Structure-function relationship and biological activity of polysaccharides from mulberry leaves: A review.

Mulberry (Latin name "Morus alba L.") is a perennial deciduous tree in the family of Moraceae, widely distributed around the world. In China, mulberry is mainly distributed in the south and the Yangtze River basin. Its leaves can be harvested 3-6 times a year, which has a great resource advantage. Mulberry leaves are regarded as the homology of medicine and food traditional Chinese medicine (TCM). Polysaccharides, as its main active ingredients, have various effects, such as antioxidant, hypoglycemic, hepatoprotective, and immunomodulatory. This review summarizes the research progress in the extraction, purification, structural characterization, and structure-function relationship of polysaccharides from mulberry leaves in the last decade, hoping to provide a reference for the subsequent development and market application of polysaccharides from mulberry leaves.

Integrating network pharmacology with microRNA microarray analysis to identify the role of miRNAs in thrombosis treated by the Dahuang Zhechong pill.

BACKGROUND: Thrombotic diseases are the leading causes of death worldwide, urging for improvements in treatment strategies. Dahuang Zhechong pill (DHZCP) is a traditional Chinese medicine widely used for treating thrombotic diseases; however, the underlying mechanisms remain unclear. This study aimed to explore the potential mechanisms of DHZCP in treating thrombosis with a focus on bioinformatics and miRNAs. METHODS: We used network pharmacology to explore the targets of thrombosis treated with DHZCP and performed microarray analysis to acquire miRNA profiles and predict the target genes in thrombin-stimulated MEG-01 cells treated with DHZCP. Based on the overlapping of targets, we carried out a component-target-miRNA network and enrichment analysis and validated the selected miRNAs and mRNAs using quantitative reverse transcription-polymerase chain reaction. RESULTS: Our data showed 850 targets of 230 active ingredients of DHZCP and 1214 thrombosis-related genes; 235 targets were common. We identified 32 miRNAs that were regulated by thrombin stimulation but regulated reversely by DHZCP treatment in MEG-01 cells, and predicted 1846 targets with function annotation. We analyzed conjointly 23 integrating targets from network pharmacology and microarray. HIF1A, PIK3CA, MAPK1 and BCL2L1 emerged as key nodes in the network diagrams. We confirmed the differential expression of seven miRNAs, one mRNA (BCL2L1) and platelet surface protein. CONCLUSIONS: This study showed that miRNAs and their targets, such as BCL2L1, played crucial roles in platelet activation during DHZCP intervention in thrombosis, highlighting their potential to alleviate platelet activation and increase cell apoptosis. The study's findings could help develop new strategies for improving thrombosis treatment.

Hysteresis analysis reveals how phytoplankton assemblage shifts with the nutrient dynamics during and between precipitation patterns.

The escalation of global eutrophication has significantly increased due to the impact of climate change, particularly the increased frequency of extreme rainfall events. Predicting and managing eutrophication requires understanding the consequences of precipitation events on algal dynamics. Here, we assessed the influence of precipitation events throughout the year on nutrient and phytoplankton dynamics in a drinking water reservoir from January 2020 to January 2022. Four distinct precipitation patterns, namely early spring flood rain (THX), Plum rain (MY), Typhoon rain (TF), and Dry season (DS), were identified based on rainfall intensity, duration time, and cumulative rainfall. The study findings indicate that rainfall is the primary driver of algal dynamics by altering nutrient levels and TN:TP ratios during wet seasons, while water temperature becomes more critical during the Dry season. Combining precipitation characteristics with the lag periods between algal proliferation and rainfall occurrence is essential for accurately assessing the impact of rainfall on algal blooms. The highest algae proliferation occurred approximately 20 and 30 days after the peak rainfall during the MY and DS periods, respectively. This was influenced by the intensity and cumulative precipitation. The reservoir exhibited two distinct TN/TP ratio stages, with average values of 52 and 19, respectively. These stages were determined by various forms of nitrogen and phosphorus in rainfall-driven inflows and were associated with shifts from Bacillariophyta-dominated to Cyanophyta-dominated blooms during the MY and DS seasons. Our findings underscore the interconnected effects of nutrients, temperature, and hydrological conditions driven by diverse rainfall patterns in shaping algal dynamics. This study provides valuable insights into forecasting algal bloom risks in the context of climate change and developing sustainable strategies for lake or reservoir restoration.

