Gloss Prior Guided Visual Feature Learning for Continuous Sign Language Recognition.

Continuous sign language recognition (CSLR) is to recognize the glosses in a sign language video. Enhancing the generalization ability of CSLR's visual feature extractor is a worthy area of investigation. In this paper, we model glosses as priors that help to learn more generalizable visual features. Specifically, the signer-invariant gloss feature is extracted by a pre-trained gloss BERT model. Then we design a gloss prior guidance network (GPGN). It contains a novel parallel densely-connected temporal feature extraction (PDC-TFE) module for multi-resolution visual feature extraction. The PDC-TFE captures the complex temporal patterns of the glosses. The pre-trained gloss feature guides the visual feature learning through a cross-modality matching loss. We propose to formulate the cross-modality feature matching into a regularized optimal transport problem, it can be efficiently solved by a variant of the Sinkhorn algorithm. The GPGN parameters are learned by optimizing a weighted sum of the cross-modality matching loss and CTC loss. The experiment results on German and Chinese sign language benchmarks demonstrate that the proposed GPGN achieves competitive performance. The ablation study verifies the effectiveness of several critical components of the GPGN. Furthermore, the proposed pre-trained gloss BERT model and cross-modality matching can be seamlessly integrated into other RGB-cue-based CSLR methods as plug-and-play formulations to enhance the generalization ability of the visual feature extractor.

Sulfonated Perylene as Three-in-One STING Agonist for Cancer Chemo-Immunotherapy.

Activation of stimulator of interferon genes (STING) by cyclic dinucleotides (CDNs) has been considered as a powerful immunotherapy strategy. While promising, the clinical translation of CDNs is still overwhelmed by its limited biostability and the resulting systemic immunotoxicity. Being differentiating from current application of exogenous CDNs to address these challenges, we herein developed one perylene STING agonist PDIC-NS, which not only promotes the production of endogenous CDNs but also inhibits its hydrolysis. More significantly, PDIC-NS can well reach lung-selective enrichment, and thus mitigates the systemic immunotoxicity upon intravenous administration. As a result, PDIC-NS had realized remarkable in vivo antitumor activity, and backward verified on STING knock out mice. Overall, this study states that PDIC-NS can function as three-in-one small-molecule STING agonist characterized by promoting the content and biostability of endogenous CDNs as well as possessing good tissue specificity, and hence presents an innovative strategy and platform for tumor chemo-immunotherapy.

Learning Self-Corrective Network via Adaptive Self-Labeling and Dynamic NMS for High-Performance Long-Term Tracking.

This article presents a self-corrective network-based long-term tracker (SCLT) including a self-modulated tracking reliability evaluator (STRE) and a self-adjusting proposal postprocessor (SPPP). The targets in the long-term sequences often suffer from severe appearance variations. Existing long-term trackers often online update their models to adapt the variations, but the inaccurate tracking results introduce cumulative error into the updated model that may cause severe drift issue. To this end, a robust long-term tracker should have the self-corrective capability that can judge whether the tracking result is reliable or not, and then it is able to recapture the target when severe drift happens caused by serious challenges (e.g., full occlusion and out-of-view). To address the first issue, the STRE designs an effective tracking reliability classifier that is built on a modulation subnetwork. The classifier is trained using the samples with pseudo labels generated by an adaptive self-labeling strategy. The adaptive self-labeling can automatically label the hard negative samples that are often neglected in existing trackers according to the statistical characteristics of target state, and the network modulation mechanism can guide the backbone network to learn more discriminative features without extra training data. To address the second issue, after the STRE has been triggered, the SPPP follows it with a dynamic NMS to recapture the target in time and accurately. In addition, the STRE and the SPPP demonstrate good transportability ability, and their performance is improved when combined with multiple baselines. Compared to the commonly used greedy NMS, the proposed dynamic NMS leverages an adaptive strategy to effectively handle the different conditions of in view and out of view, thereby being able to select the most probable object box that is essential to accurately online update the basic tracker. Extensive evaluations on four large-scale and challenging benchmark datasets including VOT2021LT, OxUvALT, TLP, and LaSOT demonstrate superiority of the proposed SCLT to a variety of state-of-the-art long-term trackers in terms of all measures. Source codes and demos can be found at https://github.com/TJUT-CV/SCLT.

