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The novel coronavirus (SARS-CoV-2) appeared in2019 in Wuhan, China, and rapidly developed into a global pandemic. The disease has affected not only health care systems and economies worldwide but has also changed the lifestyles and habits of the majority of the world's population. Among the potential targets for SARS-CoV-2 therapy, the viral spike glycoprotein has been studied most intensely, due to its key role in mediating viral entry into target cells and inducing a protective antibody response in infected individuals. In the present manuscript the molecular mechanisms that are responsible for SARS-CoV-2 infection are described and a progress report on the status of SARS-CoV-2 research is provided. A brief review of the clinical symptoms of the condition and current diagnostic methods and treatment plans for SARS-CoV-2 are also presented and the progress of preclinical research into medical intervention against SARS-CoV-2 infection are discussed. [ABSTRACT FROM AUTHOR]

The aim of the present study was to investigate the association between Ki‑67 expression and radiomics features of dynamic contrast‑enhanced magnetic resonance imaging (DCE‑MRI) in patients with invasive breast cancer. A total of 53 cases with low‑Ki‑67 expression (Ki‑67 proliferation index <14%) and 106 cases with high‑Ki‑67 expression (Ki‑67 proliferation index >14%) were investigated. A systematic approach was applied that focused on the automated segmentation of lesions and extraction of radiomics features. For each lesion 5 morphology, 4 gray‑scale histogram and 6 texture features were obtained, and statistical analyzes were performed to assess the differences in these features between the low‑ and high‑Ki‑67 expressions. One morphology metric (area), 3 gray‑scale histogram indexes (standard deviation, skewness and kurtosis) and 3 texture features (contrast, homogeneity and inverse differential moment) demonstrated a significant difference (P<0.05), with low‑Ki‑67 expression lesions tending to be smaller, clearer and heterogeneous when compared with the high‑Ki‑67 expressed cases. These results may provide a noninvasive means to better understand the proliferation of breast cancer. [ABSTRACT FROM AUTHOR]

The development of targeted tyrosine kinase inhibitors (TKIs) has succeeded in altering the course of chronic myeloid leukemia (CML). However, a number of patients have failed to respond or experienced disease relapse following TKI treatment. Proviral integration site for moloney murine leukemia virus‑1 (PIM‑1) is a serine/threonine kinase that participates in regulating apoptosis, cell cycle, signal transduction and transcriptional pathways, which are associated with tumor progression, and poor prognosis. SMI‑4a is a selective PIM‑1 kinase inhibitor that inhibits PIM‑1 kinase activity in vivo and in vitro. The present study aimed to explore the mechanism underlying the antitumor effect of SMI‑4a in K562 and imatinib‑resistant K562 (K562/G) cell lines. It was demonstrated that SMI‑4a inhibited the proliferation of K562 and K562/G cells using a WST‑8 assay. The Annexin V‑propidium iodide assay demonstrated that SMI‑4a induced apoptosis of K562 and K562/G cells in a dose‑, and time‑dependent manner. Furthermore, Hoechst 33342 staining was used to verify the apoptosis rate. The clone formation assay revealed that SMI‑4a significantly inhibited the colony formation capacity of K562 and K562/G cells. Western blot analysis demonstrated that SMI‑4a decreased phosphorylated (p)‑Ser9‑glycogen synthase kinase (GSK) 3β/pGSK3β and inhibited the translocation of β‑catenin. In addition, the downstream gene expression of apoptosis regulator Bax and poly(ADP‑ribose) polymerase‑1 was upregulated, and apoptosis regulator Bcl‑2 and Myc proto‑oncogene protein expression levels were downregulated. Immunofluorescence results demonstrated changes in the expression level of β‑catenin in the plasma and nucleus. The results of the present study suggest that SMI‑4a is an effective drug to use in combination with current chemotherapeutics for the treatment of imatinib‑resistant CML. [ABSTRACT FROM AUTHOR]

