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To report a case of onychocytic carcinoma in China. A 76-year-old female patient presented with a subnail mass on her left thumb for 3 years. Skin examination showed thickening of the left thumb plate whose surface was partially yellow and black in color, slight curving of the distal plate, obvious telangiectasia under the nail plate, and verrucous hyperplasia under the nail plate and at the lateral edge of the nail plate. Histopathological examination showed that the tumor grew and infiltrated downward in clumps, with obvious keratosis and necrosis in the center of the mass, and many "squamous vortex" structures, atypical cells, and pathological mitotic figures could be seen. Immunohistochemical study revealed that HK31 and HK85 were positively expressed in the squamous vortex region, K6/K16 was positively expressed in the basal part of the tumor, and HK75 was strongly expressed in the whole tumor region. The diagnosis of onychocytic carcinoma was confirmed. The patient received surgical excision combined with 3 sessions of photodynamic therapy, and no recurrence was observed during 18 months of follow-up.
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Objective: To investigate the clinical, pathological and immunophenotypic features, molecular biology and prognosis of fibrin-associated large B-cell lymphoma (LBCL-FA) in various sites. Methods: Six cases of LBCL-FA diagnosed from April 2016 to November 2021 at the Beijing Friendship Hospital, Capital Medical University, Beijing, China and the First Affiliated Hospital, Wenzhou Medical University, Wenzhou, China were collected. The cases were divided into atrial myxoma and cyst-related groups. Clinical characteristics, pathological morphology, immunophenotype, Epstein Barr virus infection status, B-cell gene rearrangement and fluorescence in situ hybridization of MYC, bcl-2, bcl-6 were summarized. Results: The patients' mean age was 60 years. All of them were male. Three cases occurred in atrial myxoma background, while the others were in cyst-related background, including adrenal gland, abdominal cavity and subdura. All cases showed tumor cells located in pink fibrin clot. However, three cyst-related cases showed the cyst wall with obviously fibrosis and inflammatory cells. All cases tested were non germinal center B cell origin, positive for PD-L1, EBER and EBNA2, and were negative for MYC, bcl-2 and bcl-6 rearrangements, except one case with MYC, bcl-2 and bcl-6 amplification. All of the 5 cases showed monoclonal rearrangement of the Ig gene using PCR based analysis. The patients had detailed follow-ups of 9-120 months, were treated surgically without radiotherapy or chemotherapy, and had long-term disease-free survivals. Conclusions: LBCL-FA is a group of rare diseases occurring in various sites, with predilection in the context of atrial myxoma and cyst-related lesions. Cyst-related lesions with obvious chronic inflammatory background show more scarcity of lymphoid cells and obvious degeneration, which are easy to be missed or misdiagnosed. LBCL-FA overall has a good prognosis with the potential for cure by surgery alone and postoperative chemotherapy may not be necessary.
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Humans , Male , Middle Aged , Atrial Fibrillation , Epstein-Barr Virus Infections , Fibrin/genetics , Herpesvirus 4, Human/genetics , In Situ Hybridization, Fluorescence , Lymphoma, Large B-Cell, Diffuse/pathology , Myxoma , Proto-Oncogene Proteins c-bcl-2/genetics , Proto-Oncogene Proteins c-bcl-6/geneticsABSTRACT
Objective To investigate the effect of Guizhi Fuling Capsule on NF-κB and MAPK signaling pathway in lipopolysaccharide(LPS)-induced rat endometritis model.Methods The rats were randomly divided into 6 groups according to body weight,namely sham-operation group,model group,positive group(dexamethasone,2.5 mg·kg-1),Guizhi Fuling Capsule high-dose,medium-dose and low-dose groups(0.54,0.27,0.14 g·kg-1),with 10 rats in each group.The sham operation group and the model group were given 0.5%CMC-Na by gavage,and the other groups were given corresponding drugs by gavage once a day for 7 consecutive days.One hour after the last administration,the animals were anesthetized by intraperitoneal injection of 10%chloral hydrate.The rats in the sham operation group only underwent laparotomy and abdominal closure.The left uterus of the rats in the other groups was scratched and injected with a syringe(1.0 μg·μL-1)LPS normal saline solution 0.25 mL.24 hours after LPS injection,the uterine tissues of rats were collected and the pathological changes and MPO,TNF-α,IL-1β,IL-6 were measured in uterine tissues.The expression levels of NF-κB p65,IκBα,ERK,p38 and their phosphorylated proteins were measured in uterine tissues.Results Compared with sham operation group,histopathological score,MPO,TNF-α,IL-1β and IL-6 levels in model group were significantly increased(P<0.01),and NF-κBp65,IκBα,ERK,p38 protein phosphorylation levels were significantly increased(P<0.01).Compared with model group,Guizhi Fuling capsule significantly decreased pathological score of uterus,TNF-α,IL-1β,and IL-6 levels(P<0.01),and significantly decreased NF-κBp65,IκBα,ERK,p38 protein phosphorylation levels(P<0.01).Conclusion Guizhi Fuling capsule plays an anti-inflammatory role in endometritis by inhibiting the transmission of NF-κB and MAPK signaling pathways and inhibiting the secretion of inflammatory factors IL-1β,TNF-α and IL-6 in uterine tissue.
