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1.
Plant Sci ; : 112248, 2024 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-39265654

RESUMEN

The continuous change in climate, along with irregular rainfall patterns, poses a significant threat to sustainable agricultural productivity worldwide. Both high temperatures and drought stress are key factors limiting crop growth, and with global climate change, the occurrence of combined heat and drought stress is expected to rise. This will further exacerbate the vulnerability of agricultural yield. Simultaneous heat and drought stress is prevalent in field conditions, and while extensive research has been done on the individual effects of heat and drought stress on plants, little is known about the molecular mechanisms underlying plant acclimation to a combination of these stressors. The reproductive stage, especially the flowering phase, has been identified as the most sensitive to both heat and drought stress, leading to sterility in plants. However, our understanding of the combined stress response in commonly used crop plants is still limited. Hence, it is crucial to study and comprehend the effects and interactions between high temperatures and drought stress during the reproductive stages of crops. This review delves into the morpho-physiological changes in reproductive organs of various plant species under combined heat and drought stress and also details the molecular regulation of the mechanism of combined stress tolerance in plants. Notably, the article incorporates expression analyses of candidate genes in rice flowers, emphasizing the utilization of modern biotechnological methods to enhance stress tolerance in plants. Overall, the review provides a comprehensive insight into the regulation of floral development in plants following concurrent heat and drought stress.

2.
Nat Commun ; 15(1): 7080, 2024 Aug 17.
Artículo en Inglés | MEDLINE | ID: mdl-39152141

RESUMEN

C4'-modified nucleoside analogues continue to attract global attention for their use in antiviral drug development and oligonucleotide-based therapeutics. However, current approaches to C4'-modified nucleoside analogues still involve lengthy (9-16 steps), non-modular routes that are unamenable to library synthesis. Towards addressing the challenges associated with their syntheses, we report a modular 5-step process to a diverse collection of C4'-modified nucleoside analogues through a sequence of intramolecular trans-acetalizations of readily assembled polyhydroxylated frameworks. Overall, the 2-3 fold reduction in step-count compares favorably to even recently reported biocatalytic approaches and should ultimately enable new opportunities in drug design around this popular chemotype.


Asunto(s)
Nucleósidos , Nucleósidos/química , Nucleósidos/síntesis química , Estereoisomerismo , Antivirales/síntesis química , Antivirales/química , Acetales/química , Diseño de Fármacos
3.
J Soc Cardiovasc Angiogr Interv ; 3(4): 101267, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-39130172

RESUMEN

Background: Infiltrative diseases (IDs), including amyloidosis, sarcoidosis, and hemochromatosis, are characterized by abnormal cellular infiltration in multiple organs, including the heart. The prognosis of percutaneous coronary intervention (PCI) patients with underlying IDs has not been well-studied. We evaluated the prevalence of IDs in patients undergoing PCI and their association with post-PCI outcomes. Methods: The National Inpatient Sample (NIS) 2016-2020 database was used to identify PCI patients with ICD-10 codes for a retrospective analysis. PCI patients were then divided into those with and without underlying IDs, which included amyloidosis, sarcoidosis, and hemochromatosis. Multivariable logistic regression was performed for composite post-PCI outcomes analyses. Results: Among 2,360,860 patients admitted to undergo PCI, 7855 patients had underlying IDs. The highest prevalence was observed for sarcoidosis (0.2%) followed by hemochromatosis (0.07%) and amyloidosis (0.04%). Underlying amyloidosis was associated with worse composite post-PCI outcomes (odds ratio [OR], 1.6; 95% CI, 1.1-2.44; P = .02), including higher in-hospital mortality (OR, 1.9; 95% CI, 1.1-3.4; P = .04), higher risk of intra/post-PCI stroke (OR, 4.0; 95% CI, 1.1-16.0; P = .04), but not major bleeding (OR, 2.2; 95% CI, 0.97-5.03; P = .058). In contrast, underlying sarcoidosis (OR, 1.1; 95% CI, 0.87-1.41; P = .4), and hemochromatosis (OR, 1.18; 95% CI, 0.77-1.8; P = .44) were not associated with composite post-PCI outcomes. Amyloidosis patients undergoing PCI also had higher hospitalization charges ($212,123 vs $141,137; P = .03) and longer length of stay (8.2 vs 3.9 days; P < .001). Conclusions: Underlying amyloidosis was associated with worse post-PCI outcomes including higher in-hospital mortality, intra/post-PCI stroke, and socioeconomic burden. A multidisciplinary approach and future studies are needed to investigate the screening and treatment strategies in these patients.

