Predictors of mortality in hospitalized African American COVID-19 patients with cancer.

Background: Coronavirus disease 2019 (COVID-19) manifest differently depending on patients' background and pre-existing conditions. It remains unclear how African Americans with cancer have been affected in comparison to those without. In this study, we aim to identify demographic, clinical, and laboratory markers associated with mortality in COVID-19 patients with cancer. Methods: We reviewed all COVID-19 hospitalized patients' records from Dec. 2019 to Oct. 2021 at Howard University Hospital. Patients having a history of, or active, cancer were reviewed. Clinical, treatment, lab test values, and pathological data were extracted. Univariable and multivariable analyses were conducted on the entire cohort as well as on cases and controls separately, using SPSS software. Results: Out of 512 COVID-19 infected patients, 49 had cancer, either active or history of cancer (cases) and 463 COVID-19 were cancer-free (controls), allowing for comparison. African American race was predominant in both cases and controls, 83.7% and 66.7% respectively. Cancer patients were older than non-cancer patients (mean age: 70.6 vs. 56.3 years) and had an increased length of hospital stay (mean 13.9 vs. 9.4 days). Mortality is significantly higher among cancer patients (n=10, 20.4%, P=0.03) compared to non-cancer COVID-19 patients (n=41, 8.9%). Among cancer patients, breast cancer was more prevalent in females and prostate cancer in males (54% and 52%, respectively). A comparison of patients with active vs. previous cancer showed no significant difference in the clinical outcome, death vs. discharge (P=0.34). A higher reduction in albumin level in cancer cases, from the time of admission to day 5, was significantly associated with death during the hospital stay compared to those discharged (n=24, 49.0%, P<0.001). In controls, lymphopenia (n=436, 94.2%, P=0.05), aspartate aminotransferase (AST) (n=59, 12.7%, P=0.008) and albumin (n=40, 8.6%, P=0.02) have shown an association with increased mortality. Conclusions: Albumin level has an inverse relationship with clinical outcomes among all COVID-19 infected cancer patients. Reduction in albumin level during the hospital stay, particularly in COVID-19 cancer patients should be considered as a predictor of mortality. Further research with a large cohort size is needed to verify and identify other predictors of outcomes in COVID-19 patients with cancer.

High-throughput sequencing and in-silico analysis confirm pathogenicity of novel MSH3 variants in African American colorectal cancer.

The maintenance of DNA sequence integrity is critical to avoid accumulation of cancer-causing mutations. Inactivation of DNA Mismatch Repair (MMR) genes (e.g., MLH1 and MSH2) is common among many cancers, including colorectal cancer (CRC) and is the driver of classic microsatellite instability (MSI) in tumors. Somatic MSH3 alterations have been linked to a specific form of MSI called elevated microsatellite alterations at selected tetranucleotide repeats (EMAST) that is associated with patient poor prognosis and elevated among African American (AA) rectal cancer patients. Genetic variants of MSH3 and their pathogenicity vary among different populations, such as among AA, which are not well-represented in publicly available databases. Targeted exome sequencing of MSH3 among AA CRC samples followed by computational bioinformatic pipeline and molecular dynamic simulation analysis approach confirmed six identified MSH3 variants (c.G1237A, c.C2759T, c.G1397A, c.G2926A, c.C3028T, c.G3241A) that corresponded to MSH3 amino-acid changes (p.E413K; p.S466N; p.S920F; p.E976K; p.H1010Y; p.E1081K). All identified MSH3 variants were non-synonymous, novel, pathogenic, and show loss or gain of hydrogen bonding, ionic bonding, hydrophobic bonding, and disulfide bonding and have a deleterious effect on the structure of MSH3 protein. Some variants were located within the ATPase site of MSH3, affecting ATP hydrolysis that is critical for MSH3's function. Other variants were in the MSH3-MSH2 interacting domain, important for MSH3's binding to MSH2. Overall, our data suggest that these variants among AA CRC patients affect the function of MSH3 making them pathogenic and likely contributing to the development or advancement of CRC among AA. Further clarifying functional studies will be necessary to fully understand the impact of these variants on MSH3 function and CRC development in AA patients.

Exploring the Incidence and Associated Risk Factors of Barrett's Esophagus in African Americans: A Retrospective Study.

