Effect of electroacupuncture on ventricular structure and function in rats with myocardial ischemia-reperfusion injury. / ç”µé’ˆå¯¹å¿ƒè‚Œç¼ºè¡€å†çŒæ³¨æŸä¼¤å¤§é¼ å¿ƒå®¤ç»“æž„å’ŒåŠŸèƒ½çš„å½±å“.

OBJECTIVES: To observe the effect of electroacupuncture (EA) on changes of ventricular structure and function in rats with myocardial ischemia-reperfusion injury (MIRI), so as to explore its potential mechanisms underlying improvement of ventricular remodeling after MIRI. METHODS: Forty male SD rats were randomly divided into 4 groups：sham operation group, model group, EA group and medication (sacubactril valsartan, LCZ696) group, with 10 rats in each group. The MIRI model was established by ligation of the left anterior descending coronary artery and reperfusion. EA (2 Hz/100 Hz, 2 mA) was applied to bilateral "Neiguan" (PC6) for 20 min, once every other day for 21 d. Rats of the medication group received gavage of LCZ696 (60 mg·kg-1·d-1). After the intervention, echocardiography was used to detect the ejection fraction (EF) and fractional shortening (FS) of the left ventricle, and the contents of serum tumor necrosis factor-α(TNF-α), vascular cell adhesion molecule-1(VCAM-1) and intercellular cell adhesion molecule-1(ICAM-1) were assayed by enzyme-linked immunosorbent assay. The pathological changes of myocardial tissue were observed after HE staining. The Masson staining was used to evaluate the myocardial collagen deposition and myocardial fibrosis. The mRNA expression levels of collagen Ⅰ and Ⅲ and connective tissue growth factor (CTGF) in the myocardial tissue were detected by quantitative real-time PCR, and the expression levels of IL-1ß and IL-18 were detected by Western blot. RESULTS: In contrast to the sham operation group, the EF and FS levels of the left ventricle were ob-viously decreased (P<0.001), while the contents of serum TNF-α, VCAM-1 and ICAM-1, the proportion of myocardial fibrosis area, the mRNA expression levels of myocardial collagen Ⅰ, collagen Ⅲ and CTGF, the expression levels of IL-1ß and IL-18 were significantly increased (P<0.001, P<0.000 1, P<0.05, P<0.01) in the model group. Compared with the model group, the EF and FS levels were remarkably increased (P<0.01), whereas the contents of serum TNF-α, VCAM-1 and ICAM-1, the proportion of myocardial fibrosis area, the mRNA expression levels of myocardial collagen Ⅰ, collagen Ⅲ and CTGF, and the expression levels of IL-1ß and IL-18 were significantly down-regulated (P<0.001, P<0.01, P<0.05) in both the medication and EA groups. No significant differences were found between the EA and medication groups in all the indexes mentioned above. CONCLUSIONS: EA can improve the left-ventricular fibrosis and function, delay or reverse ventricular remodeling in MIRI rats, which may be related to its functions in down-regulating myocardial inflammatory response and mRNA expression levels of myocardial collagen Ⅰ, collagen Ⅲ and CTGF.

Factors of faecal microbiota transplantation applied to cancer management.

The homeostasis of the microbiota is essential for human health. In particular, the gut microbiota plays a critical role in the regulation of the immune system. Thus, faecal microbiota transplantation (FMT), a technology that has rapidly developed in the last decade, has specifically been utilised for the treatment of intestinal inflammation and has recently been found to be able to treat tumours in combination with immunotherapy. FMT has become a breakthrough in enhancing the response rate to immunotherapy in cancer patients by altering the composition of the patient's gut microbiota. This review discusses the mechanisms of faecal microorganism effects on tumour development, drug treatment efficacy, and adverse effects and describes the recent clinical research trials on FMT. Moreover, the factors influencing the efficacy and safety of FMT are described. We summarise the possibilities of faecal transplantation in the treatment of tumours and its complications and propose directions to explore the development of FMT.

[Lidong needling therapy combined with functional exercise in treatment of upper limb lymphedema after breast cancer surgery: a randomized controlled trial].