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Monocytes are key effectors in autoimmunity-related diseases in the central nervous system (CNS) due to the critical roles of these cells in the production of proinflammatory cytokines, differentiation of T-helper (Th) cells, and antigen presentation. The JAK-STAT signaling is crucial for initiating monocytes induced immune responses by relaying cytokines signaling. However, the role of this pathway in modulating the communication between monocytes and Th cells in the pathogenesis of multiple sclerosis (MS) is unclear. Here, we show that the JAK1/2/3 and STAT1/3/5/6 subtypes involved in the demyelination mediated by the differentiation of pathological Th1 and Th17 and the CNS-infiltrating inflammatory monocytes in experimental autoimmune encephalomyelitis (EAE), a model for MS. JAK inhibition prevented the CNS-infiltrating CCR2-dependent Ly6Chi monocytes and monocyte-derived dendritic cells in EAE mice. In parallel, the proportion of GM-CSF+CD4+ T cells and GM-CSF secretion were decreased in pathological Th17 cells by JAK inhibition, which in turns converted CNS-invading monocytes into antigen-presenting cells to mediate tissue damage. Together, our data highlight the therapeutic potential of JAK inhibition in treating EAE by blocking the GM-CSF-driven inflammatory signature of monocytes.
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Tolerogenic dendritic cells (tolDCs) facilitate the suppression of autoimmune responses by differentiating regulatory T cells (Treg). The dysfunction of immunotolerance results in the development of autoimmune diseases, such as rheumatoid arthritis (RA). As multipotent progenitor cells, mesenchymal stem cells (MSCs), can regulate dendritic cells (DCs) to restore their immunosuppressive function and prevent disease development. However, the underlying mechanisms of MSCs in regulating DCs still need to be better defined. Simultaneously, the delivery system for MSCs also influences their function. Herein, MSCs are encapsulated in alginate hydrogel to improve cell survival and retention in situ, maximizing efficacy in vivo. The three-dimensional co-culture of encapsulated MSCs with DCs demonstrates that MSCs can inhibit the maturation of DCs and the secretion of pro-inflammatory cytokines. In the collagen-induced arthritis (CIA) mice model, alginate hydrogel encapsulated MSCs induce a significantly higher expression of CD39+CD73+ on MSCs. These enzymes hydrolyze ATP to adenosine and activate A2A/2B receptors on immature DCs, further promoting the phenotypic transformation of DCs to tolDCs and regulating naïve T cells to Tregs. Therefore, encapsulated MSCs obviously alleviate the inflammatory response and prevent CIA progression. This finding clarifies the mechanism of MSCs-DCs crosstalk in eliciting the immunosuppression effect and provides insights into hydrogel-promoted stem cell therapy for autoimmune diseases.
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The present study explored the underlying mechanism of Astragali Radix-Curcumae Rhizoma-Paridis Rhizoma(AR-CR-PR) in the treatment of colorectal cancer(CRC) by network pharmacology and molecular docking and animal tests and verified the core targets based on the orthotopic transplantation model in nude mice. The active components of AR-CR-PR were retrieved from databases such as TCMSP. The targets of drugs and the disease were obtained from PubChem, SwissTargetPrediction, TTD, and DrugBank, and the intersection targets were imported into STRING for the analysis of the protein-protein interaction(PPI). Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) analyses were performed through DAVID. AutoDock Vina was used to perform molecular docking and binding ability prediction between the active components and the core targets. The effects of AR-CR-PR on tumor growth, metastasis, and phosphorylation of core target proteins in tumor tissues based on the orthotopic transplantation model in nude mice. As revealed by network pharmacology, AR-CR-PR contained nine core components, such as quercetin, curcumin, and β-ecdysone, and the key targets included protein kinase B(AKT1), mitogen-activated protein kinase 3(MAPK3), MAPK1, and epithelial growth factor receptor(EGFR), which was indicated that the anti-CRC effect of AR-CR-PR was presumedly achieved by regulating tumor cell proliferation, apoptosis, migration, and angiogenesis through PI3 K-AKT, MAPK and other signaling pathways. The results of molecular docking showed that the nine core components had strong binding abilities to AKT1 and MAPK3. The results in vivo showed that AR-CR-PR could reduce the volume of the orthotopic tumor, inhibit liver metastasis, and decrease the phosphorylation of AKT1 and MAPK3 in the CRC model. The mechanism of AR-CR-PR in the intervention of CRC may be related to the activation of PI3 K-AKT and MAPK signaling pathway. This study provides a scientific basis for the clinical application of AR-CR-PR in the treatment of CRC and ideas for modern research on AR-CR-PR.
