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1.
Chem Biodivers ; : e202400642, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38822644

ABSTRACT

New 2-(4-benzothiazol-2-yl-phenoxy)-1-(3,5-diphenyl-4,5-dihydro-pyrazol-1-yl)-ethanones (9a-o) have been designed and synthesized. The antiepileptic potential of the synthesized compounds has been tested by following standard animal screening models which include maximal electroshock (MES) and subcutaneous pentylenetetrazole (scPTZ) models. The study concluded that compounds 9c, 9d, 9f, 9i, 9n, and 9o possessed good antiepileptic potential when compared with standard drugs like carbamazepine and phenytoin. The results of the rotarod performance test also established them without any neurotoxicity. The motor impairment test yielded that the synthesized compounds are also good antidepressants. In-silico studies have been performed to determine the eligibility of synthesized compounds as orally administered molecules and interactions with the target proteins. The result of in-silico studies reinforced results obtained by in vivo study of the synthesized compounds along with their possible mechanism of antiepileptic action i.e. via inhibiting voltage-gated sodium channels (VGSCs) and gamma-aminobutyric acid-A receptor.

2.
Chem Biol Drug Des ; 103(6): e14552, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38825735

ABSTRACT

The five-membered 1,3,4-oxadiazole heterocyclic ring has received considerable attention because of its unique bio-isosteric properties and an unusually wide spectrum of biological activities. After a century since 1,3,4-oxadiazole was discovered, its uncommon potential attracted medicinal chemist's attention, leading to the discovery of a few presently accessible drugs containing 1,3,4-oxadiazole units, and a large number of patents have been granted on research related to 1,3,4-oxadiazole. It is worth noting that interest in 1,3,4-oxadiazoles' biological applications has doubled in the last few years. Herein, this review presents a comprehensive overview of the recent achievements in the synthesis of 1,3,4-oxadiazole-based compounds and highlights the major advances in their biological applications in the last 10 years, as well as brief remarks on prospects for further development. We hope that researchers across the scientific streams will benefit from the presented review articles for designing their work related to 1,3,4-oxadiazoles.


Subject(s)
Oxadiazoles , Oxadiazoles/chemistry , Oxadiazoles/pharmacology , Humans
3.
EXCLI J ; 23: 570-599, 2024.
Article in English | MEDLINE | ID: mdl-38887390

ABSTRACT

Cancer poses intricate challenges to treatment due to its complexity and diversity. Ferroptosis and circular RNAs (circRNAs) are emerging as innovative therapeutic avenues amid the evolving landscape of cancer therapy. Extensive investigations into circRNAs reveal their diverse roles, ranging from molecular regulators to pivotal influencers of ferroptosis in cancer cell lines. The results underscore the significance of circRNAs in modulating molecular pathways that impact crucial aspects of cancer development, including cell survival, proliferation, and metastasis. A detailed analysis delineates these pathways, shedding light on the molecular mechanisms through which circRNAs influence ferroptosis. Building upon recent experimental findings, the study evaluates the therapeutic potential of targeting circRNAs to induce ferroptosis. By identifying specific circRNAs associated with the etiology of cancer, this analysis paves the way for the development of targeted therapeutics that exploit vulnerabilities in cancer cells. This review consolidates the existing understanding of ferroptosis and circRNAs, emphasizing their role in cancer therapy and providing impetus for ongoing research in this dynamic field. See also the graphical abstract(Fig. 1).

4.
Chem Biol Drug Des ; 103(6): e14537, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38888058

ABSTRACT

The versatile basic structure of piperazine allows for the development and production of newer bioactive molecules that can be used to treat a wide range of diseases. Piperazine derivatives are unique and can easily be modified for the desired pharmacological activity. The two opposing nitrogen atoms in a six-membered piperazine ring offer a large polar surface area, relative structural rigidity, and more acceptors and donors of hydrogen bonds. These properties frequently result in greater water solubility, oral bioavailability, and ADME characteristics, as well as improved target affinity and specificity. Various synthetic protocols have been reported for piperazine and its derivatives. In this review, we focused on recently published synthetic protocols for the synthesis of the piperazine and its derivatives. The structure-activity relationship concerning different biological activities of various piperazine-containing drugs has also been highlighted to provide a good understanding to researchers for future research on piperazines.


