Carbopol 940-based hydrogels loading synergistic combination of quercetin and luteolin from the herb Euphorbia humifusa to promote Staphylococcus aureus infected wound healing.

With the increasing prevalence of Staphylococcus aureus infections, rapid emergence of drug resistance and the slow healing of infected wounds, developing an efficient antibiotic-free multifunctional wound dressing for inhibiting S. aureus and simultaneously facilitating wound healing have become a huge challenge. Due to their excellent biocompatibility and biodegradability, some carbopol hydrogels based on plant extracts or purified compounds have already been applied in wound healing treatment. In China, Euphorbia humifusa Willd. (EuH) has been traditionally used as a medicine and food homologous medicine for the treatment of furuncles and carbuncles mainly caused by S. aureus infection. In an earlier study, EuH-originated flavonoids quercetin (QU) and luteolin (LU) could serve as a potential source for anti-S. aureus drug discovery when used in synergy. However, the in vivo effects of QU and LU on S. aureus-infected wound healing are still unknown. In this study, we found a series of Carbopol 940-based hydrogels loading QU and LU in combination could disinfect S. aureus and also could promote wound healing. In the full-thickness skin defect mouse model infected with S. aureus, the wound contraction ratio, bacterial burden, skin hyperplasia and inflammation score, as well as collagen deposition and blood vessels were then investigated. The results indicate that the optimized QL2 [QU (32 µg mL-1)-LU (8 µg mL-1)] hydrogel with biocompatibility significantly promoted S. aureus-infected wound healing through anti-infection, anti-inflammation, collagen deposition, and angiogenesis, revealing it as a promising alternative for infected wound repair.

Construction of an effective method combining in situ capping with electric field-enhanced biodegradation for treating PAH-contaminated soil at abandoned coking sites.

The simultaneous application of in situ capping and electro-enhanced biodegradation may be a suitable method for ensuring the feasibility and safety of reusing abandoned coking sites. However, the capping layer type and applied electric field pattern may affect the efficiency of sequestering and removing pollutants. This study investigated changes in electric current, soil moisture content and pH, polycyclic aromatic hydrocarbon (PAH) concentration, bacterial number, and microbial community structure and metabolic function during soil remediation at abandoned coking plant sites under different applied electric field patterns and barrier types. The results indicated that polarity-reversal electric field was more conducive to maintaining electric current, soil properties, resulting in higher microbial number, community diversity, and functional gene abundance. At 21d, the mean PAH concentrations in contaminated soil, the capping layer's clean soil and barrier were 78.79, 7.56, and 1.57 mg kg-1 lower than those with a unidirectional electric field, respectively. The mean degradation rate of PAHs in the bio-barrier was 10.12 % higher than that in the C-Fe barrier. In the experiment combining a polarity-reversal electric field and a bio-barrier, the mean PAH concentrations in contaminated soil and the capping layer were 706.68 and 27.15 mg kg-1 lower than those in other experiments, respectively, and no PAHs were detected in the clean soil, demonstrating that the combination of the polarity-reversal electric field and the bio-barrier was effective in treating soil at abandoned coking plant sites. The established method of combining in situ capping with electro-enhanced biodegradation will provide technical support for the treatment and reuse of heavily PAH-contaminated soil at abandoned coking plant sites.

[Medicinal plant resources in Inner Mongolia autonomous region of China and Mongolia: a comparative study].