Osteosarcoma is the most common primary bone tumor that occurs in children and adolescents. Osteosarcoma has a poor prognosis and is often unresponsive to chemotherapy. Therefore, it remains a challenge to identify a novel strategy to effectively treat osteosarcoma. The present study demonstrated a novel opportunity in osteosarcoma treatment using the natural compound plumbagin. Plumbagin reduced cell viability in osteosarcoma cells but not normal bone cells, as determined by MTT assay and colony formation assay. Plumbagin induced cell apoptosis by mitochondrial dysfunction, which in turn promoted Ca2+ release and endoplasmic reticulum (ER)‑stress, as determined by DAPI staining assay, DNA fragmentation assay, flow cytometry and western blotting analysis. In addition, plumbagin improved reactive oxygen species (ROS) generation, as determined by flow cytometry. Finally, these apoptotic cascades activated caspase‑3 and caspase‑9 to elicit apoptosis response. Our results demonstrated the anticancer effect of plumbagin by inducing cell apoptosis in osteosarcoma cells. In conclusion, plumbagin activated the apoptosis signaling pathway through eliciting ROS, ER stress, mitochondria dysfunction, and finally causing caspase activation. These results indicated that plumbagin may serve as potential antitumor drug by its multifunctional effects in osteosarcoma. [ABSTRACT FROM AUTHOR]

Bone marrow‑derived mesenchymal stem cells (BMSCs) and adipose tissue‑derived mesenchymal stem cells (ADSCs) are able to differentiate into neuron‑like cells when exposed to small molecule compounds, however the specific differences in their neuronal differentiation abilities remain to be fully elucidated. The present study aimed to compare the neuronal differentiation abilities of BMSCs and ADSCs. BMSCs and ADSCs from the same Sprague Dawley rats were isolated and cultured for use. The proliferation capacity was revealed using a cell counting method. Following BMSCs and ADSCs induction by four types of small‑molecular compounds, the expression of various neuronal markers and the secretion of several neurotrophic factors were detected by immunofluorescence, western blotting, reverse transcription‑quantitative polymerase chain reaction and ELISA. It was demonstrated that the ADSCs exhibited an increased proliferation capacity compared with BMSCs, according to cumulative population doubling analyses. Following a 7‑day neuronal induction period, BMSCs and ADSCs exhibited a neuron‑like morphology, and were termed neuronal induced (NI)‑BMSCs and NI‑ADSCs. They expressed neuronal markers including β‑tubulin III, microtubule associated protein 2 and choline acetyltransferase. The number of NI‑BMSCs that positively expressed the neuronal markers was significantly decreased compared with NI‑ADSCs, and the expression and secretion of the neurotrophic factors nerve growth factor and 3'‑nucleotidase in NI‑BMSCs were additionally decreased compared with NI‑ADSCs. The findings of the present study indicated that the neuronal differentiation abilities and neurotrophic factor secretion abilities of ADSCs were increased compared with BMSCs. ADSCs may therefore act as efficient candidates in cell transplantation therapy for diseases and injuries of the nervous system. [ABSTRACT FROM AUTHOR]

Hippocampal neurogenesis in temporal lobe epilepsy (TLE) may result in alteration of the excitability of neurons, which contributes to spontaneous recurrent seizures. Axon initial segment (AIS) structural and functional plasticity is important in the control of neuronal excitability. It remains to be elucidated whether the plasticity of AIS occurs in hippocampal newly‑generated neurons that are involved in recurrent seizures following pilocarpine‑induced status epilepticus (SE). The present study first established a pilocarpine‑induced TLE rat model to assess the features of newborn neurons and AIS plasticity alterations using double immunofluorescence staining of Ankyrin G and doublecortin (DCX). AIS plasticity alterations include length and distance from soma in the hippocampal newly‑generated neurons post‑SE. The results of the present study demonstrated that pilocarpine‑induced epileptic rats exhibited aberrant hippocampal neurogenesis and longer DCX‑labeled cell dendrites in the dentate gyrus. Pilocarpine‑induced epileptic rats demonstrated shortened lengths of AIS and an increased distance from the soma in hippocampal newborn neurons. Mibefradil, a T/L‑type calcium blocker, reversed the alterations in length and position of AIS in hippocampal newborn neurons post‑SE, accompanied by decreased long‑term seizure activity without increased aberrant neurogenesis. These findings indicate that the plasticity of AIS in hippocampal neurogenesis may have profound consequences in epilepsy, at least in animals. [ABSTRACT FROM AUTHOR]

