Pharmacological mechanisms of sinomenine in anti-inflammatory immunity and osteoprotection in rheumatoid arthritis: A systematic review.

BACKGROUND: Sinomenine (SIN) is the main pharmacologically active component of Sinomenii Caulis and protects against rheumatoid arthritis (RA). In recent years, many studies have been conducted to elucidate the pharmacological mechanisms of SIN in the treatment of RA. However, the molecular mechanism of SIN in RA has not been fully elucidated. PURPOSE: To summarize the pharmacological effects and molecular mechanisms of SIN in RA and clarify the most valuable regulatory mechanisms of SIN to provide clues and a basis for basic research and clinical applications. METHODS: We systematically searched SciFinder, Web of Science, PubMed, China National Knowledge Internet (CNKI), the Wanfang Databases, and the Chinese Scientific Journal Database (VIP). We organized our work based on the PRISMA statement and selected studies for review based on predefined selection criteria. OUTCOME: After screening, we identified 201 relevant studies, including 88 clinical trials and 113 in vivo and in vitro studies on molecular mechanisms. Among these studies, we selected key results for reporting and analysis. CONCLUSIONS: We found that most of the known pharmacological mechanisms of SIN are indirect effects on certain signaling pathways or proteins. SIN was manifested to reduce the release of inflammatory cytokines such as Tumor necrosis factor-α (TNF-α), Interleukin-6 (IL-6), and IL-1ß, thereby reducing the inflammatory response, and apparently blocking the destruction of bone and cartilage. The regulatory effects on inflammation and bone destruction make SIN a promising drug to treat RA. More notably, we believe that the modulation of α7nAChR and the regulation of methylation levels at specific GCG sites in the mPGES-1 promoter by SIN, and its mechanism of directly targeting GBP5, certainly enriches the possibilities and the underlying rationale for SIN in the treatment of inflammatory immune-related diseases.

Global Trends and Performances of Acupuncture Therapy on Bell's Palsy from 2000 to 2023: A Bibliometric Analysis.

Purpose: Recent studies have shown that acupuncture may have great potential in the treatment of Bell's palsy. However, the bibliometric analysis of this field has not been summarized properly. Thus, the purpose of this study is to analyze the hotspot of acupuncture for Bell's Palsy. Methods: The core collection database of Web of Science was searched for relevant publications from 2000 to 2023, and countries, institutions, authors, keywords, and literature were analyzed and visualized by bibliometric softwareCiteSpace 5.1.R6, Vosviewer, BICOMB, and gCLUTO to explore the scientific achievements, research collaboration networks, research hot spots, and research trends. Results: 229 publications were included in this study. The most cited journal is Journal of Otolaryngology-Head & Neck Surgery; the most prolific country is China; the most prolific author is Li Ying, moreover, the collaboration among scholars is poor; Kyung Hee University is the most prolific institution studying acupuncture for Bell's Palsy. Reference burst detection indicates that traditional Chinese Medicine philosophy, the role of acupuncture in the prognosis of facial palsy, mechanism of acupuncture to improve facial nerve function, and the use of electroacupuncture are starting to become new research hotspots. Conclusion: The field of acupuncture for Bell's Palsy has developed rapidly in recent years, and new research trends are mainly: combination with traditional Chinese medicine, the role of acupuncture in the prognosis of facial palsy, mechanism of acupuncture to improve facial nerve function, and the use of electroacupuncture. However, research in this field is still dominated by case reports and clinical trials, and there is a lack of large-scale, multicenter clinical trials and animal experiments there are still many problems in institutional cooperation and experimental design, which requires relevant researchers to strengthen cooperation and improve experimental design.

Simiao Yong'an decoction ameliorates murine collagen-induced arthritis by modulating neutrophil activities: An in vitro and in vivo study.

