Space Station-like Composite Nanoparticles for Co-Delivery of Multiple Natural Compounds from Chinese Medicine and Hydrogen in Combating Sensorineural Hearing Loss.

Ototoxic drugs such as aminoglycoside antibiotics and cisplatin (CDDP) can cause sensorineural hearing loss (SNHL), which is closely related to oxidative stress and the acidification of the inner ear microenvironment. Effective treatment of SNHL often requires multifaceted approach due to the complex pathology, and drug combination therapy is expected to be at the forefront of modern hearing loss treatment. Here, space-station-like composite nanoparticles (CCC@mPP NPs) with pH/oxidation dual responsiveness and multidrug simultaneous delivery capability were constructed and then loaded with various drugs including panax notoginseng saponins (PNS), tanshinone IIA (TSIIA), and ammonia borane (AB) to provide robust protection against SNHL. Molecular dynamics simulation revealed that carboxymethyl chitosan/calcium carbonate-chitosan (CCC) NPs and monomethoxy poly(ethylene glycol)-PLGA (mPP) NPs can rendezvous and dock primarily by hydrogen bonding, and electrostatic forces may be involved. Moreover, CCC@mPP NPs crossed the round window membrane (RWM) and entered the inner ear through endocytosis and paracellular pathway. The docking state was basically maintained during this process, which created favorable conditions for multidrug delivery. This nanosystem was highly sensitive to pH and reactive oxygen species (ROS) changes, as evidenced by the restricted release of payload at alkaline condition (pH 7.4) without ROS, while significantly promoting the release in acidic condition (pH 5.0 and 6.0) with ROS. TSIIA/PNS/AB-loaded CCC@mPP NPs almost completely preserved the hair cells and remained the hearing threshold shift within normal limits in aminoglycoside- or CDDP-treated guinea pigs. Further experiments demonstrated that the protective mechanisms of TSIIA/PNS/AB-loaded CCC@mPP NPs involved direct and indirect scavenging of excessive ROS, and reduced release of pro-inflammatory cytokines. Both in vitro and in vivo experiments showed the high biocompatibility of the composite NPs, even after long-term administration. Collectively, this work suggests that composite NPs is an ideal multi-drug-delivery vehicle and open new avenues for inner ear disease therapies.

Pseudotargeted metabolomics-based random forest model for tracking plant species from herbal products.

BACKGROUND: The "one-to-multiple" phenomenon is prevalent in medicinal herbs. Accurate species identification is critical to ensure the safety and efficacy of herbal products but is extremely challenging due to their complex matrices and diverse compositions. PURPOSE: This study aimed to identify the determinable chemicalome of herbs and develop a reasonable strategy to track their relevant species from herbal products. METHODS: Take Astragali Radix-the typical "one to multiple" herb, as a case. An in-house database-driven identification of the potentially bioactive chemicalome (saponins and flavonoids) in AR was performed. Furthermore, a pseudotargeted metabolomics method was first developed and validated to obtain high-quality semi-quantitative data. Then based on the data matrix, the random forest algorithm was trained to predict Astragali Radix species from commercial products. RESULTS: The pseudotargeted metabolomics method was first developed and validated to obtain high-quality semi-quantitative data (including 56 saponins and 49 flavonoids) from 26 batches of AR. Then the random forest algorithm was well-trained by importing the valid data matrix and showed high performance in predicting Astragalus species from ten commercial products. CONCLUSION: This strategy could learn species-special combination features for accurate herbal species tracing and could be expected to promote the traceability of herbal materials in herbal products, contributing to manufacturing standardization.

The crosstalk between endothelial cells and vascular smooth muscle cells aggravates high phosphorus-induced arterial calcification.

