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Gestational diabetes mellitus (GDM) is characterized by an initial diagnosis of glucose intolerance during pregnancy. There is increasing evidence supporting the association between GDM and the inhibited development of several organs in offspring. In the present study, a murine GDM model was established in mice by intraperitoneal injection of streptozotocin to evaluate the effect of maternal diabetes on the initiation of meiosis in female germ cells of offspring. The effect of GDM on the initiation of meiosis in the offspring was evaluated by reverse transcription‑quantitative polymerase chain reaction, flow cytometry and hematoxylin and eosin staining. The results showed that, compared with the control group, fetal ovary growth was inhibited, the expression levels of meiosis‑specific genes, stimulated by retinoic acid gene 8, synaptonemal complex protein, and DNA meiotic recombinase were inhibited, and the number of primordial/primary follicles was reduced in the GDM group. These may have been induced by an increase of apoptosis and inhibition of growth, as the mRNA levels of p21, a vital G1 cell cycle inhibitor, and apoptotic genes were upregulated, whereas the expression levels of genes important in folliculogenesis were decreased in the GDM group. In conclusion, the data obtained in the present study suggested that maternal diabetes may impair the initiation of meiosis and ovarian growth via growth inhibition, cell cycle arrest and the induction of apoptosis. [ABSTRACT FROM AUTHOR]

A previous study reported that Yi Guan Jian (YGJ) may increase the proliferation and differentiation of hepatic oval cells in a rat liver cirrhosis model. The aim of the present study was to investigate the effect and mechanism of action of YGJ on inducing hepatic differentiation in bone marrow‑derived mesenchymal stem cells (BM‑MSCs) via stromal‑cell derived factor‑1 (SDF‑1). Murine BM‑MSCs were isolated with whole bone marrow adherence, then identified by immunocytochemical staining and flow cytometry. Passage 2 cells were divided into 8 groups and their differentiation was induced by cell factors added to the medium, including hepatocyte growth factor (HGF), SDF‑1 and YGJ. Each of the cell factors was used alone and any two or three of them were combined to establish different cell microenvironments in the different treatment groups. Albumin (ALB) was selected as a hepatocellular marker and cytokeratin‑18 (CK‑18) as a cholangiocellular marker. The protein and mRNA expression levels of ALB and CK‑18 were used to determine the differentiation of BM‑MSCs using immunocytochemical staining, western blotting and reverse transcription‑quantitative polymerase chain reaction on days 7, 14, 21 and 28 during induction. The relative expression levels of ALB and CK‑18 resulted in time‑dependent increases in the groups supplemented only with HGF, SDF‑1 or YGJ. Combination treatment of any two HGF, SDF‑1 and YGJ led to a higher expression of ALB and CK‑18 compared with only one cell factor treatment. Additionally, when all three were used in a combined treatment the expression levels of ALB and CK‑18 occurred at an earlier time and was higher overall. Therefore, the present study suggested that YGJ had an effect on inducing hepatic differentiation in BM‑MSCs via SDF‑1 and may act in a synergistic manner with HGF and SDF‑1. [ABSTRACT FROM AUTHOR]

The present study aimed to investigate the role of transcription factor E3 (TFE3) in the regulation of proliferation in renal adenocarcinoma cells. The LV‑TFE3 overexpression (OE) lentivirus and negative control CON195 (NC) lentivirus were transfected into the ACHN cell line. Protein expression of FLAG‑tag TFE3 was determined using western blot analysis. Differences in cell proliferation, plate clone formation and cell cycle distribution between OE and NC groups were compared using MTT, plate colony formation and flow cytometry assays, respectively. The levels of mammalian target of rapamycin (mTOR) and phosphorylated ribosomal protein S6 (p‑rpS6) were analyzed by western blotting. Cell proliferation and colony formation increased significantly in the OE group compared with the NC group. The % of cells in the G1 and G2 phases of the cell cycle decreased, while the % of cells in the S phase of the cell cycle increased in the OE group compared with the NC group. In addition, mTOR and p‑rpS6 levels were increased in the OE group compared with the NC group. The results of the present study demonstrated that TFE3 overexpression resulted in increased ACHN cell proliferation and plate clone formation. TFE3 may promote renal tumor growth by regulating cell cycle progression and activating the phosphatidylinositol 3‑kinase/AKT serine/threonine kinase 1/mTOR signaling pathway. [ABSTRACT FROM AUTHOR]

Oridonin is an active constituent isolated from the traditional Chinese herb Rabdosia rubescens, which exerts antitumor effects in experimental and clinical settings. However, its antitumor effects and underlying mechanisms on prostate cancer cells have not yet been clearly identified. In the present study, the androgen-independent prostate cancer PC3 and DU145 cell lines were used as models to investigate the effects and possible mechanisms of oridonin on cellular proliferation and apoptosis. Results demonstrated that oridonin inhibited cellular proliferation, and was able to significantly induce G2/M cell cycle arrest and apoptosis. Detailed signaling pathway analysis by western blotting demonstrated that the expression levels of p53 and p21 were upregulated, whereas the expression of cyclin-dependent kinase 1 was downregulated following oridonin treatment, which led to cell cycle arrest in the G2/M phase. Oridonin also upregulated the proteolytic cleaved forms of caspase-3, caspase-9 and poly (ADP-ribose) polymerase. Furthermore, the protein expression levels of B-cell lymphoma 2 were decreased and those of Bcl-2-associated X protein were increased following oridonin treatment. In addition, oridonin treatment significantly inhibited the expression of phosphoiniositide-3 kinase (PI3K) p85 subunit and the phosphorylation of Akt. The downstream gene murine double minute 2 was also downregulated, which may contribute to the elevated expression of p53 following oridonin treatment. In conclusion, the results of the present study suggested that oridonin is able to inactivate the PI3K/Akt pathway and activate p53 pathways in prostate cancer cells, resulting in the suppression of proliferation and the induction of caspase-mediated apoptosis. [ABSTRACT FROM AUTHOR]

