Synergistic effects of electroacupuncture and bone marrow mesenchymal stem cell transplantation on rat intrauterine adhesion： an observation. / 电针联合骨髓间å è´¨å¹²ç»†èƒžç§»æ¤æ²»ç–—å¤§é¼ å®«è ”ç²˜è¿žçš„ååŒæ•ˆåº”è§‚å¯Ÿ.

OBJECTIVES: To investigate the effects of electroacupuncture(EA) combined with bone marrow mesen-chymal stem cells(BMSCs) transplantation on the endometrium of rats with intrauterine adhesions(IUA), so as to explore the possible mechanisms underlying their combined therapeutic effects. METHODS: Forty adult female SD rats were randomly divided into control, model, cell, and combined groups. The IUA rat model was established using a dual injury method of mechanical scratching and lipopolysaccharide infection. After successful modeling, on days 1, 3, and 7, rats in the model group received tail vein injection of phosphate buffered solution, while rats in the cell group received tail vein injection of BMSCs suspension for BMSCs transplantation；and rats in the combined group received BMSCs transplantation combined with EA treatment (2 Hz/15 Hz, 1-2 mA), targeting the "Guanyuan"(CV4), bilateral "Zusanli"(ST36) and "Sanyinjiao"(SP6) for 20 min daily for 3 consecutive estrous cycles. After intervention, uterine tissue was collected from 5 rats in each group. Histological analysis was performed using hematoxylin and eosin staining to evaluate endometrial thickness and glandular number. Masson staining was used to assess endometrial fibrosis area. Immunohistochemistry was performed to detect the positive expressions of vascular endothelial growth factor(VEGF), proliferating cell nuclear antigen(PCNA), and estrogen receptor(ER). Western blot analysis was conducted to determine the protein expressions of homeobox A10(HoxA10) and leukemia inhibitory factor(LIF), both key regulators of endometrial receptivity. The remaining 5 rats in each group were co-housed with male rats, and the uterine function recovery was evaluated by assessing the number of embryo implantations. RESULTS: Compared with the control group, the model group showed thinning endometrium(P<0.001), decreased glandular number(P<0.001), increased endometrial fibrosis area(P<0.001), reduced positive expressions of VEGF, PCNA, ER, expressions of HoxA10 and LIF, and decreased embryo implantation number (P<0.001) on the injured side of the uterus. Compared with the model group, the combined group showed a reversal of the aforementioned indicators(P<0.001, P<0.01)；the cell group exhibited thicker endometrium(P<0.001) and reduced endometrial fibrosis area(P<0.001). Compared with the cell group, the combined group showed increased endometrial thickness(P<0.01), elevated glandular number(P<0.05), significantly decreased endometrial fibrosis area(P<0.05), enhanced positive expressions of VEGF, PCNA and ER, expressions of HoxA10 and LIF in the endometrium, and a significant increase in embryo implantation number (P<0.001, P<0.05, P<0.01) on the injured side of the uterus, indicating better results than the cell group. CONCLUSIONS: The combination of EA and BMSCs synergistically promotes the repair of damaged endometrium, improves endometrial morphology, reduces fibrosis levels, enhances vascular regeneration and matrix cell proliferation, improves endometrial receptivity, which ultimately facilitates embryo implantation.

[Clinical observation on electroacupuncture at "four points of sacral region" on moderate to severe stress urinary incontinence after radical prostatectomy].

