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1.
World J Microbiol Biotechnol ; 40(6): 168, 2024 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-38630156

RESUMEN

Obesity is a growing epidemic worldwide. Several pharmacologic drugs are being used to treat obesity but these medicines exhibit side effects. To find out the alternatives of these drugs, we aimed to assess the probiotic properties and anti-obesity potentiality of a lactic acid bacterium E2_MCCKT, isolated from a traditional fermented rice beverage, haria. Based on the 16S rRNA sequencing, the bacterium was identified as Lactiplantibacillus plantarum E2_MCCKT. The bacterium exhibited in vitro probiotic activity in terms of high survivability in an acidic environment and 2% bile salt, moderate auto-aggregation, and hydrophobicity. Later, E2_MCCKT was applied to obese mice to prove its anti-obesity potentiality. Adult male mice (15.39 ± 0.19 g) were randomly divided into three groups (n = 5) according to the type of diet: normal diet (ND), high-fat diet (HFD), and HFD supplemented with E2_MCCKT (HFT). After four weeks of bacterial treatment on the obese mice, a significant reduction of body weight, triglyceride, and cholesterol levels, whereas, improvements in serum glucose levels were observed. The bacterial therapy led to mRNA up-regulation of lipolytic transcription factors such as peroxisome proliferator-activated receptor-α which may increase the expression of fatty acid oxidation-related genes such as acyl-CoA oxidase and carnitine palmitoyl-transferase-1. Concomitantly, both adipocytogenesis and fatty acid synthesis were arrested as reflected by the down-regulation of sterol-regulatory element-binding protein-1c, acetyl-CoA carboxylase, and fatty acid synthase genes. In protein expression study, E2_MCCKT significantly increased IL-10 expression while decreasing pro-inflammatory cytokine (IL-1Ra and TNF-α) expression. In conclusion, the probiotic Lp. plantarum E2_MCCKT might have significant anti-obesity effects on mice.


Asunto(s)
Dieta Alta en Grasa , Obesidad , Masculino , Animales , Ratones , Dieta Alta en Grasa/efectos adversos , Ratones Obesos , ARN Ribosómico 16S/genética , Ácidos Grasos
2.
J Appl Biomed ; 22(1): 49-58, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38505970

RESUMEN

We have extracted and characterized Phasa fish (Setipinna phasa) oil for the first time to evaluate the anti-obesity and related anti-inflammatory effects on obese mice. Inbred male albino BALB/c mice were segregated into three categories: control (C), Obese control group (OC), and Phasa fish oil treated group (TX). To establish the potentiality of Setipinna phasa oil for its anti-obesity and anti-inflammatory properties, it was extracted and characterized using GC-MS method. To evaluate the anti-obesity effect, different parameters were considered, such as body weight, lipid composition, obesity, and obesity associated inflammation. The physicochemical characteristics of Phasa fish oil revealed that the oil quality was good because acid value, peroxide value, p-anisidine value, Totox value, refractive index, and saponification value were within the standard value range. The GC-MS study explored the presence of fatty acids beneficial to health such as Hexadec-9-enoic acid; Octadec-11-enoic acid; EPA, DHA, Methyl Linolenate, etc. The application of Setipinna phasa oil on the treated mice group acutely lowered body weight and serum lipid profile compared to the obese group. In connection with this, leptin, FAS, and pro-inflammatory cytokines TNF-α genes expression were downregulated in the treated group compared to the obese group. The Phasa oil treated group had an elevated expression of PPAR-α, adiponectin, LPL gene, and anti-inflammatory markers IL-10 and IL-1Ra compared to the obese group. This study suggests that Phasa fish oil, enriched with essential fatty acid, might be used as an anti-obesity and anti-inflammatory supplement.