4.
PLoS One ; 19(7): e0301596, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39042606

RESUMEN

BACKGROUND: Breast Cancer and cardiovascular diseases are amongst the two leading causes of mortality in the United States, and the two conditions are connected in part because of recognized cardiotoxicity of cancer treatments. The aim of this study is to investigate the predictors risk factors for thirty-day readmission in female breast cancer survivors presenting with acute heart failure. METHODS: This is a retrospective cohort study of acute heart failure (AHF) hospitalization in female patients with breast cancer in 2019 using the National Readmission Database (NRD), which is the largest publicly available all-payer inpatient readmission database in the United States. Our study sample included adult female patients aged 18 years and older. The primary outcome of interest was the rate of 30- day readmission. RESULTS: In 2019, there were 8332 total index admissions for AHF in females with breast cancer and 7776 patients were discharged alive. The mean age was 74.4 years (95% CI: 74, 74.7). The percentage of readmission at 30 days among those discharged alive was 21.8% (n = 1699). Hypertensive heart disease with chronic kidney disease accounted for the majority of readmission in AHF with breast cancer followed by sepsis, acute kidney injury, respiratory failure, pneumonia, and atrial fibrillation. Demographic factors including higher burden of comorbidities predict readmission. The total in-hospital mortality in index admission was 6.67% (n = 556) and for readmitted patients was 8.77% (n = 149). The mean length of stay for index admission was 7.5 days (95% CI: 7.25, 7.75). CONCLUSIONS: Readmission of female breast cancer survivors presenting with AHF is common and largely be attributed to high burden of comorbidities including hypertension, and chronic kidney disease. A focus on close outpatient follow-up will be beneficial in lowering readmissions.


Asunto(s)
Neoplasias de la Mama , Bases de Datos Factuales , Insuficiencia Cardíaca , Readmisión del Paciente , Humanos , Femenino , Readmisión del Paciente/estadística & datos numéricos , Insuficiencia Cardíaca/epidemiología , Insuficiencia Cardíaca/mortalidad , Estudios Retrospectivos , Neoplasias de la Mama/complicaciones , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/mortalidad , Anciano , Persona de Mediana Edad , Estados Unidos/epidemiología , Factores de Riesgo , Enfermedad Aguda , Anciano de 80 o más Años , Adulto , Comorbilidad
5.
Plant Cell Rep ; 43(8): 193, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-39008125

RESUMEN

Soil salinity is a major constraint for sustainable agricultural productivity, which together with the incessant climate change may be transformed into a severe threat to the global food security. It is, therefore, a serious concern that needs to be addressed expeditiously. The overproduction and accumulation of reactive oxygen species (ROS) and reactive nitrogen species (RNS) are the key events occurring during salt stress, consequently employing nitro-oxidative stress and programmed cell death in plants. However, very sporadic studies have been performed concerning different aspects of nitro-oxidative stress in plants under salinity stress. The ability of plants to tolerate salinity is associated with their ability to maintain the cellular redox equilibrium mediated by both non-enzymatic and enzymatic antioxidant defense mechanisms. The present review emphasizes the mechanisms of ROS and RNS generation in plants, providing a detailed evaluation of how redox homeostasis is conserved through their effective removal. The uniqueness of this article stems from its incorporation of expression analyses of candidate genes for different antioxidant enzymes involved in ROS and RNS detoxification across various developmental stages and tissues of rice, utilizing publicly available microarray data. It underscores the utilization of modern biotechnological methods to improve salinity tolerance in crops, employing different antioxidants as markers. The review also explores how various transcription factors contribute to plants' ability to tolerate salinity by either activating or repressing the expression of stress-responsive genes. In summary, the review offers a thorough insight into the nitro-oxidative homeostasis strategy for extenuating salinity stress in plants.


Asunto(s)
Homeostasis , Especies de Nitrógeno Reactivo , Especies Reactivas de Oxígeno , Tolerancia a la Sal , Especies Reactivas de Oxígeno/metabolismo , Especies de Nitrógeno Reactivo/metabolismo , Tolerancia a la Sal/genética , Regulación de la Expresión Génica de las Plantas , Estrés Oxidativo , Antioxidantes/metabolismo , Oxidación-Reducción , Plantas/metabolismo , Salinidad
6.
Biochem Pharmacol ; 226: 116400, 2024 08.
Artículo en Inglés | MEDLINE | ID: mdl-38945275

