Recent Advancements in Reducing the Off-Target Effect of CRISPR-Cas9 Genome Editing.

The CRISPR-Cas (Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)) and the associated protein (Cas9) system, a young but well-studied genome-editing tool, holds plausible solutions to a wide range of genetic disorders. The single-guide RNA (sgRNA) with a 20-base user-defined spacer sequence and the Cas9 endonuclease form the core of the CRISPR-Cas9 system. This sgRNA can direct the Cas9 nuclease to any genomic region that includes a protospacer adjacent motif (PAM) just downstream and matches the spacer sequence. The current challenge in the clinical applications of CRISPR-Cas9 genome-editing technology is the potential off-target effects that can cause DNA cleavage at the incorrect sites. Off-target genome editing confuses and diminishes the therapeutic potential of CRISPR-Cas9 in addition to potentially casting doubt on scientific findings regarding the activities of genes. In this review, we summarize the recent technological advancements in reducing the off-target effect of CRISPR-Cas9 genome editing.

Assessment of Dispensing Malpractice in Community Drug Retail Outlets in South Gondar Zone, Northwest Ethiopia: A Simulated Patient Experience.

Background: Pharmacy professionals in community drug retail outlets, as the most accessible personnel for the community, are engaged in consultation and responding to health problems in addition to filling prescriptions. In doing so, different dispensing malpractices are observed and much is not known on the issue in Ethiopia. Objective: The study aimed at assessing dispensing malpractice at pharmacies, drug stores and drug vendors in South Gondar zone. Methodology: A cross-sectional study design with a descriptive approach was applied from April 1 to June 30. The data was collected using the simulated patient method. Seven prescription-only medicines and a diarrheal case were requested during visit. All drug retail outlets in South Gondar zone that were in service during data collection were visited. Results: Almost all prescription-only medications were dispensed without prescription at all community drug retail outlets. Of all the dispensaries, 19 (82.6%) provided a partial dosage regimen of amoxicillin. Presence of fever and pregnancy status were asked about by dispensers in only 8% and 20% of visits for diarrhea, respectively. Medication history was also rarely requested. Medication was dispensed in 80% of visits for diarrhea, all of which included antimicrobials. Oral rehydration salt was considered in only two (10%) dispensaries. Conclusion: Dispensing medications without a prescription is common in community drug retail outlets in South Gondar zone in Amhara Regional State. Our findings also showed that detailed assessments of patients' signs and symptoms are not performed properly by the dispensers to understand the diarrheal case. Training of pharmacy professionals and strict regulatory control are needed.

Evaluation of In Vivo Wound-Healing and Anti-Inflammatory Activities of Solvent Fractions of Fruits of Argemone mexicana L. (Papaveraceae).

Introduction: The solvent fractions of the fruits of Argemone mexicana L. (Papaveraceae) have not yet been explored scientifically for in vivo wound healing and anti-inflammatory activities. The objective of this study was, therefore, to evaluate in vivo wound healing and anti-inflammatory activities of the solvent fractions of the fruit of Argemone mexicana L. (Papaveraceae) in rats. Method: The crude extract of Argemone mexicana was fractionated with n-hexane, ethyl acetate, and distilled water. Wound healing activity was evaluated using excision and incision wound models while anti-inflammatory activity was evaluated using carrageenan-induced rat paw and cotton pellet-induced granuloma models. The fractions were evaluated at 5 and 10% ointments using moist-exposed burn ointment as the standard drug, and 100, 200, and 400 mg/kg test doses using aspirin, and dexamethasone as standard drugs for wound healing and anti-inflammatory activities, respectively. All treatment administrations were made orally for anti-inflammatory activity and applied topically for wound healing activity. Result: The 10% w/w ethyl acetate fraction ointment showed a significant percentage of wound contraction, reduced period of epithelialization, increased amount of fibrosis, neovascularization, and collagen tissue formation (p < 0.01). The ethyl acetate fraction also showed a significant increase in tensile strength (55%; p < 0.01) and (81.10%; p < 0.01) at the tested doses of 5 and 10% w/w ointments, which was comparable to moist-exposed burn ointment. The ethyl acetate fraction also revealed a significant percent edema inhibition (61.41%; p < 0.01), suppression of the exudate (38.09% p < 0.01), and granuloma mass formations (53.47% p < 0.01) at the tested dose of 400 mg/kg. Conclusion: The results of this study showed that the Ethyl acetate fraction of Argemone mexicana fruit has significant wound healing and anti-inflammatory activities which support the traditional claims of the experimental plant.

