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Dendrobium Officinale is a traditional Chinese medicinal and edible herb, and polysaccharides being its principal active components. We employed ultrasonic-assisted enzymatic extraction to obtain polysaccharides from Dendrobium Officinale (DOP) and optimized the extraction process using the GA-BP method. Subsequently, DOP was characterized using HPLC, SEM, and HPGPC. Finally, an immunocompromised mouse model induced by cyclophosphamide was adopted to evaluate the immunomodulatory effects. The results showed that the optimal extraction process of ultrasound-assisted enzyme method was 102 min ultrasonic extraction time, 48 °C extraction temperature, 1:80 material-liquid ratio, and 1600 U/g enzyme additions. The predicted polysaccharide yield was 29.64 %, and the actual polysaccharide yield was 29.71 ± 0.31 %. DOP is a white powder with pore-like structure, whose polysaccharide content is 90.66 ± 2.47 %, and with a composition of D-mannose, glucose, galactose, arabinose in a molar ratio of 74.17: 47.80: 9.03: 1. DOP has demonstrated the ability to improve the general condition of mice with cyclophosphamide-induced immunosuppression. It mitigates damage to the thymus and spleen tissues, increases white blood cell counts, regulates the ratio of T lymphocytes and the levels of related factors, enhances macrophage phagocytic function to improve nonspecific immune responses, and boosts the levels of immunoglobulins IgA and IgG to enhance specific immune function. Therefore, DOP can alleviate immunosuppression induced by cyclophosphamide., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 The Author(s). Published by Elsevier B.V. All rights reserved.)

Quercetin, a prevalent natural flavonoid found in various medicinal plants, including Dendrobium officinale Kimura & Migo, has garnered attention for its potential health benefits. However, foundational animal studies investigating the effects of quercetin on lowering uric acid levels remain insufficiently established, and the number of related clinical studies is limited. This scarcity hinders the practical application of quercetin in managing hyperuricemia. We systematically searched for preclinical studies published by December 2024 in nine databases, such as PubMed, Web of Science, and Embase. The results of our meta-analysis showed that, compared with the model group, quercetin not only effectively alleviated the pathological injury of the kidney and liver and improved the renal function indexes in the animal model of hyperuricemia but also played a role in lowering uric acid by modulating multiple signaling pathways such as oxidative stress, lipid metabolism, and transporter proteins. Quercetin showed a more substantial effect in decreasing serum creatinine levels (SMD = -4.29, 95 % CI [-6.48, -2.10], P = 0.0001), blood urea nitrogen levels (SMD = -3.08, 95 % CI [-4.80, -1.35], P = 0.0005), and Up-regulate organic anion transporter 1 mRNA expression levels (SMD = 2.72, 95 %CI [0.45, 4.99], P = 0.02) compared to the positive control group. Sensitivity analyses confirmed the stability of the results, while the subgroup analysis indicates that the treatment course may be the main source of heterogeneity. The results of the Dose-efficacy analysis suggested that quercetin had a more substantial protective effect against hyperuricemia at a gavage dose of 100-200 mg/kg. However, to more accurately assess the effects of quercetin on hyperuricemia, it is essential to conduct additional high-quality, large-scale animal trials to validate our findings., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Ethnopharmacological Relevance: Unhealthy dietary patterns and lifestyle changes have been linked to increased blood viscosity, which is recognized as an important pathogenic factor in cardiovascular and cerebrovascular diseases. The underlying mechanism may involve chronic inflammation resulting from intestinal barrier disruption induced by unhealthy diets. The rhizome of Atractylodes macrocephala Koidz. (Called Baizhu in China), is a well-used "spleen-reinforcing" traditional Chinese medicinal herb used for thousands of years. Previous research has demonstrated its multiple gastrointestinal health benefits and its ability to regulate metabolic disorders. However, the effects of Baizhu on blood hyperviscosity induced by long-term unhealthy diets remain unclear., Aim of the Study: This study aimed to investigate the effects of the aqueous extract of Baizhu on blood hyperviscosity induced by unhealthy diet and to explore the possible mechanisms., Materials and Methods: The blood hyperviscosity model in SD rats was established utilizing a high-fat, high-sugar, and high-salt diet (HFSSD). Subsequently, the rats underwent a twelve-week intervention with varying doses of Baizhu and a positive control. To evaluate the efficacy of Baizhu on blood hyperviscosity in model rats, we measured behavioral index, hemorheological parameters, inflammatory cytokines, hematology, adhesion molecules, as well as biochemical indicators in serum and liver. We also assessed the pathological states of the colon and liver. Furthermore, Western blotting, ELISA, IHC, and qRT-PCR were used to determine the effect of Baizhu on the IL-6/STAT3/ESRRG signaling pathway and FIB synthesis., Results: The intervention of Baizhu showed evident attenuating effects on blood viscosity and microcirculation disorders, and exhibit the capacity to moderately modulate parameters including grip, autonomous activities, vertigo time, TC, TG, LDL-c, inflammatory factors, adhesion factors, hematological indicators, etc. At the same time, it reduces liver lipid droplet deposition, restores intestinal integrity, and lowers LPS level in the serum. Subsequent experimental results showed that Baizhu downregulated the expression of TLR4 and NF-κB in colon tissue, as well as the expression of IL-6, TLR4, p-JAK2, p-STAT3, and ESRRG in liver tissue. Finally, we also found that Baizhu could regulate the levels of FIB in plasma and liver., Conclusion: Baizhu protects HFSSD-induced rats from blood hyperviscosity, likely through repairing the intestinal barrier and inhibiting LPS/TLR4-associated liver inflammatory activation, thus suppressing FIB synthesis through the downregulation of IL-6/STAT3/ESRRG pathway., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Nonalcoholic fatty liver disease (NAFLD) has developed as a leading public wellness challenge as a result of changes in dietary patterns. Unfortunately, there is still a lack of effective pharmacotherapy methods for NAFLD. Wang's empirical formula (WSF) has demonstrated considerable clinical efficacy in treating metabolic disorders for years. Nevertheless, the protective effect of WSF against NAFLD and its underlying mechanism remains poorly understood., Methods: The NAFLD model was established using a 17-week high-sucrose and high-fat (HSHF) diet with 32 ICR mice. In assessing the therapeutic efficacy of WSF on NAFLD, we detected changes in body weight, viscera weight, biomarkers of glycolipid metabolism in serum and liver, transaminase levels and histopathology of liver with H&E and Oil Red O staining after oral administration. The chemical components in WSF were extensively identified and gathered utilizing the HPLC-Q-TOF/MS system, database mining from HMDB, MassBank, and TCMSP databases, alongside literature searches from CNKI, Wanfang and VIP databases. The forecast of network pharmacology approach was then utilized to investigate the probable mechanisms by which WSF improves NAFLD based on the performance of prospective target identification and pathway enrichment analysis. Besides, molecular docking was also conducted for the verification of combination activities between active components of WSF and core proteins related to NAFLD. In final, validation experiments of obtained pathways were conducted through ELISA, immunohistochemistry (IHC), and western blot (WB) analysis., Results: Pharmacodynamic outcomes indicated that WSF intervention effectively mitigated obesity, fat accumulation in organs, lipid metabolism disorders, abnormal transaminase levels and liver pathology injury in NAFLD mice (P < 0.05, 0.01). A total of 72 existent ingredients of WSF were acquired by HPLC-Q-TOF/MS and database, and 254 common targets (11.6% in total targets) of NAFLD and WSF were identified. Network pharmacology revealed that WSF presses NAFLD via modulating TNF, IL6, AKT1, IL1B, PTGS2 (COX2), and other targets, and the probable pathways were primarily inflammatory signaling pathways, as confirmed by molecular docking. Molecular biology experiments further conformed that WSF could decrease levels of inflammatory factors like IL-1β, IL-6 and TNF-α (P < 0.01) and expression of TLR4, NF-κB and COX-2 (P < 0.05, 0.01) in the liver., Conclusion: WSF treatment effectively protects against lipid metabolism disorders and liver inflammation injury in HSHF diet-induced NAFLD mice, and its molecular mechanism might be via suppressing the TLR4/NF-κB/COX-2 inflammatory pathway to reduce the release of inflammatory cytokines in the liver., Competing Interests: Declarations. Ethics approval and consent to participate: The Animal Ethics Committee of the Zhejiang University of Technology ratified the experiment plan (No. 20211119097, 19–11-2021). Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Ethnopharmacological Relevance: Chronic pharyngitis persistently afflicts a large population and accounts for approximately one-third of otolaryngology patients. Currently, the treatment of CP remains controversial because of the poor outcomes. Dendrobium officinale is a well-used "Yin-nourishing" traditional Chinese medicinal and edible herb used for thousands of years in China. The flowers of D. officinale are often used in folk of China to make tea for voice protection on and throat clearing., Aim of the Study: This study was to evaluate beneficial effects of polysaccharides from D. officinale flower (DOFP) on CP and its potential mechanisms., Methods: Chemical characterization of DOFP, including polysaccharide content and monosaccharide composition, structural characterization using Fourier transform infrared spectroscopy were performed. A CP model was established in rats by administering a mixture of Chinese Baijiu and chili pepper liquid, combined with low-concentration ammonia spraying. The general states, amount of oral secretion, and apparent state of the pharynx of CP rats were observed during the period of DOFP administration. Furthermore, hemorheological parameters were measured using an automatic hematology analyzer. The levels of tumor necrosis factor-α (TNF-α), interleukin 1β (1L-1β), lipopolysaccharide (LPS), and D-lactate (D-LA) in the serum were measured by enzyme-linked immunosorbent assay. Morphological changes in the pharynx and colon were observed by hematoxylin-eosin staining. The expression of nuclear factor-κB p65 (NF-κB p65), p-NF-κB p65, cyclooxygenase-2 (COX-2), interleukin 1β（IL-1β）and mucin 5AC (MUC5AC) in the pharynx,Claudin-1, Occludin, and interleukin 6 (IL-6) in the colon was detected by immunohistochemistry and Western Blot. The mRNA expression of TLR4, COX-2, and IL-1β in the pharynx were determined using reverse transcription quantitative real-time PCR., Results: In this study, DOFP with a total polysaccharide content of 71.44% and a composition of D-mannose, galacturonic acid, glucose, galactose, and arabinose in a molar ratio of 3.95:2.19:1.00:0.74:1.30, was isolated from the flowers of D. officinale. DOFP improved the general state and exhibited significant effects on reducing oral secretion, alleviating pharyngeal injury, suppressing inflammatory cell infiltration in the pharynx, decreasing the serum levels of TNF-α and IL-1β, and reducing the number of white blood cells and lymphocytes in the model rats. Moreover, the expressions of TLR4, p-NF-κB p65, COX-2, IL-1β and MUC5AC in the pharynx of model rats were obviously inhibited. In addition, the levels of LPS, D-LA in the serum and the protein expression of IL-6 in the colon were downregulated when the protein expression of Occludin and Claudin-1 in the colon were upregulated., Conclusions: DOFP exerts significant ameliorating effects on CP and it likely acts by inhibiting LPS/TLR4-associated inflammatory mediator activation and reducing excessive secretion of mucus by repairing the intestinal barrier in CP rats., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objectives: This study aimed to explore the effect and mechanism of Yunkang oral liquid (YK) on polycystic ovary syndrome (PCOS). Methods: PCOS model rats were prepared by injecting exogenous androgen dehydroepiandrosterone, and YK was administered simultaneously for 28 days during modeling. The morphology of ovaries and uterus was observed using H&E staining, and serum levels of testosterone (T), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) were determined by radioimmunoassay. Additionally, serum lipids (TG, HDL-c), blood glucose (GLU), and aminotransferase (AST, ALT) levels were detected. The expression of androgen receptor (AR) protein was determined by Western blotting. Results: YK treatment resulted in reduced serum levels of T, LH and FSH, ameliorated ovarian polycystic-like pathological changes and uterine morphology in PCOS rats, and decreased serum TG, GLU, AST and ALT levels, elevated serum HDL-c levels, and improved abnormalities of glycolipid metabolism accompanying PCOS. Moreover, YK decreased the expression of ovarian AR in PCOS rats. Conclusions: This study indicates that YK may protect the ovaries by inhibiting the expression of AR, which could be a potential treatment for PCOS.

