Stress-induced modulation of the primary cellular immune response to herpes simplex virus infection is mediated by both adrenal-dependent and independent mechanisms

A murine model of herpes simplex virus (HSV) infection was ussed to examine the role of the adrenal gland in restraint stress-induced suppression of viral immunity. Adrenal-dependent mechanisms were important for suppressing the generation of HSV-specific cytotoxic T lymphocytes (CTL) but not the associated diminished lymphadenopathy in response to local HSV infection. While exogenous corticosterone administration alone was unable to suppress lymphadenopathy and CTL generation in adrenalectomized mice, an adrenal-independent mechanism induced by restraints stress functioned in synergy with corticosterone to suppress lymphadenopathy and CTL development. These results suggest that both adrenal-dependent and independent mechanisms cotribute to stress-induced modulation of HSV immunity.     

Under normoxia, 2-deoxy-D-glucose elicits cell death in select tumor types not by inhibition of glycolysis but by interfering with N-linked glycosylation

In tumor cells growing under hypoxia, inhibiting glycolysis with 2-deoxy-d-glucose (2-DG) leads to cell death, whereas under normoxic conditions cells similarly treated survive. Surprisingly, here we find that 2-DG is toxic in select tumor cell lines growing under normal oxygen tension. In contrast, a more potent glycolytic inhibitor, 2-fluorodeoxy-d-glucose, shows little or no toxicity in these cell types, indicating that a mechanism other than inhibition of glycolysis is responsible for their sensitivity to 2-DG under normoxia. A clue to this other mechanism comes from previous studies in which it was shown that 2-DG interferes with viral N-linked glycosylation and is reversible by exogenous addition of mannose. Similarly, we find that 2-DG interferes with N-linked glycosylation more potently in the tumor cell types that are sensitive to 2-DG under normoxia, which can be reversed by exogenous mannose. Additionally, 2-DG induces an unfolded protein response, including up-regulation of GADD153 (C/EBP-homologous protein), an unfolded protein response-specific mediator of apoptosis, more effectively in 2-DG-sensitive cells. We conclude that 2-DG seems to be toxic in select tumor cell types growing under normoxia by inhibition of N-linked glycosylation and not by glycolysis. Because in a phase I study 2-DG is used in combination with an anticancer agent to target hypoxic cells, our results raise the possibility that in certain cases, 2-DG could be used as a single agent to selectively kill both the aerobic (via interference with glycosylation) and hypoxic (via inhibition of glycolysis) cells of a solid tumor.     

The influence of CD4+ CD25+ Foxp3+ regulatory T cells on the immune response to rotavirus infection

Rotavirus (RV) infection of the intestine is the major cause of severe dehydrating diarrhea in infants around the world. Although protective immunity against RV, especially acquired B and T-cell responses, has been extensively studied, our understanding of RV immunity remains incomplete. In addition, the interaction between various protective immune mechanisms in the gut and specific enteric immune suppressor systems that normally exert a regulatory function on mucosal immunity has not been extensively investigated. Among the candidate suppressor systems, we hypothesized that CD4+ CD25+ Foxp3+ regulatory T (Treg) cells may play a role in modulating RV immunity since such cells are naturally present in large numbers in the intestine and function nonspecifically. Here we demonstrate that neonatal murine RV (EC) infection induces an expansion of the Treg cell population and the magnitude of the T cell mediated immune response is modulated by Treg cells. Accordingly, when natural Treg cells in neonatal mice were depleted before virus infection, both CD4+ and CD8+ T-cell responses to RV, such as proliferation and IFN-gamma secretion, were enhanced in mesenteric lymph nodes (MLNs) and the spleen. Interestingly, increased proliferation of CD19+ B cells from Treg cell depleted animals was also observed. Finally, we analyzed the in vivo effect of the Treg cell depletion on diarrheal disease, virus shedding and IgA RV-specific response. Treg cell depletion did not affect these functions. Our studies of immune modulatory Treg cells in the RV infection model may promote a better understanding of the basis for RV immunity as well as providing valuable clues for the development of more immunogenic RV vaccines.     

