Of chloroquine and COVID-19

Coronavirus Disease 2019 and the Pediatric Gastroenterologist.

Between Bench and Bedside—Which Research Manuscripts Are Truly Translational?

Microbiota in viral infection and disease in humans and farm animals

Message from Griffin P. Rodgers, M.D., M.A.C.P., Director, NIDDK, on the Institute’s Obesity Research

Gene edited animal models applied in human disease research

Ebola virus disease (EVD) is a complex zoonosis that is highly virulent in humans. The largest recorded outbreak of EVD is ongoing in West Africa, outside of its previously reported and predicted niche. We assembled location data on all recorded zoonotic transmission to humans and Ebola virus infection in bats and primates (1976–2014). Using species distribution models, these occurrence data were paired with environmental covariates to predict a zoonotic transmission niche covering 22 countries across Central and West Africa. Vegetation, elevation, temperature, evapotranspiration, and suspected reservoir bat distributions define this relationship. At-risk areas are inhabited by 22 million people; however, the rarity of human outbreaks emphasises the very low probability of transmission to humans. Increasing population sizes and international connectivity by air since the first detection of EVD in 1976 suggest that the dynamics of human-to-human secondary transmission in contemporary outbreaks will be very different to those of the past.DOI: http://dx.doi.org/10.7554/eLife.04395.001

Intestinal microecology is the largest and most complex human microecology. The intestinal microflora plays an important role in human health. Imbalance of intestinal microflora contributes to the occurrence and development of many diseases. Recently, the treatment of human diseases by regulating intestinal microflora has become a research topic of interest. Traditional Chinese medicine considers the whole human body as the central concept in disease treatment strategies. It advocates maintaining the coordination and balance of the functions of various organs and systems of the human body, including the intestinal microflora. Traditional Chinese medicine improves the metabolism and immune function of the human body by regulating the intestinal microflora. The intestinal microflora could trigger pharmacological activity or reduce toxicity of drugs through regulating metabolism, which enables traditional Chinese medicine formulations to exert their best therapeutic effects. This review summarized the relationship between the intestinal microflora and digestive system, tumors, and other diseases. Furthermore, the role of traditional Chinese medicine in the treatment of tumors, and other diseases is discussed. The relationship among traditional Chinese medicine and the common intestinal microflora, pathogenesis of human diseases, and effective intervention methods were elaborated. In addition, we explored the research progress of traditional Chinese medicine in the treatment of various human diseases by regulating intestinal microflora to provide new treatment concepts. There is a close relationship between traditional Chinese medicine and the intestinal microflora. Traditional Chinese medicine formulations contribute to maintain the natural balance of the intestinal tract and the intestinal microflora to achieve treatment effects. This paper summarizes the mechanism of action of traditional Chinese medicine formulations in regulating the intestinal microflora in the prevention and treatment of various diseases. Furthermore, it summarizes information on the application of the interaction between traditional Chinese medicine preparations and the regulation of intestinal microflora in the treatment of common human diseases. Intestinal microflora plays a key role in traditional Chinese medicine in maintaining the natural balance of physiology and metabolism of human body. It will provide a theoretical basis for the traditional Chinese medicine preparations in the prevention and treatment of common human diseases, and simulate future research on this aspect.

Comparative transcriptomics of whole blood can be used to evaluate the systemic host response and its concordance between human and mouse malaria and aid the selection of appropriate models for translational malaria research.

Of Mice, Not Men: When the Bench-to-Bedside Bridge Is Broken.

Conventional cancer and transformed cell lines are widely used in cancer biology and other fields within biology. These cells usually have abnormalities from the original tumor itself, but may also develop abnormalities due to genetic manipulation, or genetic and epigenetic changes during long‐term passages. Primary cultures may maintain lineage functions as the original tissue types, yet they have a very limited life span or population doubling time because of the nature of cellular senescence. Primary cultures usually have very low yields, and the high variability from any original tissue specimens, largely limiting their applications in research. Animal models are often used for studies of virus infections, disease modeling, development of antiviral drugs, and vaccines. Human viruses often need a series of passages in vivo to adapt to the host environment because of variable receptors on the cell surface and may have intracellular restrictions from the cell types or host species. Here, we describe a long‐term cell culture system, conditionally reprogrammed cells (CRCs), and its applications in modeling human viral diseases and drug discovery. Using feeder layer coculture in presence of Y‐27632 (conditional reprogramming, CR), CRCs can be obtained and rapidly propagated from surgical specimens, core or needle biopsies, and other minimally invasive or noninvasive specimens, for example, nasal cavity brushing. CRCs preserve their lineage functions and provide biologically relevant and physiological conditions, which are suitable for studies of viral entry and replication, innate immune responses of host cells, and discovery of antiviral drugs. In this review, we summarize the applications of CR technology in modeling host‐virus interactions and human viral diseases including severe acute respiratory syndrome coronavirus‐2 and coronavirus disease‐2019, and antiviral discovery.

