Background: Exposure to cigarette smoke (CS) is a major threat to human health worldwide. It is well established that smoking increases the risk of respiratory diseases, cardiovascular diseases and different forms of cancer, including lung, liver, and colon. CS-triggered inflammation is considered to play a central role in various pathologies by a mechanism that stimulates the release of pro-inflammatory cytokines. During this process, epigenetic alterations are known to play important roles in the specificity and duration of gene transcription. Main text: Epigenetic alterations include three major modifications: DNA modifications via methylation; various posttranslational modifications of histones, namely, methylation, acetylation, phosphorylation, and ubiquitination; and non-coding RNA sequences. These modifications work in concert to regulate gene transcription in a heritable fashion. The enzymes that regulate these epigenetic modifications can be activated by smoking, which further mediates the expression of multiple inflammatory genes. In this review, we summarize the current knowledge on the epigenetic alterations triggered by CS and assess how such alterations may affect smoking-mediated inflammatory responses. Conclusion: The recognition of the molecular mechanisms of the epigenetic changes in abnormal inflammation is expected to contribute to the understanding of the pathophysiology of CS-related diseases such that novel epigenetic therapies may be identified in the near future.

Chronic obstructive pulmonary disease (COPD) is one of the most common chronic respiratory diseases with high morbidity and mortality. It has become the fifth most burdened and the third most deadly disease in the global economy and increases year by year. The prevention and treatment of COPD are urgent. Smoking is the main and most common risk factor for COPD. Cigarette smoke (CS) contains a large number of toxic substances, can cause a series of changes in the trachea, lung tissue, pulmonary blood vessels, and promotes the occurrence and development of COPD. In recent years, the development of epigenetics and molecular biology have provided new guidance for revealing the pathogenesis, diagnosis, and treatment of diseases. The latest research indicates that pulmonary vascular endothelial cell apoptosis initiates and participates in the pathogenesis of COPD. In this review, we summarize the current research on the epigenetic mechanisms and molecular biology of CS-induced pulmonary vascular endothelial cell apoptosis in COPD, providing a new research direction for pathogenesis of COPD and a new target for the diagnosis, treatment, and prevention of COPD.

Background: The aim of this study was to analyze and summarize the clinical characteristics of elderly patients with coronavirus disease 2019 (COVID-19) and compare the differences of young-old patients (60–74 years old) and old-old patients (≥75 years old). Methods: In thisretrospective, multicenter study, the medical records of elderly patients who were diagnosed with COVID-19 in Hunan province, China, from January 21 to February 19, 2020 were reviewed. The characteristics of young-old patients and old-old patients were compared. Results: Of the 105 elderly patientsconfirmed withCOVID-19, 81.0% were young-old patients, and 19.0% were old-old patients; 54.3% of elderly patients were females. Overall, 69.5% of elderly patients had underlying diseases, and the most common comorbidities included hypertension (43.8%), diabetes (25.7%), and cardiac disease (16.2%). Of the elderly patients, 22.9% were severe and 10.5% were critical severe cases. On admission, the most frequent symptoms in elderly patients included fever (66.7%), cough (64.8%), and fatigue (33.3%). Lymphopenia (31.4%), increased D-dimer (38.1%), depressed albumin (36.2%), elevated lactate dehydrogenase (41.0%), and a high level of C-reactive protein (79.0%) were common among elderly patients with COVID-19. The median prothrombin time (PT) and the activated partial thromboplastin time (APTT) were longer in old-old patients than young-old patients (PT median 12.3 vs. 13.1 s, p = 0.007; APTT median 39.0 vs. 33.5 s, p = 0.045). Young-old patients showed fewer complications (14.1%) than old-old patients (40.0%; p = 0.0014) and fewer received invasive ventilator support (3.5 vs. 25.0%, p = 0.006). As of March 11, 2020, 85.7% of elderly patients had been discharged, 3 deaths had occurred, and 11.4% were still hospitalized. Conclusions: Elderly patients usually have chronic medical illness and are likely to have a severe or critically severe condition. They could show atypical symptoms without fever or cough and multiple organ dysfunction. Old-old patients tend to have more complications than young-old patients during hospitalization. Careful nursing, observation, and systemic treatment are very important in elderly patients.

Objective: To understand the clinical characteristics of COVID-19 patients with clinically diagnosed bacterial co-infection (CDBC), and therefore contributing to their early identification and prognosis estimation. Method: 905 COVID-19 patients from 7 different centers were enrolled. The demography data, clinical manifestations, laboratory results, and treatments were collected accordingly for further analyses. Results: Around 9.5% of the enrolled COVID-19 patients were diagnosed with CDBC. Older patients or patients with cardiovascular comorbidities have increased CDBC probability. Increased body temperature, longer fever duration, anhelation, gastrointestinal symptoms, illness severity, intensive care unit attending, ventilation treatment, glucocorticoid therapy, longer hospitalization time are correlated to CDBC. Among laboratory results, increased white blood cell counting (mainly neutrophil), lymphocytopenia, increased procalcitonin, erythrocyte sedimentation rate, C-reaction protein, D-dimer, blood urea nitrogen, lactate dehydrogenase, brain natriuretic peptide, myoglobin, blood sugar and decreased albumin are also observed, indicating multiple system functional damage. Radiology results suggested ground glass opacity mixed with high density effusion opacities and even pleural effusion. Conclusion: The aged COVID-19 patients with increased inflammatory indicators, worse lymphopenia and cardiovascular comorbidities are more likely to have clinically diagnosed bacterial co-infection. Moreover, they tend to have severer clinical manifestations and increased probability of multiple system functional damage.

The Notch signaling pathway plays critical role for determining cell fate by controlling proliferation, differentiation, and apoptosis. In the current study, we investigated the roles of the Notch signaling pathway in cigarette smoke (CS)-induced endothelial apoptosis in chronic obstructive pulmonary disease (COPD). We obtained surgical specimens from 10 patients with COPD and 10 control participants. Notch1, 2, and 4 express in endothelial cells, whereas Notch3 mainly localizes in smooth muscle cells. Compared with control groups, we found that the expression of Notch1, 3, and 4 decreased, as well as their target genes Hes1 and Hes2, while the expression of Notch2 and extracellular signal-regulated kinase (ERK)1/2 increased in COPD patients compared with controls, as well as in human pulmonary microvascular endothelial cells (HPMECs) when exposed to CS extract (CSE). Overexpression of Notch1 with N1ICD in HPMECs markedly alleviated the cell apoptosis induced by CSE. The ERK signaling pathway was significantly activated by CSE, which correlated with CSE-induced apoptosis. However, this activation can be abolished by N1ICD overexpression. Furthermore, treatment of PD98059 (ERK inhibitor) significantly alleviated CSE-induced apoptosis, as well as reduced the methylation of mitochondrial transcription factor A (mtTFA) promoter, which was correlated with CS-induced endothelial apoptosis. These results suggest that CS alters Notch signaling in pulmonary endothelial cells. Notch1 protects against CS-induced endothelial apoptosis in COPD through inhibiting the ERK pathway, while the ERK pathway further regulates the methylation of mtTFA promotor.