RNA-binding protein PCBP2 regulates pancreatic ß cell function and adaptation to glucose.

Glucose plays a key role in shaping pancreatic ß cell function. Thus, deciphering the mechanisms by which this nutrient stimulates ß cells holds therapeutic promise for combating ß cell failure in type 2 diabetes (T2D). ß Cells respond to hyperglycemia in part by rewiring their mRNA metabolism, yet the mechanisms governing these changes remain poorly understood. Here, we identify a requirement for the RNA-binding protein PCBP2 in maintaining ß cell function basally and during sustained hyperglycemic challenge. PCBP2 was induced in primary mouse islets incubated with elevated glucose and was required to adapt insulin secretion. Transcriptomic analysis of primary Pcbp2-deficient ß cells revealed impacts on basal and glucose-regulated mRNAs encoding core components of the insulin secretory pathway. Accordingly, Pcbp2-deficient ß cells exhibited defects in calcium flux, insulin granule ultrastructure and exocytosis, and the amplification pathway of insulin secretion. Further, PCBP2 was induced by glucose in primary human islets, was downregulated in islets from T2D donors, and impacted genes commonly altered in islets from donors with T2D and linked to single-nucleotide polymorphisms associated with T2D. Thus, these findings establish a paradigm for PCBP2 in governing basal and glucose-adaptive gene programs critical for shaping the functional state of ß cells.

Global, regional, and national quality of care index of cervical and ovarian cancer: a systematic analysis for the global burden of disease study 1990-2019.

BACKGROUND AND OBJECTIVE: Cervical cancer is the most preventable and ovarian cancer is the most lethal gynecological cancer. However, in the world, there are disparities in health care performances resulting in differences in the burden of these cancers. The objective of this study was to compare the health-system quality of care and inequities for these cancers using the Quality of Care Index (QCI). MATERIAL AND METHODS: The 1990-2019 data of the Global Burden of Disease (GBD) was analyzed to extract rates of incidence, prevalence, mortality, Disability-Adjusted Life Years (DALYs), Years of Life Lost (YLL), and Years of healthy life lost due to disability (YLD) of cervical and ovarian cancer. Four indices were developed as a proxy for the quality of care using the above-mentioned rates. Thereafter, a Principal Components Analysis (PCA) was applied to construct the Quality of Care Index (QCI) as a summary measure of the developed indices. RESULTS: The incidence of cervical cancer decreased from 1990 to 2019, whereas the incidence of ovarian cancer increased between these years. However, the mortality rate of both cancers decreased in this interval. The global age-standardized QCI for cervical cancer and ovarian cancer were 43.1 and 48.5 in 1990 and increased to 58.5 and 58.4 in 2019, respectively. QCI for cervical cancer and ovarian cancer generally decreased with aging, and different age groups had inequitable QCIs. Higher-income countries generally had higher QCIs for both cancers, but exceptions were also observed. CONCLUSIONS: Uncovering disparities in cervical and ovarian cancer care across locations, Socio-Demographic Index levels, and age groups necessitate urgent improvements in healthcare systems for equitable care. These findings underscore the need for targeted interventions and prompt future research to explore root causes and effective strategies for narrowing these gaps.

Microbiome modulation in inflammatory diseases: Progress to microbiome genetic engineering.

Recent developments in sequencing technology and analytical approaches have allowed researchers to show that the healthy gut microbiome is very varied and capable of performing a wide range of tasks. The importance of gut microbiota in controlling immunological, neurological, and endocrine function is becoming well-recognized. Thereby, numerous inflammatory diseases, including those that impact the gastrointestinal system, as well as less obvious ones, including Rheumatoid arthritis (RA), cancer, gestational diabetes (GD), type 1 diabetes (T1D), and type 2 diabetes (T2D), have been linked to dysbiotic gut microbiota. Microbiome engineering is a rapidly evolving frontier for solutions to improve human health. Microbiome engineering seeks to improve the function of an ecosystem by manipulating the composition of microbes. Thereby, generating potential therapies against metabolic, inflammatory, and immunological diseases will be possible through microbiome engineering. This essay first provides an overview of the traditional technological instruments that might be used for microbiome engineering, such as Fecal Microbiota Transplantation (FMT), prebiotics, and probiotics. Moreover, we will also discuss experimental genetic methods such as Metagenomic Alteration of Gut microbiome by In situ Conjugation (MAGIC), Bacteriophage, and Conjugative plasmids in manipulating intestinal microbiota.

