Cayratia albifolia C.L.Li exerts anti-rheumatoid arthritis effect by inhibiting macrophage activation and neutrophil extracellular traps (NETs).

BACKGROUND: Cayratia albifolia C.L.Li (CAC), commonly known as "Jiao-Mei-Gu" in China, has been extensively utilized by the Dong minority for several millennia to effectively alleviate symptoms associated with autoimmune diseases. CAC extract is believed to possess significant anti-inflammatory properties within the context of Dong medicine. However, an in-depth understanding of the specific pharmaceutical effects and underlying mechanisms through which CAC extract acts against rheumatoid arthritis (RA) has yet to be established. METHODS: Twenty-four Sprague-Dawley rats were divided into four groups, with six rats in each group. To induce the collagen-induced arthritis (CIA) model, the rats underwent a process of double immunization with collagen and adjuvant. CAC extract (100 mg/kg) was orally administered to rats. The anti-RA effects were evaluated in CIA rats by arthritis score, hind paw volume and histopathology analysis. Pull-down assay was conducted to identify the potential targets of CAC extract from RAW264.7 macrophage lysates. Moreover, mechanism studies of CAC extract were performed by immunofluorescence assays, real-time PCR and Western blot. RESULTS: CAC extract was found to obviously down-regulate hind paw volume of CIA rats, with diminished inflammation response and damage. 177 targets were identified from CAC extract by MS-based pull-down assay. Bioinformatics analysis found that these targets were mainly enriched in macrophage activation and neutrophils extracellular traps (NETs). Additionally, we reported that CAC extract owned significant anti-inflammatory activity by regulating PI3K-Akt-mTOR signal pathway, and inhibited NETosis in response to PMA. CONCLUSIONS: We clarified that CAC extract significantly attenuated RA by inactivating macrophage and reducing NETosis via a multi-targets regulation.

Coptis chinensis and Berberine Ameliorate Chronic Ulcerative Colitis: An Integrated Microbiome-Metabolomics Study.

Coptis chinensis Franch (RC), has historically been used for the treatment of "Xiao Ke" and "Xia Li" symptoms in China. "Xia Li" is characterized by abdominal pain and diarrhea, which are similar to the clinical symptoms of ulcerative colitis (UC). For the first time, this study aims to compare the anti-colitis effects of berberine (BBR) and total RC alkaloids (TRCA) and investigate the underlying metabolites and gut microbiota biomarkers. Metabolomics results showed that several colitis-related biomarkers, including lysophosphatidyl ethanolamine, lysophosphatidylcholine, scopolamine-methyl-bromide, N1-methyl-2-pyridone-5-carboxamide, 4-hydroxyretinoic acid, and malic acid, were significantly improved in model mice after BBR and TRCA treatments. High-dose BBR and TRCA treatments reversed the mouse colon shortening caused by dextran sodium sulfate (DSS), alleviated bowel wall swelling, and reduced inflammatory cell infiltration. BBR and TRCA restored the damaged mucosa integrity in colitis mice by upregulating claudin 1 and occludin, preventing colon epithelium apoptosis by inhibiting the cleavage of caspase 3. Additionally, BBR and TRCA significantly decreased the richness of the pathogenic bacteria Bacteroides acidifaciens but increased the abundance of the probiotic Lactobacillus spp. Notably, TRCA exhibited superior anti-colitis effects to those of BBR. Thus, this agent warrants further study and application in the treatment of inflammatory bowel disease in the clinic.

Effect of pachymaran on oxidative stress and DNA damage induced by formaldehyde.