Asunto(s)
Dieta Alta en Grasa , Obesidad , Masculino , Ratones , Animales , Dieta Alta en Grasa/efectos adversos , Ratones Endogámicos BALB C , Obesidad/tratamiento farmacológico , Obesidad/metabolismo , Aceites de Pescado/farmacología , Aceites de Pescado/uso terapéutico , Peso Corporal , Inflamación/tratamiento farmacológico , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico
4.
Nutr Neurosci ; 27(3): 271-288, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36947578

RESUMEN

OBJECTIVES: In this study mice were fed a high-fat diet for 12 weeks to establish diet-induced obesity and syringic acid (SA) was assessed for anti-obese, neuroprotective, and neurogenesis. METHOD: Animals were given HFD for 12 weeks to measure metabolic characteristics and then put through the Barns-maze and T-maze tests to measure memory. Additionally, the physiology of the blood-brain barrier, oxidative stress parameters, the expression of inflammatory genes, neurogenesis, and histopathology was evaluated in the brain. RESULT: DIO raised body weight, BMI, and other metabolic parameters after 12 weeks of overfeeding. A reduced spontaneous alternation in behavior (working memory, reference memory, and total time to complete a task), decreased enzymatic and non-enzymatic antioxidants, oxidative biomarkers, increased neurogenesis, and impaired blood-brain barrier were all seen in DIO mice. SA (50 mg/kg) treatment of DIO mice (4 weeks after 8 weeks of HFD feeding) reduced diet-induced changes in lipid parameters associated with obesity, hepatological parameters, memory, blood-brain barrier, oxidative stress, neuroinflammation, and neurogenesis. SA also reduced the impact of malondialdehyde and enhanced the effects of antioxidants such as glutathione, superoxide dismutase (SOD), and total thiol (MDA). Syringic acid improved neurogenesis, cognition, and the blood-brain barrier while reducing neurodegeneration in the hippocampal area. DISCUSSION: According to the results of the study, syringic acid therapy prevented neurodegeneration, oxidative stress, DIO, and memory loss. Syringic acid administration may be a useful treatment for obesity, memory loss, and neurogenesis, but more research and clinical testing is needed.


Asunto(s)
Ácido Gálico/análogos & derivados , Obesidad , Sobrepeso , Ratones , Animales , Obesidad/etiología , Obesidad/prevención & control , Obesidad/tratamiento farmacológico , Encéfalo/metabolismo , Antioxidantes/farmacología , Dieta Alta en Grasa/efectos adversos , Estrés Oxidativo , Trastornos de la Memoria , Neurogénesis/fisiología
5.
Int Microbiol ; 2023 Dec 03.
Artículo en Inglés | MEDLINE | ID: mdl-38044417

RESUMEN

Vibrio harveyi causes luminous vibriosis diseases in shrimp, which lead to shrimp mortalities. Considering the emergence of antibiotic-resistant bacteria, a Vibrio-infecting bacteriophage, VPMCC14, was characterized, and its lysis ability was evaluated on a laboratory scale. VPMCC14 was shown to infect V. harveyi S5A and V. harveyi ATCC 14126. VPMCC14 also exhibited a latent period of 30 min, with a burst size of 38 PFU/cell on its propagation strain. The bacteriophage was stable at a wide range of pHs (3-9), temperatures (0-45°C), and salinities (up to 40 ppt). VPMCC14 exhibited strict virulence properties as the bacteriophage entirely lysed V. harveyi S5A in liquid culture inhibition after 5 h and 4 h at very low MOIs such as MOI 0.1 and MOI 1, respectively. VPMCC14 could control V. harveyi infection in aquariums at MOI 1 and decrease the mortality of Penaeus monodon challenged by V. harveyi. VPMCC14 genome was 134,472 bp long with a 34.5 G+C% content, and 240 open reading frames. A unique characteristic of VPMCC14 was the presence of the HicB family antitoxin-coding open reading frame. Comparative genomic analyses suggested that VPMCC14 could be a representative of a new genus in the Caudoviricetes class. This novel bacteriophage, VPMCC14, could be applied as a biocontrol agent for controlling V. harveyi infection.

6.
NeuroImmune Pharm Ther ; 2(3): 293-300, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37885917

RESUMEN

Objectives: Although microglia are activated in adult and aged brains resulting in neurodegenerative and neuroinflammatory disorders, most of the cell culture studies on microglia deal with neonatal microglia because of ease of isolation. Microglia could be isolated from adult brains, but it requires separation by density gradient centrifugation, magnetic beads, etc. Here, we describe a simple protocol of isolating highly purified microglia from adult mouse brains. Methods: Our protocol involves dilution with sterile PBS or media, regular centrifugation, and plating on poly-D-lysine-coated flasks. Results: These adult microglia expressed the inducible nitric oxide synthase in response to preformed α-syn fibril, an etiological reagent of Parkinson's disease, and bacterial lipopolysaccharides, one of the prototype proinflammatory stimuli. Moreover, these adult microglia exhibited phagocytosis, which was stimulated by LPS treatment. Conclusions: These results suggest that adult microglia isolated by our procedure are functional and that these adult microglia could be used for studies related to neurodegenerative disorders.

