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1.
Crit Rev Biotechnol ; : 1-20, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38710611

RESUMO

Every year, a huge amount of lethal compounds, such as synthetic dyes, pesticides, pharmaceuticals, hydrocarbons, etc. are mass produced worldwide, which negatively affect soil, air, and water quality. At present, pesticides are used very frequently to meet the requirements of modernized agriculture. The Food and Agriculture Organization of the United Nations (FAO) estimates that food production will increase by 80% by 2050 to keep up with the growing population, consequently pesticides will continue to play a role in agriculture. However, improper handling of these highly persistent chemicals leads to pollution of the environment and accumulation in food chain. These effects necessitate the development of technologies to eliminate or degrade these pollutants. Degradation of these compounds by physical and chemical processes is expensive and usually results in secondary compounds with higher toxicity. The biological strategies proposed for the degradation of these compounds are both cost-effective and eco-friendly. Microbes play an imperative role in the degradation of xenobiotic compounds that have toxic effects on the environment. This review on the fate of xenobiotic compounds in the environment presents cutting-edge insights and novel contributions in different fields. Microbial community dynamics in water bodies, genetic modification for enhanced pesticide degradation and the use of fungi for pharmaceutical removal, white-rot fungi's versatile ligninolytic enzymes and biodegradation potential are highlighted. Here we emphasize the factors influencing bioremediation, such as microbial interactions and carbon catabolism repression, along with a nuanced view of challenges and limitations. Overall, this review provides a comprehensive perspective on the bioremediation strategies.

2.
Tuberculosis (Edinb) ; 147: 102517, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38733881

RESUMO

The extensive inability of the BCG vaccine to produce long-term immune protection has not only accelerated the disease burden but also progressed towards the onset of drug resistance. In our previous study, we have reported the promising effects of Bergenin (Berg) in imparting significant protection as an adjunct immunomodulator against tuberculosis (TB). In congruence with our investigations, we delineated the impact of Berg on T cells, wherein it enhanced adaptive memory responses by modulating key transcription factors, STAT4 and Akt. We translated this finding into the vaccine model of TB and observed a notable reduction in the burden of Mycobacterium tuberculosis (M.tb) in BCG-Berg co-immunized mice as compared to BCG vaccination. Moreover, Berg, along with BCG, also aided in a heightened proinflammatory response milieu that corroborates the host protective immune response against TB. Furthermore, this response aligns with the escalated central and resident memory responses by modulating the Akt-Foxo-Stat4 axis, which plays a crucial role in enhancing the vaccine efficacy of BCG. These findings showcase the utilization of immunomodulator Berg as an immunoprophylactic agent to upgrade immunological memory, making it a more effective defender against TB.

3.
ACS Biomater Sci Eng ; 10(4): 1966-1987, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38530973

RESUMO

A holistic biointegration of percutaneous bone-anchored metallic prostheses with both hard and soft tissues dictates their longevity in the human body. While titanium (Ti) has nearly solved osseointegration, soft tissue integration of percutaneous metallic prostheses is a perennial problem. Unlike the firm soft tissue sealing in biological percutaneous structures (fingernails and teeth), foreign body response of the skin to titanium (Ti) leads to inflammation, epidermal downgrowth and inferior peri-implant soft tissue sealing. This review discusses various implant surface treatments/texturing and coatings for osseointegration, soft tissue integration, and against bacterial attachment. While surface microroughness by SLA (sandblasting with large grit and acid etched) and porous calcium phosphate (CaP) coatings improve Ti osseointegration, smooth and textured titania nanopores, nanotubes, microgrooves, and biomolecular coatings encourage soft tissue attachment. However, the inferior peri-implant soft tissue sealing compared to natural teeth can lead to peri-implantitis. Toward this end, the application of smart multifunctional bioadhesives with strong adhesion to soft tissues, mechanical resilience, durability, antibacterial, and immunomodulatory properties for soft tissue attachment to metallic prostheses is proposed.


