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1.
Am J Physiol Cell Physiol ; 326(2): C513-C528, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38105758

RESUMO

Pathological alterations in the biomechanical properties of the Schlemm's canal (SC) inner wall endothelium and its immediate vicinity are strongly associated with ocular hypertension in glaucoma due to decreased outflow facility. Specifically, the underlying trabecular meshwork is substantially stiffer in glaucomatous eyes compared with that from normal eyes. This raises the possibility of a critical involvement of mechanotransduction processes in driving SC cell dysfunction. Yes-associated protein (YAP) has emerged as a key contributor to glaucoma pathogenesis. However, the molecular underpinnings of SC cell mechanosignaling via YAP and transcriptional coactivator with PDZ-binding motif (TAZ) in response to glaucomatous extracellular matrix (ECM) stiffening are not well understood. Using a novel biopolymer hydrogel that facilitates dynamic and reversible stiffness tuning, we investigated how ECM stiffening modulates YAP/TAZ activity in primary human SC cells, and whether disruption of YAP/TAZ mechanosignaling attenuates SC cell pathobiology and increases ex vivo outflow facility. We demonstrated that ECM stiffening drives pathologic YAP/TAZ activation and cytoskeletal reorganization in SC cells, which was fully reversible by matrix softening in a distinct time-dependent manner. Furthermore, we showed that pharmacologic or genetic disruption of YAP/TAZ mechanosignaling abrogates stiffness-induced SC cell dysfunction involving altered cytoskeletal and ECM remodeling. Finally, we found that perfusion of the clinically used, small molecule YAP/TAZ inhibitor verteporfin (without light activation) increases ex vivo outflow facility in normal mouse eyes. Collectively, our data provide new evidence for a pathologic role of aberrant YAP/TAZ mechanosignaling in SC cell dysfunction and suggest that YAP/TAZ inhibition has therapeutic value for treating ocular hypertension in glaucoma.NEW & NOTEWORTHY Pathologically altered biomechanical properties of the Schlemm's canal (SC) inner wall microenvironment were recently validated as the cause for increased outflow resistance in ocular hypertensive glaucoma. However, the involvement of specific mechanotransduction pathways in these disease processes is largely unclear. Here, we demonstrate that Yes-associated protein (YAP)/transcriptional coactivator with PDZ-binding motif (TAZ) are central regulators of glaucoma-like SC cell dysfunction in response to extracellular matrix stiffening and that targeted disruption of YAP/TAZ mechanosignaling attenuates SC cell pathobiology and enhances outflow function.


Assuntos
Glaucoma , Proteínas de Sinalização YAP , Animais , Humanos , Camundongos , Mecanotransdução Celular , Canal de Schlemm , Transativadores , Fatores de Transcrição , Proteínas com Motivo de Ligação a PDZ com Coativador Transcricional
2.
J Immunol ; 208(8): 1998-2007, 2022 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-35338093

RESUMO

Optimal transcriptional programming needed for CD4 T cells to protect against influenza A virus (IAV) is unclear. Most IAV-primed CD4 T cells fit Th1 criteria. However, cells deficient for the Th1 "master regulator," T-bet, although marked by reduced Th1 identity, retain robust protective capacity. In this study, we show that T-bet's paralog, Eomesodermin (Eomes), is largely redundant in the presence of T-bet but is essential for the residual Th1 attributes of T-bet-deficient cells. Cells lacking both T-bet and Eomes instead develop concurrent Th17 and Th2 responses driven by specific inflammatory signals in the infected lung. Furthermore, the transfer of T-bet- and Eomes-deficient Th17, but not Th2, effector cells protects mice from lethal IAV infection. Importantly, these polyfunctional Th17 effectors do not display functional plasticity in vivo promoting gain of Th1 attributes seen in wild-type Th17 cells, which has clouded evaluation of the protective nature of Th17 programming in many studies. Finally, we show that primary and heterosubtypic IAV challenge is efficiently cleared in T-bet- and Eomes double-deficient mice without enhanced morbidity despite a strongly Th17-biased inflammatory response. Our studies thus demonstrate unexpectedly potent antiviral capacity of unadulterated Th17 responses against IAV, with important implications for vaccine design.