Background: The prevalence of Barrett's esophagus (BE) in African Americans (AA) is uncertain. However, several potential risk factors, includes family history, male sex, ethnicity, chronic heartburn and acid reflux, age over 60, current or past smoking, and obesity are associated with BE. The aim of this study is to determine the incidence of BE in AA patients who underwent Esophageal Gastro Endoscopy (EGD). Methods: Medical and demographic data of 1,253 AA patients with various symptoms, including BE, Esophageal adenocarcinoma (EAC), esophageal squamous adenocarcinoma (SCC), hiatal hernia, H. pylori infection, Gastro-Esophageal Reflux Disease (GERD), Gastritis, and esophagitis, were collected from January 2004 to December 2014 at Howard University Hospital. Results: Among the 1,253 patients, the median age was 61 and 49% were male out of the total. The frequencies of EAC (p= 0.05), and SCC (p= 0.002) were significantly high in males, along with SCC frequency significantly increased with older age (p<0.001). Furthermore, esophageal polyps with hiatal hernia (p=0.008) and H. pylori (p=<0.001) were found to be associated with esophagitis, and its presence may contribute to the development of BE. Conclusion: The findings highlighted the high prevalence of GERD symptoms and pathologic gastritis along with EAC was less common than SCC and both types of esophageal cancer were associated with male gender and older age whereas, H. pylori infection was identified as a risk factor for pathologic gastritis in AA. Overall data emphasize the need for extensive research, increased awareness, diagnosis, and management of GERD, gastritis, and related conditions to uncover the underlying mechanisms and factors contributing to these conditions in the AA population.

Potential long-term neurological and gastrointestinal effects of COVID-19: A review of adult cohorts.

BACKGROUND: The respiratory infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has evolved into a multi-organ disorder, with long-term effects known as post-acute sequelae of SARS-CoV-2 infection or long coronavirus disease (COVID). AIM: To examine the current knowledge and outcomes of long-term neurological and gastrointestinal (GI) symptoms in adult cohorts, including United States minority populations. METHODS: PubMed and Google Scholar were searched using relevant terms, and data from five studies were analyzed, comprising 27383 patients with persistent neurological and GI sequelae. RESULTS: The main symptoms included anxiety, depression, dysphagia, headache, vomiting, nausea, gastroesophageal reflux, fatigue, and abdominal pain. Patients with comorbidities and metabolic syndromes were at higher risk for long COVID. While most patients were European Americans, there was a need for further study on African Americans. CONCLUSION: The underlying causes of these symptoms remain unclear, warranting more investigation into the long-term impact of the SARS-CoV-2 on different populations.

Editorial to the Special Issue 'Nutritional Intervention in Digestive Diseases in the Era of Nutraceuticals, Nutrigenomics and Microbiomics'.

Environmental exposures, particularly diet, play an important role in the prevention or exacerbation of illnesses, including gastrointestinal (GI) diseases [...].

Microbiomic and Metabolomic Analyses Unveil the Protective Effect of Saffron in a Mouse Colitis Model.

Despite the existence of effective drugs used to treat inflammatory bowel disease (IBD), many patients fail to respond or lose response over time. Further, many drugs can carry serious adverse effects, including increased risk of infections and malignancies. Saffron (Crocus sativus) has been reported to have anti-inflammatory properties. Its protective role in IBD and how the microbiome and metabolome play a role has not been explored extensively. We aimed to establish whether saffron treatment modulates the host microbiome and metabolic profile in experimental colitis. Colitis was induced in C57BL/6 mice with 3% DSS and treated with either saffron in a dose of 20 mg/kg body weight or vehicle through daily gavage. On day 10, stool pellets from mice were collected and analyzed to assess saffron's effect on fecal microbiota and metabolites through 16S rRNA sequencing and untargeted primary metabolite analysis. Saffron treatment maintained gut microbiota homeostasis by counter-selecting pro-inflammatory bacteria and maintained Firmicutes/Bacteroides ratio, which was otherwise disturbed by DSS treatment. Several metabolites (uric acid, cholesterol, 2 hydroxyglutaric acid, allantoic acid, 2 hydroxyhexanoic acid) were altered significantly with saffron treatment in DSS-treated mice, and this might play a role in mediating saffron's colitis-mitigating effects. These data demonstrate saffron's therapeutic potential, and its protective role is modulated by gut microbiota, potentially acting through changes in metabolites.

