RESUMO
Objective: To evaluate the long-term outcomes of lower extremity arteriovenous graft (AVG) in hemodialysis patients. Methods: Hemodialysis patients with lower extremity AVG from August 2015 to July 2023 in the Department of Vascular Surgery, Longhua Hospital, Shanghai University of Traditional Chinese Medicine were enrolled. Therapeutic effects and complications of AVG were retrospectively analyzed. Results: A total of 83 cases aged (58.9±13.3) years were enrolled, including 25 males and 58 females. The success rate of the operation was 100% (83/83), and no perioperative complications occurred. The follow-up time [M (Q1, Q3)] was 38.4 (22.6, 55.3) months, with a follow-up rate of 92.8% (77/83). There were 9 cases (11.7%) of puncture site infection, 5 cases (6.5%) of pseudoaneurysm, 2 cases (2.6%) of seroma, 3 cases (3.9%) of lower limb ischemia, 48 cases (62.3%) of stenosis and 24 cases (31.2%) of thrombosis during the follow-up period. The 6-month, 1-year, 2-year, 3-year and 5-year primary patency rates after surgery were 78.9%, 61.2%, 39.0%, 27.0% and 16.3%, respectively, assisted primary patency rates were 93.5%, 82.5%, 74.9%, 68.0% and 53.0%, respectively, and secondary patency rates were 96.1%, 94.7%, 93.1%, 91.3% and 75.3%, respectively. Conclusion: For patients whose vascular resources of upper limbs are exhausted, lower extremity AVG is a safe and effective hemodialysis vascular access.
Assuntos
Derivação Arteriovenosa Cirúrgica , Extremidade Inferior , Diálise Renal , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Extremidade Inferior/irrigação sanguínea , Estudos Retrospectivos , Idoso , Resultado do Tratamento , Grau de Desobstrução VascularRESUMO
Mitophagy, as an important link in maintaining mitochondrial homeostasis and environmental homeostasis in the liver, can remove damaged mitochondria and provide energy through autophagy and other processes. Additionally, it plays a dual role in the occurrence and development of liver cancer and can affect the therapeutic effect of liver cancer through a variety of signaling pathways. This article reviews the relationship between mitophagy and hepatitis B virus infection, liver cancer occurrence and development, liver cancer stem cells, mitochondrial division and fusion, therapeutic resistance and invasiveness of liver cancer, and other aspects.
Assuntos
Neoplasias Hepáticas , Mitofagia , Humanos , Autofagia , Neoplasias Hepáticas/metabolismo , MitocôndriasRESUMO
Globally, the number of patients with post-tuberculosis lung disease (PTLD) is huge, with high morbidity and mortality. PTLD is defined as chronic respiratory abnormality that affects large and small airways (bronchiectasis and obstructive lung disease), lung parenchyma, pulmonary vasculature, and pleura and may be complicated, with or without symptoms, attributable at least in part to previous pulmonary tuberculosis. The aforementioned chronic respiratory abnormality may be complicated due to coinfection such as fungi and nontuberculosis mycobacteria. Risk factors for PTLD include multiple episodes of tuberculosis, drug-resistant tuberculosis, delays in diagnosis, smoking, and possible diabetes. Empirical expert opinion advocates preventive anti-tuberculosis treatment for high-risk groups of tuberculosis, early diagnosis and treatment of tuberculosis, surgical treatment for specific groups, pulmonary rehabilitation for patients after tuberculosis treatment, early identification and treatment of co-infection. It is effective to prevent the occurrence of PTLD, improve the treatment effect, and prevent the deterioration of the disease. As a high TB burden country, PTLD has been seriously neglected in China. Internationally, there is currently a lack of epidemiological survey data on post-TB pulmonary disease, and there are few studies on its clinical characteristics, risk factors, prevention, and treatment. With an emerging literature on PTLD, collaborative research is urgently needed to inform our understanding of the natural history, prevention, and treatment of PTLD, and to allow for the development of much needed evidence-based guidelines.
