SUMOylation of TEAD1 Modulates the Mechanism of Pathological Cardiac Hypertrophy.

Pathological cardiac hypertrophy is the leading cause of heart failure and has an extremely complicated pathogenesis. TEA domain transcription factor 1 (TEAD1) is recognized as an important transcription factor that plays a key regulatory role in cardiovascular disease. This study aimed to explore the role of TEAD1 in cardiac hypertrophy and to clarify the regulatory role of small ubiquitin-like modifier (SUMO)-mediated modifications. First, the expression level of TEAD1 in patients with heart failure, mice, and cardiomyocytes is investigated. It is discovered that TEAD1 is modified by SUMO1 during cardiac hypertrophy and that the process of deSUMOylation is regulated by SUMO-specific protease 1 (SENP1). Lysine 173 is an essential site for TEAD1 SUMOylation, which affects the protein stability, nuclear localization, and DNA-binding ability of TEAD1 and enhances the interaction between TEAD1 and its transcriptional co-activator yes-associated protein 1 in the Hippo pathway. Finally, adeno-associated virus serotype 9 is used to construct TEAD1 wild-type and KR mutant mice and demonstrated that the deSUMOylation of TEAD1 markedly exacerbated cardiomyocyte enlargement in vitro and in a mouse model of cardiac hypertrophy. The results provide novel evidence that the SUMOylation of TEAD1 is a promising therapeutic strategy for hypertrophy-related heart failure.

Deep learning reconstruction improves the image quality of low-dose temporal bone CT with otitis media and mastoiditis patients.

Objective: To evaluate the image quality of low-dose temporal bone computed tomography (CT) in otitis media and mastoiditis patients by using deep learning reconstruction (DLR). Materials and methods: A total of ninety-seven temporal bones from 53 consecutive adult patients who had suspected otitis media and mastoiditis and underwent temporal bone CT were prospectively enrolled. All patients underwent high resolution CT protocol (group A) and an additional low-dose protocol (group B). In group A, high resolution data were reconstructed by filter back projection (FBP). In group B, low-dose data were reconstructed by DLR mild (B1), DLR standard (B2) and DLR strong (B3). The objective image quality was analyzed by measuring the CT value and image noise on the transverse image and calculating the signal-to-noise ratio (SNR) on incudomallear joint, retroauricular muscle, vestibule and subcutaneous fat. Subjective image quality was analyzed by using a five-point scale to evaluate nine anatomical structures of middle and inner ear. The number of temporal bone lesions which involved in five structures of middle ear were assessed in group A, B1, B2 and B3 images. Results: There were no significant differences in the CT values of the four reconstruction methods at four structures (all p > 0.05). The DLR group B1, B2 and B3 had significantly less image noise and a significantly higher SNR than group A at four structures (all p < 0.001). The group B1 had comparable subjective image quality as group A in nine structures (all p > 0.05), however, the group B3 had lower subjective image quality than group A in modiolus, spiral osseous lamina and stapes (all p < 0.001), the group B2 had lower subjective image quality than group A in modiolus and spiral osseous lamina (both p < 0.05). The number of temporal bone lesions which involved in five structures for group A, B1 and B2 images were no significant difference (all p > 0.05), however, the number of temporal bone lesions which involved in mastoid for group B3 images were significantly more than group A (p < 0.05). The radiation dose of high resolution CT protocol and low-dose protocol were 0.55 mSv and 0.11 mSv, respectively. Conclusion: Compared with high resolution CT protocol, in the low-dose protocol of temporal bone CT, DLR mild and standard could improve the objective image quality, maintain good subjective image quality and satisfy clinical diagnosis of otitis media and mastoiditis patients.

Engineered extracellular vesicles: A new approach for targeted therapy of tumors and overcoming drug resistance.

Targeted delivery of anti-tumor drugs and overcoming drug resistance in malignant tumor cells remain significant clinical challenges. However, there are only few effective methods to address these issues. Extracellular vesicles (EVs), actively secreted by cells, play a crucial role in intercellular information transmission and cargo transportation. Recent studies have demonstrated that engineered EVs can serve as drug delivery carriers and showed promising application prospects. Nevertheless, there is an urgent need for further improvements in the isolation and purification of EVs, surface modification techniques, drug assembly processes, and precise recognition of tumor cells for targeted drug delivery purposes. In this review, we summarize the applications of engineered EVs in cancer treatment and overcoming drug resistance, and current challenges associated with engineered EVs are also discussed. This review aims to provide new insights and potential directions for utilizing engineered EVs as targeted delivery systems for anti-tumor drugs and overcoming drug resistance in the near future.