Heterophyllin B ameliorates gastric cancer tumor growth through activating ER stress.

BACKGROUND: Gastric cancer (GC) is the third leading cause of cancer-related death worldwide. Heterophyllin B (HB) has been proved to be a potential drug in cancer treatment. METHODS: In the current study, GC cells were treated with 0, 10, 25, or 50 µM of HB. Cell viability was determined by utilizing MTT assay. Flow cytometry was carried out for cell apoptosis and cell cycle analysis. The expression levels of IRE1, CHOP, GRP78 and Bcl-2 in cells and tumors were measured by Western blot and immunohistochemistry, respectively. RESULTS: Our data uncovered that HB administration significantly suppressed GC cell viability, but facilitated GC cell apoptosis and cell cycle arrest at G0/G1 phase. The effects of HB on GC cell proliferation, apoptosis and cell cycle showed dosage-dependent manner. Furthermore, expression of ER stress-associated proteins like IRE1, CHOP and GRP78 was markedly upregulated, while anti-apoptosis protein Bcl2 expression was inhibited by HB treatment in a dosage-dependent manner. Our data indicated that HB treatment facilitated caspase-3 expression in a dose-dependent manner, but had no effect on caspase-8 expression. Importantly, the inhibition of HB to GC cell apoptosis and cell cycle process and the promotion of HB to GC cell proliferation were partly rescued by inhibition of ER stress utilizing 4-PBA. In animal experiments, HB administration suppressed GC tumor growth, boosted IRE1, CHOP and GRP78 expression and inhibited Bcl-2 expression. CONCLUSION: All in all, HB treatment could effectively suppress GC cells proliferation and tumors growth and facilitate GC cells apoptosis and cell cycle arrest through activating ER stress. Our data indicated that HB may be a potential drug for GC treatment.

Analysis of the typing of adenovirus and its clinical characteristics in children with acute respiratory tract infection.

BACKGROUND: The purpose of this study was to investigate the typing of adenovirus (AdV) infection in children hospitalized with acute respiratory tract infection (ARTI) and its clinical characteristics. METHODS: Samples from 7832 hospitalized children with ARTIs from January 2021 to June 2022 were tested by multiplex PCR for AdV. AdV hex neighborhood genes were amplified and sequenced for typing by nested PCR. RESULTS: Three hundred twenty-eight cases were positive for AdV with rate of 4.48% (328/7832). No statistical difference in the rate of AdV detection was observed in different ages (P > 0.05). Among the 328 cases, 305 cases underwent amplification and sequence determination of AdV five-neighborhood, six-neighborhood and fibronectin genes. Only 237 cases were sequenced successfully for all 3 genetic fragments. The typing results of 231 cases with 3 genes were consistent, with 49.78% (115/231) of type 3, 41.56% (96/231) of type 7 and 8.66% (20/231) of other types identified. The main clinical symptoms in 231 children hospitalized with ARTI who were AdV positive were cough, sputum not easily coughable, Wheezing or shortness of breath and fever. Clinical diagnoses of 231 cases included: acute bronchitis 3.03% (7/231), capillary bronchitis 16.45% (38/231), pneumonia (mild/severe) 76.62% (177/231) (68.40% (158/231) in mild and 8.23% (19/231) in severe cases), bronchial asthma combined with pulmonary infection 3.46% (8/231). Higher percentage of shortness of breath, multilobar infiltration, and pleural effusion were found in type 7. Calcitoninogen in type 7 were significantly higher than those of type 3 and other types, and the white blood cell count was lower than those of type 3 and other types, and the difference was statistically significant (P < 0.05). CONCLUSION: AdV type 3 and 7 were frequently found in hospitalized children with acute lower respiratory tract involvement. AdV type 7 seems to be associated with more severe outcome.

Tetrandrine inhibits migration and invasion of BGC-823 and MKN-45 cells by regulating PI3K/AKT/mTOR signaling pathway.

