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Cell Death Discovery Jun 2024Despite the advances in the understanding of reproductive physiology, the mechanisms underlying ovarian aging are still not deciphered. Recent research found an...
Despite the advances in the understanding of reproductive physiology, the mechanisms underlying ovarian aging are still not deciphered. Recent research found an association between impaired ATM-mediated DNA double-strand break (DSB) repair mechanisms and oocyte aging. However, direct evidence connecting ATM-mediated pathway function decline and impaired oocyte quality is lacking. The objective of this study was to determine the role of ATM-mediated DNA DSB repair in the maintenance of oocyte quality in a mouse oocyte knockdown model. Gene interference, in vitro culture, parthenogenesis coupled with genotoxicity assay approaches, as well as molecular cytogenetic analyses based upon next-generation sequencing, were used to test the hypothesis that intact ATM function is critical in the maintenance of oocyte quality. We found that ATM knockdown impaired oocyte quality, resulting in poor embryo development. ATM knockdown significantly lowered or blocked the progression of meiosis in vitro, as well as retarding and reducing embryo cleavage after parthenogenesis. After ATM knockdown, all embryos were of poor quality, and none reached the blastocyst stage. ATM knockdown was also associated with an increased aneuploidy rate compared to controls. Finally, ATM knockdown increased the sensitivity of the oocytes to a genotoxic active metabolite of cyclophosphamide, with increased formation of DNA DSBs, reduced survival, and earlier apoptotic death compared to controls. These findings suggest a key role for ATM in maintaining oocyte quality and resistance to genotoxic stress, and that the previously observed age-induced decline in oocyte ATM function may be a prime factor contributing to oocyte aging.
PubMed: 38914566
DOI: 10.1038/s41420-024-02041-z -
Cell Death & Disease Jun 2024Adipose tissues in the hypodermis, the crucial stem cell reservoir in the skin and the endocrine organ for the maintenance of skin homeostasis undergo significant... (Review)
Review
Adipose tissues in the hypodermis, the crucial stem cell reservoir in the skin and the endocrine organ for the maintenance of skin homeostasis undergo significant changes during skin aging. Dermal white adipose tissue (dWAT) has recently been recognized as an important organ for both non-metabolic and metabolic health in skin regeneration and rejuvenation. Defective differentiation, adipogenesis, improper adipocytokine production, and immunological dissonance dysfunction in dWAT lead to age-associated clinical changes. Here, we review age-related alterations in dWAT across levels, emphasizing the mechanisms underlying the regulation of aging. We also discuss the pathogenic changes involved in age-related fat dysfunction and the unfavorable consequences of accelerated skin aging, such as chronic inflammaging, immunosenescence, delayed wound healing, and fibrosis. Research has shown that adipose aging is an early initiation event and a potential target for extending longevity. We believe that adipose tissues play an essential role in aging and form a potential therapeutic target for the treatment of age-related skin diseases. Further research is needed to improve our understanding of this phenomenon.
Topics: Humans; Homeostasis; Aging; Skin Aging; Animals; Skin; Adipose Tissue, White; Adipogenesis
PubMed: 38914551
DOI: 10.1038/s41419-024-06818-z -
Genomics, Proteomics & Bioinformatics Jun 2024Hematopoietic homeostasis is maintained by hematopoietic stem cells (HSCs), and it is tightly controlled at multiple levels to sustain the self-renewal capacity and...
