A deep dive into the darning effects of biomaterials in infarct myocardium: current advances and future perspectives.

Myocardial infarction (MI) occurs due to the obstruction of coronary arteries, a major crux that restricts blood flow and thereby oxygen to the distal part of the myocardium, leading to loss of cardiomyocytes and eventually, if left untreated, leads to heart failure. MI, a potent cardiovascular disorder, requires intense therapeutic interventions and thereby presents towering challenges. Despite the concerted efforts, the treatment strategies for MI are still demanding, which has paved the way for the genesis of biomaterial applications. Biomaterials exhibit immense potentials for cardiac repair and regeneration, wherein they act as extracellular matrix replacing scaffolds or as delivery vehicles for stem cells, protein, plasmids, etc. This review concentrates on natural, synthetic, and hybrid biomaterials; their function; and interaction with the body, mechanisms of repair by which they are able to improve cardiac function in a MI milieu. We also provide focus on future perspectives that need attention. The cognizance provided by the research results certainly indicates that biomaterials could revolutionize the treatment paradigms for MI with a positive impact on clinical translation.

Enzyme Therapy: Current Perspectives.

Enzymes control all metabolic processes in human system from simple digestion of food to highly complex immune response. Physiological reactions occuring in healthy individuals are disturbed when enzymes are deficient or absent. Enzymes are administered for normalizing biological function in certain pathologies. Initially, crude proteolytic enzymes were used for the treatment of gastrointestinal disorders. Recent advances have enabled enzyme therapy as a promising tool in the treatment of cardiovascular, oncological and hereditary diseases. Now, a spectrum of other diseases are also covered under enzyme therapy. But, the available information on the use of enzymes as therapeutic agents for different diseases is scanty. This review details the enzymes which have been used to treat various diseases/disorders.

Preparation of low galactose yogurt using cultures of Gal(+) Streptococcus thermophilus in combination with Lactobacillus delbrueckii ssp. bulgaricus.

Streptococcus thermophilus is an important lactic starter used in the production of yogurt. Most strains of S. thermophilus are galactose negative (Gal(-)) and are able to metabolize only glucose portion of lactose and expel galactose into the medium. This metabolic defect leads to the accumulation of free galactose in yogurt, resulting in galactosemia among consumers. Hence there is an absolute need to develop low galactose yogurt. Therefore, in this study, three galactose positive (Gal(+)) S. thermophilus strains from National Collection of Dairy Cultures (NCDC) viz. NCDC 659 (AJM), NCDC 660 (JM1), NCDC 661 (KM3) and a reference galactose negative (Gal(-)) S. thermophilus NCDC 218 were used for preparation of low galactose yogurt. In milk fermented using S. thermophilus isolates alone, NCDC 659 released less galactose (0.27 %) followed by NCDC 661 (0.3 %) and NCDC 660 (0.45 %) after 10 h at 42 °C. Milk was fermented in combination with Gal(-) L. delbrueckii subsp. bulgaricus NCDC 04, in which NCDC 659 released least galactose upto 0.49 % followed by NCDC 661 (0.51 %) and NCDC 660 (0.60 %) than reference Gal(-) NCDC 218(0.79 %). Low galactose yogurt was prepared following standard procedure using Gal(+) S. thermophilus isolates and Gal(-) L. delbrueckii subsp. bulgaricus NCDC 04 in 1:1 ratio. Among which low galactose yogurt by NCDC 659 combination contained less galactose 0.37 % followed by NCDC 661 (0.51 %), NCDC 660 (0.65 %) and reference Gal(-) NCDC 218 (0.98 %) after 4 h of fermentation. This study clearly reveals that Gal(+) S. thermophilus isolates can be paired with Gal(-) L. delbrueckii subsp. bulgaricus for developing low galactose yogurt.

Biomimetic design of fibril-forming non-immunogenic collagen like proteins for tissue engineering.

