Yishen Huatan Huoxue decoction and quercetin ameliorate decidualization dysfunction in polycystic ovary syndrome: A comprehensive investigation combining clinical trial and experimental studies.

Polycystic ovary syndrome (PCOS) is a common gynecological endocrine disorder characterized by a complex pathogenesis and limited treatment options. Yishen Huatan and Huoxue decoction (YHHD), as a traditional Chinese Medicine formula, has shown effectiveness in treating PCOS. However, the specific mechanisms by which YHHD exerts its therapeutic effects remain unclear. In this study, we performed to investigate the therapeutic effects of YHHD and quercetin on dehydroepiandrosterone-induced PCOS mice, and examine the effect of quercetin on the decidualization of T-HESCs under hyperinsulinemic conditions. The results showed that YHHD could reduce early miscarriage rates in PCOS patients and significantly improved glucose metabolism disorders, sex hormone levels, and the estrous cycles in PCOS mice. Quercetin could alleviate effect of high insulin levels and restore the low expression of insulin receptor substrate1/2 (IRS1/2) and glucose transporte 4 (GLUT4) in T-HESCs, demonstrating its potential to mitigate hyperinsulin-induced decidualization dysfunction via the GLUT4 signaling pathway mediated by IRS1/2. This study provides valuable molecular insights of YHHD and highlight the therapeutic potential of quercetin in treating decidualization dysfunction in PCOS.

Effect of Chinese patent medicine Kunling Pill on endometrial receptivity: A clinical trial, network pharmacology, and animal-based study.

Although pregnancy success rates are raised with assisted reproductive technology, it still cannot meet clinical demands. Kunling Pill (KLP), a traditional Chinese medicine, is widely used in various gynecological disorders, particularly in improving fertility and pregnancy rates. However, the underlying mechanism of how KLP affects pregnancy outcomes remains unclear. This study aimed to explore the effects and mechanisms of KLP on endometrial receptivity. Firstly, a retrospective trial was conducted to validate the efficacy of KLP on repeated implantation failure (RIF) patients. The result indicated a significant increase in the proportion of live birth in KLP group (30.56%) compared to the control group (16.89%). Secondly, network pharmacology methods predicted the active components and network targets of KLP. Endometrial receptivity is closely associated with the activation of inflammatory factors, predicting the function of KLP on the immune system. The estrogen and apoptotic signaling pathways were also highlighted in the gene ontology enrichment analysis. Thirdly, a decreased endometrial receptivity model was established by controlled ovarian hyperstimulation (COH) in female C57BL/6 mice, divided into the COH and KLP groups. Normal female mice are as control group. In vivo, KLP administration could increase endometrial thickness and the number of endometrial glands and pinopodes. In the endometrium, KLP supplementation upregulated the expressions of estrogen receptor α, progesterone receptor, endothelial nitric oxide synthase, and integrin αVß3 in the murine uterus and reduced serum levels of estrogen and progesterone. KLP regulated the uterine immune cells and inhibited cell apoptosis in the ovary via Bcl-2/Bax/caspase-3 pathway. In conclusion, KLP administration raised the live birth rate in RIF patients to optimize medication regimens, mainly because KLP ameliorated impaired endometrial receptivity.