Assuntos
Coinfecção , Pneumopatias , Tuberculose , Antituberculosos/uso terapêutico , Humanos , Pulmão , Doenças NegligenciadasRESUMO
Objective: To systematically evaluate the efficacy and safety of vitamin D supplementation in the treatment of pulmonary tuberculosis. Methods: Biomedical Database was searched to collect randomized controlled trials (RCT) related to vitamin D supplementation in tuberculosis patients, and the retrieval time was from establishment to November 2019. Two evaluators independently screened the literature and extracted the data. The negative conversion rate of acid-fast-bacilli of sputum smear, the negative conversion rate of mycobacterium tuberculosis culture and the change of serum vitamin D level were the main outcome indicators, and the body mass index was the secondary outcome indicator. The incidence of hypercalcemia and abnormal urinary calcium were used as adverse event indicators and the RevMan 5.2 software was used for meta-analysis. Results: A total of 8 RCT(S) met the inclusion criteria, including 850 patients with tuberculosis. Meta-analysis showed that compared with the control group, negative conversion rate of acid-fast-bacilli of sputum smear and serum vitamin D level increased after 8 weeks of vitamin D supplementation [RR (95%CI) and mean deviation (MD) (95%CI) were 1.06 (1.00, 1.13) and 8.81 (1.81, 15.81), respectively; negative conversion rate of acid-fast-bacilli of sputum smear was not increased at week 4 and 12 [RR (95%CI) were 1.08 (0.97, 1.20) and 1.01 (0.91, 1.12), respectively]; negative conversion rate of mycobacterium tuberculosis culture in sputum was not increased after 4 and 8 weeks [RR (95%CI) were 1.06 (0.91, 1.22) and 1.02 (0.96, 1.08), respectively]; there was no change in body mass index [MD (95%CI):-0.02 (-0.53, 0.50)]; there was increased risk of abnormal urinary calcium [RR (95%CI): 2.45 (1.75, 3.41)], while no increase in risk of hypercalcemia [RR (95%CI): 1.99 (0.96, 4.13)]. Conclusion: Vitamin D supplementation is safe but not effective in the treatment of pulmonary tuberculosis.
Assuntos
Tuberculose Pulmonar , Tuberculose , Suplementos Nutricionais , Humanos , Escarro , Vitamina DRESUMO
Objective: To investigate the clinical efficacy of atomization inhalation combined with oral administration of oseltamivir in treatment of human infection with H7N9 avian influenza. Methods: To analyze the clinical data of 4 patients hospitalized from Mar 6th 2017 to Apr 12th 2017 with avian influenza(H7N9) infection treated by conventional therapy(oseltamivir, 150 mg, po, Bid) plus with oseltamivir inhalation(75 mg dissolved in 20 ml N. S, Bid) and administered with antibacterial treatment, blood purification and immunomodulators. Results: Undergoing these comprehensive therapies, Bronchial lavage fluid and pharynx of 1 case was negative for H7N9 RNA after 24 h, 2 cases negative for H7N9 after 3 d and 1 case negative for H7N9 RNA after 4 d. All patients were cured and discharged without any complications. Conclusions: Aseltamivir inhalation combined with oral treatment can significantly shorten the time of virus nucleic acid turning negative, improve the efficacy of anti avian influenza virus H7N9, and increase the cure rate of avian influenza H7N9 infection patients.
Assuntos
Antivirais/administração & dosagem , Subtipo H7N9 do Vírus da Influenza A , Influenza Humana/tratamento farmacológico , Oseltamivir/administração & dosagem , Administração por Inalação , Administração Oral , China , Humanos , Resultado do TratamentoRESUMO
Objective: To investigate the expression of microRNA-30a (miR-30a) in hepatocellular carcinoma (HCC) and related molecular mechanisms in regulating HCC cell proliferation. Methods: A total of 30 pairs of HCC and adjacent tissue samples were collected, and quantitative real-time PCR and Western blot were used to measure the mRNA and protein expression of forkhead-box protein A1 (FOXA1). Methyl thiazolyl tetrazolium (MTT) assay was used to evaluate the proliferation of HCC cells, luciferase reporter gene assay was performed to verify the target relationship between miR-30a and FOXA1, and MTT assay and Western blot were used to measure the proliferation of HepG2 cells and the protein expression of FOXA1 after miR-30a transfection. The t-test was used for comparison of data between two groups, and a one-way analysis of variance was used for comparison of data between multiple groups. P < 0.05 was considered statistically significant. Results: HCC tissue had significantly lower relative expression of miR-30a than adjacent tissue (1.049 ± 0.380 vs 1.982 ± 1.013, t = 3.985, P < 0.001). At 72 hours after miR-30a overexpression, there was a significant difference in the proliferative capacity of HepG2 cells between the blank control group, the miR-30a-NC group, and the miR-30a group (0.821 ± 0.006 vs 0.816 ± 0.013 vs 0.546 ± 0.020, F = 3.396, P < 0.05), suggesting that miR-30a overexpression significantly inhibited the proliferation of HepG2 cells. FOXA1 was a target gene of miR-30a and its protein expression was negatively regulated by miR-30a, and there was a significant difference in luciferase activity between wild-type and mutant FOXA1-3'UTR vectors (1.221 ± 0.024 vs 2.658 ± 0.031, F = 6.737, P < 0.05). In HepG2 cells, miR-30a overexpression significantly inhibited the protein expression of FOXA1, and there was a significant difference in the relative expression of FOXA1 between the blank control group, the miR-30a-NC group, and the miR-30a group (1.019 ± 0.016 vs 1.022 ± 0.017 vs 0.227 ± 0.021, F = 45.43, P < 0.05). Upregulating the protein expression of FOXA1 reversed the inhibitory effect of miR-30a on the proliferation of HepG2 cells, and there was a significant difference in the proliferative capacity of HepG2 cells between the miR-30a group and the miR-30a+FOXA1 group (0.524 ± 0.023 vs 0.843 ± 0.019, t = 2.507, P < 0.05). Conclusion: MiR-30a exerts its inhibitory effect on the proliferation of HCC cells by negatively regulating the expression of FOXA1.