Subject(s)
Chemistry, Pharmaceutical , Piperazines , Piperazines/chemistry , Piperazines/chemical synthesis , Humans , Structure-Activity Relationship , Animals
5.
Prev Med Rep ; 43: 102764, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38826589

ABSTRACT

Background: Noma is a neglected tropical disease and a global health concern. Objectives: To elucidate the epidemiology, management, prevention, and public health implications of Noma. Methods: PubMed, Scopus, and Web of Science, supplemented by Google Scholar and World Health Organization databases, were searched using keywords to gather both published and grey literature from 1970 to 2023 in English. Results: Approximately 30,000-40,000 cases occur annually, with varying incidences across various African countries, such as Nigeria, Niger, and Chad. Incidence in Nigerian and Ethiopian states range from 0.6 to 3300 and 1.64 to 13.4 per 100,000 population, respectively. Mortality is approximately 8.5% in Niger. Risk factors include malnutrition, immunocompromised status, poor dental hygiene, inadequate sanitation, gingival lesions, low socioeconomic status, chronic and infectious diseases, low birth weight, high parity, diarrhoea, and fever. Diagnosis is primarily made based on clinical signs/symptoms and accordingly staging of disease is done. Stage I, II and II presents with acute necrotizing gingivitis, facial edema with halitosis, and necrotizing stomatitis, respectively. If the patient survives acute stages, the progress to Stage IV and Stage V manifests as trismus, difficulty in deglutition and phonation, and facial disfigurement, with increased severity in last stage. Treatment encompasses antibiotic therapy (amoxicillin, metronidazole, chlorhexidine, ampicillin, gentamicin), surgical interventions, wound management (honey dressing, ketamine), and nutritional support. Prevention strategies include oral hygiene, vaccination, health education, and community-based interventions. Conclusion: Noma's recent inclusion in WHO list of neglected tropical diseases is a milestone in recognizing the importance of prevention and early intervention to globally enhance health outcomes.

6.
Rev Med Virol ; 34(4): e2554, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38862398

ABSTRACT

The Varicella-zoster virus (VZV), classified as a neurotropic member of the Herpesviridae family, exhibits a characteristic pathogenicity, predominantly inducing varicella, commonly known as chickenpox, during the initial infectious phase, and triggering the reactivation of herpes zoster, more commonly recognized as shingles, following its emergence from a latent state. The pathogenesis of VZV-associated neuroinflammation involves a complex interplay between viral replication within sensory ganglia and immune-mediated responses that contribute to tissue damage and dysfunction. Upon primary infection, VZV gains access to sensory ganglia, establishing latent infection within neurons. During reactivation, the virus can spread along sensory nerves, triggering a cascade of inflammatory mediators, chemokines, and immune cell infiltration in the affected neural tissues. The role of both adaptive and innate immune reactions, including the contributions of T and B cells, macrophages, and dendritic cells, in orchestrating the immune-mediated damage in the central nervous system is elucidated. Furthermore, the aberrant activation of the natural defence mechanism, characterised by the dysregulated production of immunomodulatory proteins and chemokines, has been implicated in the pathogenesis of VZV-induced neurological disorders, such as encephalitis, myelitis, and vasculopathy. The intricate balance between protective and detrimental immune responses in the context of VZV infection emphasises the necessity for an exhaustive comprehension of the immunopathogenic mechanisms propelling neuroinflammatory processes. Despite the availability of vaccines and antiviral therapies, VZV-related neurological complications remain a significant concern, particularly in immunocompromised individuals and the elderly. Elucidating these mechanisms might facilitate the emergence of innovative immunomodulatory strategies and targeted therapies aimed at mitigating VZV-induced neuroinflammatory damage and improving clinical outcomes. This comprehensive understanding enhances our grasp of viral pathogenesis and holds promise for pioneering therapeutic strategies designed to mitigate the neurological ramifications of VZV infections.


