Green synthesis of silver nanoparticles mediated Diospyros kaki L. (Persimmon): determination of chemical composition and evaluation of their antimicrobials and anticancer activities

The eco-friendly synthesis of metallic nanoparticles (MNPs) using biological materials is an encouraging and innovativeness approach to nanotechnology. Among other synthesizing methods, biological methods are chosen because of their high efficiency and purity in many aspects. In this work, using the aqueous extract obtained from the green leaves of the D. kaki L. (DK); silver nanoparticles were synthesized in a short time and simply with an eco-friendly approach. The properties of the synthesized silver nanoparticles (AgNPs) were characterized using various techniques and measurements. In the characterization data of AgNPs, Maximum absorbance at 453.34 nm wavelengths, the average size distribution of 27.12 nm, the surface charge of −22.4 mV, and spherical appearance were observed. LC-ESI-MS/MS analysis was used to assess the compound composition of D. kaki leaf extract. The chemical profiling of the crude extract of D. kaki leaves revealed the presence of a variety of phytochemicals, predominantly phenolics, resulting in the identification of five major high-feature compounds: two major phenolic acids (Chlorogenic acid and Cynarin), and tree flavonol glucosides (hyperoside, quercetin-3-glucoside, and quercetin-3- D-xyloside). The components with the highest concentrations were cynarin, chlorogenic acid, quercetin-3- D-xyloside, hyperoside, and quercetin-3-glucoside, respectively. Antimicrobial results were determined by a MIC assay. The biosynthesized AgNPs exhibited strong antibacterial activity against the human and food pathogen Gram (+ and −) bacteria and good antifungal activity against pathogenic yeast. It was determined that 0.03–0.050 μg/mL concentrations ranges of DK-AgNPs were growth suppressive concentrations on all pathogen microorganisms. The MTT technique was used to study the cytotoxic effects of produced AgNPs on cancer cell lines (Glioblastoma (U118), Human Colorectal Adenocarcinoma (Caco-2), Human Ovarian Sarcoma (Skov-3) cancer cell lines, and Human Dermal Fibroblast (HDF) healthy cell line). It has been observed that they have a suppressive effect on the proliferation of cancerous cell lines. After 48 h of treatment with Ag-NPs, the DK-AgNPs were found to be extremely cytotoxic to the CaCo-2 cell line, inhibiting cell viability by up to 59.49% at a concentration of 50 g mL−1. It was found that the viability was inversely related to the DK-AgNP concentration. The biosynthesized AgNPs had dose-dependent anticancer efficacy. Because of the high concentration of bioactive chemicals in Diospyros kaki, it may be employed as a biological resource in medicinal applications. DK-AgNPs were shown to be an effective antibacterial agent as well as a prospective anticancer agent. The results provide a potential approach for the biogenic production of DK-AgNPs utilizing D. kaki aqueous leaf extract

The roles of long noncoding RNAs in atrial fibrillation

Atrial fibrillation (AF) is a common cardiac arrhythmia that often occurs in patients with structural heart disease and is a significant cause of morbidity and mortality in clinical settings. AF is typically associated with significant changes of both the structure of the atria and the cardiac conduction system. AF can result in reduced heart function, heart failure, and various other complications. Current drug therapy for AF patients is often ineffective and may have adverse effects. Radiofrequency ablation is more effective than traditional drug therapy, but this invasive procedure carries potential risks and may lead to postoperative recurrence, limiting the clinical benefits to some extent. Therefore, in-depth research into the molecular mechanisms of AF and exploration of new treatment strategies based on research findings are prerequisites for improving the treatment of AF and the associated cardiac conditions. Long noncoding RNAs (lncRNAs) are a new class of noncoding RNA (ncRNAs) with a length exceeding 200 nt, which regulate gene expression at multiple levels. Increasing evidence suggests that lncRNAs participate in many pathological processes of AF initiation, development, and maintenance, such as structural remodeling, electrical remodeling, renin-angiotensin system anomalies, and intracellular calcium deregulation s. LncRNAs that play key roles in structural and electrical remodeling may become molecular markers and targets for AF diagnosis and treatment, respectively, while lncRNAs critical to autonomic nervous system remodeling may bring new insights into the prognosis and recurrence of AF. This review article provides a synopsis on the up-to-date research findings relevant to the roles of lncRNAs in AF

