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1.
Immunity ; 57(6): 1360-1377.e13, 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38821052

RESUMO

Limited infiltration and activity of natural killer (NK) and T cells within the tumor microenvironment (TME) correlate with poor immunotherapy responses. Here, we examined the role of the endonuclease Regnase-1 on NK cell anti-tumor activity. NK cell-specific deletion of Regnase-1 (Reg1ΔNK) augmented cytolytic activity and interferon-gamma (IFN-γ) production in vitro and increased intra-tumoral accumulation of Reg1ΔNK-NK cells in vivo, reducing tumor growth dependent on IFN-γ. Transcriptional changes in Reg1ΔNK-NK cells included elevated IFN-γ expression, cytolytic effectors, and the chemokine receptor CXCR6. IFN-γ induced expression of the CXCR6 ligand CXCL16 on myeloid cells, promoting further recruitment of Reg1ΔNK-NK cells. Mechanistically, Regnase-1 deletion increased its targets, the transcriptional regulators OCT2 and IκBζ, following interleukin (IL)-12 and IL-18 stimulation, and the resulting OCT2-IκBζ-NF-κB complex induced Ifng transcription. Silencing Regnase-1 in human NK cells increased the expression of IFNG and POU2F2. Our findings highlight NK cell dysfunction in the TME and propose that targeting Regnase-1 could augment active NK cell persistence for cancer immunotherapy.


Assuntos
Interferon gama , Células Matadoras Naturais , Microambiente Tumoral , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/metabolismo , Animais , Interferon gama/metabolismo , Humanos , Camundongos , Microambiente Tumoral/imunologia , Camundongos Endogâmicos C57BL , Ribonucleases/metabolismo , Ribonucleases/genética , Camundongos Knockout , Transcrição Gênica , Linhagem Celular Tumoral , NF-kappa B/metabolismo
2.
Nature ; 628(8008): 604-611, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38538784

RESUMO

The immune system has a critical role in orchestrating tissue healing. As a result, regenerative strategies that control immune components have proved effective1,2. This is particularly relevant when immune dysregulation that results from conditions such as diabetes or advanced age impairs tissue healing following injury2,3. Nociceptive sensory neurons have a crucial role as immunoregulators and exert both protective and harmful effects depending on the context4-12. However, how neuro-immune interactions affect tissue repair and regeneration following acute injury is unclear. Here we show that ablation of the NaV1.8 nociceptor impairs skin wound repair and muscle regeneration after acute tissue injury. Nociceptor endings grow into injured skin and muscle tissues and signal to immune cells through the neuropeptide calcitonin gene-related peptide (CGRP) during the healing process. CGRP acts via receptor activity-modifying protein 1 (RAMP1) on neutrophils, monocytes and macrophages to inhibit recruitment, accelerate death, enhance efferocytosis and polarize macrophages towards a pro-repair phenotype. The effects of CGRP on neutrophils and macrophages are mediated via thrombospondin-1 release and its subsequent autocrine and/or paracrine effects. In mice without nociceptors and diabetic mice with peripheral neuropathies, delivery of an engineered version of CGRP accelerated wound healing and promoted muscle regeneration. Harnessing neuro-immune interactions has potential to treat non-healing tissues in which dysregulated neuro-immune interactions impair tissue healing.


Assuntos
Peptídeo Relacionado com Gene de Calcitonina , Macrófagos , Neutrófilos , Nociceptores , Cicatrização , Animais , Camundongos , Comunicação Autócrina , Peptídeo Relacionado com Gene de Calcitonina/metabolismo , Peptídeo Relacionado com Gene de Calcitonina/farmacologia , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Eferocitose , Macrófagos/citologia , Macrófagos/metabolismo , Monócitos/citologia , Monócitos/metabolismo , Músculo Esquelético , Canal de Sódio Disparado por Voltagem NAV1.8/deficiência , Canal de Sódio Disparado por Voltagem NAV1.8/genética , Canal de Sódio Disparado por Voltagem NAV1.8/metabolismo , Neutrófilos/citologia , Neutrófilos/metabolismo , Nociceptores/metabolismo , Comunicação Parácrina , Doenças do Sistema Nervoso Periférico/complicações , Proteína 1 Modificadora da Atividade de Receptores/metabolismo , Regeneração/efeitos dos fármacos , Pele , Trombospondina 1/metabolismo , Cicatrização/efeitos dos fármacos , Cicatrização/imunologia , Humanos , Masculino , Feminino
3.
Gastroenterology ; 166(6): 1020-1055, 2024 06.
Artigo em Inglês | MEDLINE | ID: mdl-38763697

