The healing of wounds is a dynamic function that necessitates coordination among multiple cell types and an optimal extracellular milieu. Much of the research focused on finding new techniques to improve and manage dermal injuries, chronic injuries, burn injuries, and sepsis, which are frequent medical concerns. A new research strategy involves developing multifunctional dressings to aid innate healing and combat numerous issues that trouble incompletely healed injuries, such as extreme inflammation, ischemic damage, scarring, and wound infection. Natural origin-based compounds offer distinct characteristics, such as excellent biocompatibility, cost-effectiveness, and low toxicity. Researchers have developed biopolymer-based wound dressings with drugs, biomacromolecules, and cells that are cytocompatible, hemostatic, initiate skin rejuvenation and rapid healing, and possess anti-inflammatory and antimicrobial activity. The main goal would be to mimic characteristics of fetal tissue regeneration in the adult healing phase, including complete hair and glandular restoration without delay or scarring. Emerging treatments based on biomaterials, nanoparticles, and biomimetic proteases have the keys to improving wound care and will be a vital addition to the therapeutic toolkit for slow-healing wounds. This study focuses on recent discoveries of several dressings that have undergone extensive pre-clinical development or are now undergoing fundamental research.
Mesenchymal stem cells (MSCs) are thought to be a promising therapeutic agent due to their multiple paracrine and immunomodulatory properties, providing protection from chronic inflammation and promoting tissue repair. MSCs can regulate the balance of pro-inflammatory and anti-inflammatory factors in inflamed tissues, creating a microenvironment necessary for successful healing; however, their interactions with immune cells are still poorly studied. We examined the temporal and spatial changes in gene regulation and the paracrine milieu accompanying the MSC-mediated immunosuppression effect in mixed cultures with activated peripheral blood mononuclear cells (PBMCs). Our data reveal that the peak of suppression of PBMC proliferation was achieved within 48 h following co-culture with MSCs and subsequently did not undergo a significant change. This effect was accompanied by an increase in COX-2 expression and an induction of IDO synthesis in MSCs. At this point, the expression of IL-1, IL-6, IL-8, IFN-γ, MCP-1, and G-CSF was upregulated in co-cultured cells. On the contrary, we observed a decrease in the concentrations of IL-10, IL-13, IL-5, and MIP-1b in co-culture supernatants compared to intact cultures of activated PBMCs. The regulation of IDO, IL-1, IL-6, and G-CSF production was accomplished with the involvement of direct cell–cell contact between MSCs and PBMCs. These findings provide new insights into the use of potential precondition inducers or their combinations to obtain functionally qualified MSCs for more effective treatment of inflammatory diseases.
For many years, the primary focus has been on finding effective treatments for Alzheimer’s disease (AD), which has led to the identification of promising therapeutic targets. The necessity for AD stage-dependent optimal settings necessitated a herbal therapy strategy. The plant species Areca Catechu L. (AC) was selected based on the traditional uses against CNS-related diseases. AC leaf extract were prepared using a Soxhlet extraction method and hydroxyapatite nanoparticles (HAp-NPs) were synthesized from the same (AC-HAp-NPs). Powder X-ray diffractometer (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), selected area electron diffraction (SAED) and fourier transform infrared spectroscopy (FTIR) were used to confirm the structure and morphology of the as-prepared AC-HAp-NPs. The crystalline character of the AC-HAp-NPs was visible in the XRD pattern. The synthesized material was found to be nanoflake, with an average diameter of 15–20 nm, according to SEM analysis. The TEM and SAED pictures also revealed the form and size of AC-HAp-NPs. In vitro anti-acetylcholinesterase and butyrylcholinesterase (AChE and BChE) activities of hydroxyapatite nanoparticles produced from an AC leaf extract was tested in this study. When compared to control, AC-HAp-NPs had higher anti-AChE and BChE activity. The anti-acetylcholinesterase action of phytoconstituents generated from AC leaf extract was mediated by 4AQD and 4EY7, according to a mechanistic study conducted utilizing in silico research. The global and local descriptors, which are the underpinnings of Conceptual Density Functional Theory (CDFT), have been predicted through the MN12SX/Def2TZVP/H2O model chemistry to help in the comprehension of the chemical reactivity properties of the five ligands considered in this study. The CDFT experiments are supplemented by the calculation of several useful calculated pharmacokinetics indices, their expected biological targets connected to the bioavailability of the five ligands in order to further the goal of studying their bioactivity.