MicroRNA-122 in human cancers: from mechanistic to clinical perspectives.

MicroRNAs (miRNAs) are endogenous short non-coding RNAs that can regulate the expression of target genes post-transcriptionally and interact with mRNA-coding genes. MiRNAs play vital roles in many biological functions, and abnormal miRNA expression has been linked to various illnesses, including cancer. Among the miRNAs, miR-122, miR-206, miR-21, miR-210, miR-223, and miR-424 have been extensively studied in various cancers. Although research in miRNAs has grown considerably over the last decade, much is yet to be discovered, especially regarding their role in cancer therapies. Several kinds of cancer have been linked to dysregulation and abnormal expression of miR-122, indicating that miR-122 may serve as a diagnostic and/or prognostic biomarker for human cancer. Consequently, in this review literature, miR-122 has been analyzed in numerous cancer types to sort out the function of cancer cells miR-122 and enhance patient response to standard therapy.

Anti-diabetic Effects of Macronutrients via Modulation of Angiogenesis: A Comprehensive Review on Carbohydrates and Proteins.

BACKGROUND: Diabetes is a major global health concern, manifesting the symptoms of chronic hyperglycemia. Either insufficient or excessive angiogenesis is generally involved in the pathogenesis of diabetes and its complications. OBJECTIVE: Given that macronutrients are important dietary players in global health issues, we aimed to review the role of macronutrients, including carbohydrates and proteins, to manage diabetes via angiogenesis modulation. METHODS: Sixteen studies regarding the effects of macronutrients, including carbohydrates and proteins derived from plants, fungus, bacteria, and their derivatives, on angiogenesis in diabetes were included in our study. RESULTS: Reviewing these studies suggests that carbohydrates, including low molecular weight fucoidan (LMWF), Astragalus polysaccharide (APS), and Ganoderma lucidum polysaccharide (Gl-PS), as well as oligopeptides, like sea cucumber-isolated small molecule oligopeptides (SCCOPs), can induce angiogenesis in the process of wound healing. Considering retinopathy, carbohydrates, including Diphlorethohydroxycarmalol (DPHC), Lyciumbarbarum (LBP), Sulfated K5 Escherichia coli polysaccharide (K5-N, OS (H)), and carnosine suppressed retinal angiogenesis. Furthermore, rice bran protein (RBP) ameliorated angiogenesis in diabetic nephropathy. Carbohydrates, including DPHC, Anoectochilus roxburghii polysaccharide (ARP), and LMWF, showed beneficial effects on endothelial cell dysfunction. CONCLUSION: In conclusion, data suggest that a number of macronutrients, including proteins and carbohydrates, could have protective effects against complications of diabetes via modulation of angiogenesis.

A year of experience with COVID-19 in patients with cancer: A nationwide study.

BACKGROUND: Cancer is a major public health problem and comorbidity associated with COVID-19 infection. According to previous studies, a higher mortality rate of COVID-19 in cancer patients has been reported. AIMS: This study was undertaken to determine associated risk factors and epidemiological characteristics of hospitalized COVID-19 patients with cancer using a nationwide COVID-19 hospital data registry in Iran for the first time. METHODS: In this retrospective study, we used a national data registry of hospitalized patients with Severe Acute Respiratory Syndrome (SARS) symptoms and patients with confirmed positive COVID-19 PCR between 18 February 2020 and 18 November 2020. The patients were classified into two groups patients with/without malignancy. Logistic regression model was utilized to analyze demographic factors, clinical features, comorbidities, and their associations with the disease outcomes. RESULTS: In this study, 11 068 and 645 186 in-patients with SARS symptoms with and without malignancy were included, respectively. About 1.11% of our RT-PCR-positive patients had cancer. In patients with malignancy and COVID-19, older ages than 60 (OR: 1.88, 95% CI: 1.29-2.74, p-value: .001), male gender (OR: 1.43, 95% CI: 1.16-1.77, p-value: .001), concomitant chronic pulmonary diseases (CPD) (OR: 1.75, 95% CI: 1.14-2.68, p-value: .009), and presence of dyspnea (OR; 2.00, 95% CI: 1.60-2.48, p-value: <.001) were associated with increased mortality rate. CONCLUSION: Given the immunocompromised state of patients with malignancy and their vulnerability to Covid-19 complications, collecting data on the comorbidities and their effects on the disease outcome can build on a better clinical view and help clinicians make decisions to manage these cases better; for example, determining special clinical care, especially in the shortage of health services.

