Serum 25-hydroxyvitamin D levels and the risk of idiopathic central precocious puberty in girls.

INTRODUCTION: Prior studies have found inconsistent results regarding the relationship between vitamin D status and Idiopathic Central Precocious Puberty (ICPP). OBJECTIVE: To assess the role of serum 25-hydroxyvitamin D (25 [OH]D) levels in ICPP development. METHOD: The authors retrospectively collected data from 221 girls with ICPP and 144 healthy girls between January 2017 and December 2019. The participants' serum 25(OH)D levels were measured using an automatic chemiluminescence method, and the association between serum 25(OH)D levels and the risk of ICPP was assessed using multivariate logistic regression analysis. Odds Ratios (OR) with 95% Confidence Intervals (95% CI) were calculated as effect estimates. RESULTS: Serum 25(OH)D levels in the ICPP group were significantly lower than those in healthy controls (p < 0.001). Multivariate analysis indicated that girls with insufficient vitamin D levels (OR = 0.201; 95% CI 0.094-0.428; p < 0.001) and sufficient vitamin D levels (OR = 0.141; 95% CI 0.053-0.375; p < 0.001) both had a lower risk of ICPP than girls with vitamin D deficiency. Moreover, the authors found that the height (p = 0.014), weight (p = 0.014), breast stage (p = 0.010), mother's height (p < 0.001), and luteinizing hormone/follicle-stimulating hormone ratio (p = 0.010) in girls with ICPP could be associated with levels of vitamin D. CONCLUSION: This study found that a low serum 25(OH)D level is an independent risk factor for ICPP, and several characteristics of girls with ICPP could be affected by their vitamin D status.

Editing of rice (Oryza sativa L.) OsMKK3 gene using CRISPR/Cas9 decreases grain length by modulating the expression of photosystem components.

Grain size is one of the most important agronomic traits for grain yield determination in rice. To better understand the proteins that are regulated by the grain size regulatory gene OsMKK3, this gene was knocked out using the CRISPR/Cas9 system, and tandem mass tag (TMT) labeling combined with liquid chromatograph-tandem mass spectrometry analysis was performed to study the regulation of proteins in the panicle. Quantitative proteomic screening revealed a total of 106 differentially expressed proteins (DEPs) via comparison of the OsMKK3 mutant line to the wild-type YexiangB, including 15 and 91 up-regulated and down-regulated DEPs, respectively. Pathway analysis revealed that DEPs were enriched in metabolic pathways, biosynthesis of secondary metabolites, phenylpropanoid biosynthesis, and photosynthesis. Strong interactions were detected among seven down-regulated proteins related to photosystem components in the protein-protein interaction network, and photosynthetic rate was decreased in mutant plants. The results of the liquid chromatography-parallel reaction monitoring/mass spectromery analysis and western blot analysis were consistent with the results of the proteomic analysis, and the results of the quantitative reverse transcription polymerase chain reaction analysis revealed that the expression levels of most candidate genes were consistent with protein levels. Overall, OsMKK3 controls grain size by regulating the protein content in cells. Our findings provide new candidate genes that will aid the study of grain size regulatory mechanisms associated with the mitogen-activated protein kinase (MAPK) signaling pathway.

Serum 25-hydroxyvitamin D levels and the risk of idiopathic central precocious puberty in girls

Abstract Introduction Prior studies have found inconsistent results regarding the relationship between vitamin D status and Idiopathic Central Precocious Puberty (ICPP). Objective To assess the role of serum 25-hydroxyvitamin D (25 [OH]D) levels in ICPP development. Method The authors retrospectively collected data from 221 girls with ICPP and 144 healthy girls between January 2017 and December 2019. The participants' serum 25(OH)D levels were measured using an automatic chemiluminescence method, and the association between serum 25(OH)D levels and the risk of ICPP was assessed using multivariate logistic regression analysis. Odds Ratios (OR) with 95% Confidence Intervals (95% CI) were calculated as effect estimates. Results Serum 25(OH)D levels in the ICPP group were significantly lower than those in healthy controls (p < 0.001). Multivariate analysis indicated that girls with insufficient vitamin D levels (OR = 0.201; 95% CI 0.094-0.428; p < 0.001) and sufficient vitamin D levels (OR = 0.141; 95% CI 0.053-0.375; p < 0.001) both had a lower risk of ICPP than girls with vitamin D deficiency. Moreover, the authors found that the height (p = 0.014), weight (p = 0.014), breast stage (p = 0.010), mother's height (p < 0.001), and luteinizing hormone/follicle-stimulating hormone ratio (p = 0.010) in girls with ICPP could be associated with levels of vitamin D. Conclusion This study found that a low serum 25(OH)D level is an independent risk factor for ICPP, and several characteristics of girls with ICPP could be affected by their vitamin D status.

