Wogonin mitigates acetaminophen-induced liver injury in mice through inhibition of the PI3K/AKT signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Scutellaria baicalensis Georgi (SBG), a widely used traditional Chinese medicine, exhibits anti-inflammatory and antioxidant properties. Wogonin is one of the primary bioactive components of SBG. Acetaminophen (APAP)-induced liver injury (AILI) represents a prevalent form of drug-induced liver damage and is primarily driven by inflammatory responses and oxidative stress. AIM OF STUDY: To investigate the therapeutic effects of Wogonin on AILI and the underlying mechanisms. MATERIALS AND METHODS: C57BL/6 J mice were pre-treated with Wogonin (1, 2.5, and 5 mg/kg bodyweight) for 3 days, followed by treatment with APAP (300 mg/kg bodyweight). The serum and liver tissue samples were collected at 24 h post-APAP treatment. Bone marrow-derived macrophages and RAW264.7 cells were cultured and pre-treated with Wogonin (5, 10, and 20 µM) for 30 min, followed by stimulation with lipopolysaccharide (LPS; 100 ng/mL) for 3 h. To examine the role of the PI3K/AKT signaling pathway in the therapeutic effect of Wogonin on AILI, mice and cells were treated with LY294002 (a PI3K inhibitor) and MK2206 (an AKT inhibitor). RESULTS: Wogonin pre-treatment dose-dependently alleviated AILI in mice. Additionally, Wogonin suppressed oxidative stress and inflammatory responses. Liver transcriptome analysis indicated that Wogonin primarily regulates immune function and cytokines in AILI. Wogonin suppressed inflammatory responses of macrophages by inhibiting the PI3K/AKT signaling pathway. Consistently, Wogonin exerted therapeutic effects on AILI in mice through the PI3K/AKT signaling pathway. CONCLUSIONS: Wogonin alleviated AILI and APAP-induced hepatotoxicity in mice through the PI3K/AKT signaling pathway.

Hydrogel scaffolds in the treatment of spinal cord injury: a review.

Spinal cord injury (SCI) is a disease of the central nervous system often caused by accidents, and its prognosis is unsatisfactory, with long-term adverse effects on patients' lives. The key to its treatment lies in the improvement of the microenvironment at the injury and the reconstruction of axons, and tissue repair is a promising therapeutic strategy. Hydrogel is a three-dimensional mesh structure with high water content, which has the advantages of biocompatibility, degradability, and adjustability, and can be used to fill pathological defects by injectable flowing hydrophilic material in situ to accurately adapt to the size and shape of the injury. Hydrogels mimic the natural extracellular matrix for cell colonization, guide axon extension, and act as a biological scaffold, which can be used as an excellent carrier to participate in the treatment of SCI. The addition of different materials to make composite hydrogel scaffolds can further enhance their performance in all aspects. In this paper, we introduce several typical composite hydrogels and review the research progress of hydrogel for SCI to provide a reference for the clinical application of hydrogel therapy for SCI.

A MODIFIED SURGICAL SEPSIS MODEL SATISFYING SEPSIS-3 AND HAVING HIGH CONSISTENCY OF MORTALITY.

ABSTRACT: Background : Cecal ligation and perforation (CLP) is currently considered the criterion standard model of sepsis; however, there are some deficiencies, such as low clinical relevance, inconsistency in severity grading, and an unknown proportion of CLP animals meeting the requirements of sepsis-3. Methods : Adult rats were randomly divided into the following three groups: modified CLP (M-CLP) group, CLP group, and sham group. The vital organ function of rats was evaluated 24 hours postoperatively by blood pressure, behavioral testing, histopathology, and blood test. Cytokine levels were determined by enzyme-linked immunosorbent assay, and T-cell suppression was assessed by flow cytometry. The stability of the model was evaluated by comparing the survival rates of repeated experiments in all groups from day 1 to day 14. Results : More rats in the M-CLP group met Sepsis-3 criteria than those in the CLP group 24 hours postoperatively (53.1% vs. 21.9%, P = 0.01). Rats in the M-CLP group developed more serious hepatic, pulmonary, and renal dysfunction. Similar to human sepsis, rats in the M-CLP group demonstrated more serious immunosuppression and systemic inflammation compared with the CLP group. In addition, disease development and severity, which was indicated by the stable survival rates of model animals, were more stable in the M-CLP group. Conclusions : More rats could meet Sepsis-3 criteria with this novel surgical procedure, which may reduce the number of animals needed in preclinical sepsis experiments. This stable M-CLP model may contribute to the development of new therapies.

Platelet Rich Plasma in the Repair of Articular Cartilage Injury: A Narrative Review.

