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71.
Wang Y Srinivasan K Siddiqui MR George SP Tomar A Khurana S 《The Journal of biological chemistry》2008,283(14):9454-9464
Apoptosis is a key regulator for the normal turnover of the intestinal mucosa, and abnormalities associated with this function have been linked to inflammatory bowel disease and colorectal cancer. Despite this, little is known about the mechanism(s) mediating intestinal epithelial cell apoptosis. Villin is an actin regulatory protein that is expressed in every cell of the intestinal epithelium as well as in exocrine glands associated with the gastrointestinal tract. In this study we demonstrate for the first time that villin is an epithelial cell-specific anti-apoptotic protein. Absence of villin predisposes mice to dextran sodium sulfate-induced colitis by promoting apoptosis. To better understand the cellular and molecular mechanisms of the anti-apoptotic function of villin, we overexpressed villin in the Madin-Darby canine kidney Tet-Off epithelial cell line to demonstrate that expression of villin protects cells from apoptosis by maintaining mitochondrial integrity thus inhibiting the activation of caspase-9 and caspase-3. Furthermore, we report that the anti-apoptotic response of villin depends on activation of the pro-survival proteins, phosphatidylinositol 3-kinase and phosphorylated Akt. The results of our studies shed new light on the previously unrecognized function of villin in the regulation of apoptosis in the gastrointestinal epithelium. 相似文献
72.
Alpha-lipoic acid (LA) has recently been reported to afford protective effects in neurodegenerative disorders. However, the
mechanisms underlying LA-mediated neuroprotection remain to be investigated. This study was undertaken to determine whether
LA treatment could increase endogenous antioxidants and phase 2 enzymes in cultured human neuroblastoma SH-SY5Y cells, and
whether such increased cellular defenses could afford protection against cytotoxicity induced by neurotoxicants. Incubation
of SH-SY5Y cells with micromolar concentrations of LA for 24 h resulted in a significant increase in the levels of reduced
glutathione (GSH) and NAD(P)H:quinone oxidoreductase 1 (NQQ1) in a concentration-dependent fashion. Treatment of the cells
with LA also led to an increased mRNA expression of γ-glutamylcysteine ligase catalytic subunit (GCLC) and NQO1. To determine
the protective effects of the LA-induced cellular defenses on neurotoxicant-elicitedl cell injury, SH-SY5Y cells were pretreated
with LA for 24 h and then exposed to acrolein, 4-hydroxy-2-nonenal (HNE), H2O2 and the peroxynitrite generator, 3-morpholinosydnonimine (SIN-1). We observed that LA pretreatment of SH-SY5Y cells led to
a marked protection against acrolein, HNE, H2O2 and SIN-1-mediated cytotoxicity, as detected by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium reduction assay. Taken
together, this study demonstrates for the first time that LA can induce GSH and NQO1 in cultured human neuroblastoma cells
and LA-upregulated cellular defenses are accompanied by a markedly increased resistance to cytotoxicity induced by various
neurotoxicants. The results of this study may have important implications for the neuroprotective effects of LA. 相似文献
73.
David J. Waters Seema S. Kengeri Beth Clever Julie A. Booth Aimee H Maras Deborah L. Schlittler Michael G. Hayek 《Aging cell》2009,8(6):752-755
To move closer to understanding the mechanistic underpinnings of sex differences in human longevity, we studied pet dogs to determine whether lifetime duration of ovary exposure was associated with exceptional longevity. This hypothesis was tested by collecting and analyzing lifetime medical histories, age at death, and cause of death for a cohort of canine ‘centenarians’– exceptionally long‐lived Rottweiler dogs that lived more than 30% longer than average life expectancy for the breed. Sex and lifetime ovary exposure in the oldest‐old Rottweilers (age at death, ≥ 13 years) were compared to a cohort of Rottweilers that had usual longevity (age at death, 8.0–10.8 years). Like women, female dogs were more likely than males to achieve exceptional longevity (OR, 95% CI = 2.0, 1.2–3.3; P = 0.006). However, removal of ovaries during the first 4 years of life erased the female survival advantage. In females, a strong positive association between ovaries and longevity persisted in multivariate analysis that considered other factors, such as height, body weight, and mother with exceptional longevity. A beneficial effect of ovaries on longevity in females could not be attributed to resistance against a particular disease or major cause of death. Our results document in dogs a female sex advantage for achieving exceptional longevity and show that lifetime ovary exposure, a factor not previously evaluated in women, is associated with exceptional longevity. This work introduces a conceptual framework for designing additional studies in pet dogs to define the ovary‐sensitive biological processes that promote healthy human longevity. 相似文献
74.
Barzkar Noora Homaei Ahmad Hemmati Roohullah Patel Seema 《Extremophiles : life under extreme conditions》2018,22(3):335-346
Extremophiles - Thermostable proteases are important in biotechnological and industrial sectors, due to their stability against denaturing agents and chemicals. The feature that gives them such... 相似文献
75.