Assuntos
Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , MicroRNAs/metabolismo , Proliferação de Células , Células Hep G2 , Fator 3-alfa Nuclear de Hepatócito , HumanosRESUMO
OBJECTIVE: To prepare a novel folate-targeted magnetic nanocomposites loaded with tissue facor pathway inhibitor 2 (TFPI-2) and cisplatin (CDDP) and to investigate its targeting ability and anti-tumor effect on nasopharyngeal carcinoma HNE-1 cells in vitro. METHODS: The copolymer folic acid-polyethylene glycol-polyethyleneimine (FA-PEG-PEI) was synthesized through amidation reaction, and then FA-PEG-PEI/ magnetic nanoparticles-CDDP/TFPI-2 (MNP-CDDP/TFPI-2) nanocomposites was obtained by electrostatic adsorption between TFPI-2 plasmid and magnetic nanoparticles loaded with CDDP (MNP-CDDP) with vortex FA-PEG-PEI. (1)H Nuclear Magnetic Resonance ((1)H NMR ) was used to determine if FA-PEG-PEI was synthesized. The particle size, zeta potential and morphology were detected by dynamic light scattering (DLS) and transmission electron microscope (TEM). The content of Fe and CDDP was measured by phenanthroline and o-phenylenediamine (OPDA) colourimetry. Agarose gel electrophoresis was used to analyze the binding ability of FA-PEG-PEI/MNP-CDDP to TFPI-2 plasmid. Molecular targeted uptake of FA-PEG-PEI/ MNP-CDDP/TFPI-2 coupling with green fluorescent protein (GFP) in NPC cells were observed by Prussian-blue iron staining and fluorescence microscope. The levels of TFPI-2 protein expression after transfection were evaluated by Western blot. The effects of nanocomposites on HNE-1 cells proliferation and apoptosis were measured with Cell Counting Kit-8(CCK-8) and flow cytometry. RESULTS: Special peak value of FA, PEG and PEI were showed on (1)H NMR spectrogram. The mean size and zeta potential of FA-PEG-PEI/MNP-CDDP/TFPI-2 were 141.1 nm and 21.5 mV. The nanocomposites showed a good monodispersity and an insufficient size uniformity under TEM. The content of Fe and CDDP were 116.2 µg/ml and 92.88 µg/ml, respectively. Agarose gel electrophoresis showed TFPI-2 could be encapsulated completely and protected from digestion of DNA enzyme as the mass ratio of FA-PEG-PEI/ MNP-CDDP and TFPI-2 plasmid was equal or higher than 1â¶1. More blue-stained magnetic granulars and green fluorescence were seen in folate receptor (FR)-positive HNE-1 cells than in FR-negative CNE-2 (P<0.05) under microscope and fluorescence microscope. The level of TFPI-2 protein expression in HNE-1cells increased significantly after transfection by FA-PEG-PEI/ MNP-CDDP/TFPI-2, compared with other control groups (FA-PEG-PEI/MNP-CDDP group and TFPI-2 group), all P<0.05. The nanocomposites inhibitory effect on HNE-1 including cell growth inhibition rate (64.00%) and apoptosis rate (49.61%) were significantly higher than that in FA-PEG-PEI/MNP group (8.19%, 9.26%), FA-PEG-PEI/TFPI-2 group (40.35%, 19.85%) and FA-PEG-PEI/MNP-CDDP group(56.15%, 36.46%)(P<0.05). CONCLUSION: FA-PEG-PEI/MNP-CDDP/TFPI-2 nanocomposites was successfully synthesized using amidation and electrostatic adsorption technology and has a good molecular targeting and inhibitory effect on FR-positive HNE-1cells in vitro.
