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1.
J Environ Manage ; 360: 121136, 2024 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-38759555

RESUMEN

Waste of any origin is one of the most serious global and man-made concerns of our day. It causes climate change, environmental degradation, and human health problems. Proper waste management practices, including waste reduction, safe handling, and appropriate treatment, are essential to mitigate these consequences. It is thus essential to implement effective waste management strategies that reduce waste at the source, promote recycling and reuse, and safely dispose of waste. Transitioning to a circular economy with policies involving governments, industries, and individuals is essential for sustainable growth and waste management. The review focuses on diverse kinds of environmental waste sources around the world, such as residential, industrial, commercial, municipal services, electronic wastes, wastewater sewerage, and agricultural wastes, and their challenges in efficiently valorizing them into useful products. It highlights the need for rational waste management, circularity, and sustainable growth, and the potential of a circular economy to address these challenges. The article has explored the role of thermophilic microbes in the bioremediation of waste. Thermophiles known for their thermostability and thermostable enzymes, have emerged to have diverse applications in biotechnology and various industrial processes. Several approaches have been explored to unlock the potential of thermophiles in achieving the objective of establishing a zero-carbon sustainable bio-economy and minimizing waste generation. Various thermophiles have demonstrated substantial potential in addressing different waste challenges. The review findings affirm that thermophilic microbes have emerged as pivotal and indispensable candidates for harnessing and valorizing a range of environmental wastes into valuable products, thereby fostering the bio-circular economy.

2.
Indian J Ophthalmol ; 2024 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-38770620

RESUMEN

PURPOSE: To study ultra-widefield indocyanine green angiography (ICGA) patterns in central serous chorioretinopathy (CSC). METHODS: A cross-sectional observational study was undertaken on 30 patients aged 20 to 60 years with CSC at the retina clinic of a tertiary care center. Of them, 43 eyes were affected by CSC, whereas 17 eyes were unaffected as the bilateral disease was observed in 13 patients. All patients were evaluated for best-corrected visual acuity, intraocular pressure, detailed slit-lamp bio-microscopy, indirect ophthalmoscopy, ultra-widefield imaging for pseudo color photograph, fundus autofluorescence (FAF), fundus fluorescein angiography (FFA), and ICGA, and macular swept-source optical coherence tomography (SSOCT) characteristics. RESULTS: The mean age of patients was 41.43 ± 8.81 years (range: 25-59 years). The median log MAR visual acuity in CSC eyes was 0.30 (range: 0.17-1.0), whereas it was 0 in non-CSC fellow eyes (P < 0.001). Pachy-vessels and late hyperpermeability on ultra-widefield ICGA were observed in all eyes. Vortex vein anastomosis was present in 93% of the affected eyes versus 88.2% in unaffected fellow eyes (P = 0.61). Disc and posterior poles were the sites of the maximum number of anastomoses in both affected and unaffected eyes (P = 0.77). Asymmetry in vortex vein drainage of the macula was present in 88.4% of affected eyes and 88.2% of unaffected eyes. CONCLUSION: Studying the ICGA findings in CSC patients emphasized the role of choroidal circulation in pathogenesis as Pachy vessels were observed in all eyes affected with CSC and even fellow eyes of patients. Vortex vein anastomosis around the disc or posterior pole and asymmetric drainage from the macula were noted and could be contributing to CSC pathology.

3.
Int J Dev Biol ; 2024 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-38770834

RESUMEN

The development of skin appendages, including hair follicles, teeth and mammary glands is initiated through the formation of the placode, a local thickening of the epithelium. The Wnt/ß-catenin signaling cascade is an evolutionary conserved pathway with an essential role in placode morphogenesis, but its downstream targets and their exact functions remain ill defined. In this study, we identify Achaete-scute complex-like 4 (Ascl4) as a novel target of the Wnt/ß-catenin pathway and demonstrate its expression pattern in the signaling centers of developing hair follicles and teeth. Ascl transcription factors belong to the superfamily of basic helix-loop-helix transcriptional regulators involved in cell fate determination in many tissues. However, their specific role in the developing skin remains largely unknown. We report that Ascl4 null mice have no overt phenotype. Absence of Ascl4 did not impair hair follicle morphogenesis or hair shaft formation suggesting that it is non-essential for hair follicle development. No tooth or mammary gland abnormalities were detected either. We suggest that other transcription factors may functionally compensate for the absence of Ascl4, but further research is warranted to assess this possibility.

