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BACKGROUND: Diabetes mellitus (DM) has affected over 387 million patients globally, expected to reach 592 million by the end of 2035. It is a metabolic disorder characterized by chronic hyperglycemia caused by either insulin deficiency, insulin resistance, or both. MATERIALS AND METHODS: The present study was designed to estimate the levels of different bone markers; serum Vitamin D, alkaline phosphatase, phosphorus, and calcium in patients with type 2 DM (T2DM). The study was conducted on patients aged 20-50 years diagnosed with T2DM, who were attending the outpatient/inpatient department of internal medicine. RESULTS: The levels of calcium were decreased in the patients with diabetes and also the study proved a negative correlation between calcium and random plasma glucose (RPG). There was a significant negative correlation between RPG and serum 25(OH)D3. CONCLUSION: We conclude that Vitamin D insufficiency is frequent in Moradabad, Uttar Pradesh. Sunshine exposure daily for 15 min on the face and hands is necessary to elevate the sunlight Vitamin D levels.
Résumé Contexte:Le diabète sucré (DM) a touché plus de 387 millions de patients dans le monde et devrait atteindre 592 millions d'ici la fin de l'année. 2035. Il s'agit d'un trouble métabolique caractérisé par une hyperglycémie chronique provoquée soit par un déficit en insuline, soit par une résistance à l'insuline, ou les deux.Matériels et méthodes:La présente étude a été conçue pour estimer les niveaux de différents marqueurs osseux; sérum Vitamine D, alkaline.Résultats:Les niveaux de calcium ont diminuéles patients diabétiques ainsi que l'étude ont prouvé une corrélation négative entre le calcium et le glucose plasmatique aléatoire (RPG). Il y avaitune corrélation négative significative entre le RPG et le sérum 25(OH)D3 phosphatase, phosphore et calcium chez les patients atteints de diabète de type 2 (DT2). L'étude a été menée sur des patients âgés de 20 à 50 ansdiagnostiqués atteints de DT2, qui fréquentaient le service de médecine interneambulatoire/hospitalisé.Conclusion:Nous concluons que l'insuffisance en vitamine D est fréquente chez Moradabad, Uttar Pradesh. Une exposition quotidienne au soleil pendant 15 minutes sur le visage et les mains est nécessaire pour élever les niveaux de vitamine D du soleil.
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Fosfatase Alcalina , Biomarcadores , Glicemia , Cálcio , Diabetes Mellitus Tipo 2 , Fósforo , Deficiência de Vitamina D , Vitamina D , Humanos , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Pessoa de Meia-Idade , Masculino , Adulto , Biomarcadores/sangue , Feminino , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/complicações , Deficiência de Vitamina D/epidemiologia , Fosfatase Alcalina/sangue , Glicemia/metabolismo , Glicemia/análise , Vitamina D/sangue , Vitamina D/análogos & derivados , Fósforo/sangue , Cálcio/sangue , Índia/epidemiologia , Adulto JovemRESUMO
BACKGROUND: Climate change exacerbates abiotic stresses, which are expected to intensify their impact on crop plants. Drought, the most prevalent abiotic stress, significantly affects agricultural production worldwide. Improving eggplant varieties to withstand abiotic stress is vital due to rising drought from climate change. Despite the diversity of wild eggplant species that thrive under harsh conditions, the understanding of their drought tolerance mechanisms remains limited. In the present study, we used chlorophyll fluorescence (ChlaF) imaging, which reveals a plant's photosynthetic health, to investigate desiccation tolerance in eggplant and its wild relatives. Conventional fluorescence measurements lack spatial heterogeneity, whereas ChlaF imaging offers comprehensive insights into plant responses to environmental stresses. Hence, employing noninvasive imaging techniques is essential for understanding this heterogeneity. RESULTS: Desiccation significantly reduced the leaf tissue moisture content (TMC) across species. ChlaF and TMC displayed greater photosystem II (PSII) efficiency after 54 h of desiccation in S. macrocarpum, S. torvum, and S. indicum, with S. macrocarpum demonstrating superior efficiency due to sustained fluorescence. PSII functions declined gradually in S. macrocarpum and S. torvum, unlike those in other species, which exhibited abrupt declines after 54 h of desiccation. However, after 54 h, PSII efficiency remained above 50% of its initial quantum yield in S. macrocarpum at 35% leaf RWC (relative water content), while S. torvum and S. indicum displayed 50% decreases at 31% and 33% RWC, respectively. Conversely, the susceptible species S. gilo and S. sisymbriifolium exhibited a 50% reduction in PSII function at an early stage of 50% RWC, whereas in S. melongena, this reduction occurred at 40% RWC. CONCLUSION: Overall, our study revealed notably greater leaf desiccation tolerance, especially in S. macrocarpum, S. torvum, and S. indicum, attributed to sustained PSII efficiency at low TMC levels, indicating that these species are promising sources of drought tolerance.