Assuntos
Vírus da Influenza A , Vacinas contra Influenza , Influenza Humana , Animais , Linfócitos T CD4-Positivos , Humanos , Camundongos , Camundongos Knockout , Proteínas com Domínio T/genética , Células Th1 , Células Th17 , Células Th2
3.
Eur J Pediatr ; 183(4): 1475-1483, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38206398

RESUMO

Vitamin D deficiency is associated with obesity and its associated metabolic disorders, as specified in many epidemiological studies. The assertion that vitamin D can mitigate insulin insensitivity in obese children and adolescents lacks adequate empirical substantiation. Thus, the study utilized some clinical trials on vitamin D interventions to examine the impact of vitamin D supplementation on insulin resistance in obese children and adolescents. The literature was extracted by applying the PRISMA method through electronic databases such as Scopus, Science Direct, Medline, the Cochrane Library, and PubMed from 2012 to 2022. All the articles were in English, and the inclusion criteria for each article were based on the study design and the anthropometric and biochemical parameters of the subjects. A total of 572 research articles were acquired, out of which only seven closely adhered to the inclusion criteria of the study. The studies in this systematic review are based on randomized control trials. The age range of the children in this study spans from 2 to 19 years, and the follow-up period ranges from 3 to 12 months. The range of daily vitamin D doses provided varied from 2000 to 10,000 IU. The results indicate that four randomized controlled trials have demonstrated a positive impact on glycemic parameters, such as insulin levels, fasting blood sugar, and insulin resistance, in the subjects following vitamin D treatment. However, the three trials did not provide sufficient evidence to support a statistically significant effect. CONCLUSION: The present review highlights that a significant proportion of the studies incorporated in the analysis demonstrate that the administration of vitamin D may be a preventive measure in ameliorating insulin resistance among pediatric patients with obesity, but it is advisable to implement a prolonged intervention with a substantial sample size and perform micro-level analysis at the gene level to evaluate the impact of vitamin D treatment. WHAT IS KNOWN: • Childhood obesity and its associated metabolic disorder is a concerned global problem. • Several studies showed an association of vitamin D deficiency with adiposity- induced metabolicdisorders which are still controversial. This study focused on finding interlink between vitamin Dsupplementation with obesity induced insulin resistance in children and adolescents. WHAT IS NEW: • This study supports that high dosage of Vitamin D in long term may be protective against insulinresistance in obese paediatric individuals. • A new factor is also reported in the study that vitamin D may alter the composition of gut microbiotawhich represents a compelling approach to the therapeutic management of obesity and diabetes.


Assuntos
Intolerância à Glucose , Resistência à Insulina , Insulinas , Obesidade Infantil , Deficiência de Vitamina D , Adolescente , Criança , Humanos , Lactente , Intolerância à Glucose/complicações , Obesidade Infantil/complicações , Vitamina D , Deficiência de Vitamina D/complicações , Deficiência de Vitamina D/tratamento farmacológico , Vitaminas/uso terapêutico
4.
Int J Biometeorol ; 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38720050

RESUMO

Animal geneticists and breeders have the impending challenge of enhancing the resilience of Indian livestock to heat stress through better selection strategies. Climate change's impact on livestock is more intense in tropical countries like India where dairy cattle crossbreeds are more sensitive to heat stress. The main reason for this study was to find the missing relative changes in transcript levels in thermo-neutral and heat stress conditions in crossbred cattle through whole-transcriptome analysis of RNA-Seq data. Differentially expressed genes (DEGs) identified based on the minimum log twofold change value and false discovery rate 0.05 revealed 468 up-regulated genes and 2273 down-regulated significant genes. Functional annotation and pathway analysis of these significant DEGs were compared based on Gene Ontology (Biological process), Kyoto Encyclopedia of Genes and Genome (KEGG), and Reactome pathways using g: Profiler, ShinyGO v0.76, and iDEP.951 web tools. On finding network visualization, the most over-represented and correlated pathways were neuronal and sensory organ development, calcium signalling pathway, Mitogen-activated protein kinase (MAPK) and Smad signalling pathway, Ras-proximate-1, or Ras-related protein 1 (Rap 1) signalling pathway, apoptosis, and oxidative stress. Similarly, down-regulated genes were most expressed in mRNA processing, immune system, B-cell receptor signalling pathway, Nucleotide oligomerization domain (NOD)-like receptors (NLRs) signalling pathway and nonsense-mediated decay (NMD) pathway. The heat stress-responsive genes identified in this study will facilitate our understanding of the molecular basis for climate resilience and heat tolerance in Indian dairy crossbreeds.

