Capillary-scale Microvessel Imaging with High-frequency Ultrasound Localization Microscopy in Mouse Brain.

Ultrasound localization microscopy is a super-resolution vascular imaging technique which has garnered substantial interest as a tool for small animal neuroimaging, neuroscience research, and the characterization of vascular pathologies. In the pursuit of increasingly high-fidelity reconstructions of microvasculature, there remains several outstanding questions concerning this sub-diffraction imaging technology, including the accurate reconstruction of microvessels approaching the capillary scale and the pragmatic challenges associated with long data acquisition times. In the context of small animal neurovascular imaging, we posit that increasing the ultrasound imaging frequency is a straightforward approach to enable higher concentrations of microbubble contrast agents, thus increasing the likelihood of microvascular/capillary mapping and decreasing the imaging duration. We demonstrate that higher frequency imaging results in improved ULM fidelity and more efficient microbubble localization due to a smaller microbubble point-spread function that is easier to localize, and which can achieve a higher localizable concentration within the same unit volume of tissue. A select example of in vivo capillary-level vascular reconstruction is demonstrated for the highest frequency imaging probe, which has substantial implications for neuroscientists investigating microvascular function in disease states, regulation, and brain development. High frequency ULM yielding a spatial resolution of 7.1µm, as measured by Fourier ring correlation, throughout the entire depth of the brain, highlighting this technology as a highly relevant tool for neuroimaging research.

The Potential Value of Paraspinal Nerve Block (PVB) in Percutaneous Nephrolithotomy (PCNL) Compared with General Anesthesia and Epidural Anesthesia.

Objective: To analyze the potential value of paraspinal nerve block (PVB) in percutaneous nephrolithotomy (PCNL) and to compare it with general anesthesia and epidural anesthesia. Methods: 120 patients undergoing PCNL surgery in Shanghai Jiao Tong University Affiliated Sixth People's Hospital from January 2021 to June 2022 were selected and divided into PVB anesthesia group, general anesthesia group, and epidural anesthesia group according to different anesthesia methods, with 40 cases in each group. The anesthesia index (anesthesia operation time, anesthetic effect time, anesthesia time), the vital signs (heart rate, mean arterial pressure), postoperative pain [visual analog scale (VAS)], stress response index (cortisol and noradrenaline), the incidence of adverse reactions (nausea and vomiting, lethargy, dizziness, skin itching, bradycardia) were compared among the three groups. Results: The operation time of the anesthesia in the PVB anesthesia group was 5.72±1.25, which was significantly lower than that in the the general (7.95±1.15) and epidural anesthesia groups(8.23±1.43), and the differences were statistically significant (P = .000). The time of onset of anesthesia in the PVB anesthesia group was 6.63±1.87, which was significantly lower than that in the the general (9.84±2.41) and epidural anesthesia groups(10.14±2.89), and the differences were statistically significant (P = .000).The heart rate during percutaneous puncture and intraoperative lithotripsy in the PVB anesthesia group was statistically lower than in the general and epidural anesthesia groups (P < .05). The mean arterial pressure 20 minutes after anesthesia and at the end of operation in the PVB anesthesia group was higher than that in the general anesthesia group, and the mean arterial pressure during percutaneous puncture and intraoperative lithotomy was lower than that in the general anesthesia group (P < .05). The VAS scores of the PVB anesthesia group at 2, 6, 12, 24, and 48 hours after the operation were lower than those of general and epidural anesthesia groups (P < .05). The incidence of adverse reactions was 5.00% (2/40) in the PVB anesthesia group and 35.00% (14/40) in the general anesthesia group, which was lower than that of 27.50% (11/40) in the epidural anesthesia group. (P < .05). Conclusion: The potential value of PVB in PCNL is high is better than that of general anesthesia and epidural anesthesia, anesthesia can shorten operation time and work time, extend the time of anesthesia to maintain, and be helpful to the intraoperative vital signs in patients with stable, mild postoperative pain and stress, low incidence of adverse reactions, efficacy and safety are good, can be introduced.

Efficient Self-Assembly Preparation of 3D Carbon-Supported Ti3 C2 Tx Hollow Spheres for High-Performance Potassium Ion Batteries.