ETHNOPHARMACOLOGICAL RELEVANCE: Rheumatoid arthritis (RA) is a common systemic autoimmune disease with high morbidity and disability rate. Currently, there is no effective allopathic treatment for RA, and most of the drugs provoke many adverse effects. Simiao Yong'an decoction (SMYAD) is a traditional Chinese prescription for the treatment of sore and gangrene caused by hot poison. With the development of pharmacology and clinical research, SMYAD has remarkable anti-inflammatory properties and has been used for RA treatments for years. AIM OF THE STUDY: This study aimed to investigate the anti-arthritic effect of SMYAD and further explore the immunopharmacological mechanisms. MATERIALS AND METHODS: Arthritis was induced in DBA/1 mice by two-time immunizations. Collagen-induced rheumatoid arthritis (CIA) mice were divided into 4 groups: control, model, methotrexate (MTX), and SMYAD group (n = 6). The administration groups were given MTX (0.5 mg/kg/3 d) and SMYAD (4.5 g/kg/d) by gavage from day 14. The arthritis index (AI) score was evaluated every 3 days after the second immunization. Hematoxylin and eosin (H&E) staining, Safranin-O fast green staining, Trap staining, and Micro-CT were used to measure the histopathology injuries and bone destruction of joints. Granulocyte changes in the spleen, bone marrow, and period blood were analyzed by flow cytometry. The expression of inflammatory cytokines and chemokines in joints were detected by qRT-PCR. SMYAD-containing serum was obtained from SD rats gavaged with SMYAD. Neutrophils were isolated from peripheral blood and bone marrow for the in vitro experiments of transwell cell assay, apoptosis assay, reactive oxygen species (ROS) generation and neutrophil extracellular traps (NETs) formation. RESULTS: SMYAD significantly relieved arthritis severity in CIA mice. The AI score was significantly decreased in the SMYAD group compared with the model group. Additionally, SMYAD alleviated inflammatory infiltration, cartilage damage, osteoclast formation, and bone damage in the ankle joints. In the flow cytometry assay, SMYAD significantly reduced granulocytes number in the spleen and bone marrow, while increased in peripheral blood. Furthermore, compared with the CIA group, SMYAD suppressed the mRNA levels of inflammatory factors including TNF-α, IL-1ß, IL-6 and chemokines CXCL1, CXCL2, and IL-8 in the inflamed joints. In the in vitro studies, 20% SMYAD-containing serum effectively inhibited the migration of neutrophils, promoted neutrophils apoptosis, reduced ROS production and NETs formation. CONCLUSION: Collectively, our results demonstrated that SMYAD effectively restrained arthritis in CIA mice by modulating neutrophil activities.

Tibetan medicine salidroside improves host anti-mycobacterial response by boosting inflammatory cytokine production in zebrafish.

The treatment for tuberculosis (TB), especially multidrug-resistant TB (MDR-TB), has a prolonged cycle which can last up to a year. This is partially due to the lack of effective therapies. The development of novel anti-TB drugs from the perspective of host immune regulation can provide an important supplement for conventional treatment strategies. Salidroside (SAL), a bioactive component from the Tibetan medicine Rhodiola rosea, has been used in the treatment of TB, although its mechanism remains unclear. Here, the bacteriostatic effect of SAL in vivo was first demonstrated using a zebrafish-M. marinum infection model. To further investigate the underlying mechanism, we then examined the impact of SAL on immune cell recruitment during wound and infection. Increased macrophage and neutrophil infiltrations were found both in the vicinity of the wound and infection sites after SAL treatment compared with control, which might be due to the elevated chemokine expression levels after SAL treatment. SAL treatment alone was also demonstrated to improve the survival of infected zebrafish larvae, an effect that was amplified when combining SAL treatment with isoniazid or rifampicin. Interestingly, the reduced bacterial burden and improved survival rate under SAL treatment were compromised in tnfα-deficient embryos which suggests a requirement of Tnfα signaling on the anti-mycobacterial effects of SAL. In summary, this study provides not only the cellular and molecular mechanisms for the host anti-mycobacterial effects of the Tibetan medicine SAL but also proof of concept that combined application of SAL with traditional first-line anti-TB drugs could be a novel strategy to improve treatment efficacy.

Mammary Leukocyte-Assisted Nanoparticle Transport Enhances Targeted Milk Trace Mineral Delivery.

