Epidemiological insights into seasonal, sex­specific and age­related distribution of bacterial pathogens in urinary tract infections.

Urinary tract infections (UTIs) are prevalent and recurrent bacterial infections that affect individuals worldwide, posing a significant burden on healthcare systems. The present study aimed to explore the epidemiology of UTIs, investigating the seasonal, gender-specific and age-related bacterial pathogen distribution to guide clinical diagnosis. Data were retrospectively collected from electronic medical records and laboratory reports of 926 UTIs diagnosed in Fuding Hospital (Fujian University of Traditional Chinese Medicine, Fuding, China). Bacterial isolates were identified using standard microbiological techniques. χ2 tests were performed to assess associations between pathogens and the seasons, sex and age groups. Significant associations were found between bacterial species and seasons. Enterococcus faecium exhibited a substantial prevalence in spring (χ2, 12.824; P=0.005), while Acinetobacter baumannii demonstrated increased prevalence in autumn (χ2, 16.404; P=0.001). Female patients showed a higher incidence of UTIs. Gram-positive bacteria were more prevalent in males, with Staphylococcus aureus showing significant male predominance (χ2, 14.607; P<0.001). E. faecium displayed an age-related increase in prevalence (χ2, 17.775; P<0.001), whereas Escherichia coli tended to be more prevalent in younger patients (χ2, 12.813; P=0.005). These findings highlight the complex nature of UTIs and offer insights for tailored diagnostic and preventive strategies, potentially enhancing healthcare outcomes.

Ginkgo biloba extract ameliorates hyperglycaemia-induced enteric glial cell injury via regulation of the TLR2-related pathway.

BACKGROUND: Diabetic gastrointestinal dysfunction (DGD) is a common complication in diabetic patients, and enteric glial cells (EGCs) found in the gastrointestinal tract have been shown to play an essential role in gastrointestinal dysfunction. Thus, targeting EGCs may be helpful for the control of DGD. This study aimed to evaluate the protective effect of Ginkgo biloba extract (GBE) from G. biloba dropping pills against hyperglycaemic stress-induced EGCs injury and its underlying mechanism. METHODS: In vitro, the protective effect of GBE on CRL-2690 cells was evaluated by MTT assay and TUNEL assay. The expression of related markers was evaluated by RNA sequencing and validated by using western blotting. In vivo, STZ-induced C57BL/6J WT mice were used as models to evaluate the effects of GBE on blood glucose, body weight, and EGCs' activity and relevant signalling pathways were validated by immunofluorescence. RESULTS: The results showed that GBE (25 µg/ml) treatment significantly attenuated hyperglycaemic stress-induced cytotoxicity and cell apoptosis in CRL-2690 cells, which was verified in an STZ-induced (100 mg/kg, 3 days) diabetic mouse model with continuous GBE administration (25/100 mg/kg/day, 6/12 weeks). Further mechanistic study based on transcriptomic data revealed that GBE exerted its beneficial effect by regulating immune-related pathways, and TLR2/BTK/NF-κB/IL-1α/IL-10 comprised the main targets of this drug. CONCLUSIONS: This study demonstrates the protective effect of GBE against hyperglycaemic stress-induced EGCs injury using both in vitro and in vivo models and further reveals that the effect was achieved by targeting TLR2 and its downstream molecules BTK/NF-κB/IL-1α/IL-10. This study may be helpful for expanding the clinical application of GBE in treating DGD.

Associations between polyunsaturated fatty acid concentrations and Parkinson's disease: A two-sample Mendelian randomization study.