Anti-ageing and Anti-lung Carcinoma Effects of Vulpinic Acid and Usnic Acid Compounds and Biological Investigations with Molecular Modeling Study.

Disorganization and breakdown of extracellular matrix proteins like fibronectin, collagen, and elastin are key characteristics of skin aging due to the increased activation of important proteolytic enzymes like elastases and collagenase enzymes. Also, inhibition of their enzymatic activities by natural molecules might be a promising factor to prevent extrinsic skin aging. All chemicals were obtained from Sigma-Aldrich unless otherwise stated. The assay employed was based on spectrophotometric methods reported in the literature. The collagenase and elastase inhibition assays of some phenolic compounds were performed according to the previous studies. These compounds showed excellent to good inhibitory activities of vulpinic acid against studied these enzymes with IC50 values of 195.36 µM for collagenase and 25.24 µM for elastase. The molecular docking calculations were conducted to investigate the chemical and biological activity of vulpinic acid and usnic acid against collagenase and elastase. The results indicated that these two compounds can interact with the essential residues of the enzymes and affect their activities. The calculations of binding free energies were also performed to obtain more details about the characteristics and free energies of the ligand-enzyme complexes. Additionally, both compounds exhibited the most potent inhibition in the three lung cancer cells, with an IC50 value of 21-68 µM, indicating that vulpinic acid is more potent than Doxorubicin, which exhibited an IC50 value of 21-29 µM.

KISS1/KISS1R mediates Sertoli cell apoptosis via the PI3K/AKT signalling pathway in a high­glucose environment.

In male patients with diabetes, reduced sperm motility and fertility are observed. KiSS­1 metastasis suppressor (KISS1)/KISS1 receptor (KISS1R) serves an important role in regulating adolescent sexual maturity and reproductive system development in mammals; however, the mechanism underlying KISS1/KISS1R in reproductive dysfunction in male patients with diabetes is not completely understood. The aim of the present study was to examine the role of KISS1/KISS1R in Sertoli cells. High glucose (HG)­induced mouse Sertoli cells were used to model diabetes in vitro. KISS1/KISS1R overexpression and knockdown were established in mouse Sertoli cells. Reverse transcription­quantitative PCR and western blotting were performed to measure the expression levels of KISS1/KISS1R and apoptosis­related proteins. Cell viability and apoptosis was assessed by performing Cell Counting Kit­8, TUNEL staining and flow cytometry assays, respectively. Western blotting was performed to assess the expression levels of PI3K/AKT signalling­related proteins. KISS1/KISS1R expression levels were downregulated in HG­induced mouse Sertoli cells compared with control cells. KISS1/KISS1R overexpression significantly suppressed HG­induced apoptosis and decrease of viability in mouse Sertoli cells. Moreover, the western blotting results indicated that KISS1/KISS1R activated PI3K/AKT signalling. Treatment with PI3K/AKT pathway inhibitor significantly reversed KISS1/KISS1R­mediated protective effects. Collectively, the results of the present study suggested that KISS1/KISS1R mediated Sertoli cell apoptosis via the PI3K/AKT signalling pathway under HG conditions, which provided reliable targets for the treatment of reproductive dysfunction in male patients with diabetes.

Curcumin Inhibited Podocyte Cell Apoptosis and Accelerated Cell Autophagy in Diabetic Nephropathy via Regulating Beclin1/UVRAG/Bcl2.

