The regulatory role of E2F1 in prostate cancer / 药学学报

E2F transcription factor 1 (E2F1) is a major member of the E2F transcription factor family and participates in a wide range of physiological regulatory processes, such as cell cycle, survival, apoptosis, and metabolism. It is proved that the activity of E2F1 is related to the G1/S phase regulation of the cell cycle dependent on tumor suppressor retinoblastoma protein (RB). Recent studies have shown that E2F1 is highly expressed in prostate cancer cells, manifested as an oncogene, and its expression level is closely related to the occurrence, development, and poor clinical prognosis of prostate cancer. Androgen receptor (AR) is the main driving factor for the growth and progression of prostate cancer, and the changes of AR pathway play a key role in the pathological progression of prostate cancer. This article provide a systematic and comprehensive summary on recently published articles to review the role of the E2F1 pathway in prostate cancer.

The optimization and application of cell-based screening model for IL-17-mediated signaling pathway / 药学学报

We explore and verify the optimized condition for HEK-Blue IL-17 screening model, and screen the compounds that inhibits IL-17-medited signaling pathway. HEK-Blue IL-17 cells (5×104 cells per well) were seeded into the 96 plates followed by different concentrations of IL-17A or IL-17F alone, or in combination with tested compounds for 16 h. Then, the supernatant medium was incubated with QUANTI-Blue for 1 or 3 h to detect the OD value at λ655nm. The secreted alkaline phosphatase (SEAP) production was an index of IL-17-mediated signaling activation in HEK-Blue IL-17 cells. We found that both IL-17A and IL-17F can significantly activate the IL-17 signaling pathway in HEK-Blue IL-17 cells. The available dosage of IL-17A and IL-17F were 10 and 100 ng·mL-1, respectively. The reaction time of SEAP and QUANTI-Blue was 1 h. In this model, arctigenin and epigallocatechin gallate (EGCG) could inhibit the IL-17A and IL-17F-mediated signaling pathway. This established and optimized screening model of HEK-Blue IL-17 cells was suitable for screening inhibitors of IL-17-mediated signaling pathway.

Research progress of carnitine palmitoyltransferase 1in tumor immunotherapy / 药学学报

Carnitine palmitoyltransferase 1 (CPT1) is a fatty acid β-oxidative rate-limiting enzyme of fatty acid β-oxidation (FAO) present in the outer membrane of mitochondria, which is closely related to metabolic diseases and tumors. Numerous studies have shown that various subtypes of CPT1 are abnormally expressed in cancer cells and play an important role in resistance to metabolic stress. With the development of tumor immunotherapy, its role in immune cells and organs has also attracted attention. This article aims to review the biological functions of CPT1 and the role of different subtypes in tumor metabolism and immune regulation, and the research progress of its inhibitors, providing new ideas for cancer treatment.

Effects of Astragalus Polysaccharide on Osteoblastic Differentiation of Bone Mesenchymal Stem Cells Induced by X-ray Radiation / 中国中医药信息杂志

Objective To investigate the effects of astragalus polysaccharide (APS) on bone mesenchymal stem cells (BMSCs) to osteoblasts differentiation induced by X-rays; To discuss its mechanism of action. Methods CCK-8 method was used to select different concentrations of APS for the proliferation ability of BMSCs with 2 Gy X-ray radiation, and the best concentration was determined. Cells were divided into blank group, APS group, radiation group, radiation+APS group. APS group and radiation+APS group were given the best concentration of APS for 3 days, radiation group and radiation+APS group were given 2 Gy X-ray radiation. After radiation, 2 mL osteogenesis induced liquid was added in each group, every 3 day. After 15 day''s induction, inverting microscope was used to observe morphology, and alizarin red staining to detect the area of the calcium nodules in each group. Western blot was used to detect the specific marker protein osteopontin and osteocalcin expression of each group. Results Compared with the blank group, the proliferation ability of radiation group was obviously lower (P<0.05); compared with radiation group, the proliferation ability of radiation+APS significantly increased (P<0.05); the strongest promoting proliferation of APS was 50μg/mL, therefore, it was selected as the best concentration. In terms of morphology, inverted microscope showed that secretion of crystals of radiation group was obviously reduced compared with the blank group and APS group, and secretion of crystals of radiation+APS group was significantly elevated compared with radiation group. In osteogenesis ability, compared with the blank group, the cell calcium nodule area of APS group had a certain reduce, but the radiation group had a significantly reduced (P<0.05). Compared with the radiation group, the cell calcium nodule area of radiation+APS group obviously increased (P<0.05). In terms of osteogenesis specific marker protein expression, compared with the blank group, the expression of osteopontin of APS group was slightly declined, and the expression of osteocalcin was slightly elevated, but the expression of osteopontin and osteocalcin of radiation group was significantly lowered (P<0.05). Compared with the radiation group, the expression of osteopontin and osteocalcin of radiation+APS group was significantly higher (P<0.05). Conclusion APS has protective effects on osteoblastic differentiation ablility of BMSCs induced by X-ray radiation.

