查找使用阿拉丁产品的科研文献

Intervention effect of Potentilla discolor-Euonymus alatus on intestinal flora of type 2 diabetes mellitus rats

S.-Y. He,X.-M. Qiu,Y.-Q. Wang,Z.-Q. Su,B.-Y. Zhang,Z. Wen,Y.-F. Yang,B.-F. Xing,M. Hong,R. Liao

OBJECTIVE: With this study, we aimed at exploring the regulation mechanism of Potentilla discolor-Euonymus alatus on intestinal flora of T2DM (Type 2 Diabetes Mellitus) rats induced by high-fat diet combined with streptozotocin.MATERIALS AND METHODS: T2DM rats were induced by high-fat diet combined with streptozotocin. There were normal control group, model group, metformin group, high-dose Chinese medicine group and low-dose Chinese medicine group. Each group included 10 rats. Normal control group: normal feeding, no modeling, ordinary feed, and gavage of 0.9% normal saline. Model group: T2DM rats, high-fat diet, and gavage of 0.9% normal saline. Metformin group: T2DM rats, high-fat diet and fed with metformin solution. High-dose Chinese medicine group: T2DM rats, high-fat diet, and gavage of concentrated Chinese medicine at a dose of 6 times the clinical dose. Low-dose Chinese medicine group: T2DM rats, high-fat diet, and gavage of concentrated Chinese medicine at a dose twice the clinical dose. The general situation of T2DM rats was observed, and the changes of intestinal flora were observed with 16SrDNA sequencing.RESULTS: The T2DM rats induced by high-fat diet combined with streptozotocin were molded. After intervention, at the class level, the ratio of γ-proteobacteria was 22.30% in the model group, 11.97% in the metformin group, 3.24% in the high-dose Chinese herbs group and 1.72% in the low-dose Chinese herbs group; the ratio of Erysipelothrix insidiosa was 4.73% in the model group, 4.68% in the metformin group, 3.93% in the high-dose Chinese herbsgroup and 2.92% in the low dose group; the ratio of Lactinobacillus was 2.30% in the model group, 0.01% in the metformin group, 0.00% in the high-dose Chinese herbs group, and 0.00% low-dose Chinese herbs group; at the portal level, the Firmicutes/Bacteroides was 0.88 in the normal control group, 3.40 in the model group, 1.71 in the metformin group, 2.74 in high-dose Chinese medicine group, and 1.34 in low-dose Chinese medicine group; at the genus level, the relative abundance of Lactobacillus in the model group was 3.28%, that of Akkermansia was 1.99%, that of Shigella coli was 22.08%, and that of Vibrio phaseus was 7.67%. All of them were improved after the intervention of metformin and traditional Chinese medicine.CONCLUSIONS: Potentilla discolor-Euonymus Alatus could improve the composition and structure of intestinal flora in T2DM rats and regulate the diversity of intestinal flora. The ratio of Firmicutes/Bacteroidetes was adjusted, mainly to increase the number of Bacteroides; the flora related to intestinal barrier was adjusted, mainly to increase the number of Lactobacillus and Akkermansia bacteria.

Aldehyde dehydrogenase 2 protects against acute kidney injury by regulating autophagy via the Beclin-1 pathway

Tonghui Xu,Jialin Guo,Maozeng Wei,Jiali Wang,Kehui Yang,Chang Pan,Jiaojiao Pang,Li Xue,Qiuhuan Yuan,Mengyang Xue,Jian Zhang,Wentao Sang,Tangxing Jiang,Yuguo Chen,Feng Xu

