Antioxidant Defenses Against Air Humidity Stress in Fruit Bodies of Auricularia heimuer (Agaricomycetes).

Air humidity is an important environmental factor restricting the fruit body growth of Auricularia heimuer. Low air humidity causes the fruit body to desiccate and enter dormancy. However, the survival mechanisms to low air humidity for fruit bodies before dormancy remain poorly understood. In the present study, we cultivated A. heimuer in a greenhouse and collected the fruit bodies at different air humidities (90%, 80%, 70%, 60%, and 50%) to determine the contents of malondialdehyde (MDA) and non-enzymatic antioxidants such as ascorbic acid (AsA) and glutathione (GSH); and the activities of enzymatic antioxidants including superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), ascorbate peroxidase (APX), glutathione peroxidase (GPX) and glutathione reductase (GR). Results showed that the MDA contents tended to increase with decreasing relative air humidity. Relative air humidity below 90% caused membrane lipid peroxidation and oxidative stress (based on MDA contents) to the fruit body, which we named air humidity stress. In contrast to the control and with the degree of stress, the GSH contents and activities of SOD, CAT, GR, GPX, and APX tended to ascend, whereas AsA showed a declining trend; the POD activity only rose at 50%. The antioxidants favored the fruit body to alleviate oxidative damage and strengthened its tolerance to air humidity stress. The antioxidant defense system could be an important mechanism for the fruit body of A. heimuer in air humidity stress.

Novel Y2O3 based calcium-alginate beads for highly selective adsorption of phosphate from aqueous solution.

Recently, selective phosphorus removal from aqueous solution has been a highly desirable strategy to combat eutrophication due to the increasingly stringent phosphorous emission standards. However, conventional adsorbents pose the limitations in phosphate removal suffering from lack of selectivity and stability under complicated condition and poor separation. In this study, novel Y2O3 based calcium-alginate (Y2O3/SA) beads of feasible stability and highly selectivity towards phosphate by encapsulating Y2O3 nanoparticles inside calcium-alginate beads via Ca2+ controlled gelation process was synthesized and characterized. The phosphate adsorption performance and mechanism were investigated. In general, a high selectivity among co-existing anions was found with co-existing anion concentration up to 62.5 times of the phosphate concentration. Additionally, phosphate adsorption by Y2O3/SA beads exhibited stable performance over a wide pH range between 2 and 10, while reaching the maximum adsorption capacity at pH 3 (48.54 mg-P/g). The value of point of zero charge (pHpzc) of Y2O3/SA beads was approximately 3.45. Pseudo-second-order and Freundlich isotherm models can well accord with kinetics and isotherms data. The FTIR and XPS characterizations analyzed that inner-sphere complexes were proposed to be the major contributor of Y2O3/SA beads for phosphate removal. In conclusion, Y2O3/SA beads as the mesoporous material exhibited excellent stability and selectivity towards phosphate removal.

Rescue therapy for refractory Helicobacter pylori infection: current status and future concepts.

Helicobacter pylori infection is an important issue worldwide, and several guidelines have been published for clinicians to achieve successful eradication. However, there are still some patients who remain infected with H. pylori after treatment. Clinicians should identify the reasons that caused treatment failure and find strategies to manage them. We have searched and organized the literature and developed methods to overcome factors that contribute to prior treatment failure, such as poor compliance, inadequate intragastric acid suppression, and antibiotic resistance. To improve compliance, telemedicine or smartphone applications might play a role in the modern world by increasing doctor-patient relationships, while concomitant probiotics could be administered to reduce adverse effects and enhance adherence. For better acid suppression, high-potency and high-dose proton-pump inhibitors or potassium-competitive acid blockers have preferable efficacy. To overcome antibiotic resistance, susceptibility tests either by culture or by genotyping are the most commonly used methods and have been suggested for antibiotic selection before rescue therapy, but empirical therapy according to detailed medical history could be an alternative. Eradication with a longer treatment period (14 days) has a better outcome than shorter period (7 or 10 days). Ultimately, clinicians should select antibiotics based on the patient's history of drug allergy, previous antibiotic exposure, local antibiotic resistance, available medications, and cost. In addition, identifying patients with a high risk of cancer and shared decision-making are also essential for those who have experienced eradication failure.

Surface TREM2 on circulating M-MDSCs as a novel prognostic factor for adults with treatment-naïve diffuse large B-cell lymphoma.

