Mrj is a chaperone of the Hsp40 family that regulates Orb2 oligomerization and long-term memory in Drosophila.

Orb2 the Drosophila homolog of cytoplasmic polyadenylation element binding (CPEB) protein forms prion-like oligomers. These oligomers consist of Orb2A and Orb2B isoforms and their formation is dependent on the oligomerization of the Orb2A isoform. Drosophila with a mutation diminishing Orb2A's prion-like oligomerization forms long-term memory but fails to maintain it over time. Since this prion-like oligomerization of Orb2A plays a crucial role in the maintenance of memory, here, we aim to find what regulates this oligomerization. In an immunoprecipitation-based screen, we identify interactors of Orb2A in the Hsp40 and Hsp70 families of proteins. Among these, we find an Hsp40 family protein Mrj as a regulator of the conversion of Orb2A to its prion-like form. Mrj interacts with Hsp70 proteins and acts as a chaperone by interfering with the aggregation of pathogenic Huntingtin. Unlike its mammalian homolog, we find Drosophila Mrj is neither an essential gene nor causes any gross neurodevelopmental defect. We observe a loss of Mrj results in a reduction in Orb2 oligomers. Further, Mrj knockout exhibits a deficit in long-term memory and our observations suggest Mrj is needed in mushroom body neurons for the regulation of long-term memory. Our work implicates a chaperone Mrj in mechanisms of memory regulation through controlling the oligomerization of Orb2A and its association with the translating ribosomes.

Perceptions, Attitudes, and Knowledge of Cannabis and its Use: A Qualitative Study among Herbal Heart Study Young Adult Cannabis Consumers in South Florida.

Growing cannabis use among young adults in the United States surpasses research and public understanding, raising health concerns despite potential benefits. Limited research focuses on their knowledge, attitudes, risks, and motivations, especially in states with limited legalization. This study explores cannabis knowledge and attitudes among healthy young adult cannabis consumers to understand their risk and benefit perceptions. Data include a subsample of participants in the Herbal Heart Study, a cohort to examine subclinical cardiovascular risk among healthy young adult (18-35 years old) cannabis consumers and non-consumers. A qualitative thematic analysis of the interviews was performed using a deductive approach driven by the theory of the Health Belief Model to generate categories and codes. Dedoose was used to organize transcripts and coding. A total of 22 young adult cannabis consumers (M age = 25.3, SD = 4.4) were interviewed between May 5, 2021- September 23, 2022. Participants were predominantly female (n = 13) and Hispanic (n = 9) or non-Hispanic Black (n = 7). Five themes were identified: perceived health benefits and risks associated with cannabis use, motivation for cannabis use, knowledge of cannabis, and perceived barriers to cannabis use. Participants discussed knowledge, positive/negative attitudes toward cannabis, and perceived risks/benefits based on personal experience and gathered information. Some showed knowledge deficits, and most wanted more health-related cannabis research. Given the current climate of rising cannabis legalization, availability of novel cannabis products, and societal acceptance, further research and evidence-based cannabis literacy for young adults are essential to keep pace with liberalization trends.

A review on the treatment of intimal hyperplasia with perivascular medical devices: role of mechanical factors and drug release kinetics.

INTRODUCTION: Intimal hyperplasia (IH) is a significant factor limiting the success of revascularization surgery for blood flow restoration. IH results from a foreign body response and mechanical disparity that involves complex biochemical reactions resulting in graft failure. The available treatment option utilizes either different pharmacological interventions or mechanical support to the vascular grafts with limited success. AREAS COVERED: This review explains the pathophysiology of IH, responsible mechanical and biological factors, and treatment options, emphasizing perivascular devices. They are designed to provide mechanical support and pharmacology actions. The perivascular drug delivery concept has successfully demonstrated efficacy in various animal studies. Accurate projections of drug release mechanisms using mathematical modeling could be used to formulate prolonged drug elution devices. Numerical modeling aspects for the prediction of design outcomes have been given due importance that fulfills the unmet clinical need for better patient care. EXPERT OPINION: IH could be effectively prevented by simultaneous mechanical scaffolding and sustained local drug delivery. Future perivascular medical devices could be designed to integrate these essential features. Numerical modeling for device performance prediction should be utilized in the development of next-generation perivascular devices.

Perivascular patch using biodegradable polymers: Investigation of mechanical and drug elution characteristics.