Prognostic Analysis of Prophylactic Hyperthermic Intraperitoneal Chemotherapy for Advanced Gastric Cancer: a Propensity Score-Matched Analysis.

PURPOSE: To investigate the efficacy of prophylactic hyperthermic intraperitoneal chemotherapy (HIPEC) for advanced gastric cancer (AGC). METHODS: We included 198 patients treated from December 2016 to January 2019; of these patients, the 132 who had clinical T4 gastric cancer were divided into a hyperthermic intraperitoneal chemotherapy group (HIPEC group) and a radical gastrectomy and D2 lymph node dissection group (control group). Because this study was retrospective, we used propensity score matching (PSM) to reduce selectivity bias; we then assessed risk factors for recurrence and compared prognosis in terms of survival in the gastrectomy and prophylactic HIPEC groups. RESULTS: Prophylactic HIPEC reduced the risk of postoperative peritoneal metastasis (PM: 27.5% vs. 10.5%, P = 0.015) and did not increase the risk of postoperative complications, but there was no significant difference in the effect on hepatic metastases or other distant metastases. Risk factors for recurrence included pT4 staging and positive lymph node metastases. Both disease-free survival (DFS: HR 0.592; 95% CI 0.354-0.990; P = 0.042) and peritoneal recurrence-free survival (PFS: HR 0.314; 95% CI 0.127-0.774; P = 0.008) were better in the prophylactic HIPEC group than in the gastrectomy-only group. In addition, there was no difference in the prognosis of patients between the two groups of raltitrexed (RT) and paclitaxel (PTX) for perfusion dosing. CONCLUSION: Our study showed that prophylactic HIPEC could prevent postoperative PM in patients with AGC and did not increase the incidence of postoperative complications. However, it was not found to be effective in the prevention of other metastases, such as hepatic metastases.

Microbial community in buckwheat rhizosphere with different nitrogen application rates.

Microorganism plays a pivotal role in regulating sustainable development of agriculture. The excessive application of nitrogen fertilizer is considered to affect the microbial structure in many agricultural systems. The present study aimed to assess the impacts of nitrogen application rate on microbial diversity, community and functionality in rhizosphere of Tartary buckwheat in short-time. The nitrogen fertilizer was applied at rates of 90 kg (N90), 120 kg (N120) and 150 kg (N150) urea per hectare, respectively. The soil properties were measured chemical analysis and displayed no difference among treatments. Metagenome analysis results showed that the microbial diversity was not affected, but the microbial community and functionality were affected by the nitrogen application rate. According to the Linear discriminant analysis effect size (LEfSe) analysis, 15 taxa were significantly enriched in the N120 and N150 groups, no taxon was enriched in the N90 group. Kyoto Encyclopaedia of Genes and Genomes (KEGG) annotation results revealed that the genes related to butanoate and beta alanine metabolism were significantly enriched in the N90 group, the genes related to thiamine metabolism, lipopolysaccharide biosynthesis and biofilm formation were significantly enriched in the N120 group, and the genes related to neurodegenerative disease was significantly enriched in the N150 group. In conclusion, short-time nitrogen fertilizer application shifted the microbial community structure and functionality.

Shenqi formula delayed Alzheimer's disease-like symptoms by skn-1 pathway in Caernorhabditis elegans.

