Mechanism and consequences of herpes simplex virus 1-mediated regulation of host mRNA alternative polyadenylation.

Eukaryotic gene expression is extensively regulated by cellular stress and pathogen infections. We have previously shown that herpes simplex virus 1 (HSV-1) and several cellular stresses cause widespread disruption of transcription termination (DoTT) of RNA polymerase II (RNAPII) in host genes and that the viral immediate early factor ICP27 plays an important role in HSV-1-induced DoTT. Here, we show that HSV-1 infection also leads to widespread changes in alternative polyadenylation (APA) of host mRNAs. In the majority of cases, polyadenylation shifts to upstream poly(A) sites (PAS), including many intronic PAS. Mechanistically, ICP27 contributes to HSV-1-mediated APA regulation. HSV-1- and ICP27-induced activation of intronic PAS is sequence-dependent and does not involve general inhibition of U1 snRNP. HSV1-induced intronic polyadenylation is accompanied by early termination of RNAPII. HSV-1-induced mRNAs polyadenylated at intronic PAS (IPA) are exported into the cytoplasm while APA isoforms with extended 3' UTRs are sequestered in the nuclei, both preventing the expression of the full-length gene products. Finally we provide evidence that HSV-induced IPA isoforms are translated. Together with other recent studies, our results suggest that viral infection and cellular stresses induce a multi-faceted host response that includes DoTT and changes in APA profiles.

Microbial- and Plant-Derived Bioactive Peptides and Their Applications against Foodborne Pathogens: Current Status and Future Prospects.

Bioactive peptides (BAPs) obtained from plants and microbes have been thoroughly explored and studied due to their prophylactic properties. The use of BAPs seems to be a promising substitute for several currently available antibiotics because of their antimicrobial properties against foodborne pathogens. BAPs have several other useful properties including antitumor, antihypertensive, antioxidant, antiobesity, and antidiabetic activities. Nowadays, scientists have attempted to recombinantly synthesize bioactive peptides to study their characteristics and potential uses, since BAPs are not found in large quantities in nature. Many pathogenic microorganisms including foodborne pathogens are becoming resistant to various antibiotics. To combat these pathogens, scientists are working to find novel, innovative, and safe antimicrobial agents. Plant- and microbe-based BAPs have demonstrated noteworthy antimicrobial activity against a wide range of pathogenic microorganisms, including foodborne pathogens. BAPs can kill pathogenic microorganisms by disrupting membrane integrity, inhibiting DNA and RNA synthesis, preventing protein synthesis, blocking protein activity, or interacting with certain intracellular targets. In addition, the positive effect of BAP consumption extends to gut microbiota modulation and affects the equilibrium of reactive oxygen species in the gut. This article discusses recombinant BAPs, BAPs generated from plants and microbes, and their antimicrobial applications and modes of action for controlling foodborne pathogens.

An Update on the Study of the Molecular Mechanisms Involved in Autophagy during Bacterial Pathogenesis.

Autophagy is a unique catabolic process that degrades irrelevant or damaged components in eukaryotic cells to maintain homeostasis and eliminate infections from pathogenesis. Pathogenic bacteria have developed many autophagy manipulation techniques that affect host immune responses and intracellular bacterial pathogens have evolved to avoid xenophagy. However, reducing its effectiveness as an innate immune response has not yet been elucidated. Bacterial pathogens cause autophagy in infected cells as a cell-autonomous defense mechanism to eliminate the pathogen. However, harmful bacteria have learned to control autophagy and defeat host defenses. Intracellular bacteria can stimulate and control autophagy, while others inhibit it to prevent xenophagy and lysosomal breakdown. This review evaluates the putative functions for xenophagy in regulating bacterial infection, emphasizing that successful pathogens have evolved strategies to disrupt or exploit this defense, reducing its efficiency in innate immunity. Instead, animal models show that autophagy-associated proteins influence bacterial pathogenicity outside of xenophagy. We also examine the consequences of the complex interaction between autophagy and bacterial pathogens in light of current efforts to modify autophagy and develop host-directed therapeutics to fight bacterial infections. Therefore, effective pathogens have evolved to subvert or exploit xenophagy, although autophagy-associated proteins can influence bacterial pathogenicity outside of xenophagy. Finally, this review implies how the complex interaction between autophagy and bacterial pathogens affects host-directed therapy for bacterial pathogenesis.

Peer counselling as an approach to improve complementary feeding practices: a narrative review.

BACKGROUND: Appropriate complementary feeding can help reduce the risk of malnutrition and is especially important in Asian and African countries. Peer counselling has been used as an approach to improve complementary feeding practices and is often combined with other interventions, like food fortification or supplements, or as a part of broader nutrition education program. The aim of this narrative review is to assess the effectiveness of peer counselling on improving complementary feeding practices in Asian and African countries. METHODS: We searched through seven electronic databases: CINAHL, MEDLINE (OVID), PubMed, Embase, Web of Science, the Cochrane Library and WHO Global Health library from 2000 to April 2021, and had the following inclusion criteria. Studies were included if they were community- or hospital-based, had infants aged 5-24 months old, had individual or group peer counselling, and the effects of peer counselling on complementary feeding practices were measured. Methodological quality was assessed using the Joanna Briggs Institute's critical appraisal checklist for evidence studies. RESULTS: Out of 6 studies that met the above criteria, 3 studies were randomised controlled trials and 3 were quasi-experimental studies. In Bangladesh, India, Nepal and Somalia, peer counselling was found to be effective in improving timely initiation of complementary feeding, minimum meal frequency and minimum dietary diversity in all of our selected studies. In addition, improvement in breastfeeding practices, complementary foods preparation, hygiene, psychological stimulation for cognitive development of children and mothers' understanding of hunger cues were observed in some of our selected studies. CONCLUSIONS: This review evaluates the effectiveness of peer counselling to improve complementary feeding practices in Asian and African countries. Peer counselling improves timely complementary feeding and ensures the correct proportions and consistency of foods including adequate amounts of food is given. Other important complementary feeding indicators like minimum dietary diversity, minimum meal frequency and minimum acceptable diet can also be increased through peer-counselling interventions. Peer counselling is well known to enhance the rate of breastfeeding practices, but this review suggests it is also effective for complementary feeding and may inform future nutrition programs to extend the length of peer counselling for mothers.