OBJECTIVE: To compare the clinical therapeutic effect between electroacupuncture at "four points of sacral region" and transurethral Erbium laser in treatment of moderate to severe stress urinary incontinence after radical prostatectomy. METHODS: A total of 68 patients of moderate to severe stress urinary incontinence after radical prostatectomy were divided into an electroacupuncture group (34 cases) and an Erbium laser group (34 cases, 3 cases dropped off) according to the settings. In the electroacupuncture group, electroacupuncture was applied at "four points of sacral region", i.e. points of 0.5 cun beside bilateral sacrococcygeal joints and bilateral Huiyang (BL 35), with continuous wave, 2 Hz in frequency, 60 min each time, once every other day, 3 times a week, 12 times as one course of treatment. In the Erbium laser group, transurethral Erbium laser technology was given, once every 4 weeks as one course of treatment. Both groups were treated for 5 courses. The scores of the International Consultation on Incontinence questionnaire-short form (ICI-Q-SF) and the incontinence quality of life questionnaire (I-QOL) were observed before treatment, after each course of treatment and in follow-up after 1 and 2 months of treatment completion, respectively, and the clinical efficacy was evaluated after treatment in the two groups. RESULTS: Compared with those before treatment, the ICI-Q-SF scores were decreased while the I-QOL scores were increased after 5 courses of treatment and in follow-up after 1, 2 months of treatment completion in the two groups (P<0.01). The ICI-Q-SF score in follow-up after 2 months of treatment completion were higher than that after 5 courses of treatment in the Erbium laser group (P<0.05). After 3, 4, 5 courses of treatment and in follow-up after 1 and 2 months of treatment completion, the ICI-Q-SF scores in the electroacupuncture group were lower than those in the Erbium laser group (P<0.05, P<0.01); after 2, 3, 4, 5 courses of treatment and in follow-up after 1 and 2 months of treatment completion, the I-QOL scores in the electroacupuncture group were higher than those in the Erbium laser group (P<0.01). The change ranges of ICI-Q-SF score and I-QOL score between before treatment and after each course of treatment in the electroacupuncture group were lager than those in the Erbium laser group (P<0.01, P<0.05). The total effective rate was 61.8% (21/34) in the electroacupuncture group, which was superior to 19.4 (6/31) in the Erbium laser group (P<0.01). CONCLUSION: Both electroacupuncture at "four points of sacral region" and transurethral Erbium laser can improve the clinical symptoms and the quality of life in patients of moderate to severe stress urinary incontinence after radical prostatectomy. The short-term efficacy and long-term efficacy of electroacupuncture are superior to the Erbium laser technology.

Shen-Qi-Jiang-Tang granule ameliorates diabetic nephropathy via modulating tumor necrosis factor signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Shen-Qi-Jiang-Tang granule (SQJTG), a classic traditional Chinese medicine (TCM) prescription, has been widely used in clinical for diabetes, especially type Ⅱ diabetes. Previous anti-diabetic studies stumbled across that SQJTG has a potential kidney protective effect on diabetic nephropathy (DN). However, the protective mechanism of SQJTG on DN still needs to be explored. AIM OF THE STUDY: The purpose of the present study was to explore the therapeutic effect of SQJTG on DN through both bioinformatics analysis and in vivo experiments. METHODS AND MATERIALS: The TCMIP database was used for screening potential compounds and targets of SQJTG, and the GeneCards, OMIM, DrugBank, and TTD databases were used for collecting DN-related genes. Then protein-protein interaction analysis for the common targets of SQJTG and DN was performed by the STRING database. Meanwhile, KEGG and GO were carried out using the Metascape and DAVID databases. In vivo experiments, to testify the potential kidney protective effects of SQJTG, STZ-induced DN mice with different dosages of SQJTG treatment were collected and the renal tissues were detected by H&E, PAS, Masson and TUNEL staining. Immunohistochemistry and immunoblotting were used to assess the proteins' expressions. Flow cytometry and ELISA assay were used to detect the levels of pro-inflammatory cytokines. RESULTS: Among the 338 compounds ascertained by SQJTG, there were 789 related targets as well. Moreover, 1,221 DN-related targets were predicted and 20 core targets were screened by the PPI analyses. According to GO and KEGG pathway analysis, SQJTG may affect DN via the TNF pathway. For the in vivo experiments, renal histomorphological examinations demonstrated that SQJTG treatment significantly ameliorated STZ-induced kidney damage and had a dosage dependence. Meanwhile, mice with DN were found to have dramatic increases in IL-1, TNF-α, IL-6, and IL-12, but markedly decreased after administration of SQJTG. In addition, the protein levels of TNF signaling molecules, like p-P65, p-JNK, and p-p38, showed significantly elevated in kidney tissues of DN mice and attenuated after SQJTG treatment. CONCLUSIONS: SQJTG exerts a kidney protective effect in DN mice via modulating TNF signaling pathways, and it has promising applications for the treatment of DN.

