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1.
Cell ; 186(23): 5135-5150.e28, 2023 11 09.
Artigo em Inglês | MEDLINE | ID: mdl-37865090

RESUMO

Mycobacterium tuberculosis (Mtb) cultured axenically without detergent forms biofilm-like cords, a clinical identifier of virulence. In lung-on-chip (LoC) and mouse models, cords in alveolar cells contribute to suppression of innate immune signaling via nuclear compression. Thereafter, extracellular cords cause contact-dependent phagocyte death but grow intercellularly between epithelial cells. The absence of these mechanopathological mechanisms explains the greater proportion of alveolar lesions with increased immune infiltration and dissemination defects in cording-deficient Mtb infections. Compression of Mtb lipid monolayers induces a phase transition that enables mechanical energy storage. Agent-based simulations demonstrate that the increased energy storage capacity is sufficient for the formation of cords that maintain structural integrity despite mechanical perturbation. Bacteria in cords remain translationally active despite antibiotic exposure and regrow rapidly upon cessation of treatment. This study provides a conceptual framework for the biophysics and function in tuberculosis infection and therapy of cord architectures independent of mechanisms ascribed to single bacteria.


Assuntos
Mycobacterium tuberculosis , Tuberculose , Animais , Camundongos , Biofilmes , Pulmão/microbiologia , Pulmão/patologia , Mycobacterium tuberculosis/fisiologia , Tuberculose/microbiologia , Tuberculose/patologia , Virulência , Fenômenos Biomecânicos
2.
Plant J ; 115(3): 662-677, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37097088

RESUMO

Plants can retain a memory of previous pathogen infections to mount a more robust defense response during subsequent infections by developing systemic acquired resistance (SAR). However, the mechanism through which plants develop and retain infection memory is not known. Experiments have shown the association of epigenetic modifications of specific defense-related genes with SAR. RSI1/FLD codes for a histone demethylase and is required for the activation of SAR in Arabidopsis. Here we report the identification of RRTF1 as an epigenetic target of RSI1. RRTF1 expression is higher in pathogen-free distal tissues of the rsi1 mutant. Experiments with loss-of-function and overexpression lines suggest RRTF1 is a negative regulator of basal defense against virulent and avirulent pathogens as well as SAR. Enhanced expression of RRTF1 in a wild-type (WT) background specifically impairs SAR without impacting local resistance. RSI1 is recruited at the RRTF1 locus in a SAR-inducible manner and contributes to H3K4me2 and H3K4me3 demethylation. Introduction of the rrtf1 mutation rescues the loss-of-SAR phenotype of rsi1 plants. However, these plants fail to retain infection memory beyond 7 days post-primary inoculation, whereas WT plants retain memory for at least 11 days. Our results demonstrate that RSI1 and RRTF1 form a functional module for retaining infection memory in Arabidopsis.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Arabidopsis/metabolismo , Regulação da Expressão Gênica de Plantas/genética , Doenças das Plantas/genética , Ácido Salicílico/metabolismo , Fatores de Transcrição/metabolismo
3.
Ecotoxicol Environ Saf ; 272: 116083, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38350220

RESUMO

Various strategies have been explored to mitigate the impact of harmful algal blooms (HABs). While chemical and physical methods have traditionally been employed to regulate microalgal growth, their prolonged adverse effects on the ecosystem are a cause for concern. Recognizing the integral role of macroalgae within the ecosystem, this study reveals the anti-algal properties of solvent-based extracts derived from the red macroalga Pyropia haitanensis as a means of preventing microalgal blooms. In our investigation, we initially assessed the growth-inhibitory effects of methanol and acetone extracts from P. haitanensis on five microalgae known to contribute to bloom-formation. Significantly reduced growth was observed in all microalgal species when inoculated with both methanol and acetone extracts. Further analysis revealed the effectiveness of the methanol extract (ME), and further fractionation with petroleum ether (PE), ethyl acetate (EA), and n-butanol (NB) for testing against Skeletonema costatum and Pseudo-nitzschia pungens. The methanol fractions exhibited strong inhibition, resulting in the complete elimination of both microalgae after 96 hours of exposure to PE, EA, and NB extracts. Gas Chromatography-Mass Spectroscopy (GC-MS) analysis of the ME and its solvent fractions identified 49 confirmed compounds. These compounds are likely potential contributors to the observed inhibition of microalgal growth. In conclusion, our findings suggest that solvent extracts from P. haitanensis possess substantial potential for the control of HABs, offering a promising avenue for further research and application in ecosystem management.


