Effect of acupotomy combined with electroacupuncture on knee function of patients with knee osteoarthritis. / åˆƒé’ˆç»“åˆç”µé’ˆæ²»ç–—å¯¹è†å ³èŠ‚éª¨å ³èŠ‚ç‚Žæ‚£è€ è†å ³èŠ‚åŠŸèƒ½çš„å½±å“.

OBJECTIVES: To compare the clinical effect of combined therapy of acupotomy and electroacupuncture (EA) with the simple application of EA on knee osteoarthritis (KOA), and their influence on knee function. METHODS: Sixty-eight KOA patients were randomly divided into 2 groups, an acupotomy group and an EA group. In the acupotomy group, the combined therapy of acupotomy and EA was adopted. In the EA group, EA was simply used, delivered once every two days, 3 treatments a week；and the duration of treatment was 4 weeks. In the acupotomy group, besides the treatment as the EA group, acupotomy was combined once weekly, and the duration of treatment was 4 weeks. Separately, before and after treatment, and in 4 and 12 weeks after treatment completion (1-month and 3-month follow-up), the results of the timed up and go test (TUG), the 9-step stair climb test (9-SCT) and the knee function (Western Ontario and McMaster University osteoarthritis index visualization scale ［WOMAC］) were measured in the two groups. RESULTS: By the intention-to-treat analysis, the results of TUG, 9-SCT and WOMAC scores were reduced after treatment and in 1-month and 3-month follow-up when compared with those before treatment in the patients of the two groups (P<0.05). Compared with the EA group at the same time point, TUG results were decreased after treatment and in 1-month follow-up, and WOMAC score was reduced after treatment in the acupotomy group. WOMAC score in 1-month follow-up was reduced when compared with that before treatment within the acupotomy group (P<0.05). CONCLUSIONS: Either the simple application of EA or the combined therapy of acupotomy and EA can improve knee function, but the combined therapy obviously increases the walking speed and relieves the symptoms such as joint pain and morning stiffness. The treatment with acupotomy and EA is safe and effective on KOA and the long-term effect is satisfactory.

An ultrasound-guided percutaneous electrical nerve stimulation regimen devised using finite element modeling promotes functional recovery after median nerve transection.

Percutaneous electrical nerve stimulation of an injured nerve can promote and accelerate peripheral nerve regeneration and improve function. When performing acupuncture and moxibustion, locating the injured nerve using ultrasound before percutaneous nerve stimulation can help prevent further injury to an already injured nerve. However, stimulation parameters have not been standardized. In this study, we constructed a multi-layer human forearm model using finite element modeling. Taking current density and activated function as optimization indicators, the optimal percutaneous nerve stimulation parameters were established. The optimal parameters were parallel placement located 3 cm apart with the injury site at the midpoint between the needles. To validate the efficacy of this regimen, we performed a randomized controlled trial in 23 patients with median nerve transection who underwent neurorrhaphy. Patients who received conventional rehabilitation combined with percutaneous electrical nerve stimulation experienced greater improvement in sensory function, motor function, and grip strength than those who received conventional rehabilitation combined with transcutaneous electrical nerve stimulation. These findings suggest that the percutaneous electrical nerve stimulation regimen established in this study can improve global median nerve function in patients with median nerve transection.

Case report: Ultrasound-guided multi-site electroacupuncture stimulation for a patient with spinal cord injury.

Introduction: Spinal cord injury causes permanent neurological deficits, which have devastating physical, social, and vocational consequences for patients and their families. Traditional Chinese medicine uses acupuncture to treat neuropathic pain and improve nerve conduction velocity. This treatment can also reduce peripheral nerve injury joint contracture and muscle atrophy in affected patients. And it's got a remarkable restoration when electrical stimulation therapy on impaired peripheral nerves in animal models and clinical trials. Case description: A 48-year-old woman was hit by a heavy object that injured her lower back. The patient had a T12-L1 vertebral flexion and stretch fracture with traumatic spinal stenosis. The patient was transferred to the rehabilitation department after posterior T12-L2-segment pedicle screw system distraction and reduction, internal fixation, decompression, and bone graft fusion. Ultrasound-guided electroacupuncture was used to stimulate the sacral nerve, the spinal nerve, and the head of the patient, accompanied by spinal joint loosening training, respiratory training, lumbar comprehensive sports training, paraplegic limbs comprehensive training, and other manipulative treatment. Outcomes: After the intervention, the patient showed significant improvements in sensory and motor scores, resulting in functional recovery according to ASIA and FIM. The patient gradually showed reasonable functional remission. Discussion: The sacral nerve, the spinal cord, and the head were electrically stimulated by ultrasound-guided electroacupuncture in terms of intervention, and various functions of the patient were alleviated to a certain extent. The efficacy of ultrasound-guided electroacupuncture stimulation in treating neurologic symptoms should be validated in future clinical trials.

