Targeting fibroblast activation protein inhibits endothelial-mesenchymal transition by affecting cancer-associated fibroblasts derived exosomes / 中国药理学通报

Aim To investigate whether targeted inhibition of fibroblast activation protein (FAP) can inhibit the endothelial-to-mesenchymal transition (EndMT) of vascular endothelial cells by affecting exosomes (Exo) of cancer-associated fibroblasts (CAFs) and explore the underlying mechanisms. Methods Primary CAFs and peri-tumor fibroblasts (PTFs) were obtained from lung cancer and peri-cancer tissues, and CAFs-exo and PTFs-exo were collected from culture medium, respectively. Exosomes from CAFs treated with specific FAP inhibitor (3.3 nmol • L-

Spontaneous healing of complicated crown-root fractures in children: Two case reports.

BACKGROUND: Complicated crown-root fracture is considered a severe dental trauma and is unlikely to heal without treatment. Usually, dentists have to remove the loose coronal fragment of the fractured tooth and treat the remaining part with multidisciplinary approaches. However, we observed spontaneous healing of fracture in two pediatric cases with a history of complicated crown-root fractures over 4 years ago. CASE SUMMARY: In case 1, a 12-year-old boy complained of pain at tooth 11 following an accidental fall 1 d ago. Clinical examination showed a crack line on the crown of tooth 11. Cone beam computed tomography (CBCT) images of tooth 11 showed signs of hard tissue deposition between the fractured fragments. The patient recalled that tooth 11 had struck the floor 1 year ago without seeking any other treatment. In case 2, a 10-year-old girl fell down 1 d ago and wanted to have her teeth examined. Clinical examination showed a fracture line on the crown of tooth 21. CBCT images of tooth 21 also showed signs of hard tissue deposition between the fractured fragments. She also had a history of dental trauma 1 year ago and her tooth 11 received dental treatment by another dentist. According to her periapical radiograph at that time, tooth 21 was fractured 1 year ago and the fracture was overlooked by her dentist. Both of these two cases showed spontaneous healing of complicated crown-root fractures. After over 4 years of follow-up, both fractured teeth showed no signs of abnormality. CONCLUSION: These findings may provide new insights and perspectives on the management and treatment of crown-root fractures in children.

Myostain is involved in ginsenoside Rb1-mediated anti-obesity.

CONTEXT: Obesity, one of the major public health problems worldwide, has attracted increasing attention. Ginsenoside Rb1 is the most abundant active component of Panax ginseng C.A.Mey (Araliaceae) and is reported to have beneficial effects on obesity and diabetes. However, the mechanisms by which Rb1 regulates obesity remain to be explored. OBJECTIVE: This paper intends to further explore the mechanism of Rb1 in regulating obesity. MATERIALS AND METHODS: The C57BL/6 obese mice were divided into two groups: the control (CTR) and Rb1. The CTR group [intraperitoneally (ip) administered with saline] and the Rb1 group (ip administered with Rb1, 40 mg/kg/d) were treated daily for four weeks. In vitro, Rb1 (0, 10, 20, 40 µM) was added to differentiated C2C12 cells and Rb1 (0, 20, 40 µM) was added to 3T3-L1 cells. After 24 h, total RNA and protein from C2C12 cells and 3T3-L1 cells were used to detect myostatin (MSTN) and fibronectin type III domain-containing 5 (FNDC5) expression. RESULTS: Rb1 reduced the body weight and adipocyte size. Improved glucose tolerance and increased basic metabolic activity were also found in Rb1 treated mice. MSTN was downregulated in differentiated C2C12 cells, 3T3-L1 cells and adipose tissues upon Rb1 treatment. FNDC5 was increased after Rb1 treatment. However, MSTN overexpression attenuated Rb1-mediated decrease accumulation of lipid droplets in differentiated 3T3-L1 adipocytes. DISCUSSION & CONCLUSIONS: Rb1 may ameliorate obesity in part through the MSTN/FNDC5 signalling pathway. Our results showed that Rb1 can be used as an effective drug in the treatment of human obesity.

