Echinacoside ameliorates post-stroke depression by activating BDNF signaling through modulation of Nrf2 acetylation.

BACKGROUND: Post-stroke depression (PSD) affects approximately one-third of stroke survivors, leading to adverse outcomes in rehabilitation, reduced quality of life, and increased mortality rates. Despite these implications, the underlying causes of PSD remain unclear, posing challenges for prevention and treatment. Echinacoside (ECH), a natural compound with known neuroprotective and antidepressant properties, holds significant therapeutic potential for PSD. However, the precise mechanism of its action remains unknown. PURPOSE: To unravel the specific mechanism through which ECH alleviates PSD by exploring the intricate interplay between ECH and Nrf2, as well as its impact on the BDNF/TrkB signaling axis. STUDY DESIGN AND METHODS: A rat PSD model was established though middle cerebral artery occlusion coupled with chronic unpredictable mild stress, followed by ECH treatment. The rats' depressive state was evaluated using the sucrose preference test and force swimming test. Brain damage was assessed through TTC staining, Nissl staining, and TUNEL assay. The multifaceted mechanism of ECH in PSD was investigated using immunofluorescence, immunohistochemistry, RT-qPCR, dual-luciferase assay, and western blotting. Additionally, the interaction between ECH and Nrf2 was explored through molecular docking and microscale thermophoresis. RESULTS: Our findings unveiled a novel facet of ECH action, demonstrating its unique ability to upregulate Nrf2 through acetylation within the hippocampus of PSD-affected rats (p < 0.05). Moreover, ECH showcased its distinctive potential by enhancing BDNF transcriptional activity, activating the BDNF/TrkB signaling axis, and orchestrating a comprehensive response against oxidative stress and apoptosis, thereby alleviating PSD symptoms in rats (p < 0.05). CONCLUSIONS: This study not only provides insights into the pivotal role of Nrf2 in mediating the BDNF/TrkB axis activation by ECH but also highlights the novelty of ECH's mechanism in addressing PSD. The elucidation of these unique aspects positions ECH as a groundbreaking candidate for further exploration and development in the realm of PSD intervention.

Wild species rice OsCERK1DY-mediated arbuscular mycorrhiza symbiosis boosts yield and nutrient use efficiency in rice breeding.

Meeting the ever-increasing food demands of a growing global population while ensuring resource and environmental sustainability presents significant challenges for agriculture worldwide. Arbuscular mycorrhizal symbiosis (AMS) has emerged as a potential solution by increasing the surface area of a plant's root system and enhancing the absorption of phosphorus, nitrogen nutrients, and water. Consequently, there is a longstanding hypothesis that rice varieties exhibiting more efficient AMS could yield higher outputs at reduced input costs, paving the way for the development of Green Super Rice (GSR). Our prior research study identified a variant, OsCERK1DY, derived from Dongxiang wild-type rice, which notably enhanced AMS efficiency in the rice cultivar "ZZ35." This variant represents a promising gene for enhancing yield and nutrient use efficiency in rice breeding. In this study, we conducted a comparative analysis of biomass, crop growth characteristics, yield attributes, and nutrient absorption at varying soil nitrogen levels in the rice cultivar "ZZ35" and its chromosome single-segment substitution line, "GJDN1." In the field, GJDN1 exhibited a higher AM colonization level in its roots compared with ZZ35. Notably, GJDN1 displayed significantly higher effective panicle numbers and seed-setting rates than ZZ35. Moreover, the yield of GJDN1 with 75% nitrogen was 14.27% greater than the maximum yield achieved using ZZ35. At equivalent nitrogen levels, GJDN1 consistently outperformed ZZ35 in chlorophyll (Chl) content, dry matter accumulation, major nutrient element accumulation, N agronomic efficiency (NAE), N recovery efficiency (NRE), and N partial factor productivity (NPFP). The performance of OsCERK1DY overexpression lines corroborated these findings. These results support a model wherein the heightened level of AMS mediated by OsCERK1DY contributes to increased nitrogen, phosphorus, and potassium accumulation. This enhancement in nutrient utilization promotes higher fertilizer efficiency, dry matter accumulation, and ultimately, rice yield. Consequently, the OsCERK1DY gene emerges as a robust candidate for improving yield, reducing fertilizer usage, and facilitating a transition towards greener, lower-carbon agriculture. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-024-01459-8.

Morroniside improves the symptoms of post-stroke depression in mice through the BDNF signaling pathway mediated by MiR-409-3p.

