Transforming growth factor-β1(TGF-β1)has become an important biological marker and therapeutic target of clinical progression of chronic kidney diseases. Sma- and Mad-related protein (Smad)is a downstream signal transduction protein of the TGF-β family. TGF-β1 activates Smad2 and Smad3 before increasing the transcription of connective tissue growth factors in the nucleus. Smad3 promotes mesangial cell proliferation,extracellular matrix accumulation,epithelial-mesenchymal transition, leading to renal fibrosis. However,Smad2 and Smad7 play a negative regulatory role by inhibiting renal fibrosis. TGF-β1 specific inhibitor (SB431542,etc.) has antifibrosis effect,most of which is in the preclinical stage. The drugs on the market that are effective for DN,such as benzodiazepines,atorvastatin, losartan,and pirfenidone,can inhibit the expression of TGF-β1,while tripterygium wilfordii,cordyceps sinensis,and berberine can delay the process of diabetic nephropathy by reducing TGF-β1 levels.

To investigate the association of single nucleotide polymorphism 260 and 386 (SNP260 and SNP386) gene with male infertility, an electronic search was performed to identify case-control studies evaluating the relationship of SNP260 or SNP386 of deleted in azoospermia-like (DAZL) and male infertility. Review Manager 5 was used to process the meta-analysis and other statistical analysis. A total of 139 records were retrieved, of which 13 case-control studies with total 2715 patients and 1835 normozoospermic men were included. SNP260 was found not to play a functional role in male oligo/azoospermia either for Caucasians or for Asians. But for SNP386, models of allele (A/G), dominant (AA/AG + GG), co-dominant (AA/AG) and super-dominant (AA + GG/AG) had a strong correlation to spermatogenic failure with related odds ratio being 0.15 (95% confidence interval [95% CI] 0.07 to 0.34, P < 0.00001), 0.16 (95% CI 0.07 to 0.35, P < 0.00001), 0.15 (95% CI 0.06 to 0.33, P < 0.00001) and 0.15 (95% CI 0.06 to 0.33, P < 0.00001), respectively. Moreover, this correlation was only found in the Chinese Han population (decreasing around 85% risk of oligo/azoospermia infertility) and not found in India, Japan, and Caucasian countries. Our analysis demonstrated that SNP260 of DAZL did not contribute to oligo/azoospermia while SNP386 was correlated to male infertility. However, this correlation was only found in China with a country-specific and ethnicity-specific manner.

Objectives To investigate whether apoptosis can be induced by Octreotide in human hepatoma cells in vitro and elucidate the antineoplastic mechanism of Octreotide in hepatoma.Methods A cultured human hepatoma cell line,BEL-7402,was exposed to Octreotide and apoptosis was evaluated by cytochemical staining(Hochesst 33258),transmission electron microscopy,agarose gel electrophoresis and flow cytometry(FCM).Results After exposure to 0.2 μg/ml Octreotide,apoptosis with nuclear chromatin condensation as well as fragmentation,cell shrinkage and the formation of apoptotic bodies was observed using cytochemical staining and transmission electron microscopy.A DNA ladder in agarose gel electrophoresis was also displayed.FCM showed that the apoptotic cell number rose with an increase in the concentration of Octreotide(0- 2 iμg/ml).There was a positive correlation between Octreotide concentration and apoptotic rate in BEL-7402 cells(r=0.809,P＜0.05).Conclusion Apoptosis in human hepatoma cells can be induced by Octreotide,which may be related to the mechanism of antineoplastic action of Octreotide in hepatoma.

BRCA2 Protein ; Humans ; Leukemia, Myeloid, Acute

In December 2019, a cluster of patients with pneumonia of unknown cause were linked to a seafood wholesale market in Wuhan, China. Some studies found that the virus was a new kind of virus which had never been found in the human body. Then, the virus was named 2019 Novel Coronavirus (2019-nCoV) by the World Health Organization (WHO). 2019-nCoV nucleic acid detection is one of the essential indicators of NCP (Novel Coronavirus Pneumonia). Recently, some false-negative cases in China-Japan Friendship Hospital and Hangzhou Hospital led the clinical doctors to question the value of the nucleic acid detection. In this paper, more than 3 000 results of 2019-nCoV detection in Zhongnan Hospital, Wuhan University were analyzed. Attention should be paid to the root cause of false-negative results and the related countermeasures should be taken.

