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1.
Microb Pathog ; 183: 106280, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37541555

RESUMEN

Antibiotic resistant bacteria are immune to most antibiotics and are therefore very difficult to treat and in most cases lead to death. As such there is a pressing need for alternative and more efficient antibacterial drugs which can target these drug-resistant strains as well. The objective of this research work was to investigate the antibacterial properties of Thymus linearis essential oil (EO) against multiple disease-causing bacterial pathogens. Additionally, the study aimed to examine the molecular docking and molecular dynamic (MD) simulations of the primary components of the EO with the essential bacterial proteins and enzymes. Gas chromatography-mass spectrometry was employed to analyse the chemical composition of Thymus linearis EO. The initial screening for antibacterial properties involved the use of disc diffusion and microdilution techniques. Molecular docking studies were conducted utilising Autodock Vina. The outcomes were subsequently visualised through BIOVIA Discovery Studio. MD simulations were conducted using iMODS, an internet-based platform designed for MD simulations. The essential oil (EO) was found to contain 26 components, with thymol, carvacrol, p-cymene, and γ-terpinene being the primary constituents. The study findings revealed that Thymus linearis EO demonstrated antibacterial effects that were dependent on both the dose and time. The results of molecular docking studies revealed that the primary constituents of the EO, namely thymol, carvacrol, and p-cymene, exhibited robust interactions with the active site of the bacterial DNA gyrase enzyme. This finding provides an explanation for the antibacterial mechanism of the EO. The results indicate that Thymus linearis EO possesses potent antibacterial properties against the MDR microorganisms. Molecular docking analyses revealed that the essential oil's primary components interact with the amino acid residues of the DNA-Gyrase B enzyme, resulting in a favourable docking score.


Asunto(s)
Aceites Volátiles , Thymus (Planta) , Aceites Volátiles/farmacología , Aceites Volátiles/química , Timol , Simulación del Acoplamiento Molecular , Girasa de ADN , Novobiocina , Antibacterianos/farmacología
2.
Org Biomol Chem ; 20(42): 8197-8202, 2022 11 02.
Artículo en Inglés | MEDLINE | ID: mdl-36226505

RESUMEN

An efficient strategy towards N-formylation of amides and oxidation of indolines to isatins is described. This method employs readily available (NH4)2S2O8, I2, and DMSO. The given method features operational simplicity, excellent functional group tolerance, broad substrate scope, and fast kinetics. Moreover, the method was applied to the synthesis of the natural product alatamide. Notably, DMSO plays three vital roles: a formyl group source, an oxidant, and a solvent.


Asunto(s)
Yodo , Isatina , Amidas , Dimetilsulfóxido , Yoduros
3.
Artículo en Inglés | MEDLINE | ID: mdl-32284929

RESUMEN

Background: Type II Diabetes mellitus (T2DM) is a multifactorial disease and a leading cause of premature deaths. Inflammatory cytokines are reported that they have potential to enhance insulin resistance and hence T2DM. Assessment of immunological profile in T2DM patients of Kashmir valley is unclear. So, detection of cytokines is relevant to determine the extent and direction of immune responses. The current research was taken to study the role of inflammatory mediators in T2DM along with insulin sensitivity, biochemical and hematological parameters in mountainous valley of Kashmiri population. Methods: A total of 340 subjects were selected in this study among them 160 were T2DM cases and 180 were healthy controls. Serum expression of inflammatory mediators (TNF-α and IL-6 ) were quantified by ELISA technique, WBC count was measured on Sysmax (Germany) hematology analyzer, biochemical and Immunoassay parameters were done on Abbott c4000 (USA) and Abbott C1000 (USA) fully automatic analyzer. Data was analyzed using statistical 'software SPSS 16.1' (Chicago, IL). For all assessments, p<0.05 were considered statistically significant. Results: The expressions of candidate cytokines (TNF-α, IL-6, CRP, and WBC) were highly significant (p<0.001) in T2DM. Among inflammatory mediators, TNF-α shows a positive correlation (p<0.001) with glycemic profile and insulin sensitivity in T2DM cases in comparison with healthy normal. Biochemical (fasting sugar, HbA1c, insulin resistance, lipid profile) and anthropometric (BMI) parameters were highly significant (p<0.001) in T2DM cases as compared to non-diabetic normal. Conclusion: Low grade inflammation and up regulation of inflammatory mediators has been purported to play a significant role in pathogenesis of T2DM. Our findings confirm that positive correlation of TNF-α and IL-6 with T2DM and insulin sensitivity. These can act as early prediction biomarkers of T2DM. Further studies on wider range of pro and anti- inflammatory cytokines i.e. mediators, in association with other biochemical, immunoassay and hematological parameters are needed to help clinicians manage and treat T2DM effectively.