The therapeutic effect of wasp venom (Vespa magnifica, Smith) and its effective part on rheumatoid arthritis fibroblast-like synoviocytes through modulating inflammation, redox homeostasis and ferroptosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Rheumatoid arthritis (RA) is a chronic inflammatory disease that is related to the aberrant proliferation of fibroblast-like synoviocytes (FLS). Wasp venom (WV, Vespa magnifica, Smith), an insect secretion, has been used to treat RA in Chinese Jingpo national minority's ancient prescription. However, the potential mechanisms haven't been clarified. AIM OF THE STUDY: The purposes of this paper were two-fold. First, to investigate which was the best anti-RA effective part of WV-I (molecular weight less than 3 kDa), WV-II (molecular weight 3-10 kDa) and WV-III (molecular weight more than 10 kDa) that were separated from WV. Second, to explore the underlying molecular mechanism of WV and WV-II that was best effective part in RA. MATERIALS AND METHODS: The wasps were electrically stimulated and the secretions were collected. WV-I, WV-II and WV-III were acquired by ultracentrifuge method according to molecular weight. Next, WV, WV-I, WV-II and WV-III were identified by HPLC. Functional annotation and pathway analysis of WV used to bioinformatics analysis. RNA-seq analyses were constructed to identify differentially expressed genes (DEGs). GO and KEGG pathway analyses were performed by Metascape database. STRING was used to analyze the PPI network from DEGs. Next, PPI network was visualized using Cytoscape that based on MCODE. The pivotal genes of PPI network and MCODE analysis were verified by qRT-PCR. Subsequently, MH7A cells were performed by MTT assay to evaluate the ability of inhibiting cell proliferation. Luciferase activity assay was conducted in HepG2/STAT1 or HepG2/STAT3 cells to assess STAT1/3 sensitivity of WV, WV-I, WV-II and WV-III. Additionally, interleukin (IL)-1ß and IL-6 expression levels were detected by ELISA kits. Intracellular thioredoxin reductase (TrxR) enzyme was evaluated by TrxR activity assay kit. ROS levels, lipid ROS levels and Mitochondrial membrane potential (MMP) were assessed by fluorescence probe. Cell apoptosis and MMP were measured by using flow cytometry. Furthermore, the key proteins of JAK/STAT signaling pathway, protein levels of TrxR and glutathione peroxidase 4 axis (GPX4) were examined by Western blotting assay. RESULTS: RNA-sequencing analysis of WV displayed be related to oxidation-reduction, inflammation and apoptosis. The data displayed that WV, WV-II and WV-III inhibited significantly cells proliferation in human MH7A cell line compared to WV-I treatment group, but WV-III had no significant suppressive effect on luciferase activity of STAT3 compared with IL-6-induced group. Combined with earlier reports that WV-III contained major allergens, we selected WV and WV-II further to study the mechanism of anti-RA. In addition, WV and WV-II decreased the level of IL-1ß and IL-6 in TNF-α-induced MH7A cells via inactivating of JAK/STAT signaling pathway. On the other hand, WV and WV-II down-regulated the TrxR activity to produce ROS and induce cell apoptosis. Furthermore, WV and WV-II could accumulate lipid ROS to induce GPX4-mediated ferroptosis. CONCLUSIONS: Taken together, the experimental results revealed that WV and WV-II were potential therapeutic agents for RA through modulating JAK/STAT signaling pathways, redox homeostasis and ferroptosis in MH7A cells. Of note, WV-II was an effective part and the predominant active monomer in WV-II will be further explored in the future.

Possible Involvement of Perineuronal Nets in Anti-Depressant Effects of Electroacupuncture in Chronic-Stress-Induced Depression in Rats.

Acupuncture can alleviate depression-like behaviors. However, the neural mechanisms behind the anti-depressive effect remain unknown. Perineuronal net (PNN) abnormalities have been reported in multiple psychiatric disorders. This study investigated the modulation and neural mechanism of PNNs in the anti-depressant process of electroacupuncture (EA) at Baihui (GV20) and Yintang (GV29) points. A rat depression model was induced by chronic unpredicted mild stress (CUMS). The results revealed that CUMS, applied for four weeks, specifically reduces PNNs around parvalbumin (PV). In addition, EA and fluoxetine treatments reverse the decrease in PNNs+ cell density and the ratio of PV and PNN double-positive cells to PV+ neurons in the medial prefrontal cortex (mPFC) after CUMS. Furthermore, EA treatment can reverse the decrease in the protein expression of PNN components (aggrecan and brevican) in the mPFC caused by stress. After EA treatment, the decreased expression of GAD67, GLuA1, and PSD95 in the mPFC induced by CUMS for four weeks was also reversed. PNN degradation in mPFC brain areas potentially interferes with the anti-depressant benefits of EA in rats with depression induced by CUMS. EA treatment did not increase PNNs+ cell density and the ratio of PV and PNN double-positive cells to PV+ neurons after PNNs degradation in the mPFC brain region of rats. This finding indicated that the mechanism of acupuncture's anti-depressant effect may be based on reversing the CUMS-induced decline in PNN expression, the functional impairment of γ-aminobutyric acid (GABA) neurons, and the regulation of excitatory synaptic proteins expression.

