Therapeutic Substances Research Articles

Focused ultrasound combined with miR-1208-equipped exosomes inhibits malignant progression of glioma.

Exosomes (Exos) can safely and effectively deliver therapeutic substances to glioma cells; however, their blood-brain barrier (BBB) crossing capacity remains limited. Focused ultrasound (FUS) can transiently, reversibly, and locally open the BBB, while the effects of FUS combined with Exos-miRNA on the treatment of glioma have not been explored to date. Exos were extracted by differential centrifugation and the efficacy of miR-1208-loaded Exos combined with FUS in the treatment of glioma was detected by CCK-8, colony formation, flow cytometry, transwell and tumour xenografts assays. The METTL3-mediated regulation of IGF2BP2 on mRNA stability of NUP214 was determined by MeRIP-qPCR, half-life and RIP assays. We used Exos secreted by mesenchymal stem cells as carriers for the tumour suppressor gene miR-1208, and following FUS irradiation, more Exos carrying miR-1208 were allowed to pass through the BBB, and the uptake of miR-1208 in Exos by glioma cells was promoted, thereby achieving high-efficiency tumour-suppressive effects. Furthermore, the molecular mechanism underlying this effect was elucidated that miR-1208 downregulated the m6A methylation level of NUP214 mRNA by negatively regulating the expression of METTL3, thereby NUP214 expression and TGF-β pathway activity were suppressed. MiR-1208-loaded Exos combined with FUS is expected to become an effective glioma treatment and deserves further clinical evaluation.

Non-covalent interactions in biocompatible platforms for drug delivery: Mg2(olsalazine) Metal-Organic Framework with phenylethylamine, dopamine and sertraline

Drug delivery systems can improve the efficacy of therapeutic substances. In this investigation, the biocompatible Mg2(olsalazine) [Mg2(olz)] framework is investigated as a delivery system of phenylethylamine, dopamine and sertraline, substances related to the functioning of the Central Nervous System. Experiments previously reported show that Mg2(olz) encapsulates phenylethylamine and, under physiological conditions, releases the molecules. The hypothesis of this work is that this is possible due to the presence of non-covalent interactions. The non-covalent interactions between Mg2(olz) and phenylethylamine, dopamine and sertraline are analyzed using Quantum Theory of Atoms in Molecules and Non-covalent Interaction Index. It was found that the coordinatively unsaturated metal site of Mg2(olz) is important for the formation of non-covalent interactions. Due to similarity of systems of dopamine and sertraline with that of phenylethylamine, we conclude that Mg2(olz) is also capable to encapsulate and release these two drugs, being a good proposal as a drug delivery system.

Novel Anti-Inflammatory Therapies in Coronary Artery Disease and Acute Coronary Syndromes.

Evidence suggests that inflammation plays an important role in atherosclerosis and the consequent clinical presentation, including stable coronary artery disease (CAD) and acute coronary syndromes (ACS). The most essential elements are cytokines, proteins with hormone-like properties that are produced by the immune cells, endothelial cells, platelets, fibroblasts, and some stromal cells. Interleukins (IL-1β and IL-6), chemokines, interferon-γ (IFN-γ), and tumor necrosis factor-alpha (TNF-α) are the cytokines commonly associated with endothelial dysfunction, vascular inflammation, and atherosclerosis. These molecules can be targeted by commonly used therapeutic substances or selective molecules that exert targeted anti-inflammatory actions. The most significant anti-inflammatory therapies are aspirin, statins, colchicine, IL-1β inhibitors, and IL-6 inhibitors, along with novel therapies such as TNF-α inhibitors and IL-1 receptor antagonists. Aspirin and statins are well-established therapies for atherosclerosis and CAD and their pleiotropic and anti-inflammatory actions contribute to their efficacy and favorable profile. Colchicine may also be considered in high-risk patients if recurrent ACS episodes occur when on optimal medical therapy according to the most recent guidelines. Recent randomized studies have also shown that therapies specifically targeting inflammatory interleukins and inflammation can reduce the risk for cardiovascular events, but these therapies are yet to be fully implemented in clinical practice. Preclinical research is also intense, targeting various inflammatory mediators that are believed to be implicated in CAD, namely repeated transfers of the soluble mutant of IFN-γ receptors, NLRP3 inflammasome inhibitors, IL-10 delivery by nanocarriers, chemokine modulatory treatments, and reacting oxygen species (ROS) targeting nanoparticles. Such approaches, although intriguing and promising, ought to be tested in clinical settings before safe conclusions can be drawn. Although the link between inflammation and atherosclerosis is significant, further studies are needed in order to elucidate this association and improve outcomes in patients with CAD.

