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1.
Cell Mol Life Sci ; 76(17): 3311-3322, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31062072

RESUMO

Oxygen deprivation affects human health by modulating system as well as cellular physiology. Hypoxia generates reactive oxygen species (ROS), causes oxidative stress and affects female reproductive health by altering ovarian as well as oocyte physiology in mammals. Hypoxic conditions lead to several degenerative changes by inducing various cell death pathways like autophagy, apoptosis and necrosis in the follicle of mammalian ovary. The encircling somatic cell death interrupts supply of nutrients to the oocyte and nutrient deprivation may result in the generation of ROS. Increased level of ROS could induce granulosa cells as well as oocyte autophagy. Although autophagy removes damaged proteins and subcellular organelles to maintain the cell survival, irreparable damages could induce cell death within intra-follicular microenvironment. Hypoxia-induced autophagy is operated through 5' AMP activated protein kinase-mammalian target of rapamycin, endoplasmic reticulum stress/unfolded protein response and protein kinase C delta-c-junN terminal kinase 1 pathways in a wide variety of somatic cell types. Similar to somatic cells, we propose that hypoxia may induce granulosa cell as well as oocyte autophagy and it could be responsible at least in part for germ cell elimination from mammalian ovary. Hypoxia-mediated germ cell depletion may cause several reproductive impairments including early menopause in mammals.


Assuntos
Autofagia , Células da Granulosa/citologia , Animais , Proteína Beclina-1/metabolismo , Hipóxia Celular , Feminino , Células da Granulosa/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Oócitos/citologia , Oócitos/metabolismo , Espécies Reativas de Oxigênio/metabolismo
2.
J Cell Physiol ; 234(6): 8019-8027, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30341907

RESUMO

The maximum number of germ cells is present during the fetal life in mammals. Follicular atresia results in rapid depletion of germ cells from the cohort of the ovary. At the time of puberty, only a few hundred (<1%) germ cells are either culminated into oocytes or further get eliminated during the reproductive life. Although apoptosis plays a major role, necrosis as well as necroptosis, might also be involved in germ cell elimination from the mammalian ovary. Both necrosis and necroptosis show similar morphological features and are characterized by an increase in cell volume, cell membrane permeabilization, and rupture that lead to cellular demise. Necroptosis is initiated by tumor necrosis factor and operated through receptor interacting protein kinase as well as mixed lineage kinase domain-like protein. The acetylcholinesterase, cytokines, starvation, and oxidative stress play important roles in necroptosis-mediated granulosa cell death. The granulosa cell necroptosis directly or indirectly induces susceptibility toward necroptotic or apoptotic cell death in oocytes. Indeed, prevention of necrosis and necroptosis pathways using their specific inhibitors could enhance growth/differentiation factor-9 expression, improve survivability as well as the meiotic competency of oocytes, and prevent decline of reproductive potential in several mammalian species and early onset of menopause in women. This study updates the information and focuses on the possible involvement of necrosis and necroptosis in germ cell depletion from the mammalian ovary.


Assuntos
Necroptose/genética , Necrose/genética , Oócitos/crescimento & desenvolvimento , Ovário/crescimento & desenvolvimento , Animais , Apoptose/genética , Feminino , Células Germinativas/crescimento & desenvolvimento , Células Germinativas/metabolismo , Células da Granulosa/metabolismo , Humanos , Mamíferos , Oócitos/metabolismo , Ovário/metabolismo , Estresse Oxidativo/genética
3.
J Biomed Sci ; 26(1): 11, 2019 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-30665407

