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1.
Indian J Otolaryngol Head Neck Surg ; 76(5): 3860-3864, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39376450

RESUMO

The aim of this study was to assess the efficacy of 10% dextrose prolotherapy in the management of temporomandibular joint disorder. Thirty patients aged between 18 and 62 years, diagnosed with Temporomandibular Disorders (TMDs) persisting for more than six months and unresponsive to other conservative treatments, were enrolled in the study. Over four subsequent visits, spaced six weeks apart, each patient received injections of 3 ml of 10% dextrose solution into the temporomandibular joint space. Parameters assessed included pain levels, frequency of luxations/dislocations, episodes of locking per month, maximal mouth opening, and clicking, evaluated every six weeks for a duration of three months. All patients exhibited improvements in Temporomandibular Disorders (TMDs), manifested as reduced pain, clicking sounds, locking episodes, and increased maximal mouth opening, following prolotherapy treatment. These improvements were found to be statistically significant (p-value < 0.05). Dextrose prolotherapy is a treatment method with broad applications and should be considered prior to resorting to long-term pharmacotherapy or surgical interventions. The use of 10% dextrose prolotherapy presents a promising treatment modality for temporomandibular joint disorders, as evidenced by its therapeutic benefits.

2.
J Tradit Complement Med ; 14(5): 494-500, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39262659

RESUMO

In Ayurveda, every individual is believed to possess a unique entity known as Prakriti, which distinguishes them from others physically, physiologically, and psychologically. This entity also determines an individual's response to a particular stimulus, and it is believed that such responses are not solely determined by genetics. The present research aims to validate the Ayurvedic concept of Prakriti from a modern molecular perspective to strengthen the personalized and precise treatment approach. A study was conducted to investigate the role of the KCNJ11gene in the susceptibility of individuals to type 2 diabetes mellitus (T2DM) with their metabolic status. The research involved allele mining on three major Prakriti groups - Vata, Pitta, and Kapha - in 112 patients with T2DM and 112 healthy individuals. The KCNJ11 gene, responsible for insulin secretion membrane pore formation, was analyzed to determine the susceptibility of different Prakriti types to T2DM. The MutPred tool predicted the molecular cause of disease-related amino acid substitution. According to the study, only Pitta and Kapha Prakriti were diagnosed with diabetes, while all three Prakriti types were present in the control group of healthy individuals. A protein model was prepared, and the changes resulting from mutations were observed for each group in their protein sequence, both as synonymous and non-synonymous mutations. Ultimately, these changes contributed to the manifestation of T2DM. Based on the findings, it appears that Prakriti groups may experience changes in protein function due to nonsynonymous mutations and differences in amino acids at the protein level.

4.
Pak J Pharm Sci ; 37(4): 753-759, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39348639

RESUMO

Dengue is an important arboviral infection worldwide for which presently there is no specific medicine. Evidence suggests there are four serotypes of dengue virus (DENV1-4), of which DENV 2 is considered to cause the most sever dengue. Therefore, this study was aimed to develop the new uridine derivatives (NUDs) against dengue virus (DENV 2). In current study 2-(3,4-dihydroxy-5-(hydroxymethyl)-tetrahydrofuran-2-yl)-4-((substituted cyclohexa-2,5-dienylidene)methyl)-1,2,4-triazine-3,5(2H,4H)-dione (2a-f), were obtained via reaction of substituted uridine (1) and different aromatic aldehydes separately. Synthesized NUDs were further characterized using FTIR, 1H & 13C-NMR, mass and element analysis data. Characterized NUDs were assessed for their inhibition potential against DENV 2. Synthesized NUDs were also evaluated for their cytotoxicity towards Vero cells by MTT assay method. This investigation successfully synthesized NUDs 2a-f and reported their high inhibitory activity against DENV 2. The synthesized NUDs exhibited negligible cytotoxicity. High anti-viral activity against DENV 2 serotype and least/no cytotoxicity of NUDs suggests their importance in the treatment of dengue. Present study recommends that in future these NUDs must be investigated for their clinical importance to establish them as a choice for dengue treatment.


