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1.
J Stroke Cerebrovasc Dis ; 33(8): 107824, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38880366

RESUMO

BACKGROUND: Ischemic injury is a common mechanism in both ischemic stroke (IS) and acute coronary syndrome (ACS). Matrix metalloproteinase 9 (MMP-9), an endopeptidase that degrades extracellular matrix, is important in the pathogenesis of IS. The purpose of this study is to evaluate the association between the SNP rs17576 in MMP-9 gene with (1) the risk and severity of acute ischemic stroke in Saudi Arab individuals with recent acute coronary syndrome, and (2) the risk of acute coronary syndrome in Saudi Arab individuals without ischemic stroke. METHODS: A case control study of 200 IS patients, 520 ACS patients (without IS), and 500 aged-matched healthy controls were genotyped to detect the MMP-9 polymorphism rs17156. RESULTS: Our study demonstrated a non-significant difference in the genotype and allele frequencies of the MMP9 rs17576 polymorphism between the patients with IS and patients with ACS without IS (P = 0.31 for the GA genotype, 0.25 for the AA genotype and P = 0.20 for the A allele). AA genotype was found to be statistically significant between IS and control groups; [OR=1.84, 95 % CI (1.08-3.14), p =0.015]. A allele showed a significant difference between the two groups [OR=1.28, 95 % CI (1.00-1.64), p =0.028]. By comparing ACS without IS and controls, AA genotype was significant [OR=1.46, 95 % CI (1.01-2.12), p =0.029]. Stratification by NIHSS score revealed higher mortality and early neurologic deterioration in IS patients with NIHSS score ≥ 16 (p < 0.001, 0.044 respectively). CONCLUSION: We deduced the lack of association either with allele or genotype frequencies (p>0.05) between the IS cases and the cases of ACS without IS. In contrast there was a significant association of mutant genotype AA between either the IS group or ACS (without IS) group, and the control group. In addition, different rs17576 genotypes were not associated with raised mortality or a tendency to develop early neurologic deterioration.

2.
Metab Brain Dis ; 38(3): 1051-1066, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36437394

RESUMO

Parkinson's disease (PD) is slowly developing neurodegenerative disorder associated with gradual decline in cerebration and laboriousness to perform routine piece of work. PD imposed a social burden on society through higher medical cost and by loss of social productivity in current era. The available treatment options are expensive and associated with serious adverse effect after long term use. Therefore, there is a critical clinical need to develop alternative pharmacotherapies from natural sources to prevent and cure the pathological hall marks of PD with minimal cost. Our study aimed to scrutinize the antiparkinsonian potential of curcuminoids-rich extract and its binary and ternary inclusion complexes. In healthy rats, 1 mg/kg haloperidol daily intraperitoneally, for 3 weeks was used to provoke Parkinsonism like symptoms except control group. Curcuminoids rich extract, binary and ternary inclusion complexes formulations 15-30 mg/kg, L-dopa and carbidopa (100 + 25 mg/kg) were orally administered on each day for 3 weeks. Biochemical, histopathological and RT-qPCR analyses were conducted after neurobehavioral observations. Findings of current study indicated that all curcuminoids formulations markedly mitigated the behavioral abnormalities, recovered the level of antioxidant enzymes, acetylcholinesterase inhibitory activity and neurotransmitters. Histological analysis revealed that curcuminoids supplements stabilized the neuronal loss, pigmentation and Lewy bodies' formation. The mRNA expressions of neuro-inflammatory and specific PD pathological biomarkers were downregulated by treatment with curcuminoids formulations. Therefore, it is suggested that these curcuminoids rich extract, binary and ternary supplements should be considered as promising therapeutic agents in development of modern anti-Parkinson's disease medications.


