Summary Background Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described. Methods In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death. Findings 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p Interpretation The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. Funding Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.

Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

Therapy resistance is a characteristic of cancer cells that significantly reduces the effectiveness of drugs. Despite the popularity of cisplatin (CP) as a chemotherapeutic agent, which is widely used in the treatment of various types of cancer, resistance of cancer cells to CP chemotherapy has been extensively observed. Among various reported mechanism(s), the epithelial–mesenchymal transition (EMT) process can significantly contribute to chemoresistance by converting the motionless epithelial cells into mobile mesenchymal cells and altering cell–cell adhesion as well as the cellular extracellular matrix, leading to invasion of tumor cells. By analyzing the impact of the different molecular pathways such as microRNAs, long non-coding RNAs, nuclear factor-κB (NF-ĸB), phosphoinositide 3-kinase-related protein kinase (PI3K)/Akt, mammalian target rapamycin (mTOR), and Wnt, which play an important role in resistance exhibited to CP therapy, we first give an introduction about the EMT mechanism and its role in drug resistance. We then focus specifically on the molecular pathways involved in drug resistance and the pharmacological strategies that can be used to mitigate this resistance. Overall, we highlight the various targeted signaling pathways that could be considered in future studies to pave the way for the inhibition of EMT-mediated resistance displayed by tumor cells in response to CP exposure.

https://www.mdpi.com/1422-0067/21/11/4002/pdf

Association of the Epithelial-Mesenchymal Transition (EMT) with Cisplatin Resistance.

Dapagliflozin in patients with cardiometabolic risk factors hospitalised with COVID-19 (DARE-19): a randomised, double-blind, placebo-controlled, phase 3 trial.

Lung cancer is a main cause of death all over the world with a high incidence rate. Metastasis into neighboring and distant tissues as well as resistance of cancer cells to chemotherapy demand novel strategies in lung cancer therapy. Curcumin is a naturally occurring nutraceutical compound derived from Curcuma longa (turmeric) that has great pharmacological effects, such as anti-inflammatory, neuroprotective, and antidiabetic. The excellent antitumor activity of curcumin has led to its extensive application in the treatment of various cancers. In the present review, we describe the antitumor activity of curcumin against lung cancer. Curcumin affects different molecular pathways such as vascular endothelial growth factors, nuclear factor-κB (NF-κB), mammalian target of rapamycin, PI3/Akt, microRNAs, and long noncoding RNAs in treatment of lung cancer. Curcumin also can induce autophagy, apoptosis, and cell cycle arrest to reduce the viability and proliferation of lung cancer cells. Notably, curcumin supplementation sensitizes cancer cells to chemotherapy and enhances chemotherapy-mediated apoptosis. Curcumin can elevate the efficacy of radiotherapy in lung cancer therapy by targeting various signaling pathways, such as epidermal growth factor receptor and NF-κB. Curcumin-loaded nanocarriers enhance the bioavailability, cellular uptake, and antitumor activity of curcumin. The aforementioned effects are comprehensively discussed in the current review to further direct studies for applying curcumin in lung cancer therapy.

Versatile role of curcumin and its derivatives in lung cancer therapy

The COVID-19 disease is a multisystem disease due to in part to the vascular endothelium injury. Lasting effects and long -term sequalae could persist after the infection and may be due to persistent endothelial dysfunction. Our study focused on the evaluation of endothelial quality index (EQI) by finger thermal monitoring with E4 diagnosis Polymath in a large cohort of long COVID-19 patients to determine whether long-covid 19 symptoms are associated to endothelial dysfunction. This is a cross sectional multicenter observational study with a prospective recruitment of patients. A total of 798 patients were included in this study. A total of 618 patients (77.4%) had long COVID-19 symptoms. The mean EQI was 2.02 ± 0.99 IC95% [1.95 – 2.08]. A total of 397 (49.7%) patients had impaired EQI. Fatigue, chest pain and neuro-cognitive difficulties were significantly associated to endothelium dysfunction with an EQI <2 after adjustment with age, sex, diabetes, hypertension, dyslipidemia, coronary heart disease and the severity of acute COVID-19 infection. In multivariate analysis, endothelial dysfunction (EQI < 2), female gender and severe clinical status at acute COVID-19 infection with a need to oxygen supplementation were independent risk factors of long COVID-19 syndrome. Long COVID-19 symptoms specifically non-respiratory symptoms are due to persistent endothelial dysfunction. These findings allow a better care of patients with long COVID-19 symptoms.