RESUMEN

The emergence of multidrug-resistant fungi is of grave concern, and its infections are responsible for significant deaths among immunocompromised patients. The treatment of fungal infections primarily relies on a clinical class of antibiotics, including azoles, polyenes, echinocandins, polyketides, and a nucleotide analogue. However, the incidence of fungal infections is increasing as the treatment for human and plant fungal infections overlaps with antifungal drugs. The need for new antifungal agents acting on different targets than known targets is undeniable. Also, the pace at which loss of fungal susceptibility to antibiotics cannot be undermined. There are several modes by which fungi can develop resistance to antibiotics, including reduced drug uptake, drug target alteration, and a reduction in the cellular concentration of the drug due to active extrusions and biofilm formation. The efflux pump's overexpression in the fungi primarily reduced the antibiotic's concentration to a sub-lethal concentration, thus responsible for developing resistant fungus strains. Several strategies are used to check antibiotic resistance in multi-drug resistant fungi, including synthesizing antibiotic analogs and giving antibiotics in combination therapies. Among them, the efflux pump protein inhibitors are considered potential adjuvants to antibiotics and can block the efflux of antibiotics by inhibiting efflux pump protein transporters. Moreover, it can sensitize the antifungal drugs to multi-drug resistant fungi with overexpressed efflux pump proteins. This review discusses the natural lead molecules, repurposable drugs, and formulation strategies to overcome the efflux pump activity in the fungi.


Asunto(s)
Antifúngicos , Farmacorresistencia Fúngica Múltiple , Hongos , Antifúngicos/farmacología , Humanos , Hongos/efectos de los fármacos , Hongos/metabolismo , Proteínas de Transporte de Membrana/metabolismo , Animales , Micosis/tratamiento farmacológico , Micosis/microbiología
7.
Small ; : e2401558, 2024 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-38829043

RESUMEN

By primarily adjusting the reagent amounts, particularly the volume of AgNO3 solution introduced, Ag2O cubes with decreasing sizes from 440 to 79 nm, octahedra from 714 to 106 nm, and rhombic dodecahedra from 644 to 168 nm are synthesized. 733 nm cuboctahedra are also prepared for structural analysis. With in-house X-ray diffraction (XRD) peak calibration, shape-related peak shifts are recognizable. Synchrotron XRD measurements at 100 K reveal the presence of bulk and surface layer lattices. Bulk cell constants also deviate slightly. They show a negative thermal expansion behavior with shrinking cell constants at higher temperatures. The Ag2O crystals exhibit size- and facet-dependent optical properties. Bandgaps red-shift continuously with increasing particle sizes. Optical facet effect is also observable. Moreover, synchrotron XRD peaks of a mixture of Cu2O rhombicuboctahedra and edge- and corner-truncated cubes exposing all three crystal faces can be deconvoluted into three components with the bulk and the [111] microstrain phase as the major component. Interestingly, while the unheated Cu2O sample shows clear diffraction peak asymmetry, annealing the sample to 450 K yields nearly symmetric peaks even when returning the sample to room temperature, meaning even moderately high temperatures can permanently change the crystal lattice.

8.
Int Immunopharmacol ; 138: 112584, 2024 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-38944948

RESUMEN

Heat shock proteins are a widely distributed group of proteins. It is constitutively expressed in almost all organisms and shows little variation throughout evolution. Previously, HSPs, particularly Hsp70, were recognized as molecular chaperones that aid in the proper three-dimensional folding of newly synthesized polypeptides in cells. Recently, researchers have focused on the potential induction of immune cells, including macrophages, antigen-specific CD8+ cytotoxic T cells, and PBMCs. It induces the expression of CC chemokines such as MIP-1α and RANTES, which are responsible for the chemotactic movement and migration of immune cells at the site of infection to neutralize foreign particles in vivo and in vitro in several cell lines but their effect on tumor-associated macrophages is still not known. These cytokines are also known to influence the movement of several immune cells, including CD8+ cytotoxic T cells, toward inflammatory sites. Therefore, the effect of tumor-derived autologous Hsp70 on the expression of MIP-lα and RANTES in tumor-associated macrophages (TAMs) was investigated. Our results indicated that Hsp70 treatment-induced MIP-lα and RANTES expression was significantly greater in TAMs than in NMOs. According to the literature, the CC chemokine shares the same receptor, CCR5, as HIV does for their action, and therefore could provide better completion to the virus for ligand binding. Furthermore, Hsp70-preactivated TAMs induced increased IL-2 and IFN-γ expression in T cells during coculture for 48 h and upregulated the antitumor immune response of the host. Therefore, the outcome of our study could be useful for developing a better approach to restricting the growth and progression of tumors.


