[Intervention effect of Erchen Decoction on methionine and choline deficient diet-induced non-alcoholic steatohepatitis in mice].

This study investigated the effect of Erchen Decoction(ECD) on the prevention of non-alcoholic steatohepatitis(NASH) in mice and explored its possible mechanism, so as to provide scientific data for the clinical application of ECD in the prevention of NASH. C57BL/6 male mice were randomly divided into normal group(methionine and choline supplement, MCS), model group(methionine and choline deficient, MCD), low-dose ECD group(ECD＿L, 6 g·kg~(-1)), medium-dose ECD group(ECD＿M, 12 g·kg~(-1)), and high-dose ECD group(ECD＿H, 24 g·kg~(-1)), with eight mice in each group. The MCS group was fed with an MCS diet, and the other groups were fed with an MCD diet. The mice in each group were given corresponding diets, but the drug intervention group was given low-, medium-, and high-dose ECD(10 mL·kg~(-1)·d~(-1)) by intragastric administration for six weeks on the basis of MCD diet feeding, and the mice could eat and drink freely during the whole experiment. At the end of the experiment, mice were fasted overnight(12 h) and were anesthetized with 20% urethane. Thereafter, the blood and liver tissue were collected. The serum was used to detect the levels of alanine aminotransferase(ALT), aspartate aminotransaminase(AST), interleukin-1ß(IL-1ß), interleukin-6(IL-6), interleukin-10(IL-10), and tumor necrosis factor-α(TNF-α). Liver tissue was processed by hematoxylin-eosin(HE) staining and used for hepatic histological analysis and detection of the expression levels of genes and proteins related to nuclear factor erythroid 2-related factor 2/glutathione peroxidase 4(Nrf2/GPX4) pathway by real-time quantitative reverse transcriptase-polymerase chain reaction(RT-qPCR) and Western blot analysis, respectively. The results showed that compared with the MCS group, the MCD group showed higher serum ALT and AST levels; the HE staining exhibited fat vacuoles and obvious inflammatory cell infiltration in liver tissue; serum IL-1ß, IL-6, and TNF-α levels were significantly increased, and the serum IL-10 level was significantly decreased. The mRNA expressions of fatty acid synthase(FASN), monocyte chemoattractant protein-1(MCP-1), and IL-1ß in liver tissue were significantly up-regulated, while those of GPX4, Nrf2, and NAD(P)H:quinine oxidoreductase(NQO1) were significantly down-regulated. Compared with the MCD group, the serum ALT and AST levels of ECD＿M and ECD＿H groups were significantly decreased, and the AST level in the ECD＿L group was significantly decreased. The number of fat vacuoles and the degree of inflammatory cell infiltration in liver tissue were improved; serum IL-1ß, IL-6, and TNF-α levels were significantly decreased, but the serum IL-10 level was significantly increased only in the ECD＿H group. The mRNA expressions of FASN, MCP-1, and IL-1ß in liver tissue were significantly down-regulated, and those of GPX4 and NQO1 were significantly up-regulated. The mRNA expressions of Nrf2 in ECD＿M and ECD＿H groups were significantly up-regulated. Western blot results showed that compared with the MCD group, the protein expression levels of Nrf2 and GPX4 in each group were significantly increased after ECD administration, and the protein expression level of FASN was significantly decreased; the protein expression of NQO1 was increased in ECD＿M and ECD＿H groups. In summary, ECD can reduce hepatic lipid accumulation, oxidative stress, liver inflammation, and liver injury in NASH mice, which may be related to the activation of the Nrf2/GPX4 pathway.

Lycopene Alleviates Endoplasmic Reticulum Stress in Steatohepatitis through Inhibition of the ASK1-JNK Signaling Pathway.

Lycopene has been proven to alleviate nonalcoholic steatohepatitis (NASH), but the precise mechanisms are inadequately elucidated. In this study, we found a previously unknown regulatory effect of lycopene on the apoptosis signal-regulating kinase 1 (ASK1) signaling pathway in both in vivo and in vitro models. Lycopene supplementation (3 and 6 mg/kg/day) exhibited a significant reduction in lipid accumulation, inflammation, and fibrosis of the liver in mice fed with a high-fat/high-cholesterol diet or a methionine-choline-deficient diet. RNA sequencing uncovered that the mitogen-activated protein kinases signaling pathway, which is closely associated with inflammation and endoplasmic reticulum (ER) stress, was significantly downregulated by lycopene. Furthermore, we found lycopene ameliorated ER swelling and decreased the expression levels of ER stress markers (i.e., immunoglobulin heavy chain binding protein, C/EBP homologous protein, and X-box binding protein 1s). Especially, the inositol-requiring enzyme 1α involved in the ASK1 phosphorylation was inhibited by lycopene, resulting in the decline of the subsequent c-Jun N-terminal kinase (JNK) signaling cascade. ASK1 inhibitor DQOP-1 eliminated the lycopene-induced inhibition of the ASK1-JNK pathway in oleic acid and palmitic acid-induced HepG2 cells. Molecular docking further indicated hydrophobic interactions between lycopene and ASK1. Collectively, our research indicates that lycopene can alleviate ER stress and attenuate inflammation cascades and lipid accumulation by inhibiting the ASK1-JNK pathway.

