Exploring the effect of photobiomodulation and gamma visual stimulation induced by 808 nm and visible LED in Alzheimer's disease mouse model.

Although photobiomodulation (PBM) and gamma visual stimulatqion (GVS) have been overwhelmingly explored in the recent time as a possible light stimulation (LS) means of Alzheimer's disease (AD) therapy, their effects have not been assessed at once. In our research, the AD mouse model was stimulated using light with various parameters [continuous wave (PBM) or 40 Hz pulsed visible LED (GVS) or 40 Hz pulsed 808 nm LED (PBM and GVS treatment)]]. The brain slices collected from the LS treated AD model mice were evaluated using (i) fluorescence microscopy to image thioflavine-S labeled amy-loid-ß (Aß) plaques (the main hallmark of AD), or (ii) two-photon excited fluorescence (TPEF) imaging of unlabeled Aß plaques, showing that the amount of Aß plaques was reduced after LS treatment. The imaging results correlated well with the results of Morris water maze (MWM) test, which demonstrated that the spatial learning and memory abilities of LS treated mice were noticeably higher than those of untreated mice. The LS effect was also assessed by in vivo nonlinear optical imaging, revealing that the cerebral amyloid angiopathy decreased spe-cifically as a result of 40 Hz pulsed 808 nm irradiation, on the contrary, the angiopathy reversed after visible 40 Hz pulsed light treatment. The obtained results provide useful reference for further optimization of the LS (PBM or GVS) parameters to achieve efficient phototherapy of AD.

The Pharmacological Activity of the Wenjing Decoction in Recurrent Spontaneous Abortion.

BACKGROUND: Recurrent spontaneous abortion (RSA) is intractable infertility and can be ameliorated with the use of traditional Chinese medicine preparation, the Wenjing decoction. This study aimed to identify the therapeutic mechanism of Wenjing decoction on specific target proteins involved in RSA. METHODS: Wenjing decoction contains Wuzhuyu, Danggui, Chuanxiong, Guizhi, Shengjiang, Banxia, Gancao, Ejiao, Mudanpi, Chishao, Dangshen, and Maidong. Using TCMSP and BATMAN databases, we queried for active ingredients and predicted their target proteins by BATMAN. Using the edgeR package, we analyzed the differentially expressed genes (DEGs) in the GSE121950 database between control samples and RSA (n = 3). The interaction between DEGs and the predicted target proteins was identified by the Venn diagram. Using the Cytoscape software and clusterProfiler package, enrichment analysis was conducted for the intersected target proteins. Additionally, the protein-protein interaction (PPI) network and pharmacological network were generated using the Cytoscape software. RESULTS: In total, 31, 2, 7, 7, 5, 13, 93, 11, 29, and 21 active ingredients were identified from Wuzhuyu, Danggui, Chuanxiong, Guizhi, Shengjiang, Banxia, Gancao, Mudanpi, Chishao, and Dangshen, respectively. Additionally, 100 intersected target proteins were revealed by the Venn diagram. Moreover, 98 functional terms and 24 pathways (including C-type lectin receptor signaling pathway, chemokine signaling pathway, leukocyte transendothelial migration, fluid shear stress, and atherosclerosis, and AGE-RAGE signaling pathway in diabetic complications) were enriched. In the PPI network, 10 proteins involved in these five pathways were identified, namely, TNF-α (tumor necrosis factor-α), IL-10 (interleukin-10), TLR4 (Toll-like receptor 4), JUN (Jun proto-oncogene), IL-1B (interleukin-1-beta), CYBB (cytochrome b558 heavy chain gene), PTGS2 (prostaglandin-endoperoxide synthase 2), APOE (apolipoprotein E), SPI1 (salmonella pathogenicity island 1), and MPO (myeloperoxidase) which showed higher degrees. CONCLUSION: The abovementioned genes and pathways might be involved in the pharmacological activity of Wenjing decoction in RSA.

Research on the Potential Mechanism of Gentiopicroside Against Gastric Cancer Based on Network Pharmacology.