Assuntos
Peri-Implantite , Titânio , Humanos , Titânio/uso terapêutico , Próteses e Implantes , Osseointegração/fisiologia , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico
4.
Sci Rep ; 13(1): 21415, 2023 12 05.
Artigo em Inglês | MEDLINE | ID: mdl-38049427

RESUMO

Ornamental fish keeping is the second most preferred hobby in the world and it provides a great opportunity for entrepreneurship development and income generation. Controlling the environment in ornamental fish farm is a considerable challenge because it is affected by a variety of parameters like water temperature, dissolved oxygen, pH, and disease occurrences. One particular interesting ornamental fish species is goldfish (Carassius auratus). Machine learning (ML) and deep learning technique have significant potential in analysing voluminous data collected from fish farm. Through this technique, the fish farmers can get insight on feeding behaviour, fish growth patterns, predict diseases/stress, and environmental factors affecting fish health. The aim of the study is to analyze the behavioural changes in goldfish due to alterations in environmental parameters (water temperature and dissolved oxygen). Decision tree, Naïve Bayes classifier, K-nearest neighbour (KNN), and linear discriminant analysis (LDA) were used to analyse the behavioural change data. To compare the performance between all four classifiers, cross validation and confusion matrix used. The cross-validation error of LDA, Naïve Bayes classification, KNN and decision tree was 19.86, 28.08, 30.14 and 13.78 respectively. Decision tree was proved to be the most accurate and effective classifier. Different temperature and DO range were taken to predict fish behaviour. Some findings are, the behaviour of fish was rest between temperature 37.85 °C and 40.535 °C, erratic when temperature was greater than or equal to 40.535 °C, gasping when temperature was between 37.85 and 40.535 °C and when DO concentration was less than 6.58 mg/L. Blood parameter analysis has been done to validate the change in external behaviours with change in physiological parameters.


Assuntos
Carpa Dourada , Oxigênio , Animais , Teorema de Bayes , Carpa Dourada/fisiologia , Temperatura , Água
5.
ACS Pharmacol Transl Sci ; 6(11): 1600-1615, 2023 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-37974620

RESUMO

In the present era of the COVID-19 pandemic, viral infections remain a major cause of morbidity and mortality worldwide. In this day and age, viral infections are rampant and spreading rapidly. Among the most aggressive viral infections are ebola, AIDS (acquired immunodeficiency syndrome), influenza, and SARS (severe acute respiratory syndrome). Even though there are few treatment options for viral diseases, most of the antiviral therapies are ineffective owing to frequent mutations, the development of more aggressive strains, drug resistance, and possible side effects. Traditionally, herbal remedies have been used by healers, including for dietary and medicinal purposes. Many clinical and scientific studies have demonstrated the therapeutic potential of plant-derived natural compounds. Because of unsafe practices like blood transfusions and organ transplants from infected patients, medical supply contamination. Our antiviral therapies cannot achieve sterile immunity, and we have yet to find a cure for these pernicious infections. Herbs have been shown to improve therapeutic efficacy against a wide variety of viral diseases because of their high concentration of immunomodulatory phytochemicals (both immunoinhibitory and anti-inflammatory). Combined with biotechnology, this folk medicine system can lead to the development of novel antiviral drugs and therapies. In this Review, we will summarize some selected bioactive compounds with probable mechanisms of their antiviral actions, focusing on the immunological axis of these compounds.

6.
Front Microbiol ; 14: 1196101, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37465020

RESUMO

Population explosions, environmental deprivation, and industrial expansion led to an imbalanced agricultural system. Non-judicial uses of agrochemicals have decreased agrodiversity, degraded agroecosystems, and increased the cost of farming. In this scenario, a sustainable agriculture system could play a crucial role; however, it needs rigorous study to understand the biological interfaces within agroecosystems. Among the various biological components with respect to agriculture, mycorrhizae could be a potential candidate. Most agricultural crops are symbiotic with arbuscular mycorrhizal fungi (AMF). In this study, beetroot has been chose to study the effect of different AMFs on various parameters such as morphological traits, biochemical attributes, and gene expression analysis (ALDH7B4 and ALDH3I1). The AMF Gm-Funneliformis mosseae (Glomus mosseae), Acaulospora laevis, and GG-Gigaspora gigantean were taken as treatments to study the effect on the above-mentioned parameters in beetroot. We observed that among all the possible combinations of mycorrhizae, Gm+Al+GG performed best, and the Al-alone treatment was found to be a poor performer with respect to all the studied parameters. This study concluded that the more the combinations of mycorrhizae, the better the results will be. However, the phenomenon depends on the receptivity, infectivity, and past nutrient profile of the soil.

