Beneficial Effects of Catalpol Supplementation during In Vitro Maturation of Porcine Cumulus-Oocyte Complexes.

Oxidative stress degrades oocytes during in vitro maturation (IVM). Catalpol, a well-known iridoid glycoside, exhibits antioxidant, anti-inflammatory, and antihyperglycemic effects. In this study, catalpol supplementation was tested on porcine oocyte IVM and its mechanisms. Corticalgranule (GC) distribution, mitochondrial function, antioxidant capacity, DNA damage degree, and real-time quantitative polymerase chain reaction were used to confirm the effects of 10 µmol/L catalpol in the maturation medium during IVM. Catalpol treatment significantly increased the first-pole rate and cytoplasmic maturation in mature oocytes. It also increased oocyte glutathione (GSH), mitochondrial membrane potential and blastocyst cell number. However, DNA damage as well as reactive oxygen species (ROS) and malondialdehyde (MDA) levels. Mitochondrial membrane potential and blastocyst cell number were also increased. Thus, the supplementation of 10 µmol/L catalpol in the IVM medium improves porcine oocyte maturation and embryonic development.

[Short-term and long-term effects of all-ceramic onlay on restoration of premolars and its influence on dental function].

PURPOSE: To investigate the short-term and long-term effects of all-ceramic onlay on restoration of premolars and its influence on dental function. METHODS: Ninety-five premolars receiving root canal treatment in People's Hospital of Peking University from January 2017 to January 2018 were enrolled, and randomly divided into two groups based on different repairing methods. Patients in the control group (n=47) received full crown restoration, while patients in the experimental group(n=48) received all-ceramic onlay restoration. The success, survival and failure rates of the teeth were compared. The United States Public Health Service(USPHS) and occlusal function of the prosthesis were compared 6, 12 and 36 months after treatment. The data were processed using SPSS 19.0 software package. RESULTS: The success and survival rate of the experimental group were higher than those of the control group, but without significant difference (P＞0.05). The morphology, marginal integrity, marginal coloration, surface texture, secondary caries, gingival health and proximal contacts showed no significant difference between the two groups 12 months after treatment(P＞0.05). Thirty-six months after treatment, the marginal integrity, marginal coloration and surface texture showed no significant difference between the two groups (P＞0.05), while the morphology, secondary caries, gingival health and proximal contacts were significantly better in the experimental group than in the control group (P＜0.05). The occlusal function between the affected side and contralateral side of both groups showed no significant difference 6, 12 and 36 months after treatment(P＞0.05). CONCLUSIONS: All-ceramic onlay restoration of premolars has high success and survival rate, and good short-term and long-term restoration effect, which is beneficial to improve the occlusal function of the affected teeth.

Effect of Montelukast sodium combined with Budesonide aerosol on airway function and T lymphocytes in asthmatic children.

Objectives: To investigate the effects of Montelukast sodium combined with Budesonide aerosol on airway function and T lymphocytes in asthmatic children. Methods: The records of 86 pediatric asthma patients, treated in Huzhou Maternal and Child Health Hospital from February 2020 to March 2021, were studied retrospectively. Of them, 40 children received routine treatment + budesonide atomizer (Group-I), and 46 patients received routine treatment + budesonide atomizer + montelukast sodium (Group-II). The improvement in airway and lung function, and T-lymphocyte count in both groups after 3 months of corresponding treatment were analyzed. Results: After three months of treatment, expiratory flow rate (TEF) with the tidal volume of 25%, 50% and 75%, was significantly higher in Group-II than Group-I (P<0.05). CD8+ expression in Group-II was lower, and CD3+, CD4+ and CD4+/CD8+ were higher than those in Group-I (P<0.05). There was a significant difference in the levels of inflammatory factors between the two groups. The levels of IL-4, IL-5 and IFN-γ in Group-II were lower than those in Group-I(P<0.05). Conclusions: In the clinical treatment of asthmatic children, in combination with routine treatment, budesonide atomizer and montelukast sodium can effectively promote the improvement of airway function, regulate T lymphocytes levels, reduce inflammatory reaction and improve the total clinical curative effect.

Discovery of Zanubrutinib (BGB-3111), a Novel, Potent, and Selective Covalent Inhibitor of Bruton's Tyrosine Kinase.

Aberrant activation of Bruton's tyrosine kinase (BTK) plays an important role in pathogenesis of B-cell lymphomas, suggesting that inhibition of BTK is useful in the treatment of hematological malignancies. The discovery of a more selective on-target covalent BTK inhibitor is of high value. Herein, we disclose the discovery and preclinical characterization of a potent, selective, and irreversible BTK inhibitor as our clinical candidate by using in vitro potency, selectivity, pharmacokinetics (PK), and in vivo pharmacodynamic for prioritizing compounds. Compound BGB-3111 (31a, Zanubrutinib) demonstrates (i) potent activity against BTK and excellent selectivity over other TEC, EGFR and Src family kinases, (ii) desirable ADME, excellent in vivo pharmacodynamic in mice and efficacy in OCI-LY10 xenograft models.