5.
Perfusion ; : 2676591231223076, 2023 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-38112186

RESUMO

INTRODUCTION: The number of applications for cardiothoracic surgery has been steadily dropping over the past decades. We aim to assess whether a 1-day cardiothoracic surgical skills conference could increase interest into the speciality. METHODS: Participants included in the study had to be medical students or junior doctors. Out of 57 delegates that attended the conference, 52 were enrolled in the study, and completed the pre-conference and post-conference questionnaires. Three introductory lectures were delivered by consultants in cardiothoracic surgery or cardiology in the morning, followed by three practical surgical workshops. We assessed demographics, confidence in and knowledge of procedures, and the change in participants' interest in the speciality pre- and post-conference. This study was conducted at St George's University of London. RESULTS: The interest to pursue a career in cardiothoracic surgery increased by 23% post-conference (p = .035). Confidence and knowledge in all procedures taught improved significantly after the conference (p < .05), with the highest increase seen in anastomosis of vessels (p < .0001). Preclinical students made up 57.7% of participants, majority of whom had not seen more than three surgical procedures. CONCLUSION: Our conference has shown to increase interest in cardiothoracic surgery and improve exposure to surgical skills, especially to those in early years of medical school. The surgical workshops improved student confidence and knowledge in procedures used within the field and the use of animal tissue improved participant experience. Further research is needed at other medical schools to assess whether a change in surgical skills teaching should be made to medical school curriculums.

6.
Toxicol Mech Methods ; 33(3): 222-232, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36042574

RESUMO

The Health and environmental hazards of benzene and nitrobenzene (NB) derivatives have remained a topic of interest of researchers. In silico methods for prediction of toxicity of chemicals have proved their worth in accurate forecast of environmental as well as health toxicity and are strongly recommended by regulatory authorities. Two quantitative structure-toxicity relationship (QSTR) models explaining Scenedesmus obliquus toxicity trends among 39 benzene derivatives and Tetrahymena pyriformis toxicity of 103 NB and 392 benzene derivatives are developed using semiempirical quantum chemical parameters. The best constructed QSTR models have good fitting ability (R2 = 0.8053, 0.7591, and 0.8283) and robustness (Q2LOO = 0.7507, 0.7227, and 0.8194; Q2LMO = 0.7338, 0.7153, and 0.8172). The external predictivity of all the models are quite good (R2EXT = 0.8256, 0.9349, and 0.8698). Electronegativity, Cosmo volume, total energy, and molecular weight are responsible for the increase and decrease of toxicity of benzene derivatives against S. obliquus while electronegativity, electrophilicity index, the heat of formation, total energy, hydrophobicity, and cosmo volume are responsible for modulation of toxicity of NB and benzene derivatives toward T. pyriformis. These models fulfill the requirements of all the five OECD principles.


Assuntos
Derivados de Benzeno , Tetrahymena pyriformis , Derivados de Benzeno/química , Derivados de Benzeno/toxicidade , Relação Quantitativa Estrutura-Atividade , Nitrobenzenos
7.
Exp Eye Res ; 220: 109102, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35525298

RESUMO

In glaucoma, astrocytes within the optic nerve head (ONH) rearrange their actin cytoskeleton, while becoming reactive and upregulating intermediate filament glial fibrillary acidic protein (GFAP). Increased transforming growth factor beta 2 (TGF ß2) levels have been implicated in glaucomatous ONH dysfunction. A key limitation of using conventional 2D culture to study ONH astrocyte behavior is the inability to faithfully replicate the in vivo ONH microenvironment. Here, we engineer a 3D ONH astrocyte hydrogel to better mimic in vivo mouse ONH astrocyte (MONHA) morphology, and test induction of MONHA reactivity using TGF ß2. Primary MONHAs were isolated from C57BL/6J mice and cell purity confirmed. To engineer 3D cell-laden hydrogels, MONHAs were mixed with photoactive extracellular matrix components (collagen type I, hyaluronic acid) and crosslinked for 5 minutes using a photoinitiator (0.025% riboflavin) and UV light (405-500 nm, 10.3 mW/cm2). MONHA-encapsulated hydrogels were cultured for 3 weeks, and then treated with TGF ß2 (2.5, 5.0 or 10 ng/ml) for 7 days to assess for reactivity. Following encapsulation, MONHAs retained high cell viability in hydrogels and continued to proliferate over 4 weeks as determined by live/dead staining and MTS assays. Sholl analysis demonstrated that MONHAs within hydrogels developed increasing process complexity with increasing process length over time. Cell processes connected with neighboring cells, coinciding with Connexin43 expression within astrocytic processes. Treatment with TGF ß2 induced reactivity in MONHA-encapsulated hydrogels as determined by altered F-actin cytoskeletal morphology, increased GFAP expression, and elevated fibronectin and collagen IV deposition. Our data sets the stage for future use of this 3D biomimetic ONH astrocyte-encapsulated hydrogel to investigate astrocyte behavior in response to injury.