ETHNOPHARMACOLOGICAL RELEVANCE: Shenqi formula is composed of Codonopsis pilosula (Cp) and Lycium barbarum (Lb), and it is traditionally used for promoting qi and nourishing the spleen, liver and kidney. Cp and Lb have been reported to improve cognitive performance in APP/PS1 mice, prevent the accumulation of Aß, and reduce the neurotoxicity of Aß to achieve the anti-Alzheimer's disease (AD) effect. AIM OF THE STUDY: Shenqi formula was explored the therapeutic effect on Caenorhabditis elegans AD pathological model and the underlying mechanism of action. MATERIALS AND METHODS: Paralysis assay and serotonin sensitivity assay was used to detect whether Shenqi formula can alleviate AD paralysis phenotype, and then DPPH, ABTS, NBT and Fenton methods were applied to investigate the scavenging capacity to free radical, ROS, ·O2- and ·OH of Shenqi formula in vitro. H2DCF-DA and MitoSOX™ Red were employed to measure ROS and .O2- accumulation, respectively. RNAi was used to knock down the expression of skn-1 and daf-16 related to oxidative stress resistance signalling pathway. Fluorescence microscopy was used to record the expression of SOD-3::GFP, GST-4::GFP, SOD-1::YFP, and the nuclear translocation of SKN-1 and DAF-16. Western blot assay was carried out to test Aß monomers and oligomers. RESULTS: Shenqi formula delayed the AD-like pathological characteristics in C. elegans, and the complete Shenqi formula was more effective than Cp or Lb alone. The effect of Shenqi formula on delaying worm paralysis was partially eliminated by skn-1 RNAi, but not daf-16 RNAi. Shenqi formula significantly inhibited the abnormal deposition of Aß protein, decreased Aß protein monomers and oligomers. It increased the expressions of gst-4, sod-1, and sod-3 similar to paraquat, companied by rise then fall of ROS and .O2- in AD worms. CONCLUSIONS: Shenqi formula at least partially depended on SKN-1 signalling pathway to exert its anti-AD effect, and it is potential to be used as a kind of health food to prevent the progress of AD.

Lonicerin alleviates the progression of experimental rheumatoid arthritis by downregulating M1 macrophages through the NF-κB signaling pathway.

The present study aimed to evaluate anti-rheumatoid arthritis (RA) effect of Lonicerin (LON), a safe compound with anti-inflammatory and immunomodulatory properties. Nevertheless, the exact role of LON in RA remains elusive. In this test, the anti-RA effect of LON was evaluated in collagen-induced arthritis (CIA) mouse model. Relevant parameters were measured during the experiment; ankle tissue and serum were collected at the end of the experiment for radiology, histopathology, and inflammation analysis. ELISA, qRT-PCR, immunofluorescence, and western blot were used to explore the effect of LON on the polarization of macrophages and related signal pathways. It was discovered that LON treatment attenuated the disease progression of CIA mice with lower paw swelling, clinical score, mobility, and inflammatory response. LON treatment significantly decreased M1 marker levels in CIA mice and LPS/IFN-γ-induced RAW264.7 cells, while slightly increasing M2 marker levels in CIA mice and IL-4-induced RAW264.7 cells. Mechanistically, LON attenuated the activation of the NF-κB signaling pathway, which contributes to M1 macrophage polarization and inflammasome activation. In addition, LON inhibited NLRP3 inflammasome activation in M1 macrophages, thereby reducing inflammation by inhibiting IL-1ß and IL-18 release. These results indicated that LON might exert anti-RA effects by regulating the polarization of M1/M2 macrophage, especially by inhibiting macrophage polarization toward M1.

A Near-Infrared Light-Activated Photocage Based on a Ruthenium Complex for Cancer Phototherapy.

Conventional photocages only respond to short wavelength light, which is a significant obstacle to developing efficient phototherapy in vivo. The development of photocages activated by near-infrared (NIR) light at wavelengths from 700 to 950 nm is important for in vivo studies but remains challenging. Herein, we describe the synthesis of a photocage based on a ruthenium (Ru) complex with NIR light-triggered photocleavage reaction. The commercial anticancer drug, tetrahydrocurcumin (THC), was coordinated to the RuII center to create the Ru-based photocage that is readily responsive to NIR light at 760 nm. The photocage inherited the anticancer properties of THC. As a proof-of-concept, we further engineered a self-assembled photocage-based nanoparticle system with amphiphilic block copolymers. Upon exposure to NIR light at 760 nm, the Ru complex-based photocages were released from the polymeric nanoparticles and efficiently inhibited tumor proliferation in vivo.

Sesquiterpene lactones-enriched fractions from Xanthium mongolicum Kitag alleviate RA by regulating M1 macrophage polarization via NF-κB and MAPK signaling pathway.