The mitochondrial enzyme aldehyde dehydrogenase 2 (ALDH2) catalyzes the detoxification of acetaldehyde and endogenous lipid aldehydes. Approximately 40% of East Asians, accounting for 8% of the human population, carry the E504K mutation in ALDH2 that leads to accumulation of toxic reactive aldehydes and increases the risk for cardiovascular disease, cancer, and Alzheimer disease, among others. However, the role of ALDH2 in acute kidney injury (AKI) remains poorly defined and is therefore the subject of the present study using various cellular and organismal sources. In murine models, in which AKI was induced by either the contrast agent iohexol or renal ischemia/reperfusion, KO, activation/overexpression of ALDH2 were associated with increased and decreased renal injury, respectively. In murine renal tubular epithelial cells (RTECs), ALDH2 upregulated Beclin-1 expression, promoted autophagy activation, and eliminated ROS. In vivo and in vitro, both 3-MA and Beclin-1 siRNAs inhibited autophagy and abolished ALDH2-mediated renoprotection. In mice with iohexol-induced AKI, ALDH2 knockdown in RTECs using AAV-shRNA impaired autophagy activation and aggravated renal injury. In human renal proximal tubular epithelial HK-2 cells exposed to iohexol, ALDH2 activation potentiated autophagy and attenuated apoptosis. In mice with AKI induced by renal ischemia/reperfusion, ALDH2 overexpression or pretreatment regulated autophagy mitigating apoptosis of RTECs and renal injury. In summary, our data collectively substantiate a critical role of ALDH2 in AKI via autophagy activation involving the Beclin-1 pathway.

Streptococcus suis serotype 2 strains can induce the formation of neutrophil extracellular traps and evade trapping

Zhao Jianqing,Pan Shan,Lin Lan,Fu Lei,Yang Chao,Xu Zhongmin,Wei YanMin,Jin Meilin,Zhang Anding

Streptococcus suis (S. suis) ranks among the five most important porcine pathogens worldwide and occasionally threatens human health, especially in people that come into close contact with pigs or pork products. Streptococcus suis serotype 2 (SS2) is considered to be the most pathogenic and prevalent capsular type. As a first line of immune defense against SS2 infection, neutrophils can eliminate the invader not only by phagocytosis but also by neutrophil extracellular traps (NETs)-mediated killing. SS2 can resist phagocytosis through polysaccharide capsule (CPS), but how this strain evades the effects of NETs remains to be determined. The present study demonstrated that the epidemic strain 05ZY, the highly pathogenic strain P1/7 and the intermediately pathogenic strain A7 could induce the formation of NETs. Furthermore, SS2 strains could successfully resist NETs-mediated killing, and the CPS structure contributed to this resistance by escaping the trapping. Therefore, the CPS structure not only contributed to the SS2 strains’ resistance to phagocytosis-mediated killing but also played an essential role in evading NETs trapping and further killing in vitro. This study strengthens our understanding of how S. suis can evade innate immune surveillance and elimination.

Targeted delivery of polyamidoamine-paclitaxel conjugate functionalized with anti-human epidermal growth factor receptor 2 trastuzumab

Pengkai Ma,Xuemei Zhang,Ling Ni,Jinming Li,Fengpu Zhang,Zheng Wang,Shengnan Lian,Kaoxiang Sun

Self-supported Hierarchical Fe(PO3)2@Cu3P nanotube arrays for efficient hydrogen evolution in alkaline media

Dongmei Dai,Bo Wei,Ying Li,Xiao Ma,Shuang Liang,Shuo Wang,Lingling Xu

Developing high-efficient and Earth-abundant electrocatalysts toward hydrogen evolution reaction (HER) is strongly desired for electrochemical water splitting but remains a considerable challenge. Herein, we propose a 3D hierarchical Fe(PO 3 ) 2 @Cu 3 P heterostructure nanotube arrays on Cu foams for promising HER catalysts. The HER performance can be tuned by changing FeCl 3 concentrations and the optimized cathode exhibits excellent HER activity in 1 M KOH with a low overpotentials of 108 mV @ 10 mA cm −2 and a small Tafel slope of 84 mV dec −1 . Furthermore, this electrode delivers high electrochemical durability with stable operation for 24 h. Such high performance can be ascribed to the unique hierarchical heterostructure with large electrochemical surface area, synergistic effect and fast electron transport . Our study can provide new inspiration for rational construction of copper-based hierarchical nanomaterials for HER electrodes and other energy-related applications.