Doxorubicin induces stemness of mouse TNBC 4T1 cells through Stat3-Oct-4/CD44 signaling pathway / 中国病理生理杂志

AIM:To investigate the stemness of mouse triple-negative breast cancer (TNBC) 4T1 cells induced by doxorubicin (DOX) and the underlying mechanism.METHODS:The 4T1 cells and MDA-MB-468 cells were treated with DOX at different concentrations (0, 0.05, 0.1 and 0.5μmol/L) for 24 h, and the shape and viability of the cells were observed.The concentration of DOX at 0.1μmol/L was chosen as the optimal concentration for the following experiments.The 4T1 cells and MDA-MB-468 cells resistant to DOX were established by continuous stimulation with DOX for 4 weeks, and named as 4T1-DOX and MDA-MB-468-DOX.Sphere formation assay was used to detect the stemness of 4T1cells and MDA-MB-468 cells.The expression of CD133 was observed by immunofluorescence staining.The expression of CD44 was analyzed by flow cytometry.The protein levels of Stat3, phosphorylated Stat3 (p-Stat3) and Oct-4 were determined by Western blot.RESULTS:The sphere formation ability of the 4T1-DOX cells was stronger than that of the 4T1control cells.The 4T1-DOX cells expressed high levels of the stemness markers CD133 and CD44 as compared with the 4 T1 cells (P<0.05).Furthermore, the 4T1-DOX cells exhibited enhanced activation of Stat3 (p-Stat3) and increased expression of Oct-4 (P<0.05) , while the expression of total Stat3 had no obvious variation.In addition, when activation of Stat3 was inhibited by WP1066, the protein levels of p-Stat3, Oct-4 and CD44 were down-regulated (P<0.05).Furthermore, inhibition of Stat3 phosphorylation reduced the sphere formation ability of the 4T1-DOX cells (P<0.05).CONCLUSION:DOX induces the stemness of mouse TNBC 4T1 cells through Stat3-Oct-4 signaling pathway.

Efficacy and safety of pranoprofen in the treatment of keratoconjunctivitis sicca / 国际眼科杂志(Guoji Yanke Zazhi)

·AIM:To investigate the effect and safety of pranoprofen treatment of keratoconjunctivitis sicca. · METHODS: Totally 100 cases ( 200 eyes ) of keratoconjunctivitis sicca treated in our hospital in January 2014 to May 2016 were divided into control group and study group according to different treatment methods. The patients in the control group were treated with artificial tear and the patients in the study group were treated with artificial tear combined with pranoprofen eye drops. The clinical effects of the two groups were observed and analyzed. ·RESULTS:In the study group,20 cases (40 eyes) were cured, 26 cases (52 eyes) were effective. The total effective rate was 92.0% higher than that of the control group. The difference was statistically significant (P<0.05). The symptoms,BUT and FL scores of two groups after treatment were better than before treatment (P<0.05),but SIT score was not statistically significant (P>0.05). The symptoms and FL scores of study group after treatment were lower than those of the control group after treatment, the BUT score was higher than that of the control group (P<0.05). After treatment, the levels of TNF-α,IL-6 and IL-1β in the two groups were lower than those before treatment,and the levels of TNF-α,IL-6 and IL-1β in the study group were significantly lower than in the control group (P<0. 05). the difference of patients with adverse reactions between two groups was not statistically significant (P=1.00). ·CONCLUSION: Pranoprofen has a significant effect on the treatment of keratoconjunctivitis sicca, can improve symptoms and signs, control the infection, with high safety.