7.
Biochem Pharmacol ; 215: 115689, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37481132

RESUMO

Pseudomonas aeruginosa can utilize various virulence factors necessary for host infection and persistence. These virulence factors include pyocyanin, proteases, exotoxins, 2-heptyl-4-hydroxyquinoline N-oxide (HQNO), phospholipases, and siderophores that enable the bacteria to cause severe infections in immunocompromised individuals. P. aeruginosa falls into the category of nosocomial pathogens that are typically resistant to available antibiotics and therapeutic approaches. P. aeruginosa bio-film formation is a major concern in hospitals because it can cause chronic infection and increase the risk of mortality. Therefore, the development of new strategies to disrupt biofilm formation and improve antibiotic efficacy for the treatment of P. aeruginosa infections is crucial. Anti-biofilm and anti-quorum sensing (QS) activity can be viewed as an anti-virulence approach to control the infectious nature of P. aeruginosa. Inhibition of QS and biofilm formation can be achieved through pharmacological approaches such as phytochemicals and essential oils, which have shown promising results in laboratory studies. A regulatory protein called LasR plays a key role in QS signaling to coordinate gene expression. Designing an antagonist molecule that mimics the natural autoinducer might be the best approach for LasR inhibition. Here we reviewed the mechanism behind antibiotic resistance and alternative approaches to combat the pathogenicity of P. aeruginosa.


Assuntos
Pseudomonas aeruginosa , Transdução de Sinais , Humanos , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Biofilmes , Agregação Celular
8.
Bioresour Technol ; 376: 128836, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36898554

RESUMO

Streptomyces genera serve as adaptable cell factories for secondary metabolites with various and distinctive chemical structures that are relevant to the pharmaceutical industry. Streptomyces' complex life cycle necessitated a variety of tactics to enhance metabolite production. Identification of metabolic pathways, secondary metabolite clusters, and their controls have all been accomplished using genomic methods. Besides this, bioprocess parameters were also optimized for the regulation of morphology. Kinase families were identified as key checkpoints in the metabolic manipulation (DivIVA, Scy, FilP, matAB, and AfsK) and morphology engineering of Streptomyces. This review illustrates the role of different physiological variables during fermentation in the bioeconomy coupled with genome-based molecular characterization of biomolecules responsible for secondary metabolite production at different developmental stages of the Streptomyces life cycle.


Assuntos
Streptomyces , Streptomyces/genética , Streptomyces/metabolismo , Redes e Vias Metabólicas , Genômica
9.
Materials (Basel) ; 15(13)2022 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-35806552

RESUMO

The output of the latent heat storage devices (LHSDs), based on some phase change materials (PCMs), depends upon the thermophysical properties of the phase change material used. In this study, a paraffin-based nanofluid, blended with aluminum oxide (Al2O3) nanoparticles, is used as PCM for performance evaluation. A three-dimensional (3D) numerical model of regenerative type shell-and-tube LHSD is prepared using COMSOL Multiphysics® 4.3a software to estimate the percentage of melt and the average temperature of the analyzed nanofluids. The results of this study are in close agreement with those reported in the literature, thereby ensuring the validation of the numerically predicted results. The effects of adding the nanoparticles on the rate of melting, as well as solidification and rate of stored/liberated energy, are studied. The results revealed that, by adding 10% nanoparticles of Al2O3, the melting rate of pure-paraffin-based LHSD improved by about 2.25 times. In addition, the rate of solidification was enhanced by 1.8 times. On the other hand, the heat of fusion and specific heat capacities were reduced, which, in turn, reduced the latent and sensible heat-storing capabilities. From the outcomes of the present research, it can be inferred that combining LHSD with a solar water heater may be used in technologies such as biogas generation.