RESUMO

BACKGROUND & AIMS: Barrett's esophagus (BE) is the precursor to esophageal adenocarcinoma (EAC). Endoscopic eradication therapy (EET) can be effective in eradicating BE and related neoplasia and has greater risk of harms and resource use than surveillance endoscopy. This clinical practice guideline aims to inform clinicians and patients by providing evidence-based practice recommendations for the use of EET in BE and related neoplasia. METHODS: The Grading of Recommendations Assessment, Development and Evaluation framework was used to assess evidence and make recommendations. The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients, conducted an evidence review, and used the Evidence-to-Decision Framework to develop recommendations regarding the use of EET in patients with BE under the following scenarios: presence of (1) high-grade dysplasia, (2) low-grade dysplasia, (3) no dysplasia, and (4) choice of stepwise endoscopic mucosal resection (EMR) or focal EMR plus ablation, and (5) endoscopic submucosal dissection vs EMR. Clinical recommendations were based on the balance between desirable and undesirable effects, patient values, costs, and health equity considerations. RESULTS: The panel agreed on 5 recommendations for the use of EET in BE and related neoplasia. Based on the available evidence, the panel made a strong recommendation in favor of EET in patients with BE high-grade dysplasia and conditional recommendation against EET in BE without dysplasia. The panel made a conditional recommendation in favor of EET in BE low-grade dysplasia; patients with BE low-grade dysplasia who place a higher value on the potential harms and lower value on the benefits (which are uncertain) regarding reduction of esophageal cancer mortality could reasonably select surveillance endoscopy. In patients with visible lesions, a conditional recommendation was made in favor of focal EMR plus ablation over stepwise EMR. In patients with visible neoplastic lesions undergoing resection, the use of either endoscopic mucosal resection or endoscopic submucosal dissection was suggested based on lesion characteristics. CONCLUSIONS: This document provides a comprehensive outline of the indications for EET in the management of BE and related neoplasia. Guidance is also provided regarding the considerations surrounding implementation of EET. Providers should engage in shared decision making based on patient preferences. Limitations and gaps in the evidence are highlighted to guide future research opportunities.


Assuntos
Adenocarcinoma , Esôfago de Barrett , Ressecção Endoscópica de Mucosa , Neoplasias Esofágicas , Esofagoscopia , Esôfago de Barrett/cirurgia , Esôfago de Barrett/patologia , Humanos , Neoplasias Esofágicas/cirurgia , Neoplasias Esofágicas/patologia , Ressecção Endoscópica de Mucosa/efeitos adversos , Esofagoscopia/normas , Esofagoscopia/efeitos adversos , Adenocarcinoma/cirurgia , Adenocarcinoma/patologia , Gastroenterologia/normas , Medicina Baseada em Evidências/normas , Resultado do Tratamento , Tomada de Decisão Clínica , Técnicas de Ablação/efeitos adversos , Técnicas de Ablação/normas
4.
Int Immunol ; 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38700370

RESUMO

Regnase-1 is an RNase that plays a critical role in negatively regulating immune responses by destabilizing inflammatory mRNAs. Dysfunction of Regnase-1 can be a major cause of various inflammatory diseases with tissue injury and immune cell infiltration into organs. This study focuses on the role of RNase activity of Regnase-1 in developing inflammatory diseases. We have constructed mice with a single point mutation at the catalytic center of Regnase-1 RNase domain, which lacks endonuclease activity. D141N mutant mice demonstrated systemic inflammation, immune cell infiltration into various organs and progressive development of lung granuloma. CD4+ T cells, mainly affected by this mutation, upregulated mTORC1 pathway and facilitated the autoimmune trait in D141N mutation. Moreover, serine/threonine kinase Pim2 contributed to lung inflammation in this mutation. Inhibition of Pim2 kinase activity ameliorated granulomatous inflammation, immune cell infiltration and proliferation in the lungs. Additionally, Pim2 inhibition reduced the expression of adhesion molecules on CD4+ T cells, suggesting a role for Pim2 in facilitating leukocyte adhesion and migration to inflamed tissues. Our findings provide new insights into the role of Regnase-1 RNase activity in controlling immune function and underscore the therapeutic relevance of targeting Pim2 to modulate abnormal immune responses.