NIR-Activated Thermosensitive Liposome-Gold Nanorod Hybrids for Enhanced Drug Delivery and Stimulus Sensitivity.

Combinatorial photothermal therapy and chemotherapy is an extremely promising tumor therapeutic modality. However, such systems still remain challenges in stimulus sensitivity, avoiding drug leakage, and therapeutic safety. To solve these problems, we engineered actively loaded doxorubicin (DOX) and gold nanorod (GNR) liposomes through embedding stiff hollow mesoporous silica nanoparticles (HMSNs) in the liposomal water cavity (HMLGDB) to resist the influence of shear force of GNRs to prevent drug leakage. Under 808 nm laser irradiation, the ambient temperature was raised greatly because of the photothermal conversion of GNRs, thereby rupturing the lipid layer and then triggering the DOX release. The results of in vitro experiments showed that the low concentration of HMLGDB (15 µg/mL) could effectively overcome the MCF-7 cells (human breast cancer cell line) by the increase of DOX concentration intracellularly and the good photothermal effect of GNRs. After intravenous injection, HMLGDB exhibited intratumor aggregation and PTT capacity. Furthermore, the combined chemo-photothermal antitumor strategy demonstrated a high inhibition of tumor growth and low damage to normal tissues. The developed hybrids provide a paradigm for efficient combinatorial photothermal therapy (PTT) and chemotherapy (CT).

The effect of a traditional Chinese quadri-combination therapy and its component quercetin on recurrent spontaneous abortion: A clinical trial, network pharmacology and experiments-based study.

Objective: To explore the effect and mechanisms of a traditional Chinese quadri-combination therapy [Bushen, Yiqi, Lixue and Yangtai (BYLY)] in treating recurrent spontaneous abortion (RSA). Methods: A clinical trial was conducted to study the effect of BYLY on RSA. Pharmacological network analysis and UPLC-Q/TOF-mass spectrometry (MS) were applied to investigate the key active component in BYLY and potential targets. Cellular experiments based on former results were performed to examine the mechanism of BYLY in the treatment of RSA. Results: Four hundred and eighty participants enrolled in the clinical trial. The results showed that, compared with the use of BYLY or duphaston alone, a combination of duphaston and BYLY could decrease the early abortion rate in RSA (p < 0.001). Network pharmacological analysis indicated that BYLY contained 132 active components and 146 core targets, and the quercetin maybe the key effective component. In vitro experiments found that pretreatment of quercetin at the correct concentration (2 µM) prevented hypoxia-induced viability and proliferation reduction, and apoptosis and mitochondrial dysfunction. Furthermore, quercetin could modulate mitochondrial fission/fusion balance in trophoblasts, and specifically decrease the expression of Drp1 by regulating miR-34a-5p. Conclusion: BYLY could improve pregnancy outcomes of RSA, based on multi-components and multi-targets. The protective effect of quercetin on trophoblasts, through decreasing Drp1 expression via regulating miR-34a-5p, might be one possible effective mechanism.

Chemical Fingerprint Analysis and Quantitative Analysis of Saccharides in Morindae Officinalis Radix by HPLC-ELSD.

A method based on high performance liquid chromatography with evaporative light scattering detection (HPLC-ELSD) was developed for the quantitative analysis of three active compounds and chemical fingerprint analyses of saccharides in Morindae officinalis radix. Ten batches of Morindae officinalis radix were collected from different plantations in the Guangdong region of China and used to establish the fingerprint. The samples were separated with a COSMOIL Sugar-D column (4.6 mm × 250 mm, 5 µm) by using gradient elution with water (A) and acetonitrile (B). In addition, Trapped-Ion-Mobility (tims) Time-Of-Flight (tims TOF) was used to identify saccharides of Morindae officinalis radix. Fingerprint chromatogram presented 26 common characteristic peaks in the roots of Morinda officinalis How, and the similarities were more than 0.926. In quantitative analysis, the three compounds showed good regression (r = 0.9995-0.9998) within the test ranges, and the recoveries of the method were in the range of 96.7-101.7%. The contents of sucrose, kestose and nystose in all samples were determined as 1.21-7.92%, 1.02-3.37%, and 2.38-6.55%, respectively. The developed HPLC fingerprint method is reliable and was validated for the quality control and identification of Morindae officinalis radix and can be successfully used to assess the quality of Morindae officinalis radix.

