Maternal CBZ exposure impairs testicular development,spermatogenesis and sperm parameters in male offspring at puberty

Carbamazepine (CBZ), an anticonvulsant drug, is used by pregnant women and crosses the placental barrier, reaching the embryo/foetus. CBZ inhibits testicular steroidogenesis and may lead to alterations in testicular development, spermatogenesis and male fertility. The purpose of this study was to evaluate the CBZ effects on testicular parameters in the neonatal and pubertal phases, as well as the spermatic parameters of pubertal rats, originated from dams treated during different periods of the pregnancy. Pregnant rats were treated with CBZ (20 mg/kg/day; intraperitoneal route), from 12–20 gestation day (GD) (CBZ12 group) and 15–20 GD (CBZ15 group). The testicular morphometric and stereological analysis of rats aged 4 and 63 days was performed. The oestradiol and testosterone plasmatic levels, as well as spermatic parameters, were achieved at 63 days. CBZ12 group showed a reduction in testicular weight and volume at 4 days post-partum (dpp); however, there was an increase in the seminiferous cords’ length of the CBZ12 and CBZ15 groups. At 63 days, the CBZ12 group showed increases of the daily sperm production and damage in the seminiferous epithelium. The results suggest that CBZ interferes with the testis development and the establishment of the spermatogenic process, which can be detected in the puberty phase.     

Cyperus esculentus L. (tigernut) mitigates high salt diet-associated testicular toxicity in Wistar rats by targeting testicular steroidogenesis,oxidative stress and inflammation

High salt diet (HSD) impairs testicular function via oxidative stress. Cyperus esculentus contains antioxidants and improves testicular function. We investigated the protective effect of hydro-ethanolic extract of Cyperus esculentus on testicular function in HSD-fed Wistar rats. Twenty-five male Wistar rats (125–135 g) 8–9 weeks old were divided into five groups (n = 5): control, HSD-fed (8 % NaCl in feed), extract-treated (500 mg kg⁻¹ day⁻¹), HSD-fed +500 mg kg⁻¹ day⁻¹ of extract and HSD-fed +1,000 mg kg⁻¹ day⁻¹ of extract groups. Treatment lasted for 6 weeks. HSD decreased (p < .05) sperm parameters and serum reproductive hormones levels, while Cyperus esculentus extract improved (p < .05) sperm parameters, and serum testosterone and follicle-stimulating hormone levels in HSD-fed rats. The extract upregulated intra-testicular testosterone level and activities of 3β-hydroxysteroid dehydrogenase (3β-HSD) and 17β-HSD, downregulated malondialdehyde and nitric oxide levels, and exhibited a dose-dependent decrease in pro-inflammatory cytokines, upregulation of activities of enzymatic antioxidants and increase in total antioxidant capacity in testes of HSD-fed rats. The extract at both doses improved Johnsen's score, Leydig and Sertoli cell counts and seminiferous tubular diameter in HSD-fed rats. Cyperus esculentus exhibited a dose-dependent mitigation of HSD-associated testicular dysfunction by targeting testicular steroidogenesis, oxidative stress and inflammation.     

Thyrotropin Level and Thyroid Volume for Prediction of Hypothyroidism Following Hemithyroidectomy in an Asian Patient Cohort

Background  As more patients undergo diagnostic thyroid surgery, the development of posthemithyroidectomy hypothyroidism is becoming a major concern. We hypothesized that the preoperative thyrotropin (thyroid-stimulating hormone, TSH) level and ultrasonographically measured thyroid volume, both commonly available in thyroid nodule patients, may predict the development of posthemithyroidectomy hypothyroidism. Method  Among the 132 patients who underwent hemithyroidectomy from January 2004 to January 2006, a total of 101 patients who were followed for more than a year were included in the analysis. Results  Biochemical hypothyroidism developed in 37 patients (36.6%). Patients who developed postoperative hypothyroidism showed higher TSH levels (P < 0.001) and smaller remnant thyroid volumes (P = 0.014). Logistic regression analysis showed that the TSH level and remnant thyroid volume were independent predictors of posthemithyroidectomy hypothyroidism (P < 0.001 and P = 0.04, respectively). A risk scoring system using these two factors was created based on the results of logistic regression analyses. The incidences of hypothyroidism were 5.3%, 12.1%, 51.7%, and 85.0% according to the risk scores of 0, 1, 2, and 3, respectively. Conclusions  Patients with a high preoperative TSH level and small thyroid volume are at high risk of developing hypothyroidism following hemithyroidectomy. Potential risk of postoperative hypothyroidism should be discussed with these patients when thyroid surgery is being considered for a diagnostic purpose.     

