Understanding Economic and Health Factors Impacting the Spread of COVID-19 Disease

BackgroundThe rapid spread of the Coronavirus 2019 disease (COVID-19) had drastically impacted life all over the world. While some economies are actively recovering from this pestilence, others are experiencing fast and consistent disease spread, compelling governments to impose social distancing measures that have put a halt on routines, especially in densely populated areas. ObjectiveAiming at bringing more light on key economic and population health factors affecting the disease spread, this initial study utilizes a quantitative statistical analysis based on the most recent publicly available COVID-19 datasets. MethodsWe have applied Pearson Correlation Analysis and Clustering Analysis (X-Means Clustering) techniques on the data obtained by combining multiple datasets related to country economics, medical system & health, and COVID-19 - related statistics. The resulting dataset consisted of COVID-19 Case and Mortality Rates, Economic Statistics, and Population Public Health Statistics for 165 countries reported between 22 January 2020 and 28 March 2020. The correlation analysis was conducted with the significance level of 0.05. The clustering analysis was guided by the value of Bayesian Information Criterion (BIC) with the bin value b = 1.0 and the cutoff factor c = 0.5, and have provided a stable split into four country-level clusters. ResultsThe study showed and explained multiple significant relationships between the COVID-19 data and other country-level statistics. We also identified and statistically profiled four major country-level clusters with relation to different aspects of COVID-19 development and country-level economic and health indicators. Specifically, this study identified potential COVID-19 under-reporting traits, as well as various economic factors that impact COVID-19 Diagnosis, Reporting, and Treatment. Based on the country clusters, we also described the four disease development scenarios, which are tightly knit to country-level economic and population health factors. Finally, we highlighted the potential limitation of reporting and measuring COVID-19 and provided recommendations on further in-depth quantitative research. ConclusionsIn this study, we first identified possible COVID-19 reporting issues and biases across different countries and regions. Second, we identified crucial factors affecting the speed of COVID-19 disease spread and provided recommendations on choosing and operating economic and health system factors when analyzing COVID-19 progression. Particularly, we discovered that the political system and compliance with international disease control norms are crucial for effective COVID-19 pandemic cessation. However, the role of some widely-adopted measures, such as GHS Health Index, might have been overestimated in lieu of multiple biases and underreporting challenges. Third, we benchmarked our findings against the widely-adopted Global Health Security (GHS) model and found that the latter might be redundant when measuring and forecasting COVID-19 spread, while its individual components could potentially serve as stronger COVID-19 indicators. Fourth, we discovered four clusters of countries characterized by different COVID-19 development scenarios, highlighting the differences of the disease reporting and progression in different economic and health system settings. Finally, we provided recommendations on sophisticated measures and research approaches to be implemented for effective outbreak measurements, evaluation and forecasting. We have supported the latter recommendations by a preliminary regression analysis based on the our-collected dataset. We believe that our work would encourage further in-depth quantitative research along the direction as well as would be of support to public policy development when addressing the COVID-19 crisis worldwide.

Radiation-induced senescence in securin-deficient cancer cells promotes cell invasion involving the IL-6/STAT3 and PDGF-BB/PDGFR pathways.

Securin overexpression correlates with poor prognosis in various tumours. We have previously shown that securin depletion promotes radiation-induced senescence and enhances radiosensitivity in human cancer cells. However, the underlying molecular mechanisms and the paracrine effects remain unknown. In this study, we showed that radiation induced senescence in securin-deficient human breast cancer cells involving the ATM/Chk2 and p38 pathways. Conditioned medium (CM) from senescent cells promoted the invasion and migration of non-irradiated cancer and endothelial cells. Cytokine assay analysis showed the up-regulation of various senescence-associated secretory phenotypes (SASPs). The IL-6/STAT3 signalling loop and platelet-derived growth factor-BB (PDGF-BB)/PDGF receptor (PDGFR) pathway were important for CM-induced cell migration and invasion. Furthermore, CM promoted angiogenesis in the chicken chorioallantoic membrane though the induction of IL-6/STAT3- and PDGF-BB/PDGFR-dependent endothelial cell invasion. Taken together, our results provide the molecular mechanisms for radiation-induced senescence in securin-deficient human breast cancer cells and for the SASP responses.

Securin depletion sensitizes human colon cancer cells to fisetin-induced apoptosis.