Allicin promotes functional recovery in ischemic stroke via glutathione peroxidase-1 activation of Src-Akt-Erk.

Allicin exhibits various pharmacological activities and has been suggested to be beneficial in the treatment of stroke. However, the underlying mechanisms are largely unknown. Here, we confirmed that allicin protected the brain from cerebral injury, which could be ascribed to its anti­apoptotic and anti­inflammatory effects, as well as the regulation of lipid metabolism, using proteomics and metabolomics analysis. Our results suggested that allicin could significantly ameliorate behavioral characteristics, cerebral infarct area, cell apoptosis, inflammatory factors, and lipid metabolic-related factors (arachidonic acid, 15-hydroperoxy-eicosatetraenoic acid (15S-HPETE), palmitoylcarnitine, and acylcarnitine) by recalibrating astrocyte homeostasis in mice with photothrombotic stroke (PT). In astrocytes, allicin significantly increased glutathione peroxidase 1 (GPX1) levels and inhibited the arachidonic acid-related pathway, which was also observed in the brains of mice with PT. Allicin was proven to inhibit hypoxia-induced astrocyte apoptosis by increasing GPX1 expression, activating proto-oncogene tyrosine-protein kinase Src (Src)- protein kinase B (AKT)-extracellular signal-regulated kinase (ERK) phosphorylation, and decreasing lipid peroxidation. Thus, we concluded that allicin significantly prevented and ameliorated ischemic stroke by increasing GPX1 levels to complete the complex physiological process.

Lycopene ε-cyclase mediated transition of α-carotene and ß-carotene metabolic flow in carrot fleshy root.

The accumulation of carotenoids, such as xanthophylls, lycopene, and carotenes, is responsible for the color of carrot (Daucus carota subsp. sativus) fleshy roots. The potential role of DcLCYE, encoding a lycopene ε-cyclase associated with carrot root color, was investigated using cultivars with orange and red roots. The expression of DcLCYE in red carrot varieties was significantly lower than that in orange carrots at the mature stage. Furthermore, red carrots accumulated larger amounts of lycopene and lower levels of α-carotene. Sequence comparison and prokaryotic expression analysis revealed that amino acid differences in red carrots did not affect the cyclization function of DcLCYE. Analysis of the catalytic activity of DcLCYE revealed that it mainly formed ε-carotene, while a side activity on α-carotene and γ-carotene was also observed. Comparative analysis of the promoter region sequences indicated that differences in the promoter region may affect the transcription of DcLCYE. DcLCYE was overexpressed in the red carrot 'Benhongjinshi' under the control of the CaMV35S promoter. Lycopene in transgenic carrot roots was cyclized, resulting in the accumulation of higher levels of α-carotene and xanthophylls, while the ß-carotene content was significantly decreased. The expression levels of other genes in the carotenoid pathway were simultaneously upregulated. Knockout of DcLCYE in the orange carrot 'Kurodagosun' by CRISPR/Cas9 technology resulted in a decrease in the α-carotene and xanthophyll contents. The relative expression levels of DcPSY1, DcPSY2, and DcCHXE were sharply increased in DcLCYE knockout mutants. The results of this study provide insights into the function of DcLCYE in carrots, which could serve as a basis for creating colorful carrot germplasms.

Advances in engineering the production of the natural red pigment lycopene: A systematic review from a biotechnology perspective.

BACKGROUND: Lycopene is a natural red compound with potent antioxidant activity that can be utilized both as pigment and as a raw material in functional food, and so possesses good commercial prospects. The biosynthetic pathway has already been documented, which provides the foundation for lycopene production using biotechnology. AIM OF REVIEW: Although lycopene production has begun to take shape, there is still an urgent need to alleviate the yield of lycopene. Progress in this area can provide useful reference for metabolic engineering of lycopene production utilizing multiple approaches. KEY SCIENTIFIC CONCEPTS OF REVIEW: Using conventional microbial fermentation approaches, biotechnologists have enhanced the yield of lycopene by selecting suitable host strains, utilizing various additives, and optimizing culture conditions. With the development of modern biotechnology, genetic engineering, protein engineering, and metabolic engineering have been applied for lycopene production. Extraction from natural plants is the main way for lycopene production at present. Based on the molecular mechanism of lycopene accumulation, the production of lycopene by plant bioreactor through genetic engineering has a good prospect. Here we summarized common strategies for optimizing lycopene production engineering from a biotechnology perspective, which are mainly carried out by microbial cultivation. We reviewed the challenges and limitations of this approach, summarized the critical aspects, and provided suggestions with the aim of potential future breakthroughs for lycopene production in plants.

