Ischemic stroke (IS) is a globally life-threatening disease. Presently, few therapeutic medicines are available for treating IS, and rt-PA is the only drug approved by the US Food and Drug Administration (FDA) in the US. In fact, many agents showing excellent neuroprotection but no blood flow-improving activity in animals have not achieved ideal clinical efficacy, while thrombolytic drugs only improving blood flow without neuroprotection have limited their wider application. To address these challenges and meet the huge unmet clinical need, we have designed and identified a novel compound AAPB with dual effects of neuroprotection and cerebral blood flow improvement. AAPB significantly reduced cerebral infarction and neural function deficit in tMCAO rats, pMCAO rats, and IS rhesus monkeys, as well as displayed exceptional safety profiles and excellent pharmacokinetic properties in rats and dogs. AAPB has now entered phase I of clinical trials fighting IS in China.

Objective This study aimed to investigate the protective effect of Danggui Shaoyao Pulvis on diabetic nephropathy(DN)in rats by examining the NF-κB signaling pathway and its potential mechanism.Methods Healthy male SD rats of SPF grade were selected and induced with an early DN rat model using a dual method(high-fat and high-sugar diet+intraperitoneal injection of Streptozotocin STZ);the rats were randomly divided into the model control group,Danggui Shaoyao Pulvis group,and irbesartan group,while a blank group was set as the control,Each group received the corresponding drugs via gavage for a 4-week intervention period.Various parameters such as body mass,random blood glucose(GLU),24 h water intake,24 h urine volume,24 h urine protein,blood creatinine(Scr),urea nitrogen(BUN),and kidney hypertrophy index(KW/BW)were recorded and measured.Kidney samples were stained with HE and PAS for observation under a light microscope.The serum levels of TNF-ɑ,IL-1β,and IL-6 inflammatory factors were detected using Elisa.The positive expression of NF-κB protein in renal tissues was determined by immunohistochemistry.Results Compared to the blank control group,the model control group exhibited increased kidney volume,KW/BW,GLU,24 h urinary protein quantity,24 h water intake,24 h urine volume,Scr,BUN,serum levels of TNF-ɑ,IL-1β,IL-6,and positive expression of NF-κB in kidney tissue(P<0.05),while body weight decreased(P<0.05).The kidney tissue also showed significant pathological injury.In contrast,the Danggui Shaoyao Pulvis group demonstrated significantly decreased kidney volume,KW/BW,GLU,24 h urinary protein quantity,24 h water intake,24 h urine volume,Scr,serum levels of TNF-ɑ,IL-1β,IL-6,and positive expression of NF-κB in kidney tissue(P<0.05),along with increased body mass(P<0.05).The pathological damage of kidney tissue was alleviated.Conclusions The findings of this study suggest that Danggui Shaoyao Pulvis can effectively reduce the release of TNF-ɑ,IL-1β,and IL-6 inflammatory cytokines in DN rats.This reduction is achieved by down-regulating the expression of NF-κB protein in the inflammatory signaling pathway of kidney tissue.These results indicate that the modulation of NF-κB protein expression may be a crucial mechanism by which Danggui Shaoyao Pulvis exerts its therapeutic effects in treating DN.

Diabetic neuropathic pain (DNP) is the most common disabling complication of diabetes. Emerging evidence has linked the pathogenesis of DNP to the aberrant sprouting of sensory axons into the epidermal area; however, the underlying molecular events remain poorly understood. Here we found that an axon guidance molecule, Netrin-3 (Ntn-3), was expressed in the sensory neurons of mouse dorsal root ganglia (DRGs), and downregulation of Ntn-3 expression was highly correlated with the severity of DNP in a diabetic mouse model. Genetic ablation of Ntn-3 increased the intra-epidermal sprouting of sensory axons and worsened the DNP in diabetic mice. In contrast, the elevation of Ntn-3 levels in DRGs significantly inhibited the intra-epidermal axon sprouting and alleviated DNP in diabetic mice. In conclusion, our studies identified Ntn-3 as an important regulator of DNP pathogenesis by gating the aberrant sprouting of sensory axons, indicating that Ntn-3 is a potential druggable target for DNP treatment.
Mice ; Animals ; Diabetes Mellitus, Experimental/metabolism* ; Axons/physiology* ; Diabetic Neuropathies ; Sensory Receptor Cells/metabolism* ; Neuralgia/metabolism*