Objective: To investigate the effect of bilateral superior cervical ganglionectomy on cardiac remodeling and function in pressure-overloaded heart failure (HF) mice. Methods: Pressure-overloaded HF mouse model was produced by severe thoracic aorta banding (sTAB). Bilateral superior cervical ganglionectomy (SCGx) was performed 2 weeks after sTAB. Twenty four 6-week-old male C57BL/6 mice were randomized divided into 4 groups (n=6 each): control group: sham sTAB+sham SCGx; denervated group: sham sTAB+SCGx; HF group: sTAB+sham SCGx; denervated HF group: sTAB+SCGx. Cardiac function was measured by echocardiography at week 0, 1, 2, and 4 after sTAB, respectively. All mice were sacrificed at the end of week 4 and heart tissues were harvested. HE and Masson staining were performed. Immunohistochemical staining (IHC) for tyrosine hydroxylase (TH), adrenergic receptor β1 (AR-β1) and CD68 was performed. Western blot was used to determine the protein expression level of TH, B type natriuretic peptide (BNP), and AR-β1. Results: Left ventricular ejection fraction (LVEF) declined continuously in HF group. LVEF was similar between denervated HF group and control group at various time points (P>0.05). LVEF was significantly higher in denervated HF group than in HF group at the end of week 4 (P<0.05). HE staining showed that cross sectional cardiomyocyte area was significantly larger in HF group than in control group and denervated HF group (P<0.05), which was similar between denervated HF group and control group (P>0.05). Masson staining showed that fibrosis level was significantly lower in denervated HF group than in HF group (P<0.05). IHC showed that TH+nerves and CD68⁺ macrophages were significantly increased in HF mice as compared to control mice (P<0.05), whereas this change was abolished in denervated HF group. AR-β1 was significantly down-regulated in HF group compared with control group (P<0.05), which was not affected by denervation (P>0.05). Western blot demonstrated that the expression level of TH and BNP was significantly higher in HF group compared with the control group (P<0.05), whereas this difference was diminished in denervated HF group (P>0.05). Conclusion: Bilateral superior cervical ganglionectomy can reduce sympathetic innervation and macrophage infiltration in pressure overloaded failure heart, thus attenuate cardiac remodeling and improve cardiac function.
Animals ; Cross-Sectional Studies ; Ganglionectomy ; Heart Failure ; Male ; Mice ; Mice, Inbred C57BL ; Stroke Volume ; Ventricular Function, Left ; Ventricular Remodeling

OBJECTIVETo investigate the mechanisms of lysophosphatidic acid (LPA) in stimulating invasion and metastatic colonization of ovarian cancer cells.

METHODSThe metastatic ability in vivo of ovarian cancer SK-OV3, HEY, OVCAR3, and IGROV1 cells was determined in tumor-bearing nude mouse models. Matrigel assay was used to detect the changes of response in vitro of ovarian cancer cells to LPA after Rac(-) or Rac(+) adenovirus treatment. LPA-induced Rho GTPase activation was detected by GST-fusion protein binding assay.

RESULTSThe peritoneal metastatic colonization assay showed overt metastatic colonization in mice receiving SK-OV3 and HEY cell inoculation, indicating that they are invasive cells. Metastatic colonization was not detected in animals receiving OVCAR3 and IGROV1 cells, indicating that these cells are non-invasive cells. In the matrigel invasion assay, exposure to LPA led to a notably greater migratory response in metastatic SK-OV3 and HEY cells (Optical density: SK-OV3 cells: 0.594±0.023 vs. 1.697±0.049, P<0.01; HEY cells: 0.804±0.070 vs. 1.851±0.095, P<0.01). But LPA did little in the non-metastatic OVCAR3 and IGROV1 cells (Optical density A: OVCAR3 cells: 0.336±0.017 vs. 0.374±0.007, P>0.05; IGROV1 cells: 0.491±0.036 vs. 0.479±0.061, P>0.05). LPA migratory responses of ovarian cancer cells were closely related to their metastatic colonization capabilities (r = 0.983, P<0.05). Rac(-) blocked the LPA response of invasive SK-OV3 and HEY cells (LPA-induced fold increase of cell migration: SK-OV3 cells: 2.988±0.095 vs. 0.997±0.100,P=0.01; HEY cells: 2.404±0.059 vs. 0.901±0.072, P=0.01). But Rac(+) confered the non-invasive cells with LPA response and invasion capability (LPA-induced fold increase of cell migration: OVCAR3 cells: 1.072±0.080 vs. 1.898±0.078, P<0.01; IGROV1 cells: 1.002±0.044 vs. 2.141±0.057, P<0.05). Among Rho GTPases, only Rac activation was different between ovarian cancer cell lines with different metastatic capability after LPA stimulation: Cdc42 could not be activated in both the invasive and non-invasive cell lines. RhoA could be activated in both the invasive and non-invasive cell lines. Rac could be activated by LPA in the invasive ovarian cancer cell lines. However, Rac could not be activated in the non-invasive cell lines.