To further explore the pharmacological effect of pachymaran, this article studied the inhibition of pachymaran on oxidative stress and genetic damage induced by formaldehyde. 40 adult Kunming male mice were randomly divided into four groups with different interventions. One week later, the contents of serum SOD, GR, MDA, DNA-protein crosslink (DPC), 8-hydroxydeoxyguanosine (8-OHDG) and DNA adduct were determined by ELISA. The results showed that there were statistically significant differences in the contents of SOD, GR and MDA among the four groups (P < 0.01). The activity of SOD and GR increased along with the increase of pachymaran dosage (SOD: rs = 0.912, P < 0.01; GR: rs = 0.857, P < 0.01), while the content of MDA showing a significant negative correlation (rs = - 0.893, P < 0.01). There were statistically significant differences in the levels of DPC, 8-OHDG and DNA adduct among the four groups (DPC and DNA adduct: P < 0.01, 8-OHDG: P < 0.05), the concentration decreased along with the increase of pachymaran dosage (DPC: rs = - 0.855, P < 0.01; 8-OHDG:rs = - 0.412, P < 0.05, DNA adduct: γs = - 0.869, P < 0.01). It can be inferred that pachymaran can inhibit oxidative stress and DNA damage induced by formaldehyde with the dose-effect relationship.

The Identification of SQS/SQE/OSC Gene Families in Regulating the Biosynthesis of Triterpenes in Potentilla anserina.

The tuberous roots of Potentilla anserina (Pan) are an edible and medicinal resource in Qinghai-Tibetan Plateau, China. The triterpenoids from tuberous roots have shown promising anti-cancer, hepatoprotective, and anti-inflammatory properties. In this study, we carried out phylogenetic analysis of squalene synthases (SQSs), squalene epoxidases (SQEs), and oxidosqualene cyclases (OSCs) in the pathway of triterpenes. In total, 6, 26, and 20 genes of SQSs, SQEs, and OSCs were retrieved from the genome of Pan, respectively. Moreover, 6 SQSs and 25 SQEs genes expressed in two sub-genomes (A and B) of Pan. SQSs were not expanded after whole-genome duplication (WGD), and the duplicated genes were detected in SQEs. Twenty OSCs were divided into two clades of cycloartenol synthases (CASs) and ß-amyrin synthases (ß-ASs) by a phylogenetic tree, characterized with gene duplication and evolutionary divergence. We speculated that ß-ASs and CASs may participate in triterpenes synthesis. The data presented act as valuable references for future studies on the triterpene synthetic pathway of Pan.

Autophagy inhibition restores CD200 expression under IL-1ß microenvironment in placental mesenchymal stem cells of fetal origin and improves its pulmonary fibrosis therapeutic potential.

BACKGROUND: Mesenchymal stem cells (MSCs) are promising remedies for various inflammatory disease including pulmonary fibrosis (PF). However, the properties of MSCs in PF pathological microenvironment remain unclear. In this study, the efficacy of autophagy in placental mesenchymal stem cells of fetal origin (fPMSCs) in either IL-1ß treatment or BLM induced pulmonary fibrosis mice model was examined. METHODS: The characteristic of fPMSCs was identified by morphological observation, flow cytometry and differentiation potential. In vitro experiments, fPMSCs were stimulated with IL-1ß, to mimic inflammatory microenvironment of pulmonary fibrosis. The immunosuppressive properties and autophagic function in fPMSCs treated with IL-1ß were evaluated by both macrophage cells THP-1 activation and the expression of CD200 situation, autophagy marker and MAPK signaling pathway. The in vivo anti-fibrotic activity of fPMSCs interfering autophagy was evaluated by using BLM induced pulmonary fibrosis mice model. RESULTS: fPMSCs belonged to CD73+CD90+CD105+/CD14- CD34-CD45-HLA-DR- cells, and capable differentiation to adipogenic, osteogenic and chondrogenic cells. In addition, immunoinhibitory activity of fPMSCs for macrophage was restrained by IL-1ß treatment in CD200 dependent manner. Suppression of autophagy by sh-Atg5 lentivirus increased the expression of CD200 and ratio of CD200 positive fPMSCs, and enhanced fPMSCs immunosuppression for THP-1 activation. Mechanistically, IL-1ß induced autophagy regulated by p38 signaling cascade. In vivo, autophagy inhibition induced by Atg5 knockdown in fPMSCs resulted in strengthening antifibrotic effects on PF mice model. CONCLUSIONS: Collectively, autophagy derived from inflammatory microenvironment hampered the immunoinhibitory properties of MSCs. Based on this, adjustment of autophagy may be a valid approach to facilitate their immunomodulatory and anti-fibrotic efficacy.

