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This is a study on the relationship between the protective effect of ginsenoside Rg1 on senescent neural stem cells and Wnt-β/catenin signaling pathway. Background. Recent studies have shown that overactivation of the Wnt/β-catenin signaling pathway is closely related to stem cell senescence. Whether Rg1 delays the senescence of NSCs is related to the regulation of this signaling pathway. Methods. The whole brain of Nestin-GFP transgenic newborn rat was extracted, and NSCs were extracted and cultured to P3 generation. The following indicators were detected: (1) NSC culture identification, (2) the effect of LiCl on the proliferation and survival rate of NSCs, (3) the effect of ginsenoside Rg1 on the proliferation and survival of NSCs, (4) the growth of NSCs in each group observed by an optical microscope, (5) the cell cycle of each group detected by flow cytometry, (6) the proliferative ability of each group detected by BrdU, (7) the fluorescence intensity of Nestin and Sox2 of NSCs in each group observed by a fluorescence microscope, (8) the positive rate of senescence staining analyzed by SA-β-Gal staining, (9) the localization of β-catenin in NSCs observed by laser confocal microscopy, and (10) the changes of the Wnt/β-catenin pathway-related proteins in each group detected by Western blotting. Results. LiCl activates the Wnt/β-catenin pathway and promotes mouse neural stem cell senescence. Ginsenoside Rg1 promotes proliferation of neural stem cells and inhibits Wnt/β-catenin pathway activation. Conclusions. LiCl can activate the Wnt/β-catenin signaling pathway of NSCs, and ginsenoside Rg1 can antagonize the senescence of NSCs caused by activation of the Wnt/β-catenin signaling pathway and delay brain aging. [ABSTRACT FROM AUTHOR]

Natural killer (NK) cells recognize stress-activated NK group 2, member D (NKG2D) ligands in tumors. In the present study, the expression levels of NKG2D ligands were examined in four lung cancer cell lines (A549, PLA801D, NCI-H157 and NCI-H520). In the A549 cells, the expression of MHC class I polypeptiderelated sequence (MIC)A/B and UL16 binding protein (ULBP)1 was weak, the expression of ULBP2 was typical, and neither ULBP3 nor ULBP4 were expressed. The mechanism underlying the regulatory effect of a cancer treatment agent on the expression of NKG2D ligands was investigated using the proteasome inhibitor MG132. Following treatment for 8 h with MG132, the transcription levels of MICB and ULBP1 were upregulated 10.62- and 11.09-fold, respectively, and the expression levels of MICB and ULBP1 were increased by 68.18 and 23.65%, respectively. Notably, MICB exhibited significant time-dependent change. MG132 increased the transcription of MICB by acting at a site in the 480-bp MICB upstream promoter. The activity of the MICB promoter was upregulated 1.77-fold following treatment with MG132. MG132 treatment improved the cytotoxicity of NK cells, which was partially blocked by an antibody targeting NKG2D, and more specifically the MICB molecule. The expression of MICB induced by MG132 was inhibited by KU-55933 [ataxia telangiectasia mutated (ATM) kinase inhibitor], wortmannin (phosphoinositide 3 kinase inhibitor) and caffeine (ATM/ATM-Rad3-related inhibitor). The phosphorylation of checkpoint kinase 2 (Chk2), an event associated with DNA damage, was observed following treatment with MG132. These results indicated that MG132 selectively upregulates the expression of MICB in A549 cells, and increases the NKG2D-mediated cytotoxicity of NK cells. The regulatory effect of MG132 may be associated with the activation of Chk2, an event associated with DNA damage. The combination of MG132 with NK cell immunotherapy may have a synergistic effect that improves the therapeutic effect of lung cancer treatment. [ABSTRACT FROM AUTHOR]

The present study investigated the effect and underlying mechanisms of ginsenoside Rg1 (Rg1) in attenuating subacute liver injury induced by D-galactose (D-gal) in mice. Specific Pathogen Free (SPF) male C57BL/6J mice were randomly divided into 3 groups: i) D-gal-administration group (D-gal group), where the mice were intraperitoneally administrated with D-gal (120 mg/kg/day for 42 days); ii) D-gal + Rg1 group where the mice were treated with 120 mg/kg/day D-gal for 42 days and with Rg1 at a dose of 20 mg/kg/day for 35 days. The first dose of Rg1 was administered on the 8th day of treatment with D-gal; and iii) the normal control group, where the mice were injected with an equal volume of saline for 42 days. The day following the final injections in all groups, peripheral blood was collected and serum was prepared to measure the contents of aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin (TBiL), advanced glycation end products (AGEs) and 8-hydroxy-2 deoxyguanosine (8-OH-dG). Liver tissue homogenates were prepared to measure the contents of malondialdehyde (MDA) and glutathione (GSH), and the activities of glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD). Paraffin section were prepared to observe the microscopic structure of the liver. Transmission electron microscopy was used to observe the ultrastructure of hepatocytes. Frozen section were prepared and stained with senescence-associated β-galactosidase to detect the relative optical density value of senescence-associated markers. Compared with the D-gal group, the contents of AST, ALT, TBiL, AGEs and MDA significantly decreased in the D-gal + Rg1 group, while the activities of SOD and GSH-Px markedly increased, and liver injury and degenerative alterations of hepatocytes were reduced. Administration of Rg1 induced a protective effect on D-gal-induced liver injury in mice by inhibiting the oxidative stress, reducing DNA damage and decreasing the AGE content. [ABSTRACT FROM AUTHOR]