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Animals , Mice , Drugs, Chinese Herbal/pharmacology , Mice, Nude , Molecular Docking Simulation , Neoplasms , Network Pharmacology , RhizomeABSTRACT
Objective:To evaluate the curative effect and adverse reactions of compound acid, alpha hydroxyl acid (AHA), and salicylic acid (SA) in the treatment of mild to moderate acne.Methods:A total of 105 patients admitted in Suzhou Municipal Hospital from August 2019 to May 2020 were divided into three groups randomly and treated with compound acid, AHA and SA, once every 3 weeks, 4 times totally. The efficacy was evaluated before treatment, 3 weeks after 1 time, 2 times, 3 times, and 4 times. The number of non-inflammatory lesions (comedos) and inflammatory lesions (papules or pustules) were recorded. VISIA image was used to record the patient's facial characteristics before treatment and 3 weeks after 4 times. The occurrence of adverse reactions was recorded.Results:Three groups were all safe and effective. The efficiency of non-inflammatory lesions showed that there was no statistically significant difference between the 3 groups (χ 2= 4.58, P=0.101). The effective rate of inflammatory lesions in the compound acid and SA groups were higher than that of AHA group, and the difference was statistically significant (χ 2=6.45, P=0.040). After 4 times, the clinical data of purpurin, red area, and spot in compound acid and SA groups were higher than those before treatment, and the difference was statistically significant ( P<0.05). While in the AHA group, the purple matter was higher than that before treatment after 4 times, the difference was statistically significant ( t=3.506, P=0.010), and the change in the red area was not statistically significant ( P>0.05). Conclusions:The compound acid is safe and effective in treating mild and moderate acne. It is effective for acne inflammatory and non-inflammatory lesions. It has less adverse reactions and is worthy of clinical application.
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Objective To analyze the current status of exercise and exercise self-efficacy (ESE) and its influencing factors in middle-aged and elderly patients with high blood pressure, and to provide a basis for the intervention of patients with hypertension in the community. Methods The stratified random sampling method was used to select 546 patients with hypertension who had received hypertension management for one year in the community. The general condition, exercise condition, and ESE scores were collected using survey questionnaires. Chi-square test was applied to analyze the difference of exercise efficacy score among different characteristic objects, and analysis of regression method was applied to analyze the influencing factors of exercise self-efficacy. Results A total of 546 people were surveyed in this study, of which 67.03% of hypertension patients participated in exercise. The main exercise program was walking healthily (87.43%). A total of 262 people (47.99%) had strong performance on ESE score, while 284 people (52.01%) had weak self-efficacy. The univariate unconditional logistic regression analysis found that there were significant differences in the distribution of educational level, family monthly income, years of hypertension, whether they received the guidance from family doctors, whether they exercised and whether they warmed up before exercise (P<0.05). The multivariate unconditional logistic regression analysis showed that educational level of junior high school and low average monthly household income were the risk factors affecting exercise efficacy, and the guidance of family doctors, exercise, and hypertension less than 5 years were the protective factors affecting exercise efficacy. Conclusion The exercise self-efficacy of middle-aged and elderly patients with hypertension in this community is at a medium level, and family doctors should carry out targeted interventions based on influencing factors to improve exercise self-management ability.
