Inhibition of USP1 ameliorates hypertensive nephropathy through regulating oxidative stress and ferroptosis: A precise treatment via SJB3-019A nanodelivery.

Hypertensive nephropathy is second only to diabetes for the causation of chronic kidney disease worldwide. As the mortality and morbidity of hypertensive nephropathy keep increasing, it is important to elucidate its pathogenesis and develop new treatment strategies. In this study, an angiotensin II (Ang II)-induced renal cell system was established, and the expression of ubiquitin specific peptidase 1 (USP1) in human kidney (HK-2) cells was found to be regulated by Ang II treatment through quantitative RT-PCR and Western blot assay. The detection of glutathione peroxidase (GSH-Px), malondialdehyde (MDA) and lipid reactive oxygen species (ROS) levels revealed that interference with USP1 reversed Ang II-induced oxidative stress and ferroptosis, which was enhanced by overexpression of USP1. Subsequently, USP1 inhibitor SJB3-019A loaded in MIL-100 and PEGTK was modified to fabricate SJB3-019A@MIL-PEGTK nanoparticles, which was confirmed to exhibit excellent alleviation of hypertension-induced oxidative stress and ferroptosis in renal cells both in vitro and in vivo. Our study identified an important pathogenesis of hypertensive nephropathy and SJB3-019A@MIL-PEGTK nanoparticle was used to develop an effective clinical treatment for hypertensive nephropathy.

Optimization of the Brewing Conditions of Shanlan Rice Wine and Sterilization by Thermal and Intense Pulse Light.

This study aimed to optimize the brewing conditions of Shanlan rice wine (SRW) and select a suitable sterilization method. The response surface method experiment was used to optimize the brewing process of SRW. LC-MS/MS (liquid chromatography-tandem mass spectrometry) and GC-MS (gas chromatography-mass spectrometry) were used to analyze the physicochemical components, free amino acids, and flavor metabolites of the thermal-sterilized SRW and the SRW sterilized by intense pulsed light (IPL), respectively. Results showed that the optimum fermentation conditions of SRW were as follows: fermentation temperature, 24.5 °C; Qiuqu amount (the traditional yeast used to produce SRW), 0.78%; water content, 119%. Compared with the physicochemical properties of the control, those of the SRWs separately treated with two sterilization methods were slightly affected. The 60 s pulse treatment reduced the content of bitter amino acids, maintained sweet amino acids and umami amino acids in SRW, and balanced the taste of SRW. After pasteurization, the ester content in wine decreased by 90%, and the alcohol content decreased to different degrees. IPL sterilization slightly affected the ester content and increased the alcohol content. Further analysis of the main flavor metabolites showed that 60 s pulse enhanced the important flavor-producing substances of SRW. In conclusion, 60 s pulse is suitable for sterilizing this wine.

Mesenchymal Stem Cells in Gastric Cancer: Vicious but Hopeful.

Tumor progression depends on the collaborative interactions between tumor cells and the surrounding stroma. First-line therapies direct against cancer cells may not reach a satisfactory outcome, such as gastric cancer (GC), with high risk of recurrence and metastasis. Therefore, novel treatments and drugs target the effects of stroma components are to be promising alternatives. Mesenchymal stem cells (MSC) represent the decisive components of tumor stroma that are found to strongly affect GC development and progression. MSC from bone marrow or adjacent normal tissues express homing profiles in timely response to GC-related inflammation signals and anchor into tumor bulks. Then the newly recruited "naïve" MSC would achieve phenotype and functional alternations and adopt the greater tumor-supporting potential under the reprogramming of GC cells. Conversely, both new-comers and tumor-resident MSC are able to modulate the tumor biology via aberrant activation of oncogenic signals, metabolic reprogramming and epithelial-to-mesenchymal transition. And they also engage in remodeling the stroma better suited for tumor progression through immunosuppression, pro-angiogenesis, as well as extracellular matrix reshaping. On the account of tumor tropism, MSC could be engineered to assist earlier diagnosis of GC and deliver tumor-killing agents precisely to the tumor microenvironment. Meanwhile, intercepting and abrogating vicious signals derived from MSC are of certain significance for the combat of GC. In this review, we mainly summarize current advances concerning the reciprocal metabolic interactions between MSC and GC and their underlying therapeutic implications in the future.

Prognostic significance of chemokines CCL11 and CCL5 modulated by low-density lipoprotein cholesterol in colon cancer patients with normal body mass index.

BACKGROUND: Many studies have shown an elevated level of cholesterol in colon tumors as compared to normal tissue. Obesity and high low-density lipoprotein cholesterol (LDL-C) are known risk factors for colon cancer. However, the role of LDL-C in colon cancer patients with normal body mass index (BMI) remains elusive. METHODS: Levels of serum cholesterol and oxysterols were quantified by ultra-performance liquid chromatography-tandem mass spectrometer (UPLC-MS/MS) from 129 individuals with normal BMI, including 32 with solitary polyp, 36 with multiple polyps, and 31 with adenocarcinoma as well as 32 healthy controls. In vitro, colon cancer cells were treated with LDL-C and assayed for chemokines via RNA-Seq and mitochondrial morphology via transmission electron microscopy and immunofluorescence. Additionally, correlation analysis was performed between LDL-C-induced chemokines and the overall survival of colon cancer patients from the Cancer Genome Atlas (TCGA), the Genotype-Tissue Expression (GTEx), and the Human Protein Atlas (HPA) database. RESULTS: The serum cholesterol level was significantly higher in colon adenocarcinoma patients with normal BMI than that in healthy controls (P<0.001). LDL-C potentiated colon cancer cell invasion and resistance to glucose-deprivation in vitro via chemokine-mediated signaling, mainly upregulation of CC chemokine ligand (CCL) 5 and downregulation of CCL 11. By analyzing the RNA expression data of colorectal cancer from TCGA, GTEx, and HPA, we demonstrated that the CCL5 level in colorectal adenocarcinoma tissues was significantly increased relative to adjacent normal tissues (P=0.01) while the CCL11 level was decreased (P=0.01). Both increased CCL5 and decreased CCL11 showed a negative correlation with the 5-year overall survival in tumor node metastasis (TNM) stage II colon cancer patients (P=0.0032, 0.026 for CCL5 and CCL11, respectively). CONCLUSIONS: Our study supports the idea that LDL-C regulates the expression of CCL5 and CCL11 chemokines, which may have predictive values for survival in colon cancer patients with normal BMI, especially for patients in TNM stage II.