10.
Surg Neurol Int ; 13: 198, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35673661

RESUMO

Background: We analyzed the clinical and radiological parameters influencing functional outcomes and neurological recovery in patients with cervicothoracic junctional tuberculosis (TB). Methods: This was a retrospective analysis of 16 cases of cervicothoracic junction (CTJ) spinal TB; 11 patients were managed operatively, while five were managed conservatively. Patients' outcomes were assessed at 1 month, 1 year, and yearly thereafter and included an analysis of multiple outcome scores, various radiographic parameters, and sensitivity or resistance to anti-tubercular therapy. Results: Patients averaged 25.94 years of age, and typically had three-level vertebral involvement. They were followed for a mean duration of 24 months, and the duration of anti-tubercular therapy averaged 17 months. Patients demonstrated clinical improvement on Japanese Orthopedic Association score and Neck disability index (P < 0.005) starting from 1 month following initiation of treatment which continued in subsequent follow-up, along with change in radiological parameters consisting of mean segmental kyphotic angle from 18.98° to 15.13°, C2-C7 SVA from 16.13 mm to 22.61 mm, T1 slope from 22.80° to 14.66°, thoracic inlet angle from 75.35° to 63.25°, neck tilt from 51.81° to 48.33°, and cervical lordosis from 4.66° to -0.44° (P > 0.05) at the end of 1 year. Conclusion: Tuberculous affection of the dynamic CTJ is a challenging scenario in clinical practice and its management involves consideration of disease extent, neurological status, and effort toward restoration of normal alignment of spine in sagittal and coronal plane to get favorable clinical outcomes.

11.
Mol Biol Rep ; 49(5): 4107-4114, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35359235

RESUMO

BACKGROUND: Genetics driven interventions if adopted in conservation breeding projects may enhance the overall success by prioritizing breeding among genetically most competent individuals and delaying or completely diminishing the ill effects of inbreeding. METHODS AND RESULTS: In the present study, we investigated genetic make-up of 15 tigers housed at five different captive facilities of West Bengal in India and report the moderate level of genetic variation. We identified five tigers based on individual genetic attributes that may be prioritized for future breeding or animal exchange programmes. The occurrence of first and second order related individuals in captivity require management attention and they should be paired considering their immediate genetic background. CONCLUSION: Considering tiger as a case study, we highlight the use of genetic assessment and necessity to validate the studbook records in formulating adaptive management strategies for long-term conservation and management of species of interest.


Assuntos
Tigres , Animais , Conservação dos Recursos Naturais/métodos , DNA , Patrimônio Genético , Variação Genética , Endogamia , Tigres/genética
12.
Spinal Cord Ser Cases ; 8(1): 45, 2022 04 26.
Artigo em Inglês | MEDLINE | ID: mdl-35474303

RESUMO

INTRODUCTION: There exists sparse literature on Gunshot injuries (GSI) to the pediatric spine, its natural course, management protocols and outcomes following surgical intervention. Here, we present a projectile injury to the paediatric lumbar spine without any osseous disruption in a 5-year-old child requiring surgical management. CASE PRESENTATION: A 5-year-old child presented with a gunshot injury to the pediatric lumbar spine. On radiological imaging, there was no osseous disruption and an intraspinal canal projectile was embedded in an organised infected complex, compressing onto the left-sided L5 traversing nerve root with resultant grade 4 motor power of the left Extensor Hallucis Longus (EHL). Under fluoroscopic guidance using two separate mini-open incisions, the pellets were extracted. One from the spinal canal through left-sided L4 laminotomy and the other from the right paraspinal region. Post-surgical decompression and pellet retrieval there was gradual recovery to grade 5 motor power of Left EHL and improvement in the general condition of the child. CONCLUSION: The absence of osseous disruption can be attributed to the size of the projectile, widely spaced interlaminar spaces in the lumbar spine due to the absence of lumbar lordosis in the pediatric group and flexibility of the pediatric spine owing to its ligamentous laxity.


Assuntos
Radiculopatia , Ferimentos por Arma de Fogo , Criança , Pré-Escolar , Descompressão Cirúrgica , Humanos , Laminectomia , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/cirurgia , Radiculopatia/cirurgia , Ferimentos por Arma de Fogo/complicações , Ferimentos por Arma de Fogo/diagnóstico por imagem , Ferimentos por Arma de Fogo/cirurgia
13.
FEBS J ; 289(14): 4172-4191, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-34453865