4.
South Asian J Cancer ; 13(1): 51-56, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38721100

RESUMEN

Swati BhanIntroduction This paper aims to provide an overview of the administrative and clinical preparations done in a tertiary care cancer hospital in continuing operation theatre (OT) services through the COVID pandemic. Methods Retrospective data collection, data for the past 1.5 years (COVID period) March 2020 to August 2021 were compared to surgical output for a similar duration of time before the COVID era (September 2018-February 2020). Results A total of 1,022 surgeries were done under anesthesia in the COVID period as against 1,710 surgeries done in a similar time frame in the pre-COVID era. Overall, we saw a 40%drop in the total number of cases. Thorax, abdominal, and miscellaneous surgeries (soft tissue sarcomas, urology, and gyneconcology) saw a maximum fall in numbers; however, head and neck cases saw an increase in numbers during the pandemic. Surgical morbidity and mortality were similar in the COVID and pre-COVID era. No cases of severe COVID infection were reported among the healthcare staff working in OT. Discussion We could successfully continue our anesthesia services with minimal risk to healthcare staff throughout the pandemic by adopting major guidelines in a pragmatic and practical approach with minor changes to suit our setup.

6.
Curr Res Microb Sci ; 6: 100237, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38706494

RESUMEN

Due to an increase in industrialization and urbanization, massive amounts of solid waste biomass are speedily accumulating in our environment, which poses several adverse effects on habitat and human health thus becoming a matter of discussion in the environmental community. With reference to the circular economy, continuous efforts have been put forward for setting up an organised management approach in combination with an efficient treatment technique for increasing the profitable utilization of solid waste. This review aims to provide a systematic discussion on the recent thermochemical technologies employed for converting waste biomass generated from different sources into valuable products like biochar, bio-oil, heat, energy and syngas. The article further focuses on a few important aspects of thermochemical conversion of waste biomass to useful products like technical factors affecting thermochemical processes, applications of by-products of thermochemical conversion, and biological pretreatment of waste biomass. The review assists interesting recent and scientific trends for boosting up the systematic management and valorization of solid waste through low-cost, efficient, environment-friendly and sustainable technologies.

7.
Indian J Surg Oncol ; 15(2): 304-311, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38741624

RESUMEN

Enhanced Recovery After Surgery (ERAS) protocols have emerged as a promising approach to optimize perioperative care and improve outcomes in various surgical specialties. Despite feasibility studies on ERAS in various surgeries, there remains a paucity of research focusing on gastrointestinal cancer surgeries in the Indian context. The primary objective is to evaluate the compliance rate of the ERAS protocol and secondary objectives include the compliance rate of individual components of the protocol, the complications, the length of hospital stay, and the challenges faced during implementation in patients undergoing gastrointestinal cancer surgeries in our tertiary care cancer center. In this prospective interventional study (CTRI/2022/04/041657; registered on 05/04/2022), we evaluated 50 patients aged 18 to 70 years undergoing surgery for gastrointestinal malignancies and implemented a refined ERAS protocol tailored to our institutional resources and conditions based on standard ERAS society recommendations for gastrointestinal surgeries and specific recommendations for colorectal, pancreatic, and esophageal surgeries.Our study's mean overall compliance rate with the ERAS protocol was 88.54%. We achieved a compliance rate of 91.98%, 81.66%, and 92.00% for pre-operative, intraoperative, and post-operative components respectively. Fourteen (28%) patients experienced complications during the study. The median length of stay was 6.5 days (5.25-8). Challenges were encountered during the preoperative, intraoperative, and postoperative phases. The study highlighted the feasibility of implementing the ERAS protocol in a cancer institute, but specific challenges need to be addressed for its optimal success in gastrointestinal cancer surgeries. Supplementary Information: The online version contains supplementary material available at 10.1007/s13193-024-01897-y.