RESUMO

Stress is deeply rooted in the modern society due to limited resources and large competition to achieve the desired goal. Women are more frequently exposed to several stressors during their reproductive age that trigger generation of reactive oxygen species (ROS). Accumulation of ROS in the body causes oxidative stress (OS) and adversely affects ovarian functions. The increased OS triggers various cell death pathways in the ovary. Beside apoptosis and autophagy, OS trigger necroptosis in granulosa cell as well as in follicular oocyte. The OS could activate receptor interacting protein kinase-1(RIPK1), receptor interacting protein kinase-3 (RIPK3) and mixed lineage kinase domain-like protein (MLKL) to trigger necroptosis in mammalian ovary. The granulosa cell necroptosis may deprive follicular oocyte from nutrients, growth factors and survival factors. Under these conditions, oocyte becomes more susceptible towards OS-mediated necroptosis in the follicular oocytes. Induction of necroptosis in encircling granulosa cell and oocyte may lead to follicular atresia. Indeed, follicular atresia is one of the major events responsible for the elimination of majority of germ cells from cohort of ovary. Thus, the inhibition of necroptosis could prevent precautious germ cell depletion from ovary that may cause reproductive senescence and early menopause in several mammalian species including human.


Assuntos
Apoptose/fisiologia , Necrose/fisiopatologia , Ovário/fisiopatologia , Estresse Oxidativo/fisiologia , Espécies Reativas de Oxigênio/efeitos adversos , Estresse Fisiológico , Animais , Feminino , Humanos
4.
J Cell Physiol ; 233(8): 5530-5536, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29331044

RESUMO

In mammals, journey from metaphase-I (M-I) to metaphase-II (M-II) is important since oocyte extrude first polar body (PB-I) and gets converted into haploid gamete. The molecular and cellular changes associated with meiotic cell cycle progression from M-I to M-II stage and extrusion of PB-I remain ill understood. Several factors drive oocyte meiosis from M-I to M-II stage. The mitogen-activated protein kinase3/1 (MAPK3/1), signal molecules and Rho family GTPases act through various pathways to drive cell cycle progression from M-I to M-II stage. The down regulation of MOS/MEK/MAPK3/1 pathway results in the activation of anaphase-promoting complex/cyclosome (APC/C). The active APC/C destabilizes maturation promoting factor (MPF) and induces meiotic resumption. Several signal molecules such as, c-Jun N-terminal kinase (JNK2), SENP3, mitotic kinesin-like protein 2 (MKlp2), regulator of G-protein signaling (RGS2), Epsin2, polo-like kinase 1 (Plk1) are directly or indirectly involved in chromosomal segregation. Rho family GTPase is another enzyme that along with cell division cycle (Cdc42) to form actomyosin contractile ring required for chromosomal segregation. In the presence of origin recognition complex (ORC4), eccentrically localized haploid set of chromosomes trigger cortex differentiation and determine the division site for polar body formation. The actomyosin contractile activity at the site of division plane helps to form cytokinetic furrow that results in the formation and extrusion of PB-I. Indeed, oocyte journey from M-I to M-II stage is coordinated by several factors and pathways that enable oocyte to extrude PB-I. Quality of oocyte directly impact fertilization rate, early embryonic development, and reproductive outcome in mammals.


Assuntos
Mamíferos/fisiologia , Metáfase/fisiologia , Oócitos/fisiologia , Ciclossomo-Complexo Promotor de Anáfase/metabolismo , Animais , Ciclo Celular/fisiologia , Proteínas de Ciclo Celular/metabolismo , Segregação de Cromossomos/fisiologia , Cromossomos/fisiologia , GTP Fosfo-Hidrolases/metabolismo , Mamíferos/metabolismo , Fator Promotor de Maturação/metabolismo , Oócitos/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Transdução de Sinais/fisiologia , Quinase 1 Polo-Like
5.
J Cell Biochem ; 119(1): 123-129, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28574608

