Advances in antitumor research of bifunctional small molecule inhibitors targeting heat shock protein 90 / 药学学报

The heat shock protein 90 (Hsp90) protein family is a cluster of highly conserved molecules that play an important role in maintaining cellular homeostasis. Hsp90 and its co-chaperones regulate a variety of pathways and cellular functions, such as cell growth, cell cycle control and apoptosis. Hsp90 is closely associated with the occurrence and development of tumors and other diseases, making it an attractive target for cancer therapeutics. Inhibition of Hsp90 expression can affect multiple oncogenic pathways simultaneously. Most Hsp90 small molecule inhibitors are in clinical trials due to their low efficacy, toxicity or drug resistance, but they have obvious synergistic anti-tumor effect when used with histone deacetylase (HDAC) inhibitors, tubulin inhibitors or topoisomerase II (Topo II) inhibitors. To address this issue, the design of Hsp90 dual-target inhibitors can improve efficacy and reduce drug resistance, making it an effective tumor treatment strategy. In this paper, the domain and biological function of Hsp90 are briefly introduced, and the design, discovery and structure-activity relationship of Hsp90 dual inhibitors are discussed, in order to provide reference for the discovery of novel Hsp90 dual inhibitors and clinical drug research from the perspective of medicinal chemistry.

Twelve family members with tetramine poisoning after consumption of vegetables grown in polluted soils / 世界急诊医学杂志（英文）

@#The main toxic component of tetramine is tetramethylenedisulfotetramine (TETS). It is a sulfonamide derivative without special antidote, tasteless and tasteless, with high toxicity and high mortality.[1]It was first discovered by a German scientist Hagen in 1949. Although its use has been banned worldwide due to its high toxicity and mortality rate, it is still available in certain countries and has led to cases of intentional and unintentional poisoning. Tetramine blocks γ-neurons, leading to dizziness, fatigue, nausea, vomiting, convulsions, and other symptoms.[2-4]Due to the lack of recognized effective antidotes, many poisoned people suffocate and die as a result of continuous spasms of the respiratory muscles.[5-7] Tetramine poisoning sometimes occurs, but it is rare for vegetables grown in tetramine-contaminated soil to cause group poisoning after being eaten.

Diurnal differences in acute gout attacks: A clinical study of male gout patients / 北京大学学报(医学版)

OBJECTIVE@#To observe the diurnal difference of acute gout attacks in men, and provide reference for accurate clinical prevention and treatment.@*METHODS@#Using a single-center, cross-sectional study design, the patients diagnosed with gout in the outpatient department of Rheumatology and Immuno-logy of PLA Joint Logistic Support Force No.980 Hospital from October 2021 to April 2022 were selected. The information about the patient's current/last acute gout attacks (less than 2 weeks from visit), date and time of attacks, joint symptoms and signs, medication use, and relevant biochemical tests on the day of visit was recorded. The diurnal time difference of acute gout attacks in male patients was analyzed, and univariate comparison and multivariate Logistic regression analyses were conducted to compare the diurnal difference of acute gout attacks with clinical characteristics and biochemical indicators.@*RESULTS@#A total of 100 male gout patients were included, and 100 acute attacks were recorded. Diurnal distribution of acute gout attacks: morning (6:00~11:59, 18, 18%), afternoon (12:00~17:59, 11, 11%), the first half of the night (18:00~23:59, 22, 22%), the second half of the night (0:00~05:59, 49, 49%); During the day (included morning and afternoon, 29, 29%) and at night (included the first half of the night and the second half of the night, 71, 71%). The rate of acute gout attack was significantly higher at night than in the day (about 2.5 ∶1). No matter the first or recurrent gout, no matter the duration of the disease, the number of acute gout attacks had the difference of less in the day and more in the night. Serum urate (SU) level was higher in the patients with nocturnal attack than in those with daytime attack (P=0.044). Comorbidities were significantly different in the day-night ratio of the number of acute gout attack (P=0.028). Multiple Logistic regression analysis showed that SU level (OR=1.005, 95%CI: 1.001-1.009) and comorbidities (OR=3.812, 95%CI: 1.443-10.144) were the correlative factors of nocturnal acute gout attacks.@*CONCLUSION@#No matter the first or recurrent gout, no matter the duration of the disease, it has a diurnal variation characterized by multiple attacks at night, increased SU level and comorbidities are correlative factors for nocturnal acute attack of gout.