CONCLUSIONLysophosphatidic acid stimulates invasion and metastasis of ovarian cancer cells through Rac activation.

Animals ; Cell Movement ; Female ; Humans ; Lysophospholipids ; metabolism ; Mice ; Ovarian Neoplasms ; metabolism ; Tumor Cells, Cultured ; rho GTP-Binding Proteins ; rhoA GTP-Binding Protein

Systemic sclerosis is a disease characterized by skin and internal organ fibrosis, lacking specific therapeutic drugs and having a poor prognosis. Early diagnosis and intervention of the disease is of significant value in improving patient prognosis. This article provides a systematic review of the early diagnosis and treatment of systemic sclerosis, including early symptom recognition, laboratory testing, and drug intervention. It will provide a reference for the prevention of this disease.
Humans ; Scleroderma, Systemic/prevention & control*

Systemic sclerosis is a disease characterized by skin and internal organ fibrosis, lacking specific therapeutic drugs and having a poor prognosis. Early diagnosis and intervention of the disease is of significant value in improving patient prognosis. This article provides a systematic review of the early diagnosis and treatment of systemic sclerosis, including early symptom recognition, laboratory testing, and drug intervention. It will provide a reference for the prevention of this disease.
Humans ; Scleroderma, Systemic/prevention & control*

The mechanism underlying CD4CD25Foxp3regulatory T cells (Tregs) promoting the development of colorectal cancer (CRC) was elucidated in the present study. Forty-eight cases of colorectal carcinomas, 22 cases of colon polyps and 21 cases of normal colorectal tissues were collected. The correlation among Foxp3, IL-10 and Stat3, and the clinical relevance of these three indexes were analyzed. The results showed that the levels of Foxp3 expressed in infiltrating CD4CD25Foxp3Tregs, and IL-10 and Stat3 in CRC tissues were all significantly higher than those in polypus tissues and normal colon tissues (P< 0.01). Pearson correlation analysis indicated that the expression level of Foxp3 was positively correlated with Stat3 at mRNA level (r=0.526, P=0.036), and was positively correlated with IL-10 at protein level (r=0.314, P=0.030). The Foxp3 expressed in CD4CD25Foxp3Tregs was correlated with the histological grade, lymph node metastasis and TNM stage of CRC (P<0.05 for all). The IL-10 expression was correlated with the histological grade and TNM stage (both P<0.05). The Stat3 expression was correlated with the lymph node metastasis and TNM stage (both P<0.05). It was concluded that CD4CD25Foxp3Tregs can inhibit tumor immunity in combination with some other related inhibitory cytokines and that Foxp3 expression in CD4CD25Foxp3Tregs correlates with CRC progression.
Adult ; Aged ; CD4-Positive T-Lymphocytes ; immunology ; Colorectal Neoplasms ; genetics ; immunology ; pathology ; Female ; Forkhead Transcription Factors ; biosynthesis ; genetics ; immunology ; Gene Expression Regulation, Neoplastic ; immunology ; Humans ; Immunity ; genetics ; Interleukin-10 ; biosynthesis ; immunology ; Interleukin-2 Receptor alpha Subunit ; immunology ; Lymphatic Metastasis ; Male ; Middle Aged ; STAT3 Transcription Factor ; biosynthesis ; immunology ; T-Lymphocytes, Regulatory ; immunology