Assuntos
Microalgas , Rodófitas , Alga Marinha , Solventes , Ecossistema , Metanol , Acetona , Proliferação Nociva de Algas
4.
Soft Matter ; 19(37): 7057-7069, 2023 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-37706563

RESUMO

Recently, the study of long, slender living worms has gained attention due to their unique ability to form highly entangled physical structures, exhibiting emergent behaviors. These organisms can assemble into an active three-dimensional soft entity referred to as the "blob", which exhibits both solid-like and liquid-like properties. This blob can respond to external stimuli such as light, to move or change shape. In this perspective article, we acknowledge the extensive and rich history of polymer physics, while illustrating how these living worms provide a fascinating experimental platform for investigating the physics of active, polymer-like entities. The combination of activity, long aspect ratio, and entanglement in these worms gives rise to a diverse range of emergent behaviors. By understanding the intricate dynamics of the worm blob, we could potentially stimulate further research into the behavior of entangled active polymers, and guide the advancement of synthetic topological active matter and bioinspired tangling soft robot collectives.

5.
Mol Divers ; 2023 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-37749455

RESUMO

The WHO lists snakebite as a "neglected tropical disease". In tropical and subtropical areas, envenoming is an important public health issue. This review article describes the structure, function, chemical composition, natural inhibitors, and clinical applications of Elapids' Three Finger Toxins (3FTX) using scientific research data. The primary venomous substance belonging to Elapidae is 3FTX, that targets nAChR. Three parallel ß-sheets combine to create 3FTX, which has four or five disulfide bonds. The three primary types of 3FTX are short-chain, long-chain, and nonconventional 3FTX. The functions of 3FTX depend on the specific toxin subtype and the target receptor or ion channel. The well-known effect of 3FTX is probably neurotoxicity because of the severe consequences of muscular paralysis and respiratory failure in snakebite victims. 3FTX have also been studied for their potential clinical applications. α-bungarotoxin has been used as a molecular probe to study the structure and function of nAChRs (Nicotinic Acetylcholine Receptors). Acid-sensing ion channel (ASIC) isoforms 1a and 1b are inhibited by Mambalgins, derived from Black mamba venom, which hinders their function and provide an analgesic effect. α- Cobra toxin is a neurotoxin purified from Chinese cobra (Naja atra) binds to nAChR at the neuronal junction and causes an analgesic effect for moderate to severe pain. Some of the plants and their compounds have been shown to inhibit the activity of 3FTX, and their mechanisms of action are discussed.

6.
Int J Mol Sci ; 24(13)2023 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-37446321

RESUMO

Hepatitis B infection caused by the hepatitis B virus is a life-threatening cause of liver fibrosis, cirrhosis, and hepatocellular carcinoma. Researchers have produced multiple in vivo models for hepatitis B virus (HBV) and, currently, there are no specific laboratory animal models available to study HBV pathogenesis or immune response; nonetheless, their limitations prevent them from being used to study HBV pathogenesis, immune response, or therapeutic methods because HBV can only infect humans and chimpanzees. The current study is the first of its kind to identify a suitable chemically induced liver cirrhosis/HCC model that parallels HBV pathophysiology. Initially, data from the peer-reviewed literature and the GeneCards database were compiled to identify the genes that HBV and seven drugs (acetaminophen, isoniazid, alcohol, D-galactosamine, lipopolysaccharide, thioacetamide, and rifampicin) regulate. Functional enrichment analysis was performed in the STRING server. The network HBV/Chemical, genes, and pathways were constructed by Cytoscape 3.6.1. About 1546 genes were modulated by HBV, of which 25.2% and 17.6% of the genes were common for alcohol and lipopolysaccharide-induced hepatitis. In accordance with the enrichment analysis, HBV activates the signaling pathways for apoptosis, cell cycle, PI3K-Akt, TNF, JAK-STAT, MAPK, chemokines, NF-kappa B, and TGF-beta. In addition, alcohol and lipopolysaccharide significantly activated these pathways more than other chemicals, with higher gene counts and lower FDR scores. In conclusion, alcohol-induced hepatitis could be a suitable model to study chronic HBV infection and lipopolysaccharide-induced hepatitis for an acute inflammatory response to HBV.


