What happens to gut microorganisms and potential repair mechanisms when meet heavy metal(loid)s.

Heavy metal (loid) pollution is a significant threat to human health, as the intake of heavy metal (loid)s can cause disturbances in intestinal microbial ecology and metabolic disorders, leading to intestinal and systemic diseases. Therefore, it is important to understand the effects of heavy metal (loid)s on intestinal microorganisms and the necessary approaches to restore them after damage. This review provides a summary of the effects of common toxic elements, such as lead (Pb), cadmium (Cd), chromium (Cr), and metalloid arsenic (As), on the microbial community and structure, metabolic pathways and metabolites, and intestinal morphology and structure. The effects of heavy metal (loid)s on metabolism are focused on energy, nitrogen, and short-chain fatty acid metabolism. We also discussed the main solutions for recovery of intestinal microorganisms from the effects of heavy metal (loid)s, namely the supplementation of probiotics, recombinant bacteria with metal resistance, and the non-toxic transformation of heavy metal (loid) ions by their own intestinal flora. This article provides insight into the toxic effects of heavy metals and As on gut microorganisms and hosts and provides additional therapeutic options to mitigate the damage caused by these toxic elements.

Sendeng-4 Suppressed Melanoma Growth by Induction of Autophagy and Apoptosis.

Sendeng-4 is a traditional Chinese medicine that has been successfully applied to anti-inflammatory diseases in clinical practice. Monomers within Sendeng-4 showed promising antitumor activity against lung cancer, colon cancer, and cutaneous cancer. However, potency of Sendeng-4 in melanoma has not been explored. This study aims to explore the potential application of Sendeng-4 in melanoma treatment. In the present study, we systemically investigate the possibility of Sendeng-4 for treatment of melanoma cancer in vitro by proliferation assay, colony formation, flow cell cytometry, RNA-seq, western blot, and fluorescence-based assay. Our data demonstrated that Sendeng-4 suppresses the proliferation and colony formation capacity of melanoma cells and induces cell cycle block at G2/M phase and eventually cell death. Mechanistically, transcriptome sequencing demonstrates that the PI3K-AKT pathway was significantly inactivated upon Sendeng-4 exposure, which was confirmed by western blot showing decreased phosphorylation of AKT. In addition, decreased BCL-2 expression and increased BAX expression were observed, suggesting programmed cell death via apoptosis. Moreover, LC3-II production as well as autophagosomes formation was observed as demonstrated by western blot and immunofluorescence, indicating elevated autophagy network by Sendeng-4 stimulation. Collectively, we concluded that Sendeng-4 might be used as an anticancer drug for melanoma.

Leptin and inflammatory factors play a synergistic role in the regulation of reproduction in male mice through hypothalamic kisspeptin-mediated energy balance.

BACKGROUND: Energy balance is closely related to reproductive function, wherein hypothalamic kisspeptin mediates regulation of the energy balance. However, the central mechanism of kisspeptin in the regulation of male reproductive function under different energy balance states is unclear. Here, high-fat diet (HFD) and exercise were used to change the energy balance to explore the role of leptin and inflammation in the regulation of kisspeptin and the hypothalamic-pituitary-testis (HPT) axis. METHODS: Four-week-old male C57BL/6 J mice were randomly assigned to a normal control group (n = 16) or an HFD (n = 49) group. After 10 weeks of HFD feeding, obese mice were randomly divided into obesity control (n = 16), obesity moderate-load exercise (n = 16), or obesity high-load exercise (n = 17) groups. The obesity moderate-load exercise and obesity high-load exercise groups performed exercise (swimming) for 120 min/day and 120 min × 2 times/day (6 h interval), 5 days/week for 8 weeks, respectively. RESULTS: Compared to the mice in the normal group, in obese mice, the mRNA and protein expression of the leptin receptor, kiss, interleukin-10 (IL-10), and gonadotropin-releasing hormone (GnRH) decreased in the hypothalamus; serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone levels and sperm quality decreased; and serum leptin, estradiol, and tumor necrosis factor-α (TNF-α) levels and sperm apoptosis increased. Moderate- and high-load exercise effectively reduced body fat and serum leptin levels but had the opposite effects on the hypothalamus and serum IL-10 and TNF-α levels. Moderate-load exercise had anti-inflammatory effects accompanied by increased mRNA and protein expression of kiss and GnRH in the hypothalamus and increased serum FSH, LH, and testosterone levels and improved sperm quality. High-load exercise also promoted inflammation, with no significant effect on the mRNA and protein expression of kiss and GnRH in the hypothalamus, serum sex hormone level, or sperm quality. Moderate-load exercise improved leptin resistance and inflammation and reduced the inhibition of kisspeptin and the HPT axis in obese mice. The inflammatory response induced by high-load exercise may counteract the positive effect of improving leptin resistance on kisspeptin and HPT. CONCLUSION: During changes in energy balance, leptin and inflammation jointly regulate kisspeptin expression on the HPT axis.