Lentinan Combined with (125)I Brachytherapy for Recurrent Ovarian Cancer.

OBJECTIVE: To investigate the clinical value of lentinan combined with (125)I brachytherapy in the treatment of recurrent ovarian cancer. METHODS: A total of 160 patients with recurrent ovarian cancer admitted at Jiaozhou Central Hospital from June 2009 to October 2015 were enrolled in this study and randomly divided into observation group (80 cases) and control group (80 cases). The control group received chemotherapy. Observation group (80 cases) was treated with lentinan combined with (125)I brachytherapy on the basis of control group, and the efficacy, adverse reactions, and Karnofsky Performance Scale (KPS) and quality of life scale (QOL) scores of the two groups were analyzed and compared. RESULTS: After treatment, the levels of CA125, CA199, and CA724 in the 2 groups were markedly lower than those before treatment, and the observation group was lower than the control group (P < 0.05). After treatment, the proportion of CD4+/CD8+ cells and helper T cells and NK cells in the control group remarkably depleted, while the proportion of CD4+/CD8+ cells, NK cells, and B cells in the observation group increased significantly compared to that before treatment, and the level of IgA, IgG, and IgM in the control group decreased, while that in the observation group showed no conspicuous difference compared with that before chemotherapy (P > 0.05). The effective rate of observation group (85%) was higher than that of control group (75%) (P < 0.05). The overall survival of patients in the control group was (16.2 ± 2.04) months and that of the observation group was (24.8 ± 1.8) months. KPS and QOL scores in both groups were enormously higher than those before treatment, and the observation group was higher than the control group (P < 0.05). The incidence of hemoglobin reduction, leukopenia, aglobulia, granulocytopenia, nausea and vomiting, hepatorenal toxicity, and neurovirulence in the observation group was significantly lower than that in the control group. CONCLUSION: Lentinan combined with (125)I brachytherapy is effective in treating recurrent ovarian cancer, with mild adverse reactions and good tolerance.

Effect of Traditional Chinese Medicine Combined with Bladder Perfusion with Hydroxycamptothecin on Color Ultrasound and Clinical Efficacy in Patients with Bladder Cancer Surgery.

OBJECTIVE: To observe the clinical effect of Xiaozheng Decoction combined with bladder perfusion with hydroxycamptothecin in the treatment of bladder cancer. METHODS: A total of 92 bladder cancer patients admitted to our hospital from January to December 2018 were selected and divided into an observation group and a control group according to the random number table method, with 46 cases in each group. The observation group was given Xiaozheng Decoction combined with bladder perfusion with hydroxycamptothecin, and the control group was given hydroxycamptothecin. The levels of serum-related factors (intercellular adhesion molecule-1 (ICAM-1), E-cadherin, cell adhesion molecules (CAM), fibroblast growth factor (FGF), and vascular endothelial growth factor (VEGF)), white blood cell (WBC) level, immune function indexes, short-term total response rate, and incidence of adverse reactions were compared between the two groups before and after treatment. RESULTS: After 2 years of postoperative treatment, the levels of ICAM-1, E-cadherin, CAM-1, FGF, and VEGF (a, b, c) in both groups were improved compared with those before treatment and the observation group was better than the control group (p < 0.01). The number of WBCs was significantly higher than in the control group after Traditional Chinese Medicine (TCM) treatment. The observation group was better than the control group in increasing CD3+ and CD4+ levels and decreasing CD8+ level (p < 0.05), indicating that this prescription could improve the immune function of patients. The recurrence rate in the observation group was 6.52% after 2 years of treatment, lower than 17.39% in the control group. Color ultrasound parameters showed that there were no statistically significant differences in arrive time (AT) and time to peak (TTP) between patients with and without recurrence and peak intensity (PI) and washout time (WT) were higher in patients with recurrence than in patients without recurrence (p < 0.01). The incidence of adverse reactions was significantly lower than that of the control group (p < 0.01). CONCLUSION: The clinical effect of Xiaozheng Decoction combined with hydroxycamptothecin on the treatment of bladder cancer was clear and superior to that of hydroxycamptothecin, which could effectively improve the serological indicators of patients with a low incidence of adverse reactions and prolong the survival cycle of patients. Therefore, it is worthy of promotion and application.

