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Background: Hepatocyte growth factor (HGF) plays a role in neuronal survival and development, and has been implicated in neurodegenerative diseases. We sought to examine the associations of the CSF HGF with Alzheimer's disease (AD) pathology and cognitive function.Methods: A total of 238 participants (including 90 cognitively normal (CN) and 148 mild cognitive impairment (MCI)) who had measurements of CSF HGF were included from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. Multiple linear regression models were utilized to explore the cross-sectional associations of CSF HGF with AD biomarkers (including Aβ42, pTau, and tTau proteins) in non-demented participants. Moreover, linear mixed-effects regression models were utilized to explore the longitudinal associations of HGF subgroups with cognitive function. Mediation analyses were utilized to explore the mediation effects of AD markers.Results: MCI individuals had significantly increased CSF HGF compared with the CN individuals. Results of multiple linear regressions showed significant correlations of CSF HGF with CSF Aβ42, pTau, and tTau in non-demented participants. Higher level of baseline CSF HGF was associated with faster cognitive decline. Influences of the baseline CSF HGF on cognition were partially mediated by Aβ42, pTau, and tTau pathologies.Conclusions: High concentrations of HGF in CSF may be related to faster cognitive decline. The cognitive consequences of higher CSF HGF partly stem from AD pathology, which suggests that the CSF HGF may be an attractive biomarker candidate to track AD progression. [ABSTRACT FROM AUTHOR]

Background: Herein, we report the genetic, clinical, molecular and biochemical features of two Han Chinese pedigrees with suggested maternally transmitted non-syndromic hearing loss., Aim: To investigate the pathophysiology of hearing loss associated with mitochondrial tRNA mutations., Methods: Sixteen subjects from two Chinese families with hearing loss underwent clinical, genetic, molecular, and biochemical evaluations. Biochemical characterizations included the measurements of tRNA levels using lymphoblastoid cell lines derived from five affected matrilineal relatives of these families and three control subjects., Results: Three of the 16 matrilineal relatives in these families exhibited a variable seriousness and age-at-onset (8 years) of deafness. Analysis of mtDNA mutation identified the novel homoplasmic tRNA Ile 4268T>C mutation in two families both belonging to haplogroup D4j. The 4268T>C mutation is located in a highly conserved base pairing (6U-67A) of tRNA Ile . The elimination of 6U-67A base-pairing may change the tRNA Ile metabolism. Functional mutation was supported by an approximately 64.6% reduction in the level of tRNA Ile observed in the lymphoblastoid cell lines with the 4268T>C mutation, in contrast to the wild-type cell lines. The reduced level of tRNA was below the proposed threshold for normal respiration in lymphoblastoid cells. However, genotyping analysis did not detect any mutations in the prominent deafness-causing gene GJB2 in any members of the family., Conclusion: These data show that the novel tRNA Ile 4268T>C mutation was involved in maternally transmitted deafness. However, epigenetic, other genetic, or environmental factors may be attributed to the phenotypic variability. These findings will be useful for understanding families with maternally inherited deafness., Competing Interests: Conflict-of-interest statement: The authors have no conflict of interest related to the manuscript., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Objective: To investigate the protective effect of lycopene against cryopreservation injury of post-thawing human sperm and its mechanism., Methods: Semen samples were collected from 25 volunteers, each sample equally divided into four parts to be cryopreserved with cryoprotectant only (Ly0 control) or cryoprotectant + lycopene at the concentrations of 2 (Ly2), 5 (Ly5), and 10 µmol/L (Ly10), respectively. Before and after thawing, the semen samples were subjected to computer-assisted semen analysis ( CASA) for sperm kinematics, flow cytometry for sperm apoptosis, thiobarbituric acid assay for malondialdehyde (MDA) concentration, and JC-1 fluorescent staining for the sperm mitochondrial membrane potential (MMP)., Results: After cryopreservation, sperm motility was markedly decreased in all the groups (P < 0.01). The rate of sperm apoptosis was significantly lower in the Ly5 group than in the Ly0 control ([25.68 ± 4.36]% vs [33.26 ± 4.78]%, P < 0.05), while sperm MMP remarkably higher in the former than in the latter ([66.18 ± 14.23]% vs [55.24 ± 12.31]%, P < 0.05). The Ly2, Ly5 and Ly10 groups showed no statistically significance differences in the MDA level from the Ly0 control (P > 0.05)., Conclusion: Addition of lycopene at a proper concentration to cryoprotectant may reduce oxidative damage to sperm mitochondria in the freezing-thawing process, attenuate oxidative stress injury induced by reactive oxygen species to sperm plasma membrane, and improve the anti-apoptosis ability of sperm.

Lung cancer is the leading cause of cancer death in the world. Schizandrin B (Sch B) is one of the main dibenzocyclooctadiene lignans present in the fruit of Schisandra chinensis (Schisandraceae). Sch B has multiple functions against cancer. The aim of this study was to determine the effect of Sch B on the proliferation, cell cycling, apoptosis and invasion of lung adenocarcinoma A549 cells by MTT, flow cytometry, wound healing and transwell invasion assays. Treatment with Sch B inhibited the proliferation of A549 cells in a dose-dependent manner. Sch B induced cell cycle arrest at G0/G1 phase by down-regulating the expression of cyclin D1, cyclin-dependent kinase (CDK)4, and CDK6, but up-regulating p53 and p21 expression in A549 cells. Furthermore, Sch B triggered A549 cell apoptosis by increasing Bax, cleaved caspase-3, 9, Cyto C, but decreasing Bcl-2 and PCNA expression. In addition, Sch B inhibited the invasion and migration of A549 cells by down-regulating the expressions of HIF-1, VEGF, MMP-9 and MMP-2. Therefore, Sch B has potent anti-tumor activity and may be a promising traditional Chinese medicine for human lung carcinoma.