Associations of nadir haemoglobin level and red blood cell transfusion with mortality and length of stay in surgical specialties: a retrospective cohort study

Few studies have investigated if, and how, red cell transfusion and anaemia interact. We analysed 60,955 admissions to three metropolitan hospitals in Western Australia between 2008 and 2017 to determine whether the relationship between red cell transfusion and outcomes in surgical patients differed by lowest (nadir) level of haemoglobin. At levels above 100 g.l⁻¹, in-hospital, 30-day and 1-year mortality were higher with transfusion, the adjusted odds ratios (ORs) (95%CI) being 8.80 (4.43–17.45) p < 0.001 and 3.68 (1.93–7.02) p < 0.001 and the adjusted hazard ratio (95%CI) being 1.83 (1.28–2.61) p = 0.001, respectively. Likewise, between 90 g.l⁻¹ and 99 g.l⁻¹, in-hospital, 30-day and 1-year mortality were higher with transfusion, the adjusted odds ratio (95%CI) being 3.76 (2.23–6.34) p < 0.001 and 1.96 (1.23–3.12) p < 0.001 and the adjusted hazard ratio (95%CI) being 1.34 (1.05–1.70) p = 0.017, respectively. Length of stay was longer with transfusion at nadir haemoglobin levels above 100 g.l⁻¹ and in the following ranges: 90–99 g.l⁻¹, 80–89 g.l⁻¹, 70–79 g.l⁻¹ and 60–69 g.l⁻¹, the adjusted rate ratio (95%CI) being 1.38 (1.25–1.53) p < 0.001, 1.18 (1.10–1.27) p < 0.001, 1.17 (1.13–1.22) p < 0.001, 1.07 (1.02–1.12) p = 0.003 and 1.24 (1.13–1.36) p < 0.001, respectively. Mortality was higher with red cell transfusion at haemoglobin levels greater than 90 g.l⁻¹, whereas at all levels below 90 g.l⁻¹ mortality was not significantly higher or lower. Length of stay was longer with transfusion at nadir haemoglobin levels of 60 g.l⁻¹ or above. Our results suggest that nadir haemoglobin modified the relationship between red cell transfusion and outcomes and adds to the evidence recommending caution before transfusing red cells.     

Genome-wide association study for time to failure of kidney transplants from African American deceased donors

Two renal-risk variants in the apolipoprotein L1 gene (APOL1) in African American (AA) deceased donors (DD) are associated with shorter renal allograft survival after transplantation. To identify additional genes contributing to allograft survival, a genome-wide association study was performed in 532 AA DDs. Phenotypic data were obtained from the Scientific Registry of Transplant Recipients. Association and single-nucleotide polymorphism (SNP)-by-APOL1 interaction tests were conducted using death-censored renal allograft survival accounting for relevant covariates. Replication and inverse-variance-weighted meta-analysis were performed using data from 250 AA DD in the Genomics of Transplantation study. Accounting for APOL1, multiple SNPs near the Nudix Hydrolase 7 gene (NUDT7) showed strong independent effects (P = 1.6 × 10⁻⁸-2.2 × 10⁻⁸). Several SNPs in the Translocation protein SEC63 homolog (SEC63; P = 2 × 10⁻⁹-3.7 × 10⁻⁸) and plasmacytoma variant translocation 1 (PVT1) genes (P = 4.0 × 10⁻⁸-7 × 10⁻⁸) modified the effect of APOL1 on allograft survival. SEC63 is expressed in human renal tubule cells and glomeruli, and PVT1 is associated with diabetic kidney disease. Overall, associations were detected for 41 SNPs (P = 2 × 10⁻⁹-5 × 10⁻⁸) contributing independently or interacting with APOL1 to impact renal allograft survival after transplantation from AA DD. Given the small sample size of the discovery and replication sets, independent validations and functional genomic efforts are needed to validate these results.     