Inner Mongolia autonomous region of China and Mongolia are the primary regions where Chinese and Mongolian medicine and its medicinal plant resources are distributed. In this study, 133 families, 586 genera, and 1 497 species of medicinal plants in Inner Mongolia as well as 62 families, 261 genera, and 467 species of medicinal plants in Mongolia were collected through field investigation, specimen collection and identification, and literature research. And the species, geographic distribution, and influencing factors of the above medicinal plants were analyzed. The results revealed that there were more plant species utilized for medicinal reasons in Inner Mongolia than in Mongolia. Hotspots emerged in Hulunbuir, Chifeng, and Tongliao of Inner Mongolia, while there were several hotspots in Eastern province, Sukhbaatar province, Gobi Altai province, Bayankhongor province, Middle Gobi province, Kobdo province, South Gobi province, and Central province of Mongolia. The interplay of elevation and climate made a non-significant overall contribution to the diversity of plant types in Inner Mongolia and Mongolia. The contribution of each factor increased significantly when the vegetation types of Inner Mongolia and Mongolia were broadly divided into forest, grassland and desert. Thus, the distribution of medicinal plant resources and vegetation cover were jointly influenced by a variety of natural factors such as topography, climate and interactions between species, and these factors contributed to and constrained each other. This study provided reference for sustainable development and rational exploitation of medicinal plant resources in future.

Antibacterial and antibiofilm efficacy of the preferred fractions and compounds from Euphorbia humifusa (herba euphorbiae humifusae) against Staphylococcus aureus.

ETHNOPHARMACOLOGICAL RELEVANCE: Euphorbia humifusa Willd., known as Di-Jin-Cao in Chinese, has long been utilized as a traditional herb for the treatment of furuncles and carbuncles mainly caused by Staphylococcus aureus infection. Despite extensive chemical and pharmacological studies reported previously for E. humifusa, the antibacterial and antibiofilm activities against S. aureus as well as the related mechanism of action (MoA) remain largely obscure. AIM OF THE STUDY: To investigate the antibacterial and antibiofilm activities of the preferred fractions and compounds from E. humifusa against S. aureus and assess the associated MoA. MATERIALS AND METHODS: The bioactive fractions and compounds were obtained from the 75% ethanol extract of E. humifusa (75%-EEEH) with the assistance of the related antibacterial and antibiofilm screening. Their antibacterial activities were determined using the broth microdilution method, whilst the inhibition of biofilm formation and the disruption of preformed biofilm were assessed by crystal violet staining and confocal laser scanning microscopy (CLSM). To achieve more effective therapies, the combinatory effects of different components were also studied. The biofilm metabolic activities of isolated compounds were evaluated by 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) reduction assay. The scanning electron microscopy (SEM) and quantitative real-time polymerase chain reaction (qRT-PCR) were employed to explore the antibiofilm mechanism. RESULTS: Fractions DJC06 and DJC07 collected from the ethyl acetate extract of the 75%-EEEH exhibited antibacterial activity (MIC = 256 µg/mL) against S. aureus and further separation of these two fractions led to the isolation and characterization of 22 compounds. Among the isolates, luteolin (LU), quercetin (QU), and kaempferol (KA) are the verified components associated with the antibacterial and antibiofilm activities by displaying individual or combinational MIC values of 8-128 µg/mL and 70.9-99.7% inhibition for biofilm formation. Importantly, QU and KA can work in synergy with LU to significantly enhance the efficacy via destroying cell integrity, increasing membrane permeability, and down-regulating the biofilm-related gene expression. CONCLUSIONS: The preferred fractions and compounds from E. humifusa exerted desired antibacterial and antibiofilm efficacy against S. aureus via a MoA involving cell morphology disruption and altered genes expression. The findings herein not only support its traditional use in the treatment of furuncles and carbuncles, but reveal E. humifusa is a potential source for producing promising antibiofilm alternatives against S. aureus and highlight the isolated components (LU, QU, KA) that can potentiate the efficacy when used in synergy.

Phytochemical and biological studies on rare and endangered plants endemic to China. Part XXV. Structurally diverse triterpenoids and diterpenoids from two endangered Pinaceae plants endemic to the Chinese Qinling Mountains and their bioactivities.