Research Progress of GABA Receptors in Alzheimer’s Disease / 中国生物化学与分子生物学报

Alzheimer’s disease (AD) is a progressive neurodegenerative disease with the early symptom of A β plaque, tau hyperphosphorylation neuronal tangle formation in cells. At present, accumulated evidence shows that the changes of GABA receptors are closely related to AD. Some studies have shown that the expression level of each subunit of the GABA receptor changes in AD patients. Therefore, it is speculated that the changes of GABA subunits may be related to the pathogenesis of AD, but there is no better methods to improve AD by targeting GABA receptors. In order to further understand the relationship between the changes of GABA receptors and AD, this paper first reviewed the changes of GABA receptors in AD patients and animal models’ brains and found that there was differential expression in GABA(A) receptor subunits in AD patients. Then we summarized the changes of GABA receptor subunits in Alzheimer database. Based on the data, we found that a few GABA subunits had significant changes. The evidence shows that the change of GABA receptors alters the neural activity in the brain. Other studies have found that the treatment of mice with GABA receptor agonists and antagonists can improve the cognitive ability of mice. We hope that understanding the differential expression of GABA receptors in AD will provide a more accurate target for the treatment of AD.

Differential hydroxylation efficiency of the two non-heme carotene hydroxylases: DcBCH1, rather than DcBCH2, plays a major role in carrot taproot.

Carotene hydroxylase plays an important role in catalyzing the hydroxylation of carotene to xanthopylls, including two types: non-heme carotene hydroxylase (BCH type) and heme-containing cytochrome P450 hydroxylase (P450 type). Two BCH-encoding genes were annotated in the carrot genome. However, the role of BCHs and whether there are functional interactions between the duplicated BCHs in carrot remains unclear. In this study, two BCH encoding genes, DcBCH1 and DcBCH2, were cloned from carrot. The relative expression level of DcBCH1 was much higher than that of DcBCH2 in carrot taproots with different carotene accumulation levels. Overexpression of DcBCH1 in 'KRD' (high carotene accumulated) carrot changed the taproot color from orange to yellow, accompanied by substantial reductions in α-carotene and ß-carotene. There was no obvious change in taproot color between transgenic 'KRD' carrot overexpressing DcBCH2 and control carrot. Simultaneously, the content of α-carotene in the taproot of DcBCH2-overexpressing carrot decreased, but the content of ß-carotene did not change significantly in comparison with control carrot. Using the CRISPR/Cas9 system to knock out DcBCH1 in 'KRD' carrot lightened the taproot color from orange to pink-orange; the content of α-carotene in the taproot increased slightly, while the ß-carotene content was still significantly decreased, compared with control carrot. In DcBCH1-knockout carrot, the transcript level of DcBCH2 was significantly increased. These results indicated that in carrot taproot, DcBCH1 played the main function of BCH enzyme, which could hydroxylate α-carotene and ß-carotene; DcBCH1 and DcBCH2 had functional redundancy, and these two DcBCHs could partially compensate for each other.

Exercise-derived peptide protects against pathological cardiac remodeling.