Expression of serum inflammatory factors in patients with glaucoma at different stages and its clinical significance / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To analyze the change of serum inflammatory factors in glaucoma patients at different stages and its clinical significance. ·METHODS:Totally 70 cases of 128 eyes with primary open-angle glaucoma in our hospital from January 2014 to August 2016 were selected. According to the mean defect of visual field, they were divided into light ( observation Group 1 ) , moderate ( observation Group 2 ) and heavy group(observation Group 3). Another 65 cases of 130 eyes with cataract were taken as the control group in our hospital. The observation and expression of serum cytokines in these patients with glaucoma were taken. ·RESULTS:There was no significant difference in serum IL-2 and IFN- γlevels between the two groups (P>0. 05). The sIL-2R and IL-4 levels in the glaucoma group were higher than those in the control group, and the levels of IL-6 and IL-12 were lower than those of the control group (P0. 05). To observe the low myopia ratio in Group 3 of patients, it was less than observation Group 1 and observation Group2 ( P > 0. 05 ). There was no statistically significant difference between observation Group 1 and 2 of patients on IL-2, sIL-2R, IL-4, IL-6 and IFN-γlevels (P>0. 05). The level of sIL-2R in the Group 3 was higher than that in the Group 1, and the level of IL-12 was lower than that in the Group 1 and in the Group 2 (P0. 05). The IOP level and the proportion of myopia in the Group 3 were higher than those in the Group 1 and the Group 2 were observed, the difference was statistically significant (P0. 05). ·CONCLUSION: The levels of serum IL-12, sIL-2R and intraocular pressure in patients with primary open-angle glaucoma fluctuated significantly at different stages of the nerve injury, indicating that the immune response and intraocular pressure were involved in the process of optic nerve damage.

Knockout of LSD1 Gene by CRISPR/Cas9 System Significantly Inhibited Proliferation and Expression of CD235a in K562 Cells / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To study the effect of LSD1 knock-out on human chronic myeloid leukemia cells(K562 cells).</p><p><b>METHODS</b>The LSD1 gene in K562 cells was knocked-out specifically by using CRISPR/Cas9 system, the single cells were gained by flow cytometric sorting technique, the LSD1and LSD1cell lines were gained after amplificantion and culture, identification of Western blot and sequencing. The MTS assay was used to detect the effect of LSD1 knockout on the proliferation of K562 cells, the flow cytometry was used to examine the expression of K562 cell surface marker after LSD1 knockout.</p><p><b>RESULTS</b>The LSD1 stable knockout cell line of K562 (LSD1and LSD1)were successfully costructed. It was found that knockout of LSD1 significantly inhibited the proliferation of K562 and the expression of CD235a.</p><p><b>CONCLUSION</b>LSD1 plays a key role in the regulation of K562 cell proliferation and CD235a expression.</p>

Effects of Danggui-Shaoyao-San on the Influence of Spatial Learning and Memory Induced by Experimental Tooth Movement.

BACKGROUND: The pain caused by orthodontic treatment has been considered as tough problems in orthodontic practice. There is substantial literature on pain which has exactly effected on learning and memory; orthodontic tooth movement affected the emotional status has been showed positive outcomes. Danggui-Shaoyao-San (DSS) is a Traditional Chinese Medicine prescription that has been used for pain treatment and analgesic effect for orthodontic pain via inhibiting the activations of neuron and glia. We raised the hypothesis that DSS could restore the impaired abilities of spatial learning and memory via regulating neuron or glia expression in the hippocampus. METHODS: A total of 36 rats were randomly divided into three groups: (1) Sham group (n = 12), rats underwent all the operation procedure except for the placement of orthodontic forces and received saline treatment; (2) experimental tooth movement (ETM) group (n = 12), rats received saline treatment and ETM; (3) DSS + ETM (DETM) group (n = 12), rats received DSS treatment and ETM. All DETM group animals were administered with DSS at a dose of 150 mg/kg. Morris water maze test was evaluated; immunofluorescent histochemistry was used to identify astrocytes activation, and immunofluorescent dendritic spine analysis was used to identify the dendritic spines morphological characteristics expression levels in hippocampus. RESULTS: Maze training sessions during the 5 successive days revealed that ETM significantly deficits in progressive learning in rats, DSS that was given from day 5 prior to ETM enhanced progressive learning. The ETM group rats took longer to cross target quadrant during the probe trial and got less times to cross-platform than DETM group. The spine density in hippocampus in ETM group was significantly decreased compared to the sham group. In addition, thin and mature spine density were decreased too. However, the DSS administration could reverse the dendritic shrinkage and increase the spine density compared to the ETM group. Astrocytes activation showed the opposite trend in hippocampus dentate gyrus (DG). CONCLUSIONS: Treatment with DSS could restore the impaired abilities on ETM-induced decrease of learning and memory behavior. The decreased spines density in the hippocampus and astrocytes activation in DG of hippocampus in the ETM group rats may be related with the decline of the ability of learning and memory. The ability to change the synaptic plasticity in hippocampus after DSS administration may be correlated with the alleviation of impairment of learn and memory after ETM treatment.