Selenium-Enriched Cardamine violifolia Increases Selenium and Decreases Cholesterol Concentrations in Liver and Pectoral Muscle of Broilers.

BACKGROUND: Supernutrition of selenium (Se) in an effort to produce Se-enriched meat may inadvertently cause lipid accumulation. Se-enriched Cardamine violifolia (SeCv) contains >80% of Se in organic forms. OBJECTIVES: This study was to determine whether feeding chickens a high dose of SeCv could produce Se-biofortified muscle without altering their lipid metabolism. METHODS: Day-old male broilers were allocated to 4 groups (6 cages/group and 6 chicks/cage) and were fed either a corn-soy base diet (BD, 0.13-0.15 mg Se/kg), the BD plus 0.5 mg Se/kg as sodium selenite (SeNa) or as SeCv, or the BD plus a low-Se Cardamine violifolia (Cv, 0.20-0.21mg Se/kg). At week 6, concentrations of Se and lipid and expression of selenoprotein and lipid metabolism-related genes were determined in the pectoral muscle and liver. RESULTS: The 4 diets showed no effects on growth performance of broilers. Compared with the other 3 diets, SeCv elevated (P < 0.05) Se concentrations in the pectoral muscle and liver by 14.4-127% and decreased (P < 0.05) total cholesterol concentrations by 12.5-46.7% and/or triglyceride concentrations by 28.8-31.1% in the pectoral muscle and/or liver, respectively. Meanwhile, SeCv enhanced (P < 0.05) muscular α-linolenic acid (80.0%) and hepatic arachidonic acid (58.3%) concentrations compared with SeNa and BD, respectively. SeCv downregulated (P < 0.05) the cholesterol and triglyceride synthesis-related proteins (sterol regulatory element binding transcription factor 2 and diacylglycerol O-acyltransferase 2) and upregulated (P < 0.05) hydrolysis and ß-oxidation of fatty acid-related proteins (lipoprotein lipase, fatty acid binding protein 1, and carnitine palmitoyltransferase 1A), as well as selenoprotein P1 and thioredoxin reductase activity in the pectoral muscle and/or liver compared with SeNa. CONCLUSIONS: Compared with SeNa, SeCv effectively raised Se and reduced lipids in the liver and muscle of broilers. The effect was mediated through the regulation of the cholesterol and triglyceride biosynthesis and utilization-related genes.

A network pharmacology approach for investigating the multi-target mechanisms of Huangqi in the treatment of colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is the third most prevalent cancer globally. In the treatment of CRC, surgical resection is commonly adopted, and neoadjuvant chemotherapy or immunotherapy is mainly administered for patients with advanced disease. However, despite the developments in the field of cancer treatment, the mortality rate of CRC has remained high. Therefore, novel treatments for CRC need to be explored. Astragalus membranaceus, commonly known in China as Huangqi (HQ), a traditional Chinese medicine, has been reported to be a potential antitumorigenic agent. This study aimed to investigate the mechanisms of action of HQ. METHODS: Active ingredients and putative targets of HQ were obtained through a comprehensive search of the Traditional Chinese Medicine Systems Pharmacology database. CRC-related targets were retrieved from the GeneCards database and then overlapping targets were acquired. After visualization of the compound-disease network and protein-protein interaction (PPI) network, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of the overlapping genes were performed. Additionally, HCT116 cells were treated with the active components of HQ at a 20-µM concentration. Cell Counting Kit-8 was used to detect cell activity, and real-time quantitative polymerase chain reaction was carried out to detect the expression of genes downstream of the interleukin (IL)-17 signaling pathway. RESULTS: A PPI network comprising 177 nodes and 318 edges was obtained. The GO analysis of the overlapping genes showed enrichment in response to lipopolysaccharide and oxidative process. For the KEGG analysis, the AGE-RAGE signaling pathway and inflammation-related pathways, such as the IL-17 and tumor necrosis factor (TNF) signaling pathways, were enriched. The in vitro experiments showed that HQ promoted the apoptosis of CRC cells by inhibiting the expression of the CCL2, CXCL8, CXCL10, and PTGS2 genes. CONCLUSIONS: This study systematically revealed the multitarget mechanism of HQ in CRC through a network pharmacology approach. We verified that HQ promotes CRC cell death via the IL-17 signaling pathway. This finding provides indications for further mechanistic studies and the development of HQ as a potential treatment for CRC patients.

