Revealing active constituents within traditional Chinese Medicine used for treating bacterial pneumonia, with emphasis on the mechanism of baicalein against multi-drug resistant Klebsiella pneumoniae.

ETHNOPHARMACOLOGICAL RELEVANCE: The emergence of antibiotic-resistant bacteria has rendered it more challenging to treat bacterial pneumonia. Traditional Chinese medicine (TCM) has superior efficacy in the treatment of pneumonia, and it has the unique advantage of antibacterial resistance against multi-drug resistant (MDR) bacteria, but the medication rule and pharmacological mechanism of its antibacterial activity are not clear. AIM OF THE STUDY: This study aims to reveal Chinese medication patterns in treating bacterial pneumonia to select bioactive constituents in core herbs, predict their pharmacological mechanisms and further explore their antibacterial ability against clinically isolated MDR Klebsiella pneumoniae (KP) and their antibacterial mechanisms. MATERIALS AND METHODS: The high-frequency medicinal herbs to treat lung diseases were first screened from Pharmacopoeia of the People's Republic of China (ChP.), and then bioactive compounds in core herbs and targets for compounds and disease were collected. Potential targets, signaling pathways, and drugs' core components were determined by constructing protein-protein interaction network, enrichment analysis and "component-target-pathway-disease" network were mapped by Cytoscape 3.8.2, and the potential therapeutic value of selected core components was verified by comparing the disease targets in the GEO database with the herbal component targets in the ITCM database. The clinically isolated KP were screened by drug sensitivity tests with meropenem (MEM), polymyxin E (PE), and tigecycline and biofilm-forming assay; broth microdilution, chessboard methods and biofilm morphology and permeability experiments were employed to determine the antibacterial, bactericidal and biofilm inhibition ability of selected bioactive constituents alone and in combination with antibiotics; The mechanism of bioactive components on quorum sensing (QS) genes LuxS and LuxR was predicted by molecular docking and tested by RT-PCR. RESULTS: The 13 core Chinese medicines were obtained by mining ChP., and 615 potential targets of core herbal medicine were screened, and the PI3K-Akt signaling pathway might play crucial roles in the therapeutic process. In-vitro experiments revealed that the selected core compounds, including forsythoside B, baicalin, baicalein, and forsythin, all have antibacterial activity, in which baicalein had the strongest ability and a synergistic effect in combination with MEM or PE. Their synergy exhibited a stronger effect on biofilms of MDR KP, inhibiting biofilm formation, disrupting formed biofilms, and removing the residual structures of dead bacteria. Baicalein was predicted to have stable binding capacity to LuxS and LuxR genes by molecular docking, and RT-PCR results verified that the combination of baicalein with MEM or PE was effective in inhibiting the expression of QS genes (LuxS and LuxR) and consequently suppressing biofilm formation. CONCLUSION: The core Chinese herbal medicine in the ChP. to treat lung diseases has a multi-component, multi-target, and multi-pathway synergy to improve bacterial pneumonia. Experimental studies have confirmed that the bioactive compound baicalein was able to combat MDR KP alone and synergistic with MEM or PE, inhibited and disrupted biofilms via regulating LuxS and LuxR genes, and further disturbed quorum sensing system to promote the therapeutic efficacy, which provides a new pathway and rationale for treating MDR KP-induced bacterial pneumonia.

Progress of research into the pharmacological effect and clinical application of the traditional Chinese medicine Rehmanniae Radix.

The traditional Chinese medicine (TCM) Rehmanniae Radix (RR) refers to the fresh or dried root tuber of the plant Rehmannia glutinosa Libosch of the family Scrophulariaceae. As a traditional Chinese herbal medicine (CHM), it possesses multiple effects, including analgesia, sedation, anti-inflammation, antioxidation, anti-tumor, immunomodulation, cardiovascular and cerebrovascular regulation, and nerve damage repair, and it has been widely used in clinical practice. In recent years, scientists have extensively studied the active components and pharmacological effects of RR. Active ingredients mainly include iridoid glycosides (such as catalpol and aucuboside), phenylpropanoid glycosides (such as acteoside), other saccharides, and unsaturated fatty acids. In addition, the Chinese patent medicine (CPM) and Chinese decoction related to RR have also become major research subjects for TCM practitioners; one example is the Bolus of Six Drugs, which includes Rehmannia, Lily Bulb and Rehmannia Decoction, and Siwu Decoction. This article reviews recent literature on RR; summarizes the studies on its chemical constituents, pharmacological effects, and clinical applications; and analyzes the progress and limitations of current investigations to provide reference for further exploration and development of RR.