Asunto(s)
Proteínas HSP70 de Choque Térmico , Linfocitos T Citotóxicos , Macrófagos Asociados a Tumores , Proteínas HSP70 de Choque Térmico/metabolismo , Proteínas HSP70 de Choque Térmico/inmunología , Linfocitos T Citotóxicos/inmunología , Humanos , Macrófagos Asociados a Tumores/inmunología , Macrófagos Asociados a Tumores/metabolismo , Quimiocina CCL5/metabolismo , Línea Celular Tumoral , Neoplasias/inmunología , Neoplasias/terapia , Quimiocinas CC/metabolismo , Quimiocinas CC/inmunología , Activación de Macrófagos
9.
Pharm Nanotechnol ; 2024 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-38757164

RESUMEN

The rise in global cancer burden, notably breast cancer, emphasizes the need to address chemotherapy-induced cognitive impairment, also known as chemobrain. Although chemotherapy drugs are effective against cancer, they can trigger cognitive deficits. This has triggered the exploration of preventive strategies and novel therapeutic approaches. Nanomedicine is evolving as a promising tool to be used for the mitigation of chemobrain by overcoming the blood-brain barrier (BBB) with innovative drug delivery systems. Polymer and lipid-based nanoparticles enable targeted drug release, enhancing therapeutic effectiveness. Utilizing the intranasal route of administration may facilitate drug delivery to the central nervous system (CNS) by circumventing first-pass metabolism. Therefore, knowledge of nasal anatomy is critical for optimizing drug delivery via various pathways. Despite challenges, nanoformulations exhibit the potential in enhancing brain drug delivery. Continuous research into formulation techniques and chemobrain mechanisms is vital for developing effective treatments. The intranasal administration of nanoformulations holds promise for improving therapeutic outcomes in chemobrain management. This review offers insights into potential future research directions, such as exploring novel drug combinations, investigating alternative delivery routes, or integrating emerging technologies to enhance the efficacy and safety of nanoformulations for chemobrain management.

10.
Environ Sci Pollut Res Int ; 31(26): 38232-38250, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38801609

RESUMEN

Water pollutants of non-biodegradable toxic aromatic dye including Methylene blue (MB) and Rhodamine (RhB) are extremely carcinogenic thiazines used in various industries such as leather industry, paper industry, and the dyeing industry. The presence of dyes in wastewater causes severe threats to human health that are responsible for various harmful chronic or acute diseases and also shows an adverse impact on the environment as it reduces transparency and is harmful to water microorganisms. To overcome severe issues, many traditional techniques have been used to remove toxic pollutants, but these methods are insufficient to remove chemically stable dyes that remain in the treated wastewater. However, the photocatalytic degradation process is an efficient approach to degrade the dye up to the maximum extent with improved efficiency. Therefore, in this work, a new class of two-dimensional (2D) transition metal carbide of Titanium Carbide (Ti3C2Tx) MXene material was used for the organic dyes degradation such as MB and RhB using a photocatalytic process. A layered structure of hexagonal lattice symmetry of Ti3C2Tx MXene was successfully synthesized from the Titanium Aluminum Carbide of Ti3AlC2 bulk phase using an exfoliation process. Further, the XRD spectrum confirms the transformation of bulk MAX phase having (002) plane at 9.2° to Ti3C2Tx MXene of (002) plane at 8.88° confirms the successful removal of Al layer from MAX phase. A smooth, transparent, thin sheet-like morphology of Ti3C2Tx nanosheet size were found to be in the range of 70 to 150 nm evaluated from TEM images. Also, no holes or damages in the thin sheets were found after the treatment with strong hydrofluoric acid confirms the formation Ti3C2Tx layered sheets. The synthesized Ti3C2Tx MXene possesses excellent photocatalytic activity for the degradation of dyes MB, RhB, and mixtures of MB and RhB dyes. MB dye degraded with a degradation percentage efficiency of 99.32% in 30 min, while RhB dye was degraded upto 98.9% in 30 min. Also, experiments were conducted for degradation of mixture of MB and RhB dyes by UV light, and the degradation percentage efficiency were found to be 98.9% and 99.75% for mixture of MB and RhB dye in 45 min, respectively. Moreover, reaction rate constant (k) was determined for each dye of MB, RhB, and mixtures of MB and RhB and was found to be 0.0215 min-1 and 0.0058 min-1, and for mixtures, it was 0.0020 min-1 and 0.009 min-1, respectively.


Asunto(s)
Colorantes , Azul de Metileno , Rodaminas , Aguas Residuales , Contaminantes Químicos del Agua , Rodaminas/química , Azul de Metileno/química , Aguas Residuales/química , Colorantes/química , Contaminantes Químicos del Agua/química , Catálisis , Titanio/química
11.
Eur J Pharm Biopharm ; 200: 114323, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38754524

