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1.
Explor Target Antitumor Ther ; 5(3): 477-494, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38966181

RESUMEN

In recent times, there have been notable advancements in comprehending the potential anti-cancer effects of chrysin (CH), a naturally occurring flavonoid compound found abundantly in various plant sources like honey, propolis, and certain fruits and vegetables. This active compound has garnered significant attention due to its promising therapeutic qualities and minimal toxicity. CH's ability to combat cancer arises from its multifaceted mechanisms of action, including the initiation of apoptosis and the inhibition of proliferation, angiogenesis, metastasis, and cell cycle progression. CH also displays potent antioxidant and anti-inflammatory properties, effectively counteracting the harmful molecules that contribute to DNA damage and the development of cancer. Furthermore, CH has exhibited the potential to sensitize cancer cells to traditional chemotherapy and radiotherapy, amplifying the effectiveness of these treatments while reducing their negative impact on healthy cells. Hence, in this current review, the composition, chemistry, mechanisms of action, safety concerns of CH, along with the feasibility of its nanoformulations. To conclude, the recent investigations into CH's anti-cancer effects present a compelling glimpse into the potential of this natural compound as a complementary therapeutic element in the array of anti-cancer approaches, providing a safer and more comprehensive method of combating this devastating ailment.

2.
J Family Med Prim Care ; 13(7): 2545-2554, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39071033

RESUMEN

For medical fraternity, health system and policymakers to undertake effective countermeasures, a comprehensive assessment of the prevalence of anxiety among older adults is required; hence, we conducted a systematic review and meta-analysis using data pooled from surveys across the country. The search strategy was developed using medical subject headings (MeSH) terms and free-text keywords. We searched PubMed and Scopus for articles to report the prevalence of anxiety among older adults. The appraisal tool for cross-sectional studies was used for quality assessment. Prevalence from different studies was pooled together using the inverse variance heterogeneity method. Sensitivity analyses were performed to assess the impact of included studies' methodological quality on pooled results and to investigate potential causes of heterogeneity. Twenty-three studies were included in this systematic review. The overall pooled estimate of the prevalence of anxiety in older adults was 18.7% (95% CI: 2.4, 38.8). The studies had a high degree of heterogeneity. Publication bias was assessed using a Doi plot which showed an luis furuya-kanamori (LFK) index of 1.21 indicating minor asymmetry. Like other parts of the world, India has witnessed a rise in the number of elderly due to lower fertility rates, higher life expectancies and a shift in illness patterns from communicable to non-communicable. The number of elderly people suffering from diseases of mental health is expected to rise dramatically. This review consolidates the existing evidence to showcase anxiety as an upcoming public health problem requiring due focus from policymakers and health systems.

3.
Artículo en Inglés | MEDLINE | ID: mdl-39041320

RESUMEN

Helicobacter pylori, a leading human pathogen associated with duodenal ulcer and gastric cancer, presents a significant threat to human health due to increasing antibiotic resistance rates. This study investigates G-quadruplexes (G4s), which are non-canonical secondary structures form in G-rich regions within the H. pylori genome. Extensive research on G4s in eukaryotes has revealed their role in epigenetically regulating cellular processes like gene transcription, DNA replication, and oncogene expression. However, understanding of G4-mediated gene regulation in other organisms, especially bacterial pathogens, remains limited. Although G4 motifs have been extensively studied in a few bacterial species such as Mycobacterium, Streptococci, and Helicobacter, research on G4 motifs in other bacterial species is still sparse. Like in other organisms such as archaea, mammals, and viruses, G4s in H. pylori display a non-random distribution primarily situated within open reading frames of various protein-coding genes. The occurrence of G4s in functional regions of the genome and their conservation across different species indicates that their placement is not random, suggesting an evolutionary pressure to maintain these sequences at specific genomic sites. Moreover, G-quadruplexes show enrichment in specific gene classes, suggesting their potential involvement in regulating the expression of genes related to cell wall/membrane/envelope biogenesis, amino acid transport, and metabolism. This indicates a probable regulatory role for G4s in controlling the expression of genes essential for H. pylori survival and virulence. Biophysical techniques such as Circular Dichroism spectroscopy and Nuclear Magnetic Resonance were used to characterize G4 motifs within selected H. pylori genes. The study revealed that G-quadruplex ligand inhibited the growth of H. pylori, with minimal inhibitory concentrations in the low micromolar range. This suggests that targeting G4 structures could offer a promising approach for developing novel anti-H. pylori drugs.