BACKGROUND: Post-stroke depression (PSD) is a common psychiatric symptom after a stroke. Morroniside, an iridoid glycoside found in Cornus officinalis, has garnered significant attention for its potential to alleviate symptoms associated with depression. PURPOSE: This study aims to highlight the potential use of morroniside in the treatment of PSD and elucidate the underlying molecular mechanisms. METHODS: To establish a reliable PSD model, male C57BL/6 mice were subjected to brief MCAO in conjunction with CUMS. Post-morroniside administration, neuronal viability, and hippocampal cell apoptosis were evaluated by Nissl staining and TUNEL detection, respectively. Depression-like behaviors were evaluated using SPT, TST, and FST. The Longa score and cylinder test were used to evaluate the effect of morroniside on motor function. Furthermore, to investigate the underlying molecular mechanisms, bioinformatic analysis and the dual luciferase assay were performed to investigate the MiR-409-3p-BDNF interaction. In addition, subsequent to MiR-409-3p overexpression via AAV virus, we assessed mRNA expression and protein levels of key components within the BDNF/TrkB signaling pathway using RT-qPCR, immunohistochemistry, and western blot analysis. RESULTS: The observed decrease in apoptosis and amelioration of depression-like behaviors strongly indicate the potential of morroniside as a therapeutic agent for PSD. Furthermore, the upregulation of key proteins within the BDNF/TrkB signaling pathway in the cortex suggests that morroniside activates this pathway. Through bioinformatics analysis, MiR-409-3p was identified and found to bind to the BDNF gene, resulting in the inhibition of BDNF expression. Importantly, we demonstrate that morroniside mitigates this inhibitory effect of MiR-409-3p on BDNF, thereby facilitating the activation of the BDNF/TrkB signaling pathway. CONCLUSION: The findings suggest that morroniside demonstrates the ability to improve PSD symptoms through the BDNF/TrkB signaling pathway mediated by MiR-409-3p. These results emphasize the importance of the BDNF signaling pathway in improving PSD symptoms and provide a possible mechanism for morroniside to treat PSD.

Immune profile of patients with peritoneal carcinomatosis selected for CRS-HIPEC therapy.

Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is a treatment option for peritoneal carcinomatosis (PC) from colorectal cancer (CRC), which is otherwise a terminal stage of disease. Nevertheless, survival outcomes are only marginally superior to other treatments. This fact highlights the need for better strategies to control intra-abdominal disease recurrence after CRS-HIPEC, including the complementary use of immunotherapies. The aim of this study was therefore to investigate the immune phenotype of T cells in patients with PC. Fifty three patients with CRC (34 patients with PC and 19 patients without PC) were enrolled in a prospective study (clinicaltrials.gov: NCT04108936). Peripheral blood and omental fat were collected to isolate peripheral blood mononuclear cells (PBMCs) and adipose tissue mononuclear cells (ATMCs). These cells were analysed by flow cytometry using a panel focused upon T cell memory differentiation and exhaustion markers. We found a more naïve profile for CD8+ T cells in peripheral blood and intra-abdominal fat of PC patients compared to comparator group (CG) patients. Furthermore, there was an over-representation of CD4+ T cells expressing inhibitory receptors in adipose tissue of PC patients, but not in blood. Our description of intraperitoneal T cell subsets gives us a better understanding of how peritoneal carcinomatosis shapes local immune responses.

The mechanism of action of safflower total flavonoids in the treatment of endometritis caused by incomplete abortion based on network pharmacology and 16S rDNA sequencing.