Nanoparticles are applied as versatile platforms for drug/gene delivery in many applications owing to their long-retention and specific targeting properties in living bodies. However, the delivery mechanism and the beneficial effect of nanoparticle-retention in many organisms remain largely uncertain. Here, the transport and metabolism of mineral nanoparticles in mammary gland during lactation are explored. It is shown that maternal intravenous administration of iron oxide nanoparticles (IONPs; diameter: ≈11.0 nm, surface charge: -29.1 mV, surface area: 1.05 m2 g-1 ) provides elevated iron delivery to mammary gland and increased iron secretion into breast milk, which is inaccessible by classical iron-ion transport approaches such as the transferrin receptor-mediated endocytic pathway. Mammary macrophages and neutrophils are found to play dominant roles in uptake and delivery of IONPs through an unconventional leukocyte-assisted iron secretion pathway. This pathway bypasses the tight iron concentration regulation of liver hepcidin-ferroportin axis and mammary epithelial cells to increase milk iron-ion content derived from IONPs. This work provides keen insight into the metabolic pathway of nanoparticles in mammary gland while offering a new scheme of nutrient delivery for neonate metabolism regulation by using nanosized nutrients.

Microsomal prostaglandin E2 synthase-1 and its inhibitors: Molecular mechanisms and therapeutic significance.

Inflammation is closely linked to the abnormal phospholipid metabolism chain of cyclooxygenase-2/microsomal prostaglandin E2 synthase-1/prostaglandin E2 (COX-2/mPGES-1/PGE2). In clinical practice, non-steroidal anti-inflammatory drugs (NSAIDs) as upstream COX-2 enzyme activity inhibitors are widely used to block COX-2 cascade to relieve inflammatory response. However, NSAIDs could also cause cardiovascular and gastrointestinal side effects due to its inhibition on other prostaglandins generation. To avoid this, targeting downstream mPGES-1 instead of upstream COX is preferable to selectively block overexpressed PGE2 in inflammatory diseases. Some mPGES-1 inhibitor candidates including synthetic compounds, natural products and existing anti-inflammatory drugs have been proved to be effective in in vitro experiments. After 20 years of in-depth research on mPGES-1 and its inhibitors, ISC 27864 have completed phase II clinical trial. In this review, we intend to summarize mPGES-1 inhibitors focused on their inhibitory specificity with perspectives for future drug development.

The Effects of Non-Fiber Carbohydrate Content and Forage Type on Rumen Microbiome of Dairy Cows.

The main objective of our current study was evaluating the effects of NFC supplementation and forage type on rumen microbiota and metabolism, by comparing microbial structures and composition among samples collected from cows fed AH (alfalfa-based diet), H-NFC (CS-based diet with high NFC) and L-NFC (CS-based diet with low NFC) diets. Our results show that microbial communities were structurally different but functionally similar among groups. When compared with L-HFC, NFC increased the population of Treponema, Ruminobacter, Selenomonas and Succinimonas that were negatively correlated with ruminal NH3-N, and urea nitrogen in blood, milk and urine, as well as significantly increasing the number of genes involved in amino acid biosynthesis. However, when compared to the AH group, H-NFC showed a higher abundance of bacteria relating to starch degradation and lactate production, but a lower abundance of bacteria utilizing pectin and other soluble fibers. This may lead to a slower proliferation of lignocellulose bacteria, such as Ruminococcus, Marvinbryantia and Syntrophococcus. Lower fibrolytic capacity in the rumen may reduce rumen rotation rate and may limit dry matter intake and milk yield in cows fed H-NFC. The enzyme activity assays further confirmed that cellulase and xylanase activity in AH were significantly higher than H-NFC. In addition, the lower cobalt content in Gramineae plants compared to legumes, might have led to the significantly down-regulated microbial genes involved in vitamin B12 biosynthesis in H-NFC compared to AH. A lower dietary supply with vitamin B12 may restrict the synthesis of milk lactose, one of the key factors influencing milk yield. In conclusion, supplementation of a CS-based diet with additional NFC was beneficial for nitrogen conversion by increasing the activity of amino acid biosynthesis in rumen microbiota in dairy cattle. However, lower levels of fibrolytic capacity may limit dry matter intake of cows fed H-NFC and may prevent increased milk yield.

