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1.
Artículo en Inglés | MEDLINE | ID: mdl-37910294

RESUMEN

Cancer is a major public health concern because it is one of the main causes of morbidity and mortality worldwide. As a result, numerous studies have reported the development of new therapeutic compounds with the aim of selectively treating cancer while having little negative influence on healthy cells. In this context, earthworm coelomic fluid has been acknowledged as a rich source of several bioactive substances that may exhibit promising anticancer activity. Therefore, the objective of the present review is to evaluate the findings of the reported studies exploring the antitumor effects of coelomic fluid in the context of its possible utilization as a natural therapeutic agent to cure different types of cancer. The possible mechanisms underlying the coelomic fluid's anticancerous potential as well as the possibility for future development of cutting-edge therapeutic agents utilizing coelomic fluid-derived natural bioactive compounds to treat cancer disorders have been discussed along with future challenges. In addition, the feasibility of encapsulation of bioactive compounds derived from coelomic fluid with nanomaterials that could be further explored to attain more effective anticancer competence is discussed.

2.
Expert Rev Mol Med ; 26: e11, 2024 Apr 29.
Artículo en Inglés | MEDLINE | ID: mdl-38682637

RESUMEN

Long non-coding RNAs (lncRNAs) are progressively being perceived as prominent molecular agents controlling multiple aspects of neuronal (patho)physiology. Amongst these is the HOX transcript antisense intergenic RNA, often abbreviated as HOTAIR. HOTAIR epigenetically regulates its target genes via its interaction with two different chromatin-modifying agents; histone methyltransferase polycomb-repressive complex 2 and histone demethylase lysine-specific demethylase 1. Parenthetically, HOTAIR elicits trans-acting sponging function against multiple micro-RNA species. Oncological research studies have confirmed the pathogenic functions of HOTAIR in multiple cancer types, such as gliomas and proposed it as a pro-oncological lncRNA. In fact, its expression has been suggested to be a predictor of the severity/grade of gliomas, and as a prognostic biomarker. Moreover, a propound influence of HOTAIR in other aspects of brain heath and disease states is just beginning to be unravelled. The objective of this review is to recapitulate all the relevant data pertaining to the regulatory roles of HOTAIR in neuronal (patho)physiology. To this end, we discuss the pathogenic mechanisms of HOTAIR in multiple neuronal diseases, such as neurodegeneration, traumatic brain injury and neuropsychiatric disorders. Finally, we also summarize the results from the studies incriminating HOTAIR in the pathogeneses of gliomas and other brain cancers. Implications of HOTAIR serving as a suitable therapeutic target in neuropathologies are also discussed.


Asunto(s)
ARN Largo no Codificante , Humanos , ARN Largo no Codificante/genética , Animales , Pronóstico , Epigénesis Genética , Biomarcadores , Enfermedades del Sistema Nervioso/genética , Enfermedades del Sistema Nervioso/metabolismo , Enfermedades del Sistema Nervioso/terapia , Enfermedades del Sistema Nervioso/patología , Glioma/genética , Glioma/patología , Glioma/terapia , Glioma/metabolismo
3.
Cell Mol Neurobiol ; 44(1): 23, 2024 Feb 16.
Artículo en Inglés | MEDLINE | ID: mdl-38366205