BACKGROUND: Exercise training protects the heart against pathological cardiac remodeling and confers cardioprotection from heart failure. However, the underlying mechanism is still elusive. METHODS: An integrative analysis of multi-omics data of the skeletal muscle in response to exercise is performed to search for potential exerkine. Then, CCDC80tide is examined in humans after acute exercise. The role of CCDC80tide is assessed in a mouse model of hypertensive cardiac remodeling and in hypertension-mediated cell injury models. The transcriptomic analysis and immunoprecipitation assay are conducted to explore the mechanism. FINDINGS: The coiled-coil domain-containing protein 80 (CCDC80) is found strongly positively associated with exercise. Interestingly, exercise stimuli induce the secretion of C-terminal CCDC80 (referred as CCDC80tide hereafter) via EVs-encapsulated CCDC80tide into the circulation. Importantly, cardiac-specific expression of CCDC80tide protects against angiotensin II (Ang II)-induced cardiac hypertrophy and fibrosis in mice. In in vitro studies, the expression of CCDC80tide reduces Ang II-induced cardiomyocyte hypertrophy, cardiac microvascular endothelial cell (CMEC) inflammation, and mitigated vascular smooth muscle cell (VSMC) proliferation and collagen formation. To understand the cardioprotective effect of CCDC80tide, a transcriptomic analysis reveals a dramatic inhibition of the STAT3 (Signal transducer and activator of transcription 3) signaling pathway in CCDC80tide overexpressing cells. Mechanistically, CCDC80tide selectively interacts with the kinase-active form of JAK2 (Janus kinase 2) and consequently inhibits its kinase activity to phosphorylate and activate STAT3. INTERPRETATION: The results provide new insights into exercise-afforded cardioprotection in pathological cardiac remodeling and highlight the therapeutic potential of CCDC80tide in heart failure treatment. FUNDING: This work was supported by the National Natural Science Foundation of China [Grant/Award Numbers: 81770428, 81830010, 82130012, 81900438, 82100447); Shanghai Science and Technology Committee [Grant/Award Numbers: 21S11903000, 19JC1415702]; Emerging and Advanced Technology Programs of Hospital Development Center of Shanghai [Grant/Award Number: SHDC12018129]; China Postdoctoral Science Foundation [2021M692108]; and China National Postdoctoral Program for Innovative Talents [BX20200211].

Myeloid differential protein-2 inhibition improves diabetic cardiomyopathy via p38MAPK inhibition and AMPK pathway activation.

Myeloid differential protein-2 (MD2) has been shown to play a critical role in the progression of diabetic cardiomyopathy (DCM). This study aims to explore the non-inflammatory mechanisms mediated by MD2 in DCM and to test the therapeutic effects of MD2 inhibitor C30 on DCM. Streptozotocin (STZ) was used to construct DCM model in wild-type and MD2 knockout mice. The collected heart samples were subjected to RNA-sequencing assay. Gene set enrichment analysis of the RNA-seq data indicated that MD2 knockout was associated with energy metabolism pathways in diabetic mouse heart. Further data showed that AMPK pathway was impaired under high glucose condition, which was mediated by p38MAPK activation. MD2 knockout or pharmacological inhibitor C30 completely rescued AMPK signaling through p38MAPK inhibition. Importantly, C30 treatment significantly prevented myocardial damage and dysfunction in T1DM mice evidenced by improved cardiac function and reduced cardiomyocyte apoptosis and cardiac fibrosis. Furthermore, the therapeutic effect of C30 on DCM was correlated to p38MAPK inhibition and AMPK pathway activation in vivo and in vitro. In conclusion, MD2 inhibition exhibits therapeutic effects on DCM through p38MAPK inhibition and AMPK activation, which enables MD2 a promising target for DCM treatment by suppressing metaflammation and improving cardiac metabolism.

Antifibrotic Effect of a Novel Selective 11ß-HSD2 Inhibitor (WZ51) in a rat Model of Myocardial Fibrosis.

Myocardial fibrosis (MF) is one of the leading causes of end-stage heart disease. Many studies have confirmed that inflammation caused by aldosterone may play an important role in the process of MF. A selective 11ß-hydroxysteroid dehydrogenase type 2 (11ß-HSD2) enzyme inhibitor can reduce the inactivation of cortisol, allowing cortisol to compete for mineralocorticoid receptors. This study investigated the protective effect of a novel selective 11ßHSD2 inhibitor (WZ51) on MF and described its underlying mechanism. The administration of WZ51 in rats with MF significantly alleviated myocardial injury, accompanied by a decrease in lactate dehydrogenase and the creatine kinase myocardial band. Furthermore, WZ51 significantly inhibited the development of MF and increased the protein level of 11ß-HSD2. The results of this study demonstrate that 11ß-HSD2 plays an important pathological role in MF. Thus, WZ51 may be a potential therapeutic agent for the treatment of this condition.

Specific adsorption and determination of aspartame in soft drinks with a zein magnetic molecularly imprinted modified MGCE sensor.