Thyroid hormones: their role in testicular steroidogenesis

Thyroid hormones are important for growth and development of many tissues. Altered thyroid hormone status causes testicular abnormalities. For instance, juvenile hypothyroidism/neonatal transient hypothyroidism induces macroorchidism, increases testicular cell number (Sertoli, Leydig, and germ cells) and daily sperm production. Triiodothyronine (T3) receptors have been identified in sperm, developing germ cells, Sertoli, Leydig, and peritubular cells. T3 stimulates Sertoli cell lactate secretion as well as mRNA expression of inhibin-alpha, androgen receptor, IGF-I, and IGFBP-4. It also inhibits Sertoli cell mRNA expression of Müllerian inhibiting substance (MIS), aromatase, estradiol receptor, and androgen binding protein (ABP) and ABP secretion. T3 directly increases Leydig cell LH receptor numbers and mRNA levels of steroidogenic enzymes and steroidogenic acute regulatory protein. It stimulates basal and LH-induced secretion of progesterone, testosterone, and estradiol by Leydig cells. Steroidogenic factor-1 acts as a mediator for T3-induced Leydig cell steroidogenesis. Although the role of T3 on sperm, germ, and peritubular cells has not yet been completely studied, it is clear that T3 directly regulates Sertoli and Leydig cell functions. Further studies are required to elucidate the direct effect of T3 on sperm, germ, and peritubular cells.     

Improvement of Qilin pills on male reproductive function in tripterygium glycoside-induced oligoasthenospermia in rats

This study established an oligoasthenospermic rat model using tripterygium glycosides (TGs) and investigated the mechanism by which Qilin pills (QLPs) ameliorate reproductive hypofunction. Thirty-two male Sprague Dawley rats were allocated to four equal-sized groups: (1) the control group received continuous physiological levels of saline; (2) the oligoasthenospermia model group was induced with TGs by daily intragastric administration for 28 days; (3 and 4) oligoasthenospermic rats were treated intragastrically with low dose (1.62 g kg⁻¹ d⁻¹) and high dose (3.24 g kg⁻¹ d⁻¹) of QLPs once daily for 60 days. The QLP-treated rats showed a marked increase (p < .05) in testicular mass, testicular index and semen parameters compared with the untreated rats. Histopathologically, the QLP-treated groups exhibited restored seminiferous tubules in contrast to the model group. Reactive oxygen species and malondialdehyde levels were dramatically decreased (p < .05) in the testes of the QLP-treated rats. QLP treatment partly reverted (p < .05) the circulatory levels of reproductive hormones (FSH, LH, testosterone, prolactin and SHBG) and hepatic and renal function (AST, Cr and urea). Our results showed that oral QLP treatment had a curative effect on the testicular mass, sperm quality, testicular pathomorphology, antioxidants, plasmatic hormones, and liver and renal function of rats.     

Adenovirus Expressing Mutant p27 kip1 Enhanced Apoptosis and Inhibited the Growth of Xenografted Human Breast Cancer

Purpose To evaluate the anti-tumor effects of a novel adenovirus expressing mutant p27 ^kip1 (Adp27-mt), which consists of a mutation of Thr-187/Pro-188 to Met-187/Ile-188. Methods Using the human breast cancer cell lines, MDA-MB-231, ZR-75-1, and MCF-7, we tested Adp27-mt for cell cycle assay, growth inhibition assay, and TdT-mediated dUTP-biotin nick end labeling in a human breast cancer-grafted severe combined immunodeficiency (SCID) mouse model. Results The mutant p27 ^kip1 induced stronger apoptosis in the breast cancer cell lines than adenovirus expressing wild-type p27 ^kip1 (Adp27-wt). Adp27-mt inhibits cell growth significantly; being about 5- and 3.5-fold stronger for IC50 than Adp27-wt in the breast cancer cell lines, MDA-MD-231 and ZR-75-1, respectively. In the human breast cancer-grafted SCID mouse model, Adp27-mt induced tumor regression and antitumor effects significantly better than Adp27-wt. Furthermore, Adp27-mt mainly caused G2/M arrest in the cell cycle progression, whereas Adp27-wt mediated a G1/S arrest 48 h after infection. Conclusion The mutant p27 ^kip1 protein induced apoptosis, and inhibited cell growth more efficiently with stronger anti-tumor effects than wild-type p27 ^kip1 . Thus, the recombinant adenovirus expressing mutant p27 ^kip1 could be useful in gene therapy against breast cancer.     