Assuntos
Diarileptanoides , Doença de Parkinson , Ratos , Animais , Diarileptanoides/uso terapêutico , Haloperidol/farmacologia , Haloperidol/uso terapêutico , Acetilcolinesterase , Modelos Animais de Doenças , Doença de Parkinson/tratamento farmacológico
3.
BMC Cancer ; 22(1): 599, 2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-35650591

RESUMO

The full-length BRCA1-associated RING domain 1 (BARD1) gene encodes a 777-aa protein. BARD1 displays a dual role in cancer development and progression as it acts as a tumor suppressor and an oncogene. Structurally, BARD1 has homologous domains to BRCA1 that aid their heterodimer interaction to inhibit the progression of different cancers such as breast and ovarian cancers following the BRCA1-dependant pathway. In addition, BARD1 was shown to be involved in other pathways that are involved in tumor suppression (BRCA1-independent pathway) such as the TP53-dependent apoptotic signaling pathway. However, there are abundant BARD1 isoforms exist that are different from the full-length BARD1 due to nonsense and frameshift mutations, or deletions were found to be associated with susceptibility to various cancers including neuroblastoma, lung, breast, and cervical cancers. This article reviews the spectrum of BARD1 full-length genes and its different isoforms and their anticipated associated risk. Additionally, the study also highlights the role of BARD1 as an oncogene in breast cancer patients and its potential uses as a prognostic/diagnostic biomarker and as a therapeutic target for cancer susceptibility testing and treatment.


Assuntos
Neoplasias , Proteínas Supressoras de Tumor , Ubiquitina-Proteína Ligases , Feminino , Genes Supressores de Tumor , Humanos , Neoplasias/genética , Isoformas de Proteínas/genética , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismo , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo
4.
Global Health ; 18(1): 103, 2022 12 09.
Artigo em Inglês | MEDLINE | ID: mdl-36494695

RESUMO

This paper highlights the gap in the use of genomic data of Africans for global research efforts for disease cures. Genomic data represents an important tool used in disease research for understanding how diseases affect several populations and how these differences can be harnessed for the development of effective cures especially vaccines that have an impact at the genetic level e.g., RNA vaccines.This paper then provides a review of global genomic data status where three continents are reported to be the major contributor of genomic data to repositories used for disease research and the development of vaccines and medicines around the world.We reviewed the most recently published information about genetic data inclusiveness of populations, explaining how genomic data of Africans is lacking in global research efforts that cater towards the eradication of pandemics via the development of vaccines and other cures. We also discuss the implication of this non-inclusiveness for global disease burdens and indicate where changes need to be made in the last part of the paper.Lastly, the entire centers on some general policy recommendations to fully include African genomic data in such global genetic repositories. These recommendations can be implemented in African countries to improve genetic data collection, storage, and usage policies.


Assuntos
Carga Global da Doença , Vacinas , Humanos , Genômica , Pandemias , África
5.
J Therm Biol ; 108: 103302, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36031223

RESUMO

Global climate change is accelerating at an unprecedented rate, and the consequences of global warming are expected to worsen. Many heat waves have recently hit various parts of the world, causing major losses in livestock, particularly in the poultry sector, resulting in massive mortalities and catastrophic economic losses. Therefore, the current review sheds light on the effects of heat stress on the poultry industry, and discusses the factors relevant to these harmful effects on behavior, bone development, blood chemistry and physiological changes, pathogenesis, and immune responses. Potential methods to ameliorate the heat stress response in birds, with particular reference to the role of probiotics in controlling such problems, is further discussed.


Assuntos
Transtornos de Estresse por Calor , Probióticos , Animais , Resposta ao Choque Térmico , Gado , Aves Domésticas
6.
Inflammopharmacology ; 30(6): 2003-2016, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36183284

RESUMO

Coronavirus disease 2019 (Covid-19) is a global diastrophic disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Covid-19 leads to inflammatory, immunological, and oxidative changes, by which SARS-CoV-2 leads to endothelial dysfunction (ED), acute lung injury (ALI), acute respiratory distress syndrome (ARDS), and multi-organ failure (MOF). Despite evidence illustrating that some drugs and vaccines effectively manage and prevent Covid-19, complementary herbal medicines are urgently needed to control this pandemic disease. One of the most used herbal medicines is berberine (BBR), which has anti-inflammatory, antioxidant, antiviral, and immune-regulatory effects; thus, BBR may be a prospective candidate against SARS-CoV-2 infection. This review found that BBR has anti-SARS-CoV-2 effects with mitigation of associated inflammatory changes. BBR also reduces the risk of ALI/ARDS in Covid-19 patients by inhibiting the release of pro-inflammatory cytokines and inflammatory signaling pathways. In conclusion, BBR has potent anti-inflammatory, antioxidant, and antiviral effects. Therefore, it can be utilized as a possible anti-SARS-CoV-2 agent. BBR inhibits the proliferation of SARS-CoV-2 and attenuates the associated inflammatory disorders linked by the activation of inflammatory signaling pathways. Indeed, BBR can alleviate ALI/ARDS in patients with severe Covid-19. In this sense, clinical trials and prospective studies are suggested to illustrate the potential role of BBR in treating Covid-19.