INTRODUCTION: Circulating monocytic myeloid-derived suppressive cells (M-MDSCs) are implicated as a poor prognostic factor and cause CAR T-cell failure in diffuse large B-cell lymphoma (DLBCL). Triggering receptors expressed on myeloid cells 2 (TREM2) are a transmembrane glycoprotein that polarize macrophages to anti-inflammation phenotype but have never been explored on M-MDSCs. This study aims to elucidate the expression and clinical impact of surface TREM2 on circulating M-MDSCs derived from DLBCL adults. METHODS: This prospective, observational study enrolled 100 adults with newly diagnosed and treatment-naïve DLBCL from May 2019 to October 2021. Human circulating M-MDSCs were obtained from freshly isolated peripheral blood, and each patient's surface-TREM2 level on M-MDSCs was normalized via a healthy control at the same performance of flow-cytometry analysis. Murine MDSCs derived from bone marrow (BM-MDSCs) were adopted to assess the link between Trem2 and cytotoxic T lymphocytes. RESULTS: More circulating M-MDSCs at diagnosis of DLBCL predicted worse progression-free (PFS) and overall survival (OS). Patients with higher IPI scores, bone marrow involvement, or lower absolute counts of CD4+ or CD8+ T cells in PB had significantly higher normalized TREM2 levels on M-MDSCs. Additionally, normalized TREM2 levels on M-MDSCs could be grouped into low (< 2%), medium (2-44%), or high (> 44%) levels, and a high normalized TREM2 level on M-MDSCs was proven as an independent prognostic factor for both PFS and OS via multivariate Cox regression analysis and associated with worst PFS and OS. Interestingly, normalized levels of surface TREM2 on M-MDSCs were negatively associated with absolute counts of PB CD8+ T cells and positively correlated with levels of intracellular arginase 1 (ARG1) within M-MDSCs. Wild-type BM-MDSCs had significantly higher mRNA levels of Arg1 and showed more prominent ability to suppress the proliferation of co-cultured CD8+ T cells than BM-MDSCs from Trem2 knockout mice, and the suppressive ability could be impaired by adding Arg1 inhibitors (CB1158) or supplementing L-arginine. CONCLUSION: In treatment-naïve DLBCL adults, a high surface-TREM2 level on circulating M-MDSCs is a poor prognostic factor for both PFS and OS and warrants further investigation for its potential as a novel target in immunotherapy.

Cidan Capsule in Combination with Adjuvant Transarterial Chemoembolization Reduces Recurrence Rate after Curative Resection of Hepatocellular Carcinoma: A Multicenter, Randomized Controlled Trial.

OBJECTIVE: To evaluate the efficacy and safety of Cidan Capsule combined with adjuvant transarterial chemoembolization (TACE) in patients with a high risk of early recurrence after curative resection of hepatocellular carcinoma (HCC). METHODS: A multicenter, randomized controlled trial was conducted in patients with high-risk recurrence factors after curative resection of HCC from 9 medical centers between July 2014 and July 2018. Totally 249 patients were randomly assigned to TACE with or without Cidan Capsule administration groups by stratified block in a 1:1 ratio. Postoperative adjuvant TACE was given 4-5 weeks after hepatic resection in both groups. Additionally, 125 patients in the TACE plus Cidan group were administrated Cidan Capsule (0.27 g/capsule, 5 capsules every time, 4 times a day) for 6 months with a 24-month follow-up. Primary endpoints included disease-free survival (DFS) and tumor recurrence rate (TRR). Secondary endpoint was overall survival (OS). Any drug-related adverse events (AEs) were observed and recorded. RESULTS: As the data cutoff in July 9th, 2018, the median DFS was not reached in the TACE plus Cidan group and 234.0 days in the TACE group (hazard ratio, 0.420, 95% confidence interval, 0.290-0.608; P<0.01). The 1- and 2-year TRR in the TACE plus Cidan and TACE groups were 31.5%, 37.1%, and 60.8%, 63.4%, respectively (P<0.01). Median OS was not reached in both groups. The 1- and 2-year OS rates in TACE plus Cidan and TACE groups were 98.4%, 98.4%, and 89.5%, 87.9%, respectively (P<0.05). The most common grade 3-4 AEs included fatigue, abdominal pain, lumbar pain, and nausea. One serious AE was reported in 1 patient in the TACE plus Cidan group, the death was due to retroperitoneal mass hemorrhage and hemorrhagic shock, and was not related to study drug. CONCLUSIONS: Cidan Capsule in combination with TACE can reduce the incidence of early recurrence in HCC patients at high-risk of recurrence after radical hepatectomy and may be an appropriate option in postoperative anti-recurrence treatment. (Registration No. NCT02253511).

Through network pharmacology and molecular docking to explore the underlying mechanism of Artemisia annua L. treating in abdominal aortic aneurysm.