8.
Cureus ; 16(4): e58609, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38770471

RESUMEN

INTRODUCTION: Spiritual health is an important dimension of positive health and is often ignored as it is not amenable to measurement. The present study was conducted to generate relevant evidence on spiritual health among adolescents living in urban areas of Northern India. METHODS: A cross-sectional study was done from June 2019 - May 2020 in an urban area of Northern India on a sample of 300 adolescents selected purposively. After collection of demographic details of the participants, the Index of Core Spiritual Experiences (INSPIRIT) tool was used to capture their spiritual health. RESULTS: The Cronbach's alpha for the scale was 0.832 (0.797-0.863) indicating good internal consistency of the measure. As far as spiritual health is concerned, 217 (72.3%) of the study participants scored medium-high to high, followed by 83 (27.7%) who scored medium-low to low on the spiritual health scale. Adjusted multivariate analysis using binary logistic regression showed that positive traits like caring (odds ratio (OR) 1.19, 95% CI: 1.08-1.33), connection to school (OR 1.16, 95% CI: 1.04-1.29), having positive identity (OR 1.19, 95% CI: 1.04-1.36) and having highly educated (post-graduate) parents (OR 2.18, 95% CI: 1.13-4.21) lead to significantly higher spiritual health scores.  Discussion: Although spiritual health is not routinely measured among adolescents, the current study demonstrated high levels of spiritual health among half of the urban adolescents. Parental education was found to have a positive association with spiritual health scores, indicating the indirect effect of parental spiritual inclination. The study has important implications for policy, as it demonstrates the feasibility of measuring a covert dimension of health which tends to have an indirect effect on holistic youth development.

9.
Dalton Trans ; 2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38771593

RESUMEN

We present the use of an amine functionalized two-dimensional clay i.e., aminoclay (AC), in the chemistry of a three-dimensional metal-organic framework (MOF) i.e., MIL-101(Cr), to prepare MIL-101(Cr)/AC composites, which are exploited as catalysts for efficient conversion of CO2 gas into cyclic carbonates under ambient reaction conditions. Three different MOF nanocomposites, denoted as MIL-101(Cr)/AC-1, MIL-101(Cr)/AC-2, and MIL-101(Cr)/AC-3, were synthesized by an in situ process by adding different amounts of AC to the precursor solutions of the MIL-101(Cr). The composites were characterized by various techniques such as FT-IR, PXRD, FESEM, EDX, TGA, N2 adsorption, as well as CO2 and NH3-TPD measurements. The composites were exploited as heterogeneous catalysts for CO2 cycloaddition reactions with different epoxides and the catalytic activity was investigated at atmospheric pressure under solvent-free conditions. Among all the materials, MIL-101(Cr)/AC-2 shows the best catalytic efficiency under the optimized conditions and exhibits enhanced efficacy compared to various MIL-101(Cr)-based MOF catalysts, which typically need either high temperature and pressure or a longer reaction time or a combination of all the parameters. The present protocol using MIL-101(Cr)/AC-2 as the heterogeneous catalyst gives 99.9% conversion for all the substrates into the products at atmospheric pressure.

10.
Pediatr Nephrol ; 2024 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-38740594

RESUMEN

BACKGROUND: Sepsis associated acute kidney injury (AKI) is linked with adverse outcomes in the PICU. Doppler-based renal resistive index (RRI) has shown promising results in adults for prediction of AKI. We aimed to explore the performance of RRI in children with sepsis. METHODS: This prospective observational study (March - November 2022) included children aged 1-12 years with sepsis admitted to the PICU. RRI and urine neutrophil gelatinase associated lipocalin (NGAL) were measured within 12 h of admission. Children were followed up for 3 days. AKI (new and persistent) was defined as any child with KDIGO stage 2 or 3 AKI on day 3. RESULTS: We enrolled 90 children but included 79 in final analysis. Two thirds (n = 53, 67%) had septic shock. Median (IQR) age was 6.2 years (4.1-9.2). RRI decreased with increasing age. Twenty-six (33%) children had AKI on day 3. Mean (SD) RRI was higher in the AKI group [0.72 (0.08) vs. 0.65 (0.07), p < 0.001].The area under ROC curve for RRI to detect AKI among the 1-4 year old group was 0.75 (95% CI:0.51, 0.98; p = 0.05) and among the 5-12 year old group was 0.76 (0.62, 0.89; p = 0.001). An RRI 0.71 predicted AKI with 100% sensitivity and 46.2% specificity among the 1-4-year-old group and RRI 0.69 predicted it with 70% sensitivity and 77.5% specificity in the 5-12-year-old group. RRI and eGFR at admission were independent predictors of AKI on multivariable analysis. Urine NGAL 94.8 ng/ml predicted AKI with 76.9% sensitivity and 77.4% specificity and AUROC was 0.74 (0.62, 0.86) among the 1-12-year-old group. CONCLUSIONS: RRI values varied with age. RRI showed good diagnostic accuracy to detect new/persistent AKI on day 3 in children with sepsis; however, it was less precise as an independent predictor.