MXenes are considered a promising negative electrode material for potassium ion batteries (PIBs) in view of their low potassium ion diffusion barrier and excellent electrical conductivity. However, the stacking phenomenon in practical applications severely reduces their active surface and leads to slow K+ diffusion. Herein, a facile composite template method is proposed to construct stacking-resistance 3D carbon-supported Ti3 C2 Tx (3D-C@Ti3 C2 Tx ) hollow spheres. Due to the unique structure, when used as a negative electrode material, as-prepared 3D-C@Ti3 C2 Tx hollow spheres show not only improved rate capability with 160.4 mAh g-1 at 100 mA g-1 and 133.7 mAh g-1 at 500 mA g-1 , but also stable cycling performance with 142.5 mAh g-1 specific capacity remained at 2 A g-1 after 4200 cycles. Furthermore, the full cells with 3D-C@Ti3 C2 Tx anode can operate stably for 1000 cycles at 100 mA g-1 . Moreover, the linear fit analysis demonstrates that 3D-C@Ti3 C2 Tx hollow spheres have a fast and stable capacitive potassium storage mechanism. This method is simple and easy to implement, which provide a feasible path to solve the stacking problem of 2D materials.

Identification Mechanism of BACE1 on Inhibitors Probed by Using Multiple Separate Molecular Dynamics Simulations and Comparative Calculations of Binding Free Energies.

ß-amyloid cleaving enzyme 1 (BACE1) is regarded as an important target of drug design toward the treatment of Alzheimer's disease (AD). In this study, three separate molecular dynamics (MD) simulations and calculations of binding free energies were carried out to comparatively determine the identification mechanism of BACE1 for three inhibitors, 60W, 954 and 60X. The analyses of MD trajectories indicated that the presence of three inhibitors influences the structural stability, flexibility and internal dynamics of BACE1. Binding free energies calculated by using solvated interaction energy (SIE) and molecular mechanics generalized Born surface area (MM-GBSA) methods reveal that the hydrophobic interactions provide decisive forces for inhibitor-BACE1 binding. The calculations of residue-based free energy decomposition suggest that the sidechains of residues L91, D93, S96, V130, Q134, W137, F169 and I179 play key roles in inhibitor-BACE1 binding, which provides a direction for future drug design toward the treatment of AD.

Binding Mechanism of Inhibitors to Heat Shock Protein 90 Investigated by Multiple Independent Molecular Dynamics Simulations and Prediction of Binding Free Energy.

The heat shock protein (HSP90) has been an import target of drug design in the treatment of human disease. An exploration of the conformational changes in HSP90 can provide useful information for the development of efficient inhibitors targeting HSP90. In this work, multiple independent all-atom molecular dynamics (AAMD) simulations followed by calculations of the molecular mechanics generalized Born surface area (MM-GBSA) were performed to explore the binding mechanism of three inhibitors (W8Y, W8V, and W8S) to HSP90. The dynamics analyses verified that the presence of inhibitors impacts the structural flexibility, correlated movements, and dynamics behavior of HSP90. The results of the MM-GBSA calculations suggest that the selection of GB models and empirical parameters has important influences on the predicted results and verify that van der Waals interactions are the main forces that determine inhibitor-HSP90 binding. The contributions of separate residues to the inhibitor-HSP90 binding process indicate that hydrogen-bonding interactions (HBIs) and hydrophobic interactions play important roles in HSP90-inhibitor identifications. Moreover, residues L34, N37, D40, A41, D79, I82, G83, M84, F124, and T171 are recognized as hot spots of inhibitor-HSP90 binding and provide significant target sites of for the design of drugs related to HSP90. This study aims to contribute to the development of efficient inhibitors that target HSP90 by providing an energy-based and theoretical foundation.

Novel Nomograms Based on Gamma-Glutamyl Transpeptidase-to-Lymphocyte Ratio Predict Prognosis of Hepatocellular Carcinoma Patients After Hepatectomy.