Assuntos
Carcinoma Hepatocelular , Hepatite B Crônica , Hepatite B , Hepatite Alcoólica , Neoplasias Hepáticas , Humanos , Animais , Carcinoma Hepatocelular/genética , Vírus da Hepatite B/genética , Lipopolissacarídeos/efeitos adversos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Fosfatidilinositol 3-Quinases , Hepatite B Crônica/complicações , Hepatite B/complicações , Cirrose Hepática/complicações , Etanol , Biologia
7.
Molecules ; 28(6)2023 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-36985402

RESUMO

Finding structurally similar compounds in compound databases is highly efficient and is widely used in present-day drug discovery methodology. The most-trusted and -followed similarity indexing method is Tanimoto similarity indexing. Epigenetic proteins like histone deacetylases (HDACs) inhibitors are traditionally used to target cancer, but have only been investigated very recently for their possible effectiveness against rheumatoid arthritis (RA). The synthetic drugs that have been identified and used for the inhibition of HDACs include SAHA, which is being used to inhibit the activity of HDACs of different classes. SAHA was chosen as a compound of high importance as it is reported to inhibit the activity of many HDAC types. Similarity searching using the UNPD database as a reference identified aglaithioduline from the Aglaia leptantha compound as having a ~70% similarity of molecular fingerprints with SAHA, based on the Tanimoto indexing method using ChemmineR. Aglaithioduline is abundantly present in the shell and fruits of A. leptantha. In silico studies with aglaithioduline were carried out against the HDAC8 protein target and showed a binding affinity of -8.5 kcal mol. The complex was further subjected to molecular dynamics simulation using Gromacs. The RMSD, RMSF, compactness and SASA plots of the target with aglaithioduline, in comparison with the co-crystallized ligand (SAHA) system, showed a very stable configuration. The results of the study are supportive of the usage of A. leptantha and A. edulis in Indian traditional medicine for the treatment of pain-related ailments similar to RA. Our study therefore calls for further investigation of A. leptantha and A. edulis for their potential use against RA by targeting epigenetic changes, using in vivo and in vitro studies.


Assuntos
Artrite Reumatoide , Inibidores de Histona Desacetilases , Humanos , Inibidores de Histona Desacetilases/farmacologia , Inibidores de Histona Desacetilases/química , Amidas , Simulação de Dinâmica Molecular , Epigênese Genética , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/genética , Simulação de Acoplamento Molecular , Histona Desacetilases/genética , Proteínas Repressoras
8.
Plant Cell Rep ; 41(12): 2351-2362, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36152035