Synthetic biomaterials based on hydroxyapatite and tricalcium phosphate: analysis of current clinical trials

Introduction To date, a wide variety of synthetic materials, including metals, polymers and ceramics, have been proposed and used as a substitute for bone grafts in the field of traumatology/orthopedics, neurosurgery and oral and maxillofacial surgery (OMFS). However, the most studied materials are calcium phosphate ceramics (CPC), in particular hydroxyapatite and tricalcium phosphate, as well as their mixtures, called byphasic calcium phosphates. This interest stems from the fact that the main component of bone is the apatite mineral calcium phosphate. Hydroxyapatite and tricalcium phosphate are among the most commonly used and effective synthetic substitutes for bone grafts. They have not only osteoconductive properties, but also osteoinductive. These properties, combined with cell-mediated resorption, ensure complete regeneration of bone defects. This study will analyze existing clinical trials, registered on the clinicaltirals.gov website, on the use of hydroxyapatite and tricalcium phosphate in the field of traumatology and orthopedics, neurosurgery and OMFS. Aim To identify the potential for clinical use, as well as possible side effects, of CPC as a replacement for bone grafts. Materials and methods The search strategy was to use material from the clinicaltrials.gov website, which focused on key terms such as hydroxyapatite, tricalcium phosphate, hydroxyapatite and tricalcium phosphate, traumatology and orthopedics, maxillofacial surgery, dentistry, neurosurgery, bone, и diseases of the musculoskeletal system. Results and discussion As of November 2022, there were approximately 85 clinical trials with hydroxyapatite application, approximately 49 clinical trials with tricalcium phosphate, and approximately 16 clinical trials with the hydroxyapatite/tricalcium phosphate combination. Most of the studies were Phase 1-2, Phase 2, or Phase 4. Most focused on tibial trauma therapy, osteoporosis/osteopenia, alveolar bone resorption, and spinal surgery. It was found that full results were published only in 3, 7 and 2 clinical trials on the use of hydroxyapatite, tricalcium phosphate and their combination, respectfully. All clinical trials had similar preparation methods and all of those clinical trials produced positive results without serious side effects. Conclusion There is a wide potential for clinical use of CPC as synthetic bone graft substitutes without reports of serious side effects. Many preclinical and clinical studies are currently underway on the use of hydroxyapatite and tricalcium phosphate, and their future results will further explore their clinical potential

The Role of Long Non-Coding RNAs in Intracranial Aneurysms and Subarachnoid Hemorrhage

Intracranial aneurysms (IAs) represent the most complex and relevant problem of modern neurology and neurosurgery. They serve as one of the main causes of non-traumatic subarachnoid hemorrhage (SAH), causing up to 85% of all cases of intracranial hemorrhage, which is associated with frequent disability and high mortality among patients. Unfortunately, the molecular mechanisms of the development and rupture of IAs are still under study. Long non-coding RNAs (lncRNAs) are non-coding RNAs that typically have a length of more than 200 nucleotides. It is known that lncRNAs regulate many processes, such as transcription, translation, cell differentiation, regulation of gene expression, and regulation of the cell cycle. In recent years, a lot of evidence has established their role in human diseases from oncology to cardiovascular disease. Recent studies have shown that lncRNAs may be involved in the pathogenesis of IAs. The study of lncRNAs and its targets in various pathological conditions of a person is a rapidly developing field, and it is likely that the knowledge obtained from these studies regarding the pathogenesis of intracranial aneurysms will have the potential to use lncRNAs in therapy, as well as in the diagnosis and prediction of high aneurysms risk of rupture