OBJECTIVE: To observe the clinical efficacy of lidong needling therapy (acupuncture technique combined with therapeutic movement of the body) on upper limb lymphedema after breast cancer surgery in combination with functional exercise. METHODS: A total of 73 patients with postoperative lymphedema of breast cancer in the upper limbs were randomized into an observation group (36 cases) and a control group (37 cases). The routine nursing care and functional exercise were given in the control group, twice a day, for about 10-15 min each time, lasting 8 weeks. On the basis of the treatment as the control group, lidong needling therapy was applied to the acupionts on the affected upper limb, i.e. Jianyu (LI 15), Waiguan (TE 5), Hegu (LI 4) and ashi points (the most obvious swelling sites), as well as to bilateral Yinlingquan (SP 9) and Zusanli (ST 36), etc. The needles were retained for 30 min. While the needles retained, the patients were asked to move the affected shoulder to 90° by the sagittal anteflexion and keep it elevated. Simultaneously, the hand on the affected side was clenched and opened slowly and coordinately. Lidong needling therapy was delivered once every two days, three times weekly for 8 weeks. Before and after treatment, the difference of the circumference between the affected and healthy limbs, the score of visual analogue scale (VAS) for swelling and the score of disability of arm, shoulder and hand (DASH) were compared in the patients of the two groups. The clinical efficacy was evaluated. RESULTS: After 2, 4, 6 and 8 weeks of treatment, except for the circumference of the area 10 cm below the cubitel crease in the control group, the differences in the circumferences of the rest parts between the affected and healthy limbs were reduced in comparison with those before treatment in the two groups (P<0.01, P<0.05). After 6 weeks of treatment, in the observation group, for the circumference at the level of hand between the thumb and the index finger and that of the wrist, the differences between the affected and healthy limbs was smaller compared with those in the control group (P<0.05). After 8 weeks of treatment, except for the areas 5 cm below and above the cubitel crease, the differences of circumferences between the affected and healthy limbs in the observation group were smaller than those in the control group in the rest parts (P<0.01, P<0.05). After 8 weeks of treatment, the swelling VAS scores were reduced when compared with those before treatment in the two groups (P<0.05), and the score in the observation group was lower than that in the control group (P<0.01). After 4 and 8 weeks of treatment, DASH scores were reduced in comparison with those before treatment in the two groups (P<0.01). The total effective rate of the observation group was 83.3% (30/36), which was higher than that of the control group (35.1%, 13/37, P<0.01). CONCLUSION: Lidong needling therapy combined with the functional exercise obtains the satisfactory clinical effect on the upper limb lymphedema after breast cancer surgery. This treatment effectively relieves swelling and improves the upper limb function.

Lipoxin A4 depresses inflammation and promotes autophagy via AhR/mTOR/AKT pathway to suppress endometriosis.

BACKGROUND: Endometriosis is a benign gynecological disease with the feature of estrogen dependence and inflammation. The function of autophagy and the correlation with inflammation were not yet revealed. METHODS: Autophagosomes were detected by transmission electron microscopy. Gene Expression Omnibus (GEO) database was referred to analyze the expression of autophagy-related genes. Quantification of mRNA and protein expression was examined by qRT-PCR and Western Blot. Immunohistochemistry was performed to explore the expression of proteins in tissues. The mouse model of endometriosis was performed to analyze the autophagic activity and effect of LXA4. RESULTS: The expression of autophagy-related genes in endometriotic lesions were unusually changed. The number of autophagosomes and LC3B-II expression was diminished, and p62 was increased in ectopic lesions from both patients and mice. Interleukin 1ß (IL1ß) attenuated the expression of LC3B and promoted the level p62. The autophagy activator MG-132 upregulated the expression of LC3B and reduced IL1ß, IL6, and p62. LXA4 reversed the inhibitory effect of IL1ß on the expression of LC3B and p62, and blocking the receptor of LXA4 AhR (aryl hydrocarbon receptor) resulted in the incapacitation of LXA4 to influence the effect of IL1ß. LXA4 depressed the phosphorylation of AKT and mTOR to against IL1ß, and blocking AhR negatively regulated the effect of LXA4 on AKT/mTOR pathway. LXA4 reduced the ectopic lesions and the expression of IL1ß and p62, but enhanced LC3B-II in endometriotic mouse models. CONCLUSION: In endometriosis, increased inflammation of ectopic lesions prominently depresses autophagy. LXA4 could regulate autophagy by suppressing inflammatory response through AhR/AKT/mTOR pathway.