Olive oil cake extract stabilizes the physiological condition of lipopolysaccharide-challenged piglets by reducing oxidative stress and inflammatory responses and modulating the ileal microbiome.

Olives are a rich source of compounds with antioxidant and anti-inflammatory activities. This study was designed to investigate whether a standardized olive cake extract was able to alleviate oxidative stress, inflammation and intestinal villus damage in a model of lipopolysaccharide (LPS)-challenged piglets. Thirty weaned piglets (6.9 ± 0.9 kg) were assigned to five groups using a randomized complete block design. Piglets were fed a basal diet before intraperitoneal (i.p.) injection of physiological saline (C); fed a basal diet alone (CL) or fed a basal diet plus an olive cake extract (OL), antibiotics (AL), or olive cake extract plus antibiotics (OAL) before i.p. injection of LPS. The feeding period lasted for 2 weeks. Piglets were euthanized 4 h after the LPS injection. Systemic oxidative and inflammatory status and intestinal morphology were evaluated. LPS challenge significantly lowered the serum levels of GSH-Px, SOD and ALB and increased the serum concentration of MDA, NO, LDH, ALT, AST, TNF-α, IL-6, DAO and D-xylose (P < 0.05), as extracted from the comparison of piglets in the C and CL groups. Intestinal morphology was altered in the duodenum and ileum, displaying that the CL group had significantly lower villus height (VH), higher crypt depth (CD) and lower VH/CD compared with the control group (P < 0.05). Moreover, feed supplementation was able to partially mitigate the negative effects of LPS challenge in all groups (OL, AL, and OAL), as evidenced by the significantly increased serum levels of GSH-Px, SOD, ALB and IL-10 and decreased concentration of MDA, NO, LDH, ALT, AST, TNF-α, IL-6, DAO and D-xylose, compared with the CL group (P < 0.05). Alterations in intestinal morphology were also prevented and the OL, AL, and OAL groups had significantly lower CD and higher VH/CD compared with the CL group (P < 0.05), both in the ileum and duodenum. Furthermore, the positive effect in the relative abundance of intestinal Lactobacillus and Clostridium at the genus level was also observed for the OL group compared to the CL group. In summary, dietary supplementation with an olive cake extract stabilized the physiological condition of piglets subjected to an acute LPS challenge by reducing oxidative stress and the inflammatory status, improving intestinal morphology and increasing the abundance of beneficial intestinal bacteria. This trial was registered at Zhejiang University (http://www.lac.zju.edu.cn) as No. ZJU20170529.

Improvement of Qilin pills on male reproductive function in tripterygium glycoside-induced oligoasthenospermia in rats.

This study established an oligoasthenospermic rat model using tripterygium glycosides (TGs) and investigated the mechanism by which Qilin pills (QLPs) ameliorate reproductive hypofunction. Thirty-two male Sprague Dawley rats were allocated to four equal-sized groups: (1) the control group received continuous physiological levels of saline; (2) the oligoasthenospermia model group was induced with TGs by daily intragastric administration for 28 days; (3 and 4) oligoasthenospermic rats were treated intragastrically with low dose (1.62 g kg-1  d-1 ) and high dose (3.24 g kg-1  d-1 ) of QLPs once daily for 60 days. The QLP-treated rats showed a marked increase (p < .05) in testicular mass, testicular index and semen parameters compared with the untreated rats. Histopathologically, the QLP-treated groups exhibited restored seminiferous tubules in contrast to the model group. Reactive oxygen species and malondialdehyde levels were dramatically decreased (p < .05) in the testes of the QLP-treated rats. QLP treatment partly reverted (p < .05) the circulatory levels of reproductive hormones (FSH, LH, testosterone, prolactin and SHBG) and hepatic and renal function (AST, Cr and urea). Our results showed that oral QLP treatment had a curative effect on the testicular mass, sperm quality, testicular pathomorphology, antioxidants, plasmatic hormones, and liver and renal function of rats.

Suppression of macrophage migration by down-regulating Src/FAK/P130Cas activation contributed to the anti-inflammatory activity of sinomenine.

