Comprehensive Analysis of the Prognostic Marker and Immune Infiltrates of LDLR-Related Proteins Family Members in Breast Cancer.

Background & Objective: Breast cancer (BC) is one of the most frequent tumors worldwide, accounting for 15% of all cancer-related deaths. A timely diagnosis of BC is essential for optimal treatment and increasing patients' survival rates. LRP family proteins are important components of cell-surface receptors involved in numerous biological activities. Expression of LRP is related to breast malignancy. In this study, we initially studied the expression of LRPs in BC tissues compared to normal tissues-the relation of LRP expression with relapse-free survival (RFS) and overall survival (OS). Then, we investigated the association of LRPs relation and immune infiltrating abundance. Methods: We analyzed the LDLR family expression and prognostic value in BC by mining UALCAN, TIMER, and Kaplan-Meier plotter databases. Subsequently, we explored the association of LDLR expression and immune infiltrating abundance via the TIMER database. Results: Expression levels of LRP1/2/4/9/10 were found to be higher in the cases with positive estrogen receptors. There was a positive association between LRP1/6 expression and the infiltration of CD8+ T cells, CD4+ T Cell, Macrophage, Dendritic Cell, and Neutrophil. Conclusion: Our study recommends LDLR as a potential prognostic biomarker that can be promising to improve the survival of BC patients' survival. However, further investigations are needed to evaluate the studied LDLR members in more detail.

Combination of Quercetin or/and siRNA-loaded DDAB-mPEG-PCL hybrid nanoparticles reverse resistance to Regorafenib in colon cancer cells.

BACKGROUND: Colorectal cancer (CRC) is the second leading cause of cancer death. Although Regorafenib showed survival benefits in patients with CRC, reports imply the recurrence of malignant phenotype resulting from chemotherapy. Evidence demonstrated that a5ß1 integrin plays an important role in the Regorafenib treatment, which, may be led to resistance. In this study, the effects of /siRNA or/ and Quercetin loaded DDAB-mPEG-PCLnanoparticles could reverse this resistance phenotype in colon cancer cells in vitro. METHODS: Regorafenib-resistant Ls-180 colon cancer cell line was developed by long-term exposure to Regorafenib. Quercetin and Regorafenib were separately encapsulated into mPEG-PCL micelles through the nano-precipitation method and characterized by DLS. Optimized doses of Quercetin and Regorafenib were used for combination therapy of resistant cells followed cytotoxicity study using MTT. Gene expression levels of the ß1 subunit of integrin were determined by the real-time method of RT-PCR. RESULTS: Developed Regorafenib resistant LS-180 showed to have Regorafenib IC50 of 38.96 ± 1.72 µM whereas IC50 in non-resistant cells were 8.51 ± 0.29 µM, which meaningful was lower statistically compared to that of a resistant one. The ß1 mRNA level of whole α5ß1 integrin was significantly higher in the resistant cells compared to those of non-resistant ones. Gene expression levels in each siRNA-loaded nanoparticle and Quercetin-loaded one were lower than that in mock experiments. Finally, when these two types of nanoparticles were used to treat resistant cells, gene expression decrease of integrin indicated a greater effect that could be capable of reverse resistancy. CONCLUSION: Results of this study demonstrated another confirmation of involving integrins in cancer resistance following chemotherapy using Regorafenib. Also, it indicated how using siRNA targeting integrin could enhance the plant derivatives like Quercetin effects to reverse resistance in vitro.

Effect of Metformin on Circulating Levels of Inflammatory Markers in Patients With Type 2 Diabetes: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

BACKGROUND: Emerging evidence indicates that metformin has anti-inflammatory effect; however, the results differ concerning randomized controlled trails of the effect of metformin on inflammatory markers in type 2 diabetes (T2D) patients. OBJECTIVE: This study reassessed the data on the effect of metformin treatment on inflammatory markers in T2D patients through a systematic review and meta-analysis. METHODS: A systematic search was performed in the PubMed, ISI Web of Science, EMBASE, Cochrane Library and Scopus databases to collect relevant published data up to September 2020. Data of each study was combined using random-effects model. Subgroup analysis was performed based on subgroups of the treatment duration, dose and target population. RESULTS: Thirteen RCTs including 1776 participants with T2D were analyzed. Although CRP levels significantly decreased [SMD: -0.76 mg/L; 95% CI (-1.48, -0.049); P = 0.036] in patients with T2D following metformin treatment, circulating levels of TNF-α [SMD: -0.17 pg/mL; 95% CI (-0.55, 0.20); P = 0.37] and IL-6 [SMD: -0.06 pg/mL; 95% CI (-0.38, 0.25); P = 0.69] were insignificant after metformin treatment. Compared to treatment duration of less than 24 weeks, longer treatment duration (more than 24 weeks) was associated with reduced level of CRP. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Based on available evidence from RCTs in this meta-analysis, metformin decreased CRP level. However, strategies for the treatment of inflammation should focus on metformin in patients with T2D. CONCLUSION: The present study evidences that therapy with metformin can reduce CRP level significantly in T2D patients compared to other inflammatory markers.

Circulating Irisin Levels and Redox Status Markers in Patients with Gastric Cancer: A Case-Control Study.

OBJECTIVE: Irisin, mostly known as an exercise-induced fat browning myokine, has been recently detected in several cancer cells, and its potential for being utilized as a biomarker for early diagnosis of some cancers, such as Gastric cancer (GC), is the subject of speculation. The present study aims to compare serum irisin levels in GC patients and healthy controls and assess the interrelation between irisin and oxidative stress markers. METHODS: In this case-control study, 22 newly diagnosed GC patients and 29 healthy controls were recruited based on the inclusion criteria. Serum levels of irisin were quantified in duplicates by ELISA. Oxidative stress indices, including total antioxidant power in sera, thiol group, malondialdehyde, and superoxide dismutase concentrations, were also measured in both groups. An independent-sample t-test was used to compare the means between the two studied groups. RESULTS: Serum levels of irisin were significantly higher in the GC group compared with those of their healthy counterparts (p =0.032). No significant differences were observed between the two groups in terms of the serum total antioxidant power or the oxidative stress marker, including MDA, thiol groups, and SOD concentration in sera. Furthermore, there was no significant association between irisin, FRAP, the Thiol group, and the SOD activity. CONCLUSION: According to the finding, the increased serum levels of irisin in GC patients can play a potential role in the early diagnosis of the GC patients; hence, this peptide can be employed as a new diagnostic indicator of GC.
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