RESUMO

Epigenetics involves changing the gene function without any change in the sequence of the genes. In the case of tuberculosis (TB) infections, the bacilli, Mycobacterium tuberculosis (M.tb), uses epigenetics as a tool to protect itself from the host immune system. TB is a deadly disease-causing maximum death per year due to a single infectious agent. In the case of TB, there is an urgent need for novel host-directed therapies which can effectively target the survival and long-term persistence of the bacteria without developing drug resistance in the bacterial strains while also reducing the duration and toxicity associated with the mainstream anti-TB drugs. Recent studies have suggested that TB infection has a significant effect on the host epigenome thereby manipulating the host immune response in the favor of the pathogen. M.tb alters the activation status of key genes involved in the immune response against TB to promote its survival and subvert the antibacterial strategies of the host. These changes are reversible and can be exploited to design very efficient host-directed therapies to fight against TB. This review has been written with the purpose of discussing the role of epigenetic changes in TB pathogenesis and the therapeutic approaches involving epigenetics, which can be utilized for targeting the pathogen.


Assuntos
Mycobacterium tuberculosis , Tuberculose , Antituberculosos/farmacologia , Antituberculosos/uso terapêutico , Epigênese Genética , Epigenômica , Humanos , Mycobacterium tuberculosis/genética , Tuberculose/tratamento farmacológico , Tuberculose/genética , Tuberculose/microbiologia
14.
J Orthop Case Rep ; 12(12): 109-113, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37056591

RESUMO

Introduction: Dislocation of the carpometacarpal (CMC) joint is a rare injury that results following high-velocity trauma. Although there are a few anecdotal reports of isolated CMC joint dislocations, there is scarce literature concerning dislocations involving multiple joints, especially those that are neglected and present late after injury. The injury is often missed when the patient presents to the surgeon since the swelling obscures the characteristic deformity, and the fracture may not be apparent on radiographs. When missed at the initial presentation, they can frequently result in pain, swelling, reduced grip strength, and arthritis. Such injuries require surgical management, along with prompt post-operative physiotherapy to enable the patient to regain satisfactory grip strength and range of motion. Case Report: We retrospectively analyzed four cases of multiple CMC joint dislocations that were managed surgically at our tertiary apex center. The average duration between injury and presentation to our center was five weeks. We used the quick disabilities of the arm, shoulder, and hand (DASH) scores and the maximum handgrip strength to assess the functional outcomes and the visual analog scale (VAS) to assess the pain at regular intervals. All patients showed an improvement in the Quick DASH scores, VAS scores, and the handgrip strength at the latest follow-up. All patients were able to return to their occupation. Conclusion: Early diagnosis and stabilization followed by early mobilization is the key to managing multiple CMC dislocations. The cases that present late are generally associated with contracted soft-tissue structures that prevent the relocation of the injury. Such cases require open reduction, along with a release of the contracted structures and internal fixation. Supervised physiotherapy in the post-operative period is essential to regain a satisfactory range of motion and grip strength.

15.
J Genet Eng Biotechnol ; 19(1): 146, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34596780

RESUMO

BACKGROUND: Chromobacterium species, through their bioactive molecules, help in combating biotic and abiotic stresses in plants and humans. The present study was aimed to identify, characterize and preserve in natural gums the violet-pigmented bacterial isolate TRFM-24 recovered from the rhizosphere soil of rice collected from Tripura state. RESULTS: Based on morphological, biochemical and 16S rRNA gene sequencing, the isolate TFRM-24 was identified as Chromobacterium violaceum (NAIMCC-B-02276; MCC 4212). The bacterium is saprophytic, free living and Gram negative. The strain was found positive for production of IAA, cellulase, xylanase and protease, and showed tolerance to salt (2.5%) and drought (-1.2 MPa). However, it showed poor biocontrol activity against soil-borne phytopathogens and nutrient-solubilizing abilitiets. C. violaceum strain TRFM-24 did not survive on tryptic soya agar (TSA) beyond 12 days between 4 and 32 °C temperature hence a method of preservation of this bacterium was attempted using different natural gums namely Acacia nilotica (babul), Anogeissus latifolia (dhavda), Boswellia serrata (salai) and Butea monosperma (palash) under different temperature regime (6-32 °C). The bacterium survived in babul gum (gum acacia), dhavda and salai solution at room temperature beyond a year. CONCLUSION: Based on polyphasic approach, a violet-pigmented isolate TRFM-24 was identified as Chromobacterim violaceum which possessed some attributes of plant and human importance. Further, a simple and low-cost preservation method of strain TRFM-24 at room temperature was developed using natural gums such as babul, dhavda and salai gums which may be the first report to our knowledge.