Study of the Antimicrobial Activity of the Chinese Dong Ethnic Minority Medicine, Madeng'ai.

The overuse of antibiotics has contributed to the emergence of multidrug-resistant bacteria, which poses a challenging task for clinical therapy. Thus, new agents with antibiotic efficacy against multidrug-resistant infections are needed. The traditional Dong ethnic minority medicines have emerged as a new source for prodrug selection. Among them, Madeng'ai (PotentillafreynianaBornm) is widely used by the folk for anti-infection and wound healing, although the mechanisms remain unclear. In this study, the antimicrobial activities of Dong medicine Madeng'ai were evaluated both in vitro and in vivo. S. aureus, E. coli, E. faecalis, P. aeruginosa, K. pneumoniae, and A. baumannii were cultured in LB media, different concentrations of Madeng'ai powder solution were added to the LB agar plates to evaluate minimal inhibitory concentration. An animal study was performed on a mouse excisional wound model combined with bacterial solution injection in the wound area. After Madeng'ai or PBS treatment, hematoxylin and eosin analysis were used for pathological analysis of skin tissues from the infected area. Madeng'ai powder solution over 2 mg/mL concentration completely inhibited E. coli growth. At 4.0 mg/mL, Madeng'ai significantly inhibited the growth of E. faecalis, Pseudomonas aeruginosa (PAE), Klebsiella pneumoniae, and Acinetobacter baumannii. The mouse model revealed that Madeng'ai could suppress the growth of MRSA and PAE and accelerate healing of cutaneous wounds. Madeng'ai, a newly discovered Dong ethnic minority medicine possesses considerable antimicrobial activity against both human normal pathogenic bacteria and multiresistance bacteria such as Pseudomonas aeruginosa, S. aureus, and Acinetobacter baumannii. Therefore, Madeng'ai has great potential for further study and clinical application.

New Terpenoids from Potentilla freyniana Bornm. and Their Cytotoxic Activities.

Two new A-ring contracted triterpenoids, madengaisu A and madengaisu B, and one undescribed ent-kaurane diterpenoid, madengaisu C, along with 20 known compounds were isolated from the roots of Potentilla freyniana Bornm. The structures were elucidated using extensive spectroscopic techniques, including 1D and 2D-NMR, HR-ESI-MS, ECD spectra, IR, and UV analysis. Moreover, all isolated constituents were evaluated for their anti-proliferative activity against RA-FLS cells and cytotoxic activities against the human cancer cell lines Hep-G2, HCT-116, BGC-823, and MCF-7. Ursolic acid and pomolic acid displayed moderate inhibitory activity in RA-FLS cells with IC50 values of 24.63 ± 1.96 and 25.12 ± 1.97 µM, respectively. Hyptadienic acid and 2α,3ß-dihydroxyolean-12-en-28-oic acid 28-O-ß-d-glucopyranoside exhibited good cytotoxicity against Hep-G2 cells with IC50 values of 25.16 ± 2.55 and 17.66 ± 1.82 µM, respectively. In addition, 2α,3ß-dihydroxyolean-13(18)-en-28-oic acid and alphitolic acid were observed to inhibit HCT-116 cells (13.25 ± 1.65 and 21.62 ± 0.33 µM, respectively), while madengaisu B and 2α,3ß-dihydroxyolean-13(18)-en-28-oic acid showed cytotoxic activities against BGC-823 cells with IC50 values of 24.76 ± 0.94 and 26.83 ± 2.52 µM, respectively, which demonstrated that triterpenes from P. freyniana may serve as therapeutic agents for RA and cancer treatment.