INTRODUCTION: Curcumin has various biological properties including being anti-inflammatory and antidiabetic. Podocyte apoptosis and autophagy dysfunction have been found to be responsible for the development of diabetic nephropathy (DN). Thus, the aim of the study was to investigate the effects of curcumin on the podocyte apoptosis and autophagy in DN and clarify its potential mechanisms. METHODS: The mice with DN induced by injection of streptozotocin were treated with curcumin by gavage at a dose of 200 mg/kg/day for 8 weeks. The serum lipid levels were detected by total cholesterol (TC) and triglyceride (TG) kits at different time points. Renal damage was assessed by detecting urine albumin, serum creatinine (Scr), HE staining and PAS staining. The renal impairment was detected by immunohistochemical staining and TUNEL staining. Western blot assay tested the expression of autophagy-related and apoptotic-related proteins in vivo and vitro. The viabilities and apoptosis of MPC5 cells exposed to high glucose (HG) or curcumin were respectively detected by CCK-8 assay and flow cytometry. RESULTS: The results showed that curcumin significantly decreased the progress of DN possibly via increasing autophagy and inhibiting apoptosis of renal cell in DN mice. Besides, podocyte marker proteins (podocalyxin and nephrin) were markedly increased in DN mice by curcumin treatment. The autophagy-related proteins LC3, p62, Beclin1, UVRAG and ATG5 were significantly affected in DN mice by curcumin, along with reducing expression of pro-apoptotic protein Bax and caspase-3 and increasing anti-apoptotic protein Bcl-2. In vitro, curcumin increased the viabilities and inhibited apoptosis of MPC5 cells exposed to high glucose (HG). In addition, the podocyte autophagy was enhanced partly via regulating beclin1/UVRAG. DISCUSSION: Together, the results showed that curcumin inhibited podocyte apoptosis and accelerated cell autophagy via regulating Beclin1/UVRAG/Bcl2. Thus, the study showed that curcumin exerted significantly protective effects in DN.

Effect of recombinant human growth hormone therapy on blood lipid and carotid intima-media thickness in children with growth hormone deficiency.

BackgroundReports on the association between growth hormone deficiency (GHD) and cardiovascular risk factors in children are limited. We aim to investigate the effect of different doses of recombinant human growth hormone (rhGH) therapy on blood lipid and carotid intima-media thickness (cIMT) in Chinese GHD children.MethodsNinety children, including sixty isolated GHD children and thirty healthy children, were enrolled. GHD children were randomly divided into two groups (A and B) according to the rhGH dose given: group A received 0.23 mg/kg/week and group B received 0.35 mg/kg/week for 12 months. The TC, TG, LDL-C, HDL-C, and cIMT at baseline and after treatment were measured.ResultsThe height, weight, and height velocity improved significantly over 12 months of rhGH therapy in all GHD children. At baseline, GHD children in both the treatment groups showed significantly higher total cholesterol (TC), triglyceride (TG), low-density lipoprotein-cholesterol (LDL-C), cIMT, and lower high-density lipoprotein-cholesterol (HDL-C) than healthy children (all P≤0.033). After the 12-month rhGH therapy, a significant decrease in the TC, TG, LDL-C, and cIMT, as well as a significant increase in the HDL-C (P≤0.046), was observed in the GHD children, with change in the group B being even more marked.ConclusionsThe RhGH replacement therapy in GHD children can improve both the blood lipid profile and carotid intima-media thickness, with higher-dose rhGH therapy showing superior effects.

Effects of berberine on the pharmacokinetics of losartan and its metabolite EXP3174 in rats and its mechanism.

CONTEXT: Losartan and berberine (BBR) are often simultaneously used for the treatment of senile diabetic nephropathy in clinics. However, the potential herb-drug interaction between losartan and BBR is unknown. OBJECTIVE: This study investigates the influence of BBR on the pharmacokinetics of losartan and EXP3174, and investigates the effects of BBR on the metabolic stability of losartan. MATERIALS AND METHODS: The pharmacokinetic profiles losartan and EXP3174 of orally administered losartan (10 mg/kg) with and without pretreatment with BBR (20 mg/kg) within 24 h were determined in Sprague-Dawley rats. The inhibitory effects of BBR on the metabolic stability of losartan were investigated using rat liver microsomes. RESULTS: The Cmax (1.26 ± 0.37 versus 1.96 ± 0.45 mg/L) and the AUC(0-t) (8.25 ± 0.89 versus 12.70 ± 1.42 mg h/L) of losartan were significantly (p < 0.05) increased by BBR compared to the control, while the Cmax (0.97 ± 0.15 versus 0.77 ± 0.06 mg/L) of EXP3174 was significantly decreased compared to the control (p < 0.05). The Tmax of losartan was prolonged from 0.41 ± 0.12 to 0.52 ± 0.18 h, but the difference was not significant. However, the Tmax of EXP3174 was decreased significantly (p < 0.05) from 8.14 ± 0.36 to 3.33 ± 0.28 h. The metabolic stability of losartan was increased from 37.4 to 59.6 min. DISCUSSION AND CONCLUSION: We infer that BBR might increase the plasma concentration of losartan and decrease the concentration of EXP3174 through inhibiting the activity of CYP3A4 or CYP2C9.

