Advances in Parkinson's disease research - A computational network pharmacological approach.

Parkinson's disease (PD), the second most prevalent neurodegenerative disorder, is projected to see a significant rise in incidence over the next three decades. The precise treatment of PD remains a formidable challenge, prompting ongoing research into early diagnostic methodologies. Network pharmacology, a burgeoning field grounded in systems biology, examines the intricate networks of biological systems to identify critical signal nodes, facilitating the development of multi-target therapeutic molecules. This approach systematically maps the components of Parkinson's disease, thereby reducing its complexity. In this review, we explore the application of network pharmacology workflows in PD, discuss the techniques employed in this field, and evaluate the current advancements and status of network pharmacology in the context of Parkinson's disease. The comprehensive insights will pave newer paths to explore early disease biomarkers and to develop diagnosis with a holistic in silico, in vitro, in vivo and clinical studies.

Artificial intelligence: Machine learning approach for screening large database and drug discovery.

Recent research in drug discovery dealing with many faces difficulties, including development of new drugs during disease outbreak and drug resistance due to rapidly accumulating mutations. Virtual screening is the most widely used method in computer aided drug discovery. It has a prominent ability in screening drug targets from large molecular databases. Recently, a number of web servers have developed for quickly screening publicly accessible chemical databases. In a nutshell, deep learning algorithms and artificial neural networks have modernised the field. Several drug discovery processes have used machine learning and deep learning algorithms, including peptide synthesis, structure-based virtual screening, ligand-based virtual screening, toxicity prediction, drug monitoring and release, pharmacophore modelling, quantitative structure-activity relationship, drug repositioning, polypharmacology, and physiochemical activity. Although there are presently a wide variety of data-driven AI/ML tools available, the majority of these tools have, up to this point, been developed in the context of non-communicable diseases like cancer, and a number of obstacles have prevented the translation of these tools to the discovery of treatments against infectious diseases. In this review various aspects of AI and ML in virtual screening of large databases were discussed. Here, with an emphasis on antivirals as well as other disease, offers a perspective on the advantages, drawbacks, and hazards of AI/ML techniques in the search for innovative treatments.

Kidney Hypertrophy in Living Kidney Donors and Their Corresponding Recipients.

BACKGROUND: In this long-term study we compared kidney volume changes and function between living kidney donors and their corresponding recipients via magnetic resonance imaging after 3 to 8 years post transplantation. METHODS: For measurement of the kidney volume in magnetic resonance imaging images we used 3DSlicer. Statistical analysis was performed via t test and correlation. RESULTS: A profound volume increase was observed in both transplanted and orthotopic kidney. The volume increase of the orthotopic kidneys was with 58 cm³ ± 23.8 cm³ SD (41%) greater than in the corresponding transplanted kidneys with 43 cm³ ± 36.9 cm³ SD (30%). CONCLUSIONS: This study detected a persistent volume increase in both orthotopic and transplanted kidneys after donation. Neither significant increases of hypertension or proteinuria were observable or could be correlated to renal hypertrophy.

Adverse Events Associated With the Addition of Aspirin to Direct Oral Anticoagulant Therapy Without a Clear Indication.