Introduction: Rheumatoid arthritis (RA) is a chronic autoimmune disease, characterized by activated M1-like macrophage in the joint. Xanthium mongolicum Kitag (X. mongolicum) is a traditional medicinal plant that has long been used to treat RA and other immune diseases in China. Methods: Fractions of X. mongolicum were separated based on polarity. Anti-RA activity of the fractions were screened by LPS-stimulated RAW264.7 macrophage in vitro. The major active compounds were identified by UPLC-MS and quantified by HPLC. The anti-RA effects of the active fraction was evaluated in complete freund's adjuvant (CFA)-induced arthritis and collagen-induced arthritis (CIA) mouse models in vivo and LPS-stimulated macrophage in vitro. Results: Sesquiterpene lactones-enriched fraction from X. mongolicum (SL-XM) exhibited the strongest anti-RA activity among all components in vitro. Five major constituents i.e., Xanthinosin (1), Xanthatin (2), Mogolide D (3), Mogolide E (4), and Mogolide A (5) were identified as major compounds of SL-XM. SL-XM ameliorated symptoms of CFA and CIA induced arthritis mice model. Furthermore, SL-XM treatment inhibited LPS-induced M1 macrophages polarization. In addition, SL-XM inhibited the phosphorylation of NF-κB and MAPK signaling pathways in LPS-induced macrophage and CIA-challenged mice. Discussion: The main anti-RA active fraction of X. mongolicum may be the Sesquiterpene lactones, which includes five key compounds. SL-XM may exert its anti-RA effect by suppressing M1 macrophage polarization via the NF-κB and MAPK signaling pathway.

Baicalin Reduces Immune Cell Infiltration by Inhibiting Inflammation and Protecting Tight Junctions in Ischemic Stroke Injury.

Ischemic stroke is a serious health hazard that lacks effective treatment strategies. This study aims to investigate baicalin's effect on tight junctions and immune cell infiltration after ischemic stroke injury. Rat brain microvascular endothelial cells (BMECs) were treated with OGD/R to establish an in vitro model. Caspase-3, Bax, Bcl-2, zonula occludens-1 (ZO-1), occludin, claudin-5, tumor necrosis factor (TNF)-[Formula: see text], interleukin (IL)-6, inducible nitric oxide synthase (iNOS), Toll-like receptor (TLR) 2, TLR4, and nuclear factor-kappa B (NF-[Formula: see text]B) expressions were detected using qRT-PCR and western blotting. ZO-1, TNF-[Formula: see text], iNOS, IL6, CD31, and ZO-1 expressions were examined using immunofluorescence. A tube formation assay was performed to measure angiogenesis. An ischemia-reperfusion model in rats was established by middle cerebral artery occlusion. The infarct volume was observed using 2,3,5-triphenyltetrazolium chloride staining. TNF-[Formula: see text], iNOS, and IL6 levels in the serum were tested using ELISA. Flow cytometry was performed to examine immune cell inflammatory infiltration. Baicalin had no significant effect on the proliferation of normal BMECs. Baicalin inhibited apoptosis, protected against tight junction injury, and alleviated the inflammatory response in OGD/R-induced BMECs and IR rats, with the highest dose (25[Formula: see text][Formula: see text]g/mL) exerting a superior effect. Baicalin decreased the neurological function score, infarct volume, and brain water content, relieved brain morphological changes, and inhibited immune cell infiltration in vivo. In conclusion, baicalin could reduce BMECs apoptosis, protect tight junctions, and resist immune cell infiltration, thereby alleviating ischemic stroke. Our findings potentially provide a novel treatment strategy for ischemic stroke.

Eremophilane-type and xanthanolide-type sesquiterpenes from the aerial parts of Xanthium sibiricum and their anti-inflammatory activities.