The role of N-glycosylation in B-cell biology and IgG activity. The aspects of autoimmunity and anti-inflammatory therapy.

The immune system is strictly regulated by glycosylation through the addition of highly diverse and dynamically changing sugar structures (glycans) to the majority of immune cell receptors. Although knowledge in the field of glycoimmunology is still limited, numerous studies point to the key role of glycosylation in maintaining homeostasis, but also in reflecting its disruption. Changes in oligosaccharide patterns can lead to impairment of both innate and acquired immune responses, with important implications in the pathogenesis of diseases, including autoimmunity. B cells appear to be unique within the immune system, since they exhibit both innate and adaptive immune activity. B cell surface is rich in glycosylated proteins and lectins which recognise glycosylated ligands on other cells. Glycans are important in the development, selection, and maturation of B cells. Changes in sialylation and fucosylation of cell surface proteins affect B cell signal transduction through BCRs, CD22 inhibitory coreceptor and Siglec-G. Plasmocytes, as the final stage of B cell differentiation, produce and secrete immunoglobulins (Igs), of which IgGs are the most abundant N-glycosylated proteins in human serum with the conserved N-glycosylation site at Asn297. N-oligosaccharide composition of the IgG Fc region affects its secretion, structure, half-life and effector functions (ADCC, CDC). IgG N-glycosylation undergoes little change during homeostasis, and may gradually be modified with age and during ongoing inflammatory processes. Hyperactivated B lymphocytes secrete autoreactive antibodies responsible for the development of autoimmunity. The altered profile of IgG N-glycans contributes to disease progression and remission and is sensitive to the application of therapeutic substances and immunosuppressive agents. In this review, we focus on the role of N-glycans in B-cell biology and IgG activity, the rearrangement of IgG oligosaccharides in aging, autoimmunity and immunosuppressive therapy.

Ultrasonography in Pain Medicine and Regional Anesthesia Expert Consensus

Ultrasound has revolutionized interventional pain medicine and regional anesthesia. It allows visualization of nervoussystem structures, which are the primary targets in pain management and regional anesthesia procedures. Precise andsafe deposition of local anesthetics around nerve structures is made possible with ultrasound, resulting in rapid regionalanesthesia and modulation of pathological pain signals. In diagnostic and prognostic pain treatments, the precisionof drug administration and deposition of small volumes are crucial. Proper identification of the nerve responsible fortransmitting pathological pain signals is key to achieving the desired effect in neurodestructive procedures such asneurolysis, cryoablation, thermocoagulation, or pulsed neuromodulation. Visualization of structures to avoid, such asblood vessels or parenchymal organs, reduces the risk of adverse events like hematoma or damage to sensitive internalorgans. Real-time needle tracking during procedures shortens the duration and increases precision. Monitoring thespread of the administered therapeutic substance during the procedure enhances the effectiveness and selectivityof the block. When combined with X-ray imaging, using ultrasound reduces procedure time and exposure to X-rayradiation. Furthermore, ultrasound does not expose clinicians and patients to harmful X-ray radiation. Widespreadadoption of ultrasound in imaging nervous system structures during regional anesthesia and interventional painprocedures necessitates the development of new procedural standards.

African‐centered therapeutic community substance abuse treatment with incarcerated Black males: A pilot model

AbstractThis article proposes a pilot therapeutic intervention for counseling Black male substance abusers within the carceral system. Despite the noted fact that Black males are disproportionately represented as drug‐using offenders, few treatment models exist that are germane to this population. The current model emanated from an African‐centered theoretical framework. Additionally, it employed the therapeutic community approach that addresses substance use and mental health issues among inmates. Specific considerations for counselors and future research are discussed.

Impact and Advances in the Role of Bacterial Extracellular Vesicles in Neurodegenerative Disease and Its Therapeutics.