Assuntos
Berberina , Tratamento Farmacológico da COVID-19 , Síndrome do Desconforto Respiratório , Humanos , SARS-CoV-2 , Berberina/farmacologia , Berberina/uso terapêutico , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Estudos Prospectivos , Antivirais/farmacologia , Antivirais/uso terapêutico , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico
7.
Molecules ; 27(18)2022 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-36144719

RESUMO

Emulgel is a new innovatory technique for drug development permitting controlled release of active ingredients for topical administration. We report a stable emulgel of 4% Piper nigrum extract (PNE) prepared using 80% ethanol. The PNE-loaded formulation had an antioxidant activity of 84% and tyrosinase inhibition was 82%. Prepared formulation rendered spherical-shaped globules with high zeta potential (-45.5 mV) indicative of a stable system. Total phenolic contents were 58.01 mg GAE/g of dry extract whereas total flavonoid content was 52.63 mg QE/g of dry extract. Sun protection factor for PNE-loaded emulgel was 7.512 and formulation was stable without any evidence of physical and chemical changes following 90 days of storage. Gas chromatography-mass spectroscopy (GC-MS) revealed seventeen bioactive compounds in the PNE including monoterpenoids, triterpenoids, a tertiary alcohol, fatty acid esters, and phytosterols. In silico studies of GC-MS identified compounds show higher binding affinity in comparison to standard kojic acid indicating tyrosinase inhibition. It can be concluded that PNE-loaded emulgel had prominent antioxidant and tyrosinase inhibition and can be utilized as a promising topical system for anti-aging skin formulation.


Assuntos
Fitosteróis , Piper nigrum , Triterpenos , Alérgenos , Antioxidantes/química , Antioxidantes/farmacologia , Preparações de Ação Retardada , Etanol , Álcoois Graxos , Flavonoides , Simulação de Acoplamento Molecular , Monofenol Mono-Oxigenase , Monoterpenos , Piper nigrum/química , Extratos Vegetais/química , Sementes
8.
Saudi Pharm J ; 29(12): 1458-1465, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35002384

RESUMO

BACKGROUND: Coronary artery disease (CAD) is one of the common genetic and clinical risk factors associated with cardiovascular and multifactorial disorder. ATP-binding cassette transporter A1 (ABCA1) gene plays an important role in lipid metabolism and in multiple studies associated with CAD. However, more studies are needed to identify the exact role of single nucleotide polymorphisms which may cause CAD. OBJECTIVES: The aim of this study is to investigate the genetic association of polymorphism g.1051G > A in the ABCA1 gene with CAD patients in the Saudi population. METHODS: We included 315 confirmed CAD cases, and 205 non-CAD or control subjects in this case-control study. DNA isolation was carried out for all registered participants and the polymorphism g.1051G > A was genotyped with Polymerase Chain Reaction followed by Restriction Fragment Length Polymorphism analysis with EcoNI restriction enzyme. RESULTS: Modifiable risk factors such as Body Mass Index, smoking and diabetes were strongly associated and non-modifiable risk factors such as hypertension (Systolic Blood Pressure and Diastolic Blood Pressure) and serum analysis such as Fasting Blood Glucose, Total cholesterol (TC), Triglyceride (TG) and LDL-c were significantly associated in CAD cases (p < 0.05). Allele (OR-1.73;95% CI:1.33-2.26; p = 0.0004), GA vs GG (OR-2.26; 95% CI: 1.53-3.35; p = 0.0003 and dominant inheritance pattern (OR-2.23; 95% CI:1.56-3.20; p = 0.00009 was strongly associated with CAD cases and control subjects. The frequency level of use of atorvastatin was significantly different among GG, GA and AA subjects. Additionally, TC and TG levels were influenced by the presence of g.1051G > A polymorphism. CONCLUSION: The polymorphism g.1051G > A in the gene ABCA1 is closely associated with the existence of the CAD subjects. This polymorphism could also affect the serum levels of the lipid profile, suggesting a possible occurrence of CAD in the Saudi population.