Highly selective extraction of uranium from wastewater using amine-bridged diacetamide-functionalized silica.

A major environmental concern related to nuclear energy is wastewater contaminated with uranium, thus necessitating the development of pollutant-reducing materials with efficiency and effectiveness. Herein, highly selective mesoporous silicas functionalized with amine-bridged diacetamide ligands SBA-15-ABDMA were prepared. Different spectroscopy techniques were used to probe the chemical environment and reactivity of the chelating ligands before and after sorption. The results showed that the functionalized SBA-15-ABDMA had a strong affinity for uranium at low pH (pH = 3) with desirable sorption capacity (68.82 mg/g) and good reusability (> 5). It showed excellent separation performance with a high distribution coefficient (Kd,U > 105 mL/g) and separation factors SFU/Ln > 1000 at a pH of 3.5 in the presence of lanthanide nuclides, alkaline earth metal and transition metal ions. In particular, SiO2spheres-ABDMA was used as a column material, which achieved excellent recovery of U(VI) (> 98%) and good reusability for samples of simulated mining and nuclear industries wastewater. XPS and crystallography studies clearly illustrated the tridentate coordination mode of U(VI)/PEABDMA and the mechanism and origin behind the high selectivity for U.

A role for substance P and acid-sensing ion channel 1a in prolotherapy with dextrose-mediated analgesia in a mouse model of chronic muscle pain.

ABSTRACT: Prolotherapy is widely used in pain control and tissue repair in pain medicine. The classical mode is injection with hypertonic dextrose in muscle or perimysium. However, the analgesic mechanism is still not known. Here, we successfully established dextrose-mediated antinociception in a mouse model of fibromyalgia. The antinociceptive effects of dextrose injections were evaluated in a mouse model of fibromyalgia, in which bilateral chronic mechanical hyperalgesia was induced by unilateral intramuscular acid injection. The injectant (dextrose), dose (≥5%), and volume (>10 µL), but not osmolarity, were essential for the prolotherapy. Further studies showed that the activation of acid-sensing ion channel 1a (ASIC1a), neural activation, and the release of substance P from muscle afferents were required in the dextrose-induced reduction of mechanical hypersensitivity. Both pharmacological blockade and genetic deletion of ASIC1a or substance P as well as lidocaine abolished the dextrose-induced antinociception in mice with chronic hyperalgesia. Moreover, intramuscular dextrose injection induced phosphorylated extracellular signal-regulated kinase expression in dorsal root ganglion neurons expressing substance P; the phosphorylated extracellular signal-regulated kinase expression was inhibited by the ASIC1a antagonist PcTx1. The optimal settings for prolotherapy in fibromyalgia-like pain are dextrose dependent and volume dependent, and the peripheral antinociception involves ASIC1a and substance P signaling in muscle afferents. This study suggests a possible mechanism of action of dextrose prolotherapy in noninflammatory muscle pain such as fibromyalgia and provides insights into treating other types of chronic pain.

Plasmonics-Based Multifunctional Electrodes for Low-Power-Consumption Compact Color-Image Sensors.

High pixel density, efficient color splitting, a compact structure, superior quantum efficiency, and low power consumption are all important features for contemporary color-image sensors. In this study, we developed a surface plasmonics-based color-image sensor displaying a high photoelectric response, a microlens-free structure, and a zero-bias working voltage. Our compact sensor comprised only (i) a multifunctional electrode based on a single-layer structured aluminum (Al) film and (ii) an underlying silicon (Si) substrate. This approach significantly simplifies the device structure and fabrication processes; for example, the red, green, and blue color pixels can be prepared simultaneously in a single lithography step. Moreover, such Schottky-based plasmonic electrodes perform multiple functions, including color splitting, optical-to-electrical signal conversion, and photogenerated carrier collection for color-image detection. Our multifunctional, electrode-based device could also avoid the interference phenomenon that degrades the color-splitting spectra found in conventional color-image sensors. Furthermore, the device took advantage of the near-field surface plasmonic effect around the Al-Si junction to enhance the optical absorption of Si, resulting in a significant photoelectric current output even under low-light surroundings and zero bias voltage. These plasmonic Schottky-based color-image devices could convert a photocurrent directly into a photovoltage and provided sufficient voltage output for color-image detection even under a light intensity of only several femtowatts per square micrometer. Unlike conventional color image devices, using voltage as the output signal decreases the area of the periphery read-out circuit because it does not require a current-to-voltage conversion capacitor or its related circuit. Therefore, this strategy has great potential for direct integration with complementary metal-oxide-semiconductor (CMOS)-compatible circuit design, increasing the pixel density of imaging sensors developed using mature Si-based technology.