ETHNOPHARMACOLOGICAL RELEVANCE: Safflower is a traditional Chinese medicine used for treating gynaecological diseases. However, its material basis and mechanism of action in the treatment of endometritis induced by incomplete abortion are still unclear. AIM OF THE STUDY: This study aimed to reveal the material basis and mechanism of action of safflower in the treatment of endometritis induced by incomplete abortion through comprehensive methods, including network pharmacology and 16S rDNA sequencing. MATERIALS AND METHODS: Network pharmacology and molecular docking methods were used to screen the main active components and potential mechanisms of action of safflower in the treatment of endometritis induced by incomplete abortion in rats. A rat model of endometrial inflammation by incomplete abortion was established. The rats were treated with safflower total flavonoids (STF) based on forecasting results, serum levels of inflammatory cytokines were analysed, and immunohistochemistry, Western blots, and 16S rDNA sequencing were performed to investigate the effects of the active ingredient and the treatment mechanism. RESULTS: The network pharmacology prediction results showed 20 active components with 260 targets in safflower, 1007 targets related to endometritis caused by incomplete abortion, and 114 drug-disease intersecting targets, including TNF, IL6, TP53, AKT1, JUN, VEGFA, CASP3 and other core targets, PI3K/AKT, MAPK and other signalling pathways may be closely related to incomplete abortion leading to endometritis. The animal experiment results showed that STF could significantly repair uterine damage and reduce the amount of bleeding. Compared with the model group, STF significantly down-regulated the levels of pro-inflammatory factors (IL-6, IL-1ß, NO, TNF-α) and the expression of JNK, ASK1, Bax, caspase3, and caspase11 proteins. At the same time, the levels of anti-inflammatory factors (TGF-ß and PGE2) and the protein expression of ERα, PI3K, AKT, and Bcl2 were up-regulated. Significant differences in the intestinal flora were seen between the normal group and the model group, and the intestinal flora of the rats was closer to the normal group after the administration of STF. CONCLUSIONS: The characteristics of STF used in the treatment of endometritis induced by incomplete abortion were multi-targeted and involved multiple pathways. The mechanism may be related to the activation of the ERα/PI3K/AKT signalling pathway by regulating the composition and ratio of the gut microbiota.

SIRT1 is transcriptionally repressed by YY1 and suppresses ferroptosis in rheumatoid arthritis.

BACKGROUND: Sirtuin 1 (SIRT1) is reported downregulated in rheumatoid arthritis (RA), and the protective effects of SIRT1 on tissue damage and organ failure may be related to cellular ferroptosis. However, the exact mechanism by which SIRT1 regulates RA remains unclear. METHODS: Quantitative real-time PCR (qPCR) and western blot assays were performed to explore the expressions of SIRT1 and Yin Yang 1 (YY1). CCK-8 assay was used for cytoactive detection. The interaction between SIRT1 and YY1 was validated by dual-luciferase reporter gene assay and chromatin immunoprecipitation (ChIP). DCFH-DA assay and iron assay were applied to detect the reactive oxygen species (ROS) and iron ion levels. RESULTS: In the serum of RA patients, SIRT1 was downregulated, but YY1 was upregulated. In LPS-induced synoviocytes, SIRT1 could increase cell viability and decrease ROS and iron levels. Mechanistically, YY1 downregulated the expression of SIRT1 by inhibiting its transcription. YY1 overexpression partly revised the effects of SIRT1 on ferroptosis in synoviocytes. CONCLUSION: SIRT1 is transcriptionally repressed by YY1 and inhibits the ferroptosis of synoviocytes induced by LPS, so as to relieve the pathological process of RA. Therefore, SIRT1 might be a new diagnosis and therapeutic target of RA.

Observation on the short-term efficacy of inverse moxibustion at the Baihui point and Dazhui point in preventing post-stroke depression.

OBJECTIVE: In this study, inverse moxibustion was performed at the Baihui and Dazhui points in patients with ischemic stroke, and the Hamilton Depression Rating Scale 17 (HAMD) score, National Institute of Health Stroke Scale (NIHSS) score, modified Barthel index (MBI) score, and incidence of post-stroke depression (PSD) were observed. METHODS: Eighty patients with acute ischemic stroke were enrolled and randomly divided into two groups. All enrolled patients were given routine treatment for ischemic stroke, and those in the treatment group were also given moxibustion at the Baihui and Dazhui points. The course of treatment was four weeks. The HAMD, NIHSS, and MBI scores of the two groups were evaluated before and four weeks after the treatment. The differences between the groups and the incidence of PSD were evaluated to determine the effect of inverse moxibustion at the Baihui and Dazhui points on the HAMD, NIHSS, and MBI scores and prevention of PSD in patients with ischemic stroke. RESULTS: After the four weeks of treatment, the HAMD and NIHSS scores of the treatment group were lower than those of the control group, their MBI was higher than that of the control group, and their incidence of PSD was statistically significantly lower than that of the control group. CONCLUSION: Inverse moxibustion at the Baihui acupoint in patients with ischemic stroke can effectively promote the recovery of neurological function, improve depression, and reduce the incidence of PSD and should be considered for application in clinical practice.