Ethnopharmacological Relevance: In recent years, in addition to hypertension, hyperglycemia, and hyperlipidemia, the prevalence of hyperuricemia (HUA) has increased considerably. Being the fourth major health risk factor, HUA can affect the kidneys and cardiovascular system. Chrysanthemi Indici Flos is a flavonoid-containing traditional Chinese patent medicine that exhibits a uric acid (UA)-lowering effect. However, the mechanisms underlying Chrysanthemi Indici Flos-enriched flavonoid part (CYM.E) mediated alleviation of HUA remain unelucidated., Aim of the Study: This study aimed to elucidate the efficacy of CYM.E in preventing and treating HUA and its specific effects on UA-related transport proteins, to explore possible mechanism., Methods: The buddleoside content in CYM.E was determined through high-performance liquid chromatography. HUA was induced in mice models using adenine and potassium oxonate. Subsequently, mice were administered 10 mg/kg allopurinol, and 30, 60, and 90 mg/kg CYM.E to evaluate the effects of CYM.E on the of HUA mice model. Herein, plasma uric acid (UA), creatinine (CR), blood urea nitrogen (BUN), total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-c), and low-density lipoprotein cholesterol (LDL-c) contents, along with serum alanine aminotransferase (ALT), and aspartate aminotransferase (AST) activities were measured. Additionally, xanthine oxidase (XOD) and adenosine deaminase (ADA) activities in the liver were determined. The histomorphologies of the liver and kidney tissues were examined through hematoxylin and eosin staining. The messenger RNA (mRNA) expression of facilitated glucose transporter 9 (GLUT9), organic anion transporter (OAT)1, OAT3, and adenosine triphosphate binding cassette subfamily G2 (ABCG2) in the kidney was assessed by real-time quantitative polymerase chain reaction. Furthermore, the expression of urate transporter 1 (URAT1), GLUT9, OAT1, and OAT3 in the kidney, OAT4, and ABCG2 proteins was determined by immunohistochemistry and western blotting., Results: The buddleoside content in CYM.E was approximately 32.77%. CYM.E improved body weight and autonomous activity in HUA mice. Additionally, it reduced plasma UA, BUN, and CR levels and serum ALT and AST activities, thus improving hepatic and renal functions, which further reduced the plasma UA content. CYM.E reduced histopathological damage to the kidneys. Furthermore, it lowered plasma TC, TG, and LDL-c levels, thereby improving lipid metabolism disorder. CYM.E administration inhibited hepatic XOD and ADA activities and reduced the mRNA expression of renal GLUT9. CYM.E inhibited the protein expression of renal URAT1, GLUT9, and OAT4, and increased the mRNA and protein expression of renal OAT1, OAT3, and ABCG2. Altogether, these results show that CYM.E could inhibit the production and promote reabsorption of UA and its excretion., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Polycystic ovary syndrome (PCOS) is an endocrine disorder marked by aberrant glucose metabolism and reproductive dysfunction. It is characterized by polycystic ovaries, ovulatory dysfunction, and hyperandrogenemia. PCOS patients often experience a persistent, mild inflammation linked to various metabolic issues and insulin resistance (IR). Cordyceps polysaccharide (CP), extracted from the asexual form of the fungus Cordyceps gunnii, Hirsutella sinensis, is a bioactive crude polysaccharide with triple helix structure. CP was a spherical molecular polymer composed of rhamnose, arabinose, aminoglucose hydrochloride, galactose, glucose, and mannose, and has two molecular weights, 156.511 and 27.298 kDa. Our results corroborated that CP improve polycystic lesions in ovarian tissue and regulates hormone levels and the estrous cycle in rats with PCOS. However, the mechanism of action of this therapy in the treatment of polycystic ovary syndrome is not clear. In the present study, CP was found to modulates disturbances in glucose-lipid metabolism in model rats. In addition, it modulated gut microbiota by decreasing abundance of Gram-negative bacteria (norank&#95;f&#95;&#95;Desulfovibrionaceae, Helicobacter), hereby inhibiting the production and transfer of LPS into the systemic circulation. This suppressed the TLR4/MyD88/NF-κB inflammatory pathway in the liver and adipose tissue and restored insulin signaling, which improved IR in PCOS rats. Our findings demonstrate that based on the regulation of gut microbiota disorders and the repair of intestinal barrier damage, CP inhibited the gut-derived LPS/TLR4 inflammatory pathway in liver to attenuated IR, which led to the improvement of ovarian polycystic lesions. In addition, this study tapped into the role of Cordyceps polysaccharides in improving female reproductive function, expanding its clinical application in women with PCOS, which is innovative and offers valuable insights into the therapeutic potential of CP for treating PCOS., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Metabolic syndrome (MetS) is a precursor to the development of many diseases (atherosclerosis, diabetes, etc.). It is marked by disruptions in glucose and lipid metabolism, along with hypertension. Numerous types of risk factors contribute to the development of the MetS, inflammation and insulin resistance are present throughout the metabolic abnormalities. Chrysanthemum indicum L. is a traditional Chinese plant used for both tea and medicine, known for its high content of total flavonoids, which are important secondary metabolites. Our research led to the extraction of a Buddleoside-Rich Chrysanthemum indicum L. extract (BUDE) which has demonstrated anti-inflammatory properties. Nonetheless, the specific role and mechanism of BUDE in preventing MetS remain unclear., Methods: The study initially evaluated the role of BUDE in preventing MetS. Subsequently, it investigated the anti-inflammatory properties of BUDE in the liver and pancreas in response to unhealthy diets. It then examined the level of insulin resistance and pancreatic β-cell function induced by inflammation. Additionally, an lipopolysaccharide (LPS)-induced macrophage inflammation model was used to further investigate the ameliorative effects of BUDE in inflammation., Results: BUDE has hypotensive, hypoglycemic and hypolipidemic effects. It can also resolve the imbalance between macrophage subpopulations, impede the triggering of the NF-κB signaling pathway, reduce the secretion of inflammatory mediators, ameliorate insulin resistance, and safeguard organs such as the liver and pancreas from inflammatory damage. These effects collectively contribute to preventing the development of MetS., Discussion: BUDE has the ability to modulate macrophage-mediated inflammation, leading to improved insulin resistance. Additionally, it delivers antihypertensive, hypoglycemic, and hypolipidemic effects, offering a potential for preventing MetS., (© 2024. The Author(s).)

Wang's metabolic formula (WMF) is a traditional Chinese medicine formula developed under the guidance of Professor Kungen Wang. WMF has been clinically utilized for several years. However, the therapeutic mechanism of WMF in treating metabolic-associated fatty liver disease (MAFLD) remains unclear. In this study, we performed phytochemical analysis on WMF using LC-MS. To study the role of WMF in MAFLD, we orally administered WMF (20.6 g/kg) to male MAFLD mice induced by a high-cholesterol high-fat diet (HCHFD). Then pathological, biochemical, and metabolomic analyses were performed. The main components of WMF are chlorogenic acid, geniposide, albiflorin, paeoniflorin, and calycosin-7- O -glucoside. MAFLD mice treated with WMF exhibited significant improvements in obesity, abnormal lipid metabolism, inflammation, and liver pathology. WMF decreased aspartate aminotransferase (AST), alanine aminotransferase (ALT), and triglyceride (TG) levels in the serum of MAFLD mice while increasing high-density lipoprotein cholesterol (HDL-c) levels. WMF lowered liver TG levels and inflammatory factors (IL-1β, IL-6, TNF-α, and NF-κB). Metabolomic analysis of the liver annotated 78 differentially regulated metabolites enriched in four pathways: glycerophospholipid metabolism, retinol metabolism, PPAR signaling pathway, and choline metabolism. Western blot experiments showed that WMF increased the expression of PPAR-α, PPAR-β, and RXR in the liver while decreasing the expression of RAR. The study demonstrates that WMF has a solid preventive and therapeutic effect on MAFLD. The anti-inflammatory and regulation of abnormal liver metabolism activities of WMF involve retinol metabolism and the PPAR signaling pathway., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Background: Programmed cell death (PCD) pathways play crucial roles in the pathogenesis of skin cutaneous melanoma (SKCM). Understanding their prognostic significance and clinical implications is imperative for the development of personalized treatment strategies., Methods: A total of 1466 PCD-related genes were analyzed using data from The Cancer Genome Atlas (TCGA)-SKCM cohort (n = 353). Prognostic cell death index (CDI) was established and validated through survival analysis and predictive modeling. Functional enrichment, protein-protein interaction (PPI), consensus clustering, and tumor microenvironment assessment and drug sensitivity analysis were performed to elucidate the biological and clinical relevance of CDI., Results: CDI effectively stratified SKCM patients into high and low-risk groups, demonstrating significant differences in survival outcomes. It exhibited predictive value for survival at 1, 3, and 5 years. The concordance index (C-index) was 0.794 in the training set, and 0.792 and 0.821 in the internal and external validation sets, respectively. The corresponding area under curve (AUC) was all above 0.75 in these data sets. Functional enrichment analysis revealed significant associations with immune response and inflammatory processes. PPI analysis identified key molecular modules associated with apoptosis and chemokine signaling. Consensus clustering unveiled three discernible subtypes demonstrating notable disparities in survival outcomes based on CDI expression profiles. Assessment of the tumor microenvironment highlighted correlations with immune cell infiltration such as M1 macrophages and T cells. Drug sensitivity analysis indicated tight correlations between CDI levels and response to immunotherapy., Conclusion: Our comprehensive analysis establishes the prognostic significance of PCD-related genes in SKCM. CDI emerges as a promising prognostic biomarker, offering insights into tumor biology and potential implications for personalized treatment strategies. Further validation and clinical integration of CDI are warranted to improve SKCM management and patient outcomes., (© 2024 The Author(s). Skin Research and Technology published by John Wiley & Sons Ltd.)