Assuntos
Neoplasias Nasofaríngeas , Carcinoma , Linhagem Celular Tumoral , Cisplatino , DNA , Ácido Fólico , Glicoproteínas , Humanos , Iminas , Magnetismo , Nanocompostos , Nanopartículas , Carcinoma Nasofaríngeo , Fenilenodiaminas , Plasmídeos , Polietilenoglicóis , Polietilenoimina/análogos & derivados , Polietilenos , TransfecçãoRESUMO
Colorectal cancer (CRC) is the third common cancer and most of the chemotherapies of CRC currently used often suffer limited efficacy and large side effects. Targeted small-molecule by anti-tumor drugs are thought aâ¯promising strategy for improving the efficacy and reducing the side effects. In this investigation, we report aâ¯novel multikinase inhibitor, termed SKLB-287, which was discovered by us recently. SKLB-287 could efficiently inhibit the activation of endothelial growth factor receptor (EGFR) and vascular endothelial growth factor receptor 2 (VEGFR2). It displayed very good anti-proliferative activity against LoVo CRC cells and considerable antiangiogenic potency in transgenic zebrafish embryos. Oral administration of SKLB-287 resulted in dose-dependent suppression of tumor growth in LoVo xenograft mouse model. Immunohistochemistry was adopted to examine the in vivo anti-tumor mechanism of action of SKLB-287.
Assuntos
Antineoplásicos/farmacologia , Neoplasias Colorretais/tratamento farmacológico , Receptores ErbB/antagonistas & inibidores , Compostos Heterocíclicos de 4 ou mais Anéis/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores , Administração Oral , Inibidores da Angiogênese/farmacologia , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Neoplasias Colorretais/patologia , Feminino , Humanos , CamundongosRESUMO
Sweet sorghum silage (SS; Sorghum dochna 'Dochna') has been extensively studied in recent years as a supplementary forage-to-corn silage (CS; Zea mays L.), but there are still relatively few studies on its effects on the rumen environment of sheep. Determining the short-term impact of converting roughage from corn straws to SS compared to CS on rumen fermentation and bacterial population dynamics was the main goal of the current study. Twelve female thin-tailed Han sheep (29.8 ± 1.34 kg) were randomly divided into one of two treatments: concentrate supplemented with SS or CS, respectively. During the 15-day pretest period, concentrate was fed in two separate feedings at 0800 h and 1800 h, and ensure that the animals were all consumed within an hour of being fed. Thereafter, the animals had free access to corn straw. The feeding procedures during the pretest period were the same as during the measurement period. Rumen fluid was collected via sheep esophageal tube on the last day of adaptation phase (1-7 days) and stabilisation phase (8-30 days), respectively. The results showed that there was a similarity in the total concentration of VFA (volatile fatty acid) and the proportions of acetate, propionate, butyrate, and branched-chain VFA (P > 0.05) and microbial diversity indices (P > 0.05) between the two silage groups throughout the experimental period. The concentration of Ammonia nitrogen (P = 0.001) and proportion of valerate (P = 0.028) decreased in the CS and SS groups, respectively. The abundance and predicted function of rumen bacteria in the SS group did not differ significantly (P > 0.05) between the two measurement phases. However, the abundance of Prevotella_1 (P = 0.038) was higher in the CS group than in the SS group at 7 d. The abundances of Firmicutes (P = 0.005) and Ruminococcaceae_NK4A214_group (P = 0.002) increased, while the abundances of Bacteroidetes (P = 0.044), Proteobacteria (P = 0.046), and Prevotella_1 (P = 0.009) decreased in the CS group at 30 d. Genes related to pyruvate metabolism (P = 0.020) were significantly higher at 30 d than at 7 d, whereas purine metabolism (P = 0.007), pyrimidine metabolism (P = 0.007), and metabolic pathways (P = 0.010) were lower at 30 d in the CS group. In conclusion, this study indicated that SS maintained a steady rumen environment, while CS caused high fluctuations in bacterial abundance and predicted function for sheep.