Hematopoietic homeostasis is maintained by hematopoietic stem cells (HSCs), and it is tightly controlled at multiple levels to sustain the self-renewal capacity and differentiation potential of HSCs. Dysregulation of self-renewal and differentiation of HSCs leads to the development of hematologic diseases, including acute myeloid leukemia (AML). Thus, understanding the underlying mechanisms of HSC maintenance and the development of hematologic malignancies is one of the fundamental scientific endeavors in stem cell biology. N 6-methyladenosine (m6A) is a common modification in mammalian messenger RNAs (mRNAs) and plays important roles in various biological processes. In this study, we performed a comparative analysis of the dynamics of the RNA m6A methylome of hematopoietic stem and progenitor cells (HSPCs) and leukemia-initiating cells (LICs) in AML. We found that RNA m6A modification regulates the transformation of long-term HSCs into short-term HSCs and determines the lineage commitment of HSCs. Interestingly, m6A modification leads to reprogramming that promotes cellular transformation during AML development, and LIC-specific m6A targets are recognized by different m6A readers. Moreover, the very long chain fatty acid transporter ATP-binding cassette subfamily D member 2 (ABCD2) is a key factor that promotes AML development, and deletion of ABCD2 damages clonogenic ability, inhibits proliferation, and promotes apoptosis of human leukemia cells. This study provides a comprehensive understanding of the role of m6A in regulating cell state transition in normal hematopoiesis and leukemogenesis, and identifies ABCD2 as a key factor in AML development.
PubMed: 38913865
DOI: 10.1093/gpbjnl/qzae049 -
JMIR MHealth and UHealth Jun 2024Digital mental health services are increasingly being provided by employers as health benefit programs that can improve access to and remove barriers to mental health... (Observational Study)
Observational Study
BACKGROUND
Digital mental health services are increasingly being provided by employers as health benefit programs that can improve access to and remove barriers to mental health care. Stratified care models, in particular, offer personalized care recommendations that can offer clinically effective interventions while conserving resources. Nonetheless, clinical evaluation is needed to understand their benefits for mental health and their use in a real-world setting.
OBJECTIVE
This study aimed to examine the changes in clinical outcomes (ie, depressive and anxiety symptoms and well-being) and to evaluate the use of stratified blended care among members of an employer-sponsored digital mental health benefit.
METHODS
In a large prospective observational study, we examined the changes in depressive symptoms (9-item Patient Health Questionnaire), anxiety symptoms (7-item Generalized Anxiety Disorder scale), and well-being (5-item World Health Organization Well-Being Index) for 3 months in 509 participants (mean age 33.9, SD 8.7 years; women: n=312, 61.3%; men: n=175, 34.4%; nonbinary: n=22, 4.3%) who were newly enrolled and engaged in care with an employer-sponsored digital mental health platform (Modern Health Inc). We also investigated the extent to which participants followed the recommendations provided to them through a stratified blended care model.
RESULTS
Participants with elevated baseline symptoms of depression and anxiety exhibited significant symptom improvements, with a 37% score improvement in depression and a 29% score improvement in anxiety (P values <.001). Participants with baseline scores indicative of poorer well-being also improved over the study period (90% score improvement; P=.002). Furthermore, over half exhibited clinical improvement or recovery for depressive symptoms (n=122, 65.2%), anxiety symptoms (n=127, 59.1%), and low well-being (n=82, 64.6%). Among participants with mild or no baseline symptoms, we found high rates of maintenance for low depressive (n=297, 92.2%) and anxiety (n=255, 86.7%) symptoms and high well-being (n=344, 90.1%). In total, two-thirds of the participants (n=343, 67.4%) used their recommended care, 16.9% (n=86) intensified their care beyond their initial recommendation, and 15.7% (n=80) of participants underused care by not engaging with the highest level of care recommended to them.
CONCLUSIONS
Participants with elevated baseline depressive or anxiety symptoms improved their mental health significantly from baseline to follow-up, and most participants without symptoms or with mild symptoms at baseline maintained their mental health over time. In addition, engagement patterns indicate that the stratified blended care model was efficient in matching individuals with the most effective and least costly care while also allowing them to self-determine their care and use combinations of services that best fit their needs. Overall, the results of this study support the clinical effectiveness of the platform for improving and preserving mental health and support the utility and effectiveness of stratified blended care models to improve access to and use of digitally delivered mental health services.
Topics: Humans; Female; Male; Adult; Prospective Studies; Longitudinal Studies; Mental Health Services; Middle Aged; Surveys and Questionnaires; Depression; Telemedicine
PubMed: 38913405
DOI: 10.2196/48298 -
JCI Insight May 2024Peripheral nerve injury-induced neuronal hyperactivity in the dorsal root ganglion (DRG) participates in neuropathic pain. The calcium-activated potassium channel...