Intimal hyperplasia (IH) is the primary cause for the vascular graft stenosis. Perivascular devices offer a potential treatment option to reduce the impact of intimal hyperplasia by providing mechanical support and local administration of therapeutic agents to control cellular overgrowth. In the present study, a perivascular patch primarily made up of biodegradable polymer, Poly L-Lactide, has been designed with adequate mechanical strength and ability for sustained drug elution of anti-proliferative drug (Paclitaxel). The elastic modulus of the polymeric film has been optimized by blending the base polymer with different grades of biocompatible polyethylene glycols. Using design of experiments, the optimized parameters were obtained as PLLA with 2.5% PEG-6000 and have shown 3.14 MPa elastic modulus. The film prepared based on optimum conditions has been employed for prolonged drug delivery (about four months) under simulated physiological conditions. The addition of drug release rate enhancer (polyvinyl pyrrolidone K90F) has improved the drug elution rate and ∼83% drug was released over entire study period. The molecular weight of the base biodegradable polymer was estimated by gel permeation chromatography (GPC) which remained unchanged during the drug release study duration. Evidences of Paclitaxel drug crystallization were found to contribute to the sustained drug elution. The SEM examination of the surface morphology post-incubation revealed micropores on the surface, contributing to the overall drug release rate. The study concluded that perivascular biodegradable films could be tailored for their mechanical properties, and sustained drug elution could also be formulated with reasonable choices of biodegradable polymer and biocompatible additives.

Extraction of shikimic acid from water hyacinth (Eichhornia crassipes) using sonication: An approach towards waste valorization.

Shikimic acid (SA) is a valuable compound found in water hyacinth and is a precursor for synthesis of antiviral drug oseltamivir phosphate (Tamiflu®) which is used to treat H5N1 avian influenza. In the present work, the acid was extracted from different morphological parts (stem, leaves, and roots) of water hyacinth (a notorious aquatic weed) using sonication. The parametric study has been conducted by varying sonication time (10-50 min), solvent composition (methanol + water), solvent volume (20-50 mL), amplitude of sonication (30-60%), and pulse ratio (20-50%) for improving the recovery of shikimic acid (SA), antioxidant activity (AA) and total phenolic content (TPC) of water hyacinth extract. Also, the acid was extracted conventionally as a benchmark study. The highest yield of 2.4% at 40 min and 3.1% at 30 min was observed in case of conventional and ultrasound assisted extraction (UAE), respectively for stem. Leaves showed a higher TPC value of 7.4 mg GAE/g biomass and a higher AA was observed 83.21% at 20 min for stem in case of conventional method. The highest TPC value of 11.11 mg GAE/g biomass has been observed for leaves while stem has shown the highest AA of 87.72% at 10 min of sonication time for UAE. It was possible to recover the valuable chemicals with better processing conditions in the case of UAE.

A role of cellular translation regulation associated with toxic Huntingtin protein.

Huntington's disease (HD) is a severe neurodegenerative disorder caused by poly Q repeat expansion in the Huntingtin (Htt) gene. While the Htt amyloid aggregates are known to affect many cellular processes, their role in translation has not been addressed. Here we report that pathogenic Htt expression causes a protein synthesis deficit in cells. We find a functional prion-like protein, the translation regulator Orb2, to be sequestered by Htt aggregates in cells. Co-expression of Orb2 can partially rescue the lethality associated with poly Q expanded Htt. These findings can be relevant for HD as human homologs of Orb2 are also sequestered by pathogenic Htt aggregates. Our work suggests that translation dysfunction is one of the contributors to the pathogenesis of HD and new therapies targeting protein synthesis pathways might help to alleviate disease symptoms.

Sono hydrodistillation for isolation of citronella oil: A symbiotic effect of sonication and hydrodistillation towards energy efficiency and environment friendliness.

Environmental benign approach for extraction of essential oil was made. An essential oil rich in citronellol, linalool and citronellal was extracted from the leaves of Cymbopogon winterianus using a clean hybrid extraction technique, sono hydrodistillation. Sono hydrodistillation combines ultrasonic waves along with conventional hydrodistillation process to have symbiotic outcomes in terms of process improvement. Significant process parameters such as size of the plant material, extraction time, power, ultrasound amplitude, pulse interval and solid loading were investigated independently to study the effect on yield of oil and composition of oil. The water residue remained after extraction of volatile oil was analyzed using Folin-Ciocalteu method to determine the total phenolic content (TPC) which would help in assessing the residue as a useful by-product. Substantial reduction in time was observed with the inclusion of ultrasound compared to conventional hydrodistillation. Further, to optimize the extraction conditions, observe interactive effects of various parameters and develop mathematical model, response surface methodology was employed. The maximum yield of oil was found to be 4.118% (w/w) at 21 min extraction time, 5 g solid loading, 250 mL water volume, 500 W heating mantle power, 70% ultrasonic amplitude and 10:50 pulse interval. Total phenolic content was 13.84 mg GAE/g DM. The citronella oil was found to be composed of 27.47% of linalool, 11.52% of citronellal, 34.25% citronellol and 11.15% of elemol. Extraction time, solid loading and pulse interval had the significant influence on the yield of oil and total phenolic contents. Microscopic analysis has assisted in envisaging the probable mechanism indicating the role of sonication for rapid extraction. This novel technique was compared with the conventional hydrodistillation to ascertain the impact towards process intensification. Sono hydrodistillation was found to be a greener and cleaner process as energy consumption has been reduced by 40% while carbon footprint has shrunken by 47%.