Assuntos
Sorghum , Zea mays , Animais , Ovinos , Feminino , Zea mays/metabolismo , Silagem/análise , Fermentação , Rúmen/metabolismo , Dieta/veterinária , Bactérias/genética , Digestão , LactaçãoRESUMO
The identification of oncogenic drivers and the subsequent development of targeted therapies have been established as biomarker-based care for metastatic non-small cell lung cancer (NSCLC) patients. Rearranged during transfection (RET) events have been reported to be oncogenic drivers in NSCLC and were more common in patients who i) were young; ii) had adenocarcinoma histology; and iii) had never smoked. Phase II studies indicated the limited efficacy of multi-targeted tyrosine kinase inhibitors in patients with NSCLC that have a confirmed RET event. Consequently, there has been ongoing research to develop more potent and specific RET tyrosine kinase inhibitors. Recently, a novel and specific RET inhibitor, pralsetinib (BLU-667), has been reported to have excellent efficacy and low off-target toxicity in RET cancer patients. In this review, we summarize the clinical data regarding the use of pralsetinib in NSCLC patients.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Proteínas Proto-Oncogênicas c-ret , Pirazóis , Piridinas , PirimidinasRESUMO
OBJECTIVE: To explore the dynamic expression of programmed cell death-1 (PD-1) and its ligand PD-L1 at the maternal-fetal interface of mice post-infection with Toxoplasma gondii at early pregnancy and examine its interaction with interferon-γ (IFN-γ). METHODS: A total of 20 mice at day 0 of pregnancy were randomly assigned into 4 groups, including the 12-day pregnancy control group (12 dpn group), 12-day pregnancy and infection group (12 dpi group), 18-day pregnancy control group (18 dpn group) and 18-day pregnancy and infection group (18 dpi group), respectively. On the 6th day of the pregnancy, mice in the 12 dpi and 18 dpi groups were injected intraperitoneally with 150 tachyzoites of the T. gondii PRU strain, while mice in the 12 dpn and 18 dpn groups were injected with the same volume of PBS. All mice in the four groups were sacrificed on 12th and 18th day of the pregnancy, and the number of placenta and fetus was counted and the weight of placenta and fetus was measured. Then, the placental and uterine tissues of the pregnant mice in each group were sampled for pathological examinations. The mRNA expression of PD-1, PD-L1, T. gondii surface antigen SAG-1 and IFN-γ genes was quantified using a quantitative real-time PCR (qPCR) assay, and the correlation between PD-1 and IFN-γ expression was examined. In addition, the 12 dpn group, 12 dpi group, 18 dpn group, 18 dpi group, PBS negative control of the 12 pdi group and PBS negative control of the 18 dpi group were assigned, and the PD-1 expression was determined in the uterine and placenta tissues of the pregnant mice. RESULTS: Adverse pregnant outcomes were seen in mice in the 12 dpi and 18 dpi groups, including placental dysplasia and fetal maldevelopment, and the placental weights and fetal body weights were significantly lower in mice in the 12 dpi and 18 dpi groups than those in the 12 dpn and 18 dpn groups (t = 5.52, 11.44, 12.63 and 11.67, all P < 0.01). The histopathological examinations showed that the decidua and junctional regions of the placental tissues were loosely connected in the 12 dpi and 18 dpi groups, and a large number of inflammatory cells infiltration and congestion were seen in the placental and uterine tissues. qPCR assay detected significant differences in PD-1, PD-L1, IFN-γ and SAG-1 expression in the placental and uterine tissues among the 12 dpn, 12 dpi, 18 dpn and 18 dpi groups (F = 22.48, 51.23, 9.61, 47.49, 16.08, 21.52, 28.66 and 238.90, all P < 0.05), and the PD-1, PD - L1, IFN - γ and SAG - 1 expression was all significantly higher in the placental and uterine tissues of mice in the 12 dpi group than in the 12 dpn group (all P values < 0.05). The PD-1 and PD-L1 expression was significantly lower in the placental tissues of mice in the 18 dpi group than in the 18 dpn group (all P values < 0.05), and the IFN-γ and SAG-1 expression was significantly higher in the placental and uterine tissues of mice in the 18 dpi group than in the 18 dpn group (all P values < 0.05), while the PD-1 and PD-L1 expression was significantly lower in the placental and uterine tissues of mice in the 18 dpi group than in the 12 dpi group (all P values < 0.05). Immunohistochemical staining showed PD-1 expression in the inflammatory cells of the placental tissues of mice in the 12 dpi group, and no apparent PD-1 expression in the 18 dpi group, while strongly positive PD-1 expression was found in the uterine epithelium of mice in the 12 dpi group, and mildly strong expression was in the 18 dpi group. In addition, the IFN-γ mRNA expression was positively correlated with the PD-1 mRNA expression in placental (rs = 0.99, P < 0.01) and uterine tissues of mice in the 12 dpi group (rs = 0.97, P < 0.01) and in placental (rs = 0.82, P < 0.01) and uterine tissues of mice in the 18 dpi group (rs = 0.81, P < 0.01). CONCLUSIONS: Following T. gondii infection at early pregnancy, the PD-1 and PD-L1 expression shows a remarkable rise at middle pregnancy and a reduction at late pregnancy in placental and uterine tissues of mice, which appears the same tendency with IFN-γ expression during the same time period, and PD-1 expression positively correlates with IFN-γ expression. The dynamic expression of PD-1 and PD-L1 on the maternal-fetal interface of mice may be mutually mediated by IFN-γ induced by T. gondii infection.