5.
Int Microbiol ; 2024 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-38730211

RESUMO

The study explores the potential of an indigenous halo-tolerant microbe identified as Bacillus spp. SSAU-2 in enhancing soil fertility and promoting plant growth for sustainable agricultural practices under the influence of multiple abiotic stresses such as Cr(VI), high salinity, and artificial drought condition. The study investigated various factors influencing IAA synthesis by SSAU-2, such as pH (5 to 11), salinity (10 to 50 g/L), tryptophan concentration (0.5 to 1%), carbon (mannitol mand lactose), and nitrogen sources (peptone and tryptone). The highest IAA concentration was observed at pH 10 (1.695 mg/ml) and pH 11 (0.782 mg/ml). IAA synthesis was optimized at a salinity level of 30 g/l, with lower and higher salinity levels resulting in decreased IAA concentrations. Notably, the presence of mannitol and lactose significantly augmented IAA synthesis, while glucose and sucrose had inhibitory effects. Furthermore, peptone and tryptone played a pivotal role in enhancing IAA synthesis, while ammonium chloride exerted an inhibitory influence. SSAU-2 showed a diverse array of capabilities, including the synthesis of gibberellins, extracellular polymeric substances, siderophores, and hydrogen cyanide along with nitrogen fixation and ammonia production. The microbe could efficiently tolerate 45% PEG-6000 concentration and effectively produce IAA in 15% PEG concentration. It could also tolerate high concentration of Cr(VI) and synthesize IAA even in 50 ppm Cr(VI). The findings of this study provide valuable insights into harnessing the potential of indigenous microorganisms to promote plant growth, enhance soil fertility, and establish sustainable agricultural practices essential for restoring the health of ecosystems.

6.
BMC Med Imaging ; 24(1): 30, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38302883

RESUMO

BACKGROUND: Lung diseases, both infectious and non-infectious, are the most prevalent cause of mortality overall in the world. Medical research has identified pneumonia, lung cancer, and Corona Virus Disease 2019 (COVID-19) as prominent lung diseases prioritized over others. Imaging modalities, including X-rays, computer tomography (CT) scans, magnetic resonance imaging (MRIs), positron emission tomography (PET) scans, and others, are primarily employed in medical assessments because they provide computed data that can be utilized as input datasets for computer-assisted diagnostic systems. Imaging datasets are used to develop and evaluate machine learning (ML) methods to analyze and predict prominent lung diseases. OBJECTIVE: This review analyzes ML paradigms, imaging modalities' utilization, and recent developments for prominent lung diseases. Furthermore, the research also explores various datasets available publically that are being used for prominent lung diseases. METHODS: The well-known databases of academic studies that have been subjected to peer review, namely ScienceDirect, arXiv, IEEE Xplore, MDPI, and many more, were used for the search of relevant articles. Applied keywords and combinations used to search procedures with primary considerations for review, such as pneumonia, lung cancer, COVID-19, various imaging modalities, ML, convolutional neural networks (CNNs), transfer learning, and ensemble learning. RESULTS: This research finding indicates that X-ray datasets are preferred for detecting pneumonia, while CT scan datasets are predominantly favored for detecting lung cancer. Furthermore, in COVID-19 detection, X-ray datasets are prioritized over CT scan datasets. The analysis reveals that X-rays and CT scans have surpassed all other imaging techniques. It has been observed that using CNNs yields a high degree of accuracy and practicability in identifying prominent lung diseases. Transfer learning and ensemble learning are complementary techniques to CNNs to facilitate analysis. Furthermore, accuracy is the most favored metric for assessment.


Assuntos
COVID-19 , Pneumopatias , Neoplasias Pulmonares , Humanos , Redes Neurais de Computação , Pneumopatias/diagnóstico por imagem , Aprendizado de Máquina , COVID-19/diagnóstico por imagem , Neoplasias Pulmonares/diagnóstico por imagem
7.
Curr Microbiol ; 81(8): 231, 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38896297