Assuntos
Antivirais , Vírus da Dengue , Uridina , Vírus da Dengue/efeitos dos fármacos , Uridina/análogos & derivados , Uridina/farmacologia , Uridina/síntese química , Antivirais/farmacologia , Antivirais/síntese química , Antivirais/química , Células Vero , Chlorocebus aethiops , Animais , Dengue/tratamento farmacológico , Relação Estrutura-Atividade
5.
Ultrasound ; 32(3): 140-149, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39100794

RESUMO

Background: The advent and increased use of high-resolution ultrasonography has resulted in improved detection of thyroid nodules. Even with the use of various Thyroid Imaging-Reporting and Data System, accurate imaging diagnosis of malignant thyroid nodules has been suboptimal, which necessitated use of newer modalities like contrast-enhanced ultrasonography alone and in combination for this purpose. Although the combined use of various Thyroid Imaging-Reporting and Data System and contrast-enhanced ultrasonography has turned out to be accurate in many studies, the ideal way to integrate contrast-enhanced ultrasonography into the Thyroid Imaging-Reporting and Data System algorithm is under-investigated. Purpose: To estimate and compare the diagnostic accuracy of American College of Radiology Thyroid Imaging-Reporting and Data System and contrast-enhanced ultrasonography in differentiating benign and malignant nodules alone and in combination. To estimate the diagnostic accuracy of contrast-enhanced ultrasonography in re-categorisation of Thyroid Imaging-Reporting and Data System 3 and Thyroid Imaging-Reporting and Data System 4 thyroid nodules. Materials and methods: This was a prospective cohort study performed in a tertiary care university-based hospital for 3 years. Adult patients with clinical or previous sonographic diagnosis of thyroid nodules were selected. Each of the nodules were assessed using ultrasonography and categorised using American College of Radiology Thyroid Imaging-Reporting and Data System criteria. The lesion was then assessed for contrast-enhanced ultrasonography features. The final diagnosis of the nodules was made using fine needle aspiration cytology. The diagnostic accuracy in diagnosis of malignant thyroid nodules for each of the American College of Radiology Thyroid Imaging-Reporting and Data System and contrast-enhanced ultrasonography alone and in combination was assessed. The diagnostic accuracy of contrast-enhanced ultrasonography in diagnosis of malignant thyroid nodules categorised as Thyroid Imaging-Reporting and Data System 3 and Thyroid Imaging-Reporting and Data System 4 was also assessed. Results: American College of Radiology Thyroid Imaging-Reporting and Data System had a sensitivity, specificity, negative predictive value, positive predictive value and diagnostic accuracy of 86.6%, 54.5%, 17.4%, 97.3% and 57.7%, respectively, in diagnosis of malignant thyroid nodules. Contrast-enhanced ultrasonography had a sensitivity, specificity, negative predictive value, positive predictive value and diagnostic accuracy of 86.6%, 95.4%, 67.9%, 98.4% and 94.4%, respectively, in diagnosis of malignant thyroid nodules. Contrast-enhanced ultrasonography had sensitivity, specificity, negative predictive value, positive predictive value and diagnostic accuracy of 93.3%, 100.0%, 100.0%, 99.2% and 99.3%, respectively, in re-categorisation of Thyroid Imaging-Reporting and Data System 3 and Thyroid Imaging-Reporting and Data System 4 nodules. Conclusion: Contrast-enhanced ultrasonography can play a key role in diagnosis of malignant thyroid nodules which are categorised as indeterminate on grey-scale ultrasound.

6.
Cureus ; 16(7): e64426, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39130955

RESUMO

Social media reviews are a valuable data source, reflecting consumer experiences and interactions with businesses. This study leverages such data to develop a passive surveillance framework for food safety in urban India. By employing a Bidirectional Encoder Representations from Transformers (BERT)-powered Aspect-Based Sentiment Analysis tool, branded as Eat At Right Place (ERP), the study analyses over 100,000 reviews from 93 restaurants to identify and assess food safety signals. The Causality Assessment Index (CAI) and Severity Assessment Score (SAS) are introduced to systematically evaluate potential risks. The CAI uses pattern recognition and temporal relationships to establish causality while the SAS quantifies severity based on sub-aspects such as cleanliness, food handling, and unintended health outcomes. Results indicate that 40% of the restaurants had a CAI above 1, highlighting significant food safety concerns. The framework successfully prioritizes corrective actions by grading the severity of issues, demonstrating its potential for real-time food safety management. This study underscores the importance of integrating innovative data-driven approaches into public health monitoring systems and suggests future improvements in natural language processing algorithms and data source expansion. The findings pave the way for enhanced food safety surveillance and timely regulatory interventions.