Introduction: Observational studies demonstrated controversial effect of polyunsaturated fatty acids (PUFAs) on Parkinson's disease (PD) with limited causality evidence. Randomized control trials showed possible improvement in PD symptoms with PUFA supplement but had small study population and limited intervention time. Methods: A two-sample Mendelian randomization was designed to evaluate the causal relevance between PUFAs and PD, using genetic variants of PUFAs as instrumental variables and PD data from the largest genome-wide association study as outcome. Inverse variance weighted (IVW) method was applied to obtain the primary outcome. Mendelian randomization Egger regression, weighted median and weighted mode methods were exploited to assist result analyses. Strict Mendelian randomization and multivariable Mendelian randomization (MVMR) were used to estimate direct effects of PUFAs on PD, eliminating pleiotropic effect. Debiased inverse variance weighted estimator was implemented when weak instrument bias was introduced into the analysis. A variety of sensitivity analyses were utilized to assess validity of the results. Results: Our study included 33,674 PD cases and 449,056 controls. Higher plasma level of arachidonic acid (AA) was associated with a 3% increase of PD risk per 1-standard deviation (SD) increase of AA (IVW; Odds ratio (OR)=1.03 [95% confidence interval (CI) 1.01-1.04], P = 2.24E-04). After MVMR (IVW; OR=1.03 [95% CI 1.02-1.04], P =6.15E-08) and deletion of pleiotropic single-nucleotide polymorphisms overlapping with other lipids (IVW; OR=1.03 [95% CI 1.01-1.05], P =5.88E-04), result was still significant. Increased level of eicosapentaenoic acid (EPA) showed possible relevance with increased PD risk after adjustment of pleiotropy (MVMR; OR=1.05 [95% CI 1.01-1.08], P =5.40E-03). Linoleic acid (LA), docosahexaenoic acid (DHA), docosapentaenoic acid (DPA) and alpha-linolenic acid (ALA) were found not causally relevant to PD risk. Various sensitivity analyses verified the validity of our results. In conclusion, our findings from Mendelian randomization suggested that elevated levels of AA and possibly EPA might be linked to a higher risk of PD. No association between PD risk and LA, DHA, DPA, or ALA was found. Discussion: The odds ratio for plasma AA and PD risk was weak. It is important to approach our results with caution in clinical practice and to conduct additional studies on the relationship between PUFAs and PD risk.

Effects and pharmacological mechanism of Zhigancao Decoction on electrical and structural remodeling of the atrium of rabbits induced by rapid atrial pacing.

BACKGROUND: Zhigancao decoction (ZD) has a long history in China as a traditional Chinese medicine compound for the treatment of tachyarrhythmias. This study mainly explored the pharmacological mechanism of Zhigancao Decoction in preventing atrial fibrillation by altering the electrical and structural remodeling of the atrial in rabbits. METHODS: In total, 30 male New Zealand white rabbits were randomly divided into 3 groups (ten rabbits for each). The first group was sham-operated (control group). The second group was intervened by the rapid right atrium pacing (RAP) to induce atrial fibrillation (AF group), while the third group was given ZD gavage and RAP (AF + ZD group). All rabbits were anesthetized before two monophasic action potential (MAP) catheters were sequentially inserted into the right atrium. After 8 h of rapid right atrial pacing, the electrophysiological indexes and the induction rate of atrial fibrillation were observed in the three groups of rabbits, and the left atrial myocardium samples were taken to observe the ultrastructure. Single atrial myocytes were separated by enzymolysis, and the L-type calcium current (ICa-L) of atrial myocytes in different experimental groups was observed by whole-cell patch clamp technique. The fluorescence intensity of Ca2+ in atrial myocytes was observed after Fluo-3/AM fluorescent staining. The main components of ZD were identified by liquid chromatography-mass spectrometry-mass spectrometry (LC-MS/MS) method. RESULTS: Compared with the AF group, the maximum ascent rate (Max dV/dt) and plateau potential were significantly reduced in the ZD group, the action potential duration at 10% and 20% (APD10, APD20) were significantly shortened (P < 0.01), action potential duration at 50%, 70%, and 90% (APD50, APD70, APD90) were significantly prolonged, and atrial effective refractory period (AERP) was significantly prolonged (P < 0.01) in the ZD group. In the ZD group, the ICa-L amplitudes of rabbit atrial myocytes under each clamping voltage were significantly smaller than those in the AF group (P < 0.01) and the control group (P < 0.05). The Ca2+ fluorescence intensity in the rabbit atrial myocytes in the ZD group was significantly weaker than that in the AF group (P < 0.01) and the control group (P < 0.05). Electron microscopy displayed that the control group had neatly arranged atrial tissue myofilaments and intact mitochondria. However, the ultrastructural damage of the AF group was severe compared with that of the ZD group. LC-MS/MS analysis confirmed that ZD contained several antiarrhythmic compounds including ginsenoside, isoliensinine, catalpol, glycyrrhizinate and hesperetin. CONCLUSION: Rapid atrial pacing (RAP) could cause the electrical and structural remodeling of rabbit atrial myocytes. ZD might reverse the atrial electrical remodeling but could have little effect on structural remodeling, which might be the mechanism of ZD treatment on atrial fibrillation.