In this work, an efficient and sensitive magnetic molecularly imprinted polymer with zein and deep eutectic solvents (ZDM-MIPs) was designed and synthesized to exclusively adsorb and detect aspartame (ASP). We used zein, together with deep eutectic solvents (DESs) and Fe3O4 as the cross-linker, functional monomer and support material, respectively. A magnetic glassy carbon electrode (MGCE) modified with ZDM-MIPs was used for selective recognition of ASP. The electrochemical response of the ZDM-MIPs-MGCE for quantification of ASP was evaluated with a portable electrochemical detection station with differential pulse voltammetry and cyclic voltammetry. The responses of ZDM-MIPs-MGCE signified a good linear relationship with ASP concentrations in the range of 0.1-50 µg mL-1. The sensor systems showed good accuracy and precision, with recovery percentages between 84% and 107%. These results suggested that the obtained ZDM-MIPs exhibited good adsorption performance for ASP in soft drinks, and this method could be used to determine ASP content in actual food samples.

Selective separation and inexpensive purification of paclitaxel based on molecularly imprinted polymers modified with ternary deep eutectic solvents.

Paclitaxel (PTX) is a powerful anticancer natural product, with its separation and purification having been widely studied. In this work, new molecular imprinted polymers (MIPs) using deep eutectic solvents (DESs) with different molar ratios were prepared as functional monomers. These were then used as adsorbents in solid phase extraction (SPE) for the separation of PTX from its structural analogs. The polymers were characterized by energy disperive X-rays (EDX), scanning electron microscopy (SEM), thermogravimetric analysis (TGA) and fourier transform infrared spectroscopy (FT-IR). The results suggested that the formative regular DES-MIPs had an even pore-size distribution and a large specific surface area. The dynamic adsorption and static adsorption showed that the DES-MIPs had excellent adsorption performance, with a maximum adsorption capacity and optimum adsorption time of 87.08 mg/g and 180 min, respectively. The selective adsorption experiments showed that the material had outstanding selectivity, and the maximum selectivity factor was 6.20. For stability, after six consecutive adsorption and desorption cycles, the DES-MIPs maintained the perfect stability and reusability. Furthermore, the fabricated SPE column was successfully utilized for extracting and eluting PTX. This study provides a reliable protocol for the separation and purification PTX from its structural analogs and the DES-MIPs materials have excellent potential application value in pharmaceutical industry.

Kaempferol attenuates streptozotocin-induced diabetic nephropathy by downregulating TRAF6 expression: The role of TRAF6 in diabetic nephropathy.

ETHNOPHARMACOLOGICAL RELEVANCE: Kaempferia rhizome is a famous traditional herbal medical in tropical and subtropical areas. Kaempferol (KPF) is one of the main bioactive compounds in Kaempferia rhizome, with anti-oxidant/anti-inflammatory effects demonstrated in various disease models, including cancers, obesity and diabetes. AIM OF THE STUDY: Inflammation plays an important role in the pathogenesis of diabetic nephropathy (DN). TRAF6 functions as a signal transducer in toll-like receptor 4 and NF-κB pro-inflammatory signaling pathway. We aimed at investigate whether KPF is able to mitigate inflammatory responses by regulating TRAF6 in DN. MATERIAL AND METHODS: C57BL/6 mice were injected with streptozotocin to induce type 1 DN. NRK-52E, a tubular epithelial cell line, was used for in vitro analysis. TRAF6 was knockdown using siRNA in vitro and AAV2/2-shRNA in vivo. The anti-DN and inflammatory effects of KPF or knockdown of TRAF6 were evaluated by investigating renal filtration index, pathological changes of kidney tissue. Proinflammatory cytokine levels were detected using ELISA. NF-κB pathway and protein levels of related pathways were detected through Western blot. RESULTS: KPF significantly reduced renal inflammation, fibrosis, and kidney dysfunction in diabetic mice. These effects were associated with a downregulation of TRAF6 in diabetic mouse kidneys, indicating the potential role of TRAF6. Knockdown of TRAF6 in mice through AAV2-shTRAF6 confirmed the importance of TRAF6 in DN. In vitro, treatment of KPF in NRK-52E cells attenuated high glucose (HG)-induced inflammatory and fibrogenic responses, associated with downregulated TRAF6 expression. The conclusion was further confirmed in NRK-52E cells by knocking down the expression and by overexpression of TRAF6. CONCLUSION: Our findings provide direct evidence that TRAF6 mediates diabetes-induced inflammation leading to renal dysfunction. We also show that KPF is a potential therapeutic agent to reduce inflammatory responses in DN. Also, TRAF6 may represent an interesting target to combat DN.