BACKGROUND: Gastric cancer was still one of the commonly diagnosed cancer types and the third-most common cause of cancer-related death in the world. Gentiopicroside, which is extracted from the Gentianella acuta, is commonly used in both traditional treatment and modern clinical care; therefore, its anticancer effects have been attracted more attention. However, the systematic analysis of action mechanism of Gentiopicroside on gastric cancer (GC) has not yet been carried out. AIM: A network pharmacology-based strategy combined with molecular docking studies and in vitro validation was employed to investigate potential targets and molecular mechanism of Gentiopicroside against GC. MATERIALS AND METHODS: Potential targets of Gentiopicroside, as well as related genes of GC, were acquired from public databases. Potential targets, and signaling pathways were determined through bioinformatic analysis, including protein-protein interaction (PPI), the Gene Ontology (GO), and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Subsequently, molecular docking and cell experiments were performed to further verify the above findings. RESULTS: Our findings revealed that the anticancer activity of Gentiopicroside potentially involves 53 putative identified target genes. In addition, GO, KEGG, and network analyses revealed that these targets were associated with cell proliferation, metabolic process, and other physiological processes. Furthermore, we have proved that critical compound affected the expression of CCND1, CCNE1, p-AKT and p-P38 at protein levels. These findings provide an overview of the anticancer action of Gentiopicroside from a network perspective; meanwhile, it might also set an example for future studies of other materials used in traditional Chinese medicine (TCM). CONCLUSION: This study comprehensively illuminated the potential targets and molecular mechanism of Gentiopicroside against GC. It also provided a promising approach to uncover the scientific basis and therapeutic mechanism of TCM treating for disease.

Pin1 Is Regulated by CaMKII Activation in Glutamate-Induced Retinal Neuronal Regulated Necrosis.

In our previous study, we reported that peptidyl-prolyl isomerase 1 (Pin1)-modulated regulated necrosis (RN) occurred in cultured retinal neurons after glutamate injury. In the current study, we investigated the role of calcium/calmodulin-dependent protein kinase II (CaMKII) in Pin1-modulated RN in cultured rat retinal neurons, and in an animal in vivo model. We first demonstrated that glutamate might lead to calcium overloading mainly through ionotropic glutamate receptors activation. Furthermore, CaMKII activation induced by overloaded calcium leads to Pin1 activation and subsequent RN. Inactivation of CaMKII by KN-93 (KN, i.e., a specific CaMKII inhibitor) application can decrease the glutamate-induced retinal neuronal RN. Finally, by using an animal in vivo model, we also demonstrated the important role of CaMKII in glutamate-induced RN in rat retina. In addition, flash electroretinogram results provided evidence that the impaired visual function induced by glutamate can recover after CaMKII inhibition. In conclusion, CaMKII is an up-regulator of Pin1 and responsible for the RN induced by glutamate. This study provides further understanding of the regulatory pathway of RN and is a complementary mechanism for Pin1 activation mediated necrosis. This finding will provide a potential target to protect neurons from necrosis in neurodegenerative diseases, such as glaucoma, diabetic retinopathy, and even central nervous system diseases.

Effect of Banxia Xiexin decoction on Helicobacter pylori-related peptic ulcers and its possible mechanism via the TGF-ß/Smad signaling pathway.

OBJECTIVE: To investigate the effect of Banxia Xiexin decoction (BXD) on Helicobacter pylori (Hp)-related peptic ulcers (PUs) and the possible mechanism underlying BXD actions via the transforming growth factor-¦Â/small mothers against decapentaplegic (TGF-ß/Smad) signaling pathway. METHODS: PU patients with cold-heat complex syndrome were randomly assigned to groups that received Chinese or Western medicines with 20 patients in each group. Serum was collected after 7 d of treatment. The healthy group included 20 individuals. Gastric mucosal epithelial cell line GES-1 was cultured in vitro and randomly divided into the following seven groups: control, model, healthy, Western Medicine, prior treatment, low dosage, and high dosage. After 72 h of treatment with the corresponding serum, the mRNA and protein expression levels of TGF-ß1, Smad3, and Smad7 were measured by reverse transcription quantitative polymerase chain reaction and western blotting, respectively. RESULTS: The mRNA expression levels of TGF-ß1 and Smad3 in GES-1 cells were increased after Hp introduction, and these increased levels were reduced by the BXD-containing serum. The protein levels of p-Smad3, but not TGF-ß1 or Smad3, were significantly increased in Hp-treated GES-1 cells, and treatment with the BXD-containing serum markedly decreased the protein levels. Smad7 expression was significantly enhanced following treatment with the BXD-containing serum at transcriptional and protein levels in a dose-dependent manner. CONCLUSION: BXD regulates the TGF-ß/Smad signaling pathway by inhibiting the expression of TGF-ß1 and Smad3, and increasing the expression of Smad7.