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Clorofila , Solanum melongena , Clorofila/metabolismo , Fluorescência , Solanum melongena/fisiologia , Solanum melongena/metabolismo , Folhas de Planta/fisiologia , Folhas de Planta/metabolismo , Dessecação , Complexo de Proteína do Fotossistema II/metabolismo , Fotossíntese/fisiologia , Estresse Fisiológico , Secas , Desidratação , Especificidade da EspécieRESUMO
BACKGROUND: Shallots are infected by various viruses like Onion yellow dwarf virus (OYDV), Leek yellow stripe virus (LYSV), Shallot latent virus (SLV) and Shallot virus X (ShVX). In India, they have been found to be persistently infected by ShVX. ShVX also infects onion and garlic in combination with other carlaviruses and potyviruses. ShVX is a member of genus Allexivirus of family Alphaflexiviridae. ShVX has a monopartite genome, which is represented by positive sense single-stranded RNA. Globally, only six complete and 3 nearly complete genome sequences of ShV X are reported to date. This number is insufficient to measure a taxon's true molecular diversity. Moreover, the complete genome sequence of ShVX from Asia has not been reported as yet. Therefore, this study was undertaken to generate a complete genome sequence of ShVX from India. RESULTS: Shallot virus X (ShVX) is one of the significant threats to Allium crop production. In this study, we report the first complete genome sequence of the ShVX from India through Next-generation sequencing (NGS). The complete genome of the ShVX (Accession No. OK104171), from this study comprised 8911 nucleotides. In-silico analysis of the sequence revealed variability between this isolate and isolates from other countries. The dissimilarities are spread all over the genome specifically some non-coding intergenic regions. Statistical analysis of individual genes for site-specific selection indicates a positive selection in NABP region. The presence of a recombination event was detected in coat protein region. The sequence similarity percentage and phylogenetic analysis indicate ShVX Indian isolate is a distinctly different isolate. Recombination and site-specific selection may have a function in the evolution of this isolate. This is the first detailed study of the ShVX complete genome sequence from Southeast Asia. CONCLUSION: This study presents the first report of the entire genome sequence of an Indian isolate of ShVX along with an in-depth exploration of its evolutionary traits. The findings highlight the Indian variant as a naturally occurring recombinant, emphasizing the substantial role of recombination in the evolution of this viral species. This insight into the molecular diversity of strains within a specific geographical region holds immense significance for comprehending and forecasting potential epidemics. Consequently, the insights garnered from this research hold practical value for shaping ShVX management strategies and providing a foundation for forthcoming studies delving into its evolutionary trajectory.