Yi Guan Jian decoction (YGD) may induce the differentiation of bone marrow mesenchymal stem cells (BMSCs) into hepatocyte-like cells (HLCs); however, the underlying mechanisms remain to be elucidated. The present study aimed to investigate this process. To do this, a dimethylnitrosamine (DMN)-induced liver cirrhosis mouse model was established. The mice from the model group were randomly divided into three subgroups: i) Negative control, ii) hepatocyte growth factor and iii) YGD. The overall health, liver function and histological alterations were monitored. The expression of a-smooth muscle actin (α-SMA), C-X-C chemokine receptor type 4 (CXCR4), extracellular signal-regulated kinase (ERK1/2), nuclear factor κB p65 subunit (NF-κB p65) and β-catenin were measured by immunohistochemistry, western blotting and reverse transcription-quantitative polymerase chain reaction. Following administration of DMN, the overall health of the mice significantly decreased, with an increase in pathological developments and liver damage resulting in a decrease in liver function. Immunohistochemistry revealed that the expression of α-SMA, CXCR4, ERK1/2, NF-κB p65 and β-catenin was upregulated. Following treatment with YGD, the overall health, liver function and pathology improved. The mRNA and protein expression levels of CXCR4 and ERK1/2 were upregulated, where as α-SMA, NF-κB p65 and β-catenin levels were downregulated. The results demonstrated that YGD may induce the differentiation of BMSCs into HLCs to reverse DMN-induced liver cirrhosis; this may be achieved via an upregulation of the SDF-1/CXCR4 axis to activate the mitogen activated protein kinase/ERK1/2 signaling pathway. [ABSTRACT FROM AUTHOR]

Late-onset hypogonadism is defined as a condition caused by a decline in the levels of testosterone with aging. One of the major factors contributing to the low levels of testosterone is the accumulation of reactive oxygen species (ROS) in Leydig cells during the ageing process. Peroxiredoxin 2 (Prdx2), a member of the peroxiredoxin family, is an antioxidant protein, the predominant function of which is to neutralize ROS. However, its role in Leydig cells remains to be elucidated. In the present study, primary Leydig cells were exposed to low concentrations of hydrogen peroxide (H2O2) to induce oxidative stress. Cell apoptosis was measured using an Annexin V fluorescein isothiocyanate/propidium iodide apoptosis detection kit and flow cytometry. The level of testosterone was determined by radioimmunoassay, and the mRNA and protein expression levels of Prdx2 were detected by reverse transcription-polymerase chain reaction and western blotting, respectively. The results revealed a significant increase in cell apoptosis and decrease in testosterone production. In addition, the expression of Prdx2 was decreased by H2O2 in a dose- and time-dependent manner, and this decrease may have been caused by the induction of its molecular structure transformation due to H2O2 elimination. The above findings indicated that Prdx2 may prevent H2O2 accumulation in Leydig cells, and may be important in oxidative stress-induced apoptosis and decreased testosterone production. [ABSTRACT FROM AUTHOR]

Gliomatosis cerebri (GC) is a rare glial neoplasm, characterized by extensive diffuse brain infiltration and relative preservation of the underlying architecture. In the present case report, a patient with type 2 GC, which mimicked the clinicoradiological course of acute viral encephalitis, is presented. A 56-year-old male presented with fever, dizziness, headache and numbness in the right extremities three days prior to admission to hospital. The cerebrospinal fluid (CSF) showed mild pleocytosis. Brain magnetic resonance imaging (MRI) revealed hyperintensity on fluid-attenuated inversion recovery images in the left frontal, temporal, insular lobes and in the left thalamus. No signal enhancement was observed following gadolinium administration. The patient was diagnosed with acute viral encephalitis of unknown cause and received a 10-day course of acyclovir, intravenously. At the follow-up three months later, the patient had personality changes and memory deterioration. The results from the follow-up MRI revealed no remarkable changes. At the follow-up six months after presentation, the patient had expressive aphasia and severe headaches. Subsequently, the patient had two tonic-clonic seizure onsets. The results from the MRI showed an increase in lesion size, more edema around the lesion and irregular enhancement in the left frontal lobe. However, the lesions in the left temporal and insular lobes and in the left thalamus were nearly unchanged. Magnetic resonance spectroscopy (MRS) showed elevated choline (Cho)/creatine (Cr) and Cho/N-acetylaspartate (NAA) ratios, as well as decreased NAA/Cr ratios. Surgery was performed and the neuropathological diagnosis of WHO grade III astrocytoma was confirmed. Thus, it is important to pay attention to the differential diagnoses of GC and acute viral encephalitis in patients who have widespread MRI lesions. A brain biopsy is recommended for a diagnosis in this case. [ABSTRACT FROM AUTHOR]