Simultaneous determination of eleven volatile components in Cinnamomi Oleum by GC-MS / 中国中药杂志

A gas chromatography-triple quadrupole mass spectrometry(GC-MS) method was established for the simultaneous determination of eleven volatile components in Cinnamomi Oleum and the chemical pattern recognition was utilized to evaluate the quality of essential oil obtained from Cinnamomi Fructus medicinal materials in various habitats. The Cinnamomi Fructus medicinal materials were treated by water distillation, analyzed using GC-MS, and detected by selective ion monitoring(SIM), and the internal standards were used for quantification. The content results of Cinnamomi Oleum from various batches were analyzed by hierarchical clustering analysis(HCA), principal component analysis(PCA), and orthogonal partial least squares-discriminant analysis(OPLS-DA) for the statistic analysis. Eleven components showed good linear relationships within their respective concentration ranges(R~2>0.999 7), with average recoveries of 92.41%-102.1% and RSD of 1.2%-3.2%(n=6). The samples were classified into three categories by HCA and PCA, and 2-nonanone was screened as a marker of variability between batches in combination with OPLS-DA. This method is specific, sensitive, simple, and accurate, and the screened components can be utilized as a basis for the quality control of Cinnamomi Oleum.

Sodium butyrate activates HMGCS2 to promote ketone body production through SIRT5-mediated desuccinylation / 医学前沿

Ketone bodies have beneficial metabolic activities, and the induction of plasma ketone bodies is a health promotion strategy. Dietary supplementation of sodium butyrate (SB) is an effective approach in the induction of plasma ketone bodies. However, the cellular and molecular mechanisms are unknown. In this study, SB was found to enhance the catalytic activity of 3-hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2), a rate-limiting enzyme in ketogenesis, to promote ketone body production in hepatocytes. SB administrated by gavage or intraperitoneal injection significantly induced blood ß-hydroxybutyrate (BHB) in mice. BHB production was induced in the primary hepatocytes by SB. Protein succinylation was altered by SB in the liver tissues with down-regulation in 58 proteins and up-regulation in 26 proteins in the proteomics analysis. However, the alteration was mostly observed in mitochondrial proteins with 41% down- and 65% up-regulation, respectively. Succinylation status of HMGCS2 protein was altered by a reduction at two sites (K221 and K358) without a change in the protein level. The SB effect was significantly reduced by a SIRT5 inhibitor and in Sirt5-KO mice. The data suggests that SB activated HMGCS2 through SIRT5-mediated desuccinylation for ketone body production by the liver. The effect was not associated with an elevation in NAD+/NADH ratio according to our metabolomics analysis. The data provide a novel molecular mechanism for SB activity in the induction of ketone body production.

SIRT1 is transcriptionally repressed by YY1 and suppresses ferroptosis in rheumatoid arthritis

Abstract Background Sirtuin 1 (SIRT1) is reported downregulated in rheumatoid arthritis (RA), and the protective effects of SIRT1 on tissue damage and organ failure may be related to cellular ferroptosis. However, the exact mechanism by which SIRT1 regulates RA remains unclear. Methods Quantitative real-time PCR (qPCR) and western blot assays were performed to explore the expressions of SIRT1 and Yin Yang 1 (YY1). CCK-8 assay was used for cytoactive detection. The interaction between SIRT1 and YY1 was validated by dual-luciferase reporter gene assay and chromatin immunoprecipitation (ChIP). DCFH-DA assay and iron assay were applied to detect the reactive oxygen species (ROS) and iron ion levels. Results In the serum of RA patients, SIRT1 was downregulated, but YY1 was upregulated. In LPS-induced synoviocytes, SIRT1 could increase cell viability and decrease ROS and iron levels. Mechanistically, YY1 downregulated the expression of SIRT1 by inhibiting its transcription. YY1 overexpression partly revised the effects of SIRT1 on ferroptosis in synoviocytes. Conclusion SIRT1 is transcriptionally repressed by YY1 and inhibits the ferroptosis of synoviocytes induced by LPS, so as to relieve the pathological process of RA. Therefore, SIRT1 might be a new diagnosis and therapeutic target of RA. Highlights Combining SIRT1 with synoviocytes ferroptosis in rheumatoid arthritis for the first time. The transcription factor YY1 combined to the SIRT1 promoter in synovial cells and inhibited its expression and functional roles. The inhibition of SIRT1 with YY1 decreased the ferroptosis in synoviocytes.

An UPLC-Q-TOF/MS-Based Analysis of the Differential Composition of Dendrobium officinale in Different Regions.