RESUMEN

Cancer treatment modalities and their progression is guided by the specifics of cancer, including its type and site of localization. Surgery, radiation, and chemotherapy are the most often used conventional treatments. Conversely, emerging treatment techniques include immunotherapy, hormone therapy, anti-angiogenic therapy, dendritic cell-based immunotherapy, and stem cell therapy. Immune checkpoint inhibitors' anticancer properties have drawn considerable attention in recent studies in the cancer research domain. Programmed Cell Death Protein-1 (PD-1) and its ligand (PD-L1) checkpoint pathway are key regulators of the interactions between activated T-cells and cancer cells, protecting the latter from immune destruction. When the ligand PD-L1 attaches to the receptor PD-1, T-cells are prevented from destroying cells that contain PD-L1, including cancer cells. The PD-1/PD-L1 checkpoint inhibitors block them, boosting the immune response and strengthening the body's defenses against tumors. Recent years have seen incredible progress and tremendous advancement in developing anticancer therapies using PD-1/PD-L1 targeting antibodies. While immune-related adverse effects and low response rates significantly limit these therapies, there is a need for research on methods that raise their efficacy and lower their toxicity. This review discusses various recent innovative nanomedicine strategies such as PLGA nanoparticles, carbon nanotubes and drug loaded liposomes to treat cancer targeting PD-1/PD-L1 axis. The biological implications of PD-1/PD-L1 in cancer treatment and the fundamentals of nanotechnology, focusing on the novel strategies used in nanomedicine, are widely discussed along with the corresponding guidelines, clinical trial status, and the patent landscape of such formulations.


Asunto(s)
Antígeno B7-H1 , Ensayos Clínicos como Asunto , Inhibidores de Puntos de Control Inmunológico , Inmunoterapia , Neoplasias , Receptor de Muerte Celular Programada 1 , Humanos , Neoplasias/tratamiento farmacológico , Neoplasias/inmunología , Neoplasias/terapia , Inmunoterapia/métodos , Antígeno B7-H1/antagonistas & inhibidores , Antígeno B7-H1/inmunología , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Receptor de Muerte Celular Programada 1/inmunología , Inhibidores de Puntos de Control Inmunológico/farmacología , Patentes como Asunto , Animales
12.
Plant Physiol Biochem ; 211: 108682, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38714133

RESUMEN

Constant change in global climate has become the most important limiting factor to crop productivity. Asymmetrical precipitations are causing recurrent flood events around the world. Submergence is one of the most detrimental abiotic stresses for sustainable rice production in the rainfed ecosystems of Southeast Asia. Therefore, the development of submergence-tolerant rice is an essential requirement to encounter food security. Submergence tolerance in rice is governed by the major quantitative trait locus (QTL) designated as Submergence1 (Sub1) near the centromere of chromosome 9. The introduction of the Sub1 in high-yielding rice varieties producing near-isogenic lines (NILs) has shown extreme submergence tolerance. The present study aimed to understand the responses of rice genotype IR64 and its Sub1 NIL IR64 Sub1 following one week of complete submergence treatment. Submergence imposed severe nitro-oxidative stress in both the rice genotypes, consequently disrupting the cellular redox homeostasis. In this study, IR64 exhibited higher NADPH oxidase activity accompanied by increased reactive oxygen species, reactive nitrogen species, and malondialdehyde buildups and cell death under submergence. Higher accumulations of 1-Aminocyclopropane-1-carboxylic acid, gibberellic acid, and Indole-3-acetic acid were also observed in IR64 which accelerated the plant growth and root cortical aerenchyma development following submergence. In contrast, IR64 Sub1 had enhanced submergence tolerance associated with an improved antioxidant defense system with sustainable morpho-physiological activities and restricted root aerenchyma formation. The comprehensive analyses of the responses of rice genotypes with contrasting submergence tolerance may demonstrate the intricacies of rice under complete submergence and may potentially contribute to improving stress resilience by advancing our understanding of the mechanisms of submergence tolerance in rice.


Asunto(s)
Oryza , Reguladores del Crecimiento de las Plantas , Sitios de Carácter Cuantitativo , Oryza/genética , Oryza/metabolismo , Oryza/fisiología , Sitios de Carácter Cuantitativo/genética , Reguladores del Crecimiento de las Plantas/metabolismo , Estrés Oxidativo/genética , Transducción de Señal , Especies Reactivas de Oxígeno/metabolismo , Adaptación Fisiológica/genética , Inundaciones , Regulación de la Expresión Génica de las Plantas , Genotipo
13.
Cardiovasc Toxicol ; 24(6): 598-621, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38689163