Importance: It is unclear how many patients treated with a direct oral anticoagulant (DOAC) are using concomitant acetylsalicylic acid (ASA, or aspirin) and how this affects clinical outcomes. Objective: To evaluate the frequency and outcomes of prescription of concomitant ASA and DOAC therapy for patients with atrial fibrillation (AF) or venous thromboembolic disease (VTE). Design, Setting, and Participants: This registry-based cohort study took place at 4 anticoagulation clinics in Michigan from January 2015 to December 2019. Eligible participants were adults undergoing treatment with a DOAC for AF or VTE, without a recent myocardial infarction (MI) or history of heart valve replacement, with at least 3 months of follow-up. Exposures: Use of ASA concomitant with DOAC therapy. Main Outcomes and Measures: Rates of bleeding (any, nonmajor, major), rates of thrombosis (stroke, VTE, MI), emergency department visits, hospitalizations, and death. Results: Of the study cohort of 3280 patients (1673 [51.0%] men; mean [SD] age 68.2 [13.3] years), 1107 (33.8%) patients without a clear indication for ASA were being treated with DOACs and ASA. Two propensity score-matched cohorts, each with 1047 patients, were analyzed (DOAC plus ASA and DOAC only). Patients were followed up for a mean (SD) of 20.9 (19.0) months. Patients taking DOAC and ASA experienced more bleeding events compared with DOAC monotherapy (26.0 bleeds vs 31.6 bleeds per 100 patient years, P = .01). Specifically, patients undergoing combination therapy had significantly higher rates of nonmajor bleeding (26.1 bleeds vs 21.7 bleeds per 100 patient years, P = .02) compared with DOAC monotherapy. Major bleeding rates were similar between the 2 cohorts. Thrombotic event rates were also similar between the cohorts (2.5 events vs 2.3 events per 100 patient years for patients treated with DOAC and ASA compared with DOAC monotherapy, P = .80). Patients were more often hospitalized while undergoing combination therapy (9.1 vs 6.5 admissions per 100 patient years, P = .02). Conclusion and Relevance: Nearly one-third of patients with AF and/or VTE who were treated with a DOAC received ASA without a clear indication. Compared with DOAC monotherapy, concurrent DOAC and ASA use was associated with increased bleeding and hospitalizations but similar observed thrombosis rate. Future research should identify and deprescribe ASA for patients when the risk exceeds the anticipated benefit.

A Crude Extract Preparation and Optimization from a Genomically Engineered Escherichia coli for the Cell-Free Protein Synthesis System: Practical Laboratory Guideline.

With the advancement of synthetic biology, the cell-free protein synthesis (CFPS) system has been receiving the spotlight as a versatile toolkit for engineering natural and unnatural biological systems. The CFPS system reassembles the materials necessary for transcription and translation and recreates the in vitro protein synthesis environment by escaping a physical living boundary. The cell extract plays an essential role in this in vitro format. Here, we propose a practical protocol and method for Escherichia coli-derived cell extract preparation and optimization, which can be easily applied to both commercially available and genomically engineered E. coli strains. The protocol includes: (1) The preparation step for cell growth and harvest, (2) the thorough step-by-step procedures for E. coli cell extract preparation including the cell wash and lysis, centrifugation, runoff reaction, and dialysis, (3) the preparation for the CFPS reaction components and, (4) the quantification of cell extract and cell-free synthesized protein. We anticipate that the protocol in this research will provide a simple preparation and optimization procedure of a highly active E. coli cell extract.

Potential for Hospital Based Corneal Retreival in Hassan District Hospital.

CONTEXT: In developing countries, corneal diseases are the second leading cause of blindness. This corneal blindness can be treated through corneal transplantation. Though the present infrastructure is strong enough to increase keratoplasty numbers at a required rate, India has largest corneal blind population in the world. So a constant supply of high quality donor corneal tissue is the key factor for reduction of prevalence of corneal blindness. Considering the magnitude of corneal blindness and shortage of donor cornea, there is a huge gap in the demand and supply. AIM: To study the potential for hospital based retrieval of donor corneal tissue in Hassan district hospital after analysing the indicated and contraindicated causes of deaths, so that hospital corneal retrieval program in Hassan district hospital can be planned. MATERIALS AND METHODS: The cross-sectional, retrospective and record-based study included all hospital deaths with age group more than two years occurred during one year period (January 2014 to December 2014). Data regarding demographic profile, cause of death, treatment given and presence of any systemic diseases were collected. The causes of deaths which are contraindicated for the retrieval of corneas were analysed and noted. The contraindications were based on the NPCB guidelines for standard of eye banking in India 2009. RESULTS: Out of 855 deaths, number of deaths in males (565) was greater than females (290). Numbers of deaths were highest between 41-60 years age group (343). Deaths due to HIV, septicaemia, meningitis, encephalitis, disseminated malignancies were contraindicated for corneal retrieval. Corneas could be retrieved from 736 deaths out of 855. Potential for corneal retrieval in a period of one year in Hassan District hospital was 86%. CONCLUSION: Hospital corneal retrieval program has got a great potential to bridge the gap between the need for the cornea and actually collected corneas which will contribute enormously in eliminating corneal blindness. In present study there was 86% potential for corneal retrieval among the hospital deaths.