Detection and Management of Hypothyroidism Following Thyroid Lobectomy: Evaluation of a Clinical Algorithm

Background  

The objectives of this study were to determine: (1) the incidence permanent hypothyroidism after thyroid lobectomy (TL), (2) whether asymptomatic patients with mildly elevated thyrotropin (TSH) levels can be managed without thyroid hormone replacement, and (3) if the degree of lymphocytic infiltration (LI) and germinal center (GC) formation in the resected thyroid lobe correlates with the development of post-TL hypothyroidism.     

Disruption of biomineralization pathways in spinal tissues of a mouse model of diffuse idiopathic skeletal hyperostosis

Equilibrative nucleoside transporter 1 (ENT1) mediates passage of adenosine across the plasma membrane. We reported previously that mice lacking ENT1 (ENT1^−/−) exhibit progressive ectopic mineralization of spinal tissues resembling diffuse idiopathic skeletal hyperostosis (DISH) in humans. Here, we investigated mechanisms underlying aberrant mineralization in ENT1^−/− mice. Micro-CT revealed ectopic mineralization of spinal tissues in both male and female ENT1^−/− mice, involving the annulus fibrosus of the intervertebral discs (IVDs) of older mice. IVDs were isolated from wild-type and ENT1^−/− mice at 2 months of age (prior to disc mineralization), 4, and 6 months of age (disc mineralization present) and processed for real-time PCR, cell isolation, or histology. Relative to the expression of ENTs in other tissues, ENT1 was the primary nucleoside transporter expressed in wild-type IVDs and mediated the functional uptake of [³H]2-chloroadenosine by annulus fibrosus cells. No differences in candidate gene expression were detected in IVDs from ENT1^−/− and wild-type mice at 2 or 4 months of age. However, at 6 months of age, expression of genes that inhibit biomineralization Mgp, Enpp1, Ank, and Spp1 were reduced in IVDs from ENT1^−/− mice. To assess whether changes detected in ENT1^−/− mice were cell autonomous, annulus fibrosus cell cultures were established. Compared to wild-type cells, cells isolated from ENT1^−/− IVDs at 2 or 6 months of age demonstrated greater activity of alkaline phosphatase, a promoter of biomineralization. Cells from 2-month-old ENT1^−/− mice also showed greater mineralization than wild-type. Interestingly, altered localization of alkaline phosphatase activity was detected in the inner annulus fibrosus of ENT1^−/− mice in vivo. Alkaline phosphatase activity, together with the marked reduction in mineralization inhibitors, is consistent with the mineralization of IVDs seen in ENT1^−/− mice at older ages. These findings establish that both cell-autonomous and systemic mechanisms contribute to ectopic mineralization in ENT1^−/− mice.     

Estrogen and ghrelin decrease cytoplasmic expression of p27<Superscript>kip1</Superscript>, a cellular marker of ageing,in the striated anal sphincter and levator muscle of ovariectomized rats

A study was carried out to investigate the effect of estrogen and/or ghrelin on the cellular marker of ageing, p27^kip1, in pelvic floor muscles of ovariectomized rats. Virgin Wistar rats (13 months old) underwent ovariectomy followed (1 month) by 42 daily intraperitoneal 17-β estradiol (10 μg/kg), ghrelin (2 μg/kg), both hormones, or placebo vehicle (n=6×4 groups). Six more age-matched animals underwent sham surgery without ovariectomy. Cytoplasmic expression of p27^kip1 in the striated urethral and anal sphincters and levator muscle was measured by Western blot analysis in all animals (n=30). p27^kip1 signal intensity significantly increased postovariectomy in all muscles compared to sham animals. In the anal sphincter and levator, signal intensity decreased to sham levels with ghrelin or estrogen and decreased further after estrogen or ghrelin and estrogen/ghrelin administration. Urethral sphincter signal intensity decreased without reaching sham levels after drug administration. Estrogen and/or ghrelin replacement reverses the ovariectomy-induced exacerbation of biochemical cellular ageing in the anal sphincter and levator muscle of middle-aged rats.     