Peripheral nerve injury-induced neuronal hyperactivity in the dorsal root ganglion (DRG) participates in neuropathic pain. The calcium-activated potassium channel subfamily N member 1 (KCNN1) mediates action potential afterhyperpolarization (AHP) and gates neuronal excitability. However, the specific contribution of DRG KCNN1 to neuropathic pain is not yet clear. We report that chronic constriction injury (CCI) of the unilateral sciatic nerve or unilateral ligation of the fourth lumbar nerve produced the downregulation of Kcnn1 mRNA and KCNN1 protein in the injured DRG. This downregulation was partially attributed to a decrease in DRG estrogen-related receptor gamma (ESRRG), a transcription factor, which led to reduced binding to the Kcnn1 promoter. Rescuing this downregulation prevented CCI-induced decreases in total potassium voltage currents and AHP currents, reduced excitability in the injured DRG neurons, and alleviated CCI-induced development and maintenance of nociceptive hypersensitivities, without affecting locomotor function and acute pain. Mimicking the CCI-induced DRG KCNN1 downregulation resulted in augmented responses to mechanical, heat, and cold stimuli in naive mice. Our findings indicate that ESRRG-controlled downregulation of DRG KCNN1 is likely essential for the development and maintenance of neuropathic pain. Thus, KCNN1 may serve as a potential target for managing this disorder.
Topics: Animals; Neuralgia; Ganglia, Spinal; Mice; Down-Regulation; Sensory Receptor Cells; Male; Peripheral Nerve Injuries; Mice, Inbred C57BL; Sciatic Nerve; Disease Models, Animal; Intermediate-Conductance Calcium-Activated Potassium Channels; Action Potentials
PubMed: 38912580
DOI: 10.1172/jci.insight.180085 -
Heliyon Jun 2024This study addressed the critical problem of repairing cracks in aging aircraft structures, a safety concern of paramount importance given the extended service life of...
Enhancing aircraft crack repair efficiency through novel optimization of piezoelectric actuator parameters: A design of experiments and adaptive neuro-fuzzy inference system approach.
This study addressed the critical problem of repairing cracks in aging aircraft structures, a safety concern of paramount importance given the extended service life of modern fleets. Utilized a finite element (FE) method enhanced by the design of experiments (DOE) and adaptive neuro-fuzzy inference system (ANFIS) approaches to analyze the efficacy of piezoelectric actuators in mitigating stress intensity factors (SIF) at crack tips-a novel integration in structural repair strategies. Through simulations, we examined the impact of various factors on the repair process, including the plate, actuator, and adhesive bond size and characteristics. In this work, initially, the SIF estimation used the FE approach at crack tips in aluminum 2024-T3 plate under the uniform uniaxial tensile load. Next, numerous simulations have been performed by changing the parameters and their levels to collect the data information for the analysis of the DOE and ANFIS approach. The FE simulation results have shown that changing the parameters and their levels will result in changing of SIF. Several DOE and ANFIS optimization cases have been performed for the depth analysis of parameters. The current results indicated that optimal placement, size, and voltage applied to the piezoelectric actuators are crucial for maximizing crack repair efficiency, with the ability to significantly reduce the SIF by a quantified percentage under specific conditions. This research surpasses previous efforts by providing a comprehensive parameter optimization of piezoelectric actuator application, offering a methodologically advanced and practically relevant pathway to enhance aircraft structural integrity and maintenance practices. The study innovation lies in its methodological fusion, which holistically examines the parameters influencing SIF reduction in aircraft crack repair, marking a significant leap in applying intelligent materials in aerospace engineering.
PubMed: 38912447
DOI: 10.1016/j.heliyon.2024.e32166 -
International Journal of Applied &... 2024Pregnancy is the state of carrying a developing embryo or fetus within a female body. Once pregnancy is established, a range of endocrinological events appear in its...