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Genoma Viral , Filogenia , Sequenciamento Completo do Genoma , Índia/epidemiologia , Genoma Viral/genética , Seleção Genética , Recombinação Genética , Flexiviridae/genética , Flexiviridae/isolamento & purificação , Doenças das Plantas/virologiaRESUMO
INTRODUCTION: Tubercular meningitis (TBM) is a serious public health problem in developing countries as it leads to significant mortality and residual neurological sequelae. The estimated mortality due to TBM in India is 1.5 per 100,000 population. In resource-limited settings, only the Ziehl-Neelsen (ZN) stain, which has very little sensitivity, is available. The World Health Organization recommended the Loop Mediated Isothermal Amplification (TB LAMP) assay for pulmonary tuberculosis only. We evaluated this test for tubercular meningitis as well. METHODOLOGY: In a cross-sectional study of 2-year duration, we have taken 239 cerebrospinal fluid samples from suspected cases of tubercular meningitis patients. ZN staining along with Mycobacteria Growth Indicator Tube (MGIT) TB culture, Xpert MTB/RIF Ultra assay, and commercial TB LAMP assay were performed for each sample. RESULTS: Out of 239 samples, 40 samples (16.73%) were found TB LAMP assay positive, 48 samples (20.08%) were found Xpert ultra-assay positive, 12 samples (5.02%) were MGIT TB culture positive and acid-fast bacillus smear positive in ten samples (4.18 %). Out of 12 MGIT-positive samples, all samples (100%) were TB LAMP and Xpert ultra positive and one sample (8.33%) was ZN smear positive. In 199 negative samples from the TB LAMP assay, eight samples were positive by Xpert, none by MGIT TB culture and AFB smear. Sensitivity and specificity were found as 100% and 87.66%, respectively, for the TB LAMP assay. CONCLUSION: TB LAMP assay is a rapid, cost-effective, sensitive, and specific test for tubercular meningitis infection in resource-limited settings.
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Técnicas de Diagnóstico Molecular , Mycobacterium tuberculosis , Técnicas de Amplificação de Ácido Nucleico , Tuberculose Meníngea , Humanos , Tuberculose Meníngea/diagnóstico , Mycobacterium tuberculosis/genética , Região de Recursos Limitados , Estudos Transversais , Sensibilidade e Especificidade , Escarro/microbiologiaRESUMO
BACKGROUND: Neo-adjuvant chemotherapy (NACT) followed by response assessment is the standard treatment algorithm for locally advanced oral cavity squamous cell carcinomas (OCSCC) in the Indian subcontinent. The 3-drug NACT regimen (Docetaxel-Cisplatin-5-FU) has shown improvement in overall survival over 2-drug regimen (Docetaxel-Cisplatin) in a phase-3 randomised study. We have analysed the 10-year outcomes with this treatment algorithm. METHODS: This was an institutional review board approved retrospective analysis of a prospectively collected dataset of borderline resectable OCSCC patients who underwent NACT. Patients who became resectable after NACT underwent surgery followed by appropriate adjuvant therapy. Patients who were unresectable received definitive chemoradiation (CTRT), palliative chemotherapy, radiotherapy or best supportive care based on general condition. RESULTS: A total of 3266 patients were included. The most common subsite was buccal mucosa and the most frequent indication was peri-tumoral edema upto zygoma. More than 2-drugs NACT was offered to 32.9% patients. Overall, 32.5% patients had a response to NACT. A total of 1358 patients were offered curative treatment, of which 929 (32%) underwent surgery and the rest underwent definitive chemo-radiation (14.8%). Patients who received more than 2-drugs NACT versus those who received 2-drugs had a 10-years OS of 21% vs 5.1% (p < 0.001). Patients who underwent surgery versus those who did not had a 10-year OS of 21.8% vs 4.1% (p < 0.001). Patients who achieved pCR had a 5-year OS of 45.3% vs 13.3% for those who did not (p < 0.001). CONCLUSION: NACT leads to long term survival benefit in patients of borderline resectable oral cavity cancer.
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Carcinoma de Células Escamosas , Neoplasias Bucais , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Quimioterapia Adjuvante , Cisplatino , Docetaxel/uso terapêutico , Neoplasias Bucais/tratamento farmacológico , Neoplasias Bucais/cirurgia , Terapia Neoadjuvante , Estudos RetrospectivosRESUMO
This study aimed to investigate the three different methods for the fabrication of quercetin (1%-3% w/w of protein) incorporated soy protein isolate (SPI) films and their effect on material properties. The quercetin incorporated SPI films prepared by these methods were characterized by Fourier transform infrared (FTIR) spectroscopy, UV-Vis spectrophotometer, tensile properties, and water uptake and leaching properties. The cross-linking pattern was revealed by the FTIR spectrum that showed formation of an ester group because of interaction between the quercetin hydroxyl group and the carboxyl side chain of SPI amino acids. The tensile strength of SPI films were enhanced with the addition of quercetin as it increased to a maximum of 6.17 MPa while neat SPI film had tensile strength 4.13 MPa. The prepared films exhibit significant antibacterial activity against Listeria monocytogenes and Escherichia coli. The In-silico docking analysis demonstrates that covalent and non-covalent forces play crucial roles in binding interaction. It shows the formation of four hydrogen bonds, two salt bridges along with one pi-alkyl interaction. The simulation studies reflect the crucial amino acid residues involved in SPI-quercetin binding. The effect of quercetin binding with SPI on its stability and compactness is revealed by Root mean square deviation (RMSD) and radius of gyration studies.