4.
Environ Toxicol ; 33(3): 361-369, 2018 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-29251412

RESUMEN

This study was designed to assess the potential antifibrotic effect of D-Limonene-a component of volatile oils extracted from citrus plants. D-limonene is reported to have numerous therapeutic properties. CCl4 -intduced model of liver fibrosis in Wistar rats is most widely used model to study chemopreventive studies. CCl4 -intoxication significantly increased serum aminotransferases and total cholesterol these effects were prevented by cotreatment with D-Limonene. Also, CCl4 -intoxication caused depletion of glutathione and other antioxidant enzymes while D-Limonene preserved them within normal values. Hydroxyproline and malondialdehyde content was increased markedly by CCl4 treatment while D-Limonene prevented these alterations. Levels of TNF-α, TGF-ß, and α-SMA were also assessed; CCl4 increased the expression of α-SMA, NF-κB and other downstream inflammatory cascade while D-Limonene co-treatment inhibited them. Collectively these findings indicate that D-Limonene possesses potent antifibrotic effect which may be attributed to its antioxidant and anti-inflammatory properties.


Asunto(s)
Antiinflamatorios/uso terapéutico , Antioxidantes/uso terapéutico , Ciclohexenos/uso terapéutico , Cirrosis Hepática/tratamiento farmacológico , Terpenos/uso terapéutico , Animales , Tetracloruro de Carbono , Glutatión/metabolismo , Limoneno , Hígado/efectos de los fármacos , Hígado/metabolismo , Cirrosis Hepática/inducido químicamente , Cirrosis Hepática/metabolismo , Masculino , FN-kappa B/metabolismo , Estrés Oxidativo/efectos de los fármacos , Ratas Wistar , Factor de Crecimiento Transformador beta/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo
6.
ScientificWorldJournal ; 2015: 816364, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26106644

RESUMEN

Humans have been using natural products for medicinal use for ages. Natural products of therapeutic importance are compounds derived from plants, animals, or any microorganism. Ginger is also one of the most commonly used condiments and a natural drug in vogue. It is a traditional medicine, having some active ingredients used for the treatment of numerous diseases. During recent research on ginger, various ingredients like zingerone, shogaol, and paradol have been obtained from it. Zingerone (4-(4-hydroxy-3-methoxyphenyl)-2-butanone) is a nontoxic and inexpensive compound with varied pharmacological activities. It is the least pungent component of Zingiber officinale. Zingerone is absent in fresh ginger but cooking or heating transforms gingerol to zingerone. Zingerone closely related to vanillin from vanilla and eugenol from clove. Zingerone has potent anti-inflammatory, antidiabetic, antilipolytic, antidiarrhoeic, antispasmodic, and so forth properties. Besides, it displays the property of enhancing growth and immune stimulation. It behaves as appetite stimulant, anxiolytic, antithrombotic, radiation protective, and antimicrobial. Also, it inhibits the reactive nitrogen species which are important in causing Alzheimer's disease and many other disorders. This review is written to shed light on the various pharmacological properties of zingerone and its role in alleviating numerous human and animal diseases.


