Estimating the impact of drug addiction causes heart damage.

To date, few studies have investigated the toxicological effects of the combined use of amphetamine and heroin in the heart. Hence, the aim of this study was to identify indicators for clinical evaluation and prevention of cardiac injury induced by the combined use of amphetamine and heroin. Four different groups were analyzed: (1) normal group (n＝25；average age＝35 ± 6.8); (2) heart disease group (n＝25；average age＝58 ± 17.2); (3) drug abusers (n = 27; average age = 37 ± 7.7); (4) drug abstainers (previous amphetamine-heroin users who had been drug-free for more than two weeks; n = 22; average age = 35 ± 5.6). The activity of MMPs, and levels of TNF-α, IL-6, GH, IGF-I, and several serum biomarkers were examined to evaluate the impact of drug abuse on the heart. The selected plasma biomarkers and classic cardiac biomarkers were significantly increased compared to the normal group. The zymography data showed the changes in cardiac-remodeling enzymes MMP-9 and MMP-2 among combined users of amphetamine and heroin. The levels of TNF-α and IL-6 only increased in the heart disease group. Growth hormone was increased; however, IGF-I level decreased with drug abuse and the level was not restored by abstinence. We speculated that the amphetamine-heroin users might pose risk to initiate heart disease even though the users abstained for more than two weeks. The activity change of MMP-9 and MMP-2 can be a direct reason affecting heart function. The indirect reason may be related to liver damage by drug abuse reduce IGF-1 production to protect heart function.

Calycosin inhibits gemcitabine-resistant lung cancer cells proliferation through modulation of the LDOC1/GNL3L/NFκB.

Lung cancer is the most common malignant cancer worldwide. Combination therapies are urgently needed to increase patient survival. Calycosin is a phytoestrogen isoflavone that has been reported previously to inhibit tumor cell growth, although its effects on lung cancer remain unclear. The aim of this study was to investigate the effects of calycosin on cell proliferation and apoptosis of gemcitabine-resistant lung cancer cells. Using calycosin to treat human lung cancer cells (CL1-0) and gemcitabine-resistant lung cancer cells (CL1-0 GEMR) and examine the effects on the cells. Cultured human lung cancer cells (CL1-0) and gemcitabine-resistant lung cancer cells (CL1-0 GEMR) were treated with increasing concentrations of calycosin. Cell viability and apoptosis were studied by the 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide, flow cytometry, and TUNEL assays. Western blots were used to measure the expression levels of proliferation-related proteins and cancer stem cell proteins in CL1-0 GEMR cells. The results showed that calycosin treatment inhibited cell proliferation, decreased cell migration ability, and suppressed cancer stem cell properties in CL1-0 GEMR cells. Interestingly, in CL1-0 GEMR cells, calycosin treatment not only increased LDOC1 but also decreased GNL3L/NFκB protein levels and mRNA levels, in concentration-dependent manners. We speculate that calycosin inhibited cell proliferation of the gemcitabine-resistant cell line through regulating the LDOC1/GNL3L/NFκB pathway.

Tannic acid attenuate AKT phosphorylation to inhibit UMUC3 bladder cancer cell proliferation.

Urothelial bladder cancer is rapidly spreading across Western countries, and therapy has shown little-to-moderate effects on bladder cancer. Thus, focusing on curbing cancer incidence has become crucial. The aim of the present study was to investigate the anticancer effects of Tannic acid (TA) in human bladder cancer. UMUC3 bladder cancer cells were treated with different concentrations of TA (0-100 µM) and tested for cell viability, colony formation, and apoptosis. The involvement of the phosphoinositide-3 kinase (PI3K)/Akt pathway in the action of TA was examined. TA treatment significantly inhibited the viability and increased percentage of apoptotic cells, thereby decreasing antiapoptotic proteins (BCL2, MCL-1, and BCL-XL) expression, resulting in the Caspase-3 activation. TA treatment decreased stem cell markers expression such as SOX2, OCT4, and NANOG. Additionally, TA treatment significantly reduced the phosphorylation levels of Akt in bladder cancer cells. Our study demonstrates the growth inhibitory effects of TA in bladder cancer cells, and highlights its potential as an anticancer agent for bladder cancer.

SENP1 participates in Irinotecan resistance in human colon cancer cells.

Colorectal cancer is one of the most prevalent cancers in the world. Chemoresistance has always been a problem encountered in its treatment. It is known that SUMOylation may regulate protein stability and decomposition, and even affect the protein translocation and posttranslational modification in cells. Sentrin-specific protease 1 (SENP1) is involved in the maturation of SUMO protein, and on the other hand, plays a role in deSUMOylation, which dissociates the target protein from SUMO and prevents further degradation of the target protein. In this study, we established an Irinotecan (CPT-11) resistant human colon cancer LoVo strain (LoVoR-CPT-11 ) to investigate the role of SENP1 in the development of drug resistance in colorectal cancer. The abundant accumulation of SENP1 and HIF-1α proteins and the increase of SUMO pathway enzymes were observed in LoVoR-CPT-11 cells while the protein markers of proliferation, angiogenesis, and glycolysis were upregulated. Knockdown of SENP1 reduced the migration ability and trigged re-sensitivity of LoVoR-CPT-11 cells to CPT-11 treatment. The analysis of SENP1 and HIF-1α gene expressions from TCGA/GTEx datasets using the GEPIA web server showed a positive correlation between SENP1 and HIF-1α in colorectal cancer patients and the high expression of these two genes might predict a poor outcome clinically. In conclusion, SENP1 might play an important role in CPT-11 resistance in colorectal cancer. Targeting SENP1 to reduce the resistant property could be considered in prospective clinical studies.

