Xuebijing injection and its bioactive components alleviate nephrotic syndrome by inhibiting podocyte inflammatory injury.

Xuebijing injection (XBJ) is widely used to treat nephrotic syndrome (NS) in clinic, but its bioactive components and therapeutic mechanism are still unclear. In this study, the bioactive components of XBJ were determined by ultra-performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF/MS). The therapeutic effect of XBJ on NS was evaluated in BALB/c mice induced by adriamycin (ADR, 10 mg/kg) via a single tail vein. The protective effect of XBJ and its bioactive components on podocytes was demonstrated using mouse podocytes (MPC-5) induced by lipopolysaccharide (LPS, 4 µg/mL). The results show that 33 components of XBJ were identified. Furthermore, 12 bioactive components were detected in blood, including protocatechuic acid, salvianolic acid C, benzoyloxypaeoniflorin, danshensu, salvianolic acid A, salvianolic acid B, catechin, caffeic acid, galloylpaeoniflorin, oxypaeoniflorin, hydroxysafflor yellow A, rosmarinic acid. The relative content (%) of the bioactive components were 59.32, 16.01, 9.97, 9.73, 8.72, 8.31, 7.92, 6.54, 1.54, 1.30, 0.68 and 0.59 in this order. After XBJ treatment, the renal function, hyperlipidemia and renal pathological damage were improved in NS model mice. Moreover, the levels of nephrin and desmin which are functional proteins in podocytes were reversed, and the levels of pro-inflammatory factors were reduced by XBJ. Interestingly, protocatechuic acid and salvianolic acid C also showed good protective effects on podocyte function and reduced the level of inflammation in LPS-induced MPC-5. The study is the first time to elucidate the bioactive components of XBJ and its potential therapeutic mechanism for treating NS by protecting podocyte function.

Danshen injection induces autophagy in podocytes to alleviate nephrotic syndrome via the PI3K/AKT/mTOR pathway.

BACKGROUND: Danshen injection (DSI) is an agent extracted from the Salvia miltiorrhiza Bunge, a natural drug commonly used to alleviate kidney diseases. However, the material basis and therapeutic effects of DSI on nephrotic syndrome (NS) remain unclear. PURPOSE: To investigate the material basis of DSI and the therapeutic effects and underlying mechanisms of NS. METHODS: NS models were established using adriamycin-induced BALB/c mice and lipopolysaccharide-induced mouse podocytes (MPC-5). Following DSI and prednisone administration, kidney coefficients, 24 h urine protein, blood urea nitrogen, and serum creatinine levels were tested. Histomorphology was observed by periodic acid-Schiff staining and hematoxylin and eosin staining of the kidney sections. The glomerular basement membrane and autophagosomes of the kidneys were observed using transmission electron microscopy. Nephrin and desmin levels in the glomeruli were tested using immunohistochemistry. The viability of MPC-5 cells was tested using cell counting kit-8 after chloroquine and rapamycin administration in combination with DSI. The in vivo and in vitro protein levels of phosphatidylinositol 3-kinase (PI3K), AKT, phosphorylated AKT (Ser473), mammalian target of rapamycin (mTOR), microtubule-associated protein light chain 3 (LC3), beclin1, cleaved caspase-3, and caspase-3 were detected using western blotting. RESULTS: Our results showed that DSI contained nine main components: caffeic acid, danshensu, lithospermic acid, rosmarinic acid, salvianolic acid A, salvianolic acid B, salvianolic acid C, salvianolic acid D, and 3, 4-Dihydroxybenzaldehyde. In in vivo studies, the NS mice showed renal function and pathological impairment. Podocytes were damaged, with decreased levels of autophagy and apoptosis, accompanied by inhibition of the PI3K/AKT/mTOR signaling. DSI administration resulted in improved renal function and pathology in NS mice, with the activation of autophagy and PI3K/AKT/mTOR signaling in the kidneys. Additionally, podocytes were less damaged and intracellular autophagosomes were markedly increased. In vitro studies have shown that DSI activated MPC-5 autophagy and reduced apoptosis via the PI3K/AKT/mTOR pathway. CONCLUSION: Collectively, this study demonstrated that DSI activated podocyte autophagy and reduced apoptosis via the PI3K/AKT/mTOR signaling, ultimately attenuating NS. Our study clarified the main components of DSI and elucidated its therapeutic effects and potential mechanisms for NS, providing new targets and agents for the clinical treatment of NS.

Roles and action mechanisms of bile acid-induced gastric intestinal metaplasia: a review.