Background: The prediction of prognosis of hepatocellular carcinoma (HCC) is of great significance in improving disease outcome and optimizing clinical management, while reliable prognostic indicators are lacking. This study was conducted to develop readily-to-use nomograms for prognosis prediction of HCC after hepatectomy. Materials and Methods: Data of eligible patients were collected and analyzed retrospectively. Independent prognostic factors were identified by Cox regression, and nomograms for the prediction of disease-free survival (DFS) and overall survival (OS) were developed. The performance of the nomograms was evaluated by receiver operating characteristics (ROC) curves, C-indexes and calibration curves and was verified by the validation cohort. The predictive value of the nomograms was also compared with the 8th edition of American Joint Committee on Cancer (AJCC) Tumor-Node-Metastasis (TNM) and the Barcelona Clinic Liver Cancer (BCLC) staging systems. Results: In total, 599 patients were enrolled in the analysis: 420 in the training cohort and 179 in the validation cohort. The optimal cut-off value of Gamma-Glutamyl Transpeptidase-to-Lymphocyte Ratio (GLR) was 19.5. GLR contributed significantly to the nomograms with good predictive power. In ROC analyses, the areas under curve (AUCs) of the nomograms for 1-, 3- and 5-year DFS and OS prediction were 0.758, 0.756, 0.734 and 0.810, 0.799, 0.758, respectively. The C-indexes of the DFS nomogram were 0.697 (95% CI 0.665-0.729) in the training cohort and 0.710 (95% CI 0.664-0.756) in the validation cohort. For OS prediction, the C-indexes were 0.741 (95% CI 0.704-0.778) and 0.758 (95% CI 0.705-0.811) in the training and validation cohorts, respectively. The calibration curves demonstrated satisfactory agreement between nomogram predictions and actual observations. The nomograms demonstrated superior predictive performance to the TNM and the BCLC staging systems. Conclusion: Our novel nomograms showed adequate performance in the prediction of HCC prognosis after hepatectomy, which may facilitate the risk stratification and individualized management of HCC patients.

Tripartite Motif-Containing Protein 11 Reverses Paclitaxel Resistance in Prostate Cancer Drug-Resistant Cells by Mediating Family with Sequence Similarity 46B Expression.

Tripartite motif-containing protein 11 (TRIM11) and family with sequence similarity 46B (FAM46B) have been demonstrated to play roles in prostate cancer development, but their function in paclitaxel resistance remains unclear. The role of TRIM11 and FAM46B in paclitaxel resistance in prostate cancer was estimated. The paclitaxel-resistant cells were established with gradually increasing concentrations of paclitaxel in prostate cancer cells. The sensitivity to paclitaxel of established cells was assessed by the value of the median inhibitory concentration in the presence of 0-1000 nM paclitaxel. The expression level of TRIM11 and FAM46B was evaluated by real-time quantitative polymerase chain reaction. The proliferation, migration, and invasion of established cells were evaluated by CCK8 and Tran-swell assay. TRIM11 was upregulated in paclitaxel-resistant cells and promoted the proliferation, migration, and invasion of established cells. The significant downregulation of FAM46B was observed in paclitaxel-resistant cells. Although the overexpression of FAM46B suppressed the viability and metastasis of paclitaxel-resistant cells, which was reversed by the upregulation of TRIM11. Both the knockdown of TRIM11 and overexpression of FAM46B could enhance paclitaxel sensitivity of established resistant cells. The promoted effect of FAM46B overexpression was alleviated by the elevation of TRIM11. TRIM11 could improve the sensitivity to paclitaxel of resistant prostate cancer cells via regulating FAM46B.

Myricetin Induces Apoptosis and Protective Autophagy through Endoplasmic Reticulum Stress in Hepatocellular Carcinoma.

Myricetin, a natural flavonoid, exhibits diverse biological activities, including antitumor effects. The present study aimed to investigate the effects of myricetin on hepatocellular carcinoma (HCC) cells and explore the underlying molecular mechanisms. Our results showed that myricetin significantly inhibited cell proliferation and induced apoptosis in HCC cells. The apoptosis induced by myricetin was associated with the activation of endoplasmic reticulum (ER) stress. In addition, autophagy was enhanced in response to ER stress. Inhibition of autophagy by RNA interference or chemical inhibitors resulted in increased apoptosis in myricetin-treated HCC cells. The in vivo experiment also showed that myricetin effectively reduced tumor growth in an HCC xenograft model and that combination treatment with an autophagy inhibitor significantly enhanced this effect. These results indicated that myricetin induced apoptosis in HCC cells through the activation of ER stress. Protective autophagy was also upregulated during this process. Simultaneous inhibition of autophagy enhanced the anti-HCC activity of myricetin. Myricetin might be a promising drug candidate for HCC therapy, and the combined use of myricetin with autophagy inhibitors could be an effective therapeutic strategy.