RESUMO

KEY MESSAGE: PWR, an epigenetic regulator, and PIF4, a transcription factor coordinately regulate both local resistance and systemic acquired resistance in Arabidopsis. A plant that gets infected once becomes resistant to subsequent infections through the development of systemic acquired resistance (SAR). Primary-infected tissues generate mobile signals that travel to systemic tissues and cause epigenetic changes associated with the SAR activation. Epigenetic regulators and the process of infection memory development are largely obscure for plants. POWERDRESS (PWR), a SANT domain-containing histone deacetylation (HDAC) promoting gene, is essential for thermomorphogenesis. Here we show that PWR is required for the SAR activation in Arabidopsis. The pwr mutants in Ler and Col-0 background possess normal local resistance but are defective in SAR. PHYTOCHROME-INTERACTING FACTOR 4 (PIF4) genetically interacts with PWR for flowering and thermomorphogenesis and is a negative regulator of basal immunity. We found a cooperative function for suppressing basal immunity and SAR activation by PIF4 and PWR, respectively. PWR promotes the expression of SA biosynthesis genes and the accumulation of SA in the systemic tissues. RSI1/FLD, which influences histone methylation and acetylation, is essential to infection memory development in Arabidopsis. Our results show that PWR and RSI1 positively regulate each other's expression. Exogenous application of HDAC inhibitor sodium butyrate abolishes SAR-mediated SA accumulation, expression of PR1 gene, and protection against pathogens after challenge inoculation. The results indicate the possibility of the involvement of HDAC activity of PWR in the formation of infection memory development in Arabidopsis.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/metabolismo , Proteínas de Arabidopsis/metabolismo , Histonas/metabolismo , Regulação da Expressão Gênica de Plantas , Histona Desacetilases/genética , Histona Desacetilases/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
9.
Metab Brain Dis ; 37(2): 411-426, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35023027

RESUMO

Parkinsonism is a neurodegenerative disease, mainly imbalance in dopamine and acetylcholine neurotransimitter in mid brain, which manifestation of dysfunctions of extrapyramidal like akinesia, tremor, rigidity and catalepsy etc., even cognitive and memory loss. The current study is framed to evaluate the effect of Vitex negundo (VNL) leaf extract in Haloperidol induced PD in rats. In vitro studies of antioxidant capacity were checked via DPPH and NO assays and identified its Acetylcholinesterase (AChE) inhibitory activity. Secondly the In vivo study of anti-PD activity in Haloperidol induced in rats were evaluated by Rotarod, morris water maze (MWM), cooks pole climb (CPC), actophotometer, novel object recognition (NOR), and T-maze were utilized to assess extrapyramidal, cognitive and memory function. Thirdly, changes in biomarker level viz. (AChE), butyrylcholinesterase. (BChE) in hippocampus and cortex, reduced glutathione (GSH), malondialdehyde (MDA), total protein (TP), superoxide dismutase (SOD), catalase (CAT), and dopamine level in the whole brain were measured. Finally, histopathology of hippocampus and cortex was examined at 40x magnification to access restoring integrity and maintaining the architecture of neuronal cell in the treatment group compared to control group and L-DOPA as a standard treatment group. V. negundo showed potent antioxidant potency on scavenging of DPPH (IC50 84.81 µg/ml) and NO (IC50 133.20 µg/ml) and possess AChE inhibitory potency (IC50 114.35 µg/ml) by in vitro studies. The Rotarod, MWM, CPC, Actophotometer, NOR, T-maze demonstrated that Haloperidol group administration declines performance time, ELT, TL and decreases locomotion, cognitive and memory respectively. The treatment of VNL 100, 200, and 400 mg/kg p.o. significantly (p < 0.05 to p < 0.0001) reversed. Whole brain AChE, BChE, and MDA level were significantly raised and GSH, TP, SOD, CAT and Dopamine were significantly declined in Haloperidol treated group rats, especially V. negundo 400 mg/kg p.o. highly significantly ameliorate the Haloperidol group altered pathological changes through the restoration of the cholinergic function, enhancing the antioxidant defense and by increasing the dopaminergic function. The current study provides validation of V. negundo for its anti-PD activity and could be a valuable source for the treatment of PD in future.


