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Acrylamide (AA) has been shown to have neurological and reproductive toxicities, but little is known about transgenerational effects of AA. In this study, male C57BL/6 mice were exposed to AA (0.01, 1, 10 μg/mL) and its metabolite glycidamide (GA, 10 μg/mL) in drinking water, which were then mated with unexposed female mice to produce F1 and F2 generations. We found that both AA and GA at high concentrations decreased sperm motility in F0 mice and increased sperm malformation rates in mice from all the three generations. In addition, AA and GA increased sperm reactive oxygen species as well as decreased serum testosterone levels, and increased the escape latency time in exposed mice and their offspring. We further found that AA-induced mRNA expression changes in the hippocampus of F0 mice persist to the F2 generation. In the sperm of F0 mice, AA induced significant DNA methylation changes in genes involved in neural and reproduction; the mRNA expression levels of Dnmt3b, a DNA methyltransferase, were dramatically decreased in the testes of F0 and F1 mice. In conclusion, our study indicates that paternal AA exposure leads to DNA methylation-mediated transgenerational adverse effects on sperm parameters and leaning capability in mice.Di(2-ethylhexyl) phthalate (DEHP) is a plasticizer widely used in agricultural and industrial plastic products. Many researchers have demonstrated that DEHP can cause varying degrees of harm to the heart. This research investigated the mechanism by which DEHP causes heart damage in quail. The quail were treated with DEHP (250 mg/kg BW/day, 500 mg/kg BW/day or 750 mg/kg BW/day) for 45 days. The present study suggested that DEHP could cause varying levels of heart damage, including disordered myocardial fiber arrangements, myocardial fiber breakage and myocardial cell swelling. EN450 solubility dmso The results showed that DEHP induced mitochondrial damage, such as cavitation lesions and mitochondrial crest breakage. DEHP damaged mitochondria and inhibited nuclear respiratory factor 1 (Nrf1)-mediated mitochondrial biogenesis, which led to mitochondrial damage. DEHP caused oxidative stress in the heart and activated the defense mechanism of the nuclear factor red blood cell 2 related factor 2 (Nrf2) system. DEHP-induced mitophagy was related to a decline in mitochondrial biogenesis and disordered mitochondrial dynamics. The data indicated that DEHP exposure damaged cardiac mitochondria and caused mitophagy and cardiotoxicity. Of note, this study showed that DEHP-induced mitophagy and mitochondrial damage are associated with the dysregulation of mitochondrial biogenesis.
Menopausal symptoms can affect the physical and mental health of females and are often related to abnormal function of the hypothalamus. In this study, we evaluated changes in the hypothalamus transcriptome in ovariectomized mice to identify key mRNAs, and systematically elucidated the possible molecular mechanisms underlying the menopausal syndrome to provide a theoretical basis for clinical diagnosis and treatment.
Forty-six adult female C57BL/6J mice were randomly divided into SHAM and OVX groups, 23 mice per group. Eight weeks after the procedure, differentially expressed genes (DEGs) in the hypothalamus were identified through RNA-sequencing. DEGs were analyzed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genome (KEGG) analyses. Key DEGs were then evaluated using quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and immunohistochemical staining.
Compared with SHAM group, 7295 genes were upregulated, and 8979 genes were downregulated in the hypothalamus of OVX mice with a fold change of 1.5 (log2 fold change ≥0.585). GO and KEGG analyses suggested these key genes were involved in thermoregulation, food intake, glucose and lipid metabolism, cardiovascular regulation, biological rhythm, and endocrine regulation.
Differential expression of genes in the hypothalamus of OVX mice involved in thermoregulation, eating, sleeping, homeostasis, and endocrine regulation 8 weeks after ovariectomy suggest potential roles in the pathogenesis of climacteric syndrome.
Differential expression of genes in the hypothalamus of OVX mice involved in thermoregulation, eating, sleeping, homeostasis, and endocrine regulation 8 weeks after ovariectomy suggest potential roles in the pathogenesis of climacteric syndrome.Objective data mainly from the comparative anatomy of various organs related to human speech and language is considered to unearth clues about the mechanisms behind language development. The two organs of the larynx and hyoid bone are considered to have evolved towards suitable positions and forms in preparation for the occurrence of the large repertoire of vocalization necessary for human speech. However, some researchers have asserted that there is no significant difference of these organs between humans and non-human primates. Speech production is dependent on the voluntary control of the respiratory, laryngeal, and vocal tract musculature. Such control is fully present in humans but only partially so in non-human primates, which appear to be able to voluntarily control only supralaryngeal articulators. Both humans and non-human primates have direct cortical innervation of motor neurons controlling the supralaryngeal vocal tract but only human appear to have direct cortical innervation of motor neurons controlling the larynx. In this review, we investigate the comparative morphology and function of the wide range of components involved in vocal production, including the larynx, the hyoid bone, the tongue, and the vocal brain. We would like to emphasize the importance of the tongue in the primary development of human speech and language. It is now time to reconsider the possibility of the tongue playing a definitive role in the emergence of human speech.Pre- and postnatal development and variability in discrete vertebral traits have been poorly described in embryonic studies. Numerous authors have reported that these variations are observable only from adolescence; scientific publications on the vertebrae of fetuses and infants are scarce. Thus, the aims of this study were to (1) describe the ontogeny and variability of anatomical variations in the vertebral column of a Spanish infant population and (2) analyze the frequency and relationship between sex, age, and intertrait variables. A total of 4728 vertebrae from 197 skeletons were studied. The age at death ranged from 22 intrauterine weeks to 8 years. Twenty morphological traits related to vertebral column development were analyzed. A descriptive statistical analysis was performed, and the chi-square test was used to measure the relationship between sex, age, and intertrait variables. We observed that 88.32% of skeletons expressed discrete traits along the spine. In fetuses, the double transverse foramen and unclosed transverse process of the axis were the most prevalent traits. In infants older than one year, the appearance of the L5 cleft neural arch, unclosed transverse process of the atlas, and craniocaudal shifts were frequent. A significant result was found between sex and the unclosed transverse process in the axis. The intertrait relationship was significant for all traits that shared the same embryonic structure. Morphological variations became visible following the appearance of ossification centers during the pre- and postnatal periods, and their etiology was associated with embryonic development.