The present study aimed at investigating the selective enrichment of surface marker and functional microRNA (miRNA) profiles of cluster of differentiation (CD)34+ blast-derived microvesicles (MVs) from parental cells in chronic myelogenous leukemia (CML), thus providing an experimental basis for MVs to be used to predict characteristics of CD34+ blasts. Magnetic activated cell sorting and continuous differential centrifugation were used to isolate primary CML CD34+ blasts and MVs, in addition to utilizing flow cytometry to identify surface markers of CD34+ blasts and blast-derived MVs. Microarray analysis and the reverse transcription-quantitative polymerase chain reaction were performed to analyze miRNA profiles of CD34+ blasts and MVs. The results of the present study indicated that primary CML CD34+ blasts were able to release MVs, which were selectively enriched with the surface markers CD34 and CD123, and functional miRNAs from parental cells. A total of 15 miRNAs were upregulated in CD34+ blast derived-MVs compared with in CD34+ cells. Distinct Kyoto Encyclopedia of Genes and Genomes pathways and Gene Ontology terms characterized by altered gene expression and potentially associated miRNA were identified. Upregulated miRNAs in MVs were associated with cell development, tumorigenesis and signaling pathways involving ErbB and phosphoinositide 3-kinase/protein kinase B. The present study provides evidence, which increases the understanding of physiological functions of cancer-derived MVs, and aids the understanding of the roles of CD34+ blast-derived MVs in CML-associated processes. [ABSTRACT FROM AUTHOR]

The cytochrome P450 (CYP) 1A2 gene is involved in the metabolism of several carcinogens and clinically important drugs, generating a high potential for pharmacokinetic interactions. Since no data are available for Tibetan aborigines, the present study aimed to investigate the distribution of variant CYP1A2 alleles in a population living in Tibetan region of China. Genotyping analyses of CYP1A2 were conducted in 96 unrelated, healthy volunteers of Tibetan ancestry using direct sequencing assays. A total of 14 different CYP1A2 polymorphisms, including two novel variants (1690G>A and 2896C>T) in the intron region and a novel non-synonymous one (795G>C, Gln265His) were detected. CYP1A2*1A (6.77%), CYP1A2*1B (58.33%) and CYP1A2*1F (14.58%) were the most frequent defective alleles identified in the sample. The frequencies of the prevalent genotypes CYP1A2*1A/*1B, *1B/*1B, *1B/*1F were 13.54%, 16.67% and 29.17%, respectively. In addition, the novel non-synonymous variant 795G>C (Gln265His) was predicted to be benign by PolyPhen-2 and SIFT tools. The present study provides useful information on the pattern of CYP1A2 polymorphisms in Chinese Tibetan population. The current results may have potential benefits for the development of personalized medicine in the Tibetan population. [ABSTRACT FROM AUTHOR]

The aim of the present study was to explore the effect of silencing wild‑type p53‑induced phosphatase 1 (Wip1) on apoptosis of human ovarian cancer SKOV3 cells. SKOV3 cells cultured in vitro were divided into three groups: untreated cells, cells transfected with control small interfering RNA (siRNA) and cells transfected with siRNA targeting Wip1. Flow cytometry analysis was used to detect cell apoptosis. Western blot analysis was performed to determine expression of tumor protein 53 (p53), cleaved caspase‑3, caspase‑3, BCL2 associated X (Bax), BCL2 apoptosis regulator (Bcl‑2), p38 mitogen‑activated protein kinase (p38 MAPK) and phosphorylated (p)‑p38 MAPK. Reverse transcription‑quantitative polymerase chain reaction was used to detect expression of p53, Bax, Bcl‑2 and caspase‑3 mRNAs. Compared with control, apoptosis of SKOV3 cell was significantly increased following Wip1 siRNA silencing. Wip1 silencing also resulted in a significant increase of p53 and p‑p38 MAPK expression, as well as increased cleaved caspase‑3/caspase‑3 and Bax/Bcl‑2 protein ratios. No significant differences were observed in apoptosis and apoptosis‑related protein expression in the control siRNA transfected cells. The present study demonstrated that Wip1 silencing promotes apoptosis of human ovarian cancer SKOV3 cells by activation of the p38 MAPK signaling pathways and through subsequent upregulation of p53, and cleaved caspase‑3/caspase‑3 and Bax/Bcl‑2 protein ratios. Overall, the findings of the present study suggest that targeting Wip1 may be a potential therapeutic avenue for the treatment of human ovarian cancer in the future. [ABSTRACT FROM AUTHOR]