Assuntos
Glaucoma , Disco Óptico , Animais , Astrócitos/metabolismo , Células Cultivadas , Hidrogéis , Camundongos , Camundongos Endogâmicos C57BL , Fator de Crescimento Transformador beta2/metabolismo
8.
J Immunol ; 204(12): 3307-3314, 2020 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-32376651

RESUMO

IL-2 is a pleotropic cytokine with potent pro- and anti-inflammatory effects. These divergent impacts can be directed in vivo by forming complexes of IL-2 and anti-IL-2 mAbs (IL-2C) to target IL-2 to distinct subsets of cells based on their expression of subunits of the IL-2R. In this study, we show that treatment of mice with a prototypical anti-inflammatory IL-2C, JES6-1-IL-2C, best known to induce CD25+ regulatory CD4 T cell expansion, surprisingly causes robust induction of a suite of inflammatory factors. However, treating mice infected with influenza A virus with this IL-2C reduces lung immunopathology. We compare the spectrum of inflammatory proteins upregulated by pro- and anti-inflammatory IL-2C treatment and uncover a pattern of expression that reveals potentially beneficial versus detrimental aspects of the influenza-associated cytokine storm. Moreover, we show that anti-inflammatory IL-2C can deliver survival signals to CD4 T cells responding to influenza A virus that improve their memory fitness, indicating a novel application of IL-2 to boost pathogen-specific T cell memory while simultaneously reducing immunopathology.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Memória Imunológica/imunologia , Vírus da Influenza A/imunologia , Subunidade alfa de Receptor de Interleucina-2/imunologia , Interleucina-2/imunologia , Infecções por Orthomyxoviridae/imunologia , Animais , Anticorpos Monoclonais/imunologia , Citocinas/imunologia , Feminino , Inflamação/imunologia , Inflamação/virologia , Pulmão/imunologia , Pulmão/virologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Linfócitos T Reguladores/imunologia , Regulação para Cima/imunologia
9.
Environ Res ; 215(Pt 2): 114338, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36116499

RESUMO

The tannery industry generates a consequential threat to the environment by producing a large amount of potentially toxic metal-containing waste. Bioremediation has been a promising approach for treating potentially toxic metals, but the efficiency of remediation in microbes is one of the factors limiting their application in tanneries waste treatment. The motivation behind the present work was to explore the microbial diversity and chromate reductase genes present in the tannery effluent-contaminated soil using metagenomics approach. The use of shotgun sequencing enabled the identification of operational parameters that influence microbiome composition and their ability to reduce Chromium (Cr) concentration. The Cr concentration in Kanpur tannery effluent contaminated soil sample was 700 ppm which is many folds than the approved permissible limit by World Health Organisation (WHO) for Cr is 100 ppm. Metagenomic Deoxyribo Nucleic Acid (DNA) was extracted to explore taxonomic community structure, phylogenetic linkages, and functional profile. With a Guanine-Cytosine (GC) abundance of 54%, total of 45,163,604 high-quality filtered reads were obtained. Bacteria (83%), Archaebacteria (14%), and Viruses (3%) were discovered in the structural biodiversity. Bacteria were classified to phylum level, with Proteobacteria (52%) being the dominant population, followed by Bacteriodetes (15%), Chloroflexi (15%), Spirochaetes (7%), Thermotogae (5%), Actinobacteria (4%), and Firmicutes (1%). The OXR genes were cloned and checked for their efficiency to reduce Cr concentration. Insitu validation of OXR8 gene showed a reduction of Cr concentration from 700 ppm to 24 ppm in 72 h (96.51% reduction). The results of this study suggests that there is a huge reservoir of microbes and chromate reductase genes which are unexplored yet.