The analgesia effect of duloxetine on post-operative pain via intrathecal or intraperitoneal administration.

One promising strategy to prevent the chronicity of post-operative pain (POP) is to attenuate acute POP during the early phase by efficacious medications with fewer side effects. Duloxetine, one of the serotonin (5-HT)-norepinephrine (NE) reuptake inhibitors (SNRI), is used to treat a wide range of acute and chronic pain. However, its effect on POP has not been investigated. In the present study, we investigated the anti-hypersensitivity effect of duloxetine using a rat model of POP. The possible involvement of spinal 5-HT2A and α2-noradrenergic receptors were also evaluated by using antagonists for 5-HT2A (ketanserin) or α2-noradrenergic receptors (idazoxan). Finally, with the method of in vivo microdialysis, the increase in spinal NA and 5-HT levels after intraperitoneal (i.p.) delivery of duloxetine were investigated. The results showed that intrathecal (i.t.) or i.p. delivery of duloxetine produced an anti-hyperalgesic effect in a dose-dependent manner. The anti-hypersensitivity effect of duloxetine was partly attenuated by pretreatment with ketanserin or idazoxane. Microdialysis study revealed that 5-HT and NA concentrations at the spinal dorsal horn were increased, peaking at 30min after i.p. injection of 20mg/kg duloxetine. These findings indicate that duloxetine inhibits POP by increasing spinal NA and 5-HT levels and activating spinal 5-HT2A or α2-noradrenergic receptors.

Therapeutic effect of anti-anaphylaxis granule on chronic urticaria and its impact on serum levels of RANTES / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To investigate the therapeutic effect of Anti-anaphylaxis Granule (AAG) on chronic urticaria and its impact on cytokine of regulated upon activation of normal T cells expressed and secreted (RANTES), eosinophil chemotactic factor (Eotaxin) and tumor necrosis factor-alpha (TNF-alpha).</p><p><b>METHODS</b>The therapeutic effects of AAG and cetirizine on chronic urticaria patients allocated in two groups were observed respectively, and the serum levels of RANTES, Eotaxin and TNF-alpha in patients were measured by ELISA before and after treatment, and were compared with those in normal subjects.</p><p><b>RESULTS</b>The therapeutic effects of AAG group were better in effective rate (88.5% vs 64.0%) and lower in the recurrent rate (5.6% vs 41.9%) than those cetirizine (all P<0.05). Serum levels of RANTES, Eotaxin and TNF-alpha in patients were higher than those in normal subjects (P<0.01), and they could be significantly reduced after AAG treatment (P<0.01).</p><p><b>CONCLUSION</b>AAG has favorite effect for treatment of chronic urticaria, its regulation on serum levels of RANTES, Eotaxin and TNF-alpha may be the mechanism of action.</p>

Design and synthesis of 3'-methyl-furanonucleosides and their anti-tumor activities / 药学学报

Taking 3'-Me-Ado (3'-methyladenosine) and Cladribine as the leading compounds, seventeen 3'-C-methyl-furanonucleosides were designed and synthesized. All the structures were confirmed by 1H NMR and MS. The target compounds were tested in vitro against human pulmonary carcinoma A549, human colon carcinoma LOVO and human leukemia CEM by MTT assay. The results showed that these compounds possessed moderate cytotoxicities.

Effect of Stellate Ganglion Block on Patients with Cerebral Infarction:Report of 36 Cases / 中国康复理论与实践

@#Objective To observe the effect of stellate ganglion block on patients with cerebral infarction.Methods36 patients with cerebral infarction were randomly divided into the control group and research group.Both two groups were treated with traditional treatment.The research group was added with stellate ganglion block.ResultsAfter 20 days treatment,the Neuro-function Deficit(NFD) scores of both two groups were significantly lower than that before treatment(P<0.01);but the NFD scores of the research group were significantly lower than that of the control group(P<0.01).The scores of Fugl-Meyer Assessment(FMA) and Barthel Index(BI) of both two groups were significantly higher after treatment(P<0.01);but the scores of FMA and BI of the research group were significantly higher than that of the control group(P<0.01).ConclusionStellate ganglion block can improve the nerve function of patients with cerebral infarction.