High Prevalence of Diabetes Among Hospitalized COVID-19 Minority Patients: Data from a Single Tertiary Hospital.

BACKGROUND AND AIM: Type 2 diabetes mellitus (DM) is a common comorbidity in the minority population and is associated with poor outcomes in COVID-19 patients. We hypothesized that COVID-19 patients with pre-existing diabetes mellitus are prone to fatal outcomes compared to non-diabetic patients. We aimed to illustrate the characteristics and outcomes and identify the risk factors for in-hospital mortality of COVID-19 patients with DM. METHODS: In this single-center retrospective study, electronic medical records of hospitalized patients with confirmed COVID-19 diagnosis at Howard University Hospital (HUH) from March 2020 to Dec 2021 were analyzed. Clinical, demographic, and serological information, as well as outcomes, were recorded and analyzed. RESULTS: Among 463 COVID-19 patients, 66.3% (n = 307) were African Americans (AA) and 35.9% (n = 166) had diabetes, with a mean age of 64 years. The majority of the diabetic patients were AA (n = 123, 74.1%) and had a higher mortality rate (n = 26, 74.3%) compared to others. Length of stay in the hospital is significantly more for the diabetic than for the non-diabetic patients (11.3 vs. 8.3 days, p = 0.03). A higher proportion of ICU admission (32.3% vs. 17.9%, p = < 0.001), intubation (17% vs. 11.7%, p = 0.04), and increased mortality (21.1% vs. 12.2%, p = 0.01) were identified in COVID-19 patients with DM than in those with no DM. Among DM patients, non-survivors were older (69.9 vs. 62.9 years). DM patients were more likely to have underlying hypertension (72.3% vs. 43.3%, p = < 0.001), obesity (44.8% vs. 32.1%, p = 0.007), chronic kidney disease (23.6 vs. 11.8%, p = 0.001), and cardiovascular disease (29.5% vs. 14.3%, p = 0.001) than the non-DM patients. HbA1C above 9%, indicating poorly controlled hyperglycemia, was associated with poor outcome among the DM subjects. AST (23.5% vs. 31.3%) and creatinine (61.4% vs. 37.9%) were significantly more elevated in DM COVID-19 patients (all p-values < 0.05). The levels of serum troponin (42.5% vs. 30.9%, p = 0.03), interleukin-6 (67.2 vs. 50%, p = 0.04), ferritin (65.6% vs. 44.6%, p = 0.03), procalcitonin (58.1% vs. 46.1, p = 0.03), and D-dimers (92.8% vs. 86.5%, p = 0.04) were significantly higher in DM patients as compared to those in non-DM COVID-19 patients, indicating more susceptibility of diabetic COVID-19 patients to coagulation dysfunction and inflammatory storm. CONCLUSION: The prevalence of DM is high among hospitalized COVID-19 patients in our cohort. While DM patients have a higher mortality rate and ICU admission than non-DM patients, other factors such as underlying comorbidities, old age, elevated creatinine, AST, serum inflammatory markers, and D-dimer are more significant predictors of fatal outcomes. DM patients had higher metabolic derangements, hypercoagulability, and severe inflammatory response. No significant difference of outcome was noted between DM patients of different races in our cohort. In the diabetic group, it appears that race may not significantly contribute to the observed mortality disparity. This could be attributed to the significant influence of diabetes, which acts as a major effector, potentially overshadowing the significance of race in this context.

Researching COVID to Enhance Recovery (RECOVER) adult study protocol: Rationale, objectives, and design.