16.
Immunol Lett ; 240: 123-136, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34715236

RESUMO

Intracellular adhesion molecule 1 (ICAM-1) is one of the most extensively studied inducible cell adhesion molecules which is responsible for several immune functions like T cell activation, extravasation, inflammation, etc. The molecule is constitutively expressed over the cell surface and is regulated up / down in response to inflammatory mediators like cellular stress, proinflammatory cytokines, viral infection. These stimuli modulate the expression of ICAM-1 primarily through regulating the ICAM-1 gene transcription. On account of the presence of various binding sites for NF-κB, AP-1, SP-1, and many other transcription factors, the architecture of the ICAM-1 promoter become complex. Transcription factors in union with other transcription factors, coactivators, and suppressors promote their assembly in a stereospecific manner on ICAM-1 promoter which mediates ICAM-1 regulation in response to different stimuli. Along with transcriptional regulation, epigenetic modifications also play a pivotal role in controlling ICAM-1 expression on different cell types. In this review, we summarize the regulation of ICAM-1 expression both at the transcriptional as well as post-transcriptional level with an emphasis on transcription factors and signaling pathways involved.


Assuntos
Regulação da Expressão Gênica/imunologia , Molécula 1 de Adesão Intercelular/imunologia , Ativação Linfocitária , Transdução de Sinais/imunologia , Linfócitos T/imunologia , Transcrição Gênica/imunologia , Humanos , Elementos de Resposta/imunologia , Fatores de Transcrição/imunologia
17.
Saudi J Biol Sci ; 28(8): 4217-4223, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34354402

RESUMO

Carrot is a vital supply of dietary fiber, vitamins, and carotenoids, and it is also rich in antioxidants and minerals. Soil salinity significantly reduces the yield and quality of carrots. Mycorrhiza inoculum (AMF) is known to improve morphological and biochemical traits of vegetables even under saline conditions. But the role of AMF in combating soil salinity effect in carrot is not studied in detail. Therefore here, in the first set, carrot seeds are inoculated with microbes in a pot experiment under polyhouse condition. In total, we applied 7 treatments with different combinations of Mycorrhiza inoculum (Glomus mosseae (Gm) and Gigaspora gigantea (Gg)) and phosphate solubilizing bacteria (Pseudomonas fluroscens (Pf)). In pot experiment study the best two treatments were the combination of Gm + Pf + GG and Pf + GG. Both of these treatments were selected for validation under the open field conditions. Primarily, there seems to be a promising opportunity for AMF application to carrots under pot culture as well as under field trials because of promising effect towards morphological parameters, especially root weight, and disparities in nutrients and metabolites. Overall, our study highlights mycorrhizal fungi and other microbes' efficacy in achieving a successful carrot production under salinity stress.

18.
PLoS Pathog ; 16(12): e1009136, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33370418

RESUMO

The level of CD40 expression on dendritic cells (DCs) plays a decisive role in disease protection during Leishmania donovani (LD) infection. However, current understanding of the molecular regulation of CD40 expression remains elusive. Using molecular, cellular and functional approaches, we identified a role for Runx1 and Runx3 transcription factors in the regulation of CD40 expression in DCs. In response to lipopolysaccharide (LPS), tumor necrosis factor alpha (TNFα) or antileishmanial drug sodium antimony gluconate (SAG), both Runx1 and Runx3 translocated to the nucleus, bound to the CD40 promoter and upregulated CD40 expression on DCs. These activities of Runx proteins were mediated by the upstream phosphatidylinositol 3-kinase (PI3K)-Akt pathway. Notably, LD infection attenuated LPS- or TNFα-induced CD40 expression in DCs by inhibiting PI3K-Akt-Runx axis via protein tyrosine phosphatase SHP-1. In contrast, CD40 expression induced by SAG was unaffected by LD infection, as SAG by blocking LD-induced SHP-1 activation potentiated PI3K-Akt signaling to drive Runx-mediated CD40 upregulation. Adoptive transfer experiments further showed that Runx1 and Runx3 play a pivotal role in eliciting antileishmanial immune response of SAG-treated DCs in vivo by promoting CD40-mediated type-1 T cell responses. Importantly, antimony-resistant LD suppressed SAG-induced CD40 upregulation on DCs by blocking the PI3K-Akt-Runx pathway through sustained SHP-1 activation. These findings unveil an immunoregulatory role for Runx proteins during LD infection.


