone structure have been described so far, the current knowledge on the occupational factors that may affect bone tissue metabolism is strongly limited. Literature data suggest that night shift work, via circadian rhythm disruption, may be considered a potential risk factor. To this date, only five epidemiological studies addressing this problem have been conducted worldwide. The outcomes of three studies confirmed such relationship, namely, a higher fracture risk was found among nurses with a long lifetime duration of night shift work in one study; and a lower bone mineral density was associated with occupational activity during night-time in two studies. In adults, the bone undergoes constant remodelling through bone resorption followed by bone formation. The various molecules released into the circulatory system during these processes are called bone turnover markers. We investigated the possible associations between night shift work and selected bone turnover markers: N-terminal propeptide of type I procollagen (P1NP), C-terminal cross-linked telopeptide of type I collagen (CTX), osteocalcin, osteopontin, fibroblast growth factor 23 (FGF-23) and osteoprotegerin, measured in plasma of 189 female blue-collar workers. A significantly higher bone turnover rate was noted among the women working night shifts than among those working only during the day. This may potentially lead to a future development of osteoporosis in this population even if the macroscopic changes in the bone structure are not detectable. Night shift work is a prevailing occupational characteristics nowadays. It has been estimated that about 15–20% of the working population in Europe and the USA perform work under this system. Thus, the problem of osteoporosis can affect a large part of the working-age population. [ABSTRACT FROM AUTHOR]

Wiskott–Aldrich syndrome (WAS) serves as the prototype of how variants in a gene, which encodes a protein central to actin cytoskeletal homeostasis can manifest clinically in a variety of ways including infection, atopy, autoimmunity, inflammation, bleeding, neutropenia, non-malignant lymphoproliferation, and malignancy. Despite the discovery of the WAS gene almost 30 years ago, our understanding of the pathophysiological mechanisms underlying WAS continues to unfold. This review will provide an overview of the approach to the diagnosis of WAS as well as the management of its associated complications. Advances in the use of allogeneic hematopoietic stem cell transplantation (HSCT) and gene therapy as well as the associated challenges unique to WAS will be discussed. Basic research, combined with clinical research focusing on longitudinal analysis of WAS patients, will help clarify determinants that influence WAS pathogenesis as well as clinical complications and outcomes. Advances in curative approaches including the use of alternative donor HSCT for WAS continue to evolve. Gene therapy employing safer and more effective protocols ensuring full correction of WAS will provide life-saving benefit to WAS patients who are unable to undergo HSCT. [ABSTRACT FROM AUTHOR]

In patients with kidney dysfunction hyperphosphatemia is more evident as renal failure progresses. It is related to increased FGF-23 levels, secondary hyperparathyroidism, and accelerated progressive vascular calcification. In CKD patients advanced coronary artery calcification is strongly associated with future cardiovascular events, cardiovascular death, and all-cause mortality. Apart from the above, phosphate per se is suspected as a causal risk factor for CKD progression. Keeping serum phosphorus within the target values are linked to improvement in life expectancy. A low phosphate diet, an efficient dialysis removal of phosphate load, and the administration of phosphate binders are the main recommended steps to control hyperphosphatemia. Calcium-based phosphate binders can lead to a positive calcium balance, hypercalcaemia, parathyroid gland suppression, adynamic bone disease, and coronary artery and aortic calcification. On the other hand Sevelamer hydrochloride and Lanthanum carbonate has been shown to be effective, safe and useful therapeutic tools for hyperphosphatemia. When prescribe pharmacological agents, one must take into account the large increase in health-care expenditure and the choice of phosphate binder should be individualized. [ABSTRACT FROM AUTHOR]