高校门诊中学生呼吸道感染的统计与分析

目的通过回顾南京农业大学医院在2018、2019全年校医院的电子就诊系统,统计分析这两年在校学生在门诊就诊中呼吸道感染就诊情况。方法导出2018—2019年该医院门诊电子就诊系统中大学生呼吸道感染的发病情况,统计学生的发病时间、年龄、性别、病种、年级,数据使用Excel软件和SPSS 20.0统计学软件进行统计分析。结果这两年校内呼吸道感染就诊高峰2018年为第四季度,2019年为第二季度,不同季度的就诊人次差异有统计学意义(P<0.05)。结论春季及冬季是校医院呼吸道感染的就诊高峰,及时给出呼吸道感染风险提示及宣教,避免影响呼吸道健康的负面因素。     

糖皮质激素联合复方樟柳碱治疗急性视神经炎临床分析

目的评价甲基强的松龙联合复方樟柳碱(compound anisodine,CA)治疗急性视神经炎(optic neuritis,ON)的效果。方法对1998年1月至2010年1月在我院收治的44例(58眼)ON患者的病案资料进行回顾性分析。结果甲基强的松龙治疗ON有效率为57.14%,甲基强的松龙联合CA治疗ON有效率为83.33%,两种治疗方法比较有统计学意义(=4.7947,<0.05)。结论甲基强的松龙联合CA治疗ON的效果优于甲基强的松龙单独治疗组。     

Increased sensitivity to glucose starvation correlates with downregulation of glycogen phosphorylase isoform PYGB in tumor cell lines resistant to 2-deoxy-d-glucose

Background

As tumors evolve, they upregulate glucose metabolism while also encountering intermittent periods of glucose deprivation. Here, we investigate mechanisms by which pancreatic cancer cells respond to therapeutic (2-deoxy-d-glucose, 2-DG) and physiologic (glucose starvation, GS) forms of glucose restriction.

Methods

From a tumor cell line (1420) that is unusually sensitive to 2-DG under normoxia, low (14DG2)- and high (14DG5)-dose resistant cell lines were selected and used to probe the metabolic pathways involved with their response to different forms of glucose deprivation.

Results

Muted induction of the unfolded protein response was found to correlate with resistance to 2-DG. Additionally, 14DG2 displayed reduced 2-DG uptake, while 14DG5 was cross-resistant to tunicamycin, suggesting it has enhanced ability to manage glycosylation defects. Conversely, 2-DG-resistant cell lines were more sensitive than their parental cell line to GS, which coincided with lowered levels of glycogen phosphorylase (PYGB) and reduced breakdown of glycogen to glucose in the 2-DG-resistant cell lines. Moreover, by inhibiting PYGB in the parental cell line, sensitivity to GS was increased.

Conclusions

Overall, the data demonstrate that the manner in which glucose is restricted in tumor cells, i.e., therapeutic or physiologic, leads to differential biological responses involving distinct glucose metabolic pathways. Moreover, in evolving tumors where glucose restriction occurs, the identification of PYGB as a metabolic target may have clinical application.     

Sudden twin infant death on the same day: a case report and review of the literature

Sudden infant death syndrome (SIDS) is a major contributor to infant mortality. The cause of death is unknown: suggested possibilities include cardiovascular disease, anaphylactic shock, and suffocation. The occurrence of simultaneous sudden infant death syndrome is uncommon, such cases being extremely rare in forensic pathologic practice. We report two 10-week-old male twins who appeared well at the time of their evening feeding, yet died while sleeping on their backs. Both infants had petechial hemorrhages on the visceral pleura, epicardial surface of the heart, and thymus gland. Microscopic examination revealed pulmonary edema, intra-alveolar hemorrhage, and minor lymphocytic infiltration, again in both infants. In this report, we discuss the risk factors for SIDS, which should be considered individually or in combination as possible causes of death.