Ethnopharmacological Relevance: Hyperlipidemia is characterized by the disorder of lipid metabolism accompanied by oxidative stress damage, and low-grade inflammation, with the pathway of cholesterol and bile acid metabolic are an important triggering mechanism. Polymethoxyflavones (PMFs) are the active constituents of Aurantii Fructus Immaturus, which have many biological effects, including anti-inflammatory, antioxidant activities, anti-obesity, suppressing adipogenesis in adipocytes, and ameliorate type 2 diabetes, with potential roles for regulation of lipid metabolism. However, its associated mechanisms on hyperlipidemia remain unclear., Aim of the Study: This study aims to identify the anti-hypercholesterolemia effects and mechanisms of PMFs in a hypercholesterolemia model triggered by high-fat compounds in an excessive alcohol diet (HFD)., Materials and Methods: A hypercholesterolemia rat model was induced by HFD, and PMFs was intragastric administered at 125 and 250 mg/kg daily for 16 weeks. The effects of PMFs on hypercholesterolemia were assessed using serum lipids, inflammatory cytokines, and oxidative stress levels. Hematoxylin & eosin (H&E) and Oil Red O staining were performed to evaluate histopathological changes in the rat liver. The levels of total cholesterol (TC) and total bile acid (TBA) in the liver and feces were determined to evaluate lipid metabolism. RAW264.7 and BRL cells loaded with NBD-cholesterol were used to simulate the reverse cholesterol transport (RCT) process in vitro. The signaling pathway of cholesterol and bile acid metabolic was evaluated by Western Blotting (WB) and qRT-PCR., Results: Lipid metabolism disorders, oxidative stress injury, and low-grade inflammation in model rats were ameliorated by PMFs administration. Numerous vacuoles and lipid droplets in hepatocytes were markedly reduced. In vitro experiments results revealed decreased NBD-cholesterol levels in RAW264.7 cells and increased NBD-cholesterol levels in BRL cells following PMFs intervention. PMFs upregulated the expression of proteins associated with the RCT pathway, such as LXRα, ABCA1, LDLR, and SR-BI, thereby promoting TC entry into the liver. Meanwhile, the expression of proteins associated with cholesterol metabolism and efflux pathways such as CYP7A1, CYP27A1, CYP7B1, ABCG5/8, ABCB1, and BSEP were regulated, thereby promoting cholesterol metabolism. Moreover, PMFs treatment regulated the expression of proteins related to the pathway of enterohepatic circulation of bile acids, such as ASBT, OSTα, NTCP, FXR, FGF15, and FGFR4, thereby maintaining lipid metabolism., Conclusions: PMFs might ameliorate hypercholesterolemia by promoting the entry of cholesterol into the liver through the RCT pathway, followed by excretion via metabolism pathways of cholesterol and bile acid. These findings provide a promising therapeutic potential for PMFs to treat hypercholesterolemia., Competing Interests: Declaration of competing interest The authors declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Cold drink and high-fat diet (CDHFD) are common diet patterns. However, the potential risks remain unclear. We investigated the effects of CDHFD in adult mice and explored the mechanisms of action. Twenty adult male mice were randomly divided into control and model groups, and the control group was fed a normal diet, whereas the model group was fed CDHFD for 28 days. We found that mice in the model group developed diarrhea symptoms accompanied by fatigue and weakness. Analysis of the intestinal flora revealed that the model group had a lower diversity and richness of microorganism species in the gut than the control group. Furthermore, the characteristic analysis indicated that CDHFD downregulated specific bacteria, such as norank&#95;f&#95;Muribaculaceae, Muribaculum, and Odoribacter, which are known to be associated with the systemic inflammatory response and mucosal barrier function. Blood tests showed that immune cells and inflammatory cytokines were significantly elevated in the model group, along with increased LPS induced by CDHFD. Pathological investigations demonstrated that CDHFD damages the intestinal mucosa while affecting the expression of tight junction proteins, including ZO-1, Claudin-1, Claudin-2, and Occludin, which may be attributed to the activation of the TRAF6/IκB/p65 signaling pathway. In conclusion, impaired gut microbial and mechanical barrier function is responsible for CDHFD-induced diarrhea. In this study, we constructed a model of diet-induced diarrhea by simulating human dietary patterns, evaluated the long-term effects of CDHFD on human intestinal barriers and immune systems, and revealed its mechanism of action based on chronic inflammation. This study validated the model's fit to provide an effective screening model for drug or functional food development., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Polysaccharides are known to confer protection against glycolipid metabolism disorders (GMD) by regulating intestinal flora. In this study, a heterogeneous acidic heteropolysaccharide with high molecular weight mainly composed of fructose was isolated from Atractylodes macrocephala Koidz (AMP). Supplementation with AMP was shown to improve diet-induced GMD in a rat model, including decreasing the levels of serum triglycerides, total cholesterol, and glucose, and improving hepatic lipidosis and islet cells morphologies. AMP-treated rats also exhibited modified intestinal flora with enrichments of intestinal Lactobacillus and Rothia species, which was accompanied by increased tryptophan metabolites such as indole-3-propionic acid, indole, tryptamine, and tryptophol. These metabolites promote the expression of intestinal aryl hydrocarbon receptor (AhR) in nuclear fractions. AhR activation increased the expression levels of IL-22 and GLP-1 proteins and mRNA. IL-22 reduced systemic LPS by upregulating the expression of tight junction proteins, antimicrobial peptides, and mucin to ameliorate intestinal barrier function, and activated the hepatic IL-22R/Stat3/Acox1 signaling pathway to improve lipid metabolism. GLP-1 activated the pancreatic GLP-1R/p-CREB signaling pathway to ameliorate β-cell injury and improve insulin resistance. Therefore, the intestinal microbial-tryptophan metabolism-AhR pathway was deduced to be a mechanism by which this polysaccharide improves GMD., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Tonic Chinese herbal medicine is a type of traditional Chinese medicine, and its primary function is to restore the body's lost nutrients, improve activity levels, increase disease resistance, and alleviate physical exhaustion. The body's immunity can be strengthened by its polysaccharide components, which also have a potent immune-system-protecting effect. Several studies have demonstrated that tonic Chinese herbal medicine polysaccharides can improve the body's immune response to tumor cells, viruses, bacteria, and other harmful substances. However, the regulatory mechanisms by which various polysaccharides used in tonic Chinese herbal medicine enhance immune function vary. This study examines the regulatory effects of different tonic Chinese herbal medicine polysaccharides on immune organs, immune cells, and immune-related cytokines. It explores the immune response mechanism to understand the similarities and differences in the effects of tonic Chinese herbal medicine polysaccharides on immune function and to lay the foundation for the future development of tonic Chinese herbal medicine polysaccharide products.

Ethnopharmacological Relevance: The root of Atractylodes macrocephala Koidz. (AM) has been used for thousands of years in China, and it's extracts contain various constituents, such as volatile oils, polysaccharides, and lactones, with a myriad of pharmacological effects, including improves the healthy state of the gastrointestinal system and regulating immunity, hormone secretion, anti-inflammatory, antibacterial, antioxidation, anti-aging, and antitumor properties. Recently, researchers have focused on the effect of AM in regulating bone mass; therefore, its potential mechanism of action in regulating bone mass needs to be elucidated., Aim of Review: This study reviewed the known and possible mechanisms of bone mass regulation by AM., Materials and Methods: Cochrane, Medline via PubMed, Embase, CENTRAL, CINAHL, Web of Science, Chinese biomedical literature database, Chinese Science and Technology Periodical Database, and Wanfang Database were used to search AM root extracts-related studies. The retrieval date was from the establishment of the database to January 1, 2023., Results: By summarizing 119 natural active substances that have been isolated from AM root to date, we explored its possible targets and pathways (such as Hedgehog, Wnt/β-catenin, and BMP/Smads pathways etc.) for bone growth and presented our position on possible future research/perspectives in the regulation of bone mass using this plant., Conclusions: AM root extracts (incuding aqueous, ethanol etc.) promotes osteogenesis and inhibits osteoclastogenesis. These functions promote the absorption of nutrients, regulate gastrointestinal motility and intestinal microbial ecology, regulate endocrine function, strengthen bone immunity, and exert anti-inflammatory and antioxidant effects., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Atractylenolides, comprising atractylenolide I, II, and III, represent the principal bioactive constituents of Atractylodes macrocephala , a traditional Chinese medicine. These compounds exhibit a diverse array of pharmacological properties, including anti-inflammatory, anti-cancer, and organ-protective effects, underscoring their potential for future research and development. Recent investigations have demonstrated that the anti-cancer activity of the three atractylenolides can be attributed to their influence on the JAK2/STAT3 signaling pathway. Additionally, the TLR4/NF-κB, PI3K/Akt, and MAPK signaling pathways primarily mediate the anti-inflammatory effects of these compounds. Atractylenolides can protect multiple organs by modulating oxidative stress, attenuating the inflammatory response, activating anti-apoptotic signaling pathways, and inhibiting cell apoptosis. These protective effects extend to the heart, liver, lung, kidney, stomach, intestine, and nervous system. Consequently, atractylenolides may emerge as clinically relevant multi-organ protective agents in the future. Notably, the pharmacological activities of the three atractylenolides differ. Atractylenolide I and III demonstrate potent anti-inflammatory and organ-protective properties, whereas the effects of atractylenolide II are infrequently reported. This review systematically examines the literature on atractylenolides published in recent years, with a primary emphasis on their pharmacological properties, in order to inform future development and application efforts.

