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Enhancing Antitumor Response by simply Costimulatory Strategies Influenced to 4-1BB as well as OX40 T-cell Receptors.
To investigate the efficacy of the Danlou Fang (DL) Traditional Chinese Medicine formula on microvascular obstruction (no-reflow) through the endothelial/inducible nitric oxide synthase (eNOS/iNOS) pathway in a rat model.

Sprague-Dawley rats were subjected to 60 min of coronary artery occlusion (or sham procedure) followed by 2 h of reperfusion and were then divided into treatment groups sham, model, DL (500 mg/kg), DL (500 mg/kg) + eNOS inhibitor L-nitroarginine (L-NNA; 7.5 mg/kg), and sodium nitroprusside (SNP; 0.5 mg/kg). There were 16 per group. Areas of no-reflow were determined by thioflavin S staining of heart tissue. Cardiac function was assessed by echocardiography. Myocardial enzymes and antioxidants in serum were measured and analyzed. The relative protein expression levels of eNOS and iNOS were determined by western blotting.

DL had a myocardial protective effect on myocardial reperfusion and reduced the area of no-reflow. The serum levels of creatine kinase (CK), myocardial CK isoenzyme CK-MB, and lactate dehydrogenase were significantly lower in the DL group than in the model (P < 0.05). ASN-002 in vivo DL treatment also decreased the serum content of malondialdehyde and reactive oxygen species (ROS), increased the activity of superoxide dismutase and nitric oxide, and promoted eNOS expression (P < 0.05) while lowering iNOS expression.

DL reduced the area of no-reflow and had a myocardial protective effect that may be associated with the eNOS/iNOS pathway.
DL reduced the area of no-reflow and had a myocardial protective effect that may be associated with the eNOS/iNOS pathway.
To explore the effects of Qingguang'an () containing serum on the expression levels of autophagy related genes in the transforming growth factor beta 1 (TGF-β1)-activated human Tenon's fibroblasts (HTFs).

(a) Primary HTFs were stimulated by TGF-β1 and underwent immunohistochemistry, which established a cell model after Glaucoma filtration surgery (GFS). (b) The cell models were divided into 4 group normal group (normal cells), model group (+TGF-β1),treatment group (+TGF-β1+ medicated serum), and positive control group (TGF-β1+ rapamycin). Then, Qingguang'an medicated serum with optimum concentration was added to the corresponding group. The autophagy positive cells were identified by the Cyto-ID autophagy detection kits under fluorescent microscope and Cytation 5 multifunctional instrument for cell imaging. And the mean fluorescence intensity of autophagy positive cells was determined by flow cytometry. The expression levels of autophagy related genes － Beclin-1, autophagy related gene 5 (ATG-5), and micrgenes (Beclin1, ATG5, and LC3Ⅱ in the TGF-β1-activated HTFs.
To evaluate the efficacy of Liuwei Dihuang formula ( LWDHF) on endothelial cells, and to study the mechanism behind the action of modulating expression of estrogen receptors.

Hydrogen peroxide (H2O2) was applied to induce the apoptosis of human umbilical vein endothelial cells (HUVECs). The concentration of nitric oxide (NO), endothelial nitric oxide synthase (eNOS) and inducible NOS (iNOS) were measured by assay kits. Western blot and real-time polymerase chain reaction (RT-PCR) were used to detect the expression of iNOS, eNOS, b-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax), estrogen receptor (ER) α and ERβ. Also, small interfering RNA (siRNA) was involved to confirm whether the protective effects of LWDHF was medicated by ERs. In vivo, the female rats were ovariectomized to establish postmenopausal vascular injury model. Then the model rats were divided into three groups and treated with saline, estradiol and LWDHF respectively. The concentration of NO and NOS in serum were measured by assay kits, and the expression of Bax, Bcl-2, ERα and ERβ were detected by western blot and immunohistochemistry.

In vitro study, LWDHF significantly protected HUVECs from H2O2-induced apoptosis, with the increase of Bcl-2 and the decrease of Bax. The treatment with LWDHF inhibited concentration of NO and iNOS, and upregulated the expression of eNOS, ERα and ERβ. In addition, ERα siRNA could block the protective effects of LWDHF, while ERβ siRNA showed little influence. In vivo, the treatment with LWDHF suppressed the vascular injury and reduced the level of NO and NOS. LWDHF increased the expression of Bcl-2, ERα and ERβ, as well as inhibiting the Bax expression.

LWDHF could improve endothelial function and protect HUVECs from apoptosis via increasing the expression of ERα.
LWDHF could improve endothelial function and protect HUVECs from apoptosis via increasing the expression of ERα.
To investigate the possible antinociceptive effects of Salvia (S.) miltiorrhiza Bunge and its single components in monosodium urate (MSU)-induced pain model in mice and lipopolysaccharide (LPS)-induced inflammation model in RAW264.7 cells.

Pretreatment of S. miltiorrhiza Bunge extract (from 1 to 50 μg/mL) concentration-dependently attenuated LPS-induced nitric oxide (NO) release. The extract of S. miltiorrhiza Bunge (50 or 100 mg/kg) also caused reversals of decreased threshold for pain in the MSU-treated group as measured by Von-Frey test. Furthermore, we assessed the antinociceptive and anti-inflammatory properties of the active single components from S. miltiorrhiza Bunge such as 15, 16-dihydrotanshinone Ⅰ tanshinone Ⅱ cryptotanshinone, miltirone, tanshinone ⅡA, and salvianolic acid B. Some of them showed an anti-inflammatory effect in LPS-induced NO release model and an antinociceptive effect in MSU-treated pain model.

Our results suggest that S. miltiorrhiza Bunge extract may exert anti-inflammatory effect by reducing LPS-induced NO release and an antinociceptive property in MSU-treated pain model. Especially, tanshinoneⅡA, miltirone, cryptotanshinone, and 15,16-dihydrotanshinone Ⅰ not only appear to be responsible for LPS-induced NO release induced by S. miltiorrhiza Bunge, but also in the production of S. miltiorrhiza Bunge extract-induced antinociception in MSU-treated pain model.

Therefore, the analgesic and anti-inflammatory property of S. miltiorrhiza Bunge indicate it as a therapeutic potential candidate for the treatment of pain and inflammation.
Therefore, the analgesic and anti-inflammatory property of S. miltiorrhiza Bunge indicate it as a therapeutic potential candidate for the treatment of pain and inflammation.
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