Natural virus reservoirs such as wild bats, birds, rodents and non-human primates are generally non-model organisms that have, until recently, presented limited opportunities for in-depth study. Next-generation sequencing provides a way to partially circumvent this limitation, since the methods required for data acquisition and analysis are largely species-independent. Comparative genomics and other 'omics' provide new opportunities to study the structure and function of various biological systems of wild species that are otherwise out of reach. Genomes of natural reservoir hosts can help to identify dominant pathways of virus-host interaction and to reveal differences between susceptible and resistant organisms, populations and species. This is of great scientific interest and may also provide a resource for the rational design of treatments for viral diseases in humans and livestock. In this way, we will 'learn from nature' and one day apply this knowledge to create disease-resistant livestock or develop novel therapeutic and prevention strategies. Reservoir host genomics will also open up possibilities for developing novel vaccines for wildlife, aid in the development of new diagnostic platforms, and have broad implications for developmental and evolutionary biology. In this review, the authors focus on natural reservoir hosts of viral pathogens, although most of the discussion points should be equally applicable to natural reservoirs of pathogenic bacteria, fungi or other parasites.

The resistance to mousepox is correlated with the production of type I cytokines: interleukin (IL)-2, IL-12, interferon (IFN)-gamma and tumour necrosis factor (TNF)-alpha. We intend to describe the modulation of generalized ectromelia virus (EV) infection with exogenous administration of mrIFN-gamma and mrTNF-alpha separately and in combination using susceptible BALB/c mice. The treatment schemes presented resulted in the localization of the generalized EV infection and its development into non-fatal sloughing of the infected limb. This was accompanied by low virus titres in the treated mice due to control of systemic virus replication and virus clearance. The balance of type I versus type II cytokines was dominated by a type I response in the treated groups. The group treated with the combination of IFN-gamma and TNF-alpha exhibited the best survival with Th1-dominant (IFN-gamma and IL-12) cytokine profiles, whereas the TNF-alpha-treated group of mice was less successful in clearance of virus and demonstrated the lowest survival rate. The successful cytokine treatment schemes in this orthopoxvirus model system may have important implications in the treatment of viral diseases in humans and, in particular, of variola virus infection.

Marburg virus (MARV) is a filovirus with documented human case-fatality rates of up to 90%. Here, we evaluated the therapeutic efficacy of remdesivir (GS-5734) in nonhuman primates experimentally infected with MARV. Beginning 4 or 5 days post inoculation, cynomolgus macaques were treated once daily for 12 days with vehicle, 5 mg/kg remdesivir, or a 10-mg/kg loading dose followed by 5 mg/kg remdesivir. All vehicle-control animals died, whereas 83% of animals receiving a 10-mg/kg loading dose of remdesivir survived, as did 50% of animals receiving a 5-mg/kg remdesivir regimen. Remdesivir-treated animals exhibited improved clinical scores, lower plasma viral RNA, and improved markers of kidney function, liver function, and coagulopathy versus vehicle-control animals. The small molecule remdesivir showed therapeutic efficacy in this Marburg virus disease model with treatment initiation 5 days post inoculation, supporting further assessment of remdesivir for the treatment of Marburg virus disease in humans.

G-CSF–primed hematopoietic stem cells or G-CSF per se accelerate recovery and improve survival after liver injury, predominantly by promoting endogenous repair programs

Given their clinical importance for the treatment of acute and chronic neurodegenerative diseases in humans including nerve injuries (e.g. Alzheimer's disease, Parkinson's disease, diabetic neuropathy) a number of different approaches were pursued to obtain selectively acting FK506-binding protein (FKBP) ligands: computational methods and target-oriented screening of natural compound and synthetic product libraries. The resulting monofunctional ligands, which inhibit the peptidyl prolyl cis/trans isomerase activity of FKBPs, highlight the role of these enzymes in neuronal signaling. The exploration of the mechanisms of neuroregenerative and neuroprotective action of some of these compounds is the main focus of ongoing neuropharmaceutical research.