Bacterial Extracellular Vesicles (BEVs) possess the capability of intracellular interactions with other cells, and, hence, can be utilized as an efficient cargo for worldwide delivery of therapeutic substances such as monoclonal antibodies, proteins, plasmids, siRNA, and small molecules for the treatment of neurodegenerative diseases (NDs). BEVs additionally possess a remarkable capacity for delivering these therapeutics across the blood-brain barrier to treat Alzheimer's disease (AD). This review summarizes the role and advancement of BEVs for NDs, AD, and their treatment. Additionally, it investigates the critical BEV networks in the microbiome-gut-brain axis, their defensive and offensive roles in NDs, and their interaction with NDs. Furthermore, the part of BEVs in the neuroimmune system and their interference with ND, as well as the risk factors made by BEVs in the autophagy-lysosomal pathway and their potential outcomes on ND, are all discussed. To conclude, this review aims to gain a better understanding of the credentials of BEVs in NDs and possibly discover new therapeutic strategies.

Green approach for the synthesis of ZnO nanoparticles using Cymbopogon citratus aqueous leaf extract: characterization and evaluation of their biological activities

BackgroundThe green synthesis of metal and metal oxide nanoparticles (NPs), notably from plants, has attracted increasing attention in recent years. Although the increased popularity use of Cymbopogon citratus as a therapeutic substance, to date, there has not been any research on the chemistry of C. citratus aqueous leaf extract (ALE) or synthesis of ZnO NPs utilizing an extract from it. The ecologically safe ALE of C. citratus was employed in this study as a bio-reducing and capping agent to synthesize ZnO NPs.ResultsThe novelty of the current study is the investigation of the antioxidant, anti-inflammatory, anti-microbial, and cytotoxic potencies of biosynthesized ZnO NPs utilizing C. citratus ALE. Zinc acetate dihydrate was used as the precursor and the leaf extract serves as the reducing agent. ZnO NPs from ALE of C. citratus were characterized by the spherical in form by using high-resolution transmission electron microscopy (HR-TEM) and the Scherrer formula was used to calculate the size of the crystalline structure. The presence of numerous functional groups in both the ALE and the NPs is confirmed by FTIR analysis. The highest absorption peak is observed at 370 nm. The stability and particle size of the biosynthesized ZnO NPs are demonstrated by dynamic light scattering (DLS) analysis. The biosynthesized ZnO NPs exhibited excellent antioxidant activity with an IC50 value of 45.67 ± 0.1 μg/mL and exerted interesting anti-inflammatory activity (98.1% ± 0.04) when compared to the standard indomethacin (92.1% ± 0.07) at 1 mg/mL. They also showed anti-microbial activity for both bacterial and fungal which growth rates for both significantly decreased with the increase in ZnO NPs concentration compared to the control. The anticancer activity of biosynthesized ZnO NPs and C. citratus ALE was in vitro tested against seven human cancer cell lines (HCCL) (i.e. H1299, MDA-MB-468, HNO97, HEK, HCT116, HuH7, and HEPG2) compared to normal cells (HSF) using the sulforhodamine-B (SRB) assay. More interestingly, the biosynthesized ZnO NPs displayed remarkable selective cytotoxicity against all tested cancer cell lines without any effect on normal cells. In contrast, the cancer cell lines were not affected by the ALE of C. citratus at any concentrations tested.ConclusionsAll the findings confirm that the ZnO NPs biosynthesized in the current work are promising candidates for a variety of biological activities, and as a result, they can be helpful to the medical sector, environmental and agricultural applications.Graphical

Effect of silkworm pupae (Bombyx mori) protein on colon cancer in nude mice: inhibition of tumor growth, oxidative stress and inflammatory response.

Silkworm pupa (bombyx mori) protein (SPP) is a potential therapeutic bioactive substance that has anti-tumor activity against breast, liver, and gastric cancers. The aim of this study was to investigate the antitumor effect of SPP on colon cancer nude mice. Using a subcutaneous tumor formation method, we validated the therapeutic effect of SPP on colon cancer nude mice in vivo. Results showed that SPP was cytotoxic to tumor cells. SPP could protect the liver of the nude mice by lowering hepatic oxidative stress and regulating serum inflammation levels by decreasing TNF-α and IL-2 levels while in-creasing INF-γ levels. In addition, diminished Ki-67 protein, enhanced cleaved caspase-3 protein, di-minished Vimentin, enhanced E-cadherin. These findings suggested that SPP's antitumor activity may be achieved by reducing inflammation, inhibiting tumor proliferation and metastasis, and inducing apoptosis in cancer cells. In the future, SPP could be used as an anticancer drug, potentially providing a new source of drugs for the treatment of colon cancer.