Assuntos
Ácidos Nucleicos , Poluentes do Solo , Bactérias/genética , Biodegradação Ambiental , Bioprospecção , Cromo/análise , Citosina , DNA , Guanina , Oxirredutases , Filogenia , Solo/química , Poluentes do Solo/análise , Poluentes do Solo/toxicidade
10.
AJR Am J Roentgenol ; 207(2): 241-7, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27164302

RESUMO

OBJECTIVE: Paramedics and hospital-based providers occasionally need to place intraosseous devices to obtain vascular access in critically ill patients. Diagnostic radiologists must be prepared for the emergent administration of iodinated contrast media via the intraosseous route, and interventional radiologists should be familiar with the potential clinical uses of such access. CONCLUSION: We present a protocol for the administration of iodinated contrast media through the intraosseous route. We also highlight the clinical and radiologic aspects of intraosseous access.


Assuntos
Administração Intravenosa/métodos , Cateterismo Venoso Central/métodos , Meios de Contraste/administração & dosagem , Infusões Intraósseas/métodos , Radiologia Intervencionista , Ressuscitação/métodos , Administração Intravenosa/instrumentação , Cateterismo Venoso Central/instrumentação , Serviços Médicos de Emergência , Desenho de Equipamento , Humanos , Infusões Intraósseas/instrumentação , Ressuscitação/instrumentação , Estados Unidos
11.
Catheter Cardiovasc Interv ; 85(6): 1092-6, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25533813

RESUMO

Left ventricular pseudoaneurysm (LVPA) is a rare yet serious complication that may follow cardiac surgery, myocardial infarction, trauma, or infection. If left untreated, reported rates of rupture and sudden cardiac death are high. Although surgical intervention has traditionally been the standard treatment for LVPA, percutaneous closure is now an attractive alternative in the high-risk patient. We report a case of a successful percutaneous LVPA closure using direct chest wall entry into the pseudoaneurysm. This novel approach can be useful when access to the LVPA is a challenge, especially in the setting of small ostial size, dense left ventricular trabeculations, angulated serpiginous tract, and presence of mechanical prostheses.


Assuntos
Falso Aneurisma/terapia , Cateterismo Cardíaco/métodos , Aneurisma Cardíaco/terapia , Imageamento Tridimensional , Infarto do Miocárdio/complicações , Idoso de 80 Anos ou mais , Falso Aneurisma/diagnóstico por imagem , Falso Aneurisma/etiologia , Ecocardiografia/métodos , Ecocardiografia Transesofagiana/métodos , Eletrocardiografia/métodos , Procedimentos Endovasculares/métodos , Seguimentos , Aneurisma Cardíaco/diagnóstico por imagem , Aneurisma Cardíaco/etiologia , Ventrículos do Coração/diagnóstico por imagem , Humanos , Masculino , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/terapia , Dispositivo para Oclusão Septal , Resultado do Tratamento
12.
Skeletal Radiol ; 44(12): 1839-43, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26253133

RESUMO

Aggregomas are rare localized masses of monoclonal nonamyloid immunoglobulin light-chain deposits. To date, there have been only a few reports of isolated aggregomas, with the majority detailing renal, lymph node and brain deposition. We present a rare case of paraspinal aggregoma in a 67-year-old female who presented with a complaint of cough and chest pain. Imaging demonstrated a left-sided paravertebral mass extending from T7-T10. Pathological analysis showed lamellar deposition of extracellular eosinophilic material with an associated lymphoplasmacytic nonamyloid infiltrate. To our knowledge, this is the first report of a paraspinal aggregoma. While exceedingly rare, this tumor can be included in the radiologic differential diagnosis of paravertebral soft tissue tumors in adults. The observation of our case adds to the limited understanding of the etiology, pathogenesis, natural history, and treatment of nonamyloid light-chain depositions.


Assuntos
Cadeias Leves de Imunoglobulina/sangue , Paraproteinemias/sangue , Paraproteinemias/diagnóstico , Neoplasias da Coluna Vertebral/sangue , Neoplasias da Coluna Vertebral/diagnóstico , Idoso , Feminino , Humanos , Neoplasias da Coluna Vertebral/cirurgia , Neoplasias Torácicas/sangue , Neoplasias Torácicas/cirurgia , Resultado do Tratamento
13.
Chem Biol Drug Des ; 103(1): e14384, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37919259