Objective: To elucidate the anti-inflammatory mechanism of Reduning Injection (RDN) by analyzing the potential biomarkers and metabolic pathways of the carrageenan-induced inflammatory model from the overall metabolic level. Methods: Rat inflammatory model was established by carrageenan. UPLC-Q-TOF/MS was used to detect and analyze changes of endogenous metabolites in the serum and urine of carrageenan-induced inflammatory rats. Combined with multivariate analysis and databases analysis, inflammatory-related potential biomarkers were screened and identified to analyze possible metabolic pathways. The reliability and biological significance of these biomarkers was verified by metabolic network analysis and correlation analysis with pharmacodynamic indicators. Results: A total of 16 potential biomarkers were screened and identified by multivariate analysis and metabolite databases, among which 13 species could be adjusted by RDN. The metabolism pathway analysis revealed that histidine metabolism, sphingolipid metabolism, and tyrosine metabolism were greatly disturbed. Their biomarkers involved urocanic acid, sphingosine, and norepinephrine, all of which showed a callback trend after RDN treatment. The three biomarkers had a certain correlation with some known inflammatory-related small molecules (histamine, arachidonic acid, Leukotriene B4, and PGE

OBJECTIVE：To investigate the effects of Guizhi ful ing capsules and its principal components （paeoniflorin， paeonol and amygdalin ）on the intestinal flora of primary dysmenorrhea model rats. METHODS ：Female SD rats were randomly divided into normal group ，model group ，capsule group（Guizhi fuling capsule ，1 000 mg/kg），paeoniflorin group （15.0 mg/kg）， paeonol group （10.3 mg/kg）and amygdalin group （12.1 mg/kg），with 6 rats in each group. Except for normal group ，other groups were given estradiol benzoate subcutaneously on the back of rats and oxytocin intraperitoneally to induce primary dysmenorrhea model. From the 4th day after subcutaneous injection of estradiol benzoate ，normal group was given constant volume of normal saline intragastrically ；model group was given constant volume of 0.5％CMC-Na solution intragastrically ；administration groups were given relevant medicine intragastrically ，once a day ，for consecutive 7 days. The writhing times and the contents of and MDA in uterus tissue of rats were determined ，and then com the contents of short-chain fatty acids （SCFAs）such as acetic acid，propionic acid ，butyric acid in colonic contents were detected by GC method. Using diver sity index as index ， Rep-PCR and Eric-PCR were used to evaluate the d iversity of intestinal flora in feces of rats. RESULTS ：Compared with normal group，the writhing times of rats were increased significantly in model group ；the contents of NO and MDA in uterus were increased significantly ，while the contents of acetic acid ，propionic acid and butyric acid in colonic contents and total content of SCFAs were decreased significantly （P＜0.05 or P＜0.01）；the number of DNA electrophoresis bands of intestinal flora was significantly reduced ，the brightness of most bands was significantly reduced ，and the diversity indexes （by Rep-PCR and Eric-PCR method ，hereinafter）1 h after administration were significantly reduced （P＜0.05 or P＜0.01）. Compared with model group，writhing times of rats were decreased significantly in capsule group ，paeoniflorin group and paeonol group ；the contents of NO in uterus of rats in capsule group and paeoniflorin group as well as the contents of MDA in capsule group ，paeoniflorin group and paeonol group were decreased significantly （P＜0.05 or P＜0.01）；the propionic acid content and total content of SCFAs in colon of rats in capsule group ，the contents of acetic acid ，propionic acid and butyric acid ，total content of SCFAs in paeoniflorin group as well as the contents of propionic acid and butyric acid ，total content of SCFAs in paeonol group were increased significantly；the content of isovaleric acid was decreased significantly in paeoniflorin group （P＜0.05 or P＜0.01）；DNA electrophoresis bands and its brightness of intestinal flora changed to different extents in administration groups ，and the diversity indexes of intestinal flora 1 h after administration were increased significantly in capsule group and paeoniflorin group ，while those indexes were decreased significantly in paeonol group and amygdalin group （P＜0.05 or P＜0.01）. CONCLUSIONS ：Guizhi fuling capsules can significantly reduce writhing times and the contents of NO and MDA in uterus of primary dysmenorrhea model rats. At the same time ，the capsules also can regulate SCFAs content in colonic contents and intestinal flora diversity of rats. The above effects may be related to paeoniflorin and paeonol in the capsules.