Dendrobium officinale (D. officinale) is a valuable traditional Chinese herbal medicine with high commercial value. In Chinese Pharmacopoeia (Ch.P., 2020 edition), the quality of D. officinale is mainly evaluated by its polysaccharide content. However, varying growth and production conditions, such as cultivation environment, origin, harvesting process, or processing methods, resulting in highly variable yields, quality, and composition. The aim of this study was to investigate whether the content of secondary metabolites in D. officinale from different origins is consistent with the polysaccharide content. The results showed that the polysaccharide content and pass rate were ranked as GX > AH > GZ > YN. Based on the nontargeted metabolomics approach, we searched for differential components in 22 different regions of D. officinale, including amides, bibenzyls, disaccharide, flavonoids, organic nitrogenous compounds, and phenolic glycosides. The overall expression was opposite to the polysaccharide, and the most expressed was YN, followed by GZ, AH, and GX. These results indicated that the current quality standard for evaluating the quality of D. officinale by polysaccharide content alone is imperfect, and small molecule compounds need to be included as quality markers.

Adverse role of colonial morphology and favorable function of microcystins for Microcystis to compete with Scenedesmus.

In eutrophic freshwaters, Microcystis usually becomes dominant in phytoplankton communities due to the synergistic effects of its special eco-physiological traits and environmental factors. Colonial morphology can protect Microcystis from zooplankton grazing, which indirectly favors Microcystis to outcompete other phytoplankton, although the colonial form is not conducive to the absorption of nutrients. Moreover, unicellular Microcystis usually has competitive advantages over other phytoplankton due to its efficient absorption capacity for nutrients and releasing microcystins. However, the consequence of direct competition between toxic colonial Microcystis and green algae without external grazing pressure still remained unknown. In this study, the competition between toxic colonial Microcystis aeruginosa and a common green alga Scenedesmus obliquus was explored. Results showed that: (1) colonial M. aeruginosa had a higher requirement for key macro-nutrient phosphorus than S. obliquus, and thus its population declined and was replaced by S. obliquus eventually; (2) microcystins released by colonial M. aeruginosa inhibited the photosynthetic activity and growth of S. obliquus at early stage of the competition; (3) the photosynthetic potential of colonial M. aeruginosa was stimulated in response to the competitive stress from S. obliquus, although the population of colonial M. aeruginosa declined eventually; (4) microcystin production of colonial M. aeruginosa was enhanced by phosphorus limitation due to S. obliquus competition and was positively related to photosynthetic potential of colonial M. aeruginosa. These results indicated that, in the absence of complex natural environment, colonial Microcystis cannot outcompete Scenedesmus in a pure competition, although microcystins can play a favorable role in the competition, which clarified the opposite role of colonies and microcystins in the competition of colonial Microcystis against other phytoplankton.

Diet and Esophageal Cancer Risk: An Umbrella Review of Systematic Reviews and Meta-Analyses of Observational Studies.

Diet may play an important role in the occurrence of esophageal cancer (EC). The aim of this umbrella review was to grade the evidence for the association between dietary factors and EC risk. A protocol for this review was registered with the PROSPERO database (CRD42021283232). Publications were identified by searching PubMed, EMBASE, Web of Science, Cochrane Database of Systematic Reviews, and CINAHL databases. Only systematic reviews and meta-analyses of observational studies (cohort studies, case-cohort studies, nested case-control studies) were eligible. AMSTAR-2 (A Measurement Tool to Assess Systematic Reviews) was used to assess the methodological quality of included systematic reviews. For each association, random-effects pooled effect size, 95% CI, number of cases, 95% prediction interval, heterogeneity, small-study effect, and excess significance bias were calculated to grade the evidence. From 882 publications, 107 full-text articles were evaluated for eligibility, and 20 systematic reviews and meta-analyses describing 32 associations between dietary factors and EC risk were included in the present umbrella review. By assessing the strength and validity of the evidence, 1 association (positively associated with alcohol intake) was supported by highly suggestive evidence and 1 (inversely associated with calcium intake) showed a suggestive level of evidence. Evidence for 7 associations was weak (positively associated with red meat and processed-meat intake; inversely associated with whole grains, fruits, green leafy vegetables, green tea, and zinc intake). The remaining 23 associations were nonsignificant. In conclusion, the findings of this umbrella review emphasize that habitually consuming calcium, whole grains, fruits, green leafy vegetables, green tea, and zinc and reducing alcohol, red meat, and processed-meat intake are associated with a lower risk of EC. Since this umbrella review included only observational study data and some of the associations were graded as weak, caution should be exercised in interpreting these relations.