9.
J Infect Public Health ; 17(6): 1108-1116, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38714123

RESUMO

BACKGROUND: New Delhi metallo-beta-lactamase-1 (NDM1) confers resistance to several bacterial species against a broad range of beta-lactam antibiotics and turning them into superbugs that pose a significant threat to healthcare systems worldwide. As such, it is a potentially relevant biological target for counteracting bacterial infections. Given the lack of effective treatment options against NDM1 producing bacteria, finding a reliable inhibitor for the NDM1 enzyme is crucial. METHODS: Using molecular dynamics simulations, the binding selectivities and affinities of three ligands, viz. PNK, 3S0, and N1G were investigated against NDM1. RESULTS: The results indicate that N1G binds with more affinity to NDM1 than PNK and 3S0. The binding energy decomposition analysis revealed that residues I35, W93, H189, K211, and N220 showed significant binding energies with PNK, 3S0, and N1G, and hence are crucially involved in the binding of the ligands to NDM1. Molecular dynamics trajectory analysis further elicited that the ligands influence dynamic flexibility of NDM1 morphology, which contributes to the partial selectivities of PNK, 3S0, and N1G. CONCLUSIONS: This in silico study offers a vital information for developing potential NDM1 inhibitors with high selectivity. Nevertheless, in vitro and in vivo experimental validation is mandated to extend the possible applications of these ligands as NDM1 inhibitors that succor in combating antimicrobial resistance.


Assuntos
Simulação de Dinâmica Molecular , Inibidores de beta-Lactamases , beta-Lactamases , beta-Lactamases/metabolismo , beta-Lactamases/química , Inibidores de beta-Lactamases/farmacologia , Inibidores de beta-Lactamases/química , Antibacterianos/farmacologia , Antibacterianos/química , Ligação Proteica , Farmacorresistência Bacteriana , Ligantes
10.
Clin Chim Acta ; 559: 119687, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38663473

RESUMO

Ovarian cancers (OC) are the most common, lethal, and stage-dependent cancers at the global level, specifically in female patients. Targeted therapies involve the administration of drugs that specifically target the alterations in tumour cells responsible for their growth, proliferation, and metastasis, with the aim of treating particular patients. Presently, within the realm of gynaecological malignancies, specifically in breast and OCs, there exist various prospective therapeutic targets encompassing tumour-intrinsic signalling pathways, angiogenesis, homologous-recombination deficit, hormone receptors, and immunologic components. Breast cancers are often detected in advanced stages, primarily due to the lack of a reliable screening method. However, various tumour markers have been extensively researched and employed to evaluate the condition, progression, and effectiveness of medication treatments for this ailment. The emergence of recent technological advancements in the domains of bioinformatics, genomics, proteomics, and metabolomics has facilitated the exploration and identification of hitherto unknown biomarkers. The primary objective of this comprehensive review is to meticulously investigate and analyze both established and emerging methodologies employed in the identification of tumour markers associated with OC.


Assuntos
Biomarcadores Tumorais , Neoplasias Ovarianas , Humanos , Feminino , Biomarcadores Tumorais/metabolismo , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/metabolismo , Terapia de Alvo Molecular
11.
Int J Biol Macromol ; 268(Pt 1): 131493, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38608983

RESUMO

Chitosan (CTS), has emerged as a highly intriguing biopolymer with widespread applications, drawing significant attention in various fields ranging from medicinal to chemosensing. Key characteristics of chitosan include solubility, biocompatibility, biodegradability and reactivity, making it versatile in numerous sectors. Several derivatives have been documented for their diverse therapeutic properties, such as antibacterial, antifungal, anti-diabetic, anti-inflammatory, anticancer and antioxidant activities. Furthermore, these compounds serve as highly sensitive and selective chemosensor for the detection of various analytes such as heavy metal ions, anions and various other species in agricultural, environmental and biological matrixes. CTS derivatives interacting with these species and give analytical signals. In this review, we embark on an exploration of the latest advancements in CTS-based materials, emphasizing their noteworthy contributions to medicinal chemistry spanning the years from 2021 to 2023. The intrinsic biological and physiological properties of CTS make it an ideal platform for designing materials that interact seamlessly with biological systems. The review also explores the utilization of chitosan-based materials for the development of colorimetric and fluorimetric chemosensors capable of detecting metal ions, anions and various other species, contributing to advancements in environmental monitoring, healthcare diagnostics, and industrial processes.