[Research progress on chemical constituents and pharmacological activities of Potentilla].

There are 200-500 species of Potentilla(Rosaceae) worldwide, among which 90 species are widely distributed in China and have a long history of ethnic medicinal use. According to our statistics, a total of 367 compounds have been isolated and identified from plants of this genus, including terpenoids, flavonoids, phenolic acids, tannins, and phenylpropanoids. The medicinal materials made from these plants mainly have antioxidative, blood sugar-lowering, anti-inflammatory, anti-tumor, cardiovascular system-protecting, neuroprotective, and hepatoprotective activities. This study systematically reviews the research progress on chemical constituents and pharmacological activities of Potentilla plants to provide a basis for further research and clinical application.

Water extract of Cayratia albifolia C.L.Li root relieves zymosan A-induced inflammation by restraining M1 macrophage polarization.

BACKGROUND: Cayratia albifolia C.L.Li (CAC) is a traditional Chinese herbal medicine used to treat inflammatory diseases. Our laboratory has firstly reported that the water extract from CAC relieved lipopolysaccharide (LPS)-induced inflammation, however stronger evidence is still needed to prove its anti-inflammatory effects and the mechanisms involved are also ambiguous. PURPOSE: This study sought to provide more evidence for the application of CAC in alleviating infectious inflammation and disclose novel pharmacological mechanisms. METHODS: Mice were injected with zymA into their paws or peritoneal cavities, and then treated with CAC. ELISA, immunofluorescence and flow cytometry were performed to detect the cytokines (IL-1ß, IL-6, TNF-α and IL-10) generation, the cell infiltration, and the CD86 or CD206 expression of macrophages. Then in vitro assays were performed on bone marrow-derived macrophages (BMDMs) and peritoneal macrophages (PMs) to detect their expression of iNOS, arg-1 and the cytokines above. On mechanisms, western blotting (WB), electrophoretic mobility shift assay (EMSA) and flow cytometry were carried out to measure NF-κB transcriptional activity, mitochondrial bioactivity and the mTORC1 activation when BMDMs were stimulated by zymA and treated with CAC. Finally, the chemical components consisted in the extract were analyzed by LC-MS. RESULTS: 200 mg/kg CAC clearly inhibited zymA induced mouse paw edema and reduced the contents of IL-1ß, IL-6 and TNF-α rather than IL-10 in local tissues. CAC also reduced CD86 but not CD206 in macrophages in situ. Through in vitro experiments, it was discovered that CAC reduced the protein and mRNA levels of IL-1ß, IL-6 and TNF-α, and also inhibited iNOS expression, but showed no influence on IL-10 and arg-1 in macrophages. We found CAC reduced NF-κB transcriptional activity, down-regulated mitochondrial membrane potential and ROS levels, and inhibited mTORC1 activity. Finally, we identified 15 major compounds in the extract, among which 4-guanidinobutyric acid and kynurenic acid were the most abundant. CONCLUSION: This study provides further evidence that CAC significantly reduces zymA induced infectious inflammation. In addition, this novel data revealed that CAC restrained M1 rather than promoting M2 macrophages polarization via multi-target inhibitory effects, based on its potentially active components.

Rapid Identification and Systematic Mechanism of Flavonoids from Potentilla freyniana Bornm. Based on UHPLC-Q-Exactive Orbitrap Mass Spectrometry and Network Pharmacology.