Assuntos
Antígenos CD40/imunologia , Subunidades alfa de Fatores de Ligação ao Core/imunologia , Células Dendríticas/imunologia , Regulação da Expressão Gênica/imunologia , Leishmaniose Visceral/imunologia , Animais , Antígenos CD40/biossíntese , Cricetinae , Humanos , Leishmania donovani/imunologia , Camundongos , Camundongos Endogâmicos BALB C
19.
Int Immunopharmacol ; 87: 106809, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32693356

RESUMO

The currently available anti-tuberculosis treatment (ATT) comprises exclusively of anti-bacterial drugs, is very lengthy, has adverse side effects on the host and leads to the generation of drug-resistant variants. Therefore, a combination therapy directed against the pathogen and the host is required to counter tuberculosis (TB). Here we demonstrate that [6]-Gingerol, one of the most potent and pharmacologically active ingredients of ginger restricted mycobacterial growth inside the lungs, spleen and liver of mice infected with Mycobacterium tuberculosis (Mtb). The spleen of [6]-Gingerol treated mice displayed increased expression of pro-inflammatory cytokines and enhanced Th1/Th17 responses confirming the immunomodulatory action of [6]-Gingerol. Finally, [6]-Gingerol displayed an excellent potential as an adjunct drug, along with front line anti-TB drug isoniazid. Interestingly, [6]-Gingerol displayed stark anti-tubercular activity against dormant/starved bacilli and drug-resistant variants of Mtb. Taken together, these results indicate strong prospects of [6]-Gingerol as an adjunct anti-mycobacterial and immunomodulatory drug for the treatment of drug-susceptible and drug-resistant strains of TB.


Assuntos
Antibacterianos/uso terapêutico , Catecóis/uso terapêutico , Álcoois Graxos/uso terapêutico , Isoniazida/uso terapêutico , Mycobacterium tuberculosis/fisiologia , Células Th1/imunologia , Células Th17/imunologia , Tuberculose/tratamento farmacológico , Animais , Carga Bacteriana , Quimioterapia Adjuvante , Modelos Animais de Doenças , Feminino , Zingiber officinale/imunologia , Humanos , Imunomodulação , Camundongos , Camundongos Endogâmicos C57BL
20.
Environ Monit Assess ; 192(6): 388, 2020 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-32440902

RESUMO

Hyptis suaveolens is considered one of the most potent invaders in the eastern part of Uttar Pradesh, India. Climate change especially precipitation variability along with invasion has enormous consequences. To understand how an invasive plant (H. suaveolens) performs and interacts with precipitation variability, particularly in tropical monsoon climate, is vital. To assess the above, three rainout shelters with simulated rainfall of 1600 mm (60% more rainfall than ambient), 1100 mm (average rainfall) and 800 mm (20% less rainfall than ambient) along with one unsheltered plot (open C) were established. Three invaded grassland (IG) and three uninvaded grasslands (NIG) patches of 1 × 1 m2 size were established randomly in each sheltered and unsheltered plot. Among the studied physiological properties and growth measurements, photosynthetic rate, height, diameter and biomass varied significantly with precipitation, in general, the maximum value of these in plots receiving maximum precipitation. Also, the aboveground biomass of H. suaveolens was found to be more sensitive towards precipitation treatment than belowground biomass. H. suaveolens biomass was linearly related to soil moisture (R2 = 0.73), and a linear combination of SM and soil pH increased the R2 value by 19%. The results indicate that H. suaveolens mediates certain soil properties especially related to N-mineralisation, to maintain a constant supply of nutrient, for faster growth under the favourable condition of enhanced precipitation. These findings suggest that the population of H. suaveolens has not evolved drought tolerance, so it is likely that H. suaveolens will not spread in the part of the world which is drier either naturally or due to climate change.


Assuntos
Pradaria , Hyptis , Biomassa , Monitoramento Ambiental , Índia , Chuva
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