IMPORTANCE: SARS-CoV-2 infection can result in ongoing, relapsing, or new symptoms or other health effects after the acute phase of infection; termed post-acute sequelae of SARS-CoV-2 infection (PASC), or long COVID. The characteristics, prevalence, trajectory and mechanisms of PASC are ill-defined. The objectives of the Researching COVID to Enhance Recovery (RECOVER) Multi-site Observational Study of PASC in Adults (RECOVER-Adult) are to: (1) characterize PASC prevalence; (2) characterize the symptoms, organ dysfunction, natural history, and distinct phenotypes of PASC; (3) identify demographic, social and clinical risk factors for PASC onset and recovery; and (4) define the biological mechanisms underlying PASC pathogenesis. METHODS: RECOVER-Adult is a combined prospective/retrospective cohort currently planned to enroll 14,880 adults aged ≥18 years. Eligible participants either must meet WHO criteria for suspected, probable, or confirmed infection; or must have evidence of no prior infection. Recruitment occurs at 86 sites in 33 U.S. states, Washington, DC and Puerto Rico, via facility- and community-based outreach. Participants complete quarterly questionnaires about symptoms, social determinants, vaccination status, and interim SARS-CoV-2 infections. In addition, participants contribute biospecimens and undergo physical and laboratory examinations at approximately 0, 90 and 180 days from infection or negative test date, and yearly thereafter. Some participants undergo additional testing based on specific criteria or random sampling. Patient representatives provide input on all study processes. The primary study outcome is onset of PASC, measured by signs and symptoms. A paradigm for identifying PASC cases will be defined and updated using supervised and unsupervised learning approaches with cross-validation. Logistic regression and proportional hazards regression will be conducted to investigate associations between risk factors, onset, and resolution of PASC symptoms. DISCUSSION: RECOVER-Adult is the first national, prospective, longitudinal cohort of PASC among US adults. Results of this study are intended to inform public health, spur clinical trials, and expand treatment options. REGISTRATION: NCT05172024.

Mechanism of Antitumor Effects of Saffron in Human Prostate Cancer Cells.

Prostate cancer is the most common cancer and the second leading cause of cancer deaths among men in the USA. Several studies have demonstrated the antitumor properties of saffron in different types of cancers, including prostate cancer. The oral administration of saffron extract has been reported to have antitumor effects on aggressive prostate-cancer-cell-line-derived xenografts in nude male mice. The objective of this study was to carry out in vitro studies of saffron-treated prostate cancer cells to ascertain the effects of saffron on key intermediates in prostate carcinogenesis. Our studies demonstrated the significant inhibition of cell proliferation for androgen-sensitive prostate cancer cell lines via apoptotic pathways. We also demonstrate the statistically significant down-regulation of DNA methyltransferases (COMT, MGMT, EHMT2, and SIRT1 deacetylase) in saffron-treated prostate cancer cells. In addition, saffron-treated prostate cancer cells displayed a statistically significant dysregulation of DNA repair intermediates (WRN, p53, RECQ5, MST1R, and WDR70) in a time-dependent manner. Furthermore, Western blot analysis demonstrated that saffron treatment induced changes in the expression of other key genes (DNMT1, DNMT3b, MBD2, CD44, HDAC3, c-Myc, NF-kB, TNFα, AR, N-RAS, and PTEN) in prostate cancer cells. Collectively, our findings demonstrate the important mechanisms by which saffron mediates anti-tumor properties in prostate cancer. These findings suggest that the use of saffron supplements alongside standard treatment protocols may yield beneficial effects for individuals with prostate cancer.

Inflammation, microbiome and colorectal cancer disparity in African-Americans: Are there bugs in the genetics?

Dysregulated interactions between host inflammation and gut microbiota over the course of life increase the risk of colorectal cancer (CRC). While environmental factors and socio-economic realities of race remain predominant contributors to CRC disparities in African-Americans (AAs), this review focuses on the biological mediators of CRC disparity, namely the under-appreciated influence of inherited ancestral genetic regulation on mucosal innate immunity and its interaction with the microbiome. There remains a poor understanding of mechanisms linking immune-related genetic polymorphisms and microbiome diversity that could influence chronic inflammation and exacerbate CRC disparities in AAs. A better understanding of the relationship between host genetics, bacteria, and CRC pathogenesis will improve the prediction of cancer risk across race/ethnicity groups overall.

Saffron, Its Active Components, and Their Association with DNA and Histone Modification: A Narrative Review of Current Knowledge.

