The high affinity of baricitinib for the numb-associated kinase (NAK) family, its anti-inflammatory properties, with its advantageous pharmacokinetic properties, appear to make it a special case among the approved drugs.  In addition, the potential for combination therapy with baracitinib is high, because of its low plasma protein binding and minimal interaction with CYP enzymes and drug transporters. Combinations of baricitinib with these direct-acting antivirals could reduce viral infectivity, viral replication, and the aberrant host inflammatory response. This work demonstrates that the use of an AI-driven knowledge graph can facilitate rapid drug development.

COVID-19: combining antiviral and anti-inflammatory treatments

The intestine requires a great deal of energy to maintain its health and function; thus, energy deficits in the intestinal mucosa may lead to intestinal damage. Aspartate (Asp) is an essential energy source in the intestinal mucosa and plays a vital part in gut health. In the current study, we hypothesized that dietary supplementation of Asp could alleviate DSS-induced colitis via improvement in the colonic morphology, oxidative stress, cell apoptosis, and microbiota composition in a mouse model of dextran. Asp administration decreased the disease activity index, apoptosis, myeloperoxidase, eosinophil peroxidase, and proinflammatory cytokine (IL-1β and TNF-α) concentrations in the colonic tissue, but improved the body weight, average daily food intake, colonic morphology, and antioxidant-related gene (GPX1 and GPX4) expression in DSS-treated mice. Expression levels of RIPK1 and RIPK3 were increased in the colon following Asp administration in the DSS-induced mice, whereas the MLKL protein expression was decreased. 16S rRNA sequencing showed that Asp treatment increased the abundance of Lactobacillus and Alistipes at the gene level, and Bacteroidetes at the phylum level, but decreased the abundance of Actinobacteria and Verrucomicrobia at the phylum level. Asp may positively regulate the recovery of DSS-induced damage by improving the immunity and antioxidative capacity, regulating RIPK signaling and modulating the gut microbiota composition.

/pdf/improvement-of-ulcerative-colitis-by-aspartate-via-ripk-1ug1ibh0.pdf

Improvement of Ulcerative Colitis by Aspartate via RIPK Pathway Modulation and Gut Microbiota Composition in Mice

Pancreatic cancer remains the third leading cause of death amongst men and women in the United States. Pancreatic ductal adenocarcinoma (PDAC), the most common type of pancreatic cancer maintains its reputation of being the most aggressive with a poor prognosis. One of the contributing factors to the high mortality of PDAC is the absence of biomarkers for early detection of disease and the complexity of tumor biology and genomics. In this review, we explored the current understanding of epigenetics and diagnostic biomarkers in PDAC and summarized recent advances in molecular biology. We discussed current guidelines on diagnosis, prognosis, and treatment, especially in high-risk individuals. We also reviewed studies that have touched on identifying biomarkers and the role they play in making early diagnosis although there are currently no screening tools for PDAC. We explored the recent understanding of epigenetic alterations of PDAC and the future implications for early detection and prognosis. In conclusion, the new and emerging advances in the detection and treatment of PDAC can lead to an improvement in the current outcome of PDAC.

/pdf/molecular-markers-of-pancreatic-cancer-a-10-year-3m6elki7.pdf

Molecular Markers of Pancreatic Cancer: A 10-Year Retrospective Review of Molecular Advances

Infliximab is a monoclonal antibody that plays an important role in the management and treatment of chronic inflammatory bowel diseases (IBD). Due to its macromolecular structure, its delivery through the oral route is challenging, limiting its administration to only via the parenteral route. The rectal route offers an alternative way for administering infliximab, allowing it to be localised at the disease site and circumventing its passage across the alimentary canal and thus, maintaining its integrity and bioactivity. Three-dimensional (3D) printing is an advanced production technology that permits the creation of dose-flexible drug products from digital designs. The current study assessed the feasibility of utilising semi-solid extrusion 3D printing for the fabrication of infliximab-loaded suppositories for the local treatment of IBD. Various printing inks composed of Gelucire® (48/16 or 44/14) mixed with coconut oil and/or purified water were investigated. It was shown that following reconstitution in water, the infliximab solution can be directly incorporated into the printing ink of Gelucire® 48/16 and can withstand the extrusion process, resulting in well-defined suppositories. Since water content and temperature are critical for safeguarding infliximab's potency, the effect of changing the composition of the printing inks and printing parameters on infliximab's biologic efficiency was evaluated by measuring its binding capacity (i.e., the amount of infliximab that actively binds to its antigen to exert an effect). Despite drug loading assays showing that infliximab remains intact following printing, it was found that the incorporation of water in isolation results in only ∼65% binding capacity. However, when oil is added to the mixture, infliximab's binding capacity increases up to ∼85%. These promising results demonstrate that 3D printing has the potential to be exploited as a novel platform for fabricating dosage forms containing biopharmaceuticals, avoiding patients' compliance issues observed with injectables and addressing their unmet needs. 

https://discovery.ucl.ac.uk/id/eprint/10167891/2/Awad_3D%20printed%20infliximab%20suppositories%20for%20rectal%20biologic%20delivery_VoR.pdf