7.
Biophys Chem ; 313: 107306, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39121649

RESUMO

D-penicillamine (PA) is the primary chelator of choice to treat Wilson disease (WD). There are limitations in obtaining comprehensive data on PA metabolites in biological specimens by conventional approaches. Hence, the aim of the present was to identify the major hepatic PA metabolites and draw clear conclusions of the drug's xenobiotic in WD. Urine samples were collected from children with hepatic WD (n = 63, aged 14.8 ± 4 years) 5 h after PA administration (16.3 ± 3.8 mg/kg/day) and age-matched healthy volunteers comprised as controls (n = 30). High-resolution 800 MHz nuclear magnetic resonance spectroscopy (NMR) and mass spectrometry was applied to reveal unambiguous appraisals of different excretory by-products of PA metabolism. Four new products comprising penicillamine disulphide (PD), penicillamine cysteine disulphide (PCD), S-methyl penicillamine (SMP), and N-acetyl penicillamine (NAP) of PA xenobiotic metabolites were identified using high-resolution NMR spectroscopy. Quantitative levels of PCD and SMP were approximately three-fold higher than those of PD and NAP, respectively. High-resolution NMR identifies the major PA metabolites with certainty. Reduction, sulfation, and methylation are the predominant pathways of PA metabolism. There is a potential application for assessing therapeutic monitoring of chelation in hepatic WD.


Assuntos
Degeneração Hepatolenticular , Penicilamina , Xenobióticos , Penicilamina/química , Penicilamina/uso terapêutico , Degeneração Hepatolenticular/tratamento farmacológico , Degeneração Hepatolenticular/metabolismo , Humanos , Adolescente , Criança , Xenobióticos/metabolismo , Masculino , Feminino , Espectroscopia de Ressonância Magnética , Quelantes/química , Fígado/metabolismo , Fígado/efeitos dos fármacos
8.
Pathol Res Pract ; 261: 155489, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39111016

RESUMO

Oral squamous cell carcinoma (OSCC) is considered the most common type of head and neck squamous cell carcinoma (HNSCC) as it holds 90 % of HNSCC cases that arise from multiple locations in the oral cavity. The last three decades witnessed little progress in the diagnosis and treatment of OSCC the aggressive tumor. However, in-depth knowledge about OSCC's pathogenesis, staging & grading, hallmarks, and causative factors is a prime requirement in advanced diagnosis and treatment for OSCC patients. Therefore present review was intended to comprehend the OSCCs' prevalence, staging & grading, molecular pathogenesis including premalignant stages, various hallmarks, etiology, diagnostic methods, treatment (including FDA-approved drugs with the mechanism of action and side effects), and theranostic agents. The current review updates that for a better understanding of OSCC progress tumor-promoting inflammation, sustained proliferative signaling, and growth-suppressive signals/apoptosis capacity evasion are the three most important hallmarks to be considered. This review suggests that among all the etiology factors the consumption of tobacco is the major contributor to the high incidence rate of OSCC. In OSCC diagnosis biopsy is considered the gold standard, however, toluidine blue staining is the easiest and non-invasive method with high accuracy. Although there are various therapeutic agents available for cancer treatment, however, a few only are approved by the FDA specifically for OSCC treatment. The present review recommends that among all available OSCC treatments, the antibody-based CAR-NK is a promising therapeutic approach for future cancer treatment. Presently review also suggests that theranostics have boosted the advancement of cancer diagnosis and treatment, however, additional work is required to refine the role of theranostics in combination with different modalities in cancer treatment.