A joint phytochemical investigation on the MeOH extracts of the twigs and needles of two endangered Pinaceae plants endemic to the Chinese Qinling Mountains, Picea neoveitchii (an evergreen spruce) and Larix potaninii var. chinensis (a deciduous larch), led to the isolation and characterization of 34 and 24 structurally diverse terpenoids, respectively. Among them, seven are previously undescribed, including a picane-type [i.e., 14(13 â†’ 12)abeo-12αH-serratane] (neoveitchin A) and a serratane-type (neoveitchin B) triterpenoids, and an abietane-type (neoveitchin C) as well as four labdane-type (potalarxins A-D) diterpenoids. Their structures and absolute configurations were established by extensive spectroscopic methods and/or X-ray diffraction analyses. All isolates were evaluated for their inhibitory activities against the human protein tyrosine phosphatase 1B (PTP1B). Serrat-14-en-3α,21ß-diol, betulinic acid, 3ß-hydroxy-11-ursen-13(28)-olide, ursolic acid, and oleanolic acid were found to have considerable inhibitory effects against PTP1B, with IC50 values ranging from 1.1 to 18.1 µM. The interactions of the bioactive triterpenoids with PTP1B were thereafter performed by employing molecular docking studies. In addition, 7-oxo-dehydroabietic acid (an abietane-type diterpenoid) and mangiferonic acid (a cycloartane-type triterpenoid) inhibited acetyl-coenzyme A carboxylase 1 (ACC1), with IC50 values of 3.4 and 6.6 µM, respectively.

[Virtual screening and antiepileptic activity evaluation of COX-2 inhibitory components in Trachelospermi Caulisetfolium].

This study investigated the potential active components against cyclooxygenase-2(COX-2) from Trachelospermi Caulisetfolium and explored the pharmacodynamic material basis.A pharmacophore-based virtual screening method was adopted to establish a COX-2 ligands-based HipHop pharmacophore model on the basis of the information on compounds with COX-2 inhibitory activity reported in published research articles.The reported components in Trachelospermi Caulisetfolium were collected to establish the compound library and matched with the pharmacophores.Subsequently, the matched small molecule compounds underwent molecular docking with COX-2 targets(PDB ID: 3 LN1), and the interaction of potential active monomers and COX-2 was further explored by molecular dynamics.The antiepileptic effect of active monomer arctigenin(15) was determined based on the pentylenetetrazole(PTZ)-induced seizure model, and its modulatory effect on the COX-2 level was evaluated.A compound library containing 118 chemical constituents in Trachelospermi Caulisetfolium was established by literature retrieval.The preferred pharmacophore 04 was selected through test set verification for virtual screening of the compound library of Trachelospermi Caulisetfolium.After matching, six potential constituents with COX-2 inhibitory activity were obtained.The interaction of five compounds with COX-2 and COX-1 was analyzed by molecular docking, and 10 ns molecular dynamics was performed on two compounds.Compound 15 could prolong the latent time of PTZ-induced seizures at medium and high doses, improve the anxiety-and depression-like behaviors induced by PTZ, reduce the expression level of COX-2, and decrease the number of COX-2 immuno-posi-tive cells in the hippocampal CA1 region.The results showed that it was reasonable to investigate the components in Trachelospermi Caulisetfolium with COX-2 inhibitory activity based on virtual screening and activity evaluation.

Mechanism of Huangqi Sanxian Decoction Inhibiting Osteoclast Differentiation Based on Network Pharmacology.

Osteoclasts (OCs) have been the unique cell type exhibiting the bone-resorption activity in body. It is important to identify drugs to resist osteoclastogenesis to manage the bone-loss disorders. Huangqi Sanxian decoction (HQSXD) is utilized for the treatment of postmenopausal osteoporosis (PMOP) for a long history in East Asia. This work aimed to examine HQSXD's activity in OC differentiation. Based on staining with tartrate-resistant acid phosphatase (TRAP), it was found that HQSXD suppressed OC generation under the induction of RANKL produced in the bone marrow-derived monocytes/macrophages (BMMs), with no cytotoxic effect. Later analysis like molecular exploration and network pharmacology (NP) suggested the role of HQSXD in suppressing genes associated with osteoclastogenesis via PI3K/Akt-mediated mechanism dose-dependently. This work might illustrate the molecular pharmacological mechanism involved in HQSXD's effect on treating OC-associated disorders. Moreover, NP was found to modernize traditional Chinese medicine (TCM) research.