Opposite trends of glycosides and alkaloids in Dendrobium nobile of different age based on UPLC-Q/TOF-MS combined with multivariate statistical analyses.

INTRODUCTION: Alkaloids and glycosides are the active ingredients of the herb Dendrobium nobile, which is used in traditional Chinese medicine. The pharmacological effects of alkaloids include neuroprotective effects and regulatory effects on glucose and lipid metabolism, while glycosides improve the immune system. The pharmacological activities of the above chemical components are significantly different. In practice, the stems of 3-year-old D. nobile are usually used as the main source of Dendrobii Caulis. However, it has not been reported whether this harvesting time is appropriate. OBJECTIVE: The aim of this study was to compare the chemical characteristics of D. nobile in different growth years (1-3 years). METHODS: In this study, ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UPLC-Q/TOF-MS) was employed to analyze the constituents of D. nobile. The relative abundance of each constituent was analyzed with multivariate statistical analyses to screen the characteristic constituents that contributed to the characterization and classification of D. nobile. Dendrobine, a component of D. nobile that is used for quality control according to the Chinese Pharmacopoeia, was assayed by gas chromatography. RESULTS: As a result, 34 characteristic constituents (VIP > 2) were identified or tentatively identified as alkaloids and glycosides based on MS/MS data. Moreover, the content of alkaloids decreased over time, whereas the content of glycosides showed the opposite trend. The absolute quantification of dendrobine was consistent with the metabolomics results. CONCLUSION: Our findings provide valuable information to optimize the harvest period and a reference for the clinical application of D. nobile.

The bioactivity and applications of pomegranate peel extract: A review.

Pomegranate peel (PP) is a by-product in the processing of pomegranate products, which is usually discarded as a waste. However, a large number of researches have shown that pomegranate peel extract (PPE) is rich in a variety of phenolic substances, among which ellagic acid (EA), as one of the main active components, has significant biological activities, such as anti-oxidation, anti-tumor, anti-inflammatory, neuroprotection, anti-viral, and anti-bacterial. We analyzed the mechanism of EA's biological activity, and discussed its application in the food industry, for instance, food preservation, food additives, and functional foods. Combined with the research status of PPE, we discussed the limitations and development potential of PPE, in order to provide theoretical reference and scientific basis for the development and utilization of pomegranate by-products. PRACTICAL APPLICATIONS: Pomegranate peel (PP), the inedible part of the fruit, is usually treated as waste. In recent years, researchers have been committed to exploring various bioactive ingredients in PP and exploring its potential benefits to human health, which has far-reaching significance. In this paper, the chemical constituents of polyphenols in PP were reviewed, mainly focusing on the biological activity and mechanism of ellagic acid (EA). We reviewed the applications and invention patents of pomegranate peel extract (PPE) in food field, including food preservation, food additive, and functional foods, providing reference for the recycling and reuse of PP.

The potential mechanism of Jiajian Xuezheng Decotion in infiltrative gastric cancer through on network pharmacology and proteomics / 国际中医中药杂志

Objective:To explore the potential mechanism of Jiajian Xuezheng Decotion in infiltrative gastric cancer by network pharmacology and proteomics.Methods:The Traditional Chinese Medicine Systems Pharmacology Database (TCMSP) database was used to find the compounds and their targets of Jiajianxuezhengtang, and the targets of invasive gastric cancer were determined by high performance liquid chromatography with tandem mass spectrometry (HPLC-MS/MS). The predicted target gene of Jiajian Xuezheng Decotion and the target protein data of infiltrative gastric cancer were analyzed by Venny to obtain the target gene. The target gene set was analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment by the David. The protein interaction network diagram (PPI) was obtained by the String method, displaying the prescription-drug-compound-gene network in Cytoscape software.Results:69 active ingredients and 215 drug targets were screened from Jiajian Xuezheng Decotion; 660 proteins were significantly up-expressed in infiltrative gastric cancer, and 10 drug targets and gene targets were the common targets. There were 10 protein nodes in the PPI network, of which 3 core nodes were CASP3, BCL2L1 and STAT1. The 11 KEGG pathways were significantly enriched such as include PI3K-Akt signaling pathway, p53 signaling pathway, proteoglycan in cancer, apoptosis, Jak-STAT signaling pathway and other pathways.Conclusions:Jiajian Xuezheng Decotion plays an anti-infiltrative gastric cancer effect possibly regulated apoptosis through PI3K-Akt signaling pathway, p53 signaling pathway and Jak-STAT signaling pathway. This study provides a theoretical basis for further research on the mechanism of Jiajian Xuezheng Decotion in the treatment of invasive gastric cancer.