Potentilla freyniana Bornm. (P. freyniana), belonging to the family Rosaceae, has been used as a folk medicine in China. However, as we know, the constituents and the systematic elucidation of the mechanism were not fully investigated. Therefore, it is necessary to develop a rapid method using LC-MS and network pharmacology for the detection and identification of constituents and the systematic mechanism of P. freyniana. Firstly, the flavonoids were detected and identified based on ultra-high-performance liquid chromatography coupled with Quadrupole-Exactive Focus Orbitrap MS (UHPLC-Q-Exactive Orbitrap MS). After that, the potential targets of those constituents were obtained by database mining. Then, the core targets were predicted by protein-protein interaction network and network analysis. Finally, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were carried out via DAVID. This finding revealed that P. freyniana possessed 43 flavonoids (40 of them were first reported) with 23 core target genes, which are associated with PI3K-Akt, MAPK, TNF signaling pathway, and pathway in cancer. This study demonstrated the multicompound, multitarget, and multimechanism of P. freyniana, which are very beneficial to develop the further study and utilization of this plant including the material basis and quality control research.

Identification of Five Ferroptosis-Related LncRNAs as Novel Prognosis and Diagnosis Signatures for Renal Cancer.

Background: Ferroptosis is a novel regulated cell death that is characterized by iron-dependent oxidative damage. Renal cancer is the second most common cancer of the urinary system, which is highly correlated with iron metabolism. The aim of our present study was to identify suitable ferroptosis-related prognosis signatures for renal cancer. Methods: We downloaded the RNA-seq count data of renal cancer from The Cancer Genome Atlas database and used the DESeq2, Survival, and Cox regression analyses to screen the prognosis signatures. Results: We identified 5 ferroptosis-related differentially expressed lncRNAs (FR-DELs) (DOCK8-AS1, SNHG17, RUSC1-AS1, LINC02609, and LUCAT1) to be independently correlated with the overall survival (OS) of patients with renal cancer. The risk assessment model and diagnosis model constructed by those 5 FR-DELs could well predict the outcome and the diagnosis of renal cancer. Conclusion: Our present study not only suggested those 5 FR-DELs could be used as prognosis and diagnosis signatures for renal cancer but also provided strategies for other cancers in the screening of ferroptosis-related biomarkers.

Resveratrol rescued the pain related hypersensitivity for Cntnap2-deficient mice.

Contactin-associated protein-like 2 (CNTNAP2 or CASPR2) is a neuronal transmembrane protein of the neurexin superfamily which is correlated with pain related hypersensitivity. Recent results indicated that the hyperactive phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway may be a promising therapeutic target for pain-related hypersensitivity in patients with dysfunction of CNTNAP2. Resveratrol is one of the most widely studied polyphenols with several beneficial properties. In the present study, we investigated the effects of resveratrol on the pain related hypersensitivity. And we found that the up-regulated phosphorylation of S6 could be suppressed by resveratrol. The nocifensive behavior duration time to heat and chemical algogens stimulation in Cntnap2-deficiency (Cntnap2-/-) mice could be attenuated by resveratrol. Our results indicated that resveratrol could rescue the pain related hypersensitivity for Cntnap2-/- mice may be via mTOR signaling pathway.