Recent advances of DJ-1 regulating mitochondrial function / 中国药理学通报

Dj-l is a protein encoded by PARK7 gene, a member of the peptidase C56 protein family. Defects in PARK7 gene may lead to autosomal recessive early-onset Parkinson ' s disease. Dj-1 is a multifunctional protein that acts as an active androgen receptor-mediated transcriptional regulator, a REDOX sensitive molecular chaperone, an oxidative stress sensor, and it also protects neurons from oxidative stress and cell death. In addition, DJ-1 is also associated with mitochondria, energy metabolism, mitochondrial homeostasis, mitophagy mitochondria-associated endoplasmic reticulum membranes and other life processes. However, the precise function of DJ-1 protein is not well understood. This paper reviews the effect, mechanism and molecular basis of DJ-1 protein in regulating mitochondrial function, and discusses its potential value in combination with clinical diseases. It has good timeliness, necessity, innovation and science, and also helps to provide new targets and ideas for clinical drug development.

Application of the small private online course-based blended teaching model in Human Parasitology teaching / 中国血吸虫病防治杂志

Small private online course (SPOC), an emerging network-based, student-centered blended teaching model, combines the advantages of online teaching and flipped classroom, aiming to effectively improve students’ autonomous learning ability and learning efficiency. Considering a remarkable decline in the course of Human Parasitology, we built an SPOC-based blended teaching model for Human Parasitology, covering pre-course learning, intra-course leaning, post-course consolidation and evaluation, and such a model was applied among grade 2019 students with specialty of clinical medicine. Following the application of the SPOC-based blended teaching model, most students had improvements in autonomous learning ability and activity, and understanding of human parasitology knowledge, and the examination score disparity was avoided.

Advances in application of metabolomics techniques to diagnosis and treatment of rheumatoid arthritis / 中国药理学通报

Rheumatoid arthritis (RA) is a chronic autoimmune disease with a high disability rate and unknown etiology.Early diagnosis and early treatment are essential to prevent the further development of the disease.In reeent years, metabolomics teeh- niques have been widely used in various fields of life sciences because of its wholism, dynamics, high sensitivity and high throughput.This artiele reviews the progress of metabolomics technology in various aspects of RA investigations sueh as early diagnosis, disease classification as well as drug efficacy prediction in order to provide new ideas for clinical diagnosis and treatment of RA from the metabolic perspective.

The total terpenoids of Celastrus aggravate DNA damage and induce apoptosis of gastric cancer cells by inhibiting Chk1 / 中国药理学通报

Aim To explore the inhibitory effect of the on gastric cancer cells from the perspective of DNA total terpenoids of Celastrus orbiculatus Thunb (TTC) damage response. Methods CCK-8 experiment was conducted to investigate the toxic effects of different concentrations

Significance of Dynamic Risk Assessment in the Follow-up of Non-distant Metastatic Differentiated Thyroid Cancer Patients with Intermediate and High Risk / 中国医学科学院学报