Effects of deoxynivalenol on the porcine growth performance and intestinal microbiota and potential remediation by a modified HSCAS binder.

The objectives of this study were to determine the effects of deoxynivalenol (DON) on growth performance and intestinal microbiota in weaning piglets, and potential efficacy of a modified hydrated sodium calcium aluminosilicate (HSCAS) adsorbent to reduce DON toxicity. Four groups of 21-day-old male piglets (n = 7/group) were fed either a control diet, or diet containing 1.0 or 3.0 mg/kg DON, or 3.0 mg/kg DON plus 0.05% modified HSCAS for 28 d. Compared to the control, dietary DON at 1.0 and/or 3.0 mg/kg reduced (P < 0.05) the body weight gain (16.0-60.8%) and feed intake (18.1-38.7%) during the whole experiment, and increased (P < 0.05) the feed/gain ratio (12.8-33.8%) between d 1-28. The body weight gain and feed intake were further decreased (P < 0.05) in 3.0 mg/kg DON in comparison to 1.0 mg/kg DON during d 15-28. DON exposure reshaped gut microbial structure by drastically affecting the abundance of several bacterial phyla, families and genera, including dysbiosis of Actinobacteria, Cyanobacteria, Firmicutes, and Proteobacteria in small intestine. Notably, dietary Amdetox™ supplementation alleviated the adverse effects of DON on growth performance of piglets and improved the intestinal flora disorder. Therefore, the current study has revealed that Amdetox™, the modified HSCAS binder, can alleviate DON-induced negative effects and could be used as a promising countermeasure for reducing DON toxicity.

Botulinum toxin type A ameliorates adjuvant-arthritis pain by inhibiting microglial activation-mediated neuroinflammation and intracellular molecular signaling.

Chronic inflammatory pain is a serious clinical problem caused by inflammation of the joints and degenerative diseases and greatly affects patients' quality of life. Persistent pain states are thought to result from the central sensitization of nociceptive pathways in the spinal dorsal horn. Spinal microglia-mediated neuroinflammation plays a pivotal role in the development and maintenance of the central sensitization of chronic inflammatory pain. Botulinum toxin type A (BoNT/A) was recently reported to have analgesic and anti-inflammatory effects. However, the precise mechanism underlying its analgesic effect remains unclear. Although several studies have reported that BoNT/A could regulate neuroflammation, the reduction of neuroinflammation regulated by BoNT/A in chronic inflammatory pain in experimentally induced arthritis has not been reported. The aim of this study was to investigate whether BoNT/A could alleviate adjuvant-arthritis pain via modulating microglia-mediated neuroinflammation and intracellular molecular pathway. The pain behavioral tests were performed before and after CFA immunization as well as after BoNT/A injection. Western blotting and immunofluorescence staining were used to assess the changes of microglial activation markers (ionized calcium binding adaptor molecule 1, IBA-1) and phosphorylation of P38MAPK (P-p38MAPK) in the lumbar spinal cord. TNF-αand P2X4R gene expression were studied by real-time reverse transcriptase-polymerase chain reaction (RT-PCR). The results showed that (1) the activation of spinal microglia can be continued till 21 days after CFA injection, which suggested its role in the development and maintenance of chronic inflammatory pain. (2) The intra-articular administration of a single effective dose of BoNT/A (5U/10 U) on day 21 after CFA injection significantly reduced nociceptive behaviors and decreased protein overexpression and immunoreactivity for IBA-1 and P-p38MAPK in CFA induced rat. Simultaneously, BoNT/A (5 U) also inhibited the increase in TNF-α mRNA and P2X4R mRNA expression induced by CFA injection. These results suggested that BoNT/A is a potential therapeutic agent for relieving the neuroinflammation that occurs in chronic inflammatory pain by inhibiting the activation of microglial cells and the release of microglia-derived TNF-α. This effect is likely mediated by inhibiting the activation of the P2X4R-P38MAPK signaling pathways in spinal microglial cells.