7.
Virology ; 588: 109887, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37774603

RESUMEN

Aeromonas hydrophila, a Gram-negative pathogenic bacterium, is responsible for huge economic losses in aquaculture. In this study, we evaluated the efficacy of bacteriophage AHPMCC7 which was isolated by using A. hydrophila MTCC 1739 as a host. This bacteriophage exhibited 10 min latent period and burst size was 275. In liquid culture, bacteriophage AHPMCC7 could completely lyse A. hydrophila MTCC 1739 after 2 h. AHPMCC7 genome was 42,277 bp long with 58.9% G + C content. The genome consisted of 48 CDSs and no tRNA. The comparative genomic analyses clearly implied that AHPMCC7 might represent a novel species of the genus Aphunavirus under Autographiviridae family. Bacteriophage AHPMCC7 could survive at broad pH (3-10), temperature (4-37 °C), and salinity (0-40 ppt). In aquarium trial, AHPMCC7 could control A. hydrophila MTCC 1739 without affecting the survivability of Litopenaeus vannamei. Clearly, the bacteriophage AHPMCC7 might be used in shrimp aquaculture as a biocontrol agent.


Asunto(s)
Aeromonas , Bacteriófagos , Caudovirales , Aeromonas/genética , Aeromonas hydrophila/genética , Caudovirales/genética , Análisis de Secuencia
8.
Sci Rep ; 13(1): 14125, 2023 08 29.
Artículo en Inglés | MEDLINE | ID: mdl-37644076

RESUMEN

The implication of inflammation in the pathophysiology of several types of cancers has been under intense investigation. Conjugated fatty acids can modulate inflammation and present anticancer effects, promoting cancer cell death. In this paper, we evaluated the efficacy of new conjugated fatty acids isolated from marine Opisthopterus tardoore (Tapra fish) in human breast cancer cell lines MCF-7. Linoelaidic acid, a marine fish (O. tardoore) derived unsaturated fatty acids, showed effective anticancer activity against MCF-7. Cell viability (MTT) assay revealed a dose-dependent decline in cancer cell viability. It was noteworthy that 5 µM linoelaidic acid decreased the MCF-7 cell viability by 81.82%. Besides that, linoelaidic acid significantly (P< 0.05) increased the level of tumor necrosis factor-α (TNF-α) and interleukin-1 receptor antagonist (IL-1ra) studied by ELISA. Not only that, linoelaidic acid significantly decreased the reduced glutathione level and increased the oxidized glutathione level in MCF-7 cells indicating the oxidative stress inside the cell. Two different cell staining methods with acridine orange-ethidium bromide and DAPI confirmed that the linoelaidic acid rendered their detrimental effect on cancer cells. To decipher the mode of apoptosis Western blotting was performed in which the expression pattern of several proteins (p53, IL-10, and IL-1ra) established the apoptosis in the studied cell lines after linoelaidic acid exposure. Hence it may be conferred that linoelaidic acid has prompt anticancer activity. Therefore this drug can be used further for the treatment of cancer.


Asunto(s)
Grasas Insaturadas en la Dieta , Ácido Linoleico , Humanos , Células MCF-7 , Especies Reactivas de Oxígeno , Proteína Antagonista del Receptor de Interleucina 1 , Muerte Celular , Ácidos Grasos , Caspasas
9.
Phytother Res ; 37(7): 3097-3120, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37246823

RESUMEN

Phytoestrogens are plant secondary metabolite that is structurally and functionally similar to mammalian estrogens, which have been shown to have various health benefits in humans. Isoflavones, coumestans, and lignans are the three major bioactive classes of phytoestrogens. It has a complicated mechanism of action involving an interaction with the nuclear estrogen receptor isoforms ERα and ERß, with estrogen agonist and estrogen antagonist effects. Depending on their concentration and bioavailability in various plant sources, phytoestrogens can act as estrogen agonist or antagonists. Menopausal vasomotor symptoms, breast cancer, cardiovascular disease, prostate cancer, menopausal symptoms, and osteoporosis/bone health have all been studied using phytoestrogens as an additional standard hormone supplemental remedy. The botanical sources, techniques of identification, classification, side effects, clinical implications, pharmacological and therapeutic effects of their proposed mode of action, safety issues, and future directions for phytoestrogens have all been highlighted in this review.