RESUMEN

Cardiovascular diseases (CVDs) can be described as a global health emergency imploring possible prevention strategies. Although the pathogenesis of CVDs has been extensively studied, the role of mitochondrial dysfunction in CVD development has yet to be investigated. Diabetic cardiomyopathy, ischemic-reperfusion injury, and heart failure are some of the CVDs resulting from mitochondrial dysfunction Recent evidence from the research states that any dysfunction of mitochondria has an impact on metabolic alteration, eventually causes the death of a healthy cell and therefore, progressively directing to the predisposition of disease. Cardiovascular research investigating the targets that both protect and treat mitochondrial damage will help reduce the risk and increase the quality of life of patients suffering from various CVDs. One such target, i.e., nuclear sirtuin SIRT6 is strongly associated with cardiac function. However, the link between mitochondrial dysfunction and SIRT6 concerning cardiovascular pathologies remains poorly understood. Although the Role of SIRT6 in skeletal muscles and cardiomyocytes through mitochondrial regulation has been well understood, its specific role in mitochondrial maintenance in cardiomyocytes is poorly determined. The review aims to explore the domain-specific function of SIRT6 in cardiomyocytes and is an effort to know how SIRT6, mitochondria, and CVDs are related.


Asunto(s)
Enfermedades Cardiovasculares , Mitocondrias Cardíacas , Miocitos Cardíacos , Sirtuinas , Sirtuinas/metabolismo , Humanos , Mitocondrias Cardíacas/patología , Mitocondrias Cardíacas/metabolismo , Mitocondrias Cardíacas/enzimología , Mitocondrias Cardíacas/efectos de los fármacos , Animales , Miocitos Cardíacos/patología , Miocitos Cardíacos/enzimología , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/efectos de los fármacos , Enfermedades Cardiovasculares/metabolismo , Enfermedades Cardiovasculares/fisiopatología , Enfermedades Cardiovasculares/enzimología , Enfermedades Cardiovasculares/patología , Transducción de Señal , Metabolismo Energético/efectos de los fármacos
14.
Int J Biometeorol ; 68(7): 1397-1409, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38602552

RESUMEN

Selection of the most stably expressed reference genes is key to monitoring accurate target gene expression across any tissue or cell type. The mRNA in spermatozoa stores valuable information related to changes in spermatogenesis due to variations in environmental conditions, especially during heat stress, which affects various sperm functions. Semen quality in buffalo bulls is significantly influenced by the seasons. In the study, a panel of nine genes was evaluated to identify the most stably expressed internal control gene (ICG) for the normalization of real-time gene expression data generated across various seasons for Murrah buffalo bulls' spermatozoa. Sperm cells were purified from the semen samples collected during different seasons, with temperature-humidity index (THI) ranging from 80.80 ± 1.47 (hot summer) to 55.88 ± 1.98 (winter), using the BoviPure™ gradient purification method. The RNA isolated from the purified spermatozoa fraction was quality checked prior to reverse transcription and subjected to qPCR (quantitative real-time PCR) based expression analysis. An automated 'endoGene' pipeline was employed to apply the geNorm, NormFinder, and BestKeeper algorithms for data analysis. The result indicated that GAPDH and PP1A were the most stably expressed among the gene panel, whereas ATPSF1 and ACTB were the two least stable expressed reference genes. Further, the most suitable ICGs identified were validated by normalization of real time expression data of heat stress and sperm quality genes, HSFY2 and AKAP4, respectively. The genes identified would help in generating the most reliable results for the expression profiling of the genes dictating sperm quality and heat stress cope-up mechanism in buffalo spermatozoa, collected during different seasons.


Asunto(s)
Búfalos , Estaciones del Año , Espermatozoides , Animales , Búfalos/genética , Masculino , Espermatozoides/metabolismo , Expresión Génica , Temperatura , Reacción en Cadena en Tiempo Real de la Polimerasa , Perfilación de la Expresión Génica , Análisis de Semen/veterinaria , Humedad , Estándares de Referencia
15.
ACS Appl Bio Mater ; 7(5): 3271-3282, 2024 05 20.
Artículo en Inglés | MEDLINE | ID: mdl-38654595

RESUMEN

A thiazole-based probe, N'-((2-aminothiazol-5-yl)methylene)benzohydrazide (TBH), has been efficiently synthesized and characterized for the selective and sensitive detection of the neurotransmitter epinephrine (EP). The sensing strategy is based on the use of TBH for sequential colorimetric sensing of Ag+ and EP via in situ formation of Ag nanoparticles (Ag NPs) from the TBH-Ag+ complex. The generated Ag NPs lead to a bathochromic shift in absorption maximum and a change in color of the solution from light brown to reddish brown. TBH-Ag+ shows remarkable selectivity toward EP versus other drugs, common cations, anions, and some biomolecules. Moreover, TBH-Ag+ has a low detection limit for EP at 1.2 nM. The coordination of TBH-Ag+ has been proposed based on Job's plot, Fourier transform infrared spectroscopy (FT-IR), high-resolution mass spectrometry (HRMS), 1H NMR titration, X-ray photoelectron spectroscopy (XPS), energy-dispersive X-ray analysis (EDAX), and density functional theory (DFT) studies. The composition and morphology of the generated Ag NPs have been analyzed by XPS, scanning electron microscopy (SEM), transmission electron microscopy (TEM), and dynamic light scattering (DLS). The proposed sensing mechanism for EP has been supported by XPS of Ag after the reaction. Further, the sensitivity of TBH-Ag+ toward EP in brain tissues of an Alzheimer's disease model of mouse has been evaluated. A thorough comparison was done for evaluation of the proposed method.


