Identification and validation of a novel anoikis-related signature for predicting prognosis and immune landscape in ovarian serous cystadenocarcinoma.

Background: Ovarian serous cystadenocarcinoma (OSC) is the most prevalent histological subtype of ovarian cancer (OV) and presents a serious threat to women's health. Anoikis is an essential component of metastasis, and tumor cells can get beyond it to become viable. The impact of anoikis on OSC, however, has only been the topic of a few studies. Methods: The mRNA sequencing and clinical information of OSC came from The Cancer Genome Atlas Target Genotype-Tissue Expression (TCGA TARGET GTEx) dataset. Anoikis-related genes (ARGs) were collected by Harmonizome and GeneCards websites. Centered on these ARGs, we used unsupervised consensus clustering to explore potential tumor typing and filtered hub ARGs to create a model of predictive signature for OSC patients. Furthermore, we presented clinical specialists with a novel nomogram based on ARGs, revealing the underlying clinical relevance of this signature. Finally, we explored the immune microenvironment among various risk groups. Results: We identified 24 ARGs associated with the prognosis of OSC and classified OSC patients into three subtypes, and the subtype with the best prognosis was more enriched in immune-related pathways. Seven ARGs (ARHGEF7, NOTCH4, CASP2, SKP2, PAK4, LCK, CCDC80) were chosen to establish a risk model and a nomogram that can provide practical clinical decision support. Risk scores were found to be an independent and significant prognostic factor in OSC patients. The CIBERSORTx result revealed an inflammatory microenvironment is different for risk groups, and the proportion of immune infiltrates of Macrophages M1 is negatively correlated with risk score (rs = -0.21, P < 0.05). Ultimately, quantitative reverse transcription polymerase chain reaction (RT-PCR) was utilized to validate the expression of the seven pivotal ARGs. Conclusion: In this study, based on seven ARGs, a risk model and nomogram established can be used for risk stratification and prediction of survival outcomes in patients with OSC, providing a reliable reference for individualized therapy of OSC patients.

Downregulated calmodulin expression contributes to endothelial cell impairment in diabetes.

Endothelial dysfunction, a central hallmark of cardiovascular pathogenesis in diabetes mellitus, is characterized by impaired endothelial nitric oxide synthase (eNOS) and NO bioavailability. However, the underlying mechanisms remain unclear. Here in this study, we aimed to identify the role of calmodulin (CaM) in diabetic eNOS dysfunction. Human umbilical vein endothelial cells and murine endothelial progenitor cells (EPCs) treated with high glucose (HG) exhibited downregulated CaM mRNA/protein and vascular endothelial growth factor (VEGF) expression with impeded eNOS phosphorylation and cell migration/tube formation. These perturbations were reduplicated in CALM1-knockdown cells but prevented in CALM1-overexpressing cells. EPCs from type 2 diabetes animals behaved similarly to HG-treated normal EPCs, which could be rescued by CALM1-gene transduction. Consistently, diabetic animals displayed impaired eNOS phosphorylation, endothelium-dependent dilation, and CaM expression in the aorta, as well as deficient physical interaction of CaM and eNOS in the gastrocnemius. Local CALM1 gene delivery into a diabetic mouse ischemic hindlimb improved the blunted limb blood perfusion and gastrocnemius angiogenesis, and foot injuries. Diabetic patients showed insufficient foot microvascular autoregulation, eNOS phosphorylation, and NO production with downregulated CaM expression in the arterial endothelium, and abnormal CALM1 transcription in genome-wide sequencing analysis. Therefore, our findings demonstrated that downregulated CaM expression is responsible for endothelium dysfunction and angiogenesis impairment in diabetes, and provided a novel mechanism and target to protect against diabetic endothelial injury.

Autoimmune Disease-Related Hub Genes are Potential Biomarkers and Associated with Immune Microenvironment in Endometriosis.