Arterial calcification is highly prevalent, particularly in patients with end-stage renal disease (ESRD). The osteogenic differentiation of vascular smooth muscle cells (VSMCs) is the critical process for the development of arterial calcification. However, the detailed mechanism of VSMCs calcification remains to be elucidated. Here, we investigated the role of exosomes (Exos) derived from endothelial cells (ECs) in arterial calcification and its potential mechanisms in ESRD. Accelerated VSMCs calcification was observed when VSMCs were exposed to ECs culture media stimulated by uremic serum or high concentration of inorganic phosphate (3.5 mM Pi). and the pro-calcification effect of the ECs culture media was attenuated by exosome depletion. Exosomes derived from high concentrations of inorganic phosphate-induced ECs (ECsHPi-Exos) could be uptaken by VSMCs and promoted VSMCs calcification. Microarray analysis showed that miR-670-3p was dramatically increased in ECsHPi-Exos compared with exosomes derived from normal concentrations of inorganic phosphate (0.9 mM Pi) induced ECs (ECsNPi-Exos). Mechanistically, insulin-like growth factor 1 (IGF-1) was identified as the downstream target of miR-670-3p in regulating VSMCs calcification. Notably, ECs-specific knock-in of miR-670-3p of the 5/6 nephrectomy with a high-phosphate diet (miR-670-3pEC-KI + NTP) mice that upregulated the level of miR-670-3p in artery tissues and significantly increased artery calcification. Finally, we validated that the level of circulation of plasma exosomal miR-670-3p was much higher in patients with ESRD compared with healthy controls. Elevated levels of plasma exosomal miR-670-3p were associated with a decline in IGF-1 and more severe artery calcification in patients with ESRD. Collectively, these findings suggested that ECs-derived exosomal miR-670-3p could promote arterial calcification by targeting IGF-1, which may serve as a potential therapeutic target for arterial calcification in ESRD patients.

Sonodynamic therapy exciting the herbal nanocomposite with spider-web-like effect to combat otitis media.

Otitis media, mainly caused by bacteria, is prevalent in young children and can cause hearing loss and growth retardation. Antibiotics are the most widely utilized treatment for otitis media, however, they can cause drug resistance and harmful side effects. In this study, we reported an antibacterial nanocomposite in combination with sonodynamic therapy that consists of herbal antibacterial agents such as Curcumin (CUR) and Tanshinone IIA (TSIIA), as well as Chitosan (CS), for the treatment of acute otitis media. CUR/TSIIA/CS nanocomposite (NC) with ultrasonic irradiation demonstrated that it could eliminate Staphylococcus aureus. In vivo experiments revealed that NC-mediated sonodynamic therapy had excellent antibacterial and anti-inflammatory activity, displaying a consistent performance comparable to ofloxacin. The therapeutic efficiency was attributed to capturing bacteria through spider-web-like effect and destroying bacteria through the reactive oxygen species generated under ultrasonic irradiation. Significantly, NC did not induce bacterial resistance and showed good biocompatibility. This study provides a novel strategy to develop an ultrasound-assisted nanocomposite with an enhanced antibacterial effect. Further, it unlocks new doors for the substitute of antibiotics to combat otitis media by establishing efficient therapeutic systems.

Rapid Screening and Identification of Antitumor Ingredients from the Mangrove Endophytic Fungus Using an Enzyme-Immobilized Magnetic Nanoparticulate System.

As a consequence of recent progression in biomedicine and nanotechnology, nanoparticle-based systems have evolved as a new method with extensive applications in responsive therapy, multimodal imaging, drug delivery and natural product separation. Meanwhile, the magnetic nanoparticulate system has aroused great interest for separation and purification because of its excellent magnetic properties. Phospholipase A2 (PLA2) is a highly expressed regulator to promote the growth of various cancers and is an ideal target to treat cancers. In this study, a novel strategy based on ligand-receptor interactions to discover novel PLA2 inhibitors was established, in which PLA2-functionalized Fe3O4@PLGA-PEG-NH2 magnetic nanoparticles were used as a supporting material combined with high-performance liquid chromatography-mass spectrometry, aiming to accelerate the discovery of novel PLA2 inhibitors from natural sources such as mangrove endophytic fungi. Under the optimized ligand fishing conditions, six target compounds were ultimately fished and identified to be cyclic peptides (1-3) and sterols (4-6), which compounds 1, 2 and 4-6 have well-documented cytotoxicities. Compound 3 exerted better inhibitory effect on A549 cells by experiment. In conclusion, PLA2-functionalized Fe3O4@PLGA-PEG-NH2 magnetic nanoparticles-based ligand fishing provided a feasible, selective and effective platform for the efficient screening and identification of antitumor components from natural products.