Ginkgo biloba extracts protect human retinal Müller glial cells from t-BHP induced oxidative damage by activating the AMPK-Nrf2-NQO-1 axis.

OBJECTIVES: Retinal Müller glial cell loss is almost involved in all retinal diseases, especially diabetic retinopathy (DR). Oxidative stress significantly contributes to the development of Müller glial cell loss. Ginkgo biloba extracts (GBE) have been reported to possess antioxidant property, beneficial in treating human retinal diseases. However, little is known about its role in Müller glial cells. This study investigated the protective effect of GBE (prepared from ginkgo biloba dropping pills) in human Müller glial cells against tert-butyl hydroperoxide (t-BHP)-induced oxidative stress and its underlying molecular mechanism. METHODS: MIO-M1 cells were pretreated with or without GBE prior to the exposure to t-BHP-induced oxidative stress. Cell viability, cell death profile and lipid peroxidation were subsequently assessed. Protein expression of the key anti-oxidative signalling factors were investigated. KEY FINDINGS: We showed that GBE can effectively protect human MIO-M1 cells from t-BHP-induced oxidative injury by improving cell viability, reducing intracellular ROS accumulation and suppressing lipid peroxidation, which effect is likely mediated through activating AMPK-Nrf2-NQO-1 antioxidant respondent axis. CONCLUSIONS: Our study is the first to reveal the great potentials of GBE in protecting human retinal Müller glial cell loss against oxidative stress. GBE might be used to prevent human retinal diseases particularly DR.

Multi-omics approaches for in-depth understanding of therapeutic mechanism for Traditional Chinese Medicine.

Traditional Chinese Medicine (TCM) is extensively utilized in clinical practice due to its therapeutic and preventative treatments for various diseases. With the development of high-throughput sequencing and systems biology, TCM research was transformed from traditional experiment-based approaches to a combination of experiment-based and omics-based approaches. Numerous academics have explored the therapeutic mechanism of TCM formula by omics approaches, shifting TCM research from the "one-target, one-drug" to "multi-targets, multi-components" paradigm, which has greatly boosted the digitalization and internationalization of TCM. In this review, we concentrated on multi-omics approaches in principles and applications to gain a better understanding of TCM formulas against various diseases from several aspects. We first summarized frequently used TCM quality assessment methods, and suggested that incorporating both chemical and biological ingredients analytical methods could lead to a more comprehensive assessment of TCM. Secondly, we emphasized the significance of multi-omics approaches in deciphering the therapeutic mechanism of TCM formulas. Thirdly, we focused on TCM network analysis, which plays a vital role in TCM-diseases interaction, and serves for new drug discovery. Finally, as an essential source for storing multi-omics data, we evaluated and compared several TCM databases in terms of completeness and reliability. In summary, multi-omics approaches have infiltrated many aspects of TCM research. With the accumulation of omics data and data-mining resources, deeper understandings of the therapeutic mechanism of TCM have been acquired or will be gained in the future.

Decoding herbal materials of TCM preparations with the multi-barcode sequencing approach.

With the rapid development of high-throughput sequencing technology, approaches for assessing biological ingredients in Traditional Chinese Medicine (TCM) preparations have also advanced. Using a multi-barcode sequencing approach, all biological ingredients could be identified from TCM preparations in theory, as long as their DNA is present. The biological ingredients of several classical TCM preparations were analyzed successfully based on this approach in previous studies. However, the universality, sensitivity and reliability of this approach on a diverse set of TCM preparations remain unclear. In this study, we selected four representative TCM preparations, namely Bazhen Yimu Wan, Da Huoluo Wan, Niuhuang Jiangya Wan, and You Gui Wan, for concrete assessment of the multi-barcode sequencing approach. Based on ITS2 and trnL biomarkers, we have successfully detected the prescribed herbal materials (PHMs) in these representative TCM preparations (minimum sensitivity: 77.8%, maximum sensitivity: 100%). The results based on ITS2 have also shown higher reliability than trnL at species level, while their combination could provide higher sensitivity and reliability. The multi-barcode sequencing approach has shown good universality, sensitivity and reliability in decoding these four representative TCM preparations. In the omics big-data era, this work has undoubtedly made one step forward for applying multi-barcode sequencing approach in PHMs analysis of TCM preparation, towards better digitization and modernization of drug quality control.