Long noncoding RNA Kcnq1ot1 promotes sC5b-9-induced podocyte pyroptosis by inhibiting miR-486a-3p and upregulating NLRP3.

Podocytes are epithelial cells adhering glomerular capillaries, which regulate the integrity of glomerular filtration barrier. Irreversible podocyte injury induces glomerular inflammation and causes chronic renal diseases. Kcnq1ot1, a long noncoding RNA, participates in the pathogenesis of diabetic retinopathy and cardiomyopathy. However, its function in podocyte injury is elusive. Pyroptosis of murine podocyte MPC5 was triggered by sublytic complement C5b-9 (sC5b-9) for subsequent in vitro functional and mechanistic investigation. Gain/loss-of-function analysis was conducted to examine the functional role of Kcnq1ot1 in podocyte pyroptosis. Meanwhile, the molecular mechanism of Kcnq1ot1's effect on podocyte injury was explored by identifying downstream molecules and their intermediate interactions. Kcnq1ot1 was upregulated in sC5b-9-induced podocytes, and silencing Kcnq1ot1 could inhibit sC5b-9's effect on podocyte pyroptosis. We also identified the interaction between Kcnq1ot1 and miR-486a-3p, through which Kcnq1ot1 mediated miR-486a-3p inhibition by sC5b-9. Furthermore, miR-486a-3p reduced the transcriptional activity of NLRP3, while the overexpression of NLRP3 enhanced sC5b-9's effect on podocyte pyroptosis through activating NLRP3 inflammasome. sC5b-9 induces pyroptosis in podocytes through modulating the Kcnq1ot1/miR-486a-3p/NLRP3 regulatory axis, and these uncovered key molecules might facilitate podocyte-targeted treatment for renal inflammatory diseases.

LncRNA NCK1-AS1 Promotes Cancer Cell Proliferation and Increase Cell Stemness in Urinary Bladder Cancer Patients by Downregulating miR-143.

BACKGROUND: Long noncoding RNAs (lncRNAs) play critical and complex roles in regulating various biological processes of cancers. Our study aimed to investigate the involvement of lncRNA NCK1-AS1 in urinary bladder cancer (UBC). METHODS: qRT-PCR was used to detect the expression of lncRNA NCK1-AS1 and miR-143 in UBC tissues and cells. The dual-luciferase reporter system assays were used to confirm the interaction between NCK1-AS1 and miR-143, and flow cytometry assays were applied to examine the behavioral changes in HT-1376 and HT-1197 cell lines. RESULTS: It was observed that NCK1-AS1 was up-regulated, while miR-143 was down-regulated in tumor tissues than in adjacent healthy tissues of urinary bladder cancer (UBC) patients. A 5-year survival analysis showed that the survival rate of patients with high NCK1-AS1 level or low miR-143 level in tumor tissues appears relatively low. Correlation analysis revealed a significant inverse correlation between NCK1-AS1 and miR-143 in tumor tissues. Over-expression NCK1-AS1 reduced the expression level of miR-143, while elevating the level of miR-143 failed to affect NCK1-AS1 expression. NCK1-AS1 over-expression led to promoted proliferation and increased percentage of CD133+ (stemness) cells. CONCLUSION: Therefore, NCK1-AS1 promotes cancer cell proliferation and increases cell stemness in UBC patients by down-regulating miR-143.

[Advances in serum biomarkers for early diagnosis of gastric cancer].

Early diagnosis is the key to improve the prognosis of gastric cancer. How to screen out high-risk subjects of gastric cancer in population is a hot spot. Serum-based early detection of gastric cancer is suitable for high-risk population screening, which is more convenient and safer. This article reviews the diagnostic value of serum biomarkers for gastric cancer, including serum DNA methylation, various RNAs, pepsinogen, gastrin, osteopontin, MG7-Ag and CA724. Until now, there is still lack of ideal biomarkers for gastric cancer, and searching for specific RNAs may be promising for early diagnosis and screening of gastric cancer.

Detection of Reactive Oxygen Species in Anion Exchange Membrane Fuel Cells using In†Situ Fluorescence Spectroscopy.

The objectives of this study were: 1) to confirm superoxide anion radical (O2.- ) formation, and 2) to monitor in real time the rate of O2.- generation in an operating anion exchange membrane (AEM) fuel cell using in situ fluorescence spectroscopy. 1,3-Diphenlisobenzofuran (DPBF) was used as the fluorescent molecular probe owing to its selectivity and sensitivity toward O2.- in alkaline media. The activation energy for the in situ generation of O2.- during AEM fuel cell operation was estimated to be 18.3 kJ mol-1 . The rate of in situ generation of O2.- correlated well with the experimentally measured loss in AEM ion-exchange capacity and ionic conductivity attributable to oxidative degradation.