[Efficacy and mechanism of electroacupuncture on insulin resistant polycystic ovary syndrome].

OBJECTIVE: To explore the therapeutic effect and partial mechanism of electroacupuncture (EA) for patients with insulin resistance (IR) polycystic ovary syndrome (PCOS). METHODS: Seventy patients with IR-PCOS were randomly divided into an EA group (36 cases, 5 cases dropped off) and a medication group (34 cases, 4 cases dropped off). The patients in the medication group were treated with oral administration of metformin hydrochloride, 500 mg each time, twice a day. The patients in the EA group were treated with EA (continuous wave, 2 Hz of frequency) at Zusanli (ST 36), Zhongwan (CV 12), Qihai (CV 6), Yishu (EX-B 3), Shenshu (BL 23), Pishu (BL 20), Ciliao (BL 32) for 30 min, three times a week. One menstrual cycle or 4 weeks were taken as a course of treatment, and 3 continuous courses were given. The follow-up was 3 months. The lipid metabolism indexes of triacylglycerol (TG), total cholesterol (TC), high-density lipoprotein (HDL) and low-density lipoprotein (LDL), homeostasis model assessment-insulin resistance index (HOMA-IR) and testosterone (T) in serum were compared before and after treatment, and the clinical effects of the two groups were evaluated during the follow-up. RESULTS: The total effective rate was 67.7% (21/31) in the EA group and 60.0% (18/30) in the medication group, with no significant difference between the two groups (P>0.05). After treatment, the levels of serum T, HOMA-IR, LDL, TG and TC were decreased significantly in the two groups (P<0.01, P<0.05), and HDL was increased significantly (P<0.01); the levels of TC in the EA group after treatment was lower than that in the medication group (P<0.05). CONCLUSION: EA may adjust some dyslipidemia in patients to correct IR and improve endocrine disorder of PCOS, which had superior/similar effects to metformin.

Synergistic Treatment of Tumor by Targeted Biotherapy and Chemotherapy via Site-Specific Anchoring of Aptamers on DNA Nanotubes.

BACKGROUND: Aptamers have been widely used as targeted therapeutic agents due to its relatively small physical size, flexible structure, high specificity, and selectivity. Aptamers functionalized nanomaterials, not only enhance the targeting of nanomaterials, but can also improve the stability of the aptamers. We developed aptamer C2NP (Apt) conjugated straight DNA nanotubes (S-DNT-Apt) and twisted DNA nanotubes (T-DNT-Apt) as nanocarriers for doxorubicin (DOX). METHODS: The twisted DNA nanotubes (T-DNT) and straight DNA nanotubes (S-DNT) were assembled with a scaffold and hundreds of staples. Apt was site-specifically anchored on DNA nanotubes with either different spatial distribution (3 or 6 nm) or varied stoichiometry (15Apt or 30Apt). The developed nanocarriers were characterized with agarose gel electrophoresis and transmission electron microscopy. The drug loading and release in vitro were evaluated by measuring the fluorescence intensity of DOX using a microplate reader. The stability of DNT in cell culture medium plus 10% of FBS was evaluated by agarose gel electrophoresis. The cytotoxicity of DNA nanostructures against K299 cells was tested with a standard CCK8 method. Cellular uptake, cell apoptosis, cell cycle and reactive oxygen species level were investigated by flow cytometry. The expression of p53 was examined by Western Blot. RESULTS: T-DNT-30Apt-6 exhibited the highest cytotoxicity when the concentration of Apt was 120 nM. After intercalation of DOX, the cytotoxicity of DOX@T-DNT-30Apt-6 was further enhanced due to the combination of chemotherapy of DOX and biotherapy of Apt. The enhanced cytotoxicity of DOX@T-DNT-30Apt-6 can be explained by the increase in the cellular uptake, cell apoptosis and intracellular ROS levels. Additionally, the interaction between Apt and its receptor CD30 could upregulate the expression of p53. CONCLUSION: These results demonstrate that both stoichiometry and spatial arrangement of Apt on T-DNT-Apt influence the anticancer activity. The developed twisted DNA nanotubes may be a solution for the synergistic treatment of cancer.