5.
Artículo en Inglés | MEDLINE | ID: mdl-39009944

RESUMEN

Acute-phase inhibition of the pro-inflammatory alarmin S100A8/A9 improves cardiac function post-myocardial infarction (MI), but the mechanisms underlying the long-term benefits of this short-term treatment remain to be elucidated. Here, we assessed the effects of S100A8/A9 blockade with the small-molecule inhibitor ABR-238901 on myocardial neovascularization in mice with induced MI. The treatment significantly reduced S100A9 and increased neovascularization in the myocardium, assessed by CD31 staining. Proteomic analysis by mass-spectrometry showed strong myocardial upregulation of the pro-angiogenic proteins filamin A (~ 10-fold) and reticulon 4 (~ 5-fold), and downregulation of the anti-angiogenic proteins Ras homolog gene family member A (RhoA, ~ 4.7-fold), neutrophilic granule protein (Ngp, ~ 4.0-fold), and cathelicidin antimicrobial peptide (Camp, ~ 4.4-fold) versus controls. In-vitro, ABR-238901 protected against apoptosis induced by recombinant human S100A8/A9 in human umbilical vein endothelial cells (HUVECs). In conclusion, S100A8/A9 blockade promotes post-MI myocardial neovascularization by favorably modulating pro-angiogenic proteins in the myocardium and by inhibiting endothelial cell apoptosis.

6.
Sci Total Environ ; 948: 174474, 2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-38964407

RESUMEN

The current demand for composites reinforced with renewable fibers is greater than it has ever been. In comparison to glass fibers, natural fibers yield the advantages of lesser density and cost. Although comparable specific properties exist between glass and natural fibers, the latter shows lower strength. However, with the copper coating and chemical treatment of natural fibers, the strength of the composites can be increased nowadays. The current research investigation focuses on the life cycle assessment of the raw, chemically treated, and copper coated fiber reinforced bagasse and banana composites to compare the emissions on the environment of these samples to prove their applicability. The study includes all the processes, from the extraction of fibers to the formation of composites, i.e., from cradle to gate, and detailed inventory. The ReCiPe H midpoint method has been utilized in SimaPro software to quantify the emissions. The results indicate that the maximum global warming emission is due to the energy consumption used during the manufacturing of these composites. Electricity contribution for chemically treated and copper coated composites in global warming contribution is slightly greater than that of raw composites i.e., 73.275 % in C- BG/P, 73.06 % in Cu- BG/P, 73.65 % in C- BN/P and 74.28 % in Cu- BN/P which is comparatively higher than 63.8 % in R- BG/P and 64.97 % in R- BN/P. The next major contributions come from polylactic acid for all the three samples of bagasse fiber reinforced PLA composite and banana fiber reinforced PLA composite. The raw samples also show improved fiber strength compared to chemical and copper coated samples.

7.
MedComm (2020) ; 5(6): e582, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38827026

RESUMEN

Cancer, being the most formidable ailment, has had a profound impact on the human health. The disease is primarily associated with genetic mutations that impact oncogenes and tumor suppressor genes (TSGs). Recently, growing evidence have shown that X-linked TSGs have specific role in cancer progression and metastasis as well. Interestingly, our genome harbors around substantial portion of genes that function as tumor suppressors, and the X chromosome alone harbors a considerable number of TSGs. The scenario becomes even more compelling as X-linked TSGs are adaptive to key epigenetic processes such as X chromosome inactivation. Therefore, delineating the new paradigm related to X-linked TSGs, for instance, their crosstalk with autosome and involvement in cancer initiation, progression, and metastasis becomes utmost importance. Considering this, herein, we present a comprehensive discussion of X-linked TSG dysregulation in various cancers as a consequence of genetic variations and epigenetic alterations. In addition, the dynamic role of X-linked TSGs in sex chromosome-autosome crosstalk in cancer genome remodeling is being explored thoroughly. Besides, the functional roles of ncRNAs, role of X-linked TSG in immunomodulation and in gender-based cancer disparities has also been highlighted. Overall, the focal idea of the present article is to recapitulate the findings on X-linked TSG regulation in the cancer landscape and to redefine their role toward improving cancer treatment strategies.