Considering traditional Chinese medicine as adjunct therapy in the management of chronic constipation by regulating intestinal flora.

Chronic constipation is one of the most common gastrointestinal disorders worldwide. Due to changes in diet, lifestyle, and the aging population, the incidence of chronic constipation has increased year by year. It has had an impact on daily life and poses a considerable economic burden. Nowadays, many patients with chronic constipation try to seek help from complementary and alternative therapies, and traditional Chinese medicine (TCM) is often their choice. The intestinal flora play an important role in the pathogenesis of constipation by affecting the body's metabolism, secretion, and immunity. Regulating the intestinal flora and optimizing its composition might become an important prevention and treatment for chronic constipation. TCM has unique advantages in regulating the imbalance of intestinal flora, and its curative effect is precise. Therefore, we reviewed the relationship between intestinal flora and chronic constipation as well as advances in research on TCM as adjunct therapy in the management of chronic constipation by regulating intestinal flora. Some single Chinese herbs and their active ingredients (e.g., Rheum palmatum, Radix Astragalus, and Cistanche deserticola), some traditional herbal formulations (e.g., Jichuan decoction, Zengye decoction, and Zhizhu decoction) and some Chinese patent medicines (e.g., Maren pills and Shouhui Tongbian capsules) that are commonly used to treat chronic constipation by regulating intestinal flora are highlighted and summarized. Moreover, some external forms of TCM, and especially acupuncture, have also been found to improve intestinal movement and alleviate constipation symptoms by regulating intestinal flora. We hope this review can contribute to an understanding of TCM as an adjunct therapy for chronic constipation and that it can provide useful information for the development of more effective constipation therapies.

Antidepressant effects of Parishin C in chronic social defeat stress-induced depressive mice.

ETHNOPHARMACOLOGY RELEVANCE: Parishin C (Par), a prominent bioactive compound in Gastrodia elata Blume with little toxicity and shown neuroprotective effects. However, its impact on depression remains largely unexplored. AIM OF THE STUDY: This study aims to investigate the antidepressant effects of Par using a chronic social defeat stress (CSDS) mouse model and elucidate its molecular mechanisms. MATERIALS AND METHODS: The CSDS-induced depression mouse model was used to evaluate the therapeutic efficacy of Par. The social interaction test (SIT) and sucrose preference test (SPT), tail suspension test (TST) and forced swim test (FST) were conducted to assess the effects of Par on depressive-like behaviours. The levels of corticosterone, neurotransmitters (5-HT, DA and NE) and inflammatory cytokines (IL-1ß, TNF-α, and IL-6) were evaluated by enzyme-linked immunosorbent assay (ELISA). Activation of a microglia was assessed by immunofluorescence labeling Iba-1. The protein expressions of NLRP3, ASC, caspase-1, and IL-6 verified by Western blot. RESULT: Oral administration of Par (4 and 8 mg/kg) and fluoxetine (10 mg/kg, administration significantly ameliorate depression-like behaviors induced by CSDS, as shown by the increase social interaction in SIT, increase sucrose preference in SPT and the decrease immobility in TST and FST. Par administration decreased serum corticosterone level and increased the 5-HT, DA and NE concentration in the hippocampus and prefrontal cortex. Furthermore, Par treatment suppressed microglial activation (Iba1) as well as reduced levels of IL-1ß, TNF-α, and IL-6) with decreased protein expressions of NLRP3, ASC, caspase-1, and IL-6. CONCLUSIONS: our study provides the first evidence that Par exerts antidepressant-like effects in mice with CSDS-induced depression. This effect appears to be mediated by the normalization of neurotransmitter and corticosterone levels, inhibition of NLRP3 inflammasome activation. This newfound antidepressant property of Par offers a novel perspective on its pharmacological effects, providing valuable insights into its potential therapeutic and preventive applications in depression treatment.

Enhanced Antioxidative Capacity Transfer between Sow and Fetus via the Gut-Placenta Axis with Dietary Selenium Yeast and Glycerol Monolaurate Supplementation during Pregnancy.