RESUMO

The oocyte quality remains as one of the major problems associated with poor in vitro fertilization (IVF) rate and assisted reproductive technology (ART) failure worldwide. The oocyte quality is dependent on its meiotic maturation that begins inside the follicular microenvironment and gets completed at the time of ovulation in most of the mammalian species. Follicular oocytes are arrested at diplotene stage of first meiotic prophase. The resumption of meiosis from diplotene arrest, progression through metaphase-I (M-I) and further arrest at metaphase-II (M-II) are important physiological requirements for the achievement of meiotic competency in mammalian oocytes. The achievement of meiotic competency is dependent upon cyclic stabilization/destabilization of maturation promoting factor (MPF). The mitogen-activated protein kinase3/1 (MAPK3/1) modulates stabilization/destabilization of MPF in oocyte by interacting either with signal molecules, transcription and post-transcription factors in cumulus cells or cytostatic factors (CSFs) in oocyte. MPF regulates meiotic cell cycle progression from diplotene arrest to M-II arrest and directly impacts oocyte quality. The MAPK3/1 activity is not reported during spontaneous meiotic resumption but its activity in cumulus cells is required for gonadotropin-induced oocyte meiotic resumption. Although high MAPK3/1 activity is required for the maintenance of M-II arrest in several mammalian species, its cross-talk with MPF remains to be elucidated. Further studies are required to find out the MAPK3/1 activity and its impact on MPF destabilization/stabilization during achievement of meiotic competency, an important period that decides oocyte quality and directly impacts ARTs outcome in several mammalian species including human. J. Cell. Biochem. 119: 123-129, 2018. © 2017 Wiley Periodicals, Inc.


Assuntos
Fator Promotor de Maturação/metabolismo , Meiose , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Animais , Humanos , Mamíferos , Fator Promotor de Maturação/fisiologia , Prófase Meiótica I , Metáfase , Proteína Quinase 1 Ativada por Mitógeno/fisiologia , Proteína Quinase 3 Ativada por Mitógeno/fisiologia , Oócitos/enzimologia
6.
Growth Factors ; 36(1-2): 41-47, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29842809

RESUMO

In mammals, preovulatory oocytes are encircled by several layers of granulosa cells (GCs) in follicular microenvironment. These follicular oocytes are arrested at diplotene arrest due to high level of cyclic nucleotides from encircling GCs. Pituitary gonadotropin acts at the level of encircling GCs and increases adenosine 3',5'-cyclic monophosphate (cAMP) and guanosine 3',5'-cyclic monophosphate (cGMP) and activates mitogen-activated protein kinase 3/1 (MAPK3/1) signaling pathway. The MAPK3/1 disrupts the gap junctions between encircling GCs and oocyte. The disruption of gap junctions interrupts the transfer of cyclic nucleotides to the oocyte that results a drop in intraoocyte cAMP level. A transient decrease in oocyte cAMP level triggers maturation promoting factor (MPF) destabilization. The destabilized MPF finally triggers meiotic resumption from diplotene arrest in follicular oocyte. Thus, MAPK3/1 from GCs origin plays important role in gonadotropin-mediated meiotic resumption from diplotene arrest in follicular oocyte of mammals.


Assuntos
Células da Granulosa/enzimologia , Meiose/fisiologia , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Oócitos/fisiologia , Animais , Feminino , Gonadotropinas Hipofisárias/fisiologia , Nucleotídeos Cíclicos/metabolismo
7.
J Biomed Sci ; 25(1): 36, 2018 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-29681242

RESUMO

Mammalian ovary contains millions of germ cells during embryonic life but only few of them are culminated into oocytes that achieve meiotic competency just prior to ovulation. The majority of germ cells are depleted from ovary through several pathways. Follicular atresia is one of the major events that eliminate germ cells from ovary by engaging apoptotic as well as non-apoptotic pathways of programmed cell death. Apoptosis is characterized by several morphological changes that include cell shrinkage, nuclear condensation, membrane blebbing and cytoplasmic fragmentation by both mitochondria- as well as death receptor-mediated pathways in encircling granulosa cells and oocyte. Although necroapoptosis have been implicated in germ cell depletion, autophagy seems to play an active role in the life and death decisions of ovarian follicles. Autophagy is morphologically characterized by intracellular reorganization of membranes and increased number of autophagic vesicles that engulf bulk cytoplasm as well as organelles. Autophagy begins with the encapsulation of cytoplasmic constituents in a membrane sac known as autophagosomes. The autophagic vesicles are then destroyed by the lysosomal enzymes such as hydrolases that results in follicular atresia. It seems that apoptosis as well as autophagy could play active roles in germ cells depletion from ovary. Hence, it is important to prevent these two pathways in order to retain the germ cells in ovary of several mammalian species that are either threatened or at the verge of extinction. The involvement of apoptosis and autophagy in germ cell depletion from mammalian ovary is reviewed and possible pathways have been proposed.