Fluorescent recognition of uranyl ions by a phosphorylated cyclic peptide.

Fluorescent recognition of uranyl ions was achieved using a phosphorylated cyclic peptide, which can be used as a fluorescent sensor for the detection of uranyl ions with high selectivity and sensitivity.

[Development of biphasic drug-loading lipid emulsion of Salvia miltiorrhiza and its quality evaluation].

The feasibility of simultaneously loading both liposoluble and water-soluble components of Salvia miltiorrhiza in emulsion was discussed, in order to provide new ideas in comprehensive application of effective components in S. miltiorrhiza in terms of technology of pharmaceutics. With tanshinone II (A) and salvianolic acid B as raw materials, soybean phospholipid and poloxamer 188 as emulsifiers, and glycerin as isoosmotic regulator, the central composite design-response surface method was employed to optimize the prescription. The coarse emulsion was prepared with the high-speed shearing method and then homogenized in the high pressure homogenizer. The biphasic drug-loading intravenous emulsion was prepared to investigate its pharmaceutical properties and stability. The prepared emulsion is orange-yellow, with the average diameter of 241 nm and Zeta potential of -35.3 mV. Specifically, the drug loading capacity of tanshinone II (A) and salvianolic acid B were 0.5 g x L(-1) and 1 g x L(-1), respectively, with a good stability among long-term retention samples. According to the results, the prepared emulsion could load liposoluble tanshinone II (A) and water-soluble salvianolic acid B simultaneously, which lays a pharmaceutical foundation for giving full play to the efficacy of S. miltiorrhiza.

[Quality evaluation and stability investigation of asarone submicro emulsion injection].

The content of the asarone submicro emulsion injection was determind by HPLC method, and thereby a quality evaluation method was established based on indexes of pH value, particle size, peroxide value, methoxy aniline values, free fatty acid, lysophosphatidylcholine, visible foreign substances, insoluble particle, sterility, bacterial endotoxin and impurities, etc. The results showed that the injection exhibited uniform physical appearance and all the products were in milkwhite liquid. The content of the three batches products were respectively 102.9%, 100.8%, 97.70% of the labeled amount, with mean particle size of 210-250 nm, and other indexes all met with the standards. The reserved samples showed no obvious change in terms of detection indexes and indicated good stability after the accelerated stability test and long-term stability for 12 months. The quality evaluation method established in this study could be applied to quality control and stability investigation of asarone submicron emulsion injection, which laid a basis for further clinical research and application.

Development of intravenous lipid emulsion of α-asarone with significantly improved safety and enhanced efficacy.

Severe adverse events have been frequently associated with taking the commercially available formulation of α-asarone injection (α-asarone-I). Hence, we sought to develop an intravenous lipid emulsion of α-asarone (α-asarone-LE), where we hypothesized that these adverse events could be prevented. Using a central composite design-response surface methodology, we developed and optimized an emulsion formulation of α-asarone-LE that composed of 10.0% (w/v) soybean oil, 0.4% (w/v) α-asarone, 1.2% (w/v) soybean lecithin, 0.3% (w/v) F68, and 2.2% (w/v) glycerol. The mean particle size of α-asarone-LE was 226±11 nm, the ζ-potential was -25.6±1.2 mV, the encapsulation efficiency was 99.2±0.1% and the drug loading efficiency was 3.45%. Stability, safety, and efficacy studies of α-asarone-LE were systematically investigated and compared to those of α-asarone-I. The α-asarone-LE not only showed a desired stability, but also exhibited excellent safety and improved efficacy in vivo, indicating its great potential for clinical application in the future.

