Detection of In Vivo-like Cells by a Biosensor Chip Based on Metamaterials in Terahertz Regime.

Early diagnosis of diseases, especially cancer, is critical for effective treatment. The unique properties of terahertz technology have attracted attention in this field. However, current terahertz bio-detection methods face challenges due to differences between the test environment and the actual in vivo conditions. In this study, a novel method is proposed for detecting in vivo-like cells using a biosensor chip composed of metamaterials and a cavity. The cavity has a thickness of ~50 µm. The structure can protect cells from damage and provides a liquid environment like an in vivo state. Through simulation analysis, the metamaterials sensor exhibits a theoretical sensitivity of 0.287 THz/RIU (Refractive Index Unit) with a 50 µm thick analyte. The detection method is experimentally validated using the apoptosis of glioma cells and various cell types. The biosensor investigates the apoptosis of glioma cells under the impact of temozolomide, and the trend of the results was consistent with the Cell Counting Kit-8 method. Furthermore, at a concentration of ~5200 cells/cm2, the experimental results demonstrate that the sensor can distinguish between neurons and glioma cells with a resonance frequency difference of approximately 30 GHz. This research has significant potential for detecting glioma cells and offers an alternative approach to in vivo-like cell detection.

Roles of mechanosensitive ion channels in immune cells.

Mechanosensitive ion channels are a class of membrane-integrated proteins that convert externalmechanical forces, including stretching, pressure, gravity, and osmotic pressure changes, some of which can be caused by pathogen invasion, into electrical and chemical signals transmitted to the cytoplasm. In recent years, with the identification of many of these channels, their roles in the initiation and progression of many diseases have been gradually revealed. Multiple studies have shown that mechanosensitive ion channels regulate the proliferation, activation, and inflammatory responses of immune cells by being expressed on the surface of immune cells and further responding to mechanical forces. Nonetheless, further clarification is required regarding the signaling pathways of immune-cell pattern-recognition receptors and on the impact of microenvironmental changes and mechanical forces on immune cells. This review summarizes the roles of mechanosensitive ion channels in immune cells.

Simultaneous determination of five compounds of fried Radix Paeoniae Alba extract in beagle dogs plasma by Ultra Performance Liquid Chromatography Tandem Mass Spectrometry and its application in a pharmacokinetic study.

In this present study, we developed a reliable and simple ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) assay for the simultaneous quantification of paeoniflorin, albiflorin, oxypaeoniflorin, benzoylpaeoniflorin and isomaltopaeoniflorin in beagle dog plasma. We also analyzed the pharmacokinetics of those components after oral administration of fried Radix Paeoniae Alba (FRPA) in beagle dogs. Plasma samples were processed by protein precipitation with methanol. Chromatographic separation was performed with a Waters HSS-T3 C18 column (100 × 2.1 mm, 1.8 µm, kept at 40°C) using multiple reaction monitoring mode. A gradient elution procedure was used with solvent A (0.02% formic acid-water) and solvent B (0.02% formic acid-acetonitrile) as mobile phases. Method validation was performed as US Food and Drug Administration guidelines, and the results met the acceptance criteria. The method we establish in this experiment was successfully applied to the pharmacokinetic study after oral administration of FRPA extract to beagle dogs.

Liposome-Based Silibinin for Mitigating Nonalcoholic Fatty Liver Disease: Dual Effects via Parenteral and Intestinal Routes.

Nonalcoholic fatty liver disease (NAFLD) is a clinicopathological entity that is typically characterized by intrahepatic ectopic steatosis. Nowadays, NAFLD has surpassed viral hepatitis and become the most common chronic liver disease worldwide, which poses a great threat to human health. Silibinin (Sil), a well-known natural product, has been widely used in clinical treatment for liver disorders and exhibited therapeutic potential for NAFLD. However, the suitability of Sil for NAFLD treatment still requires further investigation due to its limited absorption and low bioavailability. This study aimed to construct a Sil-loaded liposome (Sil-Lip) to overcome the limitations of Sil, thereby enhancing its beneficial effects on NAFLD and then investigate the underlying mechanisms of action of Sil-Lip. Herein, Sil-Lip was fabricated by a well-established thin-film dispersion method and carefully characterized, followed by evaluating their therapeutic efficacy using high-fat diet-induced NAFLD mice and free fatty acid -stimulated HepG2 cells. Then, liver transcriptome analysis and 16S ribosomal RNA (16S rRNA) sequencing were utilized to elucidate the potential mechanisms of action of Sil-Lip. Our data indicated that Sil-Lip harbored good gastrointestinal tract stability, mucus layer permeation, and excellent oral absorption and bioavailability. In vivo and in vitro NAFLD models demonstrated that Sil-Lip had better effects in alleviating lipid metabolism disorders, insulin resistance, and inflammation than did Sil alone. Further investigations revealed that the beneficial effects of Sil-Lip were mediated by modulating intrahepatic insulin resistance-related and nuclear factor-kappa B (NF-κB) signaling pathways and extrahepatic gut microbiota. Our study confirmed that Sil-Lip can effectively improve the absorption and bioavailability of Sil, resultantly potentiating its ameliorative effects on NAFLD through modulating intrahepatic insulin resistance-related and NF-κB signaling pathways and extrahepatic gut microbiota.