Assuntos
Toxoplasma , Animais , Antígeno B7-H1/genética , Feminino , Interferon gama/genética , Camundongos , Placenta , Gravidez , Receptor de Morte Celular Programada 1RESUMO
OBJECTIVE: To investigate the expression and possible role of hypoxia-inducible factor-1 (HIF-1) at the maternal-fetal interface following Toxoplasma gondii infection during early pregnancy. METHODS: Twenty pregnant C57BL/6 mice, each weighing 16 to 20 g, were randomly divided into 4 groups, including the 12-d control group, 12-d infection group, 18-d control group and 18-d infection group. Mice in the 12-d and 18-d infection groups were injected intraperitoneally with 150 tachyzoites of the T. gondii PRU strain on day 6 of pregnancy, while mice in the 12-d control and 18-d control groups were injected with the same volume of phosphate buffered saline (PBS). Mice in the control and infection groups were sacrificed on days 12 and 18 of pregnancy, and the placental and uterine specimens of the pregnant mice in each group were sampled for pathological examinations. The mRNA expression of HIF-1α, HIF-1ß and vascular endothelial growth factor (VEGF) was quantified using quantitative fluorescent real-time PCR (qPCR) assay in the placental and uterine specimens, and the correlation between HIF-1α and VEGF mRNA expression was examined. In addition, and the HIF-1α expression was detected using immunohistochemical staining in the placental and uterine specimens of pregnant mice. RESULTS: Compared with the 12-d and 18-d control groups, adverse pregnant outcomes were observed in mice in 12-d and 18-d infection groups, such as teratism and placental dysplasia. HE staining showed swelling and blood stasis of cells, sinusoid reduction and inflammatory cell infiltration in the labyrinth area of the placenta specimens of mice in 12-d and 18-d infection groups relative to 12-d and 18-d control groups, and columnar epithelial cell injury and inflammatory cell infiltration were seen in the mouse uterine specimens in both infection groups. qPCR assay detected significantly higher HIF-1α (F = 132.6, P < 0.05) and HIF-1ß mRNA expression (F = 286.9, P < 0.05) in the placental specimens and lower HIF-1α (F = 111.5, P < 0.05) and HIF-1ß mRNA expression (F = 55.2, P < 0.05) in the uterine specimens in the 12-d infection group than in the 12-day control group, and significantly lower HIF-1α and HIF-1ß mRNA expression was detected in the placental and uterine specimens in the 18-d infection group than in the 18-day control group (F = 215.8, 418.9, 156.8 and 200.1; all P values < 0.05). Significantly lower VEGF-A (F = 426.2, P < 0.05), VEGF-B (F = 104.6, P < 0.05) and VEGF-C mRNA expression (F = 566.9, P < 0.05) in the placental specimens and higher VEGF-A (F = 426.2, P < 0.05), VEGF-B (F = 104.6, P < 0.05) and VEGF-C mRNA expression (F = 566.9, P < 0.05) in the uterine specimens were detected in the 12-d infection group than in the 12-d control group, and higher VEGF-A, VEGF-B and VEGF-C mRNA expression was found in the placental and uterine specimens in the 18-d infection group than in the 18-d control group (F = 521.9, 100.6, 275.9, 224.6, 108.2 and 333.4; all P values < 0.05). Immunohistochemical staining showed strongly and mildly positive HIF-1α expression in the mouse placental labyrinth area in the 12-d and 18-d infection groups relative to 12-d and 18-d control groups, while no HIF-1α expression was detected in mouse uterine specimens. CONCLUSIONS: HIF-1α expression appears a tendency towards a rise in the second trimester and a reduction in the third trimester in mice following T. gondii infection during early pregnancy, which is contrary to the changing tendency of VEGF-A, VEGF-B, and VEGF-C expression. It is hypothesized that HIF-1α inhibits placental angiogenesis in mice during pregnancy through suppressing VEGF expression, resulting in adverse pregnant outcomes.