To tailor the subsequent treatment and follow-up strategy,this study dynamically assessed the response to initial therapy in non-distant metastatic differentiated thyroid cancer (DTC) patients with intermediate and high risk. A total of 184 non-distant metastatic DTC patients (intermediate-risk 111 cases and high-risk 73 cases) were retrospectively enrolled in this study. Based on the results of initial response assessment (6-12 months after initial therapy),patients were divided into two groups:excellent response (ER) group (=113) and non-excellent response (non-ER) group (=71). We compared the differences in clinicopathological features between these 2 groups and evaluated the changes of dynamic response to therapy at the initial and final assessments after initial therapy in all patients. Compared with the ER group,the non-ER group showed a larger tumor size (=2771.500,=0.000),higher proportion of extrathyroidal invasion (=4.070,=0.044),and higher preablative-stimulated thyroglobulin levels (=1367.500,=0.000). ER was achieved in 31% of patients in the initial non-ER group [including indeterminate response (IDR) and biochemical incomplete response (BIR)] at the final follow-up only by thyroid stimulating hormone (TSH) suppression therapy,among which 63.6% were with intermediate risk (especially the patients with IDR) and 36.4% at high risk. In addition,5.2%(6/113) of patients in the initial ER group were reassessed as IDR,BIR,or even structural incomplete response at the end of the follow-up (among which one patient developed into cervical lymph node recurrence,as confirmed by pathology);the TSH level in these patients fluctuated at 0.56-10.35 μIU/ml and was not corrected in time during the follow-up after initial therapy. Some of non-distant metastatic DTC patients with intermediate and high risks who presented initial non-ER may achieve ER only by TSH suppression therapy over time;in contrast,the patients presented initial ER may develop into non-ER without normalized TSH suppression therapy. The dynamic risk assessment system may provide a real-time assessment of recurrence risk and tailor the subsequent treatment and follow-up strategies.

Effect of Traditional Chinese Medicine in Treatment of Lymphatic Metastasis of Gastric Cancer / 中国实验方剂学杂志

The incidence and mortality of gastric cancer are higher among all kinds of tumors, and the number of deaths due to gastric cancer in China is as high as 498 000.Because the pathogenesis of early gastric cancer is not obvious, most patients who have been treated in hospitals are already in middle and advanced stages of gastric cancer, which brings a heavy burden to families and the society. The postoperative survival of patients of advanced gastric cancer is significantly lower than those of early gastric cancer. The most important reason is lymphatic metastasis of gastric cancer. Lymphatic metastasis is the main metastasis pathway of gastric cancer. The lymphatic metastasis rate of progressive gastric cancer is as high as 70%, and early gastric cancer can also have lymphatic metastasis. The lymph node metastasis rate of gastric cancer was positively correlated with the infiltration depth of the tumor. In addition to surgical resection, lymphatic chemotherapy and molecular targeted therapies, traditional Chinese medicine(TCM) has also played an important role due to the advantages of a low toxicity, good therapeutic effect and low price. According to the theory of TCM, the occurrence of gastric cancer is caused by unclean diet, emotional disorders, and deficiencies, which result in phlegm, Qi resistance, blood stasis, and attack the stomach. The pathogenesis is the asthenia in origin and asthenia in superficiality, and clinical TCM therapies mostly focus on phlegm and blood stasis, spleen and Qi, warm and cold. In recent years, a number of studies have proved that TCM has a significant and effective effect in the treatment of lymphatic metastasis of gastric cancer. It may inhibit the anoikis and the tumor by inhibiting the hydrolysis of matrix metalloproteinase on the basement membrane and extracellular matrix (ECM), stimulating tumor anoikis, suppressing lymphatic neovascularization, regulating tumor-associated gene expression and other pathways, so as to treat lymphatic metastasis of gastric cancer. This article reviews the advance of theoretical research, experimental research and clinical research of TCM in the treatment of lymphatic metastasis of gastric cancer in recent years, and reveals the mechanism of TCM and its targets, in order to provide scientific basis for further studies and clinical application of the effect of TCM on the lymphatic metastasis of gastric cancer.

