ABSTRACT
BACKGROUND: The influence of sex on the clinical characteristics and prognosis of coronavirus disease (COVID-19) patients is variable. This study aimed to evaluate COVID-19 management based on sex differences. METHODS: We retrospectively reviewed COVID-19 patients who were admitted to the tertiary hospital between January 2020 and March 2021. Logistic regression analysis was used to evaluate the factors associated with in-hospital mortality. RESULTS: During the study period, 584 patients were admitted to our hospital. Among them, 305 patients (52.2%) were female, and 279 patients (47.8%) were male. Males were younger than females, and frailty scale was lower in males than in females. Fever was more common in males, and there was no difference in other initial symptoms. Among the underlying comorbidities, chronic obstructive disease was more common in males, and there were no significant differences in other comorbidities. Moreover, treatment, severity, and outcome did not significantly differ between the groups. The risk factors for in-hospital mortality were age, high white blood cell count, and c-reactive protein level. CONCLUSIONS: We found no definite sex differences in the clinical characteristics and outcomes of COVID-19 patients. However, a better understanding of sex-dependent differences in COVID-19 patients could help in understanding and treating patients.
ABSTRACT
Lung cancer organoid (LCO) is a novel model of lung cancer that facilitates drug screening. However, the success rate of LCOs varies from 7% to 87%, and the culture medium compositions are markedly different. Airway organoid media can be used for LCO cultures, but this promotes the overgrowth of normal cell organoids especially in LCOs from intrapulmonary lesions. Several modified media are specifically utilized for promoting the cancer cell's growth. For culturing high-purity LCOs, cancer cells from metastatic lesions and malignant effusions are used. Recently, single-cell RNA sequencing has identified previously unknown cell populations in the lungs and lung cancer. This sequencing technology can be used to validate whether the LCO recapitulates the heterogeneity and functional hierarchy of the primary tumor. Several groups have attempted to culture LCOs with mesenchymal cells and immune cells to recapitulate the tumor microenvironment. Disease modeling using LCO provides novel insight into the pathophysiology of lung cancer and enables high-throughput screening for drug discovery and prognosis prediction. An LCO model would help to identify new concepts as a basis for lung cancer targeting by discovering innovative therapeutic targets.
Subject(s)
Lung Neoplasms/pathology , Organoids/pathology , Animals , Clinical Trials as Topic , Disease Models, Animal , Humans , Reproducibility of Results , Tumor MicroenvironmentABSTRACT
Despite significant innovations in lung cancer treatment, such as targeted therapy and immunotherapy, lung cancer is still the principal cause of cancer-associated death. Novel strategies to overcome drug resistance and inhibit metastasis in cancer are urgently needed. The Hippo pathway and its effector, Yes-associated protein (YAP), play crucial roles in lung development and alveolar differentiation. YAP is known to mediate mechanotransduction, an important process in lung homeostasis and fibrosis. In lung cancer, YAP promotes metastasis and confers resistance against chemotherapeutic drugs and targeted agents. Recent studies revealed that YAP directly controls the expression of programmed death-ligand 1 (PD-L1) and modulates the tumor microenvironment (TME). YAP not only has a profound relationship with autophagy in lung cancer but also controls alveolar differentiation, and is responsible for tubular structure formation in lung organoids. In this review, we discuss the various roles and clinical implications of YAP in lung cancer and propose that targeting YAP can be a promising strategy for treating lung cancer.
ABSTRACT
BACKGROUND: Observational studies of the ongoing coronavirus disease 2019 (COVID-19) outbreak suggest that a 'cytokine storm' is involved in the pathogenesis of severe illness. However, the molecular mechanisms underlying the altered pathological inflammation in COVID-19 are largely unknown. We report here that toll-like receptor (TLR) 4-mediated inflammatory signaling molecules are upregulated in peripheral blood mononuclear cells (PBMCs) from COVID-19 patients, compared with healthy controls (HC). METHODS: A total of 48 subjects including 28 COVID-19 patients (8 severe/critical vs. 20 mild/moderate cases) admitted to Chungnam National University Hospital, and age/sex-matched 20 HC were enrolled in this study. PBMCs from the subjects were processed for nCounter Human Immunology gene expression assay to analyze the immune related transcriptome profiles. Recombinant proteins of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) were used to stimulate the PBMCs and monocyte-derived macrophages, and real-time polymerase chain reaction was performed to quantify the mRNA expressions of the pro-inflammatory cytokines/chemokines. RESULTS: Among the most highly increased inflammatory mediators in severe/critically ill patients, S100A9, an alarmin and TLR4 ligand, was found as a noteworthy biomarker, because it inversely correlated with the serum albumin levels. We also observed that recombinant S2 and nucleocapsid proteins of SARS-CoV-2 significantly increased pro-inflammatory cytokines/chemokines and S100A9 in human primary PBMCs. CONCLUSION: These data support a link between TLR4 signaling and pathological inflammation during COVID-19 and contribute to develop therapeutic approaches through targeting TLR4-mediated inflammation.