This study aims to investigate the impact of dietary supplementation with selenium yeast (SeY) and glycerol monolaurate (GML) on the transfer of antioxidative capacity between the mother and fetus during pregnancy and its underlying mechanisms. A total of 160 sows with similar body weight and parity of 3-6 parity sows were randomly and uniformly allocated to four groups (n = 40) as follows: CON group, SeY group, GML group, and SG (SeY + GML) group. Animal feeding started from the 85th day of gestation and continued to the day of delivery. The supplementation of SeY and GML resulted in increased placental weight and reduced lipopolysaccharide (LPS) levels in sow plasma, placental tissues, and piglet plasma. Furthermore, the redox balance and inflammatory markers exhibited significant improvements in the plasma of sows fed with either SeY or GML, as well as in their offspring. Moreover, the addition of SeY and GML activated the Nrf2 signaling pathway, while downregulating the expression of pro-inflammatory genes and proteins associated with inflammatory pathways (MAPK and NF-κB). Vascular angiogenesis and nutrient transportation (amino acids, fatty acids, and glucose) were upregulated, whereas apoptosis signaling pathways within the placenta were downregulated with the supplementation of SeY and GML. The integrity of the intestinal and placental barriers significantly improved, as indicated by the increased expression of ZO-1, occludin, and claudin-1, along with reduced levels of DLA and DAO with dietary treatment. Moreover, supplementation of SeY and GML increased the abundance of Christensenellaceae_R-7_group, Clostridium_sensus_stricto_1, and Bacteroidota, while decreasing levels of gut microbiota metabolites LPS and trimethylamine N-oxide. Correlation analysis demonstrated a significant negative relationship between plasma LPS levels and placental weight, oxidative stress, and inflammation. In summary, dietary supplementation of SeY and GML enhanced the transfer of antioxidative capacity between maternal-fetal during pregnancy via gut-placenta axis through modulating sow microbiota composition.

Melatonin alleviates high temperature exposure induced fetal growth restriction via the gut-placenta-fetus axis in pregnant mice.

INTRODUCTION: Global warming augments the risk of adverse pregnancy outcomes in vulnerable expectant mothers. Pioneering investigations into heat stress (HS) have predominantly centered on its direct impact on reproductive functions, while the potential roles of gut microbiota, despite its significant influence on distant tissues, remain largely unexplored. Our understanding of deleterious mechanisms of HS and the development of effective intervention strategies to mitigate the detrimental impacts are still limited. OBJECTIVES: In this study, we aimed to explore the mechanisms by which melatonin targets gut microbes to alleviate HS-induced reproductive impairment. METHODS: We firstly evaluated the alleviating effects of melatonin supplementation on HS-induced reproductive disorder in pregnant mice. Microbial elimination and fecal microbiota transplantation (FMT) experiments were then conducted to confirm the efficacy of melatonin through regulating gut microbiota. Finally, a lipopolysaccharide (LPS)-challenged experiment was performed to verify the mechanism by which melatonin alleviates HS-induced reproductive impairment. RESULTS: Melatonin supplementation reinstated gut microbiota in heat stressed pregnant mice, reducing LPS-producing bacteria (Aliivibrio) and increasing beneficial butyrate-producing microflora (Butyricimonas). This restoration corresponded to decreased LPS along the maternal gut-placenta-fetus axis, accompanied by enhanced intestinal and placental barrier integrity, safeguarding fetuses from oxidative stress and inflammation, and ultimately improving fetal weight. Further pseudo-sterile and fecal microbiota transplantation trials confirmed that the protective effect of melatonin on fetal intrauterine growth under HS was partially dependent on gut microbiota. In LPS-challenged pregnant mice, melatonin administration mitigated placental barrier injury and abnormal angiogenesis via the inactivation of the TLR4/MAPK/VEGF signaling pathway, ultimately leading to enhanced nutrient transportation in the placenta and thereby improving the fetal weight. CONCLUSION: Melatonin alleviates HS-induced low fetal weight during pregnancy via the gut-placenta-fetus axis, the first time highlighting the gut microbiota as a novel intervention target to mitigate the detrimental impact of global temperature rise on vulnerable populations.

Dietary methionine supplementation during the estrous cycle improves follicular development and estrogen synthesis in rats.