miR-362 is a recently discovered member of the microRNA family, and it modulates a variety of physical activities and plays an important role in the occurrence and development of many tumors. However, the biological functions of hsa-miR-362-5p in non-small-cell lung carcinoma (NSCLC) are unknown. Transwell assay and colony formation were used to determine the migration, invasion, and proliferation of NSCLC cells in vitro. A subcutaneous tumor model in nude mice was established to detect NSCLC tumor growth in vivo. The direct binding of miR-362 to the 3'UTR of Semaphorin 3A (Sema3A) was confirmed by luciferase reporter assay. In this study, we found that the level of miR-362 was higher in NSCLC tissues than in adjacent normal tissues and that the level of miR-362 expression was also elevated in five NSCLC cell lines (A549, 95-D, H1299, H292, and H460) relative to a human normal lung epithelial cell line (BEAS2B). Furthermore, miR-362 promoted NSCLC cell invasion, migration, and colony formation in vitro and tumor formation in vivo. Next, we identified the miR-362 target gene Sema3A, which is significantly correlated with metastasis. Sema3A expression was increased in normal tissues relative to NSCLC tissues. This result is consistent with the fact that miR-362 expression is negatively correlated with Sema3A expression in clinical tissue samples and indicated that miR-362 can regulate Sema3A expression in NSCLC cells and consequently affect NSCLC invasion, migration, and colony formation. Taken together, these findings on the newly identified miR-362/Sema3A axis elucidate the molecular mechanism of NSCLC invasion and migration and could lead to a potential therapeutic target in NSCLC treatment. [ABSTRACT FROM AUTHOR]

With the growing population, aging, extended lifespans and anti‑aging have become popular areas of research in the life and social sciences. With increasing age, the structure and function of the testes, the spermatogenetic and androgen‑producing organ in the male reproductive system, gradually declines. Ginsenoside Rg1 is an extract of Panax ginseng in traditional Chinese medicine. The extract facilitates anti‑aging through its anti‑inflammatory and antioxidant properties. However, it has not been reported whether ginsenoside Rg1 delays testicular aging. The present study established D‑galactose (D‑gal)‑induced aging mouse models to examine the protective effects of ginsenoside Rg1 on the structure and function of the testes, and the underlying mechanism. A total of 60 healthy specific pathogen‑free male C57BL/6 mice were randomly divided into four groups: Control group; Rg1 group; D‑gal + Rg1 group; and D‑gal group. The tissues of the mice were used for further experiments. The present study further investigated the effects of Rg1 on the volume of serum testosterone, the testicular index, testicular microscopic structures, the senescence of spermatogenetic cells, the apoptosis of spermatogenetic cells, the activity of the antioxidant enzymes, the levels of inflammatory cytokines, and the levels of S‑phase kinase‑associated protein (p19), cyclin‑dependent kinase inhibitor 1 (p21) and cellular tumor antigen p53 (p53) in D‑gal‑induced aging mice. In general, compared with the D‑gal group, the treatment of Rg1 increased the testis index, serum testosterone level and the active content of superoxide dismutase and the total antioxidant capacity. The percentage of senescence‑associated β‑galactosidase‑positive cells, the level of apoptosis and the volume of methane dicarboxylic aldehyde, tumor necrosis factor‑α, interleukin (IL)‑1β and IL‑6 in testicular tissues were significantly decreased, and the expression of p19, p53 and p21 was downregulated due to the treatment with Rg1. The results of the present study demonstrated that ginsenoside Rg1 was able to protect the testes against D‑gal‑induced aging in mice. In addition, the protective effect of Rg1 may be achieved via antioxidation and downregulation of the p19/p53/p21 signaling pathway. [ABSTRACT FROM AUTHOR]

A survey of more than 6000 participants from four distinct non-polluted and polluted regions in China was conducted to evaluate the body burden of cadmium (Cd) on the Chinese populations using urinary Cd (UCd) as a biomarker. The findings revealed that the UCd level was 1.24 μg/g creatinine (μg/g cr) for the sample population from non-polluted Shanghai, and the UCd levels exceeded 5 μg/g cr, which is the health-based exposure limit set by the World Health Organization (WHO), in 1.1% of people. The mean UCd levels in moderately polluted (Hubei and Liaoning) and highly polluted areas (Guizhou) were 4.69 μg/g cr, 3.62 μg/g cr and 6.08 μg/g cr, respectively, and these levels were 2.9 to 4.9 times the levels observed in Shanghai. Notably, the UCd levels exceeded the recently updated human biomonitoring II values (i.e., intervention or “action level”) in 44.8%–87.9% of people from these areas compared to only 5.1%–21.4% of people in Shanghai. The corresponding prevalence of elevated UCd levels (> WHO threshold, 5 μg/g cr) was also significantly higher (30.7% to 63.8% vs. 1.1%), which indicates that elevated Cd-induced health risks to residents in these areas. Age and region were significant determinants for UCd levels in a population, whereas gender did not significantly influence UCd. [ABSTRACT FROM AUTHOR]