Background: Endometriosis, a common gynecological condition, can cause symptoms such as dysmenorrhea, infertility, and abnormal bleeding, which can negatively affect a woman's quality of life. In the current study, the pathophysiological mechanisms of endometriosis are unknown, but this study suggests that endometriosis is associated with dysregulation of the autoimmune system. This study identify hub genes involved in the prevalence, identification and diagnostic value of endometriosis and autoimmune diseases, and explore the central genes and immune infiltrates, the diagnosis of endometriosis provides a new sight of thinking about diagnosis and treatment. Methods and Results: The relevant datasets for endometriosis GSE141549, GSE7305 and autoimmune disease-related genes (AIDGs) were downloaded from online database. Using the "limma" package and WGCNA to screen out the autoimmune disease related genes and endometriosis related genes, the autoimmune disease gene-related differential genes (AID-DEGs) progressive GO, KEGG enrichment analysis, and then using the protein interaction network and Cytoscape software to select hub genes (CXCL12, PECAM1, NGF, CTGF, WNT5A), using the "pROC" package to analyze the hub genes for the diagnostic value of endometriosis. The difference in the importance of hub genes for the diagnosis of endometriosis was analyzed by machine learning random forest, and the combined diagnostic value of hub genes was analyzed by using the Support Vector Machine (SVM) algorithm. The eutopic (EU) and ectopic endometrium (EC) immune microenvironment of endometriosis was evaluated using CIBERSORT, the correlation of hub genes to the immune microenvironment was analyzed. Conclusion: The hub genes associated with AIDGs are differentially expressed in EC and EU of endometriosis and possess important value for the diagnosis of endometriosis. The hub genes have a very important impact on the immune microenvironment of endometriosis, which is important for exploring the connection between endometriosis and autoimmune diseases and provides a new insight for the subsequent study of immunotherapy and diagnosis of endometriosis.

Anlotinib suppresses proliferation, migration, and immune escape of gastric cancer cells by activating the cGAS-STING/IFN-ß pathway.

This article reported the mechanism of Anlotinib in gastric cancer treatment. Gastric cancer cells were treated with Anlotinib (8 µM) and transfected by STING shRNA and STING vectors. Cell counting kit-8 assay, wounding healing assay, and Transwell experiment were applied for proliferation, migration, and invasion detection. PD-L1 fluorescence intensity in gastric cancer cells was explored by flow cytometry. IFN-ß level was researched by enzyme-linked immunosorbent reaction. Xenograft tumor experiment was performed by administering mice with Anlotinib and anti-PD-L1 antibody. Immunohistochemistry and western blot were used for proteins expression detection. Quantitative real-time reverse transcription-polymerase chain reaction was applied for mRNA expression detection. Hematoxylin and eosin staining was conducted on lung, liver, kidney, and cerebral cortex of mice. Gastric cancer cells treated with Anlotinib exhibited reduced proliferation, migration, and invasion (p<0.01). Anlotinib treatment reduced PCNA, CDK1, and MMP2 protein expressions and increased E-cadherin protein expression in gastric cancer cells (p<0.01). Anlotinib treatment suppressed PD-L1 expression and activated the cGAS-STING/IFN-ß pathway in gastric cancer cells (p<0.01). STING knockdown partially reversed the inhibition of Anlotinib on gastric cancer cells proliferation, migration, invasion, and immune escape (p<0.05 or p<0.01). However, STING overexpression exhibited the opposite effect. Anlotinib synergistically improved anti-tumor efficacy of anti-PD-L1 in vivo. Anlotinib synergistic anti-PD-L1 increased CD3+, CD8+ T cells, and activated the cGAS-STING/IFN-ß pathway in xenograft tumor. Anlotinib was non-toxic to lung, liver, cortex, and kidney. Anlotinib suppressed gastric cancer cells proliferation, migration, and immune escape by activating the cGAS-STING/IFN-ß pathway.

Clinical characteristics of coronavirus disease 2019 (COVID-19) in patients out of Wuhan from China: a case control study.

