The global cryopreservation market size rises exponentially due to increased demand for cell therapy-based products, assisted reproductive technology, and organ transplantation. Cryoprotectants (CPAs) are required to reduce ice-related damage, osmotic cell injury, and protein denaturation. Antioxidants are needed to hamper membrane lipid peroxidation under freezing stress, and antibiotics are added to the cryo-solutions to prevent contamination. The vitrification process for sized organs requires a high concentration of CPA, which is hardly achievable using conventional penetrating toxic CPAs like DMSO. Antifreeze peptides (AFpeps) are biocompatible CPAs leveraging inspiration from nature, such as freeze-tolerant and freeze-avoidant organisms, to circumvent logistic limitations in cryogenic conditions. This study aims to introduce the advances of AFpeps with cell-penetrating, antioxidant, and antimicrobial characteristics. We herein revisit the placement of AFpeps in the biobanking of cancer cells, immune cells, stem cells, blood cells, germ cells (sperms and oocytes), and probiotics. Implementing low-immunogenic AFpeps for allograft cryopreservation minimizes HLA mismatching risk after organ transplantation. Applying AFpeps to formulate bioinks with optimal rheology in extrusion-based 3D cryobiopriners expedites the bench-to-beside transition of bioprinted scaffolds. This study advocates that the fine-tuned synthetic or insect-derived AFpeps, forming round blunt-shape crystals, are biomedically broad-spectrum, and cell-permeable AFpeps from marine and plant sources, which result in sharp ice crystals, are appropriate for cryosurgery. Perspectives of the available room for developing peptide mimetics in favor of higher activity and stability and peptide-functionalized nanoparticles for enhanced delivery are delineated. Finally, antitumor immune activation by cryoimmunotherapy as an autologous in-vivo tumor lysate vaccine has been illustrated.
Any defects in bile formation, secretion, or flow may give rise to cholestasis, liver fibrosis, cirrhosis, and hepatocellular carcinoma. As the pathogenesis of hepatic disorders is multifactorial, targeting parallel pathways potentially increases the outcome of therapy. Hypericum perforatum has been famed for its anti-depressive effects. However, according to traditional Persian medicine, it helps with jaundice and acts as a choleretic medication. Here, we will discuss the underlying molecular mechanisms of Hypericum for its use in hepatobiliary disorders. Differentially expressed genes retrieved from microarray data analysis upon treatment with safe doses of Hypericum extract and intersection with the genes involved in cholestasis are identified. Target genes are located mainly at the endomembrane system with integrin-binding ability. Activation of α5β1 integrins, as osmo-sensors in the liver, activates a non-receptor tyrosine kinase, c-SRC, which leads to the insertion of bile acid transporters into the canalicular membrane to trigger choleresis. Hypericum upregulates CDK6 that controls cell proliferation, compensating for the bile acid damage to hepatocytes. It induces ICAM1 to stimulate liver regeneration and regulates nischarin, a hepatoprotective receptor. The extract targets the expression of conserved oligomeric Golgi (COG) and facilitates the movement of bile acids toward the canalicular membrane via Golgi-derived vesicles. In addition, Hypericum induces SCP2, an intracellular cholesterol transporter, to maintain cholesterol homeostasis. We have also provided a comprehensive view of the target genes affected by Hypericum's main metabolites, such as hypericin, hyperforin, quercitrin, isoquercitrin, quercetin, kaempferol, rutin, and p-coumaric acid to enlighten a new scope in the management of chronic liver disorders. Altogether, standard trials using Hypericum as a neo-adjuvant or second-line therapy in ursodeoxycholic-acid-non-responder patients define the future trajectories of cholestasis treatment with this product.
Antimicrobial peptides (AMPs) are the most favorable alternatives in overcoming multidrug resistance, alone or synergistically with conventional antibiotics. Plant-derived AMPs, as cysteine-rich peptides, widely compensate the pharmacokinetic drawbacks of peptide therapeutics. Compared to the putative genes encrypted in the genome, AMPs that are produced under stress are active forms with the ability to combat resistant microbial species. Within this study, plant-derived AMPs, namely, defensins, nodule-specific cysteine-rich peptides, snakins, lipid transfer proteins, hevein-like proteins, α-hairpinins, and aracins, expressed under biotic and abiotic stresses, are classified. We could observe that while α-hairpinins and snakins display a helix-turn-helix structure, conserved motif patterns such as β1αβ2β3 and β1β2β3 exist in plant defensins and hevein-like proteins, respectively. According to the co-expression data, several plant AMPs are expressed together to trigger synergistic effects with membrane disruption mechanisms such as toroidal pore, barrel-stave, and carpet models. The application of AMPs as an eco-friendly strategy in maintaining agricultural productivity through the development of transgenes and bio-pesticides is discussed. These AMPs can be consumed in packaging material, wound-dressing products, coating catheters, implants, and allergology. AMPs with cell-penetrating properties are verified for the clearance of intracellular pathogens. Finally, the dominant pharmacological activities of bioactive peptides derived from the gastrointestinal digestion of plant AMPs, namely, inhibitors of renin and angiotensin-converting enzymes, dipeptidyl peptidase IV and α-glucosidase inhibitors, antioxidants, anti-inflammatory, immunomodulating, and hypolipidemic peptides, are analyzed. Conclusively, as phytopathogens and human pathogens can be affected by plant-derived AMPs, they provide a bright perspective in agriculture, breeding, food, cosmetics, and pharmaceutical industries, translated as farm to bedside.