Influence of obesity and surgical weight loss on thyroid hormone levels

BACKGROUND: The pathophysiologic relationship between morbid obesity and thyroid hormones is not well understood. The goal of this study was to evaluate the influence of obesity and weight reduction after bariatric surgery on thyroid hormone levels. METHODS: Patients who underwent gastric bypass or adjustable gastric banding at our institution, had no previous diagnosis of thyroid disorder, were not taking medication that could affect the thyroid function evaluation, and who were nonsmokers were included in this retrospective evaluation. The association between the thyroid-stimulating hormone (TSH) and free thyroxine (T(4)) levels and body mass index (BMI), and the influence of weight loss after bariatric surgery on these hormones were investigated at different points (preoperatively and 6 and 12 months after bariatric surgery). RESULTS: A total of 86 patients met the study criteria. The TSH levels correlated positively with BMI (P <.001, r = .91) within the BMI range of 30-67 kg/m(2). The mean BMI change from 49 to 32 kg/m(2) after bariatric surgery was associated with a mean reduction in the TSH level from 4.5 to 1.9 microU/mL. Free T(4) showed no association with BMI and was not significantly influenced by weight loss. Before bariatric surgery, 10.5% of the subjects had laboratory values consistent with subclinical hypothyroidism. After bariatric surgery, 100% of these patients experienced significant weight reduction with simultaneous resolution of their subclinical hypothyroidism. CONCLUSION: The results of our study have demonstrated a statistically significant positive association between serum TSH within the normal range and BMI. No association was found between BMI and free T(4) serum levels. The prevalence of subclinical hypothyroidism in study group was 10.5%. Weight loss after bariatric surgery improved or normalized thyroid hormone levels.     

The value of EZH2, p27kip1, BMI‐1 and MIB‐1 on biopsy specimens with low‐risk prostate cancer in selecting men with significant prostate cancer at prostatectomy

OBJECTIVE

To assess the additional prognostic value of the molecular markers EZH2, MIB‐1, p27^kip1 and BMI‐1 on needle biopsies from men with low‐risk prostate cancer, as this disease in needle biopsies shows a heterogeneous clinical outcome, and while it is known that the expression of these tissue markers is predictive of the clinical outcome after radical prostatectomy (RP) their value in prostate biopsies is largely unknown.

PATIENTS AND METHODS

The study included men participating in a screening study, diagnosed with low‐risk prostate cancer and subsequently treated with RP. Immunohistochemical staining for EZH2, MIB‐1, p27^kip1 and BMI‐1 on the needle biopsies were (semi)quantitatively scored and expression levels were related to significant disease at RP. Clinical low‐risk prostate cancer was defined as a prostate‐specific antigen (PSA) level of ≤10 ng/mL, clinical T‐stage ≤2, biopsy Gleason score ≤6, a PSA density of <0.20 ng/mL/g and two or fewer positive cores. Significant PC at RP was defined as presence of any of extracapsular extension, Gleason pattern 4/5, or tumour volume ≥0.5 mL.

RESULTS

In all, 86 biopsy specimens were included; there was high EZH2 expression (>1.0%) in 42% and a low p27^kip expression (<90%) in 63%. Significant disease was present in 44 (51%) RP specimens. A high EZH2 (odds ratio 3.19, P = 0.043) and a low p27^kip1 (4.69, P = 0.036) were independent predictors for significant prostate cancer at RP.

CONCLUSIONS

The determination of EZH2 and p27^kip1 on diagnostic needle biopsies supports the selection of men with indolent prostate cancer at RP. Especially p27^kip1 could improve the pretreatment risk assessment of patients with low‐risk prostate cancer.     

Evaluating the ventilatory effect of transnasal humidified rapid insufflation ventilatory exchange in apnoeic small children with two different oxygen flow rates: a randomised controlled trial*

Transnasal humidified rapid insufflation ventilatory exchange prolongs safe apnoeic oxygenation time in children. In adults, transnasal humidified rapid insufflation ventilatory exchange is reported to have a ventilatory effect with PaCO₂ levels increasing less rapidly than without it. This ventilatory effect has yet to be reproduced in children. In this non-inferiority study, we tested the hypothesis that children weighing 10–15 kg exhibit no difference in carbon dioxide clearance when comparing two different high-flow nasal therapy flow rates during a 10-min apnoea period. Following standardised induction of anaesthesia including neuromuscular blockade, patients were randomly allocated to high-flow nasal therapy of 100% oxygen at 2 or 4 l.kg⁻¹.min⁻¹. Airway patency was ensured by continuous jaw thrust. The study intervention was terminated for safety reasons when SpO₂ values dropped < 95%, or transcutaneous carbon dioxide levels rose > 9.3 kPa, or near-infrared spectroscopy values dropped > 20% from their baseline values, or after an apnoeic period of 10 min. Fifteen patients were included in each group. In the 2 l.kg⁻¹.min⁻¹ group, mean (SD) transcutaneous carbon dioxide increase was 0.46 (0.11) kPa.min⁻¹, while in the 4 l.kg⁻¹.min⁻¹ group it was 0.46 (0.12) kPa.min⁻¹. The upper limit of a one-sided 95%CI for the difference between groups was 0.07 kPa.min⁻¹, lower than the predefined non-inferiority margin of 0.147 kPa.min⁻¹ (p = 0.001). The lower flow rate of 2 l.kg⁻¹.min⁻¹ was non-inferior to 4 l.kg⁻¹.min⁻¹ relative to the transcutaneous carbon dioxide increase. In conclusion, an additional ventilatory effect of either 2 or 4 l.kg⁻¹.min⁻¹ high-flow nasal therapy in apnoeic children weighing 10–15 kg appears to be absent.     

