Molecular Docking and Dynamics Simulation of Natural Phenolic Compounds with GSK-3β: A Putative Target to Combat Mortality in Patients with COVID-19

Objective: In this study, molecular docking analysis was performed to evaluate the binding affinity of 52 plant-based phenolics with the GSK-3β active sites. Moreover, Molecular Dynamics (MD) simulation was conducted to investigate the stability of interactions between the topranked phenolics and residues within the GSK-3β active sites. Methods: Molecular docking and MD simulations were performed using AutoDock and Discovery Studio Client software, respectively. Thereafter, pharmacokinetic and toxicological properties of top inhibitors were predicted using bioinformatics web tools. This study aimed to identify the most effective amino acids involved in the inhibition of GSK-3β based on the most stabilizing interactions between the residues and compounds, and also by considering the degree centrality in the ligand-amino acid interaction network for GSK-3β. Results: It was observed that procyanidin and amentoflavone could bind to the GSK-3β active sites at the picomolar (pM) scale as well as the binding affinity of ∆G binding < -13 kcal/mol, while the inhibition constant for theaflavin 3’-gallate, procyanidin B4, and rutin was calculated at the nanomolar (nM) scale, suggesting that these phenolic compounds can be considered as potential effective GSK-3β inhibitors. Furthermore, Val70, Ala83, Val135, and Tyr134 were found to be the most important amino acids involved in the inhibition of GSK-3β. Conclusion: The results of the current study may be useful in the prevention of several human disorders, including COVID-19, cancers, Alzheimer’s disease, diabetes mellitus, and cardiovascular diseases. However, wet-lab experiments need to be performed in the future.

Childhood Infectious Encephalitis: An Overview of Clinical Features, Investigations, Treatment and Recent Patents

Background:: Infectious encephalitis is a serious and challenging condition to manage. This overview summarizes the current literature regarding the etiology, clinical manifestations, diagnosis, management and recent patents of acute childhood infectious encephalitis. Methods:: We used PubMed Clinical Queries and keywords of “encephalitis” AND “childhood” as a search engine, and patents were searched using the key term “encephalitis” in google.patents.com and patentsonline.com. Results:: Viral encephalitis is the most common cause of acute infectious encephalitis in children. In young children, the clinical manifestations can be non-specific. Provision of empiric antimicrobial therapy until a specific infectious organism has been identified, which in most cases includes acyclovir, is the cornerstone of therapy. Advanced investigation tools, including nucleic acid-based test panel and metagenomic next generation sequencing, improve diagnostic yield of identifying an infectious organism. Supportive therapy includes adequate airway and oxygenation, fluid and electrolyte balance, and cerebral perfusion pressure support and seizure control. Recent patents are related to diagnosis, treatment and prevention of acute infectious encephalitis. Conclusions:: Viral encephalitis is the most common cause of acute infectious encephalitis in children and is associated with significant morbidity. Recent advances in understanding the genetic basis and immunological correlation of infectious encephalitis may improve treatment. Third-tier diagnostic tests may be incorporated into clinical practice. Treatment is targeted at the infectious process but remains mostly supportive. Specific antimicrobial agents and vaccines development is ongoing.

Nummular Eczema: An Updated Review

Background: Nummular eczema may mimic diseases that present with annular configuration and the differential diagnosis is broad. Objective: This article aimed to provide an update on the evaluation, diagnosis, and treatment of nummular eczema. Methods: A PubMed search was performed in Clinical Queries using the key terms “nummular eczema”, “discoid eczema”, OR “nummular dermatitis”. The search strategy included meta-analyses, randomized controlled trials, clinical trials, observational studies, and reviews. The search was restricted to the English literature. The information retrieved from the above search was used in the compilation of the present article. Patents were searched using the key terms “nummular eczema”, “discoid eczema”, OR “nummular dermatitis” in www.google.com/patents and www.freepatentsonline.com. Results: Nummular eczema is characterized by sharply defined, oval or coin-shaped, erythematous, eczematous plaques. Typically, the size of the lesion varies from 1 to 10 cm in diameter. The lesions are usually multiple and symmetrically distributed. Sites of predilection include the lower limbs followed by the upper limbs. The lesions are usually intensely pruritic. The diagnosis is mainly clinical based on the characteristic round to oval erythematous plaques in a patient with diffusely dry skin. Nummular eczema should be distinguished from other annular lesions. Dermoscopy can reveal additional features that can be valuable for correct diagnosis. Biopsy or laboratory tests are generally not necessary. However, a potassium hydroxide wet-mount examination of skin scrapings should be performed if tinea corporis is suspected. Because contact allergy is common with nummular eczema, patch testing should be considered in patients with chronic, recalcitrant nummular eczema. Avoidance of precipitating factors, optimal skin care, and high or ultra-high potency topical corticosteroids are the mainstay of therapy. Recent patents related to the management of nummular eczema are also discussed. Conclusion: With proper treatment, nummular eczema can be cleared over a few weeks, although the course can be chronic and characterized by relapses and remissions. Moisturizing of the skin and avoidance of identifiable exacerbating factors such as hot water baths and harsh soaps may reduce the frequency of recurrence. Diseases that present with annular lesions may mimic nummular eczema and the differential diagnosis is broad. As such, physicians must be familiar with this condition so that an accurate diagnosis can be made, and appropriate treatment initiated.