The water extract of "Jiao Mei Gu" attenuates the lipopolysaccharide-induced inflammatory response via inhibiting NF-κB activity in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Jiao Mei Gu (JMG), Cayratia albifolia C.L.Li, is a type of Dong plant widely growing in Dong autonomous counties, Hunan province, China. As a type of traditional herbal medicine, the root of JMG plant has been used to treat inflammatory-related diseases such as arthritis because of its prominent anti-inflammatory effects in Dong medicine. AIM OF THE STUDY: This work investigated the anti-inflammatory effects and mechanisms of the water extract from the root of JMG on lipopolysaccharide (LPS)-induced inflammatory models. METHODS: Endotoxemia was induced in C57BL/6 mice by intraperitoneal injection of LPS (20 mg/kg), meanwhile intraperitoneal administration of safe doses of JMG. The survival curve of mice was determined. Serum inflammatory cytokines were detected by the Bio-Plex Mouse Cytokine 23-Plex Panel Kit and enzyme-linked immunosorbent assay (ELISA) at 6 h after drug treatment. Hematoxylin-eosin (HE) staining of important organs was completed at 24 h after treatment. The mechanism of inflammatory action was investigated in vitro on LPS-stimulated macrophages. Macrophage inflammation was then induced using 10 µg/mL LPS. The anti-inflammatory effect of JMG was investigated by the quantitative polymerase chain reaction (qPCR) and ELISA. The anti-inflammatory mechanism was determined using western blotting, the electrophoretic mobility shift assay, and immunocytochemistry. Finally, the antimicrobial activity of JMG was verified by survival experiments in vivo and by bacterial culture experiments in vitro. RESULTS: A 200 mg/kg water extract of JMG was safe for mice and had a significant protective effect on LPS-induced sepsis. Organ damage of heart, liver, lung and kidney was also significantly reduced at 24 h in the JMG group, when compared with the LPS group. The serum MIP-1α (CCL-3), MIP-1ß (CCL-4), IL-1ß, and TNFα cytokines were significantly decreased at 6 h in the JMG group, when compared with the LPS group. In a similar manner, 0.2µg/ml JMG significantly reduced mRNA and protein levels of MIP-1α (CCL-3), MIP-1ß (CCL-4), IL-1ß, and TNFα in LPS-stimulated macrophage. JMG treatment inhibited the phosphorylation of NF-κB p65 and reduced nuclear transduction, thus reducing transcriptional activity. At the same time, we showed that JMG had no protective effect on Escherichia coli-induced sepsis, as well as no antimicrobial activity. CONCLUSIONS: Our results showed that a water-soluble extract of JMG inhibited LPS-induced inflammation via attenuating the NF-κB signaling pathway, which provides an important rationale for the treatment of inflammation-related diseases.

Interleukin-18 promotes fibroblast senescence in pulmonary fibrosis through down-regulating Klotho expression.

Idiopathic pulmonary fibrosis (IPF) is a lethal disease of unknown aetiology that largely presents in the elderly. The mechanisms related to aging such as fibroblast senescence have been strongly implicated in pathology of IPF. We have previously demonstrated the protective effects of IL-18 binding protein (IL-18BP) against bleomycin (BLM)-induced pulmonary fibrosis (PF) via inhibition of epithelial-to-mesenchymal transition. However, the role of IL-18 in fibroblast senescence in PF is still unknown. The aim of this study was to investigate the effects of IL-18 on fibroblast senescence in the development of PF. We found that SA-ß-gal positive cells, the proportion of cells in G1 phase, and expressions of p21 and p53 were increased in primary lung fibroblasts isolated from BLM-challenged mice, while the fibroblasts from IL-18BP-treated mice showed decreased senescence propensity. We further demonstrated that IL-18 was sufficient to trigger senescence of primary lung fibroblasts. The senescence-associated secretory phenotype (SASP) of fibroblasts treated with IL-18 robustly stimulated a fibrotic phenotype in pulmonary fibroblasts. Moreover, the expression of Klotho, an anti-senescence protein, was down-regulated after IL-18 treatment in primary lung fibroblasts. Overexpression of Klotho reversed the senescence and SASP induced by IL-18 in lung fibroblasts. In summary, we reported for the first time that IL-18 promoted the lung fibroblast senescence and SASP in PF through blocking Klotho pathway. Neutralize IL-18 by IL-18BP exhibited antifibrotic effects partly by suppressing lung fibroblast senescence in PF. It contributes to the growing evidence that IL-18 could be a therapeutic target for PF.

Sema 3A as a biomarker of the activated mTOR pathway during hexavalent chromium-induced acute kidney injury.

