BackgroundAlthough exercise has been shown to relieve depression, little is known about its mechanism or dose-response characteristics. We hypothesized that high intensity progressive resistance training (PRT) would be more effective than either low intensity PRT or standard care by a general practitioner (GP) in depressed elderly persons, and that high intensity PRT would provide superior benefits in quality of life, sleep quality, and self-efficacy.
Different modalities of DNA/collagen complexes have been utilized primarily for gene delivery studies. However, very few studies have investigated the potential of these complexes as bioactive scaffolds. Further, no studies have characterized the DNA/collagen complex formed from the interaction of the self-assembled DNA macrostructure and collagen. Toward this investigation, we report herein the fabrication of novel bioactive scaffolds formed from the interaction of sequence-specific, self-assembled DNA macrostructure and collagen type I. Varying molar ratios of DNA and collagen resulted in highly intertwined fibrous scaffolds with different fibrillar thicknesses. The formed scaffolds were biocompatible and presented as a soft matrix for cell growth and proliferation. Cells cultured on DNA/collagen scaffolds promoted the enhanced cellular uptake of transferrin, and the potential of DNA/collagen scaffolds to induce neuronal cell differentiation was further investigated. The DNA/collagen scaffolds promoted neuronal differentiation of precursor cells with extensive neurite growth in comparison to the control groups. These novel, self-assembled DNA/collagen scaffolds could serve as a platform for the development of various bioactive scaffolds with potential applications in neuroscience, drug delivery, tissue engineering, and in vitro cell culture.
Abstract Autophagy is a critical cellular pathway for degrading and recycling damaged components, essential for maintaining cellular homeostasis. Dysregulation of autophagy contributes to various diseases, including neurodegenerative disorders, cancers, and metabolic syndromes, highlighting the therapeutic potential of controlled autophagy induction. However, current autophagy inducers often lack specificity and may inadvertently trigger apoptosis, limiting their clinical utility. Here, we present a DNA tetrahedron-BH3 peptide nanosystem (Tdpep) engineered to selectively induce autophagy by disrupting the Beclin 1-Bcl2 interaction, a pivotal regulatory point in autophagy initiation. Tdpep, functionalized with a BH3 peptide targeting Bcl2, demonstrated efficient cellular uptake and minimal cytotoxicity in HeLa cells at concentrations up to 200nM. Autophagy induction was confirmed by increased LC3B puncta formation and fluorescence intensity comparable to that induced by rapamycin. Autophagy flux analysis of Tdpep with bafilomycin A1 validated enhanced autophagic activity rather than flux inhibition. Furthermore, Tdpep treatment significantly reduced cellular ROS levels, indicating effective autophagic turnover. Apoptosis assays showed that Tdpep did not induce apoptosis, confirming its selective autophagy induction. Furthermore, Tdpep nanosystem also induced autophagy in Danio rerio larvae in vivo model. Thus, this targeted DNA tetrahedron nanosystem provides a precise autophagy modulation platform with minimized off-target effects, offering a promising therapeutic strategy for diseases associated with autophagy dysfunction. Graphical abstract
DNA nanotechnology represents an innovative discipline that combines nanotechnology with biotechnology. It exploits the distinctive characteristics of deoxyribonucleic acid (DNA) to create nanoscale structures and devices with remarkable accuracy and functionality. Researchers may create complex nanostructures with precision and specialized functions using DNA's innate stability, adaptability, and capacity to self-assemble through complementary base-pairing interactions. Integrating multiple disciplines, known as nanobiotechnology, allows the production of sophisticated nanodevices with a broad range of applications. These include precise drug delivery systems, extremely sensitive biosensors, and the construction of intricate tissue scaffolds for regenerative medicine. Moreover, combining DNA nanotechnology with mechanobiology provides a new understanding of how small-scale mechanical stresses and molecular interactions affect cellular activity and tissue development. DNA nanotechnology has the potential to revolutionize molecular diagnostics, tissue engineering, and organ regeneration. This could lead to enormous improvements in biomedicine. This review emphasizes the most recent developments in DNA nanotechnology, explicitly highlighting its significant influence on mechanobiology and its growing involvement in organ engineering. It provides an extensive overview of present trends, obstacles, and future prospects in this fast-progressing area.
Lean body weight (LBW) decreases with age while total body fat increases, resulting in altered drug pharmacokinetics. A semi-mechanistic equation estimating LBW using height, weight and sex has been developed for potential use across a wide range of body compositions. The aim of this study was to determine the ability of the LBW equation to estimate dual energy x-ray absorptiometry-derived fat free mass (FFMDXA) in a population of older women with recent hip fracture. Baseline, four and 12 month data obtained from 23 women enrolled in the Sarcopenia and Hip Fracture study were pooled to give 58 measurements. LBW was estimated using the equation: $LBW(kg) = \frac{{9270 \times Wt}} {{8780 + (244 \times BMI)}} $ Body composition was classified as: ‘normal’ (BMI <25kg/m2 and not sarcopenic), ‘overweight-obese’ (BMI >25kg/m2 and not sarcopenic), ‘sarcopenic’ (sarcopenic and BMI <25kg/m2), or ‘sarcopenic-obese’ (sarcopenic and BMI >25kg/m2). The ability of the LBW equation to predict FFMDXA was determined graphically using Bland-Altman plots and quantitatively using the method of Sheiner and Beal. The mean ± SD age of female participants women was 83±7 years (n=23). Sarcopenia was frequently observed (65.2%). Bland-Altman plots demonstrated an underestimation by the LBW equation compared to FFMDXA. The bias (95% CI) and precision (95% CI) calculated using the method of Sheiner and Beal was 0.5kg (−0.7, 1.66kg) and 4.4kg (−3.7, 12.4kg) respectively for pooled data. This equation can be used to easily calculate LBW. When compared to FFMDXA, the LBW equation resulted in a small underestimation on average in this population of women with recent hip fracture. The degree of bias may not be clinically important although further studies of larger heterogeneous cohorts are needed to investigate and potentially improve the accuracy of this predictive equation in larger clinical cohorts.
