Modelling upper respiratory viral load dynamics of SARS-CoV-2.

Relationships between viral load, severity of illness, and transmissibility of virus are fundamental to understanding pathogenesis and devising better therapeutic and prevention strategies for COVID-19. Here we present within-host modelling of viral load dynamics observed in the upper respiratory tract (URT), drawing upon 2172 serial measurements from 605 subjects, collected from 17 different studies. We developed a mechanistic model to describe viral load dynamics and host response and contrast this with simpler mixed-effects regression analysis of peak viral load and its subsequent decline. We observed wide variation in URT viral load between individuals, over 5 orders of magnitude, at any given point in time since symptom onset. This variation was not explained by age, sex, or severity of illness, and these variables were not associated with the modelled early or late phases of immune-mediated control of viral load. We explored the application of the mechanistic model to identify measured immune responses associated with the control of the viral load. Neutralising antibodies correlated strongly with modelled immune-mediated control of viral load amongst subjects who produced neutralising antibodies. Our models can be used to identify host and viral factors which control URT viral load dynamics, informing future treatment and transmission blocking interventions.

The Role of Heat Shock Protein 40 in Carcinogenesis and Biology of Colorectal Cancer.

Colorectal cancer (CRC) is the third most common cancer worldwide. Despite the enormous amount of effort in the diagnosis and treatment of CRC, the overall survival rate of patients remains low. The precise molecular and cellular basis underlying CRC has not been completely understood yet. Over time, new genes and molecular pathways involved in the pathogenesis of the disease are being identified. The accurate discovery of these genes and signaling pathways are important and urgent missions for the next generation of anticancer therapy research. Chaperone DnaJ, also known as Hsp40 (heat shock protein 40), has been of particular interest in CRC pathogenesis, as it is involved in the fundamental cell activities for maintaining cellular homeostasis. Evidence shows that protein family members of DnaJ/Hsp40 play both roles, enhancing and reducing the growth of CRC cells. In the present review, we focus on the current knowledge of the molecular mechanisms responsible for DnaJ/Hsp40 in CRC carcinogenesis and biology.

The Role of Heat Shock Protein 27 in Carcinogenesis and Treatment of Colorectal Cancer.

The incidence of colorectal cancer (CRC) has significantly increased in recent decades, which has made this disease an important global health issue. Despite many efforts, there is no useful prognostic or diagnostic biomarker for CRC. Heat shock protein 27 (Hsp27) is one of the most studied members of the Hsp family. It has attracted particular attention in CRC pathogenesis since it is involved in fundamental cell functions for cell survival. Evidence shows that Hsp27 plays important role in CRC progression and metastasis. Hsp27 overexpression has been observed in CRC and is suggested to be associated with CRC's poor prognosis. In the present review, we focus on the current knowledge of the role of Hsp27 in CRC carcinogenesis and the underlying mechanisms. In addition, we discuss the value of targeting Hsp27 in CRC treatment.

The Clinical Impact of Quantitative Cell-free DNA, KRAS, and BRAF Mutations on Response to Anti-EGFR Treatment in Patients with Metastatic Colorectal Cancer.

Colorectal cancer (CRC) is one of the most common leading causes of cancer death in the world. Although EGFR inhibitors have established efficacy in metastatic colorectal cancer (mCRC), some patients do not respond to this treatment. The EGFR inhibitors' failure and acquired resistance are partly due to KRAS and BRAF mutations. Thus, prognostic biomarkers that help to select eligible patients are highly in demand. To improve patient selection, assessment of mutational status in circulating cell free DNA (cfDNA), which possibly represents the dynamicity of tumor genetic status better than tumor tissue, could be advantageous. This review summarizes the current knowledge of the prognostic value of cfDNA in patients with mCRC treated with EGFR inhibitors with emphasis on the clinical importance of identification of KRAS and BRAF mutations.

Diabetes and COVID-19; a Review of Possible Mechanisms.

Coronavirus disease 2019 (SARS-CoV-2) (COVID-19) has recently raised worldwide public health concerns. The available data on COVID-19 in patients with diabetes is limited but generally indicate that there is an increased risk of developing COVID-19 infection in diabetic patients, which ultimately impacts the overall patient's survival. Various aspects might be involved; however, the exact mechanisms and interrelationships between diabetes and the novel COVID-19 have not yet been fully elucidated. This review summarizes the possible mechanisms by which present diabetes predispose individuals to COVID-19 infection, modulates the hostviral interactions and increases the risk of mortality. We hope this review can provide beneficial information for further studies and contribute to improved disease management of diabetic patients with COVID-19.