A Network Pharmacology-Based Study on Antidepressant Effect of Salicornia europaea L. Extract with Experimental Support in Chronic Unpredictable Mild Stress Model Mice.

OBJECTIVE: To investigate the pharmacodynamic material basis, mechanism of actions and targeted diseases of Salicornia europaea L. (SE) based on the network pharmacology method, and to verify the antidepressant-like effect of the SE extract by pharmacological experiments. METHODS: Retrieval tools including Chinese medicine (CM), PubMed, PharmMapper, MAS 3.0 and Cytoscape were used to search the components of SE, predict its targets and related therapeutic diseases, and construct the "Component-Target-Pathway" network of SE for central nervous system (CNS) diseases. Further, protein-protein interaction (PPI) network, Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) function annotation of depression-related targets were analyzed to predict the antidepressant mechanism of SE. Chronic unpredictable mild stress (CUMS) model was used to construct a mouse model with depression-like symptoms. And the animals were randomly divided into 6 groups (n=10) including the normal group (nonstressed mice administered with distilled water), the CUMS group (CUMS mice administered with distilled water), the venlafaxine group (CUMS mice administered with venlafaxine 9.38 mg/kg), SE high-, medium-, and low-dose groups (CUMS mice administered with SE 1.8, 1.35 and 0.9 g/kg, respectively). Then some relevant indicators were determined for experimental verification by the forced swim test (FST), the tail suspension test (TST) and open-field test (OFT). Dopamine (DA) concentration in hippocampus and cerebral cortex, IL-2 and corticosterone (CORT) levels in blood, and nuclear factor E2 related factor 2 (Nrf2), kelch-like epichlorohydrin related protein 1 (Keap1), NAD(P) H dehydrogenase [quinone] 1 (NQO1) and heme oxygenase-1 (HO-1) levels in mice were measured by enzyme linked immunosorbent assay (ELISA) and Western blot respectively to explore the possible mechanisms. RESULTS: The "target-disease" network diagram predicted by network pharmacology, showed that the potential target of SE involves a variety of CNS diseases, among which depression accounts for the majority. The experimental results showed that SE (1.8, 1.35 g/kg) significantly decreased the immobility period, compared with the CUMS group in FST and TST in mice after 3-week treatment, while SE exhibited no significant effect on exploratory behavior in OFT in mice. Compared with CUMS group, the SE group (0.9 g/kg) showed significant differences (P<0.05) in DA levels in the hippocampus and cerebral cortex. In addition, compared with CUMS control group, SE (1.8 g/kg) group showed a significant effect on decreasing the activities of CORT (P<0.05), and serum IL-2 level with no statistical significance. Finally, Western blot results showed that compared with the model group, Nrf2, Keap1, NQO1 and HO-1 protein expressions in SE group (1.8 g/kg) were up-regulated (all P<0.01). CONCLUSION: The SE extract may have an antidepressant effect, which appeared to regulate Nrf2-ARE pathway and increased levels of DA and CORT in the hippocampus and cortex.

Preclinical efficacy and clinical safety of clinical-grade nebulized allogenic adipose mesenchymal stromal cells-derived extracellular vesicles.

Mesenchymal stromal cell-derived extracellular vesicles (MSC-EVs) turn out to be a promising source of cell-free therapy. Here, we investigated the biodistribution and effect of nebulized human adipose-derived MSC-EVs (haMSC-EVs) in the preclinical lung injury model and explored the safety of nebulized haMSC-EVs in healthy volunteers. DiR-labelled haMSC-EVs were used to explore the distribution of nebulized haMSC-EVs in the murine model. Pseudomonas aeruginosa-induced murine lung injury model was established, and survival rate, as well as WBC counts, histology, IL-6, TNF-α and IL-10 levels in bronchoalveolar lavage fluid (BALF) were measured to explore the optimal therapeutic dose of haMSC-EVs through the nebulized route. Twenty-four healthy volunteers were involved and received the haMSC-EVs once, ranging from 2 × 108 particles to 16 × 108 particles (MEXVT study, NCT04313647). Nebulizing haMSC-EVs improved survival rate to 80% at 96 h in P. aeruginosa-induced murine lung injury model by decreasing lung inflammation and histological severity. All volunteers tolerated the haMSC-EVs nebulization well, and no serious adverse events were observed from starting nebulization to the 7th day after nebulization. These findings suggest that nebulized haMSC-EVs could be a promising therapeutic strategy, offering preliminary evidence to promote the future clinical applications of nebulized haMSC-EVs in lung injury diseases.