Chemical constituents with inhibition against TNF-α from Merrillanthus hainanensis.

Two new steroidal glycosides oxystauntoside A (1) and oxystauntoside B (2), together with sixteen known compounds (3-18) were isolated from the 95% ethanol extract of Merrillanthus hainanensis. Their structures were characterized by extensive spectroscopic analysis including NMR and mass spectra and single crystal X-ray crystallography. The absolute configuration of 1 and 2 were further determined by ECD calculations. All of these compounds were isolated from M. hainanensis for the first time. All the fractions and compounds were tested for the anti-inflammatory activity against the TNF-α factor. The ethyl acetate fraction showed the most potent inhibition (71.3%) at 10 µg/mL and compounds 5 (78.9%) and 9 (73.4%) in this fraction with both carboxyl and phenolic hydroxyl groups showed significant inhibition at 10 µM. Our study provided the first scientific report for the medicinal value of M. hainanensis.

Electroacupuncture in treatment of Parkinson disease: A protocol for meta-analysis and systematic review.

BACKGROUND: Parkinson disease (PD) is a worldwide spread neurodegenerative disorder. Dopamine replacement therapy is currently the mainstream treatment, which can alleviate the symptoms but induces motor complications. Electroacupuncture (EA) is beneficial for PD as an alternative medicine. However, few reliable clinical trials or objective systematic reviews are available to give a verdict on the effectiveness of EA in the treatment of PD. Thus, we evaluate the evidence for EA in PD patients by conducting this meta-analysis. METHODS: PubMed, Cochrane Library, EMBASE, China National Knowledge Infrastructure, Chinese Scientific and Technology Journal database, WanFang Digital Periodicals, and Chinese Biomedical Literature Database (SinoMed) will be systematically searched for evidence by 2 authors individually. The analysis will be conducted by RevMan 5.3 software according to Cochrane Handbook. RESULTS: The efficacy and safety of EA for PD will be comprehensively assessed from the outcomes, including the effectiveness rate, scores of Unified Parkinson Disease Rating Scale, and Webster scale, superoxide dismutase, lipid peroxides, and dopamine content. CONCLUSION: This systematic review will provide evidence for whether EA can treatment PD. REGISTRATION INFORMATION: PROSPERO CRD42019120956.

Bu-Yin-Qian-Zheng Formula Ameliorates MPP+-Induced Mitochondrial Dysfunction in Parkinson's Disease via Parkin.

As a typical traditional Chinese medicine, Bu-Yin-Qian-Zheng Formula (BYQZF) has been shown to have neuroprotective effects in patients with Parkinson's disease (PD), particularly by ameliorating mitochondrial dysfunction and regulating expression of the parkin protein. However, the underlying mechanisms by which BYQZF affects mitochondrial function through parkin are unclear. Accordingly, in this study, we evaluated the mechanisms by which BYQZF ameliorates mitochondrial dysfunction through parkin in PD. We constructed a parkin-knockdown cell model and performed fluorescence microscopy to observe transfected SH-SY5Y cells. Quantitative real-time reverse transcription polymerase chain reaction and western blotting were conducted to detect the mRNA and protein expression levels of parkin. Additionally, we evaluated the cell survival rates, ATP levels, mitochondrial membrane potential (ΔΨm), mitochondrial morphology, parkin protein expression, PINK1 protein expression, and mitochondrial fusion and fission protein expression after treatment with MPP+ and BYQZF. Our results showed that cell survival rates, ATP levels, ΔΨm, mitochondrial morphology, parkin protein levels, PINK1 protein levels, and mitochondrial fusion protein levels were reduced after MPP+ treatment. In contrast, mitochondrial fission protein levels were increased after MPP+ treatment. Moreover, after transient transfection with a negative control plasmid, the above indices were significantly increased by BYQZF. However, there were no obvious differences in these indices after transient transfection with a parkin-knockdown plasmid. Our findings suggest that BYQZF has protective effects on mitochondrial function in MPP+-induced SH-SY5Y cells via parkin-dependent regulation of mitochondrial dynamics.