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Quercetina , Proteínas de Soja , Proteínas de Soja/química , Simulação de Acoplamento Molecular , Quercetina/farmacologia , Resistência à Tração , Antibacterianos/farmacologiaRESUMO
Introduction: The diverse subtypes of thyroid carcinoma have distinct clinical outcomes despite a comparable spectrum of underlying genetic alterations. Beyond genetic alterations, sparse efforts have been made to characterize the microbes associated with thyroid cancer. In this study, we examine the microbial profile of thyroid cancer. Methods: We sequenced the whole transcriptome of 70 thyroid cancers (40 papillary and 30 anaplastic). Using Infectious Pathogen Detector IPD 2.0, we analysed the relative abundance of 1060 microbes across 70 tumours from patients with thyroid cancer against 118 tumour samples from patients with breast, cervical, colorectal, and tongue cancer. Results: Our analysis reveals a significant prevalence of Cutibacterium acnes in 58.6% thyroid cancer samples compared to other cancer types (p=0.00038). Immune cell fraction analysis between thyroid cancer samples with high and low Cutibacterium loads identify enrichment of immunosuppressive cells, including Tregs (p=0.015), and other anti-inflammatory cytokines in the tumour microenvironment, suggesting an immune evasion/immunosuppression milieu is associated with the infection. A higher burden of Cutibacterium acnes was also found to be associated with poor survival defining a distinct sub-group of thyroid cancer. Conclusion: Cutibacterium acnes is associated with immune suppression and poor prognosis in a subpopulation of thyroid cancer. This study may help design novel therapeutic measures involving appropriate antibiotics to manage the disease better.
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Propionibacterium acnes , Neoplasias da Glândula Tireoide , Humanos , Propionibacterium acnes/genética , Antibacterianos , Sequência de Bases , Neoplasias da Glândula Tireoide/epidemiologia , Neoplasias da Glândula Tireoide/genética , Microambiente TumoralRESUMO
Iron overload is a primary cause of vital organ failure in patients with blood transfusion-dependent beta-thalassemia, and the hypoxia-inducible factor-1 α (HIF-1α) plays an important role in iron homeostasis pathway. HIF-1α modulation as a potential therapeutic target approach for iron chelation in hepatocyte cells. In this study, we used a 3D quantitative structure-activity relationship (QSAR) analysis to predict the inhibitory activity of HIF-1α inhibitors for iron chelation in liver cells. These feature descriptors were used to build a 3D-QSAR model, which was validated using Cost analysis and Fischer's randomization test. The model was used to virtually search the chemical compound libraries for potential inhibitor candidates with least inhibitory activity. The High-throughput Docking (Libdock) approach was used to dock large repositories of chemical molecules. Following Libdock score screening, the protein-ligand poses were docked using docking optimization (Cdocker) method. Binding energy were calculated for the protein-ligand poses of lowest -Cdocker Energy and -Cdocker Interaction. Further, side chain hopping method was used to generate lead novel ligand from best hit pose of ligand. Molecular dynamics simulation study to evaluate the lead novel ligand. Our study demonstrates the utility of 3D-QSAR pharmacophore screening in predicting the inhibitory activity for target. Inhibition strategy for iron chelation provides an alternative routes for reducing the iron content.
