Abstract: Cell death is a fundamental biological phenomenon that is essential for the survival and development of organisms. Cell death can be either a spontaneous programmed process by the host or an accidentally triggered process. According to the different signaling pathway activated by various stimulates, programmed cell death exhibits the lytic or non-lytic morphology. For example, apoptosis, a typical non-lytic form of cell death, exhibits cell shrinkage and induces the formation of apoptotic bodies. Pyroptosis mediated by cysteine-containing aspartate-specific protease-1/11 (caspase-1/11) and necroptosis can induce inflammatory reactions and promote cell lysis to release inflammatory cytokines via triggering the pore-forming mechanism of the cell membrane, representing a typical modes of lytic cell death. In addition, the release of reactive oxygen species caused by the damaged mitochondria may further trigger ferroptosis during the pathogen infection. Programmed cell death can play an immune defensive role by eliminating infected cells and intracellular pathogens and stimulating the innate immune response through the resulting cell corpses. Here, we discuss the molecular mechanisms of five programmed cell death pathways: apoptosis, pyroptosis, ferroptosis, necroptosis and PANoptosis. We describe their roles in the innate immune defense against bacterial infections and give a brief statement of the interactions between the different programmed cell death, hoping to provide new insights for in-depth study of the pathogenic mechanisms of infectious diseases.

Objective To understand the epidemic status quo and influencing factors of Kashin-Beck disease among children in mountain areas of Jilin Province.Methods Two hundred eighty-two severe endemic areas in 18 counties were selected and stratified by random cluster sampling method,and the status quo of KashinBeck disease prevalence was investigated among 7-12 year-old children according to the Diagnostic Criteria of Kashin-Beck Disease (WS/T 207-2010).In the meantime,the annual household income and the proportion of economic crops replanted,grain out-sourced,and returning farmlands to forests and grass were surveyed in the disease affected areas.Results A total of 14 162 children were investigated who had no clinical symptoms.Among them,28 cases were detected positive using X-ray with a detection rate of 1.98‰,while most of the cases were metaphysis positive.The annual household income (≥5 000 Yuan vs.＜ 5 000 Yuan) in the year 2009-2011 had a significant impact on the incidence of Kashin-Beck disease (1.47‰ vs.3.67‰,x2 =6.179,P ＜ 0.05),while the areas of returning farmland to forests and grass which accounted ＞ 1％ had no significant influence on the incidence compared with that ≤ 1％ (3.30‰ vs.1.57‰,x2 =3.876,P ＞ 0.05);the areas of economic crops replanting which accounted ＞ 10％ had no significant influence on the incidence compared with that ≤ 10％ (3.07‰ vs.1.65‰,x2 =2.565,P ＞ 0.05);the proportion of grain out-sourcing which accounted ＞ 50％ had no significant influence on the incidence compared with that ≤50％ (3.07‰ vs.1.65‰,x2 =2.565,P ＞ 0.05).Conehision Up to 2012,the disease among 7-12 year-old children of the mountain areas of Jilin Province have basically met the standard of Kashin-Beck disease elimination and the situation remains stable;furthermore,the household income has a significant impact on the incidence of Kashin-Beck disease.

Objective To investigate the expression of CD127 (interleukin-7 receptor α, IL-7Rα)and its association with apoptosis of CD8 + T lymphocytes in patients with chronic HIV-1 infection. Methods The expression of CD127 on T lymphocytes and spontaneous apoptosis of CD8+ T lymphocytes were measured by flow cytometry in peripheral blood from 24 patients with chronic HIV-1 infections and 12 healthy subjects. The associations of CD127 expression with CD4 +T lymphocytes counts, HIV RNA loads and cell apoptosis were analyzed. Mann-Whitney U test was performed to compare between the groups, and Spearman test was used for correlation analysis. Results The expression of CD127 on CD8 + T lymphocytes was significantly down-regulated in HIV-1 infected subjects (Z = -4.796, P ＜ 0. 01 ), which was positively correlated with CD4 + T lymphocytes (r = 0.817, P ＜ 0.01 ) and negatively correlated with HIV RNA load and CD8+T lymphocytes apoptosis (r= -0.442 and -0.688,P＜0.05 and ＜0.01). Conclusion CD127 down-regulation may play an important role in the descended ability of receiving survival signals and ascended apoptosis of CD8 + T lymphocytes during chronic HIV-1 infection, which indicates that IL-7 might be a novel strategy in treatment of HIV infection.

The relative bioavailability of roxithromycin dispersive tablet in healthy volunteers was evaluated in this study. Its concentration in plasma was detected by high performance liquid chromatography (HPLC) after twenty healthy male volunteers were given each a single dose of 300 mg roxithromycin. The experiment data were obtained using DAS programme. The values of Cmax were 10.16+/-1.46 and 10.34+/-1.66 microg x ml(-1) at 2.33+/-0.61 and 2.28+/-0.62 h respectively; of t1/2 were 9.00+/-1.58 and 8.68+/-1.66 h respectively; of AUC0-->Tn were 143.32 +/-25. 80 and 138.93+/-22. 49 microg x h x ml(-1) respectively; of AUC0-->infinity were 158.63+/-26.86 and 153.77+/-24.75 microg x h x ml(-1) for test and reference drugs. Relative bioavailability of the tested roxithromycin was 103.63%+/-14.04%. The result showed that the two dispersive tablets are bioequivalent.
Administration, Oral ; Anti-Bacterial Agents ; blood ; pharmacokinetics ; Biological Availability ; Chromatography, High Pressure Liquid ; Humans ; Male ; Roxithromycin ; blood ; pharmacokinetics ; Tablets ; Therapeutic Equivalency ; Young Adult

The original version of this article unfortunately contained a mistake. One of the authors of this article has been misspelled. Xiaoyang Zhang should be Xiaoyan Zhang. The update is also provided here.

As confusion mounts over RNA isoforms involved in phenotypic plasticity, aberrant CpG methylation-mediated disruption of alternative splicing is increasingly recognized as a driver of intratumor heterogeneity (ITH). Protease serine 3 (PRSS3), possessing four splice variants (PRSS3-SVs; PRSS3-V1-V4), is an indispensable trypsin that shows paradoxical effects on cancer development. Here, we found that PRSS3 transcripts and their isoforms were divergently expressed in lung cancer, exhibiting opposing functions and clinical outcomes, namely, oncogenic PRSS3-V1 and PRSS3-V2 versus tumor-suppressive PRSS3-V3, by targeting different downstream genes. We identified an intragenic CpG island (iCpGI) in PRSS3. Hypermethylation of iCpGI was mediated by UHRF1/DNMT1 complex interference with the binding of myeloid zinc finger 1 (MZF1) to regulate PRSS3 transcription. The garlic-derived compound diallyl trisulfide cooperated with 5-aza-2'-deoxycytidine to exert antitumor effects in lung adenocarcinoma cells through site-specific iCpGI demethylation specifically allowing MZF1 to upregulate PRSS3-V3 expression. Epigenetic silencing of PRSS3-V3 via iCpGI methylation (iCpGIm) in BALF and tumor tissues was associated with early clinical progression in patients with lung cancer but not in those with squamous cell carcinoma or inflammatory disease. Thus, UHRF1/DNMT1-MZF1 axis-modulated site-specific iCpGIm regulates divergent expression of PRSS3-SVs, conferring nongenetic functional ITH, with implications for early detection of lung cancer and targeted therapies.