The structure, biosynthesis, and biological roles of fetuin-A: A review.

Fetuin-A is a heterodimeric plasma glycoprotein containing an A-chain of 282 amino acids and a B-chain of 27 amino acid residues linked by a single inter-disulfide bond. It is predominantly expressed in embryonic cells and adult hepatocytes, and to a lesser extent in adipocytes and monocytes. Fetuin-A binds with a plethora of receptors and exhibits multifaceted physiological and pathological functions. It is involved in the regulation of calcium metabolism, osteogenesis, and the insulin signaling pathway. It also acts as an ectopic calcification inhibitor, protease inhibitor, inflammatory mediator, anti-inflammatory partner, atherogenic factor, and adipogenic factor, among other several moonlighting functions. Fetuin-A has also been demonstrated to play a crucial role in the pathogenesis of several disorders. This review mainly focuses on the structure, synthesis, and biological roles of fetuin-A. Information was gathered manually from various journals via electronic searches using PubMed, Google Scholar, HINARI, and Cochrane Library from inception to 2022. Studies written in English and cohort, case-control, cross-sectional, or experimental studies were considered in the review, otherwise excluded.

Evaluation and comparison of post-vaccination adverse effects among Janssen and Oxford-AstraZeneca vaccinated adult individuals in Debre Tabor Town: A cross- sectional survey in Northwest Ethiopia.

COVID 19 vaccination has recently been launched globally to halt the pandemic. But COVID 19 vaccines have some adverse effects that raise concerns in the global community. This study aimed to evaluate and compare the adverse effects of Janssen and Oxford-AstraZeneca vaccinated adults. A community-based cross-sectional study was conducted from March 15 to 30, 2022 among 421 (211 Janssen and 210 Astra Zeneca vaccinated) adults recruited by a convenience sampling technique in Debre Tabor Town, Northwest Ethiopia. Data were collected via face-to-face interviews and by reviewing the immunization card. Chi-square test, independent t-test, and Mann-Whitney test were used to compare the adverse symptoms and related parameters between the two vaccines. A linear regression model was also used to identify predictors of the number of post-vaccination symptoms. The majority (75.8%) of participants reported at least one side effect after vaccination. Adverse symptoms had a significantly greater occurrence (p < .05) among recipients of the AstraZeneca vaccine (84.8%) than receivers of the Janssen vaccine (66.8%). The main adverse symptoms were injection site pain, fever, fatigue, arthralgia, and myalgia in both vaccines. Significant variations (p < .05) between the receipts of the two vaccines were shown in injection site pain, fever, and arthralgia. The total number of symptoms was significantly higher (p < .05) in participants with female sex, younger age, BMI <25 kg/m2, no prior COVID 19, and those who had received AstraZeneca vaccine. Thus, the authors advise that they should receive vaccines with no hesitation, while continuous tracking of vaccine safety is kept in place.

Role of Fetuin-A in the Pathogenesis of Psoriasis and Its Potential Clinical Applications.

Fetuin-A is a plasma glycoprotein exhibiting multifaceted physiological and pathological functions. It has been determined to be involved in various essential biological functions, such as regulation of calcium metabolism, osteogenesis, and insulin signaling pathway. It also plays a crucial role in the pathogenesis of several disorders, including psoriasis. Psoriasis is a chronic systemic inflammatory disorder caused by a constellation of environmental, immunogenic, and genetic factors. It has been shown that dysregulation of cytokines mediated immune response is responsible for the development of psoriasis. Several recent publications suggest that dysregulation of fetuin-A correlates with psoriasis disease activities, revealing its putative role in the development of psoriasis. Furthermore, clinical application of fetuin-A as a diagnostic marker, prognostic predictor, and therapeutic target for different clinical conditions is in progress, and some are showing promising outcomes. This review primarily focuses on the current understanding of the role of fetuin-A in the pathogenesis of psoriasis and its potential clinical applications, with a brief highlight of psoriasis epidemiology and burden. The information was gathered systematically from various journals via electronic searches using various search engines: PubMed, Google Scholar, HINARI, and Cochrane Library from inception to 2022. The studies involved were restricted to English language. Conversely, articles written in other languages, studies done on fetuin B, or studies conducted on other dermatological diseases were excluded from the review article.