Asunto(s)
Guayacol/análogos & derivados , Extractos Vegetales/farmacología , Animales , Antiinflamatorios/química , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Antidiarreicos/química , Antidiarreicos/farmacología , Antidiarreicos/uso terapéutico , Antieméticos , Antineoplásicos/química , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Antioxidantes/química , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Zingiber officinale/química , Guayacol/química , Guayacol/farmacología , Guayacol/uso terapéutico , Humanos , Lipólisis/efectos de los fármacos , Extractos Vegetales/química , Extractos Vegetales/uso terapéutico , Protectores contra Radiación/química , Protectores contra Radiación/farmacología , Protectores contra Radiación/uso terapéutico
7.
J Pharm Health Care Sci ; 10(1): 7, 2024 Jan 24.
Artículo en Inglés | MEDLINE | ID: mdl-38268049

RESUMEN

BACKGROUND: Multidrug-resistant bacterial strains cause several serious infections that can be fatal, such as Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumonia, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacteriaceae (often referred to as ESKAPE pathogens). Since ancient times, several indigenous medical systems in India have utilized diverse medicinal plants (approximately 80,000 species) as conventional treatments for a variety of illnesses. A member of the Fabaceae family, also referred to as "Himalayan indigo," Indigofera heterantha Wall, is well known for its therapeutic properties. METHODS: The present study investigated the antibacterial, antifungal and antihelmintic properties of the roots, bark, leaves, and flowers of I. heterantha from the Kashmir Himalayas. The effectiveness of the extracts against bacteria, fungi, and earthworms. Three of the tested organisms for bacteria were ESKAPE pathogens, as they are responsible for creating fatal bacterial infections. The antifungal potency of I. heterantha aqueous and methanolic extracts was evaluated using the Agar Well Diffusion Assay. The antihelmintic activity was carried out on an adult Pheretima posthuma Indian earth worm, which shares physiological and anatomical similarities with human intestinal roundworm parasites. RESULTS: The methanolic extracts of root and bark have shown prominent activity against all bacterial strains, whereas aqueous extracts of flower, root, and leaves have shown promising activity against Staphylococcus aureus. The aqueous extract demonstrated good activity against S. cerevisiae at a concentration of 200 mg/ml with a zone of inhibition of 16 mm, while the methanolic extract displayed comparable activity against the fungal strains. The remaining two strains, P. crysogenum and A. fumigatus, were only moderately active in response to the extracts. All the extracts have shown anthelmintic activity except aqueous flower. CONCLUSION: These results will pave the way for the bioassay-guided isolation of bioactive constituents that may act as hits for further development as potential antibacterial agents against drug-resistant microbial and helminthic infections.

8.
Chem Commun (Camb) ; 60(1): 114-117, 2023 Dec 19.
Artículo en Inglés | MEDLINE | ID: mdl-38037750

RESUMEN

An efficient strategy towards stereoselective amidation of alkynes is reported. The given method features operational simplicity, excellent functional group tolerance, broad substrate scope and fast kinetics to furnish Z-enamides. Moreover, the method was successfully applied for the facile synthesis of the natural products lansiumamide A, lansiumamide B and Z-alatamide. Notably, DMSO plays two vital roles: hydrogen source and solvent.

9.
Nat Prod Res ; : 1-10, 2023 Oct 18.
Artículo en Inglés | MEDLINE | ID: mdl-37850445

RESUMEN

Novel sarracinic acid derivatives bearing triazole or N-heterocyclic moiety were prepared via two separate reaction schemes. The triazoles and the N-heterocyclic derivatives were synthesised using standard click chemistry approach and amination of 2-bromoethyl ester of sarracinic acid respectively. All the synthesised derivatives were screened for in vitro neuroprotective activity against corticosterone induced impairment in neuroblastoma cell line SH-SY5Y. Two analogs SA-2 and SA-12 exhibited strong neuroprotective activity. The cell viability, after high dose corticosterone induced cell death, increased remarkably with the pre treatment of SA-2 and SA-12. The in vitro biological activity of SA-2 and SA-12 was verified through docking studies. The docking studies were in good agreement with the biological results. SA-2 and SA-12 showed strong binding affinities with the target protein having ΔGb = -8.88 and -7.52; inhibition constant (ki) = 3.08 nM and 30.9 nM respectively.