RESUMO

Breast cancer is a common and deadly disease, so there is a constant need for research to find efficient targets and therapeutic approaches. Breast cancer can be classified on a molecular and histological base. Breast cancer can be divided into ER (estrogen receptor)-positive and ER-negative, HER2 (human epidermal growth factor receptor2)-positive and HER2-negative subtypes based on the presence of specific biomarkers. Targeting hormone receptors, such as the HER2, progesterone receptor (PR), and ER, is very significant and plays a vital role in the onset and progression of breast cancer. Endocrine treatments and HER2-targeted drugs are examples of targeted therapies now being used against these receptors. Emerging immune-based medicines with promising outcomes in the treatment of breast cancer include immune checkpoint inhibitors, cancer vaccines, and adoptive T-cell therapy. It is also explored how immune cells and the tumor microenvironment affect breast cancer development and treatment response. The major biochemical pathways, signaling cascades, and DNA repair mechanisms that are involved in the development and progression of breast cancer, include the PI3K/AKT/mTOR system, the MAPK pathway, and others. These pathways are intended to be inhibited by a variety of targeted drugs, which are then delivered with the goal of restoring normal cellular function. This review aims to shed light on types of breast cancer with the summarization of different therapeutic approaches which can target different pathways for tailored medicines and better patient outcomes.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Fosfatidilinositol 3-Quinases/metabolismo , Receptores de Estrogênio/metabolismo , Transdução de Sinais , Receptores de Progesterona/genética , Receptores de Progesterona/metabolismo , Receptores de Progesterona/uso terapêutico , Receptor ErbB-2/metabolismo , Microambiente Tumoral
14.
Cureus ; 16(5): e61182, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38933609

RESUMO

A smooth, red, oval, or rhomboid patch on the dorsal midline is the classic presentation of median rhomboid glossitis (MRG), a rare and benign lesion of the tongue. MRG is still not fully understood, which presents diagnostic hurdles and calls for additional clinical investigation. It is frequently associated with candidal infections. We describe a case of a 42-year-old man who initially appeared to have either mechanical irritation or thermal injury related to a painless patch on the dorsum surface of the tongue. We document a case of MRG that was consulted for a standard dental examination in this case report. This article also highlights a dentist's need to identify the lesion and provide appropriate education for the patient.

15.
3 Biotech ; 14(7): 177, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38855148

RESUMO

Heat stress significantly disturbs the production, reproduction, and systems biology of dairy cattle. A complex interaction among biological systems helps to combat and overcome heat stress. Indicine cattle breed Tharparkar has been well known for its thermal adaptability. Therefore, present investigation considered RNA-seq technology to explore the functional transcriptomics of Tharparkar cattle with the help of samples collected in spring and summer season. Among differentially expressed genes, about 3280 genes were highly dysregulated, in which 1207 gene were upregulated and 2073 genes were downregulated (|log2fold change|≥ 1 and p ≤ 0.05). Upregulated genes were related to insulin activation, interferons, and potassium ion transport. In contrast, downregulated genes were related to RNA processing, translation, and ubiquitination. Functional annotation revealed that the pathways associated with nervous system (NPFFR1, ROBO3) and metal ion transport (KCNG2, ATP1A2) were highly activated while mRNA processing and translation (EIF4A, EIF4B) and protein processing pathway (VPS4B, PEX13) were highly downregulated. Protein-protein interactions identified hub genes such as ATP13A3, IFNGR2, UBXN7, EIF4A2, SLC12A8 found to play an important role in immune, ubiquitination, translation and transport function. Co-expression network includes LYZ, PNRC1, SQSTM1, EIF4AB and DDX17 genes which are involved in lysosomal activity, tumor inhibition, ubiquitination, and translation initiation. Chemokine signaling pathway associated with immune response was highly upregulated in cluster analysis. The findings of this study provide insights into transcriptome expression and regulation which may better explain complex thermal resilience mechanism of Tharparkar cattle in heat stress under natural conditions. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-024-04018-2.