The traditional Chinese medicine Xanthium sibiricum Patrin ex Widder is used to treat wind-cold headache, nasal congestion, nasal discharge, allergic rhinitis, sinusitis, urticaria, and arthritis. Our previous studies found that sesquiterpene lactones, the main bioactive constituents of X. sibiricum, relieved airway inflammation in an asthma mouse model. To obtain active sesquiterpenes, five undescribed ones, including a pair of eremophilanes and three xanthanolides, together with eight known xanthanolides were isolated from X. sibiricum. Their structures were identified by IR, UV, HR-ESI-MS and NMR spectroscopic data, and their absolute configurations were determined by X-ray crystallographic diffraction analysis and the comparison between their experimental and calculated electronic circular dichroism. All isolated compounds were evaluated for their inhibitory effects on nitric oxide production, and Tnf-α, Il-1ß, and Il-6 mRNA expression induced by lipopolysaccharide in the macrophage cell line RAW264.7. Further investigation showed that xanthsibiriolide and 11ß-hydroxyl-13-chloro-8-epi-xanthatin exerted their anti-inflammatory effects by inhibiting the PI3K/AKT/mTOR signaling pathway. Analysis of the structure-activity relationships indicated that the α,ß-unsaturated lactone ring and the 1,5-epoxide group might be the bioactive groups of xanthanolides, and these results provide a basis for further exploration of sesquiterpene-type lead compounds with anti-inflammatory activity.

Updated Meta-Analysis Assessing Effects of Baduanjin on Cardiopulmonary Functions of Patients with Coronary Heart Disease.

Background: Baduanjin is a kind of moderate-intensity aerobic exercise, but its effect on the cardiac rehabilitation (CR) of patients with coronary heart disease (CHD) is controversial. Furthermore, the small sample size of a single study and the inconsistent selection of evaluation indicators among different studies all promote the necessity of conducting a meta-analysis. Objective: This meta-analysis aims to explore whether Baduanjin can effectively improve the cardiopulmonary function in patients with CHD and to assess the extrapolation of the results. Methods: Both English and Chinese databases were used for literature retrieval. The Cochrane Collaboration tool was used to evaluate the methodological quality of the included literature. A weighted mean difference and a 95% confidence interval were used to assess the effects of Baduanjin on cardiopulmonary function based on multiple CR indicators. Cochran's Q and I 2 tests were used for the heterogeneity test. A funnel plot and an Egger test were used to evaluate publication bias. Results: After literature retrieval, a total of 12 literature papers were included in this meta-analysis, but their methodological quality was unsatisfactory. By comparing differences between CHD patients with and without Baduanjin, we found that levels of 6MWT, LVEF, NT-proBNP, VO2, peak VO2, MVV, and VE, AT were significantly improved in the experimental group, but heterogeneity exists among included studies. Results of subgroup analyses were consistent with combined estimates and suggested a significant effect of Baduanjin on LVEF. The Egger test indicated no significant publication bias. Conclusion: Baduanjin is beneficial to CR in CHD patients, but multiple region-based high-quality studies are necessary to verify the results.

Efficacy of the Panax Notoginseng Ejiao Suppository in the Treatment of Patients with Ulcerative Proctitis and Its Effect on Inflammatory Response and Immune Function.

Objective: To investigate the efficacy of the Panax notoginseng Ejiao suppository in patients with ulcerative proctitis and its effect on inflammatory response and immune function. Methods: This study recruited 100 patients with ulcerative proctitis who were hospitalized to our hospital's anorectal outpatient department between May 2015 and October 2020. They were randomly separated into either a control or a study group, with 50 cases in each. The control group received the mesalazine suppository, whereas the study group received the Panax notoginseng Ejiao suppository. Outcome measures included clinical effectiveness, inflammatory response, and immunological state of patients. Results: The total efficiency in the study group was significantly higher than that in the control group (P = 0.019). The Mayo score and Baron endoscopic score between the two groups were significantly decreased after treatment, with lower results in the study group (P < 0.05). The inflammatory variables were dramatically reduced following therapy, with the study group doing worse. Following treatment, the number of Th 17 cells declined dramatically in both groups, while the proportion of Treg cells increased significantly, with greater alterations of Th17 cells and Treg cells observed in the study group than those in the control group (P < 0.05). The Panax notoginseng Ejiao suppository resulted in significantly shorter time lapses before symptom alleviation and a lower incidence of recurrence at 6 months after treatment versus mesalazine suppository (P < 0.05). Conclusion: In patients with ulcerative proctitis, the Panax notoginseng Ejiao suppository significantly improves clinical efficacy, reduces the incidence of recurrence, mitigates inflammatory response, and improves immune function.

Spatiotemporal changes of bacterial communities during a cyanobacterial bloom in a subtropical water source reservoir ecosystem in China.