Abstract Hydrogels are pivotal in tissue engineering, regenerative medicine, and drug delivery applications. DNA molecules stand out among various biomaterials due to their unparalleled precision, programmability, and customization. In this study, we introduce a palate of novel cellular scaffolding platforms made of pure DNA-based hydrogel systems while improving the shortcomings of the existing platforms. DNA strands can form complex supramolecular branched structures essential for designing novel functional materials by its precise sequence-based self-assembly. These unique geometric scaffolds offer a soft, cushiony platform, ideal for culturing cells to mimic the complex native in vivo environments better. Each hydrogel comprises repeating units of branched DNA supramolecular structures, each possessing a distinct number of branching arms. The epithelial cells grown over these hydrogels show dynamic changes at multiple levels, from morphology to protein expression patterns, enhanced membrane traffic, and proliferation. The DNA hydrogels explored here are mechanically weak and soft and thus appropriate for applications in cell biology. This research lays the groundwork for developing a DNA hydrogel system with a higher dynamic range of stiffness, which will open exciting avenues for tissue engineering and beyond. Graphical abstract illustrating diverse branched DNA supramolecular architectures forming DNA hydrogels of various geometric profiles, each put to use in the cell culture applications.
Nepal has made progress with the control of HIV infection in recent years. There have been changes in epidemiology, programme interventions in different population groups, and changes in policies over the last 10 years, particularly in diagnosis and treatment. Therefore, this review was conducted to identify the effectiveness of different interventions/policies in different sub-populations at risk, targeted towards epidemiology and treatment outcomes for those with HIV infection in Nepal. This review was prepared based on a review of published and unpublished documents from the Nepalese HIV infection control programme, published articles in different journals, different survey reports including integrated bio-behavioural surveillance (IBBS) survey reports. The prevalence of HIV infection among adults in 2014 was 0.20% with a progressive decreasing trend from 2005. The prevalence of HIV infection among injecting drug users (51.7% in 2005 and 6.4% in 2015 in Kathmandu valley) was relatively high in all years as compared to other risk groups. HIV infection prevalence among women attending antenatal clinics was higher in the year 2006 (0.25%) but there was a decreasing trend in the following years to 2015, when prevalence was 0.077%. Although different interventions were conducted to cover key populations at risk, the coverage in some risk population was very low. HIV testing status among the general population was very low (7.5% among males and 2.9% among females) in 2011. Only one-third of HIV-infected individuals were on ART in 2015, although this proportion has increased since 2005. The share of domestic budget among the total expenditure on HIV control program is below 15%. There is the need for implementation of control programmes more efficiently and effectively with expanding geographical and population coverage. Surveillance systems should be strengthened to get up-to-date information for evidence-based planning and developing strategies. The domestic budget for HIV control programme should be increased to improve their sustainability.
A significant reduction in malaria cases over the recent years in Nepal has encouraged the government to adopt a goal of "malaria-free nation by 2025." Nevertheless, to achieve this goal, it is critical to identify the epidemiological burden of malaria by specific regions and areas for an effective targeted intervention. The main objective of this study was to estimate the risk of malaria at Village Development Committee (VDC) level in Nepal based on disease, vector, parasite, and geography.In 2012, the micro-stratification of malaria risk was carried out in 75 districts of Nepal. Instruments such as a questionnaire, case record forms, and guidelines for malaria micro-stratification were developed and pre-tested for necessary adaptations. Village Development Committee (VDC)-wise malaria data were analyzed using exploratory statistics and were stratified by geographical variables that contributed to the risk of malaria. To understand the transmission risk at VDC level, overlay analysis was done using ArcGIS 10. To ensure transparent, reproducible, and comprehensible risk assessment, standard scoring method was selected and utilized for data from 2009 to 2011. Thus identified, three major variables (key determinants) were given weights (wt.) accordingly to stratification of the malaria risk (disease burden, "0.3" wt.; ecology/vector transmission, "0.5" wt.; and vulnerability-population movement, "0.2" wt.). Malaria risk in a VDC was determined based on the overall scores and classified into four categories: no risk, low risk, moderate risk, and high risk.Analyzing the overall risk based on scoring of the total VDCs (n = 3976), 54 (1.36%), 201 (5.06%), 999 (25.13%), and 2718 (68.36%) were identified as high-, moderate-, low-, and no-risk categories for malaria, respectively. Based on the population statistics, 3.62%, 9.79%, 34.52%, and 52.05% of the country's total population live in high-risk, moderate-risk, low-risk, and no-risk VDCs for malaria, respectively. Our micro-stratification study estimates are 100,000 population at high risk. Regional distribution showed that the majority of the high-risk VDCs were identified in the Far- and Mid-western regions (19 and 18 VDCs) followed by Central and Western regions (10 and 7 VDCs) with no high-risk VDCs in the Eastern region. Similarly, 77, 59, 27, 24, and 14 VDCs of the Central, Mid-western, Western, Eastern, and Far-western regions, respectively, were found under moderate malaria risk. Of the low-risk VDCs, 353, 215, 191, 148, and 92 were respectively from the Central, Eastern, Western, Far-western, and Mid-western regions.The current micro-stratification study provides insights on malaria risk up to the VDC level. This will help the malaria elimination program to target interventions at the local level thereby ensuring the best utilization of available resources to substantially narrowed-down target areas. With further updates and refinement, the micro-stratification approach can be employed to identify the risk areas up to smaller units within the VDCs (ward and villages).
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