Pyrroloquinoline quinone inhibits PCSK9-NLRP3 mediated pyroptosis of Leydig cells in obese mice.

Abnormal lipid metabolism and chronic low-grade inflammation are the main traits of obesity. Especially, the molecular mechanism of concomitant deficiency in steroidogenesis-associated enzymes related to testosterone (T) synthesis of obesity dominated a decline in male fertility is still poorly understood. Here, we found that in vivo, supplementation of pyrroloquinoline quinone (PQQ) efficaciously ameliorated the abnormal lipid metabolism and testicular spermatogenic function from high-fat-diet (HFD)-induced obese mice. Moreover, the transcriptome analysis of the liver and testicular showed that PQQ supplementation not only inhibited the high expression of proprotein convertase subtilisin/Kexin type 9 (PCSK9) but also weakened the NOD-like receptor family pyrin domain containing 3 (NLRP3)-mediated pyroptosis, which both played a negative role in T synthesis of Leydig Cells (LCs). Eventually, the function and the pyroptosis of LCs cultured with palmitic acid in vitro were simultaneously benefited by suppressing the expression of NLRP3 or PCSK9 respectively, as well the parallel effects of PQQ were affirmed. Collectively, our data revealed that PQQ supplementation is a feasible approach to protect T synthesis from PCSK9-NLRP3 crosstalk-induced LCs' pyroptosis in obese men.

Effects of Antioxidant Supplementation on Metabolic Disorders in Obese Patients from Randomized Clinical Controls: A Meta-Analysis and Systematic Review.

Purpose: This systematic review and meta-analysis aim at elucidating the heterogeneity in beneficial effects of antioxidant supplementation in obese adults by exploring the differential effects of antioxidant supplementation on basic indicators of obesity, lipid metabolism, systemic antioxidant capacity, inflammatory biomarkers, and liver function. Methods: The inclusion criteria specified randomized controlled trials with antioxidant intervention for adults (mean body mass index (BMI) > 30), from inception to Aug. 8, 2021, in the PubMed, Embase, The Cochrane Library, Web of Science, and Scopus databases. Meta-analysis and publication bias were performed using RevMan 5.4 software. Stata16 software was used to detect publication bias with Egger's and Begg's methods being mainly used. The data of basic indicators of obesity, lipid metabolism index, oxidative stress index, inflammatory biomarkers, and liver function index were collected to analyze the beneficial effects of antioxidant supplementation in obese patients. Results: A total of 30 studies were included in this study with a sample of 845 obese patients from the antioxidant supplementation group and 766 obese patients from the placebo control group. The meta-analysis showed that obese patients with antioxidant supplementation had lower BMI (mean difference (MD): - 0.44 [95%confidence interval (CI): - 0.84, -0.04], p = 0.03), waist circumference (MD : -0.78 [95%CI:-1.45, -0.11], p = 0.02), fasting blood glucose (FBG) level (standardized mean difference (SMD): - 4.92 [95%CI:-6.87, -2.98], p < 0.001) and homeostasis model assessment of insulin resistance (MD : -0.45 [95%CI:-0.61, -0.3], p < 0.001) when compared to the placebo group. Obese patients on antioxidant supplementation had lower levels of total cholesterol (SMD : -0.43 [95%CI:-0.84, -0.02], p = 0.04), triglycerides (SMD : -0.17 [95%CI:-0.31, -0.04], p = 0.01), low-density lipoprotein (SMD : -0.15 [95%CI:-0.29, -0.01], p = 0.03), malondialdehyde (SMD : -1.67 [95%CI:-2.69, -0.65], p = 0.001), and tumor necrosis factor-alpha (SMD : -0.29 [95%CI:-0.56, -0.02], p = 0.03), respectively, when compared to the placebo group. In addition, obese patients with antioxidant supplementation had higher levels of high-density lipoprotein (SMD : 0.25 [95%CI : 0.03, 0.46], p = 0.03) and superoxide dismutase (SMD : 1.09 [95%CI : 0.52, 1.65], p < 0.001) when compared to the placebo group. Antioxidant supplementation had no effects on other analyzed parameters including waist-hip ratio, leptin, fat mass, interleukin-6, C-reactive protein, alanine transaminase, and aspartate transaminase in obese patients. Conclusion: The meta-analysis results indicated that antioxidant supplementation exerted potential beneficial effects in obese patients by regulating FBG, oxidative stress, and inflammation, whilst more high-quality studies are required to confirm these effects. The present study may provide important insights for the treatment of clinical obesity and obesity-associated complications.

Effects of Sleep Disorders and Circadian Rhythm Changes on Male Reproductive Health: A Systematic Review and Meta-analysis.