Emerging management and its impact on radioiodine refractory differentiated thyroid cancer / 中国实用外科杂志

Differentiated thyroid cancer(DTC) generally carries good prognosis through standard treatment. While,it could dedifferentiate into radioiodine refractory differentiated thyroid cancer(RAIR-DTC),which progresses rapidly with high mortality and limited treatment methods. Recently,along with the increasing of studies on genetic features,signal transduction pathways and immune microenvironment of RAIR-DTC,as well as the development of new radionuclide tracers,more theoretical bases have been provided for the targeted therapy of RAIR-DTC.

Celastrus orbiculatus Extracts Inhibit Human Hepatocellular Carcinoma Growth by Targeting mTOR Signaling Pathways / 中国结合医学杂志

OBJECTIVE@#To characterize the molecular mechanism underlying the antineoplastic activity of Celastrus orbiculatus Thunb. extracts (COE).@*METHODS@#The human hepatocellular carcinoma HepG2 cells with mammalian target of rapamycin (mTOR) knockdown expressed (HepG2/mTOR) were constructed using molecular biological technology. In vitro, the HepG2/mTOR cells were treated with COE at various concentrations (10, 20, 40, 80, 160 and 320 µ g/mL). Cell viability was determined using 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assays. According to the half-maximal inhibitory concentration (IC) value (140 mg/L), the concentrations of COE in the subsequent experiment was set to alleviate cytotoxicity. The HepG2/mTOR cells were divided into 5 groups: negative control (untreated), COE treatment groups (40, 80, 120 mg/L COE) and positive control group (cisplatin, DDP, 2 mg/L), respectively. Wild-type HepG2 cells were used as a blank control. The effects of COE on the cell apoptosis were analyzed by flow cytometry and transmission electronic microscopy (TEM), respectively. The protein expression levels of mTOR signal pathways were determined by Western blotting. In vivo, HepG2/mTOR cells (2 × 10 cell/mice) were subcutaneously injected into the right flank of nude mice. Thirty-six female nude mice were randomly assigned to 6 groups according to body weight (6 mice per group) as follows: solvent vehicle control, Banmao Capsule treated group (BM, 195 mg/kg), Tegafur, Gimeracil and Oteracil Potassium Capsules (10 mg/kg) treated group, and different dosages of COE (10, 20, 40 mg/kg) groups. Tumor growth was monitored and immunohistochemical staining was used to examine the expression of apoptosis-related proteins in tumor tissues.@*RESULTS@#COE inhibited the proliferation significantly in a concentration-dependent manner in HepG2/mTOR cells (P<0.01). COE significantly induced the apoptosis of HepG2/mTOR cells (P<0.01), and the apoptotic bodies can be observed under TEM. COE significantly inhibits the proteins expression of mTOR-related signal pathways. In vivo, COE significantly inhibited tumor growth in nude mice (P<0.01). Moreover, the results showed that COE down-regulated the expression of Bcl-2 and Bcl-xL, and up-regulated the levels of Bax and caspase-3 protein (P<0.01).@*CONCLUSION@#COE was a potential chemotherapeutic drug in HCC treatments via targeting mTOR signal pathway.

Extracts of Celastrus Orbiculatus Inhibit Cancer Metastasis by Down-regulating Epithelial-Mesenchymal Transition in Hypoxia-Induced Human Hepatocellular Carcinoma Cells / 中国结合医学杂志