Subject(s)
Herpesvirus 3, Human , Humans , Herpesvirus 3, Human/immunology , Herpesvirus 3, Human/physiology , Herpesvirus 3, Human/pathogenicity , Herpes Zoster/virology , Herpes Zoster/immunology , Varicella Zoster Virus Infection/immunology , Varicella Zoster Virus Infection/virology , Nervous System Diseases/virology , Nervous System Diseases/immunology , Nervous System Diseases/etiology , Animals , Chickenpox/virology , Chickenpox/immunology , Neuroinflammatory Diseases/immunology , Neuroinflammatory Diseases/virology
9.
Med Chem ; 2024 Jun 24.
Article in English | MEDLINE | ID: mdl-38918990

ABSTRACT

The most common heterocyclic aromatic molecule with potential uses in industry and medicine is quinoline. Its chemical formula is C9H7N, and it has a distinctive double-ring structure with a pyridine moiety fused with a benzene ring. Various synthetic approaches synthesize quinoline derivatives. These approaches include solvent-free synthetic approach, mechanochemistry, ultrasonic, photolytic synthetic approach, and microwave and catalytic synthetic approaches. One of the important synthetic approaches is a catalyst-based synthetic approach in which different catalysts are used such as silver-based catalysts, titanium-based nanoparticle catalysts, new iridium catalysts, barium-based catalysts, iron-based catalysts, gold-based catalysts, nickel-based catalyst, some metal-based photocatalyst, α-amylase biocatalyst, by using multifunctional metal-organic framework-metal nanoparticle tandem catalyst etc. In the present study, we summarized different catalyst-promoted reactions that have been reported for the synthesis of quinoline. Hopefully, the study will be helpful for the researchers.

10.
JMIR Public Health Surveill ; 10: e41567, 2024 May 24.
Article in English | MEDLINE | ID: mdl-38787607

ABSTRACT

BACKGROUND: Undernutrition among children younger than 5 years is a subtle indicator of a country's health and economic status. Despite substantial macroeconomic progress in India, undernutrition remains a significant burden with geographical variations, compounded by poor access to water, sanitation, and hygiene services. OBJECTIVE: This study aimed to explore the spatial trends of child growth failure (CGF) indicators and their association with household sanitation practices in India. METHODS: We used data from the Indian Demographic and Health Surveys spanning 1998-2021. District-level CGF indicators (stunting, wasting, and underweight) were cross-referenced with sanitation and sociodemographic characteristics. Global Moran I and Local Indicator of Spatial Association were used to detect spatial clustering of the indicators. Spatial regression models were used to evaluate the significant determinants of CGF indicators. RESULTS: Our study showed a decreasing trend in stunting (44.9%-38.4%) and underweight (46.7%-35.7%) but an increasing prevalence of wasting (15.7%-21.0%) over 15 years. The positive values of Moran I between 1998 and 2021 indicate the presence of spatial autocorrelation. Geographic clustering was consistently observed in the states of Madhya Pradesh, Jharkhand, Odisha, Uttar Pradesh, Chhattisgarh, West Bengal, Rajasthan, Bihar, and Gujarat. Improved sanitation facilities, a higher wealth index, and advanced maternal education status showed a significant association in reducing stunting. Relative risk maps identified hotspots of CGF health outcomes, which could be targeted for future interventions. CONCLUSIONS: Despite numerous policies and programs, malnutrition remains a concern. Its multifaceted causes demand coordinated and sustained interventions that go above and beyond the usual. Identifying hotspot locations will aid in developing control methods for achieving objectives in target areas.


Subject(s)
Sanitation , Humans , India/epidemiology , Sanitation/standards , Sanitation/statistics & numerical data , Female , Male , Child, Preschool , Infant , Growth Disorders/epidemiology , Spatio-Temporal Analysis , Family Characteristics , Health Surveys , Child Nutrition Disorders/epidemiology
11.
Ophthalmic Epidemiol ; : 1-9, 2024 May 06.
Article in English | MEDLINE | ID: mdl-38709174

ABSTRACT

PURPOSE: In the wake of the COVID-19 pandemic, vaccines have been pivotal in curbing disease spread and severity. However, concerns over post-vaccination adverse events, including uveitis, an inflammatory ocular condition, have been noted. This systematic review and meta-analysis aimed to evaluate the incidence and association of uveitis following COVID-19 vaccination. METHODS: A literature search was performed across several databases on October 21, 2023. Human studies examining the incidence of uveitis post-COVID-19 vaccination were included. The Newcastle-Ottawa Scale was used for quality appraisal of the included studies. Meta-analysis was performed to assess the overall incidence of uveitis and the relative risk of developing the condition post-vaccination. All statistical analyses were performed using R software version 4.3. RESULTS: Six studies involving over 2 billion vaccine doses were included. The overall incidence of uveitis was 0.016% (95% CI: 0.010 to 0.026). No significant association was found between vaccination and the onset of uveitis (Relative Risk: 1.45 (95% CI: 0.82 to 2.57, p = 0.12) from four studies. The evidence quality was rated very low due to the limited number of studies and imprecision. CONCLUSION: This analysis indicates a low incidence of uveitis following COVID-19 vaccination and no significant association with the vaccine. The findings are constrained by the small number of studies and low certainty of evidence, underscoring the need for further research. Comprehensive and longitudinal studies are necessary to confirm these findings and reinforce public confidence in COVID-19 vaccination programs.