OBJECTIVE: This paper reviews the research of platelet-rich plasma (PRP) in articular cartilage injury repair, to assess the mechanism, utilization, and efficacy of PRP in the treatment of articular cartilage injury, hoping to provide a theoretical basis for the clinical application of PRP in the future. MATERIALS AND METHODS: A comprehensive database search on PRP applications in cartilage repair was performed. Among them, the retrieval time range of PRP in clinical trials of repairing knee cartilage injury was from January 1, 2021 to January 1, 2022. Non-clinical trials and studies unrelated to cartilage injury were excluded. RESULT: PRP can affect inflammation, angiogenesis, cartilage protection, and cellular proliferation and differentiation after articular cartilage injury through different pathways. In all, 13 clinical trials were included in the analysis. CONCLUSION: PRP is an emergent therapeutic approach in tissue engineering. Most studies reported that PRP has a positive effect on cartilage injury, improving the joint function, meanwhile there is a lack of standardized standards. The technology of PRP in the repair and treatment of articular cartilage injury is worthy of further research.

Effect of Hydroxyapatite Coating by Er: YAG Pulsed Laser Deposition on the Bone Formation Efficacy by Polycaprolactone Porous Scaffold.

Composite scaffolds obtained by the combination of biodegradable porous scaffolds and hydroxyapatite with bone regeneration potential are feasible materials for bone tissue engineering. However, most composite scaffolds have been fabricated by complicated procedures or under thermally harsh conditions. We have previously demonstrated that hydroxyapatite coating onto various substrates under a thermally mild condition was achieved by erbium-doped yttrium aluminum garnet (Er: YAG) pulsed laser deposition (PLD). The purpose of this study was to prepare a polycaprolactone (PCL) porous scaffold coated with the hydroxyapatite by the Er: YAG-PLD method. Hydroxyapatite coating by the Er: YAG-PLD method was confirmed by morphology, crystallographic analysis, and surface chemical characterization studies. When cultured on PCL porous scaffold coated with hydroxyapatite, rat bone marrow-derived mesenchymal stem cells adhered, spread, and proliferated well. The micro-CT and staining analyses after the implantation of scaffold into the critical-sized calvaria bone defect in rats indicate that PCL porous scaffold coated with hydroxyapatite demonstrates accelerated and widespread bone formation. In conclusion, PCL porous scaffold coated with hydroxyapatite obtained by the Er: YAG-PLD method is a promising material in bone tissue engineering.

Anti-epileptic/pro-epileptic effects of sodium channel modulators from Buthus martensii Karsch.

The East Asian scorpion Buthus martensii Karsch (BmK) is one of the classical traditional Chinese medicines for treating epilepsy for over a thousand years. Neurotoxins purified from BmK venom are considered as the main active ingredients, acting on membrane ion channels. Voltage-gated sodium channels (VGSCs) play a crucial role in the occurrence of epilepsy, which make them become important drug targets for epilepsy. Long chain toxins of BmK, composed of 60-70 amino acid residues, could specifically recognize VGSCs. Among them, α-like neurotoxins, binding to the receptor site-3 of VGSC, induce epilepsy in rodents and can be used to establish seizure models. The ß or ß-like neurotoxins, binding to the receptor site-4 of VGSC, have significant anticonvulsant effects in epileptic models. This review aims to illuminate the anticonvulsant/convulsant effects of BmK polypeptides by acting on VGSCs, and provide potential frameworks for the anti-epileptic drug-design.

Characterization of Hydroxyapatite Film Obtained by Er:YAG Pulsed Laser Deposition on Sandblasted Titanium: An In Vitro Study.

The surface of titanium (Ti) dental implants must be modified to improve their applicability, owing to the biological inertness of Ti. This study aims to use sandblasting as a pretreatment method and prepare a hydroxyapatite (HA) coating on Ti to improve its biocompatibility and induce bone bonding and osteogenesis. In this paper, sandblasted Ti discs were coated with α-tricalcium phosphate (α-TCP) via Er:YAG pulsed laser deposition (Er:YAG-PLD). An HA coating was then obtained via the hydrothermal treatment of the discs at 90 °C for 10 h. The surface characteristics of the samples were evaluated by SEM, SPM, XPS, XRD, FTIR, and tensile tests. Rat bone marrow mesenchymal stem cells were seeded on the HA-coated discs to determine cellular responses in vitro. The surface characterization results indicated the successful transformation of the HA coating with a nanorod-like morphology, and its surface roughness increased. In vitro experiments revealed increased cell attachment on the HA-coated discs, as did the cell morphology of fluorescence staining and SEM analysis; in contrast, there was no increase in cell proliferation. This study confirms that Er:YAG-PLD could be used as an implant surface-modification technique to prepare HA coatings with a nanorod-like morphology on Ti discs.