Non-small-cell lung cancer (NSCLC) may establish an immunosuppressive tumor microenvironment that is conducive to tumor growth. Natural killer (NK) cells play a pivotal role in immunological surveillance. Activation of NK cells partially depends on the interactions between killer-cell immunoglobulin-like receptors (KIRs) and human leukocyte antigen (HLA) class I ligands. We herein investigated the association of KIRs and HLA ligands with survival in metastatic NSCLC (mNSCLC) patients treated with chemotherapy in a Chinese Han population. Polymerase chain reaction with sequence-specific primers was used to type 15 KIRs at the DNA and mRNA level and 6 HLA ligands in 70 mNSCLC patients. Survival curves were estimated using the Kaplan-Meier method and compared with the log-rank test. Cox proportional hazard regression model was applied for multivariate survival analysis, with the stepwise selection, to determine independent predictors of survival. It was observed that patients with KIR2DS4del gene expression at the mRNA level or HLA-Bw4T80 exhibited poor overall survival (OS). The multivariate analysis revealed that HLA-Bw4T80 and KIR2DS4del expression were independent predictors of OS. This observation indicated that the KIR/HLA ligand is a promising predictor of survival in mNSCLC and may also provide a strategy for treatment stratification and patient management. [ABSTRACT FROM AUTHOR]

The present study aimed to prepare cisplatin (CDDP)-loaded magnetic nanoparticles (MNPs), which target folate receptors via a pH-sensitive release system (FA-PEG-NH-N=MNPs-CDDP). This is of interest for the development of intelligent drug delivery systems that target tumors of the head and neck. The chemical coprecipitation method was used to prepare ferroferric oxide MNPs. These were modified with aldehyde sodium alginate complexed with the chemotherapeutic agent, CDDP on the surface of the nanoparticles. Double hydrazine-poly(ethylene glycol; PEG) was also prepared by attaching the carboxyl group of hydrazine-folate on one side of the double hydrazine-PEG, obtaining folate-hydrazine-PEG-diazenyl. This binds the aldehyde group of sodium alginic acid on the MNP to enclose CDDP, in order that it is sequestered within the carrier. This method obtained a pH-sensitive, FA-modified CDDP-loaded MNP (FA-PEG-NH-N=MNPs-CDDP), which acts as an intelligent tumor targeting drug delivery system. The mean size of the MNPs was ~10.2±1.5 nm, the mean hydrodynamic diameter detected by laser particle sizing instruments was 176.6±1.1 nm, and the ζ-potential was -20.91±1.76 mV. The CDDP content was 0.773 mg/ml, the iron content was ~1.908 mg/ml and the maximum saturation magnetization was 16.3±0.2 emu/g. The current study produced a pH-sensitive FA-modified CDDP-loaded MNP that is stable and exhibits magnetic responsiveness, which releases CDDP in a low pH environment. [ABSTRACT FROM AUTHOR]

Neuro-Sweet disease (NSD) is Sweet disease with central nervous system (CNS) involvement. To the best of our knowledge, the present case report is the first to describe NSD complicated by endogenous infection with Mycobacterium tuberculosis. The present case report describes a male patient who developed NSD-induced meningitis, which initially manifested as a fever, headache and neck stiffness. Painful erythematous plaques subsequently developed on his face, neck and upper trunk. Brain magnetic resonance imaging was performed and the results were normal, whereas modi- fied acid-fast stain analysis of the cerebrospinal fluid (CSF) provided a positive result. The patient was thus diagnosed with viral meningitis and tuberculosis. However, subsequent skin biopsy results demonstrated neutrophilic infiltration into the dermis without vasculitis, and subsequent human leukocyte antigen typing was positive for Cw1 and negative for B51 and the patient was diagnosed with NSD. Following treatment with corticosteroids, and antiviral and anti-tuberculotic agents, the clinical symptoms were reduced and the previously abnormal findings in the CSF examinations and associated laboratory data were improved. The present case indicates that the diagnosis of NSD is not easily achieved, and early skin biopsy is vital to ensure a fast and effective diagnosis. In addition to systemic corticosteroids, comprehensive treatment is also recommended for patients with NSD complicated by additional complex medical problems. [ABSTRACT FROM AUTHOR]