Tetrandrine (Tet), a traditional Chinese herbal medicine extract, exhibits anti-cancer effect on many types of cancer. Nonetheless, the action mechanism of Tet in gastric cancer (GC) is still largely unclear. In the current study, proliferation, invasion, and migration of the BGC-823 and MKN-45 cells were effectively suppressed by Tet treatment in a dose-dependent manner. Moreover, Tet suppressed expression of the proliferation-associated protein PCNA, the interstitial cell phenotype N-cadherin, and the extracellular matrix-associated MMP-2 and MMP-9 in BGC-823 and MKN-45 cells in a dose-dependent manner. PI3K/AKT/mTOR, a cancer promoting signaling, was inactivated by Tet in a dose-dependent manner in BGC-823 and MKN-45 cells. Furthermore, our results demonstrated that the inhibition of Tet to PCNA, N-cadherin, MMP-2, and MMP-9 expression was partly rescuedby AKT inhibitor or mTOR inhibitor. In animal experiments, tumor growth was inhibited by Tet administration in a dose-dependent manner. In conclusion, the current data indicated that Tet had a critical effect on inhibiting BGC-823 and MKN-45 cells proliferation, migration, invasion, and tumor growth via regulating PI3K/AKT/mTOR signaling pathway, suggesting that Tet might be a potential treatment for GC.

DIMY: Enabling privacy-preserving contact tracing.

The infection rate of COVID-19 and the rapid mutation ability of the virus has forced governments and health authorities to adopt lockdowns, increased testing, and contact tracing to reduce the virus's spread. Digital contact tracing has become a supplement to the traditional manual contact tracing process. However, although several digital contact tracing apps are proposed and deployed, these have not been widely adopted due to apprehensions surrounding privacy and security. In this paper, we present a blockchain-based privacy-preserving contact tracing protocol,"Did I Meet You" (DIMY). The protocol provides full-lifecycle data privacy protection on the devices as well as the back-end servers to address most of the privacy concerns associated with existing protocols. We have employed Bloom filters to provide efficient privacy-preserving storage and have used the Diffie-Hellman key exchange for secret sharing among the participants. We show that DIMY provides resilience against many well-known attacks while introducing negligible overheads. DIMY's footprint on the storage space of clients' devices and back-end servers is also significantly lower than other similar state-of-the-art apps.

A randomized controlled trial on the effect of dietary guidance on the treatment of Henoch-Schonlein purpura in children.

The amino acid-based formulae were extensively added to diet of children for the treatment of Henoch-Schonlein purpura (HSP), and the nutrition and growth situation of children were evaluated after giving new dietary intervention. Patients were randomly divided into restricted diet group (n=30) and dietary guidance group (n=30). Besides, 30 cases with bronchiolitis who had normal diet were selected as the control group. The dietary questionnaire was designed to record the types and intakes of various foods taken by children every day, and the intake levels of nutrients were analyzed. Physical examination, biochemical analysis of blood and urine routine were carried out to evaluate the effect of dietary guidance on their growth and development. The results showed that restricted diet group had lower levels of nutrient intake and the actual/recommended percentage. However, overall nutrient intake level of the dietary guidance group was higher, basically equal to the recommended intake level. Besides, the actual intake and actual/recommended percentage of nutrients of dietary guidance group were significantly higher than those of restricted diet group (p<0.05). Dietary guidance can improve nutrients and protein intake of children with HSP, and reduce the relapse of rash and incidence of complications.

Hsa_circ_0054633 mediates apoptosis and insulin secretion in human pancreatic ß cells through miR-409-3p/caspase-8 axis.