Mechanism of Huangqi Guizhi Wuwu Decoction in treatment of rheumatoid arthritis based on UPLC-LTQ-Orbitrap-MS, network pharmacology, and cell experiment / 中国中药杂志

In this study, ultra-high performance liquid chromatography-linear ion trap/electrostatic field orbit trap combined-type mass spectrometry(UPLC-LTQ-Orbitrap-MS) was used to analyze the main active components of Huangqi Guizhi Wuwu Decoction(HQGZ). A total of 50 active components were identified from HQGZ and 108 potential targets of the components related to the treatment of rheumatoid arthritis were retrieved based on network pharmacology, including 87 key targets, followed by Gene Ontology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment of the targets. The result indicated that HQGZ may exert therapeutic effects mainly through the sphingolipid signaling pathway, tumor necrosis factor(TNF) signaling pathway, as well as the positive regulation of ribonucleic acid(RNA) polymerase Ⅱ promoter transcription, inflammatory response and other biological processes. At the same time, cell experiment was performed to verify the key proteins in the TNF signaling pathway. The results demonstrated that HQGZ significantly reduced the expression of caspase-3(CASP3), TNF, relaxed(RELA) protein, and IkappaB kinase beta(IKBKB) in fibroblast-like synoviocytes induced by TNF-α. The results of UPLC-LTQ-Orbitrap-MS, network pharmacology and cell experiment showed that the active components in HQGZ may inhibit inflammatory response and regulate immune function and cell apoptosis by modulating key proteins in TNF signaling pathway to treat rheumatoid arthritis.

Effect of electroacupuncture on lung dysplasia in rats with intrauterine growth restriction induced by maternal food restriction / 中国针灸

OBJECTIVE@#To investigate the protective effect of electroacupuncture (EA) at "Zusanli" (ST 36) in pregnant rats on lung dysplasia of newborn rats with intrauterine growth restriction (IUGR) induced by maternal food restriction.@*METHODS@#Twenty-four female SD rats were randomly divided into a control group, a control+EA group, a model group and a model+EA group, 6 rats in each group. From the 10th day into pregnancy to the time of delivery, the rats in the model group and the model+EA group were given with 50% dietary restriction to prepare IUGR model. From the 10th day into pregnancy to the time of delivery, the rats in the control+EA group and the model+EA group were treated with EA at bilateral "Zusanli" (ST 36), once a day. The body weight of offspring rats was measured at birth, and the body weight and lung weight of offspring rats were measured on the 21st day after birth. The lung function was measured by small animal lung function detection system; the lung tissue morphology was observed by HE staining; the content of peroxisome proliferator activated receptor γ (PPARγ) in lung tissue was detected by ELISA.@*RESULTS@#Compared with the control group, the body weight at birth as well as the body weight, lung weight, lung dynamic compliance (Cdyn) and PPARγ at 21 days after birth in the model group were significantly decreased (@*CONCLUSION@#EA at "Zusanli" (ST 36) may protect the lung function and lung histomorphology changes by regulating the level of PPARγ of lung in IUGR rats induced by maternal food restriction.

Adenine-Functionalized Supramolecular Micelles for Selective Cancer Chemotherapy.

Functional supramolecular micelles containing self-complementary multiple hydrogen bonding adenine groups (A-PPG) can spontaneously self-assemble into stable nanosized micelles in aqueous solution. These micelles can be used to selectively deliver anticancer drugs to cancer cells and effectively promote tumor cell death via apoptosis, without harming normal cells. The drug-loaded micelles exhibit tunable drug-loading capacity and rapid pH-triggered drug release under acidic conditions, as well as a high drug-entrapment stability in serum-rich media due to the reversible hydrogen-bonded adenine-adenine interactions within the micellar interior; these properties are critical to achieving effective chemotherapeutic drug delivery and controlled drug release. In vitro assays show that the drug-loaded micelles exert significant cytotoxic effects on cancer cells, with minimal effects on normal cells under physiological conditions. Cytotoxicity assays using A-PPG micelles loaded with different anticancer drugs confirm these effects. Importantly, cellular internalization and flow cytometric analyses demonstrate that the adenine moieties within A-PPG micelles significantly increase selective endocytic uptake of the supramolecular micelles by cancer cells, which in turn induce apoptotic cell death and substantially enhance the response to chemotherapy. Thus, A-PPG micelles can improve the safety and efficacy of cancer chemotherapy.