Cyanobacterial blooms, which not only threaten the health and stability of aquatic ecosystems but also influence the microbial community within, emerges as one of the most concerning problems in China. However, how cyanobacterial blooms affect the spatiotemporal variation of aquatic microbial communities remains relatively unclear. In this study, we used high-throughput sequencing to investigate how the cyanobacterial and bacterial community spatiotemporally vary along with main cyanobacterial bloom phases in upstream rivers of a eutrophicated water source reservoir. Both cyanobacterial and bacterial diversities in each river were significantly lower (P < 0.05) during the bloom outbreak phase, showing the apparent influence of cyanobacterial bloom. Dominant cyanobacterial taxa included Cyanobacteriales and Synechococcales, and dominant bacterial taxa comprised Acinetobacter, CL500-29, hgcI clade, Limnohabitans, Flavobacterium, Rhodoluna, Porphyrobacter, Rhodobacter, Pseudomonas, and Rhizobiales, whose changes of relative abundance along with the bloom indicated distinct community composition. Non-metric multidimensional scaling analysis proved that community composition had significant difference amongst bloom phases. Linear discriminant analysis (LDA) with LDA effect size analysis (LEfSe) identified unique dominant cyanobacterial and bacterial OTUs at different phases in each river, indicating spatiotemporal variations of communities. Canonical correlation analysis or redundancy analysis revealed that at different bloom phases communities of each river had distinct correlation patterns with the environmental parameters (temperature, ammonium, nitrate, and total phosphorus etc.), implying the spatial variations of microbial communities. Overall, these results expand current understanding on the spatiotemporal variations of microbial communities due to cyanobacterial blooms. Microbial interactions during the bloom may shed light on controlling cyanobacterial blooms in the similar aquatic ecosystems.

The Clinical Application Value of the Prognostic Nutritional Index for the Overall Survival Prognosis of Patients with Esophageal Cancer: A Robust Real-World Observational Study in China.

Esophageal cancer is a kind of cancer with high morbidity and mortality, which is accompanied by a profound poor prognosis. A prognostic nutritional index, based on serum albumin levels and peripheral lymphocyte count, has been confirmed to be significantly associated with various cancers. This study was aimed at exploring the prognostic significance of PNI in the overall survival prognosis of patients with esophageal cancer. As a real-world study based on the big database, clinical data of 2661 patients with esophageal cancer were evaluated retrospectively, and the individuals were randomly divided into training and testing cohorts. In these two cohorts, patients are classified into a high-risk group (PNI < 49) and a low-risk group (PNI ≥ 49). Univariate and multivariate analyses were performed to analyze the independent risk factors for the prognosis of esophageal cancer patients by using the Cox proportional hazards regression model. In this study, whether in the training cohort or the testing cohort, according to the univariate analysis, gender, tumor size, tumor grade, T stage, N stage, M stage, TNM stage, and PNI were significantly correlated with overall survival. Furthermore, the multivariate analysis showed that gender, T stage, N stage, M stage, TNM stage, and PNI were independent prognostic risk factors for esophageal cancer. PNI can be regarded as an independent prognostic factor combined with gender, T stage, N stage, M stage, and TNM stage, and it might be a novel reliable biomarker for esophageal cancer.

cep-1 mediated the mitohormesis effect of Shengmai formula in regulating Caenorhabditis elegans lifespan.

Ageing is one of the major causes of many diseases such as cardiovascular diseases, diabetes, neurodegenerative disorders, and cancer. It has been found that mitochondrion acts as a crucial regulator of healthy lifespan. In this work, traditional Chinese medicine Shengmai formula (SMH) was used to treat mitochondrial mutants of Caenorhabditis elegans. The results showed that SMH shortened the lifespan of short-lived mev-1 mutant, but lengthened the lifespan of long-lived isp-1 mutant. Acute SMH treatment has benefit effect by increasing resistance capacity and motion activity in both ETC mutants and wild type N2. Compared with N2, the genome-wide transcriptome profile of ETC mutants showed on a similar pattern after SMH treatment. GO and KEGG enrichment analysis addressed that SMH-induced genes mainly enriched in metabolic process and oxidation-reduction process. The ROS levels in ETC mutants and N2 firstly rose then fell after SMH treatment, in company with the elevation of SOD-1, SOD-3 and GST-4, the increment of HSP-16.2 combined with heat shock. SMH increased oxygen consumption and ATP content, improved the restoration of mitochondrial homeostasis. SMH-induced opposed lifespan outcomes were markedly counteracted by cep-1 RNAi, together with the mitochondrial dynamics. Western blot assay also demonstrated a SMH-induced CEP-1 expression. Collectively, SMH acts as a prooxidant to regulate mitochondrial homeostasis and causes mitohormesis to exert therapeutic effect based on the redox background of the recipients, and cep-1 was required for the mitochondrial hormetic responses. The results shed a light on the rational clinical anti-ageing applications of SMH in the future.