Identification and Characterization of Potential Biomarkers by Quantitative Tissue Proteomics of Primary Lung Adenocarcinoma.

Lung cancer is the leading cause of cancer-related death worldwide. Both diagnostic and prognostic biomarkers are urgently needed to increase patient survival. In this study, we identified/quantified 1763 proteins from paired adenocarcinoma (ADC) tissues with different extents of lymph node (LN) involvement using an iTRAQ-based quantitative proteomic analysis. Based on a bioinformatics analysis and literature search, we selected six candidates (ERO1L, PABPC4, RCC1, RPS25, NARS, and TARS) from a set of 133 proteins that presented a 1.5-fold increase in expression in ADC tumors without LN metastasis compared with adjacent normal tissues. These six proteins were further verified using immunohistochemical staining and Western blot analyses. The protein levels of these six candidates were higher in tumor tissues compared with adjacent normal tissues. The ERO1L and NARS levels were positively associated with LN metastasis. Importantly, ERO1L overexpression in patients with early-stage ADC was positively correlated with poor survival, suggesting that ERO1L overexpression in primary sites of early-stage cancer tissues indicates a high risk for cancer micrometastasis. Moreover, we found that knockdown of either ERO1L or NARS reduced the viability and migration ability of ADC cells. Our results collectively provide a potential biomarker data set for ADC diagnosis/prognosis and reveal novel roles of ERO1L and NARS in ADC progression.

Tannic Acid Impedes the Proliferation of Bladder Cancer Cells by Elevating Mitochondrial Pathways of Apoptosis.

Bladder cancer stands as a prevailing neoplasm among men globally, distinguished for its pronounced malignancy attributed to invasiveness and metastatic proclivity. Tannic acid (TA), an organic compound in many plants, has garnered recent attention for its discernible anti-mutagenic attributes. This investigation endeavored to scrutinize the repercussions of TA on grade II bladder cancer, with a concerted focus on unraveling its anti-cancer mechanisms. The cytotoxic effects of TA on grade II bladder cancer cells were investigated using multiple techniques, including MTT assay, flow cytometry, TUNEL assay, and western blot. Our findings revealed that elevated concentrations of TA induced cytotoxic effects in grade II bladder cancer cells. Both flow cytometry and the TUNEL assay substantiated the dose-dependent capacity of TA to prompt apoptosis. Western blot analysis corroborated that TA treatment in bladder cancer cells resulted in the upregulation of cleaved caspase-3 expression and PARP. Furthermore, heightened TA dosage elicited an augmentation in the expression of pro-apoptotic proteins, namely Bax and Bak, alongside a reduction in the expression of the anti-apoptotic protein Bcl-2 within bladder cancer cells. This study confirms TA as a potential anticancer agent, demonstrably diminishing the viability of bladder cancer cells. TA exerts cytotoxicity through the activation of mitochondrial apoptotic pathways. Specifically, TA initiates the cleavage of PARP and caspase-3, concurrently augmenting the expression of pro-apoptotic proteins to facilitate apoptosis. Collectively, the present study indicates that TA effectively impedes the proliferation of bladder cancer cells by instigating apoptosis through the intrinsic mitochondrial pathway.

AGR2 expression as a predictive biomarker for therapy response in esophageal squamous cell carcinoma.

Despite multidisciplinary therapy, the prognosis is poor for esophageal squamous cell carcinoma (ESCC). In the locally advanced stage, neoadjuvant chemoradiotherapy (nCRT) followed by surgery could provide survival benefits to some patients. Here, we aimed to identify for tumor therapy response a biomarker based on RNA sequencing. We collected endoscopic biopsies of 32 ESCC patients, who were divided according to nCRT response, into two groups: the complete response group (n = 13) and the non-complete response group (n = 19). RNA-sequencing data showed that 464 genes were differentially expressed. Increased in non-complete response group, 4 genes increased expressions were AGR2 (anterior gradient 2), GADD45B (growth arrest and DNA damage inducible beta), PPP1R15A (protein phosphatase 1 regulatory subunit 15A) and LRG1 (leucine rich alpha-2-glycoprotein 1). The areas under the curve (AUC) of the AGR2 gene was 0.671 according to read counts of RNA-seq and therapy response of nCRT. In vitro study showed that apoptosis cell was significantly increased in the AGR2-knockdown TE-2 cell line treated with cisplatin and 5-Fluorouracil (5-FU), when compared with si-control. Results suggest that in ESCC, the AGR2 gene is a promising and predictive gene marker for the response to anti-tumor therapy.