Assuntos
Apoptose , Autofagia , Células Germinativas/fisiologia , Mamíferos/fisiologia , Ovário/fisiologia , Animais , Feminino , Atresia Folicular/fisiologia , Folículo Ovariano/fisiologia
8.
Arch Pharm (Weinheim) ; 349(3): 193-201, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26773437

RESUMO

A series of benzimidazole-based quinazoline derivatives with different substitutions of primary and secondary amines at the C2 position (1-12) were evaluated for their Aurora kinase inhibitory activities. All compounds except for 3 and 6 showed good activity against Aurora kinase inhibitors, with IC50 values in the range of 0.035-0.532 µM. The ligand efficiency (LE) of the compounds with Aurora A kinase was also determined. The structure-activity relationship and the quantitative structure-activity relationship revealed that the Aurora inhibitory activities of these derivatives primarily depend on the different substitutions of the amine present at the C2 position of the quinazoline core. Molecular docking studies in the active binding site also provided theoretical support for the experimental biological data acquired. The current study identifies a novel class of Aurora kinase inhibitors, which can further be used for the treatment of cancer.


Assuntos
Aurora Quinases/antagonistas & inibidores , Benzimidazóis/química , Quinazolinas/química , Aurora Quinase A/antagonistas & inibidores , Aurora Quinase A/química , Aurora Quinases/química , Benzimidazóis/síntese química , Simulação de Acoplamento Molecular , Relação Quantitativa Estrutura-Atividade , Quinazolinas/síntese química
9.
Indian J Med Res ; 142(2): 165-74, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26354213

RESUMO

BACKGROUND & OBJECTIVES: Acute myocardial infarction (AMI) is characterized by irreparable and irreversible loss of cardiac myocytes. Despite major advances in the management of AMI, a large number of patients are left with reduced left ventricular ejection fraction (LVEF), which is a major determinant of short and long term morbidity and mortality. A review of 33 randomized control trials has shown varying improvement in left ventricular (LV) function in patients receiving stem cells compared to standard medical therapy. Most trials had small sample size and were underpowered. This phase III prospective, open labelled, randomized multicenteric trial was undertaken to evaluate the efficacy in improving the LVEF over a period of six months, after injecting a predefined dose of 5-10 × 10 [8] autologous mononuclear cells (MNC) by intra-coronary route, in patients, one to three weeks post ST elevation AMI, in addition to the standard medical therapy. METHODS: In this phase III prospective, multicentric trial 250 patients with AMI were included and randomized into stem cell therapy (SCT) and non SCT groups. All patients were followed up for six months. Patients with AMI having left ventricular ejection fraction (LVEF) of 20-50 per cent were included and were randomized to receive intracoronary stem cell infusion after successfully completing percutaneous coronary intervention (PCI). RESULTS: On intention-to-treat analysis the infusion of MNCs had no positive impact on LVEF improvement of ≥ 5 per cent. The improvement in LVEF after six months was 5.17 ± 8.90 per cent in non SCT group and 4.82 ± 10.32 per cent in SCT group. The adverse effects were comparable in both the groups. On post hoc analysis it was noted that the cell dose had a positive impact when infused in the dose of ≥ 5 X 10 [8] (n=71). This benefit was noted upto three weeks post AMI. There were 38 trial deviates in the SCT group which was a limitation of the study. INTERPRETATION & CONCLUSIONS: Infusion of stem cells was found to have no benefit in ST elevation AMI. However, the procedure was safe. A possible benefit was seen when the predefined cell dose was administered which was noted upto three weeks post AMI, but this was not significant and needs confirmation by larger trials.


