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1.
Nutr Metab Cardiovasc Dis ; 33(3): 483-493, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36653284

RESUMO

AIMS: Adipose tissue is considered as an endocrine organ that releases bioactive factors known as adipokines which contribute to the pathogenesis of rotundity-linked metabolic and cardiovascular complications. Rotundity is a major predisposer for the development and progression of coronary artery disease (CAD). DATA SYNTHESIS: The literature survey from various databases such as Pubmed/Medline, DOAJ, Scopus, Clarivate analytics/Web of Science and Google Scholar were used to prepare this article. The epidemic of rotundity has gained significant attention to understand the biology of adipocytes and the metabolism of adipose tissue in obese individuals. In CAD, visfatin/NAMPT was primarily indicated as a clinical marker of atherosclerosis, endothelial dysfunction and vascular injury having a prognostic significance. Visfatin/NAMPT is a factor that promotes vascular inflammation and atherosclerosis. Omentin is an anti-inflammatory and anti-atherogenic adipokine regulating cardiovascular functions. CONCLUSIONS: This review highlights and summarizes the scientific information pertaining to the role of the adipokines - omentin and visfatin in CAD.


Assuntos
Aterosclerose , Doença da Artéria Coronariana , Humanos , Adipocinas/metabolismo , Tecido Adiposo/metabolismo , Aterosclerose/metabolismo , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/metabolismo , Citocinas/metabolismo , Nicotinamida Fosforribosiltransferase
2.
Endocr Regul ; 57(1): 292-303, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38127687

RESUMO

Hypothalamic-pituitary gonadal (HPG) axis is responsible for the development and regulation of the female reproductive system. In polycystic ovary syndrome (PCOS), there is a disturbance in the HPG axis. Kisspeptin, a neuropeptide produced by the KISS1 gene, plays a vital role in the regulation of HPG axis by binding with its receptors KISS1R/GPR54, and stimulates gonadotropin secretion from the hypothalamus into pituitary to release luteinizing hormone (LH) and follicle stimulating hormone (FSH). Polymorphisms or mutations in the KISS1 gene can cause disturbance in the kisspeptin signaling pathway and is thought to disrupt HPG axis. Altered signaling of kisspeptin can cause abnormal secretion of GnRH pulse, which leads to increased LH/FSH ratio, thereby affecting androgen levels and ovulation. The increased levels of androgen worsen the symptoms of PCOS. In the present article, we review the molecular physiology and pathology of kisspeptin and how it is responsible for the development of PCOS. The goal of this review article is to provide an overview and metabolic profile of kisspeptin in PCOS patients and the expression of kisspeptin in PCOS animal models. In the present article, we also review the molecular physiology and pathology of kisspeptin and how it is responsible for the development of PCOS.


Assuntos
Síndrome do Ovário Policístico , Animais , Feminino , Humanos , Síndrome do Ovário Policístico/genética , Síndrome do Ovário Policístico/metabolismo , Kisspeptinas/genética , Kisspeptinas/metabolismo , Androgênios , Hormônio Luteinizante , Hormônio Foliculoestimulante
3.
Endocr Regul ; 57(1): 262-268, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38127689

RESUMO

Objective. Adipose tissue is considered to be an endocrine organ that secretes bioactive substances known as adipokines that contribute to the pathophysiology of metabolic and coronary diseases related to obesity. In this study, various novel biomarkers, such as inflammatory markers that are pro-inflammatory (visfatin) and anti-inflammatory (omentin-1), as prognostic indicators for people with coronary artery disease (CAD) were investigated. Methods. In this study, 30 diabetic patients with CAD, 30 diabetic patients without CAD, and 30 healthy control counterparts were included. Serum omentin and visfatin concentrations were evaluated by solid-phase enzyme linked immunosorbent assay (ELISA) kit. Patients with established diagnosis of CAD based on angiography, ECG, and elevated cardiac marker level were included into the study. Patients with cardioembolic stroke, cerebral venous sinus thrombosis, CNS vasculitis, and hemorrhage due to trauma, tumor, vascular malformation, and coagulopathy were excluded. Results. The serum omentin-1 levels were significantly higher in the healthy controls in comparison with the diabetic group (p<0.0001) and serum visfatin levels were significantly higher in the diabetic group in comparison with the healthy controls (p<0.0001). The serum omentin levels were significantly higher in the diabetic group in comparison with the cardio-diabetic group (p<0.0001) and serum visfatin levels were significantly higher in the cardio-diabetic group in comparison with the diabetic group (p<0.0001). The serum omentin-1 showed negative correlation with the serum visfatin in the cardio-diabetic group. Conclusion. The adipokines, such as omentin and visfatin, may be good therapeutic candidates in preventing or ameliorating CAD.