RESUMEN

HOX transcript antisense intergenic RNA (HOTAIR) is a long non-coding RNA (lncRNA) which is increasingly being perceived as a tremendous molecular mediator of brain pathophysiology at multiple levels. Epigenetic regulation of target gene expression carried out by HOTAIR is thorough modulation of chromatin modifiers; histone methyltransferase polycomb repressive complex 2 (PRC2) and histone demethylase lysine-specific demethylase 1 (LSD1). Incidentally, HOTAIR was the first lncRNA shown to elicit sponging of specific microRNA (miRNA or miR) species in a trans-acting manner. It has been extensively studied in various cancers, including gliomas and is regarded as a prominent pro-tumorigenic and pro-oncogenic lncRNA. Indeed, the expression of HOTAIR may serve as glioma grade predictor and prognostic biomarker. The objective of this timely review is not only to outline the multifaceted pathogenic roles of HOTAIR in the development and pathophysiology of gliomas and brain cancers, but also to delineate the research findings implicating it as a critical regulator of overall brain pathophysiology. While the major focus is on neuro-oncology, wherein HOTAIR represents a particularly potent underlying pathogenic player and a suitable therapeutic target, mechanisms underlying the regulatory actions of HOTAIR in neurodegeneration, traumatic, hypoxic and ischemic brain injuries, and neuropsychiatric disorders are also presented.


Asunto(s)
Enfermedades del Sistema Nervioso Central , Glioma , MicroARNs , ARN Largo no Codificante , Humanos , Enfermedades del Sistema Nervioso Central/genética , Epigénesis Genética , Regulación Neoplásica de la Expresión Génica , Glioma/genética , Complejo Represivo Polycomb 2/genética , Complejo Represivo Polycomb 2/metabolismo , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo
4.
J Biochem Mol Toxicol ; 38(6): e23735, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38773908

RESUMEN

Cancer is one of the major causes of death worldwide, with more than 10 million deaths annually. Despite tremendous advances in the health sciences, cancer continues to be a substantial global contributor to mortality. The current treatment methods demand a paradigm shift that not only improves therapeutic efficacy but also minimizes the side effects of conventional medications. Recently, an increased interest in the potential of natural bioactive compounds in the treatment of several types of cancer has been observed. Ononin, also referred to as formononetin-7-O-ß-d-glucoside, is a natural isoflavone glycoside, derived from the roots, stems, and rhizomes of various plants. It exhibits a variety of pharmacological effects, including Antiangiogenic, anti-inflammatory, antiproliferative, proapoptotic, and antimetastatic activities. The current review presents a thorough overview of sources, chemistry, pharmacokinetics, and the role of ononin in affecting various mechanisms involved in cancer. The review also discusses potential synergistic interactions with other compounds and therapies. The combined synergistic effect of ononin with other compounds increased the efficacy of treatment methods. Finally, the safety studies, comprising both in vitro and in vivo assessments of ononin's anticancer activities, are described.


Asunto(s)
Isoflavonas , Neoplasias , Isoflavonas/farmacología , Isoflavonas/química , Isoflavonas/uso terapéutico , Humanos , Animales , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismo , Neoplasias/patología , Glucósidos/farmacología , Glucósidos/uso terapéutico , Glucósidos/química , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/uso terapéutico , Glicósidos/farmacología , Glicósidos/uso terapéutico , Glicósidos/química , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Antineoplásicos/química
5.
Ann Clin Microbiol Antimicrob ; 23(1): 11, 2024 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-38303011

RESUMEN

Global impact of COVID-19 pandemic has heightened the urgency for efficient virus detection and identification of variants such as the Q57H mutation. Early and efficient detection of SARS-CoV-2 among densely populated developing countries is paramount objective. Although RT-PCR assays offer accuracy, however, dependence on expansive kits and availability of allied health resources pose an immense challenge for developing countries. In the current study, RT-LAMP based detection of SARS-Cov-2 with subsequent confirmation of Q57H variant through ARMS-PCR was performed. Among the 212 collected samples, 134 yielded positive results, while 78 tested negative using RT-LAMP. Oropharyngeal swabs of suspected individuals were collected and processed for viral RNA isolation. Isolated viral RNA was processed further by using either commercially available WarmStart Master Mix or our in house developed LAMP master mix separately. Subsequently, the end results of each specimen were evaluated by colorimetry. For LAMP assays, primers targeting three genes (ORF1ab, N and S) were designed using PrimerExplorer software. Interestingly, pooling of these three genes in single reaction tube increased sensitivity (95.5%) and specificity (93.5%) of LAMP assay. SARS-CoV-2 positive specimens were screened further for Q57H mutation using ARMS-PCR. Based on amplicon size variation, later confirmed by sequencing, our data showed 18.5% samples positive for Q57H mutation. Hence, these findings strongly advocate use of RT-LAMP-based assay for SARS-CoV-2 screening within suspected general population. Furthermore, ARMS-PCR also provides an efficient mean to detect prevalent mutations against SARS-Cov-2.