Assuntos
Infarto do Miocárdio/terapia , Transplante de Células-Tronco , Células-Tronco/citologia , Disfunção Ventricular Esquerda/terapia , Idoso , Medula Óssea , Ecocardiografia , Feminino , Humanos , Índia , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/patologia , Resultado do Tratamento , Disfunção Ventricular Esquerda/patologia
10.
J Food Sci Technol ; 52(4): 1857-71, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25829567

RESUMO

There is currently much interest in phytochemicals as bioactive molecules of food. Functional foods are an emerging field in food science due to their increasing popularity among health conscious consumers. Flaxseed is cultivated in many parts of world for fiber, oil as well as for medicinal purposes and also as nutritional product. In this review, nutrients, anti-nutrients, functional properties, processing, metabolism and health benefits of bioactive molecules viz., essential fatty acids, lignans and dietary fiber of flaxseed are discussed.

11.
J Food Sci Technol ; 52(12): 7783-94, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26604351

RESUMO

In present study, influence of grinding (hammer and pin mills) and moisture content (range: 6.4-13.6 % dry basis) on the quality traits of coriander powder were investigated. These include grinding parameters, colour parameters, specific heat, thermal conductivity, thermal diffusivity, glass transition temperature, essential oil, total phenolic content, total flavonoid content and DPPH scavenging (%) of coriander powder. For coriander seed, the geometric properties such as major, medium, minor dimensions, geometric mean diameter, arithmetic mean diameter, sphericity, surface area and volume of coriander seeds increased significantly with increasing moisture (6.4-13.6 % db). For coriander powder, the grinding parameters such as average particle size, volume surface mean diameter and volume mean diameter increased significantly with increasing moisture (6.4-13.6 % db). With the grinding method, the colour attributes of coriander powder such as L-value, a-value, b-value, hue angle and browning index varied significantly. It was observed that the specific heat followed second order polynomial relationship with temperature and moisture whereas thermal conductivity varied linearly with temperature and moisture content. The variation of glass transition temperature with moisture can be best represented in quadratic manner. Total flavonoid content (mg QE/g crude seed extract) and DPPH scavenging % activity of coriander powder is significantly affected by grinding methods. A lower value of specific heat was observed for hammer ground coriander powder as compared to pin mill ground coriander powder. The thermal conductivity of hammer mill ground coriander powder was higher as compared to pin mill ground coriander. It was observed that hammer mill yields more fine coriander powder in comparison to pin mill. The browning index was more in hammer mill ground coriander powder.

12.
Stroke ; 45(12): 3618-24, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25378424

RESUMO

BACKGROUND AND PURPOSE: Pilot studies have suggested benefit from intravenous administration of bone marrow mononuclear stem cells (BMSCs) in stroke. We explored the efficacy and safety of autologous BMSCs in subacute ischemic stroke. METHODS: This was a phase II, multicenter, parallel group, randomized trial with blinded outcome assessment that included 120 patients. Patients with subacute ischemic stroke were randomly assigned to the arm that received intravenous infusion of autologous BMSCs or to control arm. Coprimary clinical efficacy outcomes were Barthel Index score and modified Rankin scale at day 180. Secondary outcomes were change in infarct volume, National Institute of Health Stroke Scale (NIHSS) at day 90 and 180. Main safety outcomes were adverse events, any new area of (18)fluorodeoxyglucose positron emission tomography uptake in any body part over 365 days. RESULTS: Fifty-eight patients received a mean of 280.75 million BMSCs at median of 18.5 days after stroke onset. There was no significant difference between BMSCs arm and control arm in the Barthel Index score (63.1 versus 63.6; P=0.92), modified Rankin scale shift analysis (P=0.53) or score >3 (47.5% versus 49.2%; P=0.85), NIHSS score (6.3 versus 7.0; P=0.53), change in infarct volume (-11.1 versus -7.36; P=0.63) at day 180. Adverse events were also similar in the 2 arms, and no patient showed any new area of (18)fluorodeoxyglucose uptake. CONCLUSIONS: With the methods used, results of this hitherto first randomized controlled trial indicate that intravenous infusion of BMSCs is safe, but there is no beneficial effect of treatment on stroke outcome. CLINICAL TRIAL REGISTRATION: URLs: http://ctri.nic.in/Clinicaltrials and http://www.clinicaltrials.gov. Unique identifiers: CTRI-ROVCTRI/2008/091/0004 and NCT0150177.