BACKGROUND: A large-scale global outbreak of coronavirus disease-19 (COVID-19) out of Wuhan, from China, occurred in January 2020. To examine the clinical characteristics of COVID-19 in infected patients out of Wuhan, from China. METHODS: Thirteen patients were confirmed to be infected with novel coronavirus-2019 (2019-nCoV) between January 27 and February 8, 2020, in Baoji city, Shannxi, northwestern China. Epidemiological and clinical information, and computed to morphology imaging data from all COVID-19 patients were collected; cases were divided into two groups according to the severity of infection (mild or severe). RESULTS: Nine (9/13) COVID-19 patients exhibited mild disease severity, and defined as second-generation human-to-human transmission cases. Most patients (11/13) had a history of travel to or from Wuhan. There were no differences in sex and age between the mild and severe cases (all P > 0.05). A moderate degree of fever (11/13), cough (13/13), and fatigue (8/13) were common symptoms; however, there was no statistical difference between mild and severe cases in this regard (all P > 0.05). Oxyhemoglobin saturation and oxygenation index decreased, and C-reactive protein (CRP) and serum amyloid A (SAA) levels were elevated in all patients with COVID-19 infection, with statistically significant differences between those with severe disease and mild infection (all P < 0.05). Twelve of 13 COVID-19 patients exhibited changes in chest CT imaging features, and time course changes were different between mild and severe cases (all P < 0.05). CONCLUSION: Most cases of COVID-19 infection were second-generation human-to-human transmissions from Wuhan and were mild in severity. The clinical characteristics of COVID-19 varied. Oxyhemoglobin saturation, oxygenation index, CRP and SAA levels, and CT features were reliable parameters to evaluate the severity of COVID-19 infection. However, a few patients with mild COVID-19 disease lacked typical characteristics such as fever and changes in CT imaging features.

Fast-response concentration measurement of bromotrifluoromethane using a quantum cascade laser (QCL) at 8.280 µm.

In this study, a measurement system for a gaseous fire extinguisher bromotrifluoromethane (Halon 1301) was developed, using a quantum cascade laser (QCL) at ~8.280 µm. The performance parameters of this system were also analyzed. Much higher sensitivity and faster response time were achieved compared to non-dispersive infrared (NDIR) sensors and differential-pressure method. A response time of 90 ms from 0% to the targeted concentration 6% was obtained. The detection limit of 500 ppm was obtained with a short optical path length of 2.8 mm. In conclusion, the proposed system can be applied in the airworthiness certification test of an aircraft fire suppression system.

Rabies Outbreaks and Vaccination in Domestic Camels and Cattle in Northwest China.

In contrast to many countries where rabies has been well controlled in humans and livestock, even in wildlife, rabies is still endemic in almost regions of China. In Northwest China, rabies transmitted by stray dogs and wild foxes has caused heavy economic losses to local herdsmen, as well as causing numbers of human cases. In this study, as part of an investigation of ways to prevent rabies epidemics in livestock, we report an analysis of domestic cattle and camel rabies cases in Ningxia Hui (NHAR) and Inner Mongolia Autonomous Region (IMAR) and the immune efficacy of canine inactivated rabies vaccines in these animals. We found that rabies viruses from these animals are closely related to dog-hosted China I and fox-associated China III lineages, respectively, indicating that the infections originated from two different sources (dogs and wild foxes). As well as the previously reported Arctic and Arctic-related China IV lineage in IMAR, at least three separate phylogenetic groups of rabies virus consistently exist and spread throughout Northwest China. Since there is no licensed oral vaccine for wild foxes and no inactivated vaccine for large livestock, local canine inactivated vaccine products were used for emergency immunization of beef and milk cattle and bactrian (two-humped) camels in local farms. Compared with a single injection with one (low-efficacy) or three doses (high-cost), a single injection of a double dose of canine vaccine provided low-price and convenience for local veterinarians while inducing levels of virus neutralizing antibodies indicative of protection against rabies for at least 1 year in the cattle and camels. However, licensed vaccines for wildlife and large domestic animals are still needed in China.