Toosendanin suppresses oncogenic phenotypes of human gastric carcinoma SGC­7901 cells partly via miR­200a­mediated downregulation of ß-catenin pathway.

Aberrant activation of ß-catenin signaling due to low expression of miR­200a is found in gastric carcinoma (GC) tissues promoting GC evolution. Toosendanin (TSN) has exhibited antitumor effects on various human cancer cells, but its influence on GC is largely unidentified. The potential roles of TSN on GC cells were examined and it was found that TSN inhibited growth, migration, invasion and TGF­ß1-induced epithelial-mesenchymal transition (EMT) and induced cell cycle arrest and apoptosis in SGC­7901 cells which were most sensitive to TSN among various GC cell lines. TSN also inactivated ß-catenin pathway in SGC­7901 cells and the above effects were reversed following induction of ß-catenin overexpression. Moreover, TSN facilitated the level of miR­200a which targets ß-catenin and miR­200a silencing attenuated the antitumor effects of TSN on SGC­7901 cells. Nonetheless, knockdown of miR­200a did not relieve the suppressive effects of TSN on p­AKT, p­ERK and p­GSK3ß which were upstream regulators of ß-catenin. In addition, TSN administration inhibited growth and liver metastasis of orthotopically implanted SGC­7901 tumors in vivo through miR­200a­mediated ß-catenin pathway. Our data suggest that TSN may suppress oncogenic phenotypes of human GC cells partly via miR­200a/ß-catenin axis. Hence, TSN may have a promising chemotherapeutic activity for GC therapy.

Effects of terlipressin on microcirculation of small bowel mesentery in rats with endotoxic shock.

BACKGROUND: Septic shock is still related to unacceptably high morbidity and mortality. Microcirculatory alteration has been demonstrated to be one important reason associated with this evolution. Vasoactive drugs are often used to restore adequate arterial pressure and tissue perfusion in septic shock. To define the roles of different drugs, the effects of terlipressin (TP) on the microcirculation of small bowel mesentery in rats with endotoxic shock were evaluated and compared with those of norepinephrine (NE). METHODS: Twenty-five adult male Wistar rats were randomized to the control (n = 5), TP (n = 10), and NE (n = 10) groups. After endotoxic shock was induced by intravenous lipopolysaccharide administration for 30 min, rats in the NE and TP groups were infused with saline 5 mL/kg/h and simultaneously given NE 4 µg/kg/min or TP 8 µg/kg/h. The mean arterial pressure, heart rate, blood gas analysis, and microvascular blood flow images of small bowel mesentery were recorded. RESULTS: After fluid resuscitation and vasopressor infusion, the mean arterial pressure was restored to the baseline values in the NE and TP groups. In the TP group, the heart rate was significantly lower compared with the NE group (P = 0.013). The proportion of perfused vessels and the microvascular flow index (MFI) were significantly increased; furthermore, the heterogeneity index of small vessels was markedly decreased in both the interventional groups with respect to the control group. Compared with the NE group, the MFI was significantly higher (P < 0.05) and the heterogeneity index was significantly lower (P < 0.05) in the TP group. CONCLUSIONS: Both TP and NE improved hemodynamic and microcirculatory alterations in rats with endotoxic shock. Compared with NE, TP was more effective in promoting MFI and improving the heterogeneity of small bowel mesentery in rats.

[Clinical study of combined treatment of remifemin and paroxetine for perimenopausal depression].