Preventive effects of Aframomum melegueta extracts on the reproductive complications of propylthiouracil‐induced hypothyroidism in male rat

Recent studies have demonstrated that hypothyroidism is associated with infertility. This work was undertaken to evaluate the protective effects of Aframomum melegueta on testicular functions and fertility of hypothyroid male rats. Male rats were orally treated with propylthiouracil (PTU: 10 mg/kg) in combination with plant aqueous or methanol seed extract (20 and 100 mg/kg) for 56 days. Vitamin E and clomiphene citrate served as positive controls. On day 47 of treatment, each male was mated with two adult females for fertilization potential evaluation. At the end of the treatment, genital sex organ weights, sperm characteristics, testicular histology, oxidative status, plasmatic hormones and fertility potential were evaluated. Results indicated that PTU created hypothyroidism characterised by a significant increase in TSH with reduction of T3 and T4. PTU also lowered genital sex organ weights, sperm count, viability and motility, plasmatic levels of luteinising hormone, follicle‐stimulating hormone and testosterone, and increased prolactin, cholesterol and testicular oxidative stress. Alteration in sperm morphology, testis and epididymis histology, and fertilization potential was also noticed. Co‐administration with A. melegueta extracts successfully reversed PTU‐induced infertility without any effect on thyroid hormones. These results provide evidence that A. melegueta has a protective effect on fertility in hypothyroid condition.     

Associations Between Late Pregnancy Dietary Inflammatory Index (DII) and Offspring Bone Mass: A Meta-Analysis of the Southampton Women's Survey (SWS) and the Avon Longitudinal Study of Parents and Children (ALSPAC)

Systemic inflammation is associated with reduced bone mineral density and may be influenced by pro-inflammatory diets. We undertook an observational analysis of associations between late pregnancy energy-adjusted dietary inflammatory index (E-DII) scores and offspring bone outcomes in childhood. E-DII scores (higher scores indicating pro-inflammatory diets) were derived from food frequency questionnaires in late pregnancy in two prospective mother-offspring cohorts: the Southampton Women's Survey (SWS) and the Avon Longitudinal Study of Parents and Children (ALSPAC). The mean (SD) offspring age at dual-energy X-ray absorptiometry (DXA) scanning was 9.2 (0.2) years. Linear regression was used to assess associations between E-DII and bone outcomes, adjusting for offspring sex and age at DXA and maternal age at childbirth, educational level, pre-pregnancy body mass index (BMI), parity, physical activity level, and smoking in pregnancy. Associations were synthesized using fixed-effect meta-analysis. Beta coefficients represent the association per unit E-DII increment. In fully adjusted models (total n = 5910) late pregnancy E-DII was negatively associated with offspring whole body minus head bone area (BA: β = −3.68 [95% confidence interval −6.09, −1.27] cm²/unit), bone mineral content (BMC: β = −4.16 [95% CI −6.70, −1.62] g/unit), and areal bone mineral density (aBMD: β = −0.0012 [95% CI −0.0020, −0.0004] g.cm⁻²/unit), but there was only a weak association with BMC adjusted for BA (β = −0.48 [95% CI −1.11, 0.15] g/unit) at 9 years. Adjustment for child height partly or, for weight, fully attenuated the associations. Higher late pregnancy E-DII scores (representing a more pro-inflammatory diet) are negatively associated with offspring bone measures, supporting the importance of maternal and childhood diet on longitudinal offspring bone health. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).     

