Microbiome Dysbiosis, Dietary Intake and Lifestyle-Associated Factors Involve in Epigenetic Modulations in Colorectal Cancer: A Narrative Review.

Background: Colorectal cancer is the second cause of cancer mortality and the third most commonly diagnosed cancer worldwide. Current data available implicate epigenetic modulations in colorectal cancer development. The health of the large bowel is impacted by gut microbiome dysbiosis, which may lead to colon and rectum cancers. The release of microbial metabolites and toxins by these microbiotas has been shown to activate epigenetic processes leading to colorectal cancer development. Increased consumption of a 'Westernized diet' and certain lifestyle factors such as excessive consumption of alcohol have been associated with colorectal cancer.Purpose: In this review, we seek to examine current knowledge on the involvement of gut microbiota, dietary factors, and alcohol consumption in colorectal cancer development through epigenetic modulations.Methods: A review of several published articles focusing on the mechanism of how changes in the gut microbiome, diet, and excessive alcohol consumption contribute to colorectal cancer development and the potential of using these factors as biomarkers for colorectal cancer diagnosis.Conclusions: This review presents scientific findings that provide a hopeful future for manipulating gut microbiome, diet, and alcohol consumption in colorectal cancer patients' management and care.

HPV18 L1 and long control region sequences variation and E6/E7 differential expression in nasopharyngeal and cervical cancers: a comparative study.

BACKGROUND: The role of high-risk human papillomaviruses (hr-HPVs) in cervical cancer (CC) pathogenesis has long been established. Knowledge about the involvement of hr-HPVs in the etiology of nasopharyngeal cancers (NPC) was not well appreciated until the early 2000s when a clear link began to emerge. However, it is not clear whether HPV oncogenesis in the different epithelial cancers is associated with L1 gene and long-control region (LCR) sequences variation. This study aimed to investigate the HPV18 L1 gene and LCR sequences variation in cervical and nasopharyngeal biopsies, and assessed E6 and E7 genes expression level in both cancers. METHOD: Four-hundred and three (403) formalin-fixed paraffin-embedded tissues originating from nasopharyngeal (NPC) (279) and cervical (CC) (124) sites were collected from a pathology laboratory, Pathologist Without Borders, Accra, Ghana. Haematoxylin and eosin staining was carried out to confirm the presence of cancer on prepared biopsy sections. DNA was extracted from the confirmed cancer biopsies, followed by PCR using MY09/GP5+ /6+ primers to detect the presence of HPV and specific primers for the amplification of L1 gene and LCR. Sanger sequencing was carried out to determine HPV genotypes, and L1 and LCR sequences variant of HPV18s in CC and NPC biopsies. The HPV18 E6/E7 mRNA expression pattern in both cancers was determined using RT-qPCR. RESULTS: Most of the NPC (45%) and CC (55%) biopsies were HPV18 positive. Comparison of HPV18 L1 sequences obtained from cervical and nasopharyngeal cancer tissues, the L1 sequences from the NPC were highly dissimilar with a 59-100% variation among themselves, and in relation to the reference strains. However, the L1 sequences from the CC were more similar with a 91.0-100% variation among the amplified sequences. Also, the LCR sequences from CC were quite different relative to that of NPC. Results for the differential expression of E6/E7 in the two cancers showed a higher fold change in E6 expression in the CC tissues than the NPC tissues while a reverse expression pattern was found for E7 gene. CONCLUSION: The current study reports for the first-time variations in HPV18 L1 and LCR sequences, and differential expression of E6/E7 genes in NPC compared to CC, suggesting a possible adaptation mechanism of the virus at different cancer sites.

Paradox of COVID-19 in pregnancy: are pregnant women more protected against or at elevated risk of severe COVID-19?

Many underlying medical conditions have been linked to worse COVID-19 prognosis. Based on reports on SARS-CoV-1 and Middle East respiratory syndrome infections, pregnancy has been considered a predisposing factor to severe COVID-19, with pregnant women being a high-risk group for several physiological reasons. Specifically, pregnant women undergo physiological adaptations that predispose them to severe respiratory viral diseases, including SARS-CoV-2. However, a significant amount of evidence suggests that the clinical outcome of COVID-19 among pregnant women is not different from the general population. In view of this, this report discusses the physiological conditions in pregnant women that adversely affect their immunity, cardiovascular homeostasis, and their endothelial and coagulopathic functions, thereby making them more prone to severe viral infections. We also discuss how these physiological adaptations appear to paradoxically offer protection against severe COVID-19 among pregnant women.

Helicobacter Pylori Variants with ABC-Type Tyrosine Phosphorylation Motif in Gastric Biopsies of Ghanaian Patients.