Ginkgo biloba extract protects human neuroblastoma SH-SY5Y cells against oxidative glutamate toxicity by activating redoxosome-p66Shc.

Ginkgo biloba extract (GBE), a traditional Chinese herbal medicine component, is widely used to alleviate symptoms of neurodegenerative diseases. It has been confirmed that GBE exerts its pharmacological effect mainly due to its antioxidant activity; however, the molecular mechanism responsible for this effect remains unclear. The aim of the present study was to investigate the detailed mechanism of GBE, the main component of Gingko biloba dropping medicine, against oxidative glutamate toxicity in human neuroblastoma SH-SY5Y cells. The SH-SY5Y cells were untreated or pretreated with GBE followed by glutamate stimulation. Cell viability was assessed using an MTT assay. In addition, oxidative stress indexes, including intracellular ROS generation and NADPH oxidase and caspase activity, were also measured. The protein expression of key signaling factors involved in the redoxosome-p66Shc pathway was evaluated to elucidate the neuroprotective effect of GBE. The results showed that GBE treatment significantly attenuated the glutamate-induced cytotoxicity in SH-SY5Y cells by suppressing oxidative stress. A mechanical study revealed that redoxosome-p66Shc activation was associated with glutamate-induced cytotoxicity, which caused mitochondrial dysfunction and cell death. Interestingly, GBE treatment attenuated the activation of redoxosome-p66Shc in a dose-dependent manner, which suggested that the protective effect of GBE on SH-SY5Y cells against oxidative glutamate toxicity may be mediated by the modulation of redoxosome-p66Shc signaling. The current findings contribute to a better understanding of the therapeutic effect of GBE and indicate that redoxosome-p66Shc signaling might be a novel therapeutic target in the prevention and/or treatment of neurodegenerative diseases.

Coronary Heart Disease and Depression or Anxiety: A Bibliometric Analysis.

This study aimed to conduct a bibliometric analysis of published studies on the association between coronary heart disease (CHD) and depression or anxiety. The study also aimed to identify leading authors, institutions, and countries to determine research hotspots and obtain some hints from the speculated future frontiers. Publications about CHD and depression or anxiety between 2004 and 2020 were collected from the Web of Science Core Collection (WOSCC) database. Bibliographic information, such as authorship, country, citation frequency, and interactive visualization, was generated using VOSviewer1.6.16 and CiteSpace5.6.R5. In total, 8,073 articles were identified in the WOSCC database. The United States (2,953 publications), Duke University and Harvard University (214 publications), Psychosomatic Medicine (297 publications), and Denollet Johan. (99 publications) were the most productive country, institutions, journal, and author, respectively. The three hotspots of the research were "The relationship between depression and CHD," "depression and myocardial infarction," and "The characteristic of women suffering depression after MI." The four future research frontiers are predicted to be "treating depression in CHD patients with multimorbidity," "psychometric properties of instruments for assessing depression and anxiety in CHD patients," "depression or anxiety in post-PCI patients," and "other mental diseases in CHD patients." Bibliometric analysis of the association between CHD and depressive disorders might identify new directions for future research.

Study of the Mechanism of Action of Guanxin Shutong Capsules in the Treatment of Coronary Heart Disease Based on Metabolomics.