Association between the rs2910164 polymorphism in pre-mir-146a and oral carcinoma progression.

MicroRNAs are short non-coding RNAs that regulate gene expression by RNA interference. Oral squamous cell carcinoma (OSCC) is a prevalent malignancy worldwide. miR-146a has been reported to regulate Toll-like receptors and cytokine signaling, which are both crucial for inflammation and oncogenesis. This study identifies that areca nut extract, TNFα and TGFß up-regulates miR-146a in OSCC cells. The increased expression of miR-146a enhanced the oncogenicity of OSCC cells. In addition, a G to C polymorphism (rs2910164), which is located in the pre-miR-146a and has been associated with functional alterations in miR-146a, was significantly more prevalent among OSCC patients having more advanced nodal involvement. Our analysis also suggested a higher miR-146a expression in OSCC tissues of patients carrying C polymorphism. The present study concluded a higher prevalence of the pre-mir-146a C-variant was associated with OSCC progression in patients with this disease.

Arctigenin from Arctium lappa inhibits interleukin-2 and interferon gene expression in primary human T lymphocytes.

BACKGROUND: Arctium lappa (Niubang), a Chinese herbal medicine, is used to treat tissue inflammation. This study investigates the effects of arctigenin (AC), isolated from A. lappa, on anti-CD3/CD28 Ab-stimulated cell proliferation and cytokine gene expression in primary human T lymphocytes. METHODS: Cell proliferation was determined with enzyme immunoassays and the tritiated thymidine uptake method. Cytokine production and gene expression were analyzed with reverse transcription-polymerase chain reaction. RESULTS: AC inhibited primary human T lymphocytes proliferation activated by anti-CD3/CD28 Ab. Cell viability test indicated that the inhibitory effects of AC on primary human T lymphocyte proliferation were not due to direct cytotoxicity. AC suppressed interleukin-2 (IL-2) and interferon-γ (IFN-γ) production in a concentration-dependent manner. Furthermore, AC decreased the IL-2 and IFN-γ gene expression in primary human T lymphocytes induced by anti-CD3/CD28 Ab. Reporter gene analyses revealed that AC decreased NF-AT-mediated reporter gene expression. CONCLUSION: AC inhibited T lymphocyte proliferation and decreased the gene expression of IL-2, IFN-γ and NF-AT.

[Inhibitory effect of tanshinones on proliferation of K562 cell line and its structure-activity relationship].

The study was purposed to investigate the growth inhibitory effect of tanshinones on K562 cell line and the relationship between their structures and cytotoxicity. The modified MTT assay was adopted to measure the inhibitory effect of tanshinones at different concentrations and chemical structures on K562 cells, and the changes of cell morphology were observed by inverted phase contrast microscopy. The results indicated that the tanshinones could inhibit the proliferation of K562 cells effectively, and their cytotoxicities on K562 cells showed concentration- and time-dependent manners. The IC(50) of dihydrotanshinone I, tanshinone I, tanshinone IIA and cryptotanshinone at 24 hours were 0.91, 4.04, 5.95, 13.85 µg/ml at 48 hours were 0.37, 1.35, 1.71, 6.71 µg/ml; at 72 hours were 0.33, 0.46, 0.82, 6.02 µg/ml, respectively. It is concluded that all of the four tanshinones have proliferation inhibitory effect on K562 cell line, among them the dihydrotanshinone I is the most active one, followed by tanshinone I, tanshinone IIA and cryptotanshinone subsequently, indicating that the chemical structure of aromatic ring A of tanshinones can enhance their cytotoxicity and the structure of furan ring C may influence the cytotoxicity, but their mechanism is still remained to be further investigated.

[Preparation and quality evaluation of intravenous tanshinone II (A) emulsion].