BACKGROUND: CircRNAs are reported to be aberrantly expressed and perform biological functions in diverse processes. This study aimed to investigate the potential involvement of hsa_circ_0054633 in high glucose (HG)­induced diabetic model and its potential mechanism. METHODS: The expression of hsa_circ_0054633, miR-409-3p and caspase-8 was detected by real-time PCR and western blotting. Cell viability, apoptosis and the protein levels of apoptosis-related factors were revealed by CCK-8 colorimetry, flow cytometry and western blotting, respectively. Insulin secretion was determined by enzyme-linked immunosorbent assay (ELISA) and the measurement of insulin-related transcription factors. The target association between miR-409-3p and hsa_circ_0054633 or caspase-8 was confirmed by dual-luciferase reporter assays and biotin-based pulldown assay. RESULTS: Hsa_circ_0054633 was highly expressed and the expression of miR-409-3p was downregulated in serum of DM patients and HG-treated human pancreatic ß cell line NES2Y. Further investigation indicated that hsa_circ_0054633 suppression promoted cell proliferation, inhibited apoptosis and facilitated insulin secretion in HG-treated NES2Y cells. Mechanical analysis revealed that hsa_circ_0054633 regulated caspase-8 expression via sponging miR-409-3p. Rescue experiments demonstrated that miR-409-3p knockdown or caspase-8 overexpression reversed the effects of hsa_circ_0054633 in HG-stimulated NES2Y cells. CONCLUSION: Inhibition of hsa_circ_0054633 protected against HG-induced NES2Y cell apoptosis and impairment of insulin secretion by regulating miR-409-3p/caspase-8 axis.

Riemannian Spatio-Temporal Features of Locomotion for Individual Recognition.

Individual recognition based on skeletal sequence is a challenging computer vision task with multiple important applications, such as public security, human⁻computer interaction, and surveillance. However, much of the existing work usually fails to provide any explicit quantitative differences between different individuals. In this paper, we propose a novel 3D spatio-temporal geometric feature representation of locomotion on Riemannian manifold, which explicitly reveals the intrinsic differences between individuals. To this end, we construct mean sequence by aligning related motion sequences on the Riemannian manifold. The differences in respect to this mean sequence are modeled as spatial state descriptors. Subsequently, a temporal hierarchy of covariance are imposed on the state descriptors, making it a higher-order statistical spatio-temporal feature representation, showing unique biometric characteristics for individuals. Finally, we introduce a kernel metric learning method to improve the classification accuracy. We evaluated our method on two public databases: the CMU Mocap database and the UPCV Gait database. Furthermore, we also constructed a new database for evaluating running and analyzing two major influence factors of walking. As a result, the proposed approach achieves promising results in all experiments.

Emotion Recognition Based on Multichannel Physiological Signals with Comprehensive Nonlinear Processing.

Multichannel physiological datasets are usually nonlinear and separable in the field of emotion recognition. Many researchers have applied linear or partial nonlinear processing in feature reduction and classification, but these applications did not work well. Therefore, this paper proposed a comprehensive nonlinear method to solve this problem. On the one hand, as traditional feature reduction may cause the loss of significant amounts of feature information, Kernel Principal Component Analysis (KPCA) based on radial basis function (RBF) was introduced to map the data into a high-dimensional space, extract the nonlinear information of the features, and then reduce the dimension. This method can provide many features carrying information about the structure in the physiological dataset. On the other hand, considering its advantages of predictive power and feature selection from a large number of features, Gradient Boosting Decision Tree (GBDT) was used as a nonlinear ensemble classifier to improve the recognition accuracy. The comprehensive nonlinear processing method had a great performance on our physiological dataset. Classification accuracy of four emotions in 29 participants achieved 93.42%.

Adaptive Object Tracking via Multi-Angle Analysis Collaboration.

Although tracking research has achieved excellent performance in mathematical angles, it is still meaningful to analyze tracking problems from multiple perspectives. This motivation not only promotes the independence of tracking research but also increases the flexibility of practical applications. This paper presents a significant tracking framework based on the multi-dimensional state⁻action space reinforcement learning, termed as multi-angle analysis collaboration tracking (MACT). MACT is comprised of a basic tracking framework and a strategic framework which assists the former. Especially, the strategic framework is extensible and currently includes feature selection strategy (FSS) and movement trend strategy (MTS). These strategies are abstracted from the multi-angle analysis of tracking problems (observer's attention and object's motion). The content of the analysis corresponds to the specific actions in the multidimensional action space. Concretely, the tracker, regarded as an agent, is trained with Q-learning algorithm and ϵ -greedy exploration strategy, where we adopt a customized rewarding function to encourage robust object tracking. Numerous contrast experimental evaluations on the OTB50 benchmark demonstrate the effectiveness of the strategies and improvement in speed and accuracy of MACT tracker.