8.
South Asian J Cancer ; 13(2): 150-156, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38919654

RESUMEN

AashitaBackground Primary intramedullary high-grade glioma (HGG) and glioblastoma of spinal cord are uncommon tumors of central nervous system. Treatment recommendations are based on current guidelines of intracranial HGG and glioblastoma multiforme (GBM). Methods We retrospectively analyzed records of 9,686 patients who reported to our center over past 7 years. Only three cases of primary intramedullary HGG of spinal cord were found. Results In this article, we have reported three cases of primary intramedullary HGG of spinal cord. A comparison of intracranial and intramedullary spinal HGG and review of literature is presented. Conclusion Despite aggressive treatment using surgery, radiation, and chemotherapy, the survival rates are dismal. Emerging evidence has shown difference in biological behavior of intracranial and spinal HGG. Genetic studies to understand the biology and prospective studies are needed.

9.
Neuroscience ; 552: 126-141, 2024 Aug 06.
Artículo en Inglés | MEDLINE | ID: mdl-38936458

RESUMEN

The mammalian brain's complete dependence on oxygen for ATP production makes it highly susceptible to hypoxia, at high altitudes or in clinical scenarios including anemia or pulmonary disease. Hypoxia plays a crucial role in the development of various brain disorders, such as Alzheimer's, Parkinson's, and other age-related neurodegenerative diseases. On the other hand, a decrease in environmental oxygen levels, such as prolonged stays at high elevations, may have beneficial impacts on the process of ageing and the likelihood of death. Additionally, the utilization of controlled hypoxia exposure could potentially serve as a therapeutic approach for age-related brain diseases. Recent findings indicate that the involvement of HIF-1α and the NLRP3 inflammasome is of significant importance in the development of Alzheimer's disease. HIF-1α serves as a pivotal controller of various cellular reactions to oxygen deprivation, exerting influence on a multitude of physiological mechanisms such as energy metabolism and inflammatory responses. The NLRP3 plays a crucial role in the innate immune system by coordinating the initiation of inflammatory reactions through the assembly of the inflammasome complex. This review examines the information pertaining to the contrasting effects of hypoxia on the brain, highlighting both its positive and deleterious effects and molecular pathways that are involved in mediating these different effects. This study explores potential strategies for therapeutic intervention that focus on restoring cellular balance and reducing neuroinflammation, which are critical aspects in addressing this severe neurodegenerative condition and addresses crucial inquiries that warrant further future investigations.


Asunto(s)
Hipoxia , Inflamación , Enfermedades Neurodegenerativas , Estrés Oxidativo , Humanos , Enfermedades Neurodegenerativas/metabolismo , Animales , Estrés Oxidativo/fisiología , Hipoxia/metabolismo , Inflamación/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Inflamasomas/metabolismo , Encéfalo/metabolismo
10.
Curr Protoc ; 4(6): e1030, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38923763