Postoperative Ileus with the Topical Application of Tongfu Decoction Based on Network Pharmacology and Experimental Validation.

Objective: Postoperative gastrointestinal dysfunction is a common and important complication of surgery. This study aimed to explore the key pharmacological mechanisms of Tongfu decoction in treating postoperative ileus (POI). Methods: The active ingredients of Tongfu decoction and their targets were screened using the TCMSP database and STITCH and SwissTargetPrediction databases, respectively. The GeneCards and DisGeNET databases were used to obtain POI dysfunction-related therapeutic targets. After screening, a drug-active-ingredient-therapeutic target network was constructed and the key target functional enrichment analysis was carried out. The Sprague-Dawley rats with POI were used for in vivo experimental verification. The serum levels of IL-1ß, IL-6, IL-10, IFN-γ, and MCP-1 were measured after surgery using enzyme-linked immunosorbent assay. The Western blot analysis was used to determine the expression of key proteins of the PI3K-Akt signaling pathway in colon tissues. Results: An interaction network was constructed containing 7 Chinese medicine components, 36 compounds, and 85 target proteins. The functional enrichment analysis showed that the target proteins mainly acted on the POI through the PI3K-Akt signaling pathway. In in vivo experiments, Tongfu decoction had a promoting effect on the serum level of IL-10, an inhibitory effect on the serum levels of IL-1ß and CCL2, and an inhibitory effect on the local expression of PI3K, pAkt, and mTOR in colon tissue. In addition, the Tongfu decoction increased the intestinal ink advancing rate. Conclusion: Nonoral Tongfu decoction can also be used to treat POI; its mechanism is affected by IL-10 and IL-1ß.The inhibition of the PI3K-Akt signaling pathway affected the treatment with Tongfu decoction by inducing an immune-inflammatory storm in POI.

An Intrinsically Micro-/Nanostructured Pollen Substrate with Tunable Optical Properties for Optoelectronic Applications.

There is broad interest in developing photonically active substrates from naturally abundant, minimally processed materials that can help to overcome the environmental challenges of synthetic plastic substrates while also gaining inspiration from biological design principles. To date, most efforts have focused on rationally engineering the micro- and nanoscale structural properties of cellulose-based materials by tuning fibril and fiber dimensions and packing along with chemical modifications, while there is largely untapped potential to design photonically active substrates from other classes of natural materials with distinct morphological features. Herein, the fabrication of a flexible pollen-derived substrate is reported, which exhibits high transparency (>92%) and high haze (>84%) on account of the micro- and nanostructure properties of constituent pollen particles that are readily obtained from nature and require minimal extraction or processing to form the paper-like substrate based on colloidal self-assembly. Experiments and simulations confirm that the optical properties of the pollen substrate are tunable and arise from light-matter interactions with the spiky surface of pollen particles. In a proof-of-concept example, the pollen substrate is incorporated into a functional perovskite solar cell while the tunable optical properties of the intrinsically micro-/nanostructured pollen substrate can be useful for a wide range of optoelectronic applications.

A retrospective study on 221 patients with granulomatous lobular mastitis treated by a combination of traditional Chinese medicine and western medicine.

