Protein phosphatase PP2Cα S-glutathionylation regulates cell migration.

Redox signaling is a fundamental mechanism that controls all major biological processes partly via protein cysteine oxidations, including S-glutathionylation. Despite over 2000 cysteines identified to form S-glutathionylation in databases, the identification of redox cysteines functionally linked to a biological process of interest remains challenging. Here, we demonstrate a strategy combining glutathionylation proteomic database, bioinformatics, and biological screening, which resulted in the identification of S-glutathionylated proteins, including PP2Cα, as redox players of cell migration.

A review and comparison of post registration midwifery curriculum in Sri Lanka with global standards.

This paper presents the findings of a study comparing the post-registration midwifery curriculum (PRMC) taught in Sri Lanka with the International Confederation of Midwives (ICM) curriculum and five other selected curricula from other parts of the world to train midwifery trained registered nurses (MTRNs). In so doing, we consider the historical origins of post-registration midwifery training and its implications for modern teachings in Sri Lanka and other low-middle income countries (LMICs). Data collected through document review are read, summarized, and compared using checklists across different curricula components, content, and length.

Experiences of family caregivers of the older people with limitations in activities: A qualitative study.

Functional disabilities increase with ageing and limitations in daily living activities (ADLs) occurred as a consequence. Older people living at home may therefore become dependent on family members in managing activities in daily living. As the informal caregivers' role is known to be challenging, their experiences need to be explored to strengthen their new roles as family caregivers.

Health-related quality of life in patients with substance use disorders enrolled to the residential treatment in Sri Lanka: a retrospective cross-sectional study.

Purpose: Substance use disorder (SUD) is a serious public health concern that requires continuum care with effective treatment modalities such as residential rehabilitation. Improvement in health-related quality of life (HRQoL) is one of the determinants of treatment and rehabilitation effectiveness. Therefore, a retrospective cross-sectional study was carried out in seven residential rehabilitation centres in Sri Lanka to determine the HRQoL of the rehabilitees with SUD.

OligoTRAFTACs: A generalizable method for transcription factor degradation.

Dysregulated transcription factors (TFs) that rewire gene expression circuitry are frequently identified as key players in disease. Although several TFs have been drugged with small molecules, the majority of oncogenic TFs are not currently pharmaceutically tractable due to their paucity of ligandable pockets. The first generation of transcription factor targeting chimeras (TRAFTACs) was developed to target TFs for proteasomal degradation by exploiting their DNA binding ability.

The Pattern of Substance Use and Characteristics of the Individuals Enrolled in Residential Treatment at Selected Rehabilitation Centers in Sri Lanka: A Descriptive Cross-Sectional Study.

Introduction: Substance use becomes censorious when it leads to harmful effects on individuals, their families, and the community. The nature of substance use in Sri Lankan context is poorly understood and empirical evidences are sparse. The study aimed to describe patterns of substance use and characteristics of the individuals enrolled in residential treatment at selected rehabilitation centers in Sri Lanka.

Identification and Quantification of Glutathionylated Cysteines under Ischemic Stress.

Ischemia reperfusion injury contributes to adverse cardiovascular diseases in part by producing a burst of reactive oxygen species that induce oxidations of many muscular proteins. Glutathionylation is one of the major protein cysteine oxidations that often serve as molecular mechanisms behind the pathophysiology associated with ischemic stress. Despite the biological significance of glutathionylation in ischemia reperfusion, identification of specific glutathionylated cysteines under ischemic stress has been limited.

Fecal microbial transplantation and fiber supplementation in patients with severe obesity and metabolic syndrome: a randomized double-blind, placebo-controlled phase 2 trial.

Fecal microbial transplantation (FMT) from lean donors to patients with obesity has been associated with metabolic benefits, yet results so far have been inconsistent. In this study, we tested the application of daily fiber supplementation as an adjunct to FMT therapy to modulate cardiometabolic outcomes. We performed a double-blind randomized trial in patients with severe obesity and metabolic syndrome receiving oral FMT, to test high-fermentable (HF) and low-fermentable (LF) fiber supplements (NCT03477916).

Targeted protein degradation: A promise for undruggable proteins.

Protein homeostasis, or "proteostasis," is indispensable for a balanced, healthy environment within the cell. However, when natural proteostasis mechanisms are overwhelmed from excessive loads of dysregulated proteins, their accumulation can lead to disease initiation and progression. Recently, the induced degradation of such disease-causing proteins by heterobifunctional molecules, i.

Algae-based antioxidant containing selenium yeast (Economase®) enhanced the growth performance, oxidative stability, and meat quality of broiler chickens.

Objective: An experiment was conducted to determine the effect of algae-based antioxidant containing Se yeast (EconomasE®) on the growth performance, visceral organ weight, meat quality, and oxidative stability of broiler chickens.

Methods: Nine hundred sixty, day-old male broiler chickens (Cobb, 43.97±0.

Targeted degradation of transcription factors by TRAFTACs: TRAnscription Factor TArgeting Chimeras.

Many diseases, including cancer, stem from aberrant activation or overexpression of oncoproteins that are associated with multiple signaling pathways. Although proteins with catalytic activity can be successfully drugged, the majority of other protein families, such as transcription factors, remain intractable due to their lack of ligandable sites. In this study, we report the development of TRAnscription Factor TArgeting Chimeras (TRAFTACs) as a generalizable strategy for targeted transcription factor degradation.

Mutant-selective degradation by BRAF-targeting PROTACs.