12.
Pathol Res Pract ; 258: 155329, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38692083

ABSTRACT

Fibrosarcoma is a challenging cancer originating from fibrous tissues, marked by aggressive growth and limited treatment options. The discovery of non-coding RNAs (ncRNAs), including long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and small interfering RNAs (siRNAs), has opened new pathways for understanding and treating this malignancy. These ncRNAs play crucial roles in gene regulation, cellular processes, and the tumor microenvironment. This review aims to explore the impact of ncRNAs on fibrosarcoma's pathogenesis, progression, and resistance to treatment, focusing on their mechanistic roles and therapeutic potential. A comprehensive review of literature from databases like PubMed and Google Scholar was conducted, focusing on the dysregulation of ncRNAs in fibrosarcoma, their contribution to tumor growth, metastasis, drug resistance, and their cellular pathway interactions. NcRNAs significantly influence fibrosarcoma, affecting cell proliferation, apoptosis, invasion, and angiogenesis. Their function as oncogenes or tumor suppressors makes them promising biomarkers and therapeutic targets. Understanding their interaction with the tumor microenvironment is essential for developing more effective treatments for fibrosarcoma. Targeting ncRNAs emerges as a promising strategy for fibrosarcoma therapy, offering hope to overcome the shortcomings of existing treatments. Further investigation is needed to clarify specific ncRNAs' roles in fibrosarcoma and to develop ncRNA-based therapies, highlighting the significance of ncRNAs in improving patient outcomes in this challenging cancer.


Subject(s)
Fibrosarcoma , RNA, Untranslated , Humans , Fibrosarcoma/genetics , Fibrosarcoma/pathology , RNA, Untranslated/genetics , Gene Expression Regulation, Neoplastic , Oncogenes/genetics , Tumor Microenvironment/genetics , Genes, Tumor Suppressor/physiology , MicroRNAs/genetics , MicroRNAs/metabolism , Animals
13.
Pathol Res Pract ; 258: 155303, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38728793

ABSTRACT

Hepatocellular carcinoma (HCC) is among the primary reasons for fatalities caused by cancer globally, highlighting the need for comprehensive knowledge of its molecular aetiology to develop successful treatment approaches. The PI3K/Akt system is essential in the course of HCC, rendering it an intriguing candidate for treatment. Non-coding RNAs (ncRNAs), such as long ncRNAs (lncRNAs), microRNAs (miRNAs), and circular RNAs (circRNAs), are important mediators of the PI3K/Akt network in HCC. The article delves into the complex regulatory functions of ncRNAs in influencing the PI3K/Akt system in HCC. The study explores how lncRNAs, miRNAs, and circRNAs impact the expression as well as the function of the PI3K/Akt network, either supporting or preventing HCC growth. Additionally, treatment strategies focusing on ncRNAs in HCC are examined, such as antisense oligonucleotide-based methods, RNA interference, and small molecule inhibitor technologies. Emphasizing the necessity of ensuring safety and effectiveness in clinical settings, limitations, and future approaches in using ncRNAs as therapies for HCC are underlined. The present study offers useful insights into the complex regulation system of ncRNAs and the PI3K/Akt cascade in HCC, suggesting possible opportunities for developing innovative treatment approaches to address this lethal tumor.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Phosphatidylinositol 3-Kinases , Proto-Oncogene Proteins c-akt , RNA, Untranslated , Signal Transduction , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/pathology , Humans , Liver Neoplasms/genetics , Liver Neoplasms/pathology , Proto-Oncogene Proteins c-akt/metabolism , Proto-Oncogene Proteins c-akt/genetics , Phosphatidylinositol 3-Kinases/metabolism , Phosphatidylinositol 3-Kinases/genetics , Signal Transduction/genetics , RNA, Untranslated/genetics , Gene Expression Regulation, Neoplastic/genetics , RNA, Circular/genetics , RNA, Circular/metabolism , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism
14.
BMC Public Health ; 24(1): 1361, 2024 May 20.
Article in English | MEDLINE | ID: mdl-38769491