Upregulation of Yin-Yang-1 Associates with Proliferation and Glutamine Metabolism in Esophageal Carcinoma.

Objective: To investigate the expression of Yin-Yang-1 (YY1) in esophageal carcinoma (ESCA) and its effect on glutamine metabolism in ESCA. Methods: The expression and roles of YY1 in ESCA were investigated using a series of bioinformatics databases and tools. The expression of YY1 between ESCA tissues with the corresponding adjacent tissues was validated using real-time PCR, western blot, and immunohistochemical staining method. Furthermore, the effects of YY1 on ESCC cell proliferation and migration were examined. The correlation between the YY1 and glutamine metabolism was evaluated by western blot. Results: YY1 gene was highly conserved in evolution and upregulated in ESCA tissues and ESCC cell lines (ECA109 and TE-1). In addition, YY1 may affect the level of immune cell infiltration and promote tumor cell immune escape. Functional enrichment analysis found that YY1 involved in many biological processes, such as cell division and glutathione and glutamine metabolism. After siRNA knockdown of YY1 in ECA109 and TE-1, the proliferation and the migration of ECA109 and TE-1 were suppressed. The glutamine consumption and glutamate production were significantly decreased. The protein expression of alanine-, serine-, cysteine-preferring transporter 2 (ASCT2), glutaminase (GLS), and glutamate dehydrogenase (GLUD1) was significantly downregulated. Conclusion: YY1 is highly expressed in ESCA and may promote glutamine metabolism of ESCC cells, indicating it may be as a diagnostic biomarker for ESCA.

Sesquiterpene lactones from Xanthium sibiricum Patrin alleviate asthma by modulating the Th1/Th2 balance in a murine model.

BACKGROUND: Asthma is a complex airway disease involving a variety of cells and cytokines. Xanthium sibiricum Patrin ex Widder (X. sibiricum) is a traditional Chinese medicine for various immune diseases, especially allergic rhinitis and asthma. Sesquiterpene lactones are the main bioactive and most abundant constituent, and are characteristic component of the plant. We explore whether sesquiterpene lactones from X. sibiricum (SL-XS) is the main active constitute for its anti-asthma activity. PURPOSE: In the present study, SL-XS was isolated, the major compounds were isolated and identified in extract of SL-XS, and the anti-asthma activity of SL-XS was validated in vivo. METHODS: SL-XS was isolated by a standard phytochemical method. The structures of major sesquiterpene lactones were identified by NMR and LC-MS spectra. The contents of major SL-XS were analyzed by HPLC. The anti-asthma effect of SL-XS was evaluated in a house dust mite (HDM)-induced mouse model. RESULTS: The sesquiterpene lactones were isolated from X. sibiricum, and five major constituents i.e., 8­epi-xanthatin-1ß, 5ß-epoxide (1), tomentosin (2), 8­epi-xanthatin (3), 2­epi-xanthumin (4) and sibiriolide B (5) were identified from SL-XS. Oral administration of SL-XS dose-dependently ameliorated airway inflammation and remodeling in HDM-challenged asthma mouse model. Furthermore, SL-XS treatment inhibited the upregulation of proinflammatory and Th2 cytokines, while reversed the downregulation of Th1 related cytokines. In addition, SL-XS regulated the balance between T-bet and GATA-3. Moreover, SL-XS inhibited the upregulation of JAK1, p-JAK1, JAK2, p-JAK2, JAK3, p-JAK3 and p-STAT6 in HDM-challenged mice. CONCLUSION: The sesquiterpene lactones including five major constituents may be the main anti-asthma active constituent of X. sibiricum. SL-XS exerted its anti-asthma effect by modulating the Th1/Th2 balance via the JAK/STAT signaling pathway.

