Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 14.977
Filtrar
Mais filtros








Intervalo de ano de publicação
1.
Heliyon ; 10(16): e35560, 2024 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-39224243

RESUMO

As a common cardiovascular disease (CVD), Arrhythmia refers to any abnormality in the origin, frequency, rhythm, conduction velocity, timing, pathway, sequence, or other aspect of cardiac impulses, and it is one of the common cardiovascular diseases in clinical practice. At present, various ion channel blockers are used for treatment of arrhythmia that include Na+ ion channel blockers, K+ ion channel blockers and Ca2+ ion channel blockers. While these drugs offer benefits, they have led to a gradual increase in drug-related adverse reactions across various systems. As a result, the quest for safe and effective antiarrhythmic drugs is pressing. Recent years have seen some advancements in the treatment of ventricular arrhythmias using traditional Chinese medicine(TCM). The theory of Luobing in TCM has proposed a new drug intervention strategy of "fast and slow treatment, integrated regulation" leading to a shift in mindset from "antiarrhythmic" to "rhythm-regulating". Guided by this theory, the development of Shen Song Yang Xin Capsules (SSYX) has involved various Chinese medicinal ingredients that comprehensively regulate the myocardial electrophysiological mechanism, exerting antiarrhythmic effects on multiple ion channels and non-ion channels. Similarly, in clinical studies, evidence-based research has confirmed that SSYX combined with conventional antiarrhythmic drugs can more effectively reduce the occurrence of arrhythmias. Therefore, this article provides a comprehensive review of the composition and mechanisms of action, pharmacological components, network pharmacology analysis, and clinical applications of SSYX guided by the theory of Luobing, aiming to offer valuable insights for improved clinical management of arrhythmias and related research.

2.
Pathol Res Pract ; 262: 155572, 2024 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-39226804

RESUMO

Breast cancer, a pervasive and complex disease, continues to pose significant challenges in the field of oncology. Its heterogeneous nature and diverse molecular profiles necessitate a nuanced understanding of the underlying mechanisms driving tumorigenesis and progression. MicroRNA-21 (miR-21) has emerged as a crucial player in breast cancer development and progression by modulating apoptosis, a programmed cell death mechanism that eliminates aberrant cells. MiR-21 overexpression is a hallmark of breast cancer, and it is associated with poor prognosis and resistance to conventional therapies. This miRNA exerts its oncogenic effects by targeting various pro-apoptotic genes, including Fas ligand (FasL), programmed cell death protein 4 (PDCD4), and phosphatase and tensin homolog (PTEN). By suppressing these genes, miR-21 promotes breast cancer cell survival, proliferation, invasion, and metastasis. The identification of miR-21 as a critical regulator of apoptosis in breast cancer has opened new avenues for therapeutic intervention. This review investigates the intricate mechanisms through which miR-21 influences apoptosis, offering insights into the molecular pathways and signaling cascades involved. The dysregulation of apoptosis is a hallmark of cancer, and understanding the role of miR-21 in this context holds immense therapeutic potential. Additionally, the review highlights the clinical significance of miR-21 as a diagnostic and prognostic biomarker in breast cancer, underscoring its potential as a therapeutic target.

3.
J Colloid Interface Sci ; 678(Pt A): 920-936, 2024 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-39226833

RESUMO

Layered double hydroxide (LDH) material with abundant OH was successfully prepared by co-precipitation method, and a water purification system of Ni2Fe0.25Al0.75-LDH activated peroxymonosulfate (PMS) was constructed to rapidly degrade sulfamethoxazole (SMX) pollutants. The optimal conditions for the degradation of SMX in the system were as follows: 0.30 g/L Ni2Fe0.25Al0.75-LDH, 0.30 mM PMS, pH = 7 and 90 % SMX was removed in 10 min and almost completely in 40 min, which was consistent with the predicted results of response surface methodology (RSM) analysis. The abundant OH in Ni2Fe0.25Al0.75-LDH could form M(O)OSO3 complexes with PMS, accelerating the generation of reactive oxygen species (ROS) and promoting the removal of SMX. Quenching experiments and electron paramagnetic resonance (EPR) spectra showed that SO4-, OH, O2- and 1O2 also existed in the system. The surface-bound SO4- and O2- contributed greatly to the removal of SMX and the electron transfer between metals was also conducive to the production of active substances. The possible degradation pathways and intermediates of SMX were proposed. The toxicity assessment software tool (T.E.S.T) and total organic carbon (TOC) results indicated that the Ni2Fe0.25Al0.75-LDH/PMS system could reduce the overall environmental risk of SMX to some extent. This study provided a new strategy for the practical application of heterogeneous catalysts in sewage treatment.