Background: Crocetin is a bioactive ingredient in saffron, derived from the Crocus sativus stigmas of the Iridaceae family. As a chemically carotenoid derivative, crocetin exhibites effects like anti-inflammatory, antioxidant, neuroprotective, etc. However, the protective effect of crocetin on glaucoma and its mechanism remains unclear. The current study assesed the neuroprotective and anti-inflammatory effects of crocetin on retinal neurons in glaucoma rats which were induced by 0.3% carbomer injection into the anterior chamber., Methods and Results: The pathological structures on the retina and optic nerve were observed and examined by H&E staining and transmission electron microscopy. Immunohistochemical staining was used to detect the expression of TNF-α, IL-1β, and IL-6 of the retina and the expression of a brain-derived neurotrophic factor (BDNF) in the primary visual cortex (PVC). Western blot was carried out to detect the expression of PI3K, Akt, and NF-κB in the retina. It was found that crocetin ameliorated the pathological changes of the retina and ON and reduced the number of apoptotic retinal ganglion cells. Immunohistochemical staining showed that crocetin could decrease the contents of TNF-α, IL-1β, and IL-6 and increase the contents of BDNF. Western blot showed that crocetin was found to suppress the expression of PI3K, Akt, and NF-κB., Conclusion: The results obtained in this study have indicated that crocetin showes neuroprotective effects on retinal ganglion cells in glaucoma rats and inhibits retinal dysfunction. Meanwhile, crocetin exerted an anti-inflammatory effect to protect the retina by inhibiting the expression of the PI3K/Akt/NF-κB signaling pathway. This work provides substantial evidence that crocetin may be a potential drug for the treatment of glaucoma., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Metabolic hypertension (MH) has become the most common type of hypertension in recent years due to unhealthy eating habits and lifestyles of people, such as over-eating alcohol, high fat, and sugar diets (ACHFSDs). Therefore, effective means to combat MH are needed. Previous studies have shown that Panax notoginseng (Burkill) F. H. Chen flower saponins (PNFS) can lower blood pressure in spontaneously hypertensive rats (SHR). However, whether it acts on MH and its mechanism of action remain unclear.  METHODS: The pharmacodynamic effects of PNFS were evaluated in rats with ACHFSDs-induced MH. The blood pressure, blood biochemical, grip strength, face temperature, vertigo time, and liver index were estimated. The histological changes in the liver and aorta were observed using hematoxylin and eosin staining. The levels of ET-1, TXB 2 , NO, PGI 2 , Renin, ACE, Ang II, and ALD in plasma were detected using ELISA. The levels of C3, KLF5, LXRα, and Renin in kidney tissues were measured using qRT-PCR.The expression levels of C3, KLF5, LXRα, and Renin in kidney tissues were examined using Western blotting., Results: In the present study, PNFS was found to reduce blood pressure, face temperature, and vertigo time, increase grip strength and improve dyslipidemia in rats with MH. In addition, PNFS decreased the plasma levels of ET-1 and TXB 2 , elevated the levels of NO and PGI 2 , and improved pathological aortic injury. Meanwhile, PNFS decreased the plasma levels of Renin, ACE, Ang II, and ALD. QRT-PCR and Western bolt showed that PNFS downregulated C3, KLF5, LXRα, and Renin protein and mRNA expression in the kidneys of rats with MH., Conclusion: The finding of the present study suggested that PNFS could downregulate C3 and KLF-5 expression in rats with MH, thereby inhibiting the overactivation of the renin-angiotensin-aldosterone system, while improving vascular endothelial function and ultimately reducing blood pressure in rats with MH., (© 2023. The Author(s).)

Ethnopharmacological Relevance: Saffron, the dried stigma of Crocus sativus L., has a long history of use in the treatment of depression in traditional Chinese medicine and Islamic medicine. The unique aroma of saffron, primarily derived from its volatile oil, has been widely used by folk to mitigate anxiety and depression via sniffing because the aroma of saffron has a pleasant and invigorating effect., Aim of the Study: This study aimed to investigate the antidepressant effect and the underlying mechanism of saffron essential oil (SEO) in mice exposed to chronic unpredictable mild stress (CUMS)., Materials and Methods: In this study, compounds of SEO were identified using gas chromatography-mass spectrometry analysis, while network pharmacology was used to predict potential active compounds, antidepressant targets, and related signaling pathways of SEO. The CUMS depression model was further used to explore the therapeutic effect and possible mechanism of SEO. During the modeling period, mice were regularly administered fluoxetine (3.6 mg/kg, i.g.) or diluted SEO (2%, 4%, and 6% SEO, inhalation). The antidepressant and neuroprotective effects of SEO were evaluated by behavior tests (the open field test, the sucrose preference test, the tail suspension test, and the forced swimming test), hematoxylin-eosin staining, and Nissl staining. The enzyme-linked immunosorbent assay kits were used to measure dopamine (DA), 5-serotonin (5-HT), brain-derived neurotrophic factor (BDNF), and γ-aminobutyric acid (GABA) levels in serum. The relative abundance of Raf1, MEK1, P-ERK1/2/ERK1/2, P-CREB1/CREB1, BDNF, and P-Trk B/Trk B in the hippocampus was determined using western blot (WB)., Results: According to the network pharmacology analysis, seven active SEO compounds mediated 113 targets related to depression treatment, most of which were enriched in the 5-HT synapse, calcium signaling pathway, and cAMP signaling pathway. In vivo experiments indicated that fluoxetine and SEO improved depression-like behaviors in depressed mice. The levels of 5-HT, DA, BDNF, and GABA in serum increased significantly. Histopathological examinations revealed that fluoxetine and SEO ameliorated neuronal damage in the hippocampus. WB analysis showed that the relative expressions of Raf1, MEK1, P-ERK1/2/ERK1/2, P-CREB1/CREB1, BDNF, and P-Trk B/Trk B were significantly higher in the fluoxetine and SEO groups than in the CUMS group., Conclusion: Overall, these findings suggest that SEO significantly alleviates the depressive symptoms in CUMS exposed mice and partially restores hippocampal neuronal damage. Meanwhile, the best efficacy was observed in 4% SEO. Furthermore, the antidepressant mechanism of SEO is primarily dependent on the regulation of the MAPK-CREB1-BDNF signaling pathway., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Dendrobium officinalis Six nostrum (DOS) can be prepared by adding Dendrobium officinalis into Simiao Wan in accordance with the Traditional Chinese Medicine (TCM) theory and other previous findings. Our previous study has shown that DOS treatment can lead to a marked decrease in Serum UA (SUA) levels. The purpose of this study was to explore the effects of DOS on intestinal UA excretion in hyperuricemia and its underlying mechanisms., Methods: DOS was administered intragastrically to hyperuricemic rats induced by oral administration of HX and PO for 7 weeks. The SUA level, fecal UA and XOD activity were detected. The expressions of UA transporters (ABCG2, GLUT9, and PDZK1), CNT2, and tight junction proteins (ZO- 1 and claudin-1) in the intestine were assayed by IHC staining. The serum LPS and DAO levels were detected by ELISA kits. The intestinal histological changes were assessed using H&E staining., Results: DOS treatment decreased the SUA level while markedly increasing the fecal UA level by 28.85%~35.72%. Moreover, DOS effectively up-regulated the expression of ABCG2 and PDZK1 and down-regulated the expression of GLUT9 in the intestine. DOS markedly decreased the serum LPS level by 21.4%~32.1% and DAO activity by 12.3%~19.7%, which in turn ameliorated the intestinal pathology. As a result, it could protect intestinal barrier function, as indicated by the increase of villus height (V), the reduction of the crypt depth (C), and the elevation of the V/C ratio. It also increased the expression of ZO-1 and claudin-1. In addition, DOS significantly down-regulated the expression of CNT2, which reduced purine nucleoside transportation from the intestine into the blood, and inhibited XOD activity, leading to a decrease in UA production., Conclusion: DOS exerted anti-hyperuricemic effects via regulation of intestinal urate transporters and could protect intestinal barrier function by restoring the expressions of ZO-1 and claudin-1., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Rationale: Depression is a serious mood disorder, and crocetin has a variety of pharmacological activities, including antidepressant effect. The alterations of intestinal flora have a significant correlation with depression, and crocetin can alter the composition of intestinal flora in mice with depression-like behaviors., Objective: This study investigated the underlying antidepressant mechanisms of crocetin through multi-omics coupled with biochemical technique validation., Methods: Chronic unpredictable stress (CUMS) was used to induce mice model of depression to evaluate the antidepressant effect of crocetin through behavioral tests, and the metagenomic and metabolomic were used to explore the potential mechanisms involved. In order to verify its underlying mechanism, western blot (WB), Elisa, immune histological and HPLC techniques were used to detect the level of inflammatory cytokines and the level of metabolites/proteins related to tryptophan metabolism in crocetin-treated mice., Results: Crocetin ameliorated depression-like behaviors and increased mobility in depressive mice induced by CUMS. Metagenomic results showed that crocetin regulated the structure of intestinal flora, as well as significantly regulated the function gene related to derangements in energy metabolism and amino acid metabolism in mice with depression-like behaviors. Metabolomic results showed that the tryptophan metabolism, arginine metabolism and arachidonic acid metabolism played an essential role in exerting antidepressant-like effect of crocetin. According to multi-omics approaches and validation results, tryptophan metabolism and inflammation were identified and validated as valuable biological processes involved in the antidepressant effects of crocetin. Crocetin regulated the tryptophan metabolism in mice with depression-like behaviors, including increased aryl hydrocarbon receptor (AhR) expression, reduced indoleamine 2,3-dioxygenase 1 (IDO1) and serotonin transporter (SERT) expression in the hippocampus, elevated the content of 5-HT, kynurenic acid in serum and 5-HT, tryptophan in hippocampus. In addition, crocetin also attenuated inflammation in mice with depression-like behaviors, which presented with reducing the production of inflammatory cytokines in serum and colon. Meanwhile, crocetin up-regulated the expression of zonula occludens 1 (ZO-1) and occludin in ileum and colon to repair the intestinal barrier for preventing inflammation transfer., Conclusion: Our findings clarify that crocetin exerted antidepressant effects through its anti-inflammation, repairment of intestinal barrier, modulatory on the intestinal flora and metabolic disorders, which further regulated tryptophan metabolism and impacted mitogen-activated protein kinase (MAPK) signaling pathway to enhance neural plasticity, thereby protect neural., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Metabolic hypertension (MH) is characterized by elevated blood pressure accompanied by metabolic abnormalities, with the gut-derived lipopolysaccharide/toll like receptor 4 (LPS/TLR4) pathway an important triggering mechanism. The conventional Chinese plant Polygonatum sibiricum Red. is traditionally used as a medicinal and edible food source. Currently, several studies have examined its anti-obesity and anti-diabetic actions, with potential roles for MH treatment; however, specific P. sibiricum Red. roles in MH and associated mechanisms remain unclear., Objectives: Our purpose was to identify the effects and mechanisms of P. sibiricum Red. superfine powder (PSP) in a MH rat model triggered by high sugar and high fat compounds in an excessive alcohol diet (ACHSFDs)., Methods: A MH rat model was induced by ACHSFDs, and PSP was administered daily at 0.5 and 1.0 g/kg doses, respectively. Firstly, the effects of PSP on MH were assessed using blood pressure, serum lipid, and lipid deposition assays in the liver. Changes in intestinal flora were detected by high-throughput 16S rRNA sequencing, while metabolite short-chain fatty acids (SCFAs) and LPS levels were quantified by gas chromatography (GC) and enzyme-linked immunosorbent assay (ELISA), respectively. Hematoxylin & eosin (H&E) staining and transmission electron microscopy (TEM) were performed to evaluate histopathological changes in the rat colon. d-lactic acid (d-LA) levels and tight junction proteins (TJPs) expression were also measured to assess intestinal barrier function. Also, aortic endothelial microstructures, serum endothelin 1 (ET-1), and nitric oxide (NO) levels were investigated to determine vascular endothelial function. Finally, the TLR4/MyD88 signaling pathway in the aorta and gut was evaluated by western blotting, immunohistochemistry (IHC), and quantitative real-time polymerase chain reaction (qRT-PCR)., Results: Blood pressure and blood lipid metabolism disorders induced by ACHSFDs in MH rats were improved by PSP administration. Intestinal flora analyses revealed decreased SCFAs and LPS levels following PSP administration, which was accompanied by increased Streptococcus species levels and decreased Desulfobacter and Desulfovibrio species levels. PSP increased SCFAs levels, and the expression of SCFAs receptors GPCR41 and GPCR43 in the colon. Meanwhile, the expression of tight junction proteins (TJPs) such as Claudin-1, occludin were upregulated in the ileum and colon, while TLR4 and MyD88 were downregulated, thereby strengthening intestinal barrier integrity and reducing serum LPS levels. Additionally, PSP treatment improved vascular endothelial function by inhibiting the TLR4/MyD88 pathway in vessels, improving vascular endothelial cell shedding, and regulating the NO and ET-1 balance., Conclusions: We demonstrated the beneficial effects and potential mechanisms of PSP in our MH rat model. Based on gut microbiota structure modulation and intestinal barrier improvements, PSP inhibited LPS-induced vascular TLR4/MyD88 signaling activation to improve vascular endothelial function, which in turn reduced blood pressure. Our study provides valuable insights on PSP therapy for MH., Competing Interests: Declaration of Competing Interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022. Published by Elsevier GmbH.)