16.
J Infect Public Health ; 17(1): 60-69, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37992435

RESUMO

BACKGROUND: The recent re-emergence of the monkeypox (mpox) epidemic in nonendemic regions has raised concerns regarding a potential global outbreak. The mpox virus (MPV) is a smallpox-like virus belonging to the genus Orthopoxvirus (family: Poxviridae). Although studies suggest that MPV infection suppresses the Toll-like receptor-3- and tumor necrosis factor-α-related signaling pathways, whether MPV regulates other immune-related pathways remains unclear. METHODS: In this study, two distinct temporal patterns were used for establishing an MPV-infected human immortal epithelial cancer cell line (HeLa). These two durations 2 and 12 h of incubation were selected to identify the coregulated genes and pathways affected by MPV infection. RESULTS: The use of the Gene Ontology framework, Kyoto Encyclopedia of Genes and Genome database, and MetaCore software yielded valuable insights. Specifically, various pathways were found to be enriched in HeLa cells infected with MPV for 2 and 12 h. These pathways included Notch, CD40, CD95, hypoxia-inducible factor-1-α, interleukin (IL)- 1, IL-6, phosphoinositide 3-kinase, nuclear factor-κB, mitogen-activated protein kinase, and oxidative stress-induced signalling pathways. Clusters and pathways of metabolism and viral replication cycles were significantly associated with the 2-hour infection group. This association was identified based on the regulation of genes such as HSPG2, RHPN2, MYL1, ASPHD2, CA9, VIPR1, SNX12, MGC2752, SLC25A1, PEX19, and AREG. Furthermore, clusters and pathways related to immunity and cell movement were found to be associated with the 12-hour infection group. This association was identified based on the regulation of genes such as C1orf21, C19orf48, HRK, IL8, GULP1, SCAND2, ATP5C1, FEZ1, SGSH, TACC2, CYP4X1, MMP1, CPB1, P2RY13, WDR27, PRPF4, and ENDOD1. CONCLUSIONS: This study can improve our understanding of the mechanisms underlying the pathophysiology and post-infection sequelae of mpox. Our findings provide valuable insights into the various modes of MPV infection.


Assuntos
Mpox , Humanos , Células HeLa , Fosfatidilinositol 3-Quinases , Perfilação da Expressão Gênica , Biologia Computacional , Proteínas Adaptadoras de Transdução de Sinal
17.
J Thorac Imaging ; 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38798201

RESUMO

PURPOSE: Apical pleuroparenchymal scarring (APPS) is commonly seen on chest computed tomography (CT), though the imaging and clinical features, to the best of our knowledge, have never been studied. The purpose was to understand APPS's typical morphologic appearance and associated clinical features. PATIENTS AND METHODS: A random generator selected 1000 adult patients from all 21516 chest CTs performed at urban outpatient centers from January 1, 2016 to December 31, 2016. Patients with obscuring apical diseases were excluded to eliminate confounding factors. After exclusions, 780 patients (median age: 64 y; interquartile range: 56 to 72 y; 55% males) were included for analysis. Two radiologists evaluated the lung apices of each CT for the extent of abnormality in the axial plane (mild: <5 mm, moderate: 5 to 10 mm, severe: >10 mm), craniocaudal plane (extension halfway to the aortic arch, more than halfway, vs below the arch), the predominant pattern (nodular vs reticular and symmetry), and progression. Cohen kappa coefficient was used to assess radiologists' agreement in scoring. Ordinal logistic regression was used to determine associations of clinical and imaging variables with APPS. RESULTS: APPS was present on 65% (507/780) of chest CTs (54% mild axial; 80% mild craniocaudal). The predominant pattern was nodular and symmetric. Greater age, female sex, lower body mass index, greater height, and white race were associated with more extensive APPS. APPS was not found to be associated with lung cancer in this cohort. CONCLUSION: Classifying APPS by the extent of disease in the axial or craniocaudal planes, in addition to the predominant pattern, enabled statistically significant associations to be determined, which may aid in understanding the pathophysiology of apical scarring and potential associated risks.