4.
Artigo em Inglês | MEDLINE | ID: mdl-39227554

RESUMO

The mdx mouse phenotype, aggravated by chronic exercise on a treadmill, makes this murine model more reliable for the study of Duchenne muscular dystrophy (DMD) and allows the efficacy of therapeutic interventions to be evaluated. This study aims to investigate the effects of photobiomodulation by light-emitting diode (LED) therapy on functional, biochemical and morphological parameters in treadmill-trained adult mdx animals. Mdx mice were trained for 30 min of treadmill running at a speed of 12 m/min, twice a week for 4 weeks. The LED therapy (850 nm) was applied twice a week to the quadriceps muscle throughout the treadmill running period. LED therapy improved behavioral activity (open field) and muscle function (grip strength and four limb hanging test). Functional benefits correlated with reduced muscle damage; a decrease in the inflammatory process; modulation of the regenerative muscular process and calcium signalling pathways; and a decrease in oxidative stress markers. The striking finding of this work is that LED therapy leads to a shift from the M1 to M2 macrophage phenotype in the treadmill-trained mdx mice, enhancing tissue repair and mitigating the dystrophic features. Our data also imply that the beneficial effects of LED therapy in the dystrophic muscle correlate with the interplay between calcium, oxidative stress and inflammation signalling pathways. Together, these results suggest that photobiomodulation could be a potential adjuvant therapy for dystrophinopathies.

5.
Funct Integr Genomics ; 24(5): 152, 2024 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-39223429

RESUMO

In the complex landscape of cancer biology, the discovery of microproteins has triggered a paradigm shift, thereby, challenging the conventional conceptions of gene regulation. Though overlooked for years, these entities encoded by the small open reading frames (100-150 codons), have a significant impact on various cellular processes. As precision medicine pioneers delve deeper into the genome and proteome, microproteins have come into the limelight. Typically characterized by a single protein domain that directly binds to the target protein complex and regulates their assembly, these microproteins have been shown to play a key role in fundamental biological processes such as RNA processing, DNA repair, and metabolism regulation. Techniques for identification and characterization, such as ribosome profiling and proteogenomic approaches, have unraveled unique mechanisms by which these microproteins regulate cell signaling or pathological processes in most diseases including cancer. However, the functional relevance of these microproteins in cancer remains unclear. In this context, the current review aims to "rethink the essence of these genes" and explore "how these hidden players-microproteins orchestrate the signaling cascades of cancer, both as accelerators and brakes.".


Assuntos
Neoplasias , Humanos , Neoplasias/genética , Neoplasias/metabolismo , Transdução de Sinais , Fases de Leitura Aberta , Animais , Ribossomos/metabolismo , Ribossomos/genética , Micropeptídeos
6.
Curr Mol Pharmacol ; 2024 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-39225205

RESUMO

The main cause of cancer-related fatalities is cancer metastasis to other body parts, and increased glycolysis is crucial for cancer cells to maintain their elevated levels of growth and energy requirements, ultimately facilitating the invasion and spread of tumors. The Warburg effect plays a significant role in the advancement of cancer, and focusing on the suppression of aerobic glycolysis could offer a promising strategy for anti-cancer treatment. Various glycolysis processes are associated with tumor metastasis, primarily involving non-coding RNA (ncRNAs), signaling pathways, transcription factors, and more. Various categories of noncoding RNAs, including microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs), have shown promise in influencing glucose metabolism associated with the spread of tumors. Additionally, circular RNAs (circRNAs) and long non-coding RNAs (lncRNAs) predominantly act as competitive endogenous RNAs (ceRNAs) by sequestering microRNAs, thereby modulating the expression of target genes and exerting significant influence on the metabolic processes of cancerous cells. Furthermore, the process of tumor metastasis through glycolysis also encompasses various signaling pathways (such as PI3K/AKT, HIF, Wnt/ß- Catenin, and ERK, among others) and transcription factors. This article delineates the primary mechanisms through which non-coding RNAs, signaling pathways, and transcription factors contribute to glycolysis in tumor metastasis. It also investigates the potential use of these factors as prognostic markers and targets for cancer treatment. The manuscript also explores the innovative applications of specific traditional Chinese medicine and clinical Western medications in inhibiting tumor spread through glycolysis mechanisms, offering potential as new candidates for anti-cancer drugs.