Ethnopharmacological Relevance: Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD), that is associated with a significantly increased risk of colon cancer. As a classic traditional Chinese medicine, Ganluyin (GLY) has a long history as an anti-inflammatory medication, but its impacts on UC has not been established., Aim of the Study: This study aims to evaluate the protective effect and mechanism of GLY on a pathway involving enteric-origin lipopolysaccharide (LPS), toll-like receptor (TLR)4, and NF-κB in mice with dextran sulfate sodium (DSS)-induced UC., Materials and Methods: After three weeks of intragastric administration of GLY, a UC model was induced in mice by administration of 4% DSS in drinking water for one week. The disease activity index (DAI) was measured, and histological staining was used to detect histopathological changes of colon. LPS content of the serum was measured by ELISA, and the expression of tight junction proteins and proteins related to TLR4/NF-κB pathway in colon were analyzed by immunohistochemistry or Western Blotting. The intestinal flora was analyzed by 16S rRNA sequencing., Results: GLY improved the histological pathological changes of DSS-induced UC, as assessed by DAI, colonic mucosal damage, inflammatory cell infiltration, and goblet cell and mucus reduction. GLY also protected the intestinal mucosal barrier by increasing the expression of the tight junction proteins, occludin, claudin-1, and ZO-1 and by reducing the serum LPS content and decreasing the expression of TLR4, MyD88, NF-κB, IL-6, IL-1β, and TNF-α proteins in colon. Analyses of the intestinal flora showed that GLY restored the homeostasis of the intestinal flora through increases in the abundance of Firmicutes and decreases in the abundance of Proteobacteria and Bacteroidetes, which is associated with the production of LPS., Conclusion: GLY might exert an anti-UC effect by improving the colonic mucosal barrier and inhibiting the enteric-origin LPS/TLR4/NF-κB inflammatory pathway, and restoring the homeostasis of the intestinal flora in UC mice. These discoveries lay a strong foundation for GLY as a UC treatment., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objective: This study was aimed at clarifying the application effect of silicone mattress combined with hydrocolloid dressing in ICU patients with liver failure., Methods: A total of 86 patients with liver failure admitted to the intensive care unit (ICU) of the Fifth Medical Center of Chinese PLA General Hospital from September 2018 to September 2020 were selected as the research subjects. Patients treated with conventional sponge mattress and routine nursing care were included in group A ( n = 43), and those treated with silicone mattress combined with hydrocolloid dressing were included in group B ( n = 43). The incidence of pressure ulcers and phlebitis, the scores of Visual Analogue Scale (VAS) and Pittsburgh Sleep Quality Index (PSQI), and the nursing satisfaction were observed and compared between the two groups., Results: The incidence of pressure ulcers in group B (6.98%) was lower than that in group A (25.58%). The incidence of phlebitis in group B was lower than that in group A (20.93% vs. 53.49%). The VAS score of group B was 2.16 ± 0.38, which was lower than that of group A (4.86 ± 1.09). The PSQI score of group B was lower than that of group A (9.74 ± 2.76 vs. 14.84 ± 3.95). A higher nursing satisfaction was determined in group B compared with group A (93.02% vs. 76.74%)., Conclusions: Silicone mattress combined with hydrocolloid dressing can reduce the incidence of pressure ulcers and phlebitis in ICU patients with liver failure, reduce complications, and improve nursing satisfaction, which is worthy of clinical promotion., Competing Interests: The authors declare no competing interests., (Copyright © 2022 Suhong Chen et al.)

Ethnopharmacological Relevance: Traditional Chinese medicine considers that the etiology and pathogenesis of non-alcoholic fatty liver disease (NAFLD) are related to liver depression and qi stagnation. Saffron and its active ingredient, crocetin (CCT), are used for the treatment of metabolic diseases owing to their "Liver deobstruent" and "Liver tonic" effects. However, the effect of CCT on NAFLD has not been fully elucidated. In the present study, the effect and potential molecular mechanism of CCT were explored in both in vivo and in vitro models of NAFLD., Materials and Methods: CCT was isolated from saffron and purity and structure characterization were performed using HPLC, MS, 1 H-NMR, and 13 C-NMR. The effect of CCT on the viability of L02 cells and its maximum tolerable concentration (MTC) in zebrafish were investigated. Free fatty acids (FFA) and thioacetamide (TAA) were used to induce lipid accumulation in L02 cells and steatosis in zebrafish, respectively. The effects of CCT on indexes related to lipid metabolism, oxidative stress, and mitochondrial function in NAFLD models were explored using biochemical assay kits, Western blot analysis, Reverse Transcription-Polymerase Chain Reaction (RT-PCR), histopathology analysis, and determination of mitochondrial membrane potential (ΔΨm). Morphological analysis of mitochondria was performed using transmission electron microscopy (TEM)., Results: The levels of triglyceride (TG), total cholesterol (TC), malondialdehyde (MDA), and alanine/aspartate aminotransferases (ALT/AST) activities in FFA treated L02 cells were significantly reduced after CCT treatment. CCT treatment significantly increased ATP concentration, ΔΨm, and activities of superoxide dismutase (SOD), catalase (CAT), and cytochrome c oxidase (COX IV) in FFA treated L02 cells. TEM images showed restoration of mitochondrial morphology. CCT decreased ATP concentration and upregulated expression of B-cell lymphoma-2 (Bcl-2) and COX IV, whereas, CCT downregulated expression of BCL2-Associated X (Bax) and cleaved caspase-3 in TAA treated zebrafish. These findings indicated that mitochondrial dysfunction was alleviated after CCT treatment. Oil Red O staining of L02 cells and zebrafish showed that CCT treatment reversed the accumulation of lipid droplets., Conclusion: In summary, CCT treatment effectively alleviated the symptoms of NAFLD and restored mitochondrial function in L02 cells and zebrafish NAFLD model., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: The root of Paeonia lactiflora is a traditionally-used whitening medicine in China for thousands of years. Although some tyrosinase inhibitors and/or antioxidants such as 1,2,3,4,6-pentagalloylglucose, gallic acid, have been isolated and identified, their tyrosinase inhibition pathway (monophenolase or diphenolase inhibition, or both two) have not been systematically studied and the underlying tyrosinase inhibition mechanism has not been revealed yet. Moreover, the exploring of new natural tyrosinase inhibitors and antioxidants is urgently needed., Aim of the Study: This review aimed to develop a new microplate-based high-resolution tyrosinase inhibition profiling assay and establish a furthermore triple high-resolution monophenolase/diphenolase/radical scavenging profiling for accelerating identification bioactive compounds from complicated plant extract., Materials and Methods: The targeted isolation and structure elucidation were performed with high-performance liquid chromatography-high-resolution mass spectrometry and preparative high-performance liquid chromatography. It allows to be a proof of concept with the root of Paeonia lactiflora crude extract as a natural whitening herbal drug., Results: The result showed that galloylpaeoniflorin specifically inhibited monophenolase activity. While 1,2,3,4,6-pentagalloylglucose, gallic acid and catechin demonstrated the inhibition towards both monophenolase and diphenolase. Among them, 1,2,3,4,6-pentagalloylglucose can inhibit monophenolase activity was reported for the first time. In addition, antioxidant properties were attributed to catechin, 1,2,3,4,6-pentagalloylglucose and gallic acid. Due to its low content and complicated configuration in the root of Paeonia lactiflora, a new potential tyrosinase inhibitor and radical scavenger which tentatively identified as hexagalloylglucose by high-resolution MS was still need further verification. What's more, the molecular docking unveiled that bioactive enzymatic inhibitors mainly interacted with amino acid catalytic residues of tyrosinase via H-bonds and van der wals, which may be helpful to understand their inhibition mechanisms with tyrosinase in the skin whitening., Conclusions: The platform provided a promising and efficient strategy for the rapid screening of whitening active components from natural sources., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Generalized Anxiety Disorder (GAD) is a common but urgent mental health problem during disease outbreaks. Resilience buffers against the negative impacts of life stressors on common internalizing psychopathology such as GAD. This study assesses the prevalence of GAD and examines the protective or compensatory effect of resilience against worry factors during the COVID-19 outbreak., Methods: A cross-sectional online survey was conducted among Chinese citizens aged ≥18 years from January 31 to February 2, 2020. A total of 4827 participants across 31 provinces and autonomous regions of the mainland of China participated in this study. The Generalized Anxiety Disorder scale (GAD-7), the Connor-Davidson Resilience Scale (CD-RISC), and a self-designed worry questionnaire were used to asses anxiety disorder prevalence, resilience level, and anxiety risk factors. Multivariable logistic regression was used to identify the associations of resilience and worry factors with GAD prevalence after controlling for other covariates., Results: The prevalence of anxiety disorder was 22.6% across the 31 areas, and the highest prevalence was 35.4% in Hubei province. After controlling for covariates, the results suggested a higher GAD prevalence among participants who were worried about themselves or family members being infected with COVID-19 (adjusted odds ratio, AOR 3.40, 95%CI 2.43-4.75), worried about difficulty obtaining masks (AOR 1.92, 95%CI 1.47-2.50), worried about difficulty of distinguishing true information (AOR 1.65, 95%CI 1.36-2.02), worried about the prognosis of COVID-19 (AOR 2.41, 95%CI 1.75-3.33), worried about delays in working (AOR 1.71, 95%CI 1.27-.31), or worried about decreased income (AOR 1.45, 95%CI 1.14-1.85) compared with those without such worries. Additionally, those with a higher resilience level had a lower prevalence of GAD (AOR 0.59, 95%CI 0.51-0.70). Resilience also showed a mediating effect, with a negative influence on worry factors and thereby a negative association with GAD prevalence., Conclusion: It may be beneficial to promote public mental health during the COVID-19 outbreak through enhancing resilience, which may buffer against adverse psychological effects from worry factors., (© 2021. The Author(s).)