Asunto(s)
COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , COVID-19/diagnóstico , Pandemias , Sensibilidad y Especificidad , Técnicas de Diagnóstico Molecular/métodos , ARN Viral/genética , Reacción en Cadena de la Polimerasa , Prueba de COVID-19
6.
Semin Cancer Biol ; 83: 353-376, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-33434642

RESUMEN

Cell cycle, growth, survival and metabolism are tightly regulated together and failure in cellular regulation leads to carcinogenesis. Several signaling pathways like the PI3K, WNT, MAPK and NFKb pathway exhibit aberrations in cancer and help achieve hallmark capabilities. Clinical research and in vitro studies have highlighted the role of epigenetic alterations in cancer onset and development. Altered gene expression patterns enabled by changes in DNA methylation, histone modifications and RNA processing have proven roles in cancer hallmark acquisition. The reversible nature of epigenetic processes offers robust therapeutic targets. Dietary bioactive compounds offer a vast compendium of effective therapeutic moieties. Isothiocyanates (ITCs) sourced from cruciferous vegetables demonstrate anti-proliferative, pro-apoptotic, anti-inflammatory, anti-migratory and anti-angiogenic effect against several cancers. ITCs also modulate the redox environment, modulate signaling pathways including PI3K, MAPK, WNT, and NFkB. They also modulate the epigenetic machinery by regulating the expression and activity of DNA methyltransferases, histone modifiers and miRNA. This further enhances their transcriptional modulation of key cellular regulators. In this review, we comprehensively assess the impact of ITCs such as sulforaphane, phenethyl isothiocyanate, benzyl isothiocyanate and allyl isothiocyanate on cancer and document their effect on various molecular targets. Overall, this will facilitate consolidation of the current understanding of the anti-cancer and epigenetic modulatory potential of these compounds and recognize the gaps in literature. Further, we discuss avenues of future research to develop these compounds as potential therapeutic entities.


Asunto(s)
Epigenoma , Neoplasias , Epigénesis Genética , Humanos , Isotiocianatos/farmacología , Isotiocianatos/uso terapéutico , Neoplasias/tratamiento farmacológico , Neoplasias/genética , Fosfatidilinositol 3-Quinasas
7.
Semin Cancer Biol ; 83: 441-451, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-34182144

RESUMEN

The role of epigenetics in the etiology of cancer progression is being emphasized for the past two decades to check the impact of chromatin modifiers and remodelers. Histone modifications, DNA methylation, chromatin remodeling, nucleosome positioning, regulation by non-coding RNAs and precisely microRNAs are influential epigenetic marks in the field of progressive cancer sub-types. Furthermore, constant epigenetic changes due to hyper or hypomethylation could efficiently serve as effective biomarkers of cancer diagnosis and therapeutic development. Ongoing research in the field of epigenetics has resulted in the resolutory role of various epigenetic markers and their inhibition using specific inhibitors to arrest their key cellular functions in in-vitro and pre-clinical studies. Although, the mechanism of epigenetics in cancer largely remains unexplored. Nevertheless, various advancements in the field of epigenetics have been made through transcriptome analysis and in-vitro genome targeting technologies to unravel the applicability of epigenetic markers for future cancer therapeutics and management. Therefore, this review emphasizes on recent advances in epigenetic landscapes that could be targeted/explored using novel approaches as personalized treatment modalities for cancer containment.