Manipulation and Mechanical Deformation of Leukemia Cells by High-Frequency Ultrasound Single Beam.

Ultrasound single-beam acoustic tweezer system has attracted increasing attention in the field of biomechanics. Cell biomechanics play a pivotal role in leukemia cell functions. To better understand and compare the cell mechanics of the leukemia cells, herein, we fabricated an acoustic tweezer system in-house connected with a 50-MHz high-frequency cylinder ultrasound transducer. Selected leukemia cells (Jurkat, K562, and MV-411 cells) were cultured, trapped, and manipulated by high-frequency ultrasound single beam, which was transmitted from the ultrasound transducer without contacting any cells. The relative deformability of each leukemia cell was measured, characterized, and compared, and the leukemia cell (Jurkat cell) gaining the highest deformability was highlighted. Our results demonstrate that the high-frequency ultrasound single beam can be utilized to manipulate and characterize leukemia cells, which can be applied to study potential mechanisms in the immune system and cell biomechanics in other cell types.

Single-cell RNA sequencing identify SDCBP in ACE2-positive bronchial epithelial cells negatively correlates with COVID-19 severity.

The coronavirus disease 2019 (COVID-19), caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has resulted in many deaths throughout the world. It is vital to identify the novel prognostic biomarkers and therapeutic targets to assist with the subsequent diagnosis and treatment plan to mitigate the expansion of COVID-19. Since angiotensin-converting enzyme 2 (ACE2)-positive cells are hosts for COVID-19, we focussed on this cell type to explore the underlying mechanisms of COVID-19. In this study, we identified that ACE2-positive cells from the bronchoalveolar lavage fluid (BALF) of patients with COVID-19 belong to bronchial epithelial cells. Comparing with patients of COVID-19 showing severe symptoms, the antigen processing and presentation pathway was increased and 12 typical genes, HLA-DRB5, HLA-DRB1, CD74, HLA-DRA, HLA-DPA1, HLA-DQA1, HSP90AA1, HSP90AB1, HLA-DPB1, HLA-DQB1, HLA-DQA2, and HLA-DMA, particularly HLA-DPB1, were obviously up-regulated in ACE2-positive bronchial epithelial cells of patients with mild disease. We further discovered SDCBP was positively correlated with above 12 genes particularly with HLA-DPB1 in ACE2-positive bronchial epithelial cells of COVID-19 patients. Moreover, SDCBP may increase the immune infiltration of B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils and dendritic cells in different lung carcinoma. Moreover, we found the expression of SDCBP was positively correlated with the expression of antigen processing and presentation genes in post-mortem lung biopsies tissues, which is consistent with previous discoveries. These results suggest that SDCBP has good potential to be further developed as a novel diagnostic and therapeutic target in the treatment of COVID-19.

SphK2/S1P Promotes Metastasis of Triple-Negative Breast Cancer Through the PAK1/LIMK1/Cofilin1 Signaling Pathway.

BACKGROUND: Triple-negative breast cancer (TNBC) features a poor prognosis, which is partially attributed to its high metastatic rate. However, there is no effective target for systemic TNBC therapy due to the absence of estrogen, progesterone, and human epidermal growth factor 2 receptors (ER, PR, and HER-2, respectively) in cancer. In the present study, we evaluated the role of sphingosine kinase 2 (SphK2) and its catalyst sphingosine-1-phosphate (S1P) in TNBC metastasis and the effect of the SphK2-specific inhibitor ABC294640 on TNBC metastasis. METHODS: The function of SphK2 and S1P in TNBC cell metastasis was evaluated using transwell migration and wound-healing assays. The molecular mechanism of SphK2/S1P mediating TNBC metastasis was investigated using Western blot, histological examination, and immunohistochemistry assays. The antitumor activity of ABC294640 was examined in an in vivo TNBC lung metastatic model. RESULTS: Sphingosine kinase 2 promoted TNBC cell migration through the generation of S1P. Targeting SphK2 with ABC294640 inhibited TNBC lung metastasis in vivo. p21-activated kinase 1 (PAK1), p-Lin-11/Isl-1/Mec-3 kinase 1 (LIMK1), and Cofilin1 were the downstream signaling molecules of SphK2/S1P. Inhibition of PAK1 suppressed SphK2/S1P-induced TNBC cell migration. CONCLUSION: Sphingosine kinase 2/sphingosine-1-phosphate promotes TNBC metastasis through the activation of the PAK1/LIMK1/Cofilin1 signaling pathway. ABC294640 inhibits TNBC metastasis in vivo and could be developed as a novel agent for the clinical treatment of TNBC.