Treatment of Idiopathic Pulmonary Fibrosis by Inhaled Silybin Dry Powder Prepared via the Nanosuspension Spray Drying Technology.

Idiopathic pulmonary fibrosis (IPF) is a kind of life-threatening interstitial lung disease characterized by progressive dyspnea with accurate pathogenesis unknown. At present, heat shock protein inhibitors are gradually used to treat IPF. Silybin, a heat shock protein C-terminal inhibitor, has high safety and good application prospects. In this work, we have developed a silybin powder able to be used for inhalation administration for the treatment of IPF. Silybin powder was prepared by the spray drying method and identified using cascade impactometry, particle size, scanning electron microscopy (SEM), differential scanning calorimetry (DSC), X-ray diffraction (XRD), and Fourier transform infrared (FT-IR) spectroscopy. A rat model of bleomycin-induced IPF was used to assess the effect of inhaled silybin spray-dried powder. Lung hydroxyproline content, wet weight, histology, inflammatory factor expression, and gene expression were examined. The results showed that inhaled silybin spray-dried powder alleviated inflammation and fibrosis, limited hydroxyproline accumulation in the lungs, modulated gene expression in the development of IPF, and improved postoperative survival. The results of this study suggest that silybin spray-dried powder is an attractive candidate for the treatment of IPF.

Herb-Drug Interactions and Their Impact on Pharmacokinetics: An Update.

Herb medicine has a long history of application and is still used worldwide. With the development of complementary and alternative medicine, the interaction between herb and drugs has attracted more and more attention. Herb-drug interactions (HDI) could cause decreased efficiency, increased toxicity, and affect the drug absorption and disposition processes due to the interference of their pharmacological or pharmacokinetic effects. Hence, the mechanisms and results of herb-pharmacokinetic interactions should be comprehensively summarized. Here, we have summarized the mechanisms of HDI and pharmacokinetic interactions in the last ten years based on searching on PubMed, Science Direct, and Web of Science with different keywords. Besides, the pharmacokinetic interactions were related to nine commonly used herbs and drugs, including Ginseng, Salvia miltiorrhiza, Ginkgo biloba, Garlic, Coptis chinensis, St. John's wort, Ginger, Licorice, Silythistle and Fructus Schisandrae. This review provides an overview of HDI to provide a reference for the rational and safe clinical use of herbs and drugs.

Simultaneous determination and pharmacokinetic study of six components in beagle dog plasma by UPLC-MS/MS after oral administration of Astragalus Membranaceus aqueous extract.

Astragalus Membranaceus (AM) is widely applied in Chinese herbal compound formulas for treating various kinds of diseases. However, relative pharmacokinetics data on AM in nonrodents is still lacking. Here, an UPLC-MS/MS method for determining the six main compounds of AM was developed. The chromatographic separation was carried out by a Waters Acquity UPLC HSS T3 column (100 × 2.1 mm, 1.8 µm) with gradient elution of water-formic acid (99.98:0.02, v/v) and acetonitrile-formic acid (99.98:0.02, v/v) at a flow rate of 0.3 ml/min within 11 min. Analyses of all compounds were conducted in multiple reaction monitoring mode with a positive/negative ion-switching mode of an electrospray ionization source in a single run. The analytical method was validated in terms of specificity, linearity, accuracy, precision, stability, etc. The method showed excellent linearity (r > 0.999) over certain concentration ranges. The intra-day and inter-day precisions were evaluated, and the RSD values were <12.4%. Furthermore, the validated method was successfully applied to determine the six components in plasma after oral administration of AM aqueous extract to beagle dogs and the pharmacokinetic parameters were obtained. Together, this study provides a reference for medication in the clinical practice of AM.

Pharmacokinetics, Tissue Distribution, and Excretion Characteristics of a Radix Polygoni Multiflori Extract in Rats.

Although progress has been achieved in the pharmacological activity and toxicity of Radix Polygoni Multiflori (RPM), the chemical basis of its toxicity is still unclear. Here, we performed a multicompound pharmacokinetic analysis and investigated the tissue distribution and excretion characteristics of RPM components after oral administration in rats. The findings demonstrated that the active ingredients of the RPM extract were quickly absorbed after oral administration, with high exposure levels of emodin, 2,3,5,4'-teterahydroxystilbene-2-O-ß-D-glucoside (TSG), citreorosein, torachrysone-8-O-glucoside (TG), emodin-8-O-ß-D-glucoside (EG), and physcion-8-O-ß-D-glucoside (PG). The tissue distributions of emodin, TSG, TG, EG, and PG were high in the liver and kidney. These components were the key contributors to the effectiveness and toxicity of RPM on the liver and kidney. Most of the active ingredients were mainly excreted through feces and bile, while a few were converted into other products in the body and excreted through urine and feces.