Long COVID 19 Syndrome: Is It Related to Microcirculation and Endothelial Dysfunction? Insights From TUN-EndCOV Study

Introduction Coronavirus disease 2019 (COVID-19) has the characteristics of high transmission, diverse clinical manifestations, and a long incubation period. In addition to infecting the respiratory system, COVID-19 also has adverse effects on the cardiovascular system. COVID-19 causes acute myocardial injuries, as well as chronic damage to the cardiovascular system. Areas covered The present review is aimed at providing current information on COVID-19 and the cardiovascular system. PubMed, Scopus, Science direct, and Google Scholar were searched. Expert opinion It is suggested that heart injury caused by COVID-19 infection might be an important cause of severe clinical phenotypes or adverse events in affected patients. Myocardial damage is closely related to the severity of the disease and even the prognosis in patients with COVID-19. In addition to disorders that are caused by COVID-19 on the cardiovascular system, more protection should be employed for patients with preexisting cardiovascular disease (CVD). Hence, it is very important that once relevant symptoms appear, patients with COVID-19 be rapidly treated to reduce mortality. Thus, early measurements of cardiac damage via biomarkers following hospitalization for COVID-19 infections in a patient with preexisting CVD are recommended, together with careful monitoring of any myocardial injury that might be caused by the infection.Abbreviations: ICU: An intensive care unit; 2019-nCoV: 2019 novel coronavirus; ACEI: ACE inhibitor; ACS: Acute coronary syndrome; ARDS: Acute respiratory distress syndrome; AT1R: Ang II type 1 receptor; ATP: Adenosine triphosphate; ACC: American College of Cardiology; ACE: Angiotensin converting enzyme; Ang II: Angiotensin II; ARB: Angiotensin II receptor blocker; AV block: Atrioventricular block; CAD: Coronary artery disease; CVD: Cardiovascular disease; CT: Computerized tomography; CHF: Congestive heart failure; CHD: Coronary heart disease; CK-MB: Creatine kinase isoenzyme-MB; CRP: C-reactive protein; cTnI: Cardiac troponin I; EAT: Epicardial adipose tissue; ECMO: Extracorporeal membrane oxygenation; FDA: Food and Drug Administration; G-CSF: Granulocyte colony-stimulating factor; HFrEF: HF with a reduced ejection fraction; synhACE2: Human isoform of ACE2; IL: Interleukin; IABP: Intra-aortic balloon counterpulsation; IP10: Interferon γ-induced protein 10 kDa; LPC: Lysophosphatidylcholine; Mas: Mitochondrial assembly receptor; MCP1: Monocyte chemoattractant protein-1; MERS: Middle East respiratory syndrome; MIP1a: macrophage inflammatory protein 1a: MOF: Multiple organ failure; MI: Myocardial infarction; MRI: Magnetic resonance imaging; MYO: Myohe-moglobin; NT-proBNP: N-terminal pro-brain natriuretic peptide; PCPS: Percutaneous cardiopulmonary assistance; rhACE2: Recombinant human ACE2; SARS: Severe acute respiratory syndrome; Th: T helper; RAS: Renin-angiotensin system; TNF-α: Tumor necrosis factor-α; WHO: World Health Organization.

https://www.tandfonline.com/doi/pdf/10.1080/14787210.2020.1822737

COVID-19 and cardiac injury: clinical manifestations, biomarkers, mechanisms, diagnosis, treatment, and follow up.

Osteosarcoma (OS) is a kind of primary bone cancer that is considered as the leading cause of children death. Surgery and chemotherapy are considered as common treatment approaches for OS; the rate of survival for patients is almost 60-70%. Besides the used therapeutic approaches, it seems that there is a crucial need to launch new treatments for OS. In this regard, more understanding about cellular and molecular pathways involved in OS can contribute to recovery and develop new therapeutic platforms. Autophagy is a cellular machinery that digests and degrades dysfunctional proteins and organelles, so it can regulate the cell proliferation and survival. Most of the time, OS cells use autophagy to increase their survival and proliferation and to gain the ability to resist chemotherapy. Although, there are several controversial evidences on how OS cells use autophagy. A variety of cellular and molecular pathways, that is, microRNAs (miRNAs) can modulate autophagy. MiRNAs are some endogenous, approximately 22 nucleotide RNAs that have an important role in posttranscriptional regulation of mRNAs by targeting them. There are many evidences that the various miRNA expressions in OS cells are dysregulated, so it can propel a normal cell to cancerous one by influencing the cell survival, apoptosis, and autophagy, and eventually increased chemoresitance. Hence, miRNAs can be considered as new biomarkers for OS diagnosis, and according to the role of autophagy in OS progression, miRNAs can use inhibiting or promoting autophagy agents. The present review summarizes the effects of aberrant expression of miRNAs in OS diagnosis and treatment with focus on their roles in autophagy.