Assuntos
Quitosana , Quitosana/química , Humanos , Materiais Biocompatíveis/química , Animais
12.
Int J Biol Macromol ; 268(Pt 1): 131644, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38642691

RESUMO

Diabetes is a chronic metabolic disorder. Diabetes complications can affect many organs and systems in the body. Ganoderma lucidum (G. lucidum) contains various compounds that have been studied for their potential antidiabetic effects, including polysaccharides, triterpenoids (ganoderic acids, ganoderol B), proteoglycans, and G. lucidum extracts. G. lucidum polysaccharides (GLPs) and triterpenoids have been shown to act through distinct mechanisms, such as improving glucose metabolism, modulating the mitogen-activated protein kinase (MAPK) system, inhibiting the nuclear factor-kappa B (NF-κB) pathway, and protecting the pancreatic beta cells. While GLPs exhibit a significant role in controlling diabetic nephropathy and other associated complications. This review states the G. lucidum antidiabetic mechanisms of action and potential biologically active compounds that contribute to diabetes management and associated complications. To make G. lucidum an appropriate replacement for the treatment of diabetes with fewer side effects, more study is required to completely comprehend the number of physiologically active compounds present in it as well as the underlying cellular mechanisms that influence their effects on diabetes.


Assuntos
Diabetes Mellitus , Hipoglicemiantes , Polissacarídeos , Reishi , Triterpenos , Triterpenos/farmacologia , Triterpenos/química , Triterpenos/uso terapêutico , Humanos , Reishi/química , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Hipoglicemiantes/química , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/metabolismo , Animais , Polissacarídeos/farmacologia , Polissacarídeos/química , Polissacarídeos/uso terapêutico , Polissacarídeos Fúngicos/farmacologia , Polissacarídeos Fúngicos/química , Polissacarídeos Fúngicos/uso terapêutico
13.
J Biomol Struct Dyn ; : 1-14, 2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38407210

RESUMO

Citrobacter koseri is a gram-negative rod that has been linked to infections in people with significant comorbidities and immunocompromised immune systems. It is most commonly known to cause urinary tract infections. Thus, the development of an efficacious C. koseri vaccine is imperative, as the pathogen has acquired resistance to current antibiotics. Subtractive proteomics was employed during this research to identify potential antigenic proteins to design an effective vaccine against C. koseri. The pipeline identified two antigenic proteins as potential vaccine targets: DP-3-O-acyl-N-acetylglucosamine deacetylase and Arabinose 5-phosphate isomerase. B and T cell epitopes from the specific proteins were forecasted employing several immunoinformatic and bioinformatics resources. A vaccine was created using a combination of seven cytotoxic T cell lymphocytes (CTL), five helper T cell lymphocyte (HTL), and seven linear B cell lymphocyte (LBL) epitopes. An adjuvant (ß-defensin) was added to the vaccine to enhance immunological responses. The created vaccine was stable for use in humans, highly antigenic, and non-allergenic. The vaccine's molecular and interactions binding affinity with the human immunological receptor TLR3 were studied using MMGBSA, molecular dynamics (MD) simulations, and molecular docking analyses. E. coli (strain-K12) plasmid vector pET-28a (+) was used to examine the ability of the vaccine to be expressed. The vaccine shows great promise in terms of developing protective immunity against diseases, based on the results of these computer experiments. However, in vitro and animal research are required to validate our findings.Communicated by Ramaswamy H. Sarma.