Phytochemical Profiles and Antioxidant Activity of Rehmannia glutinosa from Different Production Locations.

The chemical components and antioxidant activity of 16 Rehmannia glutinosa samples were investigated to reveal the high-quality raw resource for pharmaceutical products. 22 main chemical components were detected with significant content differences (P<0.05). The contents of 14 substances reached the maximum in S1 sample such as catalpol (6.74 mg g-1 ), rehmaionoside A (1.93 mg g-1 ) and rehmannioside D (5.13 mg g-1 ). However, the content distribution of the other eight substances had no obvious change regulation. Three antioxidant evaluation methods commonly showed that S1 sample had strong antioxidant activity with a low IC50 value of 0.022 mg mL-1 , a high ABTS value of 524.196 µmol equiv. Trolox g-1 , and a high FRAP value of 200.517 µmol equiv. Trolox g-1 . Considered the medicinal value, S1 had high quality based on the present phytochemical profiles and antioxidant activity. These results also indicated that the root extracts of R. glutinosa could become useful supplement for pharmaceutical products as new antioxidant agents.

Mechanism of Jingfang Granule in treatment of coronavirus infection by biological information technology / 中草药

Objective: To explore the mechanism of Jingfang Granule in treatment of corona virus infection through biological information technology based on network pharmacology and molecular docking. Methods: The databases of TCMIP and TCMSP were used to summarize the flavor and meridian tropism and active compounds of Jingfang Granule, and the potential targets of active compounds were searched by PubChem and SwissTargetPrediction. The corona virus targets were collected from the GeneCards database. And common targets were enriched and analyzed by DAVID database after the intersection of the compounds targets and the disease targets. Then the network of "TCM-Ingredients-Common targets" was established by Cytoscape 3.7.2, the main active components and key targets were screened for molecular docking. Results: Totally 139 active components of Jingfang Granule and 27 common targets were obtained. GO enrichment analysis and KEGG enrichment analysis found that the pathways in cancer, MAPK signaling pathway, PI3K-Akt signaling pathway, TNF signaling pathway were the main pathways of Jingfang Granule in treatment of corona virus infection. The network of "TCM-Ingredients-Common targets" was successfully constructed, and results of molecular docking showed that the main components in this network such as β-sitosterol, cerevisterol, isorhamnetin, hesperetin, and luteolin etc., have good affinity with key targets of VEGFA, IL6, TNF, PPARγ, APP, ACE2, and SARS-CoV-2 3CL hydrolase. Conclusion: Jingfang Granule treats corona virus infectious diseases through the compatibility of multiple traditional Chinese medicine. Its resistance to corona virus infection may be through the β-sitosterol, cerevisterol, isorhamnetin, hesperetin, and luteolin act on the VEGFA, IL6, TNF, PPARγ, APP and other targets, and then affects the pathways in cancer, MAPK signal pathway, PI3K-Akt signal pathway, TNF signal pathways to achieve.

Phosphorus chemical speciation and seasonal variations in surface sediments of the Maowei Sea, northern Beibu Gulf.

This study presents the distribution, seasonal variations and factors influencing phosphorus (P) forms in surface sediments from the Maowei Sea. P forms were measured using the sequential extraction (SEDEX) procedures. Inorganic P (IP) was the predominant chemical form of total P (TP). Fe-bound P (FeP) was the main IP form. Sediment particle sizes, organic matter distribution, terrestrial input and aquaculture activity were responsible for the seasonal variations of different forms of P in sediment. In summer, the average proportions of P fractions in TP followed the order of organic P (OP) > Fe-P > authigenic P (CaP) > detrital P (De-P) > exchangeable P (Ex-P); in winter, the corresponding order was OP > Fe-P > De-P > Ca-P > Ex-P. The potential bio-available P accounted for 71.1 ±â€¯4.9% and 70.6 ±â€¯6.3% of TP in summer and winter, respectively. Sedimentary organic matter mainly came from land-based sources in winter.