The targeting of non­coding RNAs by curcumin: Facts and hopes for cancer therapy (Review).

Curcumin [(1E,6E)­1,7­bis(4­hydroxy­3­-methoxyphenyl) hepta­1,6­diene­3,5­dione] is a natural polyphenol that is derived from the turmeric plant (curcuma longa L.). Curcumin is widely used in food coloring, preservatives, and condiments. Curcumin possesses anti­tumor, anti­oxidative and anti­inflammatory efficacy, as well as other pharmacological effects. Emerging evidence indicates that curcumin alters microRNAs (miRNAs) and long non­coding RNAs (lncRNAs) in various types of cancers. Both miRNAs and lncRNAs are non­coding RNAs that can epigenetically modulate the expression of multiple genes via post­transcriptional regulation. In the present review, the interactions between curcumin and non­coding RNAs are summarized in numerous types of cancers, including lung, colorectal, prostate, breast, nasopharyngeal, pancreatic, blood, and ovarian cancer, and the vital non­coding RNAs and their downstream targets are described.

[Cloning and expression analysis in resurrection process of trehalose-6-phosphate synthase gene from Selaginella tamariscina].

Selaginella tamariscina is a typical resuscitation medicinal plant with extreme drought tolerance. Trehalose plays an important role in the resurrection process, and the trehalose-6-phosphate synthase(TPS) is the key enzyme to synthesize trehalose in plants. In this study, the sequence of TPS was obtained by splicing from the transcriptome data of S. tamariscina. After the synthesis of cDNA based on the template of total RNA, the sequence was cloned by RT-PCR for verification and then analyzed by bioinformatics methods. The results indicated that the full-length coding sequence of StTPS was 2 799 bp (GenBank accession no. MH155231), and the encoded protein contained 932 amino acids. StTPS could be located in the chloroplastid according to subcellular localization prediction. There were two conserved domains belonging to glycogen phosphorylase glycosyltransferase (GPGTF) family but no signal peptide or transmembrane domain in StTPS. The expression of StTPS was determined by qRT-PCR and the variation of trehalose content was measured by HPLC-ELSD during the resurrection process of S. tamariscina. Meanwhile, the correlation between them was analyzed. The results showed that both the expression level of StTPS and the trehalose content increased associated with the extension of dehydration time, and declined associated with the extension of rehydration time which proved a significant positive correlation between the StTPS expression level and the trehalose content. The results suggested that the StTPS probably plays a central role in recovery process in S. tamariscina.

Structure Identification and In Vitro Anticancer Activity of Lathyrol-3-phenylacetate-5,15-diacetate.

Natural products from the genus Euphorbia show attention-attracting activities, such as anticancer activity. In this article, classical isolation and structure identification were used in a study on Caper Euphorbia Seed. Subsequently, MTT and wound healing assays, flow cytometry, western blotting, Hoechst 33258 staining and fluorescence microscopy examination were applied to investigate the anticancer activity of the obtained compounds. In a result, lathyrol-3-phenyl- acetate-5,15-diacetate (deoxy Euphorbia factor L1, DEFL1) was isolated from Caper Euphorbia Seed. Moreover, the NMR signals were totally assigned. DEFL1 showed potent inhibition against lung cancer A549 cells, with an IC50 value of 17.51 ± 0.85 µM. Furthermore, DEFL1 suppressed wound healing of A549 cells in a concentration-dependent manner. Mechanically, DEFL1 induced apoptosis, with involvement of an increase of reactive oxygen species (ROS), decrease of mitochondrial membrane potential (ΔΨm), release of cytochrome c, activity raise of caspase-9 and 3. Characteristic features of apoptosis were observed by fluorescence microscopy. In summary, DEFL1 inhibited growth and induced apoptosis in lung cancer A549 cells via a mitochondrial pathway.