Background: Guan-Xin-Shu-Tong capsule (GXSTC) is a traditional Chinese medicine (TCM) that has been used to treat coronary heart disease (CHD) for many years in China. However, the holistic mechanism of GXSTC against CHD is still unclear. Therefore, the purpose of this paper was to systematically explore the mechanism of action GXSTC in the treatment of CHD rats using a metabolomics strategy. Methods: A CHD model was induced by ligation of the left anterior descending coronary artery (LAD). In each group, echocardiography was performed; the contents of creatine kinase (CK), lactate dehydrogenase (LDH) and aspartate transaminase (AST) in serum were determined; and the myocardial infarct size was measured. The metabolites in plasma were analyzed by UHPLC-MS/MS-based untargeted metabolomics. Then, multivariate statistical analysis was performed to screen potential biomarkers associated with the GXSTC treatment in the LAD-induced rat CHD model. Finally, the MetaboAnalyst 4.0 platform was used for metabolic pathway enrichment analysis. Results: GXSTC was able to regulate the contents of CK, LDH and AST; restore impaired cardiac function; and significantly reduce the myocardial infarction area in model rats. Twenty-two biomarkers and nine metabolic pathways of GXSTC in the treatment of CHD were identified through UHPLC-MS/MS-based untargeted metabolomics analysis. Conclusion: GXSTC regulates metabolic disorders of endogenous components in LAD-induced CHD rats. The anti-CHD mechanism of GXSTC is mainly related to the regulation of amino acid, lipid and hormonal metabolism. This study provides an overall view of the mechanism underlying the action of GXSTC against CHD.

Procyanidin B2 and rutin in Ginkgo biloba extracts protect human retinal pigment epithelial (RPE) cells from oxidative stress by modulating Nrf2 and Erk1/2 signalling.

Oxidative stress plays an important role in the pathogenesis of human retinal diseases. Ginkgo biloba products are widely consumed herbal supplements that contain ingredients with anti-oxidant potentials. However, the active agents in ginkgo biloba extracts (GBE) are unclear. This study assessed the anti-oxidant effects of 19 natural compounds isolated from GBE to provide a rational basis for their use in preventing retinal diseases. The compounds were tested in retinal pigment epithelial (RPE) cells subjected to tert-butyl hydroperoxide (t-BHP)-induced oxidative stress. Cell viability and intracellular reactive oxygen species (ROS) were assessed and flow cytometry was used to delineate the cell death profile. The expression of nuclear factor erythroid 2-related factor-2 (Nrf2) was activated in RPE cells by t-BHP accompanied with an activation of Erk1/2 signaling. GBE-derived rutin and procyanidin B2 ameliorated t-BHP-induced cell death and promoted cell viability by suppressing intracellular ROS generation. These agents also enhanced Nrf2 expression with activating Erk1/2 signaling in RPE cells. In contrast, the other compounds tested were minimally active and did not prevent the loss of cell viability elicited by t-BHP. The present findings suggest that rutin and procyanidin B2 may have potential therapeutic values in the prevention of retinal diseases induced by oxidative damage.

[Effect of hot or warm property on skin toxicity of essential oil as penetration enhancer and its mechanism].

To compare the effect of hot or warm property of Chinese medicine(CM) on the skin toxicity of essential oils(EOs) as penetration enhancer in vitro and in vivo, and explore the mechanism. EOs were extracted from WIM of Bichengqie(Litseae Fructus), Dingxiang(Flos Syzygii Aromatici), Huajiao(Pericarpium Zanthoxyli Bungeani), and Xiaohuixiang(Fructus Foeniculi) with warm property, and Ganjiang(Rhizoma Zingiberis), Gaoliangjiang(Rhizoma Alpiniae Officinari), Hujiao(Fructus Piperis), and Wuzhuyu(Fructus Evodiae Rutaecarpae) with hot property, respectively. Then the in vitro toxicity was evaluated by human keratinocyte cytotoxicity. In vivo skin irritation potency was also evaluated through pathological observation after topical administration. The components, especially those located in stratum corneum, were analyzed by GC-MS. The main components, namely monoterpenes and sesquiterpenes, of EOs extracted from CM with hot property,were detected for the interaction with keratino-lipid ceramide 3 by molecular simulation technology; and the interaction energy value was calculated based on the optimal conformation. It was found that the skin cell toxicity of EOs from CM with hot property was significantly higher than that of EOs from CM with warm property. However, there was no significant difference between them by in vivo skin irritation evaluation. Whether from CM with hot property or warm property, EOs showed a significant reduced toxicity compared with azone. Sesquiterpenes(33.56%±19.38%) were found to be one of the main components in EOs from CM with hot property, while almost no sesquiterpenes was found in EOs from CM with warm property. After topical administration of EOs from CM with hot property, sesquiterpenes were demonstrated to be prone to locate in stratum corneum. The results of molecular simulation also revealed that the interaction between sesquiterpenes and ceramide 3 was significantly stronger than that of monoterpenes(P<0.01). In conclusion, the location of sesquiterpenes in stratum corneum resulted in the significant difference between in vitro skin cell toxicity and in vivo skin irritation potency. The EOs from CM with hot property shall be taken into account for further development of potent penetration enhancer.