18.
J Health Popul Nutr ; 42(1): 85, 2023 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-37626344

RESUMO

BACKGROUND AND OBJECTIVE: Hypertension is a key risk factor for cardiovascular disease and the leading cause of mortality among Indian adults. The difference in health status between men and women is becoming a great burden in itself worldwide. This study aimed to examine the differences between men and women in the prevalence, awareness, treatment, and control of hypertension and related risk factors among people aged 45 and older in India using data from the Longitudinal Ageing Study in India in 2017-2018. METHODS: Descriptive statistics were presented separately for males and females. Multivariable logistic regression was used to analyze the socio-demographic, lifestyle behaviours, and biological factors associated with the prevalence of hypertension. All statistical analyses were conducted using Stata Version 16.0 statistical software. The study of the data was conducted using survey weights available in the LASI datasets. KEY FINDINGS: Overall, the study found that 45.1% of the study population had hypertension, with 26.9% self-reporting their condition and 30% having hypertension at the time of measurement. Approximately 41% of males and 59% of females had hypertension. The self-reported hypertension of men was found to differ significantly from measured hypertension by 8.7%, while in women the difference was only 1.2%. Diabetes was found to increase the odds of having hypertension in both males (OR = 3.65, 95% CI (3.37-3.97)) and females (OR = 3.46, 95% CI (3.21-3.74)). CONCLUSION: The difference between self-reported and measured hypertension in men and women is contributing to sex-gender and health inequalities that must be addressed. For adult females with hypertension, it is important to prioritize obesity, education level, physical activity, and regular clinic visits to manage chronic conditions. Based on our findings, policy recommendations can be made to focus on increasing women's literacy, promoting men's screening for hypertension, banning tobacco and alcohol sales, and organizing hypertension awareness campaigns specifically for men and in rural areas.


Assuntos
Hipertensão , Homens , Masculino , Humanos , Adulto , Feminino , Prevalência , Hipertensão/epidemiologia , Hipertensão/prevenção & controle , Envelhecimento , Índia/epidemiologia
19.
J Oral Biol Craniofac Res ; 13(2): 315-320, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36891284

RESUMO

Background: Statins are lipid-lowering medications that work by blocking rate-limiting enzyme in cholesterol formation. In patients with Chronic periodontitis (CP) and Diabetes mellitus (DM), subgingival delivery of simvastatin (SMV) and rosuvastatin (RSV) have demonstrated to have bone-stimulatory and anti-inflammatory properties. The current study intended to assess and compare the efficacy of sub-gingivally delivered SMV gel and RSV gel as an adjunctive medication to scaling and root planing (SRP) in the management of intrabony defects in CP patients with type 2 DM. Methods: 30 patients with CP and type 2 DM were classified into three treatment groups - SRP + placebo, SRP +1.2% SMV and SRP +1.2% RSV. Clinical parameters: site-specific plaque index, modified sulcus bleeding index (mSBI), pocket probing depth (PPD), and relative attachment level (RAL) were documented at baseline, 3 and 6 months and radiographic parameter: intrabony defect depth (IBD) at baseline and 6 months post-treatment. Results: - LDD of 1.2% SMV and 1.2% RSV demonstrated greater clinical and radiographic improvement than placebo, the improvement being statistically significant for PI, mSBI, and PPD for 1.2% SMV and statistically significant for all clinical and radiological parameters for the 1.2% RSV. 1.2% RSV demonstrated greater IBD fill and RAL gain than 1.2% SMV. Conclusion: - Localized sub-gingival delivery of statins was beneficial in the treatment intrabony defects in patients with CP and well-controlled type 2 DM. IBD fill and RAL gain were higher with 1.2% RSV than with 1.2% SMV.

20.
Curr Drug Targets ; 24(1): 89-102, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36111764

RESUMO

BACKGROUND: Flavonoids belong to the chemical class of polyphenols and are in the category of secondary metabolites imparting a wide protective effect against acute and chronic diseases. OBJECTIVE: The study aims to investigate and summarize the information of various flavonoids extracted, isolated from various sources, and possess different pharmacological properties by acting on multiple targets. METHODS: This comprehensive review summarizes the research information related to flavonoids and their pharmacological action targets from various sources like PubMed, Google Scholar and Google websites. RESULTS: Extracted information in the paper discusses various therapeutic effects of flavonoids isolated from medicinal plant sources, which have the property to inhibit several enzymes, which finally results in health benefits like anti-cancer, anti-bacterial, antioxidant, anti-allergic, and anti-viral effects. This study also showed the different solvents and methods involved in the extraction and characterization of the isolated phytochemical constituents. CONCLUSION: The findings showed the contribution of several flavonoids in the management and inhibition of various acute and chronic sicknesses by acting on different sites in the body. This study may lead to gaining interest for more research on the bioactives of different medicinal plants for the discovery of new lead compounds or further improvement of the efficacy of the existing compound.


Assuntos
Fitoterapia , Plantas Medicinais , Humanos , Fitoterapia/métodos , Flavonoides/farmacologia , Flavonoides/uso terapêutico , Plantas Medicinais/química , Extratos Vegetais/farmacologia , Polifenóis/farmacologia , Polifenóis/uso terapêutico , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/uso terapêutico
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