Background: Abdominal aortic aneurysm (AAA) is a degenerative disease that causes health problems in humans. However, there are no effective drugs for the treatment of AAA. Artemisia annua L. (A. annua) is a traditional herbal that has been widely used in cardiovascular disease. Based on network pharmacology and molecular docking technology, this study predicted the practical components and potential mechanisms of A. annua inhibiting the occurrence and development of AAA. Methods: The main active ingredients and targets of A. annua were screened through the TCMSP database; the GeneCards, OMIM, PharmGkb, and TTD databases were used to search for the targeted genes of AAA and map them to the targets of the active ingredients to obtain the active ingredient therapy of A. annua. The targets of AAA were to construct a protein interaction network through the STRING platform. R software was used to carry out the enrichment analysis of GO and KEGG for relevant targets, and Cytoscape was used to construct the active ingredient-target network prediction model of A. annua. Finally, AutoDock Vina was used to verify the results of the active ingredients and critical targets. Results: The main active ingredients obtained from A. annua for the treatment of AAA include quercetin, luteolin, kaempferol, isorhamnetin, and artemetin, as well as 117 effective targets, including RELA, MAPK14, CCND1, MAPK1, AKT1, MYC, MAPK8, TP53, ESR1, FOS, and JUN. The 11 targeted genes might play a key role in disease treatment. Enriched in 2115 GO biological processes, 159 molecular functions, 56 cellular components, and 156 KEGG pathways, inferred that its mechanism of action might be related to PI3K-Akt signaling pathway, fluid shear stress, atherosclerosis, and AGE-RAGE signaling pathway. Molecular docking results showed that the top five active components of A. annua had a good affinity for core disease targets and played a central role in treating AAA. The low binding energy molecular docking results provided valuable information for the development of drugs to treat AAA. Conclusion: Therefore, A. annua may have multiple components, multiple targets, and multiple signaling pathways to play a role in treating AAA. A. annua may have the potential to treat AAA.

Secondary Metabolites of Osmanthus fragrans: Metabolism and Medicinal Value.

Osmanthus fragrans (scientific name: Osmanthus fragrans (Thunb.) Lour.) is a species of the Osmanthus genus in the family Oleaceae, and it has a long history of cultivation in China. O. fragrans is edible and is well known for conferring a natural fragrance to desserts. This flowering plant has long been cultivated for ornamental purposes. Most contemporary literature related to O. fragrans focuses on its edible value and new species discovery, but the functional use of O. fragrans is often neglected. O, fragrans has many properties that are beneficial to human health, and its roots, stems, leaves, flowers and fruits have medicinal value. These characteristics are recorded in the classics of traditional Chinese medicine. Studies on the metabolites and medicinal value of O. fragrans published in recent years were used in this study to evaluate the medicinal value of O. fragrans. Using keywords such as metabolites and Osmanthus fragrans, a systematic and nonexhaustive search of articles, papers and books related to the medicinal use of Osmanthus fragrans metabolites was conducted. Fifteen metabolites were identified through this literature search and classified into three categories according to their properties and structure: flavonoids, terpenes and phenolic acids. It was found that the pharmacological activities of these secondary metabolites mainly include antioxidant, anticancer, anti-inflammatory and antibacterial activities and that these metabolites can be used to treat many human diseases, such as cancer, skin diseases, cardiovascular diseases, and neurological diseases. Most of the reports that are currently available and concern the secondary metabolites of Osmanthus fragrans have limitations. Some reports introduce only the general classification of compounds in Osmanthus fragrans, and some reports introduce only a single compound. In contrast, the introduction section of this paper includes both the category and the functional value of each compound. While reviewing the data for this study, the authors found that the specific action sites of these compounds and their mechanisms of action in plants are relatively weak, and in the future, additional research should be conducted to investigate this topic further.

Protective Effect of Cordycepin on Impairment of Endothelial Function in Type 2 Diabetes Mellitus.

Type 2 diabetes mellitus (T2DM) is a major risk factor for cardiovascular diseases. The reduction of mitochondrial protein sirtuin protein 3 (SIRT3) has been reported to contribute to the development of T2DM by impacting mitochondrial respiration. Cordycepin is an adenosine derivative and is isolated from the culture filtrate of Cordyceps militaris. This study explored the protective effect of cordycepin on vascular impairment induced by T2DM and its properties and protective mechanism. In this study, a T2DM rat model was established. The endothelium-dependent relaxation of the thoracic aorta ring decreased in T2DM rats could be reversed by cordycepin. Next, mitochondrial impairment in human umbilical vein endothelial cells was detected by JC-1 staining. In vitro studies revealed that cordycepin plays a beneficial role in advanced glycation end product-induced endothelial mitochondrial impairment. Moreover, according to the cordycepin molecular docking analysis, cordycepin can bind to SIRT3. Cordycepin increased the expression and activation of SIRT3 in a dose-dependent manner. SIRT3 interruption blocked the protective effect of cordycepin on mitochondria in human umbilical vein endothelial cells. Cordycepin can conclusively protect vascular function impaired by T2DM, and the mechanism may potentially be involved in SIRT3 signaling pathways.