BACKGROUND:Previous studies have confirmed that ethanol can promote adipogenic differentiation of bone marrow mesenchymal stem cells (BMSCs), and up-regulate the expression of PPARγ and aP2 in the tumor necrosis factor α (TNF-α) signaling pathway. As a member of the ZIP protein family, Zrt/Irt-like protein 1 (ZIP1) is closely related to bone metabolism and osteogenic differentiation.OBJECTIVE:To study the effect of BMSCs transfected by ZIP1 on TNF-α signaling pathway in the process of adipogenic differentiation.METHODS:The BMSCs from rabbits were isolated and cultured under different concentrations of alcohol (0.03, 0.09,0.15, 0.21 mol/L), followed by transfection by ZIP1 siRNA and ZIP1 expression vector.RESULTS AND CONCLUSION:After culture in alcohol, the expression levels of aP2 and PPARγ proteins were both significantly increased (P < 0.05), and the level of triglyceride was increased in all alcohol groups except for 0.03 mol/L alcohol group (P < 0.05). After siRNA transfection, the expression levels of aP2 and PPARγ as well as the level of triglyceride were increased significantly in all the alcohol groups (P < 0.05); however, ZIP1 transfection decreased the expression levels of aP2 and PPARγ proteins (P < 0.05). To conclude, ZIP1 siRNA could promote the adipogenic differentiation of BMSCs through the activation of TNF-α signaling pathway.

This study was aimed to establish a method for simultaneous determination of seven anions and organic acids in Huo-Xue Tong-Luo (HXTL) injection by HPCE. With tartaric acid as the internal standard, separation was performed on an uncoated fused silica capillary (50 μm × 64. 5 cm, 56 cm of effective length). The 14 mmol·L-1 potassium acid phthalate and 0.1 mmol·L-1 hexadecyl trimethyl ammonium chloride were selected for the running buffer solution (pH 5.6). The separation voltage was -16 kV. The detection wavelength was set at 210 nm. The column temperature was maintained at 25 ℃ . The sample was injected at 50 mbar×4 s. The results showed that
calibration curves of chloride ion, sulfuric acid root ion, formate ions, malic acid, succinic acid, iodate ion and acetic acid ions showed good linear relationship 41.4-248.2 μg·mL-1 (r = 0.999 3), 12.5-74.8 μg·mL-1 (r = 0.999 8), 18.2-109.1 μg·mL-1 (r = 0.999 8), 20.3-121.6 μg·mL-1 (r = 0.999 5), 17.2-103.1 μg·mL-1 (r=0.999 1), 17.6-105.6μg·mL-1 (r=0.999 6), 51.6-309.6μg·mL-1 (r=0.999 7), respectively. The average recoveries were 102.6%, 97.3%, 102.2%, 99.0%, 99.2%, 97.8%, and 103.4%, respectively. The RSD were 1.7%, 2.0%, 1.6%, 2.6%, 2.1%, 2.9%, and 1.0%, respectively (n = 6). It was concluded that the method was accurate and reproducible. It was suitable for the determination of anions and organic acids in HXTL injection.

This medical kit developed for marine mobile medical team is adopted glassfibre reinforced plastic material as the body of the kit.It is characterized by its light weight,high specific intensity and corrosion resisting.It's a complete set of combined kit with relevant function.