11.
Mol Biol Rep ; 51(1): 508, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38622474

RESUMEN

Advances in plant molecular breeding have resulted in the development of new varieties with superior traits, thus improving the crop germplasm. Breeders can screen a large number of accessions without rigorous and time-consuming phenotyping by marker-assisted selection (MAS). Molecular markers are one of the most imperative tools in plant breeding programmes for MAS to develop new cultivars possessing multiple superior traits. Single nucleotide polymorphisms (SNPs) are ideal for MAS due to their low cost, low genotyping error rates, and reproducibility. Kompetitive Allele Specific PCR (KASP) is a globally recognized technology for SNP genotyping. KASP is an allele-specific oligo extension-based PCR assay that uses fluorescence resonance energy transfer (FRET) to detect genetic variations such as SNPs and insertions/deletions (InDels) at a specific locus. Additionally, KASP allows greater flexibility in assay design, which leads to a higher success rate and the capability to genotype a large population. Its versatility and ease of use make it a valuable tool in various fields, including genetics, agriculture, and medical research. KASP has been extensively used in various plant-breeding applications, such as the identification of germplasm resources, quality control (QC) analysis, allele mining, linkage mapping, quantitative trait locus (QTL) mapping, genetic map construction, trait-specific marker development, and MAS. This review provides an overview of the KASP assay and emphasizes its validation in crop improvement related to various biotic and abiotic stress tolerance and quality traits.


Asunto(s)
Fitomejoramiento , Plantas , Genotipo , Alelos , Reproducibilidad de los Resultados , Fenotipo , Plantas/genética , Polimorfismo de Nucleótido Simple/genética
12.
Mol Divers ; 2024 Apr 04.
Artículo en Inglés | MEDLINE | ID: mdl-38573427

RESUMEN

Alzheimer's disease (AD) is a complex neurological disorder and no effective drug is available for its treatment. Numerous pathological conditions are believed to be responsible for the initiation and development of AD including c-Jun N-terminal kinases (JNKs). The JNKs are one of the enzymes from the mitogen-activated protein kinase (MAPK) family that controls the phosphorylation of various transcription factors on serine and threonine residues, and hold significant responsibilities in tasks like gene expression, cell proliferation, differentiation, and apoptosis. Since, JNK3 is primarily expressed in the brain hence its increased levels in the brain are associated with the AD pathology promoting neurofibrillary tangles, senile plaques, neuroinflammation, and nerve cell apoptosis. The current research work is focused on the development of novel JNK inhibitors as therapeutics for AD employing a structure-based virtual screening (SBVS) approach. The ZINC database (14634052 compounds) was investigated after employing pan assay interference (PAINs), drug-likeness, and diversity picking filter to distinguish molecules interacting with JNK3 by following three docking precision criteria: High Throughput Virtual Screening (HTVS), Standard Precision (SP), and Extra Precision (XP) & MMGBSA. Five lead molecules showed a better docking score in the range of -13.091 to -14.051 kcal/mol better than the reference compound (- 11.828 kcal/mol). The lead compounds displayed acceptable pharmacokinetic properties and were subjected to molecular dynamic simulations of 100 ns and binding free energy calculations. All the lead molecules showed stable RMSD and hydrogen bond interactions throughout the trajectory. The ∆GMM/PBSA_total score for the lead compounds ZINC220382956, ZINC147071339, ZINC207081127, ZINC205151456, ZINC1228819126, and CC-930 was calculated and found to be - 31.39, - 42.8, - 37.04, - 39.01, - 36.5, - 34.16 kcal/mol, respectively. Thus, it was concluded that the lead molecules identified in these studies have the potential to be explored as potent JNK3 inhibitors.