Structure Characterization and Otoprotective Effects of a New Endophytic Exopolysaccharide from Saffron.

Saffron, a kind of rare medicinal herb with antioxidant, antitumor, and anti-inflammatory activities, is the dry stigma of Crocus sativus L. A new water-soluble endophytic exopolysaccharide (EPS-2) was isolated from saffron by anion exchange chromatography and gel filtration. The chemical structure was characterized by FT-IR, GC-MS, and 1D and 2D-NMR spectra, indicating that EPS-2 has a main backbone of (1→2)-linked α-d-Manp, (1→2, 4)-linked α-d-Manp, (1→4)-linked α-d-Xylp, (1→2, 3, 5)-linked ß-d-Araf, (1→6)- linked α-d-Glcp with α-d-Glcp-(1→ and α-d-Galp-(1→ as sidegroups. Furthermore, EPS-2 significantly attenuated gentamicin-induced cell damage in cultured HEI-OC1 cells and increased cell survival in zebrafish model. The results suggested that EPS-2 could protect cochlear hair cells from ototoxicity exposure. This study could provide new insights for studies on the pharmacological mechanisms of endophytic exopolysaccharides from saffron as otoprotective agents.

Curcumin relieves depressive-like behaviors via inhibition of the NLRP3 inflammasome and kynurenine pathway in rats suffering from chronic unpredictable mild stress.

Increasing evidence suggests that inflammation is related to the pathophysiology of depression. Curcumin (CUR), which is a natural component extracted from the rhizome of Curcuma longa, seems to be efficacious in depression treatment. Hence, the present study aims to explore whether the anti-depressive effect of curcumin is connected to its anti-inflammatory features. Twenty-one SD rats were randomly divided into three groups, namely, control, CUMS (chronic unpredictable mild stress), and CUMS + CUR. After stress exposure for four weeks, the CUMS group showed depressive-like behaviors, and the curcumin treatment successfully corrected the depressive-like behaviors in stressed rats. Additionally, the curcumin could effectively decrease mRNA expression of proinflammatory cytokines (IL-1ß, IL-6, and TNF-α) and suppress NF-κB activation. Curcumin also inhibited the stressed-induced P2X7R/NLRP3 inflammasome axis activation, along with the reduced transformation of pro-IL-1ß to mature IL-1ß. The stress-induced activation of indolamine-2, 3-dioxygenase (IDO) and an increased kynurenine/tryptophan ratio were also ameliorated by curcumin supplementation. In conclusion, the study revealed that curcumin relieves a depressive-like state through the inhibition of the NLRP3 inflammasome and kynurenine pathway.

Current state of researches on mechanisms of acupuncture in improvement of hypoxia-ischemic diseases of the central nervous system / 针刺研究

Acupuncture is widely used in the treatment of ischemic diseases of the central nervous system in different clinical stages and has achieved a good clinical effect. The current research showed that acupuncture can improve cerebral blood flow perfusion via increasing blood flow volume, blood flow velocity, the levels of vasomotor substances and reduction of blood viscosity and erythrocyte aggregation index. In recent years, many studies focused on the pathophysiological mechanism of acupuncture in improving cerebral ischemia via triggering the cholinergic vasodilatation, up-regulation of expression of vascular-related proteins and genes，attenuation of inflammatory reaction, etc. Currently, the methods for evaluating the effect of acupuncture are mostly noninvasive functional magnetic resonance imaging in healthy subjects. Future studies should include united selection of acupoints and acupuncture needle manipulations, more reasonable combination of different acupoints, united outcome evaluative standards, better repeatability, employment of big data, etc.