Asunto(s)
Epigénesis Genética , Neoplasias , Carcinogénesis/genética , Metilación de ADN , Epigenómica , Humanos , Neoplasias/tratamiento farmacológico , Neoplasias/genética
8.
Semin Cancer Biol ; 86(Pt 3): 666-681, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-34216789

RESUMEN

An overwhelming number of research articles have reported a strong relationship of the microbiome with cancer. Microbes have been observed more commonly in the body fluids like urine, stool, mucus of people with cancer compared to the healthy controls. The microbiota is responsible for both progression and suppression activities of various diseases. Thus, to maintain healthy human physiology, host and microbiota relationship should be in a balanced state. Any disturbance in this equilibrium, referred as microbiome dysbiosis becomes a prime cause for the human body to become more prone to immunodeficiency and cancer. It is well established that some of these microbes are the causative agents, whereas others may encourage the formation of tumours, but very little is known about how these microbial communications causing change at gene and epigenome level and trigger as well as encourage the tumour growth. Various studies have reported that microbes in the gut influence DNA methylation, DNA repair and DNA damage. The genes and pathways that are altered by gut microbes are also associated with cancer advancement, predominantly those implicated in cell growth and cell signalling pathways. This study exhaustively reviews the current research advancements in understanding of dysbiosis linked with colon, lung, ovarian, breast cancers and insights into the potential molecular targets of the microbiome promoting carcinogenesis, the epigenetic alterations of various potential targets by altered microbiota, as well as the role of various chemopreventive agents for timely prevention and customized treatment against various types of cancers.


Asunto(s)
Microbiota , Neoplasias , Humanos , Disbiosis/complicaciones , Disbiosis/genética , Epigenómica , Epigénesis Genética , Neoplasias/genética
9.
Semin Cancer Biol ; 86(Pt 2): 1120-1137, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-34052413

RESUMEN

Lichens, algae and fungi-based symbiotic associations, are sources of many important secondary metabolites, such as antibiotics, anti-inflammatory, antioxidants, and anticancer agents. Wide range of experiments based on in vivo and in vitro studies revealed that lichens are a rich treasure of anti-cancer compounds. Lichen extracts and isolated lichen compounds can interact with all biological entities currently identified to be responsible for tumor development. The critical ways to control the cancer development include induction of cell cycle arrests, blocking communication of growth factors, activation of anti-tumor immunity, inhibition of tumor-friendly inflammation, inhibition of tumor metastasis, and suppressing chromosome dysfunction. Also, lichen-based compounds induce the killing of cells by the process of apoptosis, autophagy, and necrosis, that inturn positively modulates metabolic networks of cells against uncontrolled cell division. Many lichen-based compounds have proven to possess potential anti-cancer activity against a wide range of cancer cells, either alone or in conjunction with other anti-cancer compounds. This review primarily emphasizes on an updated account of the repository of secondary metabolites reported in lichens. Besides, we discuss the anti-cancer potential and possible mechanism of the most frequently reported secondary metabolites derived from lichens.


Asunto(s)
Antineoplásicos , Líquenes , Neoplasias , Humanos , Líquenes/metabolismo , Antioxidantes/metabolismo , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Antineoplásicos/metabolismo , Apoptosis , Neoplasias/tratamiento farmacológico
10.
Environ Res ; 237(Pt 2): 116983, 2023 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-37640091

