Novel HYDIN variants associated with male infertility in two Chinese families

IntroductionInfertility is a major disease affecting human life and health, among which male factors account for about half. Asthenoteratozoospermia accounts for the majority of male infertility. High-throughput sequencing techniques have identified numerous variants in genes responsible for asthenoteratozoospermia; however, its etiology still needs to be studied.MethodIn this study, we performed whole-exome sequencing on samples from 375 patients with asthenoteratozoospermia and identified two HYDIN compound heterozygous variants, a primary ciliary dyskinesia (PCD)-associated gene, in two unrelated subjects. H&E staining, SEM were employed to analyze the varies on sperm of patients, further, TEM was employed to determine the ultrastructure defects. And westernblot and immunostaining were chose to evaluate the variation of structural protein. ICSI was applied to assist the mutational patient to achieve offspring.ResultWe identified two HYDIN compound heterozygous variants. Patient AY078 had novel compound heterozygous splice variants (c.5969-2A>G, c.6316+1G>A), altering the consensus splice acceptor site of HYDIN. He was diagnosed with male infertility and PCD, presenting with decreased sperm progressive motility and morphological abnormalities, and bronchial dilatation in the inferior lobe. Compared to the fertile control, HYDIN levels, acrosome and centrosome markers (ACTL7A, ACROSIN, PLCζ1, and Centrin1), and flagella components (TOMM20, SEPT4, SPEF2, SPAG6, and RSPHs) were significantly reduced in HYDIN-deficient patients. Using intracytoplasmic sperm injection (ICSI), the patient successfully achieved clinical pregnancy. AY079 had deleterious compound heterozygous missense variants, c.9507C>G (p. Asn3169Lys) and c.14081G>A (p. Arg4694His), presenting with infertility; however, semen samples and PCD examination were unavailable.DiscussionOur findings provide the first evidence that the loss of HYDIN function causes asthenoteratozoospermia presenting with various defects in the flagella structure and the disassembly of the acrosome and neck. Additionally, ICSI could rescue this failure of insemination caused by immobile and malformed sperm induced by HYDIN deficiency

PM2.5 exposure aggravates acute liver injury by creating an inflammatory microenvironment through Kupffer cell

Aim: This work aimed to investigate the impact of PM2.5 exposure on acute liver injury Methods: C57BL/6 mice were used to examine the hepatic histopathological changes in PM2.5-exposed mice, as well as in CCl4-mediated acute liver injury mice after long-term exposure to PM2.5. During in vitro experiments, Kupffer cells were detected for M1 polarization level after treating with PM2.5, and the activation level of NLRP3 inflammasomes were assessed. Results: According to our findings, PM2.5 can induce M1 polarization of Kupffer cells in the liver to create an inflammatory microenvironment. Long-term exposure to PM2.5 can aggravate acute liver injury in mice. Treatment with MCC950, an NLRP3 inhibitor, can inhibit the effect of PM2.5. As demonstrated by in vitro analysis, PM2.5 can promote M1 polarization of Kupffer cells. Conclusion: As suggested by our results, long-term exposure to PM2.5 can create an inflammatory microenvironment to aggravate mouse acute liver injury. The effect is related to NLRP3-mediated M1 polarization in Kupffer cells

Research Progress on Effects of Ginsenoside Rg2 and Rh1 on Nervous System and Related Mechanisms

Neurological-related disorders are diseases that affect the body’s neurons or peripheral nerve tissue, such as Parkinson’s disease (PD) and Alzheimer’s disease (AD). The development of neurological disorders can cause serious harm to the quality of life and functioning of the patient. The use of traditional therapeutic agents such as dopamine-promoting drugs, anticholinergic drugs, cholinesterase inhibitors, and NMDA receptor antagonists is often accompanied by a series of side effects such as drug resistance, cardiac arrhythmia, liver function abnormalities, and blurred vision. Therefore, there is an urgent need to find a therapeutic drug with a high safety profile and few side effects. Herbal medicines are rich in active ingredients that are natural macromolecules. Ginsenoside is the main active ingredient of ginseng, which has a variety of pharmacological effects and is considered to have potential value in the treatment of human diseases. Modern pharmacological studies have shown that ginsenosides Rg2 and Rh1 have strong pharmacological activities in the nervous system, with protective effects on nerve cells, improved resistance to neuronal injury, modulation of neural activity, resistance to cerebral ischemia/reperfusion injury, improvement of brain damage after eclampsia hemorrhage, improvement of memory and cognitive deficits, treatment of AD and vascular dementia, alleviation of anxiety, pain, and inhibition of ionic-like behavior. In this article, we searched the pharmacological research literature of Rg2 and Rh1 in the field of neurological diseases, summarized the latest research progress of the two ginsenosides, and reviewed the pharmacological effects and mechanisms of Rg2 and Rh1, which provided a new way of thinking for the research of the active ingredients in ginseng anti-neurological diseases and the development of new drugs