La2B3O4(OH)3(SO4)2: A new rare-earth borate-sulfate with second-harmonic generation response

Hui Yang,Ziyu Wang,Cuixia Xu,Yuan Lin,Guoliang Liu

The first example of lanthanide borate-sulfate compound, namely, La 2 B 3 O 4 (OH) 3 (SO 4 ) 2 has been obtained through hydrothermal synthesis , which belongs to polar space group Pna 2(1) (No. 33). Its structure possesses double lanthanum sulfate layers in the ab plane in which the lanthanide ions are bridged by SO 4 tetrahedra. These layers are further cross-linked by borate chains into the final 3D framework. It is noteworthy that this compound is the first lanthanide borate-sulfate which crystalizes in polar space group and it displays second-harmonic generation (SHG) signal of about 0.1 times that of KH 2 PO 4 . The SHG coefficient of the compound is ascribed to the synergistic effect of SO 4 units and borate units. Meanwhile, distorted LaO x polyhedra also play an important role in the contribution to SHG response.

Hernandezine, a natural herbal alkaloid, ameliorates type 2 diabetes by activating AMPK in two mouse models

Jing Bai,Shuai Zhang,Jinjing Cao,Hongbin Sun,Zhiguo Mang,Wei L. Shen,Hao Li

Background AMP-activated protein kinase (AMPK) is an effective target for treating diabetes. However, successful drug development is delayed due to issues including toxicity. Plant-derived natural product AMPK activators have emerged as a new way to treat diabetes due to its potential low safety risks. Here, we studied the effect of hernandezine (HER), a natural product derived from Thalictrum , in activating AMPK and treating T2D in mouse models. Method We tested HER in various cells and tissues, including primary hepatocytes, skeletal myotubes cell lines, as well as major metabolic tissues from diabetic (db/db) and diet-induced obesity (DIO) model mice. The effect of HER on glucose uptake via AMPK in vitro and in vivo was confirmed utilizing cell transfection and adenovirus interference analysis. Tissue staining assessed the effect of HER on adipogenesis. Real-time quantitative polymerase chain reaction (real-time PCR) was applied to verify the effect of HER on transcription factors. Western blot analysis was used to determine the activation of phosphorylated AMPK and ACC pathways. Results Biochemically, we found that HER prevented pAMPK from dephosphorylation to prolong its activity, disproving previous direct activation model and providing a new model to explain HER-mediated AMPK activation. HER could be orally delivered to animals and has a 3-fold long half-life in vivo as compared to metformin. Importantly, long-term oral HER treatment potently reduced body weight and blood glucose in both type 2 diabetes mullitus (T2DM) mouse models by increasing glucose disposal and reducing lipogenesis, and appeared not to induce cardiac hypertrophy. Conclusion Natural product HER indirectly activates AMPK by suppressing its dephosphorylation. Oral HER effectively alleviated hyperglycemia and reduced body weight in T2D mouse models, appeared to have a low risk of causing cardiac hypertrophy, and might be a potential therapeutic option for T2DM.

Synthesis and Evaluation of Anti-inflammatory N-Substituted 3,5-Bis(2-(trifluoromethyl)benzylidene)piperidin-4-ones

Zixin Xie,Zaikui Zhang,Shufang Yu,Donghua Cheng,Huan Zhang,Chao Han,Handeng Lv,Faqing Ye