Effect of electroacupuncture at "Zusanli" (ST 36) and "Yanglingquan" (GB 34) on perinatal nicotine-exposure-induced lung function and morphology of neonatal rats / 中国针灸

OBJECTIVE@#To compare the effects of electroacupuncture (EA) at "Zusanli" (ST 36) versus "Yanglingquan" (GB 34) in the pregnant rats on perinatal nicotineexposureinduced lung function and morphology of newborn rats and explore the rule of acupoint effect in EA for the prevention from lung dysplasia in newborn rats.@*METHODS@#A total of 24 female SD rats were randomized into a normal saline group (S group), a nicotine group (N group), a nicotineST 36 group (N + ST 36 group) and a nicotineGB 34 group (N+GB 34 group), 6 rats in each one. Starting at the 6th day of pregnancy, 0.9% sodium chloride solution was injected subcutaneously in the S group, 1 mg/kg; and in the rest 3 groups, nicotine of the same dose was injected through to the 21st postnatal day to establish the perinatal nicotineexposure model. Simultaneously, during model preparation, EA was applied at "Zusanli" (ST 36) and "Yanglingquan" (GB 34) in the N+ST 36 group and the N+GB 34 group respectively, once a day, through to the 21st postnatal day. The lung function analytic system for small animal was adopted to observe the changes in lung function indicators in newborn rats, such as peak inspiratory flow (PIF), peak expiratory flow (PEF), expiratory resistance (RE), inspiratory resistance (RI) and dynamic compliance (Cdyn). HE staining was used to observe the morphological changes of lung, such as alveolar fusion and rupture.@*RESULTS@#Compared with the S group, PEF and Cdyn were lower and PIF, RI and RE higher in the N group (all 0.05).@*CONCLUSION@#Electroacupuncture at "Zusanli" (ST 36) in the pregnant rats significantly improves the perinatal nicotineexposureinduced lung function and morphology of newborn rats than electroacupuncture at "Yanglingquan" (GB 34).

SIRT3 restricts hepatitis B virus transcription and replication through epigenetic regulation of covalently closed circular DNA involving suppressor of variegation 3-9 homolog 1 and SET domain containing 1A histone methyltransferases.

Hepatitis B virus (HBV) infection remains a major health problem worldwide. Maintenance of the covalently closed circular DNA (cccDNA), which serves as a template for HBV RNA transcription, is responsible for the failure of eradicating chronic HBV during current antiviral therapy. cccDNA is assembled with cellular histone proteins into chromatin, but little is known about the regulation of HBV chromatin by histone posttranslational modifications. In this study, we identified silent mating type information regulation 2 homolog 3 (SIRT3) as a host factor restricting HBV transcription and replication by screening seven members of the sirtuin family, which is the class III histone deacetylase. Ectopic SIRT3 expression significantly reduced total HBV RNAs, 3.5-kb RNA, as well as replicative intermediate DNA in HBV-infected HepG2-Na+ /taurocholate cotransporting polypeptide cells and primary human hepatocytes. In contrast, gene silencing of SIRT3 promoted HBV transcription and replication. A mechanistic study found that nuclear SIRT3 was recruited to the HBV cccDNA, where it deacetylated histone 3 lysine 9. Importantly, occupancy of SIRT3 on cccDNA could increase the recruitment of histone methyltransferase suppressor of variegation 3-9 homolog 1 to cccDNA and decrease recruitment of SET domain containing 1A, leading to a marked increase of trimethyl-histone H3 (Lys9) and a decrease of trimethyl-histone H3 (Lys4) on cccDNA. Moreover, SIRT3-mediated HBV cccDNA transcriptional repression involved decreased binding of host RNA polymerase II and transcription factor Yin Yang 1 to cccDNA. Finally, hepatitis B viral X protein could relieve SIRT3-mediated cccDNA transcriptional repression by inhibiting both SIRT3 expression and its recruitment to cccDNA. CONCLUSION: SIRT3 is a host factor epigenetically restricting HBV cccDNA transcription by acting cooperatively with histone methyltransferase; these data provide a rationale for the use of SIRT3 activators in the prevention or treatment of HBV infection. (Hepatology 2018).