OBJECTIVE@#To evaluate the effects of Celastrus Orbiculatus extracts (COE) on metastasis in hypoxia-induced hepatocellular carcinoma cells (HepG2) and to explore the underlying molecular mechanisms.@*METHODS@#The effect of COE (160, 200 and 240 µ g/mL) on cell viability, scratch-wound, invasion and migration were studied by 3-4,5-dimethyl-2-thiazolyl-2,5-diphenyl-2-H-tetrazolium bromide (MTT), scratch-wound and transwell assays, respectively. CoCl was used to establish a hypoxia model in vitro. Effects of COE on the expressions of E-cadherin, vimentin and N-cadherin were investigated with Western blot and immunofluorescence analysis, respectively.@*RESULTS@#COE inhibited proliferation and metastasis of hypoxia-induced hepatocellular carcinoma cells in a dose-dependent manner (P<0.01). Furthermore, the expression of epithelial-mesenchymal transition (EMT) related markers were also remarkably suppressed in a dose-dependent manner (P<0.01). In addition, the upstream signaling pathways, including the hypoxia-inducible factor 1 α (Hif-1 α) and Twist1 were suppressed by COE. Additionally, the Hif-1 α inhibitor 3-5'-hydroxymethyl-2'-furyl)-1-benzylindazole (YC-1), potently suppressed cell invasion and migration as well as expression of EMT in hypoxia-induced HepG2 cells. Similarly, the combined treatment with COE and YC-1 showed a synergistic effect (P<0.01) compared with the treatment with COE or YC-1 alone in hypoxia-induced HepG2 cells.@*CONCLUSIONS@#COE significantly inhibited the tumor metastasis and EMT by suppressing Hif-1 α/Twist1 signaling pathway in hypoxia-induced HepG2 cell. Thus, COE might have potential effect to inhibit the progression of HepG2 in the context of tumor hypoxia.

Bone marrow mesenchymal stem cells improve learning ability of the aging rat / 中国组织工程研究

BACKGROUND: At present, studies have shown that bone marrow mesenchymal stem cells (BMSCs) have self-renewal ability, which can be used as ideal seed cells for repairing tissue and organ damages caused by aging and lesions. OBJECTIVE: To study the changes in the levels of oxidation, inflammatory factors and neurotrophic factors (BDNF) in the brain of aging rats undergoing BMSCs transplantation, and to analyze the mechanism underlying the repair of learning and memory ability in the aging rats. METHODS: A total of 30 clean Sprague-Dawley rats were randomly divided into control group, model group and BMSCs group, 10 rats in each group. Aging models were made in the rats by 3-month subcutaneous injection of D-galactose. After modeling, BMSCs treatment was performed via tail vein injection in the BMSCs group.The injection was performed once a week,for 8 continuous weeks.Morris water maze was used to detect the learning and memory abilities of the rats in each group after the final injection of BMSCs. Superoxide dismutase activity in the brain tissue of rats was detected by xanthine oxidase method. Level of malondialdehyde in the rat brain tissue was detected by thiobarbituric acid method. Total antioxidant capacity of the brain tissue was detected by Fe3+reduction method. Real-time PCR and western blot assay were used to detect the expression of brain-derived neurotrophic factor mRNA and protein in the brain tissue of the aging rat, respectively. RESULTS AND CONCLUSION: Compared with the model group, the BMSCs group exhibited significantly higher activity of superoxide dismutase, stronger total antioxidant capacity, and higher levels of brain-derived neurotrophic factor mRNA and protein (P < 0.05), but the lower malondialdehyde level in the brain (P < 0.05). Compared with the model group, there was less time and higher frequency for passing through the platform in the BMSCs group (P < 0.05). Our findings further indicate that BMSCs can improve the abilities of learning and memory in aging rats, and the underlying mechanism is likely to improve antioxidant capacity and to regulate the level of brain-derived neurotrophic factors.