BACKGROUND: Helicobacter pylori pathogenicity and disease severity are determined by the tyrosine phosphorylation motifs of CagA protein. This study is aimed at detecting the presence of H. pylori and identifying the CagA tyrosine phosphorylation motifs in Ghanaian patients. Material and Methods. A total of 94 archival genomic DNA samples from gastric biopsies were used for the study, and H. pylori was detected by amplifying the 16S rRNA gene. The 3'-end variable region of the cagA gene was amplified, and the entire 3'-end was sequenced and translated into amino acids. RESULTS: H. pylori was detected in 53.2% (50/94) of the samples, and all the detected bacteria harboured the cagA gene. Two variants of the bacteria were identified based on the size of the amplified cagA gene: 207 bp and 285 bp. The 207 bp and 285 bp variants accounted for 74% and 22%, respectively, and 4% showed both fragments. Translated amino acid sequence of the cagA gene showed EPIYA-A, EPIYA-B, and EPIYA-C (ABC type) motifs, indicating the Western variant. The CagA protein C-terminal showed insertion of amino acids in the sequence flanking the EPIYA-A motif at the N-terminal and a complete deletion of the EPIYA-CC and EPIYA-CCC motifs together with the flanking sequences. CONCLUSIONS: H. pylori identified were Western variant (ABC type) with unique amino acid insertions, suggesting unique variants in Ghanaian patients. Further investigation is however required to understand the role of the molecular diversity of the variant in gastric disease outcome.

High atherogenic index of plasma and cardiovascular risk factors among Ghanaian breast cancer patients.

Comorbidities impact negatively on breast cancer prognosis, especially in developing countries where cases are usually presented to clinics at advanced stages. This study aimed to determine the atherogenic index of plasma (AIP) and cardiovascular risk factors among Ghanaian women diagnosed with breast cancer. A total of 52 breast cancer patients were age-matched with 52 healthy controls. Sociodemographics of participants were obtained using a well-structured questionnaire. Pathological data of patients were obtained from medical records, and all clinical and anthropometric measurements were done using standard instruments. Lipid profile was determined from serum using enzymatic assays, and cardiovascular risk factors were calculated from estimated lipid parameters. Blood pressure, AIP, total cholesterol (T. chol), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-c) were significantly elevated (P < 0.05) in the breast cancer patients compared to the controls, but the reverse was observed for high-density lipoprotein cholesterol (HDL-c) (P < 0.01). Obesity (odds ratio [OR] = 2.51, P = 0.015), hypertension (OR = 4.04, P < 0.001), AIP (OR = 10.44, P < 0.001), and dyslipidemia (P < 0.01) were significantly associated with breast cancer. AIP correlated positively with age (r = 0.244, P < 0.05), body mass index (r = 0.225, P < 0.05), blood pressure (P < 0.01), T. chol (r =0.418, P< 0.01), and TG (r = 0.880, P < 0.01), but inversely correlated with HDL-c (r = -0.460, P < 0.01). A greater proportion (88%) of the patients presented with advanced breast cancer. AIP and cardiovascular risk factors were high in the breast cancer patients. Considering that AIP and cardiovascular disease risk factors are of interest in breast cancer patients, further studies are needed to understand the effect of AIP and cardiovascular risk factors on breast cancer outcomes.

Dyslipidaemia is common among patients with type 2 diabetes: a cross-sectional study at Tema Port Clinic.

OBJECTIVE: This study aimed to evaluate dyslipidemia in Ghanaian subjects with type 2 diabetes. RESULTS: Hundred individuals with type 2 diabetes and 61 apparently healthy controls participated. The prevalence of hypercholesterolemia among persons with type 2 diabetes was 53%. Blood pressure, fasting blood glucose (FBG), triglyceride (TG), low-density lipoproteins (LDL) and alanine transaminase (ALT) levels were higher in persons with type 2 diabetes compared with the control group (p < 0.01). Positive correlations were found within persons with type 2 diabetes for triglyceride vs FBG; ALT vs age and aspartate transaminase (AST) vs TG (p < 0.05 respectively). This study demonstrated hyperlipidemia and poor liver health in persons with type 2 diabetes.

Helicobacter pylori-induced alteration of epithelial cell signaling and polarity: a possible mechanism of gastric carcinoma etiology and disparity.

Gastric cancer, a disease of disparity associated with Helicobacter pylori (H. pylori) infection, is the world's second leading cause of cancer deaths. The pathogen H. pylori target the epithelial adhesion receptors, E-cadherin, and ß1-integrin, to modulate the host cytoskeleton via disruption of the epithelial cell polarity necessary for maintaining the infection, but how this leads to the development of the carcinoma is widely unclear. While Rho family GTPases' signaling to the cytoskeleton and these receptors is required for initiating and maintaining the infection, the responsible effectors, and how they might influence the etiology of the carcinomas are currently unknown. Here we discuss the potential role of the Cdc42-IQGAP1 axis, a negative regulator of the tumor suppressors E-cadherin and ß1-integrin, as a potential driver of H. pylori-induced gastric carcinoma and propose avenues for addressing its disparity. Chronic dysfunction of the IQGAP1-signaling pathway, resulting from H. pylori-induced disruption of cell polarity, can explain the pathogenesis of the carcinoma, at least, in subsets of infected population, and thus could provide a potential means for personalized medicine.