Collagen, a key component of extracellular matrix serves as a linchpin for maintaining structural integrity and functional resilience. Concerns over purity and immunogenicity of animal-derived collagens have spurred efforts to develop synthetic collagen-based biomaterials. Despite several collagen mimics, there remains limited exploration of non-immunogenic biomaterials with the capacity for effective self-assembly. To combat the lacuna, collagen like protein (CLP) variants were rationally designed and recombinantly expressed, incorporating human telopeptide sequences (CLP-N and CLP-NC) and bioactive binding sites (CLP-NB). Circular dichroism analyses of the variants confirmed the triple helical conformation, with variations in thermal stability and conformation attributed to the presence of telopeptides at one or both ends of CLP. The variants had propensity to form oligomers, setting the stage for fibrillogenesis. The CLP variants were biocompatible, hemocompatible and supported cell proliferation and migration, particularly CLP-NB with integrin-binding sites. Gene expression indicated a lack of significant upregulation of inflammatory markers, highlighting the non-immunogenic nature of these variants. Lyophilized CLP scaffolds maintained their triple-helical structure and offered favorable biomaterial characteristics. These results accentuate the potential of designed CLP variants in tissue engineering, regenerative medicine and industrial sectors, supporting the development of biocompatible scaffolds and implants for therapeutic and cosmetic purposes.

Enzymes in clinical medicine: an overview.

Enzymes are biocatalysts and because of their remarkable properties, they are extensively used in medical diagnosis. Researches in the last two decades have concentrated more on enzymes such as creatine kinase-MB, alanine transaminase, aspartate transaminase, acid phosphatase, alkaline phosphatase etc. for clinical applications. Enzymes are the preferred markers in various disease states such as myocardial infarction, jaundice, pancreatitis, cancer, neurodegenerative disorders, etc. They provide insight into the disease process by diagnosis, prognosis and assessment of response therapy. Even though the literature on the use of enzymes in various disease conditions has accumulated, a comprehensive analysis is lacking and hence this review.

Myocardial expression of PDECGF is associated with extracellular matrix remodeling in experimental myocardial infarction in rats.

Platelet-derived endothelial cell growth factor (PDECGF) is a potent angiogenic peptide with anti-apoptotic activity expressed widely in tumours. However, its expression in myocardial infarction (MI) is not yet established. This study aimed to assess the myocardial expression of PDECGF in rats after MI. Extracellular matrix (ECM) remodeling plays an important role in angiogenesis; hence, changes in the ECM components were investigated in the myocardium after MI, which was induced in rats by coronary artery ligation (CAL) and verified using biochemical markers and histopathology. Immunohistochemistry, RT-PCR, and activity assays identified the expression pattern of PDECGF on days 1, 2, 4, 8, 16, and 32 after CAL. The levels of TNF-alpha, MMP-2, collagen, and glycosaminoglycans in the ECM were assessed. Studies on immunohistochemistry, RT-PCR, and PDECGF activity demonstrated elevated levels of PDECGF expression from day 2 after CAL. Macrophages, endothelial cells, fibroblasts, and cardiomyocytes, especially at the border region of the lesion, showed an enhanced expression for PDECGF. Remodeling of the ECM was depicted by changes in the levels of TNF-alpha, MMP-2, collagen, and GAG. Hence, this study clearly indicated PDECGF as an important angiogenic molecule expressed during MI and the alterations in ECM components facilitated the process of angiogenesis.

Arjunolic acid: a novel phytomedicine with multifunctional therapeutic applications.