14.
Crit Rev Anal Chem ; : 1-16, 2023 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-36880659

RESUMO

Fluorometric determination of different biologically, industrially, and environmentally important analytes is a powerful technique because this technique has excellent selectivity, high sensitivity, rapid photoluminescence response, low cost, applicability to bioimaging, and low detection limit. Fluorescence imaging is a powerful technique for screening different analytes in the living system. Heterocyclic organic compounds have been extensively used as a fluorescence chemosensor for the determination of different biologically important cations like Co2+, Zn2+, Cu2+, Hg2+, Ag+, Ni2+, Cr3+, Al3+, Pd2+, Fe3+ Pt2+, Mn2+, Sn2+, Pd2+, Au3+, Pd2+, Cd2+, Pb2+ and other ions in biological and environmental systems. These compounds also showed significant biological applications such as anti-cancer, anti-ulcerogenic, antifungal, anti-inflammatory, anti neuropathic, antihistaminic, antihypertensive, analgesic, antitubercular, antioxidant, antimalarial, antiparasitic, antiglycation, antiviral anti-obesity, and antibacterial potency. In this review, we summarize the heterocyclic organic compounds based on fluorescent chemosensors and their applications in bioimaging studies for the recognition of different biologically important metal ions.

15.
Life Sci ; 316: 121389, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36646376

RESUMO

BACKGROUND: Thousands of people worldwide pass away yearly due to neurological disorders, cardiovascular illnesses, cancer, metabolic disorders, and microbial infections. Additionally, a sizable population has also been impacted by hepatotoxicity, ulcers, gastroesophageal reflux disease, and breast fissure. These ailments are likewise steadily increasing along with the increase in life expectancy. Finding innovative therapies to cure and consequently lessen the impact of these ailments is, therefore, a global concern. METHODS AND MATERIALS: All provided literature on Guaiazulene (GA) and its related compounds were searched using various electronic databases such as PubMed, Google Scholar, Web of Science, Elsevier, Springer, ACS, CNKI, and books via the keywords Guaiazulene, Matricaria chamomilla, GA-related compounds, and Guaiazulene analogous. RESULTS: The FDA has approved the bicyclic sesquiterpene GA, commonly referred to as azulon or 1,4-dimethyl-7-isopropylazulene, as a component in cosmetic colorants. The pleiotropic health advantages of GA and related substances, especially their antioxidant and anti-inflammatory effects, attracted a lot of research. Numerous studies have found that GA can help to manage various conditions, including bacterial infections, tumors, immunomodulation, expectorants, diuretics, diaphoresis, ulcers, dermatitis, proliferation, and gastritis. These conditions all involve lipid peroxidation and inflammatory response. In this review, we have covered the biomedical applications of GA. Moreover, we also emphasize the therapeutic potential of guaiazulene derivatives in pre-clinical and clinical settings, along with their underlying mechanism(s). CONCLUSION: GA and its related compounds exhibit therapeutic potential in several diseases. Still, it is necessary to investigate their potential in animal models for various other ailments and establish their safety profile. They might be a good candidate to advance to clinical trials.


Assuntos
Neoplasias , Úlcera , Animais , Úlcera/tratamento farmacológico , Azulenos/farmacologia , Azulenos/uso terapêutico , Sesquiterpenos de Guaiano/farmacologia , Sesquiterpenos de Guaiano/uso terapêutico , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Neoplasias/tratamento farmacológico , Compostos Fitoquímicos , Extratos Vegetais/uso terapêutico
16.
BMC Complement Med Ther ; 23(1): 69, 2023 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-36870998

RESUMO

BACKGROUND: Traditional herbal medicine has been used for centuries to cure many pathological disorders, including cancer. Thymoquinone (TQ) and piperine (PIP) are major bioactive constituents of the black seed (Nigella sativa) and black pepper (Piper nigrum), respectively. The current study aimed to explore the potential chemo-modulatory effects, mechanisms of action, molecular targets, and binding interactions after TQ and PIP treatments and their combination with sorafenib (SOR) against human triple-negative breast cancer (MDA-MB-231) and liver cancer (HepG2) cells. METHODS: We determined drug cytotoxicity by MTT assay, cell cycle, and death mechanism by flow cytometry. Besides, the potential effect of TQ, PIP, and SOR treatment on genome methylation and acetylation by determination of DNA methyltransferase (DNMT3B), histone deacetylase (HDAC3) and miRNA-29c expression levels. Finally, a molecular docking study was performed to propose potential mechanisms of action and binding affinity of TQ, PIP, and SOR with DNMT3B and HDAC3. RESULTS: Collectively, our data show that combinations of TQ and/or PIP with SOR have significantly enhanced the SOR anti-proliferative and cytotoxic effects depending on the dose and cell line by enhancing G2/M phase arrest, inducing apoptosis, downregulation of DNMT3B and HDAC3 expression and upregulation of the tumor suppressor, miRNA-29c. Finally, the molecular docking study has identified strong interactions between SOR, PIP, and TQ with DNMT3B and HDAC3, inhibiting their normal oncogenic activities and leading to growth arrest and cell death. CONCLUSION: This study reported TQ and PIP as enhancers of the antiproliferative and cytotoxic effects of SOR and addressed the mechanisms, and identified molecular targets involved in their action.