The follicle is an important unit for the synthesis of steroid hormones and the oocyte development and maturation in mammals. However, the effect of methionine supply on follicle development and its regulatory mechanism are still unclear. In the present study, we found that dietary methionine supplementation during the estrous cycle significantly increased the number of embryo implantation sites, as well as serum contents of a variety of amino acids and methionine metabolic enzymes in rats. Additionally, methionine supplementation markedly enhanced the expression of rat ovarian neutral amino acid transporters, DNA methyltransferases (DNMTs), and cystathionine gamma-lyase (CSE); meanwhile, it significantly increased the ovarian concentrations of the metabolite S-adenosylmethionine (SAM) and glutathione (GSH). In vitro data showed that methionine supply promotes rat follicle development through enhancing the expression of critical gene growth differentiation factor 9 and bone morphogenetic protein 15. Furthermore, methionine enhanced the relative protein and mRNA expression of critical genes related to estrogen synthesis, ultimately increasing estrogen synthesis in primary ovarian granulosa cells. Taken together, our results suggested that methionine promoted follicular growth and estrogen synthesis in rats during the estrus cycle, which improved embryo implantation during early pregnancy. These findings provided a potential nutritional strategy to improve the reproductive performance of animals.

A Review of Healthy Dietary Choices for Cardiovascular Disease: From Individual Nutrients and Foods to Dietary Patterns.

Cardiovascular disease (CVD) remains the first cause of mortality globally. Diet plays a fundamental role in cardiovascular health and is closely linked to the development of CVD. Numerous human studies have provided evidence on the relationship between diet and CVD. By discussing the available findings on the dietary components that potentially influence CVD progression and prevention, this review attempted to provide the current state of evidence on healthy dietary choices for CVD. We focus on the effects of individual macronutrients, whole food products, and dietary patterns on the risks of CVD, and the data from population-based trials, observational studies, and meta-analyses are summarized. Unhealthy dietary habits, such as high intake of saturated fatty acids, sugar-sweetened beverages, red meat, and processed meat as well as high salt intake are associated with the increased risk of CVD. Conversely, increased consumption of plant-based components such as dietary fiber, nuts, fruits, and vegetables is shown to be effective in reducing CVD risk factors. The Mediterranean diet appears to be one of the most evidence-based dietary patterns beneficial for CVD prevention. However, there is still great debate regarding whether the supplementation of vitamins and minerals confers cardioprotective benefits. This review provides new insights into the role of dietary factors that are harmful or protective in CVD, which can be adopted for improved cardiovascular health.

Efficacy and safety comparison of infrared laser moxibustion and traditional moxibustion in knee osteoarthritis: study protocol for a Zelen-design randomized controlled non-inferiority clinical trial.

BACKGROUND: Knee osteoarthritis (KOA) is the most common chronic degenerative joint disease and places a substantial burden on the public health resources in China. The purpose of this study is to preliminarily evaluate whether infrared laser moxibustion (ILM) is non-inferior to traditional moxibustion (TM) in the treatment of KOA. MATERIALS AND METHODS: In the designed Zelen-design randomized controlled non-inferiority clinical trial, a total of 74 patients with KOA will be randomly allocated to one of two interventions: ILM treatment or TM treatment. All participants will receive a 6-week treatment and a follow-up 4 weeks after treatment. The primary outcomes will be the mean change in pain scores on the numeric rating scale (NRS) measured at baseline and the end of last treatment at week 6. The secondary outcomes will be the pain scores on the NRS from weeks 1 to 5 after the start of treatment and the changes from baseline to endpoints (weeks 6 and 10) in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), SF-36, knee circumference, and 6-min walking test. In addition, safety assessment will be performed throughout the trial. CONCLUSION: The results of our study will help determine whether a 6-week treatment with ILM is non-inferior to TM in patients with KOA, therefore providing evidence to verify if ILM can become a safer alternative for TM in clinical applications in the future. TRIAL REGISTRATION: Clinical Trial Registration Platform (ChiCTR2200065264); Pre-results. Registered on 1 November 2022.

Methods on improvements of the poor oral bioavailability of ginsenosides: Pre-processing, structural modification, drug combination, and micro- or nano- delivery system.

Panax ginseng Meyer is a traditional Chinese medicine that is widely used as tonic in Asia. The main pharmacologically active components of ginseng are the dammarane-type ginsenosides, which have been shown to have anti-cancer, anti-inflammatory, immunoregulatory, neuroprotective, and metabolic regulatory activities. Moreover, some of ginsenosides (eg, Rh2 and Rg3) have been developed into nutraceuticals. However, the utilization of ginsenosides in clinic is restrictive due to poor permeability in cells and low bioavailability in human body. Obviously, the dammarane skeleton and glycosyls of ginsenosides are responsible for these limitations. Therefore, improving the oral bioavailability of ginsenosides has become a pressing issue. Here, based on the structures of ginsenosides, we summarized the understanding of the factors affecting the oral bioavailability of ginsenosides, introduced the methods to enhance the oral bioavailability and proposed the future perspectives on improving the oral bioavailability of ginsenosides.

[Chemical constituents of Lindera aggregata and their bioactivities: a review].