Food-advanced glycation end products aggravate the diabetic vascular complications via modulating the AGEs/RAGE pathway.

The aim of this study was to investigate the effects of high-advanced glycation end products (AGEs) diet on diabetic vascular complications. The Streptozocin (STZ)-induced diabetic mice were fed with high-AGEs diet. Diabetic characteristics, indicators of renal and cardiovascular functions, and pathohistology of pancreas, heart and renal were evaluated. AGEs/RAGE/ROS pathway parameters were determined. During the experiments, the diabetic mice exhibited typical characteristics including weight loss, polydipsia, polyphagia, polyuria, high-blood glucose, and low-serum insulin levels. However, high-AGEs diet effectively aggravated these diabetic characteristics. It also increased the 24-h urine protein levels, serum levels of urea nitrogen, creatinine, c-reactive protein (CRP), low density lipoprotein (LDL), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) in the diabetic mice. High-AGEs diet deteriorated the histology of pancreas, heart, and kidneys, and caused structural alterations of endothelial cells, mesangial cells and podocytes in renal cortex. Eventually, high-AGEs diet contributed to the high-AGE levels in serum and kidneys, high-levels of reactive oxygen species (ROS) and low-levels of superoxide dismutase (SOD) in serum, heart, and kidneys. It also upregulated RAGE mRNA and protein expression in heart and kidneys. Our results showed that high-AGEs diet deteriorated vascular complications in the diabetic mice. The activation of AGEs/RAGE/ROS pathway may be involved in the pathogenesis of vascular complications in diabetes.

[Effect of Small Knife Needle on ß-enorpin and Enkehalin Contents of Tansverse Process Syndrome of the Third Vertebra].

OBJECTIVE: To explore the analgesic mechanism of small knife needle for treating transverse process syndrome of the third vertebra (TPSTV) by observing peripheral and central changesof ß-endorphin (ß-EP) and enkephalin (ENK) contents. METHODS: Totally 30 Japanese white big-ear rabbits of clean grade were divided into 5 groups according to random digit table, i.e., the normal control group, the model group, the small knife needle group, the electroacupunture (EA) group, and the small knife needle plus EA group, 6 in each group. The TPSTV model was established by inserting a piece of gelatin sponge into the left transverse process of 3rd lumbar vertebrae. Rabbits in the small knife needlegroup were intervened by small knife needle. Those in the EA group were intervened by EA at bilateralWeizhong (BL40). Those in the small knife needle plus EA group were intervened by small knife needleand EA at bilateral Weizhong (BL40). Contents of ß-EP and ENK in plasma, muscle, spinal cord, and hypothalamus were determined after sample collection at day 28 after modeling. RESULTS: Compared with the normal control group, contents of ß-EP and ENK in plasma and muscle increased significantly, and contents of ß-EP and ENK in spinal cord and hypothalamus decreased significantly in the model group (P < 0.05, P < 0.01). Contents of ß-EP and ENK approximated normal levels in the three treatment groups after respective treatment. Compared with the model group, the content of ß-EP in muscle decreased, and contents of ß-EP and ENK in hypothalamus increased in the three treatment groups after respective treatment (P < 0.05). There were no significant difference among the three treatment groups (P > 0.05). CONCLUSIONS: Small knife needle treatment and EA had benign regulation on peripheral and central ß-EP and ENK in TPSTV rabbits. Small knife needle treatment showed better effect than that of EA.

Somatic embryogenesis and direct as well as indirect organogenesis in Lilium pumilum DC. Fisch., an endangered ornamental and medicinal plant.