Asunto(s)
Neoplasias de la Mama , Isoflavonas , Neoplasias de la Próstata , Animales , Masculino , Humanos , Fitoestrógenos/farmacología , Fitoestrógenos/uso terapéutico , Estrógenos/uso terapéutico , Receptores de Estrógenos/metabolismo , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Próstata/tratamiento farmacológico , Isoflavonas/farmacología , Isoflavonas/uso terapéutico , Mamíferos/metabolismo
10.
Virusdisease ; 33(4): 371-382, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36447816

RESUMEN

Nasopharyngeal Carcinoma (NPC) is one of the leading cancers in India's north-eastern (NE) region affecting a section of the population each year. A proportion of the NPC cases are observed to recur even after therapy, indicating the involvement of other factors. We aimed to explore the NPC and Epstein-Barr virus (EBV) burden in the NE region and investigate the prognostic factors for the NPC patients' poor survival and recurrence. NPC patients' information was obtained from different state hospitals between 2014 and 2019. PCR and Sanger sequencing were performed to detect EBV types. Statistical analysis, including forest plot analysis, Kaplan-Mayer survival plot, Log-rank test, cox hazard regression, and Aalen's additive regression model, were performed to determine prognostic factors for the NPC patients' lower survival and recurrence. We observed an increased incidence of NPC and EBV infection in the past five years. Step-wise statistical analyses pointed out that variable such as non-professionals (B = 1.02, HR = 2.8, 95%CI = 1.5,4.9) workers (B = 0.92, HR = 2.5, 95%CI = 1.4,4.4), kitchen cum bedroom (B = 0.61, HR = 1.8, 95%CI = 1.2,2.8), mosquito repellent (B = 0.60, HR = 1.7, 95%CI = 1.1,2.7), nasal congestion (B = 0.60, HR = 1.8, 95%CI = 1.2,2.8), lower haemoglobin level (B = 0.92, HR = 2.5, 95%CI = 1.3,4.9), tumor stage IV (B = 2.8, HR = 1.8, 95%CI = 1.6,14.3), N2 (B = 1.4, HR = 4.0, 95%CI = 1.8,9.1), N3 (B = 1.9, HR = 6.4, 95%CI = 2.8,15.3), and M+ (B = 2.02, HR = 7.5, 95%CI = 4.1,13.7) revealed significant correlation with NPC patients' poor prognosis (p < 0.05). The presence of viral factors also showed a significant association with NPC patients' decreased survival. We concluded that factors related to day-to-day life with EBV infection could be the individual predictor for NPC incidence, lower survival, and disease recurrence. Supplementary Information: The online version contains supplementary material available at 10.1007/s13337-022-00789-5.

11.
Virus Res ; 321: 198904, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-36044930

RESUMEN

Vibrio harveyi is a Gram-negative pathogenic bacterium responsible for luminous vibriosis in shrimp and causes mass mortality of shrimp that leads to economic losses. Considering the emergence of multi-drug resistant bacteria, there is always a need for an alternative to antibiotics. In this study, we have aimed to characterize the Vibrio-infecting bacteriophage VPMCC5 (isolated from an environmental sample by using V. harveyi S2A) and evaluate its efficacy in controlling the pathogen. The bacteriophage exhibited an isometric head and short non-contractile tail. The latent period of the bacteriophage was 10 min and the burst size was 20. The genome of the bacteriophage was 48938 bp long with 40.7 mol% G+C content. A total of 71 ORFs were identified and no tRNA and antibiotic-associated genes were detected. Comparative genomic analyses (CLANS, dot plot, progressiveMauve alignment, and phylogenetic tree) strongly suggest that the bacteriophage VPMCC5 might be a new genus in the family of Zobellviridae. A distinguishing feature of this bacteriophage among the other reported Vibrio-infecting bacteriophages is the presence of putative alginate lyase family protein-coding open reading frame. The bacteriophage was found to be surviving at pH 3-9 and in a wide range of temperatures (4-45 ᵒC). In liquid culture inhibition, the bacteriophage could completely lyse the host bacteria after 3 h. This bacteriophage might be used as a biocontrol agent in the extreme environment of shrimp culture.