Assuntos
Neoplasias Bucais , Humanos , Neoplasias Bucais/patologia , Neoplasias Bucais/diagnóstico , Neoplasias Bucais/terapia , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/diagnóstico , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/terapia , Carcinoma de Células Escamosas/patologia
9.
J Med Chem ; 67(17): 15041-15060, 2024 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-39213648

RESUMO

To date, the use of corannulene has been restricted in the area of material science, but its application in biomedical research has yet to be established due to its nonsolubility in an aqueous environment and synthetic infeasibility. Herein, we detail the development of a new family of highly curved π-conjugated corannulene-containing unnatural α-amino acid (CAA) derivatives to overcome this challenge. These CAAs have been extended as novel constituents for the synthesis of corannulene-containing water-soluble cationic peptides (CCPs), which display inhibitory activity against broad-spectrum pathogenic bacteria along with drug-resistant bacteria via a membrane-damaging mechanism. Importantly, several of the synthesized peptides were found to be appreciably nonhemolytic against hRBCs and noncytotoxic against mammalian 3T3 cells. In vivo efficacy studies of the potent and least cytotoxic peptide 6a demonstrated clearance of bacteria from the spleen, liver, lung, and blood of mice infected with S. aureus ATCC 25923.


Assuntos
Aminoácidos , Antibacterianos , Testes de Sensibilidade Microbiana , Solubilidade , Água , Animais , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/síntese química , Camundongos , Aminoácidos/química , Aminoácidos/farmacologia , Água/química , Humanos , Staphylococcus aureus/efeitos dos fármacos , Hidrocarbonetos Policíclicos Aromáticos/farmacologia , Hidrocarbonetos Policíclicos Aromáticos/química , Hidrocarbonetos Policíclicos Aromáticos/síntese química , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Peptídeos Catiônicos Antimicrobianos/farmacologia , Peptídeos Catiônicos Antimicrobianos/química , Peptídeos Catiônicos Antimicrobianos/síntese química , Relação Estrutura-Atividade , Infecções Estafilocócicas/tratamento farmacológico
10.
Mol Cell Biochem ; 2024 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-39033212

RESUMO

Mitochondrial dysfunction is critical for the development and progression of cardiovascular diseases (CVDs). Complex-1 (CI) is an essential component of the mitochondrial electron transport chain that participates in oxidative phosphorylation and energy production. CI is the largest multisubunit complex (~ 1 Mda) and comprises 45 protein subunits encoded by seven mt-DNA genes and 38 nuclear genes. These subunits function as the enzyme nicotinamide adenine dinucleotide hydrogen (NADH): ubiquinone oxidoreductase. CI dysregulation has been implicated in various CVDs, including heart failure, ischemic heart disease, pressure overload, hypertrophy, and cardiomyopathy. Several studies demonstrated that impaired CI function contributes to increased oxidative stress, altered calcium homeostasis, and mitochondrial DNA damage in cardiac cells, leading to cardiomyocyte dysfunction and apoptosis. CI dysfunction has been associated with endothelial dysfunction, inflammation, and vascular remodeling, critical processes in developing atherosclerosis and hypertension. Although CI is crucial in physiological and pathological conditions, no potential therapeutics targeting CI are available to treat CVDs. We believe that a lack of understanding of CI's precise mechanisms and contributions to CVDs limits the development of therapeutic strategies. In this review, we comprehensively analyze the role of CI in cardiovascular health and disease to shed light on its potential therapeutic target role in CVDs.

11.
Pharmaceutics ; 16(7)2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-39065610

RESUMO

Our hypothesis posited that incorporating alpha-linolenic acid (ALA) into liposomes containing Paclitaxel (PTX) could augment cellular uptake, decrease the therapeutic dosage, and alleviate PTX-related side effects. Our investigation encompassed characterization of the liposomal formulation, encompassing aspects like particle size, surface morphology, chemical structure, drug release kinetics, and stability. Compatibility studies were performed through Fourier transform infrared spectroscopy (FTIR). By utilizing the Box-Behnken design (BBD), we developed ALA-based liposomes with satisfactory particle size and entrapment efficiency. It is noteworthy that ALA incorporation led to a slight increase in particle size but did not notably affect drug entrapment. In vitro drug release assessments unveiled a sustained release pattern, with ALA-PTX liposomes demonstrating release profiles comparable to PTX liposomes. Morphological examinations confirmed the spherical structure of the liposomes, indicating that substituting ALA with phosphatidylcholine did not alter the physicochemical properties. Cellular uptake investigations showcased enhanced uptake of ALA-based liposomes in contrast to PTX liposomes, likely attributed to the heightened fluidity conferred by ALA. Efficacy against MCF-7 cells demonstrated concentration-dependent reductions in cell viability, with ALA-PTX liposomes exhibiting the lowest IC50 value. Morphological analysis confirmed apoptotic changes in cells treated with all formulations, with ALA-PTX liposomes eliciting more pronounced changes, indicative of enhanced anticancer efficacy.