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Ammonia and arsenic pollution, along with the impact of climate change, represent critical factors influencing both the quantity and quality of aquaculture production. Recent developments have underscored the significance of these issues, as they not only disrupt aquatic ecosystems but also have far reaching consequences for human health. To addressed above challenges, an experiment was conducted to delineate the potential of manganese nanoparticles (Mn-NPs) to mitigate arsenic and ammonia pollution as well as high temperature stress in Pangasianodon hypophthalmus. The fish were exposed to different combination of arsenic and ammonia pollution as well as high temperature stress, while simultaneously incorporating diets enriched with Mn-NPs. The inclusion of Mn-NPs at 3 mg kg-1 in the diet led to a noteworthy downregulation of cortisol and HSP 70 gene expression, indicating their potential in mitigating stress responses. Furthermore, immune related gene expressions were markedly altered in response to the stressors but demonstrated improvement with the Mn-NPs diet. Interestingly, the expression of inducible nitric oxide synthase (iNOS), caspase (CAS), metallothionine (MT) and cytochrome P450 (CYP450) genes expression were prominently upregulated, signifying a stress response. Whereas, Mn-NPs at 3 mg kg-1 diet was significantly downregulated theses gene expression and reduces the stress. In addition to stress-related genes, we evaluated the growth-related gene expressions such as growth hormone (GH), growth hormone regulator 1 (GHR1 and GHRß), Insulin like growth factor (IGF1 and IGF2) were significantly upregulated whereas, myostatin and somatostatin were downregulated upon the supplementation of dietary Mn-NPs with or without stressors in fish. The gene expression of DNA damage inducible protein and DNA damage in response to head DNA % and tail DNA % was protected by Mn-NPs diets. Furthermore, Mn-NPs demonstrated a capacity to enhance the detoxification of arsenic in different fish tissues, resulting in reduced bioaccumulation of arsenic in muscle and other tissues. This finding highlights Mn-NPs as a potential solution for addressing bioaccumulation associated risks. Our study aimed to comprehensively examined the role of dietary Mn-NPs in mitigating the multiple stressors using gene regulation mechanisms, with enhancing the productive performance of P. hypophthalmus.
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Arsênio , Peixes-Gato , Hormônio do Crescimento Humano , Animais , Humanos , Manganês/toxicidade , Amônia , Ecossistema , Peixes-Gato/genética , Hormônio do CrescimentoRESUMO
It is an established fact that cancer is one of the most serious public health issues after coronary artery disease. Thus, exploring more effective and efficient therapeutic protocols over the traditional chemotherapeutic strategy is imperative to improving cancer survivorship and patient quality of life. In this respect, recent reports on molecularly engineered meso-substituted BODIPY have shown remarkable effects as a photoresponsive CO-releasing platform for the on-demand release of CO to treat cancer. Herein, we designed and synthesized two meso-substituted BODIPY photoresponsive CO-releasing molecules (photoCORMs). These BODIPY derivatives were tethered to a phenoxymethylpyridine moiety and oligoethylene glycol to maintain a hydrophilic-hydrophobic balance and improved cell permeability. The cell imaging experiments demonstrated that oligoethylene glycol containing photoCORM-1 efficiently internalized and preferentially localized at the mitochondria. To understand the mechanistic aspect of preferential localization into the mitochondria, live cell imaging was also carried out. Photorelease of CO was directly monitored by the inline IR spectroscopic technique. Finally, in vitro cytotoxicity and apoptosis assays on MDA-MB-231 cell lines clearly showed that photoCORM-1 induced apoptosis-mediated cell killing on account of photoreleased CO, which otherwise showed insignificant toxicity even at a very high concentration of â¼50 µM.
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Neoplasias , Qualidade de Vida , Humanos , Apoptose , Glicóis , Mitocôndrias , Neoplasias/tratamento farmacológicoRESUMO
Mycoplasma genitalium (M. genitalium) has evolved as a superbug, and the developing antimicrobial resistance with just a few treatment options available is an imminent concern. Due to the emergence of antibiotic resistance, a new antibiotic class or medications are required to combat this pathogen. The phosphate acetyltransferase (PTA) enzyme can be a suitable drug target which is essential for M. genitalium survival and involves in acetate metabolism. To efficiently find potent inhibitors, structure-based drug design approaches targeting the PTA of M. genitalium have been established. In this study, the three most potent phytochemical inhibitors were predicted from virtual screening and these are sitostanyl ferulate, beta-sitosterol-beta-D-glucoside, and brassinolide, with binding energies of - 9.66, - 9.60, and - 9.48 kcal/mol, respectively. The active site residues Thr-125, Arg-300, Ser-299, Tyr-272, and Lys-273 appear to be critical in binding the three predicted potent inhibitors. The results of the molecular dynamics study indicate that the three predicted phytochemical inhibitors have formed stable bonds with PTA. Molecular Mechanics Poisson-Boltzmann Surface Area (MM-PBSA) was utilized for the estimation of binding free energy of PTA-phytochemical complexes. Taken together, the findings of our computational work might aid in the development of possible potential drugs to treat and ameliorate the severity of M. genitalium infection.