Mechanism of action of vinegared Cornu Cervi Degelatinatum in suppressing spleen kidney yang deficient ulcerative colitis through NCK2-JNK pathway

Background: As a traditional Chinese herbal medicine, Cornu Cervi Degelatinatum (CCD) has the effect of warming the kidney to support yang, astringing, and stopping bleeding, and is used for spleen kidney yang deficient (SKYD). This experiment was to investigate the therapeutic effects of different processes of CCD on SKYD type ulcerative colitis (UC) rats and to explore its impact on the intestinal flora of rats. Methods: ELISA was used to study the anti-inflammatory activity of Cornu Cervi Degelatinatum processed with water (WCCD) and Cornu Cervi Degelatinatum processed with vinegar (VCCD). 16SrRNA and transcriptome sequencing were used to detect the composition of rat intestinal flora and gene expression; RT-PCR and Western blot were used to verify the role of WCCD and VCCD in treating UC. Results: WCCD and VCCD have therapeutic effects on UC, could reduce tissue damage. VCCD performed better in improving Bacteroidetes/Firmicutes ratios and species evenness and abundance; performed better in increasing the quantity of lactobacillus. VCCD simultaneously inhibit the intestinal inflammatory response through NCK2, PAK4, and JNK signaling pathways. Conclusions: WCCD and VCCD play a therapeutic role in UC by regulating the proportion of different flora in the intestinal flora. VCCD regulates the intestinal flora and inflammatory response by interfering with the NCK2, PAK4 and JNK signaling pathways

Protective Effect of Baicalin on Chlorpyrifos-Induced Liver Injury and Its Mechanism

Chlorpyrifos (CPF) plays a vital role in the control of various pests in agriculture and household life, even though some studies have indicated that CPF residues pose a significant risk to human health. Baicalin (BA) is a flavonoid drug with an obvious effect on the prevention and treatment of liver diseases. In this study, the protective effect of BA in vitro and in vivo was investigated by establishing a CPF-induced AML12 cell damage model and a CPF-induced Kunming female mouse liver injury model. The AML12 cell damage model indicated that BA had a good positive regulatory effect on various inflammatory factors, redox indexes, and abnormal apoptosis factors induced by CPF. The liver injury model of female mice in Kunming showed that BA significantly improved the liver function indexes, inflammatory response, and fibrosis of mice. In addition, BA alleviated CPF-induced AML12 cell damage and Kunming female mouse liver injury by enhancing autophagy and regulating apoptosis pathways through Western blotting. Collectively, these data suggest that the potential mechanism of BA is a multi-target and multi-channel treatment for chlorpyrifos-induced liver injury

Sedative and hypnotic effects of supercritical carbon dioxide fluid extraction from Schisandra chinensis in mice

Schisandra chinensis is a traditional Chinese medicine that has been used for treating insomnia and neurasthenia for centuries. Lignans, which are considered to be the bioactive components, are apt to be extracted by supercritical carbon dioxide. This study was conducted to investigate the sedative and hypnotic activities of the supercritical carbon dioxide fluid extraction of S. chinensis (SFES) in mice and the possible mechanisms. SFES exhibited an obvious sedative effect on shortening the locomotor activity in mice in a dose-dependent (10–200 mg/kg) manner. SFES (50 mg/kg, 100 mg/kg, and 200 mg/kg, intragstrically) showed a strong hypnotic effect in synergy with pentobarbital in mouse sleep, and reversal of insomnia induced by caffeine, p-chlorophenylalanine and flumazenil by decreasing sleep latency, sleep recovery, and increasing sleeping time. In addition, it produced a synergistic effect with 5-hydroxytryptophan (2.5 mg/kg, intraperitoneally). The behavioral pharmacological results suggest that SFES has significant sedative and hypnotic activities, and the mechanisms might be relevant to the serotonergic and γ-aminobutyric acid (GABA)ergic system

Study on Dihydromyricetin Improving Aflatoxin Induced Liver Injury Based on Network Pharmacology and Molecular Docking

