Cascading effects of hypobaric hypoxia on the testis: insights from a single-cell RNA sequencing analysis.

Most mammals tolerate exposure to hypobaric hypoxia poorly as it may affect multiple regulatory mechanisms and inhibit cell proliferation, promote apoptosis, limit tissue vascularization, and disrupt the acid-base equilibrium. Here, we quantified the functional state of germ cell development and demonstrated the interaction between the germ and somatic cells via single-cell RNA sequencing (scRNA-seq). The present study elucidated the regulatory effects of hypobaric hypoxia exposure on germ cell formation and sperm differentiation by applying enrichment analysis to genomic regions. Hypobaric hypoxia downregulates the genes controlling granule secretion and organic matter biosynthesis, upregulates tektin 1 (TEKT1) and kinesin family member 2C (KIF2C), and downregulates 60S ribosomal protein 11 (RPL11) and cilia- and flagella-associated protein 206 (CFAP206). Our research indicated that prosaposin-G protein-coupled receptor 37 (PSAP-GPR37) ligands mediate the damage to supporting cells caused by hypobaric hypoxic exposure. The present work revealed that hypoxia injures peritubular myoid (PTM) cells and spermatocytes in the S phase. It also showed that elongating spermatids promote maturation toward the G2 phase and increase their functional reserve for sperm-egg binding. The results of this study provide a theoretical basis for future investigations on prophylactic and therapeutic approaches toward protecting the reproductive system against the harmful effects of hypobaric hypoxic exposure.

Association between hydrogen sulfide and OSA-associated hypertension: a clinical study.

PURPOSE: We sought to unravel the role of hydrogen sulfide (H2S) in the development of hypertension in patients with obstructive sleep apnea (OSA). METHODS: The study sample included 80 patients with OSA and 45 healthy controls. All subjects underwent measurement of blood pressure (BP) and serum H2S level in the morning. Twentynine of the 39 patients with OSA and concomitant hypertension and 23 of the 41 patients with OSA but no concomitant hypertension received continuous positive alveolar pressure (CPAP) therapy for 4 weeks. Twenty-four-hour ambulatory BP and serum H2S were determined before and after CPAP. Respiratory indices including apnea hypopnea index (AHI), lowest oxygen saturation (SaO2), and length of time < 90% saturated (T90) were determined by polysomnography. RESULTS: Associations between H2S, BP, respiratory indices, and changes with CPAP were analyzed. OSA patients had significantly higher systolic BP (p = 0.003) and diastolic BP (p = 0.009) and lower H2S levels (p = 0.02) compared to healthy controls. H2S negatively correlated with AHI (p = 0.005), T90 (p = 0.009), morning systolic BP (p = 0.02), and morning diastolic BP (p = 0.03). All respiratory indices were significantly improved (p < 0.05) after CPAP in OSA patients with or without hypertension. BP was significantly reduced and H2S significantly increased after CPAP in OSA patients with hypertension (p < 0.05) but not in OSA patients without hypertension (p > 0.05). CONCLUSION: Multivariate linear regression analysis demonstrated that 24h systolic BP and 24h diastolic BP correlated with H2S as well as their changes after CPAP treatment. Reduction in H2S may play a role in the pathogenesis of hypertension in patients with OSA.

Comparison of the Effects and Inhibitory Pathways of the Constituents from Gynostemma pentaphyllum against LPS-Induced Inflammatory Response.

Saponins, the primary phytochemicals contributing to the health properties of G. pentaphyllum were frequently studied. However, compounds responsible for its bioactivities were still poorly understood. The saponin-rich fraction (GPMS), 3- O-[2G-( E)-Coumaroyl-3G- O-ß-d-glucosyl-3R- O-ß-d-glucosylrutinoside] (KCGG), gypenoside XLVI and gypenoside L were obtained by purification of G. pentaphyllum. The compounds were examined and compared with GPMS for their inhibitory effects on LPS-induced nitric oxide (NO) production. GPMS and KCGG differed in their inhibitory capacities against pro-inflammatory cytokines secretion. GPMS exhibited strong inhibition on inducible nitric oxide synthase (iNOS) and interleukin-6 (IL-6) mRNA expression but weak inhibition on tumor necrosis factor-α (TNF-α) and interleukin-1ß mRNA expression. KCGG was better at inhibiting iNOS, IL-6, TNF-α, and cyclooxygenase-2 (COX-2) mRNA expression. GPMS showed similar inhibitory potency on mitogen-activated protein kinase phosphorylation and nuclear factor-κB (NF-κB) activation, as evidenced by their regulatory effects on LPS-induced P65 phosphorylation, NF-κB nuclear translocation, IκBα phosphorylation and degradation, IκKα/ß phosphorylation, c-Jun N-terminal kinase phosphorylation, P38 phosphorylation, and COX-2 expression. KCGG was more powerful in inhibiting the NF-κB pathway, suggesting that KCGG might be used in the management of inflammatory-associated diseases in which NF-κB played pivotal roles. Furthermore, KCGG might be mainly responsible for the predominant effects of GPMS.