Increasing hypothalamic nucleobindin 2 levels and decreasing hypothalamic inflammation in obese male mice via diet and exercise alleviate obesity-associated hypogonadism.

To explore the role of nesfatin-1 in regulating male reproductive function during energy balance variation, we employed an obese mouse model which was first induced by a high-fat diet (HFD) and followed by interventions of a normal diet (ND) and/or moderate exercise, and then serum reproductive hormones of male mice, hypothalamic nucleobindin 2 (NUCB2)/nesfatin-1, inflammatory factors, and gonadotropin-releasing hormone (GnRH) levels were tested. Our findings showed that both serum nesfatin-1, follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone (T) levels and hypothalamic NUCB2/nesfatin-1 and Gnrh mRNA levels were reduced, whereas, the mRNA and protein levels of hypothalamic tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß, inhibitor kappa B kinase ß (IKKß), and nuclear factor (NF)-κB were increased in obese male mice. Diet, exercise, and diet combined with exercise interventions reversed the decreases in serum nesfatin-1, FSH, LH, and T levels; increased hypothalamic NUCB2/nesfatin-1 and Gnrh mRNA levels; and reduced hypothalamic TNF-α, IL-1ß, IKKß, and NF-κB levels. These changes were accompanied by reduced adiposity, and these effects were more obvious in the diet combined with exercise group. Overall, our findings suggested that the hypogonadotropic hypogonadism associated with obesity may be induced by reduced hypothalamic NUCB2/nesfatin-1 levels, which attenuated the stimulatory effect on GnRH directly or indirectly by suppressing its anti-inflammatory effect in the brain. Diet and/or exercise interventions were able to alleviate the hypogonadotropic hypogonadism associated with obesity, potentially by increasing hypothalamic NUCB2/nesfatin-1 levels.

Effect of electroacupuncture at Ximen (PC 4) and Hegu (LI 4) on expression of Akt in rats with myocardial ischemia-reperfusion injury.

OBJECTIVE: To investigate the effect of electroacupuncture (EA) at acupoints on the pericardium meridian on the expression of phosphorylated Akt (p-Akt) protein in rat myocardium after ischemia and reperfusion. METHODS: Seventy Wistar rats were evenly randomized into seven groups: the sham operation group (group A), ischemia-reperfusion model Ⅰ group (group B), ischemia-reperfusion model Ⅱ group (group C), EA at Neiguan (PC 6) group (group D), EA at Ximen (PC 4) group (group E), EA at Hegu (LI 4) group (group F), and LY294002 + EA at Neiguan (PC 6) group (group G). All processes were monitored by electrocardiography. In group A, the left anterior descending coronary artery was only threaded without ligation for 100 min. In group B, the left anterior descending coronary artery was ligated for 40 min and reperfused for 60 min. The left anterior descending coronary artery in group C was ligated for 40 min and reperfused for 100 min. Groups D, E, and F received EA for 20 min before undergoing ischemia for 40 min, and then received EA for 20 min before undergoing reperfusion for 60 min. Before modeling, group G was injected with LY294002 (0.3 mg/kg) into the tail vein, and then underwent the same intervention as the other EA groups. After reperfusion, myocardial tissue from the left cardiac ventricle was collected to enable Western blot analysis of the p-Akt level, and analysis of electrocardiographic changes. RESULTS: In groups B and C, electrocardiography showed obvious elevation of the ST-segment Ⅱ lead (ECG-STⅡ), while the ECG-ST Ⅱ values were significantly lower in groups D, E, and G (P < 0.01). The p-Akt levels in groups D and E were significantly greater than those in groups B and C (P < 0.01). Compared with all other groups, group G showed a significantly different expression of p-Akt (P < 0.01). CONCLUSION: The expression of p-Akt protein in cardiomyocytes was significantly greater in rats that were injected with LY294002 and received EA at Ximen (PC 4) compared with all other groups. This suggests that EA at Ximen (PC 4) resulted in activation of the phosphoinositide 3-kinase/Akt signaling pathway and phosphorylation of Akt.