7.
Alzheimers Dement ; 2024 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-39229896

RESUMO

INTRODUCTION: Dementia often involves comorbid Alzheimer's and vascular pathology, but their combined impact warrants additional study. METHODS: We analyzed the Systolic Blood Pressure Intervention Trial and categorized white matter hyperintensity (WMH) volume into highest versus lowest/mid tertile and the amyloid beta (Aß)42/40 ratio into lowest versus mid/highest ratio tertile. Using these binary variables, we created four exposure categories: (1) combined low risk, (2) Aß risk, (3) WMH risk, and (4) combined high risk. RESULTS: In the cohort of 467 participants (mean age 69.7 ± 7.1, 41.8% female, 31.9% nonwhite or Hispanic) during 4.8 years of follow-up and across the four exposure categories the rates of cognitive impairment were 5.3%, 7.8%, 11.8%, and 22.6%. Compared to the combined low-risk category, the adjusted hazard ratio for cognitive impairment was 4.12 (95% confidence interval, 1.71 to 9.94) in the combined high-risk category. DISCUSSION: This study emphasizes the potential impact of therapeutic approaches to dementia prevention that target both vascular and amyloid pathology. HIGHLIGHTS: White matter hyperintensity (WMH) and plasma amyloid (Aß42/40) are additive risk factors for the development of cognitive impairment in the SPRINT MIND trial. Individuals in the high-risk categories of both WMH and Aß42/40 had a near fivefold increase in risk of cognitive impairment during 4.8 years of follow-up on average. These findings suggest that treatment strategies targeting both vascular health and amyloid burden warrant further research.

8.
Future Oncol ; : 1-17, 2024 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-39229967

RESUMO

Aim: Little is known regarding uptake of epithelial ovarian cancer (EOC) treatments or patient burden in UK real-world practice.Methods: Cross-sectional surveys of patients with advanced EOC and healthcare professionals (HCPs).Results: 101 HCPs and 142 patients participated. Time from initial primary care consultation to diagnosis was ∼7 weeks. 83% patients were offered hereditary genetic testing, with 89% uptake. 53% HCPs reported surgery was performed ≤1 month in non-neoadjuvant setting. Surgery delay negatively impacted patient quality of life (61%), mental health (89%), and surgical outcomes (63%). 56% patients received active first-line maintenance treatment; patients on active surveillance had greater emotional/psychological distress.Conclusion: Treatment delays and low uptake of active first-line treatment should be addressed. Emotional support must be readily accessible throughout treatment.


What is this article about? New treatments for ovarian cancer mean that patients could be treated and live with the disease for many years. However, not much is known about the treatments that are actually received by patients with ovarian cancer in real-life. These surveys were done to learn more about the treatment and experience of patients with ovarian cancer in the UK.What were the results? 101 healthcare professionals (HCPs) and 142 patients took the surveys. The surveys found that patients usually waited about 7 weeks from their first GP visit to diagnosis of ovarian cancer. Half of HCPs reported that patients had surgery within 1 month of the decision that surgery was needed. HCPs reported that delays in surgery had a negative impact on patient quality of life, mental health, and the success of the surgery. After finishing their first line of chemotherapy, about half of patients had a maintenance treatment to control their ovarian cancer and give them as long as possible between recurrences. The remaining patients were not given treatment but were watched for further signs of cancer. Patients on maintenance treatment experienced less emotional/psychological distress than those managed by watchful waiting.What do the results of the study mean? This survey shows that more needs to be done to make sure that patients with ovarian cancer in the UK are diagnosed and treated quickly and offered the right treatment. Emotional support should be available to patients during their treatment.