OBJECTIVE: This study aims to investigate the clinical efficacy and safety of integrative Chinese and Western medicine in the treatment of granulomatous lobular mastitis. METHODS: In the present study, the clinical data of patients with granulomatous lobular mastitis in our hospital were retrospectively analyzed. According to the treatment regimens, these patients were divided into two groups: observation group (n=92) and control group (n=129). Patients in the observation group were treated with traditional Chinese medicine in combination with the surgical treatment of Western medicine, while the patents in the control group received surgical treatment alone. The main observation indexes included clinical cure rate, mass size, prolactin level and aesthetic evaluation results of the breasts. RESULTS: The results revealed that there was no significant correlation between the observation group and control group, in terms of age, prolactin level, and marriage and childbearing history (P>0.05). Furthermore, the recurrence rate was lower in the observation group, when compared to the control group, and the difference was statistically significant (P<0.05). The aesthetic evaluation was higher in the observation group than in the control group, and the difference was statistically significant (P<0.05). However, the difference in the transverse diameter and long diameter of the tumor and clinical cure rate was not statistically significant (P>0.05) between the observation group and control group. CONCLUSION: Compared with the simple surgical treatment of Western medicine, the combination of traditional Chinese medicine and Western medicine in the treatment of granulomatous lobular mastitis can significantly reduce the recurrence rate, and improve the symmetry and beauty of bilateral breasts, which is worthy of clinical application. KEY WORDS: Granulomatous lobular mastitis, Integrated Chinese and western medicine treatment, Unclog lacteal, Prolactin, Aesthetic evaluation of milk preservation.

Sodium Butyrate Supplementation Inhibits Hepatic Steatosis by Stimulating Liver Kinase B1 and Insulin-Induced Gene.

BACKGROUND AND AIMS: Butyric acid is an intestinal microbiota-produced short-chain fatty acid, which exerts salutary effects on alleviating nonalcoholic fatty liver disease (NAFLD). However, the underlying mechanism of butyrate on regulating hepatic lipid metabolism is largely unexplored. METHODS: A mouse model of NAFLD was induced with high-fat diet feeding, and sodium butyrate (NaB) intervention was initiated at the eighth week and lasted for 8 weeks. Hepatic steatosis was evaluated and metabolic pathways concerning lipid homeostasis were analyzed. RESULTS: Here, we report that administration of NaB by gavage once daily for 8 weeks causes an augmentation of insulin-induced gene (Insig) activity and inhibition of lipogenic gene in mice fed with high-fat diet. Mechanistically, NaB is sufficient to enhance the interaction between Insig and its upstream kinase AMP-activated protein kinase (AMPK). The stimulatory effects of NaB on Insig-1 activity are abolished in AMPKα1/α2 double knockout (AMPK-/-) mouse primary hepatocytes. Moreover, AMPK activation by NaB is mediated by LKB1, as evidenced by the observations showing NaB-mediated induction of phosphorylation of AMPK, and its downstream target acetyl-CoA carboxylase is diminished in LKB1-/- mouse embryonic fibroblasts. CONCLUSIONS: These studies indicate that NaB serves as a negative regulator of hepatic lipogenesis in NAFLD and that NaB attenuates hepatic steatosis and improves lipid profile and liver function largely through the activation of LKB1-AMPK-Insig signaling pathway. Therefore, NaB has therapeutic potential for treating NAFLD and related metabolic diseases.

[Virtual screen of effective AChE inhibitory constituents from Glycyrrhizae Radix et Rhizoma based on pharmacophore and molecular docking].

This research is to predict anti-Alzheimer's disease active constituents on the target of acetylcholinesterase(AChE) from Glycyrrhizae Radix et Rhizoma with the help of pharmacophore and molecular docking. AChE ligand-based pharmacophore model was set up and the molecular library of the constituents from Glycyrrhizae Radix et Rhizoma were established by collecting literature. Then the constituents from Glycyrrhizae Radix et Rhizoma were screen for the potential AChE inhibitory potency in silico through matching with the best pharmacophore model. The flexible docking was used to evaluate the interactions between compounds screened from pharmacophore model and AChE protein(PDB ID:4 EY7). The interactions were expressed including but not limited to CDOCKER interaction energy, hydrogen bonds and non-bonding interactions. The molecular library of Glycyrrhizae Radix et Rhizoma contains 44 chemical constituents. As for the pharmacophore model, six kinds of potential AChE inhibitory constituents from Glycyrrhizae Radix et Rhizoma were considered to be the promising compounds according to the results of searching 3 D database of pharmacophore model. The molecular docking was possessed and the interaction patterns were given to show the detail interactions. The compounds screening from the pharmacophore model were consistent with the existing studies to some degree, indicating that the virtual screen protocols of AChE inhibitory constituents from Glycyrrhizae Radix et Rhizoma based on pharmacophore and molecular docking was reliable.