Effects of Osthole on Apoptosis of HL-60 Cells Induced by TRAIL and Its Related Mechanism / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To explore the effects of Osthole on apoptosis of HL-60 cells induced by tumor necrosis factor related apoptosis inducing ligand (TRAIL) and its possible mechanism.</p><p><b>METHODS</b>The proliferative inhibition of HL-60 cells treated with different concentrations of Osthole, TRAIL alone and Osthole combined with TRAIL was measured by MTT assay. The HL-60 cells were treated with Osthole, TRAIL alone and Osthole combined with TRAIL at the concentration<ICvalue, i.e. 100µmol/L for Osthole and 40 ng/ml for TRAIL. Apoptosis and mitochondrial membrane potential (MMP) of HL-60 cells were detected by flow cytometry; the mRNA expression of BCL-2, BAX and DR5 was determined by RT-PCR; and the levels of Caspase-3,-8,-9 activity were detected by spectrophotometry.</p><p><b>RESULTS</b>The combined treatment (100µmol/L Osthole + 40 ng/ml TRAIL) of HL-60 cells for 48 h induced an apoptotic rate of (33.9±2.7) %, which was significantly higher than that of cells treated with Osthole or TRAIL alone (P<0.05); at the same time, the combined treatment promoted the decrease of MMP and the expression rate of BCL-2/BAX, and potentiated the expression of DR5 and Caspase-3,-8,-9 activity.</p><p><b>CONCLUSION</b>Osthole can sensitize HL-60 cells to TRAIL-induced apoptosis, which may be related with the activation of mitochondrial pathways and up-regulation of DR5.</p>

Clinical Observations on Acupuncture Point Injection plus Wen Dan Decoction for Cervical Vertigo of Wind-phlegm Stagnation Type / 上海针灸杂志

Objective To investigate the clinical efficacy of acupuncture point injection plus Wen Dan decoction in treating cervical vertigo of wind-phlegm stagnation type. Method Sixty patients with cervical vertigo of wind-phlegm stagnation type were randomized to treatment and control groups, 30 cases each. The control group was treated with Betahistine mesilate tablets and the treatment group, acupuncture point injection plus Wen Dan decoction in addition. One course of treatment consisted of 14 days. The effects on cervical vertigo were evaluated after two courses of treatment. Result The total efficacy rate was 90.0% in the treatment group and 73.3% in the control group; there was a statistically significant difference between the two groups (P<0.05). Blood lipid levels, hemorheological indicators, and bilateral vertebral artery (VA) and basilar artery (BA) mean flow velocity were better in the treatment group than in the control group (P<0.05). Conclusion Acupuncture point injection plus Wen Dan decoction based on Betahistine mesilate tablets has clinically a better therapeutic effect on cervical vertigo of wind-phlegm stagnation type.

Evaluation of the Morphology and Function of Medial Collateral Ligament afterTotal Knee Arthroplasty with High-frequency Ultrasound / 中国医学科学院学报

Objective To explore the feasibility and clinical value of ultrasonography in evaluating the morphology and function of medial collateral ligaments (MCL) after total knee arthroplasty (TKA). Methods Totally 38 patients undergoing routine KTA (group A) and 22 patients undergoing constrained condylar knee arthroplasty KTA with MCL injury (group B) were included. Long axis views of MCL were taken and the MCL thickness was measured on femur side and tibial side 1 cm away from the joint line, respectively. The thicknesses were compared between the two groups. Subsequently, the gap between the metal part of the femoral prosthesis and the spacer after dynamic valgus stress was measured. The distribution and composition of the gap between the two groups were compared. Results High-frequency ultrasound clearly showed the prosthesis and MCL after TKA. MCL fiber structures of both groups were intact. The MCL thickness on the tibial side in group B was (0.25±0.06)cm, which was significantly thinner than group A [(0.32±0.14)cm] (t=2.12, P=0.040).For the femur side, there was no significant difference (t=1.65, P=0.110) between these two groups [(0.37±0.09) cm in group B versus (0.42±0.12)cm in group A]. Under the condition of valgus stress, the gaps between the metal part of the femoral prosthesis and the spacer could be found in 11 cases in group B but only in 1 case in group A. The proportion of gaps in group B was significantly higher than that in group A (Fisher's exact test, P=0.000). Conclusions High-frequency ultrasound can clearly show the prosthesis and MCL after TKA. The injured MCL can be well joined but the thickness is thinner. Under the condition of valgus stress of the knee, the stability of the TKA can be evaluated according to the gap between the prosthesis and the spacer.