RESUMO

Spirulina platensis, a photosynthetic cyanobacterium, has garnered attention for its potential role in environmental remediation due to its ability to absorb and metabolize toxic heavy metals. Understanding its response toward toxicity of one of the most common contaminants, Cr(VI) is crucial for assessing its efficacy in bioremediation efforts. This study aims to investigate the physiological and biochemical responses of Spirulina platensis to varying concentrations of Cr(VI) from 0.5 to 5 ppm, shedding light on its potential as a bioindicator for environmental contamination and its suitability for bioremediation purposes. The impact of Cr(VI) on cell density, biosorption, pigment levels, nutrient content, fluorescence response, and photosynthetic efficiency was examined. The study revealed a gradual reduction in cell density, biomass production, and biosorption efficiency with increasing Cr(VI) concentrations. Pigment levels, carbohydrate, protein, and lipid content showed significant decreases, indicating physiological stress. Fluorescence response and photosynthetic efficiency were also adversely affected, suggesting alterations in electron transfer dynamics. A threshold for chromium toxicity was observed at 0.5 ppm, beyond which significant physiological disturbances occurred. This investigation highlights the sensitivity of Spirulina platensis to Cr(VI) toxicity and its potential as a bioindicator for heavy metal contamination. Metal sorption was highest in 0.5 ppm Cr(VI) with 56.56% removal. Notably, at lower concentrations, Cr(VI) acted as an intermediate electron acceptor, enhancing the electron transport chain and potentially increasing biomass under controlled conditions. The findings underscore the importance of understanding the mechanisms underlying heavy metal stress in microalgae for effective environmental remediation strategies. The research highlights the dual role of chromium(VI) in influencing S. platensis, depending on the concentration, and underscores the importance of understanding metal ion interactions with photosynthetic organisms for potential applications in bioremediation.


Assuntos
Biodegradação Ambiental , Cromo , Fotossíntese , Spirulina , Cromo/metabolismo , Cromo/toxicidade , Spirulina/metabolismo , Spirulina/crescimento & desenvolvimento , Spirulina/efeitos dos fármacos , Spirulina/química , Fotossíntese/efeitos dos fármacos , Biomassa , Adsorção
8.
BMC Oral Health ; 24(1): 400, 2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38553672

RESUMO

BACKGROUND: Endodontic literature search revealed that no study has been conducted to evaluate the prevalence of apical periodontitis (AP) in root canal treated teeth from an adult Nepalese population of Madhesh Province. Consequently, little is known about the extent and risk factors associated with it. This study aimed to determine AP prevalence in root canal treated teeth from an adult Nepalese subpopulation and to analyze the related risk factors including age, sex, tooth type, type of coronal restoration and quality of root canal treatment and coronal restoration as predictors of AP. METHODS: Digital panoramic radiographs were evaluated. Periapical status of 300 root canal-treated teeth was scored by using the periapical index. The quality of root canal treatment and coronal restorations were categorized as adequate or inadequate through radiographic and clinical evaluation. The data were analyzed using univariate and multivariate logistic regression models. RESULTS: Prevalence of AP in the present study was 31.7%. In 45.7% of the treated teeth, quality of root canal treatment was adequate whereas 46% of the cases had adequate coronal restorations. Multivariate logistic regression analysis revealed statistically significant associations and remarkably increased risk for AP in teeth with inadequate root canal treatment (odds ratio [OR] = 7.92; 95% CI: 3.96-15.82; p < 0.001) whereas lower risk for AP was found in females (OR = 0.51; 95% CI: 0.28-0.90; p = 0.021) and in teeth restored with crown (OR = 0.22; 95% CI: 0.09-0.51; p < 0.001) and filling (OR = 0.18; 95% CI: 0.08-0.42; p < 0.001). Quality of coronal restoration, tooth type and age of the patient were not found to be the predictors of AP. CONCLUSIONS: Within the limits of this study, a high prevalence of AP and poor overall quality of root canal treatment and coronal restoration was found in the subpopulation studied. Quality of root canal treatment, type of coronal restoration and sex of the patient are significant predictors of possible AP development in root canal treated teeth. Substantial efforts are needed to improve the endodontic treatment standards.


Assuntos
Periodontite Periapical , Dente não Vital , Adulto , Feminino , Humanos , Estudos Transversais , Cavidade Pulpar , Nepal/epidemiologia , Restauração Dentária Permanente/efeitos adversos , Tratamento do Canal Radicular/efeitos adversos , Periodontite Periapical/epidemiologia , Prevalência , Obturação do Canal Radicular , Dente não Vital/epidemiologia
9.
Gastrointest Endosc ; 98(1): 122-129, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36889364