12.
Heliyon ; 10(12): e33239, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-39022080

RESUMO

Refractory metals that can withstand at high temperatures and harsh conditions are of utmost importance for solar-thermal and energy storage applications. Thin films of TiN have been deposited using cathodic vacuum arc deposition at relatively low temperatures ∼300 °C using the substrate bias âˆ¼ -60 V. The nanomechanical properties of these films were investigated using nanoindentation and the spatial fluctuations were observed. The nanoindentation results were simulated using finite element method through Johnson-Cook model. A parametric study was conducted, and 16 different models were simulated to predict the hardening modulus, hardening exponent, and yield stress of the deposited film. The predicted values of elastic modulus, yield stress, hardening modulus and hardening exponent as 246 GPa, 2500 MPa, 25000 MPa and 0.1 respectively are found to satisfactorily explain the experimental load-indentation curves. We have found the local nitridation plays an important role on nanomechanical properties of TiN thin films and confirms that the nitrogen deficient regions are ductile with low yield stress and hardening modulus. This study further opens the opportunities of modelling the nanoscale system using FEM analysis.

13.
Int Immunopharmacol ; 137: 112496, 2024 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-38901240

RESUMO

Lung cancer (LC) is the most common cancer in males. As per GLOBOCAN 2020, 8.1 % of deaths and 5.9 % of cases of LC were reported in India. Our laboratory has previously reported the significant anticancer potential of 5H-benzo[h]thiazolo[2,3-b]quinazoline analogues. In this study, we have explored the anticancer potential of 7A {4-(6,7-dihydro-5H-benzo[h]thiazolo[2,3-b]quinazolin-7-yl)phenol} and 9A {7-(4-chlorophenyl)-9-methyl-6,7-dihydro-5H-benzo[h]thiazolo[2,3-b]quinazoline}by using in-vitro and in-vivo models of LC. In this study, we investigated the antiproliferative potential of quinazoline analogues using A549 cell line to identify the best compound of the series. The in-vitro and molecular docking studies revealed 7A and 9A compounds as potential analogues. We also performed acute toxicity study to determine the dose. After that, in-vivo studies using urethane-induced LC in male albino Wistar rats carried out further physiological, biochemical, and morphological evaluation (SEM and H&E) of the lung tissue. We have also evaluated the antioxidant level, inflammatory, and apoptotic marker expressions. 7A and 9A did not demonstrate any signs of acute toxicity. Animals treated with urethane showed a significant upregulation of oxidative stress. However, treatment with 7A and 9A restored antioxidant markers near-normal levels. SEM and H&E staining of the lung tissue demonstrated recovered architecture after treatment with 7A and 9A. Both analogues significantly restore inflammatory markers to normal level and upregulate the intrinsic apoptosis protein expression in the lung tissue. These experimental findings demonstrated the antiproliferative potential of the synthetic analogues 7A and 9A, potentially due to their anti-inflammatory and apoptotic properties.


Assuntos
Anti-Inflamatórios , Antineoplásicos , Apoptose , Proliferação de Células , Neoplasias Pulmonares , Simulação de Acoplamento Molecular , Quinazolinas , Animais , Humanos , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios/química , Células A549 , Quinazolinas/farmacologia , Quinazolinas/química , Quinazolinas/uso terapêutico , Masculino , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Ratos Wistar , Ratos
14.
Cancer Cell Int ; 24(1): 219, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38926695