Asunto(s)
Bacteriófagos , Vibrio , Antibacterianos , Composición de Base , Genoma Viral , Filogenia , Vibrio/genética
12.
Front Microbiol ; 13: 794503, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35607594

RESUMEN

The present study has been aimed at evaluating the antiobesity, antihyperglycemic, and antidepressive potentials of Asparagus racemosus starter-based rice fermented foods. High-throughput NGS technology has revealed a number of bacterial genera in the prepared fermented rice, such as Lactobacillus (29.44%), Brevundimonas (16.21%), Stenotrophomonas (6.18%), Pseudomonas (3.11%), Bacillus (2.88%), and others (<2%). Eight-week administration of rice fermented food has increased food intake, whole-body weight, organ weight, different fat masses, serum lipid profiles, and histology of liver and adipose tissues in HFD-induced obese mice. In addition, upregulation of fatty acid oxidation and downregulation of adipocytogenesis- and lypogenesis-related genes along with the expression of their regulatory nuclear factors such as PPARα, PPARγ, PPARδ, and SREBP-1c have also been noted. Moreover, fermented food decreases fasting blood glucose level and improves glucose and insulin tolerance as well as the expression of GLUT4 receptor. Antiobesity and antihyperglycemic effects are also supported by the changes in insulin, leptin, and adiponectin hormone levels. The real-time polymerase chain reaction (RT-PCR) and denaturing gradient gel electrophoresis (DGGE) analyses have clearly demonstrated the intense colonization of Bacteroides, Lactobacillus, and Bifidobacterium, as well as the suppressed growth rate of γ- and δ-Proteobacteria and Firmicutes in the gut after fermented food intake. In the intestine, the latter group of microorganisms possibly modulate short-chain fatty acid (SCFA) levels such as acetate, butyrate, and propionate more than twofold. The impairment of memory-learning and anxiety-like obesity-associated cognitive phenotypes is mitigated significantly (p < 0.01) by fermented food as well. Thus, the formulated fermented food could be used as a natural therapeutic to alleviate obesity and its associated psychological and pathophysiological ailments.

13.
J Cancer Res Ther ; 18(1): 49-54, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35381761

RESUMEN

Background: Head-and-neck squamous cell carcinomas (HNSCCs) are one of the most common malignancies worldwide. Emerging evidence reveals that tumor-infiltrating lymphocytes (TIL) provide valuable prognostic information in various malignancies, including HNSCC. Aims and Objectives: The present study aimed to evaluate a simple yet accurate method of counting TILs in HNSCCs. It was also done to determine if there is any correlation between different clinicopathological parameters of HNSCC and TIL counts. Materials and Methods: A.retrospective institutional-based, observational study was undertaken for 1 year. Patients with histologically proven HNSCCs were included. All clinicopathological parameters were noted, and evaluation of TIL was meticulously done both in the stromal and intratumoral regions for each case. Standard statistical methods were employed for data analysis. Results: The present study included 81 patients, among which 51 (63%) were male and the rest (30, 37%) were female. The mean age of the patients was 55.3 ± 10.5 years. Most tumors were located in the oral cavity (73, 90.1%). The most common histologic type was moderately differentiated (MD) squamous cell carcinoma (SCC) (50 cases, 61.7%). Stromal TIL score was high in 45 cases (55.6%). In 69 cases (85.2%), the intratumoral TIL level was low. A statistically significant correlation was found between TIL levels (both stromal and intratumoral TIL) and tumor differentiation, pT stage, and lymphovascular invasion. The correlation between intratumoral TIL level, age of patients, and pN stage was also statistically significant. Conclusion: TIL evaluation is an inexpensive, simple, and reproducible method, which furnishes relevant prognostic data. It has the potential for consideration of its inclusion in routine histopathological reports of HNSCCs.