OBJECTIVE: To prepare and evaluate an intravenous emulsion of tanshinone II(A). METHOD: Soybean phospholipid mixing with poloxamer 188 was used as emulsifier. Oleic acid and glycerol were used as co-emulsifier and isoosmotic adjusting agent, respectively. The coarse emulsion was first prepared and following homogenization was carried out for the coarse emulsion by using a high pressure homogenizer. RESULT: The average diameter of the prepared tanshinone II (A) emulsion was 211 nm with a zeta potential of -32. 1 mV. There had no changes of diameter, zeta potential, pH value, content and physical appearance for the tanshinone II (A) emulsion stored at 25 degrees C away from light during one year. CONCLUSION: The physicochemical properties of the prepared tanshinone II (A) emulsion was stable, which could meet the requirements of intravenous administration.

Antioxidative and in vitro hepatoprotective activity of Bupleurum kaoi leaf infusion.

The roots of Bupleurus spp. have been used in traditional Chinese herbal medicine for curing liver diseases. Although bioactive saikosaponins have been detected in the leaves as well as in the roots, the aerial parts of the plants are discarded as waste. In the present study, a leaf infusion of B. kaoi Liu, Chao et Chuang, an indigenous Bupleurus species in Taiwan, was prepared and the antioxidant properties and in vitro hepatoprotective activity were demonstrated. The results show that the leaf infusion exerted DPPH free radical scavenging activity, inhibitory capacity on superoxide anion formation and superoxide anion scavenging activity. The hepatotoxicity of acetaminophen (APAP) and carbon tetrachloride (CCl4) on the rat liver cells were also decreased by the leaf infusion.

Ultrasound-assisted extraction methodology as a tool to improve the antioxidant properties of herbal drug Xiao-chia-hu-tang.

Xiao-chai-hu-tang (XCHT) is an important Chinese herbal prescription for curing many types of liver diseases. The contents of bioactive constituents (saikosaponins a, c and d, baicalin, baicalein, and glycyrrhizic acid), and antioxidant properties of XCHT extracts prepared with ultrasound-assisted (US) extraction in combination with ethanol (up to 95%) as extraction modifier were studied. The results showed that the US extraction significantly increased the bioactive constituents concentrations and antioxidant properties of XCHT extracts when compared with the XCHT prepared with traditional boiling-water extraction. Among the XCHT extracts made with US extraction, the sample prepared with 95% ethanol showed the highest bioactive constituent concentrations and the best antioxidant functionalities. The results suggest that US extraction of XCHT is feasible to replace the traditional time-consuming and low efficiency preparation procedure in the future modernized and commercialized manufacture of this highly valuable Chinese herbal medicine.

Hepatoprotective and antioxidant effects of Bupleurum kaoi Liu (Chao et Chuang) extract and its fractions fractionated using supercritical CO(2) on CCl(4)-induced liver damage.

Fractionation with supercritical CO(2) is employed to divide ethanolic extract (E) of B. kaoi into four fractions (R, F1, F2 and F3). To assess the selectivity of the fractionation, extracts of the four fractions were characterized in terms of the hepatoprotective capacity and activity of antioxidant enzymes to against CCl(4)-induced damage. The in vitro study revealed that pretreatment with B. kaoi extract or its fractions, except F3, significantly protected primary hepatocytes against damage by CCl(4) (P<0.05). The R and F1 fractions had the highest saikosaponins content (175 and 200 mg/g dry weight, respectively) and most effectively protected the liver from damage by CCl(4). This study demonstrated that the oral pretreatment of B. kaoi (100 and 500 mg/kg), except F3, three days before a single dose of CCl(4) (CCl(4)/olive oil=1:1, 3 ml/kg, sc) was administered significantly lowered the serum levels of hepatic enzyme markers (AST and ALT) (P<0.05). A pathological examination showed that lesions, including ballooning degeneration, necrosis, hepatitis and portal triaditis were partially healed by treatment with B. kaoi extract and fractions. Oxidative stress induced by CCl(4) led to lipid peroxidation (MDA) and changes in the levels of the antioxidant enzymes in the liver. However, all the fractions, except F3, markedly suppressed lipid peroxidation and reversed the activities of the antioxidant enzymes to the normal levels.