Protein kinase C activation induces platelet apoptosis / 中国实验血液学杂志

Platelet apoptosis elucidated by either physical or chemical compound or platelet storage occurs wildly, which might play important roles in controlling the numbers and functions of circulated platelets, or in the development of some platelet-related diseases. However, up to now, a little is known about the regulatory mechanisms of platelet apoptosis. Protein kinase C (PKC) is highly expressed in platelets and plays central roles in regulating platelet functions. Although there is evidence indicating that PKC is involved in the regulation of apoptosis of nucleated cells, it is still unclear whether PKC plays a role in platelet apoptosis. The aim of this study was to investigate the role of PKC in platelet apoptosis. The effects of PKC on mitochondrial membrane potential (ΔΨm), phosphatidylserine (PS) exposure, and caspase-3 activation of platelets were analyzed by flow cytometry and Western blot. The results showed that the ΔΨm depolarization in platelets was induced by PKC activator in time-dependent manner, and the caspase-3 activation in platelets was induced by PKC in concentration-dependent manner. However, the platelets incubated with PKC inhibitor did not results in ΔΨm depolarization and PS exposure. It is concluded that the PKC activation induces platelet apoptosis through influencing the mitochondrial functions and activating caspase 3. The finds suggest a novel mechanism for PKC in regulating platelet numbers and functions, which has important pathophysiological implications for thrombosis and hemostasis.

Endothelial progenitor cells with Alzheimer's disease / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Endothelial dysfunction is thought to be critical events in the pathogenesis of Alzheimer's disease (AD). Endothelial progenitor cells (EPCs) have provided insight into maintaining and repairing endothelial function. To study the relation between EPCs and AD, we explored the number of circulating EPCs in patients with AD.</p><p><b>METHODS</b>A total of 104 patients were recruited from both the outpatients and inpatients of the geriatric neurology department at General Hospital, Tianjin Medical University. Consecutive patients with newly diagnosed AD (n = 30), patients with vascular dementia (VaD, n = 34), and healthy elderly control subjects with normal cognition (n = 40) were enrolled after matching for age, gender, body mass index, medical history, current medication and Mini Mental State Examination. Middle cerebral artery flow velocity was examined with transcranial Doppler. Endothelial function was evaluated according to the level of EPCs, and peripheral blood EPCs was counted by flow cytometry.</p><p><b>RESULTS</b>There were no significant statistical differences of clinical data in AD, VaD and control groups (P > 0.05). The patients with AD showed decreased CD34-positive (CD34(+)) or CD133-positive (CD133(+)) levels compared to the control subjects, but there were no significant statistical differences in patients with AD. The patients with AD had significantly lower CD34(+)CD133(+) EPCs (CD34 and CD133 double positive endothelial progenitor cells) than the control subjects (P < 0.05). In the patients with AD, a lower CD34(+)CD133(+) EPCs count was independently associated with a lower Mini-Mental State Examination score (r = 0.514,P = 0.004). Patients with VaD also showed a significant decrease in CD34(+)CD133(+) EPCs levels, but this was not evidently associated with the Mini-Mental State Examination score. The changes of middle cerebral artery flow velocity were similar between AD and VaD. Middle cerebral artery flow velocity was decreased in the AD and VaD groups and significantly lower than the normal control group (P < 0.01). There was no significant difference of the blood flow velocity between the AD and VaD patients (P > 0.05).</p><p><b>CONCLUSIONS</b>The results provided evidence that patients with AD have reduced circulating EPCs. Endothelial function is impaired in patients with AD and vascular factors have a role in the pathogenesis of AD. CD34(+)CD133(+) EPCs may be a novel biomarker of AD dementia.</p>