RESUMEN

Functional characterization of enzymes/proteins requires determination of the binding affinity of small molecules or other biomolecules with the target proteins. Several available techniques, such as proteomics and drug discovery strategies, require a precise and high-throughput assay for rapid and reliable screening of potential candidates for further testing. Surface plasmon resonance (SPR), a well-established label-free technique, directly measures biomolecular affinities. SPR assays require immobilization of one interacting component (ligand) on a conductive metal (mostly gold or silver) and a continuous flow of solution containing potential binding partner (analyte) across the surface. The SPR phenomenon occurs when polarized light excites the electrons at the interface of the metal and the dielectric medium to generate electromagnetic waves that propagate parallel to the surface. Changes in the refractive index due to interaction between the ligand and analyte are measured by detecting the reflected light, providing real-time data on kinetics and specificity. A prominent use of SPR is identifying compounds in crude plant extracts that bind to specific molecules. Procedures that utilize SPR are becoming increasingly applicable outside the laboratory setting, and SPR imaging and localized SPR (LSPR) are cheaper and more portable alternative for in situ detection of plant or mammalian pathogens and drug discovery studies. LSPR, in particular, has the advantage of direct attachment to test tissues in live-plant studies. Here, we describe three protocols utilizing SPR-based assays for precise analysis of protein-ligand interactions. © 2024 Wiley Periodicals LLC. Basic Protocol 1: SPR comparison of binding affinities of viral reverse transcriptase polymorphisms Basic Protocol 2: SPR screening of crude plant extract for protein-binding agents Basic Protocol 3: Localized SPR-based antigen detection using antibody-conjugated gold nanoparticles.


Asunto(s)
Resonancia por Plasmón de Superficie , Resonancia por Plasmón de Superficie/métodos , Ligandos , Unión Proteica , Proteínas/química , Proteínas/metabolismo , Oro/química
11.
Ind Psychiatry J ; 33(1): 13-29, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38853803

RESUMEN

Anxiety symptoms when coexisting with tuberculosis (TB), can have deleterious effects on treatment continuation that could contribute to the development of treatment resistance in TB. It is essential to understand the prevalence of anxiety in TB to develop clinical recommendations for its management. The primary objective of our review was to estimate the pooled prevalence of anxiety in TB patients along with the estimation of stress and quality of life in such patients. The relevant literature search on observational studies published in the English language till the year 2020 was carried out. A total of 8086 participants from 29 studies were included, of which 24 were cross-sectional studies and the remaining were case-control, and cohort studies. The estimated pooled prevalence of anxiety, comorbid depression, stress, and poor quality of life in TB patients was 32.54% [24.95, 41.18], 32.87% [25.79, 40.82], 52.68% [48.60, 56.72], and 79.51% [45.67, 94.72] respectively. When comparing the prevalence of anxiety across World Health Organization (WHO) regions, there was a statistically significant difference, with the African Region (AFR) having the highest prevalence i.e. 37.87% [29.59, 46.92], and the Western Pacific Region (WPR) having the lowest prevalence i.e. 15.83 % [12.72, 19.53]. The higher prevalence of anxiety in TB in the AFR and South-East Asian Region (SEAR) suggests a strong correlation with the developing status of these regions which calls for efforts to identify and treat the risk factors common to both anxiety and TB.

12.
SA J Radiol ; 28(1): 2766, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38725971

RESUMEN

Horseshoe lung (HL) is a rare congenital anomaly represented by the fusion of both lungs, posterior to the heart, and is typically associated with various bronchopulmonary and cardiovascular malformations. Multi-detector contrast enhanced CT is the imaging modality of choice to demonstrate the pathology and associated malformations. There has been inconsistency in the nomenclature used for such cases in literature. To resolve ambiguity, the authors emphasise that only two terms: HL and pseudo-HL be used on imaging to describe variants of this congenital malformation. Contribution: A description of the imaging features in four cases of HL, with their associated malformations and a review of the nomenclature.

13.
Cancers (Basel) ; 16(9)2024 Apr 27.
Artículo en Inglés | MEDLINE | ID: mdl-38730663

RESUMEN

In recent years, kaempferol, a natural flavonoid present in various fruits and vegetables, has received significant attention in gastrointestinal cancer research due to its varied therapeutic effects. Kaempferol has been proven to alter several molecular mechanisms and pathways, such as the PI3/Akt, mTOR, and Erk/MAPK pathway involved in cancer progression, showing its inhibitory effects on cell proliferation, survival, angiogenesis, metastasis, and migration. Kaempferol is processed in the liver and small intestine, but limited bioavailability has been a major concern in the clinical implications of kaempferol. Nano formulations have been proven to enhance kaempferol's efficacy in cancer prevention. The synergy of nanotechnology and kaempferol has shown promising results in in vitro studies, highlighting the importance for more in vivo research and clinical trials to determine safety and efficacy. This review aims to focus on the role of kaempferol in various types of gastrointestinal cancer and how the combination of kaempferol with nanotechnology helps in improving therapeutic efficacy in cancer treatment.