Purpose: To compare the results of surgical treatment and changes in biomarkers of cholestasis, endotoxicosis, cytolysis, lipid peroxidation, glycolysis disorders, and inflammation in patients with benign and malignant obstructive jaundice (OJ) in patients receiving and not receiving antioxidant pharmacotherapy (AOT). Patients and methods: The study included 113 patients (aged 21–90 years; 47 males and 66 females) who received surgical intervention for OJ due to non-malignant (71%) or malignant tumor (29%) etiologies. Patients were divided into two groups: Group I (n = 61) who did not receive AOT and Group II (n = 51) who received AOT (succinate-containing drug Reamberin) as part of detoxification infusion therapy. The surgical approach and scope of interventions in both groups were identical. Dynamic indicators of endotoxicosis, cholestasis, and cytolysis (total, direct, and indirect bilirubin, alanine aminotransferase [ALT], aspartate aminotransferase [AST], alkaline phosphatase [AP] and gamma-glutamyltransferase [GGT]), kidney function (urea), lipid peroxidation (malonic dialdehyde, MDA), inflammation (leukocytosis), and glycolysis disorders (lactate dehydrogenase (LDH), glucose) were evaluated. Results: Tumor jaundice, unlike non-tumor jaundice, persisted and was characterized by a more severe course, a higher level of hyperbilirubinemia, and lipid peroxidation. The prognostic value of the direct (and total) bilirubin, MDA, glycemia, and leukocytosis levels on the day of hospitalization, which increased significantly in severe jaundice and, especially, in deceased patients, was established. Decompression interventions significantly reduced levels of markers of liver failure, cytolysis, cholestasis, and lipid peroxidation on day 3 after decompression by 1.5–3 times from initial levels; this is better achieved in non-tumor OJ. However, 8 days after decompression, most patients did not normalize the parameters studied in both groups. AOT favorably influenced the dynamics (on day 8 after decompression) of total and direct bilirubin, ALT, AST, MDA, and leukocytosis in non-tumor jaundice, as well as the dynamics of direct bilirubin, AST, MDA, glucose, and LDH in tumor jaundice. Clinically, in the AOT group, a two-fold reduction in the operative and non-operative complications was recorded (from 23% to 11.5%), a reduction in the duration of biliary drainage by 30%, the length of stay in intensive care units was reduced by 5 days, and even hospital mortality decreased, especially in malignancy-induced OJ. Conclusion: A mechanism for the development of liver failure in OJ is oxidative stress with the appearance of enhanced lipid peroxidation and accompanied by hepatocyte necrosis. Inclusion of AOT in perioperative treatment in these patients improves treatment outcomes.
We studied the efficacy of using mesenchymal stem cells (MSC) and a polymeric compound (based on chitosan and cellulose with integrated cerium dioxide nanoparticles (PCCD)) in wound healing, and to compare the effects with various invasive and external drugs used for the same purpose. Two wounds were made on the backs of each of 112 Wistar rats, removing the skin. Eight groups were studied: Control_0—intact wounds; Control_ss—0.9% NaCl injections; MSC injections; Control_msc—intact wounds on the opposite side of the body from the MSC group; external application of the PCCD; external application of a combination of the drugs PCCD + MSC; DCh –ointment Dioxomethyltetrahydropyrimidine + Chloramphenicol; and DHCB—injections of a deproteinized hemoderivative of calf blood. After 14 days, we evaluated the state and size of the wounds, studied the level of microcirculation, performed a histological study, and identified and counted the different types of cells. The most effective remedy was combination PCCD + MSC. The treatments in the PCCD and MSC groups were more effective than in the DHCB and DCh groups. Invasive drugs and DCh slowed the regeneration process. DHCB did not affect the rate of healing for acute wounds without ischemia during the first week. The proven efficacy of developed polymeric compounds demonstrates the feasibility of further studies in clinical practice.
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