Targeting the CCL2-CCR2 signaling pathway: potential implications of statins beyond cardiovascular diseases.

BACKGROUND: The chemokine ligand CCL2 and its cognate receptor CCR2 have been implicated in the pathogenesis of a wide variety of diseases. Hence, the inhibition of the CCL2/CCR2 signaling pathway has been of great attention in recent studies. Among suggested medications, statins known as HMG-COA reductase inhibitors with their pleiotropic effects are widely under investigation. METHOD: A comprehensive literature search on Scopus and PubMed databases was conducted using the keywords 'CCL2', 'CCR2', 'monocyte chemoattractant protein-1', 'HMG-COA reductase inhibitor', and 'statin'. Both experimental and clinical studies measuring CCL2/CCR2 expressions following statin therapy were identified excluding the ones focused on cardiovascular diseases. RESULTS: Herein, we summarized the effects of statins on CCL2 and CCR2 expression in various pathologic conditions including immune-mediated diseases, nephropathies, diabetes, rheumatic diseases, neuroinflammation, inflammatory bowel diseases, gynecologic diseases, and cancers. CONCLUSION: For the most part, statins play an inhibitory role on the CCL2-CCR2 axis which implies their potential to be further developed as therapeutic options in non-cardiovascular diseases either alone or in combination with other conventional treatments. However, the existing literature mostly focused on experimental models and is therefore inadequate to reach a conclusion.

Prognostic value of primary tumor location in colorectal cancer: an updated meta-analysis.

The clinical, histological, and molecular differences between right-sided colon cancer (RCC) and left-sided colon cancer (RCC) have received considerable attention. Over the past decade, many articles have been published concerning the association between primary tumor location (PTL) of colorectal cancer and survival outcomes. Therefore, there is a growing need for an updated meta-analysis integrating the outcomes of recent studies to determine the prognostic role of right vs left-sidedness of PTL in patients with colorectal cancer. We conducted a comprehensive database review using PubMed, SCOPUS, and Cochrane library databases from February 2016 to March 2023 for prospective or retrospective studies reporting data on overall survival (OS) and cancer-specific survival (CSS) of RCC compared with LCC. A total of 60 cohort studies comprising 1,494,445 patients were included in the meta-analysis. We demonstrated that RCC is associated with a significantly increased risk of death compared with LCC by 25% (hazard ratio (HR), 1.25; 95% confidence interval (CI), 1.19-1.31; I2 = 78.4%; Z = 43.68). Results showed that patients with RCC have a worse OS compared with LCC only in advanced stages (Stage III: HR, 1.275; 95% CI 1.16-1.4; P = 0.0002; I2 = 85.8%; Stage IV: HR, 1.34; 95% CI 1.25-1.44; P < 0.0001; I2 = 69.2%) but not in primary stages (Stage I/II: HR, 1.275; 95% CI 1.16-1.4; P = 0.0002; I2 = 85.8%). Moreover, a meta-analysis of 13 studies including 812,644 patients revealed that there is no significant difference in CSS between RCC and LCC (HR, 1.121; 95% CI 0.97-1.3; P = 0.112). Findings from the present meta-analysis highlight the importance of PTL in clinical decision-making for patients with CRC, especially in advanced stages. We provide further evidence supporting the hypothesis that RCC and LCC are distinct disease entities that should be managed differently.

Serum level and tumor tissue expression of Ribonucleotide-diphosphate Reductase subunit M2 B: a potential biomarker for colorectal cancer.

BACKGROUND: This study explored the applicability of serum level and tissue expression of Ribonucleotide-diphosphate Reductase subunit M2 B (RRM2B) as reliable biomarkers for colorectal cancer (CRC) progression and metastasis. METHODS AND RESULTS: The present descriptive-analytic cohort study was conducted on 50 newly diagnosed CRC patients (stage II, III) and 50 healthy individuals. The new cases had not received any therapeutic intervention and underwent surgery immediately after the initial diagnosis. Tumorous tissues and marginal healthy tissues (as control) were excised to determine the mRNA tissue expression of RRM2B by Real-Time PCR. Serum RRM2B protein was measured using an ELISA method once in the control group. In the patients, serum RRM2B protein was evaluated before, 1 and 3 months after surgery. The tumor metastasis node (TMN) classification system and liver metastasis were evaluated in CRC patients. The results showed significantly lower RRM2B serum levels in 1 and 3 months after surgery compared with the pre-surgery condition (P = 0.014, P < 0.001 respectively). The mean RRM2B gene expression was 51% lower in tumor tissue than its adjacent normal tissue (P < 0.001). No significant relationship was found between serum level of RRM2B and tumor staging and metastasis in patients before surgery (P = 0.373, P = 0.189), 1 month after surgery (P = 0.960, P = 0.088), and 3 months after surgery (P = 0.407, P = 0.724). RRM2B expression in tumor tissue is not associated with tumor staging and metastasis (P = 0.254, P = 0.721). CONCLUSION: These data suggest measuring serum protein level of RRM2B could have a role in CRC progression, although this study should be considered preliminary due to small sample size and short follow-up duration.

Gastrointestinal and hepatic abnormalities in patients with confirmed COVID-19: A systematic review and meta-analysis.

Although not common, gastrointestinal and liver symptoms have reportedly been the initial presentation of coronavirus disease-2019 (COVID-19) in a large group of patients. Therefore, knowing the frequency and characteristics of these manifestations of COVID-19 is important for both clinicians and health policy makers. A systematic review and meta-analysis of the available data on the gastrointestinal and liver manifestations of patients with COVID-19 was performed. PubMed and Scopus databases and Google Scholar search engine were searched for published and unpublished preprint articles up to 10 April 2020. Original studies providing information on clinical digestive symptoms or biomarkers of liver function in patients with polymerase chain reaction confirmed diagnosis of COVID-19 were included. After quality appraisal, data were extracted. Prevalence data from individual studies were pooled using a random-effects model. Overall, 67 studies were included in this systematic review and meta-analysis, comprising a pooled population of 13 251 patients with confirmed COVID-19. The most common gastrointestinal symptoms were anorexia (10.2%, 95% confidence interval [CI] = 6.2%-16.4%), diarrhea (8.4%, 95% CI = 6.2%-11.2%), and nausea (5.7%, 95% CI = 3.7%-8.6%), respectively. Decreased albumin levels (39.8%, 95% CI = 15.3%-70.8%), increased aspartate aminotransferase (22.8%, 95% CI = 18.1%-28.4%), and alanine aminotransferase (20.6%, 95% CI = 16.7%-25.1%) were common hepatic findings. After adjusting for preexisting gastrointestinal (5.9%) and liver diseases (4.2%), the most common gastrointestinal findings were diarrhea (8.7%, 95% CI = 5.4%-13.9%), anorexia (8.0%, 95% CI = 3.0%-19.8%), and nausea (5.1%, 95% CI = 2.2%-14.3%). Gastrointestinal and liver manifestations are not rare in patients with COVID-19, but their prevalence might be affected by preexisting diseases. Diarrhea and mild liver abnormalities seem to be relatively common in COVID-19, regardless of comorbidities.