Delayed autumnal leaf senescence following nutrient fertilization results in altered nitrogen resorption.

Increased atmospheric nitrogen (N) deposition could create an imbalance between N and phosphorus (P), which may substantially impact ecosystem functioning. Changes in autumnal phenology (i.e., leaf senescence) and associated leaf nutrient resorption may profoundly impact plant fitness and productivity. However, we know little about how and to what extent nutrient addition affects leaf senescence in tree species, or how changes in senescence may influence resorption. We thus investigated the impacts of N and P addition on leaf senescence and leaf N resorption in 2-year-old larch (Larix principisrupprechtii) seedlings in northern China. Results showed that nutrient addition (i.e., N, P or N + P addition) significantly delayed autumnal leaf senescence, and decreased leaf N resorption efficiency (NRE) and proficiency (NRP), particularly in the N and N + P treatments. Improved leaf N concentrations were correlated with delayed leaf senescence, as indicated by the positive relationship between mature leaf N concentrations and the timing of leaf senescence. Following nutrient addition, larch seedlings shifted toward delayed onset, but more rapid, leaf senescence. Additionally, we observed an initial negative correlation between the timing of leaf senescence and NRE and NRP, followed by a positive correlation, indicating delayed and less efficient remobilization during the early stages of senescence, followed by accelerated resorption in the later stages. However, the latter effect was potentially impaired by the increased risk of early autumn frost damage, thus failed to fully compensate for the negative effects observed during the early stages of senescence. Improved soil P availability increased leaf N resorption and thus weakened the negative impact of delayed leaf senescence on leaf N resorption, so P addition had no significant impact on leaf N resorption. Overall, our findings clarify the relationship between nutrient addition-resorption and the linkage with leaf senescence, and would have important implications for plant nutrient conservation strategy and nutrient cycling.

Alleviation of Diabetic Tendon Injury via Activation of Tendon Fibroblasts Autophagy under Berberine Treatment.

Berberine (BBR) is an isoquinoline alkaloid isolated from Coptis chinensis and possesses valuable pharmacological activities, including anti-inflammatory, anti-tumor, and alleviating several complications of type 2 diabetes mellitus (T2DM). However, the role of BBR in regulating diabetic tendon injury remains poorly understood. In this study, a rat model of T2DM was constructed, and cell apoptosis and autophagy were assessed in tendon tissues after BBR treatment through TdT-Mediated dUTP nick-end labeling (TUNEL) assay and immunohistochemical analysis. Tendon fibroblasts were obtained from the rat Achilles tendon, and the role of BBR in regulating cell apoptosis, the production of inflammatory cytokines, and autophagy activation were assessed using flow cytometry, quantitative real-time PCR (qRT-PCR), and western blot analysis. We demonstrated that BBR treatment significantly increased autophagy activation and decreased cell apoptosis in tendon tissues of T2DM rats. In tendon fibroblasts, BBR repressed High glucose (HG)-induced cell apoptosis and production of proinflammatory cytokines. HG treatment resulted in a decrease of autophagy activation in tendon fibroblasts, whereas BBR restored autophagy activation. More important, pharmacological inhibition of autophagy by 3-MA weakened the protective effects of BBR against HG-induced tendon fibroblasts injury. Taken together, the current results demonstrate that BBR helps relieve diabetic tendon injury by activating autophagy of tendon fibroblasts.

Synthesis of Hemiprotonic Phenanthroline-Phenanthroline+ Compounds with both Antitumor and Antimicrobial Activity.

Currently, cancer patients with microbial infection are a severe challenge in clinical treatment. To address the problem, we synthesized hemiprotonic compounds based on the unique structure of hemiprotonic nucleotide base pairs in a DNA i-motif. These compounds were produced from phenanthroline (ph) dimerization with phenanthroline as a proton receptor and ammonium as a donor. The biological activity shows that the compounds have a selective antitumor effect through inducing cell apoptosis. The molecular mechanism could be related to specific inhibition of transcription factor PLAGL2 of tumor cells, assessed by transcriptomic analysis. Moreover, results show that the hemiprotonic ph-ph+ has broad-spectrum antibacterial and antifungal activities, and drug-resistant bacteria, including methicillin-resistant Staphylococcus aureus, are sensitive to the compound. In animal models of liver cancer with fungal infection, the ph-ph+ retards proliferation of hepatoma cells in tumor-bearing mice and remedies pneumonia and encephalitis caused by Cryptococcus neoformans. The study provides a novel therapeutic candidate for cancer patients accompanied by infection.