A large number of macrophages in inflamed sites not only amplify the severity of inflammatory responses but also contribute to the deleterious progression of many chronic inflammatory diseases, autoimmune diseases and cancers. Macrophage migration is a prerequisite for their entry into inflammatory sites and their participation of macrophages in the pathologic processes. Inhibition of macrophage migration is therefore a potential anti-inflammatory mechanism. Moreover, alleviation of inflammation also prevents the macrophages infiltration. Sinomenine (SIN) is an alkaloid derived from the Chinese medicinal plant Sinomenium acutum. It has multiple pharmacological effects, including anti-inflammation, immunosuppression, and anti-arthritis. However, its anti-inflammatory molecular mechanisms and effect on macrophage migration are not fully understood. The purpose of this research was to investigate the pharmacological effects and the molecular mechanism of SIN on macrophage migration in vivo and in vitro as well as to elucidate its anti-inflammatory mechanisms associated with macrophage migration. Our results showed that SIN reduced the number of RAW264.7 cells migrating into inflammatory paws and blocked lipopolysaccharide (LPS)-induced RAW264.7 cells and bone marrow-derived macrophages (BMDMs) migration in vitro. Furthermore, SIN attenuated the 3D mesenchymal migration of BMDMs. The absence of macrophage migration after circulatory and periphery macrophages depletion led to a reduction in the severity of inflammatory response. In macrophages depleted (macrophages-/-) mice, as inflammatory severity decreased, RAW264.7 cells migration was suppressed. A non-obvious effect of SIN on the inflammatory response was found in macrophages-/- mice, while the inhibitory effect of SIN on RAW264.7 cells migration was still observed. Furthermore, the migration of RAW264.7 cells pre-treated with SIN was suppressed in normal mice. Finally, Src/focal adhesion kinase (FAK)/P130Cas axis activation, which supports macrophages mesenchymal migration, and iNOS expression, NO production, integrin αV and in integrin ß3 expressions, which promote Src/FAK/P130Cas activation, were down-regulated by SIN. However, SIN had no obvious effect on the expression of the monocyte chemoattractant protein-1 (MCP-1), which is an important chemokine for macrophage migration. These results indicated that SIN significantly inhibited macrophage mesenchymal migration by down-regulating on Src/FAK/P130Cas axis activation. There was a mutual regulatory correlation between the inflammatory response and macrophage migration, and the effects of SIN on macrophage migration were involved in its anti-inflammatory activity.

Altered protein S-glutathionylation depicts redox imbalance triggered by transition metal oxide nanoparticles in a breastfeeding system.

Nanosafety has become a public concern following nanotechnology development. By now, attention has seldom been paid to breastfeeding system, which is constructed by mammary physiological structure and derived substances (endogenous or exogenous), cells, tissues, organs, and individuals (mother and child), connecting environment and organism, and spans across mother-child dyad. Thus, breastfeeding system is a center of nutrients transport and a unique window of toxic susceptibility in the mother-child dyad. We applied metabolomics combined with redox proteomics to depict how nanoparticles cause metabolic burden via their spontaneous redox cycling in lactating mammary glands. Two widely used nanoparticles [titanium dioxide (nTiO2) and zinc oxide (nZnO)] were exposed to lactating mice via intranasal administration. Biodistribution and biopersistence of nTiO2 and nZnO in mammary glands destroyed its structure, reflective of significantly reduced claudin-3 protein level by 32.1% (P < 0.01) and 47.8% (P < 0.01), and significantly increased apoptosis index by 85.7 (P < 0.01) and 100.3 (P < 0.01) fold change, respectively. Airway exposure of nTiO2 trended to reduced milk production by 22.7% (P = 0.06), while nZnO significantly reduced milk production by 33.0% (P < 0.01). Metabolomics analysis revealed a metabolic shift by nTiO2 or nZnO, such as increased glycolysis (nTiO2: fold enrichment = 3.31, P < 0.05; nZnO: fold enrichment = 3.68, P < 0.05), glutathione metabolism (nTiO2: fold enrichment = 5.57, P < 0.01; nZnO: fold enrichment = 4.43, P < 0.05), and fatty acid biosynthesis (nTiO2: fold enrichment = 3.52, P < 0.05; nZnO: fold enrichment = 3.51, P < 0.05) for tissue repair at expense of lower milk fat synthesis (35.7% reduction by nTiO2; 51.8% reduction by nZnO), and finally led to oxidative stress of mammary glands. The increased GSSG/GSH ratio (57.5% increase by nTiO2; 105% increase by nZnO) with nanoparticle exposure confirmed an alteration in the redox state and a metabolic shift in mammary glands. Redox proteomics showed that nanoparticles induced S-glutathionylation (SSG) modification at Cys sites of proteins in a nanoparticle type-dependent manner. The nTiO2 induced more protein SSG modification sites (nTiO2: 21; nZnO:16), whereas nZnO induced fewer protein SSG modification sites but at deeper SSG levels (26.6% higher in average of nZnO than that of nTiO2). In detail, SSG modification by nTiO2 was characterized by Ltf at Cys423 (25.3% increase), and Trf at Cys386;395;583 (42.3%, 42.3%, 22.8% increase) compared with control group. While, SSG modification by nZnO was characterized by Trfc at Cys365 (71.3% increase) and Fasn at Cys1010 (41.0% increase). The discovery of SSG-modified proteins under airway nanoparticle exposure further supplemented the oxidative stress index and mammary injury index, and deciphered precise mechanisms of nanotoxicity into a molecular level. The unique quantitative site-specific redox proteomics and metabolomics can serve as a new technique to identify nanotoxicity and provide deep insights into nanoparticle-triggered oxidative stress, contributing to a healthy breastfeeding environment.