13.
Indian J Nephrol ; 34(1): 88-89, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38645924

RESUMEN

A 39-year-old woman presented with inflammatory polyarthritis, low-grade fever, progressive pedal edema, and frothy urination of three weeks duration. She had nephrotic range proteinuria and elevated creatinine. Kidney biopsy showed collapse of capillary tuft in the glomeruli and proliferation, hyperplasia, and hypertrophy of the overlying podocytes suggestive of collapsing glomerulopathy. Histology of the cervical lymph node showed necrotizing granulomatous inflammation suggestive of tuberculosis. With all other possible causes of polyarthritis ruled out, a diagnosis of Poncet's disease-a form of polyarthritis observed in patients suffering from an active form of extrapulmonary tuberculosis (TB)-was considered. Association between TB lymphadenitis and collapsing glomerulopathy (CG) is very rare, and the patient had partial remission of the disease after being started on anti-tuberculosis therapy (ATT) along with steroids.

14.
J Biol Chem ; : 107328, 2024 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-38679332

RESUMEN

Management of chronic obesity-associated metabolic disorders is a key challenge for biomedical researchers. During chronic obesity, visceral adipose tissue (VAT) undergoes substantial transformation characterized by a unique lipid-rich hypoxic AT microenvironment (ATenv) which plays a crucial role in VAT dysfunction, leading to insulin resistance (IR) and type 2 diabetes(T2D). Here, we demonstrate that obese ATenv triggers the release of miR-210-3p microRNA-loaded extracellular vesicles (EVs) from adipose tissue macrophages (ATMs), which disseminate miR-210-3p to neighboring adipocytes, skeletal muscle cells, and hepatocytes through paracrine and endocrine actions, thereby influencing insulin sensitivity. Moreover, EVs collected from Dicer-silenced miR-210-3p-overexpressed bone marrow-derived macrophages (BMDMs), induce glucose intolerance and IR in lean mice. Mechanistically, miR-210-3p interacts with the 3'-UTR of GLUT4 mRNA and silences its expression, compromising cellular glucose uptake and insulin sensitivity. Therapeutic inhibition of miR-210-3p in VAT notably rescues high-fat diet (HFD)-fed mice from obesity-induced systemic glucose intolerance. Thus, targeting ATM-specific miR-210-3p during obesity could be a promising strategy for managing IR and T2D.

15.
Sci Transl Med ; 16(744): eadg5768, 2024 04 24.
Artículo en Inglés | MEDLINE | ID: mdl-38657024

RESUMEN

Sepsis is a life-threatening disease caused by a dysregulated host response to infection, resulting in 11 million deaths globally each year. Vascular endothelial cell dysfunction results in the loss of endothelial barrier integrity, which contributes to sepsis-induced multiple organ failure and mortality. Erythropoietin-producing hepatocellular carcinoma (Eph) receptors and their ephrin ligands play a key role in vascular endothelial barrier disruption but are currently not a therapeutic target in sepsis. Using a cecal ligation and puncture (CLP) mouse model of sepsis, we showed that prophylactic or therapeutic treatment of mice with EphA4-Fc, a decoy receptor and pan-ephrin inhibitor, resulted in improved survival and a reduction in vascular leak, lung injury, and endothelial cell dysfunction. EphA2-/- mice also exhibited reduced mortality and pathology after CLP compared with wild-type mice. Proteomics of plasma samples from mice with sepsis after CLP revealed dysregulation of a number of Eph/ephrins, including EphA2/ephrin A1. Administration of EphA4-Fc to cultured human endothelial cells pretreated with TNF-α or ephrin-A1 prevented loss of endothelial junction proteins, specifically VE-cadherin, with maintenance of endothelial barrier integrity. In children admitted to hospital with fever and suspected infection, we observed that changes in EphA2/ephrin A1 in serum samples correlated with endothelial and organ dysfunction. Targeting Eph/ephrin signaling may be a potential therapeutic strategy to reduce sepsis-induced endothelial dysfunction and mortality.