Effect of Serum Vitamin D Levels on Cellular Immunity and Antiviral Effects in Chronic Hepatitis B Patients.

BACKGROUND: To study the effect of 25-hydroxyl vitamin D3 on peripheral blood T lymphocyte immune function and antiviral effects in chronic hepatitis B patients. METHODS: The clinical data for 70 patients with chronic hepatitis B were analyzed. Serum 25-hydroxyl vitamin D was determined by electrochemical luminescence, and hepatitis B virus serological markers were determined by fluorescence quantitative polymerase chain reaction. Subsets of T lymphocytes were determined by immune fluorescence labeling method. These patients were divided into three groups based on serum 25-hydroxyl vitamin D level. After six months of pegylated interferon treatment, three groups have their number of T lymphocyte, liver functions, and virological indexes examined at the corresponding time. RESULTS: The years and ratio of gender have no statistical differences in these three groups. The proportion of CD3+, CD4+ T lymphocytes and the ratio of CD4+/CD8+ significantly increased (p < 0.05) as the level of 25-hydroxyl vitamin D increased, but the proportion of CD8+ decreased. Interferon treatment can improve the T cells subgroup, and the high level group of serum 25-hydroxyl vitamin D improved more obviously. The positive ratio of HBeAg, HBsAg and the titer of HBV DNA decreased with the increase of serum vitamin D, and the difference between the high and low level 25-hydroxyl vitamin D groups was significant (p < 0.05). The treatment of interferon can obviously improve the hepatitis B virus serological markers; the high level group of serum 25-hydroxyl vitamin D can obtain better virological response. However, there was no significant difference between the three groups of serological markers of liver function. CONCLUSIONS: Vitamin D may play a part in the immunologic function adjustment and immune tolerance in the natural course of chronic HBV infection, and high levels of vitamin D may be able to achieve sustained virological response. These findings may shed light on the research and treatment of chronic hepatitis B pathogenesis.

Interference of Notch 2 inhibits the progression of gliomas and induces cell apoptosis by induction of the cell cycle at the G0/G1 phase.

Glioblastoma is the most common type of malignant brain tumor with a poor prognosis. The Notch signaling pathway is often aberrantly activated in glioma cells. In order to determine the expression of Notch 2 and to evaluate its possible prognostic value in malignant glioblastoma, specimens from 32 patients and 20 controls were analyzed using immunohistochemical staining and reverse transcription quantitative polymerase chain reaction. The expression of Notch 2 in the glioma tissues was significantly higher compared with that in the normal brain tissues (P<0.01). Subsequently, endogenous Notch 2 interference was effectively performed by specific small hairpin (sh)RNA in the glioma cancer cell line U251. The results from an MTT assay and from Annexin V-fluorescein isothiocyanate/propidium iodide staining indicated that interference of Notch 2 significantly inhibited the proliferation and induced the apoptosis of U251 cells. In addition, the cell cycle was analyzed using flow cytometry and the results revealed that Notch 2 shRNA induced cell cycle arrest at the G0/G1 phase in U251 cells. Additionally, proteins associated with the cell cycle and cell proliferation were detected using western blot analysis. The data demonstrated that the expression of P21, cyclin D and phosphorylated retinoblastoma was significantly inhibited in the Notch 2 shRNA-transfected U251 cells. The results of the present study provide further insights into the effects of Notch 2 and a molecular reference for brain tumor therapy.

[Effects of topography on the diversity and distribution pattern of ground plants in karst montane forests in Southwest Guangxi, China].