Straight-segment mandibulectomy: a reproducible porcine mandibular critical-size defect model.

Porcine mandibular defect models are commonly used for the preclinical evaluation of reconstruction techniques. Existing studies vary in technique, complexity, and postoperative outcomes. The procedures are complex and often described without sufficient detail. We describe in detail a simple and reproducible method for creating a critical-size mandibular defect in a porcine model. Seven hemimandibular critical size defects were created in five male Yorkshire-Landrace pigs, three with unilateral defects and two with bilateral defects. A transverse incision was made over the mandibular body. Periosteum was incised and elevated to expose the mandibular body and a critical-size defect of 30 × 20 mm created using an oscillating saw. The implant was inserted and fixed with a titanium reconstruction plate and bicortical locking screws, and the wound closed in layers with resorbable sutures. Intraoral contamination was avoided. Dentition was retained and the mental nerve and its branches preserved. The marginal mandibular nerve was not encountered during dissection. All pigs retained normal masticatory function, and there were no cases of infection, wound breakdown, haematoma, salivary leak, or implant-related complications. The procedure can be performed bilaterally on both hemimandibles without affecting load-bearing function. All pigs survived until the end point of three months. Postoperative computed tomographic scans and histology showed new bone formation, and a three-point bend test showed the restoration of biomechanical strength. Straight-segment mandibulectomy is a simple and reproducible method for the creation of critical-size mandibular defects in a porcine model, simulating a load-bearing situation.

Circulating Tumor-Macrophage Fusion Cells and Circulating Tumor Cells Complement Non-Small-Cell Lung Cancer Screening in Patients With Suspicious Lung-RADS 4 Nodules.

PURPOSE: Low-dose computed tomography (LDCT) screening of high-risk patients decreases lung cancer-related mortality. However, high false-positive rates associated with LDCT result in unnecessary interventions. To distinguish non-small-cell lung cancer (NSCLC) from benign nodules, in the present study, we integrated cellular liquid biomarkers in patients with suspicious lung nodules (lung cancer screening reporting and data system [Lung-RADS] 4). METHODS: Prospectively, 7.5 mL of blood was collected from 221 individuals (training set: 90 nonscreened NSCLC patients, 74 high-risk screening patients with no/benign nodules [Lung-RADS 1-3], and 20 never smokers; validation set: 37 patients with suspicious nodules [Lung-RADS 4]). Circulating tumor cells (CTCs), CTC clusters, and tumor-macrophage fusion (TMF) cells were identified by blinded analyses. Screening patients underwent a median of two LDCTs (range, 1-4) with a median surveillance time of 30 (range, 11-50) months. RESULTS: In the validation set of 37 Lung-RADS 4 patients, all circulating cellular biomarker counts (P < .005; Wilcoxon test) and positivity rates were significantly higher in 23 biopsy-proven NSCLC patients (CTCs: 23 of 23 [100%], CTC clusters: 6 of 23 [26.1%], and TMF cells: 15 of 23 [65.2%]) than in 14 patients with biopsy-proven benign nodules (6 of 14 [42.9%], 0 of 14 [0%], and 2 of 14 [14.3%]). On the basis of cutoff values from the training set, logistic regression with receiver operating characteristic and area under the curve analyses demonstrated that CTCs (sensitivity: 0.870, specificity: 1.0, and area under the curve: 0.989) and TMF cells (0.652; 0.880; 0.790) complement LDCT in diagnosing NSCLC in Lung-RADS 4 patients. CONCLUSION: Cellular liquid biomarkers have a potential to complement LDCT interpretation of suspicious Lung-RADS 4 nodules to distinguish NSCLC from benign lung nodules. A future prospective, large-scale, multicenter clinical trial should validate the role of cellular liquid biomarkers in improving diagnostic accuracy in high-risk patients with Lung-RADS 4 nodules.

Hybrid ZnO/chitosan antimicrobial coatings with enhanced mechanical and bioactive properties for titanium implants.

