Therapeutic enzymes present excellent opportunities for the treatment of human disease, modulation of metabolic pathways and system detoxification. However, current use of enzyme therapy in the clinic is limited as naturally occurring enzymes are seldom optimal for such applications and require substantial improvement by protein engineering. Engineering strategies such as design and directed evolution that have been successfully implemented for industrial biocatalysis can significantly advance the field of therapeutic enzymes, leading to biocatalysts with new-to-nature therapeutic activities, high selectivity, and suitability for medical applications. This minireview highlights case studies of how state-of-the-art and emerging methods in protein engineering are explored for the generation of therapeutic enzymes and discusses gaps and future opportunities in the field of enzyme therapy.
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http://dx.doi.org/10.1002/anie.202308814 | DOI Listing |
J Oral Biol Craniofac Res
January 2025
Department of Periodontics, Vivekanandha Dental College for Women, India.
Background And Objective: Periodontitis and dental caries are among the most prevalent oral diseases, with chronic periodontitis being a multifactorial, infectious condition that leads to inflammation in the supporting structures of the teeth, progressive attachment loss, and bone resorption. Chronic periodontitis is driven by a consortium of pathogenic microorganisms. This study aimed to evaluate the efficacy of virgin coconut oil (VCO) pulling in reducing the microbial load and inflammatory mediators responsible for chronic periodontitis, in comparison to chlorhexidine (CHX) mouthwash and distilled water.
View Article and Find Full Text PDFPeerJ
January 2025
Gastrointestinal Cancer Center, Chongqing University Cancer Hospital, Chongqing, China.
Objective: To evaluate the safety profiles of EZH2-targeted inhibitors in cancer treatment, focusing on treatment-related adverse events (TRAEs) across various clinical trials.
Methods: We conducted a systematic review and meta-analysis using data from clinical trials involving EZH2 inhibitors reported up to May 31, 2024. Databases searched included PubMed, Embase, CENTRAL (Cochrane Central Register of Controlled Trials), and ClinicalTrials.
Front Immunol
January 2025
International Collaboration on Repair Discoveries (ICORD) Centre, Vancouver Coastal Health Research Institute (VCHRI), University of British Columbia (UBC), Vancouver, BC, Canada.
Keloid scars (KS) and hypertrophic scars (HS) are fibroproliferative wound healing defects characterized by excessive accumulation of extracellular matrix (ECM) in the dermis of affected individuals. Although transforming growth factor (TGF)-β is known to be involved in the formation of KS and HS, the molecular mechanisms responsible for its activation remain unclear. In this study we investigated Granzyme B (GzmB), a serine protease with established roles in fibrosis and scarring through the cleavage of ECM proteins, as a potential new mediator of TGF-β activation in KS and HS.
View Article and Find Full Text PDFJ Diabetes Res
January 2025
Department of Nutrition and Food Technology, Jashore University of Science and Technology, Jashore, Bangladesh.
Mushrooms and fenugreek are widely used to reduce hyperglycemia, and fenugreek is also used as a culinary ingredient to enhance flavor and aroma. This study is aimed at investigating the underlying mechanisms of the hypoglycemic effects of mushrooms and fenugreek in a Type 2 diabetic rat model. Adenosine monophosphate (AMP)-activated protein kinase (AMPK) functions to reduce hyperglycemia through insulin-independent pathways and protects beta-cells.
View Article and Find Full Text PDFFuture Med Chem
January 2025
Department of Organic Chemistry, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia.
Aim: With the aim of simultaneously modulating the epigenetic system and the protein kinase pathway, we selected the enzyme histone deacetylase (HDAC) and the Rho-associated protein kinases (ROCK) as desired targets to develop potential multitarget anticancer agents with additional antimetastatic properties. We report here the rational design, synthesis, and biological evaluation of the HDAC/ROCK multitarget inhibitors in pancreatic ductal adenocarcinoma (PDAC) and triple-negative breast cancer (TNBC).
Materials And Methods: A molecular docking study performed with the Gold software was used to develop HDAC/ROCK multitarget inhibitors.
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