Graphical Taking the heat off : The 24 curcumin analogues in this study were found to have no toxicity toward mouse bone marrow cells, and some of them showed potent anti-inflammatory activity by inhibiting LPS-stimulated TNFα, IL-6, IL-1β, PGE2, and NO production in rat macrophages. Pharmacokinetic studies indicated that compound c6 has better bioavailability than curcumin in vivo. Both c6 and c10 may be valuable leads for the development of new anti-inflammatory agents. A total of 24 N-substituted 3,5-bis(2-(trifluoromethyl)benzylidene)piperidin-4-one derivatives were synthesized via aldol condensation, and their anti-inflammatory activities were evaluated. These compounds were found to have no significant cytotoxicity against mouse bone marrow cells in vitro. However, some compounds, such as c6 ( N -(3-methylbenzoyl)-3,5-bis-(2-(trifluoromethyl)benzylidene)piperidin-4-one) and c10 ( N -(2-chlorobenzoyl)-3,5-bis-(2-(trifluoromethyl)benzylidene)piperidin-4-one), displayed potent anti-inflammatory activity by inhibiting lipopolysaccharide (LPS)-stimulated tumor necrosis factor (TNF)-α, interleukin-6 (IL-6), IL-1β, prostaglandin E2 (PGE2), and nitric oxide (NO) production in RAW 264.7 cells. Treatment with c6 or c10 at 2.5 or 10 mg kg −1 significantly decreased the paw edema induced by carrageenan in rats, and the anti-inflammatory effects of these compounds were found to be better than those of celecoxib or indomethacin as well as their parent compound C66 (2,6-bis-(2-(trifluoromethyl)benzylidene)cyclohexanone). Pharmacokinetic analysis indicated that c6 has better bioavailability than curcumin. Therefore, these compounds may be valuable leads for the development of new anti-inflammatory drugs.

Leucine-Rich Alpha-2-Glycoprotein1 Gene Interferes with Regulation of Apoptosis in Leukemia KASUMI-1 Cells

Shishan Xiao,Hongqian Zhu

Background Leukemia cells have strong proliferation and anti-apoptosis capabilities. The purpose of this study was to investigate the effect of silencing the leucine-rich alpha-2-glycoprotein1 (LRG1) gene, which was found to regulate tumor proliferation and apoptosis in acute myeloid leukemia (AML) cell lines. Material/Methods Plasmid interference technique was used to silence the LRG1 gene in the KASUMI-1 cell line. The cell counting kit-8 (CCK-8) assay was used to test the effect of transduction on cell viability. Cell cycle and apoptosis were detected by flow cytometry. Western blot and quantitative real-time polymerase chain reaction (RT-qPCR) were applied to detect the expression levels of proteins and mRNA, respectively. Results KASUMI-1 cells with the CD34 + CD38 − phenotype were sorted by flow cytometry. After transfection of the siLRG1 plasmid, the level of LRG1 expression was downregulated and cell viability was reduced. Silencing of LRG1 gene blocked KASUMI-1 cells in G0/G1 phase and promoted apoptosis. Further experiments found that LRG1 gene silencing significantly downregulated cell cycle-associated proteins and anti-apoptotic proteins, while upregulating pro-apoptotic proteins. Downregulation of LRG1 gene expression also inhibits signal transduction of the JAK-STAT pathway. Conclusions LRG1 gene silencing regulates the expression of cyclin and apoptosis-related proteins to reduce cell viability and promote apoptosis, probably through inhibition of the JAK-STAT pathway.

Transport mechanism and subcellular localization of a polysaccharide from Cucurbia Moschata across Caco-2 cells model

Fei Li,Yunlu Wei,Jing Zhao,Guoyong Yu,Linlin Huang,Quanhong Li

Pumpkin polysaccharides with various bioactivities are mainly taken orally, thus detailed knowledge of the intestinal transport of which are essential for understanding its bioactivities. The Caco-2 cells monolayer model (mimic intestinal epithelium) was successfully constructed and Cucurbia moschata polysaccharides (PPc-F) were successfully conjugated with fluorescein isothiocyanate (FITC) to evaluate the transcellular transport mechanism and subcellular localization of PPc. The transport process of PPc-F was energy-dependent, and a moderately-absorbed biological macromolecule according to the apparent permeability coefficients (P app ) value. The endocytosis process of PPc-F in Caco-2 cells included the clathrin- and caveolae (or lipid draft)-medicated routes. And the translocation process was related to endoplasmic reticulum (ER), golgi apparatus (GA), tubulin and the acidification of endosomes. As for the intracellular location of PPc-F, it was mainly accumulated in ER. The study provided an understanding of the transmembrane transport of PPc-F, and could help studying the mechanisms of its effects.