Covariance analysis, curve-fitting, and canonical correspondence analysis (CCA) were used to explore the effects of topographic factors on the plant diversity and distribution patterns of ground flora with different growth forms in the karst mountains of Southwest Guangxi, China. A total of 152 ground plants were recorded. Among them, 37 species were ferns, 44 species herbs, 9 species lianas, and 62 species shrubs. Covariance analysis revealed that altitude significantly correlated with the individual number and richness of ground plants, and slope aspect had a significant effect on richness. Statistical analyses showed a highly significant nonlinear correlation between the individual number or richness of ground plants and altitude. Results of CCA revealed that slope aspect had a significant effect on the distribution pattern of ferns, and slope had a significant effect on the distribution patterns of herbs, lianas and shrubs. Ferns were more sensitive than herbs, lianas and shrubs to changes in heat and soil water caused by aspect. The effect of slope was stronger than that of elevation on soil water and nutrients, and it was the most important topographic factor that affected the distribution patterns of herbs, lianas and shrubs in this region.

Microencapsulation of Bifidobacterium bifidum F-35 in whey protein-based microcapsules by transglutaminase-induced gelation.

Bifidobacterium bifidum F-35 was microencapsulated into whey protein microcapsules (WPMs) by a transglutaminase (TGase)-induced method after optimization of gelation conditions. The performance of these WPMs was compared with that produced by a spray drying method (WPMs-A). WPMs produced by the TGase-induced gelation method (WPMs-B) had larger and denser structures in morphological examinations. Native gel and SDS-PAGE analyses showed that most of the polymerization observed in WPMs-B was due to stable covalent crosslinks catalyzed by TGase. The degradation properties of these WPMs were investigated in simulated gastric juice (SGJ) with or without pepsin. In the presence of pepsin, WPMs-A degraded more quickly than did WPMs-B. Finally, survival rates of the microencapsulated cells in both WPMs were significantly better than that of free cells and varied with the microencapsulation method. However, WPMs-B produced by TGase-induced gelation could provide better protection for microencapsulated cells in low pH conditions and during 1 mo of storage at 4 °C or at ambient temperature.

Preliminary study of the internal margin of the gross tumor volume in thoracic esophageal cancer.

PURPOSE: To measure the displacement of the tumor of the gross tumor volume (GTV) of thoracic esophageal cancer in the calm states of end-inspiration and end-expiration for determining the internal margin of the GTV (IGTV). METHODS: Twenty-two patients with thoracic esophageal cancer who were unable to undergo surgery were identified in our hospital. The patients received radiotherapy. By using 16-slice spiral computed tomography (CT), we acquired the calm states of end-inspiration and end-expiration. The displacement and volume changes in tumor target volume were measured, and the changes were analyzed to determine if these were associated with the tidal volume and the location and length of the target volume V. In the end, we analyzed the displacement of tumor target volume and calculated the internal margin of the GTV by empirical formula. RESULTS: The average tidal volume was 463.6 ml. The average GTV at end-inspiration was 33.3 ml and at end-expiration was 33.35 ml. Three was not any significant between two groups (T=-0.034, P>0.05). The IGTV (X-axis direction) was 3.09 mm for the right sector and 4.08 mm for the left border; the IGTV (Z-axis direction) was 3.96 mm for the anterior border and 2.83 mm for the posterior border; and the IGTV (Y-axis direction) was 7.31 mm for the upper boundary (head direction) and 10.16 mm for the lower boundary (feet direction). The motion of the GTV showed no significant correlation with the tidal volume of patients and the length of the tumor, but in relation to the tumor location, the displacement of the lower thoracic and the middle thoracic target volumes occurred in the direction of the anterior and right, which were not significantly different (T=0.859, 0.229, P>0.05) The significant differences were observed for the other directions (P<0.05). CONCLUSIONS: Because of respiratory and organ movements, the displacement of the tumor target volume was different in all directions. Therefore, we recommend that expansion of the planning target volume during clinical radiation treatment needs to include the displacement of the tumor target volume caused by respiratory and organ movements during each radiotherapy session.

Different radiation treatment in esophageal carcinoma: a clinical comparative study.