10.
Org Lett ; 25(14): 2382-2387, 2023 Apr 14.
Artículo en Inglés | MEDLINE | ID: mdl-36999789

RESUMEN

An unprecedented, one-step strategy for the synthesis of 5-(methylthio)pyridazin-3(2H)-one derivatives has been developed through iodine triggered deaminative coupling of glycine esters with methyl ketones and hydrazine hydrate in DMSO. These transformations in the absence of hydrazine helped to generate different 3-methylthio-4-oxo-enoates in good yields. Notably, DMSO played multiple roles such as oxidant, methylthiolating reagent, and solvent.

11.
Pathol Oncol Res ; 27: 1609826, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34924820

RESUMEN

AT-rich interactive domain-containing protein 1A (ARID1A), TP53 and programmed cell death-ligand 1 (PDL1) are involved in several protein interactions that regulate the expression of various cancer-related genes involved in the progression of the cell cycle, cell proliferation, DNA repair, and apoptosis. In addition, gene expression analysis identified some common downstream targets of ARID1A and TP53. It has been established that tumors formed by ARID1A-deficient cancer cells exhibited elevated PDL1 expression. However, the aberrations in these molecules have not been studied in this population especially in Gastric Cancer (GC). In this backdrop we aimed to investigate the role of the ARID1A mutation and expression of ARID1A, TP53 and PDL1 genes in the etiopathogenesis of Gastric Cancer (GC) in the ethnic Kashmiri population (North India). The study included 103 histologically confirmed GC cases. The mutations, if any, in exon-9 of ARID1A gene was analysed by Polymerase Chain Reaction (PCR) followed by Sanger sequencing. The mRNA expression of the ARID1A, TP53 and PDL1 genes was analysed by Quantitative real time-PCR (qRT-PCR). We identified a nonsense mutation (c.3219; C > T) in exon-9 among two GC patients (∼2.0%), which introduces a premature stop codon at protein position 1073. The mRNA expression of the ARID1A, TP53 and PDL1 gene was significantly reduced in 25.3% and elevated in 47.6 and 39.8% of GC cases respectively with a mean fold change of 0.63, 2.93 and 2.43. The data revealed that reduced mRNA expression of ARID1A and elevated mRNA expression of TP53 and PDL1 was significantly associated with the high-grade and advanced stage of cancer. Our study proposes that ARAD1A under-expression and overexpression of TP53 and PDL1 might be crucial for tumor progression with TP53 and PDL1 acting synergistically.


Asunto(s)
Antígeno B7-H1/genética , Proteínas de Unión al ADN/genética , Neoplasias Gástricas/genética , Factores de Transcripción/genética , Proteína p53 Supresora de Tumor/genética , Anciano , Estudios Transversales , Progresión de la Enfermedad , Femenino , Expresión Génica , Humanos , India/epidemiología , Masculino , Persona de Mediana Edad , Mutación , ARN Mensajero/genética , Neoplasias Gástricas/epidemiología , Neoplasias Gástricas/patología
12.
Naunyn Schmiedebergs Arch Pharmacol ; 394(12): 2389-2399, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34554266