Objectives: The purpose of this study was to elucidate the relationship between sleep disorders and male reproductive health, and to explore the underlying mechanisms via a systematic review and meta-analysis. Methods: PubMed, Embase, The Cochrane library, Web of Science, Scopus databases were searched to collect clinical research on the effects of sleep disorders on male semen parameters from inception to February 24, 2022. RevMan 5.4 was used for meta-statistical analysis. Stata16 software was used to detect publication bias. Results: The results of meta-analysis showed that sleep disorders were associated with reduced total sperm count (mean difference (MD) = -27.91, 95% CI = (-37.82, -18.01), p < 0.001), reduced sperm concentration (MD = -5.16, 95% CI = (-9.67, -0.65), p = 0.02), reduced progressive motility (MD = -2.94, 95% CI = (-5.28, -0.59), p = 0.01), and reduced normal morphology (MD = -0.52, 95% CI = (-0.80, -0.24), p < 0.001). However, there is no significant association between sleep disorders and semen volume/reproductive hormones. Further bioinformatics mining revealed that related clock genes (PER1, PER2, CRY2, NR1D1 and NPAS2) were down-regulated in non-obstructive azoospermia patients. Conclusion: In conclusion, current evidence suggests that sleep disorders have a negative impact on male reproductive health, and its underlying mechanism may be related to circadian rhythm disorders. However, the relationship between sleep disorders and reproductive hormone levels has not been found. Due to the limited number and quality of included studies, the above findings need to be validated by more high-quality studies.

Antioxidant for treatment of diabetic complications: A meta-analysis and systematic review.

Antioxidants may provide a complementary treatment for patients with chronic diseases. Nevertheless, studies that have measured the effects of antioxidant on diabetes complications have provided conflicting results. This study aimed to elucidate the association between antioxidant and diabetic complications and to develop robust evidence for clinical decisions by systematic reviews and meta-analysis. PubMed, Embase, The Cochrane Library, Web of Science, Scopus databases were searched to collect clinical studies related to the efficacy of antioxidants in the treatment of diabetes complications from inception to May 5, 2021. Statistical meta-analyses were performed using the RevMan 5.4 software. Stata16 software was used to detect publication bias. The data of diabetic nephropathy (DN), diabetic nonalcoholic fatty liver disease (NAFLD), and diabetic periodontitis were collected to analyze the effect of antioxidant on diabetes and the above three complications. The meta-analysis results showed that antioxidant treatment was associated with significantly changes in the fasting plasma glucose (FPG) (standardized mean difference [SMD]: - 0.21 [95% confidence interval [CI]: - 0.33, -0.10], p < 0.001), hemoglobin A1c (HbA1c) (MD: - 0.41 [95% CI: - 0.63, -0.18], p < 0.001), total antioxidant capacity (TAC) (SMD: 0.44 [95% CI: 0.24, 0.63], p < 0.001) and malondialdehyde (MDA) (SMD: - 0.82 [95% CI: - 1.24, -0.41], p < 0.001) than the control group. Antioxidant supplements have the potential to treat three complications of diabetes. In conclusion, the meta-analysis results indicate that antioxidant treatment is effective clinically for diabetes mellitus and its complications.

Effects of NAD+ precursor supplementation on glucose and lipid metabolism in humans: a meta-analysis.

BACKGROUND: This meta-analysis was performed to investigate the effects of nicotinamide adenine dinucleotide (NAD+) precursor supplementation on glucose and lipid metabolism in human body. METHODS: PubMed, Embase, CENTRAL, Web of Science, Scopus databases were searched to collect clinical studies related to the supplement of NAD+ precursor from inception to February 2021. Then the retrieved documents were screened, the content of the documents that met the requirements was extracted. Meta-analysis and quality evaluation was performed detection were performed using RevMan5.4 software. Stata16 software was used to detect publication bias, Egger and Begg methods were mainly used. The main research terms of NAD+ precursors were Nicotinamide Riboside (NR), Nicotinamide Mononucleotide (NMN), Nicotinic Acid (NA), Nicotinamide (NAM). The changes in the levels of triglyceride (TG), total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), and fasting blood glucose were mainly concerned. RESULTS: A total of 40 articles were included in the meta-analysis, with a sample of 14,750 cases, including 7406 cases in the drug group and 7344 cases in the control group. The results of meta-analysis showed that: NAD+ precursor can significantly reduce TG level (SMD = - 0.35, 95% CI (- 0.52, - 0.18), P < 0.0001), and TC (SMD = - 0.33, 95% CI (- 0.51, - 0.14), P = 0.0005), and LDL (SMD = - 0.38, 95% CI (- 0.50, - 0.27), P < 0.00001), increase HDL level (SMD = 0.66, 95% CI (0.56, 0.76), P < 0.00001), and plasma glucose level in the patients (SMD = 0.27, 95% CI (0.12, 0.42), P = 0.0004). Subgroup analysis showed that supplementation of NA had the most significant effect on the levels of TG, TC, LDL, HDL and plasma glucose. CONCLUSIONS: In this study, a meta-analysis based on currently published clinical trials with NAD+ precursors showed that supplementation with NAD+ precursors improved TG, TC, LDL, and HDL levels in humans, but resulted in hyperglycemia, compared with placebo or no treatment. Among them, NA has the most significant effect on improving lipid metabolism. In addition, although NR and NAM supplementation had no significant effect on improving human lipid metabolism, the role of NR and NAM could not be directly denied due to the few relevant studies at present. Based on subgroup analysis, we found that the supplement of NAD+ precursors seems to have little effect on healthy people, but it has a significant beneficial effect on patients with cardiovascular disease and dyslipidemia. Due to the limitation of the number and quality of included studies, the above conclusions need to be verified by more high-quality studies.