RESUMO

Lung cancer (LC) ranks second most prevalent cancer in females after breast cancer and second in males after prostate cancer. Based on the GLOBOCAN 2020 report, India represented 5.9% of LC cases and 8.1% of deaths caused by the disease. Several clinical studies have shown that LC occurs because of biological and morphological abnormalities and the involvement of altered level of antioxidants, cytokines, and apoptotic markers. In the present study, we explored the antiproliferative activity of indeno[1,2-d]thiazolo[3,2-a]pyrimidine analogues against LC using in-vitro, in-silico, and in-vivo models. In-vitro screening against A549 cells revealed compounds 9B (8-methoxy-5-(3,4,5-trimethoxyphenyl)-5,6-dihydroindeno[1,2-d]thiazolo[3,2-a]pyrimidine) and 12B (5-(4-chlorophenyl)-5,6-dihydroindeno[1,2-d]thiazolo[3,2-a]pyrimidine) as potential pyrimidine analogues against LC. Compounds 9B and 12B were docked with different molecular targets IL-6, Cyt-C, Caspase9, and Caspase3 using AutoDock Vina 4.1 to evaluate the binding affinity. Subsequently, in-vivo studies were conducted in albino Wistar rats through ethyl-carbamate (EC)- induced LC. 9B and 12B imparted significant effects on physiological (weight variation), and biochemical (anti-oxidant [TBAR's, SOD, ProC, and GSH), lipid (TC, TG, LDL, VLDL, and HDL)], and cytokine (IL-2, IL-6, IL-10, and IL-1ß) markers in EC-induced LC in albino Wistar rats. Morphological examination (SEM and H&E) and western blotting (IL-6, STAT3, Cyt-C, BAX, Bcl-2, Caspase3, and caspase9) showed that compounds 9B and 12B had antiproliferative effects. Accordingly, from the in-vitro, in-silico, and in-vivo experimental findings, we concluded that 9B and 12B have significant antiproliferative potential and are potential candidates for further evaluation to meet the requirements of investigation of new drug application.

15.
Nat Commun ; 15(1): 5467, 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38937463

RESUMO

The genome of Mycobacterium tuberculosis encodes for a large repertoire of toxin-antitoxin systems. In the present study, MenT3 and MenT4 toxins belonging to MenAT subfamily of TA systems have been functionally characterized. We demonstrate that ectopic expression of these toxins inhibits bacterial growth and this is rescued upon co-expression of their cognate antitoxins. Here, we show that simultaneous deletion of menT3 and menT4 results in enhanced susceptibility of M. tuberculosis upon exposure to oxidative stress and attenuated growth in guinea pigs and mice. We observed reduced expression of transcripts encoding for proteins that are essential or required for intracellular growth in mid-log phase cultures of ΔmenT4ΔT3 compared to parental strain. Further, the transcript levels of proteins involved in efficient bacterial clearance were increased in lung tissues of ΔmenT4ΔT3 infected mice relative to parental strain infected mice. We show that immunization of mice and guinea pigs with ΔmenT4ΔT3 confers significant protection against M. tuberculosis infection. Remarkably, immunization of mice with ΔmenT4ΔT3 results in increased antigen-specific TH1 bias and activated memory T cell response. We conclude that MenT3 and MenT4 are important for M. tuberculosis pathogenicity and strains lacking menT3 and menT4 have the potential to be explored further as vaccine candidates.


Assuntos
Proteínas de Bactérias , Mycobacterium tuberculosis , Tuberculose , Animais , Cobaias , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/imunologia , Camundongos , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/imunologia , Tuberculose/prevenção & controle , Tuberculose/imunologia , Tuberculose/microbiologia , Feminino , Pulmão/microbiologia , Pulmão/patologia , Pulmão/imunologia , Deleção de Genes , Toxinas Bacterianas/genética , Toxinas Bacterianas/imunologia , Toxinas Bacterianas/metabolismo , Camundongos Endogâmicos C57BL , Vacinas contra a Tuberculose/imunologia , Estresse Oxidativo , Virulência/genética
16.
Drug Dev Res ; 85(4): e22215, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38837718