Oncogenic potential of macrophage­capping protein in clear cell renal cell carcinoma.

Macrophage­capping protein (CapG) is a newly characterized oncogene involved in several types of cancer. However, the expression patterns and biological mechanisms of CapG in clear cell renal cell carcinoma (ccRCC) are unclear. The present study aimed to investigate the roles of CapG in the prognosis, proliferation and metastasis of ccRCC. In the present study, the expression of CapG was analyzed by western blotting in 24 paired ccRCC and adjacent normal tissue samples. Another 152 tissue samples from 152 patients with ccRCC were examined by immunohistochemistry. Compared with normal tissue, CapG expression was significantly increased in ccRCC tissue, and high CapG expression was associated with advanced tumor stage, histological grade, lymph node metastasis, and poor overall survival. Moreover, CapG was an independent predictor of survival. Lentivirus­mediated CapG knockdown significantly inhibited 786­O cell proliferation, migration, and invasion, induced cell cycle arrest at the G2/M phase, and increased apoptosis in vitro. Microarray analysis indicated that RAC, CDC42 and ERK/MAPK signaling were disrupted by CapG knockdown in 786­O cells. In conclusion, the present findings indicate that CapG plays an oncogenic role in ccRCC and may represent a potential therapeutic target for this disease.

Risk-adapted treatment reduced chemotherapy exposure for clinical stage I pediatric testicular cancer.

BACKGROUND: Different from adult clinical stage I (CS1) testicular cancer, surveillance has been recommended for CS1 pediatric testicular cancer. However, among high-risk children, more than 50% suffer a relapse and progression during surveillance, and adjuvant chemotherapy needs to be administered. Risk-adapted treatment might reduce chemotherapy exposure among these children. METHODS: A decision model was designed and calculated using TreeAge Pro 2011 software. Clinical utilities such as the relapse rates of different groups during surveillance or after chemotherapy were collected from the literature. A survey of urologists was conducted to evaluate the toxicity of first-line and second-line chemotherapy. Using the decision analysis model, chemotherapy exposure of the risk-adapted treatment and surveillance strategies were compared based on this series of clinical utilities. One-way and two-way tests were applied to check the feasibility. RESULTS: In the base case decision analysis of CS1 pediatric testicular cancer, risk-adapted treatment resulted in a lower exposure to chemotherapy than surveillance (average: 0.7965 cycles verse 1.3419 cycles). The sensitivity analysis demonstrated that when the relapse rate after primary chemotherapy was ≤ 0.10 and the relapse rate of the high-risk group was ≥ 0.40, risk-adapted treatment would result in a lower exposure to chemotherapy, without any association with the proportion of low-risk patients, the relapse rate of the low-risk group, the relapse rate after salvage chemotherapy or the toxicity utility of second-line chemotherapy compared to first-line chemotherapy. CONCLUSIONS: Based on the decision analysis, risk-adapted treatment might decrease chemotherapy exposure for these high-risk patients, and an evaluation after orchiectomy was critical to this process. Additional clinical studies are needed to validate this statement.

Endothelial microparticles induced by cyclic stretch activate Src and modulate cell apoptosis.

Endothelial microparticles (EMPs) are involved in various cardiovascular pathologies and play remarkable roles in communication between endothelial cells (ECs), which are constantly exposed to mechanical cyclic stretch (CS) following blood pressure. However, the roles of EMPs induced by CS in EC homeostasis are still unclear. Both fluorescence resonance energy transfer (FRET) and western blotting revealed the activation of Src in ECs was significantly increased by 5% CS-induced EMPs. Furthermore, proteomic analysis revealed that the contents were obvious different in the EMPs between 5%- and 15%-group. Based on the bioinformatic analysis, CD151 on EMPs was predicted to activate Src, which was further confirmed by both FRET and western blotting. Moreover, the expression of CD151 on EMPs was significantly increased by 5% CS and involved in the binding of EMPs to ECs. EC apoptosis, which was significantly decreased by 5% CS-derived EMPs, showed obvious increase after pretreatment with Src inhibitor in target ECs. Our present research suggests that mechanical stretch changes the components of EMPs, which in turn modulates EC apoptosis by Src activation. CD151 expressed on CS-induced EMPs may play important roles in EC communication and homeostasis.