The medicinal Lindera aggregata(Lindera, Lauraceae) boasts abundant resources, which is widely used in clinical settings. It has been found that the main chemical constituents of this medicinal species are sesquiterpenoids, alkaloids, sesquiterpenoid dimers, flavonoids, and phenolic acids. Some unreported novel structures, including lindenane-type sesquiterpene dimers and trimers, have been discovered from L. aggregata in recent years. The extracts and active components of L. aggregata have anti-tumor, anti-inflammatory, antalgic, liver-protecting, antioxidant, lipid-lowering, and glucose-lowering activities, and their mechanisms of action have been comprehensively investigated. This study summarizes the research on the chemical constituents and bioactivities of L. aggregata over the past decade, which is expected to serve as a reference for the future research and utilization of L. aggregata.

Maternal Selenium-Enriched Yeast Supplementation in Sows Enhances Offspring Growth and Antioxidant Status through the Nrf2/Keap1 Pathway.

This study evaluated the effects of maternal selenium-enriched yeast (SeY) supplementation during late gestation and lactation on sow performance, transfer of selenium (Se) and redox status, and gut microbiota community, as well as on the gut health of offspring. Seventy pregnant sows on day 85 of gestation were randomly allocated to the following two treatments: (1) sows who were fed a basal diet (basal diet contained 0.3 mg/kg Se as Na2SeO3, n = 35); (2) and sows who were fed a SeY-supplemented diet (basal diet with 0.2 mg/kg Se as SeY, n = 35). The offspring piglets were only cross-fostered within the group on day 3 of lactation (L3) according to the pig farm epidemic prevention policy. The plasma, milk, and feces samples from 10 sows, as well as plasma and intestinal samples per treatment, were collected on L1 and L21, respectively. Our results showed that maternal SeY supplementation increased the first week average weight and ADG of piglets (p < 0.05). Compared with the CON group, the SeY supplementation increased the Se content in the plasma and milk of sows and the plasma of piglets on L1 and L21 (p < 0.05). In addition, in sows, the levels of fat in the milk on L21, the level of IgA, T-AOC, and GSH-Px in the plasma on L21, and the level of T-AOC and GSH-Px in the colostrum were increased, while the MDA content was decreased in the plasma on L1 and in the colostrum and milk on L14 (p < 0.05). In the piglet plasma, the levels of IgA on L1 and L21, GSH-Px on L1, and GSH on L21 were increased, while the MDA content was decreased on L1 (p < 0.05). Maternal SeY supplementation up-regulated the small intestinal protein abundances of MUC1, E-cadherin, ZO-1, occludin, and claudin and activated the Nrf2/Keap1 signaling pathway in weaned offspring piglets. The 16S rRNA sequencing results showed that fecal microbiota had distinct separations during lactation, and the relative abundances of unclassified_f_Lachnospiraceae, Prevotaceae_UCG-001, and Lachnospiraceae_NK4A136_group were increased on L1. Collectively, the current findings suggest that maternal SeY supplementation during late gestation and lactation could improve the piglet's growth performance, Se status, antioxidant capacity and immunoglobulins transfer at the first week of lactation, as well as alter the fecal microbiota composition by increasing antioxidative-related and SCFA-producing microbiota in sows. These changes contributed to enhancing the small intestinal barrier function and activating the Nrf2/Keap1 pathway in offspring.

Effect of Shao's five-needle therapy pretreatment on airway inflammatory response in asthmatic rats based on ROS/TXNIP/NLRP3 pathway. / 基于ROS/TXNIP/NLRP3通路探讨"邵氏五针法"é¢„å¤„ç†å¯¹å“®å–˜å¤§é¼ æ°”é“ç‚Žæ€§ååº”çš„å½±å“.