BACKGROUND
Pregnancy is the state of carrying a developing embryo or fetus within a female body. Once pregnancy is established, a range of endocrinological events appear in its maintenance, finally helping in the successful pregnancy. The complications which are usually observed in pregnancy are gestational diabetes, preeclampsia, preterm labor, and spontaneous pregnancy loss or miscarriage, while 10%-15% of clinically recognized pregnancies terminate into spontaneous miscarriage. Thus, many attempts have been made by different researchers for the diagnosis of high-risk pregnancy on altered protein pattern using placental villous tissue or follicular fluid, but these are difficult to obtain and results of different studies are not constant.
AIM
This study was designed to identify the association (if any) among serum protein(s) electrophoretic pattern and different serum hormones in normal pregnant women (controls) and gestational age-matched women with spontaneous pregnancy loss (cases).
MATERIALS AND METHODS
This study was carried out for 1½ year from October 2018 to March 2020 and included 120 participants (60 normal pregnant women and 60 women with spontaneous pregnancy loss) between 20 and 45 years of age with no mean age difference. The electrophoresis of serum was carried out using slab gel electrophoretic unit and serum thyroid-stimulating hormone (TSH), total tri-iodothyronine (TT), total thyroxine (TT), prolactin, and beta human chorionic gonadotropin (β-hCG) levels were analyzed using TSOSH AIA analyzer at Adesh University, Bathinda.
RESULTS
Significant variations in the expression of proteins with molecular weight around ~150 kDa, ~50 kDa, and ~25 kDa were observed in normal pregnant women and women with spontaneous pregnancy loss. However, the protein band of ~50 kDa was found to be highly expressed in the serum of 1 and 2 trimester women experiencing spontaneous pregnancy loss. Therefore, selected protein band of ~50 kDa was further processed by ECI-mass spectrophotometry QUAD time of flight and 365 different proteins were found, out of these; 34 proteins were found to be unidentified protein products ( ). Further, TT, total proteins, β-hCG, and prolactin level were found to be low, whereas, TSH was found to be high in women experiencing spontaneous pregnancy loss. However, difference in the level of β-hCG in the 1 trimester and TT among normal pregnant women and women with spontaneous pregnancy loss was observed to be statistically insignificant.
CONCLUSION
This study indicated that the evaluation of serum protein variations along with hormonal profile may provide valuable information about high-risk pregnancy. Moreover, the differential expression of proteins in women with spontaneous pregnancy loss can be further explored to develop potential biomarker for the early identification of high-risk pregnancy and appropriate preventive measure.
PubMed: 38912357
DOI: 10.4103/ijabmr.ijabmr_383_23 -
Frontiers in Public Health 2024Traffic accidents on the road is an accident is a terrible accident that causes death, injury, and property damage. However, limited studies were addressed to...
BACKGROUND
Traffic accidents on the road is an accident is a terrible accident that causes death, injury, and property damage. However, limited studies were addressed to investigate the prevalence of traffic accidents on the road and the contributing factors among drivers that help in developing strategies to cop-up the incidence within the research domain in Ethiopia, particularly in the study area.
OBJECTIVE
This study aimed to assess the prevalence of road traffic accidents and the contributing factors among drivers of public transportation in Mizan Aman town, Ethiopia.
METHODS
A community-based cross-sectional survey was employed among 376 drivers of public transportation. Every research subject was selected by using a simple random sampling technique. Semi-structured and open-ended questionnaires which comprised demographic characteristics, risky personal behaviors and lifestyles, driver's factors, vehicle condition, and environmental conditions were used to gather data. And then after, data was collected through interviewer-administered using KoBo Collect tools. Completed data were edited and cleaned in the Kobo collect toolbox and then exported for additional analysis to a statistical tool for social science statistics version 26. The descriptive statistics were displayed as figures, tables, and texts. Binary logistic regression was analyzed to identify the contributing factors. Statistically significant was decided with a -value of ≤ 0.05.
RESULTS
The results showed that the prevalence of road traffic accidents among drivers of public transportation in Mizan Aman town was 17%. The study identified factors influencing traffic accidents on the roads including marital status (being single), employee condition (permanent), monthly income (1001-2500 Ethiopia Birr), alcohol use, vehicle maintenance (not), road type (non-asphalt), and weather conditions (being windy).
