Early diagnosis and prognosis monitoring are very important for the survival of patients with bladder cancer. To identify candidate biomarkers of bladder cancer, we used a combination of techniques including 2-DE, co-IP, western blot, LC-MS/MS, and immunohistochemistry. Hsp74 was identified with high expression in bladder cancer. The cellular location of expression products of gene Hsp74 showed that they were distributed into cytoplasm and keratin 1 was found to be associated with Hsp74. The results provide a new idea to understand the molecular basis of bladder cancer progression and pinpoint new potential molecular target for early diagnosis and therapeutic monitoring of bladder cancer.
Abstract PurposeEsophageal cancer (EC) is the sixth leading cause of cancer death worldwide. Esophageal squamous cell carcinoma (ESCC) is a predominant subtype of EC. Identifying diagnostic biomarkers for ESCC is necessary for cancer practice. Increasing evidence illustrates that apolipoprotein C-1 (APOC1) participates in the carcinogenesis. However, the biological function of APOC1 in ESCC remains unclear. Patients and methodsWe investigated the expression level of APOC1 using TIMER2.0 and GEO databases, the prognostic value of APOC1 in ESCC using Kaplan-Meier plotter and TCGA databases. We used LinkedOmics to identify co-expressed genes with APOC1 and perform GO and KEGG pathway analysis. The target networks of kinases, miRNAs and transcription factors were predicted by gene set enrichment analysis (GSEA). The correlations between APOC1 and immune infiltration were calculated using TIMER2.0 and CIBERSORT databases. We further performed the prognostic analysis based on APOC1 expression levels in related immune cells subgroups via Kaplan-Meier plotter database. ResultsAPOC1 was found overexpressed in tumor tissues in multiple ESCC cohorts and high APOC1 expression was related to a dismal prognosis. Multivariate analysis confirmed that APOC1 overexpression was an independent indicator of poor OS. Functional network analysis indicated that APOC1 might regulate the natural killer cell mediated cytotoxicity, phagosome, AMPK and hippo signaling through pathways involving some cancer-related kinases, miRNA and transcription factors. Immune infiltration analysis showed that APOC1 was significantly positively correlated with M0 macrophages cells, M1 macrophages cells and activated NK cells, negatively correlated with regulatory T cells, CD8 T cells, neutrophils and monocytes. High APOC1 expression had a poor prognosis in server immune cells subgroups in ESCC, including decreased CD8+ T cells subgroups. ConclusionThese findings suggest that increased expression of APOC1 is related to poor prognosis and immune infiltration in ESCC. APOC1 holds promise for serving as a valuable diagnostic and prognostic marker in ESCC.
Almost all of cervical carcinoma arises as a result of persistent infection with high-risk human papillomaviruses (HPVs) where E7 oncogene plays an important role. In addition, estrogen is a confirmed cofactor in HPV related cervical carcinoma working synergistically with E7. There are two pathways involved in the E7 carcinogenesis of cervical cancer, the pRb-dependent and pRb-independent pathway. In this study we analyzed that whether estrogen contributes to high-risk HPV E7 in cervical carcinogenesis via pRb-independent pathway or not. E7(DeltaRB), which can not bind to and degrade pRb protein, hence no transformation ability, worked synergistically with estrogen in cell proliferation and transformation. Estrogen combined with PTD-HPV18E7(DeltaRB) enhanced cell proliferation rate, induced genomic instability, including abnormal centrosome duplication and chromosomal instability, and exhibited malignant transformation with anchorage-independent growth. We also observed that, PTD-HPV18E7(DeltaRB) can interact with c-Jun and c-Myc proteins, but this interaction was limited to the estrogen-treated cells where c-Jun and c-Myc were expressed highly and no such interaction was observed in estrogen-untreated cells where c-Jun and c-Myc expression levels were low. In conclusion, estrogen can cooperate with E7 through a pRB-independent manner in cervical carcinogenesis. The functional interaction between E7 and c-Jun or between E7 and c-Myc could only be triggered when the c-Jun or c-Myc expression level reaches a certain threshold.
Neural stem cells in brains have capacities of proliferation and differentiation, which is very critical to rebuild the cerebral cortex functions. Therefore, it is of great importance to find key targets and network pathways that regulate the proliferation of neural stem cells, which is also a pressing problem in the medical circle. With the Notch pathway as the core of the network, this paper summarized the advance of the bimolecular network system composed of Wnt, Shh, EGFR, cytokines and Notch signal, and analyzed such key nodes as Notch receptor, CBF1, NICD, Hesl, which may become potential targets of new-type drugs in the future. With the multi-component, multi-target, multi-lever characteristics, traditional Chinese medicines have many common grounds with the network pharmacology. The active component groups or active ingredients in traditional Chinese medicines are one of the material bases for showing their network pharmacological effect, which is worth exploring. This paper aims to provide a new strategy for the treatment of neurodegenerative disease and nerve injury with traditional Chinese medicines.