A biocomposite coating comprising chitosan and ZnO deposited on a porous Ti oxide is developed to avoid orthopedic and dental implant-related infections. The coating comprised of an inner layer of nanoporous TiO2 and the outer layer of the chitosan matrix with ZnO nanoparticles. Microbiological tests show that chitosan coating is effective against Escherichia coli (E. coli), however, its ability to inhibit bacterial adhesion is very limited. A 1.2-fold increase in the antibacterial activity of chitosan/ZnO coating against E. coli was detected as compared to the chitosan coating alone, and the chitosan/ZnO efficiently inhibited biofilm formation. In addition, the chitosan/ZnO coating exhibited improved bioactivity compared to the chitosan coating. The improvement in antibacterial properties and bioactivity of the chitosan/ZnO coating is attributed to the release of Zn2+ ions. The critical force of scratching the chitosan/ZnO coating was approximately twice that of the chitosan coating. The potentiodynamic polarization results confirmed that the corrosion resistance of the implant with ZnO/chitosan/Ti structure was improved. In addition, cytocompatibility evaluation indicated that the chitosan/ZnO coating has good cytocompatibility in MG-63 cells as compared to pure Ti.

Reducible Fraction Dominates the Mobility of Vanadium in Soil Around an Iron Smelter.

Soil samples were collected to determine the pollution status, spatial distribution and mobility of Vanadium (V) in soil around an iron smelter in Panzhihua. The results showed that the topsoils and deep soils were unpolluted to moderately polluted and the subsurface soils was unpolluted with V. V concentrations in the topsoils decreased with the increase of the altitudes and the distances to the smelter. There was a great potential mobility of V in soil and the reductive dissolution of reducible V in the topsoils was responsible for the high concentration of V in the deep soils. Therefore, more attention should be paid to the reducible V when evaluating the mobility of V in soil.

Proteomic and metabolomic characterization of cardiac tissue in acute myocardial ischemia injury rats.

The pathological process and mechanism of myocardial ischemia (MI) is very complicated, and remains unclear. An integrated proteomic-metabolomics analysis was applied to comprehensively understand the pathological changes and mechanism of MI. Male Sprague-Dawley rats were randomly divided into a mock surgery (MS) group and an MI group. The MI model was made by ligating the left anterior descending coronary artery, twenty-four hours after which, echocardiography was employed to assess left ventricular (LV) function variables. Blood samples and left ventricular tissues were collected for ELISA, metabolomics and proteomics analysis. The results showed that LV function, including ejection fraction (EF) and fractional shortening (FS), was significantly reduced and the level of cTnT in the serum increased after MI. iTRAQ proteomics showed that a total of 169 proteins were altered including 52 and 117 proteins with increased and decreased expression, respectively, which were mainly involved in the following activities: complement and coagulation cascades, tight junction, regulation of actin cytoskeleton, MAPK signaling pathway, endocytosis, NOD-like receptor signaling pathway, as well as phagosome coupled with vitamin digestion and absorption. Altered metabolomic profiling of this transition was mostly enriched in pathways including ABC transporters, glycerophospholipid metabolism, protein digestion and absorption and aminoacyl-tRNA biosynthesis. The integrated metabolomics and proteomics analysis indicated that myocardial injury after MI is closely related to several metabolic pathways, especially energy metabolism, amino acid metabolism, vascular smooth muscle contraction, gap junction and neuroactive ligand-receptor interaction. These findings may contribute to understanding the mechanism of MI and have implication for new therapeutic targets.

Establishment and characterization of immortalized human eutopic endometrial stromal cells.