Gastric intestinal metaplasia (IM) is a precancerous lesion that increases the risk of subsequent gastric cancer (GC) development. Therefore, the mechanism of IM has been the focus of basic and clinical research. Helicobacter pylori (H. pylori) infection has been recognized as the main pathogenesis of gastric IM. However, more and more studies have shown that chronic inflammation of gastric mucosa caused by bile reflux is the key pathogenic factor of gastric IM. Bile reflux activates the expression of IM biomarkers via the bile acid receptor. In addition, microRNAs, exosomes, and epigenetics are also involved in the occurrence and development of bile acid-induced gastric IM. Currently, the relevant research is still very few. The molecular mechanism of the phenotypic transformation of gastrointestinal epithelial cells induced by bile acids has not been fully understood. This article mainly reviews the physiology and pathology of bile acid, mechanism of gastric IM induced by bile acid, bile acid receptors, and so on, in order to provide reference for further research.

Above room-temperature dielectric switching and semiconducting properties of a layered organic-inorganic hybrid compound: (C6H12N)2Pb(NO3)4.

The well-studied star compound, CH3NH3PbI3, has attracted plenty of attention because of its remarkable optical and electrical properties. Consequently, new switching multifunctional hybrid compounds can be widely used in many fields such as solar cells, light-emitting diodes, optical data storage and so on. Therefore, switching multifunctional hybrid compounds with dielectric and semiconducting properties simultaneously will also find roles in the next generation of optoelectronic coupling materials. In fact, discovering an effective method to synthesize (multi)functional hybrid materials remains a pressing challenge. Thanks to the "quasi-spherical theory" proposed by Xiong et al., we used 7-azabicyclo[2.2.1]heptane as the quasi-spherical cation to construct molecule-based crystalline materials that exhibit responsive properties. Then, we tried to exploit the knowledge of crystal engineering and coordination chemistry to explain (multi)functional molecular materials. A layered organic-inorganic hybrid compound, (C6H12N)2Pb(NO3)4 (1), was grown and its dielectric switching property and semiconducting behaviour were investigated. Insights from differential scanning calorimetry measurements, variable-temperature X-ray structural studies, and dielectric spectroscopy revealed the origin of the phase transition, which is related to the motion of the organic ammonium and inorganic framework in solid-state crystals. Furthermore, 1 is also a wide bandgap semiconductor with an optical bandgap of 3.53 eV. The realization of switching and semiconducting properties simultaneously in layered Pb-based perovskites has a great significance toward research into hybrid compounds and the development of dielectric-optoelectronic integrated materials.

Large Piezoelectric Response in Hybrid Rare-Earth Double Perovskite Relaxor Ferroelectrics.

Piezoelectric materials are technologically important, and the most used are perovskite ferroelectrics. In recent years, more and more emerging areas have put forward new requirements for piezoelectric materials, such as light weight, low acoustic impedance, good flexibility, and biocompatibility. In this context, hybrid organic-inorganic perovskite ferroelectrics have emerged as promising supplements, because they combine attractive features of inorganic and organic materials. Among them, hybrid double-metal perovskites have recently been found to exhibit excellent ferroelectricity. However, their potential as piezoelectric materials has not been exploited. Here, we describe large piezoelectric response in hybrid rare-earth double perovskite relaxor ferroelectrics (RM3HQ)2RbLa(NO3)6 and (RM3HQ)2NH4La(NO3)6 (RM3HQ = R-N-methyl-3-hydroxylquinuclidinium). They are simultaneously ferroelectric and ferroelastic crystals, with the R3 ferroelectric phase and P213 paraelectric phase. We found that ferroelectric polar microdomains and paraelectric nonpolar regions coexist in a wide temperature range through variable-temperature piezoresponse force microscopy images. The two-phase coexistence reveals low energy barriers of transitions between the two phases and between the polar microdomains with different polarization directions. These lead to the easy polarization rotation of the polar microdomains upon applying a stress and, accordingly, the large piezoelectric response up to 106 pC N-1 for (RM3HQ)2RbLa(NO3)6. This finding represents a significant step toward novel applications of piezoelectric materials based on lead-free hybrid perovskites.

Hybrid Organic-Inorganic Antiperovskites.

Substitution of A-site and/or X-site ions of ABX3 -type perovskites with organic groups can give rise to hybrid perovskites, many of which display intriguing properties beyond their parent compounds. However, this method cannot be extended effectively to hybrid antiperovskites. Now, the design of hybrid antiperovskites under the guidance of the concept of Goldschmidt's tolerance factor is presented. Spherical anions were chosen for the A and B sites and spherical organic cations for the X site, and seven hybrid antiperovskites were obtained, including (F3 (H2 O)x )(AlF6 )(H2 dabco)3 , ((Co(CN)6 )(H2 O)5 )(MF6 )(H2 dabco)3 (M=Al3+ , Cr3+ , or In3+ ), (Co(CN)6 )(MF6 )(H2 pip)3 (M=Al3+ or Cr3+ ), and (SbI6 )(AlF6 )(H2 dabco)3 . These new structures reveal that all ions at A, B, and X sites of inorganic antiperovskites can be replaced by molecular ions to form hybrid antiperovskites. This work will lead to the synthesis of a large family of hybrid antiperovskites.