Predictive macrosomia birthweight thresholds for adverse maternal and neonatal outcomes.

OBJECTIVE: We examined the predictive macrosomia birthweight thresholds for adverse maternal and neonatal outcomes. STUDY DESIGN: This was a multicenter, retrospective cohort study conducted in China. We selected 178 709 singletons weighing ≥2500 g with gestational age 37-44 weeks. We categorized macrosomia with two gradations (4000-4499 g and ≥4500 g) and compared them with a normosomic reference group of infants with birthweight 2500-3999 g. RESULTS: The risks of obstetric and neonatal complications increased when infants had a birthweight of ≥4000 g. The rates of infant mortality, Apgar score ≤3 at 5 min, respiratory and neurological disorders rose significantly among neonates weighing ≥4500 g. CONCLUSION: A definition of macrosomia as birthweight ≥4000 g could be beneficial as an indicator of obstetric and newborn complications, and birthweight ≥4500 g might be predictive of severe infant morbidity and mortality risk.

Evaluation of a rapid method for the simultaneous quantification of ribavirin, sofosbuvir and its metabolite in rat plasma by UPLC-MS/MS.

A rapid and sensitive ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method for the determination of ribavirin, sofosbuvir and its metabolite GS-331007 in rat plasma was established. The analytes and the internal standard (midazolam) were separated on an Acquity UPLC BEH C18 chromatography column (2.1mm×50mm, 1.7µm) using gradient elution with a mobile phase of acetonitrile and 0.1% formic acid in water at a flow rate of 0.4mL/min. The detection was performed on a triple quadrupole tandem mass spectrometer by multiple reaction monitoring (MRM) mode to monitor the precursor-to-product ion transitions of m/z 245.1→113.1 for ribavirin, m/z 530.3→243.1 for sofosbuvir, m/z 261.5→113.1 for GS-331007 and m/z 326.2→291.1 for midazolam (IS) using a positive electrospray ionization interface. The method was validated over a concentration range of 5-1000ng/mL for ribavirin, 10-2000ng/mL for sofosbuvir and 10-2000ng/mL for GS-331007. Total time for each chromatograph was 3.0min. The intra- and inter-day precision and accuracy of the quality control samples at low, medium, and high concentration levels exhibited relative standard deviations (RSD) <10.0% and the accuracy values ranged from -10.6% to 11.6%. The method was successfully applied to a pharmacokinetic study of ribavirin, sofosbuvir and GS-331007 in rats.

Association between alendronate and atypical femur fractures: a meta-analysis.

Alendronate (ALN) is a commonly used drug for the treatment of osteoporosis. Atypical femur fractures (AFFs) have been associated with long-term use of ALN and have recently become the subject of considerable attention as ALN use increases. This meta-analysis aimed to determine the relationship between ALN and AFF. The Embase, PubMed, and Cochrane library databases were searched for relevant studies published before November 6, 2014. Studies clearly reporting the relationship between ALN and AFF were selected for our analysis. From these results, the relationship between ALN and AFF was analyzed. Weighted mean differences were calculated using a random-effects model. Five studies were included in this meta-analysis. The results revealed that the use of ALN will not increase the risk of AFF in short term (P>0.05), but there will be a risk of AFF (P<0.05) with long-term (>5 years) use of ALN. These findings indicate that long-term use of ALN is a risk factor for AFF and that more attention should be paid to the clinical applications of ALN.