Background: Yeju Jiangya decoction (CIF) is an herbal formula from traditional Chinese medicine (TCM) for the treatment of hypertension., Materials and Methods: Based on the analysis of network pharmacology, combined with in animal experiments, the network pharmacology was used to explore the potential proteins and mechanisms of CIF against hypertension. The bioactive compounds of CIF were screened by using the platform, and the targets of hypertension and CIF were collected. Then, the Kyoto Encyclopedia of Genes and Genomes (KEGG) and protein-protein interaction network (PPI) core targets were carried out, and the useful proteins were found by molecular docking technology. Finally, we used N-nitro-L-arginine (L-NNA) induced hypertension model rats to confirm the effect and mechanism of CIF on hypertension., Results: 14 bioactive compounds of CIF passed the virtual screening criteria, and 178 overlapping targets were identified as core targets of CIF against hypertension. The CIF-related target network with 178 nodes and 344 edges is constructed. The topological results show that quercetin and luteolin are the key components in the network. The key targets NOS3 (nitric oxide synthase 3) and NOS2 (nitric oxide synthase 2) were screened by the protein-protein interaction network. The analysis of target protein pathway enrichment showed that the accumulation pathway is related to the vascular structure of CIF regulation of hypertension. Further verification based on molecular docking results showed that NOS3 had the good binding ability with quercetin and luteolin. On the other hand, NOS3 has an important relationship with the composition of blood vessels. Furthermore, the animal experiment indicated that after the L-NNA-induced hypertension rat model was established, CIF intervention was given by gavage for 3 weeks, and it can decrease serum concentrations of endothelin-1 (ET-1) and thromboxane B2 (TXB 2 ), increase the expression of nitric oxide (NO) and prostacyclin 2 (PGI 2 ), and improve renal, cardiac, and aortic lesions. At the same time, it can reduce blood pressure and shorten vertigo time. Western blot (WB) and immunohistochemistry (IHC) analyses indicated that CIF may downregulate the expression of NOS3, guanylyl cyclase-alpha 1 (GC- α 1), guanylyl cyclase-alpha 2 (GC- α 2), and protein kinase CGMP-dependent 1 (PRKG1). These results suggest that CIF may play an antihypertensive role by inhibiting the activation of the NOS3/PRKG1 pathway., Conclusions: The results of this study indicate that CIF has the ability to improve target organs, protect endothelial function, and reduce blood pressure and that CIF might be a potential therapeutic drug for the prevention of hypertension. It provides new insight into hypertension and the potential biological basis and mechanism for CIF clinical research., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Ting Wang et al.)

Oral squamous cell carcinoma (OSCC) is one of the most common types of cancers in developing countries. A major contributor to the high mortality rate of OSCC is the tendency of oral cancer cells to metastasize to lymph nodes around the head and neck during the early stages of cancer development. Matrix metalloproteinase 9 (MMP-9), an endopeptidase, can degrade the extracellular matrix and basement membrane and plays a key role in tumor invasion and metastasis. In vitro , cell migration ability was conducted by scratching assays. We also investigated the interaction abilities between OSCC cells and vascular endothelial cells (ECs) by an adhesion assay and transendothelial migration assay. And we established a BALB/c nude mouse tongue-xenografted metastasis model to investigate the role of MMP-9 and explore its potential underlying mechanism in OSCC growth, lymph node metastasis, and angiogenesis in vivo . The results showed that knockdown of MMP-9 could significantly suppress OSCC cell migration, proliferation, interactions between endothelial cells, xenografted tumor growth, and angiogenesis and simultaneously markedly inhibited OSCC cell metastasis to mouse lymphonodi cervicales superficiales, axillary lymph nodes, and even distant inguinal lymph nodes. Mechanistic studies revealed that knockdown of MMP-9 also led to a decreased expression of RhoC, Src, and F-actin by RT-PCR, western blotting, and immunohistochemistry. And the bioinformatic analysis showed that MMP-9, RhoC, and Src mRNA expression was positively and linearly correlated in OSCC on TCGA database. Together, our findings indicated that MMP-9 plays a very important role in OSCC growth, migration, angiogenesis, and lymph node metastasis, and its potential mechanism may be mediated by RhoC and Src gene expression., Competing Interests: The authors declare that they have no conflict of interests., (Copyright © 2021 Panpan Yin et al.)

Objectives: The aims of this study were to assess the uptake of preventive behaviour during the COVID-19 outbreak and to investigate the factors influencing the uptake of preventive behaviour based on the theory of planned behaviour (TPB）., Design, Setting and Participants: A cross-sectional online survey was conducted among Chinese residents aged ≥18 years and 4827 participants from 31 provinces and autonomous regions were included in the current study. Uptake of preventive behaviour, attitude towards the spread of COVID-19 and preventive behaviour, subjective norms, perceived behavioural control, demographic characteristics and the information attention and processing mode were measured. Multivariate logistic regressions were used to identify associations between the potential influencing factors and uptake of preventive behaviour., Results: There were 2393 (52.8%) respondents reported high uptake of preventive behaviour. Multivariate analyses demonstrated that attitude towards the behaviour, subjective norms and perceived behavioural control were significantly correlated with uptake of preventive behaviour, and perceived behavioural control was the strongest influencing factor (OR=4.09, 95% CI 3.57 to 4.69). Furthermore, systematic information processing mode was positively associated with high uptake of preventive behaviour compared with heuristic information processing mode (OR=2.16, 95% CI 1.67 to 2.81)., Conclusions: These findings are helpful for developing education and interventions to promote high uptake of preventive behaviour and enhance public health outcomes during pandemic., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To investigate the effect of Chinese medicine Wubi Shanyao pills on sexual function of kidney-yang-deficiency mice induced by hydrocortisone., Methods: Male Kunming mice were injected with hydrocortisone for 10 days to prepare the kidney-yang-deficiency model, and administrated with Wubi Shanyao pills (0.91, 1.82, 2.73 g/kg) for 9 weeks. The general behaviors of mice (autonomous activity, grasping power) were observed; sexual behaviors (capture, straddle, ejaculation frequency and incubation period) of mice were detected by mating experiment. The serum levels of cortisol, adrenocorticotropic hormone (ACTH), luteinizing hormone (LH), follicle stimulating hormone (FSH), estradiol (E 2 ) and testosterone were measured by ELIZA. The organ indexes of kidney, epididymis, testis and seminal vesicle were calculated. The histomorphology of testis was observed by HE staining. The apoptosis of testis cells was detected by TUNEL; and the expression level of proliferating cell nuclear antigen (PCNA) in testis was detected by immunohistochemistry., Results: Wubi Shanyao pills increased the number of independent activities, grasping power, capture frequency of model mice and shortened the capture latency (all P <0.01); and also increased the serum levels of testosterone, cortisol, ACTH, decreased the serum levels of FSH ( P <0.05 or P <0.01); increased testis index ( P <0.05), improved the pathological changes of testis, inhibited cell apoptosis, and promoted PCNA protein expression in testis., Conclusions: Wubi Shanyao pills can improve the sexual function of mice with kidney-yang-deficiency induced by hydrocortisone, which may be related to regulating the hypothalamus-pituitary-adrenal axis (HPA axis), promoting the proliferation of testicular cells, and inhibiting cell apoptosis.

Ethanol-induced gastric mucosal injury is a common gastrointestinal disorder. Polysaccharides separated from herbs have been shown to be effective for ethanol-induced gastric mucosal injury, but whether the polysaccharides from Dendrobium officinale Kimura & Migo leaves (LDOP-1) protected mucosa from ethanol-induced injury remains unknown. Thus, the present study carried out gastric mucosal protection and the mechanism of LDOP-1 in vivo and vitro . The chemical composition of LDOP-1 was a heteropolysaccharide comprising mannose, galacturonic acid, glucose, galactose, and arabinose at a molar ratio of 2.0:1.1:0.7:0.5:0.4. Pharmacological results showed that LDOP-1 significantly reduced gastric mucosal injury score and pathological injury, improved antioxidant capacity, reduced the level of reactive oxygen species, and reversed the apoptosis of GES-1 in vivo and vitro . Research showed that LDOP-1 pretreatment upregulated the expression level of p-AMPK, LC3β, HO-1, and Beclin-1; downregulated the expression level of p-mTOR and p62; and reversed the expression level of caspase3, Bax, and Bcl-2. This study was the first to demonstrate that LDOP-1 could protect against ethanol-induced gastric mucosal injury via the AMPK/mTOR signaling pathway in vitro and vivo ., (Copyright © 2020 Ke, Zhan, Lu, Zhou, Chen, Dong, Lv and Chen.)