Assuntos
Doenças Neurodegenerativas , Doença de Parkinson , Vitex , Acetilcolinesterase , Animais , Butirilcolinesterase/farmacologia , Haloperidol/farmacologia , Neuroproteção , Estresse Oxidativo , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Ratos
10.
Molecules ; 27(3)2022 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-35164341

RESUMO

Terminalia chebula Retz. forms a key component of traditional folk medicine and is also reported to possess antihepatitis C virus (HCV) and immunomodulatory activities. However, information on the intermolecular interactions of phytochemicals from this plant with HCV and human proteins are yet to be established. Thus, by this current study, we investigated the HCV NS3/4A inhibitory and host immune-modulatory activity of phytocompounds from T. chebula through in silico strategies involving network pharmacology and structural bioinformatics techniques. To start with, the phytochemical dataset of T. chebula was curated from biological databases and the published literature. Further, the target ability of the phytocompounds was predicted using BindingDB for both HCV NS3/4A and other probable host targets involved in the immune system. Further, the identified targets were docked to the phytochemical dataset using AutoDock Vina executed through the POAP pipeline. The resultant docked complexes with significant binding energy were subjected to 50 ns molecular dynamics (MD) simulation in order to infer the stability of complex formation. During network pharmacology analysis, the gene set pathway enrichment of host targets was performed using the STRING and Reactome pathway databases. Further, the biological network among compounds, proteins, and pathways was constructed using Cytoscape 3.6.1. Furthermore, the druglikeness, side effects, and toxicity of the phytocompounds were also predicted using the MolSoft, ADVERpred, and PreADMET methods, respectively. Out of 41 selected compounds, 10 were predicted to target HCV NS3/4A and also to possess druglike and nontoxic properties. Among these 10 molecules, Chebulagic acid and 1,2,3,4,6-Pentagalloyl glucose exhibited potent HCV NS3/4A inhibitory activity, as these scored a lowest binding energy (BE) of -8.6 kcal/mol and -7.7 kcal/mol with 11 and 20 intermolecular interactions with active site residues, respectively. These findings are highly comparable with Asunaprevir (known inhibitor of HCV NS3/4A), which scored a BE of -7.4 kcal/mol with 20 key intermolecular interactions. MD studies also strongly suggest that chebulagic acid and 1,2,3,4,6-Pentagalloyl glucose as promising leads, as these molecules showed stable binding during 50 ns of production run. Further, the gene set enrichment and network analysis of 18 protein targets prioritized 10 compounds and were predicted to potentially modulate the host immune system, hemostasis, cytokine levels, interleukins signaling pathways, and platelet aggregation. On overall analysis, this present study predicts that tannins from T. chebula have a potential HCV NS3/4A inhibitory and host immune-modulatory activity. However, further experimental studies are required to confirm the efficacies.


Assuntos
Antivirais/farmacologia , Hepacivirus/enzimologia , Serina Proteases/química , Serina Proteases/metabolismo , Taninos/farmacologia , Terminalia/química , Proteínas não Estruturais Virais/química , Proteínas não Estruturais Virais/metabolismo , Antivirais/efeitos adversos , Antivirais/química , Benzopiranos/farmacologia , Domínio Catalítico , Simulação por Computador , Glucosídeos/farmacologia , Hepacivirus/efeitos dos fármacos , Taninos Hidrolisáveis/farmacologia , Modelos Moleculares , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Farmacologia em Rede , Extratos Vegetais/farmacologia , Ligação Proteica , Conformação Proteica , Taninos/efeitos adversos , Taninos/química , Proteínas não Estruturais Virais/antagonistas & inibidores
11.
J Anim Physiol Anim Nutr (Berl) ; 106(5): 968-977, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34747072

RESUMO

An elaborate multiple regression analysis was done to arrive a nutrient requirement equation for goat including dry matter intake, DMI (kg/day), total digestible nutrient, TDN (g/day) and crude protein, CP (g/day) based on animal body weight (BW) (kg) and average daily gain (ADG)(g/day). The derived equations were highly significant (p < 0.001) and had high R2 (0.99) values. The estimated values of TDN, CP and DMI are compared with NRC (1981), Kearl (Nutrient Requirements of Ruminants in Developing Countries, All Graduate Theses and Dissertations, 1982), as well as ICAR (Livestock Management, 2013). The estimated total TDN and CP requirements at different body weights and ADG are close to the values of recommended feeding standards of Mandal et al. (Small Ruminant Res., 58, 2005, 201). The estimated DMI values are close to the values of ICAR (Livestock Management, 2013) but lower (26.5%-43.8%) as compared to NRC (1981). Regressed values are used to develop a linear programming (LP) model and a stochastic model (SM) for least-cost ration formulation for the Indian goat breed, whose average BW is about 45 kg and ADG is 130 (g/day), and which is solved using LP simplex and Generalised Reduced Gradient (GRG) nonlinear of Microsoft Excel. The models satisfy the nutrient requirement calculated by regression equations with minimum specified level of variation (usually 5%-10%) in CP and TDN. Both methods adequately meet the nutritional requirements. Therefore, an electronic sheet is developed in Excel to calculate DMI, TDN and CP for different body weights, ADG and formulate the ration by LP and stochastic model.