Assuntos
Neoplasias Hepáticas , MicroRNAs , Humanos , Sorafenibe , Simulação de Acoplamento Molecular , Epigênese Genética
17.
Heliyon ; 9(3): e14194, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36938391

RESUMO

The main purpose of the existing experiment was to assess the allelic and genotypic polymorphisms of the Growth hormone (GH) gene and its correlation with growth indices, efficiency of consumed feed, some body indices and carcass traits of the Egyptian Awassi sheep. Forty Egyptian Awassi male lambs were selected for their growing indices (post-weaning daily gain, marketing weight, and weaning weight), feed efficiency (consumed feed and of consumed feed), body conformational indicators (skeletal muscle index, relative body index, body mass index, and body index), and carcass features (dressing %, hot carcass weight, fore-legs %, neck %, loin %, ribs %, abdominal fat %, Tail % and hind-legs %). The polymerase chain reaction-restricted fragment length polymorphism (PCR-RFLP) tool was applied to detect the genotypic and allelic GH gene polymorphisms properties. The PCR-RFLP analysis identified three main genotypes (AA, AB and BB) and two main alleles (A and B). The GH genotype (AA or AB) exhibited moderate significant influence (P < 0.05) on marketing weight, Loin% and Tail%. Also, genotype (AB or BB) of expressed GH gene significantly (P < 0.01) influence on consumed feed, post-weaning daily gain, neck% and body mass index, whereas, it had no influence on the phenotypic values of the other characteristics investigated. The presence of the A allele in the genotype was markedly associated (P < 0.01) with consumed feed, body mass index and post-weaning daily growth; conversely, the presence of the B allele in the genotype was significantly related (P < 0.05) with marketing weight, loin %, and tail %. While, GH gene expression was revealed to be highly significant (P < 0.01) in relation to post-weaning daily growth, feed intake, and neck %. According to the findings, determining the associations between GH gene variation and growth, efficiency of consumed feed, body measurements, and carcass features of Egyptian Awassi sheep and applying marker assisted selection with the GH gene to improve these traits is warranted and will be of significant economic value to sheep production.

18.
Front Chem ; 11: 1143614, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37035117

RESUMO

Magnesium oxide nanostructured particles (NP) were prepared using a simple solution combustion technique using different leaf extracts such as Mangifera indica (Mango - Ma), Azadirachta indica (Neem-Ne), and Carica papaya (Papaya-Pa) as surfactants. The highly crystalline phase of MgO nanostructures was confirmed by PXRD and FTIR studies for 2 h 500°C calcined samples. To analyze the characteristics of obtained material-MaNP, NeNP, and PaNP for dosimetry applications, thermoluminescence (TL) studies were carried out for Co-60 gamma rays irradiated samples in the dose range 10-50 KGy; PaNP and NeNP exhibited well-defined glow curve when compared with MaNP samples. In addition, it was observed that the TL intensity decreases, with increase in gamma dose and the glow peak temperature is shifted towards the higher temperature with the increase in heating rate. The glow peak was segregated using glow curve deconvolution and thermal cleaning method. Kinetic parameters estimated using Chen's method, trap depth (E), and frequency factor (s) were found to be 0.699, 7.408, 0.4929, and 38.71, 11.008, and 10.71 for PaNP, NeNP, and MaNP respectively. The well-resolved glow curve, good linear behavior in the dose range of 10-50, KGy, and less fading were observed in PaNP as compared with MaNP and NeNP. Further, the antibacterial activity was checked against human pathogens such as Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa. A visible zone of clearance was observed at 200 and 100 µg/mL by the PaNP and NeNP, indicating the death of colonies by the nanoparticles. Therefore, PaNP nanomaterial is a potential phosphor material for dosimetry and antibacterial application compared to NeNP and MaNP.