Molecular level interaction of solvents (water, benzene and DMSO) analysis of the 2-Bromo-6-nitrotoluene's reactive charge transfer, docking, and spectroscopic properties

The chemical structure of 2-Bromo-6-nitrotoluene was optimized using the B3LYP/6–311++G (d, p) basis set and density functional theory. Calculations were made on the molecules of the substance 2-Bromo-6-nitrotoluene's geometrical-parameters. A variety of DFT techniques, including border atomic orbitals, essential binding orbitals, local reaction descriptors, and molecular electrostatic potentials, are worn to test the reactivity of molecules. Several solvents (water, benzene and DMSO) were examined by UV–vis spectroscopy and vapor phase electronic transition. Estimated efficiency for the most heavily inhabited molecular orbital and even the least vacant molecular orbital describes electron excitation properties. Environmental toxicity, pharmacological similarity, localized orbital location, and electron localized function were assessed. To evaluate the material's metabolic processes, chemical interaction modelling was used. In conclusion, this paper offers a thorough investigation combining spectroscopic and quantum computational methods to evaluate the metabolic function and solvation impact of selected therapeutic substances. The information gathered is therefore very useful in planning for future study.

Amelioration of experimental colitis by a site-specific novel plant polysaccharide (Opuntia ficusindica) based macroparticles contains probiotic biomass and mesalazine

The availability of therapeutic substances at colonic regions is always challenging for researchers. In this work, we aimed to evaluate the colon-targeting ability of mesalazine and probiotic biomass using Opuntia ficusindica polysaccharide. The present work will explore the application of novel plant polysaccharides as a rate-controlling polymer for colon drug delivery. Opuntia ficusindica polysaccharide was extracted and evaluated for the in-vitro toxicity study on HT-29 cell lines. Drug-loaded macroparticles were prepared and compressed into the tablet. In-vitro drug release was determined in simulated gastric fluid. Disease models were developed in Sprague Dawley rats to determine the efficacy of prepared formulation in the presence of probiotic biomass. Colon targeting efficiency of 99mTc-pertechnetate labeled mesalazine was monitored in human volunteers. Investigation of the polysaccharide's in-vitro toxicity revealed that the polysaccharide was safe for colon applications. Drug release data increased (p < 0.05) in the presence of rat cecal material at 6 h. The study also revealed that drug release from the different batches was directly proportional to polysaccharide concentration. In-vivo animal study confirms the better prevention of the disease in the presence of probiotic mass and drug. Gamma scintigraphy further supports the minimal drug release from the radiolabeled formulation in the upper gastrointestinal tract (GIT), despite the fact that it started drug release after 360 min, which was then disseminated during the subsequent 720–960 min in the colon. The study shows that Opuntia ficusindica polysaccharide can be used to deliver mesalazine to the colon.

Zn, Fe, Se, I, phytochemicals assessed in honey and antibacterial activity of sokoto honey on Staphylococcus aureus, and Escherichia coli isolated from WOUND

Antibacterial activity of honey obtained from Specialist Hospital, Sokoto on Staphylococcus aureus and Escherichia coli isolated from wound was studied. the results depicting the levels of iron, selenium, zinc, and iodine micronutrients assessed in honey samples collected from three different zones of Sokoto state, Nigeria. Atomic absorption spectroscopy was used to determine Fe, Zn, se, and I as follows: 7.3± 0.5 to 10.11± 0.15 ppm, 0.50 ± 0.01 to 0.60± 0.01 ppm, 2.6± 0.1 to 11.0 ± 0.05 ppm, 0.05±0.001 to 1.30±0.01 ppm are concentration ranges of Fe, Se, Zn, and I respectively assessed from samples of honey obtained from 3 zones of Sokoto. Agar well diffusion method was used to determine the antibacterial activity of the honey on the test microorganisms. The result revealed that the honey samples have heavy antibacterial activities against the test organisms and zones of inhibition were obtained showing high antibacterial activity. The antibacterial activity increased with increase in the concentrations and the honey produced a high antibacterial activity (clearer zone) on Staphylococcus aureus and Escherichia coli at all concentration. The use of honey as a therapeutic substance has been rediscovered by the medical profession on more recent times, and it is gaining acceptance as an antibacterial agent for the treatment of ulcers and bed sores, and other infections resulting from burns and wounds. Likewise, the honey contains phytochemicals and Zn, Se, Fe, and I micronutrients.&#x0D; &#x0D;

The Impact of Hypromellose on Pharmaceutical Properties of Alginate Microparticles as Novel Drug Carriers for Posaconazole.