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Objective:To explore the possible mechanism of Astragali Radix-Curcumae Rhizoma (AC) in inhibiting tumor growth in the orthotopic transplantation model of colon cancer in mice. Method:The molecular docking technology was used to predict the intermolecular interaction between the main active components of AC and the pathway target proteins, such as stromal cell-derived factor-1 (SDF-1), C-X-C motif chemokine receptor 4 (CXCR4), and nuclear factor kappa-B p65 (NF-<italic>κ</italic>B p65). The orthotopic transplantation model of CT26.WT colon cancer was established in mice for <italic>in vivo</italic> experimental verification. Sixty BALB/c male mice were randomly divided into a sham operation group, a model group, a 5-fluorouracil (5-Fu, 30 mg·kg<sup>-1</sup>) group,and low- (0.32 g·kg<sup>-1</sup>), medium- (0.64 g·kg<sup>-1</sup>), and high-dose (1.28 g·kg<sup>-1</sup>) AC groups, with 10 mice in each group. The sham operation group and the model group received normal saline by gavage. The corresponding drugs were administered by gavage in the 5-Fu group and by intraperitoneal injection in the AC groups. After intervention for 15 days, the tumor <italic>in situ</italic> was completely stripped, and the colon tissues 5-6 cm in length adjacent to the tumor were taken. The tumor volume was measured and calculated. The pathological changes of tumor tissues and colon tissues were observed by Hematoxylin-Eosin (HE) staining. Western blot was used to detect the protein expression of SDF-1, CXCR4, p-NF-<italic>κ</italic>B p65 in colon tissues. Western blot and Real-time quantitative polymerase chain reaction (Real-time PCR) were used to detect SDF-1, CXCR4, NF-<italic>κ</italic>B p65, Cyclin D<sub>1</sub>, oncogene c-Myc protein and mRNA expression in tumor tissues. Result:Compared with the model group, 5-Fu and AC groups showed reduced tumor volumes <italic>in situ</italic> (<italic>P</italic><0.05, <italic>P</italic><0.01), with the tumor inhibition rate in the 5-Fu group as high as (61.38±2.34)%. The tumor-inhibiting effect was optimal in the medium-dose AC group, with the tumor inhibition rate of (43.43±3.71)%. Compared with the model group, 5-Fu and AC groups showed relieved pathological changes of tumor and colon tissues. Specifically, AC down-regulated the protein expression levels of SDF-1, CXCR4, and p-NF-<italic>κ</italic>B p65 in colon tissues (<italic>P</italic><0.01), and down-regulated the protein and mRNA expression levels of SDF-1, CXCR4, NF-<italic>κ</italic>B p65, Cyclin D<sub>1</sub>, and c-Myc in tumor tissues (<italic>P</italic><0.05, <italic>P</italic><0.01). Conclusion:AC can inhibit the growth of orthotopic transplantation tumor of colon cancer, and its intervention mechanism may be related to the regulation of related protein and mRNA expression in the SDF-1/CXCR4/NF-<italic>κ</italic>B signaling pathway.
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Cerebral ischemia is one of the most common diseases in China, and the drug pair of Chuanxiong Rhizoma and Paeoniae Radix Rubra can intervene in cerebral ischemia to reduce the inflammatory response of cerebral ischemia and apoptosis. To reveal the intervention mechanism of Chuanxiong Rhizoma-Paeoniae Radix Rubra drug pair on cerebral ischemia systematically, computer network pharmacology technology was used in this paper to predict the target and signaling pathway of the drug pair on the intervention of cerebral ischemia, and then the molecular docking technology was used to further analyze the mechanism of the intervention. The target results were then verified by the rat cerebral ischemia model. The target network results showed that the active compounds of Chuanxiong Rhizoma-Paeoniae Radix Rubra for cerebral ischemic disease contained 30 compounds, 38 targets and 9 pathways. The main compounds included phenolic acids in Chuanxiong Rhizoma and monoterpene glycosides in Paeoniae Radix Rubra. The key targets involved mitogen-activated protein kinase 1(MAPK1), steroid receptor coactivator(SRC), epidermal growth factor receptor(EGFR), mitogen-activated protein kinase 14(MAPK14), caspase-3(CASP3), caspase-7(CASP7), estrogen receptor 1(ESR1), and mitogen-activated protein kinase 8(MAPK8), etc. The target gene functions were biased towards protein kinase activity, protein autophosphorylation, peptidyl-serine phosphorylation and protein serine/threonine kinase activity, etc. The important KEGG pathways involved Ras signaling pathway, ErbB signaling pathway and VEGF signaling pathway. Molecular docking results showed that catechin, oxypaeoniflorin, albiflorin, paeoniflorin and benzoylpaeoniflorin had strong binding ability with MAPK1, SRC, EGFR, MAPK14 and CASP7. MCAO rat experimental results showed that Chuanxiong Rhizoma-Paeoniae Radix Rubra significantly improved the cerebral ischemia injury and interstitial edema, and significantly reduced the activation of caspase-7 and the phosphorylation of ERK1/2. The Chuanxiong Rhizoma-Paeoniae Radix Rubra drug pair alleviated cerebral ischemia injury through a network model of multi-phenotype intervention by promoting cell proliferation and differentiation, reducing inflammatory factor expression, protecting nerve cells from death and figh-ting against neuronal cell apoptosis, with its action signaling pathway most related to Ras signaling pathway, ErbB signaling pathway and VEGF signaling pathway. This study provides the basis for clinical intervention of Chuanxiong Rhizoma-Paeoniae Radix Rubra drug pair on cerebral ischemia, and also provides ideas for the modernization of drug pairs.