PROBLEM: The application of primary eutopic endometrial cells from endometriosis patients in research is restricted for short life span, dedifferentiation of hormone responsiveness. METHOD OF STUDY: Human telomerase reverse transcriptase (hTERT)-induced immortalized cells (iheESCs) were infected by lentivirus. mRNA level was examined by qRT-PCR, and protein expression was quantified by Western blot. CCK-8 and EdU assay were assigned to assess the proliferation. The migration and invasion of cells were assessed by transwell assay. Clone formation assay and nude mouse tumorigenicity assay were used to evaluate colony-formation and tumorigenesis abilities. RESULTS: hTERT mRNA and protein were significantly expressed higher in iheESCs compared to primary cells. iheESCs grew without morphological change for 42 passages which is much longer than 18 passages of primary cells. There was no obvious difference between primary cells and iheESCs in growth, mobility, and chromosome karyotype. Furthermore, the expression of epithelial-mesenchymal transition (EMT) markers and estrogen/progesterone receptors remained unchanged. The decidualization of iheESCs could be induced by progesterone and cAMP. Estrogen increased the proliferation and mobility of iheESCs, and lipopolysaccharides (LPS) induced the IL-1ß and IL-6 promoting inflammatory response. The colony-forming ability of iheESCs, like primary cells, was lower than Ishikawa cells. In addition, tumorigenicity assay indicated that iheESCs were unable to trigger tumor formation in BALB/c nude mouse. CONCLUSIONS: This study established and characterized iheESCs that kept the cellular physiology of primary cells and were not available with tumorigenic ability. Thus, iheESCs would be useful as in vitro cell model to investigate pathogenesis of endometriosis.

[Molecular mechanisms of non-coding RNA regulating autophagy and interventional effects of Chinese herbal medicine].

Long non-coding RNAs(lncRNAs) and microRNAs(miRNAs),as members of the non-coding RNA family,play important roles in upstream processes that regulate autophagy in mammalian cells. LncRNA and miRNA participate in various phases of the process of autophagy,including initiation,vesicle nucleation,autophagosome maturation and autophagosome fusion. Some non-coding RNAs exert bidirectional regulatory functions in the process of autophagy,include the maternally expressed gene 3(MEG3),H19 and miR-21,whereas others either inhibit autophagy(including GAS5,miR-34 a and miR-30 a) or promote autophagy(including MALAT1,miR-152 and miR-24). The regulation of autophagy by non-coding RNAs has characteristics of conditionality,diversity and complexity. In recent years,researchers at home and abroad have constantly found that some extracts from the individual Chinese herbal medicine(CHM) such as ampelopsin,salvianolic acid B and paeonol,as well as the Chinese herbal compound named Eight Ingredients Decoction,can regulate autophagy by interacting with non-coding RNA in vitro and in vivo. The latest studies have shown that plant-derived small non-coding RNAs(sncRNAs) as one of the active ingredients of CHMs can directly enter the bloodstream and internal organs to regulate gene expressions in humans. In addition,it has been reported that rhein,hyperoside and mycelium of Cordyceps sinensis all can modulate autophagy in renal tubular epithelial cell via regulating the autophagy-related signaling pathways in vivo and in vitro to reduce renal damage and aging,which is likely mediated by the miR-34 a pathway. In summary,the understanding of molecular mechanisms underlying the regulation of autophagy by non-coding RNAs(such as lncRNAs and miRNAs) is essential and required to develop new strategies for the treatments and managements of tumors,immune diseases,metabolic diseases,neurodegenerative diseases and other common diseases and decipher pharmacologic actions of CHMs.

Antibacterial Property of Composites of Reduced Graphene Oxide with Nano-Silver and Zinc Oxide Nanoparticles Synthesized Using a Microwave-Assisted Approach.

Graphene oxide (GO) composites with various metal nanoparticles (NPs) are attracting increasing interest owing to their broad scope in biomedical applications. Here, microwave-assisted chemical reduction was used to deposit nano-silver and zinc oxide NPs (Ag and ZnO NPs) on the surface of reduced GO (rGO) at the following weight percentages: 5.34% Ag/rGO, 7.49% Ag/rGO, 6.85% ZnO/rGO, 16.45% ZnO/rGO, 3.47/34.91% Ag/ZnO/rGO, and 7.08/15.28% Ag/ZnO/rGO. These materials were tested for antibacterial activity, and 3.47/34.91% Ag/ZnO/rGO and 7.08/15.28% Ag/ZnO/rGO exhibited better antibacterial activity than the other tested materials against the gram-negative bacterium Escherichia coli K12. At 1000 ppm, both these Ag/ZnO/rGO composites had better killing properties against both E. coli K12 and the gram-positive bacterium Staphylococcus aureus SA113 than Ag/rGO and ZnO/rGO did. RedoxSensor flow cytometry showed that 3.47/34.91% Ag/ZnO/rGO and 7.08/15.28% Ag/ZnO/rGO decreased reductase activity and affected membrane integrity in the bacteria. At 100 ppm, these two composites affected membrane integrity more in E. coli, while 7.08/15.28% Ag/ZnO/rGO considerably decreased reductase activity in S. aureus. Thus, the 3.47/34.91% and 7.08%/15.28% Ag/ZnO/rGO nanocomposites can be applied not only as antibacterial agents but also in a variety of biomedical materials such as sensors, photothermal therapy, drug delivery, and catalysis, in the future.