The regulatory effect of genistein on P450 aromatase and follicle-stimulating hormone receptor in mouse experimental model of menopausal metabolic syndrome.

In order to investigate the mechanism of genistein (Gen) in the treatment of climacteric syndrome, an in vivo study was performed to investigate the beneficial effects of genistein on the expression of P450 aromatase (P450 arom) and follicle-stimulating hormone receptor (FSHR) in the mouse ovary and uterus. Fifty female ICR mice (45 ± 5g, n = 50), aged 12 months, were divided into the following five groups with 10 animals in each: blank control group (CG), low-dose genistein group (L-Gen), middle-dose genistein group (M-Gen) and high-dose genistein group (H-Gen) (received 15, 30 and 60 mg/kg of genistein, respectively), and oestrogen group (EG; received 0.5 mg/kg diethylstilbestrol). The expression levels of the FSHR protein were determined by an immunohistochemical staining method. The expression of P450 arom, Cytochrome P450 19 (CYP19) and FSHR was quantified by real-time PCR. Immunohistochemical results showed that the expression levels of the FSHR protein in the M-Gen (average stained area: 20.79) and the H-Gen (average stained area: 21.21) groups were significantly stronger than in the CG (average area was 17.24) group (p < .05). The expression levels of CYP19 mRNA and P450 arom were positively correlated with the dose of genistein. Specifically, the relative expression levels in the H-Gen and EG groups were more than 1.5 times higher than in the CG group (p < .05). Genistein played a significant role in regulating aromatase and FSHR gene expression to improve perimenopausal ovarian and uterine function.

Improving antitumor outcomes for palliative intratumoral injection therapy through lecithin- chitosan nanoparticles loading paclitaxel- cholesterol complex.

BACKGROUND: Intratumoral injection is a palliative treatment that aims at further improvement in the survival and quality of life of patients with advanced or recurrent carcinomas, or cancer patients with severe comorbidities or those with a poor performance status. METHODS: In this study, a solvent-injection method was used to prepare paclitaxel-cholesterol complex-loaded lecithin-chitosan nanoparticles (PTX-CH-loaded LCS_NPs) for intratumoral injection therapy, and the physicochemical properties of NPs were well characterized. RESULTS: The particle size and zeta potential of PTX-CH-loaded LCS_NPs were 142.83±0.25 nm and 13.50±0.20 mV, respectively. Release behavior of PTX from PTX-CH-loaded LCS_NPs showed a pH-sensitive pattern. The result of cell uptake assay showed that PTX-CH-loaded LCS_NPs could effectively enter cells via the energy-dependent caveolae-mediated endocytosis and macropinocytosis in company with the Golgi apparatus. Meanwhile, PTX-CH-loaded LCS_NPs had a better ability to induce cell apoptosis than PTX solution. The in vivo antitumor results suggested that PTX-CH-loaded LCS_NPs effectively inhibited mouse mammary cancer growth and metastasis to distant organs and significantly improved the survival rate of tumor-bearing mice by intratumoral administration. CONCLUSION: In general, our study demonstrated that PTX-CH-loaded LCS_NPs used for palliative treatment by intratumoral injection showed improved safety and antitumor efficacy, which provided an alternative approach in the field of palliative chemotherapy.

Repeated evolutionary transitions of flavobacteria from marine to non-marine habitats.