Assuntos
Dieta , Cabras , Ração Animal/análise , Animais , Peso Corporal , Dieta/veterinária , Complexo Ferro-Dextran , Nutrientes , Necessidades Nutricionais , Análise de Regressão
12.
J Indian Assoc Pediatr Surg ; 27(5): 613-616, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36530809

RESUMO

We present a case of left proximal femoral artery transection injury in 1½-year-old male child due to a fall over a bike handle after sustaining a road traffic accident. He was presented to the emergency room with a cut proximal end of the left femoral artery and a fracture upper end of the shaft of the femur seen at the wound site. Following initial resuscitation, the patient was planned for wound exploration, fracture stabilization, and femoral artery repair which were executed, and salvage of the lower limb of 1½-year-old child was achieved. We conclude that teamwork, training, and experience in repairing pediatric vessels and timely pediatric vascular repair play a pivotal role in the salvage of a limb and improvement of the quality of life of a child.

13.
Proc Natl Acad Sci U S A ; 115(35): 8665-8670, 2018 08 28.
Artigo em Inglês | MEDLINE | ID: mdl-30104353

RESUMO

Fracture fundamentally limits the structural stability of macroscopic and microscopic matter, from beams and bones to microtubules and nanotubes. Despite substantial recent experimental and theoretical progress, fracture control continues to present profound practical and theoretical challenges. While bending-induced fracture of elongated rod-like objects has been intensely studied, the effects of twist and quench dynamics have yet to be explored systematically. Here, we show how twist and quench protocols may be used to control such fracture processes, by revisiting Feynman's observation that dry spaghetti typically breaks into three or more pieces when exposed to large pure bending stresses. Combining theory and experiment, we demonstrate controlled binary fracture of brittle elastic rods for two distinct protocols based on twisting and nonadiabatic quenching. Our experimental data for twist-controlled fracture agree quantitatively with a theoretically predicted phase diagram, and we establish asymptotic scaling relations for quenched fracture. Due to their general character, these results are expected to apply to torsional and kinetic fracture processes in a wide range of systems.

14.
Trop Anim Health Prod ; 53(2): 315, 2021 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-33970344

RESUMO

The dairy farmers in the tropical region have limitations regarding "feedstuffs" available. A software program is required to meet the nutrient requirement with the available feeds at the cheapest cost. There are many techniques/software that are implemented to meet dairy animal nutrient requirements. However, there are no specific techniques that are appropriate for formulating rations for dairy cattle in the least cost manner. An android application Dairy Cattle Nutrition and Feed Calculator (DCN & FC) is developed with an aim of least-cost feed balancing system which will help a farmer to choose feeds to meet the nutrient requirement set for ration. The quantity of feed, fed to the cattle to meet the required needs, is determined by nutrient content, dry matter intake (DMI), crude protein (CP) and total digestible nutrients (TDN) of the feed. This program works in three phases. The first phase consists of creating equations for the estimation of DMI, TDN and CP based on the nutrient tables provided by ICAR (2013) for different categories of cattle such as Milch cattle, dry cattle, male calves, female calves and pre-ruminant animals for different physiological stages such as body weight, average daily gain, fat and milk, using regression analysis. The second phase is the development of a linear programming (LP) model to solve different cases of nutrient requirements for least cost. The final phase is the use of the android framework that uses linear programming to suggest sufficient feed that meets the nutrient requirements. The developed application is user friendly and available in different languages. With the combination of linear programming and regression analysis, the ration can be effectively formed using available feeds, and control the cost of the feeds.