Ameliorative Effects of Malonyl Ginsenoside from Panax ginseng on Glucose-Lipid Metabolism and Insulin Resistance via IRS1/PI3K/Akt and AMPK Signaling Pathways in Type 2 Diabetic Mice.

Our previous study has revealed that malonyl-ginsenosides from Panax ginseng (PG-MGR) play a crucial role in the treatment of T2DM. However, its potential mechanism was still unclear. In this study, we investigated the anti-diabetic mechanisms of action of PG-MGR in high fat diet-fed (HFD) and streptozotocin-induced diabetic mice and determined the main constituents of PG-MGR responsible for its anti-diabetic effects. Our results showed that 16 malonyl ginsenosides were identified in PG-MGR by HPLC-ESI-MS/MS. PG-MGR treatment significantly reduced fasting blood glucose (FBG), triglyceride (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) levels and improved insulin resistance and glucose tolerance. Simultaneously, PG-MGR treatment improved liver injury by decreasing aspartate aminotransferase (AST) and alanine aminotransferase (ALT) expression. Furthermore, Western blot analysis demonstrated that the protein expression levels of p-PI3K/PI3K, p-AKT/AKT, p-AMPK/AMPK, p-ACC/ACC and GLUT4 in liver and skeletal muscle were significantly up-regulated after PG-MGR treatment, and the protein expression levels of p-IRS-1/IRS-1, Fas and SREBP-1c were significantly reduced. These findings revealed that PG-MGR has the potential to improve glucose and lipid metabolism and insulin resistance by activating the IRS-1/PI3K/AKT and AMPK signal pathways.

Bai-Hu-Tang regulates endothelin-1 and its signalling pathway in vascular endothelial cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Bai-Hu-Tang (BHT) is traditionally used to treat human and animal fever syndrome with four symptoms: large and vigorous pulse, large thirst, high sweat, and high heat. AIM OF THE STUDY: To investigate the mechanism of vasodilation regulation of Bai-Hu-Tang in primary vascular endothelial cells stimulated by lipopolysaccharide (LPS). MATERIALS AND METHODS: A hydrophilic concentrate of BHT was prepared, and the main components of mangiferin and timosaponin BⅡ were determined by HLPC analysis. The rabbit fever model was constructed by intravenous injection of LPS (15 µg/kg body weight), and BHT was gavaged to treat febrile rabbits. After treatment for 6 h, animal peripheral blood was collected, and serum was isolated for endothelin-1 (ET-1) and nitric oxide (NO) assays. Rabbit vascular endothelial cells (RVECs) were isolated and stimulated with 1 µg/mL LPS, and then inflammatory cells were treated with 125 or 250 µg/mL BHT for 24 h. The supernatant cytokines TNF-ɑ, IL-1ß, IL-6, and ET-1 were detected by ELISA kits. Gene expression levels of endothelin receptor type B (ETB receptor) were analysed by real-time polymerase chain reaction (RT-PCR), and protein expression levels of PI3K and Akt were detected by Western blot. A nitrite assay was used to measure intracellular nitric oxide (NO) production, and nitric oxide synthase (NOS) was measured by the T-NOS colorimetric method. RESULTS: Animal experiments demonstrated that BHT significantly restored ET-1 and NO in animal peripheral blood, which were disordered in LPS-induced fever rabbits. Moreover, a cytotoxicity assay demonstrated that BHT ≤700 µg/mL is innoxious to RVECs. BHT significantly repressed cellular TNF-α, IL-1ß, and ET-1, which were originally elevated by LPS in RVECs. Meanwhile, BHT elevated the gene expression level of the ETB receptor and promoted NOS and NO production in RVECs induced by LPS. CONCLUSION: BHT can inhibit excessive ET-1 secretion induced by LPS in vascular endothelial cells and activate the classic ET-1 signalling pathway to promote NO production, which may facilitate vasodilation of smooth muscle cells.