ABSTRACT
Globozoospermia has been reported to be a rare but severe causation of male infertility, which results from the failure of acrosome biogenesis and sperm head shaping. Variants of dpy-19-like 2 (DPY19L2) are highly related to globozoospermia, but related investigations have been mainly performed in patients from Western countries. Here, we performed a screening of DPY19L2 variants in a cohort of Chinese globozoospermic patients and found that five of nine patients carried DPY19L2 deletions and the other four patients contained novel DPY19L2 point mutations, as revealed by whole-exome sequencing. Patient 3 (P3) contained a heterozygous variant (c.2126+5G>A), P6 contained a homozygous nonsense mutation (c.1720C>T, p.Arg574*), P8 contained compound heterozygous variants (c.1182-1184delATC, p.Leu394_Ser395delinsPhe; c.368A>T, p.His123Arg), and P9 contained a heterozygous variant (c.1182-1184delATCTT, frameshift). We also reported intracytoplasmic sperm injection (ICSI) outcomes in the related patients, finding that ICSI followed by assisted oocyte activation (AOA) with calcium ionophore achieved high rates of live births. In summary, the infertility of these patients results from DPY19L2 dysfunction and can be treated by ICSI together with AOA.
Subject(s)
Adult , Female , Humans , Male , Pregnancy , Acrosome , China , Codon, Nonsense , Membrane Proteins/genetics , Point Mutation , Pregnancy Outcome , Pregnancy Rate , Sequence Deletion , Sperm Head , Sperm Injections, Intracytoplasmic , Teratozoospermia/genetics , Exome SequencingABSTRACT
<p><b>OBJECTIVE</b>To evaluate the effects of ginsenoside Rg-1 on the proliferation and osteogenic differentiation of human periodontal ligament stem cells (hPDLSCs) and to explore the possible application on the alveolar bone regeneration.</p><p><b>METHODS</b>To determine the optimum concentration, the effects of ginsenoside Rg-1 ranging from 10 to 100 μmol/L were evaluated by 3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-di-phenytetrazoliumromide, alkaline phosphatase activity and calcium deposition. Expressions of runt-related transcription factor 2, collagen alpha-2(I) chain, osteopontin, osteocalcin protein were examined using real-time polymerase chain reaction.</p><p><b>RESULTS</b>Compared with the control group, a certain concentration (10 μmol/L) of the Rg-1 solution significantly enhanced the proliferation and osteogenic differentiation of hPDLSCs (P<0.05). However, concentrations that exceeds 100 μmol/L led to cytotoxicity whereas concentrations below 10 nmol/L showed no significant effect as compared with the control.</p><p><b>CONCLUSION</b>Ginsenoside Rg-1 can enhance the proliferation and osteogenic differentiation of hPDLSCs at an optimal concentration of 10 μmol/L.</p>
Subject(s)
Adolescent , Humans , Young Adult , Alkaline Phosphatase , Metabolism , Biomarkers , Metabolism , Calcification, Physiologic , Cell Differentiation , Cell Proliferation , Cell Separation , Cell Shape , Cells, Cultured , Flow Cytometry , Ginsenosides , Pharmacology , Osteoblasts , Metabolism , Osteogenesis , Genetics , Periodontal Ligament , Cell Biology , Real-Time Polymerase Chain Reaction , Stem Cells , Cell Biology , Time FactorsABSTRACT
The effects of a non-selective inhibitor of cyclo-oxygenase (COX) indomethacin, and exogenous prostaglandin E(2) (PGE(2)) on A(delta) units and C units in the saphenous nerve of diabetic hyperalgesic rats were studied. The results showed that the conduction velocity of A(delta) units and C units and their mechanical threshold in diabetic hyperalgesic rats were obviously decreased, and a small number of A(delta) units (4/24) and C units (2/18) produced increased spontaneous activities. Intraperitoneal injection of indomethacin in diabetic hyperalgesic rats significantly relieved mechanical hyperalgesia, and resulted in a decrease in spontaneous afferent activities of the A(delta) units and C units. Subcutaneous injection of exogenous PGE(2) into the diabetic hyperalgesic and control rats produced a significant decrease in mechanical threshold of the A(delta) units and C units, and elicited discharge from 3 A(delta) units (3/24) and 1 C unit (1/18) in diabetic hyperalgesic rats and from 2 A(delta) units (2/13) in control rats. The present data suggest that the synthesis and release of PGs are increased in diabetic neuropathy, PGs can sensitize and /or activate A(delta) units and C units and elicit hyperalgesia and allodynia in diabetic rats.
Subject(s)
Animals , Male , Rats , Afferent Pathways , Diabetes Mellitus, Experimental , Femoral Nerve , Hyperalgesia , Indomethacin , Pharmacology , Pain Threshold , Prostaglandin Antagonists , Pharmacology , Rats, Sprague-DawleyABSTRACT
Objective To study the mechanism of killing and apoptosis-inducing effects of Capparis spinosa alkaloid (CSA) on human hepatocarcinoma cell line HepG2. Methods The killing effect of CSA on human hepatocarcinoma cell line HepG2 was studied by MTT method. Morphological observation of HepG2 cells was carried out by fluorescence microscope. Results The CSA had obvious cytotoxicity on the HepG2 in a dose-dependent manner and its IC50 value was 142.82 ?g/mL. The HepG2 cells showed the characteristic morphologic changes of apoptosis by the function of CSA and the apoptosis percentage is higher than that of the natural one. The progress of cells cycle from S phase to G2 phase had been blocked by CSA. The intracellular Ca2+ level had been increased by the function of CSA, which was positively related with drug concentration. Conclusion CSA has obviously killing and apoptosis-inducing effects on human hepatocarcinoma cell line HepG2 and calcium overload might also be invovled in these events.