RESUMEN

Senecio graciliflorus DC root extract was studied for secondary metabolite composition following the bioactivity-guided isolation technique. The ethyl acetate extract of Senecio graciliflorus root yielded nine chemical constituents: 3,4-di-tert-butyl toluene, stigmasterol, ß-sitosterol, 2ß-(angeloyloxy)furanoeremophilane, gallic acid, 2ß-{[(Z)-2-hydroxymethylbut-2-enoyl]oxy}furanoeremophilane, 1-hydroxypentan-2-yl-4-methylbenzoate, sarcinic acid, and sitosterol 3-O-ß-D-glucopyranoside. The structures of the chemical constituents were elucidated on the basis of spectral data analysis in the light of literature. All the compounds are being reported for the first time from this plant. The isolated constituents were screened for neuroprotective effects against corticosterone-induced impairment in neuroblastoma cell lines (SH-SY5S cells). The viability of SH-SY5S cells was determined using MTT assay. Among various isolated compounds, three natural products (sarcinic acid, gallic acid, and ß-sitosterol) displayed robust neurotropic activity. The compounds increased neuronal cell survival in differentiated neuroblastoma cells (SH-SY5Y) from high-dose corticosterone (400 µM)-induced cell death. All the three constituents showed maximum AKT/ERK pathway activation at 20 µM concentration. The studies are aimed to explore small molecules for treating neurodegeneration underlying various neurological disorders to restore neuronal cell plasticity.


Asunto(s)
Fármacos Neuroprotectores/farmacología , Extractos Vegetales/farmacología , Senecio/química , Productos Biológicos/aislamiento & purificación , Productos Biológicos/farmacología , Muerte Celular/efectos de los fármacos , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Corticosterona , Humanos , Neuroblastoma/patología , Fármacos Neuroprotectores/aislamiento & purificación , Raíces de Plantas , Metabolismo Secundario , Senecio/metabolismo
13.
Curr Clin Microbiol Rep ; 8(3): 152-166, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33614398

RESUMEN

PURPOSE OF REVIEW: Human race is currently facing the wrath of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a highly transmittable and pathogenic RNA virus, causing coronavirus disease 2019 (COVID-19), the worst ever global pandemic. Coronaviruses (CoVs) have emerged as a major public health concern. Urgent global response to COVID-19 outbreak has been to limit spread of SARS-CoV-2 via extensive monitoring and containment. Various treatment regimens have been adopted to manage COVID-19, with known drugs and drug combinations used to decrease the morbidity and mortality associated with COVID-19. Intensive research on various fronts including studying molecular and structural aspects of these viruses and unraveling the pathophysiology and mechanistic basis of COVID-19 aimed at developing effective prophylactic, therapeutic agents and vaccines has been carried out globally. RECENT FINDINGS: No approved antiviral treatment except remdesivir exists for SARS-CoV-2 till date though novel drug targets have been identified. However, worldwide frantic and competitive vaccine development pharmaceutical race has borne fruit in the form of a number of promising candidate vaccines, out of which few have already received emergency use authorization by regulatory bodies in record time. SUMMARY: This review highlights the painstaking efforts of healthcare workers and scientific community to successfully address the COVID-19 pandemic-though damage in the form of severe illness, loss of lives, and livelihood has left a serious mark. Focusing on extensive research on various therapeutic options and antiviral strategies including neutralizing antibodies, potential drugs, and drug targets, light has been shed on various diagnostic options and the amazing vaccine development process as well.

14.
Maedica (Bucur) ; 16(2): 170-178, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-34621335

RESUMEN

Introduction: Lung cancer was considered to be rare at the beginning of the 20th century, but it has now reached almost epidemic proportions. It is the leading cause of cancer deaths in developed countries and is also rising at alarming rates in developing countries. Introduction: Coronavirus disease 2019 (COVID-19) is an emerging viral infection without any approved treatment. Investigational therapies for COVID-19 may cause clinically important drug-drug interactions (DDIs). We aimed to study drug-drug interactions (DDIs) and their risk factors in hospitalised COVID-19 patients. Aim: The aim of our study is to establish an effect on serum levels of vascular endothelial growth factor (VEGF) after surgery in lung cancer patients. Methods:This was a prospective study. For the estimation of VEGF, 50 lung cancer patients were studied. Both preoperative and postoperative levels of VEGF were estimated for all subjects. Blood samples were obtained from all cases both preoperatively and postoperatively (four weeks after surgery). Blood samples of 100 age and sex matched healthy controls were collected from the Outpatient Departments of SKIMS to establish normal serum VEGF levels. Conclusion: Our findings show that serum VEGF levels are higher as the tumor stage progresses and tumor size increases, which explains the lower serum VEGF levels observed by us in the operable patient group.