Herbal plants with antioxidant activities are widely used in Ayurvedic medicine for cardiac and other problems. Arjunolic acid is one such novel phytomedicine with multifunctional therapeutic applications. It is a triterpenoid saponin, isolated earlier from Terminalia arjuna and later from Combretum nelsonii, Leandra chaeton etc. Arjunolic acid is a potent antioxidant and free radical scavenger. The scientific basis for the use of arjunolic acid as cardiotonic in Ayurvedic medicine is proven by its vibrant functions such as prevention of myocardial necrosis, platelet aggregation and coagulation and lowering of blood pressure, heart rate and cholesterol levels. Its antioxidant property combined with metal chelating property protects organs from metal and drug induced toxicity. It also plays an effective role in exerting protection against both type I and type II diabetes and also ameliorates diabetic renal dysfunctions. Its therapeutic multifunctionality is shown by its wound healing, antimutagenic and antimicrobial activity. The mechanism of cytoprotection conferred by arjunolic acid can be explained by its property to reduce the oxidative stress by enhancing the antioxidant levels. Apart from its pathophysiological functions, it possesses dynamic insecticidal property and it is used as a structural molecular framework in supramolecular chemistry and nanoscience. Esters of ajunolic acid function as gelators of a wide variety of organic liquids. Experimental studies demonstrate the versatile effects of arjunolic acid, but still, further investigations are necessary to identify the functional groups responsible for its multivarious effects and to study the molecular mechanisms as well as the probable side effects/toxicity owing to its long-term use. Though the beneficial role of this triterpenoid has been assessed from various angles, a comprehensive review of its effects on biochemistry and organ pathophysiology is lacking and this forms the rationale of this review.

Platelet-derived endothelial cell growth factor mediates angiogenesis and antiapoptosis in rat aortic endothelial cells.

This study explores the angiogenic and antiapoptotic activities of platelet-derived endothelial cell growth factor (PDECGF) in rat aortic endothelial cells. The effects of PDECGF on rat aortic endothelial cell (RAEC) proliferation, migration, chemotaxis, and tubule formation were investigated in vitro at various concentrations viz., 1, 2, 4, 8, 16, and 32 ng x mL(-1) on endothelial cells. Endothelial cells were induced with hypoxic stress and the antiapoptotic effects of PDECGF were analysed by cell survival assay, fluorescence microscopy, cell viability assay, and flow cytometry. The results demonstrated the angiogenic potential of PDECGF on endothelial cells in a dose-dependent manner. PDECGF at 16 and 32 ng x mL(-1) increased cell proliferation (>80%), induced cell migration (>4 fold), stimulated chemotaxis (>2 fold), and increased tubule formation (>3 fold) compared with the control. Studies on hypoxic stress revealed the antiapoptotic nature of PDECGF on endothelial cells. PDECGF treatment enhanced cell survival by 14%, as well as cell viability by 13%, and decreased the percentage of apoptotic cells by 13% as demonstrated by fluorescence-activated cell sorter studies (FACS). In conclusion, this study demonstrated the angiogenic and antiapoptotic potentials of PDECGF on RAEC.

Augmentation of therapeutic potential of curcumin using nanotechnology: current perspectives.

Curcumin, an active principle of Curcuma longa, is extracted from the rhizome. Its therapeutic efficiency has been proved using various in vitro and in vivo models. Inflammatory, neoplastic and preneoplastic diseases are the major targets using curcumin as therapeutic agent. Feasible clinical formulations could not be obtained because of its lack of solubility, stability and higher degradation rate. Recently, many techniques have been evolved to improve the physicochemical properties of pharmacological compounds, thereby increasing their biological activity. Curcumin has been developed using various techniques, particularly micro and nanotechnology to improve its stability and bioavailability. This review focuses on the studies pertaining to the delivery of curcumin in the form of micro and nanosize formulations for the treatment of a variety of diseases.

Fabrication and characterization of dual acting oleyl chitosan functionalised iron oxide/gold hybrid nanoparticles for MRI and CT imaging.