Ki-67 is overexpressed in human laryngeal carcinoma and contributes to the proliferation of HEp2 cells.

Ki-67 is one of the most useful markers to evaluate cell proliferative activity and has been widely used in tumor treatment and research. However, its role in human laryngeal carcinoma remains poorly defined. The aim of the present study was to investigate the expression of Ki-67 in human laryngeal squamous carcinoma and the effect of Ki-67 gene silencing by small interfering (si)RNA on the proliferation of human laryngocarcinoma HEp2 cells. Immunohistochemistry and reverse transcription-quantitative polymerase chain reaction were performed to examine the expression of Ki-67 in human laryngeal squamous carcinoma tissues and adjacent non-cancer tissues from 50 patients with laryngeal squamous carcinoma. RNA interference was used to knock down the expression of Ki-67 in the HEp2 cell line, and the proliferation of the treated cells was observed in vitro. Western blot analysis was used to determine the expression levels of epidermal growth factor receptor (EGFR) and E-cadherin in the treated cells. The expression of Ki-67 in the laryngeal squamous carcinoma tissues was significantly higher than that of the adjacent non-tumor tissues (P=0.028). The high expression of Ki-67 in cancer was significantly correlated with cervical lymph node metastasis and clinical outcomes (all P<0.001). The silencing of Ki-67 resulted in the inhibition of proliferation of the HEp2 human laryngocarcinoma cells (P<0.001). In addition, compared with the control group, the expression levels of EGFR and E-cadherin in the Ki-67 siRNA-treated cells were significantly decreased (P<0.001) and increased (P<0.001), respectively. These results suggested that Ki-67 is important in regulating the proliferation of human laryngocarcinoma HEp2 cells and that the mechanism may at least partially be associated with the upregulation of EGFR and the downregulation of E-cadherin. Overall, Ki-67 can be used as an important indicator for judging clinical progress and estimating prognosis in human laryngeal squamous carcinoma.

Early prophylactic anticoagulation for portal vein system thrombosis after splenectomy: A systematic review and meta-analysis.

A systematic review and meta-analysis were conducted to evaluate the efficacy and safety of early prophylactic anticoagulation for the prevention of portal vein system thrombosis (PVST) after splenectomy. A systematic search of the PubMed, EMBASE, Springer and Cochrane Library databases was performed to identify studies comparing the outcomes in patients receiving or not receiving regular prophylactic anticoagulation after splenectomy. The quality of the included studies was assessed using the Jadad Score and the Newcastle-Ottawa Scale. Heterogeneity was evaluated using the χ2 and I2 tests. The parameters that were analyzed included the incidence of PVST and anticoagulation-associated complications. A total of seven studies qualified for the review, involving 383 and 283 patients receiving or not receiving regular prophylactic anticoagulation, respectively. The incidence of PVST was significantly reduced with an odds ratio (OR) of 0.31 [95% confidence interval (CI), 0.21-0.46; P<0.00001] in the regular prophylactic anticoagulation group compared with the control group. No difference in the incidence of anticoagulation-associated complications was identified between the two groups (OR=0.60, 95% CI, 0.23-1.56; P=0.30). Early prophylactic anticoagulation was associated with a reduced incidence of PVST, although it was not associated with the incidence of anticoagulation-associated complications. These results indicate that prophylactic anticoagulation could be safely administered after splenectomy, even to cirrhotic patients.

Resveratrol Reduces the Incidence of Portal Vein System Thrombosis after Splenectomy in a Rat Fibrosis Model.