15.
SN Compr Clin Med ; 2(10): 1767-1776, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32864575

RESUMEN

Coronavirus disease 2019 (COVID-19), an ongoing global health emergency, is a highly transmittable and pathogenic viral infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Emerging in Wuhan, China, in December 2019, it spread widely across the world causing panic-worst ever economic depression is visibly predictable. Coronaviruses (CoVs) have emerged as a major public health concern having caused three zoonotic outbreaks; severe acute respiratory syndrome-CoV (SARS-CoV) in 2002-2003, Middle East respiratory syndrome-CoV (MERS-CoV) in 2012, and currently this devastating COVID-19. Research strategies focused on understanding the evolutionary origin, transmission, and molecular basis of SARS-CoV-2 and its pathogenesis need to be urgently formulated to manage the current and possible future coronaviral outbreaks. Current response to the COVID-19 outbreak has been largely limited to monitoring/containment. Although frantic global efforts for developing safe and effective prophylactic and therapeutic agents are on, no licensed antiviral treatment or vaccine exists till date. In this review, research strategies for coping with COVID-19 based on evolutionary and molecular aspects of coronaviruses have been proposed.

16.
Cancer Treat Res Commun ; 19: 100125, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30802811

RESUMEN

Epigenetic alterations are clearly involved in cancer initiation and progression as recent epigenetic studies of genomic DNA, histone modifications and micro-RNA alterations suggest that these are playing an important role in the incidence of breast cancer. Epigenetic information has recently gained the attention of researchers because epigenetic modification of the genome in breast cancer is still an evolving area for researchers. Several active compounds present in foods, poisons, drugs, and industrial chemicals may as a result of epigenetic mechanisms increase or decrease the risk of breast cancer. Epigenetic regulation is critical in normal growth and development and closely conditions the transcriptional potential of genes. Epigenetic mechanisms convey genomic adaption to an environment thereby ultimately contributing towards given phenotype. In addition to the use of epigenetic alterations as a means of screening, epigenetic alterations in a tumor or adjacent tissues or peripheral blood may also help clinicians in determining prognosis and treatment of breast cancer. As we understand specific epigenetic alterations contributing to breast tumorigenesis and prognosis, these discoveries will lead to significant advances for breast cancer treatment, like in therapeutics that target methylation and histone modifications in breast cancer and the newer versions of the drugs are likely to play an important role in future clinical treatment.


Asunto(s)
Biomarcadores de Tumor/genética , Neoplasias de la Mama/diagnóstico , Metilación de ADN , Epigénesis Genética , Neoplasias de la Mama/genética , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Pronóstico
17.
Iran J Basic Med Sci ; 22(4): 345-352, 2019 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-31168337

RESUMEN

Carcinoma of the stomach is one of the major prevalent and principal causes of cancer-related deaths worldwide. Current advancement in technology has improved the understanding of the pathogenesis and pathology of gastric cancers (GC). But, high mortality rates, unfavorable prognosis and lack of clinical predictive biomarkers provide an impetus to investigate novel early diagnostic/prognostic markers and therapeutic targets for GC, which are sufficiently sensitive to GC. Current biomedical investigations have explored several budding GC biomarker by utilizing serum proteins, natural oncogenic genes during improvement in molecular technologies as microarray, and RNA/DNA-Seq. Recently, small non-coding microRNAs (miRNAs) are becoming vital regulators in oncogenesis pathways and can act as handy clinical biomarkers. The newly introduced class of biomarkers is rising as new molecules for cancer diagnosis and prognosis. For better understanding of the gastric carcinogenesis, miRNAs may help to elucidate the mechanisms of tumor growth and can help to discover novel untimely potent markers for early detection of GC. Here in this review, we summarize the recent research studies supporting the utility of miRNAs as novel early diagnostic/prognostic tools and therapeutic targets. Thus, here we introduce potential future treatment strategies for gastrointestinal (GI) cancers, which indicate the practicality and clinical applications of miRNAs in GC.

