Current Pharmaceutical Biotechnology - Volume 21, Issue 6, 2020

Celiac Disease (CD) is an immune-mediated enteropathy, generally of the proximal intestine, that occurs in genetically susceptible individuals triggered by the ingestion of gluten. The incidence and frequency of CD are increasing, and it is predicted that CD affects approximately 1% of the people worldwide. The common clinical manifestations of CD are divided in two sections, including classic and non-classic symptoms that can be created in childhood and adulthood. The relationship between pathogenic and non-pathogenic bacteria with CD is complex and multidirectional. In previous published studies, results demonstrated the triggering impact of bacteria, viruses, and parasites on initiation and development of Inflammatory Bowel Disease (IBD) and Irritable Bowel Syndrome (IBS). Different studies revealed the inducing effect of pathogenic and non-pathogenic bacteria on CD. However, increasing evidence proposes that some of these microorganisms can also play several positive roles in CD process. Although information of the pathogenesis of the CD is quickly expanding, the possible role of bacteria needs further examination. In conclusion, with respect to the possible correlation between different bacteria in CD, the current review-based study aims to discuss the possible relationship between CD and pathogenic and non-pathogenic bacteria and to show various and significant aspects of mechanisms involved in the CD process.

Objective: The high cost of orphan drugs limits their access by many patients, especially in low- and middle-income countries. Many orphan drugs are off-patent without alternative generic or biosimilar versions available. Production of these drugs at the point-of-care, when feasible, could be a cost-effective alternative. Methods: The financial feasibility of this approach was estimated by setting up a small-scale production of recombinant human acid alpha-glucosidase (rhGAA). The commercial version of rhGAA is Myozyme™, and Lumizyme™ in the United States, which is used to treat Pompe disease. The rhGAA was produced in CHO-K1 mammalian cells and purified using multiple purification steps to obtain a protein profile comparable to Myozyme™. Results: The established small-scale production of rhGAA was used to obtain a realistic cost estimation for the magistral production of this biological drug. The treatment cost of rhGAA using bedside production was estimated at $3,484/gram, which is 71% lower than the commercial price of Myozyme ™. Conclusion: This study shows that bedside production might be a cost-effective approach to increase the access of patients to particular life-saving drugs.

Background: Arthrophytum scoparium (Pomel) Iljin (Amaranthaceae family) has been widely used in traditional Tunisian medicine to treat many disorders such as migraine, headache, and neurological disorders. This study investigates the effect of Arthrophytum scoparium Aqueous Extract (ASAE) on cognitive impairments and oxidative injury induced by galactose (10%) in a mouse model. Materials and Methods: The mice were divided randomly into 4 experimental groups, including the control group (saline water 9 ‰), Galactose group, Scop group (300 mg/kg/d), and Scop+Gal group (300 mg/kg/d). Mice received the corresponding solutions by intraperitoneal injection (i.p.) for 7 days before the Y-maze active tests. Galactose 10% was given to all groups except control and Scop groups, 30 min before the trial. Levels of Acetylcholinesterase Activity (AChE), Ascorbic Acid (AA), Gluthatione (GSH) and Malondialdehyde (MDA) in mice brains were examined. Results: Chronic administration of galactose significantly impaired cognitive performance in Y maze, caused marked oxidative damages and a significant increase in the acetylcholinesterase activity as compared to other groups. On the contrary, ASAE (300 mg/kg) treatment suppressed galactoseinduced oxidative damage by ameliorating the increased levels of GSH and AA. Moreover, ASAE treatment reduced brain AChE activities in the galactose-induced model. Conclusion: These findings suggest that ASAE exerts potent anti-amnesic effects via the modulation of cholinergic and antioxidant activities. The observed pharmacological activities should be further evaluated by detailed experimental studies and validated by clinical trials.

Background and Objective: This study was designed to estimate the long-term effects of zinc oxide nanoparticles/green tea (ZnONPs/GTE) complex against monosodium glutamate (MSG). The antioxidant/oxidative status, testosterone levels, DNA damage, and histopathological changes of testis were evaluated. Methods: The rats were divided into eight groups that were treated as follows: saline, the lower dosage of MSG (6.0 mg/kg), the higher dosage of MSG (17.5 mg/Kg), GTE, ZnONPs, ZnONPs/GTE and the last two groups were treated with the lower dosage of MSG or the higher dosage of MSG with ZnONPs/GTE complex. The data showed minimal toxicity in testicular tissue after the administration of ZnONPs. Results: The MSG treatment in the adult male rats reduced testosterone levels and disrupted testicular histology, which revealed dose-dependence of MSG. Also, ZnONPs induced testicular dysfunction through the interference of antioxidant/oxidant balance and suppression of testosterone levels as well as induction of cellular damage of testis. The combination of ZnONPs with GTE complex significantly protects against MSG or ZnONPs toxicity by decreasing the DNA damage, oxidative stress, and enhancement of antioxidant as well as histological structure of testis. Conclusion: We could recommend using ZnONPs/GTE complex to reduce the toxicity of ZnONPs and MSG on the testis at the cellular and oxidative stress levels.