Pancancer Analysis of Neurovascular-Related NRP Family Genes as Potential Prognostic Biomarkers of Bladder Urothelial Carcinoma.

BACKGROUND: Neurovascular-related genes have been implicated in the development of cancer. Studies have shown that a high expression of neuropilins (NRPs) promotes tumourigenesis and tumour malignancy. METHOD: A multidimensional bioinformatics analysis was performed to examine the relationship between NRP genes and prognostic and pathological features, tumour mutational burden (TMB), microsatellite instability (MSI), and immunological features based on public databases and find the potential prognostic value of NRPs in pancancer. RESULTS: Survival analysis revealed that a low NRP1 expression in adrenocortical carcinoma (ACC), cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC), low-grade glioma (LGG), and stomach adenocarcinoma (STAD) was associated with poor prognosis. A high NRP2 expression in bladder urothelial carcinoma (BLCA), kidney renal papillary cell carcinoma (KIRP), and mesothelioma (MESO) was associated with poor prognosis. Moreover, NRP1 and NRP2 were associated with TMB and MSI. Subsequent analyses showed that NRP1 and NRP2 were correlated with immune infiltration and immune checkpoints. Genome-wide association analysis revealed that the NRP1 expression was strongly associated with kidney renal clear cell carcinoma (KIRC), whereas the NRP2 expression was closely associated with BLCA. Ultimately, NRP2 was found to be involved in the development of BLCA. CONCLUSIONS: Neurovascular-related NRP family genes are significantly correlated with cancer prognosis, TME, and immune infiltration, particularly in BLCA.

FAM46B Promotes Apoptosis and Inhibits Glycolysis of Prostate Cancer Through Inhibition of the MYC-LDHA Axis.

OBJECTIVE: Increased dependence on glycolysis is a known element of cancer. This study was designed to examine critical glycolysis components including transcription factor MYC and its downstream target lactate dehydrogenase A (LDHA), potential upstream regulators of glycolysis such as family with sequence similarity 46 member B (FAM46B), and the impact of the abundance of these proteins on apoptosis and glycolysis in prostate cancer. MATERIALS AND METHODS: A total of 70 primary prostate cancer patient samples were compared to normal tissues for FAM46B and LDHA expression and the corresponding patients' survival was monitored for 60 months. Prostate cancer cell lines were employed for protein expression manipulation, glucose uptake and LDH assays, and apoptosis measurements. A xenograft mouse model was used to quantify the role of FAM46B and LDHA on tumor growth in vivo. RESULTS: FAM46B expression was reduced in prostate tumor tissue compared to normal tissue and prostate cancer patients who expressed low amounts of FAM46B had shortened average lifespans compared to those who expressed higher amounts of FAM46B (p=0.008). FAM46B overexpression reduced glucose uptake, decreased LDH activity, and induced apoptosis in prostate cancer cell lines while FAM46B shRNA increased MYC levels in a non-malignant prostate cell line (P69). Conversely, forced expression of LDHA in LNCaP cells produced an increase in glycolysis markers with a corresponding decrease in apoptosis. FAM46B-overexpressing xenografts had starkly blunted growth which was restored with co-overexpression of LDHA. CONCLUSION: FAM46B plays a central role in regulating glycolysis and apoptosis in prostate cancer and operates through the regulation of LDHA via MYC. FAM46B's keystone status in prostate cancer makes it a potential, robust biomarker for prostate cancer prognosis and a promising therapeutic target.

Targeting SphK2 Reverses Acquired Resistance of Regorafenib in Hepatocellular Carcinoma.