Bioassay-guided isolation and identification of anticancer and antioxidant compounds from Gynostemma pentaphyllum (Thunb.) Makino.

Gynostemma pentaphyllum (Thunb.) Makino is a medicinal and edible plant in China whose buds and leaves are used for making a popular kind of tea drink. The anticancer and antioxidant properties of the ethyl acetate (EA) and n-butanol (n-Bu) fractions provide a basis for conducting experiments for isolation and identification of key compounds that may be responsible for the aforementioned properties of G. pentaphyllum. Four compounds were isolated from the two fractions using ODS packing column, silica gel column, polyamide column, Sephadex LH-20 gel column and HPLC. With the aid of 1H, 13C NMR and mass spectrometry, they were identified as 3,4-dihydroxy phenyl-O-ß-d-glucoside, gypenoside XLVI, gypenoside L and ginsenoside Rd. 3,4-Dihydroxy phenyl-O-ß-d-glucoside showed the strongest DPPH (97.23%) and ABTS (101.37%) scavenging effect and ferric ion reducing power (FRAP value 0.8846), which may be closely related to the hydrogen atoms of phenolic hydroxyls. Gypenoside L and ginsenoside Rd displayed the highest inhibition of tumor cell proliferation of A549 and MCF-7 cell lines, which had to do with the chemical structure of the compounds bearing glycosylated parts and free hydroxyls at the 20th or 21st carbon atom of dammarane-type saponin.

Beneficial effects of antidepressant mirtazapine in functional dyspepsia patients with weight loss.

AIM: To explore the effects and mechanism of action of antidepressant mirtazapine in functional dyspepsia (FD) patients with weight loss. METHODS: Sixty depressive FD patients with weight loss were randomly divided into a mirtazapine group (MG), a paroxetine group (PG) or a conventional therapy group (CG) for an 8-wk clinical trial. Adverse effects and treatment response were recorded. The Nepean Dyspepsia Index-symptom (NDSI) checklist and the 17-item Hamilton Rating Scale of Depression (HAMD-17) were used to evaluate dyspepsia and depressive symptoms, respectively. The body composition analyzer was used to measure body weight and fat. Serum hormone levels were measured by ELISA. RESULTS: (1) After 2 wk of treatment, NDSI scores were significantly lower for the MG than for the PG and CG; (2) After 4 or 8 wk of treatment, HAMD-17 scores were significantly lower for the MG and PG than for the CG; (3) After 8 wk of treatment, patients in the MG experienced a weight gain of 3.58 ± 1.57 kg, which was significantly higher than that observed for patients in the PG and CG. Body fat increased by 2.77 ± 0.14 kg, the body fat ratio rose by 4%, and the visceral fat area increased by 7.56 ± 2.25 cm(2); and (4) For the MG, serum hormone levels of ghrelin, neuropeptide Y (NPY), motilin (MTL) and gastrin (GAS) were significantly upregulated; in contrast, those of leptin, 5-hydroxytryptamine (5-HT) and cholecystokinin (CCK) were significantly downregulated. CONCLUSION: Mirtazapine not only alleviates symptoms associated with dyspepsia and depression linked to FD in patients with weight loss but also significantly increases body weight (mainly the visceral fat in body fat). The likely mechanism of mirtazapine action is regulation of brain-gut or gastrointestinal hormone levels.

Chinese medicines with sedative-hypnotic effects and their active components.

The main pharmacological effects of sedative agents are sedation, hypnosis, antianxiety, and antidepression. Traditional Chinese medicine (TCM) has a long history of clinical experience in treating insomnia. This review focuses mainly on the role of active ingredients from TCM in the treatment of insomnia. Single herbs and their active ingredients from TCM with hypnotic effects are summarized through reviewing the relevant literature published in the past 20 y. The active ingredients are divided into alkaloids, terpenoids, and volatile oils, flavonoids, lignanoids and coumarins, saponins, and others. Current studies on TCM in treating insomnia are described from the aspects of active ingredients, sources, experimental models and methods, results, and mechanisms. In addition, Chinese compound prescriptions developed from a variety of single herbs with sedative-hypnotic effects are introduced. The acting pathways of TCM are covered from the perspectives of regulating central neurotransmitters, influencing sleep-related cytokines, and improving the structure of the central nervous system.