Semaphorin 3A (sema 3A) is one of a class of secretory proteins belonging to a family of axon-directed factors found in podocytes, distal tubules, and collecting tubes of the kidney. It is considered to be a potential target molecule involved in the mammalian target of the rapamycin (mTOR) pathway in renal injury or renal diseases, but it has an unknown role in the course of hexavalent chromium-Cr(VI) induced nephrotoxicity. In the present study, an acute kidney injury (AKI) model in rats or cultured tubular epithelial HK-2 cells was employed for Cr(VI) exposure alone or in combination with rapamycin (Rap) or N-acetyl-l-cysteine (NAC) or recombinant sema 3A. The methods of histopathology, biochemics, and western blotting were applied to evaluate tubular injury and the role of sema 3A. The results showed that a significant increase of urinary sema 3A indicates an early occurrence of AKI exposed to Cr(VI), accompanied with a significant increase of tubular injury score and phosphorylated mTOR proteins. Further, Cr(VI) treatment, in combination with pretreatment of the mTOR pathway inhibitor, Rap, showed a considerably stronger protective effect of Rap in protecting against Cr(VI)-induced nephrotoxicity than that seen with the free radical scavenger NAC, highlighting the dominant renal protective role of the mTOR pathway in inhibiting toxicity by downregulating the expressed levels of sema 3A in renal tissue. This study has demonstrated that an increased expression of sema 3A occurs in Cr(VI)-induced AKI resulting from activation of the mTOR pathway, and that inhibition of this pathway has been shown to decrease the severity of the toxicity. In conclusion, this study has shown that increased urinary sema 3A is indicative of an activated mTOR pathway and is a valuable biomarker of the early AKI induced by Cr(VI) exposure.

Hypolipidemic effects of Myrica rubra extracts and main compounds in C57BL/6j mice.

The present study evaluated the antihyperlipidemic activity of myricetin, myricetrin, the alcohol fraction (AF) and the ethyl acetate fraction (EF) obtained from the bark of Myrica rubra (MR) in high-fat and high-cholesterol (HFHC) induced hyperlipidemic C57BL/6j mice. Mice were treated with myricetin, myricetrin, AF and EF with a dose of 130 mg per kg per day for 35 days. After treatment, serum parameters including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), total bile acids (TBA), etc., were examined. The results revealed that EF showed the highest weight lowering activity (P < 0.01). All tested samples decreased the levels of the TC, TG, LDL-C, TBA and LPS (lipopolysaccharide) content in the serum of mice to different extents. Liver fat deposition was significantly reduced after myricetin, myricetrin, AF and EF therapy (P < 0.01). Additionally, the cell size of epididymal adipose tissue was also decreased in myricetin, AF and EF groups (P < 0.05). The antihyperlipidemic activity of these samples may be attributed to the inhibition of lipid synthesis via suppressing the expression of HMGCR (3-hydroxy-3-methylglutaryl coenzyme A reductase) and ACC1 (acetyl-CoA carboxylase), promoting the metabolism and excretion of lipids via up-regulating the expression of SREBP2 (sterol regulatory element binding proteins), LDLR (low density lipoprotein receptor), UCP2 (uncoupling protein 2) and CYP7A1 (cholesterol 7α-hydroxylase). These results may provide a powerful foundation for seeking and utilizing Myrica rubra bio-active compounds for the treatment of hyperlipidemia and cardiovascular diseases.

Synergy effects of herb extracts: pharmacokinetics and pharmacodynamic basis.