Background: Regorafenib is a second-line therapy drug used for advanced hepatocellular carcinoma (HCC). Unfortunately, the survival benefit of the patients receiving this treatment is modest, which may be attributed to drug resistance. In the present study, sphingosine kinase 2 (SphK2) was targeted to reverse regorafenib resistance in HCC. Methods: The functions of SphK2 and sphingosine-1-phosphate (S1P), the catalytic product of SphK2 in regorafenib resistance of HCC cells, were evaluated by cell counting kit-8 assay, colony formation, cell cycle evaluation, and annexin V-fluorescein isothiocyanate/propidium iodide double-staining assay. The antitumor activity of combined treatment of regorafenib and the SphK2-specific inhibitor ABC294640 was examined in HCC cells in vitro and xenograft model in vivo. The molecular mechanisms of SphK2/S1P-mediating regorafenib resistance were investigated using cell line establishment and Western blot analysis. Results: Well-developed regorafenib-resistant HCC cells indicated high expression levels of SphK2. The sensitivity to regorafenib of regorafenib-resistant HCC cells was restored following SphK2 knockdown or pharmacological inhibition by ABC294640. In addition, ectopic expression of SphK2 and exogenous addition of S1P decreased the sensitivity of HCC cells to regorafenib. Furthermore, the combination treatment with ABC294640 sensitized resistant tumor to regorafenib in xenograft model of HCC. The phosphorylation levels of nuclear factor κB (NF-κB), as well as those of signal transducer and activator of transcription 3 (STAT3), were positively associated with SphK2 and S1P. Conclusions: SphK2/S1P mediates regorafenib resistance of HCC through NF-κB and STAT3 activation. Targeting SphK2 by ABC294640 potently reduces regorafenib resistance of HCC cells both in vitro and in vivo. The combination of ABC294640 and regorafenib could be developed as a novel potential treatment strategy for advanced HCC.

DEP Domain-Containing Protein 1B (DEPDC1B) Promotes Migration and Invasion in Pancreatic Cancer Through the Rac1/PAK1-LIMK1-Cofilin1 Signaling Pathway.

BACKGROUND: With increasing incidence, pancreatic cancer (PC) is one of the most common digestive tract tumors. However, the prognosis of PC is particularly dismal due to the highly invasive and metastatic behavior of this deadly disease. DEP domain-containing protein 1B (DEPDC1B), which is overexpressed in multiple tumors, such as breast cancer, oral cancer and non-small cell lung cancer, plays a significant role in cell movement, cell cycle and cytoskeleton reorganization. However, the function of DEPDC1B in PC remains poorly understood. METHODS: The function of DEPDC1B in the migration and invasion of PC was evaluated by wound healing and Transwell assays in vitro and PC-derived liver metastasis models in vivo. The molecular mechanisms of DEPDC1B were investigated through cell line establishment, Western blotting, qRT-PCR, immunoprecipitation, histological examination and immunohistochemistry analysis. RESULTS: DEPDC1B was overexpressed in PC cell lines. DEPDC1B regulated cell migration and invasion. DEPDC1B regulated the Rac1/PAK1-LIMK1-cofilin1 signaling pathway by interacting with Rac1. Rac1 inhibition suppressed DEPDC1B-induced migration and invasion in PC in vitro and DEPDC1B-induced liver metastasis in vivo. CONCLUSION: DEPDC1B promoted cell migration and invasion by activating the Rac1/PAK1-LIMK1-cofilin1 signaling pathway, thus providing a potential therapeutic target against PC.

MSRB3 promotes the progression of clear cell renal cell carcinoma via regulating endoplasmic reticulum stress.

BACKGROUND: Renal cancer represents about 3 % of all human cancers. Clear cell renal cell carcinoma (ccRCC) is the main type of renal cancer. Methionine sulfoxide reductase B3 (MSRB3) is a protein repair enzyme that specifically catalyzes the reduction of methionine-R-sulfoxide residues and has an antioxidant function. However, MSRB3's role in ccRCC is still obscure. METHODS: Immunohistochemical staining and Real-time PCR were used to compare the expression level of MSRB3 in ccRCC tissues and adjacent tissues. Western blot was used to detect the expression of MSRB3 in cell lines. Chi-square test were applied to evaluate the potential of MSRB3 to function as a cancer biomarker. RNA interference was used to inhibit MSRB3 expression in ccRCC cells, followed by detecting cell proliferation, apoptosis, migration and invasion. The markers of endoplasmic reticulum stress were then detected by western blot. RESULTS: In this study, we validated that MSRB3 was significantly up-regulated in ccRCC samples and cell lines. It was also demonstrated that the up-regulation of MSRB3 was associated with several clinicopathologic features. Knockdown of MSRB3 remarkably arrested the proliferation, migration and invasion, while promoted apoptosis, and induced the changes of markers of endoplasmic reticulum stress. CONCLUSION: In conclusion, we demonstrated that MSRB3 was an oncogene of ccRCC associated with patients' pathological characteristics and modulated endoplasmic reticulum stress of cancer cells.