Assuntos
Toxoplasma , Fator A de Crescimento do Endotélio Vascular , Animais , Feminino , Hipóxia , Camundongos , Camundongos Endogâmicos C57BL , Placenta , GravidezRESUMO
Objective: Regulatory quantitative trait loci (regQTL) theory can help to evaluate the regulation function of single nucleotide polymorphisms (SNPs) on crucial biological signals from a three-dimensional perspective. The aim of this study was to investigate the effect of these regQTL-SNPs on the susceptibility of lung cancer. Methods: Based on the regQTL theory, using the database of identified lung cancer regQTL-SNPs, we screened the SNPs that may function as regQTL in the reported susceptible regions of lung cancer by genome-wide association study(GWAS), and a two-stage case-control study was conducted (screening stage: 2 331 lung cancer cases and 3 077 healthy controls; validation stage: 626 lung cancer cases and 667 healthy controls) to definite the association of related regQTL-SNPs with the susceptibility of lung cancer. Results: A total of 8 regQTL-SNPs were screened in the reported susceptible regions of lung cancer by GWAS. Among which, 3 SNPs were significantly associated with the risk of lung cancer (P<0.05) in the screening stage. Further validation results indicated that the variant T allele of rs6998591 in ADRA1A was significantly associated with increased risk of lung cancer (additive model: OR=1.33, 95%CI:1.01-1.74, P=0.040). In addition, the variant G allele of rs11202916 in ACTA2 was significantly associated with decreased risk of lung cancer (recessive model: OR=0.71, 95%CI:0.52-0.96, P=0.026). Stratified analysis indicated that the variant T allele of rs6998591 significantly increased lung squamous cell carcinoma risk (additive model: OR=1.53, 95%CI: 1.01-2.32, P=0.043), while the variant G allele of rs11202916 significantly decreased lung adenocarcinoma risk (additive model: OR=0.83, 95%CI: 0.69-0.98, P=0.031). Gene-environment interaction analysis indicated that the risk of developing lung cancer increased by 235% in smoking individuals carrying rs6998591 variant T allele compared with those non-smoking individuals carrying no rs6998591 variant T allele(OR=3.35,95%CI:2.10-5.34,P<0.001). Conclusion: There are two regQTL-SNPs that could significantly affect the susceptibility of lung cancer in the GWAS reported susceptible regions of lung cancer.
Assuntos
Estudo de Associação Genômica Ampla , Neoplasias Pulmonares , Estudos de Casos e Controles , China/epidemiologia , Predisposição Genética para Doença , Genótipo , Humanos , Pulmão , Neoplasias Pulmonares/genética , Polimorfismo de Nucleotídeo ÚnicoRESUMO
OBJECTIVE: To explore the mechanism of the intestinal barrier damage caused by Blastocystis hominis infections in rats. METHODS: Thirty SD rats were randomly divided into the control group, and the 1-, 3-, 6- and 9-week-infection groups, of 6 rats in each group. Rats in each infection group were orally infected with B. hominis trophozoites at a density of 2 × 108 parasites per rat, and the control group was given an equal volume of phosphate buffered saline solution. The 7-hour urine samples were collected 1, 3, 6 and 9 weeks post-infection for the measurement of the intestinal permeability. Then, rats were sacrificed using the cervical dislocation method, and the cecum specimens were collected for the detection of the intestinal epithelial cell permeability. The expression of tight junction-related Occludin and Claudin - 1 genes and apoptosis-related Bcl - 2 and Bax genes was quantified in cecum epithelial cells using the real-time fluorescent quantitative PCR (qPCR) assay, and cell apoptosis was detected in the rat cecum using the TdT-mediated dUTP nick-end labeling (TUNEL) assay. RESULTS: The median urinary lactolose to mannitol ratios were 0.29, 0.72, 0.44, 0.46 and 0.38 in the control group, and the 1-, 3-, 6- and 9-week-infection groups, respectively, and the difference was statistically significant (H = 12.09, P < 0.05). B. hominis invasion and epithelial injury were observed in intestinal epithelial cells of rats infected with B. hominis, and transmission electron microscopy displayed the destruction of tight junctions between intestinal epithelial cells. The relative expression of Occludin, Claudin-1, Bcl-2 and Bax genes was 1.04, 0.62, 0.71, 0.68 and 0.96; 1.03, 0.61, 0.63, 0.76 and 0.86; 1.08, 0.70, 0.75, 0.74 and 1.03; and 1.00, 1.57, 1.33, 1.35 and 1.10 in the control group and the 1-, 3-, 6- and 9-week-infection groups, respectively, and all differences were statistically significant (F = 2.86, 2.85, 3.37 and 4.45, all P values < 0.05). The median number of positive staining cells were 1.00, 13.00, 9.00, 3.50 and 1.00 in rat cecum specimens in the control group, and the 1-, 3-, 6- and 9-week-infection groups, respectively, and the difference was statistically significant (H = 22.95, P < 0.01). CONCLUSIONS: B. hominis infection may cause an increase in the rat intestinal permeability through triggering the apoptosis of intestinal epithelial cells to destroy the tight junction between intestinal epithelial cells, thereby destroying the intestinal barrier function.