RESUMO

BACKGROUND AND AIMS: Large colon polyps removed by EMR can be complicated by delayed bleeding. Prophylactic defect clip closure can reduce post-EMR bleeding. Larger defects can be challenging to close using through-the-scope clips (TTSCs), and proximal defects are difficult to reach using over-the-scope techniques. A novel, through-the-scope suturing (TTSS) device allows direct closure of mucosal defects without scope withdrawal. The goal of this study was to evaluate the rate of delayed bleeding after the closure of large colon polyp EMR sites with TTSS. METHODS: A multicenter retrospective cohort study was performed involving 13 centers. All defect closure by TTSS after EMR of colon polyps ≥2 cm from January 2021 to February 2022 were included. The primary outcome was rate of delayed bleeding. RESULTS: A total of 94 patients (52% female; mean age, 65 years) underwent EMR of predominantly right-sided (n = 62 [66%]) colon polyps (median size, 35 mm; interquartile range, 30-40 mm) followed by defect closure with TTSS during the study period. All defects were successfully closed with TTSS alone (n = 62 [66%]) or with TTSS and TTSCs (n = 32 [34%]), using a median of 1 (interquartile range, 1-1) TTSS system. Delayed bleeding occurred in 3 patients (3.2%), with 2 requiring repeated endoscopic evaluation/treatment (moderate). CONCLUSION: TTSS alone or with TTSCs was effective in achieving complete closure of all post-EMR defects, despite a large lesion size. After TTSS closure with or without adjunctive devices, delayed bleeding was seen in 3.2% of cases. Further prospective studies are needed to validate these findings before wider adoption of TTSS for large polypectomy closure.


Assuntos
Pólipos do Colo , Ressecção Endoscópica de Mucosa , Idoso , Feminino , Humanos , Masculino , Colo/cirurgia , Colo/patologia , Pólipos do Colo/patologia , Colonoscopia/métodos , Ressecção Endoscópica de Mucosa/efeitos adversos , Hemorragia Pós-Operatória/epidemiologia , Hemorragia Pós-Operatória/etiologia , Estudos Retrospectivos , Instrumentos Cirúrgicos
10.
Endoscopy ; 55(8): 766-772, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-36693419

RESUMO

BACKGROUND : Multiple devices are available for tissue approximation. A new through-the-scope suturing (TTSS) device has recently been introduced; however, data on its scope of use and clinical effectiveness are limited. We aimed to assess the clinical course and effectiveness of this TTSS device. METHODS : A retrospective review was performed for consecutive patients who underwent TTSS application. Primary outcomes were technical and clinical success, and secondary outcomes included adverse events and long-term clinical success. RESULTS : 53 patients (mean age 67.8 years; 69.8 % females) were included, with a mean defect size of 32.6 mm (SD 11.9). Technical success was achieved in 51 patients (96.2 %). Clinical success was achieved in 49 patients (92.4 %). Two patients (3.8 %) experienced failed fistula closure after technical success. Long-term follow-up (> 30 days) was available for 45 patients (84.9 %), with a mean follow-up of 7.2 months. One patient (1.9 %) had self-reported bleeding that did not require further intervention. CONCLUSIONS : TTTS was an effective and safe method for the closure of large gastrointestinal defects and could be used for fistula closure and stent fixation, making it a valuable addition to the armamentarium of endoscopic closure devices.


Assuntos
Endoscopia Gastrointestinal , Fístula , Feminino , Humanos , Idoso , Masculino , Endoscopia Gastrointestinal/métodos , Estudos Retrospectivos , Resultado do Tratamento , Fístula/etiologia , Stents , Suturas
11.
Endoscopy ; 55(9): 865-870, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37207666

RESUMO

BACKGROUND: Delayed bleeding is among the most common adverse events associated with endoscopic mucosal resection (EMR) of nonampullary duodenal polyps. We evaluated the rate of delayed bleeding and complete defect closure using a novel through-the-scope (TTS) suturing system for the closure of duodenal EMR defects. METHODS: We reviewed the electronic medical records of patients who underwent EMR for nonampullary duodenal polyps of ≥ 10 mm and prophylactic defect closure with TTS suturing between March 2021 and May 2022 at centers in the USA. We evaluated the rates of delayed bleeding and complete defect closure. RESULTS: 36 nonconsecutive patients (61 % women; mean [SD] age, 65 [12] years) underwent EMR of ≥ 10-mm duodenal polyps followed by attempted defect closure with TTS suturing. The mean (SD) lesion size was 29 (19) mm, defect size was 37 (25) mm; eight polyps (22 %) involved > 50 % of the lumen circumference. Complete closure was achieved in all cases (78 % with TTS suturing alone), using a median of one TTS suturing kit. There were no cases of delayed bleeding and no adverse events attributed to application of the TTS suturing device. CONCLUSION: Prophylactic closure of nonampullary duodenal EMR defects using TTS suturing resulted in a high rate of complete closure and no delayed bleeding events.