Assuntos
Ração Animal , Dieta , Ração Animal/análise , Animais , Peso Corporal , Bovinos , Dieta/veterinária , Feminino , Masculino , Leite , Necessidades Nutricionais
15.
Eur Heart J Suppl ; 22(Suppl H): H62-H65, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32884473

RESUMO

Hypertension (HTN) is the greatest attributable risk factor for cardiovascular disease in India. Recent studies have reported the crude prevalence of HTN in India to be 25.3%. In the May Measurement Month (MMM) screening campaign of 2017 conducted in India, 31.8% had HTN. In order to ratify earlier results, and further understand the awareness and control levels of HTN in India, organizations that participated in MMM 2017 decided to participate in the MMM global screening initiative of the International Society of Hypertension for a 2nd consecutive year. A total of 345 234 individuals were screened in MMM 2018. There were more than 1000 screening locations that included hospitals, clinics, workplaces, and special health camps organized across the country. After applying multiple imputation, a total of 111 462 (32.3%) individuals had HTN of whom 63 415 (55.6%) were aware of HTN and 61 646 (55.3%) were on antihypertensive medicines, out of which 15 583 (25.3%) were uncontrolled. Overall 57 864 (41.3%) hypertensives were uncontrolled. About half (44.7%) of hypertensive population in India were not on treatment. Around two-thirds (65.7%, n = 226 924) had not measured their blood pressure (BP) in last 12 months and 64% measured their BP for the first time in their life during the campaign, which strongly indicates the need for large scale awareness drives. This study suggests that opportunistic periodic public health screening at a national level is needed to increase HTN detection, treatment, control, and countrywide awareness in highly populated nations like India.

17.
RNA ; 18(9): 1605-11, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22832025

RESUMO

The removal of intervening sequences (introns) from a primary RNA transcript is catalyzed by the spliceosome, a large ribonucleoprotein complex. At the start of each splicing cycle, the spliceosome assembles anew in a sequentially ordered manner on the pre-mRNA intron to be removed. We describe here the identification of a series of naphthalen-2-yl hydroxamate compounds that inhibit pre-mRNA splicing in vitro with mid- to high-micromolar values of IC(50). These hydroxamates stall spliceosome assembly at the A complex stage. A structure-activity analysis of lead compounds revealed three pharmacophores that are essential for splicing inhibition. Specifically, a hydroxamate as a zinc-binding group and a 6-methoxynaphthalene cap group are both critical, and a linker chain comprising eight to nine methylene groups is also important, for the specific binding to the docking site of a target protein molecule and precise positioning of the zinc binding group. As we found no correlation between the inhibition patterns of known histone deacetylases on the one hand and pre-mRNA splicing on the other, we conclude that these compounds may function through the inhibition of the activities of other, at present, unknown spliceosome-associated zinc metalloprotein(s).


Assuntos
Quelantes/química , Inibidores de Histona Desacetilases/química , Spliceossomos/metabolismo , Zinco/metabolismo , Quelantes/farmacologia , Células HeLa , Inibidores de Histona Desacetilases/farmacologia , Humanos , Precursores de RNA/metabolismo , Splicing de RNA/efeitos dos fármacos , Relação Estrutura-Atividade
18.
Bioorg Med Chem Lett ; 24(20): 4826-30, 2014 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-25240614

RESUMO

Histone deacetylase inhibitors (HDACi) pleiotropy is largely due to their nonselective inhibition of various cellular HDAC isoforms. Connecting inhibition of a specific isoform to biological responses and/or phenotypes is essential toward deconvoluting HDACi pleiotropy. The contribution of classes I and II HDACs to the antileishmanial activity of HDACi was investigated using the amastigote and promastigote forms of Leishmania donovani. We observed that the antileishmanial activities of HDACi are largely due to the inhibition of HDAC6-like activity. This observation could facilitate the development of HDACi as antileishmanial agents.