The taxonomy of marine and non-marine organisms rarely overlap, but the mechanisms underlying this distinction are often unknown. Here, we predicted three major ocean-to-land transitions in the evolutionary history of Flavobacteriaceae, a family known for polysaccharide and peptide degradation. These unidirectional transitions were associated with repeated losses of marine signature genes and repeated gains of non-marine adaptive genes. This included various Na+ -dependent transporters, osmolyte transporters and glycoside hydrolases (GH) for sulfated polysaccharide utilization in marine descendants, and in non-marine descendants genes for utilizing the land plant material pectin and genes facilitating terrestrial host interactions. The K+ scavenging ATPase was repeatedly gained whereas the corresponding low-affinity transporter repeatedly lost upon transitions, reflecting K+ ions are less available to non-marine bacteria. Strikingly, the central metabolism Na+ -translocating NADH: quinone dehydrogenase gene was repeatedly gained in marine descendants, whereas the H+ -translocating counterpart was repeatedly gained in non-marine lineages. Furthermore, GH genes were depleted in isolates colonizing animal hosts but abundant in bacteria inhabiting other non-marine niches; thus relative abundances of GH versus peptidase genes among Flavobacteriaceae lineages were inconsistent with the marine versus non-marine dichotomy. We suggest that phylogenomic analyses can cast novel light on mechanisms explaining the distribution and ecology of key microbiome components.

[Rheological properties of sinomenine in situ liquid crystal as liquid embolic agent].

Three different kinds of sinomenine in situ liquid crystal were prepared for different prescriptions, to investigate the rheological properties before and after in situ treatment and evaluate its feasibility for embolization. Rheological experiments were carried out with cone plate fixtures. Both the steady-state rheological and non-steady-state rheological properties of in-situ gels and the swelling gels were studied and compared. Steady-state rheological study results showed that all the three liquid embolic agents were non-newtonian fluid before and after in situ treatment, which would become less ropy when they were pressed with shear stress; their viscosities differed by 2-5 orders of magnitude. It had a yield value of about 10 Pa before in situ treatment and about 4 500 Pa after in situ treatment. All the six systems had thixotropy while their dynamic viscosities were not influenced by the shear rate, all less than 0.3 Pa·s before in situ treatment more than 1 Pa·s after in situ treatment, differing by an order of magnitude. The results of temperature sweeping showed a slight decrease with a steady rate in viscosity within the range of 10-50 °C, differing by 3-4 orders of magnitude. The results of unsteady rheology showed that there was no obvious linear viscoelastic region in the three kinds of agents, indicating the properties of liquid. After in situ treatment, their linear viscoelastic range γ<1% (No.3 was 5%), and their elastic modulus G' was larger than the viscous modulus G", indicating the properties of solid. Frequency scanning results showed that for the systems at low frequencies, G">G', system viscosity in a dominant position; while at high frequencies, G'>G", system elasticity in a dominant position. The results of compound viscosity test also proved that the liquid embolic agent in situ can form a cubic liquid crystal (the structure of No. 3 was destroyed after in situ treatment). The DHR-2 rheometer was used to investigate the rheological properties of in situ gels with three different prescriptions. The method is simple and the result is reliable, which can provide more theoretical reference for the in vitro evaluation and practical application of the product.

Central neuromechanisms underlying control of intragastric pressure through acupuncture at Zusanli (ST36) in rats: the upper cervical cord is the key link between the ascending and descending pathways.

Sensory inputs stimulated by Zusanli (ST36) acupuncture in the abdomen are known to converge in the upper cervical cord. However, it is unclear whether these inputs are subsequently conveyed to the hypothalamic paraventricular nucleus and what kind of afferent fibers are involved. We focused on the upper cervical cord, where afferent inputs converge, and detected c-fos expression in oxytocinergic neurons. We found that Zusanli acupuncture therapy effectively elevated intragastric pressure, but inhibited expression of c-fos in oxytocinergic neurons of the paraventricular nucleus in upper cervical cord injured rats. These Zusanli acupuncture effects remained even after complete dorsal cord transection. However, after complete transection of the spinal cord or dorsolateral funiculus, the effects were significantly attenuated and even disappeared. These findings suggest that the paraventricular nucleus is responsible for pooling and integrating signals from the Zusanli acupuncture and sensory information from the intragastric pressure variation, thereby contributing to the regulation of intragastric pressure. The upper cervical cord serves as the key link between ascending and descending pathways, which conveys afferent inputs to the paraventricular nucleus through the dorsolateral funiculus.