The effect of vasopressin on the neuronal injury following the restoration of spontaneous circulation (ROSC) in cardiac arrest (CA) is not yet fully understood. The present study was conducted in order to investigate the effect of vasopressin alone, or in combination with epinephrine, on the ROSC and hippocampal injury in a rat model of asphyxial CA. Asphyxial CA was induced in 144 rats by clamping the tracheal tube, and animals were allocated equally into the following three groups: Treatment with vasopressin (0.8 U/kg); epinephrine (0.2 mg/kg); or vasopressin (0.8 U/kg) plus epinephrine (0.2 mg/kg). An additional 48 rats underwent a sham surgical procedure without asphyxial CA and cardiopulmonary resuscitation. Hippocampal tissue was harvested at 1, 3, 6 and 12 h post-ROSC, and the levels of p38 mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) p65 were determined using immunohistochemistry. In comparison with rats treated with epinephrine alone, higher ROSC success rates were observed in rats treated with vasopressin, or vasopressin plus epinephrine. In addition, treatment with vasopressin attenuated hippocampal injury and reduced hippocampal p38 MAPK and NF-κB expression more efficiently compared with epinephrine alone. In conclusion, treatment with vasopressin exhibits a protective effect in patients experiencing CA, and this may be attributed to the inhibition of p38 MAPK and NF-κB expression. [ABSTRACT FROM AUTHOR]

At present, variants of the 5-hydroxytryptamine receptor 2A (5-HTR2A) and interleukin-6 (IL-6) genes may be susceptible markers to develop for obstructive sleep apnea-hypopnea syndrome (OSAHS). Therefore, the aim of the present study was to explore the potential associations between the 5-HTR2A and IL-6 single-nucleotide polymorphisms (SNPs) and OSAHS. In total there were 130 cases and 136 controls collected for genotyping of 5-HTR2A (rs6311) and IL-6 (rs1800796) SNPs. The association of these SNPs with OSAHS risk were evaluated by computing the odds ratio (OR) and 95% confidence interval (CI) from multivariate unconditional logistic regression analyses with adjustment for gender and age. The results indicated that the genotype and allele frequencies in these two loci (rs6311 and rs1800796) were not significantly different between the cases and controls. However, carrying the 'C' allele of rs6311 has a protective effect against OSAHS via the gender-specific comparison (P=0.0409; OR, 1.744; 95% CI, 1.021-2.978). The 'G' allele and 'CG' genotype distribution of rs1800796, and 'C' allele and 'CT' genotype distribution of rs6311 have significant differences between the mild and moderate group (P<0.05). Similarly, the genotype distribution of rs6311 has differences between mild and severe cases (P=0.0026). The current research demonstrated that variants of rs6311 have an association with OSAHS in males. Additionally, polymorphisms of rs6311 and rs1800796 have relevance to the severity of OSAHS. [ABSTRACT FROM AUTHOR]

Hepatitis B virus (HBV) infection is one of the major causes of hepatocellular carcinoma (HCC). Kinesin family member 4A (KIF4A) is a microtubule-based motor protein, which is upregulated in cervical and lung cancer. However, the expression of KIF4A in HBV-associated HCC, and the effect of HBV on the expression of KIF4A remain to be elucidated. In the present study, the expression profiles of KIF4A were examined in cancerous tissues and paracancerous tissues from patients with HCC, who presented with histories of chronic HBV infection, and the role of HBV in the induction of the expression of KIF4A was investigated. HepG2 cells were transfected with the pHBV1.3, HBV infectious clone and a construct, which contained the luciferase gene under the control of the KIF4A gene promoter. The results demonstrated that the expression of KIF4A was significantly higher in the HCC tissues than in the paracancerous tissues. HBV activated the KIF4A gene promoter and upregulated the mRNA and protein expression of KIF4A. Furthermore, activation of the gene expression of KIF4A increased in a pHBV1.3 concentration-dependent manner. These results provide novel insights into the understanding of HCC oncogenesis caused by HBV. [ABSTRACT FROM AUTHOR]