Assuntos
Transplante de Medula Óssea/métodos , Transplante de Células-Tronco Hematopoéticas/métodos , Acidente Vascular Cerebral/cirurgia , Idoso , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Recuperação de Função Fisiológica , Acidente Vascular Cerebral/patologia
13.
Bioorg Med Chem Lett ; 24(2): 624-9, 2014 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-24360999

RESUMO

By combining the structural features of quinazoline and benzimidazole, new hybrid regioisomeric molecules with substituted primary amines have been synthesized. Evaluation of these molecules over 60 cancer cell line panel has identified three molecules as most potent anticancer agents. Compound 10 showed ten and eleven folds more activity than respective quinazoline and benzimidazole class of compounds with GI50 value of 1.64 µM. Compound 11 (GI50 value of 0.81 µM) showed almost twenty and twenty-two fold more activity than quinazoline and benzimidazole analogue, respectively while compound 12 (GI50 value of 4.52 µM) has four fold more activity than quinazoline and benzimidazole analogue. In vitro evaluation of compound 11 exhibited remarkable anticancer activity towards colon cancer cell lines and prostate cancer cell lines at five dose concentrations with GI50 values of 0.34 and 0.31 µM, respectively.


Assuntos
Antineoplásicos/síntese química , Benzimidazóis/síntese química , Quinazolinas/síntese química , Antineoplásicos/farmacologia , Benzimidazóis/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais/métodos , Humanos , Quinazolinas/farmacologia , Relação Estrutura-Atividade
14.
J Food Sci Technol ; 51(7): 1294-301, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24966422

RESUMO

The effect of hot water blanching treatment on thin layer drying kinetics of aonla shreds was studied at drying air temperatures of 50, 55 and 60 °C with the air velocity of 1.2 m/s. The drying time decreased with the increase in air temperature and blanching. The drying process was observed in falling rate. Drying after blanching reduced the vitamin C content of aonla shreds by 69.36% whereas it decreased by 27.78% in unblanched shreds. Eight commonly used mathematical models were evaluated to predict the drying behavior of aonla shreds. The Midilli model described the drying behaviour of unblanched aonla shreds at all temperatures better than other models whereas two-term model described the drying kinetics of blanched aonla shreds satisfactorily. The effective diffusivities of the unblanched and blanched aonla shreds were determined using Fick's law of diffusion. The activation energy was found to be 47.21 kJ/mol for unblanched and 43.98 kJ/mol for blanched aonla shreds.