Modeling and Optimum Extraction of Multiple Bioactive Exopolysaccharide from an Endophytic Fungus of Crocus sativus L.

BACKGROUND: Crocus sativus L. (saffron) is a scarce plant that has been used as food flavoring agent, coloring agent, and traditional herbal medicine. METHODS: The bioactivity of exopolysaccharide (EPS) extracted from an endophytic fungus of C. sativus was examined for the first time by antioxidative, antitumor, and antibacterial assays. The extraction conditions for EPS were optimized by combining the response surface methodology with Box-Behnken design. RESULTS: EPS exhibited excellent scavenging activities against 1,1-diphenyl-2-picrylhydrazyl, hydroxyl and superoxide anion radicals, and moderate cytotoxicities against K562, A549, HL-60, and HeLa cells. The optimum extraction conditions for EPS were as follows: precipitation time of 16 h, precipitation temperature of 3.7°C, pH 7.2, and ratio of ethanol to fermented broth of 5:1 (L/L). Under the optimized conditions, the yield of EPS reached 162 ± 6 µg/L which was close to the predicted one (165 µg/L). Moreover, high-performance liquid chromatography of monosaccharide composition showed that EPS comprised mannose, glucose, galactose xylose, and arabinose in a molar ratio of 25.6:16.5:1.0:3.8:5.4. CONCLUSION: EPS may be an eligible substitute for C. sativus and a potential bioactive source applicable to pharmaceutical and food industries. SUMMARY: Exopolysaccharide (EPS) from endophytic fungus of Crocus sativus was studied for the first timeEPS extraction was optimized by combining response surface methodology with Box-Behnken designMonosaccharide composition and EPS structure were identified by high-performance liquid chromatography and Fourier-transform infrared spectroscopy. Abbreviations used: EPS: Exopolysaccharide, RSM: Response surface methodology, BBD: Box-Behnken design, DPPH: 1,1-diphenyl-2-picrylhydrazyl, VC: Ascorbic acid, MTT: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, LB: Luria Bertani, DMSO: dimethyl sulfoxide, PMP: 1-phenyl-3-methyl-5-pyrazolone, FT-IR: Fourier transform-infrared, HPLC: High-performance liquid chromatography, 3D: Three-dimensional, 2D: Two-Dimensional.

Effect of acupoint catgut embedding, fire needle, auricular acupuncture on female post-adolescent acne and serum sex hormone / 中国针灸

<p><b>OBJECTIVE</b>To compare the difference of serum sex hormone between female patients with post-adolescent acne and healthy women, and to explore the efficacy and action mechanism of acupoint catgut embedding, fire needle, auricular acupuncture on skin lesion in female patients of post-adolescent acne.</p><p><b>METHODS</b>A total of 107 female patients of post-adolescent acne were divided into an integrated acupuncture group (54 cases, 4 cases were excluded) and a medication group (53 cases, 5 cases were excluded). The patients in the integrated acupuncture group were treated with comprehensive treatment of acupoint catgut embedding, fire needle, auricular acupuncture; the acupoint catgut embedding was applied at Dazhui (GV 14), Yintang (GV 29), Yangbai (GB 14) through Yuyao (EX-HN 4) and other acupoints based on syndrome differentiation; the fire needle was applied at skin lesion; the auricular acupuncture was applied at erjian (HX), e (AT), kou (CO), etc. The patients in the medication group were treated with oral administration of tanshinone capsules (4 capsules each time, 3 times a day) and external use of adapalene gel (one treatment per day at night). Patients in the two groups were treated for 8 weeks. The skin lesion of acne was evaluated before treatment as well as 4 weeks and 8 weeks after treatment in the two groups; the serum levels of testosterone (T) and estradiol (E) were tested 24 hours before menstruation in the integrated acupuncture group (50 cases) and healthy control group (46 cases), and the change of serum sex hormone after treatment was observed in 21 patients with sex hormone disorder in the integrated acupuncture group.</p><p><b>RESULTS</b>Before treatment, the level of E in the integrated acupuncture group was significantly lower than that in the healthy control group (<0.01), but T/E in the integrated acupuncture group was significantly higher than that in the healthy control group (<0.01). After treatment, the level of E was significantly increased (<0.01) and T/E was reduced (<0.01) in the 21 patients with sex hormone disorder in the integrated acupuncture group. The skin lesion scale of acne was significantly reduced in the two groups after 4-week and 8-week treatment (all <0.01); the difference between the two groups was not significant after 4-week treatment (>0.05); the skin lesion scale of acne in the integrated acupuncture group was significantly lower than that in the medication group after 8-week treatment (<0.01). The efficacy between the two groups was not significant after 4-week the treatment (>0.05); after 8-week treatment, the cured and effective rate was 66.0% (33/50) in the integrated acupuncture group, which was superior to 45.8% (22/48) in the medication group (<0.05).</p><p><b>CONCLUSION</b>Compared with healthy women, the level of serum sex hormone of E is reduced in the female patients of post-adolescent acne, resulting in relative increased level of T; the acupoint catgut embedding, fire needle, auricular acupuncture have better efficacy than medication for post-adolescent acne, which have regulation effects on sex hormone disorder.</p>