Huge citizens expose to social media during a novel coronavirus disease (COVID-19) outbroke in Wuhan, China. We assess the prevalence of mental health problems and examine their association with social media exposure. A cross-sectional study among Chinese citizens aged≥18 years old was conducted during Jan 31 to Feb 2, 2020. Online survey was used to do rapid assessment. Total of 4872 participants from 31 provinces and autonomous regions were involved in the current study. Besides demographics and social media exposure (SME), depression was assessed by The Chinese version of WHO-Five Well-Being Index (WHO-5) and anxiety was assessed by Chinese version of generalized anxiety disorder scale (GAD-7). multivariable logistic regressions were used to identify associations between social media exposure with mental health problems after controlling for covariates. The prevalence of depression, anxiety and combination of depression and anxiety (CDA) was 48.3% (95%CI: 46.9%-49.7%), 22.6% (95%CI: 21.4%-23.8%) and 19.4% (95%CI: 18.3%-20.6%) during COVID-19 outbroke in Wuhan, China. More than 80% (95%CI:80.9%-83.1%) of participants reported frequently exposed to social media. After controlling for covariates, frequently SME was positively associated with high odds of anxiety (OR = 1.72, 95%CI: 1.31-2.26) and CDA (OR = 1.91, 95%CI: 1.52-2.41) compared with less SME. Our findings show there are high prevalence of mental health problems, which positively associated with frequently SME during the COVID-19 outbreak. These findings implicated the government need pay more attention to mental health problems, especially depression and anxiety among general population and combating with "infodemic" while combating during public health emergency., Competing Interests: The authors have declared that no competing interests exist.

The polysaccharide was first successfully isolated from the leaf of Dendrobium officinale by hot water extraction and alcohol precipitation and further purified using DEAE-52 and Sephadex G-100 chromatography. The structure of LDOP-1 was characterized by HPLC, GPC, and FT-IR and NMR spectroscopy, and its protective effect on LPS-induced GES-1 cell injury was analyzed. Results showed that LDOP was a homogeneous polysaccharide with average molecular weight of 91.8 kDa and consisted of Man, Gla, Glc, Glc acid, and Ara at a molar ratio of 2.0:1.3:1.6:1.7:0.7. LDOP had two types of residues, including 1,6-linked α-d-Glup and 1,4-linked α-d-Manp. Activity studies indicated that LDOP-1 can significantly suppress the release of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-6 from LPS-induced GES-1 cell injury, decreased the protein expressions of TLR4, phospho-NF-κB, ASC, NLRP3, cleaved-IL-1β, IL-6, and Bax, increased the protein expression of Bcl-2, and downregulated the ratios of cleaved caspase-1 to pro-caspase-1, phospho-IκBα to IκBα, and phospho-NF-кB to NF-κB. These findings strongly suggested that LDOP can prevent LPS-induced GES-1 cell injury by inhibiting the release of inflammatory cytokines regulated via the TLR4/NF-κB signal pathways., Competing Interests: Declaration of competing interest All authors declared no conflict of interest., (Copyright © 2020. Published by Elsevier B.V.)

Alcohol-induced liver injury is characterized by strong inflammation. Polysaccharides separated from herbs can prevent ethanol-induced liver injury. Dendrobium officinale Kimura et Migo leaves (D. officinale) are a new food resource that contains a certain amount of polysaccharide. However, the hepatoprotective effects and the potential mechanisms of D. officinale polysaccharide (DOP) remain unknown. Thus, this study aimed to assess the hepatoprotective effects and potential mechanism in vivo and in vitro of DOP. Male Sprague-Dawley rats were used to establish alcohol-induced liver injury models through the oral gavage of absolute alcohol (5 mL/kg) after the oral administration of DOP (400 and 100 mg/kg) for 30 days. Hematoxylin-eosin staining was used for the histological assessments of hepatocyte degeneration, and the AST and ALT levels in the serum and liver tissue were measured. The inflammatory markers were evaluated using ELISA and immunohistochemistry. The potential mechanism of DOP in alcohol-induced liver cell (LO 2 ) injury in vitro was further identified. Results showed that DOP clearly decreased the AST in the serum and hepatic tissue, obviously reduced the production of inflammatory cytokines (such as IL-1β, IL-6, and TNF-α), and can successfully inhibit NF-κB phosphorylation in vivo. In vitro experiments indicated that DOP increased the LO 2 cell viability; prevented LDH release prominently; reduced the secretion of IL-1β, IL-6, and TNF-α; and reversed the expression of IL-1β, IL-6, TNF-α, caspase 1, NLRP3, p-NF-κB, and TLR4. Overall, DOP can alleviate ethanol-induced acute liver injury via the TLR4/NF-κB signaling pathway., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020. Published by Elsevier Ltd.)

Brigatinib and brigatinib-analog are potent and selective ALK inhibitors with the similar structure. A simple and sensitive high-performance liquid chromatography with tandem mass spectrometry (LC-MS/MS) method for simultaneous determination of brigatinib and brigatinib-analog in rat plasma and brain homogenate was developed and validated. Chromatographic separation was carried out on an ODS column with acetonitrile and 0.1% formic acid in water as the mobile phase with gradient elution at a flow rate of 0.5 mL/min. Detections were performed using a TSQ Quantum Ultra mass spectrometric detector with electrospray ionization (ESI) interface, which was operated in the positive ion mode. A simple protein precipitation preparation process was used. The lower limits of quantification (LLOQs) were 1.0 ng/mL and 0.5 ng/mL for analytes in rat plasma and brain homogenate, respectively. The intrabatch and interbatch precision and accuracy of brigatinib and brigatinib-analog were well within the acceptable limits of variation. The simple and sensitive LC-MS/MS method was successfully applied to the pharmacokinetic and brain distribution studies following a single oral administration of brigatinib and brigatinib-analog to rats. The above studies would lay a good foundation for the further applications of brigatinib and brigatinib-analog., Competing Interests: The authors have declared no conflicts of interest., (Copyright © 2019 Bo Li et al.)

We aimed to investigate the pharmacokinetics, bioavailability and urinary excretion of scopolin and its metabolite scopoletin in rats. An LC-tandem mass spectrometry (MS/MS) method for simultaneous determination of scopolin and scopoletin in rat biomatrices was developed and validated over a plasma and urine concentration range of 5.0-2000 ng/mL. Chromatographic separation was performed on a Hypersil GOLD C 18 column with acetonitrile and 0.1% formic acid in water as mobile phase with gradient elution. Detection was performed in the positive ionization and selected reaction monitoring mode. The intra- and inter-batch precision and accuracy, extraction recovery and matrix effect and stability of scopolin and scopoletin were well within the acceptable limits of variation. There was no gender-related difference in the pharmacokinetic profiles of scopolin. There were significant differences in total area under the concentration-time curve (AUC), time required to achieve a maximal concentration (T max ) and apparent clearance from plasma (Cl/F) of scopoletin between the male and female rats (p < .05). The bioavailability (F) of scopolin was exceptionally low. The maximal excretion rates were 7.61 μg/h and 7.15 μg/h for scopolin and 31.68 μg/h and 25.58 μg/h for scopoletin in male and female rats, respectively. The LC-MS/MS method was successfully applied to the pharmacokinetic, bioavailability and urinary excretion studies of scopolin and its metabolite scopoletin following a single administration of scopolin to rats., (© 2019 John Wiley & Sons, Ltd.)

To investigate the possibility of tedizolid phosphate's application in the treatment of intracranial infection, a preclinical comparative pharmacokinetic study was designed. Based on the assumption that the classic efflux transporters P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) may participate in the transportation of TDZ, two groups of rats were intravenously administered 6 mg/kg tedizolid phosphate alone or 6 mg/kg tedizolid phosphate combined with 1 mg/kg elacridar which was an inhibitor of P-gp and BCRP. Plasma and cerebrospinal fluid samples were collected according to a pharmacokinetic schedule. All the plasma and cerebrospinal fluid samples were assessed with a validated LC-MS/MS method. The penetration ratio of tedizolid from the blood to cerebrospinal fluid was calculated, and a comparison of the penetration ratios between the two groups was made. The mean C max of tedizolid in the CSF in the tedizolid phosphate group and the tedizolid phosphate combined with elacridar group was 154 ng/mL and 300 ng/mL, respectively, and the mean penetration ratio of tedizolid in the tedizolid phosphate group and the tedizolid phosphate combined with elacridar group was 2.16% and 3.53%, respectively. The relatively high C max in the CSF proved the possibility of tedizolid phosphate's application in the treatment of intracranial infection, and the higher penetration ratios, C max, csf and AUC csf of the rats in co-administered elacridar group than those in the single-administration group indicated that the transporters P-gp and BCRP might be involved in the transportation of tedizolid., (Copyright © 2019. Published by Elsevier Inc.)

In order to establish the extraction technology of flavonoids from Dendrobium officinale leaves, a method combining Plackett-Burman design (PBD), steepest ascent design, and central composite design was developed to optimize the extraction of flavonoids. In addition, the tyrosinase activity inhibition of flavonoids was further tested in vitro. PBD results showed that ethanol concentration and number of extractions were key factors. Response surface methodology (RSM) indicated that the optimal extraction conditions were 78% ethanol concentration, six extraction times, 2 h, and 1:50 solid-liquid ratio. Under these conditions, the total flavonoid content could reach 35 mg/50 mL. In vitro tyrosinase experiment, the extracted total flavonoids had better inhibitory effect on tyrosinase activity than β -arbutin, and its inhibition rate for monophenolase and diphenolase exceeded 100% and 70%, respectively. These results indicate that RSM can effectively improve the extraction of flavonoids from Dendrobium officinale leaves and the flavonoids have the prospect of being applied to foods and cosmetics.