Intensive screening for better and safer medications to treat diseases such as cancer and inflammatory diseases continue, and some phytochemicals have been discovered to have anti-cancer and many therapeutical activities. Among the traditionally used spices, Crocus sativus (saffron) and its principal bioactive constituents have anti-inflammatory, antioxidant, and chemopreventive properties against multiple malignancies. Early reports have shown that the epigenetic profiles of healthy and tumor cells vary significantly in the context of different epigenetic factors. Multiple components, such as carotenoids as bioactive dietary phytochemicals, can directly or indirectly regulate epigenetic factors and alter gene expression profiles. Previous reports have shown the interaction between active saffron compounds with linker histone H1. Other reports have shown that high concentrations of saffron bind to the minor groove of calf thymus DNA, resulting in specific structural changes from B- to C-form of DNA. Moreover, the interaction of crocin G-quadruplex was reported. A recent in silico study has shown that residues of SIRT1 interact with saffron bio-active compounds and might enhance SIRT1 activation. Other reports have shown that the treatment of Saffron bio-active compounds increases γH2AX, decreases HDAC1 and phosphorylated histone H3 (p-H3). However, the question that still remains to be addressed how saffron triggers various epigenetic changes? Therefore, this review discusses the literature published till 2022 regarding saffron as dietary components and its impact on epigenetic mechanisms. Novel bioactive compounds such as saffron components that lead to epigenetic alterations might be a valuable strategy as an adjuvant therapeutic drug.

Metagenomics Approaches to Investigate the Neonatal Gut Microbiome.

Early infancy is critical for the development of an infant's gut flora. Many factors can influence microbiota development during the pre- and postnatal periods, including maternal factors, antibiotic exposure, mode of delivery, dietary patterns, and feeding type. Therefore, investigating the connection between these variables and host and microbiome interactions in neonatal development would be of great interest. As the "unculturable" era of microbiome research gives way to an intrinsically multidisciplinary field, microbiome research has reaped the advantages of technological advancements in next-generation sequencing, particularly 16S rRNA gene amplicon and shotgun sequencing, which have considerably expanded our knowledge about gut microbiota development during early life. Using omics approaches to explore the neonatal microbiome may help to better understand the link between the microbiome and newborn diseases. Herein, we summarized the metagenomics methods and tools used to advance knowledge on the neonatal microbiome origin and evolution and how the microbiome shapes early and late individuals' lives for health and disease. The way to overcome limitations in neonatal microbiome studies will be discussed.

Symptomatic, clinical and biomarker associations for mortality in hospitalized COVID-19 patients enriched for African Americans.

BACKGROUND AND AIMS: Initial reports on US COVID-19 showed different outcomes in different races. In this study we use a diverse large cohort of hospitalized COVID-19 patients to determine predictors of mortality. METHODS: We analyzed data from hospitalized COVID-19 patients (n = 5852) between March 2020- August 2020 from 8 hospitals across the US. Demographics, comorbidities, symptoms and laboratory data were collected. RESULTS: The cohort contained 3,662 (61.7%) African Americans (AA), 286 (5%) American Latinx (LAT), 1,407 (23.9%), European Americans (EA), and 93 (1.5%) American Asians (AS). Survivors and non-survivors mean ages in years were 58 and 68 for AA, 58 and 77 for EA, 44 and 61 for LAT, and 51 and 63 for AS. Mortality rates for AA, LAT, EA and AS were 14.8, 7.3, 16.3 and 2.2%. Mortality increased among patients with the following characteristics: age, male gender, New York region, cardiac disease, COPD, diabetes mellitus, hypertension, history of cancer, immunosuppression, elevated lymphocytes, CRP, ferritin, D-Dimer, creatinine, troponin, and procalcitonin. Use of mechanical ventilation (p = 0.001), shortness of breath (SOB) (p < 0.01), fatigue (p = 0.04), diarrhea (p = 0.02), and increased AST (p < 0.01), significantly correlated with death in multivariate analysis. Male sex and EA and AA race/ethnicity had higher frequency of death. Diarrhea was among the most common GI symptom amongst AAs (6.8%). When adjusting for comorbidities, significant variables among the demographics of study population were age (over 45 years old), male sex, EA, and patients hospitalized in New York. When adjusting for disease severity, significant variables were age over 65 years old, male sex, EA as well as having SOB, elevated CRP and D-dimer. Glucocorticoid usage was associated with an increased risk of COVID-19 death in our cohort. CONCLUSION: Among this large cohort of hospitalized COVID-19 patients enriched for African Americans, our study findings may reflect the extent of systemic organ involvement by SARS-CoV-2 and subsequent progression to multi-system organ failure. High mortality in AA in comparison with LAT is likely related to high frequency of comorbidities and older age among AA. Glucocorticoids should be used carefully considering the poor outcomes associated with it. Special focus in treating patients with elevated liver enzymes and other inflammatory biomarkers such as CRP, troponin, ferritin, procalcitonin, and D-dimer are required to prevent poor outcomes.