14.
Foods ; 13(10)2024 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-38790890

RESUMEN

The shelf life of whole wheat bread (WWB) significantly impacts its freshness and overall quality. This research investigated the impact of chitosan lactate (CL) on various characteristics influencing the shelf life of WWB, including its physical, chemical, textural, antimicrobial, and sensory attributes. These characteristics were evaluated by conducting various experiments such as physical inspection, moisture, impedance, swelling, color, texture, FTIR, microbiological, and sensory analysis. CL with different concentrations was incorporated into WWB formulations: P0.0 (0.0% w/w CL, control), P0.5 (0.5% w/w CL), P1.0 (1.0% w/w CL), P2.0 (2.0% w/w CL), and P3.0 (3.0% w/w CL). The inclusion of CL promoted the Maillard reaction (MR) compared to P0.0. The promotion of MR resulted in the formation of a shinier crust, which increased as the CL content was increased. P0.5 comprised large-sized pores and exhibited increased loaf height. CL-containing WWB formulations showed an increased moisture content and decreased impedance values compared to the control. FTIR analysis of P0.5 demonstrated the enhanced interaction and bonding of water molecules. P0.5 demonstrated optimal textural, colorimetric, and antimicrobial properties compared to other formulations. The sensory attributes of WWBs remain unchanged despite CL addition. In conclusion, P0.5 exhibited optimal characteristics associated with better quality and prolonged shelf life.

15.
Front Microbiol ; 15: 1403168, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38741745

RESUMEN

Overuse of antibiotics is accelerating the antimicrobial resistance among pathogenic microbes which is a growing public health challenge at the global level. Higher resistance causes severe infections, high complications, longer stays at hospitals and even increased mortality rates. Antimicrobial resistance (AMR) has a significant impact on national economies and their health systems, as it affects the productivity of patients or caregivers due to prolonged hospital stays with high economic costs. The main factor of AMR includes improper and excessive use of antimicrobials; lack of access to clean water, sanitation, and hygiene for humans and animals; poor infection prevention and control measures in hospitals; poor access to medicines and vaccines; lack of awareness and knowledge; and irregularities with legislation. AMR represents a global public health problem, for which epidemiological surveillance systems have been established, aiming to promote collaborations directed at the well-being of human and animal health and the balance of the ecosystem. MDR bacteria such as E. coli, Staphylococcus aureus, Pseudomonas aeruginosa, Enterococcus spp., Acinetobacter spp., and Klebsiella pneumonia can even cause death. These microorganisms use a variety of antibiotic resistance mechanisms, such as the development of drug-deactivating targets, alterations in antibiotic targets, or a decrease in intracellular antibiotic concentration, to render themselves resistant to numerous antibiotics. In context, the United Nations issued the Sustainable Development Goals (SDGs) in 2015 to serve as a worldwide blueprint for a better, more equal, and more sustainable existence on our planet. The SDGs place antimicrobial resistance (AMR) in the context of global public health and socioeconomic issues; also, the continued growth of AMR may hinder the achievement of numerous SDGs. In this review, we discuss the role of environmental pollution in the rise of AMR, different mechanisms underlying the antibiotic resistance, the threats posed by pathogenic microbes, novel antibiotics, strategies such as One Health to combat AMR, and the impact of resistance on sustainability and sustainable development goals.