CONCLUSION
The overall prevalence of road traffic accidents among drivers of public transportation in Mizan Aman town was relatively low. Despite this, sociodemographic characteristics, driver factors, vehicle conditions, and environmental conditions [road type and weather conditions] were the predicting factors of traffic accidents in town. Therefore, reduction strategies should be the highest priority duty for concerned bodies like Mizan Aman town road and transport office, Bench Sheko zone transport and logistics office, and Southwest Ethiopia People Regional State (SWEPRS) transport bureau in the study area.
Topics: Humans; Accidents, Traffic; Cross-Sectional Studies; Ethiopia; Adult; Male; Female; Middle Aged; Surveys and Questionnaires; Automobile Driving; Prevalence; Risk Factors; Transportation; Young Adult; Risk-Taking; Adolescent
PubMed: 38912259
DOI: 10.3389/fpubh.2024.1307884 -
Iranian Journal of Public Health May 2024An important route of microbial transmission is the shared use of these products in beauty salons. We aimed to investigate level of contamination with microorganisms and...
BACKGROUND
An important route of microbial transmission is the shared use of these products in beauty salons. We aimed to investigate level of contamination with microorganisms and their metabolites in shared-use cosmetics in several women's beauty salons.
METHODS
Bacterial and fungal strains from 320 opened/used cosmetic samples were identified according to the Iranian standards for microbial quality of cosmetic products in Golestan Province (North of Iran) during Jul-Sep 2021. In order to assess production of toxins and protease by the predominant bacterial and fungal isolates, multiplex-polymerase chain reaction and the Lowry protein assay were performed, respectively.
RESULTS
Microbial contamination was detected in 180 samples (56.5%), and the highest and lowest rates of microbial contamination were related to skin products (63.88%) and eye beauty products (20%), respectively. The highest level of contamination (> 4,000 colony-forming units/g) was found in toner and face wash samples, and the highest level of contamination was seen in lipstick samples (>20,000 colony-forming units/g). Only one (2%) isolate produced staphylococcal enterotoxin B, while 3 out of 12 (25%) isolates were able to produce protease.
CONCLUSION
The shared-used health and beauty products, face products, in the study area are heavily contaminated. Therefore, it is essential to store used cosmetics in dry and cool places, establish strict inspection regulations for cosmetic products before and after entering the market, and increase awareness of beauty salon workers regarding the appropriate use, sanitary control, and maintenance of health and beauty products.
PubMed: 38912148
DOI: 10.18502/ijph.v53i5.15599 -
Applications in Plant Sciences 2024Although ex situ collections of threatened plants are most useful when they contain maximal genetic variation, the conservation and maintenance of genetic diversity in...
PREMISE
Although ex situ collections of threatened plants are most useful when they contain maximal genetic variation, the conservation and maintenance of genetic diversity in collections are often poorly known. We present a case study using population genomic analyses of an ex situ collection of , a critically endangered tropical tree from Tanzania. Only ~43 individuals are known in two wild populations, and ex situ collections containing 34 individuals were established in two sites from wild-collected seed. The study aimed to understand how much diversity is represented in the collection, analyze the parentage of ex situ individuals, and identify efficient strategies to capture and maintain genetic diversity.
METHODS
We genotyped all known individuals using a 2b-RADseq approach, compared genetic diversity in wild populations and ex situ collections, and conducted parentage analysis of the collections.
RESULTS
Wild populations were found to have greater levels of genetic diversity than ex situ populations as measured by number of private alleles, number of polymorphic sites, observed and expected heterozygosity, nucleotide diversity, and allelic richness. In addition, only 32.6% of wild individuals are represented ex situ and many individuals were found to be the product of selfing by a single wild individual.
DISCUSSION
Population genomic analyses provided important insights into the conservation of genetic diversity in , identifying gaps and inefficiencies, but also highlighting strategies to conserve genetic diversity ex situ. Genomic analyses provide essential information to ensure that collections effectively conserve genetic diversity in threatened tropical trees.
PubMed: 38912126
DOI: 10.1002/aps3.11589