Effects and therapeutic mechanism of Yinzhihuang on steatohepatitis in rats induced by a high-fat, high-cholesterol diet.

OBJECTIVES: We aimed to investigate the therapeutic mechanism of Yinzhihuang (YZH) liquid, a traditional Chinese medicine mainly composed of extracts of four components, on nonalcoholic steatohepatitis (NASH) induced by a high-fat, high-cholesterol diet (HFHCD) in rats. METHODS: Altogether 30 Sprague-Dawley rats were randomized into three groups: control, the model group (HFHCD + saline) and the treatment group (HFHCD + YZH). Liver histological features and serum biochemical parameters were assessed by the end of the 16th week. RNA sequencing and protein mass spectrometry detection were performed. The genes and proteins expressed differentially were subjected to KEGG pathway enrichment analysis and included in a network-based regulatory model. RESULTS: The weight, liver and fat indices and serum alanine transaminase, aspartate transaminase and total cholesterol levels of the HFHCD + YZH group were all significantly lower than those of the HFHCD + saline group. Moreover, their hepatic steatosis, ballooning and lobular inflammation were relieved, and 64 hepatic genes and 73 hepatic proteins were found to be reversed in their expression patterns after YZH treatment (P < 0.05). The network-based regulatory model showed that these deregulated genes and proteins were mainly involved in oxidative phosphorylation, Toll-like receptor, nucleotide-binding oligomerization domain-like receptor, peroxisome proliferator-activated receptor signaling, nuclear factor-kappa B tumor necrosis factor signaling pathways and fatty acid metabolism. CONCLUSION: YZH could alleviate NASH in HFHCD-fed rats by inhibiting lipogenesis, accelerating lipid ß-oxidation, alleviating oxidative stress and relieving necroinflammation in the liver.

Prospects for improving cosmological parameter estimation with gravitational-wave standard sirens from Taiji.

Taiji, a space-based gravitational-wave observatory, consists of three satellites forming an equilateral triangle with arm length of 3×106 km, orbiting around the Sun. Taiji is able to observe the gravitational-wave standard siren events of massive black hole binary (MBHB) merger, which is helpful in probing the expansion of the universe. In this paper, we preliminarily forecast the capability of Taiji for improving cosmological parameter estimation with the gravitational-wave standard siren data. We simulate five-year standard siren data based on three fiducial cosmological models and three models of MBHB's formation and growth. It is found that the standard siren data from Taiji can effectively break the cosmological parameter degeneracies generated by the cosmic microwave background (CMB) anisotropies data, especially for dynamical dark energy models. The constraints on cosmological parameters are significantly improved by the data combination CMB + Taiji, compared to the CMB data alone. Compared to the current optical cosmological observations, Taiji can still provide help in improving the cosmological parameter estimation to some extent. In addition, we consider an ideal scenario to investigate the potential of Taiji on constraining cosmological parameters. We conclude that the standard sirens of MBHB from Taiji will become a powerful cosmological probe in the future.

[TCR immune repertoire characteristics of patients with drug-induced liver injury due to Polygonum multiflorum preparations].