The Potential Application of Pentacyclic Triterpenoids in the Prevention and Treatment of Retinal Diseases.

Retinal diseases are a leading cause of impaired vision and blindness but some lack effective treatments. New therapies are required urgently to better manage retinal diseases. Natural pentacyclic triterpenoids and their derivatives have a wide range of activities, including antioxidative, anti-inflammatory, cytoprotective, neuroprotective, and antiangiogenic properties. Pentacyclic triterpenoids have great potential in preventing and/or treating retinal pathologies. The pharmacological effects of pentacyclic triterpenoids are often mediated through the modulation of signalling pathways, including nuclear factor erythroid-2 related factor 2, high-mobility group box protein 1, 11ß-hydroxysteroid dehydrogenase type 1, and Src homology region 2 domain-containing phosphatase-1. This review summarizes recent in vitro and in vivo evidence for the pharmacological potential of pentacyclic triterpenoids in the prevention and treatment of retinal diseases. The present literature supports the further development of pentacyclic triterpenoids. Future research should now attempt to improve the efficacy and pharmacokinetic behaviour of the agents, possibly by the use of medicinal chemistry and targeted drug delivery strategies.

Tubeimoside II inhibits TGF-ß1-induced metastatic progression of human retinoblastoma cells through suppressing redoxosome-dependent EGFR activation.

Metastasis is the leading cause of death in retinoblastoma (Rb) patients. Tubeimoside II (TBMS II) is a compound enriched in the Traditional Chinese Medicine (TCM) Tu Bei Mu. It has been shown to induce cytotoxicity of several types of tumors; however, littler is known about its effect on Rb. This study investigated the influence of TBMS II on TGF-ß1-induced metastasis of human retinoblastoma Y-79 and WERI-Rb-1 cells. The data showed that TBMS II significantly inhibited epithelial-mesenchymal transition (EMT), cell adhesion, migration and invasion via reducing TGF-ß1-induced oxidative stress in Rb cells. Further findings revealed that TBMS II exerted its inhibitory effect against TGF-ß1-induced metastatic progression of Rb cells via suppressing redoxosome-dependent EGFR activation including EGFR phosphorylation and oxidation, and the activation of such signaling attenuated TBMS II's effect. Our study reveals that TBMS II impacts on TGF-ß1-induced metastatic progression of Rb cells, and this information may contribute to better understanding the therapeutic potentials of TBMS II on metastatic Rb.

Efficacy and safety of traditional Chinese medicine combined with routine western medicine for the asymptomatic novel coronavirus disease (COVID-19): A Bayesian network meta-analysis protocol.

BACKGROUND: The number of patients infected with novel coronavirus disease (COVID-19) has exceeded 10 million in 2020, and a large proportion of them are asymptomatic. At present, there is still no effective treatment for this disease. Traditional Chinese medicine (TCM) shows a good therapeutic effect on COVID-19, especially for asymptomatic patients. According to the search results, we found that although there are many studies on COVID-19, there are no studies targeting asymptomatic infections. Therefore, we design a network meta-analysis (NMA) to evaluate the therapeutic effect of TCM on asymptomatic COVID-19. METHODS: We will search Chinese and English databases to collect all randomized controlled trials (RCTs) of TCM combined with conventional western medicine or using only TCM to treat asymptomatic COVID-19 from December 2019 to July 2020. Then, two investigators will independently filter the articles, extract data, and evaluate the risk of bias. We will conduct a Bayesian NMA to evaluate the effects of different therapies. All data will be processed by Stata 16.0 and WinBUGS. RESULTS: This study will evaluate the effectiveness of various treatments for asymptomatic COVID-19. The outcome indicators include the time when the nucleic acid turned negative, the proportion of patients with disease progression, changes in laboratory indicators, and the side effects of drugs. CONCLUSION: This analysis will further improve the treatment of asymptomatic COVID-19. INPLASY REGISTRATION NUMBER: INPLASY202070022.

Ophiopogonin D suppresses TGF-ß1-mediated metastatic behavior of MDA-MB-231 breast carcinoma cells via regulating ITGB1/FAK/Src/AKT/ß-catenin/MMP-9 signaling axis.