https://iubmb.onlinelibrary.wiley.com/doi/epdf/10.1002/iub.2277

Autophagy regulation by microRNAs: Novel insights into osteosarcoma therapy

Cystic echinococcosis (CE) is considered as a neglected disease with significant mortality and morbidity in most of the developing countries The current study aimed to retrospectively assess the demographic and epidemiologic features of human CE surgical cases in a 15-year period in Fars province, southwestern Iran A 15-year (2004–2018) retrospective study was conducted to find out the epidemiological and clinical picture of CE in patients who undergone surgeries for CE in two main hospitals in Fars Province, southwestern Iran Hospital records were reviewed, and data were retrieved from each CE patient’s record A total of 501 CE surgical cases were recorded during a 15-year period, corresponding to an average annual incidence of 334 and a surgical incidence rate of 074/100,000 population Of these, 242 (486%) were male, and 256 (524%) were female Patients’ age ranged from 2 to 96 years, with a mean age of 3492 (± 1987) years A significantly higher rate of CE cases was noted in subject’s ≥ 50 years of age The highest frequency of cases (62:125%) was recorded in the year 2017 The most commonly involved organs were liver (339 cases; 578%) and lung (279 cases; 476%) Concurrent involvement of two organs was seen in 58 (99%) cases of both lung and liver, 10 (16%) cases of lung and other locations (but not liver), and 23 (39%) cases of liver and other locations (but not lung) Reoperation was noted in 67 (134%) of the cases The size of the lung hydatid cyst varied, ranging between 2 and 24 cm (mean = 733, SD = 3737) The size of liver hydatid cysts ranged from 1 to 26 cm (mean 904, SD = 4275) The findings of the current study demonstrated a nearly constant prevalence of CE during the last 15 years in southern Iran Further studies are needed to find out the reasons behind the recurrence of the disease, which is substantial, in surgically-treated patients

/pdf/human-cystic-echinococcosis-in-southwest-iran-a-15-year-1h2jllxje0.pdf

Human cystic echinococcosis in southwest Iran: a 15-year retrospective epidemiological study of hospitalized cases.

Background: Seroprevalence of toxoplasmosis in different populations in Iran varies according to the people eating behaviors and also geographic and climatic differences of each area. Objective: The current study aimed to provide recent data regarding the seroprevalence of toxoplasmosis among female university students in Shiraz University of Medical Sciences, in Fars province, southern Iran. Materials and Methods: The subjects of the study were 503 female university students. Blood samples were collected from each participant and tested for anti-Toxoplasma IgG and IgM antibodies, using a commercial Enzyme-Linked Immunosorbent Assays (ELISA) kit. Demographic characteristics and risk factor related to Toxoplasma were also recorded during the samples collection. Results: The mean age of participants was 22.2 (±3.83) years and the majority (54.9%) of subjects was in the age group of 20-25 years old. Anti T. gondii antibodies was detected in sera of 43 out of 503 enrolled students, corresponding to an overall seroprevalence of 8.5%. Of these, 37 (7.4%) were seropositive for only IgG, 7 (1.4%) were seropositive for only IgM and 1 (0.2%) were seropositive for both IgG and IgM. The differences between age and animal contact with seropositivity to toxoplasmosis were not statistically significant. Conclusion: The findings of the study indicated that more than 90 % of the female university students in this study were seronegative for toxoplasmosis. As these students are in their childbearing age, there is a possibility for their newborns to become infected with Toxoplasma. The control and preventative measurements are necessary to reduce the rate of T. gondii infection in such individuals.

Hajar Taghizadeh

Papers

COVID-19 and cardiac injury: clinical manifestations, biomarkers, mechanisms, diagnosis, treatment, and follow up.

Autophagy regulation by microRNAs: Novel insights into osteosarcoma therapy

Human cystic echinococcosis in southwest Iran: a 15-year retrospective epidemiological study of hospitalized cases.

Seroepidemiological survey of toxoplasmosis among female university students in Shiraz, southern Iran