Remote ischemic preconditioning (RIPC) and postconditioning (RpostC) have protective effects on ischemia and reperfusion injury. The effects have been reported to activate heme oxygenase-1 (HO-1) and attenuate nuclear factor kappa B (NF-κB) and subsequently reduce systemic inflammation. Ischemic preconditioning prevented inflammatory responses by modulating HO-1 expression in endotoxic shock model. Therefore, we investigated whether RpostC could have protective effects on lipopolysaccharide (LPS)-induced systemic inflammation.

Introduction: Poly (ADP-ribose) polymerase (PARP) participates in inflammation by cellular necrosis and the nuclear factor-kappa-B (NF-κB)-dependent transcription. The purpose of this study was to examine the roles of PARP in ventilator-induced lung injury (VILI) in normal mice lung. Methods: Male C57BL/6 mice were divided into four groups: sham tracheostomized (sham), lung-protective ventilation (LPV), VILI, and VILI with PARP inhibitor PJ34 pretreatment (PJ34+VILI) groups. Mechanical ventilation (MV) settings were peak inspiratory pressure (PIP) 15 cm H₂O + positive end-expiratory pressure (PEEP) 3 cm H₂O + 90 breaths per minute for the LPV group and PIP 40 cm H₂O + PEEP 0 cm H₂O + 90 breaths per minute for the VILI and PJ34+VILI groups. After 2 hours of MV, acute lung injury (ALI) score, wet-to-dry (W/D) weight ratio, PARP activity, and dynamic compliance (C_D) were recorded. Tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), myeloperoxidase (MPO) activity, and nitrite/nitrate (NO_X) in the bronchoalveolar lavage fluid and NF-κB DNA-binding activity in tissue homogenates were measured. Results: The VILI group showed higher ALI score, W/D weight ratio, MPO activity, NO_X, and concentrations of TNF-α and IL-6 along with lower C_D than the sham and LPV groups (P < 0.05). In the PJ34+VILI group, PJ34 pretreatment improved all histopathologic ALI, inflammatory profiles, and pulmonary dynamics (P < 0.05). NF-κB activity was increased in the VILI group as compared with the sham and LPV groups (P < 0.05) and was decreased in the PJ34+VILI group as compared with the VILI group (P = 0.009). Changes in all parameters were closely correlated with the PARP activity (P < 0.05). Conclusion: Overactivation of PARP plays an important role in the inflammatory and transcriptional pathogenesis of VILI, and PARP inhibition has potentially beneficial effects on the prevention and treatment of VILI.

Interferon-inducible guanylate-binding proteins (GBPs) are well-known for mediating host-defense mechanisms against cellular pathogens. Emerging evidence suggests that GBPs are also implicated in tumorigenesis; however, their underlying molecular mechanism is still unknown. In this study, we identified that GBP1 and GBP2 interact with MCL-1, the key prosurvival member of the BCL-2 family, via its BH3 domain. GBPs induce caspase-dependent apoptosis in chronic myeloid leukemia (CML) and acute myeloid leukemia (AML) cells, where the proapoptotic BCL-2 member, BAK, is an indispensable mediator. In particular, GBP2 completely inhibited the MCL-1-mediated promotion of the survival of CML cells through competitive inhibition, resulting in BAK liberation from MCL-1. Concurrently, GBP2 dramatically upregulates BAK expression via its inhibition of the PI3K/AKT pathway. Moreover, paclitaxel upregulates GBP2 expression, and paclitaxel-induced apoptotic activity was distinctively compromised by knockout of GBP2 in CML cells. Bioinformatics analyses of leukemia databases revealed that transcripts of GBPs were generally downregulated in leukemia patients and that GBPs were favorable prognosis markers. Thus, these findings provide molecular evidence of GBPs as apoptosis-inducing proteins of leukemia cells and suggest that GBPs are attractive targets for the development of chemotherapeutics.

Lee SH, et al. Yonsei Med J. 2013 Nov;54(6):1394-1399. https://doi.org/10.3349/ymj.2013.54.6.1394

Syphilis is a sexually transmitted disease caused by Treponema pallidum. The prevalence of this disease has recently increased worldwide. However, pulmonary involvement in secondary syphilis is extremely rare. A 51-year-old heterosexual male patient presented with multiple pulmonary nodules with reactive serology from the Venereal Disease Research Laboratory test and positive fluorescent treponemal antibody absorption testing. A hematogenous metastatic malignancy was suspected and an excisional lung biopsy was performed. Histopathological examination showed only central necrosis with abscess and plasma cell infiltration, but no malignant cells. The patient reported sexual contact with a prostitute 8 weeks previously and a penile lesion 6 weeks earlier. Physical examination revealed an erythematous papular rash on the trunk. Secondary syphilis with pulmonary nodules was suspected, and benzathine penicillin G, 2.4 million units, was administered. Subsequently, the clinical signs of syphilis improved and the pulmonary nodules resolved. The final diagnosis was secondary syphilis with pulmonary nodular involvement.

Background: Socioeconomic status (SES) is a strong determinant in the development of various diseases. We evaluated the relationship between SES and the incidence of chronic obstructive pulmonary disease (COPD) by using a community-based cohort data. Patients and Methods: Four-year follow-up data of 6341 adults (aged ≥ 40 years), who underwent serial pulmonary function test were analyzed. Incidence of COPD in the participants was defined as the absence of airflow obstruction compatible with COPD (pre-bronchodilator forced expiratory volume in 1 second/forced vital capacity ratio of < 0.7) at baseline but documentation of airflow obstruction in serial testing. SES of patients was divided into quartiles according to household income and educational level. Multivariate logistic regression analyses were performed to estimate the association between SES and COPD incidence. Results: A total of 280 (4.4%) patients developed COPD during the follow-up. The proportion of subjects with lowest education (elementary school) and lowest household income levels (1st quartile) was significantly higher in the COPD group than in the non-COPD group (37.9% vs 29.5%, p< 0.011 and 48.4% vs 30.8%, p< 0.001, respectively). Logistic regression analysis revealed that education level of elementary school was independently associated with COPD incidence after adjustment for sex, age, body mass index, white blood cell count, residence area, and occupation (odds ratio 1.879, 95% confidence interval 1.124– 3.141, p=0.016). Conclusion: In the general population, educational level of elementary school was an independent risk factor for COPD among the components comprising SES. Our results indicate that the implementation of preventive strategies for COPD in those with low educational status could be beneficial.