Ameliorative effect of selenium nanoparticles on the structure and function of testis and in vitro embryo development in Aflatoxin B1-exposed male mice

The purpose of the research was to investigate the therapeutic ability of selenium nanoparticles (Se-NPs) on the aflatoxin B1 (AFB1) toxicity induced in the male reproductive system. For this experiment, the mature male mice were put into four groups. Control (0.5 ml PBS, 60 days; IP, n = 7), Se-NPs (0.5 µg kg⁻¹ day⁻¹ for 60 days; IP), AFB1 (4.5 mg kg⁻¹ day⁻¹ for 60 days; IP) and AFB1 + Se-NPs (4.5 mg kg⁻¹ day⁻¹ + 0.5 µg kg⁻¹ day⁻¹ for 60 days; IP). After treatment, the histological structure of testis, serum testosterone level and sperm parameters, including concentration, motility, viability, morphology and DNA fragmentation, were examined. The results demonstrated that the AFB1 destroyed the testicular tissue structure and decreased the sperm concentration, motility, viability and normal morphology significantly. AFB1 also could significantly increase sperm DNA fragmentation and reduce in vitro fertilisation and embryo development compared to the control group (p < .001). Our data show that Se-NPs could inhibit AFB1-induced damage to the testis and improve sperm parameters as well as in vitro fertilisation and embryo production in AFB1 exposed male mice. This study revealed that the administration of Se-NPs could attenuate the testicular injury of AFB1 and improve the male reproductive system function in AFB1 exposed mice.     

Foxo3a和p27kip1在大鼠坐骨神经损伤后背根神经节中的表达

目的 探讨坐骨神经夹伤后Foxo3a和p27kip1在腰段背根神经节(DRG)中表达变化及其意义.方法 将成年SD大鼠随机分为正常对照组和实验组.对实验组实行坐骨神经夹伤术.运用蛋白质印迹、免疫荧光双标,研究大鼠坐骨神经夹伤后,腰段DRG中Foxo3a和p27kip1的表达、分布以及细胞增殖和轴突再生情况.结果 Foxo3a在坐骨神经夹伤后1 d表达值(7.0±3.5)开始明显下降,2 d表达值(6.0±3.8)达到最低值,随之逐渐升高,p27kip1在坐骨神经夹伤后2 d表达值(29.0±3.5)表达开始明显下降,7 d表达值(21.0±3.0)达到最低值,随之逐渐升高;Foxo3a和p27kip1分布于神经元和神经胶质细胞内且在坐骨神经夹伤后2d DRG中,Foxo3a和p27kip1在神经元细胞[(37.8±5.7)%、(43.3±4.3)%]和神经胶质细胞[(22.4±3.9)%、(13.8±3.2)%]中表达较在正常组神经元细胞[(73.6±2.5)%、(84.1±3.7)%]和神经胶质细胞[(61.3±4.4)%、(68.7±5.6)%]减少;细胞核增殖抗原(proliferating cell nuclear antigen,PCNA)和神经元生长相关蛋白(GAP-43)在坐骨神经夹伤后2 d DRG中表达值[12±2.6,15±1.9]均开始上调,PCNA在7 d表达值(25.0±3.2)达到最高点,GAP-43则保持较高水平;此外,PCNA与神经胶质细胞共定位明显,与神经元细胞几乎无共定位.结论 大鼠坐骨神经损伤后,Foxo3a和p27kip1在腰段DRG中的表达减少与神经胶质细胞增殖和轴突再生密切相关.     

Temperature Dependence of Sertoli Cell Function

Spermatogenesis as well as Sertoli cell function, monitored by ABP secretion, is severely impaired at 37°C in vivo and in vitro . A closer understanding of the biochemical mechanisms behind this phenomenon may lead to future methods for fertility control.
The cryptorchid Sertoli cell was shown to be exposed to normal or increased levels of the two main stimulatory hormones, testosterone and FSH. Androgen receptor concentrations in hypophysectomized rat testes were not changed by cryptorchidism. However, FSH and to some extent LH receptors showed a gradual decline during 28 days of cryptorchidism. Even in the absence of hormones, Sertoli cells in vitro produced less ABP at 37 than at 32°C. This shows that 1) Testicular FSH receptors can be practically eliminated in vivo. 2) The basal secretion of protein by the Sertoli cell, in the absence of hormones, is impaired at elevated temperature. An elucidation of the biochemistry involved in that impairment may also yield possible points of attack in the search for a male contraceptive.