This systematic review aims to assess the effects of continuous glucose monitoring (CGM) on maternal and neonatal outcomes in perinatal women with diabetes.
A three-step comprehensive search was conducted based on the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guideline. Randomized controlled trials (RCTs) were retrieved from international databases of PubMed, Embase, Cochrane Library, CINAHL, PsycINFO and Scopus from their respective inception dates until 5th January 2021. Comprehensive Meta-Analysis Software Version 3 was used. The overall effect was determined using Hedges' g. Cochrane collaboration's tool version 1 and grading of recommendations, assessment, development and evaluation criteria were used for quality assessment.
A total of 1215 records were identified and 10 RCTs involving a total of 1358 perinatal women were selected. The meta-analysis revealed that CGM significantly improved HbA1c levels (g=-0.43, 95% CI -0.63, -0.22), lowered cesarean section rate (g=-0.17, 95% CI -0.33, -0.02) and neonatal birth weight (g=-0.16, 95% CI -0.27, -0.04) when compared to the comparator. The majority (86.67%) has a low risk of biases and certainty of evidence ranged from very low to moderate.
CGM improves maternal and neonatal outcomes. Future studies should use well-designed large-scale trials.
CGM improves maternal and neonatal outcomes. Future studies should use well-designed large-scale trials.
Duodenal mucosal resurfacing (DMR) is an endoscopic procedure developed to improve metabolic parameters and restore insulin sensitivity in patients with diabetes. Here we report long-term DMR safety and efficacy from the REVITA-1 study.
REVITA-1 was a prospective, single-arm, open-label, multicenter study of DMR feasibility, safety, and efficacy in patients with type 2 diabetes (hemoglobin A1c [HbA1c] of 7.5-10.0% (58-86mmol/mol)) on oral medication. Safety and glycemic (HbA1c), hepatic (alanine aminotransferase [ALT]), and cardiovascular (HDL, triglyceride [TG]/HDL ratio) efficacy parameters were assessed (P values presented for LS mean change).
Mean±SD HbA1c levels reduced from 8.5±0.7% (69.1±7.1mmol/mol) at baseline (N=34) to 7.5±0.8% (58.9±8.8mmol/mol) at 6months (P<0.001); and this reduction was sustained through 24months post-DMR (7.5±1.1% [59.0±12.3mmol/mol], P<0.001) while ingreater than50% of patients, glucose-lowering therapy was reduced or unchanged. ALT decreased from 38.1±21.1 U/L at baseline to 32.5±22.1 U/L at 24months (P=0.048). HDL and TG/HDL improved during 24-months of follow-up. No device- or procedure-related serious adverse events, unanticipated device effects, or hypoglycemic events were noted between 12 and 24months post-DMR.
DMR is associated with durable improvements in insulin sensitivity and multiple downstream metabolic parameters through 24months post-treatment in type 2 diabetes. Clinical trial reg. no. NCT02413567, clinicaltrials.gov.
DMR is associated with durable improvements in insulin sensitivity and multiple downstream metabolic parameters through 24 months post-treatment in type 2 diabetes. Clinical trial reg. no. NCT02413567, clinicaltrials.gov.
To examine the predictive factors associated with the progression of different prediabetic status to diabetes.
A two-year retrospective cohort study was conducted on 5741 participants aged 40years or older. Finally, 1685 participants with prediabetes defined by IFG (impaired fasting glucose), IGT (impaired glucose tolerance) and CGI (combined IFG and IGT) were included. Logistic regression model was used to evaluate the risk of prediabetes progression to diabetes.
Of the 1685 subjects with prediabetes at baseline, 212 (12.6%) subjects progressed to diabetes and 1473 (87.4%) subjects did not. Logistic regression analysis demonstrated that people with CGI were associated with an increased risk of progressing to diabetes compared to those with IFG (OR, 95% CI 3.127, 2.047-4.776). Moreover, males, obese people, people with increased BMI and WHR (Waist/ Hip ratio), and hypertension were positively associated with the progression to diabetes, while HOMA-β was negatively associated with the progression to diabetes.