Ophiopogonin D, a steroidal glycoside extracted from the Traditional Chinese Medicine Ophiopogon japonicus, shows anti-tumor property in several lines of cancers; however, its effect on triple-negative breast cancer (TNBC) has not been investigated. In this study, the anti-metastatic effect of Ophiopogonin D in TNBC cells as well as the underlying mechanism in such process was explored. Ophiopogonin D dose-dependently decreased cell proliferation of MDA-MB-231 cells. Meanwhile, Ophiopogonin D significantly inhibited TGF-ß1-induced metastatic behavior of MDA-MB-231 cells, including EMT, anoikis resistance as well as migration and invasion, via suppressing MMP-9 activity. Mechanically, Ophiopogonin D achieved its effect through efficiently abolishing ITGB1 expression, thus reducing the phosphorylation of FAK, Src and AKT, as well as upregulating nuclear ß-catenin. ITGB1 overexpression partly recovered Ophiopogonin D's inhibitory effect on metastatic behavior via activating MMP-9. These results demonstrated that Ophiopogonin D could suppress TGF-ß1-mediated metastatic behavior of MDA-MB-231 cells by regulating ITGB1/FAK/Src/AKT/ß-catenin/MMP-9 signaling axis, which might provide new insight for the control of TNBC metastasis.

Cardioprotective effect of acupuncture for percutaneous coronary intervention-related myocardial injury in patients with coronary artery disease: A protocol for systematic review and meta-analysis.

BACKGROUND: Although patients with coronary artery disease (CAD) rely increasingly upon percutaneous coronary intervention (PCI), this therapy causes subsequent the complications of myocardial injury. Acupuncture safely protects the heart from ischemic injury; however, the efficacy of acupuncture for periprocedural myocardial injury after PCI remains unclear. METHODS: Seven databases in English and Chinese including PubMed, Web of Science, Cochrane Library, Embase, Chinese Biomedical Literature Database, Chinese National Knowledge Infrastructure, and Wanfang Database will be searched. Randomized controlled trials (RCTs) that use acupuncture to treat PCI-related myocardial injury in patients with CAD, regardless of blinding. The crossover randomized trials will be included, but only the pre-crossover data will be analyzed to avoid carryover effects. We will exclude non-RCTs, qualitative studies, uncontrolled clinical trials, and laboratory studies. The measurement of concentration of cardiac troponin (T or I) and MB isoenzyme of creatine kinase will be used as primary outcome. Postprocedural cardiac function and the major adverse cardiac/cerebrovascular event rate will be assessed as secondary outcome. Relevant data were collected independently by 2 reviewers and the third reviewer was responsible for resolving discrepancies through discussion. The Review Manager V.5.3.3 s will be used to perform the data synthesis and subgroup analysis. DISCUSSION: This systematic review and meta-analysis would provide convincing evidence of various types of acupuncture that specifically focuses on cardioprotective effect of acupuncture on PCI-related myocardial injury. REGISTRATION: Open Science Framework (OSF) registries (osf.io/n2e6t) with the registration DOI: 10.17605/OSF.IO/79H2E.

Network Pharmacology Databases for Traditional Chinese Medicine: Review and Assessment.

The research field of systems biology has greatly advanced and, as a result, the concept of network pharmacology has been developed. This advancement, in turn, has shifted the paradigm from a "one-target, one-drug" mode to a "network-target, multiple-component-therapeutics" mode. Network pharmacology is more effective for establishing a "compound-protein/gene-disease" network and revealing the regulation principles of small molecules in a high-throughput manner. This approach makes it very powerful for the analysis of drug combinations, especially Traditional Chinese Medicine (TCM) preparations. In this work, we first summarized the databases and tools currently used for TCM research. Second, we focused on several representative applications of network pharmacology for TCM research, including studies on TCM compatibility, TCM target prediction, and TCM network toxicology research. Third, we compared the general statistics of several current TCM databases and evaluated and compared the search results of these databases based on 10 famous herbs. In summary, network pharmacology is a rational approach for TCM studies, and with the development of TCM research, powerful and comprehensive TCM databases have emerged but need further improvements. Additionally, given that several diseases could be treated by TCMs, with the mediation of gut microbiota, future studies should focus on both the microbiome and TCMs to better understand and treat microbiome-related diseases.