Asunto(s)
Neoplasias de Cabeza y Cuello , Linfocitos Infiltrantes de Tumor , Adulto , Anciano , Femenino , Neoplasias de Cabeza y Cuello/diagnóstico , Neoplasias de Cabeza y Cuello/metabolismo , Humanos , Linfocitos Infiltrantes de Tumor/metabolismo , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Carcinoma de Células Escamosas de Cabeza y Cuello/metabolismo
14.
Indian J Pathol Microbiol ; 65(2): 262-267, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35435357

RESUMEN

Background: : The dismal survival of one of the commonest malignancies of the world, head neck squamous cell carcinomas (HNSCC), has prompted researchers to probe into its various characteristics, especially those which reflect the outcome. Over the years, even though epidermal growth factor receptor (EGFR) and tumor-infiltrating lymphocytes (TIL) have emerged as useful biomarkers of the disease, the two parameters have rarely been considered in conjunction. Aims and Objectives: The study aimed to assess if there is any correlation between TIL levels (both stromal and intratumoral) and site, grade, stage, and EGFR score of HNSCC. Materials and Methods: A retrospective observational study was conducted in which histopathologically confirmed cases of HNSCC were included. The site of tumor, grade, stage, stromal and intratumoral TIL levels, and EGFR score were noted for each case. The data were analyzed using standard statistical tests. Results: The study population consisted of 122 patients with a mean age of 53.8 ± 9.2 years. The oral cavity was the commonest site of tumor (109 cases, 89.3%). Most cases were moderately differentiated (75, 61.5%). Pathological staging showed 66 cases (54%) to be in pT1, and 92 cases (75.4%) to be in pN0. In 68 cases (55.7%), stromal TIL level was high, and intratumoral TIL was low in 102 cases (83.6%). A statistically significant correlation was found between TIL levels and site, grade, pathological stage, and EGFR score of HNSCC. Conclusion: This pioneering study is unique in its exploration of the correlation between two significant biomarkers of HNSCC - TIL and EGFR score.


Asunto(s)
Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Adulto , Receptores ErbB/genética , Neoplasias de Cabeza y Cuello/diagnóstico , Humanos , Linfocitos Infiltrantes de Tumor , Persona de Mediana Edad , Carcinoma de Células Escamosas de Cabeza y Cuello
15.
J Alzheimers Dis ; 84(4): 1747-1762, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34744082

RESUMEN

BACKGROUND: Doublecortin (DCX), a microtubule associated protein, has emerged as a central biomarker of hippocampal neurogenesis. However, molecular mechanisms by which DCX is regulated are poorly understood. OBJECTIVE: Since sleep is involved with the acquisition of memory and oleamide or 9-Octadecenamide (OCT) is a sleep-inducing supplement in human, we examined whether OCT could upregulate DCX in hippocampal progenitor cells (HPCs). METHODS: We employed real-time PCR, western blot, immunostaining, chromatin immunoprecipitation, lentiviral transduction in HPCs, and the calcium influx assay. RESULTS: OCT directly upregulated the transcription of Dcx in HPCs via activation of peroxisome proliferator-activated receptor α (PPARα), a lipid-lowering transcription factor. We observed that, HPCs of Ppara-null mice displayed significant impairment in DCX expression and neuronal differentiation as compared to that of wild-type mice. Interestingly, treatment with OCT stimulated the differentiation process of HPCs in wild-type, but not Ppara-null mice. Reconstruction of PPARα in mouse Ppara-null HPCs restored the expression of DCX, which was further stimulated with OCT treatment. In contrast, a dominant-negative mutant of PPARα significantly attenuated the stimulatory effect of OCT on DCX expression and suppressed neuronal differentiation of human neural progenitor cells. Furthermore, RNA microarray, STRING, chromatin immunoprecipitation, site-directed mutagenesis, and promoter reporter assay have identified DCX as a new target of PPARα. CONCLUSION: These results indicate that OCT, a sleep supplement, directly controls the expression of DCX and suggest that OCT may be repurposed for stimulating the hippocampal neurogenesis.