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Introduction: Sinonasal carcinomas are a rare type of head and neck malignancy with various histologies. The outcomes of patients with unresectable locally advanced sinonasal carcinomas are poor. Hence, we performed this analysis to study the long-term outcomes of sinonasal adenocarcinoma (SNAC) and sinonasal undifferentiated carcinomas (SNUC) where neoadjuvant chemotherapy (NACT) has been given followed by local therapy. Methods: 16 patients with SNUC and adenocarcinoma who received NACT were found eligible for the study. Descriptive statistical analysis was performed for baseline characteristics, adverse events and treatment compliance. Kaplan Meir methods were used for the estimation of progression-free survival (PFS) and overall survival (OS). Results: Seven (43.75%) adenocarcinoma and nine (56.25%) SNUC patients were identified. The median age of the whole cohort was 48.5 years. The median number of cycles delivered was 3 (IQR 1-8). The incidence of grade 3-4 toxicity (CTCAE version 5.0) was 18.75%. The response was partial response or better in seven patients (43.75%). Post-NACT 11 patients (n = 15, 73%) were eligible for definitive therapy. The median PFS was 7.63 months (95% CI, 3.23 - NA months) and the median OS was 10.6 months (95% CI, 5.2-51.5 months). Median PFS and OS for those who underwent surgery post-NACT versus those who did not undergo surgery were 36.267 versus 3.7 months (p = 0.012) and 51.5 versus 10.633 months (p = 0.190), respectively. Conclusion: The study shows a favourable role of NACT in improving resectability, significant improvement in PFS and non-significant improvement in OS after surgery.
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The need for power-efficient devices, such as smart sensor nodes, mobile devices, and portable digital gadgets, is markedly increasing and these devices are becoming commonly used in daily life. These devices continue to demand an energy-efficient cache memory designed on Static Random-Access Memory (SRAM) with enhanced speed, performance, and stability to perform on-chip data processing and faster computations. This paper presents an energy-efficient and variability-resilient 11T (E2VR11T) SRAM cell, which is designed with a novel Data-Aware Read-Write Assist (DARWA) technique. The E2VR11T cell comprises 11 transistors and operates with single-ended read and dynamic differential write circuits. The simulated results in a 45 nm CMOS technology exhibit 71.63% and 58.77% lower read energy than ST9T and LP10T and lower write energies of 28.25% and 51.79% against S8T and LP10T cells, respectively. The leakage power is reduced by 56.32% and 40.90% compared to ST9T and LP10T cells. The read static noise margin (RSNM) is improved by 1.94× and 0.18×, while the write noise margin (WNM) is improved by 19.57% and 8.70% against C6T and S8T cells. The variability investigation using the Monte Carlo simulation on 5000 samples highly validates the robustness and variability resilience of the proposed cell. The improved overall performance of the proposed E2VR11T cell makes it suitable for low-power applications.
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Computadores de Mão , Simulação por Computador , Fenômenos FísicosRESUMO
Climate change has resulted in extreme temperature and drought around the globe, which poses serious threat to food security. Both heat and drought stress affects the production and productivity of wheat crop. The present study was undertaken to evaluate 34 landraces and elite cultivars of Triticum spp. for phenological and yield-related traits under optimum, heat, and combined heat-drought stress environments during 2020-2021 and 2021-2022. The pooled analysis of variance showed significant genotype × environment interaction, suggesting an influence of stress on trait expression. The trait performance of genotypes exhibited significant reduction under combined heat-drought stress as compared to optimum and heat stress environments. The maximum seed yield penalty was observed under combined heat-drought stress environment as compared to heat stress alone. Regression analysis indicated significant contribution of number of grains per spike towards stress tolerance. Based on Stress Tolerance Index (STI), genotypes Local-17, PDW 274, HI-8802, and HI-8713 were identified to be tolerant to both heat and combined heat and drought stress at Banda, whereas genotypes DBW 187, HI-8777, Raj 4120, and PDW 274 were tolerant at Jhansi location. The genotype PDW 274 showed stress tolerance under all treatments at both the locations. The genotypes PDW 233 and PDW 291 showed highest stress susceptibility index (SSI) across the environments. The number of grains per spike and test kernel weight were positively associated with seed yield across the environments and locations. The selected genotypes Local-17, HI 8802, and PDW 274 were identified to be the potential sources of heat and combined heat-drought tolerance, which may be utilized in hybridization to develop tolerant wheat genotypes and also for mapping of underlying genes/quantitative trait loci (QTLs).