Syn-2, 3-diols and anti-inflammatory indole derivatives from Streptomyces sp. CB09001.

Two new natural diols, (2S, 3S, 4S)-4-methyl-1-phenylhexane-2,3-diol (1) and (2S, 3S)-4-methyl-1-phenylpentane-2,3-diol (2), together with five known compounds, xenocyloins B-D (3-5), lumichrome (6) and thymidine (7) were isolated from Streptomyces sp. CB09001. The absolute configurations of 1 and 2 were established by crystallographic structure analysis. The anti-inflammatory effects of 1-7 were also investigated in RAW246.7 murine macrophage cells stimulated by lipopolysaccharide. The indole derivative xenocyloin B (3) significantly inhibited inducible nitric oxide synthase expression in RAW264.7 cells and could be a potential anti-inflammatory drug lead.

Acupuncture Medical Therapy and its Underlying Mechanisms: A Systematic Review.

As a traditional Chinese alternative health care approach, acupuncture is gaining increasing attention and reputation in China and overseas. While becoming increasingly popular globally, some consumers and professionals still know little about the therapy and underlying mechanisms of acupuncture. Due to local superiority, there are large numbers of both clinical applications and mechanistic studies performed in China compared to countries overseas. Herein, this review attempts to give a comprehensive profile of the development, application, and mechanisms of acupuncture in treating major diseases. The number of clinical publications concerning acupuncture-treated neurological diseases, endocrine and metabolic diseases, circulatory diseases, respiratory diseases, etc. is first counted, and then, the application and therapeutic mechanisms of acupuncture on the predominant diseases in each category, including obesity, facial paralysis, sciatica, depression, hypertension, asthma, etc., are specifically discussed in this paper. The evolution of acupuncture tools and the rationality of acupoints are also discussed. This review not only summarizes the mechanisms of acupuncture but also provides useful information, such as specific acupoints and acupuncture procedures, for treating common diseases. Therefore, the current study provides useful information for both investigators and acupuncturists.

Qingjie Fuzheng Granule Inhibited the Migration and Invasion of Colorectal Cancer Cells by Regulating the lncRNA ANRIL/let-7a/TGF-ß1/Smad Axis.