Prevalence and Correlates of Underweight among Women of Reproductive Age in Nepal: A Cross-Sectional Study.

This study aimed to examine the prevalence of underweight and determine the sociodemographic and household environmental correlates of underweight among women of reproductive age in Nepal. This study also compared the time trends in the prevalence of underweight with the trends in the prevalence of overweight and obesity. This cross-sectional study was a secondary data analysis of the nationally representative population-based Nepal Demographic and Health Surveys (NDHSs). Firstly, the time trends of the prevalence of underweight (body mass index (BMI) < 18.5 kg/m2) among women aged 15-49 years were examined at five-year intervals, from the 1996, 2001, 2006, 2011, and 2016 NDHSs (n = 33,507). Secondly, the sociodemographic and household environmental correlates of underweight were examined from the latest NDHS 2016 (n = 6165). Univariable and multivariable logistic regression analyses were performed to examine the sociodemographic and household environmental correlates of underweight. From 1996 to 2016, the prevalence of underweight decreased from 25.3% (95% confidence interval (CI) 23.8%, 26.8%) to 16.9% (95%CI 16.0%, 17.8%), while the prevalence of overweight and obesity increased from 1.6% (95%CI 1.2%, 2.1%) to 15.6% (95%CI 14.7%, 16.5%) and 0.2% (95%CI 0.1%, 0.4%) to 4.1% (95%CI 3.6%, 4.6%), respectively. Sociodemographic factors, such as age, educational status, marital status, wealth index, and religion, were independently associated with the risk of underweight. Similarly, household environmental factors, such as province of residence, ecological zone, type of toilet facility, and household possessions, including television and mobile phone, were independently associated with the risk of underweight. Despite the declining trends, the prevalence of underweight among Nepalese women remains a public health challenge. Understanding the key sociodemographic and household environmental correlates of underweight may assist in streamlining the content of health promotion campaigns to address undernutrition and potentially mitigate adverse health outcomes.

Prevalence and impact of comorbidities on disease prognosis among patients with COVID-19 in Bangladesh: A nationwide study amid the second wave.

BACKGROUND: Socio-demographics and comorbidities are involved in determining the severity and fatality in patients with COVID-19 suggested by studies in various countries, but study in Bangladesh is insufficient. AIMS: We designed the study to evaluate the association of sociodemographic and comorbidities with the prognosis of adverse health outcomes in patients with COVID-19 in Bangladesh. METHODS: A multivariate retrospective cohort study was conducted on data from 966 RT-PCR positive patients from eight divisions during December 13, 2020, to February 13, 2021. Variables included sociodemographic, comorbidities, symptoms, Charlson comorbidity index (CCI) and access to health facilities. Major outcome was fatality. Secondary outcomes included hospitalization, duration of hospital stay, requirement of mechanical ventilation and severity. RESULTS: Male (65.8%, 636 of 966) was predominant and mean age was 39.8 ± 12.6 years. Fever (79%), dry cough (55%), and loss of test/smell (51%) were frequent and 74% patients had >3 symptoms. Fatality was recorded in 10.5% patients. Comorbidities were found in 44% patients. Hypertension (21.5%) diabetes (14.6%), and cardiovascular diseases (11.3%) were most prevalent. Age >60 years (OR: 4.83, 95% CI: 2.45-6.49), and CCI >3 (OR: 5.48, 95% CI: 3.95-7.24) were predictors of hospitalizations. CCI >4 (aOR: 3.41, 95% CI: 2.57-6.09) was predictor of severity. Age >60 years (aOR: 3.77, 95% CI: 1.07-6.34), >3 symptoms (aOR: 2.14, 95% CI: 0.97-4.91) and CCI >3 vs. CCI <3 (aOR: 5.23, 95% CI: 3.77-8.09) were independently associated with fatality. CONCLUSIONS: Increased age, >3 symptoms, increasing comorbidities, higher CCI were associated with increased hospitalization, severity and fatality in patients with COVID-19.

In vitro functional testing of endothelial progenitor cells that overexpress thrombomodulin.

This study investigated the augmentation of endothelial progenitor cell (EPC) thromboresistance by using gene therapy to overexpress thrombomodulin (TM), an endothelial cell membrane glycoprotein that has potent anti-coagulant properties. Late outgrowth EPCs were isolated from peripheral blood of patients with documented coronary artery disease and transfected with an adenoviral vector containing human TM. EPC transfection conditions for maximizing TM expression, transfection efficiency, and cell viability were employed. TM-overexpressing EPCs had a fivefold increase in the rate of activated protein C production over native EPCs and EPCs transfected with an adenoviral control vector expressing ß-galactosidase (p<0.05). TM upregulation caused a significant threefold reduction in platelet adhesion compared to native EPCs, and a 12-fold reduction compared to collagen I-coated wells. Additionally, the clotting time of TM-transfected EPCs incubated with whole blood was significantly extended by 19% over native cells (p<0.05). These data indicate that TM-overexpression has the potential to improve the antithrombotic performance of patient-derived EPCs for endothelialization applications.