The relationship between expression of ICAM-1 and VEGF-D in gastric cancer and its significance / 肿瘤

Objective: To investigate the relationship between intercellular adhesion molecule-1 (ICAM-1) and the signaling pathway of vascular endothelial growth factor receptor-3 (VEGFR-3) in gastric cancer and explore the mechanism underlying the lymphatic metastasis of gastric cancer. Methods: Totally 100 grastic cancer patients were recruited in the study including 13 cases of early gastric cancer and 87 cases of advanced gastric cancer with lymphatic metastasis (50 cases) and without lymphatic metastasis (37 cases). Thirty cases of normal gastric mucosa in the distance of > 5 cm from gastric cancer lesions were used as controls. The expressions of VEGF-C, VEGF-D, VEGFR-3, ICAM-1 and lymphatic microvessel density (LMVD) were detected using immunobistochemical method (EnVision™). The lymphatic and vascular invasions of gastric cancer were observed by microscopy. Results: The positive expression rate of ICAM-1 was increased with The increase in infiltration depth. It was 0% in the control, 7.7% in early stage gastric cancer, and 31.0% in advanced gastric cancer, respectively (P < 0.05). The positive rate of ICAM-1 expression was related with lymphatic metastasis (P < 0.005), depth of tumor invasion (P < 0.025), VEGF-C expression (P < 0.025), and VEGF-D expression (P < 0.005). Logistic regression analysis showed that the positive expression of ICAM-1 correlated with lymph node metastasis and expression of VEGF-D (P = 0.001 2, P = 0.023 7). Conclusion: ICAM-1 expression has positive correlation with expression of VEGF-D. The mechanism may be contributed to regulation of ICAM-1 expression by VEGF-D via VEGFR-2 signaling pathway.

HLA-DQB1 allele polymorphism and clinical characteristics of 15 familial myasthenia gravis cases in north China / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the relationship between the HLA-DQB1 allele polymorphisms and the clinical features of 15 familial myasthenia gravis (MG) cases in north China.</p><p><b>METHODS</b>By polymerase chain reaction-sequence specific primers (PCR-SSP), the HLA-DQB1 gene polymorphisms were determined in 64 MG patients (15 familial and 49 sporadic) and 52 healthy individuals as control group. The clinical characteristics of 15 familial MG patients and 49 sporadic were analyzed. The measurement data was analyzed by t test and enumeration data by chi-square test.</p><p><b>RESULTS</b>The frequency of DQB1*0501 was significantly increased in familial MG, especially in the ocular type, compared with sporadic MG (P<0.05, OR=3.08) and healthy controls (P<0.01, OR=4.439). Comparing with healthy controls, the frequency of DQB1*0301/4 was increased (P<0.05, OR=2.56), while the frequency of DQB1*0601 was significantly decreased (P<0.05, OR=0.33) in sporadic MG. The familial patients had an early age of disease onset, but less severity and good prognosis.</p><p><b>CONCLUSION</b>The familial MG has distinctive clinical features. DQB1*0501 allele is positively related to the genetic susceptibility to familial MG patients in north China, especially to the ocular type. DQB1*0301/4 allele is positively related to the pathogenesis of sporadic MG. DQB1*0601 may be a protecting allele for sporadic MG. The phenotype of MG may be the result of interaction of hereditary defects and environmental factors. The familial MG may be different from sporadic patients in genetic immune mechanism.</p>