Purpose. To investigate the preventive effect of resveratrol (RES) on the formation of portal vein system thrombosis (PVST) in a rat fibrosis model. Methods. A total of 64 male SD rats, weighing 200-300 g, were divided into five groups: Sham operation, Splenectomy I, Splenectomy II, RES, and low molecular weight heparin (LMWH), with the former two groups as nonfibrosis controls. Blood samples were subjected to biochemical assays. Platelet apoptosis was measured by flow cytometry. All rats were euthanized for PVST detection one week after operation. Results. No PVST occurred in nonfibrosis controls. Compared to Splenectomy II, the incidences of PVST in RES and LMWH groups were significantly decreased (both p < 0.05). Two rats in LMWH group died before euthanasia due to intra-abdominal hemorrhage. In RES group, significant decreases in platelet aggregation, platelet radical oxygen species (ROS) production, and increase in platelet nitric oxide (NO) synthesis and platelet apoptosis were observed when compared with Splenectomy II (all p < 0.001), while in LMWH group only significant decrease in platelet aggregation was observed. Conclusion. Prophylactic application of RES could safely reduce the incidence of PVST after splenectomy in cirrhotic rat. Regulation of platelet function and induction of platelet apoptosis might be the underlying mechanisms.

Biological effects of ray cartilage extract on human breast cancer cell line MCF-7 and its mechanism.

OBJECTIVE: To explore the biological effects of ray cartilage extract (RCE) on human breast cancer cell line MCF-7 and its mechanism. METHODS: MCF-7 cells were treated with RCE of different concentrations for different durations, and then MCF-7 cell proliferation was evaluated with MTT test, cell cycle was detected with flow cytometer and the protein levels of cyclin D1 and p21 were determined with Western blot. RESULTS: MTT test indicated that MCF-7 cell proliferation was inhibited by RCE with an optimal inhibiting concentration of 10 µmol/L and an optimal action time of 48 h. Flow cytometer displayed that with the time prolongation of RCE action, the cells in S phase were significantly increased, but the cells in G2/M phase were significantly decreased; and MCF-7 apoptosis significantly increased as compared with blank control group (all P<0.05). Western blot found that with the time prolongation of RCE action, the level of cyclin D1 was significantly decreased, but the level of p21 was significantly increased as compared with blank control group (all P<0.05). CONCLUSION: RCE inhibits MCF-7 cell proliferation via arresting MCF-7 cell transformation from S phase to G2 phase. This may be associated with regulating the expressions of cyclin D1 and p21. RCE may be used as a drug for treatment of breast cancer in the future.

Activation of HIF-1 by metallothionein contributes to cardiac protection in the diabetic heart.

Metallothionein (MT) protects against heavy metal-induced cellular damage and may participate in other fundamental physiological and pathological processes, such as antioxidation, proliferation, and cell survival. Previously, we have shown that elevation of MT by transgene or by induction with zinc protects the heart against diabetic cardiomyopathy by mechanisms such as antidiabetes-induced oxidative stress and inactivation of glycogen synthase kinase-3, which mediates glucose metabolism. We also reported that MT overexpression rescued the diabetic-induced reduction of hypoxia-inducible factor (HIF)-1α, which plays an important role in glucose utilization and angiogenesis. Here, we showed that overexpression of MT increased hexokinase (HK)-II expression under control conditions and attenuated diabetes-decreased HK-II expression. Glycolytic flux assay demonstrated that MT increased glycolysis output in high glucose-containing media-cultured H9c2 cells. The diabetes-induced reduction in cardiac capillaries was also attenuated by MT overexpression. Furthermore, MT induction significantly increased HIF-1 expression under both control and diabetic conditions. Moreover, in the present study, we demonstrated that MT-enhanced HIF-1α activity is likely through a mechanism of protein nuclear translocation. These results suggest that MT induces HIF-1α expression, leading to increased HK-II in the diabetic heart.

SNP-induced apoptosis may be mediated with caspase inhibitor by JNK signaling pathways in rabbit articular chondrocytes.