Assuntos
Neoplasias Duodenais , Ressecção Endoscópica de Mucosa , Humanos , Feminino , Idoso , Masculino , Ressecção Endoscópica de Mucosa/efeitos adversos , Ressecção Endoscópica de Mucosa/métodos , Estudos de Coortes , Resultado do Tratamento , Neoplasias Duodenais/cirurgia , Neoplasias Duodenais/patologia , Estudos Retrospectivos , Pólipos Intestinais/patologia , Estudos Multicêntricos como Assunto
12.
Bioorg Chem ; 138: 106658, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37331170

RESUMO

Multiple malignancies exhibit aberrant FASN expression, associated with enhanced de novo lipogenesis to meet the metabolic demands of rapidly proliferating tumour cells. Furthermore, elevated FASN expression has been linked to tumour aggressiveness and poor prognosis in a variety of malignant tumours, making FASN is an attractive target for anticancer drug discovery. Herein, we report the de novo design and synthesis of (2-(2-hydroxyphenyl)-1H-benzo[d]imidazol-5-yl)(piperazin-1-yl)methanone derivatives as novel FASN inhibitors with potential therapeutic applications in breast and colorectal cancers. Twelve (2-(2-hydroxyphenyl)-1H-benzo[d]imidazol-5-yl)(piperazin-1-yl)methanone derivatives (CTL) were synthesized and evaluated for FASN inhibition and cytotoxicity against colon cancer (HCT-116, Caco-2 cell lines), breast cancer (MCF-7 cell line) and normal cell line (HEK-293). Compounds CTL-06 and CTL-12 were chosen as the most promising lead molecules based on FASN inhibition and selective cytotoxicity profiles against colon and breast cancer cell lines. Compounds CTL-06 and CTL-12 demonstrate promising FASN inhibitory activity at IC50 of 3 ± 0.25 µM and 2.5 ± 0.25 µM when compared to the FASN inhibitor orlistat, which has an IC50 of 13.5 ± 1.0 µM. Mechanistic investigations on HCT-116 revealed that CTL-06 and CTL-12 treatment led to cell cycle arrest in Sub-G1/S phase along with apoptosis induction. Western blot studies indicated that CTL-06 and CTL-12 inhibited FASN expression in a dose-dependent manner. CTL-06 and CTL-12 treatment of HCT-116 cells enhanced caspase-9 expression in a dose-dependent manner, while upregulating proapoptotic marker Bax and downregulating antiapoptotic Bcl-xL. Molecular docking experiments of CTL-06 and CTL-12 with FASN enzyme revealed the mode of binding of these analogues in the KR domain of the enzyme.


Assuntos
Antineoplásicos , Neoplasias da Mama , Humanos , Feminino , Simulação de Acoplamento Molecular , Células CACO-2 , Células HEK293 , Ácido Graxo Sintases/química , Ácido Graxo Sintases/metabolismo , Imidazóis/farmacologia , Linhagem Celular Tumoral , Apoptose , Antineoplásicos/química
13.
Curr Microbiol ; 81(1): 4, 2023 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-37947887

RESUMO

The growing demand for Artemisia annua plants in healthcare, food, and pharmaceutical industries has led to increased cultivation efforts to extract a vital compound, Artemisinin. The efficacy of Artemisinin as a potent drug against malaria disease is well established but its limited natural abundance. However, the common practice of using chemical fertilizers for maximum yield has adverse effects on plant growth, development, and the quality of phytochemicals. To address these issues, the review discusses the alternative approach of harnessing beneficial rhizosphere microbiota, particularly plant growth-promoting rhizobacteria (PGPR). Microbes hold substantial biotechnological potential for augmenting medicinal plant production, offering an environmentally friendly and cost-effective means to enhance medicinal plant production. This review article aims to identify a suitable endophytic population capable of enabling Artemisia sp. to thrive amidst abiotic stress while simultaneously enhancing Artemisinin production, thereby broadening its availability to a larger population. Furthermore, by subjecting endophytes to diverse combinations of harsh conditions, this review sheds light on the modulation of essential artemisinin biosynthesis pathway genes, both up regulated and down regulated. The collective findings suggest that through the in vitro engineering of endophytic communities and their in vivo application to Artemisia plants cultivated in tribal population fields, artemisinin production can be significantly augmented. The overall aim of this review to explore the potential of harnessing microbial communities, their functions, and services to enhance the cultivation of medicinal plants. It outlines a promising path toward bolstering artemisinin production, which holds immense promise in the fight against malaria.