Association of diabetes and obesity with sperm parameters and testosterone levels: a meta-analysis.

BACKGROUND: The present study performed two distinct meta-analyses with common outcomes (sperm parameters); one was performed in obese individuals (and non-obese controls) and the other in diabetic individuals (and non-diabetic controls). METHODS: PubMed, Embase, The Cochrane library, Web of Science, Scopus databases were searched to collect clinical studies related to the effects of obesity and diabetes on male sperm from inception to on 1st February 2021. Statistical meta-analyses were performed using the RevMan 5.4 software. Stata16 software was used to detect publication bias. The methodological quality of the included studies was assessed with the Ottawa-Newcastle scale using a star-based system. RESULTS: A total of 44 studies were finally included in the present study, which enrolled 20,367 obese patients and 1386 patients with diabetes. The meta-analysis results showed that both obesity and diabetes were associated with reduced semen volume (obese versus non-obese controls: mean difference (MD) = - 0.25, 95% CI = (- 0.33, - 0.16), p < 0.001; diabetes versus non-diabetic controls: MD = - 0.45, 95% CI = (- 0.63, - 0.27), p < 0.001), reduced sperm count (obese versus non-obese controls: MD = - 23.84, 95% CI = (- 30.36, - 17.33), p < 0.001; diabetes versus non-diabetic controls: MD = - 13.12, 95% CI = (- 18.43, - 7.82), p < 0.001), reduced sperm concentration (obese versus non-obese controls: MD = - 7.26, 95% CI = (- 10.07, - 4.46), p < 0.001; diabetes versus non-diabetic controls: MD = - 11.73, 95% CI = (- 21.44, - 2.01), p = 0.02), reduced progressive motility (obese versus non-obese controls: MD = - 5.68, 95% CI = (- 8.79, - 2.56), p < 0.001; diabetes versus non-diabetic controls: MD = - 14.37, 95% CI = (- 21.79, - 6.96), p = 0.001), and decreased testosterone levels (obese versus non-obese controls: MD = - 1.11, 95% CI = (- 1.92, - 0.30), p = 0.007; diabetes versus non-diabetic controls: MD = - 0.37, 95% CI = (- 0.63, - 0.12), p = 0.004). CONCLUSIONS: Current evidence suggests that obesity and diabetes negatively affect sperm parameters in men and are associated with low testosterone levels. Due to the limitation of the number and quality of included studies, the above conclusions need to be verified by more high-quality studies.

[Effect of electroacupuncture on plasma estrin and bone mineral density in ovariectomized rats].

OBJECTIVE: To observe the effect of electroacupuncture (EA) on plasma estrin (E) 2 and bone mineral density (BMD) in ovariectomized (OVX) rats for studying its underlying mechanism in treating osteoporosis. METHODS: Thirty-two female SD rats were randomized into normal control, model, EA, and medication groups with 8 rats in each group. Postmenopausal osteoporosis model was established by removing the uterus under anesthesia (2% Phenobarbital, 40 mg/kg). In EA group, bilateral "Zusanli" (ST 32) and "Sanyinjiao" (SP 6) were punctured and stimulated electrically for 20 minutes with 1-3 Hz in frequency, 1 ms in duration of waves, and 0.7-1.0 mA in strength, once daily and 8 weeks altogether. Rats of medication group were drenched with 5% Nilestriol, 5 mL/week and for 8 weeks. At the end of experiments, blood samples were collected after removing the rat eyeball, and the left femoral bone tissue was taken. Serum E2 was assayed by using enzyme linked immunosorbent assay (ELISA) and BMD was measured by using double functional X-ray digital bone density meter. RESULTS: Compared with normal group, the body weight of model group was significantly bigger (P < 0.05), and that of model group was also significantly bigger than that of EA and medication groups (P < 0.11). No significant differences were found among the 4 groups before experiments and among normal control and EA groups after treatment (P > 0.05). In comparison with normal group, BMD and serum E2 of model group decreased significantly (P < 0. 01), while compared with model group, BMD and E2 of EA and medication groups increased significantly (P < 0.01, < 0.05). No significant differences were found among normal, EA and medication groups (P > 0.05). CONCLUSION: Both EA and medication can increase BMD and serum E2 in OVX rats, which may be one of the mechanisms of acupuncture in treating osteoporosis.