Asunto(s)
Células Endoteliales , Efrinas , Sepsis , Transducción de Señal , Animales , Sepsis/complicaciones , Sepsis/metabolismo , Sepsis/patología , Humanos , Células Endoteliales/metabolismo , Ratones , Efrinas/metabolismo , Ratones Endogámicos C57BL , Receptores de la Familia Eph/metabolismo , Ciego/patología , Masculino , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Modelos Animales de Enfermedad
16.
Curr Microbiol ; 81(6): 147, 2024 Apr 20.
Artículo en Inglés | MEDLINE | ID: mdl-38642080

RESUMEN

Dicarboxylic acid (DCA) is a multifaceted chemical intermediate, recoursed to produce many industrially important products such as adhesives, plasticizers, lubricants, polymers, etc. To bypass the shortcomings of the chemical methods of synthesis of DCA and to reduce fossil fuel footprints, bio-based synthesis is gaining attention. In pursuit of an eco-friendly sustainable alternative method of DCA production, microbial cell factories, and renewable organic resources are gaining popularity. Among the plethora of microbial communities, yeast is being favored industrially compared to bacterial fermentation due to its hyperosmotic and low pH tolerance and flexibility for gene manipulations. By application of rapidly evolving genetic manipulation techniques, the bio-based DCA production could be made more precise and economical. To bridge the gap between supply and demand of DCA, many strategies are employed to improve the fermentation. This review briefly outlines the advancements in DCA production using yeast cell factories with the exemplification of strain improvement strategies.


Asunto(s)
Ácidos Dicarboxílicos , Saccharomyces cerevisiae , Saccharomyces cerevisiae/genética , Fermentación , Ingeniería Metabólica/métodos
17.
Support Care Cancer ; 32(5): 274, 2024 Apr 08.
Artículo en Inglés | MEDLINE | ID: mdl-38587678

RESUMEN

PURPOSE: Hematopoietic stem cell transplant (HSCT) is an intense form of treatment, resulting in major symptom burden but can prove curative. The quality of life (QOL) is a major endpoint for these patients as the survival rate in them has improved over time. The aim of the study is to assess the QOL and symptom burden of hematological malignancy patients at admission to hospital for HSCT, at 1 month and at 3 months following HSCT. METHODS: This prospective observational study was done on hematological malignancy patients who were admitted for HSCT in a regional cancer center. The study subjects were assessed by the Functional Assessment of Cancer Therapy-Bone Marrow Transplant Scale (FACT-BMT Scale), Edmonton Symptom Assessment Scale-revised (r-ESAS), and Depression, Anxiety and Stress Scale-21 Items (DASS-21) at the time of hospital admission for transplantation, on day 30 (~ 1 month) and day100 (~ 3 months) of transplantation. RESULTS: A total of 68 patients were included in this study. FACT-BMT scores have decreased from baseline (F0) to the first follow-up (F1) and then increased in the third follow-up (F2). The maximum r-ESAS mean score was for tiredness among all other symptoms at F0 as well as at F1 and at F2. The DASS 21 scores for depression, anxiety, and stress were maximum during F1 and minimum during F2. CONCLUSION: Symptom burden is maximum during the first month of BMT, which improves later and QOL becomes improved with time.


Asunto(s)
Neoplasias Hematológicas , Trasplante de Células Madre Hematopoyéticas , Neoplasias , Humanos , Calidad de Vida , Carga Sintomática , Neoplasias Hematológicas/terapia , India/epidemiología
18.
Crit Rev Oncol Hematol ; 198: 104374, 2024 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-38679402

RESUMEN

The PD-1/PD-L1 pathway plays a significant role in inhibiting, escaping from immune response, and promoting self-tolerance of the tumour. Dostarlimab is a selective humanized monoclonal antibody designed to target PD-1 and block its activity with PD-L1, which further prevents the escape of tumour cells from immune surveillance. It got accelerated approval from the FDA for treating adults with mismatch repair deficient, recurrent, or advanced endometrial cancer, and studies confirmed its beneficial effects. A recently published clinical trial reported 100 % remission of advanced rectal cancer without significant side effects in the participants. This clinical trial is still going on and enrolling patients with different types of cancer, including ovarian cancer, melanoma, head and neck cancer, and breast cancer therapy. The clinical trial result gave hope and proof to the medical fraternity and patients for better treatment. The focus of this review is to summarise pre-clinical and clinical studies of Dostarlimab.