9.
AAPS PharmSciTech ; 25(7): 207, 2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-39237748

RESUMO

Alzheimer's disease (AD), characterized by cognitive impairment, brain plaques, and tangles, is a global health concern affecting millions. It involves the build-up of amyloid-ß (Aß) and tau proteins, the formation of neuritic plaques and neurofibrillary tangles, cholinergic system dysfunction, genetic variations, and mitochondrial dysfunction. Various signaling pathways and metabolic processes are implicated in AD, along with numerous biomarkers used for diagnosis, risk assessment, and research. Despite these, there is no cure or effective treatment for AD. It is critically important to address this immediately to develop novel drug delivery systems (NDDS) capable of targeting the brain and delivering therapeutic agents to modulate the pathological processes of AD. This review summarizes AD, its pathogenesis, related signaling pathways, biomarkers, conventional treatments, the need for NDDS, and their application in AD treatment. It also covers preclinical, clinical, and ongoing trials, patents, and marketed AD formulations.


Assuntos
Doença de Alzheimer , Sistemas de Liberação de Medicamentos , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Humanos , Sistemas de Liberação de Medicamentos/métodos , Animais , Biomarcadores/metabolismo , Peptídeos beta-Amiloides/metabolismo , Encéfalo/metabolismo , Encéfalo/efeitos dos fármacos , Proteínas tau/metabolismo
10.
Exp Cell Res ; : 114236, 2024 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-39245198

RESUMO

Widespread changes in the expression of microRNAs in cancer result in abnormal gene expression for the miRNAs that control those genes, which in turn causes changes to entire molecular networks and pathways. The frequently altered miR-31, which is found in a wide range of cancers, is one cancer-related miRNA that is particularly intriguing. MiR-31 has a very complicated set of biological functions, and depending on the type of tumor, it may act both as a tumor suppressor and an oncogene. The endogenous expression levels of miR-31 appear to be a key determinant of the phenotype brought on by aberrant expression. Varied expression levels of miR-31 could affect cell growth, metastasis, drug resistance, and other process by several mechanisms like targeting BRCA1-associated protein-1 (BAP1), large tumor suppressor kinase 1 (LATS1) and protein phosphatase 2 (PP2A). This review highlights the current understanding of the genes that miR-31 targets while summarizing the complex expression patterns of miR-31 in human cancers and the diverse phenotypes brought on by altered miR-31 expression.

11.
J Pediatr (Rio J) ; 2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-39245235

RESUMO

OBJECTIVE: This study aims to evaluate the central auditory system of children and adolescents with cystic fibrosis through behavioral assessment of central auditory processing and electrophysiological tests to investigate short and long-latency auditory potentials, comparing them with the results obtained in the control group. METHODS: 117 from 7 to 21 years old patients were evaluated, 57 of them with cystic fibrosis and 60 of the control group, using behavioral evaluation of central auditory processing, auditory brainstem response and long latency auditory evoked potential. The comparison of the research groups was performed using ANOVA for Auditory Brain Response and P300 responses and Wilcoxon and Mann-Whitney tests for Central Auditory Processing responses. RESULTS: A statistically significant difference was found in the results of the GIN test between the groups and in the auditory brainstem response latency responses in waves I and V in the comparison between the groups with higher latencies in the study group. A difference was also found between latencies in the interpeak intervals I-III and III-V. The long latency auditory evoked potential analysis shows a statistically significant difference in the latency of the P300 potential, with higher latencies in the study group. CONCLUSION: Cystic fibrosis participants presented worse performance in the gaps-in-noise test compared to the control group in the evaluation of central auditory processing, which indicates impairment of temporal resolution auditory ability. They also showed increased latency in I and V waves of auditory brainstem response, as well as an increase P300 latency in long latency auditory evoked potential.

12.
Sci Total Environ ; : 176097, 2024 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-39245379

RESUMO

A novel near-zero-discharge recirculating aquaculture system was successfully set up and ran for six months or above. A uniquely designed and 3D printed poly (lactic acid) (PLA) structure was applied as carbon source. The system achieved over 50 % daily nitrogen removal capability and maintained a low NO3-N level of <0.5 mg/L. Steady water quality was observed throughout the experiment period. Microbial distribution was studied and top abundant microorganisms and their general functions in carbon and nitrogen utilization were discussed. Denitrification and L-glutamate formation were identified as two main nitrogen pathways. The cooccurrence network connecting various genera and multiple functions was revealed. Subtilisin was one important PLA degrading enzymes in the system.