The vasculature niches required for hematopoiesis.

Endothelial cells play a critical role in supporting postnatal hematopoiesis in the bone marrow. Unique endothelial cells, together with various perivascular cells, form different types of vascular structures, constructing a vast microvascular delivery and trafficking network for blood cells, oxygen, and nutrition. These blood vessels build distinct hematopoietic stem and progenitor cell niches, which offer not only sites of residence for blood cells but also indispensable signals directing HSPC homing, self-renewal, and multilineage differentiation. Deep insight into the structure and function of the BM vasculature niche and its participation in hematopoiesis is necessary to develop advanced strategies for the reconstitution of hematopoiesis.

Hydroxyapatite Film Coating by Er:YAG Pulsed Laser Deposition Method for the Repair of Enamel Defects.

There are treatments available for enamel demineralization or acid erosion, but they have limitations. We aimed to manufacture a device that could directly form a hydroxyapatite (HAp) film coating on the enamel with a chairside erbium-doped yttrium aluminum garnet (Er:YAG) laser using the pulsed laser deposition (PLD) method for repairing enamel defects. We used decalcified bovine enamel specimens and compacted α-tricalcium phosphate (α-TCP) as targets of Er:YAG-PLD. With irradiation, an α-TCP coating layer was immediately deposited on the specimen surface. The morphological, mechanical, and chemical characteristics of the coatings were evaluated using scanning electron microscopy (SEM), scanning probe microscopy (SPM), X-ray diffractometry (XRD), and a micro-Vickers hardness tester. Wear resistance, cell attachment of the HAp coatings, and temperature changes during the Er:YAG-PLD procedure were also observed. SEM demonstrated that the α-TCP powder turned into microparticles by irradiation. XRD peaks revealed that the coatings were almost hydrolyzed into HAp within 2 days. Micro-Vickers hardness indicated that the hardness lost by decalcification was almost recovered by the coatings. The results suggest that the Er:YAG-PLD technique is useful for repairing enamel defects and has great potential for future clinical applications.

LncRNA CASC19 accelerates chondrocytes apoptosis and proinflammatory cytokine production to exacerbate osteoarthritis development through regulating the miR-152-3p/DDX6 axis.

BACKGROUND: Osteoarthritis (OA) is one kind of degenerative joint disease that happens in articular cartilage and other joint tissues. Long non-coding RNAs (lncRNAs) have been reported to serve as pivotal regulators in many diseases, including OA. However, the role and relevant regulatory mechanisms of CASC19 in OA remain unknown. METHODS: The expression levels of CASC19, miR-152-3p, and DDX6 were identified by reverse-transcription polymerase chain reaction (RT-qPCR). Cell viability and apoptosis were determined by Cell Counting Kit-8 (CCK-8) and flow cytometry assays, respectively. The relationship between miR-152-3p and CASC19 or DDX6 was predicted by bioinformatics tools and verified by the dual-luciferase reporter assay. RESULTS: CASC19 was verified to exhibit higher expression in OA tissues and cells. Moreover, inhibition of CASC19 weakened proinflammatory cytokine (IL-6, IL-8, and TNF-α) production and cell apoptosis but facilitated cell viability. Experiments of the ceRNA mechanism elucidated that miR-152-3p was a sponge for CASC19, and miR-152-3p targeted DDX6, suggesting that CASC19 sponged miR-152-3p to release DDX6. Finally, results from rescue assays proved that the impacts of CASC19 silencing on chondrocytes apoptosis and proinflammatory cytokine production could be reversed by DDX6 overexpression. CONCLUSIONS: It was concluded that lncRNA CASC19 accelerated chondrocytes apoptosis and proinflammatory cytokine production to exacerbate osteoarthritis development through regulating the miR-152-3p/DDX6 axis. These findings may offer an effective biological target for OA treatment.

Biocompatibility of a High-Plasticity, Calcium Silicate-Based, Ready-to-Use Material.