Childhood Alopecia Areata: An Overview of Treatment and Recent Patents

Background: Alopecia Areata (AA) is a systemic autoimmune condition which usually starts in childhood. Objective: This article aims to review genetics, therapy, prognosis and recent patents for AA. Methods: We used clinical queries and keywords of “alopecia areata” AND “childhood” as search engine. Patents were searched using the key term “alopecia areata” in Patents.google.com and freepatentsonline.com. Results: Due to an immune mediated damage of the hair follicles, hair is lost from the scalp and other areas of the body temporarily or even permanently. Children with AA are generally healthy. Evidence of genetic association and increased predisposition for AA was found by studying families with affected members. Pathophysiologically, T- lymphocytes attack hair follicles and cause inflammation and destruction of the hair follicles and hair loss. In mild cases, there would be well demarcated round patchy scalp hair loss. The pathognomonic “exclamation mark hairs” may be seen at lesion periphery. In more severe cases, the hair loss may affect the whole scalp and even the whole body. The clinical course is also variable which may range from transient episodes of recurrent patchy hair loss to an indolent gradually deteriorating severe hair loss. The treatment of AA depends on factors including patients’ age, extent of the hair loss, duration of disease, psychological impact, availability and side effect profile of the treatments. For localized patchy alopecia, topical application of corticosteroids and/or intralesional corticosteroids are the treatment of choice. Other topical treatments include minoxidil, anthralin, coal tar and immunotherapy. In severe resistant cases, systemic immunosuppressants may be considered. Although herbal medicine, acupuncture, complementary and alternative medicine may be tried on children in some Asian communities, the evidence to support these practices are lacking. To date, only few recent patents exist in topical treatments including Il-31, laser and herbal medications. Clinical efficacy is pending for these treatment modalities. Conclusions: None of the established therapeutic options are curative. However, newer treatment modalities including excimer laser, interleukin-31 antibodies and biologics are evolving so that there may be significant advances in treatment in the near future. AA can be psychosocially devastating. It is important to assess the quality of life, degree of anxiety, social phobia and mood of the patients and their families. Psychological support is imperative for those who are adversely affected psychosocially.

Human Ascariasis: An Updated Review

Background: Ascaris lumbricoides is the most common helminthic infection. More than 1.2 billion people have ascariasis worldwide. Objective: This article aimed to provide an update on the evaluation, diagnosis, and treatment of ascariasis. Methods: A PubMed search was conducted in February 2020 in Clinical Queries using the key terms “ascariasis” OR "Ascaris lumbricoides". The search strategy included meta-analyses, randomized controlled trials, clinical trials, observational studies, and reviews published within the past 10 years. The search was restricted to the English literature. The information retrieved from the above search was used in the compilation of the present article. Patents were searched using the key term “ascariasis” OR "Ascaris lumbricoides" in www.freepatentsonline.com. Results: Ascaris lumbricoides is transmitted through ingestion of embryonated eggs from fecal-contaminated material. Ascariasis has high endemicity in tropical and subtropical areas. Predisposing factors include poverty, poor sanitation, inadequate sewage disposal, and poor personal hygiene. The prevalence is greatest in children younger than 5 years of age. The majority of patients with intestinal ascariasis are asymptomatic. For those with symptoms, anorexia, nausea, bloating, abdominal discomfort, recurrent abdominal pain, abdominal distension, and intermittent diarrhea are not uncommon. Other clinical manifestations vary widely, depending on the underlying complications. Complications include Löeffler syndrome, intestinal obstruction, biliary colic, recurrent pyogenic cholangitis, cholecystitis, acalculous cholecystitis, obstructive jaundice, cholelithiasis, pancreatitis, and malnutrition. The diagnosis is best established by microscopic examination of fecal smears or following concentration techniques for the characteristic ova. Patients with A. lumbricoides infection warrant anthelminthic treatment, even if they are asymptomatic, to prevent complications from migration of the parasite. Albendazole and mebendazole are the drugs of choice for children and nonpregnant individuals with ascariasis. Pregnant women with ascariasis should be treated with pyrantel pamoate. Recent patents related to the management of ascariasis are also discussed. Conclusion: The average cure rate with anthelminthic treatment is over 95%. Unfortunately, most treated patients in endemic areas become re-infected within months. Health education, personal hygiene, improved sanitary conditions, proper disposal of human excreta, and discontinuing the use of human fecal matter as a fertilizer are effective long-term preventive measures. Targeting deworming treatment and mass anthelminthic treatment should be considered in regions where A. lumbricoides is prevalent.

Anti-Inflammatory and Gastroprotective Properties of Aspirin - Entrapped Solid Lipid Microparticles

Background: Aspirin is a nonsteroidal anti-inflammatory drug that is very effective in the treatment of inflammation and other health conditions, however, it causes gastric irritation. Recently, researchers have developed patents (US9757529, 2019) of inhalable aspirin for rapid absorption and circumvention of gastric irritation. Objective: The aim of this work was to formulate aspirin-loaded lipid based formulation in order to enhance oral bioavailability and inhibit gastric irritation. Methods: This solid lipid microparticles loaded with aspirin (SLM) was formulated by a modified cold homogenization-solvent evaporation method. In vitro studies such as in vitro drug release, particle size, Encapsulation Efficiency (EE), micromeritic properties and loading capacity were carried out. Pharmacodynamics studies such as anti-inflammatory and ulcerative properties of the SLM were also carried out in Wistar rats. Results: The results showed that aspirin entrapped SLM exhibited the highest EE of 72% and particle size range of 7.60 + 0.141µm to 20.25 + 0.070µm. Formulations had about 55% drug release at 6h in simulated intestinal fluid pH 6.8. The formulations had good flowability that could facilitate filling into hard gelatin capsule shells. The SLM exhibited 100% gastroprotection against aspirin-induced ulcers (p < 0.05). The percentage of anti-inflammatory activities also showed that aspirin-entrapped SLM had 78% oedema inhibition at 7h, while the reference had 68% inhibition at 7h. Conclusion: Aspirin-entrapped SLM showed good sustained-release properties, enhanced antiinflammatory properties and total gastric protection from aspirin-induced ulcers and could be used as once-daily oral aspirin.