Assuntos
Doença da Artéria Coronariana , Diabetes Mellitus , Humanos , Adipocinas/metabolismo , Nicotinamida Fosforribosiltransferase , Citocinas , Tecido Adiposo/metabolismo
4.
J Biol Phys ; 49(2): 235-255, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36913165

RESUMO

Alpha-2-macroglobulin (α2M) is an essential antiproteinase that is widely distributed in human plasma. The present study was aimed at investigating the binding of a potential therapeutic dietary flavonol, morin, with human α2M using a multi-spectroscopic and molecular docking approach. Recently, flavonoid-protein interaction has gained significant attention, because a majority of dietary bioactive components interact with proteins, thereby altering their structure and function. The results of the activity assay exhibited a 48% reduction in the antiproteolytic potential of α2M upon interaction with morin. Fluorescence quenching tests unequivocally confirmed quenching in the fluorescence of α2M in the presence of morin, conforming complex formation and demonstrating that the binding mechanism involves a dynamic mode of interaction. Synchronous fluorescence spectra of α2M with morin showed perturbation in the microenvironment around tryptophan residues. Furthermore, structural changes were observed through CD and FT-IR, showing alterations in the secondary structure of α2M induced by morin. FRET further supports the results of the dynamic mode of quenching. Moderate interaction is shown by binding constant values using Stern-Volmer's fluorescence spectroscopy. Morin binds to α2M at 298 K with a binding constant of 2.7 × 104 M-1, indicating the strength of the association. The α2M-morin system was found to have negative ΔG values, which suggests that the binding process was spontaneous. Molecular docking also reveals the different amino acid residues involved in this binding process, revealing that the binding energy is -8.1 kcal/mol.


Assuntos
alfa 2-Macroglobulinas Associadas à Gravidez , Humanos , Gravidez , Feminino , alfa 2-Macroglobulinas Associadas à Gravidez/química , alfa 2-Macroglobulinas Associadas à Gravidez/metabolismo , Simulação de Acoplamento Molecular , Espectroscopia de Infravermelho com Transformada de Fourier , Flavonoides , Ligação Proteica
5.
J Biol Phys ; 49(1): 29-48, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36662317

RESUMO

Myricetin (MYR) is a bioactive secondary metabolite found in plants that is recognized for its nutraceutical value and is an essential constituent of various foods and beverages. It is reported to exhibit a plethora of activities, including antioxidant, antimicrobial, antidiabetic, anticancer, and anti-inflammatory. Alpha-2-macroglobulin (α2M) is a major plasma anti-proteinase that can inhibit proteinases of both human and non-human origin, regardless of their specificity and catalytic mechanism. Here, we explored the interaction of MYR-α2M using various biochemical and biophysical techniques. It was found that the interaction of MYR brings subtle change in its anti-proteolytic potential and thereby alters its structure and function, as can be seen from absorbance and fluorescence spectroscopy. UV spectroscopy of α2M in presence of MYR indicated the occurrence of hyperchromism, suggesting complex formation. Fluorescence spectroscopy reveals that MYR reduces the fluorescence intensity of native α2M with a shift in the wavelength maxima. At 318.15 K, MYR binds to α2M with a binding constant of 2.4 × 103 M-1, which indicates significant binding. The ΔG value was found to be - 7.56 kcal mol-1 at 298.15 K, suggesting the interaction to be spontaneous and thermodynamically favorable. The secondary structure of α2M does not involve any major change as was confirmed by CD analysis. The molecular docking indicates that Asp-146, Ser-172, Glu-174, and Tyr-180 were the key residues involved in α2M-MYR complex formation. This study contributes to our understanding of the function and mechanism of protein and flavonoid binding by providing a molecular basis of the interaction between MYR and α2M.


Assuntos
alfa 2-Macroglobulinas Associadas à Gravidez , Humanos , Gravidez , Feminino , Simulação de Acoplamento Molecular , alfa 2-Macroglobulinas Associadas à Gravidez/química , alfa 2-Macroglobulinas Associadas à Gravidez/metabolismo , Análise Espectral , Flavonoides
6.
Cell Mol Biol (Noisy-le-grand) ; 68(10): 8-14, 2022 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-37114277

RESUMO

Paspalidium flavidum (watercrown grass), a medicinal plant, is traditionally used in liver ailments and stomach problems. The hepatoprotective and gastroprotective activities of the aqueous methanol extract of Paspalidium flavidum (AMEPF) were studied in experimental animal models. Paracetamol and aspirin were used to induce hepatotoxicity and gastric ulcer in rats, respectively. Biochemical hepatic parameters, gastric pH, total acidity, ulcer index, percentage protection, nitric oxide and TNF-α were measured in AMEPF-treated groups. Moreover, GC-MS analysis of AMEPF was performed. Pretreatment with AMEPF improved the blood lipid profile and restored liver function tests in paracetamol-induced hepatotoxicity. While in aspirin-induced gastric ulcer, oral administration of AMEPF significantly reduced (P<0.05) the gastric lesions, total acidity and ulcer scoring index, TNF-α with upregulation of nitric oxide when compared with the Diseased group. AMEPF exhibited anti-lipid peroxidation activity. Histopathological studies were in good agreement with the biochemical findings. GC-MS analysis revealed the presence of anti-oxidant phyto-constituents, including oleic acid and 1,2-benzenedicarboxylic acid, mono(2-ethylhexyl) in AMEPF. This study suggested that aqueous methanol extract from the leaves of P. flavidum has beneficial hepatoprotective and gastroprotective activities related to its anti-oxidant phytochemicals.


Assuntos
Antiulcerosos , Doença Hepática Induzida por Substâncias e Drogas , Úlcera Gástrica , Ratos , Animais , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/tratamento farmacológico , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Mucosa Gástrica , Metanol , Antiulcerosos/efeitos adversos , Úlcera/tratamento farmacológico , Úlcera/patologia , Acetaminofen/efeitos adversos , Óxido Nítrico , Fator de Necrose Tumoral alfa , Modelos Animais de Doenças , Aspirina/efeitos adversos , Poaceae , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Doença Hepática Induzida por Substâncias e Drogas/patologia , Folhas de Planta , Fitoterapia
7.
J Immunoassay Immunochem ; 43(2): 119-128, 2022 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-34228594

RESUMO

Autoimmune disorders are typically categorized into systematic and local diseases that affect a single organ or tissue. Organs and tissues affected by autoimmune disorders include components of the endocrine system, such as thyroid, pancreas, and adrenal glands; blood, such as red blood cells; and the connective tissues, skin, muscles, and joints. Rhupus is a complex musculoskeletal autoimmune disease (AD) in which features of both rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) are simultaneously present. The cause and trigger of rhupus is still unknown, suggesting the role of genetic, immunological, hormonal, and environmental factors in the initiation and progression of the disease. The role of immune system has been established by the presence of specific autoantibodies as markers for diagnosis of rhupus and the formation of immune complex in serum. The complications of rhupus include the presence of rheumatoid factor (RF) and nodules and the involvement of nervous and renal systems that complicates its diagnosis and prognosis. The rhupus arthritis resembles RA-like pathophysiology and leads to inflammation, deformation, and disability. Due to the heterogeneity and rarity of the disease, the prevalence, pathophysiology, and natural history as well as radiological and immunological profiles of rhupus are still not properly understood.


Assuntos
Artrite Reumatoide , Lúpus Eritematoso Sistêmico , Autoanticorpos , Humanos , Prevalência , Fator Reumatoide
8.
J Immunoassay Immunochem ; 43(1): 22-32, 2022 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-34672900

RESUMO

Human race has survived several outbreak of pandemics in the past and their impact was long lasting. Some of the recent pandemics have been caused by a viruses known as Coronaviruses (CoVs) which are diverse, complex, adaptable viruses that have a significant impact on human health and animal productivity. The novel coronavirus that emerged in Wuhan, China (SARS-CoV-2) in 2019 has quickly spread throughout the world. Human coronaviruses (HCoVs), including severe acute respiratory syndrome coronavirus (SARS-CoV) and 2019 novel coronavirus (2019-nCoV, also known as SARS-CoV-2), have led to a global epidemic with high morbidity and mortality. Human pathogenic coronaviruses, SARS-CoV and SARS-CoV-2, bind to their target cells through angiotensin-converting enzyme 2 (ACE2), which is expressed by epithelial cells of the lung, intestine, kidneys, and blood vessels. The efforts to contain the virus are undergoing throughout the world, given the many uncertainties regarding pathogen transmissibility and virulence. Thus, the ongoing studies to promote the understanding of HCoVs will help to avoid or/and minimize the impact of anticipated pandemics in future.


Assuntos
COVID-19 , Pandemias , SARS-CoV-2 , Síndrome Respiratória Aguda Grave , Coronavírus Relacionado à Síndrome Respiratória Aguda Grave , Animais , China/epidemiologia , Humanos
9.
Int J Mol Sci ; 23(24)2022 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-36555406

RESUMO

Cancer is one of the deadliest non communicable diseases. Numerous anticancer medications have been developed to target the molecular pathways driving cancer. However, there has been no discernible increase in the overall survival rate in cancer patients. Therefore, innovative chemo-preventive techniques and agents are required to supplement standard cancer treatments and boost their efficacy. Fruits and vegetables should be tapped into as a source of compounds that can serve as cancer therapy. Phytochemicals play an important role as sources of new medication in cancer treatment. Some synthetic and natural chemicals are effective for cancer chemoprevention, i.e., the use of exogenous medicine to inhibit or impede tumor development. They help regulate molecular pathways linked to the development and spread of cancer. They can enhance antioxidant status, inactivating carcinogens, suppressing proliferation, inducing cell cycle arrest and death, and regulating the immune system. While focusing on four main categories of plant-based anticancer agents, i.e., epipodophyllotoxin, camptothecin derivatives, taxane diterpenoids, and vinca alkaloids and their mode of action, we review the anticancer effects of phytochemicals, like quercetin, curcumin, piperine, epigallocatechin gallate (EGCG), and gingerol. We examine the different signaling pathways associated with cancer and how inflammation as a key mechanism is linked to cancer growth.


Assuntos
Antineoplásicos , Neoplasias , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/prevenção & controle , Neoplasias/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Transdução de Sinais , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/uso terapêutico , Inflamação/tratamento farmacológico
10.
J Immunoassay Immunochem ; 42(5): 493-512, 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-33788668

RESUMO

In this review, we present an elaborate account of coronavirus in context to Covid-19 focusing on its origin, genome, life cycle, and immunology with a basic understanding of the disease and its cause. Further, the transmission, prevention and advances in therapeutics have also been discussed anticipating the possible outcomes in the near future. Moreover, the recently emerged unconventional approaches to this viral disease like drug repurposing, plasma therapy, nasal spray, and other preventive measures worldwide are studied for a long-term impact and relevance. Hence, this account on coronavirus and the ongoing pandemic serves a purpose of spreading awareness and to pass on relevant knowledge for a better chance to combat such unfortunate health crisis in future.


Assuntos
COVID-19/imunologia , Pandemias , SARS-CoV-2 , Enzima de Conversão de Angiotensina 2/metabolismo , COVID-19/terapia , COVID-19/virologia , Vacinas contra COVID-19/farmacologia , Reposicionamento de Medicamentos , Genoma Viral , Interações entre Hospedeiro e Microrganismos , Humanos , Imunização Passiva , SARS-CoV-2/genética , SARS-CoV-2/imunologia , SARS-CoV-2/fisiologia , Soroterapia para COVID-19
11.
J Immunoassay Immunochem ; 42(2): 138-153, 2021 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-33086912

RESUMO

Organophosphate class of pesticides causes neurotoxicity and carcinogenicity in humans. Once inside the human body, these pesticides often interact with plasma proteins, such as alpha-2-macroglobulin (α2M) which is the key anti-proteinase. Our work focuses on the structural and functional alteration of α2M by chlorpyrifos (CPF), a member of organophosphates. We explored the binding interaction between alpha-2-macroglobulin and CPF by using UV absorption and fluorescence spectroscopy (steady state and synchronous), circular dichroism and molecular docking approach. The functional activity of α2M was analyzed by anti-proteinase trypsin inhibitory assay which showed dose-dependent decrease in alpha-2-macroglobulin antiproteolytic potential. UV absorption studies and fluorescence quenching experiments suggested the formation of a complex between α2M and CPF. The CD spectra suggested a reduction in the beta helical (ß helix) content of α2M. Analysis of thermodynamic parameters suggested the process is spontaneous and endothermic with the ΔG and ΔH values being -5.501 kJ/mol, 11.49 kJ/mol, respectively. CPF binds with Ile-1390, Pro-1391, Leu-1392, Lys-1393, Val-1396, Lys-1397, Arg-1407, Thr-1408, Glu-1409, Val-1410, Asp-282, Glu-281 of α2M as suggested by molecular docking.


Assuntos
Clorpirifos/química , Simulação de Acoplamento Molecular , alfa 2-Macroglobulinas Associadas à Gravidez/química , Clorpirifos/metabolismo , Estrutura Molecular , alfa 2-Macroglobulinas Associadas à Gravidez/isolamento & purificação , alfa 2-Macroglobulinas Associadas à Gravidez/metabolismo , Termodinâmica
12.
Inflammopharmacology ; 29(4): 1119-1129, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34224070

RESUMO

Rheumatoid arthritis (RA) is a slowly progressing inflammatory autoimmune disease. Several features are involved in the RA pathogenesis in addition to environmental and genetic factors. Previously it has been reported that acetyl cholinesterase (AChE) activity is enhanced in old age and may contribute in the progression of RA. The current experimental work was projected to assess the activity of physostigmine (a cholinesterase inhibitor) for treatment of RA. In vitro and in vivo approaches were used for such evaluation. However, enzyme linked immunosorbent assays (ELISA) was performed to determine the concentrations of Prostaglandins E2 (PGE2) and tumor necrosis factor-α in arthritic rats after treatment with physostigmine. Moreover, anti-oxidant assays were employed to calculate the level of super oxide dismutase (SOD) and catalase peroxidase (CAT) in tissue of treated animals. The results claimed the dose dependent protective and stabilizing effect of physostigmine on denaturation of albumin (egg and bovine serum) protein and human red blood cell membrane, respectively, through in vitro studies. Furthermore, the physostigmine (10 and 20 mg/kg) significantly (p < 0.001) reduced the swelling of paw after induction of arthritis with formaldehyde or complete Freund's adjuvant (CFA) as compared to arthritic control animals. Moreover, significant (p < 0.001) reduction in the levels of inflammatory markers (PGE2 and TNF-α) at doses of 10 and 20 mg/kg of physostigmine has been observed in ELISA test. Likewise, there was a prominent rise in levels of SOD and CAT in animals treated with physostigmine. These findings pharmacologically conclude the anti-arthritic effect of physostigmine.


Assuntos
Antirreumáticos/farmacologia , Artrite Experimental/tratamento farmacológico , Artrite Experimental/patologia , Membrana Celular/efeitos dos fármacos , Eritrócitos/efeitos dos fármacos , Fisostigmina/farmacologia , Animais , Antirreumáticos/uso terapêutico , Artrite Experimental/metabolismo , Membrana Celular/metabolismo , Inibidores da Colinesterase/farmacologia , Inibidores da Colinesterase/uso terapêutico , Relação Dose-Resposta a Droga , Eritrócitos/metabolismo , Humanos , Masculino , Fisostigmina/uso terapêutico , Ratos , Ratos Sprague-Dawley , Soroalbumina Bovina/antagonistas & inibidores , Soroalbumina Bovina/metabolismo
13.
Inflammopharmacology ; 29(3): 673-682, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33772383

RESUMO

Pseudoephedrine (substituted phenethylamine) is well known as psychotic and bronchodilator. Numerous studies on phenethylamine derivatives indicated that these agents have the potential to abolish inflammatory responses in the non-biological and biological systems. These facts provided the basis to conduct a study on pseudoephedrine to explore its therapeutics in Complete Freund's Adjuvant (CFA)-induced arthritis. Furthermore, existing treatment approaches for RA associated with limited effect on chronic immunological models. Real-time polymerase chain reaction (q-PCR) was performed to execute the expression of pro and anti-inflammatory cytokines in treated and non-treated arthritic rats. These findings were further co investigate by histological observations. The paw volume, paw diameter, weight variations and arthritic score were determined at specific days throughout the experiment of 28 days. Pseudoephedrine at all doses significantly (p < 0.001) suppressed the expression of PGE2, TNF-α, IL-1ß and IL-6. Moreover, pseudoephedrine (20 and 40 mg/kg) caused significant augmentation of IL-4 and IL-10. Similarly, the drug expressed a significant anti-arthritic effect by reducing the paw volume, paw diameter and arthritic score. Similarly, it also reverts the reduction in body weight of arthritic rats at all above-mentioned doses. These findings supported the anti-arthritic potential of pseudoephedrine and recommended it for clinical trials.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Experimental/tratamento farmacológico , Citocinas/antagonistas & inibidores , Pseudoefedrina/uso terapêutico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Antirreumáticos/química , Antirreumáticos/farmacologia , Artrite Experimental/metabolismo , Artrite Experimental/patologia , Citocinas/metabolismo , Relação Dose-Resposta a Droga , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/fisiologia , Adjuvante de Freund , Interleucina-10/agonistas , Interleucina-10/metabolismo , Interleucina-1beta/antagonistas & inibidores , Interleucina-1beta/metabolismo , Interleucina-4/agonistas , Interleucina-4/metabolismo , Interleucina-6/antagonistas & inibidores , Interleucina-6/metabolismo , Fenetilaminas/química , Fenetilaminas/farmacologia , Fenetilaminas/uso terapêutico , Pseudoefedrina/química , Pseudoefedrina/farmacologia , Ratos , Ratos Sprague-Dawley , Fator de Necrose Tumoral alfa/metabolismo
14.
Pak J Pharm Sci ; 34(4(Supplementary)): 1549-1554, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34799331

RESUMO

Ephedra, natural flora has been used traditionally to treat rheumatism since decades. The scientific evidence of anti-rheumatic effect of this plant has also been reported. But the anti-rheumatic activity of major constituent of this plant (ephedrine) has not been evaluated. Based on this, the current study was aimed to assess anti-arthritic activity of ephedrine by using in vitro and in vivo approaches. Correspondingly, enzyme linked immunosorbent assay was performed for the estimation of prostaglandins E2 (PGE2) and tumor necrosis factor-α (TNF-α) in serum of formaldehyde-induced arthritic animals. The results elaborated significant reduction in albumin denaturation and remarkable progress on stabilization of red blood cells outer membrane at higher concentration during in vitro experiments. The ephedrine (40mg/kg) revealed noteworthy (p<0.001) inhibition in paw swelling in animals intoxicated with albumin as well as formaldehyde as compared to animals of control group by in vivo results. In this assay, ephedrine (20 & 40 mg/kg orally) significantly suppressed the level of these inflammatory markers (PGE2 & TNF-α). Ephedrine exhibited anti-arthritic effect by decreasing pro-inflammatory cytokines (PGE2 & TNF-α). This experimental work pharmacologically supports the use of ephedrine as anti-rheumatic drug but limited to evaluate in immunological arthritic model.


Assuntos
Artrite Reumatoide/tratamento farmacológico , Efedrina/uso terapêutico , Albuminas/química , Albuminas/toxicidade , Animais , Artrite Reumatoide/induzido quimicamente , Bovinos , Dinoprostona/sangue , Relação Dose-Resposta a Droga , Edema/induzido quimicamente , Efedrina/administração & dosagem , Efedrina/química , Membrana Eritrocítica/efeitos dos fármacos , Humanos , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Ratos , Fator de Necrose Tumoral alfa/sangue
15.
Cancer Invest ; 38(4): 185-208, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31971023

RESUMO

Cancer is a multi-step process during which cells acquire mutations that eventually lead to uncontrolled cell growth and division and evasion of programmed cell death. The oncogenes such as Ras and c-Myc may be responsible in all three major stages of cancer i.e., early, intermediate, and late. The NF-κB has been shown to control the expression of genes linked with tumor pathways such as chronic inflammation, tumor cell survival, anti-apoptosis, proliferation, invasion, and angiogenesis. In the last few decades, various biomarker pathways have been identified that play a critical role in carcinogenesis such as Ras, NF-κB and DNA damage.


Assuntos
Carcinogênese/genética , Reparo do DNA , NF-kappa B/metabolismo , Neoplasias/genética , Proteínas ras/metabolismo , Carcinogênese/patologia , Dano ao DNA , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias/patologia , Transdução de Sinais/genética
16.
J Immunoassay Immunochem ; 41(3): 257-271, 2020 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-32046582

RESUMO

The review article focuses on free radicals and oxidative stress involved in ophthalmological diseases such as retinopathy, cataract, glaucoma, etc. Oxidative stress is considered as a key factor involved in the pathology of many chronic diseases including ophthalmic complication and inflammatory process. Oxidative stress and inflammation are closely related pathophysiological processes and are simultaneously found in many pathological conditions. The free radicals produced oxidize cellular components such as lipids and phospholipids leading to lipid peroxidation and trigger the onset of retinopathy. Cataract is a significant cause of visual disability and it is proposed that the high incidence is related to oxidative stress induced by continued intraocular penetration of light and consequent photochemical generation of free radical oxidants. Glaucoma is the leading cause of irreversible blindness and comprises a group of diseases characterized by progressive optic nerve degeneration. Oxidative injury and altered antioxidant defense mechanisms in glaucoma appear to play a role in the pathophysiology of glaucomatous neurodegeneration that is characterized by death of retinal ganglion cells. The UVB radiations through this way may cause a number of diseases like photo-keratitis, pterygium, damage to epithelium, edema, and corneal cell apoptosis.Abbreviations: ROS: reactive oxygen species; RNS: reactive nitrogen species; O2.: superoxide anion; H2O2: hydrogen peroxide;. OH: hydroxyl radicals; ONOO-, ONO2-: peroxynitrite; NO: nitric oxide; IOP: intraocular pressure; RGC: retinal ganglion cells. WHO: World Health Organization; IAPB: International Agency for the Prevention of Blindness.


Assuntos
Catarata/diagnóstico , Glaucoma/diagnóstico , Inflamação/diagnóstico , Estresse Oxidativo , Transtornos da Visão/diagnóstico , Animais , Biomarcadores/análise , Biomarcadores/metabolismo , Catarata/metabolismo , Glaucoma/metabolismo , Humanos , Inflamação/metabolismo , Transtornos da Visão/metabolismo
17.
J Immunoassay Immunochem ; 41(5): 841-851, 2020 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-32579060

RESUMO

Bilirubin is an endogenous antioxidant that is a metabolite of the heme in red blood cells (RBC). In blood, bilirubin is associated with albumin to form a water-soluble complex, known as unconjugated bilirubin. Alpha-2-macroglobulin (α2M) is a proteinase inhibitor found in the plasma of vertebrates. In the present study, we have investigated the interaction of photo-illuminated bilirubin with serum α2M using various biophysical and thermodynamic techniques. The binding of bilirubin to α2M leads to various functional and structural changes in α2M protein. The result of ultraviolet (UV) and fluorescence spectroscopy suggests that binding of bilirubin to α2M induces a conformational change in the secondary structure of protein which was corroborated by circular dichroism (CD) and Fourier-transform infrared spectroscopy (FT-IR). This binding leads to the conversion of ß-sheet into α-helical conformation and subsequently loss in protein activity. The thermodynamic parameters of bilirubin-α2M binding indicate that the binding is exothermic, and the reaction spontaneous. Our studies show that binding of bilirubin with α2M in the presence of light induces structural and functional modifications in the protein. Bilirubin possesses multiple biological activities, including immunomodulatory property which has not been extensively explored and which may be of interest for further study.


Assuntos
Bilirrubina/metabolismo , alfa 2-Macroglobulinas Associadas à Gravidez/metabolismo , Animais , Bilirrubina/química , Relação Dose-Resposta a Droga , Peptídeo Hidrolases/metabolismo , alfa 2-Macroglobulinas Associadas à Gravidez/química , alfa 2-Macroglobulinas Associadas à Gravidez/isolamento & purificação , Ligação Proteica , Ovinos , Termodinâmica
18.
Arch Biochem Biophys ; 675: 108118, 2019 10 30.
Artigo em Inglês | MEDLINE | ID: mdl-31574256

RESUMO

Methotrexate (MTX) is advised in the treatment of solid tumours, hematologic malignancies and autoimmune disorders. On reaching the circulation, 60% of MTX is bound to the proteins present in serum. Alpha-2-macroglobulin (α2M) is a plasma proteinase inhibitor with numerous functions such as binding, transportation and targeting of molecules. Our studies are the first attempt to investigate the binding interaction of pharmacologically important drug MTX, and highly abundant proteinase inhibitor- α2M. The protein functional activity assay shows 53% decrease in antiproteolytic potential of α2M upon drug interaction. The binding of MTX with α2M was studied by various biophysical methods. UV-visible absorption spectroscopy reveals hyperchromicity of α2M spectra upon drug binding. The intrinsic fluorescence spectra show quenching in fluorescence intensity of α2M and the mechanism of quenching was found to be static in nature. Far UV-CD spectra unveil slight alteration in secondary structure of α2M upon drug binding. Isothermal titration calorimetry (ITC) reveals the value of thermodynamic parameters and which affirms the binding process to be spontaneous and exothermic. Molecular docking illustrates that Asn173, Leu1298, Gly172, Lys1240, Gln1325, Ser1327, Glu913, Asn1139, Lys1236, Leu951 and Arg1297 were the key residues involved during interaction process. Molecular dynamics (MD) simulation studies suggest that MTX form a stable complex with α2M. Our study assumes importance from the fact that MTX is known to bind plasma proteins quite efficiently.


Assuntos
Simulação por Computador , Metotrexato/metabolismo , alfa 2-Macroglobulinas Associadas à Gravidez/metabolismo , Análise Espectral/métodos , Humanos , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Ligação Proteica
19.
J Fluoresc ; 29(4): 969-979, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31327087

RESUMO

Gallic acid is a naturally occurring plant polyphenol found in green tea and various fruits. Under certain conditions gallic acid exhibits pro-oxidant characteristics rather than its well known antioxidant property. In the present work, we explored the interaction of gallic acid with sheep alpha-2-macroglobulin (α2M) in the presence of light and determined the functional alteration and conformational modifications induced in α2M structure. α2M is a highly abundant homotetrameric antiproteinase glycoprotein having diverse functions. Our result suggests α2M loses almost 54% of its proteinase inhibitory activity after 2 h incubation with gallic acid in presence of light. The inactivation of α2M was due to photodynamic generation of superoxide radical and hydrogen peroxide by gallic acid. The UV/visible absorption spectra of α2M showed increase in absorbance due to complex formation with gallic acid. Intrinsic fluorescence study shows that α2M-gallic acid interaction leads to quenching of fluorescence intensity of α2M and the mechanism of quenching is found to be static in nature. Synchronous fluorescence measurements reveal that gallic acid interaction leads to change in the microenvironment around tryptophan residues of α2M. Moreover, Fourier transform infrared spectroscopy and circular dichroism spectra suggests perturbation in secondary structure of α2M. Binding parameters were investigated by spectroscopic as well as calorimetric measurements. Negative value of enthalpy change and Gibbs free energy confirms the binding process to be exothermic and spontaneous.


Assuntos
Ácido Gálico/farmacologia , Luz , alfa 2-Macroglobulinas Associadas à Gravidez/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Espectrometria de Fluorescência
20.
J Immunoassay Immunochem ; 40(1): 52-69, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30497330

RESUMO

The oral mucosa protects the host against invading antigens and pathogenic microorganisms and contains an elaborate immune system and remains in a relative state of health despite the heavy antigen load. The oral barrier is exposed to unique and diverse communities of commensal microbial communities that are known to play immune-stimulatory roles in oral inflammatory diseases. Saliva is secreted from the salivary glands and has multiple functions, including mouth cleaning and protection, antibacterial effects, and digestion. The major protective function of salivary secretions in the oral cavity is through immunological and non-immunological means as well as direct antimicrobial activity. A biomarker is an objectively measured and evaluated indicator of normal biologic processes, pathogenic processes, or pharmacologic responses to therapeutic intervention. With the rapid advancement in salivaomics, saliva is well recognized as a pool of biological markers. Saliva biomarkers include the changes in the biomolecules, such as DNA, RNA and proteins, and the microbial biofilm. There are numerous defense and protective proteins present in the saliva that are involved in oral homeostasis, immunity, and tolerance. This review article attempts to categorize and analyze the various biomolecules and biomarkers in the oral cavity that may be important in pathophysiology.


Assuntos
Bioensaio , DNA/análise , Boca/imunologia , Boca/patologia , Proteínas/análise , RNA/análise , Biofilmes , Biomarcadores/análise , Humanos , Boca/efeitos dos fármacos , Boca/metabolismo
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