PURPOSE: Conventional fractionation radiation therapy (CFRT), 3-dimensional conformal radiation therapy (3DCRT) and intensity modulated radiation therapy (IMRT), are always applied to treat esophageal carcinoma. The purpose of this study was to analyse the therapeutic results and acute radiation side effects of radiotherapy in the treatment of esophageal carcinoma. METHODS: From March 2008 to May 2010, 117 patients with esophageal carcinoma treated at our hospital were included into this study. Thirty-eight (32.48%?) patients were treated with CFRT, 32 with 3DCRT and 47 with IMRT. The data were retrospectively collected and analysed. RESULTS: The objective response rates (complete/CR plus partial response/PR) in the CFRT group, 3DCRT group and IMRT group were 96.88, 92.11, and 91.49%, respectively (p=0.617). Furthermore, the one-year survival of the 3 groups was 77.9, 87.5 and 86.7%, respectively (p=0.193), and the 2-year survival 38.6, 55.1 and 57.7%, respectively (p=0.211). The incidence of acute radiation esophagitis in the IMRT+3DCRT groups was significantly higher compared with the CFRT group (p=0.012) and the incidence of acute radiation- induced pneumonitis, bronchitis and myelosuppression in the IMRT+3DCRT groups were lower compared with the CFRT group (p<0.01, p=0.028, and p=0.01, respectively). CONCLUSION: Both IMRT and 3DCRT methods can improve the clinical therapeutic outcome of patients with esophageal carcinoma and decrease the incidence of acute radiation pneumonitis, radiation bronchitis and bone marrow suppression.

Transcriptome analysis of probiotic Lactobacillus casei Zhang during fermentation in soymilk.

Lactobacillus casei Zhang is a widely recognized probiotic bacterium, which is being commercially used in China. To study the gene expression dynamics of L. casei Zhang during fermentation in soymilk, a whole genome microarray was used to screen for differentially expressed genes when grown to the lag phase, the late logarithmic phase, and the stationary phase. Comparisons of different transcripts next to each other revealed 162 and 63 significantly induced genes in the late logarithmic phase and stationary phase, of which the expression was at least threefold up-regulated and down-regulated, respectively. Approximately 38.4% of the up-regulated genes were associated with amino acid transport and metabolism notably for histidine and lysine biosynthesis, followed by genes/gene clusters involved in carbohydrate transport and metabolism, lipid transport and metabolism, and inorganic ion transport and metabolism. The analysis results suggest a complex stimulatory effect of soymilk-based ecosystem on the L. casei Zhang growth. On the other hand, it provides the very first insight into the molecular mechanism of L. casei strain for how it will adapt to the protein-rich environment.

Antagonistic activities of lactobacilli against Helicobacter pylori growth and infection in human gastric epithelial cells.

UNLABELLED: Lactobacilli have positive effects on bowel microflora and health in humans and animals. In this study, the antagonistic activities of Lactobacillus gasseri Chen, and L. plantarum 18 were assessed by agar plate diffusion assay and tests that determined the growth and urease activity of Helicobacter pylori cocultured with lactobacilli and the adherence of H. pylori to human gastric epithelial cells in the presence of lactobacilli. The results showed that the 2 Lactobacillus strains had significant anti-H.pylori activity, and this activity may be contributed by the cell-free supernatants (CFS) of lactobacilli and live Lactobacillus strains in vitro. The antagonistic activity of the CFS against H. pylori depended on the pH and the presence of metabolites, such as organic acids and proteases. Our results also indicated that 2 Lactobacillus strains could inhibit H. pylori adherence human gastric epithelial cells. PRACTICAL APPLICATION: Helicobacter pylori causes chronic gastritis, peptic ulcer disease, and gastric cancer, and it infects about 50% of the world's population. Lactobacilli have been reported to have an inhibitory effect on H. pylori and can be used as probiotic to manufacture dairy products preventing H. pylori infection.

[Multicenter phase II clinical trial of arsenic trioxide injection in the treatment of primary hepatocarcinoma].