Tunable Resistive Switching Behaviors and Mechanism of the W/ZnO/ITO Memory Cell.

A facile sol-gel spin coating method has been proposed for the synthesis of spin-coated ZnO nanofilms on ITO substrates. The as-prepared ZnO-nanofilm-based W/ZnO/ITO memory cell showed forming-free and tunable nonvolatile multilevel resistive switching behaviors with a high resistance ratio of about two orders of magnitude, which can be maintained for over 103 s and without evident deterioration. The tunable nonvolatile multilevel resistive switching phenomena were achieved by modulating the different set voltages of the W/ZnO/ITO memory cell. In addition, the tunable nonvolatile resistive switching behaviors of the ZnO-nanofilm-based W/ZnO/ITO memory cell can be interpreted by the partial formation and rupture of conductive nanofilaments modified by the oxygen vacancies. This work demonstrates that the ZnO-nanofilm-based W/ZnO/ITO memory cell may be a potential candidate for future high-density, nonvolatile, memory applications.

A Facile Hydrothermal Synthesis and Resistive Switching Behavior of α-Fe2O3 Nanowire Arrays.

A facile hydrothermal process has been developed to synthesize the α-Fe2O3 nanowire arrays with a preferential growth orientation along the [110] direction. The W/α-Fe2O3/FTO memory device with the nonvolatile resistive switching behavior has been achieved. The resistance ratio (RHRS/RLRS) of the W/α-Fe2O3/FTO memory device exceeds two orders of magnitude, which can be preserved for more than 103s without obvious decline. Furthermore, the carrier transport properties of the W/α-Fe2O3/FTO memory device are dominated by the Ohmic conduction mechanism in the low resistance state and trap-controlled space-charge-limited current conduction mechanism in the high resistance state, respectively. The partial formation and rupture of conducting nanofilaments modified by the intrinsic oxygen vacancies have been suggested to be responsible for the nonvolatile resistive switching behavior of the W/α-Fe2O3/FTO memory device. This work suggests that the as-prepared α-Fe2O3 nanowire-based W/α-Fe2O3/FTO memory device may be a potential candidate for applications in the next-generation nonvolatile memory devices.

Therapeutic effects on cancer of the active ingredients in rhizoma paridis.

Cancer is a major threat to human health, with high mortality and a low cure rate, continuously challenging public health worldwide. Extensive clinical application of traditional Chinese medicine (TCM) for patients with poor outcomes of radiotherapy and chemotherapy provides a new direction in anticancer therapy. Anticancer mechanisms of the active ingredients in TCM have also been extensively studied in the medical field. As a type of TCM against cancer, Rhizoma Paridis (Chinese name: Chonglou) has important antitumor effects in clinical application. The main active ingredients of Rhizoma Paridis (e.g., total saponins, polyphyllin I, polyphyllin II, polyphyllin VI, and polyphyllin VII) have shown strong antitumor activities in various cancers, such as breast cancer, lung cancer, colorectal cancer, hepatocellular carcinoma (HCC), and gastric cancer. Rhizoma Paridis also has low concentrations of certain other active ingredients with antitumor effects, such as saponins polyphyllin E, polyphyllin H, Paris polyphylla-22, gracillin, and formosanin-C. Many researchers have studied the anticancer mechanism of Rhizoma Paridis and its active ingredients. This review article describes research progress regarding the molecular mechanism and antitumor effects of the active ingredients in Rhizoma Paridis, suggesting that various active ingredients in Rhizoma Paridis may be potentially therapeutic against cancer.