Phosphorus Co-Existing in Water: A New Mechanism to Boost Boron Removal by Calcined Oyster Shell Powder.

The removal of boron (B) from water by co-precipitation with hydroxyapatite (HAP) has been extensively studied due to its low cost, ease of use and high efficiency. However, there is no explicit mechanism to express how resolved B was trapped by HAP. Thus, in this work, the process of removing B from water was studied using a low-cost calcium (Ca) precipitation agent derived from used waste oyster shells. The results showed that the removal rate of B in the simulated wastewater by calcined oyster shell (COS) in the presence of phosphorus (P) is up to more than 90%, as opposed to virtually no removal without phosphate. For B removal, the treated water needs to be an alkaline solution with a high pH above 12, where B is removed as [CaB(OH)4]+ but is not molecular. Finally, the synergistic mechanism of co-precipitation between HAP and dissolved B, occlusion co-precipitation, was explained in detail. The proposed method discovered the relationship between Ca, P and B, and was aimed at removing B without secondary pollution through co-precipitation.

Effect of Xintong Oral Liquid in Improving Cardiac Function of Patients with Heart Failure and Syndrome of Qi Deficiency and Phlegm and Blood Stasis Caused by Acute Myocardial Infarction / 中国实验方剂学杂志

Objective:To discuss the clinical efficacy of Xintong oral liquid on heart failure with syndrome of Qi deficiency， phlegm and blood stasis caused by acute myocardial infarction （AMI） and the effect on inflammatory factors. Method:One hundred patients were randomly divided into observation group （50 cases） and control group （50 cases） by random number table. Both groups got comprehensive treatment of western medicine. Patients in control group got simulated medicine of Xintong oral liquid， 20 mL/time， 3 times/day. Patients in observation group got Xintong oral liquid， 20 mL/time， 3 times/day. The treatment lasted for 4 weeks. Before the treatment， and at the second week and forth week after treatment， levels of cardiac troponin I （cTnI）， cardiac troponin T （cTnT）， heart type fatty acid binding protein （H-FABP）， left ventricular ejection fraction （LVEF）， cardiac output （CO）， cardiac output per stroke （SV） and left ventricular end diastolic diameter （LVEDd）， N-terminal B-type natriuretic peptide （NT-proBNP）， lipoprotein phospholipase A2 （Lp-PLA2）， high sensitive C-reactive protein （hs-CRP）， interleukin-6 （IL-6） and tumor necrosis factor-α （TNF-α） were detected. The 6-minute walking test was performed to record the 6-minute walking distance and the ratio of 6 min walking distance to estimated value. Scores of traditional Chinese medicine （TCM） syndromes， minnesota Heart Failure quality of life questionnaire （MLHFQ） and Killip classification of cardiac function were recorded. During the 2 months' follow-up， adverse cardiovascular events （MACE） were recorded， and the safety was evaluated. Result:At the second and fourth week， levels of cTnI， cTnT， H-FABP， NT-proBNP， Lp-PLA2， hs-CRP， IL-6 and TNF-α were lower than those in control group （P<0.01）， and levels of LVEF， CO and SV were higher than those in control group （P<0.05， P<0.01）. NT-proBNP was lower than control group （P<0.01）. The 6-minute walking distance and the ratio of 6-minute walking distance to estimated value were all more than those in control group （P<0.01）. Scores of TCM syndrome integral， MLHFQ， Killip heart function grading were lower than those in control group （P<0.05， P<0.01）. Cumulative incidence of MACE was 12.0% （6/50）， which was lower than 28.0% （14/50） in control group （χ2=4.251， P<0.05）. Levels of Lp-PLA2， hs-CRP， IL-6 and TNF-α in observation group were lower those in control group （P<0.01）.And there was no adverse reactions related to Xintong oral liquid. Conclusion:Based on the comprehensive treatment of Western medicine， Xintong oral liquid can reduce the degree of myocardial injury， protect myocardium， improve cardiac function， reduce inflammatory reaction， reduce the occurrence of mace， effectively control clinical symptoms， and improve exercise tolerance and quality of life.