Cholesterol Microdomain Enhances the Biofilm Eradication of Antibiotic Liposomes.

Resistance and tolerance of biofilms to antibiotics is the greatest challenge in the treatment of bacterial infections. Therefore, developing an effective strategy against biofilms is a top priority. Liposomes are widely used as antibiotic drug carriers; however, common liposomes lack affinity for biofilms. Herein, biofilm-targeted antibiotic liposomes are created by simply adjusting their cholesterol content. The tailored liposomes exhibit significantly enhanced bacterial inhibition and biofilm eradication effects that are positively correlated with the cholesterol content of liposomes. The experiments further demonstrate that this enhanced effect can be ascribed to the effective drug release through the pores, which are formed by the combination of cholesterol microdomains in liposomal lipid bilayers with membrane-damaged toxins in biofilms. Consequently, liposome encapsulation with a high cholesterol concentration improves noticeably the pharmacodynamics and biocompatibility of antibiotics after pulmonary administration. This work may provide a new direction for the development of antibiofilm formulations that can be widely used for the treatment of infections caused by bacterial biofilms.

Exosomal Micro-RNA-96 Derived From Bone Marrow Mesenchymal Stem Cells Inhibits Doxorubicin-Induced Myocardial Toxicity by Inhibiting the Rac1/Nuclear Factor-κB Signaling Pathway.

Background Exosomes are small membranous structures released from cells into the blood, regulating various biological processes. However, the role of exosomes in cardiotoxicity remains largely unclear. This study investigated the functional mechanism of exosomal microRNA-96 (miR-96) derived from bone marrow mesenchymal stem cells (BMSCs) in myocardial toxicity induced by doxorubicin. Methods and Results BMSCs were transfected with miR-96 mimic, miR-96 inhibitor, or the negative control before exosome isolation. The functional mechanism of BMSC-derived exosomal miR-96 was investigated in doxorubicin-induced cell and rat models. The cardiac function, histological morphology, and fiber content of myocardium were examined. The expression levels of the following biomarkers were measured for assessment of cardiac injury: creatine kinase isoenzyme MB, cardiac troponin I, brain natriuretic peptide, soluble suppression of tumorigenesis-2, tumor necrosis factor-α, interleukin-1ß, interleukin-6, superoxide dismutase, glutathione peroxidase, and malondialdehyde. Cell Counting Kit-8 assay was used to measure the survival rate of cardiomyocytes. The expressions of miR-96, Rac1, p-IKKα/IKKα, p-IKKß/IKKß, p-IκBα/IκBα and p-p65/p65 in myocardium and cardiomyocytes were also assessed. The targeting relationship between miR-96 and Rac1 was verified by dual-luciferase reporter assay. miR-96 was downregulated, Rac1 was upregulated and the nuclear factor-κB signaling pathway was activated in doxorubicin-induced cell and animal models. Doxorubicin decreased antioxidative enzymes (superoxide dismutase and glutathione peroxidase) and increased myocardial injury biomarkers (creatine kinase isoenzyme MB, cardiac troponin I, and brain natriuretic peptide), proinflammatory cytokines (tumor necrosis factor-α, interleukin-1ß, and interleukin-6), malondialdehyde, and myocardial fibers. Exosomes derived from BMSCs ameliorated doxorubicin-induced myocardial injuries. Overexpression of miR-96 in exosomes derived from BMSCs further enhanced the protection of myocardium and cardiomyocytes against doxorubicin-induced toxicity while miR-96 knockdown abolished the protective effects of exosomes derived from BMSCs. Rac1 was a target gene of miR-96. Rac1 inhibition could downregulate the expression of the nuclear factor-κB signaling and further reverse the promotion of miR-96 knockdown on doxorubicin-induced myocardial toxicity. Conclusions BMSC-derived exosomal miR-96 protects myocardium against doxorubicin-induced toxicity by inhibiting the Rac/nuclear factor-κB signaling pathway.

An Alternative to Lithium Metal Anodes: Non-dendritic and Highly Reversible Sodium Metal Anodes for Li-Na Hybrid Batteries.

Highly reversible, stable, and non-dendritic metal anode (Li, Na etc.) is a crucial requirement for next-generation high-energy batteries. Herein, we have built a Li-Na hybrid battery (LNHB) based on Na plating/stripping, which features a high and stable coulombic efficiency of 99.2 % after 100 cycles, low voltage hysteresis (42 mV at 2 mA cm-2 ), and fast charge transfer. As a result of the Li+ electrostatic shield layer, the Na deposition showed cubic morphology rather than dendritic, even at high current density of 5 mA cm-2 . The solvation/desolvation of Li+ and Na+ were modelled by density functional theory calculations, demonstrating the fast desolvation kinetics of Na+ . Owing to the superior performance of the Na metal anode, the LNHB coupled with LiFePO4 cathode exhibited low voltage hysteresis and stable cycling performance that demonstrates its feasibility in practical applications.