NG@B87@HA Hydrogel regulates glycolysis bidirectionally to promote wound healing in type 2 diabetes mellitus

Xudong Xie,Weixian Hu,Yue An,Yuheng Liao,Shengming Zhang,Yanzhi Zhao,Kangkang Zha,Wenqian Zhang,Zhenhe Zhang,Fan Xia,Bobin Mi,Benjie Zhou,Hankun Hu,Mengfei Liu,Guohui Liu

Diabetic wounds are characterized by an imbalance between impaired angiogenesis and persistent pro-inflammatory immune responses, leading to chronic non-healing. Under hyperglycemic and oxidative stress conditions, the glycolytic function of endothelial cells is significantly compromised. However, solely enhancing angiogenesis does not effectively promote diabetic wound healing due to concomitant dysregulation of the local immune microenvironment, which further suppresses vascularization. Notably, Th1 cells dominate the diabetic wound immune milieu and exacerbate inflammatory responses, thereby aggravating immune imbalance. Thus, an optimal therapeutic strategy should simultaneously target both inflammatory dysregulation and vascular dysfunction. To address the phenomenon of cell-specific metabolic reprogramming within diabetic wounds, where glycolytic activity is impaired in endothelial cells yet enhanced in Th1 cells, this study developed a glucose-responsive NG@B87@HA hydrogel system designed to reprogram the local metabolic network and modulate Th1 cell metabolism while restoring endothelial function. The hydrogel incorporates nanoparticles functionalized with CXCR3 antibody to specifically target Th1 cells and deliver the glycolysis inhibitor Bay87-2243 (B87), thereby suppressing their glycolytic flux and inflammatory activity via inhibition of the HIF-1α–GLUT1 signaling axis. Simultaneously, naringin (NG), which acts as a crosslinker, forms dynamic boronic ester bonds with HA-PBA and PVA, enabling glucose-dependent responsiveness. This mechanism not only mitigates local oxidative stress but also enhances the tube-forming capacity of endothelial cells, ultimately promoting angiogenesis. The results demonstrated that the NG@B87@HA hydrogel effectively restores the dysregulated metabolic network in diabetic wounds. By concurrently rectifying immune microenvironment imbalance and endothelial dysfunction, this system provides a novel therapeutic strategy for accelerating diabetic wound healing.

Facet-Engineered Parallel Ni(OH)2 Arrays for Enhanced Bubble Dynamics and Durable Alkaline Seawater Electrolysis

Luan Liu,Hongru Liu,Baorui Jia,Xuanhui Qu,Mingli Qin

Electrolysis of seawater is considered a green route for hydrogen generation; however, its practical application is limited by strong electrode corrosion and slow OER kinetics in chloride-rich media. Herein, we report a crystal-facet engineering strategy to construct nickel hydroxide with a parallel array structure on nickel foil (denoted as Ni(OH)2/NFPA, where NFPA represents nickel foil with parallel array) via a facile two-step etching-hydrothermal method. Structural characterization confirms the formation of high-index Ni(220) surfaces and well-aligned hydroxide nanostripes, which promote more favorable bubble–electrode interactions and contribute to improved interfacial stability. Owing to its characteristic parallel array configuration, Ni(OH)2/NFPA exhibits outstanding OER performance in alkaline electrolyte, delivering a low overpotential of 256 mV at 10 mA·cm−2together with a Tafel slope as small as 74.9 mV·dec−1, surpassing commercial RuO2and disordered Ni(OH)2nanosheets. The optimized electrode also delivers remarkable durability, maintaining stable operation for 48 h at 100 mA·cm−2even under harsh alkaline seawater conditions at 80 °C. Bubble dynamics analysis reveals that the ordered array morphology produces a superaerophobic surface, enabling rapid detachment of oxygen bubbles and ensuring efficient mass transport. This study highlights facet-controlled construction of parallel nanoarrays as a promising approach to improve catalytic efficiency, corrosion resistance, and bubble management in seawater electrolysis, offering useful implications for the rational design of high-performance electrodes for practical hydrogen production.