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The similarities between thallium and potassium have suggested the use of calcium polystyrene sulfonate (CPS), an oral ion exchange resin, as a potential agent against thallium intoxication. Therefore, the study was an attempt to evaluate the efficacy of CPS and Prussian blue when given alone or in combination against thallium toxicity. The effect on binding capacity was investigated in terms of contact time, amount of CPS, influence of pH, simulated physiological solutions and interference of potassium ions. Also, rats were given single dose of thallium chloride (20 mg kg-1) and the treatment with PB and CPS was given for 28 days as CPS 30 g kg-1, orally, twice a day, PB 3 g kg-1, orally, twice a day and their combination. The effect of antidotal treatment was evaluated by calculating the thallium levels in various organs, blood, urine and feces. The results of the in vitro study indicated exceedingly quick binding in the combination of CPS and PB as compared to PB alone. Also, it was found that the binding capacity at pH 2.0 was considerably increased for PB with CPS (184.656 mg g-1) as compared to PB (37.771 mg g-1). Furthermore, statistically significant results were obtained in the in vivo study as after 7th day, thallium levels in blood of rats treated with combination were reduced by 64% as compared to control group and 52% as compared to alone PB treated group. Also, Tl retention in liver, kidney, stomach, colon and small intestine of combination treated rats was significantly reduced to 46%, 28%, 41%, 32% and 33% respectively, as compared to alone PB treated group. These findings demonstrate this as a good antidotal option against thallium intoxication.
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Antídotos , Tálio , Ratos , Animais , Tálio/metabolismo , Antídotos/farmacologia , Antídotos/uso terapêutico , Ferrocianetos/farmacologia , Ferrocianetos/uso terapêuticoRESUMO
Oral cancer is among the most common cancer in the world. Tobacco, alcohol, and viruses have been regarded as a well- known risk factors of OCC however, 15% of OSCC cases occurred each year without these known risk factors. Recently a myriad of studies has shown that bacterial infections lead to cancer. Accumulated shreds of evidence have demonstrated the role of Porphyromonas gingivalis (P. gingivalis) in OSCC. The virulence factor FimA of P. gingivalis activates the oncogenic pathways in OSCC by upregulating various cytokines. It also led to the inactivation of a tumor suppressor protein p53. The present Insilico study uses High-Throughput Virtual Screening, molecular docking, and molecular dynamics techniques to find the potential compounds against the target protein FimA. The goal of this study is to identify the anti-cancer lead compounds retrieved from natural sources that can be used to develop potent drug molecules to treat P.gingivalis-related OSCC. The anticancer natural compounds library was screened to identify the potential lead compounds. Furthermore, these lead compounds were subjected to precise docking, and based on the docking score potential lead compounds were identified. The top docked receptor-ligand complex was subjected to molecular dynamics simulation. A study of this insilico finding provides potent lead molecules which help in the development of therapeutic drugs against the target protein FimA in OSCC. Workflow of Structure based High-Throughput Virtual Screening, Molecular Docking and Molecular Dynamics Study of anticancer natural compounds against Fimbriae (FimA) protein of P. gingivalis in oral squamous cell carcinoma.