Predictors of Mortality in Hospitalized African American Covid-19 Cancer Patients.

Background: Coronavirus disease 2019 (COVID-19) and associated outcomes manifest differently depending on patients' background and pre-existing conditions. It remains unclear how African Americans with and without cancer have been affected. Aim: To determine epidemiological, clinical comorbidities, and laboratory test results to identify markers associated with mortality in COVID-19 cancer patients. Methods: We reviewed all Covid-19 hospitalized patients records from Dec. 2019 to Oct. 2021 at Howard University Hospital. Patients having a history of, or active cancer status were reviewed. All the clinical, treatment, lab values, and pathological data were extracted. Statical analysis of the Covid-19 cancer patients and comparison with non-cancer Covid-19 patients was performed using univariate and multivariate analyses. Results: Out of 512 COVID-19 infected patients, a total of 49 patients were identified with different types of cancer, with both active and previous history. Females consisted of 26 cancer patients (53%). African American race was predominant in both cases and controls, 83.6% and 66.7% respectively. Cancer patients were older than non-cancer patients (Mean Age-70.6 vs. 56.3 years) and had an increased length of hospital stay (Mean 13.9 vs 9.4 days). Among cancer patients, breast cancer was more prevalent in females and prostate cancer in males, (54% and 52% respectively). Comparison of patients with active vs. previous cancer showed no significant difference in the clinical outcome, death vs. discharge (P=0.34). A higher reduction in albumin level in cancer cases, from the time of admission to day five, was significantly associated with death during the same hospital stay compared to those discharged (n=24, 48.9%, p<0.001). In controls, Lymphopenia (n=436, 94.1%, p=0.05), AST (n=59, 12%, p=0.008) and Albumin (n=40, 10.7%, p=0.02) have shown an association with increased mortality. Conclusion: Albumin level has shown to have an inverse relationship with clinical outcomes among all COVID infected African American patients. Reduction in Albumin level during the hospital stay, particularly in COVID-19 cancer patients should be considered as a predictor of mortality. No significant difference was noticed in the clinical outcome in patients with previous versus active cancer. Further research with a large cohort size is needed to verify and identify other predictors of outcome in Covid-19 cancer patients and develop appropriate treatment modalities.

Clinical and Endoscopic Outcomes in Coronavirus Disease-2019 Patients With Gastrointestinal Bleeding.

Background and Aims: Over 404 million people worldwide have been infected with coronavirus disease-2019 (COVID-19), 145 million in the United States (77 million) and Europe (151 million) alone (as of February 10, 2022). This paper aims to analyze data from studies reporting gastrointestinal bleeding (GIB) and/or endoscopic findings in COVID-19 patients in Western countries. Methods: We conducted a systematic review of articles on confirmed COVID-19 cases with GIB in Western countries published in PubMed and Google Scholar databases from June 20, 2020, to July 10, 2021. Results: A total of 12 studies reporting GIB and/or endoscopic findings in 808 COVID-19 patients in Western countries were collected and analyzed. Outcomes and comorbidities were compared with 18,179 non-GIB COVID-19 patients from Italy and the United States. As per our study findings, the overall incidence of GIB in COVID-19 patients was found to be 0.06%. When compared to the non-GIB cohort, the death rate was significantly high in COVID-19 patients with GIB (16.4% vs 25.4%, P < .001, respectively). Endoscopic treatment was rarely necessary, and blood transfusion was the most common GIB treatment. The most common presentation in GIB patients is melena (n = 117, 47.5%). Peptic, esophageal, and rectal ulcers were the most common endoscopic findings in upper (48.4%) and lower (36.4%) endoscopies. The GIB cohort had worse outcomes and higher incidence of hypertension (61.1%), liver disease (11.2%), and cancer (13.6%) than the non-GIB cohort. Death was strongly associated with hypertension (P < .001, r = 0.814), hematochezia (P < .001, r = 0.646), and esophagogastroduodenoscopy (P < .001, r = 0.591) in COVID-19 patients with GIB. Conclusions: Overall, the incidence of GIB in COVID-19 patients is similar to that estimated in the overall population, with melena being the most common presentation. The common endoscopic findings in GIB COVID-19 patients were ulcers, esophagitis, gastritis, and colitis. Patients with GIB were more prone to death than non-GIB COVID-19 patients.