Changes in the Serum Metabolome of Acute Myocardial Ischemia Rat Pretreatment with Electroacupuncture.

Myocardial infarction (MI), the most common symptom is chest pain, occurs when blood flow decreases or stops to a part of the heart, causing damage to the heart muscle. Electroacupuncture pretreatment (EP) is a recent observation which has been shown to induce ischemic tolerance like the ischemia preconditioning, suggesting that EP may be a promising preventive strategy for individual susceptibility to MI. This study investigated mechanisms that underlie the effect of EP on MI through the use of gas chromatography-mass spectrometry (GC-MS)-based metabolic profiling. Male Sprague-Dawley rats were randomly divided to receive or not receive three days of EP at PC6 (Neiguan). Then on the fourth day, each group was further divided to undergo mock surgery or MI, induced by ligation of the left anterior descending coronary artery. After 24h, the blood samples and hearts were collected for the follow-up research. The results showed that treatment by EP significantly reduced the levels of CK-MB, cTnT, AST, and MDH in serum and decreased myocardial infarction area. According to GC-MS-based serum metabolic profiling and analysis, a total of 636 characteristic peaks were identified, including 158 known and 478 unknown metabolites. MI caused comprehensive metabolic changes in glycolysis-related metabolites, malate-aspartate shuttle (MAS) metabolites, and purine metabolites with anti-oxidant functions, while EP reversed more than half of the differential metabolic changes, mainly affecting amino acid and energy metabolism, especially the glutamate metabolism and MAS. In a word, our findings suggest that EP exerts its cardioprotective effect on MI by regulating amino acid and energy metabolisms. Meanwhile, GC-MS-based metabolomics provided a powerful way to characterize the metabolic features of MI, with and without EP, and thereby improved our understanding of the effect and mechanisms of EP.

Aesthetic and Functional Evaluation of Large Full-Thickness Vermilion and Lower Lip Defects Reconstruction.

BACKGROUND: It is hardly to reconstruct a huge defect of lower lip by using of partial flap which brings no mouth closing functional problem. In this study, we would like to introduce our experience in large full-thickness vermilion and lower lip/chin defects reconstruction, and also focus on the evaluation of the surgery effects. METHODS: The large lower lip and chin (include vermilion) reconstruction were performed in Sichuan Provincial People's Hospital (2012-2015). The surgery experience was introduced in this study first. In the following section, after a statement of these basic problems, various situations involving are investigated, such as the surgical effects of aesthetic and function that were evaluated through a visual analogue scale (VAS) by doctors and patients separately. The VAS score assessments of 2 kinds of surgery were collected and compared. RESULTS: A total of 7 patients use the tongue flap alone. Four patients use the combination of the free forearm flap and the anterior ventral tongue flap (COMBO flap). The VAS score of doctors group was significantly lower than the patients group (P < 0.05), and the aesthetic appearance was excellent (>90 points). Language features were not affected (>90 points). Slight mouth opening problems exist on these patients who were used COMBO flaps (>80 points; <90 points). The drooling and drumming gas problems were not observed. These 11 patients had no recurrence within 12 months after the operation. CONCLUSION: The 1:1 ratio between upper and lower lip is crucial to the design of anterior ventral tongue flap which brings with an excellent 3-dimensional morphologic and anatomic structure outcome. The bite block might become an essential operation step for vermilion reconstruction by using of tongue flap. And the COMBO flap may enhance the facial aesthetics and oral function for the reconstruction.