Synthesis and evaluation of benzylisoquinoline derivatives for their inhibition on pancreatic lipase and preadipocyte proliferation.

The present study was designed to synthesize and evaluate a series of benzylisoquinoline derivatives. These compounds were synthesized by Bischler-Napieralski cyclization to yield 1-benzyl-3,4-dihydroisoquinolines, and the products were obtained by reductions. All these compounds were identified by MS, (1)H NMR and (13)C NMR. The inhibitory activities on pancreatic lipase and preadipocyte proliferation for the synthesized compounds and alkaloids from Nulembo nucifera were assessed in vitro. Most of the compounds showed inhibitory activities on both pancreatic lipase and preadipocyte proliferation. Particularly, compounds 7p-7u and 9d-9f exhibited significant inhibitory activity on pancreatic lipase while compounds 7c, 7d, 7f, 7g, 7i, and 7j potently inhibited the proliferation of 3T3-L1 preadipocytes. Our results provided a basis for future evaluation and development of these compounds as leads for therapeutics for human diseases.

[Histomorphological study on folk medicine Lysimachia fortunei].

To set standards for histomorphological studies on Lysimachia fortunei, an efficacious and widely applied folk medicine in this study, in order to develop its resources. Its species were identified by observing plant morphology and herbs appearance characters, preparing slices with routine methods and defining structural characters. According to the results of morphologic observation, leaves, stamen and pistil of this plant were different from the descriptions in Flora of China. The whole herb can be used in medicines, mainly including rhizomes, stems and leaves. According to the findings in the first study on microscopic structures, its rhizomes, stems and leaves were characteristic and worth identifying. The transaction tissue structures of rhizomes and stems were under developed and contained endodermis, secretory structures; Stems had sclerenchymata of different shapes of sclereids; Leaves were bifacial and had vascular bundles under midribs, which were surrounded by parenchymal sheathes. On the surface of leaves, stomata, glandular hairs and keratin lines were morphologically different in upper and lower epidermis. The herbal power had glandular hairs, sclereids and vessels. In conclusion, herbs of L. fortunei can be identified by the above histomorphological characteristics, which lays a foundation for further development and application of L. fortunei.

Antithrombotic effects of the effective components group of Xiaoshuantongluo formula in vivo and in vitro.

The present study was designed to investigate the antithrombotic effects and underlying mechanisms of the effective components group (ECG) of Xiaoshuantongluo recipe (XECG) and to further verify the rationality and feasibility of ECG-guided methodology in traditional Chinese medicine (TCM) research. The arterial thrombosis model induced by ferric chloride (FeCl3) oxidation and the venous thrombosis model induced by inferior vena cava ligation were established to evaluate the antithrombotic potential of XECG. Our results indicated that XECG significantly prolonged the time to occlusion, activated partial thromboplastin time (APTT), and prothrombin time (PT), and markedly inhibited adenosine diphosphate (ADP)-induced platelet aggregation in the 20% FeCl3-induced arterial thrombosis model. The superoxide dismutase (SOD) activity was significantly increased and the levels of malondialdehyde (MDA) and nitric oxide (NO) were dramatically decreased in the plasma of arterial thrombosis rats after XECG treatment for 12 days. Furthermore, XECG markedly reduced the weight of thrombus formed by inferior vena cava ligation. Additionally, XECG exhibited 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging activity and protective effect on mitochondrial lipid peroxidation. In summary, XECG played an important role in the prevention of thrombosis through interacting with multiple targets, including inhibition of platelet aggregation and coagulation and repression of oxidative stress. The ECG-guided methodology was validated as a feasible tool in TCM research.

Tumorigenic effects of endocrine-disrupting chemicals are alleviated by licorice (Glycyrrhiza glabra) root extract through suppression of AhR expression in mammalian cells.