13.
Phytother Res ; 2024 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-39246209

RESUMO

SARS-CoV-2 infection causes disruptions in inflammatory pathways, which fundamentally contribute to COVID-19 pathophysiology. The present review critically evaluates the gaps in scientific literature and presents the current status regarding the inflammatory signaling pathways in COVID-19. We propose that phytoconstituents can be used to treat COVID-19 associated inflammation, several already formulated in traditional medications. For this purpose, extensive literature analysis was conducted in the PubMed database to collect relevant in vitro, in vivo, and human patient studies where inflammation pathways were shown to be upregulated in COVID-19. Parallelly, scientific literature was screened for phytoconstituents with known cellular mechanisms implicated for inflammation or COVID-19 associated inflammation. Studies with insufficient evidence on cellular pathways for autophagy and mitophagy were considered out of scope and excluded from the study. The final analysis was visualized in figures and evaluated for accuracy. Our findings demonstrate the frequent participation of NF-κB, a transcription factor, in inflammatory signaling pathways linked to COVID-19. Moreover, the MAPK signaling pathway is also implicated in producing inflammatory molecules. Furthermore, it was also analyzed that the phytoconstituents with flavonoid and phenolic backbones could inhibit either the TLR4 receptor or its consecutive signaling molecules, thereby, decreasing NF-κB activity and suppressing cytokine production. Although, allopathy has treated the early phase of COVID-19, anti-inflammatory phytoconstituents and existing ayurvedic formulations may act on the COVID-19 associated inflammatory pathways and provide an additional treatment strategy. Therefore, we recommend the usage of flavonoids and phenolic phytoconstituents for the treatment of inflammation associated with COVID-19 infection and similar viral ailments.

14.
Front Pharmacol ; 15: 1414790, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39246660

RESUMO

Cancer prevention is currently envisioned as a molecular-based approach to prevent carcinogenesis in pre-cancerous stages, i.e., dysplasia and carcinoma in situ. Cancer is the second-leading cause of mortality worldwide, and a more than 61% increase is expected by 2040. A detailed exploration of cancer progression pathways, including the NF-kß signaling pathway, Wnt-B catenin signaling pathway, JAK-STAT pathway, TNF-α-mediated pathway, MAPK/mTOR pathway, and apoptotic and angiogenic pathways and effector molecules involved in cancer development, has been discussed in the manuscript. Critical evaluation of these effector molecules through molecular approaches using phytomolecules can intersect cancer formation and its metastasis. Manipulation of effector molecules like NF-kß, SOCS, ß-catenin, BAX, BAK, VEGF, STAT, Bcl2, p53, caspases, and CDKs has played an important role in inhibiting tumor growth and its spread. Plant-derived secondary metabolites obtained from natural sources have been extensively studied for their cancer-preventing potential in the last few decades. Eugenol, anethole, capsaicin, sanguinarine, EGCG, 6-gingerol, and resveratrol are some examples of such interesting lead molecules and are mentioned in the manuscript. This work is an attempt to put forward a comprehensive approach to understanding cancer progression pathways and their management using effector herbal molecules. The role of different plant metabolites and their chronic toxicity profiling in modulating cancer development pathways has also been highlighted.

15.
Acta Trop ; 259: 107365, 2024 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-39218379

RESUMO

The fungus Malassezia globosa is often responsible for superficial mycoses posing significant treatment challenges because of the unfavourable side effects of available antifungal drugs. To reduce potential hazards to the host and overcome these hurdles, new therapeutic medicines must be developed that selectively target enzymes unique to the pathogen. This study focuses on the enzyme anthranilate phosphoribosyltransferase (AnPRT), which is vital to M. globosa's tryptophan production pathway. To learn more about the function of the AnPRT enzyme, we modeled, validated, and simulated its structure. Moreover, many bioactive components were found in different extracts from the plant Albizia amara after phytochemical screening. Interestingly, at doses ranging from 500 to 2000 µg/ml, the chloroform extract showed significant antifungal activity, with inhibition zones measured between 11.0 ± 0.0 and 25.6 ± 0.6 mm. According to molecular docking analyses, the compounds from the active extract, particularly 2-tert-Butyl-4-isopropyl-5-methylphenol, interacted with the AnPRT enzyme's critical residues, ARG 205 and PHE 214, with an effective binding energy of -4.9 kcal/mol. The extract's revealed component satisfies the requirements for drug-likeness and shows promise as a strong antifungal agent against infections caused by M. globosa. These findings imply that using plant-derived chemicals to target the AnPRT enzyme is a viable path for the creation of innovative antifungal treatments.