18.
Arch Physiol Biochem ; 125(3): 201-209, 2019 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-29537332

RESUMEN

Development of diabetic nephropathy (DN) is directly linked to oxidative stress and inflammation. In this context, inflammatory and oxidative markers have gained much attention as targets for therapeutic intervention. We studied the effect of zingerone in a streptozotocin/high fat diet (STZ/HFD)-induced type 2 diabetic Wistar rat model. Zingerone also known as vanillyl acetone is a pharmacologically active compound present usually in dry ginger. STZ/HFD caused excessive increase in ROS and inflammation in experimental animals. The treatment with zingerone markedly abrogated ROS levels, inhibited the NF-кB activation and considerably reduced level of other downstream inflammatory molecules (TNF-α, IL-6, IL-1ß), furthermore, zingerone treatment improved renal functioning by significantly decreasing the levels of kidney toxicity markers KIM-1, BUN, creatinine, and LDH and suppressed TGF-ß. Collectively, these findings indicate that zingerone treatment improved renal function by anti-hyperglycaemic, anti-oxidant, and anti-inflammatory effects, suggesting the efficacy of zingerone in the treatment of DN.


Asunto(s)
Diabetes Mellitus Experimental/complicaciones , Nefropatías Diabéticas/tratamiento farmacológico , Guayacol/análogos & derivados , Inflamación/prevención & control , Estrés Oxidativo/efectos de los fármacos , Estallido Respiratorio/efectos de los fármacos , Animales , Glucemia/análisis , Nefropatías Diabéticas/etiología , Nefropatías Diabéticas/metabolismo , Dieta Alta en Grasa/efectos adversos , Regulación de la Expresión Génica , Guayacol/farmacología , Inflamación/etiología , Inflamación/metabolismo , Pruebas de Función Renal , Masculino , FN-kappa B/metabolismo , Ratas , Ratas Wistar , Transducción de Señal , Factor de Necrosis Tumoral alfa/metabolismo
19.
Eur J Cancer Prev ; 28(2): 68-75, 2019 03.
Artículo en Inglés | MEDLINE | ID: mdl-30379684

RESUMEN

Globally, colorectal cancer (CRC) is the third most commonly diagnosed cancer in males and the second most commonly diagnosed cancer in females, with 1.4 million new cases and almost 694 000 deaths estimated to have occurred in 2012. The development and progression of CRC is dictated by a series of alterations in diverse genes mostly proto-oncogenes and tumor suppressor genes. In this dreadful disease disturbances different from mutations called as epigenetic regulations are also taken into consideration and are thoroughly investigated. The present study was designed to analyze the promoter hypermethylation of CpG (cytosine, followed by guanine nucleotide) islands of cyclin-dependent kinase inhibitor 2A (P16) and O-methylguanine-DNA methyltransferase (MGMT) genes and its subsequent effect on the protein expression in CRC. The impact of the common functional polymorphism of the catechol-O-methyltransferase (COMT) gene, Val158Met, on promoter hypermethylation of P16 and MGMT genes in CRC was also investigated. The study included 200 CRC cases and equal numbers of normal samples. DNA was extracted using the kit method and methylation specific-PCR was performed for analysis of the promoter hypermethylation status. Total protein was isolated form all CRC cases and western blotting was performed for P16 and MGMT proteins. The COMT Val158Met polymorphism was analyzed by a PCR-restriction fragment length polymorphism assay. Epigenetic analysis showed that unlike other high-risk regions, the Kashmiri population has a different promoter hypermethylation profile of both P16 and MGMT genes, with frequent and significant promoter hypermethylation of both in CRC. The frequency of promoter hypermethylation of both genes was significantly higher in males and was insignificantly found to be higher in stage III/IV. The degree of P16 and MGMT promoter hypermethylation increased significantly with increasing severity of the lesion. We also found a significant correlation between P16 and MGMT promoter hypermethylation and loss of protein expression in CRC. A significant association was found between COMT polymorphism (homozygous variant) and P16 methylation status. Similar results were also found for MGMT hypermethylated cases.