OBJECTIVES: To explore the possible mechanism of Shao's five-needle therapy pretreatment on relieving airway inflammatory response in asthmatic rats. METHODS: Forty SPF-grade SD rats were randomly divided into a blank group, a model group, an acupuncture group, and a medication group, with 10 rats in each group. Except the blank group, asthma model was established by aerosol inhalation of ovalbumin in the other 3 groups. The rats in the acupuncture group were treated with acupuncture at "Dazhui" (GV 14) and bilateral "Feishu" (BL 13) and "Fengmen" (BL 12), with each session lasting for 20 min. Acupuncture was given before each motivating, once daily for 7 consecutive days. The rats in the medication group were treated with intraperitoneal injection of dexamethasone sodium phosphate solution before each motivating, once daily for 7 days. General situation of the rats was observed in each group; ELISA method was used to detect the levels of inflammatory cytokines interleukin (IL)-1ß and IL-18 in serum; immunofluorescence staining method was performed to assess the expression of reactive oxygen species (ROS) in lung tissues; Western blot method was used to measure the protein expression of thioredoxin interacting protein (TXNIP), NOD-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD (ASC), and Caspase-1 in lung tissues. RESULTS: The rats in the blank group exhibited normal behavior, while those in the model group showed signs of respiratory distress, ear scratching, cheek rubbing, and dysphoria. Compared with the model group, the rats in the acupuncture group and the medication group showed stable respiration and relatively agile responses. Compared with those in the blank group, the serum levels of IL-18 and IL-1ß were elevated (P<0.01), the expression intensity of ROS was increased, and the protein expressions of TXNIP, NLRP3, ASC and Caspase-1 in lung tissues were increased (P<0.01) in the model group. Compared with those in the model group, the serum levels of IL-18 and IL-1ß were reduced (P<0.01), the expression intensity of ROS was lowered, and the protein expressions of TXNIP, NLRP3, ASC and Caspase-1 in lung tissues were reduced (P<0.01) in the acupuncture group and the medication group. Compared with the medication group, the protein expression of ASC in lung tissue was reduced in the acupuncture group (P<0.05). CONCLUSIONS: Pretreatment of Shao's five-needle therapy could alleviate airway inflammatory response in asthmatic rats by reducing ROS levels and decreasing the aggregation and activation of pathway-related proteins in the ROS/TXNIP/NLRP3 pathway, ultimately leading to decreased secretion of IL-1ß and IL-18. This mechanism may contribute to the effectiveness of Shao's five-needle therapy in preventing and treating asthma.

Ginsenoside Rh2 and its octyl ester derivative inhibited invasion and metastasis of hepatocellular carcinoma via the c-Jun/COX2/PGE2 pathway.

BACKGROUND: Liver cancer is a topical global health issue. The treatment of liver cancer meets significant challenges in the high recurrence rate and invasive incidence. Therefore, the treatment strategies that target epithelial-mesenchymal transition (EMT) induced by cyclooxygenase 2 (COX2)/ prostaglandin E2 (PGE2) pathway have become epidemic. Ginsenoside Rh2 has been proved to inhibit the EMT. However, the underlying mechanisms remain unclear. Moreover, the octyl ester derivative of Rh2 (Rh2-O) exhibited superior anti-proliferative and immunomodulatory effects than Rh2 in our previous researches, which indicated that Rh2-O might also exert inhibitory effects on invasion and metastasis. PURPOSE: The aim of current study is to explore the inhibitory effects of Rh2 and Rh2-O on invasion and metastasis of hepatocellular carcinoma, and to investigate whether these effects are dependent on the c-Jun/COX2/PGE2 pathway. STUDY DESIGN: The Huh-7 liver cancer cells and the H22 tumor-bearing mice were treated with Rh2 and Rh2-O. METHOD: In this paper, the inhibitory effects of Rh2 and Rh2-O on invasion and metastasis were tested by wound healing, trans-well assay and tumor-bearing mice, and the involvement of c-Jun/COX2/PGE2 pathway were verified by exogenous PGE2, activation of COX2 and overexpression of c-Jun. RESULTS: The results showed that Rh2 and Rh2-O could efficiently inhibit the invasion and metastasis in a dose-dependent manner (p < 0.05). And the Rh2-O showed stronger effects than Rh2. Moreover, the exogenous PGE2, activation of COX2 by exogenous LPS and the overexpression of c-Jun by transfection all reversed the inhibitory effects of Rh2 and Rh2-O on metastasis or EMT (p < 0.05). CONCLUSION: Rh2 and Rh2-O could inhibit the invasion and metastasis of hepatocellular carcinoma via restraining the EMT, which was mediated by c-Jun/COX2/PGE2 pathway.

Exploring the potential mechanism of Xuebijing injection against sepsis based on metabolomics and network pharmacology.

Sepsis is a major contributor to the death of critically ill patients globally, in which metabolic disturbance is observed. Xuebijing injection (XBJ), a well-known traditional Chinese medicine, has received approval by the State Food and Drug Administration (SFDA) of China owing to its satisfactory clinical therapeutic effect. Nowadays, it has been applied clinically to the treatment of sepsis, but its effect on metabolic disorders remains unclear. In the present study, we sought to explore its underlying mechanism by employing a combination of network pharmacology and metabolomics. Initially, its protective effects were validated using a sepsis rat model created through cecal ligation puncture (CLP). Subsequently, the metabonomic strategy was utilized to discriminate the differential metabolic markers. Meanwhile, a comprehensive view of the potential ingredient-target-disease network was constructed based on a network pharmacology analysis. Next, the network diagram was constructed by integrating the results of network pharmacology and metabonomics. Finally, qRT-PCR together with Western blot was used to validate the expression levels of the associated genes. Based on our findings, we identified 34 differential metabolites in the sepsis group and 26 distinct metabolites in the XBJ group, with 8 common biological metabolites predominantly associated with arginine and proline metabolism. Through comprehensive analysis, we identified 21 genes that regulate metabolites, and qRT-PCR validation was conducted on six of these genes in both liver and kidney tissues. Additionally, XBJ demonstrated the capability to inhibit the activation of the NF-kB signaling pathway in both liver and kidney tissues, leading to a reduction in the occurrence of inflammatory responses. In summary, our study has validated the complexity of the natural compounds within XBJ and elucidated their potential mechanisms for addressing CLP-induced metabolic disturbances. This work contributes to our understanding of the bioactive compounds and their associated targets, providing insights into the potential molecular mechanisms involved.