Huotan Jiedu Tongluo decoction alleviates early atherosclerosis of rabbits by inhibiting eNOS uncoupling pathway / 中国中药杂志

The aim of this paper was to study the curative effect of Huotan Jiedu Tongluo (HTJDTL) decoction on a rabbit model with early atherosclerosis (AS),and furtherly to explore whether it could inhibit the BH4/eNOS uncoupling ROS or not. Twenty-four Japanese white rabbits were randomly divided into sham operation group, model group, HTJDTL decoction group and atorvastatin group. Rabbit models with early atherosclerosis were established by high fat diet, nitrogen drying and carotid artery balloon injury. The rabbits were sacrificed at 7th days after balloon injury and several parameters were measured. The pathological morphology of the common carotid artery was observed by HE staining. The blood lipids were detected by peroxidase method. The ratio of vascular eNOS dimer and monomer was measured by Western blot. The ELISA and biochemical technology were respectively used for testing BH4 and ROS levels in serum. The results showed that compared with the sham operation group, the model group had mild stenosis of the common carotid artery lumen, uneven intimal hyperplasia, lipid deposition in the intima and media, and obvious hyperplasia of the adventitia with inflammatory cell infiltration. The HTJDTL decoction could significantly inhibit the intimal hyperplasia compared with the model group, meanwhile, reduce the lipid deposition of the media and the infiltration of the adventitial cells. Compared with the sham operation group, the blood lipids and ROS of the model animals significantly increased, but BH4 and the ratio of eNOS dimer/monomer decreased. Compared with the model group, HTJDTL decoction significantly reduced the TC, ox-LDL and ROS levels, and also up-regulated eNOS dimer/monomer ratio, but it increased BH4 trend without statistical difference. According to the results, it was found that HTJDTL decoction couldsignificantly prevent and improve the vascular remodeling of rabbits model with early atherosclerosis. The mechanism of decoction may largely be related to the inhibition of BH4/eNOS uncoupling and the reduction of oxidative stress.

Rescue vitrectomy with blocked artery massage and bloodletting for branch retinal artery occlusion.

A 61-year-old male suffered from sudden blurred vision and superior visual field defect oculus dexter. His vision was counting fingers at 20 cm. Fundoscopy demonstrated inferior pale retina and a large embolus located at the proximal inferior retinal artery. Branch retinal artery occlusion (BRAO) was diagnosed. Initial paracentesis, topical brimonidine tartrate, oral pentoxifylline, and hyperbaric oxygen therapy were performed but showed limited improvement. Hence, he received 25-gauge vitrectomy, artificial posterior vitreous detachment, blocked retinal artery massage, and bloodletting 5 days after onset. After the surgery, his vision improved to 20/25. Fundoscopy showed reperfused retina, and optical coherence tomography revealed resolved retinal edema. RAO is an ophthalmological emergency; however, no standard guideline is available. Vitrectomy with blocked retinal artery massage and bloodletting showed favorable results in this case of BRAO with a large embolus. More prospective clinical trials are needed for setting up the standard treatment.