15.
JGH Open ; 8(1): e13033, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38283070

RESUMO

Sarcopenia is a condition marked by progressive loss of skeletal muscle mass and function while frailty is a multidimensional concept characterized by diminished physiological reserve and increased vulnerability to stressors. Both of these were previously considered as related to aging and shown to impact the quality of life and carry prognostic significance. Emerging data show that both sarcopenia and frailty carry similar relevance in chronic illness. Inflammatory bowel disease (IBD) is characterized by chronic inflammation of the gastrointestinal tract and malnourishment, both of which contribute to the development of sarcopenia by increasing protein breakdown and reducing protein synthesis. The coexistence of frailty further compounds the clinical complexity of IBD patients. Published evidence suggests a bidirectional association with IBD contributing to muscle wasting, while the resultant sarcopenia and frailty could further exacerbate the disease course. Sarcopenia and frailty are independently associated with adverse outcomes, including hospitalizations, increased surgical interventions, and surgical complications. As therapeutic strategies for IBD evolve, understanding the nuanced relationship between inflammatory bowel disease, sarcopenia, and frailty is crucial for devising holistic management. Comprehensive care should encompass not only disease-modifying therapies but also interventions targeting frailty and sarcopenia, as they have been shown to have a significant impact not only on the disease course but also on the quality of life. Future research could focus on further elucidating underlying mechanisms, simple screening strategies, and developing targeted interventions to improve the overall quality of life for individuals grappling with the complex interplay of IBD, sarcopenia, and frailty.

16.
Am J Reprod Immunol ; 91(2): e13825, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38389407

RESUMO

BACKGROUND: To achieve oocyte competence for successful fertilization, bidirectional communication between oocyte and granulosa cells is crucial. The acquisition of meiotic competency in oocyte is facilitated by various regulatory genes however, expression pattern of these genes is not well documented during meiotic transition from Metaphase-I to Metaphase-II stage. Therefore, the present research analyzed the expression pattern of regulatory genes that are involved in the transition from M-I to M-II stages in rat oocyte. METHODS: The analysis of the data was conducted by applying an array of bioinformatic tools. The investigation of gene group interactions was carried out by employing the STRING database, which relies on co-expression information. The gene ontology (GO) analysis was performed utilizing the comparative GO database. Functional annotation for GO and pathway enrichment analysis were performed for genes involved in networking. The GO obtained through computational simulations was subsequently validated using quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis. RESULTS: The findings of our study suggest that there is a distinct gene expression pattern in both the oocyte and granulosa cells. This pattern indicates that oocyte-secreted factors, such as BMP15 and GDF9, play a crucial role in regulating the progression of the meiotic cell cycle from the M-I to M-II stages. We have also examined the level of mRNA expression of genes including CYP11A1, CYP19A1, and STAR, which are crucial for the steroidogenesis. CONCLUSIONS: It is fascinating to observe that the oscillatory pattern of specific key genes may hold significance in the process of in vitro oocyte maturation, specifically during the transition from the M-I to M-II stage. It might be useful for determining biomarker genes and potential pathways that play a role in attaining oocyte competency, thereby aiding in the assessment of oocyte quality for the purpose of achieving successful fertilization.


Assuntos
Oócitos , Ovário , Feminino , Animais , Ratos , Oócitos/fisiologia , Células da Granulosa/metabolismo
17.
Eur J Gastroenterol Hepatol ; 36(5): 513-519, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38407895

RESUMO

BACKGROUND: The relationship of inflammatory bowel disease (IBD) with osteonecrosis or avascular necrosis (AVN) is uncertain. METHODS: Systematic review to estimate the frequency of osteonecrosis in IBD was performed. Electronic databases were searched on 12 December 2022 to identify relevant studies. We planned to estimate the pooled prevalence of AVN in IBD, the risk in IBD when compared to the healthy population (without any chronic disease), and the impact of steroid use on osteonecrosis (IBD with and without steroid use). The risk of Bias was assessed with the Joanna Briggs Institute appraisal tool. RESULTS: Fifteen studies including 105 154 individuals were included. The pooled rate AVN was 10.39 per 1000 patients (95% confidence interval, 4.44-24.11, I 2  = 97%). Subgroup analysis suggested that the prevalence was lower in larger studies (>1000 participants) at 3.10, 1.07; 8.98, I 2  = 98% versus 21.03, 8.69; 50.01, I 2  = 83%. The use of steroids did not seem to increase the risk of osteonecrosis in the included studies (pooled odds ratio: 1.88, 0.55-6.41, I 2  = 39%). The systematic review was limited by the absence of comparison with the control population free of chronic disease. CONCLUSION: IBD may be associated with a risk of osteonecrosis. Future studies should assess the risk in comparison to the healthy population and the impact of disease activity and IBD therapies on the risk.