Rehmannioside A improves cognitive impairment and alleviates ferroptosis via activating PI3K/AKT/Nrf2 and SLC7A11/GPX4 signaling pathway after ischemia.

ETHNOPHARMACOLOGICAL RELEVANCE: Rehmannioside A is derived from Rehmannia glutinosa Libosch, which is widely used as an important ingredient in diverse traditional Chinese medicines to treat diseases caused by "kidney deficiency" such as cerebral arteriosclerosis, aging-related stroke and dementia in China. Recent studies have proved that Rehmannia glutinosa Libosch and Rehmannioside A can improve memory capability and recover nerve damage. AIM OF THE STUDY: To investigate the effect of Rehmannioside A on cognitive impairment after ischemia in rats and SH-SY5Y cells, and further evaluate the anti-oxidative and anti-ferroptosis mechanisms. MATERIALS AND METHODS: Differentially expressed proteins (DEPs) in patients after cerebral ischemic stroke were revealed by a RayBio protein array. Cognitive impairment model was established by middle cerebral artery occlusion and reperfusion (MCAO) 14 days in rats. Rehmannioside A was administered intraperitoneally injection at dose of 80 mg/kg. The SH-SY5Y cells were exposed to H2O2 for 24 h and treated with Rehmannioside A (80 µM) for 24 h. The neuroprotecion of Rehmannioside A were evaluated by infarct volume (TTC), neurological defects (Garcia score) and learning memory (Morris water maze test) in vivo, and cell viability (CCK-8 or LDH) in vitro. Superoxide dismutase (SOD), malondialdehyde (MDA) and myeloperoxidase (MPO) activity of rats, glutathione (GSH), oxidized glutathione (GSSG) and nicotinamide adenine dinucleotide phosphate (NADPH) of cells were detected by biochemical assay. Intracellular reactive oxygen species (ROS) were measured by DCFH-DA assay. Myeloperoxidase (MPO), PI3 kinase (PI3K), p-PI3K, Akt, p-Akt, heme oxygenase-1 (HO-1), nuclear factor-E2-related factor 2 (Nrf2), SLC7A11, glutathione peroxidase 4 (GPX4) of the cerebral cortex in rats or SH-SY5Y cells were examined by western blotting. RESULTS: Compared with model group, the cognitive impairment and neurological deficits of Rehmannioside A group were significantly improved, and the cerebral infarction was reduced in MCAO rats. Moreover, the cell viability obviously increased and the H2O2-induced toxicity was reduced in Rehmannioside A group. Further research indicated that the expression of p-PI3K, p-Akt, nuclear Nrf2, HO-1 and SLC7A11 in Rehmannioside A group was significantly higher than model group. CONCLUSION: Rehmannioside A has neuroprotection effect and improves cognitive impairment after cerebral ischemia by inhibiting ferroptosis and activating PI3K/AKT/Nrf2 and SLC7A11/GPX4 signaling pathway. These findings provide valuable insight into the pathogenesis and therapeutic target of ischemic stroke.

Prevalence of hyperhomocysteinemia (HHcy) and its major determinants among hypertensive patients over 35 years of age.

OBJECTIVE: Hyperhomocysteinemia (HHcy) and hypertension are associated with cardiovascular events. However, effects of Hcy-lowing interventions on cardiovascular outcome were conflicting. Serum folate level was proposed to be a possible determinant of efficacy of extra folate supplementation on cardiovascular outcome. The aims of the present study were to describe representative information on the levels of serum homocysteine and folate in hypertensive patients, and to explore the major determinants of HHcy. METHODS: 11,007 participants with hypertension were analyzed in this cross-sectional study. Blood pressure and serum levels of biochemical indicators were measured. Multivariate logistic regression model was used to assess the associated factors of HHcy. RESULTS: Geometric mean of serum total homocysteine was 14.1 (95% CI: 13.9, 14.4) µmol/L and prevalence of HHcy was 36.1 (95% CI: 34.0, 38.1) % in hypertensive patients. HHcy was strongly associated with factors including male sex, older age, elevated serum creatinine (SCr), lower serum folate and vitamin B12, and uncontrolled blood pressure in hypertensive patients. Elevated SCr attributed to HHcy with the etiologic fraction of 0.29. The change of the odds ratio of HHcy associated with folate was significantly higher in patients with elevated SCr compared with that of patients with normal SCr. CONCLUSION: The results suggested the protection of female sex and higher levels of folate and vitamin B12 from HHcy and attribution of older age and elevated SCr to HHcy. Restoring renal function deserved attention for hypertensive patients to benefit from Hcy-lowing measures.