Assuntos
Artemisia annua , Artemisininas , Malária , Plantas Medicinais , Endófitos/genética , Endófitos/metabolismo , Artemisininas/metabolismo , Artemisia annua/genética , Artemisia annua/metabolismo , Fatores Socioeconômicos
14.
Postgrad Med J ; 99(1178): 1220-1225, 2023 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-37777188

RESUMO

The relationship between diabetes mellitus (DM) and high serum uric acid is complex and controversial. Many epidemiological studies have reported a positive association, whereas others have reported an inverse association or none. In the pathogenesis of DM it is the intracellular urate that is more important than the extracellular and dissociation between the two is possible. Evidence suggests that high serum uric acid induces insulin resistance and beta cell failure in animal models. Reduction of intracellular uric acid can be achieved by dietary measures such as reducing fructose and salt intake, and uric acid-lowering drugs. We suggest that in the Western diet, these elements play a crucial role in pathogenesis of DM. To determine the precise and exact interrelationship between intracellular and extracellular uric acid, well-designed studies are required. Besides this, clinical trials are needed to determine whether intracellular and extracellular urate reduction will provide benefit in prevention and treatment of DM and complications associated with it.


Assuntos
Diabetes Mellitus , Resistência à Insulina , Animais , Humanos , Ácido Úrico , Diabetes Mellitus/tratamento farmacológico
15.
Anim Biotechnol ; 34(7): 3267-3273, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36007588

RESUMO

To understand the pathology of natural cases of E. coli pathotypes infection in bovine calves, 45 cases of bovine calves, below one month of age, died due to enteritis were studied. Total seventeen cases (37.77%) turned positive for different pathotypes of E. coli by RT-PCR. Out of seventeen positive samples for E. coli, six cases (35.29%) were positive for eae gene, three cases (17.64%) for bfp gene and eight cases (47.05) for fimA gene of E. coli. Gross lesions in these cases showed pin-point to ecchymotic hemorrhages in the mucosa of jejunum, ileum and colon. The draining mesenteric lymph nodes were swollen, enlarged and showed cord -like structure. Histopathology of small intestine showed, villi lining cells were sloughed off, tips of villi capillary plexus were congested and hemorrhagic, and skipping lesions of microabscesses in the crypts of mucosa were observed. In the duodenum, necrosis of crypts and infiltration of mononuclear cells in the lamina propria and around Brunner's gland. In mesenteric lymph nodes the subscapular space were infiltrated with mononuclear cells with depletion of lymphoid follicles in cortical area. Peri-trabecular and medullary sinuses of mesenteric lymph nodes were necrosed.


Assuntos
Doenças dos Bovinos , Infecções por Escherichia coli , Animais , Bovinos , Escherichia coli/genética , Diarreia/veterinária , Diarreia/patologia , Infecções por Escherichia coli/veterinária , Infecções por Escherichia coli/patologia , Íleo/patologia , Jejuno/patologia
16.
J Assoc Physicians India ; 71(5): 11-12, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37355818

RESUMO

INTRODUCTION: The prevalence of hyperuricemia (HU) and hypouricemia (Hypo-U) is highly variable in different parts of India and there is a lack of data from the Eastern part of Uttar Pradesh. We designed this study in order to know the exact prevalence of HU and Hypo-U. MATERIALS AND METHODS: This is a cross-sectional study conducted in Varanasi. Data were collected from newly onset diabetic patients over a period of 1 year. RESULTS: Among the 312 diabetic patients, 12.5 and 19.23% were found to have HU and Hypo-U, respectively. Hypouricemic diabetic patients are phenotypically different. They are characterized by the female sex, higher glycated hemoglobin A1c (GlyHbA1c), higher estimated glomerular filtration rate (eGFR), lower body mass index (BMI), and less insulin resistance. CONCLUSION: The prevalence of HU and Hypo-U is high in newly-onset diabetic patients. Hypouricemic diabetic patients are phenotypically different. Hence routine screening of uric acid is essential for proper diagnosis and appropriate treatment of hypouricemic diabetic patients.