Endocrine-disrupting chemicals (EDCs) have been reported to interfere with estrogen signaling. Exposure to these chemicals decreases the immune response and causes a wide range of diseases in animals and humans. Recently, many studies showed that licorice (Glycyrrhiza glabra) root extract (LRE) commonly called "gamcho" in Korea exhibits antioxidative, chemoprotective, and detoxifying properties. This study aimed to investigate the mechanism of action of LRE and to determine if and how LRE can alleviate the toxicity of EDCs. LRE was prepared by vacuum evaporation and freeze-drying after homogenization of licorice root powder that was soaked in 80% ethanol for 72 h. We used 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) as a representative EDC, which is known to induce tumors or cancers; MCF-7 breast cancer cells, used as a tumor model, were treated with TCDD and various concentrations of LRE (0, 50, 100, 200, 400 µg/mL) for 24, 48, and 72 h. As a result, TCDD stimulated MCF-7 cell proliferation, but LRE significantly inhibited TCDD-induced MCF-7 cell proliferation in a dose- and time-dependent manner. The expression of TCDD toxicity-related genes, i.e., aryl hydrocarbon receptor (AhR), AhR nuclear translocator, and cytochrome P450 1A1, was also down-regulated by LRE in a dose-dependent manner. Analysis of cell cycle distribution after treatment of MCF-7 cells with TCDD showed that LRE inhibited the proliferation of MCF-7 cells via G2/M phase arrest. Reverse transcription-polymerase chain reaction and Western blot analysis also revealed that LRE dose-dependently increased the expression of the tumor suppressor genes p53 and p27 and down-regulated the expression of cell cycle-related genes. These data suggest that LRE can mitigate the tumorigenic effects of TCDD in breast cancer cells by suppression of AhR expression and cell cycle arrest. Thus, LRE can be used as a potential toxicity-alleviating agent against EDC-mediated diseases.

Antioxidant properties and PC12 cell protective effects of a novel curcumin analogue (2E,6E)-2,6-bis(3,5- dimethoxybenzylidene)cyclohexanone (MCH).

The antioxidative properties of a novel curcumin analogue (2E,6E)-2,6-bis(3,5-dimethoxybenzylidene)cyclohexanone (MCH) were assessed by several in vitro models, including superoxide anion, hydroxyl radical and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging and PC12 cell protection from H2O2 damage. MCH displayed superior O2•- quenching abilities compared to curcumin and vitamin C. In vitro stability of MCH was also improved compared with curcumin. Exposure of PC12 cells to 150 µM H2O2 caused a decrease of antioxidant enzyme activities, glutathione (GSH) loss, an increase in malondialdehyde (MDA) level, and leakage of lactate dehydrogenase (LDH), cell apoptosis and reduction in cell viability. Pretreatment of the cells with MCH at 0.63-5.00 µM before H2O2 exposure significantly attenuated those changes in a dose-dependent manner. MCH enhanced cellular expression of transcription factor NF-E2-related factor 2 (Nrf2) at the transcriptional level. Moreover, MCH could mitigate intracellular accumulation of reactive oxygen species (ROS), the loss of mitochondrial membrane potential (MMP), and the increase of cleaved caspase-3 activity induced by H2O2. These results show that MCH protects PC12 cells from H2O2 injury by modulating endogenous antioxidant enzymes, scavenging ROS, activating the Nrf2 cytoprotective pathway and prevention of apoptosis.

Protection of mice against lipopolysaccharide-induced endotoxic shock by pinocembrin is correlated with regulation of cytokine secretion.

Natural products have been used as potentially important sources of anti-inflammatory drugs. This study examined the effects of pinocembrin against lipopolysaccharide (LPS)-induced endotoxemia to ascertain whether pinocembrin could protect mice from ensuing death. Cytokine responses were also assessed in serum isolated from blood collected at 0, 2, 4, 6, 8, and 24 h after LPS administration of the mice (with or without drug treatment). The results showed that there was a lower production of TNFα, IL-6, and IL-1ß in the serum of LPS-challenged mice that had been pre-treated with pinocembrin. In addition, pre-treatment with pinocembrin improved host survival against the LPS-induced lethal endotoxemia. These results suggest that this new flavonoid could potentially be a novel candidate for preventing development/mitigation progression of septic shock.