19.
Artigo em Inglês | MEDLINE | ID: mdl-35600963

RESUMO

For the treatment and maintenance of postprandial blood glucose increases (i.e., diabetes mellitus), alpha (α)-amylase is a well-known therapeutic target. In this paper, we report an initial exploration of the work, i.e., in vitro alpha-amylase activity of the hydroalcoholic polyherbal extract of the selected plants. After drying, the plant material is ground individually, and at least 100 gm of the crude powder is prepared from each plant. 100 gm of each plant was combined, and a total of 500 gm of the crude powder (Ichnocarpus frutescens (100 gm) + Ficus dalhousie (100 gm) + Crateva magna (100 gm) + Alpinia galangal (100 gm) + Swertia chirata (100 gm)) was prepared to carry out the extraction. This obtained extract was subjected to preliminary phytochemical screening and in vitro alpha-amylase activity. At 16 mg/mL, acarbose displayed 78.40 ± 0.36% inhibition, whereas the extract exhibited 72.96 ± 0.70% inhibition, which is significantly comparable. The IC50 value of acarbose was 12.9 ± 1.12, whereas the extract exhibited 13.31 ± 1.12 mg/mL. The extract possesses numerous classes of chemicals such as alkaloids, glycosides, tannins, polyphenols, and terpenoids, which can contribute to the antidiabetic activity through alpha-amylase inhibition. This was an initial exploration of the work as a proof of concept for the development of polyherbal tea bag formulation for the treatment of diabetes. In the future, we are aiming to investigate the effectiveness of polyherbal tea bags in the treatment of diabetes using more in vitro and in vivo models. From the present investigation, we have concluded that this extract can be used for the treatment of diabetes.

20.
Antioxidants (Basel) ; 11(8)2022 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-35892646

RESUMO

Nanoparticles (NPs) exhibit distinct features compared to traditional physico-chemical synthesis and they have many applications in a wide range of fields of life sciences such as surface coating agents, catalysts, food packaging, corrosion protection, environmental remediation, electronics, biomedical and antimicrobial. Green-synthesized metal NPs, mainly from plant sources, have gained a lot of attention due to their intrinsic characteristics like eco-friendliness, rapidity and cost-effectiveness. In this study, zinc oxide (ZnO) NPs have been synthesized employing an aqueous leaf extract of Pelargonium odoratissimum (L.) as a reducing agent; subsequently, the biosynthesized ZnO NPs were characterized by ultraviolet-visible spectroscopy (UV-Vis), dynamic light scattering (DLS), Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), field emission scanning electron microscopy (FESEM) and energy-dispersive X-ray spectroscopy (EDX), high-resolution transmission electron microscopy (HRTEM) and selected area electron diffraction (SAED). Moreover, aqueous plant leaf extract was subjected to both qualitative and quantitative analysis. Antioxidant activity of ZnO NPs was assessed by DPPH assay, with varying concentrations of ZnO NPs, which revealed scavenging activity with IC50 = 28.11 µg mL-1. Furthermore, the anti-bacterial efficacy of the green synthesized ZnO NPs against four foodborne pathogenic bacterial strains was examined using the disk diffusion assay, and Staphylococcus aureus (ATCC 8095), Pseudomonas aeruginosa (ATCC10662) and Escherichia coli (ATCC 25922) were found to be the most sensitive against biosynthesized ZnO NPs, whereas the least sensitivity was shown by Bacillus cereus (ATCC 13753). The anti-inflammatory effect was also evaluated for both ZnO NPs and the aqueous leaf extract of P. odoratissimum through the human red blood cells (HRBC) membrane stabilization method (MSM) in vitro models which includes hypotonicity-induced hemolysis. A maximum membrane stabilization of ZnO NPs was found to be 95.6% at a dose of 1000 µg mL-1 compared with the standard indomethacin. The results demonstrated that leaf extract of P. odoratissimum is suitable for synthesizing ZnO NPs, with antioxidant, antibacterial as well as superior anti-inflammatory activity by improving the membrane stability of lysosome cells, which have physiological properties similar to erythrocyte membrane cells and have no hemolytic activity. Overall, this study provides biosynthesized ZnO NPs that can be used as a safe alternative to synthetic substances as well as a potential candidate for antioxidants, antibacterial and anti-inflammatory uses in the biomedical and pharmaceutical industries.

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