Design, synthesis, and structure-activity-relationship of a novel series of CXCR4 antagonists.

The important roles of the CXCL12/CXCR4 axis in numerous pathogenic pathways involving HIV infection and cancer metastasis make the CXCR4 receptor an attractive target for the development of therapeutic agents. Through scaffold hybridization of a few known CXCR4 antagonists, a series of novel aminopyrimidine derivatives was developed. Compound 3 from this new scaffold demonstrates excellent binding affinity with CXCR4 receptor (IC50 = 54 nM) and inhibits CXCL12 induced cytosolic calcium increase (IC50 = 2.3 nM). Furthermore, compound 3 possesses good physicochemical properties (MW 353, clogP 2.0, PSA 48, pKa 6.7) and exhibits minimal hERG and CYP isozyme (e.g. 3A4, 2D6) inhibition. Collectively, these results strongly support further optimization of this novel scaffold to develop better CXCR4 antagonists.

A novel role of human holliday junction resolvase GEN1 in the maintenance of centrosome integrity.

The maintenance of genomic stability requires accurate genome replication, repair of DNA damage, and the precise segregation of chromosomes in mitosis. GEN1 possesses Holliday junction resolvase activity in vitro and presumably functions in homology driven repair of DNA double strand breaks. However, little is currently known about the cellular functions of human GEN1. In the present study we demonstrate that GEN1 is a novel centrosome associated protein and we characterize the various phenotypes associated with GEN1 deficiency. We identify an N-terminal centrosome localization signal in GEN1, which is required and sufficient for centrosome localization. We report that GEN1 depletion results in aberrant centrosome numbers associated with the formation of multiple spindle poles in mitosis, an increased number of cells with multi-nuclei, increased apoptosis and an elevated level of spontaneous DNA damage. We find homologous recombination severely impaired in GEN1 deficient cells, suggesting that GEN1 functions as a Holliday junction resolvase in vivo as well as in vitro. Complementation of GEN1 depleted cells with various GEN1 constructs revealed that centrosome association but not catalytic activity of GEN1 is required for preventing centrosome hyper-amplification, formation of multiple mitotic spindles, and multi-nucleation. Our findings provide novel insight into the biological functions of GEN1 by uncovering an important role of GEN1 in the regulation of centrosome integrity.

Study on olfactory function in GABAC receptor/channel rho1 subunit knockout mice.

The GABAC receptor/channel rho1 subunit plays an important role in the inhibitory pathway and sensory processing in the retina and spinal cord. Although it was suggested that the rho1 subunit plays a role in olfactory sensations, the precise role of the rho1 subunit in olfactory sensory function is still not clear. In the present study, we report that olfactory function was significantly altered in rho1 subunit knockout (rho1-/-) mice compared to its wildtype counterpart. The rho1 subunit mRNA, detected by reverse transcription (RT)-PCR experiments, was expressed in the olfactory bulb of wild-type mice. Expression of rho1 subunit proteins in the olfactory bulb was detected by immunohistochemistry in mitral cells in the mitral cell layer. Neither mRNA nor proteins of the rho1 subunit were found in olfactory bulb neurons in rho1-/- mice. Alterations of olfactory function in rho1-/- mutant mice compared to their wildtype littermates were examined by olfactory behavioral test. We found that sensitivity to the smell of citral odorant in rho1-/- mice was significantly greater compared to that of wildtype mice. Our results indicate that the GABAC rho1 subunit acts in olfactory bulb neurons as an inhibitory modulator that affects the process of olfactory signaling transmission.

[Detection of hepatitis C virus antibody in saliva and its clinical significance].

OBJECTIVE: To detect hepatitis C virus (HCV) antibody in saliva and find its clinical significance. METHODS: Sera and saliva samples from eighty-six patients were parallely detected HCV antibodies (anti-HCV) with EIA using a modified protocol. RESULTS: Twenty-nine of 86 patients were positive for anti-HCV in sera samples; and, 27/29 were also anti-HCV positive with saliva samples. For the 57 anti-HCV negative sera, the saliva samples were all negative. Comparing with the results of sera, the sensitivity (93.1%, 27/29) and specificity (100%, 57/57) of salivary detection for anti-HCV could be accepted. CONCLUSION: If the results of sera are considered as "golden standard", these results suggest that tests on saliva can be useful in HCV clinical diagnosis and epidemiological studies for estimating the prevalence of HCV in populations.