ABSTRACT

Smokeless tobacco (SLT) poses many negative health impacts. Despite its longstanding presence in societies across the world, the health implications of SLT have only been rigorously studied in recent decades. This systematic review and meta-analysis aimed to consolidate existing research to provide a comprehensive understanding of the global prevalence of SLT use among women of reproductive age. Relevant articles were extracted from databases such as PubMed, EMBASE, Web of Science, and Scopus from their inception until November 11, 2023. Observational studies reporting the number of SLT users among women of reproductive age were included. The quality of the studies was assessed using the Joanna Briggs Institute (JBI) tool. The meta-analysis used a random-effects model to determine SLT prevalence, supported by statistical tools like forest plots, I2 statistics, and sensitivity analyses to ensure the accuracy and comprehensiveness of the results. All statistical analyses were performed in R version 4.3. From 10 studies involving 2,053,667 participants, a pooled prevalence for SLT use among women of reproductive age was found to be 9.3% (95% CI: 0.038 to 0.21), with significant heterogeneity among studies (I2 = 100%). Publication bias was suspected among the studies. Sensitivity analysis and subgroup analysis couldn't resolve the heterogeneity. Our analysis shows a significant prevalence of SLT use in women of reproductive age, especially in low socioeconomic and developing countries like India, Pakistan, and Nepal. For women of reproductive age, the use of smokeless tobacco (SLT) can lead to infertility, pregnancy complications, and adverse fetal outcomes, including low birth weight and preterm birth. The results highlight the necessity for specific public health measures and policy changes to decrease SLT consumption among reproductive-age women. Further studies are needed to investigate the reasons behind SLT usage in this group and to assess the impact of intervention strategies, to guide more effective public health initiatives and policies.


Subject(s)
Tobacco Use , Tobacco, Smokeless , Humans , Tobacco, Smokeless/statistics & numerical data , Female , Tobacco Use/epidemiology , Prevalence , Adult , Pregnancy
15.
Heliyon ; 10(7): e28810, 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38596114

ABSTRACT

Hepatitis A Virus (HAV) is a significant threat in terms of food safety. A systematic literature search with the research question "What are the clinical outcomes of foodborne Hepatitis A virus infections?" was conducted. The pooled estimate of the outcomes-mortality, hospitalization, and severity rates, along with a 95% confidence interval (CI), was estimated. After screening, 33 studies were included for the data extraction and meta-analysis. The pooled prevalence of hospitalization among the HAV-positive patients was estimated to be 32% (95% CI 21-44), with high heterogeneity (I2 = 98%, p < 0.01). Australia had the highest hospitalization rate, with 82%, followed by Europe (42%). The hospitalization rate showed a significantly increasing trend (beta = 0.015, p=0.002) over the period. The pooled prevalence of mortality among the HAV-positive patients was estimated to be <1%, with low heterogeneity (I2 = 5%, p = 0.39). A wide range of food products were linked with the HAV outbreaks.

16.
Life Sci ; 345: 122613, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38582393

ABSTRACT

Glioblastoma (GBM) is the most prevalent and deadly primary brain tumor type, with a discouragingly low survival rate and few effective treatments. An important function of the EGFR signalling pathway in the development of GBM is to affect tumor proliferation, persistence, and treatment resistance. Advances in molecular biology in the last several years have shown how important ncRNAs are for controlling a wide range of biological activities, including cancer progression and development. NcRNAs have become important post-transcriptional regulators of gene expression, and they may affect the EGFR pathway by either directly targeting EGFR or by modifying important transcription factors and downstream signalling molecules. The EGFR pathway is aberrantly activated in response to the dysregulation of certain ncRNAs, which has been linked to GBM carcinogenesis, treatment resistance, and unfavourable patient outcomes. We review the literature on miRNAs, circRNAs and lncRNAs that are implicated in the regulation of EGFR signalling in GBM, discussing their mechanisms of action, interactions with the signalling pathway, and implications for GBM therapy. Furthermore, we explore the potential of ncRNA-based strategies to overcome resistance to EGFR-targeted therapies, including the use of ncRNA mimics or inhibitors to modulate the activity of key regulators within the pathway.