Assuntos
Antiprotozoários/farmacologia , Inibidores de Histona Desacetilases/farmacologia , Histona Desacetilases/metabolismo , Leishmania donovani/efeitos dos fármacos , Antiprotozoários/síntese química , Antiprotozoários/química , Relação Dose-Resposta a Droga , Inibidores de Histona Desacetilases/síntese química , Inibidores de Histona Desacetilases/química , Isoenzimas/antagonistas & inibidores , Isoenzimas/metabolismo , Leishmania donovani/enzimologia , Estrutura Molecular , Testes de Sensibilidade Parasitária , Relação Estrutura-Atividade
19.
Cureus ; 16(8): e67177, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39295710

RESUMO

Constrained implants have become more common in difficult primary total knee arthroplasty (TKA) cases in recent years because they may more effectively and conveniently handle the substantial instability that is evident in osteoarthritis of knees with severe varus deformity. However, the need for a constrained TKA in such conditions is controversial, as constraint implants come with a bargain of stability for longitivity. In this case report, we have successfully shown that even in cases of significant instability and bone loss, intraoperative conversion to a restricted device is rarely necessary. In our case report, a 83-year-old female had complaints of severe pain in bilateral knees, with the right knee more than the left knee, since 12 years with severe varus deformity in the right knee. Physical examination revealed swelling and medial joint line tenderness with restriction of range of motion in bilateral knees. Pre-anesthetic checkup of the patient was done and patient was given clearance for surgery under American Society of Anesthesiologist (ASA)-2, total knee arthroplasty with a long stem was done, extreme varus deformity was corrected, osteophytes removed and tibial bone loss was repaired with bone cement. Post operatively patient showed significant improvement and McMaster University and Western Ontario Osteoarthritis Index (WOMAC) and Knee Society Scores (KSS) for pain, stiffness, and physical function during everyday activities were significantly improved compared to pre-operative assessment.

20.
J Orthop Case Rep ; 14(10): 275-281, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39381308

RESUMO

Introduction: Pes planus, commonly known as flat foot, is characterized by the lowering of the medial longitudinal arch of the foot, leading to alterations in lower limb biomechanics and potential pain and injury. This condition can affect the mechanical alignment and dynamic function of the lower limb, potentially contributing to the development and progression of knee osteoarthritis (OA). This study aims to investigate the association between pes planus and medial compartment knee OA as well as its impact on the knee functional score. Materials and Methods: This cross-sectional study included 165 patients aged 20-72 years. Inclusion criteria were individuals with unilateral or bilateral flat feet, while exclusion criteria were other foot conditions, history of knee or ankle surgeries, rheumatoid arthritis, and limb length discrepancies. Clinical assessments included knee joint tenderness, foot arch measurement using the foot arch index, and radiographic evaluations of Meary's angle and tibiofemoral (TF) angle. The knee injury and osteoarthritis outcome score (KOOS) was used to assess knee function. Results: The study population had a mean age of 43.98 ± 13.17 years. Meary's angle ranged from 5 to 19° (mean 9.46), and the foot arch index ranged from 0.220 to 0.520 (mean 0.33). The TF angle ranged from 1.7 to 7.5° (mean 4.98). KOOS scores varied from 10 to 100 (mean 62.40). Patients with more severe flat feet (higher Meary's angle and foot arch index) had significantly lower KOOS scores, indicating worse knee function and greater pain. The correlations between foot arch index, Meary's angle, and KOOS scores were statistically significant (P = 0.001). Conclusion: This study demonstrates a strong association between flat foot severity and knee OA. Increased Meary's angle and foot arch index were correlated with worsened knee function and increased pain, as measured by KOOS scores. These findings highlight the importance of assessing foot posture in patients with medial compartment OA and suggest that early intervention and orthotic management could be beneficial in mitigating the progression and severity of knee OA in patients with pes planus.

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