RESUMEN

A microbial-driven approach for effluent treatment, recycling, and management of Pharmaceutical and Personal Care Products (PPCPs) has been undertaken to mitigate the menace of water contamination. Bioremediation processes are mainly considered the first preference in pharmaceutical wastewater recycling and management. PPCPs are reported as one of the primary sources of emerging contaminants in various water matrices, which raises concern and requires efficient management. Their widespread utilization, persistently high level, and resistance to breaking down make them one of the potentially dangerous compounds causing harm to the ecosystem. Continually increasing PPCPs level PPCPs contaminants in water bodies raised concern for human health as they can produce potential risks with harmful and untoward impacts on our health. PPCPs are composed of multiple diverse compounds used by humans and animals, which include biopharmaceuticals, vitamins and nutritional supplements, antibiotics, counter-prescription drugs, cosmetics products, and unused pharmaceutical products. Personal care products are found to be bioaccumulative, reduce water quality and potentially impact ecological health. However, continual exposure to PPCPs in aquatic organisms, impacts their endocrine function disruption, gene toxicity, and antibiotic resistance. Decreased water quality may result in an outbreak of various water-borne diseases, which could have acute or long-term health complications and may result in an outbreak of various water-borne diseases, which could have acute or long-term effects on public and community health. Polluted water consumption by humans and animals produces serious health hazards and increased susceptibility to water-borne diseases such as carcinogenic organic or inorganic contaminants and infectious pathogens present in water bodies. Many water resource recovery facilities working on various conventional and advanced methods involve the utilization of microbes for filtration and advanced oxidation processes. Therefore, there is an immense need for bioremediation techniques facilitated by mixed cultures of bacteria, algae, and other microbes that can be used as an alternative approach for removing pharmaceutical content from effluent. This review highlights the various sources of PPCPs and their impacts on soil and water bodies, resulting in bioaccumulation. Different techniques are utilized to detect PPCPs, and various control strategies imply controlling, recycling, and managing waste.

11.
Environ Res ; 233: 116476, 2023 09 15.
Artículo en Inglés | MEDLINE | ID: mdl-37348632

RESUMEN

Curcumin, derived from turmeric, has a strong anticancer potential known for millennia. The development of this phytochemical as a medicine has been hampered by several significant deficiencies, including its poor water solubility and low bioavailability. This review article discusses possibilities to overcome these bottlenecks by focusing on this natural polyphenol's nanoformulation. Moreover, preparation of curcumin conjugates containing folates as ligands for folic acid receptors can add a new important dimension in this field, allowing specific targeting of cancer cells, considering the significantly higher expression of these receptors in malignant tissues compared to normal cells. It is highly expected that simultaneous improvement of different aspects of curcumin in fighting against such a complex and multifaceted disease like cancer. Therefore, we can better comprehend cancer biology by developing a mechanistic understanding of curcumin, which will also inspire the scientific community to develop new pharmacological models, and exploration of emerging directions to revitalize application of natural products in cancer therapy.


Asunto(s)
Curcumina , Neoplasias , Humanos , Curcumina/uso terapéutico , Curcumina/farmacología , Ácido Fólico/uso terapéutico , Neoplasias/tratamiento farmacológico , Solubilidad
12.
Environ Res ; 238(Pt 2): 116909, 2023 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-37673119

RESUMEN

Xenobiotic pollution in environment is a potential risk to marine life, and human health. Nanobiotechnology is an advanced and emerging solution for the removal of environmental pollutants. Adsorption-based technologies are being used to alleviate the global prevalence of xenobiotics like dyes, due to their high efficacy and cost effectiveness. Current study explored the potential of nanobiochar syntehsized via ultrasonication and centrifugation from rice husk for dye removal from water. It involves the synthesis of nanobiochar from rice husk biochar for removal of Safranin, Malachite green, and a mixture of both from aqueous water. Biochar was synthesized through pyrolysis at 600 °C for 2 h. To convert it into nanobiochar, sonication and centrifugation techniques were applied. The yield obtained was 27.5% for biochar and 0.9% for nanobiochar. Nanobiochar analysis through Fourier-Transform Spectrometer (FTIR), X-ray Power Diffraction (XRD) and scanning electron microscopy (SEM) suggested its crystalline nature having minerals rich in silicon, with a cracked and disintegrated carbon structure due to high temperature and processing treatments. Removal of dyes by nanobiochar was evaluated by changing different physical parameters i.e., nanobiochar dose, pH, and temperature. Pseudo-first order model and pseudo-second order model were applied to studying the adsorption kinetics mechanism. Kinetics for adsorption of dyes followed the pseudo-second order model suggesting the removal of dyes by process of chemical sorption. High adsorption was found at a higher concentration of nanobiochar, high temperature, and neutral pH. Maximum elimination percentages of safranin, malachite green, and a mixture of dyes were obtained as 91.7%, 87.5%, and 85% respectively. We conclude that nanobiochar could be a solution for dye removal from aqueous media.