Qingjie Fuzheng granule (QFG) promotes cancer cell apoptosis and ameliorates intestinal mucosal damage caused by 5-fluorouracil. However, the antitumor role of QFG in colorectal cancer (CRC) progression remains unclear. In this study, the growth of HCT-8 and HCT116 cells incubated with various concentrations of QFG for 24 and 48 h was evaluated using MTT assays; their abilities of migration and invasion were investigated through wound healing and Transwell assays. The expression of lncRNA ANRIL, let-7a, and the TGF-ß1/Smad signaling pathway components was assessed using real-time PCR and western blotting. The results elicited that QFG significantly suppressed the growth of HCT-8 and HCT116 cells; the half-maximal inhibitory concentrations (IC50) of QFG for HCT-8 and HCT116 cells for 48 h were 1.849 and 1.608 mg/mL, respectively. The abilities of wound healing, migration, and invasion of HCT-8 and HCT116 cells were dose-dependently decreased by QFG treatment for 24 h, respectively. QFG decreased the expression of lncRNA ANRIL, TGF-ß1, phosphorylated (p)-Smad2/3, Smad4, and N-cadherin and upregulated the expression of let-7a in HCT-8 and HCT116 cells. Collectively, our data demonstrated that QFG inhibited the metastasis of CRC cells by regulating the lncRNA ANRIL/let-7a/TGF-ß1/Smad axis, indicating that they might serve as an adjunctive medicine for CRC treatment.

Babao Dan inhibits the migration and invasion of gastric cancer cells by suppressing epithelial-mesenchymal transition through the TGF-ß/Smad pathway.

OBJECTIVE: To investigate the anti-metastatic effects of Babao Dan (BBD) on gastric cancer (GC) cells (AGS and MGC80-3) and explore the underlying molecular mechanisms by which it inhibits epithelial-mesenchymal transition (EMT). METHODS: AGS and MGC80-3 cells were treated with BBD. In addition, cells were treated with the EMT inducer transforming growth factor-ß1 (TGF-ß1). Cell viability was determined using the MTT assay, and the live cell ratio was calculated via cell counting. Cell invasion and migration were evaluated using the Transwell assay. Western blotting was performed to measure the protein expression of EMT biomarkers and related genes. RESULTS: BBD inhibited the viability, migration, and invasion of AGS and MGC80-3 cells, but it did not reduce the live cell ratio. Furthermore, BBD inhibited the expression of N-cadherin, vimentin, zinc finger E-box binding homeobox (ZEB)1, ZEB2, Twist1, matrix metalloproteinase (MMP)2, MMP9, TGF-ß1, and p-Smad2/3, whereas E-cadherin expression was increased in AGS and MGC80-3 cells to different degrees. Using a GC cell model of EMT induced by TGF-ß1, we proved that BBD inhibited p-Smad2/3 and N-cadherin expression, cell migration, and cell invasion. CONCLUSION: BBD suppressed cell migration and invasion by inhibiting TGF-ß-induced EMT and inactivating TGF-ß/Smad signaling in GC cells.

Effects of Dietary Rumen-Protected Betaine on Lactation Performance and Serum Metabolites of Mid-lactation Holstein Dairy Cows.

This experiment was conducted to investigate the effects of dietary rumen-protected betaine (RPB) supplementation, as partial replacement for methionine, on the lactation performance of mid-lactation dairy cows. A total of 36 Holstein dairy cows were randomly assigned to three groups [control, 20 g/day RPB, or 15 g/day rumen-protected methionine (RPM)]. The experiment was conducted over 9 weeks, with the first week for adaptation. Blood metabolites were analyzed with metabolomics in the control and RPB groups. The results revealed that the milk yield and milk protein content were higher in cows fed RPB and RPM compared to those in the control group. Concentrations of nine metabolites differed between cows in the RPB and control groups. These metabolites were mainly concentrated in six pathways, such as arginine synthesis and proline degradation and cyanoamino acid synthesis. This study revealed that RPB can spare methionine and improve lactation performance of dairy cows fed with diets moderately deficient in methionine.

Effects of Qilin pills on spermatogenesis, reproductive hormones, oxidative stress, and the TSSK2 gene in a rat model of oligoasthenospermia.