The Combined Beneficial Effects of Postbiotic Butyrate on Active Vitamin D3-Orchestrated Innate Immunity to Salmonella Colitis.

Salmonella spp. Remains a major public health problem globally. Biomedicine is the cornerstone of modern health care and could be a solution for antibiotic-resistant Salmonellosis. Although postbiotics seem to be an effective treatment in various clinical conditions, their clinical effects on Salmonella colitis have not been reported. Our previous report revealed that active vitamin D attenuates the severity of Salmonella colitis and invasiveness by reducing inflammation and enhancing the production of antimicrobial peptides. Therefore, we investigated the synergistic effects of butyrate, the most studied postbiotic, and active vitamin D on the severity of Salmonella colitis, invasiveness of Salmonella, and host immune responses, as well as its novel mechanisms, using in vitro and in vivo studies. We demonstrated that a combination of butyrate and active vitamin D (1 alpha, 25-dihydroxyvitamin D3) synergically reduced the severity of Salmonella colitis in C57BL/6 mice and reduced cecal inflammatory mIL-6, mIL-8, mTNF-α, and mIL-1ß mRNA expression, but enhanced the antimicrobial peptide mhBD-3 mRNA, compared to a single treatment. Additionally, upregulated vitamin D receptor (VDR) plays a critical role in the synergistic effects. This suggests combined benefits of butyrate and active vitamin D on Salmonella colitis through VDR-mediated antibacterial and anti-inflammatory responses. The combined use of both supplements could be a potential biomedicine for infectious and autoimmune colitis.

[Effect of electroacupuncture on 5-HT7R in gastric antrum and colon tissues of functional diarrhea rats].

OBJECTIVE: To observe the effect of electroacupuncture(EA) at "Zusanli"(ST36), "Yinlingquan" (SP9) or "Yingu"(KI10) on the expression of 5-hydroxytryptamine type 7 receptor (5-HT7R) in the gastric antrum and colon tissues in functional diarrhea (FD) model rats, so as to explore its mechanisms underlying improving FD. METHODS: Forty male SD rats were randomly divided into control, model, ST36, SP9 and KI10 groups，with 8 rats in each group. The FD model was established by combined administration of restriction (four-limbs' banding) + abdominal cold stimulation + feeding every other day, for 14 days. EA (2 Hz, 0.5 mA) was applied to bilateral ST36 or bilateral SP9 or bilateral KI10 in the 3 corresponding groups for 30 min, once a day for 7 days after successful modeling. Rats of the control group received restriction only. The fecal water content was calculated and the stool form score was given according to the Bristol's methods. The gastric residual rate (GRR) and small intestine propulsion rate (SIPR) were determined to assess the motility of the gastrointestinal tract. Immunohistochemical and real-time fluorescent quantitative PCR were used to detect the expression of 5-HT7R protein and mRNA of the gastric antrum and colon tissues, respectively. RESULTS: Compared with the control group, the fecal water content, the stool form score, the SIPR and the expression levels of 5-HT7R protein and 5-HT7R mRNA were significantly increased (P<0.01,P<0.05) and the GRR was considerably decreased in the model group (P<0.01). The fecal water content, stool form score and SIPR, and expression level of 5-HT7R protein and mRNA in the gastric antrum and colon were significantly lower in both the ST36 and SP9 groups (not in the KI10 group) than in the model group (P<0.01, P<0.05), but the GRR was significantly higher in the ST36 and SP9 groups (not in the KI10 group) than in the model group (P<0.01). The effects of both ST36 and SP9 were significantly superior to those of KI10 in improving all the indexes mentioned above （except SIPR and the mRNA level of 5-HT7R in the colon in SP9 group）(P<0.01, P<0.05). No significant differences were found between the ST36 and SP9 groups in lowering the levels of fecal water content, stool form score, SIPR, and the expression of 5-HT7R protein and mRNA, as well as in up-regulating GRR (P>0.05). CONCLUSION: EA of ST36 and SP9 can improve the motility of gastrointestinal tract in FD rats, which may be related to its functions in down-regulating the expression of 5-HT7R protein and mRNA in gastric antrum and colon tissues. The effects of ST36 and SP9 were obviously better than those of KI10 in ameliorating the gastric and intestinal motility (except GRR) and in lowering the expression of 5-HT7R protein and mRNA.