Many anticancer agents exert cytotoxicity and trigger apoptosis through the induction of mitochondrial dysfunction. Mitophagy, as a key mitochondrial quality control mechanism, can remove damaged mitochondria in an effective and timely manner, which may result in drug resistance. Although the implication of mitophagy in neurodegenerative diseases has been extensively studied, the role and mechanism of mitophagy in tumorigenesis and cancer therapy are largely unknown. In a recent study, we found that the inhibition of PINK1-PRKN-mediated mitophagy can significantly enhance the anticancer efficacy of magnolol, a natural product with potential anticancer properties. On the one hand, magnolol can induce severe mitochondrial dysfunction, including mitochondrial depolarization, excessive mitochondrial fragmentation and the generation of mitochondrial ROS, leading to apoptosis. On the other hand, magnolol induces PINK1-PRKN-dependent mitophagy via activation of two rounds of feedforward amplification loops. The blockage of mitophagy through genetic or pharmacological approaches promotes rather than attenuates magnolol-induced cell death. Furthermore, inhibition of mitophagy by using distinct inhibitors targeting different mitophagic stages effectively enhances magnolol's anticancer efficacy in vivo. Taken together, our findings strongly indicate that manipulation of mitophagy in cancer treatment will be a promising therapeutic strategy for overcoming cancer drug resistance and improving the therapeutic efficacy of anticancer agents. [ABSTRACT FROM AUTHOR]

Optimum body composition in terms of higher muscle and bone mass is crucial for balancing metabolic activities for sustainability of healthy human life. Individuals with lesser muscle mass respond poorly to stressed states such as traumatic injury, sepsis and advanced cancers. Most common diseases like obesity, heart disease, cancer and diabetes can be prevented by muscle mass modification. The nutrients like protein, lysine, calcium and vitamin D play a critical role in the maintenance of muscle mass and bone health. Poor dietary protein quality owing to high amounts of cereals and little animal foods have a marked negative impact on health in resource-limited settings. Lysine intake in developing countries is low mainly due to lesser food intake, consumption of cereals as staple diet and processing loss of lysine. Furthermore, lysine intakes have been shown to be marginal in low socio-economic groups which are of even greater concern. Cereal-based diets and cereal-based food subsidy programs offer low quality proteins and pose a risk of quality protein deficiency. Diets lacking in vitamin D contribute to vitamin D deficiency which is prevalent in epidemic proportions in large part of the world. Cereal-based vegetarian diets are responsible for lesser bioaccessibility of calcium as well. For obtaining optimal health, optimal muscle mass should be maintained at a younger age, which can be achieved by improving nutritional quality of diets. Dietary and medicinal supplementation of lysine, calcium and vitamin D may improve the body composition of young adult women in the form of proportionally more muscle mass, bone mass and lesser fat mass, which in turn, may prove helpful in improving general well-being, physical fitness as well as preventing metabolic diseases in developing countries. [ABSTRACT FROM AUTHOR]

Having vitamin D levels within normal limits is important for bone and muscle health and its deficiency may increase the risk of injury. The aim of this cross-sectional study was to investigate whether vitamin D levels are different in indoor and outdoor athletes and its levels increase the risk of injury. Serum vitamin D levels were measured in Caucasian adolescent athletes, who admitted to the sports medicine polyclinic due to a routine health check or injury. The study was carried out at 38°26′ north latitude in İzmir between June and September 2019. After the physical examination of the injured athletes, the diagnoses were made accompanied by the findings obtained by imaging methods in cases of necessity. A total of 256 athletes, including swimmers (n = 87), basketball players (n = 104), and football (n = 65) players aged 13.2 (± 2.2) years, were investigated. The average serum vitamin D (25(OH)D) level in athletes was 29.2 (±10.0) ng/mL (6.0–66.0 ng/mL). Forty-six of all athletes (18%) had vitamin D deficiency, with a mean value of 15.7 (±4.0) ng/mL, and 93 of them (36.3%) had vitamin D deficiency with a mean value of 25.2 (±2.4) ng/mL. While vitamin D levels were significantly higher in football players (32 ng/mL) than in other athletes (p < 0.05), it was similar in basketball players (27 ng/mL) and swimmers (26 ng/mL) (p > 0.05). Vitamin D levels (26 ng/mL) of the injured athletes were significantly lower than those of the non-injured athletes (30 ng/mL) (p = 0.001). Bone injuries were significantly related to Vitamin D levels (p < 0.001) but not with muscle injuries (p > 0.05). Frequency of vitamin D deficiency and insufficiency is higher in indoor athletes andis especially associated with risk of bone injuries. In order to examine the effect of vitamin D level on bone mineral density, comprehensive prospective studies are required. [ABSTRACT FROM AUTHOR]