Structural Moieties Required for Cinnamaldehyde-Related Compounds to Inhibit Canonical IL-1ß Secretion.

Suppressing canonical NOD-like receptor protein 3 (NLRP3) inflammasome-mediated interleukin (IL)-1ß secretion is a reliable strategy for the development of nutraceutical to prevent chronic inflammatory diseases. This study aimed to find out the functional group responsible for the inhibitory effects of cinnamaldehyde-related compounds on the canonical IL-1ß secretion. To address this, the suppressing capacities of six cinnamaldehyde-related compounds were evaluated and compared by using the lipopolysaccharide (LPS)-primed and adenosine 5'-triphosphate (ATP)-activated macrophages. At concentrations of 25~100 µM, cinnamaldehyde and 2-methoxy cinnamaldehyde dose-dependently inhibited IL-1ß secretion. In contrast, cinnamic acid, cinnamyl acetate, cinnamyl alcohol and α-methyl cinnamaldehyde did not exert any inhibition. Furthermore, cinnamaldehyde and 2-methoxy cinnamaldehyde diminished expressions of NLRP3 and pro-IL-1ß. Meanwhile, cinnamaldehyde and 2-methoxy cinnamaldehyde prevented the ATP-induced reduction of cytosolic pro-caspase-1 and increase of secreted caspase-1. In conclusion, for cinnamaldehyde-related compounds to suppress NLRP3 inflammasome-mediated IL-1ß secretion, the propenal group of the side chain was essential, while the substituted group of the aromatic ring played a modifying role. Cinnamaldehyde and 2-methoxy cinnamaldehyde exerted dual abilities to inhibit canonical IL-1ß secretion at both stages of priming and activation. Therefore, there might be potential to serve as complementary supplements for the prevention of chronic inflammatory diseases.

[Progress of Research on Mechanisms of Moxibustion Intervention Underlying Improvement of Blood Circulation].

OBJECTIVE: Moxibustion is one of the commonly used therapy of traditional Chinese medicine by applying burning dried mugwort on particular acupoints of the body surface. In the present paper，we reviewed progress of researches about the mechanisms of moxibustion treatment undering imporvement of blood circulation in recent 15 years. Research results displayed that moxibustion can dilate blood vessels to increase blood flow and improve microcirculation, not only in the local superficial vessels of body, but also in the deep tissues as the brain, stomach and mesentery, kidney, heart, etc., as well as in the distal blood vessels. The vasodilator action of moxibustion stimulation is related to nerve regulation, endothelium derived relaxing factors and vasodilator mediator, etc. through 1) interaction of acetylcholine (Ach)/muscarinic receptor (MR) and noradrenaline (NE)/α- or ß-receptor; 2) nitric oxide synthase (NOS)/NO/arachidonic acid/prostacyclin (PGI2)/endothelium-derived hyperpolarizing factor (EDHF) pathway; 3) EDHF/TRPV 4/KCa channel, cytochrome P 450 oxidase/epoxyeicosatrienoicacid (EET); 4) EET/TRPV 4/big conductance calcium-activated potassium channel (BKCa); 5) sulfuretted hydrogen (H2S)/ATP-sensitive potassium channel (KATP) or voltage-gated potassium channels (Kv 7); 6) NO/substance P (SP) or CGRP and adrenergic ß 2 receptor(R)/TRPV 1/adenosin A 1 R and A 2 R/NK 1 R pathway; 7) PGI2/adenylyl cyclase (cAMP)/PKA and vasoactive intestinal peptide (VIP), etc. in the vascular endothelium and smooth muscle. These research results may help us understand the effects and mechanisms of moxibustion in the treatment of different clinical conditions by improving microcirculation.

Comparison of Inhibitory Capacities of 6-, 8- and 10-Gingerols/Shogaols on the Canonical NLRP3 Inflammasome-Mediated IL-1ß Secretion.