To explore the immune status of patients with drug-induced liver injury caused by Polygonum multiflorum preparations,and analyze their immune characteristics. Case-control design was used to collect the cases of drug-induced liver injury caused by P. multiflorum preparations through key specialized surveillance. Five matching factors,namely type of P. multiflorum preparations,gender,age,basic diseases and concomitant medication were controlled. According to the ratio of 1 ∶ 1,cases of patients who took P. multiflorum preparations but with no liver injury were monitored at prospective hospitals. The demographic information,disease information,medication information and laboratory examination information of the two groups were recorded,and venous blood was collected. The gene sequence was detected by high-throughput sequencing technology,and the characteristics of TCR immune repertoire of the two groups were analyzed. A total of 46 pairs of patients were enrolled in the study. The results showed significant differences in the number of CDR3 and clone species,the length of amino acid sequence in CDR3 region,the abundance of V gene and J gene,the cross-linking of V-J gene and the diversity of immune repertoire between patients with drug-induced liver injury and patients without liver injury. The immunohistochemical diversity and high-frequency V-J cross-linking characteristics of patients with liver injury caused by P. multiflorum preparations were found,which provided a reference for screening out drug users to reduce the occurrence of liver injury caused by P. multiflorum preparations.

Trimethylamine N-oxide attenuates high-fat high-cholesterol diet-induced steatohepatitis by reducing hepatic cholesterol overload in rats.

BACKGROUND: Trimethylamine N-oxide (TMAO) has been shown to be involved in cardiovascular disease (CVD). However, its role in nonalcoholic steatohepatitis (NASH) is unknown. AIM: To determine the effect of TMAO on the progression of NASH. METHODS: A rat model was induced by 16-wk high-fat high-cholesterol (HFHC) diet feeding and TMAO was administrated by daily oral gavage for 8 wk. RESULTS: Oral TMAO intervention attenuated HFHC diet-induced steatohepatitis in rats. Histological evaluation showed that TMAO treatment significantly alleviated lobular inflammation and hepatocyte ballooning in the livers of rats fed a HFHC diet. Serum levels of alanine aminotransferase and aspartate aminotransferase were also decreased by TMAO treatment. Moreover, hepatic endoplasmic reticulum (ER) stress and cell death were mitigated in HFHC diet-fed TMAO-treated rats. Hepatic and serum levels of cholesterol were both decreased by TMAO treatment in rats fed a HFHC diet. Furthermore, the expression levels of intestinal cholesterol transporters were detected. Interestingly, cholesterol influx-related Niemann-Pick C1-like 1 was downregulated and cholesterol efflux-related ABCG5/8 were upregulated by TMAO treatment in the small intestine. Gut microbiota analysis showed that TMAO could alter the gut microbial profile and restore the diversity of gut flora. CONCLUSION: These data suggest that TMAO may modulate the gut microbiota, inhibit intestinal cholesterol absorption, and ameliorate hepatic ER stress and cell death under cholesterol overload, thereby attenuating HFHC diet-induced steatohepatitis in rats. Further studies are needed to evaluate the influence on CVD and define the safe does of TMAO treatment.

Fastigial nucleus electrostimulation promotes axonal regeneration after experimental stroke via cAMP/PKA pathway.

Axon regeneration after cerebral ischemia in mammals is inadequate to restore function, illustrating the need to design better strategies for improving outcomes. Improvement of axon regeneration has been achieved through fastigial nucleus electrostimulation (FNS) in animal researches. However, the mechanisms underlying this neuroprotection remain poorly understood. Increasing the levels of the second messenger cyclic AMP (cAMP) enhances axon regeneration, making it an excellent candidate molecule that has therapeutic potential. In the present study, we examined the expression of cAMP signaling in ischemic brain tissues following focal cerebral ischemia. Adult rats were subjected to ischemia induced by middle cerebral artery occlusion (MCAO). A dipolar electrode was placed into the cerebellum to stimulate the cerebellar fastigial nucleus for 1 h after ischemia. Neurological deficits and the expressions of cAMP, PKA (protein kinase A) and ROCK (Rho-kinase) were determined. Axonal regeneration was measured by upregulation of growth-associated protein 43 (GAP43). The data indicated that FNS significantly enhanced axonal regeneration and motor function recovery after cerebral ischemia. FNS also significantly increased cAMP and PKA levels after ischemic brain injury. All the beneficial effects of FNS were blocked by Rp-cAMP, an antagonist of PKA. Our research suggested that the axonal regeneration conferred by FNS was likely achieved via the regulation of cAMP/PKA pathway.