Securin is highly-expressed in various tumors including those of the colon. In this study, the role of securin in the anticancer effects of fisetin on human colon cancer cells was investigated. Fisetin-induced apoptosis in HCT116 cells as indicated by TUNEL assay, Annexin V-FITC/PI double staining, Ser15-phosphorylation of p53, and cleavages of procaspase-3 and PARP. These effects were enhanced in HCT116 securin-null cells or in wild-type cells in which securin was knockdown by siRNA, but attenuated when wild-type or non-degradable securin was reconstituted. Moreover, fisetin did not induce apoptosis in HCT116 p53-null and HT-29 p53-mutant cells. Knockdown of securin in HCT116 p53-null cells potentiated fisetin-induced cytotoxicity by induction of apoptosis. Our results provide the first evidence to support that securin depletion sensitizes human colon cancer cells to fisetin-induced apoptosis.

Enhancement of p53-mutant human colorectal cancer cells radiosensitivity by flavonoid fisetin.

PURPOSE: The aim of this study was to investigate whether fisetin is a potential radiosensitizer for human colorectal cancer cells, which are relatively resistant to radiotherapy. METHODS AND MATERIALS: Cell survival was examined by clonogenic survival assay, and DNA fragmentation was assessed by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay. The effects of treatments on cell cycle distribution and apoptosis were examined by flow cytometry. Western blot analysis was performed to ascertain the protein levels of gamma-H2AX, phospho-Chk2, active caspase-3, PARP cleavage, phospho-p38, phospho-AKT, and phospho-ERK1/2. RESULTS: Fisetin pretreatment enhanced the radiosensitivity of p53-mutant HT-29 human colorectal cancer cells but not human keratocyte HaCaT cells; it also prolonged radiation-induced G(2)/M arrest, enhanced radiation-induced cell growth arrest in HT-29 cells, and suppressed radiation-induced phospho-H2AX (Ser-139) and phospho-Chk2 (Thr-68) in p53-mutant HT-29 cells. Pretreatment with fisetin enhanced radiation-induced caspase-dependent apoptosis in HT-29 cells. Fisetin pretreatment augmented radiation-induced phosphorylation of p38 mitogen-activated protein kinase, which is involved in caspase-mediated apoptosis, and SB202190 significantly reduced apoptosis and radiosensitivity in fisetin-pretreated HT-29 cells. By contrast, both phospho-AKT and phospho-ERK1/2, which are involved in cell proliferation and antiapoptotic pathways, were suppressed after irradiation combined with fisetin pretreatment. CONCLUSIONS: To our knowledge, this study is the first to provide evidence that fisetin exerts a radiosensitizing effect in p53-mutant HT-29 cells. Fisetin could potentially be developed as a novel radiosensitizer against radioresistant human cancer cells.

Depletion of securin induces senescence after irradiation and enhances radiosensitivity in human cancer cells regardless of functional p53 expression.

PURPOSE: Radiotherapy is one of the best choices for cancer treatment. However, various tumor cells exhibit resistance to irradiation-induced apoptosis. The development of new strategies to trigger cancer cell death besides apoptosis is necessary. This study investigated the role of securin in radiation-induced apoptosis and senescence in human cancer cells. METHODS AND MATERIALS: Cell survival was determined using clonogenic assays. Western blot analysis was used to analyze levels of securin, caspase-3, PARP, p53, p21, Rb, gamma-H2AX, and phospho-Chk2. Senescent cells were analyzed using a beta-galactosidase staining assay. A securin-expressed vector (pcDNA-securin) was stably transfected into securin-null HCT116 cells. Securin gene knockdown was performed by small interfering RNA and small hairpin RNA in HCT116 and MDA-MB-231 cells, respectively. RESULTS: Radiation was found to induce apoptosis in securin wild type HCT116 cells but induced senescence in securin-null cells. Restoration of securin reduced senescence and increased cell survival in securin-null HCT116 cells after irradiation. Radiation-induced gamma-H2AX and Chk2 phosphorylation were induced transiently in securin-wild-type cells but exhibited sustained activation in securin-null cells. Securin gene knockdown switches irradiation-induced apoptosis to senescence in both HCT116 p53-null and MDA-MB-231 cells. CONCLUSIONS: Our results demonstrated that the level of securin expression plays a determining role in the radiosensitivity and fate of cells. Depletion of securin impairs DNA repair after irradiation, increasing DNA damage and promoting senescence in the residual surviving cells regardless of functional p53 expression. The knockdown of securin may contribute to a novel radiotherapy protocol for the treatment of human cancer cells that are resistant to irradiation.