The toxicities of conventional chemotherapeutic agents to normal cells restrict their dosage and clinical efficacy in acute leukemia; therefore, it is important to develop novel chemotherapeutics, including natural products, which selectively target cancer-specific pathways. The present study aimed to explore the effect of the chemopreventive agent asiatic acid (AA) on the proliferation and apoptotic rate of the leukemia cell line HL-60 and investigated the mechanisms underlying its anti-tumor activity. The effect of AA on the proliferation of HL-60 cells was evaluated using the MTT assay. Annexin V-fluorescein isothiocyanate/propidium iodide double staining followed by flow cytometric analysis as well as Hoechst 33258 staining were used to analyze the apoptotic rate of the cells. Furthermore, changes of survivin, B-cell lymphoma 2 (Bcl-2), myeloid cell leukemia 1 (Mcl-1), extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and p38 expressions were detected by western blot analysis. AA blocked the growth of HL-60 cells in a dose- and time-dependent manner. The IC50-value of AA on HL-60 cells was 46.67±5.08 µmol/l for 24 h. AA induced apoptosis in a dose-dependent manner, which was inhibited in the presence of Z-DEVD-FMK, a specific inhibitor of caspase. The anti-apoptotic proteins Bcl-2, Mcl-1 and survivin were downregulated by AA in a dose-dependent manner. Concurrently, AA inhibited ERK and p38 phosphorylation in a dose-dependent manner, while JNK phosphorylation was not affected. In conclusion, the present study indicated that the p38 and ERK pathways, as well as modulation of Bcl-2 family and survivin proteins were key regulators of apoptosis induced in HL-60 cells in response to AA. [ABSTRACT FROM AUTHOR]

The pathogenesis of atherosclerosis is multi factorial. The proliferation and migration of vascular smooth muscle cells (VSMCs) are significant in the genesis and development of atherosclerosis plaques, and the degradation of VSMCs plays a crucial role in the process. Mimecan is a member of the Keratan sulfate family of proteoglycans, which are leucine-rich proteoglycans. It has been demonstrated that mimecan is associated with arteriogenesis and atherosclerosis. In the present study, the effect of mimecan on the characteristics of cultured human aortic smooth muscle cells (HASMCs) was investigated. In vitro, human mimecan was stably overexpressed in HASMCs using a lentiviral system. It was observed that the proliferation rate of HASMCs transduced with mimecan was lower compared with that of control cells; overexpression of mimecan induced HASMC apoptosis. To determine the effect of mimecan on HASMC migration, a Transwell cell culture chamber and sterile cloning cylinder assays were used, and it was noted that mimecan enhanced the migration of HASMCs horizontally and vertically. These data indicated that mimecan may be involved in the pathogenesis of atherosclerosis by regulating the proliferation, apoptosis and migration of VSMCs. [ABSTRACT FROM AUTHOR]

Non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related mortality despite the fact that great advances have been made in therapeutic treatment methods. Therefore, in the present study, the role of adenovirus- mediated retinoblastoma 94 (Ad-RB94) gene therapy in NSCLC was investigated. Following treatment with Ad-RB94, the proportion of A549 cells in the G2/M phase was increased. In the mouse xenograft model, the overexpression of RB94 inhibited the tumor growth compared with the control group and the Ad-LacZ- treated group. In the transplanted tumors, the overexpression of RB94 induced the apoptosis of tumors as well as an increase in the mRNA levels of cyclinB1. In conclusion, the results of the present study suggested that RB94 may effectively inhibit NSCLC tumor cell growth by inducing G2/M cell cycle arrest and apoptosis, indicating that RB94 may be a promising candidate for adjuvant therapy with radiation or chemotherapy in NSCLC. [ABSTRACT FROM AUTHOR]