Sodium butyrate reduces high-fat diet-induced non-alcoholic steatohepatitis through upregulation of hepatic GLP-1R expression.

Glucagon-like peptide-1 (GLP-1) has a broad spectrum of biological activity by regulating metabolic processes via both the direct activation of the class B family of G protein-coupled receptors and indirect nonreceptor-mediated pathways. GLP-1 receptor (GLP-1R) agonists have significant therapeutic effects on non-alcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH) in animal models. However, clinical studies indicated that GLP-1 treatment had little effect on hepatic steatosis in some NAFLD patients, suggesting that GLP-1 resistance may occur in these patients. It is well-known that the gut metabolite sodium butyrate (NaB) could promote GLP-1 secretion from intestinal L cells. However, it is unclear whether NaB improves hepatic GLP-1 responsiveness in NAFLD. In the current study, we showed that the serum GLP-1 levels of NAFLD patients were similar to those of normal controls, but hepatic GLP-1R expression was significantly downregulated in NAFLD patients. Similarly, in the NAFLD mouse model, mice fed with a high-fat diet showed reduced hepatic GLP-1R expression, which was reversed by NaB treatment and accompanied by markedly alleviated liver steatosis. In addition, NaB treatment also upregulated the hepatic p-AMPK/p-ACC and insulin receptor/insulin receptor substrate-1 expression levels. Furthermore, NaB-enhanced GLP-1R expression in HepG2 cells by inhibiting histone deacetylase-2 independent of GPR43/GPR109a. These results indicate that NaB is able to prevent the progression of NAFL to NASH via promoting hepatic GLP-1R expression. NaB is a GLP-1 sensitizer and represents a potential therapeutic adjuvant to prevent NAFL progression to NASH.

[Comparative study on anti-inflammatory and immunomodulation of different Isatidis Radix strains growing in Gansu Province].

OBJECTIVE: To investigate anti-inflammatory and immunomodulation effects of different ecotype from Isatidis Radix growing in Gansu province. METHODS: Mice were randomly divided into 6 groups (n=11)and used the auricular swelling and paw edema to observe the anti-inflammatory effects of Isatidis Radix; Mice were randomly divided into 7 groups (n=11) and through the gasbag synovitis model to observe the anti-inflammatory effects of Isatidis Radix; Mice were randomly divided into 6 groups (n=11), the immunosuppressed model were established by injection of cyclophosphamide (CTX) to study the effects of Isatidis Radix on index of thymus, blood routine and cytokines. RESULTS: Gansu different ecotype from Isatidis Radix could reduce the swelling of the mice auricle, paw edema and total protein, leukotriene B4(LTB4)and malonaldehyde(MDA) in airbag synovitis exudates, and upgrade serum levels of superoxide dismutase (SOD); Degrade the tumor necrosis factor-α (TNF-α) and upgrade the index of thymus, the number of red and white corpuscles, the level of interferon-γ (IFN-γ), interleukin-4 (IL-4) (P<0.05, 0.01) of mice immunosuppressed model; Above the research of anti-inflammatory and immunomodulation, there were no significant differences between Isatidis Radix of Gansu different ecotype and tetraploid. CONCLUSIONS: Different ecotype of Isatidis Radix has obvious functions in anti-inflammatory and immunomodulation, but there are no significant differences between Gansu different ecotype and tetraploid.

[Chemical constituents, biological activities and quality control of plants from genus Pyrola].

Plants from the genus Pyrola are widely distributed in North Temperate zone. The quinones, phenol glycosides, terpenoids, flavonoids and volatile oil compounds have been identified from these plants. The in vivo and in vitro studies have shown that the genus Pyrola plants exhibit a wide range of pharmacological properties, including antioxidant, antitumor, antibacterial, anti-ischemia and anti-inflammatory activities. Based on analysis of the literature of the genus Pyrola plant, this review summarized the research on chemical constituents, pharmacology and quality control in recent years which can provide evidences for further investigation on the genus Pyrola plants.