16.
Compr Rev Food Sci Food Saf ; 23(5): e13420, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39217506

RESUMO

Flavor is a major sensory attribute affecting consumers' preference for cheese products. Differences in cheesemaking change the cheese microenvironment, thereby affecting cheese flavor profiles. A framework for tuning cheese flavor is proposed in this study, which depicts the full picture of flavor development and modulation, from manufacturing and ripening factors through the main biochemical pathways to flavor compounds and flavor notes. Taking semi-hard and hard cheeses as examples, this review describes how cheese flavor profiles are affected by milk type and applied treatment, fat and salt content, microbiota composition and microbial interactions, ripening time, temperature, and environmental humidity, together with packaging method and material. Moreover, these factors are linked to flavor profiles through their effects on proteolysis, the further catabolism of amino acids, and lipolysis. Acids, alcohols, ketones, esters, aldehydes, lactones, and sulfur compounds are key volatiles, which elicit fruity, sweet, rancid, green, creamy, pungent, alcoholic, nutty, fatty, and sweaty flavor notes, contributing to the overall flavor profiles. Additionally, this review demonstrates how data-driven modeling techniques can link these influencing factors to resulting flavor profiles. This is done by providing a comprehensive review on the (i) identification of key factors and flavor compounds, (ii) discrimination of cheeses, and (iii) prediction of flavor notes. Overall, this review provides knowledge tools for cheese flavor modulation and sheds light on using data-driven modeling techniques to aid cheese flavor analysis and flavor prediction.


Assuntos
Queijo , Paladar , Queijo/análise , Queijo/microbiologia , Manipulação de Alimentos/métodos , Animais , Leite/química , Humanos
17.
Biochem Biophys Res Commun ; 734: 150593, 2024 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-39217812

RESUMO

Asthma is a complex inflammatory airway disease that arises from the interplay between genetic predisposition and environmental influences. Leucine-rich repeat kinase 2 (LRRK2), a gene commonly associated with Parkinson's disease, has recently gained attention for its role in immune regulation and inflammation beyond the brain. However, its involvement in asthma has not yet been reported. In this study, we used LRRK2 G2019S transgenic mice and LRRK2 knockout mice to establish asthmatic models to explore LRRK2 impact on asthma. We found that LRRK2 G2019S transgenic mice showed exacerbated airway hyperresponsiveness (AHR) and airway inflammation in asthma mouse models induced by house dust mite. RNA sequencing data unveiled that the LRRK2 G2019S mutation enhanced immune response pathways, including NOD-like receptor, cellular response to interferon ß and activation of innate immune response signaling. Conversely, LRRK2 deficiency attenuated AHR and airway inflammation in the same asthma models. Our study offers new insights into the role of LRRK2 in allergic inflammation and highlights its potential as a therapeutic target for asthma.