Fungal infections are a group of diseases which are challenging to treat because of drug-resistant fungi species, drug toxicity, and often severe patient conditions. Hence, research into new treatments, including new therapeutic substances and novel drug delivery systems, is being performed. Mucoadhesive dosage forms are beneficial to improving drug bioavailability by prolonging the residence time at the site of application. Sodium alginate is a natural polymer with favorable mucoadhesive and gelling properties, although its precipitation in acidic pH significantly disrupts the process of drug release in gastric conditions. Hypromellose is a hydrophilic, semi-synthetic cellulose derivative with mucoadhesive properties, which is widely used as a control release agent in pharmaceutical technology. The aim of this study was to evaluate the impact of hypromellose on alginate microparticles with posaconazole, designed to modify drug release and to improve their mucoadhesive properties for both oral or vaginal application.

#5919 PATIENT-SPECIFIC HUMAN INDUCED PLURIPOTENT STEM CELL (HIPSC)-DERIVED PODOCYTES

Abstract Background and Aims Podocytes typically represent a distinct morphology with long, interdigitating primary and secondary foot processes wrapping around glomerular capillaries forming the filtration unit of the kidney. In glomerular diseases like genetic focal segmental glomerulosclerosis (FSGS), podocyte alterations are often related to dysfunction of the glomerular filtration barrier and the development of proteinuria. Genetic mutations in podocyte relevant genes, important for foot process or actin cytoskeleton dynamics, are known to induce severe podocyte injury. Analysis of podocyte alterations ex vivo is limited because of their inability to proliferate due to their terminal differentiated state and limited access to primary podocytes. Instead, immortalized podocytes regained proliferation capacity by insertion of a thermosensitive SV40 large T antigen and are useful for many research questions. However, these podocytes usually do not express all podocyte marker and foot process development is often restricted. Since we aim to characterize personalized podocytes from patients suffering from genetic FSGS ex vivo, we generated podocytes from dermal fibroblasts via reprogramming into hiPSCs and subsequent differentiation into hiPSC-derived podocytes keeping the patients’ genetic background. Method Dermal fibroblasts were outgrown from a skin punch biopsy from a patient or a healthy donor and subsequently reprogrammed into hiPSCs by electroporation of the common OKSM plasmids and finally differentiated into podocytes. Cells were characterized phenotypically regarding morphology and marker expression using RNA bulk sequencing, western blot, qPCR and immunofluorescence staining. Potential functional alterations of diseased podocytes regarding actin cytoskeleton were assessed by actin polymerization assay. Results Patient-specific podocytes could be generated ex vivo by reprogramming dermal fibroblasts into hiPSCs and subsequently differentiating them into mature podocytes representing the patients’ background. During this process, cell morphology changed from spindle-like fibroblasts to small and round hiPSCs growing in colonies and representing a high nuclei-to body ratio as well as high proliferation rate. During differentiation, hiPSCs were induced into intermediate mesoderm, resulting in increased cell size and decreased proliferation rate terminating in 300 nm large star-shaped podocytes developing a distinct network of long primary and secondary foot processes. Patient-derived hiPSC-podocytes with a mutation in the INF2 gene lacked filamentous actin and only develop a limited number of only short foot processes compared to hiPSC-podocytes derived from a healthy control donor. Moreover, expression of actin cytoskeleton associated genes like SYNPO, ACTN4 and CD2AP was decreased while other actin isoforms, cortactin and the GTPase RhoA were increased in diseased patient-specific podocytes. Actin polymerization assay showed that polymerization process itself was not altered in healthy and diseased hiPSC-podocytes. Conclusion Analysis of patient-specific podocytes is possible ex vivo via differentiation of hiPSCs, generated from patients’ dermal fibroblasts by episomal reprogramming, into hiPSC-derived podocytes, with the potential to study alterations of disease-specific mutations regarding phenotypical and functional behavior in a personalized manner. The use of hiPSCs bypasses the limitation of restricted podocyte cell number and has the advantage of maintaining the patients’ genetic background at podocyte cell level. This enables future large-scale experiments regarding intercell-cell communication and interaction in glomerular three-dimensional co-cultures or via treatment with therapeutic substances or stress factors.