19.
Bioorg Chem ; 147: 107341, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38593531

RESUMEN

A series of new indole-oxadiazole derivatives was designed and synthesized to develop potential anti-breast cancer agents. The compounds exhibited significant inhibitory activity with IC50 values ranging from 1.78 to 19.74 µM against ER-positive human breast cancer (BC) cell lines T-47D and MCF-7. Among them, compounds (5a, 5c, 5e-5h, 5j-5o) displayed superior activity against ER-α dominant (ratio of ER-α/ER-ß is 9/1) T-47D cells compared to the standard drug bazedoxifene (IC50 = 12.78 ± 0.92 µM). Compounds 5c and 5o exhibited remarkable anti-proliferative activity with IC50 values of 3.24 ± 0.46 and 1.72 ± 1.67 µM against T-47D cells, respectively. Further, compound 5o manifested 1589-fold higher ER-α binding affinity (213.4 pM) relative to bazedoxifene (339.2 nM) in a competitive ER-α binding assay, while compound 5c showed a binding affinity of 446.6 nM. The Western blot analysis proved that both compounds influenced the ER-α protein's expression, impeding its subsequent transactivation and signalling pathway within T-47D cells. Additionally, a molecular docking study suggests that compounds 5c and 5o bind in such a fashion that induces conformational changes in the protein, culminating in their antagonistic effect. Also, pharmacokinetic profiles showed that all compounds have drug-like properties. Further, molecular dynamic (MD) simulations and density functional theory (DFT) analysis confirmed the stability, conformational behaviour, reactivity, and biological feasibility of compounds 5c and 5o. In conclusion, based on our findings, compounds 5c and 5o, which exhibit significant ER-α antagonistic activity, can act as potential lead compounds for developing anti-breast cancer agents.


Asunto(s)
Antineoplásicos , Proliferación Celular , Relación Dosis-Respuesta a Droga , Diseño de Fármacos , Ensayos de Selección de Medicamentos Antitumorales , Receptor alfa de Estrógeno , Indoles , Oxadiazoles , Humanos , Receptor alfa de Estrógeno/metabolismo , Receptor alfa de Estrógeno/antagonistas & inhibidores , Indoles/química , Indoles/farmacología , Indoles/síntesis química , Oxadiazoles/química , Oxadiazoles/farmacología , Oxadiazoles/síntesis química , Relación Estructura-Actividad , Antineoplásicos/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/química , Proliferación Celular/efectos de los fármacos , Estructura Molecular , Simulación del Acoplamiento Molecular , Línea Celular Tumoral
20.
Sci Rep ; 14(1): 9342, 2024 04 23.
Artículo en Inglés | MEDLINE | ID: mdl-38653763

RESUMEN

Chickpea is a highly nutritious protein-rich source and one of the major crops to alleviate global malnutrition, but poor seed quality affects its productivity. Seed quality is essential for better crop establishment and higher yields, particularly in the uncertain climate change. The present study investigated the impact of botanical priming versus hydropriming and bavistin seed treatment on chickpea seeds. A detailed physiological (germination percentage, root and shoot length, vigour index) and biochemical (amylase, protease, dehydrogenase, phytase, and lipid peroxidation) analysis was carried out in order to assess the effect of priming treatments. Turmeric-primed seeds showed better germination rate (94.5%), seedling length, enzyme activity, and lower malondialdehyde (MDA) content. Sodium dodecyl-sulfate polyacrylamide gel electrophoresis (SDS-PAGE) analysis revealed the expression of minor polypeptides of albumin and globulin in the primed seeds. Moreover, field experiments indicated increased crop growth, vigour, days to 50% flowering, yield and its attributing traits in turmeric-primed seeds. Botanical priming can increase chickpea yield by up to 16% over the control group. This low-cost and eco-friendly technique enhances seed and crop performance, making it a powerful tool for augmenting chickpea growth. Therefore, chickpea growers must adopt botanical priming techniques to enhance the quality of seed and crop performance. Moreover, this approach is environmentally sustainable and can help conserve natural resources in the long term. Therefore, this new approach must be widely adopted across the agricultural industry to ensure sustainable and profitable farming practices.


Asunto(s)
Cicer , Productos Agrícolas , Germinación , Semillas , Cicer/crecimiento & desarrollo , Cicer/efectos de los fármacos , Cicer/metabolismo , Semillas/crecimiento & desarrollo , Semillas/efectos de los fármacos , Semillas/metabolismo , Germinación/efectos de los fármacos , Productos Agrícolas/crecimiento & desarrollo , Productos Agrícolas/efectos de los fármacos , Plantones/crecimiento & desarrollo , Plantones/efectos de los fármacos , Plantones/metabolismo , Proteínas de Plantas/metabolismo , Malondialdehído/metabolismo
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