Over 300 BRAF missense mutations have been identified in patients, yet currently approved drugs target V600 mutants alone. Moreover, acquired resistance inevitably emerges, primarily due to RAF lesions that prevent inhibition of BRAF V600 with current treatments. Therefore, there is a need for new therapies that target other mechanisms of activated BRAF.

Menopause is a natural stage of aging: a qualitative study.

Background: Menopause is a biopsychosocial phenomenon encompassing the transition in a woman's life from being fertile to infertile. Although menopause may result in extremely unpleasant physical symptoms there is evidence of a low rate of reported menopausal symptoms amongst women in Asian cultures. Women's experiences, views, and responses to menopause which influences women's daily life and well-being, may vary between different societies and cultures.

Serum sex hormone levels and hormone receptor status in identifying breast cancer risk in women.

Background: The association of sex hormones with receptor status and breast cancer (BC) incidence is studied with inconclusive results. The present work assessed the serum estrogen, progesterone, and testosterone concentrations and estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) status of newly diagnosed Sri Lankan BC patients and studied the possibility of risk assessment for BC using these parameters.

Methods: Serum estrogen, progesterone, and testosterone concentrations of newly diagnosed BC patients (n = 155) were assessed and compared with apparently healthy age-matched women (n = 75).

Acute and Subchronic Oral Safety Profiles of the Sudarshana Suspension.

powder (SP) is an Ayurvedic preparation, which contains 53 herbal ingredients along with 50% of and is clinically used with bees honey. This study was aimed to determine the safety profile of the SP, and its novel preparation Sudarshana suspension (SS) on male Wistar rats and tolerance studies were conducted for healthy adult volunteers. Acute and subacute toxicity studies of the SS and hot water extract of SP were assessed in Wistar rats by observing the general behavior, analyzing biochemical and haematological parameters, and pathological observation.

Double-Barreled CRISPR Technology as a Novel Treatment Strategy For COVID-19.

Coronavirus is one of the causative agents for multiple human respiratory illnesses. A novel coronavirus, similar to the one that caused severe acute respiratory syndrome (SARS) in 2003, was identified as the cause of the current pandemic of coronavirus disease (COVID-19), which was first reported in late December 2019 in Wuhan, China. Since then, this novel coronavirus has spread across the globe, with most identified COVID-19 cases and fatalities occurring in the United States.

Reversible Spatiotemporal Control of Induced Protein Degradation by Bistable PhotoPROTACs.

Off-tissue effects are persistent issues of modern inhibition-based therapies. By merging the strategies of photopharmacology and small-molecule degraders, we introduce a novel concept for persistent spatiotemporal control of induced protein degradation that potentially prevents off-tissue toxicity. Building on the successful principle of bifunctional all-small-molecule Proteolysis Targeting Chimeras (PROTACs), we designed photoswitchable PROTACs () by including F-azobenzene linkers between both warhead ligands.

Loneliness among older people living in care homes in Sri Lanka.

Aim And Objectives: The aim of this study was to explore loneliness in older people (aged 65+) living in care homes in Colombo, Sri Lanka.

Background: Loneliness, defined as the subjective, unwelcome feeling of the lack or loss of companionship, is known to be associated with old age, especially among older people living in care homes. Although several studies have shown that loneliness is highly prevalent, we lack knowledge about older people's personal experience of loneliness when residing in a care home and the strategies that older people use by themselves on a day-to-day basis to alleviate loneliness.

Addressing Kinase-Independent Functions of Fak via PROTAC-Mediated Degradation.

Enzymatic inhibition has proven to be a successful modality for the development of many small-molecule drugs. In recent years, small-molecule-induced protein degradation has emerged as an orthogonal therapeutic strategy that has the potential to expand the druggable target space. Focal adhesion kinase (Fak) is a key player in tumor invasion and metastasis, acting simultaneously as a kinase and a scaffold for several signaling proteins.

SMYD2 glutathionylation contributes to degradation of sarcomeric proteins.

Reactive oxygen species (ROS) contribute to the etiology of multiple muscle-related diseases. There is emerging evidence that cellular stress can lead to destabilization of sarcomeres, the contractile unit of muscle. However, it is incompletely understood how cellular stress induces structural destabilization of sarcomeres.

Could Anthropometric and Lipid Parameters Reflect Susceptibility to Breast Cancer? Comparison of Newly Diagnosed Breast Cancer and Apparently Healthy Women.

Objectives: To determine and compare the serum lipid profiles and anthropometric parameters of newly diagnosed BC patients and healthy women. Methods: Serum total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), very low density lipoprotein cholesterol (VLDL-C), triglyceride (TG) and TC: HDL-C were measured in consent obtained newly diagnosed BC patients (n=155) and age matched apparently healthy females (n=75). Weight (W), height (H), waist circumference (WC), hip circumference (HC) and mid upper arm circumference (MUC) of each women were recorded.

Caring for stroke survivors: experiences of family caregivers in Sri Lanka - a qualitative study.

Background: Stroke is a life-changing event for both stroke survivors and their family caregivers. After receiving acute care at the hospital, family members are expected to take care of stroke survivors at home and to continue treatment and rehabilitation. The new role of "informal caregiver" is a challenge that creates many difficulties for family caregivers that are not explicit in the Sri Lankan context.

Correction: Clickable glutathione using tetrazine-alkene bioorthogonal chemistry for detecting protein glutathionylation.

Correction for 'Clickable glutathione using tetrazine-alkene bioorthogonal chemistry for detecting protein glutathionylation' by Dilini N. Kekulandara et al., Org.