Two-Dimensional Organic-Inorganic Hybrid Rare-Earth Double Perovskite Ferroelectrics.

As a major branch of hybrid perovskites, two-dimensional (2D) hybrid double perovskites are expected to be ideal systems for exploring novel ferroelectric properties, because they can accommodate a variety of organic cations and allow diverse combinations of different metal elements. However, no 2D hybrid double perovskite ferroelectric has been reported since the discovery of halide double perovskites in the 1930s. Based on trivalent rare-earth ions and chiral organic cations, we have designed a new family of 2D rare-earth double perovskite ferroelectrics, A4MIMIII(NO3)8, where A is the organic cation, MI is the alkaline metal or ammonium ion, and MIII is the rare-earth ion. This is the first time that ferroelectricity is realized in 2D hybrid double perovskite systems. These ferroelectrics have achieved high-temperature ferroelectricity and photoluminescent properties. By varying the rare-earth ion, variable photoluminescent properties can be achieved. The results reveal that the 2D rare-earth double perovskite systems provide a promising platform for achieving multifunctional ferroelectricity.

DNA methylation regulated by ascorbic acids in yak preimplantation embryo helps to improve blastocyst quality.

DNA methylation as an important, essential epigenetic modification is critical for the successful development of mammalian embryos. In recent years, the important role of ascorbic acid (AA) as an irreplaceable cofactor for epigenetic regulation has been confirmed. However, the effect of AA on DNA methylation in preimplantation embryo development of plateau yak remains unknown. In this study, we explored whether AA can help regulates DNA methylation in yak preimplantation embryos to improve the blastocyst quality. First, our results indicate that the preimplantation of the yak still follows the classical pattern of DNA demethylation and remethylation, however, remethylation occurs in the blastocyst stage. Second, the unique expression pattern of the ten-eleven translocation enzyme (TET3) in the cytoplasm plays a key role in the demethylation mechanism. Third, in the blastocyst stage, the pluripotency gene CDX2 promoter region was in a hypomethylated state, and the POU5F1, SOX2, and NANOG promoter regions were in moderate methylation states. In addition, treatment with 50 µg/ml AA mainly improved the expression levels of DNMT1, DNMT3a, and TET3, ensured the establishment, maintenance and transition of 5-methylcytosine. After AA treatment, the methylation level of the pluripotency genes NANOG promoter regions was significantly reduced, and the mRNA transcript abundance of the pluripotency genes NANOG, POU5F1, and CDX2 was upregulated. In conclusion, our findings suggest that AA could increase blastocyst cell numbers by regulating DNA methylation of yak preimplantation embryos .

Nedaplatin salvage chemotherapy for cervical cancer.

PURPOSE: This systematic analysis was conducted to evaluate the efficacy and safety of nedaplatin based salvage chemotherapy for treatment of patients with advanced cervical cancer. METHODS: Clinical studies evaluating the efficacy and safety of nedaplatin based regimens on response and safety for patients with cervical cancer were identified using a predefined search strategy. Pooled response rates (RRs) were calculated. RESULTS: For nedaplatin based regimens, 5 clinical studies including 264 patients with advanced cervical cancer were considered eligible for inclusion. The analysis showed that, in all patients, pooled RR was 74.6% (197/264). Major adverse effects were leukopenia, thrombocytopenia and nausea/vomiting. No treatment related death occurred with nedaplatin based treatment. CONCLUSION: This systematic analysis suggests that nedaplatin based regimens are associated with good activity with acceptable tolerability in treating patients with advanced cervical cancer.

IQ-related fMRI differences during cognitive set shifting.

This event-related functional magnetic resonance imaging study compared neural correlates of executive function (cognitive set-shifting) in 28 healthy participants with either high (HIQ) or average (AIQ) intelligence. Despite comparable behavioral performance (except for slower reactions), the AIQ participants showed greater (especially prefrontal) activation during response selection; the HIQ participants showed greater activation (especially parietal) during feedback evaluation. HIQ participants appeared to engage cognitive resources to support more efficient strategies (planning during feedback in preparation for the upcoming response) which resulted in faster responses and less need for response inhibition and conflict resolution. Whether greater intelligence is associated with more or less brain activity (the "neural efficiency" debate) depends therefore on the specific component of the task being examined as well as the brain region recruited. One implication is that caution must be exercised when drawing conclusions from differences in activation between groups of individuals in whom IQ may differ (e.g., psychiatric vs. control samples).