Asunto(s)
Enfermedad de Alzheimer , Encéfalo , Colorimetría , Epinefrina , Plata , Tiazoles , Enfermedad de Alzheimer/diagnóstico por imagen , Enfermedad de Alzheimer/diagnóstico , Enfermedad de Alzheimer/metabolismo , Plata/química , Animales , Ratones , Epinefrina/análisis , Tiazoles/química , Encéfalo/metabolismo , Encéfalo/diagnóstico por imagen , Ensayo de Materiales , Modelos Animales de Enfermedad , Materiales Biocompatibles/química , Materiales Biocompatibles/síntesis química , Tamaño de la Partícula , Nanopartículas del Metal/química , Estructura Molecular , Iones/química
16.
Phytother Res ; 38(5): 2406-2447, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38433568

RESUMEN

The epidermal growth factor receptor (EGFR) is a transmembrane receptor tyrosine kinase (RTK) that maintains normal tissues and cell signaling pathways. EGFR is overactivated and overexpressed in many malignancies, including breast, lung, pancreatic, and kidney. Further, the EGFR gene mutations and protein overexpression activate downstream signaling pathways in cancerous cells, stimulating the growth, survival, resistance to apoptosis, and progression of tumors. Anti-EGFR therapy is the potential approach for treating malignancies and has demonstrated clinical success in treating specific cancers. The recent report suggests most of the clinically used EGFR tyrosine kinase inhibitors developed resistance to the cancer cells. This perspective provides a brief overview of EGFR and its implications in cancer. We have summarized natural products-derived anticancer compounds with the mechanistic basis of tumor inhibition via the EGFR pathway. We propose that developing natural lead molecules into new anticancer agents has a bright future after clinical investigation.


Asunto(s)
Productos Biológicos , Receptores ErbB , Neoplasias , Transducción de Señal , Receptores ErbB/metabolismo , Receptores ErbB/antagonistas & inhibidores , Humanos , Transducción de Señal/efectos de los fármacos , Productos Biológicos/farmacología , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismo , Inhibidores de Proteínas Quinasas/farmacología , Antineoplásicos/farmacología , Animales
17.
J Appl Genet ; 2024 Mar 29.
Artículo en Inglés | MEDLINE | ID: mdl-38551768

RESUMEN

Genetic cardiomyopathies (CM) are disorders that affect morphology and function of cardiac muscle. Significant number of genes have been implicated in causing the phenotype. It is one of the leading genetic causes of death in young. We performed a study to understand the genetic variants in primary cardiomyopathies in an Indian cohort. Study comprised of 22 probands (13 with family history) representing hypertrophic (n = 10), dilated (n = 7), restrictive (n = 2) and arrhythmogenic ventricular(n = 3) cardiomyopathies. Genomic DNA was target captured with a panel of 46 genes and libraries sequenced on Illumina platform. Analysis identified, reported pathogenic as well as novel pathogenic (n = 6) variants in 16 probands. Of the 10 HCM patients, candidate variants were identified in nine of them involving sarcomere genes (62%, MYBPC3, MYH6, MYH7, MYL3, TTN), Z-disc (10%, ACTN2, LDB3, NEXN,), desmosome (10%, DSG2, DSP, PKP2) cytoskeletal (4%, DTNA) and ion channel (10% RYR2). In four DCM patients, variants were identified in genes NEXN, LMNA and TTN. Three arrhythmogenic right ventricular cardiomyopathy (ARVD) patients carried mutations in desmosome genes. Rare TTN variants were identified in multiple patients. Targeted capture and sequencing resulted in identification of candidate variants in about 70% of the samples which will help in management of disease in affected individual as well as in screening and early diagnosis in asymptomatic family members. Amongst the analysed cases, 22% were inconclusive without any significant variant identified. Study illustrates the utility of next-generation multi-gene panel as a cost-effective genetic testing to screen all forms of primary cardiomyopathies.