Protective Effect of Saffron in Mouse Colitis Models Through Immune Modulation.

BACKGROUND: People with inflammatory bowel disease (IBD) including ulcerative colitis are at risk for colorectal cancer. Despite available effective drugs used to treat IBD, many patients fail or lose response over time with some displaying drug-induced adverse events. Saffron (Crocus sativus) has been reported to have anti-inflammatory properties. Its protective role in IBD has not been explored extensively. AIM: To establish whether saffron treatment alleviates inflammation in experimental colitis. METHODS: Colitis was induced in C57BL/6 mice with 3% DSS and treated with either saffron doses (7.5, 15, 20, 25 mg/kg body weight) or vehicle through daily gavage. On day 11, mice were euthanized and analyzed for gross and microscopic inflammation. Distal colon segments were collected for mRNA and protein expression of HO-1 protein and GPX2, (the downstream targets of NRF-2). Nrf-2 translocation from cytosol to nucleus was confirmed by immunofluorescence, and further Nrf-2 protein expression in nuclear and cytosolic fraction of colon was analyzed by immunoblot. Immune cells were isolated from the lamina propria of mouse colon for flow cytometry-based immunophenotyping. Colitis was also induced in C57BL/6 Ahr knockout and wild type mice to explore the involvement of Ahr-dependent pathways in saffron's protective effect(s). The therapeutic effect of saffron was further validated in another TNBS model of colitis. RESULTS: Saffron 20 mg/kg body weight showed improved colon gross and histology features and led to better body weight, colon length, histology score, and reduced disease activity index (DAI). Saffron significantly decreased pro-inflammatory macrophages (M1), while increasing anti-inflammatory macrophages (M2) and IL10 + dendritic cells. Saffron treatment also enhanced CD3 + T and CD3 + CD8 + T cells followed by increase in different CD3 + CD4 + T cells subsets like CD25 + T cells, FoxP3 + CD25 + regulatory T cells, and CD4 + FOXP3 + CD25-regulatory T cells. Immunoblot analysis showed a significant increase in HO-1/GPX2 protein expression. With saffron treatment, Nrf-2 translocation into nucleus from cytosol also supports the involvement of Nrf-2 and its downstream targets in the protective effect of saffron. Further, we demonstrated that saffron in part exert anti-inflammatory effect through activation of aryl hydrocarbon receptor (AhR)-nuclear factor erythroid 2-related factor 2 (Nrf2)-dependent pathways. CONCLUSION: These data demonstrate saffron's therapeutic potential and its protective role in part via Ahr/Nrf-2 pathways and regulatory innate and adaptive immune cells.

PIWI interacting RNAs perspectives: a new avenues in future cancer investigations.

As a currently identified small non-coding RNAs (ncRNAs) category, the PIWI-interacting RNAs (piRNAs) are crucial mediators of cell biology. The human genome comprises over 30.000 piRNA genes. Although considered a new field in cancer research, the piRNA pathway is shown by the existing evidence as an active pathway in a variety of different types of cancers with critical impacts on main aspects of cancer progression. Among the regulatory molecules that contribute to maintaining the dynamics of cancer cells, the P-element Induced WImpy testis (PIWI) proteins and piRNAs, as new players, have not been broadly studied so far. Therefore, the identification of cancer-related piRNAs and the assessment of target genes of piRNAs may lead to better cancer prevention and therapy strategies. This review articleaimed to highlight the role and function of piRNAs based on existing data. Understanding the role of piRNA in cancer may provide perspectives on their applications as particular biomarker signature in diagnosis in early stage, prognosis and therapeutic strategies.