Investigation of human parvovirus B19 prevalence in a large healthy umbilical cord blood donors.

Background and Objectives: Umbilical cord blood (UCB) was used to source hematopoietic stem cells in the past. Despite the apparent advantages of UCB transplantation, virus reactivation poses a considerable danger in allogeneic hematopoietic stem cell transplantation (HSCT). Human Parvovirus B19 is regarded as a potential threat to UCB contamination. This study aimed to evaluate the prevalence of parvovirus B19 in cord blood donors by Semi-Nested PCR. This study is the first largescale report of the B19 DNA in cord blood donors in Iran. Materials and Methods: A total of 691 umbilical cord blood were collected under standard procedure. Then, DNA from buffy coat and plasma were extracted, and semi-nested PCR was performed for all samples. Results: Two out of 691 samples (0.29%) indicated viremia in plasma and buffy coat. Conclusion: In this line, designing and validating a quantitative PCR assay for detection, quantification, and discrimination of Human B19 DNA genotypes of cord blood donors is necessary to enhance the safety of this source of stem cells.

Anti-Diabetic Effects of Isolated Lipids from Natural Sources through Modulation of Angiogenesis.

BACKGROUND: Aberrant angiogenesis plays a fateful role in the development of diabetes and diabetic complications. Lipids, as a diverse group of biomacromolecules, are able to relieve diabetes through the modulation of angiogenesis. OBJECTIVES: Owing to the present remarkable anti-diabetic effects with no or few side effects of lipids, the aim of this study was to assess the state-of-the-art research on anti-diabetic effects of lipids via the modulation of angiogenesis. METHODS: To study the effects of lipids in diabetes via modulation of angiogenesis, we have searched the electronic databases including Scopus, PubMed, and Cochrane. RESULTS: The promising anti-diabetic effects of lipids were reported in several studies. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) from fish oil (FO) were reported to significantly induce neovasculogenesis in high glucose (HG)-mediated endothelial progenitor cells (EPCs) with neovasculogenesis dysfunction in type 2 diabetic mice. Linoleic acid, mono-epoxy-tocotrienol- α (MeT3α), and ginsenoside Rg1 facilitate wound closure and vessel formation. N-Palmitoylethanolamine (PEA), α-linolenic acid (ALA), omega-3 (ω3) lipids from flaxseed (FS) oil, ω-3 polyunsaturated fatty acids (PUFA), lipoic acid, taurine, and zeaxanthin (Zx) are effective in diabetic retinopathy via suppression of angiogenesis. Lysophosphatidic acid, alkyl-glycerophosphate, crocin, arjunolic acid, α-lipoic acid, and FS oil are involved in the management of diabetes and its cardiac complications. Furthermore, in two clinical trials, R-(+)-lipoic acid (RLA) in combination with hyperbaric oxygenation therapy (HBOT) for treatment of chronic wound healing in DM patients, as well as supplementation with DHA plus antioxidants along with intravitreal ranibizumab were investigated for its effects on diabetic macular edema. CONCLUSION: Proof-of-concept studies presented here seem to well shed light on the anti-diabetic effects of lipids via modulation of angiogenesis.

Acute pancreatitis induced by Tadalafil: a case report.

Acute pancreatitis is commonly caused by gallstones or alcohol abuse. Also, this complication has rarely been associated with other etiologies like drugs in some reports. We report the case of a 43-year-old man with 10-days history of taking Tadalafil for erectile dysfunction. The patient was presented to the emergency room with manifestations of acute pancreatitis. This diagnosis was confirmed after clinical examination, laboratory tests, and radiologic evaluation. Other probable etiological factors were ruled out. A total score of seven using Naranjo Adverse Drug Reaction Probability Scale clarifies a probable diagnosis of drug-induced acute pancreatitis in this case. The reported case of acute pancreatitis was most likely induced with Tadalafil.