The Bio-C Sealer is a recently developed high-plasticity, calcium-silicate-based, ready-to-use material. In the present study, chemical elements of the materials were characterized using scanning electron microscopy (SEM), X-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FTIR). The biocompatibility of the Bio-C Sealer was investigated using cytotoxicity tests and histological responses in the roots of dogs' teeth. XRD, SEM, and FTIR produced hydrated calcium silicate in the presence of water molecules. In addition, FTIR showed the formation of calcium hydroxide and polyethylene glycol, a dispersing agent. The 1:4 dilutions of Bio-C Sealer presented weaker cytotoxicity than the Calcipex II in an in vitro system using the V-79 cell line. After 90 d, the periradicular tissue response of beagle dog roots was histologically evaluated. Absence of periradicular inflammation was reported in 17 of the 18 roots assessed with the Bio-C Sealer, whereas mature vertical periodontal ligament fibers were observed in the apical root ends filled with the Bio-C Sealer. Based on these results and previous investigations, the Bio-C Sealer is recommended as an effective root-end filling material. These results are relevant for clinicians considering the use of Bio-C Sealer for treating their patients.

Decontamination of Titanium Surface Using Different Methods: An In Vitro Study.

Contamination of implants is inevitable during different steps of production as well as during the clinical use. We devised a new implant cleaning strategy to restore the bioactivities on dental implant surfaces. We evaluated the efficiency of the Finevo cleaning system, and Ultraviolet and Plasma treatments to decontaminate hydrocarbon-contaminated titanium disks. The surfaces of the contaminated titanium disks cleaned using the Finevo cleaning system were similar to those of the uncontaminated titanium disks in scanning electron microscopy and X-ray photoelectron spectroscopy analysis, but no obvious change in the roughness was observed in the scanning probe microscopy analysis. The rat bone marrow mesenchymal stem cells (rBMMSCs) cultured on the treated titanium disks attached to and covered the surfaces of disks cleaned with the Finevo cleaning system. The alkaline phosphatase activity, calcium deposition, and osteogenesis-related gene expression in rBMMSCs on disks cleaned using the Finevo cleaning system were higher compared to those in the ultraviolet and plasma treatments, displaying better cell functionality. Thus, the Finevo cleaning system can enhance the attachment, differentiation, and mineralization of rBMMSCs on treated titanium disk surfaces. This research provides a new strategy for cleaning the surface of contaminated titanium dental implants and for restoration of their biological functions.

Scalable Device for Automated Microbial Electroporation in a Digital Microfluidic Platform.

Electrowetting-on-dielectric (EWD) digital microfluidic laboratory-on-a-chip platforms demonstrate excellent performance in automating labor-intensive protocols. When coupled with an on-chip electroporation capability, these systems hold promise for streamlining cumbersome processes such as multiplex automated genome engineering (MAGE). We integrated a single Ti:Au electroporation electrode into an otherwise standard parallel-plate EWD geometry to enable high-efficiency transformation of Escherichia coli with reporter plasmid DNA in a 200 nL droplet. Test devices exhibited robust operation with more than 10 transformation experiments performed per device without cross-contamination or failure. Despite intrinsic electric-field nonuniformity present in the EP/EWD device, the peak on-chip transformation efficiency was measured to be 8.6 ± 1.0 × 108 cfu·µg-1 for an average applied electric field strength of 2.25 ± 0.50 kV·mm-1. Cell survival and transformation fractions at this electroporation pulse strength were found to be 1.5 ± 0.3 and 2.3 ± 0.1%, respectively. Our work expands the EWD toolkit to include on-chip microbial electroporation and opens the possibility of scaling advanced genome engineering methods, like MAGE, into the submicroliter regime.

Psychological maladjustment of Asian and African peacekeepers in Liberia and its related factors.

This study aimed to investigate the maladjustment of Asian (Bangladeshi, Pakistani) and African (Nigerian, Namibian, Ghanaian) peacekeepers and its major influence factors. By random cluster sampling, 300 Asian peacekeepers and 271 African peacekeepers were administered the military psychological maladjustment scale (MPMS) and risk factors questionnaire. Investigation at Day 7 and Day 120 into the peacekeeping deployment period indicated that MPMS total score and factor scores of the Asian peacekeepers were significantly lower than those of the African peacekeepers (p < .01). The total score and each factor score of MPMS of the Asian peacekeepers significantly decreased (p < .01); for the African peacekeepers, only the factor score of emotional disorder of MPMS significantly decreased (p < .05). Stepwise regression analysis showed that the education duration was the influence factor for the emotional disorder factor score in the Asian peacekeepers, and the two factors were positively correlated. Age, military service duration, education duration and marital status were the major influence factors for the MPMS factors of the African peacekeepers, among which age was negatively correlated with the total score and each factor score, and military service duration, education duration and marital status were positively related. We conclude that the Asian peacekeepers are more adaptable and resilient than the African peacekeepers. Education duration was the major influence factor for Emotional Disorder in the Asian peacekeepers. The major influence factors for maladjustment in the African peacekeepers were age, military service duration, education duration and marital status.