Herbal medicine, especially traditional Chinese medicine and Ayurvedic medicine have played and still play an important role in fighting against various diseases. Emerging clinical studies regarding traditional Chinese medicine have provided convincing evidence for the first time to gain credibility and reputation outside China. Although synergistic therapeutic actions of herbal ingredients have been frequently reported, few reports have offered clear underlying mechanisms. This might be the main reason for the conflicting views with respect to the therapeutic efficacy of medicinal herbs. Therefore, this paper reviews the herb synergisms reported in the recent literature and discusses thoroughly the mechanisms underlying synergistic actions of herbal ingredients. The authors conducted an electronic literature search to detect articles published mainly in the last five years. Articles were included if they pertained to synergy research of ethnomedicines or the active compounds derived from them, included verification of synergy effects using modern analytical tools and molecular-biological methods. Results have revealed that the multi-component nature of medicinal herbs makes them particularly suitable for treating complex diseases and offers great potential for exhibiting synergistic actions. The mechanisms underlying synergistic therapeutic actions of herb medicines are (1): different agents may regulate either the same or different target in various pathways, and therefore cooperate in an agonistic, synergistic way; (2): regulate the enzymes and transporters that are involved in hepatic and intestinal metabolism to improve oral drug bioavailability; (3): overcome the drug resistance mechanisms of microbial and cancer cells; and (4): eliminate the adverse effects and enhance pharmacological potency of agents by "processing" or by drug-drug interaction. The exploration of synergistic mechanisms of herbal ingredients will not only help researchers to discover new phytomedicines or drug combinations but also help to avoid the possible negative synergy. Further clinical research is required for verifying these reported drug combinations and discovered synergistic mechanisms.

A de novo 1.38 Mb duplication of 1q31.1 in a boy with hemifacial microsomia, anophthalmia, anotia, macrostomia, and cleft lip and palate.

We reported a 2-year-old boy with developmental delay, mild mental retardation, and severe craniofacial malformation, including facial asymmetry with hypoplasia of the left zygoma, maxilla, and mandible, and left anophthalmia and anotia. A genome-wide screen revealed a 1.38 Mb duplication on chromosome 1q31.1, which was absent in his parents and 27 healthy controls. The duplication region contains two Refseq genes, PLA2G4A and C1orf99, which have not been reported to be implicated in craniofacial malformation. Functional studies of these genes and additional clinical analysis are necessary to elucidate the pathogenesis of craniofacial malformation.

[The epidemiological characteristic of 97,823 cases of pre-hospital medical care in Guangzhou city].

OBJECTIVE: To investigate the epidemiological information of patients in pre-hospital medical care in Guangzhou city, and to explore the characteristics of the patients. METHODS: The data in the year of 2008 were retrieved from the computer database of Guangzhou Emergency Medical Rescue Command Center. RESULTS: (1)In a total of 969 410 calls received, the time of distribution was found to be mainly between 16:00 and 18:00 [11.78% (114 224)], and least frequently between 04:00 and 06:00 [2.40% (23 237)]. (2)Among 109 682 dispatches of ambulances, Baiyun district received the most [26.77% (29 364)], and followed by Haizhu district [18.30% (20 069)], Tianhe district [18.20% (19 962)], respectively. (3)Among 97 823 cases of pre-hospital medical care, death rate of the male patients was higher than the female [amount: 57.65% (56 394) vs. 38.48% (37 641), mortality: 59.17% (3 269) vs. 33.95% (1 876)]. (4)In 9 7823 cases of pre-hospital medical care, trauma constituted the highest rate [34.57% (33 820)], especially traffic accidents [11.56% (11 307)], and the age of most of the patients ranged between 21 and 50. Disease of the nervous system ranged the second, followed by diseases of circulatory system, respiratory system and digestive system, and most of them were over 51 years old, and most frequently above 70. (5)In 97 823 cases of pre-hospital medical care, there were 5 525 deaths (5.65%), in whom the circulatory system diseases ranged first (especially sudden death) [33.07% (1 827)], followed by unclassified diseases [29.79% (1 646)], trauma [15.67% (866)], respiratory diseases [7.48% (413)], and neurological emergency illnesses [5.95% (329)]. The age of deceased was far older than 51, particularly 70. The age of most of the deceased was above 61, and age of traumatic death was 21-40. CONCLUSION: (1) It is very important to reduce the death rate of the middle-old aged patients by strengthening prevention and timely treatment of cardiovascular and cerebrovascular diseases, and improve the medical strategies in emergency care, in order to lower the death rate during emergency.(2)It is very important to emphasize safely in production lines and to strengthen traffic regulations in order to reduce the incidence of trauma, thus it is especially traffic accident, expect that the death rate of trauma could be lowered.