Asunto(s)
Proteínas de Dominio Doblecortina , Aditivos Alimentarios/administración & dosificación , Ácidos Oléicos/administración & dosificación , PPAR alfa/metabolismo , Regiones Promotoras Genéticas , Fármacos Inductores del Sueño/farmacología , Regulación hacia Arriba , Animales , Diferenciación Celular/efectos de los fármacos , Regulación de la Expresión Génica , Hipocampo/metabolismo , Humanos , Ratones , Ratones Noqueados , Sueño/efectos de los fármacos , Factores de Transcripción/genética
16.
J Alzheimers Dis Rep ; 5(1): 647-661, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34632302

RESUMEN

BACKGROUND: Neuroinflammation is a recognized aspect of Alzheimer's disease (AD) and other neurological illnesses. Interleukin 1 receptor antagonist (IL-1Ra) is an anti-inflammatory molecule, which inhibits inflammatory molecules in different cells including brain cells. However, mechanisms for upregulating IL-1Ra in brain cells are poorly understood. OBJECTIVE: Since aspirin is a widely available pain reliever that shows promise beyond its known pain-relieving capacity, we examined whether aspirin could upregulate the IL-1Ra in the brain. METHODS: We employed PCR, real-time PCR, western blot, immunostaining, chromatin immunoprecipitation (ChIP), and lentiviral transduction in glial cells. 5xFAD mice, an animal model of AD, were treated with aspirin orally via gavage. RESULTS: Aspirin increased the expression of IL-1Ra mRNA and protein in primary mouse astrocytes and mouse BV-2 microglial cells. While investigating the mechanism, we found that the IL-1Ra gene promoter harbors peroxisome proliferator response element (PPRE) and that aspirin upregulated IL-1Ra in astrocytes isolated from peroxisome proliferator-activated receptor-beta knockout (PPARß-/-), but not PPARα-/-, mice. Moreover, we observed that aspirin bound to tyrosine 314 residue of PPARα to stimulate IL-1Ra and that aspirin treatment also increased the recruitment of PPARα to the IL-1Ra promoter. Accordingly, aspirin increased IL-1Ra in vivo in the brain of wild type and PPARß-/-, but not in PPARα-/- mice. Similarly, aspirin treatment also increased astroglial and microglial IL-1Ra in the cortex of 5xFAD, but not 5xFAD/PPARα-/- mice. CONCLUSION: Aspirin may reduce the severity of different neurological conditions by upregulating IL-1Ra and reducing the inflammation.

17.
J Food Biochem ; 44(11): e13448, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-32881000

RESUMEN

In this present investigation, we have extracted and characterized the Tapra fish oil as well as applied it to evaluate anti-obesity potentiality. The Tapra fish oil had 1.14 ± 0.10 mg KOH/g of acid value, 129.8 ± 5.09 mg KOH/g of saponification number, 2.67 ± 0.67 mEq/kg of peroxide value, 121.9 ± 2.14 mg of iodine value, and 17.67 ± 1.45 totox value. Gas Chromatography-Mass Spectrometric analysis clearly revealed the presence of nine different fatty acids. When the fish oil was applied to high-fat diet-induced obese mice, it showed significant reduction of body weight, Body Mass Index, and serum lipid profiles compared to the high-fat diet-induced obese mice. The levels of leptin and TNF-α were moderately reduced in fish oil treated high-fat diet-induced obese mice than control obese mice. In conclusion, the Tapra fish oil was enriched with essential fatty acids and it could be used as an antiobese food supplement. PRACTICAL APPLICATIONS: Considering the adverse effects of drugs used for the treatment of obesity, there is always a need to find out the alternatives. While the anti-obesity potentialities of different sea fish oil have been documented, the same for the Tapra fish (Opisthopterus tardoore) oil has not been studied at all. The extracted Tapra fish oil was found good in quality. Administration of fish oil in the mice exhibited anti-obesity effect in terms of lowering body weight, Body Mass Index, and serum lipid profiles, leptin, and TNF-α in mice model. These findings are fostering new therapeutic approaches to obesity treatment.


Asunto(s)
Dieta Alta en Grasa , Aceites de Pescado , Obesidad , Animales , Peso Corporal , Peces , Leptina , Ratones , Obesidad/tratamiento farmacológico
18.
iScience ; 23(3): 100937, 2020 Mar 27.
Artículo en Inglés | MEDLINE | ID: mdl-32179470

RESUMEN

Nasopharyngeal carcinoma (NPC) is a rare malignancy in most parts of the world, but is endemic in some ethnic groups. The association of NPC with the Epstein-Barr virus (EBV) is firmly established; however, the mechanism is still unclear. TLR9 is well known for its essential role in viral pathogen recognition and activation of innate immunity. Here, we report a set of TLR9 polymorphisms in the TIR-2 domain of the TLR9 protein collected from the EBV-infected NPC samples from northeast Indian populations sharing the aforesaid ethnicity. The occurrence of mutations is significantly high in these samples as we found a p value of <0.0001 at a significance level of 0.05. These might play an important role for the lack of function of TLR9 and thus for the higher occurrence of EBV-mediated NPC in such ethnic groups.