RESUMO

Breast cancer is the second most frequent cancer among women. Out of various subtypes, triple-negative breast cancers (TNBCs) account for 15% of breast cancers and exhibit more aggressive characteristics as well as a worse prognosis due to their proclivity for metastatic progression and limited therapeutic strategies. It has been demonstrated that AMP-activated protein kinase (AMPK) has context-specific protumorigenic implications in breast cancer cells. A set of glucosyltriazole amphiphiles, consisting of acetylated (9a-h) and unmodified sugar hydroxyl groups (10a-h), were synthesized and subjected to in vitro biological evaluation. Among them, 9h exhibited significant anticancer activity against MDA-MB-231, MCF-7, and 4T1 cell lines with IC50 values of 12.5, 15, and 12.55 µM, respectively. Further, compound 9h was evaluated for apoptosis and cell cycle analysis in in vitro models (using breast cancer cells) and antitumour activity in an in vivo model (orthotopic mouse model using 4T1 cells). Annexin-V assay results revealed that treatment with 9h caused 34% and 28% cell death at a concentration of 15 or 7.5 µM, respectively, while cell cycle analysis demonstrated that 9h arrested the cells at the G2/M or G1 phase in MCF-7, MDA-MB-231 and 4T1 cells, respectively. Further, in vivo, investigation showed that compound 9h exhibited equipotent as doxorubicin at 7.5 mg/kg, and superior efficacy than doxorubicin at 15 mg/kg. The mechanistic approach revealed that 9h showed potent anticancer activity in an in vivo orthotopic model (4T1 cells) partly by suppressing the AMPK activation. Therefore, modulating the AMPK activation could be a probable approach for targeting breast cancer and mitigating cancer progression.


Assuntos
Proteínas Quinases Ativadas por AMP , Antineoplásicos , Apoptose , Transdução de Sinais , Triazóis , Humanos , Feminino , Animais , Proteínas Quinases Ativadas por AMP/metabolismo , Triazóis/farmacologia , Transdução de Sinais/efeitos dos fármacos , Camundongos , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Apoptose/efeitos dos fármacos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Camundongos Endogâmicos BALB C , Células MCF-7 , Proliferação de Células/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
17.
Sci Rep ; 14(1): 13083, 2024 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-38844568

RESUMO

In bread wheat, a literature search gave 228 QTLs for six traits, including resistance against spot blotch and the following five other related traits: (i) stay green; (ii) flag leaf senescence; (iii) green leaf area duration; (iv) green leaf area of the main stem; and (v) black point resistance. These QTLs were used for metaQTL (MQTL) analysis. For this purpose, a consensus map with 72,788 markers was prepared; 69 of the above 228 QTLs, which were suitable for MQTL analysis, were projected on the consensus map. This exercise resulted in the identification of 16 meta-QTLs (MQTLs) located on 11 chromosomes, with the PVE ranging from 5.4% (MQTL7) to 21.8% (MQTL5), and the confidence intervals ranging from 1.5 to 20.7 cM (except five MQTLs with a range of 36.1-57.8 cM). The number of QTLs associated with individual MQTLs ranged from a maximum of 17 in MQTL3 to 8 each in MQTL5 and MQTL8 and 5 each in MQTL7 and MQTL14. The 16 MQTLs, included 12 multi-trait MQTLs; one of the MQTL also overlapped a genomic region carrying the major spot blotch resistance gene Sb1. Of the total 16 MQTLs, 12 MQTLs were also validated through marker-trait associations that were available from earlier genome-wide association studies. The genomic regions associated with MQTLs were also used for the identification of candidate genes (CGs) and led to the identification of 516 CGs encoding 508 proteins; 411 of these proteins are known to be associated with resistance against several biotic stresses. In silico expression analysis of CGs using transcriptome data allowed the identification of 71 differentially expressed CGs, which were examined for further possible studies. The findings of the present study should facilitate fine-mapping and cloning of genes, enabling Marker Assisted Selection.


Assuntos
Mapeamento Cromossômico , Resistência à Doença , Doenças das Plantas , Locos de Características Quantitativas , Triticum , Triticum/genética , Triticum/microbiologia , Resistência à Doença/genética , Doenças das Plantas/genética , Doenças das Plantas/microbiologia , Cromossomos de Plantas/genética , Genes de Plantas , Fenótipo , Pão
18.
Int J Nurs Pract ; 30(5): e13263, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38747251