OBJECTIVE: To explore the efficacies and safety of combined treatment of remifemin and paroxetine for perimenopausal depression. METHODS: A total of 120 patients with perimenopausal depression were digital randomly divided into the treatment and control groups (n = 60 each). The treatment group received oral remifemin one tablet twice daily and paroxetine 20 mg once daily for 2 months while the control group oral paroxetine 20 mg once daily for 2 months. The Hamilton depression scale (HAMD) and Kupperman scale were used to assess the therapeutic efficacies. Blood and urine routine, electrocardiography, liver function, kidney function and blood pressure before and after treatment were examined to assess the side effects. RESULTS: For the improvement of perimenopausal depression on HAMD, the total effective rates of the treatment and control groups were 88.3% and 78.3% respectively. The therapeutic efficacy of the treatment group was significantly higher than that of the control group (P < 0.05). After 8-week treatment, Kupperman menopausal indices of the treatment and control groups were 9.89 ± 3.76 and 15.75 ± 5.84 respectively. There was also significant difference (P < 0.01). No significant changes existed in blood routine, urine routine, liver function, kidney function, blood pressure, ECG or blood pressure before and after treatment (P > 0.05). CONCLUSION: The combined treatment of remifemin and paroxetine for perimenopausal depression can improve the efficacies. It is easily accepted by patients for its higher safety and fewer side-effects. It is worthy of a wider application and further researches.

[Clinical observation on treatment of active rheumatoid arthritis with Chinese herbal medicine].

OBJECTIVE: To study the efficacy and safety of Chinese drugs for expelling evil-wind, removing dampness, promoting blood circulation and invigorating yin in treating active rheumatoid arthritis (RA). METHODS: Sixty-seven patients with active RA were randomized into 3 groups, the Group A, B and C. They were made coequal in terms of age, sex and condition of disease and treated respectively with basic treatment (non-steroid anti-inflammation drug combined with immune inhibitor) only, basic treatment + small dose prednisone, and basic treatment + Chinese herbal medicine, all for 8 weeks. The efficacy and adverse effects of treatment were analyzed by scoring. RESULTS: The total effective rate was 20.0% (4/20) in Group A, 810% (17/21) in Group B and 85.7% (18/21) in Group C, the latter two were superior to the former one (P <0.01). Before treatment, comparison of disease activity score (DAS) among the three groups showed no significant difference (P > 0.05). After treatment, improvements of Ritchie arthritis index (RAI), number of swollen joint, erythrocyte sedimentation rate (ESR), general health (GH), and DAS were shown in Group B and C (P <0.05), while in Group A, improvement was only shown in GH (P <0.05). The difference of DAS between pre- and post-treatment was 0.25 +/- 0.77 in Group A, 0.87 +/- 0.60 in Group B and 0.92 +/- 0.59 in Group C, showing statistical significance between Group A vs B and A vs C (P = 0.0000). The total accumulative score of adverse reaction was 3.76 +/- 2.72 in Group C, 9.10 +/- 6.01 in Group A and 14.38 +/- 9.36 in Group B, also showing statistical significance among groups (P < 0.05). CONCLUSION: The combination of Chinese and Western medicine for active RA is effective and safe.

[Study on relationship between TCM Syndrome types (Xin-qi and Xin-yang deficiency) and contents of cytokines (tumor necrosis factor-alpha and interleukins) in patients with congestive heart failure].

OBJECTIVE: To explore the relationship between TCM Syndromes types, Xin-qi deficiency (XQD) and Xin-yang deficiency (XYD), and contents of cytokines, including tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6), IL-1beta and IL-10 in patients with congestive heart failure (CHF). METHODS: Sixty-seven CHF in-patients with Xin-qi deficiency or Xin-yang deficiency syndrome were enrolled, their NYHA (New York Heart Association) cardiac function was assessed, ejection fraction (EF) and E peak/A peak (E/A) ratio were determined by Doppler ultrasonic echocardiograph, and serum TNF-alpha, II-6, IL-1beta and IL-10 were measured by double antibody sandwich ELISA assay. RESULTS: The cardiac function grading in patients of XQD was mostly of I and II grade, while that in patients of XYD was mostly of III and IV grade (by Ridit analysis, P<0.01). The E/A and EF values were higher in patients of XQD than those in patients of XYD (P<0.01). Levels of TNF-alpha, IL-6 and IL-1beta were higher and IL-10 was lower in patients of XYD than those in patients of XQD (P<0.05 or P<0.01) respectively. CONCLUSION: TNF-alpha, IL-6, IL-1beta and IL-10 probably play an important role in the development process of XQD to XYD, and could be taken as the microcosmic indexes for differentiation of the two syndromes.