MiRNAs and lncRNAs in the regulation of innate immune signaling

The detection and defense against foreign agents and pathogens by the innate immune system is a crucial mechanism in the body. A comprehensive understanding of the signaling mechanisms involved in innate immunity is essential for developing effective diagnostic tools and therapies for infectious diseases. Innate immune response is a complex process involving recognition of pathogens through receptors, activation of signaling pathways, and cytokine production, which are all crucial for deploying appropriate countermeasures. Non-coding RNAs (ncRNAs) are vital regulators of the immune response during infections, mediating the body's defense mechanisms. However, an overactive immune response can lead to tissue damage, and maintaining immune homeostasis is a complex process in which ncRNAs play a significant role. Recent studies have identified microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) as key players in controlling gene expression in innate immune pathways, thereby participating in antiviral defenses, tumor immunity, and autoimmune diseases. MiRNAs act by regulating host defense mechanisms against viruses, bacteria, and fungi by targeting mRNA at the post-transcriptional level, while lncRNAs function as competing RNAs, blocking the binding of miRNAs to mRNA. This review provides an overview of the regulatory role of miRNAs and lncRNAs in innate immunity and its mechanisms, as well as highlights potential future research directions, including the expression and maturation of new ncRNAs and the conservation of ncRNAs in evolution

Identification of hub genes and small-molecule compounds related to intracerebral hemorrhage with bioinformatics analysis

Background Because of the complex mechanisms of injury, conventional surgical treatment and early blood pressure control does not significantly reduce mortality or improve patient prognosis in cases of intracerebral hemorrhage (ICH). We aimed to identify the hub genes associated with intracerebral hemorrhage, to act as therapeutic targets, and to identify potential small-molecule compounds for treating ICH. Methods The GSE24265 dataset, consisting of data from four perihematomal brain tissues and seven contralateral brain tissues, was downloaded from the Gene Expression Omnibus (GEO) database and screened for differentially expressed genes (DEGs) in ICH, with a fold change (FC) value of (|log2FC|) > 2 and a P-value of <0.05 set as cut-offs. The functional annotation of DEGs was performed using Gene Ontology (GO) resources, and the cell signaling pathway analysis of DEGs was performed using the Kyoto Encyclopedia of Genes and Genomes (KEGG), with a P-value of <0.05 set as the cut-off. We constructed a protein-protein interaction (PPI) network to clarify the interrelationships between the different DEGs and to select the hub genes with significant interactions. Next, the DEGs were analyzed using the CMap tool to identify small-molecule compounds with potential therapeutic effects. Finally, we verified the expression levels of the hub genes by RT-qPCR on the rat ICH model. Result A total of 59 up-regulated genes and eight down-regulated genes associated with ICH were identified. The biological functions of DEGs associated with ICH are mainly involved in the inflammatory response, chemokine activity, and immune response. The KEGG analysis identified several pathways significantly associated with ICH, including but not limited to HIF-1, TNF, toll-like receptor, cytokine-cytokine receptor interaction, and chemokine molecules. A PPI network consisting of 57 nodes and 373 edges was constructed using STRING, and 10 hub genes were identified with Cytoscape software. These hub genes are closely related to secondary brain injury induced by ICH. RT-qPCR results showed that the expression of ten hub genes was significantly increased in the rat model of ICH. In addition, a CMap analysis of three small-molecule compounds revealed their therapeutic potential. Conclusion In this study we obtained ten hub genes, such as IL6, TLR2, CXCL1, TIMP1, PLAUR, SERPINE1, SELE, CCL4, CCL20, and CD163, which play an important role in the pathology of ICH. At the same time, the ten hub genes obtained through PPI network analysis were verified in the rat model of ICH. In addition, we obtained three small molecule compounds that will have therapeutic effects on ICH, including Hecogenin, Lidocaine, and NU-1025