16.
JBJS Case Connect ; 14(2)2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38635780

RESUMEN

CASE: A 47-year-old orthopaedic surgeon presented with acute volar left wrist pain. He performed over 250 robot-assisted knee arthroplasties each year. Color Doppler evaluation revealed bilateral persistent median arteries and bifid median nerves, with focal occlusive thrombosis of the left median artery. He was advised rest and oral aspirin. He could return to his professional activities after 1 month. He had no recurrence of symptoms at 1 year of follow-up. CONCLUSION: Orthopaedic surgeons use vibrating hand tools on a daily basis. The possibility of hand-arm vibration syndrome must be considered in the differential diagnosis of wrist pain among orthopaedic surgeons.


Asunto(s)
Artroplastia de Reemplazo de Rodilla , Síndrome del Túnel Carpiano , Procedimientos Quirúrgicos Robotizados , Robótica , Cirujanos , Trombosis , Humanos , Masculino , Persona de Mediana Edad , Arterias , Artralgia/cirugía , Síndrome del Túnel Carpiano/cirugía , Nervio Mediano/cirugía , Trombosis/etiología , Trombosis/complicaciones
17.
Cureus ; 16(3): e55942, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38601398

RESUMEN

Background Diarrhea is a major public health problem in under-five children worldwide. Various sociodemographic, environmental, and behavioral factors play a role in the occurrence of diarrheal disease in children under the age of five. This study aims to estimate the cumulative incidence of acute diarrheal diseases during a one-year study period and examine its association with the built environment factors among children under the age of five in selected underprivileged areas of Bhopal. Methodology We conducted this study in Bhopal, a city in central India. We surveyed the underprivileged dwellers of Vajpayee Nagar, Sanjay Nagar, and Mother India Colony of Bhopal city. This is a prospective cohort study with a one-year follow-up period to examine the cumulative incidence of acute diarrheal diseases among under-five-year-old children in the study area. Data were analyzed using SPSS version 25 (IBM Corp., Armonk, NY, USA). Results Data were collected from February 2021 to February 2022. A total of 658 families of eligible children were contacted to participate in the study. After excluding 38 participants for various reasons (denied consent: 3; lost to follow-up: 32; moved out of the study area: 3), data were finally analyzed for 620 participants. In the study among the under-five-year-old children, the cumulative incidence of acute diarrheal diseases was 23.8% (148 out of 620). In our study, lower age (adjusted odds ratio (OR) = 0.86, 95% confidence interval (CI) = 0.75-0.99, p = 0.041) and non-availability of flush latrine in the house (adjusted OR = 4.95, 95% CI = 1.80-13.59, p = 0.002) were statistically associated with a higher incidence of acute diarrheal disease among the study population. Conclusions In our investigation, we observed a cumulative incidence of diarrhea at 23.8% (148 out of 620) among the underprivileged under-five population residing in Bhopal, India. This incidence exhibited significant associations with younger age and the absence of in-house flush latrines.

18.
Health Sci Rep ; 7(4): e2072, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38660003

RESUMEN

Background: Scleroderma, also referred to as systemic sclerosis, is a multifaceted autoimmune condition characterized by abnormal fibrosis and impaired vascular function. Pathologically, it encompasses the persistent presence of inflammation, abnormal collagen buildup, and restructuring of blood vessels in various organs, resulting in a wide range of clinical symptoms. This review incorporates the most recent scientific literature on scleroderma, with a particular emphasis on its pathophysiology, clinical manifestations, diagnostic approaches, and treatment options. Methodology: A comprehensive investigation was carried out on numerous databases, such as PubMed, MEDLINE, Scopus, Web of Science, and Google Scholar, to collect pertinent studies covering diverse facets of scleroderma research. Results: Scleroderma presents with a range of systemic manifestations, such as interstitial lung disease, gastrointestinal dysmotility, Raynaud's phenomenon, pulmonary arterial hypertension, renal complications, neurological symptoms, and cardiac abnormalities. Serological markers, such as antinuclear antibodies, anti-centromere antibodies, and anti-topoisomerase antibodies, are important for classifying diseases and predicting their outcomes. Discussion: The precise identification of scleroderma is crucial for promptly and correctly implementing effective treatment plans. Treatment approaches aim to improve symptoms, reduce complications, and slow down the progression of the disease. An integrated approach that combines pharmacological agents, including immunosuppressants, endothelin receptor antagonists, and prostanoids, with nonpharmacological interventions such as physical and occupational therapy is essential for maximizing patient care. Conclusion: Through the clarification of existing gaps in knowledge and identification of emerging trends, our goal is to improve the accuracy of diagnosis, enhance the effectiveness of therapeutic interventions, and ultimately enhance the overall quality of life for individuals suffering from scleroderma. Ongoing cooperation and creative research are necessary to advance the field and achieve improved patient outcomes and new therapeutic discoveries.