Asunto(s)
Oryza , Contaminantes Químicos del Agua , Humanos , Oryza/química , Agua , Colorantes/química , Adsorción , Cinética , Contaminantes Químicos del Agua/análisis , Concentración de Iones de Hidrógeno
13.
Int J Mol Sci ; 24(6)2023 Mar 10.
Artículo en Inglés | MEDLINE | ID: mdl-36982429

RESUMEN

Colorectal cancer is one of the leading causes of cancer-associated mortality across the worldwide. One of the major challenges in colorectal cancer is the understanding of the regulatory mechanisms of biological molecules. In this study, we aimed to identify novel key molecules in colorectal cancer by using a computational systems biology approach. We constructed the colorectal protein-protein interaction network which followed hierarchical scale-free nature. We identified TP53, CTNBB1, AKT1, EGFR, HRAS, JUN, RHOA, and EGF as bottleneck-hubs. The HRAS showed the largest interacting strength with functional subnetworks, having strong correlation with protein phosphorylation, kinase activity, signal transduction, and apoptotic processes. Furthermore, we constructed the bottleneck-hubs' regulatory networks with their transcriptional (transcription factor) and post-transcriptional (miRNAs) regulators, which exhibited the important key regulators. We observed miR-429, miR-622, and miR-133b and transcription factors (EZH2, HDAC1, HDAC4, AR, NFKB1, and KLF4) regulates four bottleneck-hubs (TP53, JUN, AKT1 and EGFR) at the motif level. In future, biochemical investigation of the observed key regulators could provide further understanding about their role in the pathophysiology of colorectal cancer.


Asunto(s)
Neoplasias Colorrectales , MicroARNs , Humanos , MicroARNs/metabolismo , Redes Reguladoras de Genes , Regulación de la Expresión Génica , Factores de Transcripción/metabolismo , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/metabolismo , Receptores ErbB/genética , Receptores ErbB/metabolismo , Biología Computacional , Regulación Neoplásica de la Expresión Génica
14.
Molecules ; 28(22)2023 Nov 10.
Artículo en Inglés | MEDLINE | ID: mdl-38005250

RESUMEN

Flavopiridol is a flavone synthesized from the natural product rohitukine, which is derived from an Indian medicinal plant, namely Dysoxylum binectariferum Hiern. A deeper understanding of the biological mechanisms by which such molecules act may allow scientists to develop effective therapeutic strategies against a variety of life-threatening diseases, such as cancer, viruses, fungal infections, parasites, and neurodegenerative diseases. Mechanistic insight of flavopiridol reveals its potential for kinase inhibitory activity of CDKs (cyclin-dependent kinases) and other kinases, leading to the inhibition of various processes, including cell cycle progression, apoptosis, tumor proliferation, angiogenesis, tumor metastasis, and the inflammation process. The synthetic derivatives of flavopiridol have overcome a few demerits of its parent compound. Moreover, these derivatives have much improved CDK-inhibitory activity and therapeutic abilities for treating severe human diseases. It appears that flavopiridol has potential as a candidate for the formulation of an integrated strategy to combat and alleviate human diseases. This review article aims to unravel the potential therapeutic effectiveness of flavopiridol and its possible mechanism of action.