Aflatoxin B1 (AFB1) is a toxic food/feed contaminant and the liver is its main target organ, thus it poses a great danger to organisms. Dihydromyricetin (DHM), a natural flavonoid compound, can be used as a food additive with high safety and has been shown to have strong hepatoprotective effects. In this experiment, PPI network and KEGG pathway analysis were constructed by network pharmacological analysis technique using software and platforms such as Swiss, String, and David and Cytoscape. We screened AFB1 and DHM cross-targets and pathways of action, followed by molecular docking based on the strength of binding affinity of genes to DHM. In addition, we exposed AFB1 (200 μg/kg) to mice to establish a liver injury model. Histological observation, biochemical assay, oxidative stress indicator assay, TUNEL staining and Western blot were used to evaluate the liver injury. Network pharmacological results were screened to obtain 25 cross-targets of action and 20 pathways of action. It was found that DHM may exert anti-hepatic injury effects by inhibiting the overexpression of Caspase-3 protein and increasing the expression of Bcl-2 protein. DHM (200 mg/kg) was found to reduce AFB1-induced liver indices such as alanine aminotransferase (ALT) and aspartate acyltransferase (AST), and attenuate hepatic histopathological damage through animal models. Importantly, DHM inhibited malondialdehyde (MDA) formation in liver tissue and attenuated AFB1-induced oxidative stress injury by increasing glutathione-S-transferase (GST) glutathione (GPX) catalase (CAT) and superoxide dismutase (SOD). Meanwhile, DHM also restored the expression of anti-apoptotic protein Bcl-2 and antioxidant proteins, Nrf2, Keap1 and its downstream HO-1, and down-regulated the expression of pro-apoptotic proteins Bax and Caspase-3 in AFB1-induced liver tissues. The results confirmed that liver injury caused by AFB1 exposure could be alleviated by DHM, providing valuable guidance for in-depth study of DHM in the treatment of liver-related diseases, and laying the foundation for in-depth development and utilization of DHM

Extraction, Structural Analysis, and Biofunctional Properties of Exopolysaccharide from Lactiplantibacillus pentosus B8 Isolated from Sichuan Pickle

Two novel exopolysaccharides, named LPB8-0 and LPB8-1, were isolated and purified from Lactiplantibacillus pentosus B8. Moreover, their structure and bioactivities were evaluated through chemical and spectral means. The study results demonstrated that LPB8-0 was primarily composed of mannose and glucose and had an average molecular weight of 1.12 × 104 Da, while LPB8-1 was composed of mannose, glucose, and galactose and had an average molecular weight of 1.78 × 105 Da. Their carbohydrate contents were 96.2% ± 1.0% and 99.1% ± 0.5%, respectively. The backbone of LPB8-1 was composed of (1→2)-linked α-D-Manp and (1→6)-linked α-D-Manp. LPB8-0 and LPB8-1 had semicrystalline structures with good thermal stability (308.3 and 311.7 °C, respectively). SEM results displayed that both LPB8-0 and LPB8-1 had irregular thin-slice shapes and spherical body structures. Additionally, an emulsifying ability assay confirmed that LPB8-0 and LPB8-1 had good emulsifying activity against several edible oils, and this activity was retained under acidic, neutral, and high temperature conditions. Furthermore, an antioxidant assay confirmed that LPB8-1 had stronger scavenging activity than LPB8-0. Overall, these results provide a theoretical basis for the potential application of these two novel exopolysaccharides as natural antioxidants and emulsifiers in the food and pharmaceutical industries

Soil dissolved organic carbon in terrestrial ecosystems: Global budget, spatial distribution and controls

Aims Soil dissolved organic carbon (DOC) is a primary form of labile carbon in terrestrial ecosystems, and therefore plays a vital role in soil carbon cycling. This study aims to quantify the budgets of soil DOC at biome and global levels and to examine the variations in soil DOC and their environmental controls. Location Global. Time period 1981-2019. Methods We compiled a global dataset and analysed the concentration and distribution of DOC across 10 biomes. Results Large variations in DOC are found among biomes across space and the soil DOC concentration declines exponentially along soil depths. Tundra has the highest soil DOC concentration in 0-30 cm soils [453.75 (95% confidence interval: 324.95-633.5) mg/kg], whereas tropical and temperate forests have relatively lower DOC concentrations, ranging from 30.20 (24.78-36.80) to 54.54 (49.77-59.77) mg/kg. DOC generally accounts for < 1% of total organic carbon in soils, and DOC in 0-30 cm contributes more than half of the total DOC in the 0-100 cm soil profile. Furthermore, variations in DOC are primarily controlled by soil texture, moisture, and total organic carbon. Main conclusions A global synthesis is combined with an empirical model to extrapolate the DOC concentration along soil profiles across the globe, and global budgets of DOC are estimated as 7.20 Pg C in the top 0-30 cm and 12.97 Pg C in the 0-100 cm soil profile, respectively, with a considerable variation among biomes. The strong soil texture control but weak total organic carbon (TOC) control on DOC variations suggest that the investigation of physical protection of soil organic carbon might need to expand to consider the labile C in soils. The global maps of DOC concentration serve as a benchmark for validating land surface models in estimating carbon storage in soils