RESUMO

AIM: To assess the prevalence of non-communicable disease risk factors among the nursing staff and educate them on prevention. BACKGROUND: Nursing staff is integral to the Indian community healthcare systems. Recent studies report a high prevalence of non-communicable diseases in Indian nursing staff. Therefore, data on the prevalence of non-communicable disease risk factors among nursing staff are crucial for education on prevention. DESIGN: A cross-sectional digital survey-based study. METHOD: We invited 4435 nursing staff to attend our online survey. We used a customized questionnaire for data collection, including a digitized version of the Community-Based Assessment Checklist form. A score of >4 was considered high risk and warranted screening. RESULT: Among 682 nursing staff who attended, 70% had never undergone screening for non-communicable diseases. The prevalence of non-communicable disease risk factors was significantly higher in male nursing staff. In addition, logistic regression analysis showed that age, tobacco and alcohol use, increased waist circumference, physical inactivity and family history of non-communicable diseases were significant risk factors among nursing staff. CONCLUSION: The study findings suggest that the nursing staff have suboptimal self-health concerns on non-communicable diseases. This situation warrants continued medical education, awareness campaigns on adopting a healthy lifestyle and health promotion.


Assuntos
Doenças não Transmissíveis , Humanos , Estudos Transversais , Masculino , Fatores de Risco , Feminino , Adulto , Doenças não Transmissíveis/epidemiologia , Prevalência , Pessoa de Meia-Idade , Índia/epidemiologia , Inquéritos e Questionários , Recursos Humanos de Enfermagem , Países em Desenvolvimento
19.
Angew Chem Int Ed Engl ; 63(32): e202404319, 2024 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-38785101

RESUMO

We report an unprecedented iron-catalyzed C-H annulation using readily available 2-vinylbenzofurans as the reaction pattern. The redox-neutral strategy, based on cheap, non-toxic, and earth-abundant iron catalysts, exploits triazole assistance to promote a cascade C-H alkylation, benzofuran ring-opening and insertion into a Fe-N bond, to form highly functionalized isoquinolones. Detailed mechanistic studies supported by DFT calculations fully disclosed the manifold of the iron catalysis.

20.
Pathol Res Pract ; 259: 155346, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38781762

RESUMO

Osteosarcoma (OS) is a bone cancer which stems from several sources and presents with diverse clinical features, making evaluation and treatment difficult. Chemotherapy tolerance and restricted treatment regimens hinder progress in survival rates, requiring new and creative therapeutic strategies. The Wnt/ß-catenin system has been recognised as an essential driver of OS development, providing potential avenues for therapy. Non-coding RNAs (ncRNAs), such as circular RNAs (circRNAs), long non-coding RNAs (lncRNAs), and microRNAs (miRNAs), are essential in modulating the Wnt/ß-catenin cascade in OS. MiRNAs control the system by targeting vital elements, while lncRNAs and circRNAs interact with system genes, impacting OS growth and advancement. This paper thoroughly analyses the intricate interplay between ncRNAs and the Wnt/ß-catenin cascade in OS. We examine how uncontrolled levels of miRNAs, lncRNAs, and circRNAs lead to an abnormal Wnt/ß-catenin network, which elevates the development, spread, and susceptibility to the treatment of OS. We emphasise the potential of ncRNAs as diagnostic indicators and avenues for treatment in OS care. The review offers valuable insights for academics and clinicians studying OS aetiology and creating new treatment techniques for the ncRNA-Wnt/ß-catenin cascade. Utilising the oversight roles of ncRNAs in the Wnt/ß-catenin system shows potential for enhancing the outcomes of patients and progressing precision medicine in OS therapy.


Assuntos
Biomarcadores Tumorais , Neoplasias Ósseas , Osteossarcoma , RNA não Traduzido , Via de Sinalização Wnt , Humanos , Osteossarcoma/genética , Osteossarcoma/patologia , Osteossarcoma/metabolismo , Osteossarcoma/tratamento farmacológico , Via de Sinalização Wnt/genética , Neoplasias Ósseas/genética , Neoplasias Ósseas/patologia , Neoplasias Ósseas/metabolismo , Neoplasias Ósseas/tratamento farmacológico , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , RNA não Traduzido/genética , RNA não Traduzido/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , RNA Circular/genética , RNA Circular/metabolismo , beta Catenina/genética , beta Catenina/metabolismo , Regulação Neoplásica da Expressão Gênica
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