Shen-Qi-Jiang-Tang granule ameliorates diabetic nephropathy via modulating tumor necrosis factor signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Shen-Qi-Jiang-Tang granule (SQJTG), a classic traditional Chinese medicine (TCM) prescription, has been widely used in clinical for diabetes, especially type Ⅱ diabetes. Previous anti-diabetic studies stumbled across that SQJTG has a potential kidney protective effect on diabetic nephropathy (DN). However, the protective mechanism of SQJTG on DN still needs to be explored. AIM OF THE STUDY: The purpose of the present study was to explore the therapeutic effect of SQJTG on DN through both bioinformatics analysis and in vivo experiments. METHODS AND MATERIALS: The TCMIP database was used for screening potential compounds and targets of SQJTG, and the GeneCards, OMIM, DrugBank, and TTD databases were used for collecting DN-related genes. Then protein-protein interaction analysis for the common targets of SQJTG and DN was performed by the STRING database. Meanwhile, KEGG and GO were carried out using the Metascape and DAVID databases. In vivo experiments, to testify the potential kidney protective effects of SQJTG, STZ-induced DN mice with different dosages of SQJTG treatment were collected and the renal tissues were detected by H&E, PAS, Masson and TUNEL staining. Immunohistochemistry and immunoblotting were used to assess the proteins' expressions. Flow cytometry and ELISA assay were used to detect the levels of pro-inflammatory cytokines. RESULTS: Among the 338 compounds ascertained by SQJTG, there were 789 related targets as well. Moreover, 1,221 DN-related targets were predicted and 20 core targets were screened by the PPI analyses. According to GO and KEGG pathway analysis, SQJTG may affect DN via the TNF pathway. For the in vivo experiments, renal histomorphological examinations demonstrated that SQJTG treatment significantly ameliorated STZ-induced kidney damage and had a dosage dependence. Meanwhile, mice with DN were found to have dramatic increases in IL-1, TNF-α, IL-6, and IL-12, but markedly decreased after administration of SQJTG. In addition, the protein levels of TNF signaling molecules, like p-P65, p-JNK, and p-p38, showed significantly elevated in kidney tissues of DN mice and attenuated after SQJTG treatment. CONCLUSIONS: SQJTG exerts a kidney protective effect in DN mice via modulating TNF signaling pathways, and it has promising applications for the treatment of DN.

The mechanism of Renshen-Fuzi herb pair for treating heart failure-Integrating a cardiovascular pharmacological assessment with serum metabolomics.

Background: Renshen-Fuzi herb pair (RS-FZ) is often used in the clinical treatment of heart failure (HF) and has a remarkable therapeutic effect. However, the mechanism of RS-FZ for treating HF remains unclear. In our study, we explored the mechanism of RS-FZ for treating HF. Methods: Evaluation of RS-FZ efficacy by cardiovascular pharmacology. Moreover, Global metabolomics profiling of the serum was detected by UPLC-QTOF/MS. Multivariate statistics analyzed the specific serum metabolites and corresponding metabolic pathways. Combining serum metabolomics with network pharmacology, animal experiments screened and validated the critical targets of RS-FZ intervention in HF. Results: RS-FZ significantly ameliorated myocardial fibrosis, enhanced cardiac function, and reduced the serum HF marker (brain natriuretic peptide) level in rats with HF. Through topological analysis of the "Metabolite-Target-Component" interaction network, we found that 79 compounds of RS-FZ directly regulated the downstream specific serum metabolites by acting on four critical target proteins (CYP2D6, EPHX2, MAOB, and ENPP2). The immunohistochemistry results showed that RS-FZ observably improved the expression of CYP2D6 and ENPP2 proteins while decreasing the expression of EPHX2 and MAOB proteins dramatically. Conclusion: The integrated cardiovascular pharmacological assessment with serum metabolomics revealed that RS-FZ plays a crucial role in the treatment of HF by intervening in CYP2D6, EPHX2, MAOB, and ENPP2 target proteins. It provides a theoretical basis for RS-FZ for treating HF.

A research update on the antitumor effects of active components of Chinese medicine ChanSu.

Clinical data show that the incidence and mortality rates of cancer are rising continuously, and cancer has become an ongoing public health challenge worldwide. Excitingly, the extensive clinical application of traditional Chinese medicine may suggest a new direction to combat cancer, and the therapeutic effects of active ingredients from Chinese herbal medicine on cancer are now being widely studied in the medical community. As a traditional anticancer Chinese medicine, ChanSu has been clinically applied since the 1980s and has achieved excellent antitumor efficacy. Meanwhile, the ChanSu active components (e.g., telocinobufagin, bufotalin, bufalin, cinobufotalin, and cinobufagin) exert great antitumor activity in many cancers, such as breast cancer, colorectal cancer, hepatocellular carcinoma and esophageal squamous cell carcinoma. Many pharmaceutical scientists have investigated the anticancer mechanisms of ChanSu or the ChanSu active components and obtained certain research progress. This article reviews the research progress and antitumor mechanisms of ChanSu active components and proposes that multiple active components of ChanSu may be potential anticancer drugs.

[Comparison on distribution of 8 components from ethanol extract of Psoraleae Fructus between normal and lipopolysaccharide-induced model rats].