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Animals , Rats , Brain Ischemia/genetics , Cerebral Infarction , Drugs, Chinese Herbal , Molecular Docking Simulation , Paeonia , RhizomeABSTRACT
This study explored the effects of resveratrol(Res) on the expression of phosphatase and tensin homolog deleted on chromosome ten(PTEN) and the fibrosis of rat renal tubular epithelial cells in a high-glucose environment and the possible mechanism underlying the fibrosis reduction. After the pretreatment of rat renal tubular epithelial cells(NRK-52 E) cultured in a high-glucose condition with Res or PTEN inhibitor SF1670, they were divided into several groups, i.e., normal glucose(NG), normal glucose + SF1670(NS), high glucose(HG), high glucose + SF1670(HS), high glucose + Res at different concentrations(5, 10, 25 μmol·L~(-1)). The expression and distribution of E-cadherin and α-SMA in renal tubular epithelial cells were observed by immunofluorescence cytochemistry. The protein expression levels of PTEN, E-cadherin, α-SMA, p-Akt~((Thr308)) and collagen Ⅳ were determined by Western blot. Real-time PCR was employed to detect the expression of PTEN mRNA. Compared with the NG group, the HG group witnessed the reduced expression of PTEN mRNA, PTEN protein and E-cadherin protein, but saw the increased expression of α-SMA, p-Akt~((Thr308)) and collagen Ⅳ proteins. Besides, with the increase in Res concentration, the expression levels of PTEN mRNA, PTEN protein and E-cadherin protein gradually increased, while those of α-SMA, collagen Ⅳ, p-Akt~((Thr308)) proteins gradually decreased in the Res groups, showing a dose-effect dependence, compared with the HG group. No distinct difference was found between the NS group and the NG group. The expression level of E-cadherin was even lower and those of α-SMA, p-Akt~((Thr308)), and collagen Ⅳ were higher in the HS group than in the HG group, with no marked difference shown in the two groups in terms of PTEN mRNA and protein. Although the PTEN inhibitor did not affect PTEN, the expression changes of the other proteins were opposite to the results after Res treatment and the fibrosis was aggravated, which suggested that SF1670 promoted the fibrosis by inhibiting PTEN, activating Akt and increasing the synthesis of collagen Ⅳ and other extracellular matrix. The results show that Res can antagonize the high glucose-mediated fibrosis of renal tubular epithelial cells. This may be achieved via the up-regulation of PTEN and the inhibition of PI3 K/Akt signaling pathway.
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Animals , Rats , Epithelial Cells , Fibrosis , Glucose , PTEN Phosphohydrolase/genetics , Resveratrol/pharmacologyABSTRACT
Astragali Radix-Curcumae Rhizoma is a classic drug pair mainly used for the treatment of digestive tract-related inflammation and tumors, but the ratio is not fixed in clinical practice. In order to study whether the anti-tumor effect of the drug pair is diffe-rent under different ratios, orthotopic transplantation model of colon cancer was established in mice. Then the principal component analysis(PCA) and cluster analysis(CA) were used to explore the effect of different ratios of the drug pair on the tumor growth and metastasis, and select the optimal ratio of Astragali Radix-Curcumae Rhizoma for anti-colon cancer effect. After administration for 15 days, the body weight of colon cancer mice with the tumor removed, the tumor volume and the number of liver metastases were mea-sured; the pathological changes of tumor tissue and liver tissue were observed by HE staining. At the same time, Western blot method was used to detect the protein expression level of tumor growth-related indicators in tumor tissue(Ki67, HBP1, AFP) and tumor metastasis-related indicators in liver tissue(β-catenin, E-cadherin, vimentin, p53) of the tumor-bearing mice. Subsequently, PCA and CA were used to select the optimal ratio of Astragali Radix-Curcumae Rhizoma for anti-colon cancer effect. The experimental results showed that different ratios of Astragali Radix-Curcumae Rhizoma inhibited tumor growth and metastasis to varying degrees. The ratio at 1∶1 of Astragali Radix-Curcumae Rhizoma had the best inhibitory effect on tumor growth, and the 2∶1 ratio group had the best effect on inhibiting liver metastasis and improving weighed loss. Astragali Radix-Curcumae Rhizoma significantly up-regulated the protein expression of HBP1 in tumor tissue of colon cancer mice, and significantly down-regulated the protein expression of Ki67 and AFP in tumor tissue; meanwhile, Astragali Radix-Curcumae Rhizoma significantly up-regulated the protein expression of E-cadherin in liver tissue of colon cancer mice, and significantly reduced the protein expression of β-catenin, vimentin and p53 in liver tissue. PCA results showed that the first three groups in the Astragali Radix-Curcumae Rhizoma compatibility group that were closer to the sham operation group were in the order of 2∶1, 1∶1 and 3∶2, among which the center distance of the 2∶1 group was the shortest from the sham operation group, indicating that the ratio 2∶1 of Astragali Radix-Curcumae Rhizoma had the best intervention effect on colon cancer in mice, consistent with the commonly used clinical proportion. CA results showed that 11 groups of colon cancer mice were classified into 3 categories: Astragali Radix-Curcumae Rhizoma compatibility group, sham operation group and model group, which was consistent with the theory. The results of this study provide a basis for more effective clinical application of Astragali Radix-Curcumae Rhizoma in the treatment of colon cancer, and provide new ideas for the development of classic drug pairs.