The present study aimed to investigate the effects of the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway on the Wnt/β-catenin signaling pathway in rats with focal cerebral ischemia-reperfusion injury. A total of 96 rat focal cerebral ischemia-reperfusion models, established according to a modified version of Longa's method, were randomly divided into four groups: Sham-operated (S), cerebral ischemia-reperfusion injury (I), cerebral ischemia-reperfusion + basic fibroblast growth factor (bFGF) post-processing and, finally, cerebral ischemia-reperfusion + bFGF post-processing + PI3K inhibitor LY294002 (LY). Each group consisted of 24 rats and each group was divided into four subgroups according to the indicated reperfusion times of 12, 24, 48 and 72 h. The morphological changes of the cortical tissue and the cellular apoptosis were determined using hematoxylin and eosin staining and the terminal deoxynucleotidyl transferase dUTP nick end labeling method, respectively. The expression levels of phosphorylated (p-)Akt, glycogen synthase kinase-3β (GSK-3β) mRNA and β-catenin in the cortical tissue were detected at different time-points. The number of apoptotic cells and the expression levels of p-Akt, GSK-3β mRNA and β-catenin in the I and LY groups were significantly higher compared with those in the S group (P<0.05). In the bFGF group, the number of apoptotic cells and the mRNA expression levels of GSK-3β were significantly decreased, whereas the expression levels of p-Akt and β-catenin were significantly increased compared with those in the I and LY groups (P<0.05). In cerebral ischemia-reperfusion injury, the PI3K/Akt signaling pathway regulated β-catenin, the main member of the Wnt signaling pathway, via GSK-3β, providing information to assist in further investigation of the mechanism of β-catenin in ischemia-reperfusion injury. [ABSTRACT FROM AUTHOR]

Hydrogen sulfide (H2S) is believed to be involved in numerous physiological and pathophysiological processes, and now it is recognized as the third endogenous signaling gasotransmitter, following nitric oxide and carbon monoxide; however, the effects of H2S on inflammatory factors in acute myocardial ischemia injury in rats have not been clarified. In the present study, sodium hydrosulfide (NaHS) was used as the H2S donor. Thirty-six male Sprague Dawley rats were randomly divided into five groups: Sham, ischemia, ischemia + low-dose (0.78 mg/kg) NaHS, ischemia + medium-dose (1.56 mg/kg) NaHS, ischemia + high-dose (3.12 mg/kg) NaHS and ischemia + propargylglycine (PPG) (30 mg/kg). The rats in each group were sacrificed 6 h after the surgery for sample collection. Compared with the ischemia group, the cardiac damage in the rats in the ischemia + NaHS groups was significantly reduced, particularly in the high-dose group; in the ischemia + PPG group, the myocardial injury was aggravated compared with that in the ischemia group. Compared with the ischemia group, the levels of interleukin (IL)-1β, IL-6 and tumor necrosis factor-α (TNF-α) in the serum of rats in the ischemia + medium- and high-dose NaHS groups were significantly reduced, and the expression of intercellular adhesion molecule-1 (ICAM-1) mRNA and nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) protein in the myocardial tissues of rats was significantly reduced. In the ischemia + PPG group, the TNF-α, IL-1β and IL-6 levels in the serum were significantly increased, the expression of ICAM-1 mRNA was increased, although without a significant difference, and the expression of NF-κB was increased. The findings of the present study provide novel evidence for the dual effects of H2S on acute myocardial ischemia injury via the modulation of inflammatory factors. [ABSTRACT FROM AUTHOR]