Subject(s)
Brain Neoplasms , Glioblastoma , MicroRNAs , Humans , ErbB Receptors/metabolism , Glioblastoma/drug therapy , Glioblastoma/genetics , Glioblastoma/metabolism , Signal Transduction , MicroRNAs/metabolism , RNA, Untranslated/genetics , Brain Neoplasms/drug therapy , Brain Neoplasms/genetics , Brain Neoplasms/metabolism
17.
Int J Surg ; 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38626410

ABSTRACT

BACKGROUND: Migraine affects approximately 14-15% of the global population, contributing to nearly 5% of the world's health burden. When drug treatments prove ineffective for intractable migraines, highly specific surgical interventions emerge as potential solutions. We aimed to analyze surgical approaches for these refractory or intractable migraines through a systematic review and meta-analysis. METHODS: We conducted a literature search across databases such as PubMed, Scopus, Web of Science, and Embase, focusing on studies related to migraines and surgical outcomes. We considered clinical trials or observational studies that included any surgical intervention for refractory or intractable migraines, emphasizing key outcomes such as reductions in migraine intensity, Migraine Disability Assessment scores (MIDAS), and 50% Migraine Headache Index (MHI) reduction rates. Statistical analyses were performed using R version 4.3. RESULTS: Eleven studies were included in the systematic review. A meta-analysis of four studies involving overall 95 patients showed a significant reduction in mean migraine intensity scores using ONS (-2.27, 95% CI: -3.92 to -0.63, P=0.021). Three studies with 85 patients showed an average MIDAS score reduction of -52.3, though this was not statistically significant (95% CI: -136.85 to 32.19, P=0.116). Two additional studies corroborated these reductions in MIDAS scores. Nerve decompression surgery showed a substantial decrease in the average migraine intensity (from 8.31 down to 4.06). Median MIDAS score dropped from 57 to 20. Two studies indicated a success rate of 40% and 82%, respectively, in achieving a 50% reduction in the Migraine MHI through nerve decompression. Findings from two studies suggest that septorhinoplasty and sinus surgery effectively decrease migraine intensity scores. CONCLUSION: The existing evidence emphasizes the potential advantages of surgical interventions as a promising approach to managing intractable or refractory migraines. However, robust and comprehensive research is crucial to refine and solidify the efficacy of these surgical methods, aiming for widespread benefits for patients, considering cost-effectiveness factors.

18.
Chem Biol Drug Des ; 103(4): e14515, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38570333

ABSTRACT

Neurodegenerative disorders are devastating disorders characterized by gradual loss of neurons and cognition or mobility impairment. The common pathological features of these diseases are associated with the accumulation of misfolded or aggregation of proteins. The pivotal roles of autophagy and proteostasis in maintaining cellular health and preventing the accumulation of misfolded proteins, which are associated with neurodegenerative diseases like Huntington's disease (HD), Alzheimer's disease (AD), and Parkinson's disease (PD). This article presents an in-depth examination of the interplay between autophagy and proteostasis, highlighting how these processes cooperatively contribute to cellular homeostasis and prevent pathogenic protein aggregate accumulation. Furthermore, the review emphasises the potential therapeutic implications of targeting autophagy and proteostasis to mitigate neurodegenerative diseases. While advancements in research hold promise for developing novel treatments, the article also addresses the challenges and complexities associated with modulating these intricate cellular pathways. Ultimately, advancing understanding of the underlying mechanism of autophagy and proteostasis in neurodegenerative disorders provides valuable insights into potential therapeutic avenues and future research directions.


Subject(s)
Huntington Disease , Neurodegenerative Diseases , Humans , Neurodegenerative Diseases/drug therapy , Neurodegenerative Diseases/metabolism , Proteostasis , Proteins/metabolism , Huntington Disease/drug therapy , Huntington Disease/metabolism , Autophagy
19.
Neurotoxicology ; 102: 106-113, 2024 May.
Article in English | MEDLINE | ID: mdl-38636605