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Animals , Mice , Astragalus Plant , Colonic Neoplasms/drug therapy , Drugs, Chinese Herbal , Plant Roots , RhizomeABSTRACT
The aim of this paper was to observe the effect of salvianolic acid B(Sal B) on high-glucose induced renal tubular epithelial-mesenchymal transition(EMT) in rats, and to explore its possible mechanisms of prevention and treatment of diabetic nephropathy. The rat renal tubular epithelial NRK-52 E cells were cultured in vitro. The cells were divided into control group, high glucose group, high glucose+10 μmol·L~(-1)Sal B group(Sal B), the above 3 groups were set at 6, 12, 24 and 48 h for dynamic observation; high glucose+Sal B different concentration(1, 5, 10 μmol·L~(-1)) groups, high glucose+5.0 μmol·L~(-1) pioglitazone group, high glucose+10 μmol·L~(-1)Sal B+5 μmol·L~(-1)GW9662 group. The protein expression levels of PPARγ, PTEN, α-SMA, E-cadherin and PI3 K/Akt signaling molecules were determined by Western blot. The mRNA expression of PPARγ and PTEN were detected by Real-time PCR. The viabi-lity of NRK52 E cells was determined by MTT assay. The results showed that as compared with control group, the mRNA and protein expression levels of PPARγ and PTEN in high glucose group gradually reduced, the protein expression levels of α-SMA and p-Akt~((Thr308))gradually increased, and the protein expression of E-cadherin gradually reduced(P<0.05). As compared with high glucose group, when increases in Sal B doses, the mRNA and protein expression levels of PPARγ, PTEN in high glucose + different concentrations of Sal B groups gradually increased, the protein expression levels of α-SMA and p-Akt~((Thr308)) gradually reduced, and the protein expression of E-cadherin gradually increased(P<0.05), however, the effect of 1 μmol·L~(-1)concentration of Sal B on the expression of PPARγ mRNA and protein and PTEN mRNA was not significantly different. As compared with high glucose group, the mRNA and protein expression levels of PPARγ mRNA(except 6 h) and protein(except 6 h), PTEN mRNA(except 6 h) and protein(except 6, 12 h) kept increasing, the protein expression levels of α-SMA and p-Akt~((Thr308))(except 6 h) continued to reduce, the protein expression of E-cadherin kept increasing in high glucose+10 μmol·L~(-1) Sal B dynamic observation group(P<0.05). As compared with high glucose group, Sal B and the pioglitazone(PIO) can greatly enhance the expression of PPARγ, PTEN at mRNA and protein levels, enhance the expression of E-cadherin at protein levels, and reduce the expression of α-SMA, p-Akt~((Thr308))protein level(P<0.05), there was no significant difference between the two groups. However, the expression levels of PPARγ and PTEN mRNA and protein, E-cadherin, α-SMA and p-Akt(Thr308) protein in the Sal B+GW9662 control group were not statistically significant compared with the high glucose group. The effect of Sal B was blocked by the PPARγ antagonist GW9662. It can be concluded that Sal B can suppress the NRK52 E cells induced by high-glucose EMT. The mechanism may be related to the activation of PPARγ with Sal B, and the up-regulation of PTEN expression, and thereby inhibiting the fibrosis effect of PI3 K/Akt signaling pathway.
Subject(s)
Animals , Rats , Benzofurans , Epithelial Cells , Epithelial-Mesenchymal Transition , Glucose , Transforming Growth Factor beta1ABSTRACT
Objective:To evaluate the effect of nalbuphine combined with propofol for esophageal dilation with gastroscope in the pediatric patients.Methods:A total of 150 pediatric patients with esophageal stenosis, aged 6 months-2 yr, weighing 6-15 kg, of American Society of Anesthesiologists physical status Ⅰ or Ⅱ, scheduled for elective painless balloon dilation with gastroscope under general anesthesia, were randomized into 3 groups ( n=50 each) according to the random number table method: nalbuphine 0.1 mg/kg plus propofol group (N 1P group), nalbuphine 0.2 mg/kg plus propofol group (N 2P group), and fentanyl plus propofol group (FP group). Nalbuphine 0.1 and 0.2 mg/kg and fentanyl 1 μg/kg were intravenously injected in N 1P, N 2P and FP groups, respectively, and 2 min later propofol 1.5-2.0 mg/kg was intravenously injected for sedation until the eyelash reflex disappeared in the three groups.Propofol 1.0 mg/kg was added when body movement occurred during surgery.The amount of propofol consumed during surgery, occurrence of body movement and respiratory depression, occurrence of adverse reactions such as postoperative nausea and vomiting, and laryngospasm, emergence time, Face Legs Activity Cry Consolability (FLACC) pain scale score and surgeons′ satisfaction were recorded. Results:Compared with group N 1P, the consumption of propofol, body movement classification ratio and FLACC score were significantly decreased, and the emergence time was shortened in group N 2P ( P<0.05), and no significant change was found in the parameters mentioned above in group FP ( P>0.05). There was no significant difference in the incidence of perioperative adverse reactions and degree of surgeons′ satisfaction among the three groups ( P>0.05). Conclusion:Nalbuphine combined with propofol can provide satisfactory anesthetic efficacy with fewer adverse reactions when used for esophageal dilation with gastroscope in the pediatric patients.