OBJECTIVE: To evaluate the effect and adverse effects of arsenic trioxide (As2O3) in the treatment of primary hepatocarcinoma patients, and conduct the pharmacokinetics study. METHODS: A total of one hundred and eleven advanced primary hepatocarcinoma patients in five centers were treated with As2O3 injection 7 - 8 mg/m(2) i.v. qd for 14 days and was repeated after 7 - 14 days. Evaluation of the clinical response and adverse effects was conducted after two cycles of treatment. The patient who had reached partial PR and SD was treated continuously until disease progression or intolerance. RESULTS: Among the 102 patients evaluable for clinical efficacy analysis, there were 7 PR, 71 SD and 24 PD, the response rate was 6.9% and the clinical benefit rate was 76.5%. The quality of life was improved in 22.5% of patients. The pain relief rate was 71.7%, time to progress (TTP) was 97 days, and the median survival time (MST) was 195 days. The major adverse effects were reversible WHO I-II grade gastrointestinal reactions and bone marrow suppression. The results of pharmacokinetic study showed that the distribution and elimination characteristics in vivo was found to be a two-compartment model. The plasma elimination half-life was (23.94 ± 18.39) h. CONCLUSIONS: As2O3 is effective in the management of primary hepatocarcinoma, with a significant analgesic effect. To some extent, it can extend TTP and MST in advanced liver cancer patients, while the treatment is well tolerated in the majority of patients.

[Leukemia inhibitory factor suppresses renal interstitial fibroblast activation induced by transforming growth factor].

OBJECTIVE: To investigate the effects of leukemia inhibitory factor (LIF) on renal interstitial fibroblast activation following induction by transforming growth factor beta 1 (TGF-beta1). METHODS: Normal rat interstitial fibroblast cells (NRK/49F) were treated with TGF-beta1 and TGF-beta1, combining with LIF respectively for different duration with different concentration. Changes in cell morphology and expression of alpha-SMA were evaluated with electronic microscope and Western blot respectively. The collagen I in the supernatant was detected with ABC-ELISA. RESULTS: TGF-beta1 induced renal interstitial fibroblast activation, and this was accompanied by significant morphological transformations and secretion of collagen I. Co-culturing of cells with LIF blocked the morphological transformation. In addition, LIF inhibited TGF-beta1-induced expression of alpha-SMA mRNA and protein (P < 0.01), and decreased the levels of collagen I (P < 0.01) in a dose-dependent manner. CONCLUSION: LIF suppresses TGF-beta1-induced activation and collagen I secretion of cultured renal interstitial fibroblasts.

[Transforming growth TGF-beta1 mediates the expression of stromal cell derived factor-1 in kidney interstitial fibroblast cells in rats].

OBJECTIVE: To study the expression pattern of SDF-1 in the NRK49F cells and the role of TGF-beta1 in mediating the expression of SDF-1. METHODS: The SDF-1 mRNA and protein expression in the NRK49F cells with or without stimulating by TGF-beta1 was assayed with RT-PCR or Western blot or Immunohistochemistry. RESULTS: The SDF-1 mRNA expression stimulated by TGF-beta1 appeared in a time-dependent manner. The peak value appeared at 24 hours and was (2.924 +/- 0.235) times as high as the initial level. The dose-course studies suggested that TGF-beta1 stimulation resulted in marked promotion of SDF-1 mRNA expression, which peaked at the concentration of 5 ng/mL. At this concentration, the expression of SDF-1 mRNA was (2.113 +/- 0.314) times as high as that of the control. Corresponding with the pattern of mRNA expression of SDF-1, protein expression of SDF-1 was observed in NRK49F cells. A time-dependent manner was also observed in the protein expression of SDF-1 stimulated by 5 ng/mL of TGF-beta1. The protein expression of SDF-1 at 36 hours was (2.572 +/- 0.238) times as high as that of the control. TGF-beta1 neutralizing antibody reduced the expression of SDF-1 protein. CONCLUSION: SDF-1 expresses in NRK49F cells. TGF-beta1 up-regulates the mRNA and protein expressions of SDF-1 in NRK49F cells in a time- and concentration-dependent manner. As a chemokine, the increased expression of SDF-1 induced by TGF-beta1 may play an important role in renal inflammation and fibrosis.