The imidazopyridine derivative X22 prevents diabetic kidney dysfunction through inactivating NF-κB signaling.

Diabetic kidney disease (DKD) is considered a chronic inflammatory renal disease induced by hyperglycemia. Therefore, even meticulous control of blood glucose levels cannot prevent the progression of DKD efficiently. Management of the inflammatory response could be one of the most promising strategies for treatment. We previously validated an imidazopyridine derivative (X22) as an active compound in suppressing lipopolysaccharide-induced inflammation. However, its potential for protection against DKD has not been exanimated. In the present study, streptozotocin-induced type 1 diabetic mice were used to study the effect of X22 on DKD associated inflammation and fibrosis by Q-PCR and immunoblotting assays. The results showed that X22 significantly inhibited the production of inflammatory cytokines (IL-6, TNF-α) and fibrosis biomarkers. At the same time, kidney function was dramatically improved. To elucidate the mechanism of action of X22, we examined its effects on the NRK-52E cell line. Strikingly, X22 restored the protein level of IKB-α and blocked the nuclear translocation of P65. Collectively, the data indicate that X22 can attenuate diabetic kidney dysfunction and inflammatory injury and may represent a potential agent for the treatment of DKD. It could be a potential agent for use in the treatment of DKD.

Rapid measurements of curcumin from complex samples coupled with magnetic biocompatibility molecularly imprinted polymer using electrochemical detection.

Curcumin widely exists in food, and rapid selective and accurate detection of curcumin have great significance in chemical industry. In this experiment, a new magnetic biocompatibility molecularly imprinted polymer was prepared with nontoxic and biocompatible Zein to adsorb curcumin selectively. The polymer has high biocompatibility, good adsorption capacity, and specific adsorption for curcumin. Combined with portable electrochemical workstations, the polymer can be used to detect curcumin rapidly and cost-effectively. Using curcumin as a template and Zein as the crosslinking agent, the polymers were synthesized on the surface of Fe3 O4 particles for solid phase extraction. The experimental results showed that the polymer reached large adsorption capacity (32.12 mg/g) with fast kinetics (20 min). The adsorption characteristic of the polymer followed the Langmuir isotherm and pseudo-second-order kinetic models. Hexacyanoferrate was used as electrochemical probe to generate signals, and the linear range was 5-200 µg/mL for measuring curcumin. The experimental analysis showed that the polymer was an ideal material for selective accumulation of curcumin from complex samples. This approach has been successfully applied to the determination of curcumin in food samples with electrochemical detection, indicating that this is a feasible and practical technique.

Endothelial microvesicles induced by physiological cyclic stretch inhibit ICAM1-Dependent leukocyte adhesion.

Physiological cyclic stretch (CS), caused by artery deformation following blood pressure, plays important roles in the homeostasis of endothelial cells (ECs). Here, we detected the effect of physiological CS on endothelial microvesicles (EMVs) and their roles in leukocyte recruitment to ECs, which is a crucial event in EC inflammation. The results showed compared with the static treatment, pretreatment of 5%-CS-derived EMVs with ECs significantly decreased the adherence level of leukocytes. Comparative proteomic analysis revealed 373 proteins differentially expressed between static-derived and 5%-CS-derived EMVs, in which 314 proteins were uniquely identified in static-derived EMVs, 34 proteins uniquely in 5%-CS-derived EMVs, and 25 proteins showed obvious differences. Based on the proteomic data, Ingenuity Pathways Analysis predicted intercellular adhesion molecule 1 (ICAM1) in EMVs might be the potential molecule involved in EC-leukocyte adhesion. Western blot and flow cytometry analyses confirmed the significant decrease of ICAM1 in 5%-CS-derived EMVs, which subsequently inhibited the phosphorylation of VE-cadherin at Tyr731 in target ECs. Moreover, leukocyte adhesion was obviously decreased after pretreatment with ICAM1 neutralizing antibody. Our present research suggested that physiological stretch changes the components of EMVs, which in turn inhibits leukocyte adhesion. ICAM1 expressed on CS-induced EMVs may play an important role in maintaining EC homeostasis.