Ashley K. Hagaman Seema Khadka Amber Wutich Shyam Lohani Brandon A. Kohrt 《Culture, medicine and psychiatry》2018,42(3):704-734
South Asia accounts for the majority of the world’s suicide deaths, but typical psychiatric or surveillance-based research approaches are limited due to incomplete vital surveillance. Despite rich anthropological scholarship in the region, such work has not been used to address public health gaps in surveillance and nor inform prevention programs designed based on surveillance data. Our goal was to leverage useful strategies from both public health and anthropological approaches to provide rich narrative reconstructions of suicide events, told by family members or loved ones of the deceased, to further contextualize the circumstances of suicide. Specifically, we sought to untangle socio-cultural and structural patterns in suicide cases to better inform systems-level surveillance strategies and salient community-level suicide prevention opportunities. Using a mixed-methods psychological autopsy approach for cross-cultural research (MPAC) in both urban and rural Nepal, 39 suicide deaths were examined. MPAC was used to document antecedent events, characteristics of persons completing suicide, and perceived drivers of each suicide. Patterns across suicide cases include (1) lack of education (72% of cases); (2) life stressors such as poverty (54%), violence (61.1%), migrant labor (33% of men), and family disputes often resulting in isolation or shame (56.4%); (3) family histories of suicidal behavior (62%), with the majority involving an immediate family member; (4) gender differences: female suicides were attributed to hopeless situations, such as spousal abuse, with high degrees of social stigma. In contrast, male suicides were most commonly associated with drinking and resulted from internalized stigma, such as financial failure or an inability to provide for their family; (5) justifications for suicide were attributions to ‘fate’ and personality characteristics such as ‘stubbornness’ and ‘egoism’; (5) power dynamics and available agency precluded some families from disputing the death as a suicide and also had implications for the condemnation or justification of particular suicides. Importantly, only 1 out of 3 men and 1 out of 6 women had any communication to family members about suicidal ideation prior to completion. Findings illustrate the importance of MPAC methods for capturing cultural narratives evoked after completed suicides, recognizing culturally salient warning signs, and identifying potential barriers to disclosure and justice seeking by families. These findings elucidate how suicide narratives are structured by family members and reveal public health opportunities for creating or supplementing mortality surveillance, intervening in higher risk populations such as survivors of suicide, and encouraging disclosure. 相似文献
76.
A dysmorphic male child of 8 months age presented with microphthalmia, micrognathia, hypertelorism, wide anterior fontanelles, large forehead, short neck, prominent ears, macrotestis and delayed developmental milestones. The patient presented with generalised seizures hydrocephalaus and Coarctation of aorta (Pre subclavian). He also had mild hypocalcaemia with normal renal function. Cytogenetic study revealed 18p(-) picture due to translocation between 14 p & 18q. Since the spectrum of clinical expression is similar to that is seen in 18p(-) syndrome it is suggested that not only whole of 18p but part of chromosome no. 18 proximal to 18 q 11.2 may also be involved in this phenotype. 相似文献
77.
E. S. Santhosh Kumar A. E. Shanavas Khan Seema G. Gopal 《Nordic Journal of Botany》2002,22(6):683-685
A new species of Andrographis, A. chendurunii is described and illustrated from Kerala, India. 相似文献
78.
Wormmeester Louktje; De Medina Fermin Sanchez; Kokke Freddy; Tse Chung-Ming; Khurana Seema; Bowser Joellyn; Cohen Michael E.; Donowitz Mark 《American journal of physiology. Cell physiology》1998,274(5):C1261
Intestinal neutral NaCl absorption, which is made up ofbrush-border (BB)Na+/H+exchange linked to BBCl/HCO3exchange, is up- and downregulated as part of digestion and diarrhealdiseases. Glucocorticoids stimulate ileal NaCl absorption and BBNa+/H+exchange. Intestinal BB contains twoNa+/H+exchanger isoforms, NHE2 and NHE3, but their relative roles in rabbitileal BBNa+/H+exchange has not been determined. A technique to separate the contribution of NHE2 and NHE3 to ileal BBNa+/H+exchange activity was standardized by using an amiloride-related compound, HOE-694. Under basal conditions, both NHE2 and NHE3 contribute ~50% to ilealNa+/H+exchange. Glucocorticoids (methylprednisolone) increase BBNa+/H+exchange (2.5 times) but increase only ileal NHE3 activity (4.1 times),without an effect on NHE2 activity. Thus ileal BBNa+/H+exchange in animals treated with glucocorticoids is 69% via NHE3. Aquantitative Western analysis for NHE3 was developed, using as aninternal standard a fusion protein of the COOH-terminal 85 amino acidsof NHE3 and maltose binding protein. Glucocorticoid treatment increasedthe amount of BB NHE3. The quantitative Western analysis showed thatNHE3 makes up 0.018% of ileal BB protein in control rabbits and0.042% (2.3 times as much) in methylprednisolone-treated rabbits.Methylprednisolone treatment did not alter the amount of ileal BB NHE2protein. NHE3 turnover number was estimated to be 458 cycles/s underbasal conditions and 708 cycles/s in glucocorticoid-treated ileum. Thusmethylprednisolone stimulates ileal BBNa+/H+exchange activity only by an effect on NHE3 and not on NHE2; it does soprimarily by increasing the amount of BB NHE3, although it alsoincreases the NHE3 turnover number. 相似文献
79.
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