19.
Immunology ; 172(3): 392-407, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38504502

RESUMEN

Treatment of tuberculosis (TB) is faced with several challenges including the long treatment duration, drug toxicity and tissue pathology. Host-directed therapy provides promising avenues to find compounds for adjunctively assisting antimycobacterials in the TB treatment regimen, by promoting pathogen eradication or limiting tissue destruction. Eicosanoids are a class of lipid molecules that are potent mediators of inflammation and have been implicated in aspects of the host response against TB. Here, we have explored the blood transcriptome of pulmonary TB patients to understand the activity of leukotriene B4, a pro-inflammatory eicosanoid. Our study shows a significant upregulation in the leukotriene B4 signalling pathway in active TB patients, which is reversed with TB treatment. We have further utilized our in-house network analysis algorithm, ResponseNet, to identify potential downstream signal effectors of leukotriene B4 in TB patients including STAT1/2 and NADPH oxidase at a systemic as well as local level, followed by experimental validation of the same. Finally, we show the potential of inhibiting leukotriene B4 signalling as a mode of adjunctive host-directed therapy against TB. This study provides a new mode of TB treatment along with mechanistic insights which can be further explored in pre-clinical trials.


Asunto(s)
Leucotrieno B4 , Mycobacterium tuberculosis , Transducción de Señal , Tuberculosis Pulmonar , Humanos , Leucotrieno B4/metabolismo , Tuberculosis Pulmonar/inmunología , Tuberculosis Pulmonar/tratamiento farmacológico , Tuberculosis Pulmonar/metabolismo , Mycobacterium tuberculosis/inmunología , Antituberculosos/uso terapéutico , Antituberculosos/farmacología , Masculino , Femenino , Adulto , Persona de Mediana Edad , NADPH Oxidasas/metabolismo , Interacciones Huésped-Patógeno
20.
J Interferon Cytokine Res ; 44(5): 221-231, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38530079

RESUMEN

Interleukin-17A is a pro-inflammatory cytokine that plays a key role in the immune response to many pathogens and implicated in autoimmune diseases. This molecule is also involved in providing protection to many bacterial and fungal infections of gastro-intestinal tract and respiratory mucosa. Although molecular aspect of IL-17A has been studied in few species, no data are available for buffalo, which is one of the major sources of milk production in India. Therefore, in the present study, IL-17A gene of Indian Murrah Buffalo origin was cloned, expressed, and analyzed using bioinformatic tools. The coding sequence of buffalo IL-17A gene was cloned in prokaryotic expression vector (pET-28a) followed by its expression, purification, and characterization. A computational analysis was performed to understand the sequence, structure, and evolutionary relationship of buIL-17A. It revealed that the length of buIL-17A sequence without signal peptide is 132 amino acids as in cattle. However, sequence identity is found to be 99% due to one amino substitution difference between buffalo and cattle. After analysis, it can be concluded that buIL-17A recombinant protein can be used as a potential immunobiological reagent for diagnostic and therapeutic purpose.


Asunto(s)
Secuencia de Aminoácidos , Búfalos , Interleucina-17 , Búfalos/genética , Búfalos/inmunología , Animales , Interleucina-17/genética , Interleucina-17/metabolismo , Interleucina-17/inmunología , Interleucina-17/química , Clonación Molecular , Filogenia , Bovinos , Modelos Moleculares , Proteínas Recombinantes/genética , Proteínas Recombinantes/química , Proteínas Recombinantes/inmunología
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