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Objective To analyze the visual acuity and refractive status of kindergarten children and primary and middle school students in Xinhong Community of Shanghai from 2015 to 2018, and to provide basis and reference for the prevention and control of students' myopia. Methods The data of 3 904 person-times of complete visual acuity and refraction records from 2015 to 2018 was derived from the "Shanghai Residents' Eye Health Information Service System". Results From 2015-2018, the total detection rate of poor vision of kindergarten children and primary and middle school students was 60.86%, and the detection rate of poor vision in kindergarten, primary school and middle school was 29.90%,62.63% and 87.26% respectively,showing an increasing trend with the education stage (χ2=727.206,P2=19.949, P2=1099.978, P<0.05). In terms of growth rate, the increase in myopia in the first grade of primary school was the largest. Conclusion The myopia rate of primary and secondary school students was higher than that of kindergarten children, and showed an increasing trend with the education stage. The critical period of myopia prevention and control should be advanced to the kindergarten stage.
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Bexarotene is a synthetic analogue of retinoic acid and exerts protective effects on the nervous system. However, low bioavailability and poor solubility of the crystal type I form severely limits the application of bexarotene in the clinic. A co-amorphous sample of bexarotene-PVP-K30 was prepared and the structure was characterized by X-ray diffraction and infrared spectroscopy. To determine the pharmacokinetics and tissue distribution of bexarotene, an LC-MS method was established to profile and quantify bexarotene in plasma and tissues of SD rats. In vitro dissolution indicated that the co-amorphous form improved the dissolution of bexarotene in pure water 4.17-fold. After rats were orally administered bexarotene or bexarotene-PVP-K30 co-amorphous (equivalent to 30 mg·kg-1 bexarotene) the AUC of bexarotene was 7 034.89 and 10 174.03 μg·L-1·h respectively, the peak time was advanced from 7.33 h to 0.9 h with the amorphous form, and Cmax was enhanced from 627.76 to 3 011.88 μg·L-1. The co-amorphous form yielded higher concentrations of bexarotene in various tissues, especially brain, liver and kidney. Animal welfare and experimental procedures complied with the rules of the Animal Ethics Committee of the Institute of Materia Medica, Chinese Academy of Medical Sciences. The results indicate that bexarotene-PVP-K30 co-amorphous improves the pharmacokinetic characteristics of bexarotene and provides preclinical data in support of bexarotene-PVP-K30 for the treatment of brain diseases.
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OBJECTIVE:To investigate the effects o f pioglitazone (PIO)on high glucose-induced epithelial-mesenchymal transition(EMT)in renal tubular epithelial cells of rat and its possible mechanism ,and to provide theoretic reference and new target for the prevention and treatment of diabetic nephropathy. METHODS :The rat renal tubular epithelial NRK- 52E cells were randomly divided into control group (5.5 mmol/L glucose ),high-glucose group (30 mmol/L glucose ),PIO intervention group (30 mmol/L glucose+ 5.0 μmol/L PIO),GW9662 intervention group (30 mmol/L glucose+ 5.0 μmol/L PIO+5.0 μmol/L specific anta- gonist GW 9662). The cells of the first 3 groups were detected at 6,12,24,48 h of culture ,while those in GW 9662 intervention group were detected at 48 h of culture. mRNA expression of PTEN and PPARγ were detected by real-time PCR. The protein expression of PTEN ,PPARγ,α-SMA and E-cadherin as well as the changes of PI 3K/AKT signaling pathway were determined by Western blotting assay. RESULTS :With the extension of culture time ,compared with control group ,the mRNA and protein expression of PPARγ(except for protein expression at 6 h)and PTEN in high-glucose group reduced significantly ,while the protein expression of α-SMA and p-AKT (Thr308)increased significantly ,and the protein expression of E-cadherin reduced significantly (P<0.05),showing time-dependent trend. Compared with high-glucose group ,the mRNA and the protein expression (except for 6 h) of PPAR γ and PTEN were increased significantly in PIO intervention group , while the protein expression of α-SMA and p-AKT (Thr308) were decreased significantly,and the protein expression of E-cadherin wasincreased significantly (P<0.05), showing time-dependent trend. There was no statistical significance in mRNA and protein expression of PPAR γ and PTEN,protein expression of E-cadherin ,α-SMA and p-AKT (Thr308) between GW 9662 intervention group and high-glucose group ;the effect of PIO was blocked by PPAR γ antagonist GW9662. CONCLUSIONS :PIO may up-regulate the expression of PTEN by activating PPARγ,inhibit PI 3K/AKT signaling pathway so as to inhibit the occurrence of EMT of renal tubular epithelial cells .