Objective:To evaluate the therapeutic methods of patients with severe acute pancreatitis(SAP).Methods: A comparative study was carried out in 64 patients with SAP by allocating them to surgical(n=31) or nonsurgical treatment group(n=33).Factors as complication incidence,case-fatality rate,timing of operation and procedures were taken into consideration retrospectively.Results: Serious complications(ARDS,renal inadequacy,)and case-fatality rate in nonsurgical group were significantly lower than that in surgical group(P0.05).In surgical therapy group,patients treated with operation within 48 hours in their earlier period,the fatality rate(9.5%) was evidently lower than that(50.0%) over 48 hours(P0.05).It was necessary to consider the removal of necrotic tissues in surgery.Conclusion: Expectant treatment should be considered as the best choice in treating SAP patients in their earlier period,for surgical treatment can not reduce complication incidence and fatality in such cases.Timing of operation should be favorable within 48 hours after the onset if surgery is necessary.However,it is wise to remove necrotic tissues and employ peritoneal lavage and drainage after operation.
Systemic lupus erythematosus (SLE) is a chronic inflammatory disease mainly characterized by B cell hyperactivity. Glucocorticoid (GC) is widely used in SLE for its potent anti-inflammatory and immunosuppressive effects. Despite its important clinical efficacy, high-dose or long-term use of GC can cause severe side effects, such as osteoporosis, osteonecrosis, cataracts, hyperglycemia, coronary heart disease and cognitive impairment. Our early clinical studies have shown that Jieduquyuzishen prescription (JP) can effectively reduce the adverse effects and improve the curative effect of GC in the treatment of SLE. The BAFF/BAFF-R signaling pathway plays an important role in the development of SLE and has been regarded as a potential target for the therapy of SLE. In this study, we attempt to investigate the effect of JP on the BAFF/BAFF-R signaling pathway to explore the mechanism of JP in reducing the toxicity and enhancing the efficacy of GC. YAC-1 cells, isolated rat peripheral blood lymphocytes, polymorphonuclear neutrophils and spleen lymphocytes were treated with drug-containing serum. The results of RT-PCR, Western blot and dual-luciferase reporter gene assays indicate that either JP or GC can inhibit the mBAFF-induced up-regulation of BAFF, BAFF-R, Bcl-2, IL-10 and NF-κB in YAC-1 cells and WEHI-231 cells. Furthermore, MTS, flow cytometry and CFSE results reveal that the proliferation and survival of lymphocytes activated by mBAFF are suppressed by JP, GC and their combination. Contrary to GC, JP can reduce the apoptosis and raise the survival of polymorphonuclear neutrophils and can't increase the apoptosis of the peripheral blood lymphocytes and spleen lymphocytes. Therefore, it is possible that JP can down-regulate the BAFF/BAFF-R signaling pathway as effectively as GC, which may result in the dosage reduction of GC, thus decreasing the toxicity and improving the efficacy of GC-based treatment of SLE.
Abstract Background Sodium-glucose cotransporter 2 (SGLT2) inhibitors lowered the risk of cardiovascular events in patients with diabetes or heart failure (HF) with reduced ejection fraction, whether they directly promote cardiac function remains unclear. Therefore, we sought to determine whether SGLT2 inhibitors could improve left ventricular (LV) function in these patients. Methods A literature search was conducted using MEDLINE, EMBASE, and Cochrane Library databases from their inception to July 9, 2021. Randomized clinical trials and cohort studies that reported LV function-related variables were included. Results Thirteen studies comprising 1437 patients (830 SGLT2 inhibitor-treated and 607 non-SGLT2 inhibitor-treated patients) and representing 7 randomized controlled trials with 640 individuals and 6 cohort studies with 797 individuals were included in this meta-analysis. LV regression [LV mass (LVM)], LV ejection fractions (LVEF), LV volumes [LV end-diastolic volumes and systolic volumes (LVEDV and LVESV, respectively], and LV diastolic function [mitral inflow E velocity to tissue Doppler e’ ratio, E/e’ and left atrial volume index (LAVI)] were all significantly improved in patients treated with SGLT2 inhibitors (weighted mean differences, 95% CI, LVM: −6.319 g, −10.850 to −1.789; LVEF: 2.458%, 0.693 to 4.224; LVEDV: −9.134 mL, −15.808 to −2.460; LVESV: −8.440 mL, −15.093 to −1.787; LAVI: −2.791 mL/m2, −.554 to −1.027; E/e’: −1.567, −2.440 to −0.698). Subgroup analysis further confirmed the improvement of LV function mainly in patients with HF or those receiving empagliflozin treatment. Conclusions Treatment with SGLT2 inhibitors can significantly improve LV function in patients with or without diabetes (especially those with HF or undergoing empagliflozin treatment).
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