Invasive Salmonella has been reported to induce apoptosis of macrophages as a part of its infection process, which may allow it to avoid detection by the innate immune system. However, the bacterial components capable of inducing apoptosis, particularly under the environments offered by the host have not been fully identified. Therefore, in the present study, attempts were made to evaluate the apoptotic potential of Salmonella enterica serovar Typhi (S. typhi) outer membrane protein expressed under stress conditions like iron, oxidative and anaerobic simulating the in vivo situations encountered by the pathogen. Analysis of data revealed that a coordinately expressed 69kDa outer membrane protein (OMP) expressed with enhanced intensity under iron, oxidative and anaerobic stress conditions caused apoptotic cell death in 51% of macrophages, whereas OMPs of S. typhi extracted under normal conditions accounted for apoptotic cell death in only 31% of macrophages. A significantly enhanced activity of caspase-3 was observed during macrophage-apoptosis induced by this protein. A significant increase in the extent of lipid peroxidation (levels of oxidant) and decrease in the activities of antioxidants was also observed which correlated with the increased generation of tumor necrosis factor-alpha, interleukine-1alpha and interleukine-6. These results suggest that caspase-3 and tumor necrosis factor-alpha in conjunction with other cytokines may induce apoptotic cell death through the up-regulation of oxidants and down-regulation of antioxidants. These findings may be relevant for the better understanding of the disease pathophysiology and for the future developments of diagnostic and preventive strategies during the host-pathogen interactions. 相似文献
The study consisted of application of anti-ubiquitin antibodies (Abs)-coated iron oxide-nanoparticles (IONPs) for minimisation of oxidative stress to contemporary live spermatozoa from the raw semen. Round-shaped IONPs (12.09 ± 0.91 nm) after two-stage functionalisation (silanisation and pegylation) were conjugated with Abs. Four aliquots from each of the 24 ejaculates (4 buffalo bulls) formed Control (Group I) and treatment (II, III and IV) groups; each containing 150 ± 25 million dead/damaged spermatozoa. IONPs-Abs complex were added at ratio of 1:1 (0.5 µg/ml), 1:2 (1.0 µg/ml) and 1:4 (2.0 µg/ml), respectively, in Groups II, III and IV. The semen quality parameters showed improvement at lag-stage (post-nano-purification before processing for cryopreservation). The mean post-thaw motility (%) in Group IV was found to be greater (p < .05) than Group I. Moreover, the overall DNA integrity (%) at post-thaw stage was improved in the nano-purified semen samples. The value of malondialdehyde was greater (p < .001) in Group I than Groups II, III and IV. The mean total antioxidant capacity and superoxide dismutase (U/mg protein) activity values in Group IV was greater (p < .05) than Group I. The study results show that IONPs conjugated with anti-ubiquitin Abs at 2.0 µg/ml can be an effective dose for depletion of dead/damaged spermatozoa from buffalo ejaculates to minimise oxidative stress. 相似文献
Influential neurocomputational models emphasize dopamine (DA) as an electrophysiological and neurochemical correlate of reinforcement learning. However, evidence of a specific causal role of DA receptors in learning has been less forthcoming, especially in humans. Here we combine, in a between-subjects design, administration of a high dose of the selective DA D2/3-receptor antagonist sulpiride with genetic analysis of the DA D2 receptor in a behavioral study of reinforcement learning in a sample of 78 healthy male volunteers. In contrast to predictions of prevailing models emphasizing DA''s pivotal role in learning via prediction errors, we found that sulpiride did not disrupt learning, but rather induced profound impairments in choice performance. The disruption was selective for stimuli indicating reward, whereas loss avoidance performance was unaffected. Effects were driven by volunteers with higher serum levels of the drug, and in those with genetically determined lower density of striatal DA D2 receptors. This is the clearest demonstration to date for a causal modulatory role of the DA D2 receptor in choice performance that might be distinct from learning. Our findings challenge current reward prediction error models of reinforcement learning, and suggest that classical animal models emphasizing a role of postsynaptic DA D2 receptors in motivational aspects of reinforcement learning may apply to humans as well. 相似文献
The traditional way to tackle Zenker’s diverticulum (ZD) has been flexible endoscopic septum division (FESD). Recently, the concept of per oral endoscopic myotomy has been found useful for managing diverticular diseases of the esophagus and has been termed DPOEM. We performed a systematic review and meta-analysis to evaluate the efficacy and safety of D-POEM in diverticular disease of the esophagus and to compare it with FESD. We systematically searched PubMed and Embase, for studies reporting clinical success, technical success and adverse events in D-POEM alone or D-POEM comparing with FESD. We computed pooled prevalence for D-POEM alone and risk ratio for D-POEM vs FESD using random effect method with inverse variance approach. Subgroup analysis for ZD, non-ZD and mixed diverticulum was conducted. Totally 19 studies including 341 patients were identified reporting on D-POEM. The pooled clinical, technical success and adverse event rates for D-POEM were 87.07%, 95.19% and 10.22%, respectively. The clinical success was significantly better than FESD while the technical success, adverse event rate, procedure time and length of hospital stay were comparable with FESD. The recurrence rate was negligible for D-POEM compared to FESD. On subgroup analysis by dividing into three groups of ZD, non-ZD and mixed, there was no difference between clinical, technical success and adverse event rate among the three groups. D-POEM is an effective and safe technique among both ZD and non-ZD patients and has better clinical success than FESD.
Background and aimsEver since COVID-19 was declared a pandemic by WHO in late March 2020, more and more people began to share their opinions online about the anxiety, stress, and trauma they suffered because of the pandemic. However, very few studies were conducted to analyze the general public’s perception of what causes stress, anxiety, and trauma during COVID-19. This study focuses particularly on understanding Indian citizens.MethodsBy using Machine learning techniques, particularly Natural language processing, this study focuses on understanding the attitude of Indian citizens while discussing the anxiety, stress, and trauma created because of COVID-19 and the major reasons that cause it. We used Tweets as data for this study. We have used 840,000 tweets for this study.ResultsOur sentiment analysis study revealed the interesting fact that, even while discussing about the stress, anxiety, and trauma caused by COVID-19, most of the tweets were in neutral sentiments. Death and Lockdown caused by the COVID-19 were the two most important aspects that cause stress, anxiety, and Trauma among Indian citizens.ConclusionIt is important for policymakers and health professionals to understand common citizen’s perspectives of what causes them stress, anxiety, and trauma to formulate policies and treat the patients. Our study shows that Indian citizens use social media to share their opinions about COVID-19 and as a coping mechanism in unprecedented time. 相似文献