Combining hybrid nanoflowers with hybridization chain reaction for highly sensitive detection of SARS-CoV-2 nucleocapsid protein.

BACKGROUND: COVID-19 (coronavirus disease 2019) pandemic has had enormous social and economic impacts so far. The nucleocapsid protein (N protein) is highly conserved and is a key antigenic marker for the diagnosis of early SARS-CoV-2 infection. RESULTS: In this study, the N protein was first captured by an aptamer (Aptamer 58) coupled to magnetic beads (MBs), which in turn were bound to another DNA sequence containing the aptamer (Aptamer 48-Initiator). After adding 5'-biotinylated hairpin DNA Amplifier 1 and Amplifier 2 with cohesive ends for complementary hybridization, the Initiator in the Aptamer 48-Initiator began to trigger the hybridization chain reaction (HCR), generating multiple biotin-labeled DNA concatamers. When incubated with synthetic streptavidin-invertase-Ca3(PO4)2 hybrid nanoflower (SICa), DNA concatamers could specifically bind to SICa through biotin-streptavidin interaction with high affinity. After adding sucrose, invertase in SICa hydrolyzed sucrose to glucose, whose concentration could be directly read with a portable glucometer, and its concentration was positively correlated with the amount of captured N protein. The method is highly sensitive with a detection limit as low as 1 pg/mL. SIGNIFICANCE: We believe this study provided a practical solution for the early detection of SARS-CoV-2 infection, and offered a new method for detecting other viruses through different target proteins.

Optimisation and Effect Analysis of the Blood Collection Method in Pre-Deposit Autotransfusion Patients Undergoing Thoracotomy Surgery.

Background and Purpose: To explore the feasibility of the modified blood collection method in pre-deposit autotransfusion in patients undergoing thoracotomy surgery. Methods: This double-blinded randomised controlled trial enrolled 92 patients from the cardiothoracic surgery department from February 2019 to October 2020. Results: Compared with the conventional blood collection method, the modified blood collection method avoided blood overflow from the oblique plane of the needle (χ2 = 61.986, P < 0.01) and reduced the diameter of the bruising area after 24 hours (χ2 = 24.611, P < 0.01). Furthermore, due to optimising the blood collection method, diastolic blood pressure reduced slightly before and after blood collection (t = 2.036, P < 0.05), and patients in the test group had less pain (based on the numerical rating score) (t = 5.556, P < 0.01). Meanwhile, the time required to collect 400 mL of blood was shortened (t = 17.744, p < 0.01). Conclusion: An improved blood collection method can enhance the blood donation experience, avoid blood spillage, lessen pain and reduce adverse reactions. This may be of great significance in ensuring blood quality and the safety of subsequent transfusions. Clinical Trials Registration: ClinicalTrials.gov Identifier: NCT05539846.

Is acupuncture safe in the ICU? A systematic review and meta-analysis.

Background and purpose: The safety of interventions for critically ill patients is a crucial issue. In recent years, several studies have treated critically ill patients with acupuncture. However, the safety of acupuncture in this setting remains to be systematically measured. Methods: In May 2022, the electronic databases of PubMed and the Cochrane Library were searched for studies comparing acupuncture interventions to control interventions in critically ill patients. Study outcomes examined the incidence of severe adverse events (AEs), minor AEs, adverse reactions, ICU stays, and 28-day mortality. Results: A total of 31 articles were analyzed, and no serious AEs related to acupuncture treatment were identified. No significant differences were found between the groups in the meta-analysis of minor AEs (risk ratio [RR] 5.69 [0.34, 96.60], P = 0.23, I2 = 76%). A reduced risk in the incidence of adverse reactions following acupuncture intervention was evidenced (RR 0.33 [0.22, 0.50], P = 0.00001, I2 = 44%). The patients in the acupuncture arm spent significantly less time in the intensive care unit (ICU) (Mean difference -1.45 [-11.94, -10.97], P = 0.00001, I2 = 56%) and also exhibited lower 28-day mortality rates (odds ratio 0.61 [0.48, 0.78], P = 0.0001, I2 = 0%). Conclusion: There is no evidence to indicate a higher risk of severe or minor AEs in patients who receive acupuncture. Acupuncture demonstrated favorable results in both ICU stay and 28-day mortality measurements, in addition to presenting with fewer adverse reactions compared to routine ICU care. However, the low certainty of the evidence resulting from a high risk of bias in the included studies merits substantial consideration, and further research is still warranted. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=142131, identifier: CRD42020142131.