Bionanocomposites fabricated using metal nanoparticles serve a wide range of biomedical applications viz., site targeted drug delivery, imaging etc. Theranostics emerge as an important field of science, which focuses on the use of single entity for both disease diagnosis and treatment. The present work aimed at designing a multifunctional nanocomposite comprising of iron/gold hybrid nanoparticles, coated with oleyl chitosan and conjugated with methotrexate. The HR-TEM images revealed the spherical nature of the composite, while it's nontoxic and biocompatible property was proved by the MTT assay in NIH 3T3 cells and hemolysis assay. Though the VSM results exhibited the magnetic property, the MRI phantom images and X-ray contrast images demonstrated the potential of the composite to be used as contrast agent. Thus the prepared nanocomposite possess good cytocompatibility, magnetic property and also high X-ray attenuation, wherein it could serve as a novel platform for both MRI and CT diagnosis, as well as drug conjugation could aid in targeted drug delivery.

Studies on biochemical markers in cryoinfarction in rats.

Cryoinfarction in rats was carried out by placing the cooled probe directly on the midway of left anterior descending coronary artery. This caused damage to the blood vessel, hindering blood flow to the distal part of the left ventricle. Gross pathology showed around 26% infarction at 24 h. Histopathology revealed death of cardiomyocytes with blood vessel congestion at the end of 24 h, inflammatory infiltrate at 48 h, fibrotic scar by 96 h and collagen deposition by 192 h. Acute myocardial infarction biomarkers such as Cardiac Troponin T, Creatine Kinase MB and NT pro BNP were shown to be elevated by 4 h. ECG showed an ST segment elevation by 96 h. This cryoinfarction model was suitable to study changes taking place during acute myocardial infarction in humans.

A possible wound dressing material from marine food waste.

PURPOSE: Bluefin Trevally (Caranx melampygus) fish is mainly used for fillet production, the bones of which are discarded as a major solid waste in the fish food processing industry. In the present study, novel collagen films were prepared using the bones of Bluefin Trevally (BT). The study investigates the potential of using this collagen film as a wound dressing material. METHODS: The prepared collagen films (CFs) were characterized for their physicochemical properties using Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), scanning electron microscopy (SEM), atomic force microscopy (AFM), tensile strength, elongation at break, etc. In vitro studies using human keratinocyte cell line (HaCaT) also proved the biocompatibility of CF. The CFs were used as wound dressing material on the experimental wounds of rats and the healing pattern was evaluated using planimetric and histopathological studies. RESULTS: CF prepared from the bones of BT possessed better mechanical properties. The in vitro studies demonstrated its biocompatible nature. Acceleration of wound healing in CF-treated rats was evident in the in vivo studies. CONCLUSIONS: The study has devised a process for using fish waste in the preparation of a value-added product like wound dressing material. The CF with the required strength, biocompatibility and wound healing properties may be tried as a wound dressing material in large animals after obtaining the necessary approval.

Myocardial ischemia and reperfusion injury in rats: lysosomal hydrolases and matrix metalloproteinases mediated cellular damage.

The aim of this study was to evaluate the time course events of cellular damage during myocardial ischemia and reperfusion injury in rats and to find out a correlation between the structural alterations with respect to the biochemical changes. Cardiac biomarkers and lysosomal enzymes viz. cathepsin D, acid phosphatase and beta-glucuronidase and matrix metalloproteinases (MMPs) were evaluated at different time points, in response to ischemia-reperfusion induced oxidative stress in an isolated rat heart model perfused in Langendorff mode. Microscopically, changes in myocardial architecture, myofibrillar degradation, and collagen (COL) integrity were studied using hematoxylin-eosin, Masson's trichrome and toluidine blue staining techniques. A three-fold increase in the level of myoglobin was observed after 30 min of ischemia followed by 120 min of reperfusion as compared to 15 min ischemia, 120 min reperfusion. Similarly, a significant increase (P<0.05) in the levels of lipid peroxides and superoxide anion coupled with a decrease in enzymatic and nonenzymatic antioxidant levels were observed. A concomitant increase in the activity of cathepsin D (24.07+/-0.95) and a higher expression of MMPs after 120 min of reperfusion following 30 min ischemia were shown to correlate with the myocardial damage as shown by histopathology, suggesting that free radical induced activation of cathepsin D and MMPs could mediate early damage during myocardial ischemia and reperfusion.