BACKGROUND: Qilin pills (QLPs), a classic Traditional Chinese Medicine (TCM) formula for treating male infertility, effectively improve semen quality in clinical trials. This study was designed to evaluate the effects of QLPs on spermatogenesis, reproductive hormones, oxidative stress, and the testis-specific serinekinase-2 (TSSK2) gene in a rat model of oligoasthenospermia. METHODS: Forty adult male Sprague-Dawley (SD) rats were randomly divided into four groups. The rat model with oligoasthenospermia was generated by intragastric administration of tripterygium glycosides (TGs) once daily for 4 weeks. Then, two treatment groups were given different doses (1.62 g/kg and 3.24 g/kg) of QLPs once daily for 60 days. Sperm parameters, testicular histology and reproductive hormone measurements, oxidative stress tests, and TSSK2 expression tests were carried out. RESULTS: QLPs effectively improved semen parameters and testicular histology; restored the levels of FSH, LH, PRL, fT, and SHBG; reduced the levels of oxidative stress products (ROS and MDA); increased testicular SOD activity; and restored the expression of spermatogenesis-related gene TSSK2. CONCLUSION: QLPs have a therapeutic effect on a rat model of oligoasthenospermia, and this effect is manifested as improvement of semen quality and testis histology, gonadal axis stability, decreased oxidative stress, and the regulation of testis-specific spermatogenesis-related gene TSSK2.

Nardosinanone N suppresses LPS-induced macrophage activation by modulating the Nrf2 pathway and mPGES-1.

The side effects of nonsteroidal anti-inflammatory drugs (NSAIDs) in the cardiovascular system mainly result from its inhibitory effect on cyclooxygenase-2 (COX-2). Since NSAIDs are one of the most commonly used anti-inflammatory drugs in the clinic, it is necessary to identify new anti-inflammatory drugs that are safer than NSAIDs. Nardosinanone N (NAN), a compound isolated from the roots and rhizomes of Nardostachys chinensis, was evaluated for its anti-inflammatory effects using the lipopolysaccharide (LPS)-stimulated RAW264.7 cell line and rat peritoneal macrophage models. First, we found that NAN down regulated the levels of nitric oxide (NO), inducible nitric oxide synthase (iNOS) and prostaglandin E2 (PGE2), but not cyclooxygenase-2 (COX-2). Additionally, NAN reduced the M1 macrophage phenotype and increased the M2 macrophage phenotype. Furthermore, mechanistic studies showed that NAN activated the nuclear factor-erythroid 2 -related factor 2 (Nrf2) signaling pathway, which, in turn, increased the expression of antioxidant protein heme oxygenase-1 (HO-1) to achieve its anti-inflammatory effect. Finally, Nrf2 siRNA and the HO-1 inhibitor significantly attenuated the anti-inflammatory effect of NAN. More interestingly, we found that NAN did not affect COX-2 expression and activity but reduced the PGE2 concentration by selective inhibition of microsomal prostaglandin E synthase-1 (mPGES-1). In conclusion, NAN may be a new anti-inflammatory drug that has fewer side effects than NSAIDs and can be a new potential Nrf2 activator and mPGES-1 inhibitor.

Transcriptional changes in the hypothalamus, pituitary, and mammary gland underlying decreased lactation performance in mice under heat stress.

Because of climate change, heat stress (HS) causes more and more impacts on dairy animals to decrease lactation performance. The neuroendocrine system is key in regulating systemic physiological processes and milk synthesis. However, the hypothalamic-pituitary axis response to HS is still unclear. In this study, a group of lactating mice underwent a daily 2-h heat treatment (36°C) for 14 d to explore possible cross-talk between the hypothalamic-pituitary axis and mammary gland under HS. Transcriptome analyses by multitissue RNA-Seq indicated the possible mechanisms of reduced lactation performance in animals under HS. In the hypothalamus, the cAMP signaling pathway was activated to resist neuronal death, and the expression of downstream genes was increased to promote cell survival under HS. Reduced food intake might be caused by down-regulated appetite-related peptide, whereas up-regulated neuropeptide Y acted to attenuate reduced food intake. In pituitary, energy stress from lower food intake might result in reduced secretion of prolactin and growth hormone. Under HS, the mammary gland may undergo hypoxic stress, causing mammary epithelial cell apoptosis. Together, these data showed systemic changes in tissues to accommodate the effects of HS on lactation.-Han, J., Shao, J., Chen, Q., Sun, H., Guan, L., Li, Y., Liu, J., Liu, H. Transcriptional changes in the hypothalamus, pituitary, and mammary gland underlying decreased lactation performance in mice under heat stress.