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The Nucleoside diphosphate kinase (NDK) protein of Porphyromonas gingivalis (P. gingivalis) plays a crucial role in immune evasion and inhibition of apoptosis in host cells and has the potential to cause cancer. However, its structure has not yet been characterized. We used an in-silico approach to determine the 3D structure of the P. gingivalis NDK. Furthermore, structural characterization and functional annotation were performed using computational approaches. The 3D structure of NDK was predicted through homology modeling. The structural domains predicted for the model protein belong to the NDK family. Structural alignment of prokaryotic and eukaryotic NDKs with the model protein revealed the conservation of the domain region. Structure-based phylogenetic analysis depicted a significant evolutionary relationship between the model protein and the prokaryotic NDK. Functional annotation of the model confirmed structural homology, exhibiting similar enzymatic functions as NDK, including ATP binding and nucleoside diphosphate kinase activity. Furthermore, molecular dynamic (MD) simulation technique stabilized the model structure and provides a thermo-stable protein structure that can be used as a therapeutic target for further studies.
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Núcleosídeo-Difosfato Quinase , Núcleosídeo-Difosfato Quinase/genética , Núcleosídeo-Difosfato Quinase/química , Núcleosídeo-Difosfato Quinase/metabolismo , Proteínas Reguladoras de Apoptose , Porphyromonas gingivalis/genética , Porphyromonas gingivalis/metabolismo , Filogenia , ApoptoseRESUMO
The wandering spleen, wandering liver, and wandering kidney are rare diagnoses that can be asymptomatic or are associated with nonspecific symptoms, making the clinical diagnosis elusive. In addition, given the small number of cases, these conditions are not well understood. Major complications of wandering spleen result from torsion of the vascular pedicle with resultant ischemia, physiologic dysfunction, and/or infarction. Wandering liver is commonly associated with bowel obstruction, particularly colonic volvulus, with very rare reports of hepatic ischemia or infarct. Wandering kidneys are not commonly associated with serious complications. In many cases, the wandering spleen, liver or kidney can be found in their anatomic position on static imaging and are only diagnosed during ultrasound or with serial radiographic or cross-sectional imaging with different patient positioning, or with prior studies demonstrating different locations of the involved organ. Treatment approaches for uncomplicated wandering spleen, liver, or kidney include watchful waiting and splenopexy, hepatopexy, or nephropexy, respectively. Complicated wandering spleens are treated with splenectomy. Given the variable clinical presentation of these conditions, imaging plays a pivotal role in diagnosing these rare and often incidentally discovered phenomena.
Assuntos
Baço Flutuante , Humanos , Baço Flutuante/complicações , Baço Flutuante/diagnóstico por imagem , Baço Flutuante/cirurgia , Anormalidade Torcional/diagnóstico por imagem , Anormalidade Torcional/cirurgia , Fígado , Infarto , Rim/diagnóstico por imagem , RadiologistasRESUMO
Introduction: ALK inhibitors are one of the success stories in precision medicine for treating patients with advanced ALK-positive NSCLC. Nevertheless, developing countries have substantial constraints in using ALK inhibitors, with limited data from India. Methods: An audit of a prospectively collected database of patients with advanced ALK-positive NSCLC treated from January 2013 to March 2018 was conducted. The SPSS version 20.0 was used for statistical analysis. Results: A total of 441 patients were available for analysis; 62.5% were males, median age was 50 (range: 19-75) years, and 78.3% had Eastern Cooperative Oncology Group performance status of 0 to 1. When all the lines of therapies were included in the analysis, ALK inhibitors could be used in 379 (85.9%) of the total ALK-positive patients and 292 patients (66.2%) received ALK inhibitors in the first line in any strategy. The major reason for not starting ALK inhibitors upfront was financial constraints in 69% of the patients. The median progression-free survival on first-line therapy for the entire cohort was 14.1 months (95% confidence interval [CI]: 12.2-15.9), with a significant difference between patients receiving ALK inhibitor in first line in any strategy versus not in first line (17.2 mo [95% CI: 14.5-19.9] versus 5.9 mo [95% CI: 4.2-7.6], p < 0.001). The median overall survival was 30.7 months (95% CI: 27.3-34.2), with 37.6 months (95% CI: 28.1-47.1) for ALK inhibitor in the first line versus 20.5 months (95% CI: 15.8-25.1) for subsequent lines of therapy (p < 0.001). Conclusions: Most of our patients with ALK-positive NSCLC were exposed to ALK inhibitors through various support mechanisms. Those patients who could receive ALK inhibitors in the first line had a significant survival advantage as compared with others.