18.
Artigo em Inglês | MEDLINE | ID: mdl-39218845

RESUMO

Precipitation extremes have surged in frequency and duration in recent decades, significantly impacting various sectors, including agriculture, water resources, energy, and public health worldwide. Pakistan, being highly susceptible to climate change and extremes, has experienced adverse events in recent times, emphasizing the need for a comprehensive investigation into the relationship between precipitation extremes and crops production. This study focuses on assessing the association between precipitation extremes on crops production, with a particular emphasis on the Punjab province, a crucial region for the country's food production. The initial phase of the study involved exploring the associations between precipitation extremes and crops production for the duration of 1980-2014. Notably, certain precipitation extremes, such as maximum CDDs (consecutive dry days), R99p (extreme precipitation events), PRCPTOT (precipitation total) and SDII (simple daily intensity index) exhibited strong correlations with the production of key crops like wheat, rice, garlic, dates, moong, and masoor. In the subsequent step, four machine learning (ML) algorithms were trained and tested using observed daily climate data (including maximum and minimum temperatures and precipitation) alongside model reference data (1985-2014) as predictors. Gradient boosting machine (GBM) was selected for its superior performance and employed to project precipitation extremes for three distinct future periods (F1: 2025-2049, F2: 2050-2074, F3: 2075-2099) under the SSP2-4.5 and SSP5-8.5 derived from the CMIP6 (Coupled Model Intercomparison Project Phase 6) archive. The projection results indicated an increasing and decreasing trend in CWDs (maximum consecutive wet days) and CDDs, respectively, at various meteorological stations. Furthermore, R10mm (the number of days with precipitation equal to or exceeding 10 mm) and R25mm displayed an overall increasing trend at most of the stations, though some exhibited a decreasing trend. These trends in precipitation extremes have potential consequences, including the risk of flash floods and damage to agriculture and infrastructure. However, the study emphasizes that with proper planning, adaptation measures, and mitigation strategies, the potential losses and damages can be significantly minimized in the future.

19.
Ann Med Surg (Lond) ; 86(9): 5252-5255, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39239020

RESUMO

Sickle cell anemia (SCA) is a genetically inherited hemoglobinopathy characterized by the abnormal morphology of red blood cells, resulting in vaso-occlusive events and diverse clinical complications. Recent investigations have unveiled a novel dimension in understanding SCA severity through the lens of eosinophilic dialogues. This review article synthesizes current knowledge on the molecular intricacies of eosinophils in the context of SCA, exploring their biology, molecular markers, and interactions with other cellular components. Eosinophil-mediated inflammation and oxidative stress are dissected to elucidate their impact on the disease course. Furthermore, the review evaluates potential therapeutic interventions and outlines future directions in this burgeoning field. The term "Eosinophilic Dialogues" encapsulates the multifaceted molecular exchanges that influence SCA severity, presenting a promising avenue for targeted interventions and improved clinical outcomes. This review serves as a comprehensive resource for researchers, clinicians, and healthcare practitioners engaged in unraveling the complex pathophysiology of SCA and exploring novel therapeutic avenues.

20.
Int J Med Sci ; 21(11): 2189-2200, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39239553

RESUMO

In the realm of this study, obtaining a comprehensive understanding of ischemic brain injury and its molecular foundations is of paramount importance. Our study delved into single-cell data analysis, with a specific focus on sub-celltypes and differentially expressed genes in the aftermath of ischemic injury. Notably, we observed a significant enrichment of the "ATP METABOLIC PROCESS" and "ATP HYDROLYSIS ACTIVITY" pathways, featuring pivotal genes such as Pbx3, Dguok, and Kif21b. A remarkable finding was the consistent upregulation of genes like Fabp7 and Bcl11a within the MCAO group, highlighting their crucial roles in regulating the pathway of mitochondrial ATP synthesis coupled proton transport. Furthermore, our network analysis unveiled pathways like "Neuron differentiation" and "T cell differentiation" as central in the regulatory processes of sub-celltypes. These findings provide valuable insights into the intricate molecular responses and regulatory mechanisms that govern brain injury. The shared differentially expressed genes among sub-celltypes emphasize their significance in orchestrating responses post-ischemic injury. Our research, viewed from the perspective of a medical researcher, contributes to the evolving understanding of the molecular landscape underlying ischemic brain injury, potentially paving the way for targeted therapeutic strategies and improved patient outcomes.


Assuntos
Trifosfato de Adenosina , Infarto da Artéria Cerebral Média , Cinesinas , Mitocôndrias , Células Precursoras de Oligodendrócitos , Transdução de Sinais , Animais , Transdução de Sinais/genética , Infarto da Artéria Cerebral Média/patologia , Infarto da Artéria Cerebral Média/metabolismo , Mitocôndrias/metabolismo , Trifosfato de Adenosina/metabolismo , Trifosfato de Adenosina/biossíntese , Cinesinas/genética , Cinesinas/metabolismo , Células Precursoras de Oligodendrócitos/metabolismo , Humanos , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Masculino , Isquemia Encefálica/genética , Isquemia Encefálica/metabolismo , Isquemia Encefálica/patologia , Ratos , Proteínas Proto-Oncogênicas
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA