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1.
Biochem Biophys Res Commun ; 608: 90-95, 2022 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-35397428

RESUMO

Obesity is associated with low-grade chronic inflammation and has a remarkable role in the pathophysiology of metabolic complications. In triggering these inflammatory responses, the arachidonic acid (AA) cascade plays a key role. However, there is a lack of data on how supplementary AA would affect obesity, adipose tissue inflammation, and the AA cascade in obesity. This study aims to investigate how AA supplementation affects obesity, adipocyte morphology, inflammation, and AA cascade signaling. Male Swiss Albino mice were used in our experiment. The mice were fed high-fat diets to induce obesity, and these obese mice were treated with two different doses of AA for 3 weeks. A normal diet non-obese group and an untreated obese group were kept as controls. Bodyweight and daily food intake data were recorded during that period. After the treatment period, blood serum and white adipose tissue of the experimental mice were collected for colorimetric lipid profile tests, histology, and mRNA extraction. The ΔΔCT method was employed for calculating the relative mRNA expression of target genes. The findings of our study suggest that AA has no significant effects on body weight, visceral adiposity, adipose tissue morphology, and serum lipid profile. However, AA treatment has resulted in a significant down-regulation of pro-inflammatory markers as well as the COX pathway. Besides, up-regulation of 12/15-LOX has been observed, indicating the metabolism pathway of supplementary AA through the LOX pathway. Our findings indicate that AA treatment may not provide significant benefits in terms of body weight, visceral fat mass, or serum lipid profile. However, it has effectively alleviated obesity-induced adipocyte inflammation in high-fat diet-induced obese mice.


Assuntos
Adiposidade , Dieta Hiperlipídica , Adipócitos/metabolismo , Animais , Ácido Araquidônico/metabolismo , Peso Corporal , Dieta Hiperlipídica/efeitos adversos , Suplementos Nutricionais , Inflamação/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Obesos , Obesidade/tratamento farmacológico , Obesidade/etiologia , Obesidade/metabolismo , RNA Mensageiro/metabolismo
2.
Prostaglandins Other Lipid Mediat ; 162: 106664, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35843503

RESUMO

The prevalence of obesity is increasing at an alarming rate and keeps on being one of the significant challenges of this century. Obesity promotes adipose tissue hypertrophy and causes the release of different pro-inflammatory cytokines, playing a significant role in the pathophysiology of metabolic syndrome. Aspirin is known as a potent anti-inflammatory drug, but its role in adipogenesis, adipocyte-specific inflammation, and metabolic syndrome is not well characterized. Thus, in this experiment, we aimed to determine the effect of low-dose aspirin on obesity, obesity-induced inflammation, and metabolic syndrome. High-fat diet-induced obese female mice (Swiss Albino) were used in our study. Mice were fed on a normal diet, a high-fat diet, and a low dose of aspirin (LDA) in the presence of a high-fat diet for 11 weeks. Body weight, lipid profile, adipose tissue size, and inflammatory status were analyzed after that period. The ∆∆CT method was used to calculate the relative mRNA expression of target genes. Treatment with a low dose of aspirin resulted in a significant reduction of body weight, visceral fat mass and serum total cholesterols, serum and adipose tissue triglycerides, and blood glucose levels in high-fat diet-induced obese mice compared to the untreated obese group. Consistent with these biochemical results, a significant reduction in mRNA expression of different genes like PPARγ, GLUT4, IL-6, TNFα, MCP-1, ICAM-I, and VCAM-I associated with adipogenesis and inflammation were noticed. Overall, current study findings indicate that low-dose aspirin reduces obesity, hyperlipidemia, adipocyte-specific inflammation, and metabolic syndrome in high-fat diet-induced obese mice.


Assuntos
Dieta Hiperlipídica , Síndrome Metabólica , Tecido Adiposo/metabolismo , Animais , Anti-Inflamatórios/farmacologia , Aspirina/farmacologia , Aspirina/uso terapêutico , Glicemia/metabolismo , Peso Corporal , Feminino , Inflamação/metabolismo , Interleucina-6/metabolismo , Síndrome Metabólica/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Obesos , Obesidade/metabolismo , PPAR gama/metabolismo , RNA Mensageiro/metabolismo , Triglicerídeos/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
3.
Prostaglandins Other Lipid Mediat ; 154: 106539, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33592322

RESUMO

The World Health Organization has described the 2019 Coronavirus disease caused by an influenza-like virus called SARS-CoV-2 as a pandemic. Millions of people worldwide are already infected by this virus, and severe infection causes hyper inflammation, thus disrupting lung function, exacerbating breath difficulties, and death. Various inflammatory mediators bio-synthesized through the arachidonic acid pathway play roles in developing cytokine storms, injuring virus-infected cells. Since pro-inflammatory eicosanoids, including prostaglandins, and leukotrienes, are key brokers for physiological processes such as inflammation, fever, allergy, and pain but, their function in COVID-19 is not well defined. This study addresses eicosanoid's crucial role through the arachidonic pathway in inflammatory cascading and recommends using bioactive lipids, NSAIDs, steroids, cell phospholipase A2 (cPLA2) inhibitors, and specialized pro-resolving mediators (SPMs) to treat COVID-19 disease. The role of soluble epoxide hydrolase inhibitors (SEHIs) in promoting the activity of epoxyeicosatrienoic acids (EETs) and 17-hydroxide-docosahexaenoic acid (17-HDHA) is also discussed. Additional research that assesses the eicosanoid profile in COVID-19 patients or preclinical models generates novel insights into coronavirus-host interaction and inflammation regulation.


Assuntos
Ácidos Araquidônicos/metabolismo , COVID-19 , Mediadores da Inflamação/metabolismo , Pandemias , SARS-CoV-2/metabolismo , COVID-19/epidemiologia , COVID-19/metabolismo , Síndrome da Liberação de Citocina/epidemiologia , Síndrome da Liberação de Citocina/metabolismo , Humanos
4.
J Res Med Sci ; 23: 77, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30181759

RESUMO

BACKGROUND: Diabetes is associated with oxidative stress and considered as a major risk factor for cardiac disease. We attempted to investigate the role of oral antidiabetic (OAD) agents gliclazide and metformin in lowering the lipid peroxidation and managing the risk for cardiovascular (CV) complications in diabetic patients in comparison with nondiabetic healthy individuals. MATERIALS AND METHODS: This cross-sectional study was comprised of 150 individuals grouped in three, namely, Group A (n = 60) healthy volunteers, Group B (n = 30) newly diagnosed diabetes, and Group C (n = 60) diabetes treated with OAD. Serum malondialdehyde (MDA), nitric oxide (NO), and Vitamin C were assessed for studying lipid peroxidation status, whereas serum triglyceride (TG) and total cholesterol were monitored as predictors for CV risk. RESULTS: We found significantly higher concentrations of MDA and NO levels (P < 0.001) in both groups of patients (Group B and C) in comparison to control group (Group A). Regarding antioxidants, significantly lower concentrations of Vitamin C (P = 0.046) were found in Group B and C compared to Group A. Moreover, there was significant difference exhibited in concentration level of MDA (P = 0.001) and NO (P = 0.015) between Group B and C, whereas difference of Vitamin C (P = 0.147) was not statistically significant. CONCLUSION: Our data confirmed that treatment with gliclazide and metformin significantly reduced the lipid peroxidation accompanied with attenuated levels of serum TGs and cholesterol and suggested that oral hypoglycemic agents have great impact to reduce the oxidative stress and increase the antioxidant status in diabetes.

5.
Biol Res ; 47: 55, 2014 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-25418519

RESUMO

BACKGROUND: The current study aims at evaluating the analgesic, anti-pyretic and anti-inflammatory properties of methanolic extract of the stem, bark and leaves of Launaea sarmentosa and Aegialitis rotundifolia roxb. RESULTS: The AELS and AEAR extract presented a significant (***p < 0.001) dose dependent increase in reaction time in writhing method and showed inhibition of 63.1% and 57.1% respectively at the doses of 400 mg/kg body weight while standard drug showed (P < 0.001) inhibition of 69.23%. In tail immersion method, AELS and AEAR showed maximum time of tail retention at 30 min in hot water i.e. 6.93 sec and 6.54 sec respectively at highest doses of 400 mg/kg body weight than lower dose while standard pentazocine showed reaction time of 7.62 sec. The AELS and AEAR extract also exhibited promising anti-inflammatory effect as demonstrated by statistically significant inhibition of paw volume by 32.48% and 26.75% respectively at the dose of 400 mg/kg body weight while the value at the dose of 200 mg/kg body weight were linear to higher dose at the 3rd hour of study. On the other hand, Standard indomethacin inhibited 40.13% of inflammation (***P < 0.001). In Cotton-pellet granuloma method, AELS and AEAR extract at the dose of 400 mg/kg body weight exhibited inhibition of inflammation of 34.7% and 29.1% respectively while standard drug showed (P < 0.001) inhibition of 63.22%. Intraperitoneal administration of AELS and AEAR showed dose dependent decrease in body temperature in brewer's yeast induced hyperthermia in rats at both doses. However, AELS significantly decreased body temperature (***p < 0.001) at 400 mg/kg compared to control. CONCLUSIONS: Present work propose that the methanolic extract of Launaea sarmentosa and Aegialitis rotundifolia roxb possesses dose dependent pharmacological action which supports its therapeutic use in folk medicine possibly mediated through the inhibition or blocking of release of prostaglandin and/or actions of vasoactive substances such as histamine, serotonin and kinins.


Assuntos
Antipiréticos/uso terapêutico , Asteraceae/química , Febre/tratamento farmacológico , Manejo da Dor , Fitoterapia , Plumbaginaceae/química , Analgésicos/uso terapêutico , Animais , Anti-Inflamatórios não Esteroides/uso terapêutico , Aspirina/uso terapêutico , Bangladesh , Edema/induzido quimicamente , Edema/tratamento farmacológico , Feminino , Indometacina/uso terapêutico , Inflamação/tratamento farmacológico , Masculino , Camundongos , Extratos Vegetais/uso terapêutico , Folhas de Planta/efeitos dos fármacos , Folhas de Planta/metabolismo , Ratos Wistar , Fatores de Tempo , Testes de Toxicidade Aguda
6.
Exp Cell Res ; 318(4): 408-15, 2012 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-22100987

RESUMO

Lipocalin-type prostaglandin D synthase (L-PGDS) expressed preferentially in adipocytes is responsible for the synthesis of PGD(2) and its non-enzymatic dehydration products, PGJ(2) series, serving as pro-adipogenic factors. However, the role of L-PGDS in the regulation of adipogenesis is complex because of the occurrence of several derivatives from PGD(2) and their distinct receptor subtypes as well as other functions such as a transporter of lipophilic molecules. To manipulate the expression levels of L-PGDS in cultured adipocytes, cultured preadipogenic 3T3-L1 cells were transfected stably with a mammalian expression vector having cDNA encoding murine L-PGDS oriented in the sense direction. The isolated cloned stable transfectants with L-PGDS expressed higher levels of the transcript and protein levels of L-PGDS, and synthesized PGD(2) from exogenous arachidonic acid at significantly higher levels. By contrast, the synthesis of PGE(2) remained unchanged, indicating no influence on the reactions of cyclooxygenase (COX) and PGE synthase. Furthermore, the ability of those transfectants to synthesize Δ(12)-PGJ(2) increased more greatly during the maturation phase. The sustained expression of L-PGDS in cultured stable transfectants hampered the storage of fats during the maturation phase of adipocytes, which was accompanied by the reduced gene expression of adipocyte-specific markers reflecting the down-regulation of the adipogenesis program. The suppressed adipogenesis was not rescued by either exogenous aspirin or peroxisome proliferator-activated receptor γ (PPARγ) agonists including troglitazone and Δ(12)-PGJ(2). Taken together, the results indicate the negative regulation of the adipogenesis program by the enhanced expression of L-PGDS through a cellular mechanism involving the interference of the PPARγ signaling pathway without the contribution of endogenous pro-adipogenic prostanoids.


Assuntos
Adipócitos/fisiologia , Adipogenia/genética , Oxirredutases Intramoleculares/genética , Lipocalinas/genética , Prostaglandinas/fisiologia , Células-Tronco/fisiologia , Células 3T3-L1 , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Adipogenia/efeitos dos fármacos , Animais , Aspirina/farmacologia , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/genética , Células Cultivadas , Inibidores de Ciclo-Oxigenase 2/farmacologia , Avaliação Pré-Clínica de Medicamentos , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Regulação Enzimológica da Expressão Gênica/fisiologia , Oxirredutases Intramoleculares/antagonistas & inibidores , Oxirredutases Intramoleculares/fisiologia , Lipocalinas/antagonistas & inibidores , Lipocalinas/fisiologia , Camundongos , Camundongos Endogâmicos BALB C , PPAR gama/agonistas , PPAR gama/fisiologia , Prostaglandina D2/análogos & derivados , Prostaglandina D2/farmacologia , Prostaglandinas/metabolismo , Prostaglandinas/farmacologia , Células-Tronco/efeitos dos fármacos , Células-Tronco/metabolismo , Transfecção
7.
Mol Biotechnol ; 2023 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-37878227

RESUMO

SARS-CoV-2 mediated infection instigated a scary pandemic state since 2019. They created havoc comprising death, imbalanced social structures, and a wrecked global economy. During infection, the inflammation and associated cytokine storm generate a critical pathological situation in the human body, especially in the lungs. By the passage of time of infection, inflammatory disorders, and multiple organ damage happen which might lead to death, if not treated properly. Until now, many pathological parameters have been used to understand the progress of the severity of COVID-19 but with limited success. Bioactive lipid mediators have the potential of initiating and resolving inflammation in any disease. The connection between lipid storm and inflammatory states of SARS-CoV-2 infection has surfaced and got importance to understand and mitigate the pathological states of COVID-19. As the role of eicosanoids in COVID-19 infection is not well defined, available information regarding this issue has been accumulated to address the possible network of eicosanoids related to the initiation of inflammation, promotion of cytokine storm, and resolution of inflammation, and highlight possible strategies for treatment and drug discovery related to SARS-CoV-2 infection in this study. Understanding the involvement of eicosanoids in exploration of cellular events provoked by SARS-CoV-2 infection has been summarized as an important factor to deescalate any upcoming catastrophe imposed by the lethal variants of this micro-monster. Additionally, this study also recognized the eicosanoid based drug discovery, treatment, and strategies for managing the severity of SARS-COV-2 infection.

8.
Mol Biotechnol ; 2023 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-37393414

RESUMO

Metabolic syndrome refers to a group of several disease conditions together with high glucose triglyceride levels, high blood pressure, lower high-density lipoprotein level, and large waist circumference. About 400 million people worldwide, one-third of the Euro-American population and 27% Chinese population over age 50 have it. microRNAs, an abundant novel class of endogenous small, non-coding RNAs in eukaryotic cells, act as negative controllers of gene expression by promoting either degradation/translational repression of target messenger RNA. More than 2000 microRNAs in the human genome have been identified and they are implicated in various biological & pathophysiological processes, including glucose homeostasis, inflammatory response, and angiogenesis. Destruction of microRNAs has a crucial role in the pathogenesis of obesity, cardiovascular disease, and diabetes. Recently the discovery of circulating microRNAs in human serum may help to promote metabolic crosstalk between organs and serves as a novel approach for the identification of various diseases, like Type 2 diabetes & atherosclerosis. In this review, we will discuss the most recent and up-to-date research on the pathophysiology and histopathology of metabolic syndrome besides their historical background and epidemiological highlight. As well as search the methodologies employed in this field of research and the potential role of microRNAs as novel biomarkers and therapeutic targets for metabolic syndrome in the human body. Furthermore, the significance of microRNAs in promising strategies, like stem cell therapy, which holds enormous promise for regenerative medicine in the treatment of metabolic disorders will also be discussed.

9.
Life Sci ; 334: 122211, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-38084672

RESUMO

In recent years, the obesity epidemic has escalated into a serious public health catastrophe that is only getting worse. However, research into the pathophysiological pathways behind the obesity development and the illnesses that it is associated with is ongoing. In the last decades, it is now clear that the gut microbiota plays a significant role in the genesis and progression of obesity and obesity-related illnesses, particularly changes in its metabolites and composition as obesity progresses. Here, we provide a summary of the processes by which variations in gut metabolite levels and the composition of gut microbiota affect obesity and associated disorders. The bacteria residing in the gut release several chemicals that influence the appetite control, metabolism, and other systems. Since it can either encourage or restrict the deposition of fat in several different ways, the gut microbiota's role in obesity is debatable. Additionally, we go over potential therapeutic approaches that could be utilized to alter gut microbiota composition and focus on the important metabolic pathways associated with obesity and metabolic disorders linked to obesity.


Assuntos
Microbioma Gastrointestinal , Humanos , Obesidade/metabolismo , Bactérias , Estudos Longitudinais
10.
Heliyon ; 9(1): e12737, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36685474

RESUMO

Obesity is a severe public health burden and a major component of metabolic syndrome. It is critical to identify treatment medicines for obesity and associated inflammation. We examined the anti-obesity and anti-inflammatory properties of Musa acuminate seeds methanol extract in high-fat diet-induced obesity. Changes in body weight, Lee index, fat mass accumulation, serum cholesterol, and serum triglyceride were monitored. Alteration in the expression of PPARγ, GLUT4, and MCP-1 at the transcript level in adipose tissue was also studied. After tabulation of our data, a significant reduction (p < 0.05) was recorded for body weight gain, and fat mass accumulation followed by significant changes (p < 0.05) in serum cholesterol, and serum triglyceride levels by the extract. In agreement with the biochemical data, the extract was capable enough (p < 0.05) to reduce the mRNA expression of PPARγ, and MCP-1, confirming the ability of the extract to ameliorate the risk of obesity and obesity-associated inflammation. Moreover, an in-silico study showed the high binding affinity of the reported compounds from M. acuminate like Delphinidin, Umbelliferon with COX-2, PPARγ, and MCP-1, supporting the notion of the risk-reducing potential of M.acuminate for obesity and obesity mediated inflammatory.

11.
Sci Total Environ ; 858(Pt 3): 159350, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36265620

RESUMO

Wastewater based epidemiology (WBE) is an important tool to fight against COVID-19 as it provides insights into the health status of the targeted population from a small single house to a large municipality in a cost-effective, rapid, and non-invasive way. The implementation of wastewater based surveillance (WBS) could reduce the burden on the public health system, management of pandemics, help to make informed decisions, and protect public health. In this study, a house with COVID-19 patients was targeted for monitoring the prevalence of SARS-CoV-2 genetic markers in wastewater samples (WS) with clinical specimens (CS) for a period of 30 days. RT-qPCR technique was employed to target nonstructural (ORF1ab) and structural-nucleocapsid (N) protein genes of SARS-CoV-2, according to a validated experimental protocol. Physiological, environmental, and biological parameters were also measured following the American Public Health Association (APHA) standard protocols. SARS-CoV-2 viral shedding in wastewater peaked when the highest number of COVID-19 cases were clinically diagnosed. Throughout the study period, 7450 to 23,000 gene copies/1000 mL were detected, where we identified 47 % (57/120) positive samples from WS and 35 % (128/360) from CS. When the COVID-19 patient number was the lowest (2), the highest CT value (39.4; i.e., lowest copy number) was identified from WS. On the other hand, when the COVID-19 patients were the highest (6), the lowest CT value (25.2 i.e., highest copy numbers) was obtained from WS. An advance signal of increased SARS-CoV-2 viral load from the COVID-19 patient was found in WS earlier than in the CS. Using customized primer sets in a traditional PCR approach, we confirmed that all SARS-CoV-2 variants identified in both CS and WS were Delta variants (B.1.617.2). To our knowledge, this is the first follow-up study to determine a temporal relationship between COVID-19 patients and their discharge of SARS-CoV-2 RNA genetic markers in wastewater from a single house including all family members for clinical sampling from a developing country (Bangladesh), where a proper sewage system is lacking. The salient findings of the study indicate that monitoring the genetic markers of the SARS-CoV-2 virus in wastewater could identify COVID-19 cases, which reduces the burden on the public health system during COVID-19 pandemics.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , COVID-19/epidemiologia , Seguimentos , Águas Residuárias , Marcadores Genéticos , RNA Viral
12.
Expert Rev Endocrinol Metab ; 17(1): 83-93, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34781810

RESUMO

INTRODUCTION: Coronavirus disease (COVID-19) is a highly contagious disease that poses major public health risks. Fewer studies link high CRP and D-dimer levels to severe COVID-19 infection. Therefore, this study investigates the association of serum CRP and D-dimer concentration with COVID-19 severity in diabetic and non-diabetic patients. AREAS COVERED: Relevant published articles were identified using electronic search engines, such as Google Scholar, PubMed, Springer, Science Direct, and Researchgate. A total of 29 articles reporting on 15,282 patients (4,733 diabetes and 10,549 non-diabetes) were included in this systematic review and meta-analysis. RevMan V5.4, STATA V14 software, and SPSS V25 were used for the meta-analysis. Egger's regression and Begg-Mazumdar's test were used for assessing publication bias. The pooled result of all studies revealed that serum CRP (Standard mean difference (SMD) 0.41 mg/L; P < 0.0001; I2 93%) and D-dimer (SMD 0.32 mg/L; P < 0.0001; I2 83%) concentration was significantly higher in COVID-19 diabetic patients. The prevalence of COVID-19 infection was comparatively higher in male diabetic patients (OR 2.41; P < 0.00001; I2 88%). There was no publication bias. CRP and D-dimer rose with age in COVID-19 diabetic and non-diabetic patients. EXPERT OPINION: Overall, the serum CRP and D-dimer concentration in COVID-19 diabetic patients was significantly higher than non-diabetic patients indicating severe illness.


Assuntos
Proteína C-Reativa/análise , COVID-19 , Diabetes Mellitus , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , COVID-19/sangue , COVID-19/diagnóstico , Humanos
13.
Rev Bras Farmacogn ; 32(1): 50-64, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34876760

RESUMO

Pooled evidence conveys the association between polyunsaturated fatty acids and infectious disease. SARS-CoV-2, an enveloped mRNA virus, was also reported to interact with polyunsaturated fatty acids. The present review explores the possible mode of action, immunology, and consequences of these polyunsaturated fatty acids during the viral infection. Polyunsaturated fatty acids control protein complex formation in lipid rafts associated with the function of two SARS-CoV-2 entry gateways: angiotensin-converting enzyme-2 and cellular protease transmembrane protease serine-2. Therefore, the viral entry can be mitigated by modulating polyunsaturated fatty acids contents in the body. α-Linolenic acid is the precursor of two clinically important eicosanoids eicosapentaenoic acid and docosahexaenoic acid, the members of ω-3 fats. Resolvins, protectins, and maresins derived from docosahexaenoic acid suppress inflammation and augment phagocytosis that lessens microbial loads. Prostaglandins of 3 series, leukotrienes of 5 series, and thromboxane A3 from eicosapentaenoic acid exhibit anti-inflammatory, vasodilatory, and platelet anti-aggregatory effects that may also contribute to the control of pre-existing pulmonary and cardiac diseases. In contrast, ω-6 linoleic acid-derived arachidonic acid increases the prostaglandin G2, lipoxins A4 and B4, and thromboxane A2. These cytokines are pro-inflammatory and enhance the immune response but aggravate the COVID-19 severity. Therefore, the rational intake of ω-3-enriched foods or supplements might lessen the complications in COVID-19 and might be a preventive measure.

14.
Biochem Biophys Res Commun ; 411(2): 287-92, 2011 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-21726533

RESUMO

Adipocytes express preferentially lipocalin-type prostaglandin (PG)D synthase (L-PGDS) that is responsible for the biosynthesis of PGD(2) and other related prostanoids with pro-adipogenic or anti-adipogenic effects. To evaluate the role of L-PGDS in cultured adipocytes and the precursor cells, we attempted to interfere the intracellular expression of L-PGDS in cultured 3T3-L1 preadipocytes by stable transfection with a mammalian expression vector having the full-length cDNA of L-PGDS oriented in the antisense direction. The cloned transfectants with antisense L-PGDS exhibited the reduction in the transcript and protein levels of L-PGDS, resulting in the significant inhibition of the PGD(2) synthesis from exogenous and endogenous arachidonic acid. By contrast, the synthesis of PGE(2) was not influenced appreciably, indicating no interfering effects on cyclooxygenases and PGE synthases. The stable transfection with antisense L-PGDS induced markedly the stimulation of fat storage in cultured adipocytes during the maturation phase. In addition, the spontaneous accumulation of fats occurred in the transfectants with antisense L-PGDS without undergoing the stimulation with inducing factors. The gene expression studies revealed the enhanced expression of adipocyte-specific markers in the transfectants with antisense L-PGDS, indicating the up-regulation of adipogenesis program. The stimulated adipogenesis was significantly reversed by anti-adipogenic prostanoids including PGE(2) and PGF(2α), while the storage of fats was additionally enhanced by pro-adipogenic 15-deoxy- Δ(12,14)-prostaglandin J(2). These results suggest that the stably reduced expression levels of L-PGDS regulates positively adipogenesis program in a cellular mechanism independent of pro-adipogenic action of PGJ(2) series.


Assuntos
Adipócitos/citologia , Adipogenia/genética , Oxirredutases Intramoleculares/biossíntese , Lipocalinas/biossíntese , RNA Antissenso/genética , Células 3T3-L1 , Adipócitos/enzimologia , Animais , Células Cultivadas , Células Clonais , Oxirredutases Intramoleculares/genética , Lipocalinas/genética , Camundongos , Camundongos Endogâmicos BALB C , Prostaglandina D2/biossíntese
15.
Prostaglandins Other Lipid Mediat ; 94(3-4): 73-80, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21237281

RESUMO

Peroxisome proliferator-activated receptor (PPAR)γ is a well-known master regulator for the differentiation and maturation of adipocytes. Prostaglandin (PG) D(2) can be produced in adipocytes and dehydrated to J(2) series of PGs including 15-deoxy-Δ(12,14)-PGJ(2) (15d-PGJ(2)) and Δ(12)-PGJ(2), which serve as pro-adipogenic prostanoids through the activation of PPARγ. However, the quantitative determination of Δ(12)-PGJ(2) has not been attempted during the life stage of adipocytes. In this study, we developed an enzyme-linked immunosorbent assay using mouse antiserum specific for Δ(12)-PGJ(2). According to the standard curve, the amount of Δ(12)-PGJ(2) can be measured from 0.5 pg to 14.4 ng in an assay. Our antiserum did not recognize most other prostanoids including 15d-PGJ(2), while it only showed the cross-reaction of 28% with unstable PGJ(2). This immunological assay was applied to the determination of the endogenous formation of Δ(12)-PGJ(2) in cultured 3T3-L1 adipocytes during the maturation phase. The ability of cultured adipocytes to form endogenous Δ(12)-PGJ(2) increased gradually at an earlier stage of the maturation phase and detectable at higher levels than 15d-PGJ(2). Treatment of cultured cells with either aspirin or indomethacin, a general cyclooxygenase inhibitor, significantly reduced the production of endogenous Δ(12)-PGJ(2) in the maturation medium as expected. Furthermore, we evaluated individually the exogenous effects of PGJ(2) series at various doses on adipogenesis during the maturation phase. Although Δ(12)-PGJ(2) was slightly less potent than 15d-PGJ(2), each of these PGJ(2) series rescued effectively both the accumulation of fats and the gene expression of typical adipocyte-markers that were attenuated in the presence of aspirin. Taken together, our findings indicate that endogenous Δ(12)-PGJ(2) contributes substantially to the up-regulation of adipogenesis program through the activation of PPARγ together with 15d-PGJ(2) during the maturation phase of cultured adipocytes.


Assuntos
Adipócitos/química , Adipogenia , Ensaio de Imunoadsorção Enzimática , PPAR gama/metabolismo , Prostaglandina D2/análise , Células 3T3-L1 , Adipócitos/citologia , Adipócitos/metabolismo , Animais , Camundongos , Prostaglandina D2/metabolismo
16.
Biosci Rep ; 41(8)2021 08 27.
Artigo em Inglês | MEDLINE | ID: mdl-34350941

RESUMO

An influenza-like virus named severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is responsible for COVID-19 disease and spread worldwide within a short time. COVID-19 has now become a significant concern for public health. Obesity is highly prevalent worldwide and is considered a risk factor for impairing the adaptive immune system. Although diabetes, hypertension, cardiovascular disease (CVD), and renal failure are considered the risk factors for COVID-19, obesity is not yet well-considered. The present study approaches establishing a systemic association between the prevalence of obesity and its impact on immunity concerning the severe outcomes of COVID-19 utilizing existing knowledge. Overall study outcomes documented the worldwide prevalence of obesity, its effects on immunity, and a possible underlying mechanism covering obesity-related risk pathways for the severe outcomes of COVID-19. Overall understanding from the present study is that being an immune system impairing factor, the role of obesity in the severe outcomes of COVID-19 is worthy.


Assuntos
Imunidade Adaptativa/imunologia , COVID-19/patologia , Obesidade/imunologia , Obesidade/patologia , Humanos , Inflamação/patologia , Obesidade/epidemiologia , Fatores de Risco , SARS-CoV-2/imunologia
17.
Biosci Rep ; 40(4)2020 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-32207527

RESUMO

The antidiabetic, hypoglycemic and oral glucose tolerance test (OGTT) activities of zinc oxide nanoparticles (ZnONPs) were assessed in mice. ZnONPs were prepared by reacting Zn(NO3)2.6H2O and NaOH solution at 70°C with continuous stirring and then characterized by transmission electron microscopy (TEM) and scanning electron microscopy (SEM) techniques. Diabetes was induced by the intraperitoneal injection of streptozotocin (STZ) in mice, and then the blood glucose levels were determined by the glucose oxidase method. The experimental results revealed that ZnONPs suggestively (p<0.001) declined the blood glucose levels (39.79%), while these reductions were 38.78% for the cotreatment of ZnONPs and insulin, and 48.60% for insulin, respectively. In the hypoglycemic study, ZnONPs (8 and 14 mg/kg b.w) reduced approximately 25.13 and 29.15% of blood glucose levels, respectively. A similar reduction was found in the OGTT test, which is also a dose- and time-dependent manner. Overall, ZnONPs possess a potential antidiabetic activity, which could be validated by further mechanistic studies.


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Nanopartículas/administração & dosagem , Óxido de Zinco/administração & dosagem , Administração Oral , Animais , Glicemia/análise , Glicemia/efeitos dos fármacos , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/diagnóstico , Avaliação Pré-Clínica de Medicamentos , Teste de Tolerância a Glucose , Humanos , Injeções Intraperitoneais , Camundongos , Estreptozocina/administração & dosagem , Estreptozocina/toxicidade
18.
Heliyon ; 5(5): e01739, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31193394

RESUMO

The global prevalence of hyperlipidaemia is increasing rapidly and high dietary fat intake is a major risk factor for developing hyperlipidaemia. An in-vivo biological investigation was carried out on ethanolic extract of Momordica charantia, a plant belonging to the family Cucurbitaceae for the evaluation of antihyperlipidemic activity and serum uric acid reducing potential. In our study, 25 healthy male mice were selected randomly and grouped into 5 groups (5 animals in each group). Lipid and uric acid profile were estimated after 21 days of treatment by using the enzymatic colourimetric GPO-PAP method. Results showed that ethanolic extract of M. charantia at a dose of 200 mg/kg body weight showed significant (p < 0.05) cholesterol and triglyceride level reduction profile when co-administrated with 20% fat and normal feed respectively. Atorvastatin was used as standard. Data from pathological examination showed that the average weight of the heart of the mice was normal for every group when compared with control. Gr-2 (normal and extract feed) showed significant (p ˂ 0.05) increased of liver and kidney weight rather than experimental groups; however, these values were lower than the values for the control group. Uric acid level determination revealed that the ethanolic extract of M. charantia reduced serum uric acid level both in experimental groups (Gr-2 and Gr-3). Thus a considerable correlation was found between serum uric acid reducing potentials of the present plant extract with a lipid-lowering profile. This plant can be further investigated thoroughly as a potential source of chemically interesting and biologically important drug candidates.

19.
Biol Trace Elem Res ; 178(2): 189-193, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28058664

RESUMO

Chronic liver disease (CLD) is associated with the destruction of liver parenchyma cell. It is the main cause of morbidity and mortality in most of the developed countries. Oxidative stress and altered levels of different trace elements in serum have been documented for different diseases including inflammation and many liver diseases. This study aims to evaluate the serum level of malondialdehyde (MDA), nitric oxide (NO), antioxidant vitamin C, C-reactive protein (CRP), and zinc (Zn) in CLD patients and to establish a correlation among the study parameters with the severity of inflammatory conditions of CLD. In this study, CLD patients and healthy volunteers were recruited. Total cholesterol and triglyceride were determined by colorimeter using enzymatic method. Serum non-enzymatic antioxidant vitamin C, reactive oxygen species nitric oxide (NO), and malondialdehyde (MDA) were determined by UV-spectrophotometric method. Trace element (Zn) levels were determined by graphite furnace atomic absorption spectroscopy. Independent sample t test and Pearson's correlation test were performed for statistical analysis using the statistical software package SPSS, Version 20. Studies showed that the MDA (p < 0.001), NO (p < 0.001), and CRP levels were significantly higher in CLD patients than in control subjects. The antioxidant vitamin C (p < 0.001) and trace element zinc (p < 0.001) were comparatively lower in the CLD patients than in control subjects. Elemental Zn showed an inverse relationship with MDA, NO, and CRP but positively correlated with antioxidant capacity, whereas MDA showed a positive correlation with CRP level. Thus, we conclude that attenuated level of Zn and antioxidant in serum play an important role in the inflammatory status of CLD patients by elevating the concentration of MDA, NO, and CRP.


Assuntos
Proteína C-Reativa/metabolismo , Hepatopatias/sangue , Estresse Oxidativo , Zinco/sangue , Adulto , Idoso , Doença Crônica , Estudos Transversais , Humanos , Pessoa de Meia-Idade
20.
Anc Sci Life ; 33(3): 162-4, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25538351

RESUMO

CONTEXT: Thrombus formation inside the blood vessels obstructs blood flow through the circulatory system leading hypertension, stroke to the heart, anoxia, and so on. Thrombolytic drugs are widely used for the management of cerebral venous sinus thrombosis patients, but they have certain limitations. Medicinal plants and their components possessing antithrombotic activity have been reported before. However, plants that could be used for thrombolysis has not been reported so far. AIMS: This study's aim was to evaluate the thrombolytic potential of selected plants' root extracts. SETTINGS AND DESIGN: Plants were collected, dried, powdered and extracted by methanol and then fractionated by n-hexane for getting the sample root extracts. Venous blood samples were drawn from 10 healthy volunteers for the purposes of investigation. SUBJECTS AND METHODS: An in vitro thrombolytic model was used to check the clot lysis potential of four n-hexane soluble roots extracts viz., Acacia nilotica, Justicia adhatoda, Azadirachta indica, and Lagerstroemia speciosa along with streptokinase as a positive control and saline water as a negative control. STATISTICAL ANALYSIS USED: Dunnett t-test analysis was performed using SPSS is a statistical analysis program developed by IBM Corporation, USA. on Windows. RESULTS: Using an in vitro thrombolytic model, A. nilotica, L. speciosa, A. indica, and J. adhatoda at 5 mg extract/ml NaCl solution concentration showed 15.1%, 15.49%, 21.26%, and 19.63% clot lysis activity respectively. The reference streptokinase showed 47.21%, and 24.73% clot lysis for 30,000 IU and 15,000 IU concentrations, respectively whereas 0.9% normal saline showed 5.35% clot lysis. CONCLUSIONS: The selected extracts of the plant roots possess marked thrombolytic properties that could lyse blood clots in vitro; however, in vivo clot dissolving properties and active components responsible for clot lysis are yet to be discovered.

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