Predictive factors for bone metastases of prostate cancer / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the correlation between a diverse of clinical factors and bone metastases of prostate cancer.</p><p><b>METHODS</b>The clinical data of 80 patients with prostate cancer were collected and analyzed. The correlations of age, alkaline phosphotase (ALP), prostate specific antigen (PSA), erythrocyte sedimentation rate (ESR), Gleason score, and expressions of androgen receptor (AR) and Ki-67 with bone metastases were analyzed by one-way ANOVA and Logistic regression analysis. The cutoff value, sensitivity and specificity of the independent correlation factors were calculated.</p><p><b>RESULTS</b>Forty-five of the 80 patients (56%) were found to have bone metastasis, who had significantly older age and higher levels of ALP, PSA, ESR, Gleason score, and expressions of AR and Ki-67 than those without bone metastasis (P<0.05). Logistic regression analysis identified PSA, Gleason score and AR expression as independent factors correlated with bone metastasis with OR (95% CI) of 1.005 (1.001, 1.009) (P=0.008), 5.356 (1.431, 20.039) (P=0.013), and 18.594 (2.460, 140.524) (P=0.005), respectively. The cutoff values of PSA, Gleason Score and AR were 67.1 ng/ml, 7.5, and 2.5, respectively; their sensitivities were 55.6%, 75.6%, and 84.0% for predicting bone metastasis with specificities of 97.1%, 82.9%, and 91.4%, respectively.</p><p><b>CONCLUSION</b>Of the factors analyzed, PSA, Gleason score and AR expression, but not age, ALP, PSA, ESR, or Ki-67 expression, are the predictive factors of bone metastasis of prostate cancer.</p>

Sensitization of human colon cancer HT-29 cells to TRAIL-induced apoptosis by gambognic acid / 药学学报

To investigate the effects of gambognic acid (GA) on TRAIL-induced apoptosis of cancer cells, human colon HT-29 cancer cells were treated with GA to promote apoptosis. Inhibition of the cell proliferation was measured with MTT assay and cell apoptosis was detected with formation of DNA ladders in agarose gel electrophoresis, and activation of caspase activity. The content of cytosolic reactive oxygen species (ROS) was measured with flow cytometry. The activities of Caspase-3, -8, -9 were detected using spectrophotometric assay. The levels of c-FLIP, CHOP, DR4 and DR5 in cells were tested by Western blot. Combination of GA (1 µg · mL(-1)) and TRAIL (40 ng · mL(-1)) significantly reduced proliferation and increased apoptosis of HT-29 cells over those induced by each agent alone. Percentage of apoptotic cells was increased to 45.5%. GA markedly enhanced the intracellular ROS generation. Expression of CHOP, DR4 and DR5 was up-regulated to 7.38, 5.41, and 4.85 times of the control group, respectively. GA promoted activation of Caspase-3, -8, and -9 by TRAIL (P<0.05). Furthermore, the expression of anti-apoptotic protein c-FLIP was down-regulated to 0.22 ± 0.08 times of the control group. In conclusion, GA sensitizes HT-29 cells to TRAIL-induced apoptosis by promoting ROS-activated ERS pathways, up-regulating of DR4 and DR5, and inhibiting c-FLIP expression.

Pathological changes in the sinoatrial node tissues of rats caused by pulsed microwave exposure / 生物医学与环境科学（英文）

To observe microwave induced dynamic pathological changes in the sinus nodes, wistar rats were exposed to 0, 5, 10, 50 mW/cm2 microwave. In 10 and 50 mW/cm2 groups, disorganized sinoatrial node cells, cell swelling, cytoplasmic condensation, nuclear pyknosis, and anachromasis, swollen, and empty mitochondria, and blurred and focally dissolved myofibrils could be detected from 1 to 28 d, while reduced parenchymal cells, increased collagen fibers, and extracellular matrix remodeling of interstitial cells were observed from 6 to 12 months. In conclusion, 10 and 50 mW/cm2 microwave could cause structural damages in the sinoatrial node and extracellular matrix remodeling in rats.