3D printed infliximab suppositories for rectal biologic delivery

Oral hemorrhagic blister and its possible related factors: Analyzes of reported cases in the literature

Inflammatory bowel disease (IBD) is a term that encompasses conditions characterized by chronic inflammation of the gastrointestinal tract (GIT). It includes Crohn's disease and ulcerative colitis. Major scientific organizations interested in gastrointestinal systems or GIT-focused organizations worldwide release guidelines for diagnosing, classifying, managing, and treating IBD. However, there are subtle differences among each of these guidelines. This review evaluates four evidence-based guidelines in the management of IBD and seeks to highlight the differences and similarities between them. The main differences in the evaluated guidelines were in diagnosis and treatment recommendations. The diagnosing recommendations were comparable amongst the four guidelines; however, some were more specific about limiting the number of interventions necessary to confirm a diagnosis. Regarding treatment options, each guideline had clear suggestions about what was considered ideal. Although the treatment options were identical, the main differences existed in the recommended diets and initial therapy in patients with moderate disease. Clinical practice guidelines (CPGs) recommend evidence-based practice from opinion leaders in clinical decision-making. Rather than dictating a one-size-fits-all approach in IBD management, reviewing various guidelines can enhance the cross-pollination of ideas amongst clinicians to improve decision-making. Clearly describing and appraising evidence-based reasoning for scientific recommendations remain driving factors for quality patient care. The effectiveness of CPGs in improving health and the complexities of their formation requires constant review to maximize constructive criticisms and explore possible improvements.

A Review of Four Practice Guidelines of Inflammatory Bowel Disease.

# Background
The ongoing coronavirus disease-19 (COVID-19) pandemic, caused by the novel coronavirus 2 (SARS-CoV-2) has triggered a worldwide search for medications addressing the morbidity and mortality associated with it. Various medications have been proposed and applied to control COVID-19 based on previous experiences with other viral infections. Some of these have been shown to be harmful or lack efficacy. This review discusses the medications that have been repurposed for SARS-CoV-2, experimental medications undergoing clinical trials, as well as the regional variations in COVID-19 treatments. 

# Methods
A literature search was conducted to cover the period of January 2020 to September 2020 using the keywords “medications, treatment, therapeutics, pharmacological management for COVID-19” in various combinations as search strings. PubMed, LitCOVID, Google Scholar, Science Direct, and clinicaltrials.gov were the databases utilized.

# Results
Evidence from ongoing clinical trials has shown promise with antiviral medications such as remdesivir, as well as corticosteroids, and convalescent plasma for severe cases of COVID-19. There is still, however, some conflicting evidence on the true benefits of these treatments. Other medications such as interferons, monoclonal antibodies, immune modulators, do not have enough clinical evidence of their safety and efficacy in COVID-19 patients for their recommended use. The role of anticoagulants and pulmonary vasodilators is still being explored. The efficacy of hydroxychloroquine is yet to be demonstrated in COVID-19 patients and is currently no longer recommended. Experimental medications targeting specific viral proteases are future promising therapies. 

# Conclusions
The retinue of medications being used to treat COVID-19 is evolving and expanding as more clinical trials provide results. Several potential medication therapies are currently being investigated. While awaiting an approved safe and efficacious medication to treat this virus, a periodic review of on-going research is highly encouraged.

/pdf/pharmacological-treatment-of-covid-19-an-update-31ebxovai1.pdf

Pharmacological treatment of COVID-19: an update

Angina bullosa haemorrhagica (ABH) is a benign disorder of the oral mucosa. Patients present with blood-filled blisters in the oral cavity that are not associated with bleeding disorders. These blisters can sometimes be painful. This case report aims to highlight the features of ABH, which will help to distinguish it from other oral diseases and improve the quality of care for patients with this rare disease.

https://www.cureus.com/articles/88683-angina-bullosa-hemorrhagica-a-rare-and-interesting-presentation.pdf

Angina Bullosa Hemorrhagica: A Rare and Interesting Presentation

Gianotti-Crosti syndrome (GCS) is a benign acral dermatitis commonly seen in children younger than five years of age with no gender predilection. Clinical features are often vague, including but not limited to fever, lymphadenopathy, and erythematous papular rash that commonly spares the trunk, palms, and soles of the feet. It is presumably underdiagnosed as most children presenting with a widespread papular rash are diagnosed with non-specific viral exanthem. This benign condition has been linked to multiple viruses, and treatment is mainly supportive. We present a previously healthy 18-month-old girl who presented to the emergency room with a progressive skin rash and low-grade fever 10 days after receiving routine immunizations. GCS was diagnosed, and she received supportive care with spontaneous resolution of symptoms in four weeks.

/pdf/gianotti-crosti-syndrome-a-benign-dermatosis-3kdv00wn.pdf

Imoh L Ebong

Papers

A Review of Four Practice Guidelines of Inflammatory Bowel Disease.

Pharmacological treatment of COVID-19: an update

Angina Bullosa Hemorrhagica: A Rare and Interesting Presentation

Gianotti-Crosti Syndrome: A Benign Dermatosis