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BACKGROUND@#Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), such as erlotinib and gefitinib, are widely used to treat non-small cell lung cancer (NSCLC). However, acquired resistance is unavoidable, impairing the anti-tumor effects of EGFR-TKIs. It is reported that histone deacetylase (HDAC) inhibitors could enhance the anti-tumor effects of other antineoplastic agents and radiotherapy. However, whether the HDAC inhibitor suberoylanilide hydroxamic acid (SAHA) can overcome erlotinib-acquired resistance is not fully clear.@*METHODS@#An erlotinib-resistant PC-9/ER cell line was established through cell maintenance in a series of erlotinib-containing cultures. NSCLC cells were co-cultured with SAHA, erlotinib, or their combination, and then the viability of cells was measured by the 3-(4,5-Dimethyl thiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay and apoptosis was determined by flow cytometry and western blotting. Finally, the expression of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) was assessed by western blotting.@*RESULTS@#The half-maximal inhibitory concentration of parental PC-9 cells was significantly lower than the established erlotinib-acquired resistant PC-9/ER cell line. PC-9/ER cells demonstrated reduced expression of PTEN compared with PC-9 and H1975 cells, and the combination of SAHA and erlotinib significantly inhibited cell growth and increased apoptosis in both PC-9/ER and H1975 cells. Furthermore, treating PC-9/ER cells with SAHA or SAHA combined with erlotinib significantly upregulated the expression of PTEN mRNA and protein compared with erlotinib treatment alone.@*CONCLUSIONS@#PTEN deletion is closely related to acquired resistance to EGFR-TKIs, and treatment with the combination of SAHA and erlotinib showed a greater inhibitory effect on NSCLC cells than single-drug therapy. SAHA enhances the suppressive effects of erlotinib in lung cancer cells, increasing cellular apoptosis and PTEN expression. SAHA can be a potential adjuvant to erlotinib treatment, and thus, can improve the efficacy of NSCLC therapy.
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Objective To observe the change of expression of WNT4/β-catenin signaling pathway and its inhibitory factor secreted frizzled-related protein 1 (SFRP1) in renal tissue in diabetic nephropathy(DN) rats, and to explore its possible role in the development of renal fibrosis. Methods Rats were randomly divided into normal control(NC) group and DN group, and equipped with 8 in each group. The IDDM model was prepared by tail vein injection of STZ 55 mg/kg. Hemotoxyin and eosin、Periodic Acid-Schiff and Masson stain were used to observe the morphological structure and fibrotic lesions in renal tissue;Immunohistochemical analysis was used to observe the protein expression of WNT4 and β-catenin in renal tissue;Western blot was used to detect the protein expression changes of WNT4, SFRP1, β-catenin, p-GSK-3β, GSK-3β, Collagenl, a-SMA, E-cadherin in renal tissue in each group;The mRNA expression of WNT4 and SFRPl in renal tissues of rat was detected by realtime PCR. Results Compared with NC group, renal tissue fibrosis was obvious in DN group. Compared with NC group, the protein and mRNA expressions of WNT4 significantly increased (P<0.05), the protein expressions of β-catenin, p-GSK-3β, α-SMA and collagen I significantly increased (P < 0.05), the protein expressions of Ecadherin significantly decreased (P<0. 05), the protein and mRNA expression of SFRPl significantly decreased (P<0.05). Conclusions In the case of DN, the signal pathway of WNT4/β-catenin is abnormal activation. The expression of SFRPl is decreased, and that may inhibit this pathway and promote the development of renal fibrosis in DN.
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AIM:To describe the outcomes of corneal stromal lenticules in repairing of corneal ulcer and/or perforation.METHODS:This was a retrospective chart review of 6 eyes of 6 patients from January to June 2017,who underwent corneal ulcer repair with the corneal,stromal lenticules harvested from femtosecond laser refractive surgery and kept in pure glycerin for use.Three cases of infectious corneal ulcers were bacterial,fungal,and infection with foreign bodies in corneal deep layer,one each.The other 3 were corneal ulcer perforation.Making sure no air bubble between donor graft and Descemet membrane.The mean follow-up time was 3.71 ±1.56mo (range 1-6mo).RESULTS:All eyes were successfully treated under control of infection without intra-operative complications,and early postoperative evaluation showed a clear graft in all cases.The last follow-up visit showed the mean best corrected visual acuity (VA) significantly improved after surgery.There was significant difference from 0.48±0.12 to 1.50±0.08 (P<0.01).CONCLUSION:The preliminary results suggest that the use of corneal stromal lenticules may be a safe and effective surgical alternative for corneal ulcer,even though the long-term outcome of the graft needs to be further observed.