18.
Eur J Med Chem ; 267: 116172, 2024 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-38330869

RESUMEN

Influenza outbreaks cause pandemics in millions of people. The treatment of influenza remains a challenge due to significant genetic polymorphism in the influenza virus. Also, developing vaccines to protect against seasonal and pandemic influenza infections is constantly impeded. Thus, antibiotics are the only first line of defense against antigenically distinct strains or new subtypes of influenza viruses. Among several anti-influenza targets, the M2 protein of the influenza virus performs several activities. M2 protein is an ion channel that permits proton conductance through the virion envelope and the deacidification of the Golgi apparatus. Both these functions are critical for viral replication. Thus, targeting the M2 protein of the influenza virus is an essential target. Rimantadine and amantadine are two well-known drugs that act on the M2 protein. However, these drugs acquired resistance to influenza and thus are not recommended to treat influenza infections. This review discusses an overview of anti-influenza therapy, M2 ion channel functions, and its working principle. It also discusses the M2 structure and its role, and the change in the structure leads to mutant variants of influenza A virus. We also shed light on the recently identified compounds acting against wild-type and mutated M2 proteins of influenza virus A. These scaffolds could be an alternative to M2 inhibitors and be developed as antibiotics for treating influenza infections.


Asunto(s)
Virus de la Influenza A , Gripe Humana , Orthomyxoviridae , Humanos , Virus de la Influenza A/genética , Antivirales/química , Gripe Humana/tratamiento farmacológico , Amantadina/metabolismo , Amantadina/farmacología , Amantadina/uso terapéutico , Canales Iónicos/metabolismo , Canales Iónicos/uso terapéutico , Antibacterianos/uso terapéutico , Proteínas de la Matriz Viral/genética , Proteínas de la Matriz Viral/metabolismo
19.
Gene ; 906: 148233, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38331117

RESUMEN

Semen production and quality are closely correlated with different environmental factors in bovines, particularly for the buffalo (Bubalus bubalis) bulls reared under tropical and sub-tropical conditions. Factors including DNA methylation patterns, an intricate process in sperm cells, have an impact on the production of quality semen in buffalo bulls under abiotic stress conditions. The present study was conducted to identify DNA methylome signatures for semen quality in Murrah buffalo bulls, acclaimed as a major dairy breed globally, under summer heat stress. Based on semen quality parameters that significantly varied between the two groups over the seasons, the breeding bulls were classified into seasonally affected (SA = 6) and seasonally non-affected (SNA = 6) categories. DNA was isolated from purified sperm cells and sequenced using the RRBS (Reduced Representation Bisulfite Sequencing) technique for genome-wide methylome data generation. During the hot summer months, the physiological parameters such as scrotal surface temperature, rectal temperature, and respiration rate for both the SA and SNA bulls were significantly higher in the afternoon than in the morning. Whereas, the global CpG% of SA bulls was positively correlated with the afternoon's scrotal surface and rectal temperature. The RRBS results conveyed differentially methylated cytosines in the promoter region of the genes encoding the channels responsible for Ca2+ exchange, NPTN, Ca2+ activated chloride channels, ANO1, and a few structure-related units such as septins (SEPT4 and SEPT6), SPATA, etc. Additionally, the hypermethylated set of genes in SA was significantly enriched for pathways such as the FOXO signaling pathway and oocyte meiosis. The methylation patterns suggest promoter methylation in the genes regulating the sperm structure as well as surface transporters, which could contribute to the reduced semen quality in the Murrah buffalo bulls during the season-related heat stress.


Asunto(s)
Análisis de Semen , Semen , Animales , Masculino , Bovinos/genética , Semen/fisiología , Búfalos/genética , Fosfatos , Espermatozoides , Metilación de ADN , Respuesta al Choque Térmico/genética , Motilidad Espermática
20.
Heliyon ; 10(1): e24074, 2024 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-38230249

RESUMEN

A diarylethene-based probe (Z)-N'-((2-amino-5-chlorophenyl)(phenyl)methylene)-2-hydroxy benzohydrazide (KBH) has been proficiently developed and its structure has been confirmed by single crystal X-ray diffraction technique. It displays a selective and sensitive colorimetric sensing of Cu2+ ions in aqueous medium with a naked eye colour change from colourless to yellow. It exhibits a significantly low limit of detection as 1.5 nM. A plausible binding mechanism has been proposed using Job's plot, FT-IR, 1H NMR titration, HRMS and DFT studies. The chemosensor is effectively reversible and reusable with EDTA. Test strip kit and real water sample analysis have been shown to establish its practical applicability. Further, the potential of KBH for the early diagnosis of Cu2+ ion-induced amyloid toxicity has been investigated in eye imaginal disc of Alzheimer's disease model of Drosophila 3rd instar larvae. The in-vivo interaction of KBH with Cu2+ in gut tissues of Drosophila larvae establishes its sensing capability in biological system. Interestingly, the in-vivo detection of Cu2+ has been done using bright field imaging which eliminates the necessity of a fluorescent label, hence making the method highly economical.

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