Assuntos
Doenças Inflamatórias Intestinais , Osteonecrose , Humanos , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/epidemiologia , Osteonecrose/epidemiologia , Osteonecrose/complicações , Nível de Saúde , Esteroides , Doença Crônica
18.
Bioorg Med Chem Lett ; 23(11): 3288-94, 2013 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-23611732

RESUMO

A series of novel regioisomeric hybrids of quinazoline/benzimidazole viz. (3-allyl-2-methyl-3H-benzimidazol-5-yl)-(2-substituted-quinazolin-4-yl)-amine and (1-allyl-2-methyl-1H-benzimidazol-5-yl)-(2-substituted-quinazolin-4-yl)-amine of biological interest were synthesized. All the synthesized compounds were well characterized by (1)H and (13)C NMR as well as mass spectroscopy. The newly synthesized compounds were screened for in vitro antitumor activities against 60 tumor cell lines panel assay. A significant inhibition for cancer cells were observed with compound 9 and also more active against known drug 5-fluorouracil (5-FU) in some tumor cell lines. Compound 9 displayed appreciable anticancer activity against leukemia, colon, melanoma, renal and breast cancer cell lines.


Assuntos
Antineoplásicos/síntese química , Benzimidazóis/química , Quinazolinas/química , Antineoplásicos/química , Antineoplásicos/toxicidade , Sítios de Ligação , Domínio Catalítico , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cristalografia por Raios X , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Conformação Molecular , Simulação de Acoplamento Molecular , Receptores Nucleares Órfãos/química , Receptores Nucleares Órfãos/metabolismo , Relação Estrutura-Atividade
19.
Polymers (Basel) ; 15(2)2023 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-36679283

RESUMO

The substantial fluorescence (FL) capabilities, exceptional photophysical qualities, and long-term colloidal stability of quantum dots (QDs) have aroused a lot of interest in recent years. QDs have strong and wide optical absorption, good chemical stability, quick transfer characteristics, and facile customization. Adding polymeric materials to QDs improves their effectiveness. QDs/polymer hybrids have implications in sensors, photonics, transistors, pharmaceutical transport, and other domains. There are a great number of review articles available online discussing the creation of CDs and their many uses. There are certain review papers that can be found online that describe the creation of composites as well as their many different uses. For QDs/polymer hybrids, the emission spectra were nearly equal to those of QDs, indicating that the optical characteristics of QDs were substantially preserved. They performed well as biochemical and biophysical detectors/sensors for a variety of targets because of their FL quenching efficacy. This article concludes by discussing the difficulties that still need to be overcome as well as the outlook for the future of QDs/polymer hybrids.

20.
JOP ; 13(2): 215-6, 2012 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-22406604

RESUMO

CONTEXT: Acute pancreatitis is most commonly linked to gallstone disease or alcohol consumption. Occasionally it can follow infectious disease. Malaria, especially Plasmodium falciparum infection, has been associated with acute pancreatitis. CASE REPORT: We present the case of a 17-year-old male who presented with a history of fever, abdominal pain and hypotension and revealing acute pancreatitis associated with infection by Plasmodium vivax. CONCLUSION: Acute pancreatitis can accompany malaria, including Plasmodium vivax.


Assuntos
Malária Vivax/complicações , Pancreatite/parasitologia , Plasmodium vivax/isolamento & purificação , Dor Abdominal/diagnóstico , Dor Abdominal/parasitologia , Doença Aguda , Adolescente , Evolução Fatal , Humanos , Malária Vivax/diagnóstico , Masculino , Pancreatite/diagnóstico
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