Dendrobium officinale Regulates Fatty Acid Metabolism to Ameliorate Liver Lipid Accumulation in NAFLD Mice.

Dendrobium officinale (DOF) is a traditional Chinese edible and officinal plant. Ultrafine DOF powder (DOFP) can regulate lipids and histopathology in the liver, but the underlying mechanisms of hepatic fatty acid (FA) metabolism, which is generally correlated with the development of nonalcoholic fatty liver disease (NAFLD), remain unclear. The purpose of the present study was to investigate whether DOFP treatment alters hepatic FA metabolism in NAFLD mice by using multidimensional mass spectrometry-based shotgun lipidomics (MDMS-SL) and analyse the underlying mechanisms. A 3-week DOFP treatment prevented lipid deposition and improved hepatic histopathology in NAFLD mice after withdrawal from the high-sucrose, high-fat (HSHF) diet, and it decreased triglyceride and FA content in the liver. Furthermore, the C16 : 0/C14 : 0 and C18 : 1/18 : 0 ratios in FAs were significantly decreased in the DOFP treatment group, and the C20 : 4/C20 : 3 and C22 : 4/C22 : 3 ratios were increased, and saturated FA was inhibited. Additionally, DOFP treatment significantly increased the content of two FA ß-oxidation-related proteins (carnitine palmitoyltransferase 1-α and acyl-coenzyme A oxidase 1). It also decreased the content of a FA synthesis-related protein (fatty acid synthase), a FA desaturation-related protein (stearoyl-coenzyme A desaturase-1), and a FA uptake-related protein (fatty acid transport protein 2). Moreover, DOFP treatment improved dysregulated levels of major phospholipids in the livers of model mice. The results of this study confirm that DOFP treatment in NAFLD mice has liver recovery effects by regulating FA metabolism.

Beneficial effects of Dendrobium officinale on metabolic hypertensive rats by triggering the enteric-origin SCFA-GPCR43/41 pathway.

Given the increasing global trend toward unhealthy lifestyles and dietary decisions, such as "over-consumption of alcohol, and high sugar and fat diets" (ACHSFDs), it is not surprising that metabolic hypertension (MH) is now the most common type of hypertension. There is an urgent, global need for effective measures for the prevention and treatment of MH. Improper diet leads to decreased short-chain fatty acid (SCFA) production in the gut, leading to decreased gastrointestinal function, metabolism, and blood pressure as a result of signaling through G-protein-coupled receptors (GPCRs), ultimately causing MH. Previous studies have suggested that Dendrobium officinale (DO) may improve gastrointestinal function, lower blood pressure, and regulate metabolic abnormalities, but it is not clear whether it acts on MH by increasing SCFA and, if so, how. In this research, it was observed that Dendrobium officinale ultrafine powder (DOFP) could lower blood pressure and improve lipid abnormalities in ACHSFD-induced MH model rats. Moreover, DOFP was found to improve the intestinal flora and increased the SCFA level in feces and serum, as well as increased the expressions of GPCR43/41 and eNOS and the nitric oxide (NO) level. An experiment on isolated aorta rings revealed that DOFP improved the vascular endothelial relaxation function in MH rats, and this effect could be blocked by the eNOS inhibitor l-NAME. These experimental results suggest that DOFP improved the intestinal flora and increased the production, transportation, and utilization of SCFA, activated the intestinal-vascular axis SCFA-GPCR43/41 pathway, improved vascular endothelial function, and finally lowered blood pressure in MH model rats. This research provides a new focus for the mechanism of the effect of DOFP against MH by triggering the enteric-origin SCFA-GPCR43/41 pathway.

Benefit Effect of Dendrobium officinale Ultrafine Powder on DSS-Induced Ulcerative Colitis Rats by Improving Colon Mucosal Barrier.