Asunto(s)
Antineoplásicos , Neoplasias , Humanos , Flavonoides/farmacología , Flavonoides/uso terapéutico , Quinasas Ciclina-Dependientes , Fosforilación , Neoplasias/tratamiento farmacológico , Antineoplásicos/farmacología , Apoptosis
15.
Molecules ; 28(4)2023 Feb 08.
Artículo en Inglés | MEDLINE | ID: mdl-36838640

RESUMEN

The emergence of multi-drug-resistant Mycobacterium tuberculosis (Mtb) strains has rendered many of the currently available anti-TB drugs ineffective. Hence, there is a pressing need to discover new potential drug targets/candidates. In this study, attempts have been made to identify novel inhibitors of the ribonuclease VapC2 of Mtb H37Rv using various computational techniques. Ribonuclease VapC2 Mtb H37Rv's protein structure was retrieved from the PDB databank, 22 currently used anti-TB drugs were retrieved from the PubChem database, and protein-ligand interactions were analyzed by docking studies. Out of the 22 drugs, rifampicin (RIF), being a first-line drug, showed the best binding energy (-8.8 Kcal/mol) with Mtb H37Rv VapC2; hence, it was selected as a parent molecule for the design of its derivatives. Based on shape score and radial plot criteria, out of 500 derivatives designed through SPARK (Cresset®, Royston, UK) program, the 10 best RIF derivatives were selected for further studies. All the selected derivatives followed the ADME criteria concerning drug-likeness. The docking of ribonuclease VapC2 with RIF derivatives revealed the best binding energy of -8.1 Kcal/mol with derivative 1 (i.e., RIF-155841). A quantitative structure-activity relationship study revealed that derivative 1's activity assists in the inhibition of ribonuclease VapC2. The stability of the VapC2-RIF155841 complex was evaluated using molecular dynamics simulations for 50 ns and the complex was found to be stable after 10 nsec. Further, a chemical synthesis scheme was designed for the newly identified RIF derivative (RIF-155841), which verified that its chemical synthesis is possible for future in vitro/in vivo experimental validation. Overall, this study evaluated the potential of the newly designed RIF derivatives with respect to the Mtb VapC2 protein, which is predicted to be involved in some indispensable processes of the related pathogen. Future experimental studies regarding RIF-155841, including the exploration of the remaining RIF derivatives, are warranted to verify our current findings.


Asunto(s)
Mycobacterium tuberculosis , Tuberculosis , Humanos , Rifampin/farmacología , Ribonucleasas/farmacología , Simulación de Dinámica Molecular , Sensibilidad y Especificidad
16.
Environ Res ; 215(Pt 2): 114292, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-36100106

RESUMEN

At present, development and production of advanced green energy sources are highly demanded, and this may offer a clean and sustainable environment to our modern society. In this reference, biogas is emerging as a promising green energy source and seems to have high potential to replace fossil-fuel based energy sources in the coming future. Further, lignocellulosic biomass (LCB) based biogas production technology has been found to be highly promising owing to several advantages associated therewith. Rich inorganic content, renewable nature, huge availability and low-cost are the key beneficial factors of LCB-based feedstock l to produce biogas. Among the varieties of LCB, paddy straw is one of the most demanding feedstocks and is highly rich in organic compounds that are imperative to producing biogas. Nevertheless, it is noticed that paddy straw as a waste material is usually disposed-off by direct burning, whereas it exhibits low natural digestibility due to the presence of high lignin and silica content which causes severe environmental pollution. On the other hand, paddy straw can be a potential feedstock to produce biogas through anaerobic digestion. Therefore, based on the current ongoing research studies worldwide, this review evaluates the advancements made in the AD process. Meanwhile, existing limitations and future recommendations to improve the yield and productivity of the biogas using paddy straw have been discussed. The emphasis has also been given to various operational parameters developments, related shortcomings, and strategies to improve biogas production at pilot scale.