Rescue fecal microbiota transplantation for antibiotic-associated diarrhea in critically ill patients.

BACKGROUND: Antibiotic-associated diarrhea (AAD) is a risk factor for exacerbating the outcome of critically ill patients. Dysbiosis induced by the exposure to antibiotics reveals the potential therapeutic role of fecal microbiota transplantation (FMT) in these patients. Herein, we aimed to evaluate the safety and potential benefit of rescue FMT for AAD in critically ill patients. METHODS: A series of critically ill patients with AAD received rescue FMT from Chinese fmtBank, from September 2015 to February 2019. Adverse events (AEs) and rescue FMT success which focused on the improvement of abdominal symptoms and post-ICU survival rate during a minimum of 12 weeks follow-up were assessed. RESULTS: Twenty critically ill patients with AAD underwent rescue FMT, and 18 of them were included for analysis. The mean of Acute Physiology and Chronic Health Evaluation (APACHE) II scores at intensive care unit (ICU) admission was 21.7 ± 8.3 (range 11-37). Thirteen patients received FMT through nasojejunal tube, four through gastroscopy, and one through enema. Patients were treated with four (4.2 ± 2.1, range 2-9) types of antibiotics before and during the onset of AAD. 38.9% (7/18) of patients had FMT-related AEs during follow-up, including increased diarrhea frequency, abdominal pain, increased serum amylase, and fever. Eight deaths unrelated to FMT occurred during follow-up. One hundred percent (2/2) of abdominal pain, 86.7% (13/15) of diarrhea, 69.2% (9/13) of abdominal distention, and 50% (1/2) of hematochezia were improved after FMT. 44.4% (8/18) of patients recovered from abdominal symptoms without recurrence and survived for a minimum of 12 weeks after being discharged from ICU. CONCLUSION: In this case series studying the use of FMT in critically ill patients with AAD, good clinical outcomes without infectious complications were observed. These findings could potentially encourage researchers to set up new clinical trials that will provide more insight into the potential benefit and safety of the procedure in the ICU. TRIAL REGISTRATION: ClinicalTrials.gov, Number NCT03895593 . Registered 29 March 2019 (retrospectively registered).

Explore Regulation Mechanism of “Spleen Qi to Dispersing Essence” on Blood Glucose Homeostasis from Microcirculation of Pancreatic Islet / 中国实验方剂学杂志

Reducing glycemic excursion is of great importance to the successful practice for diabetes intervention and complication prevention. This is also an advantage of traditional Chinese medicine (TCM) in the treatment of diabetes. More and more studies have shown that the dysfunction of islet microcirculation is the key pathological link for glycemic excursion caused by decrease of islet function. The over-activation of local renin-angiotensin system (RAS) in islet microcirculation is a key ring to the islet decompensation, intimately related to the functionality of islet endocrine cells, and has gradually become the focus in the study of islet functionality. In TCM, it is believed that glycemic excursion in diabetes mellitus is closely related to the incapability of "spleen Qi to dispersing essence". If spleen fails to disperse essence, the essence will be accumulated in the body and become harmful stuffs. The stuffs further break the blood glucose homeostasis, acting as the key pathogenesis of diabetes. By supplementing the "spleen" Qi and promoting the dispersion of nutrient substance (hormone) in "pancreas", the balance between sugar-regulated hormones can be restored and therefore glycemic excursion can be reduced. However, the regulation mechanism of "spleen Qi to dispersing essence" on glycemic excursion remains unclear at present. Based on the previous clinical and scientific work, the following ideas were proposed by the authors:the effects of "spleen Qi to dispersing essence" on the improvement of islet function and the regulation of glycemic excursion may be achieved by promoting islet microcirculation, and its mechanism may be related to inhibiting the activation status of local RAS in islet microcirculation. It is important to note that the mutual antagonistic relationship between the signal pathways of RAS in islet microcirculation is similar to the antagonistic relationship between "spleen Qi to dispersing essence" and spermatozoa in TCM. Thus, the mechanism of "spleen Qi to dispersing essence" on the regulation mechanism of blood glucose fluctuations needs to be further explored from the perspective of the overall regulation of RAS in islet microcirculation, so as to reveal the scientific connotation of TCM on regulating the body's environmental homeostasis and reducing glycemic excursion in diabetic patients.