Biosynthesis of selenium nanoparticles and their effect on changes in urinary nanocrystallites in calcium oxalate stone formation.

Plant bio constituents have the ability to prepare nanoparticles, and usually, plant polyphenols are tested to reduce sodium selenite to selenium nanoparticles (SeNPs). In this work, we showed the biosynthesis of SeNPs using Ocimum tenuiflorum leaf extract. The as obtained SeNPs were in the size range of 15-20 nm and spherical in shape. Also, TEM microscopic images represented the aggregation of crystal structures as extracellular deposits. Moreover, scanning electron microscopy was performed to examine the chemical transition of calcium oxalate (CaC2O4) crystal's shape and structure due to the influence of SeNPs. SeNPs inhibited the aggregation and growth of CaC2O4 monohydrate crystals and hence the prepared SeNPs could have important prospects in medical and pharmaceutical applications as a potential inhibitor of CaC2O4 urinary stones.

Plantamajoside exerts antifibrosis effects in the liver by inhibiting hepatic stellate cell activation.

The pathogenesis of liver fibrosis involves the activation of hepatic stellate cells (HSCs) into muscle fiber cells and fibroblasts. The aim of the current study was to investigate whether plantamajoside (PMS) exerted antifibrosis effects by affecting HSCs activation and survival during liver fibrosis, and to investigate the underlying mechanism. HSC-T6 cells were activated by exposure to platelet-derived growth factor BB (PDGF-BB), and were subsequently treated with increasing concentrations of PMS (0, 20, 40, 80 and 160 µg/ml). Cell viability, apoptosis, migration and invasion were determined using the Cell Counting Kit-8 (CCK-8) assay, flow cytometry and the Transwell assay, respectively. Results indicated that PDGF-BB significantly activated HSC-T6 cells, demonstrated by increased cell proliferation, enhanced cell migration and invasion as well as increased expression of α-smooth muscle actin (α-SMA) and collagen type 1 α 1 (Col1α1). PMS inhibited proliferation, induced cell apoptosis and prevented cell migration and invasion in PDGF-BB-treated HSC-T6 cells in what appeared to be a dose-dependent manner. PMS appeared to dose-dependently reduce the protein and mRNA levels of α-SMA and Col1α1 in PDGF-BB-treated HSC-T6 cells. Furthermore, the results of the present study suggested that PMS administration inhibited the protein expression of phosphorylated-protein kinase B in what appeared to be a dose-dependent manner. In conclusion, the data indicated that PMS exhibited an antifibrotic effect in the liver by inhibiting hepatic stellate cell activation and survival.

Down-Regulation of Nfatc1 Suppresses Proliferation, Migration, Invasion, and Warburg Effect in Prostate Cancer Cells.

BACKGROUND Prostate cancer (PCa), accounting for 28% of all male cancer cases, is the second leading cause of cancer-related death among men. NFATc1, belonging to the NFAT family, is overexpressed in PCa and is correlated with the risk of recurrence after radical prostatectomy. MATERIAL AND METHODS In the present study, the expression of NFATc, c-myc, and PKM2 in PCa cells was regulated by lentiviruses and then detected by real-time PCR and Western blot analysis. Further, proliferation, invasion, and migration assays were performed. The glucose consumption and lactate production were assessed by biochemical detection. RESULTS We found that NFATc1 down-regulation significantly suppressed the proliferation and Warburg effect of PCa cells, concurrent with a decrease of c-myc and PKM2 expression. Likewise, the abilities of migration and invasion were also inhibited in NFATc1-silenced PCa cells. In addition, NFATc1 down-regulation-induced inhibition of cell proliferation, migration, invasion, and Warburg effect were counteracted by up-regulation of c-myc or PKM2. The expression of PKM2 was positively regulated by NFATc1 and c-myc expression. CONCLUSIONS These results indicate that NFATc1 down-regulation can suppress the proliferation, Warburg effect, and migration and invasion abilities of PCa cells, probably by regulating c-myc and PKM2 expression. NFATc1 may be a potential therapeutic target for PCa and could be used as a diagnosis or prognosis indicator of PCa.