Delivery of Genetic Materials for the Management of Biological Disorders: Advancement and Roles of Polysaccharides and their Derivatives.

Advancement in nanotechnology leads to the development of polysaccharides which are very efficient carriers in delivering therapeutic substances like drugs, proteins, and genes. This review describes the role of polysaccharides and their derivatives in the cellular targeting of genetic materials for the treatment of various biological disorders. Applications, challenges, advantages, and disadvantages of polysaccharides used in gene delivery are discussed in the manuscript. Cationic and natural polysaccharides are generally used for RNA and DNA delivery and exhibit better performance in gene transfection. After a substantial literature survey, it can be concluded that different polysaccharides and their derivatives are effectively used in the delivery of genetic material. Natural polysaccharides are widely used due to their advantageous properties like biocompatibility, biodegradability, and low toxicity in the biological environment.

Generation of Patient-Derived Podocytes from Skin Biopsies.

Podocytes are epithelial cells sitting on the urinary site of the glomerular filtration barrier that contribute to the selective filter function of the glomerulus. Mutations in podocyte-specific genes can cause focal segmental glomerulosclerosis (FSGS), and podocytes are also affected in many other primary and secondary nephropathies. Due to their differentiated nature, primary cell culture models are limited for podocytes.Therefore, commonly conditionally immortalized cells are used. However, these conditionally immortalized podocytes (ciPodocytes) have several limitations: the cells can dedifferentiate in culture, especially when they reach confluency, and several podocyte-specific markers are either only slightly or not expressed at all. This brings the use of ciPodocytes and their applicability for physiological, pathophysiological, and clinical reach into question. Here, we describe a protocol for the generation of human podocytes-including patient-specific podocytes-from a skin punch biopsy by episomal reprogramming of dermal fibroblasts into hiPSCs and subsequent differentiation into podocytes. These podocytes resemble in vivo podocytes much better in terms of morphological characteristics, like the development of foot processes and the expression of the podocyte-specific marker. Finally, yet importantly, these cells maintain patients' mutations, resulting in an improved ex vivo model to study podocyte diseases and potential therapeutic substances in an individualized approach.

Alginate/polyacrylamide host-guest supramolecular hydrogels with enhanced adhesion

Although injectable hydrogels with minimally invasive delivery have garnered significant interest, their potential applications have been restricted by a singular property. In this study, a supramolecular hydrogel system with improved adhesion was constructed through host-guest interactions between alginate and polyacrylamide. The maximum tensile adhesion strength between the β-cyclodextrin and dopamine-grafted alginate/adamantane-grafted polyacrylamide (Alg-βCD-DA/PAAm-Ad, namely AβCDPA) hydrogels and pigskin reached 19.2 kPa, which was 76 % stronger than the non-catechol-based control hydrogel (β-cyclodextrin-grafted alginate/adamantane-grafted polyacrylamide, Alg-βCD/PAAm-Ad). Moreover, the hydrogels demonstrated excellent self-healing, shear-thinning, and injectable properties. The required pressure to extrude the AβCDPA2 hydrogel from a 16G needle at a rate of 2.0 mL/min was 67.4 N. As the polymer concentration and adamantane substitution degree increased, the hydrogels exhibited higher modulus, stronger network structure, and lower swelling ratio and degradation rate. Encapsulating and culturing cells within these hydrogels demonstrated good cytocompatibility. Therefore, this hydrogel can serve as a viscosity extender or bioadhesive, and as a carrier material to deliver encapsulated therapeutic substances into the body through minimally invasive injection methods.

Functional hydrogels for the repair and regeneration of tissue defects.

Tissue defects can be accompanied by functional impairments that affect the health and quality of life of patients. Hydrogels are three-dimensional (3D) hydrophilic polymer networks that can be used as bionic functional tissues to fill or repair damaged tissue as a promising therapeutic strategy in the field of tissue engineering and regenerative medicine. This paper summarises and discusses four outstanding advantages of hydrogels and their applications and advances in the repair and regeneration of tissue defects. First, hydrogels have physicochemical properties similar to the extracellular matrix of natural tissues, providing a good microenvironment for cell proliferation, migration and differentiation. Second, hydrogels have excellent shape adaptation and tissue adhesion properties, allowing them to be applied to a wide range of irregularly shaped tissue defects and to adhere well to the defect for sustained and efficient repair function. Third, the hydrogel is an intelligent delivery system capable of releasing therapeutic agents on demand. Hydrogels are capable of delivering therapeutic reagents and releasing therapeutic substances with temporal and spatial precision depending on the site and state of the defect. Fourth, hydrogels are self-healing and can maintain their integrity when damaged. We then describe the application and research progress of functional hydrogels in the repair and regeneration of defects in bone, cartilage, skin, muscle and nerve tissues. Finally, we discuss the challenges faced by hydrogels in the field of tissue regeneration and provide an outlook on their future trends.