This is a study on the relationship between the protective effect of ginsenoside Rg1 on senescent neural stem cells and Wnt- β /catenin signaling pathway. Background . Recent studies have shown that overactivation of the Wnt/ β -catenin signaling pathway is closely related to stem cell senescence. Whether Rg1 delays the senescence of NSCs is related to the regulation of this signaling pathway. Methods . The whole brain of Nestin-GFP transgenic newborn rat was extracted, and NSCs were extracted and cultured to P3 generation. The following indicators were detected: (1) NSC culture identification, (2) the effect of LiCl on the proliferation and survival rate of NSCs, (3) the effect of ginsenoside Rg1 on the proliferation and survival of NSCs, (4) the growth of NSCs in each group observed by an optical microscope, (5) the cell cycle of each group detected by flow cytometry, (6) the proliferative ability of each group detected by BrdU, (7) the fluorescence intensity of Nestin and Sox2 of NSCs in each group observed by a fluorescence microscope, (8) the positive rate of senescence staining analyzed by SA- β -Gal staining, (9) the localization of β -catenin in NSCs observed by laser confocal microscopy, and (10) the changes of the Wnt/ β -catenin pathway-related proteins in each group detected by Western blotting. Results . LiCl activates the Wnt/ β -catenin pathway and promotes mouse neural stem cell senescence. Ginsenoside Rg1 promotes proliferation of neural stem cells and inhibits Wnt/ β -catenin pathway activation. Conclusions . LiCl can activate the Wnt/ β -catenin signaling pathway of NSCs, and ginsenoside Rg1 can antagonize the senescence of NSCs caused by activation of the Wnt/ β -catenin signaling pathway and delay brain aging., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2019 Yue Xiang et al.)

CD147, encoded by BSG , is a highly glycosylated transmembrane protein that belongs to the immunological superfamily and expressed on the surface of many types of cancer cells. While CD147 is best known as a potent inducer of extracellular matrix metalloproteinases, it can also function as a key mediator of inflammatory and immune responses. To systematically elucidate the function of CD147 in cancer cells, we performed an analysis of genome-wide profiling across the Cancer Cell Line Encyclopedia (CCLE). We showed that CD147 mRNA expression was much higher than that of most other genes in cancer cell lines. CD147 varied widely across these cell lines, with the highest levels in the ovary (COLO704) and stomach (SNU668), intermediate levels in the lung (RERFLCKJ, NCIH596 and NCIH1651) and lowest levels in hematopoietic and lymphoid tissue (UT7, HEL9217, HEL and MHHCALL3) and the kidney (A704 and SLR20). Genome-wide analyses showed that CD147 expression was significantly negatively correlated with immune-related genes. Our findings implicated CD147 as a novel regulator of immune-related genes and suggest its important role as a master regulator of immune-related responses in cancer cell lines. We also found a high correlation between the expression of CD147 and FOXC1, and proved that CD147 was a direct transcriptional target of FOXC1. Our findings demonstrate that FOXC1 is a novel regulator of CD147 and confirms its role as a master regulator of the immune response., Competing Interests: CONFLICTS OF INTEREST The authors declare no conflicts of interest.

Mycobacteriosis is on the increase. Nontuberculous mycobacteria (NTM) are resistant to most antituberculosis drugs naturally. We determined the complete genome sequence of a novel NTM strain, JDM601, of the Mycobacterium terrae complex, which was isolated from a patient with tuberculosis-like disease and with various antibiotic resistances.

In present study, a method for genotyping for human platelet antigen (HPA) systems by means of the polymerase chain reaction amplification with sequence-specific primers (PCR-SSP) technique was developed and employed to determine the human platelet antigen frequencies in the Chinese population. Primers sets were designed to allow PCR amplification for five systems using the same assay conditions. Platelets from 110 random Chinese blood donors were typed for human platelet alloantigens HPA-1 to -5 by the method. The results showed that the HPA genotypic frequencies observed in the 110 donors were 0.91 and 0.09 for HPA-1a and HPA-1b, 0.86 and 0.14 for HPA-2a and HPA-2b, 0.60 and 0.40 for HPA-3a and HPA-3b, 0.92 and 0.08 for HPA-4a and HPA-4b, and 0.85 and 0.15 for HPA-5a and HPA-5b, respectively. In conclusion the method is feasible and practical and may be available to typing for HPA in the clinical laboratories.