19.
J Neurochem ; 151(1): 50-63, 2019 10.
Artículo en Inglés | MEDLINE | ID: mdl-31273781

RESUMEN

Neuroinflammation is being recognized as a hallmark of different neurodegenerative disorders, including Alzheimer's disease. Suppressor of cytokine signaling 3 (SOCS3) is an anti-inflammatory molecule, which is known to inhibit cytokine signaling and inflammatory gene expression in different cells. However, the pathways by which SOCS3 could be up-regulated in brain cells are poorly understood. Aspirin is a widely available pain reliever that is showing promise beyond its known pain-relieving capacity. This study underlines the importance of aspirin in upregulating SOCS3 in astrocytes and microglia. Aspirin increased the expression of Socs3 mRNA and protein in mouse astrocytes and BV-2 microglial cells in both a time- and dose-dependent manner. While investigating the mechanism, we found that Socs3 gene promoter harbors peroxisome proliferator response element and that aspirin up-regulated SOCS3 in astrocytes isolated from PPARß (-/-), but not PPARα (-/-), mice. Accordingly, aspirin increased SOCS3 in vivo in the cortex of wild type and PPARß (-/-), but not PPARα (-/-), mice. Similarly, aspirin treatment increased astroglial and microglial SOCS3 in the cortex of FAD5X, but not FAD5X/PPARα (-/-), mice. Finally, recruitment of PPARα by aspirin to the proximal, but not distal, peroxisome proliferator response element of the Socs3 promoter suggests that aspirin increases the transcription of Socs3 gene via PPARα. This study describes a novel property of aspirin in elevating SOCS3 in glial cells via PPARα and suggests that aspirin may be further considered for therapeutic application in neuroinflammatory and neurodegenerative disorders.


Asunto(s)
Antiinflamatorios no Esteroideos/farmacología , Aspirina/farmacología , Neuroglía/efectos de los fármacos , PPAR alfa/metabolismo , Proteína 3 Supresora de la Señalización de Citocinas/metabolismo , Enfermedad de Alzheimer/metabolismo , Animales , Femenino , Masculino , Ratones , Ratones Endogámicos C57BL , Neuroglía/metabolismo , Transducción de Señal/efectos de los fármacos , Transducción de Señal/fisiología , Regulación hacia Arriba
20.
Scand J Immunol ; 90(4): e12796, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31145476

RESUMEN

Nasopharyngeal carcinoma (NPC) is one the most confusing and rare malignancy in most part of the world with significantly high occurrence in some populations of Southeast Asia, North Africa and Alaska. Apart from the dietary and environmental factors, NPC is well-associated with Epstein-Barr virus (EBV) infection in these ethnic groups. However, the internal molecular mechanism(s) for such association in specific populations is not known till date. Polymorphisms in the genes of histocompatibility locus antigens (HLA) are reported in NPC, but association of any particular polymorphism with ethnicity is not established yet. Here, we report a set of HLA polymorphisms in EBV-infected NPC samples from Northeast Indian population. These polymorphisms might play an important role for the lack of proper immune function against EBV infection and thus, eventually, for NPC generation in endemic populations like those of Northeast India.


Asunto(s)
Infecciones por Virus de Epstein-Barr/inmunología , Etnicidad , Genotipo , Antígenos HLA/genética , Herpesvirus Humano 4/fisiología , Carcinoma Nasofaríngeo/inmunología , Neoplasias Nasofaríngeas/inmunología , Sesgo , Infecciones por Virus de Epstein-Barr/epidemiología , Infecciones por Virus de Epstein-Barr/genética , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Histocompatibilidad/genética , Humanos , Inmunidad/genética , India/epidemiología , India/etnología , Carcinoma Nasofaríngeo/epidemiología , Carcinoma Nasofaríngeo/genética , Neoplasias Nasofaríngeas/epidemiología , Neoplasias Nasofaríngeas/genética , Polimorfismo Genético
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