Antibacterial Effect of Raw Honey on Clinical Bacterial Isolates of Pseudomonas aeruginosa, Staphylococcus aureus, And Escherichia coli

The development of multiple drug resistant bacteria, causing human infection in clinical practice unfold the use of natural sources like honey, medicinal plants of non-antibiotic drugs, having antibacterial potentiality. Beside the medicinal plants, the antibacterial effects of raw honey on clinical bacterial isolates of Pseudomonas aeruginosa, Staphylococcus aureus, and Escherichia coli were studied. The raw honey samples were collected from the beekeepers at Umugwu Ezedike in Udi Local Government Area Enugu State Nigeria. The honey samples were prepared by diluting the honey with distilled water to produce honey of various concentrations, i.e. 20% v/v, 40% v/v, 60% v/v, 80% v/v and 100% v/v. The clinical isolates from Accident and Emergency Department University of Nigeria Teaching Hospital Ituku-Ozalla Enugu were cultured in Nutrient agar, Cetrimide agar, Macconkey agar, and Methylene Blue agar (EMB) for identification and confirmation. The antibacterial effects of raw honey on the clinical bacterial isolates were evaluated in-vitro using agar well diffusion methods with Gentamicin as control. The results showed that raw honey demonstrated antibacterial effect against the test isolates with higher effect in Staphylococcus aureus (with zone of inhibition of 21mm) followed by Pseudomonas aeruginosa (19mm) and Escherichia coli (18mm). The minimum inhibitory concentration (MIC) of the extract from this study ranges from 12.5-50mg/ml while the minimum bactericidal concentration (MBC) of the extracts ranges from 25-50mg/ ml. Hence, raw honey has antibacterial properties and can also serve as a therapeutic substance for the treatment of bed sores, and other infections resulting from burns.

Protective effects of flavonoids in Coreopsis tinctoria Nutt. in a mouse model of type 2 diabetes.

Coreopsis tinctoria Nutt., a popular tea drink used in the Xinjiang region of China, has been traditionally used to treat diabetes and chronic metabolic diseases in China, Portugal, and North America. The bioactive extraction and potential mechanism have not been fully elucidated until now. Traditional herbal medicines usually share network targets due to multicomponent therapeutics. Therefore, we tried to explore the protective effects of C. tinctoria on diabetes and the related molecular mechanism. A flavonoid-rich fraction of C. tinctoria (CTF) was prepared. After 15 weeks of continuous treatment with CTF, the blood glucose and blood lipid levels of experimental mice were evaluated. Tissue was collected for differentially expressed genes (DEGs), bioinformatics analysis, RT‒PCR and Western blot for target-related DEGs. After 15 weeks of continuous treatment with CTF, db/db mice showed reversed levels of glucose, insulin, glucagon and glycated hemoglobin A1c. CTF treatment also regulated total cholesterol, triglycerides, low density lipoprotein, nonesterified fatty acid, alanine transaminase, and aspartate transaminase. Major metabolic pathways were found to be dysregulated in the liver using a combined analysis of transcriptomics and network pharmacology. CTF treatment regulated 48.2% of 6357 dysregulated genes in db/db mice. The mitochondrial electron transport chain and tricarboxylic acid cycle were mainly affected. The sequencing data showed that fifty-nine predicted target genes for CTF were reverse regulated. Together with 1528 coexpressed genes, these genes reflected the main characteristics of the whole perturbed transcriptomic profile, i.e., dysregulated mitochondrial metabolism. The important genes of the target and coexpressed genes were further verified at the gene and protein levels. The results confirm that the metabolic changes induced by hyperglycemia are closely related to mitochondrial metabolism in the liver. CTF alters a core gene set that exerts regulatory effects at the biological pathway level in db/db mice. In conclusion, our data reveal that an important molecular event for CTF treatment is the regulation of mitochondrial metabolism and support the idea that herbs or natural compounds are potential therapeutic substances for mitochondrial dysfunction-related diabetes.