MATERIALS AND METHODS: After intragastric administration of DOFP for 3 weeks, the rat UC model was made by the administration of 4% oral DSS solution for one week, and the drug was given at the same time. During the experiment, the disease activity index (DAI) score of the rats was regularly computed. At the end of the experiment, the blood routine indexes of rats were obtained. The histopathological changes in the colon were monitored by hematoxylin-eosin (H&E) and PAS staining and observation of ultrastructural changes in the colon by transmission electron microscope. Occludin expression in the colon was monitored by Western blot, the expression of claudin-1 and ZO-1 in the colon was detected by immunofluorescence, and the expression of TNF-α, IL-6, and IL-1ß in the colon was detected by immunohistochemistry. RESULTS: The results firstly indicated that DOFP could significantly alleviate the signs and symptoms of the DSS-induced rats UC model, which manifested as improvement of body weight loss, increase of colon length, and improvement of the symptoms of diarrhea and hematochezia. Then, results from histopathology, blood routine examination, and transmission electron microscope analysis further implied that DOFP could dramatically reduce inflammatory cell infiltration and restore intestinal epithelial barrier integrity. In addition, the experiments of Western Blot analysis, immunofluorescence, and PAS staining also further confirmed that DOFP could markedly increase related protein expressions of the intestinal barrier and mucus barrier, as the expression of occludin, claudin-1, and ZO-1 in the colon significantly decreased. The experiments of immunohistochemistry confirmed that DOFP could markedly decrease protein expression levels of inflammatory cytokines TNF-α, IL-6, and IL-1ß. CONCLUSION: DOFP notably alleviated inflammatory lesions, repaired the colon mucosa damage by promoting the expression of tight junction proteins occludin, claudin-1, and ZO-1 and inhibiting the release of inflammatory factors TNF-α, IL-6, and IL-1ß, and finally achieved the purpose of treating UC.

[Brief discussion about role and measures of scientific fertilization in ecological cultivation of Chinese medicinal materials].

The ecological planting of Chinese medicinal materials is a cultivation technology that takes into account both ecological and economic benefits, and takes scientific planting technology as a guide to achieve the goal of high quality, high yield and efficiency of Chinese medicinal materials and the sustainable and healthy development of Chinese medicinal materials planting. Among them, scientific fertilization is an important measure to realize the ecological planting of Chinese medicinal materials. In recent years, the social economy has developed rapidly. In the production of Chinese herbal medicines, a large amount of chemical fertilizers and pesticides have been gradually used to increase short-term economic benefits. The unreasonable use of chemical fertilizers and pesticides has neglected the output, quality, safety, environmental pollution and environmental protection of medicinal materials. The impact of continuous development. Therefore, from the perspective of research on cultivation of Chinese medicinal materials, this article briefly describes the role and measures of scientific fertilization in ecological planting of Chinese medicinal materials. The roles of scientific fertilization in solving soil pollution and soil quality deterioration of Chinese herbal medicine cultivation, sustainable deve-lopment of Chinese herbal medicine production, unstable production quality of Chinese herbal medicine products, and quality safety are summarized separately. It is proposed measures based on the characteristics of soil fertilization, the growth and development characteristics of Chinese medicinal materials as the core, and the industrial planting model as the carrier to promote scientific fertilization in the cultivation of Chinese medicinal materials. Finally, the development direction of scientific fertilization and ecological plan-ting of traditional Chinese medicine is prospected, in order to provide support and reference for the development of ecological planting of traditional Chinese medicine.

Ameliorative effects of the traditional Chinese medicine formula Qing-Mai-Yin on arteriosclerosis obliterans in a rabbit model.

CONTEXT: Qing-Mai-Yin (QMY) is a clinically used herbal formula for treating arteriosclerosis obliterans (ASO). OBJECTIVE: To evaluate the chemical constituents and effects of QMY on ASO rabbit model. MATERIALS AND METHODS: Forty-eight New Zealand rabbits were divided into six groups (n = 8): normal (normal rabbits treated with 0.5% CMC-Na), vehicle (ASO rabbits treated with 0.5% CMC-Na), positive (simvastatin, 1.53 mg/kg), and QMY treatment (300, 600, and 1200 mg/kg). ASO rabbit model was prepared by high fatty feeding, roundly shortening artery, and bovine serum albumin immune injury. QMY (300, 600 and 1200 mg/kg) was orally administered for 8 weeks. The effects and possible mechanisms of QMY on ASO rabbits were evaluated by pathological examination, biochemical assays, and immunohistochemical assays. The compositions of QMY were analysed using HPLC-Q-TOF-MS/MS analysis. RESULTS: Compared to the vehicle rabbit, QMY treatment suppressed plaque formation and intima thickness in aorta, and decreased intima thickness, whereas increased lumen area of femoral artery. Additionally, QMY treatment decreased TC, TG and LDL, decreased CRP and ET, and increased NO and 6-K-PGF1α in serum. Furthermore, the potential mechanisms studied revealed that QMY treatment could suppress expression of TNF-α, IL-6, ICAM-1 and NF-κB in endothelial tissues, and increase IκB. In addition, HPLC analysis showed QMY had abundant anthraquinones, stilbenes, and flavonoids. CONCLUSION: QMY has ameliorative effects on ASO rabbit, and the potential mechanisms are correlated to reducing inflammation and down-regulating NF-κB. Our study provides a scientific basis for the future application and investigation of QMY.