Background: With the increasing number of dementia patients in China, there is a pressing need for a reliable and valid Chinese instrument that can measure neuropsychiatric symptoms in institutionalized dementia patients. This study examined the reliability and structural validity of the Chinese version of the Neuropsychiatric Inventory, Nursing Home version (NPI-NH), in a sample of institutionalized dementia patients in China., Methods: A total of 112 residents with dementia (Clinical Dementia Rating = 1: 10.7%; Clinical Dementia Rating = 2: 39.3%; Clinical Dementia Rating = 3: 50.0%) and 30 informants participated in this cross-sectional study. Reliability was tested using Cronbach's α and intra-class correlation coefficient. Principal component analysis was used to evaluate the factor structure of the inventory., Results: Of the patients, 92.9% had at least one neuropsychiatric symptom. Apathy (57%) was the most common symptom. The Chinese version of the Neuropsychiatric Inventory, Nursing Home version, showed acceptable internal consistency (Cronbach's α for the total scale, frequency, severity, and disturbance subscales were 0.64, 0.70, 0.73, and 0.80, respectively) and test-retest reliability (intra-class correlation coefficient for the total scale, frequency, severity, and disturbance subscales were 0.93, 0.92, 0.89, and 0.91, respectively). Five factors-psychomotor behaviour, affective symptoms, psychosis, sleep disorders, and eating disorders-were identified for the total scale. The cluster symptoms aggression and irritability, depression and anxiety, and delusions and hallucinations were three of the optimally stable groups of symptoms., Conclusions: This study demonstrated that the Chinese version of the Neuropsychiatric Inventory, Nursing Home version, is a valid and reliable instrument for evaluating neuropsychiatric symptoms in institutionalized dementia patients., (© 2018 Japanese Psychogeriatric Society.)

Esophageal squamous cell carcinoma (ESCC) is an aggressive malignancy that is often resistant to therapy. Nowadays, chemotherapy is still one of the main methods for the treatment of ESCC. However, the multidrug resistance (MDR)-mediated chemotherapy resistance is one of the leading causes of death. Exploring agents able to reverse MDR, which thereby increase the sensitivity with clinical first-line chemotherapy drugs, could significantly improve cancer treatment. Cepharanthine hydrochloride (CEH) has the ability to reverse the MDR in ESCC and the mechanism involved have not been reported. The aim of the study was to investigate the potential of CEH to sensitize chemotherapeutic drugs in ESCC and explore the underlying mechanisms by in vitro and in vivo studies. Our data demonstrated that CEH significantly inhibited ESCC cell proliferation in a dose-dependent manner, induced G2/M phase cell cycle arrest and apoptosis, and increased the sensitivity of cell lines resistant to cisplatin (cDDP). Mechanistically, CEH inhibited ESCC cell growth and induced apoptosis through activation of c-Jun, thereby inhibiting the expression of P-gp, and enhancing p21 expression via activation of the p53 signaling pathway. In this study, we observed that growth of xenograft tumors derived from ESCC cell lines in nude mice was also significantly inhibited by combination therapy. To our knowledge, we demonstrate for the first time that CEH is a potentially effective MDR reversal agent for ESCC, based on downregulation of the mRNA expression of MDR1 and P-gp. Together, these results reveal emphasize CEH putative role as a resistance reversal agent for ESCC., Competing Interests: CONFLICTS OF INTEREST The authors have no conflicts of interest.

BACKGROUND Paeoniflorin is a monoterpene glycoside extracted from the roots of Paeonia lactiflora and is used in Chinese herbal medicine to treat hyperlipidemia. The aim of this study was to evaluate the effects of an enriched extract of paeoniflorin on cholesterol levels, hemodynamics, and oxidative stress in a hyperlipidemic rat model. MATERIAL AND METHODS Male Sprague-Dawley rats were fed high-cholesterol diets and treated with three different doses of paeoniflorin for 12 weeks. The effects of paeoniflorin treatment were assessed on cholesterol levels, cholesterol metabolism, red blood cell vascular flow using hemorheology, antioxidant enzymes, and expression of the rate-limiting enzyme in the mevalonate pathway, 3-hydroxy-3-methylglutharyl-coenzyme A reductase (HMG-CoAR). Rat liver histology and immunohistochemical analysis were performed to evaluate the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), cytochrome P450 7A1 (CYP7A1), and peroxisome proliferator-activated receptors (PPAR)-α. Protein expression HMG-CoAR, low-density lipoprotein receptor (LDLR), PPAR-α and CYP7A1 was measured by Western blotting. Antioxidant activity in rat liver was determined by measuring superoxide dismutase (SOD) and malondialdehyde (MDA). RESULTS Serum and hepatic cholesterol, hepatic steatosis and the products of cholesterol metabolism were reduced by paeoniflorin treatment, which also reduced the activity of HMG-CoAR and upregulated the expression of LDLR, PPAR-α, and CYP7A1 expression, increased SOD, decreased MDA, and upregulated Nrf2 expression. CONCLUSIONS The findings of this study in a rat model of hyperlipidemia have shown that paeoniflorin regulates hepatic cholesterol synthesis and metabolism and may also protect the liver from oxidative stress.

BACKGROUND The aim of this study was to study the effects of gypenosides (GPS) on lowering uric acid (UA) levels in hyperuricemic rats induced by lipid emulsion (LE) and the related mechanisms. GPS are natural saponins extracted from Gynostemma pentaphyllum. MATERIAL AND METHODS Forty-eight male SD rats were randomly divided into six groups: normal, model, two positive controls, and two GPS treated groups (two different doses of GPS). The normal group rats were fed a basic diet, and the other rats were orally pretreated with LE. Urine and blood were collected at regular intervals. Full automatic biochemical analyzer was used to detect the concentration levels of serum UA (SUA), serum creatinine (SCr), BUN, and urine UA (UUA), and urine creatinine (UCr) and fractional excretion of UA (FEUA). ELISA kits were used to detect enzymes activities: xanthine oxidase (XOD), adenosime deaminase (ADA), guanine deaminase (GDA), and xanthine dehydrogenase (XDH). Immunohistochemistry was used to observe kidney changes and protein (URAT1, GLUT9, and OAT1) expression levels. RT-PCR was used to detect the relevant mRNA expression levels. RESULTS Treatment with GPS significantly reduced the SUA, prevented abnormal weight loss caused by LE, and improved kidney pathomorphology. Treatment with GPS also decreased the levels of XOD, ADA, and XDH expression, increased the kidney index and FEUA, downregulated URAT1 and GLUT9 expression and upregulated OAT1 expression in the kidney. CONCLUSIONS GPS may be an effective treatment for hyperuricemia via a decrease in xanthine oxidoreductase through the XOD/XDH system; and via an increase in urate excretion through regulating URAT1, GLUT9, and OAT1 transporters.

Background: Mosquito-borne viruses (MBVs) and parasites (MBPs) are transmitted through hematophagous arthropods-mosquitoes to homoiothermous vertebrates. This study aims at developing a detection method to monitor the spread of mosquito-borne diseases to new areas and diagnose the infections caused by MBVs and MBPs., Methods: In this assay, an ultra-sensitive chemiluminescence (CL) detection method was developed and used to simultaneously detect 19 common MBVs and MBPs. In vitro transcript RNA, virus-like particles (VLPs), and plasmids were established as positive or limit of detection (LOD) reference materials., Results: MBVs and MBPs could be genotyped with high sensitivity and specificity. The cut-off values of probes were calculated. The absolute LODs of this strategy to detect serially diluted in vitro transcribed RNAs of MBVs and serially diluted plasmids of MBPs were 10 2 -10 3 copies/μl and 10 1 -10 2 copies/μl, respectively. Further, the LOD of detecting a strain of pre-quantified JEV was 10 1.8 -10 0.8 PFU/ml, fitted well in a linear regression model (coefficient of determination = 0.9678)., Conclusions: Ultra-sensitive CL imaging DNA hybridization was developed and could simultaneously detect various MBVs and MBPs. The method described here has the potential to provide considerable labor savings due to its ability to screen for 19 mosquito-borne pathogens simultaneously.

Background: Transarterial chemoembolization (TACE), a well-established treatment for unresectable hepatocellular carcinoma (HCC), blocks the arterial blood supply to the tumor, which can be short-lived as development of collateral neovessels, leading to the failure of treatment. Metastasis-associated protein 1 (MTA1) is involved in development of tumors and metastases. However, the role of MTA1 in angiogenesis is still obscure., Methods: We detected the expression of MTA1 and hypoxia-inducible factor-1 α (HIF-1 α ) and microvessel density (MVD) value in liver tumor tissues and tumor periphery before and after TACE treatment. Hepatocellular carcinoma cell line HepG2, tube formation assay, and chorioallantoic membrane (CAM) assay were applied to explore the mechanism of MTA1 in angiogenesis., Results: We found that expression of MTA1 increased after TACE treatment, especially in tumor periphery, which was accompanied by markedly elevated MVD value, indicating a significant correlation between MTA1 and MVD value. Moreover, MTA1 contributed to neovascularization of residual tumors. Cellular experiments further revealed that MTA1 increased the stability and the expression of HIF-1 α , and overexpression of MTA1 enhanced tube formation and neovessels of chick embryos., Conclusions: MTA1 is an active angiogenic regulator; our results shed light on better understanding in neovascularization, which are helpful to predict prognosis of TACE, and provide evidences for intervention to improve therapeutic effects on HCC.

Chronic hepatitis B (CHB) is prevalent worldwide and can develop into liver cirrhosis and liver carcinoma. Early discrimination of liver cirrhosis from chronic hepatitis is critical for effective treatment and optimal prognosis. The aim of the present study was to assess the diagnostic value of a panel of cellular proteins that can be recognized by autoantibodies in patient serum for hepatitis B virus (HBV)‑related liver cirrhosis. Twenty‑two candidate autoantigens screened using a serum proteomics assay in our previous study were assessed retrospectively in 443 participants, comprising 89 patients with HBV‑related liver cirrhosis, 89 patients with CHB, and 265 healthy controls. The levels of autoantibodies against the candidate autoantigens were measured by protein microarrays containing the candidate antigen proteins. Receiver operating characteristic (ROC) curves were used to calculate the diagnostic accuracy. The present study determined that seven of the 22 candidate autoantibodies differed significantly in serum level between HBV‑related liver cirrhosis and CHB (P<0.0001), with area under curve (AUC) values >0.7. The seven autoantibodies recognized aminoacylase‑1 (ACY1), histidine triad nucleotide‑binding protein 1, insulin‑like growth factor 2 mRNA‑binding protein 2, heat shock 70 kDa protein 6, peroxiredoxin 3, apoptosis‑inducing factor and regucalcin. Among these, the ACY1 autoantibody had the highest value for discriminating HBV‑related liver cirrhosis from CHB, with an AUC value of 0.872 (95% confidence interval: 0.810‑0.934, P<0.0001), sensitivity of 77.3% and specificity of 85.0%. In conclusion, with the elevated level in the disease progression of CHB, ACY1 autoantibody may be a valuable serum biomarker for discriminating HBV‑related liver cirrhosis from CHB.