Somatic embryogenesis and organogenesis in Lilium pumilum were successfully regulated by picloram, α-naphthaleneacetic acid (NAA), and 6-benzyladenine (BA). In organogenesis, the highest shoot regeneration frequency (92.5%) was obtained directly from bulb scales on Murashige and Skoog (MS) medium containing 2.0 mg L(-1) BA and 0.2 mg L(-1) NAA, while organogenic callus (OC) formed from leaves on MS medium supplemented with 1.0 mg L(-1) BA and 0.5 mg L(-1) NAA. Following subculture, 76.7% of OC regenerated shoots. In somatic embryogenesis, the combination of picloram and NAA increased the amount of embryogenic callus (EC) that formed with a maximum on 90.7% of all explants which formed 11 somatic embryos (SEs) per explant. Differences between EC and OC in cellular morphology and cell differentiation fate were easily observed. SEs initially formed via an exogenous or an endogenous origin. The appearance of a protoderm in heart-shaped SE and the bipolar shoot-root development in oval-shaped SE indicated true somatic embryogenesis. This protocol provides a new and detailed regulation and histological examination of regeneration pattern in L. pumilum.

Protective effects of DJ-1 medicated Akt phosphorylation on mitochondrial function are promoted by Da-Bu-Yin-Wan in 1-methyl-4-phenylpyridinium-treated human neuroblastoma SH-SY5Y cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Da-Bu-Yin-Wan (DBYW), a historically traditional Chinese medicine formula, was originally defined over 600 years ago. In recent decades, DBYW was clinically employed to treat Parkinson's disease (PD). AIM OF THE STUDY: To explore the underlying mechanism of DBYW on mitochondrial function, we investigated the effect of DBYW on mitochondrial function from the perspectives of DJ-1 and Akt signaling. MATERIALS AND METHODS: Human derived neuroblastoma SH-SY5Y cells were transiently transfected with the plasmid pcDNA3-Flag-DJ-1 aimed to overexpress the DJ-1 protein. Transfected cells were treated with 1-methyl-4-phenylpyridinium (MPP(+)), a PD-related mitochondrial complex I inhibitor, in the absence and presence of DBYW. The cell viability was assessed by Cell Counting Kit-8 assay. The protein expressions of DJ-1 and Akt signaling were examined by western blotting. The mitochondrial mass was evaluated by confocal fluorescence microscopy. The mitochondrial complex I activity and cellular ATP content were measured by commercial kits. RESULTS: Transfection with pcDNA3-Flag-DJ-1 decreased the MPP(+)-induced toxicity and overexpressed the DJ-1. In DJ-1 overexpressed cells, the mitochondrial mass was raised, mitochondrial complex I activity was improved, and cellular ATP content was increased. In addition, overexpression of DJ-1 augmented the Akt phosphorylation on threonine 308 and serine 473. Moreover, DBYW promoted the above effects in DJ-1 expressed cells. CONCLUSIONS: These data suggest that DJ-1 protects the mitochondrial function by medicating Akt phosphorylation in MPP(+)-treated SH-SY5Y cells. Moreover, DBYW enhances the protective effect of DJ-1 medicated Akt phosphorylation on mitochondrial function.

Systematic review of traditional chinese medicine for depression in Parkinson's disease.

Depression is the most common non-motor symptom of Parkinson's disease (PD). Recent clinical trials have evaluated the effectiveness of traditional Chinese medicine (TCM) in the treatment of depression in PD (dPD). However, the results are conflicting rather than conclusive. To investigate the effectiveness of TCM for the treatment of dPD, a systematic review was conducted. Literature searches and collections were performed to identify studies addressing the treatment of TCM for dPD. The methodological quality and risk of bias in all studies included were evaluated. Weighted mean difference (WMD) with 95% confidence interval (CI) was used as the effect measure. Finally, a total of 10 studies involving 582 patients were identified. The pooled results revealed that TCM combined with conventional drugs significantly improved the total scores of the unified Parkinson's disease rating scale (WMD = -7.35, 95% CI: -11.24 to -3.47) and the score of the Hamilton rating scale for depression (HAM-D) (WMD = -4.19, 95% CI: -5.14 to -3.24) compared with conventional drug, respectively. Conclusively, there is evidence that TCM may be beneficial to the treatment of dPD in spite of the methodological weakness of the included studies.