Assuntos
Diabetes Mellitus Tipo 2 , Hiperuricemia , Humanos , Feminino , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Ácido Úrico , Estudos Transversais , Hiperuricemia/epidemiologia , Prevalência , Fatores de Risco
17.
J Assoc Physicians India ; 71(12): 104, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38736065

RESUMO

We read with great interest the article "the deadly duo of hypertension and diabetes in India: further affirmation from a new epidemiological study" by Metri et al.1 They rightly pointed out that the prevalence of hypertension in Indian patients with type 2 diabetes patients is high and therefore early screening and management of hypertension should be included in the treatment of patients with type 2 diabetes. We wish to share our study findings on the prevalence of hypertension in newly onset diabetes mellitus (DM). We find that the prevalence of hypertension in all males and females with DM was 44.59, 44.34, and 45.16%, respectively.2.


Assuntos
Diabetes Mellitus Tipo 2 , Hipertensão , Humanos , Hipertensão/epidemiologia , Índia/epidemiologia , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/complicações , Prevalência , Masculino , Feminino , Pessoa de Meia-Idade , Adulto
18.
Entropy (Basel) ; 25(10)2023 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-37895583

RESUMO

We suggest a method to improve quantum correlations in cavity magnomechanics, through the use of a coherent feedback loop and magnon squeezing. The entanglement of three bipartition subsystems: photon-phonon, photon-magnon, and phonon-magnon, is significantly improved by the coherent feedback-control method that has been proposed. In addition, we investigate Einstein-Podolsky-Rosen steering under thermal effects in each of the subsystems. We also evaluate the scheme's performance and sensitivity to magnon squeezing. Furthermore, we study the comparison between entanglement and Gaussian quantum discord in both steady and dynamical states.

19.
Physiol Mol Biol Plants ; 29(12): 1915-1930, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38222287

RESUMO

Cyanobacteria are ancestors of chloroplast and perform oxygen-evolving photosynthesis similar to higher plants and algae. However, an obligatory requirement of photons for their growth results in the exposure of cyanobacteria to varying light conditions. Therefore, the light environment could act as a signal to drive the developmental processes, in addition to photosynthesis, in cyanobacteria. These Gram-negative prokaryotes exhibit characteristic light-dependent developmental processes that maximize their fitness and resource utilization. The development occurring in response to radiance (photomorphogenesis) involves fine-tuning cellular physiology, morphology and metabolism. The best-studied example of cyanobacterial photomorphogenesis is chromatic acclimation (CA), which allows a selected number of cyanobacteria to tailor their light-harvesting antenna called phycobilisome (PBS). The tailoring of PBS under existing wavelengths and abundance of light gives an advantage to cyanobacteria over another photoautotroph. In this work, we will provide a comprehensive update on light-sensing, molecular signaling and signal cascades found in cyanobacteria. We also include recent developments made in other aspects of CA, such as mechanistic insights into changes in the size and shape of cells, filaments and carboxysomes.

20.
J Lesbian Stud ; 27(2): 160-175, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36089860

RESUMO

In recent years, there has been an emerging critical discourse in South Asia that examines the changing contours of representational politics that could, in turn, be strategically mobilized to introduce an alternative idiom of same-sex love within a standard template of heterosexual storytelling. This has been complemented by an evaluation of alternative modes of sexual politics that need not necessarily conform to Western labels or paradigms of queer identities. Taking its cue from such discursive readings, this article demonstrates how Roopa Rao's web series, The "Other" Love Story (2016), revisits some of the dominant tropes, practices, and narrative conventions of the Hindi films, released in the 1990s, to create a counter-archive for the lesbian subject who, for the most part, was conspicuous by her very absence in the popular figurations of that period in South Asia. There is a perceptible strand of lingering nostalgia and artistic homage that undergirds such an experimental project that nevertheless also becomes a disruptive site for articulating an oppositional esthetics of romance. The subtlety and restraint of such a nuanced portrayal of dissident desires and queer intimacies thus not only resist the easy appropriations that women in the subcontinent are routinely subjected to (as veritable repositories of tradition and national identity) but also retrospectively reclaim a voice for an otherwise historically silenced discourse of sexuality for the masses.


Assuntos
Homossexualidade Feminina , Minorias Sexuais e de Gênero , Feminino , Humanos , Estudos Retrospectivos , Comportamento Sexual , Heterossexualidade
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