Polysaccharides from Platycodon grandiflorus attenuates high-fat diet induced obesity in mice through targeting gut microbiota.

The root of Platycodon grandiflorus (PG), abundant in soluble polysaccharides, has a long history in traditional Asian diets and herbal medicine due to its anti-inflammatory activity and anti-obesity effects. Our previous study was the first to establish a link between the beneficial effects of PG and changes in the gut microbiota, and suggested potential roles that the polysaccharide components play. However, more evidence was needed to understand the anti-obesity functions of polysaccharides from PG (PS) and their relationship with the regulation of the gut microbiota. In this study, we first performed an experiment to explore the anti-obesity activities of PS: Male C57BL/6 mice (six-weeks-old) were fed either a standard control diet (CON), or a high-fat diet (HFD) to induce obesity, or a HFD supplemented with PS (HFPS) for 8 weeks. Body weight and food intake were monitored throughout. Lipid metabolism were determined and related gene expression changes in adipose tissues were analyzed by RNA-seq. Amplicon sequencing of the bacterial 16 S rRNA gene was used to explore gut microbiota structure in fecal samples. Then, we performed the second experiment to explore whether the anti-obesity activities of PS were dependent on the regulation of the gut microbiota: Male C57BL/6 mice (six-weeks-old), treated with an antibiotic cocktail to reduce the gut microbial load, were fed either a HFD (A-HFD) or a HFPS (A-HFPS) diet for 8 weeks. Finally, we used in vitro fermentation experiments to verify the effects of PS on the growth and metabolic activities of the gut microbes. We found that PS significantly reduced HFD-induced weight gain and excessive fat accumulation, changed the expression of key genes involved in lipid metabolism, and attenuated HFD-induced changes in the gut microbiota. However, PS did not affect fat accumulation or lipid metabolism in the gut microbiota depleted mice. Overall, our results show that PS has significant effects on the gut microbiota in the mouse model, and the anti-obesity effects of PS are mediated via changes in the gut microbiota composition and metabolic activity.

Pregnancy characteristics and adverse outcomes in offspring of women with epilepsy: a prospective registry study from Mainland China.

Objective: This study aimed to explore the influencing factors of adverse outcomes in the offspring of women with epilepsy (WWE) and to analyze the changes brought about by the epilepsy knowledge popularization campaign in China (EKPCIC). Methods: This nested case-control study focused on WWE and their offspring from a female epilepsy cohort in mainland China. From January 2009 to August 2022, WWE was prospectively enrolled in 32 study centers. This study aimed to observe the health outcomes of their offspring within 1 year of age. The main outcome measure assessed the health status of the offspring within their first year of age. We aimed to analyze the effects of seizures, anti-seizure medicines (ASMs), and a lack of folic acid supplementation on adverse outcomes in the offspring of WWE and to explore the changes in perinatal management and adverse outcomes of the offspring after dissemination of the EKPCIC in 2015. Additionally, subgroup analyses were conducted to compare seizure control during pregnancy between the valproate and non-valproate groups. Results: In total, 781 pregnancies in 695 WWE were included, of which 186 (23.69%) had adverse outcomes. The National Hospital Epilepsy Severity Scale score, number of seizures, status epilepticus, ASM type, and valproate and folic acid doses were associated with a high risk of adverse outcomes. After the EKPCIC, the use of ASMs (P = 0.013) and folic acid (P < 0.001), the seizure-free rate during pregnancy (P = 0.013), and the breastfeeding rate (P < 0.001) increased, whereas the incidence of complications during pregnancy decreased (P = 0.013). However, there was no significant difference in the incidence of adverse outcomes between the analyzed offspring pre-/post-EKPCIC. Additionally, there was no association between the frequency of seizures at different time points during pregnancy and the use of valproate (F = 1.514, P = 0.221). Conclusion: Possible factors influencing adverse outcomes in the offspring of WWE include seizures, type and number of ASM usage, and a lack of folic acid supplementation. Although the management of WWE during pregnancy is now more standardized, further efforts are needed to reduce adverse outcomes in offspring.