UPLC-TQ/MS was employed to determine the content of 8 main components(psoralen, isopsoralen, psoralenoside, isopsoralenoside, bavachin, psoralidin, corylin, and neobavaisoflavone) in tissues of normal and lipopolysaccharide(LPS)-induced model rats 0.5, 1, 2, 6, and 12 h after intragastric administration of 3.6 g·kg~(-1) ethanol extract of Psoraleae Fructus. The distribution characteristics of the 8 main components in the different tissues(liver, kidney, spleen, heart, and lung) were studied and compared. The results showed that the distribution behaviors of the components varied among different tissues. At different time points, the components presented wide and uneven distribution in the body. Liver and kidney had higher content of the components, followed by spleen, heart, and lung. In both normal and LPS-induced model rats, the content of the 8 main components was higher in liver and kidney and varied significantly among different tissues. The content of psoralen in the tissues of LPS-induced model rat was significantly higher than that of the normal group 12 h after administration. The reason may be that the modeling slowed down the absorption and distribution of psoralen. The LPS-induced model rats had higher content of psoralenoside and isopsoralenoside in the liver tissue than the normal rats, which indicated that the modeling increased the absorption and distribution of psoralenoside and isopsoralenoside in the liver tissue. Further, it is hypothesized that psoralenoside and isopsoralenoside may be toxic substances of Psoraleae Fructus-induced liver injury.

MOF-derived porous carbon inlaid with MnO2 nanoparticles as stable aqueous Zn-ion battery cathodes.

Cathodes derived from metal-organic framework materials offer unique advantages in terms of improved structural reversibility and electron conduction efficiency. Nevertheless, the capacity contribution of cathodes based on the carbon framework system has not been clearly discussed or is controversial in aqueous batteries. In this essay, we have uncovered the capacity contribution arising from the adsorption of anions/cations onto the carbon surface by examining the bonds of the carbon and the details of unsteady voltage in the CV/GITT during the discharge. Benefiting from the synergistic contribution of the double-layer capacitance and pseudocapacitance, Zn/C-MnO2 exhibits excellent long-cycling stability and fast kinetics. To the best of our knowledge, this is the first report on the ion adsorption-based double layer effect in aqueous zinc ion batteries. Such a capacity contribution mechanism, and a renewed knowledge of the discharge mechanism, will contribute to the development of high-performance aqueous zinc ion batteries.

Genomic alterations and clinical outcomes in patients with lung adenocarcinoma with transformation to small cell lung cancer after treatment with EGFR tyrosine kinase inhibitors: A multicenter retrospective study.

BACKGROUND: Transformation to small cell lung cancer (SCLC) is a resistance mechanism to tyrosine kinase inhibitor (TKI) treatment that develops in lung adenocarcinoma. The genomic and treatment outcomes in these populations have not been comprehensively reported in China. METHODS: We performed a retrospective study analyzing patients with advanced non-SCLC (NSCLC) from eight sites who were diagnosed with SCLC transformation after receiving epidermal growth factor receptor (EGFR)-TKI treatment including first/second- or third-generation EGFR-TKIs. We assessed the genomic features and clinical prognosis in these patients with EGFR-mutated lung cancer. RESULTS: Thirty-two eligible patients with EGFR mutations were identified, 25 of whom had sufficient tumor tissues for detection of genes by next-generation sequencing. The median progression free survival (mPFS) for first/second-generation TKIs was 14.0 months. The most common mutations identified in samples with transformation to SCLC were in TP53 (17/25, 68.0 %), RB1 (9/25, 36.0 %), and PIK3CA (3/25, 12.0 %), and the incidence rates of RB1 and TP53 mutations were similar between patients receiving first/second-generation and third-generation TKI treatment. The estimated median time to SCLC transformation was 17.0 months. After SCLC transformation, platinum-etoposide was the most common treatment regimen, and the mPFS after platinum-etoposide treatment was 3.5 months. Anlotinib showed good efficacy in these patients (overall response rate, 66.7 %; mPFS, 6.2 months). The median overall survival after the initial diagnosis of metastatic lung cancer was 34.5 months, and patients with small cell transformation after third-generation TKI treatment had better prognosis than patients with transformation after first/second-generation treatment (49.4 months vs. 20.0 months, P = 0.013). CONCLUSION: We observed that TP53 and RB1 mutations were common in Chinese patients with SCLC transformation, regardless of whether first/second-generation or third-generation EGFR-TKI treatments were used. Earlier occurrence of small cell transformation after EGFR-TKI treatment was associated with poorer prognosis of patients. After the standard chemotherapy regimens for the management of primary SCLC, anlotinib may be a therapeutic option.