Asunto(s)
Biocombustibles , Lignina , Anaerobiosis , Combustibles Fósiles , Dióxido de Silicio
17.
Adv Exp Med Biol ; 2022 Apr 08.
Artículo en Inglés | MEDLINE | ID: mdl-35389198

RESUMEN

Stem cells are very promising for the treatment of a plethora of human diseases. Numerous clinical studies have been conducted to assess the safety and efficacy of various stem cell types. Factors that ensure successful therapeutic outcomes in patients are cell-based parameters such as source, viability, and number, as well as frequency and timing of intervention and disease stage. Stem cell administration routes should be appropriately chosen as these can affect homing and engraftment of the cells and hence reduce therapeutic effects, or compromise safety, resulting in serious adverse events. In this chapter, we will describe the use of stem cells in organ repair and regeneration, in particular, the liver and the available routes of cell delivery in the clinic for end-stage liver diseases. Factors affecting homing and engraftment of stem cells for each administration route will be discussed.

18.
Adv Exp Med Biol ; 1391: 17-32, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36472814

RESUMEN

Infertility is a serious public health issue affecting around 15% of couples globally. Of the 60-80 million people of reproductive age affected by infertility, 40-50% are due to male factor while 30-40% of cases are still idiopathic. The recent global deterioration in sperm quality raises apprehensions regarding the toxic effects of environmental pollutants on reproductive health of males. Environmental toxicants have shown strong evidences for inducing oxidative stress affecting spermatogenesis severely, thereby leading to reduced sperm motility, count, and DNA damage. Reactive oxygen species (ROS) influences the spermatozoa development and transit process both internally and externally. Low level of ROS is indispensable for critical physiological sperm processes like sperm capacitation, motility, acrosome reaction, hyper-activation, sperm-oocyte interaction, etc., while excessive ROS disrupt antioxidant molecules which is detrimental to normal functioning of the sperm. Hence, identification of potential environmental toxicant may have clinical relevance for early screening and diagnosis of male infertility.


Asunto(s)
Infertilidad Masculina , Semen , Masculino , Humanos , Motilidad Espermática , Infertilidad Masculina/inducido químicamente , Estrés Oxidativo
19.
Adv Exp Med Biol ; 1391: 59-69, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36472816

RESUMEN

Pesticides have benefited mankind in many ways like agriculture, industrial and health sectors. On the other hand, conversely their deleterious effects in both, humans and animals are also alarming. Pesticides including organophosphates, organochlorines, carbamates, pyrethrins and pyrethroids are found sufficiently in the environment resulting in everyday human exposure. This is of a huge concern because most of the pesticides are known to target all the physiological functions of both humans and animals. Indeed, reproduction, being one of the most important physiological processes, that is affected by the daily exposure to pesticides and leading to infertility issues. The present study summarizes the exposure of men and women to certain pesticides resulting in different infertility concerns like sperm abnormalities, decreased fertility, abnormal sperm count and motility, testicular atrophy, ovarian dysfunction, spontaneous abortions, disruption of hypothalamic-pituitary-gonadal axis, etc. So, this article will be helpful in perceiving the mechanism of reproductive toxicity of different pesticides and their management before any alarm of danger.


Asunto(s)
Fertilidad , Plaguicidas , Femenino , Humanos , Masculino , Semen , Plaguicidas/toxicidad , Animales , Fertilidad/efectos de los fármacos
20.
Med Teach ; 44(12): 1340-1346, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-34634989

RESUMEN

There is increasing evidence on the positive outcomes of engaging students and community partners in medical education, especially in achieving social accountability. However, less is known about the steps through which these engagements are established. This paper outlines twelve tips on establishing a robust and enduring partnership with students and community partners in medical education, using examples from the Western Sydney University School of Medicine. While context is paramount in any engagement program, these tips are formulated to be transferable to medical education settings in different countries, education systems, and the broader context of health professional education.


Asunto(s)
Educación Médica , Estudiantes de Medicina , Humanos , Curriculum , Estudiantes , Universidades
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