Assuntos
Infecções por Blastocystis , Junções Íntimas , Animais , Mucosa Intestinal , Ocludina , Ratos , Ratos Sprague-DawleyRESUMO
OBJECTIVE: Transmembrane-4-L- Six-Family-1 (TM4SF1) has been found involved in the development and progression of tumor. This study aims to investigate the effect of TM4SF1 on the proliferation, migration, and invasion of non-small cell lung cancer (NSCLC) and reveal its underlying mechanisms. MATERIALS AND METHODS: qRT-PCR, immunohistochemical analysis, and Western blot were used to evaluate the expression of TM4SF1 in human NSCLC tissues and cells. Cell proliferation was measured by CCK-8 and colony formation assay. Cell apoptosis was evaluated by flow cytometry assay. Cell migration and invasion were detected by wound healing and transwell assays. Co-immunoprecipitation (Co-IP) assay was used to examine the interactions between proteins. Expression levels of related proteins were determined by Western blot. For in vivo experiment, xenograft tumor models were used. RESULTS: TM4SF1 was upregulated in NSCLC tissues and cell lines and closely correlated to survival time, tumor size, lymph node metastasis, distant metastasis, and clinical stage. Gain-of function and loss-of function experiments demonstrated the oncogenic effect of TM4SF1 on NSCLC cell proliferation, apoptosis, migration, and invasion. Notably, mechanism studies showed that TM4SF1 regulated the interaction between YAP and TEAD and the level of downstream target genes. Besides, sh-YAP or Peptide 17 treatment (YAP-TEAD protein-protein interaction inhibitor) reversed the effect of TM4SF1 on NSCLC cells. The in vivo research suggested that the knockdown of TM4SF1 inhibited the growth of xenograft tumor of NSCLC. CONCLUSIONS: This is the first evidence demonstrating that TM4SF1 could promote proliferation, migration, and invasion in NSCLC, at least partially through a potential YAP-TEAD signaling pathway-dependent mechanism. This study might provide a potential therapeutic target for the treatment of NSCLC.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Antígenos de Superfície/metabolismo , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Neoplasias Pulmonares/metabolismo , Proteínas de Neoplasias/metabolismo , Fatores de Transcrição/metabolismo , Idoso , Animais , Antígenos de Superfície/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Células Cultivadas , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Proteínas de Neoplasias/genética , Neoplasias Experimentais/metabolismo , Neoplasias Experimentais/patologia , Proteínas de Sinalização YAPRESUMO
Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "Long noncoding RNA DARS-AS1 acts as an oncogene by targeting miR-532-3p in ovarian cancer, by K. Huang, W.-S. Fan, X.-Y. Fu, Y.-L. Li, Y.-G. Meng, published in Eur Rev Med Pharmacol Sci 2019; 23 (6): 2353-2359. DOI: 10.26355/eurrev_201903_17379. PMID: 30964159" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/17379.
RESUMO
Signaling by members of the epidermal growth factor receptor family plays an important role in breast development and breast cancer. Earlier work suggested that one of these receptors, ErbB4, is coupled to unique responses in this tissue. To determine the function of ErbB4 signaling in the normal mouse mammary gland, we inactivated ErbB4 signaling by expressing a COOH terminally deleted dominant-negative allele of ErbB4 (ErbB4DeltaIC) as a transgene in the mammary gland. Despite the expression of ErbB4DeltaIC from puberty through later stages of mammary development, an ErbB4DeltaIC-specific phenotype was not observed until mid-lactation. At 12-d postpartum, lobuloalveoli expressing ErbB4DeltaIC protein were condensed and lacked normal lumenal lactation products. In these lobuloalveoli, beta-casein mRNA, detected by in situ hybridization, was normal. However, whey acidic protein mRNA was reduced, and alpha-lactalbumin mRNA was undetectable. Stat5 expression was detected by immunohistochemistry in ErbB4DeltaIC-expressing tissue. However, Stat5 was not phosphorylated at Y694 and was, therefore, probably inactive. When expressed transiently in 293T cells, ErbB4 induced phosphorylation of Stat5. This phosphorylation required an intact Stat5 SH2 domain. In summary, our results demonstrate that ErbB4 signaling is necessary for mammary terminal differentiation and Stat5 activation at mid-lactation.