Endogenous noninfectious substances that mediate the nucleotide oligomerization domain (NOD)-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome activation and interleukin (IL)-1ß secretion causes inappropriate sterile inflammation and is implicated in the pathogenesis of several chronic diseases, such as type 2 diabetes mellitus, gout, atherosclerosis and Alzheimer's disease. Consequently, dietary phytochemicals exhibiting capacities to suppress canonical NLRP3 inflammasome-mediated IL-1ß secretion can be a reliable supplement to prevent such diseases. The purpose of this study was to investigate and compare the inhibitory effects of ginger phytochemicals, including 6-, 8- and 10-gingerols/shogaols on the canonical NLRP3 inflammasome-mediated IL-1ß secretion in THP-1 macrophages with ordered stimulations of lipopolysaccharide (LPS) and adenosine 5'-triphosphate (ATP). At 20 µM, the 10-gingerol and all the shogaols significantly inhibited canonical IL-1ß secretion. The shogaols had a more potent inhibitory capacity than that of corresponding gingerols. Increase of alkyl chain length impacted negatively the inhibitory activity of shogaols. Additionally, these effective ginger phytochemicals not only inhibited the LPS-primed expression of pro-IL-1ß and NLRP3, but also decreased ATP-activated caspase-1. The results demonstrated that ginger phytochemicals, especially the most potent, 6-shogaol, might be promising for developing as an inhibitor of the canonical NLRP3 inflammasome-mediated IL-1ß secretion and further applied in prevention of NLRP3 inflammasome-associated diseases.

Antimicrobial effects of zero-valent iron nanoparticles on gram-positive Bacillus strains and gram-negative Escherichia coli strains.

BACKGROUND: Zero-valent iron nanoparticles (ZVI NPs) have been used extensively for the remediation of contaminated soil and groundwater. Owing to their large active surface area, they serve as strong and effective reductants. However, the ecotoxicity and bioavailability of ZVI NPs in diverse ecological media have not been evaluated in detail and most studies have focused on non-nano ZVI or Fe0. In addition, the antimicrobial properties of ZVI NPs have rarely been investigated, and the underlying mechanism of their toxicity remains unknown. RESULTS: In the present study, we demonstrate that ZVI NPs exhibited significant toxicity at 1000 ppm against two distinct gram-positive bacterial strains (Bacillus subtilis 3610 and Bacillus thuringiensis 407) but not against two gram-negative strains (Escherichia coli K12 and ATCC11634). Specifically, ZVI NPs caused at least a 4-log and 1-log reductions in cell numbers, respectively, in the two Bacillus strains, whereas no change was detected in the two E. coli strains. X-ray photoelectron spectroscopy, X-ray absorption near-edge, and extended X-ray absorption fine structure spectra confirmed that Bacillus cells exposed to ZVI NPs contained mostly Fe2O3 with some detectable FeS. This finding indicated that Fe0 nanoparticles penetrated the bacterial cells, where they were subsequently oxidized to Fe2O3 and FeS. RedoxSensor analysis and propidium iodide (PI) staining showed decreased reductase activity and increased PI in both Bacillus strains treated with a high (1000 ppm) concentration of ZVI NPs. CONCLUSION: Taken together, these data show that the toxicity of ZVI NPs was derived from their oxidative properties, which may increase the levels of reactive oxygen species and lead to cell death.

[Molecular regulative mechanisms of aging and interventional effects of Chinese herbal medicine].

Aging is a gradual process during the loss of functions in cells,organs and tissues by time. The molecular mechanisms of aging-related theories include the classical ones such as telomere,oxygen radical and nonenzymatic glycosylation,as well as the newly proposed ones such as DNA methylation,mitochondrial DNA （mtDNA）and autophagy. The latest study showed the anti-aging effect of autophagy in hematopoietic stem cells. In recent years,based on the molecular regulative mechanisms of aging,a number of the promising anti-aging drugs have been found,including nicotinamide mononucleotide（NMN）and FOXO4-DRI,a peptide of anti-aging. In addition,there are many new discoveries in the field of plant extracts,in which,the extracts from Chinese herbal medicine（CHM）,some single CHMs and the classical prescriptions of CHM,represented by curcumin and resveratrol,have the partial anti-aging effects by regulating the molecular mechanisms of aging both in vivo and in vitro. In brief,developing or exploring anti-aging drugs,especially the natural drugs,is one of the main development directions in the field of anti-aging research in the basis of the molecular regulative mechanisms of aging.