Puerarin, a predominant isoflavonoid compound extracted from the Chinese medicinal herb Radix Puerariae, is considered to exhibit an antitumor effect. In the present study, the effects of puerarin on SMMC-7721 human hepatocellular carcinoma cells were investigated. Cell viability was assessed by MTT assay. Apoptosis was detected by flow cytometry with Annexin V-fluorescein isothiocyante staining and morphological observation of nuclear changes by Hoechst staining. The mitochondrial membrane potential (MMP) was monitored using rhodamine 123. The generation of reactive oxygen species (ROS) was quantified using dichloro-dihydro-fluorescein diacetate. Polymerase chain reaction and western blot analysis were used to detect the expression levels of apoptosis-associated genes. The results revealed that high concentrations of puerarin (500, 1,000 and 1,500 μg/ml) significantly inhibited the proliferation of SMMC-7721 cells in a time- and dose-dependent manner. Simultaneously, apoptotic rates were increased and cell morphology was changed following puerarin treatment. Furthermore, puerarin-induced apoptosis of SMMC-7721 cells was associated with loss of MMP and generation of ROS. Puerarin treatment increased caspase-3,8,9 and apoptosis-inducing factor (AIF) mRNA expression levels in SMMC-7721 cells, while the phosphorylation levels of P38, extracellular signal-regulated kinase (ERK1) and c-Jun N-terminal kinase were also increased. Furthermore, caspase-9 and AIF protein expression was upregulated. In conclusion, puerarin inhibited proliferation and induced apoptosis in SMMC-7721 cells via the mitochondria-dependent pathway; however, the specific mechanisms require further investigation. [ABSTRACT FROM AUTHOR]

GATA binding protein 1 (GATA-1) is one of the most important hematopoietic transcription factors in the production of blood cells, such as platelets, eosinophils, mast cells and erythrocytes. GATA-1 regulates the participation of microRNA (miRNAs/miRs) in erythroid differentiation under normoxia. However, GATA-1 expression and the regulation of miR-210-3p in the context of erythroid differentiation under hypoxia remain unknown. The present study examined the expression levels of GATA-1 and miR-210-3p in the model of erythroid differentiation in K562 cells under hypoxia, and determined the effects of GATA-1, miR-210-3p and SMAD2 on erythroid differentiation through lentivirus transfection experiments. The present study detected increased GATA-1 expression under hypoxia. Moreover, miR-210-3p was identified as a positive regulator of erythroid differentiation, which was upregulated both during erythroid differentiation and in GATA-1 overexpression experiments under hypoxia. Importantly, in the K562 cell model of erythroid differentiation under hypoxia, miR-210-3p was upregulated in a GATA-1-dependent manner. Using a double luciferase reporter assay, miR-210-3p was identified as a downstream target of GATA-1-mediated regulation of erythropoiesis. Gain- or loss-of-function analysis of miR-210-3p identified its importance in erythroid differentiation. Furthermore, it was found that SMAD2 may be a downstream target gene for miR-210-3p. Bioinformatics predictions suggested that SMAD2 mediated miR-210-3p-induced regulation of erythroid differentiation. Collectively, the present study provides novel insights into the miRNA regulation of erythroid differentiation. [ABSTRACT FROM AUTHOR]

The sporoderm-broken spores of Ganoderma lucidum (G. lucidum) polysaccharide (BSGLP) have been demonstrated to inhibit carcinogenesis in several types of cancer. However, to the best of our knowledge, the anticancer effects of polysaccharides extracted from the newly developed sporoderm-removed spores of G. lucidum (RSGLP) have not been assessed. The present study first compared the anticancer effects of RSGLP and BSGLP in three gastric cancer cell lines and it was found that RSGLP was more potent than BSGLP in decreasing gastric cancer cell viability. RSGLP significantly induced apoptosis in AGS cells, accompanied by downregulation of Bcl-2 and pro-caspase-3 expression levels, and upregulation of cleaved-PARP. Furthermore, RSGLP increased LC3-II and p62 expression, indicative of induction of autophagy and disruption of autophagic flux in AGS cells. These results were further verified by combined treatment of AGS cells with the late-stage autophagy inhibitor chloroquine, or early-stage autophagy inducer rapamycin. Adenoviral transfection with mRFP-GFP-LC3 further confirmed that autophagic flux was inhibited by RSGLP in AGS cells. Finally, the present study demonstrated that the RSGLP-induced autophagy and disruption of autophagic flux disruption was, at least in part, responsible for RSGLP-induced apoptosis in AGS cells. The results of the present study demonstrated for the first time that RSGLP is more effective than BSGLP in inhibiting gastric cancer cell viability, and RSGLP may serve as a promising autophagy inhibitor in the management of gastric cancer. [ABSTRACT FROM AUTHOR]