Background: Alternative medicine is available for those diseases which cannot be treated by conventional medicine. Ayurveda and herbal medicines are important alternative methods in which the treatment is done with extracts of different medicinal plants. This work is concerned with the evaluation of anti-stress bioactive compounds from the ethanolic root extract of Hemidesmus indicus. Methods: Gas chromatography and Mass Spectrum studies are used to identify the compounds present in the ethanolic extract based on the retention time, area. In order to perform docking studies, Vasopressin model is generated using modeling by Modeller 9v7. Vasopressin structure is developed based on the crystal structure of neurophysin-oxytocin from Bos taurus (PDB ID: 1NPO_A) collected from the PDB data bank. Using molecular dynamics simulation methods, the final predicted structure is obtained and further analyzed by verifying 3D and PROCHECK programs, confirmed that the final model is reliable. The identified compounds are docked to vasopressin for the prediction of anti-stress activity using GOLD 3.0.1 software. Results: The predicted model of Vasopressin structure is stabilized and confirmed that it is a reliable structure for docking studies. The results indicated ARG4, THR7, ASP9, ASP26, ALA32, ALA 80 in Vasopressin are important determinant residues in binding as they have strong hydrogen bonding with phytocompounds. Among the 21 phytocompounds identified and docked, molecule Deoxiinositol, pentakis- O-(trimethylsilyl) showed the best docking results with Vasopressin. Conclusion: The identified compounds were used for anti-stress activity by insilico method with Vasopressin which plays an important role in causing stress and hence selected for inhibitory studies with phytocompounds. The phytocompounds are inhibiting vasopressin through hydrogen bodings and are important in protein-ligand interactions. Docking results showed that out of twenty-one compounds, Deoxiinositol, pentakis-O-(trimethylsilyl) showed best docking energy to the Vasopressin.

Background: Tropane Alkaloids (TAs) are important drugs for curing many diseases in the medical industry. Methods: To sustainably exploit TA resources in endangered traditional Tibetan herbs, the hairy root (HR) systems of Przewalskia tangutica Maxim. and Anisodus tanguticus Maxim. were compared under the same culture conditions. Results: The results indicated that both the Agrobacterium rhizogenes strains and explants affected the HR induction frequency, MSU440, A4 and LBA9402 strains could induce hairy roots following infection of cotyledon and hypocotyl of A. tanguticus while LBA9402 could not induce HR on either explants of P. tangutica. The efficiency of LBA9402 was higher than A4 and MSU440 on A. tanguticus and A4 was better strain than MSU440 on P. tangutica. The hypocotyl explant was more suitable for P.tangutica and cotyledon explant was better for A.tangutica with a transformation frequency of 33.3% (P. tangutica) and 82.5% (A. tanguticus), respectively. In a flask reactor system, both the growth curves of HR for two species both appeared to be “S” curve; however, the HR of P. tangutica grew more rapidly than that of A. tanguticus, and the latter accumulated more biomass than the former. As the culture volume increased, the HR proliferation coefficient of both the species increased. HPLC analysis results showed that the content of TAs in the HR of P. tangutica was 257.24mg/100g·DW, which was more than that of A. tanguticus HR (251.08mg/100g·DW), and the anisodamine in the Pt- HR was significantly higher than that in At-HR. Moreover, tropane alkaloids in the HR of the two species were all significantly higher than that of the roots of aseptic seedlings. Conclusion: Our results suggest that HR of P. tangutica and A. tanguticus both could provide a useful platform for sustainable utilization of two Tibetan medicinal plants in the Qinghai-Tibetan Plateau in the future.

Background/Aims: This case series presents the novel Genetic Addiction Risk Score (GARS®) coupled with a customized pro-dopamine regulator matched to polymorphic reward genes having a hypodopaminergic risk. Methods: The proband is a female with a history of drug abuse and alcoholism. She experienced a car accident under the influence and voluntarily entered treatment. Following an assessment, she was genotyped using the GARS, and started a neuronutrient with a KB220 base indicated by the identified polymorphisms. She began taking it in April 2018 and continues. Results: She had success in recovery from Substance Use Disorder (SUD) and improvement in socialization, family, economic status, well-being, and attenuation of Major Depression. She tested negative over the first two months in treatment and a recent screening. After approximately two months, her parents also decided to take the GARS and started taking the recommended variants. The proband’s father (a binge drinker) and mother (no SUD) both showed improvement in various behavioral issues. Finally, the proband’s biological children were also GARS tested, showing a high risk for SUD. Conclusion: This three-generation case series represents an example of the impact of genetic information coupled with an appropriate DNA guided “Pro-Dopamine Regulator” in recovery and enhancement of life.