NO plays an important role in cartilage destruction by inducing apoptosis of chondrocytes. Here we investigated the role of c-Jun N-terminal kinase (JNK) signal transduction pathways in the apoptosis induced by NO donor sodium nitroprusside (SNP) in rabbit articular chondrocytes. We used Annexin V-FITC/PI flow cytometry and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay (TUNEL) assay to detect apoptosis rate. The expressions of p38, NF-κB p65, caspase-3 and p53 genes at protein levels were measured by Western blotting assay. RT-PCR was performed to show the mRNA expression of caspase-3, and the activity of caspase-3 was also detected. To investigate the effect of JNK-specific inhibitor SP600125, chondrocytes were pretreated with SP600125 ahead of SNP treatment. Treatment with SNP accelerated apoptosis in a concentration dependent manner, while such acceleration was reduced by SP600125 pretreatment. Moreover, we found that SP600125 significantly decreased NO-induced NF-κB, p53, caspase-3 protein expressions and caspase-3 mRNA expression, as well as intracellular caspase-3 activity (P < 0.05). Collectively, these data suggest that JNK plays an important role through stimulating NF-κB, p53 and caspase-3 activation.

Trigonella foenum graecum seed extract protects kidney function and morphology in diabetic rats via its antioxidant activity.

Oxidative stress is involved in the development and progression of diabetic nephropathy (DN). Because Trigonella foenum graecum has been reported to have antidiabetic and antioxidative effects, we hypothesized that T foenum graecum seed aqueous extract (TE) restores the kidney function of diabetic rats via its antioxidant activity. Rats were fed diets enriched with sucrose (50%, wt/wt), lard (30%, wt/wt), and cholesterol (2.5%, wt/wt) for 8 weeks to induce insulin resistance. After a DN model was induced by streptozotocin, the rats were administered a low (440 mg/kg), medium (870 mg/kg), or high (1740 mg/kg) dose of TE by oral intragastric intubation for 6 weeks. In TE-treated DN rats, blood glucose, kidney/body weight ratio, serum creatinine, blood urea nitrogen, 24-hour content of urinary protein, and creatinine clearance were significantly decreased compared with nontreated DN rats. Diabetic rats showed decreased activities of superoxide dismutase and catalase, increased concentrations of malondialdehyde in the serum and kidney, and increased levels of 8-hydroxy-2'-deoxyguanosine in urine and renal cortex DNA. Treatment with TE restored the altered parameters in a dose-dependent manner. Furthermore, all of the ultramorphologic abnormalities in the kidney of diabetic rats, including the uneven thickening of the glomerular base membrane, were markedly ameliorated by TE treatment. We conclude that TE confers protection against functional and morphologic injuries in the kidneys of diabetic rats by increasing activities of antioxidants and inhibiting accumulation of oxidized DNA in the kidney, suggesting a potential drug for the prevention and therapy of DN.

Cardiac-specific overexpression of HIF-1{alpha} prevents deterioration of glycolytic pathway and cardiac remodeling in streptozotocin-induced diabetic mice.

Defective glycolysis and angiogenesis in the heart of diabetic patients and in experimental diabetic animal models have been reported. The aim of this study was to determine whether overexpression of hypoxia-inducible factor (HIF)-1alpha protects from myocardial injury in diabetic mice by increasing myocardial glycolysis and angiogenesis. Cardiac-specific HIF-1alpha-overexpressing transgenic and age-matched wild-type control mice were treated with streptozotocin to induce diabetes. Changes in glucose transporters, glycolytic enzymes, angiogenic factors and cardiac morphology were examined in the hearts by real-time RT-PCR, Western blotting, enzymatic assay, and histological assays. HIF-1alpha overexpression elevated hexokinase II (HK-II) protein level and total HK activity in nondiabetic heart and prevented the decreases in HK-II mRNA, protein, and total HK activity in diabetic heart. In addition, the reduction of glucose transporter I, but not glucose transporter 4, was restored in HIF transgenic mouse heart along with a recovery of myocardium ATP production. HIF-1alpha overexpression also normalized diabetes-reduced vascular endothelial growth factor concentration along with a sustained myocardial capillary density and an inhibition of cardiomyocyte hypertrophy and cardiac fibrosis. Therefore, elevation of HIF-1alpha provides a cardiac protection from diabetic-induced impairment in glucose metabolism and angiogenesis via up-regulation of HIF-1 target genes.