Asunto(s)
Biomarcadores de Tumor/genética , Catecol O-Metiltransferasa/genética , Neoplasias Colorrectales/genética , Inhibidor p16 de la Quinasa Dependiente de Ciclina/genética , Metilación de ADN , Metilasas de Modificación del ADN/genética , Enzimas Reparadoras del ADN/genética , Polimorfismo Genético , Proteínas Supresoras de Tumor/genética , Biomarcadores de Tumor/metabolismo , Estudios de Casos y Controles , Catecol O-Metiltransferasa/metabolismo , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/patología , Inhibidor p16 de la Quinasa Dependiente de Ciclina/metabolismo , Metilasas de Modificación del ADN/metabolismo , Enzimas Reparadoras del ADN/metabolismo , Regulación hacia Abajo , Femenino , Estudios de Seguimiento , Regulación Neoplásica de la Expresión Génica , Humanos , Masculino , Pronóstico , Regiones Promotoras Genéticas , Proteínas Supresoras de Tumor/metabolismo
20.
Rev. Headache Med. (Online) ; 14(2): 89-96, 2023.
Artículo en Inglés | LILACS-Express | LILACS | ID: biblio-1531764

RESUMEN

Introduction: Chronic migraine is a debilitating condition that affects a significant portion of the population. Accurate diagnosis and treatment of chronic migraine remain a challenge due to the lack of objective biomarkers. Calcitonin gene-related peptide (CGRP) is a neuropeptide involved in the pathophysiology of migraine and has been proposed as a potential biomarker for migraine. Methods: We measured CGRP levels in peripheral blood samples collected from 142 participants with chronic or episodic migraine and 24 healthy controls during ictal periods, i.e., outside migraine attacks. We compared CGRP levels between the three groups and assessed the correlation between CGRP levels and clinical features of chronic migraine. Conclusion: Our study provides evidence that CGRP levels in peripheral blood during ictal periods may serve as a potential biomarker for chronic migraine. Further studies are needed to validate these findings and to explore the clinical utility of CGRP as a biomarker for chronic migraine.


Introdução: A enxaqueca crônica é uma condição debilitante que afeta uma parcela significativa da população. O diagnóstico preciso e o tratamento da enxaqueca crónica continuam a ser um desafio devido à falta de biomarcadores objetivos. O peptídeo relacionado ao gene da calcitonina (CGRP) é um neuropeptídeo envolvido na fisiopatologia da enxaqueca e foi proposto como um potencial biomarcador para enxaqueca. Métodos: Medimos os níveis de CGRP em amostras de sangue periférico coletadas de 142 participantes com enxaqueca crônica ou episódica e 24 controles saudáveis ​​durante períodos ictais, ou seja, fora das crises de enxaqueca. Comparamos os níveis de CGRP entre os três grupos e avaliamos a correlação entre os níveis de CGRP e as características clínicas da enxaqueca crônica. Conclusão: Nosso estudo fornece evidências de que os níveis de CGRP no sangue periférico durante os períodos ictais podem servir como um potencial biomarcador para enxaqueca crônica. Mais estudos são necessários para validar estes resultados e explorar a utilidade clínica do CGRP como biomarcador para enxaqueca crónica.

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