ABSTRACT

BACKGROUND: Obstructive Sleep Apnea (OSA) is a significant health concern characterized by recurrent upper airway blockages during sleep, causing various health issues. There's growing evidence of a link between air pollution and OSA, though research results have been inconsistent. This systematic review and meta-analysis aims to consolidate and examine data on the relationship between air pollution and OSA's risk and severity. METHODS: A literature search across PubMed, EMBASE, and Web of Science was conducted until January 10, 2024. The selection criteria targeted studies involving OSA participants or those at risk, with quantitative air pollution assessments. The Nested Knowledge software facilitated screening and data extraction, while the Newcastle-Ottawa Scale was used for quality assessment. Meta-analyses, utilizing random-effects models, computed pooled odds ratios (ORs) for the OSA risk associated with PM2.5 and NO2 exposure, analyzed using R software version 4.3. RESULTS: The systematic review included twelve studies, four of which were analyzed in the meta-analysis. The meta-analysis revealed diverse results on the association of PM2.5 and NO2 with OSA risk. PM2.5 exposure showed a pooled OR of 0.987 (95 % CI: 0.836-1.138), indicating no substantial overall impact on OSA risk. Conversely, NO2 exposure was linked to a pooled OR of 1.095 (95 % CI: 0.920-1.270), a non-significant increase in risk. Many studies found a relationship between air pollution exposure and elevated Apnea-Hypopnea Index (AHI) levels, indicating a relationship between air pollution and OSA severity. CONCLUSION: The findings suggest air pollutants, especially NO2, might play a role in worsening OSA risk and severity, but the evidence isn't definitive. This highlights the variability of different pollutants' effects and the necessity for more research. Understanding these links is vital for shaping public health policies and clinical approaches to address OSA amidst high air pollution.


Subject(s)
Air Pollution , Sleep Apnea, Obstructive , Sleep Apnea, Obstructive/epidemiology , Humans , Air Pollution/adverse effects , Particulate Matter/adverse effects , Air Pollutants/adverse effects , Severity of Illness Index , Risk Factors , Nitrogen Dioxide/adverse effects , Environmental Exposure/adverse effects
20.
JMIR Public Health Surveill ; 10: e54769, 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38687992

ABSTRACT

BACKGROUND: The unprecedented emergence of the COVID-19 pandemic necessitated the development and global distribution of vaccines, making the understanding of global vaccine acceptance and hesitancy crucial to overcoming barriers to vaccination and achieving widespread immunization. OBJECTIVE: This umbrella review synthesizes findings from systematic reviews and meta-analyses to provide insights into global perceptions on COVID-19 vaccine acceptance and hesitancy across diverse populations and regions. METHODS: We conducted a literature search across major databases to identify systematic reviews and meta-analysis that reported COVID-19 vaccine acceptance and hesitancy. The AMSTAR-2 (A Measurement Tool to Assess Systematic Reviews) criteria were used to assess the methodological quality of included systematic reviews. Meta-analysis was performed using STATA 17 with a random effect model. The data synthesis is presented in a table format and via a narrative. RESULTS: Our inclusion criteria were met by 78 meta-analyses published between 2021 and 2023. Our analysis revealed a moderate vaccine acceptance rate of 63% (95% CI 0.60%-0.67%) in the general population, with significant heterogeneity (I2 = 97.59%). Higher acceptance rates were observed among health care workers and individuals with chronic diseases, at 64% (95% CI 0.57%-0.71%) and 69% (95% CI 0.61%-0.76%), respectively. However, lower acceptance was noted among pregnant women, at 48% (95% CI 0.42%-0.53%), and parents consenting for their children, at 61.29% (95% CI 0.56%-0.67%). The pooled vaccine hesitancy rate was 32% (95% CI 0.25%-0.39%) in the general population. The quality assessment revealed 19 high-quality, 38 moderate-quality, 15 low-quality, and 6 critically low-quality meta-analyses. CONCLUSIONS: This review revealed the presence of vaccine hesitancy globally, emphasizing the necessity for population-specific, culturally sensitive interventions and clear, credible information dissemination to foster vaccine acceptance. The observed disparities accentuate the need for continuous research to understand evolving vaccine perceptions and to address the unique concerns and needs of diverse populations, thereby aiding in the formulation of effective and inclusive vaccination strategies. TRIAL REGISTRATION: PROSPERO CRD42023468363; https://tinyurl.com/2p9kv9cr.


Subject(s)
COVID-19 Vaccines , COVID-19 , Systematic Reviews as Topic , Vaccination Hesitancy , Humans , COVID-19/prevention & control , COVID-19 Vaccines/administration & dosage , Meta-Analysis as Topic , Patient Acceptance of Health Care/statistics & numerical data , Patient Acceptance of Health Care/psychology , Vaccination Hesitancy/psychology , Vaccination Hesitancy/statistics & numerical data
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