Monolayer NbSe2 Favors Ultralow Friction and Super Wear Resistance.

The urgent demand for atomically thin, superlubricating, and super wear-resistant materials in micro/nanoelectromechanical systems has stimulated the research of friction-reducing and antiwear materials. However, the fabrication of subnanometer-thick films with superlubricating and super wear-resistant properties under ambient conditions remains a huge challenge. Herein, high-quality monolayer (ML) NbSe2 (∼0.8 nm) with ultralow friction and super wear resistance in an atmospheric environment was successfully grown by chemical vapor deposition (CVD) for the first time. Moreover, compared with few-layered (FL) NbSe2, ML NbSe2 has a lower friction coefficient and better wear resistance. On the basis of density function theory (DFT) calculations, the adhesion and the degree of charge transfer between ML NbSe2 and the substrate is larger than that of the topmost layer to the underlying layers of NbSe2 with two or more layers, which can be used to explain that the ML NbSe2 favors ultralow friction and super wear resistance.

Long noncoding RNA-LINC00478 promotes the progression of clear cell renal cell carcinoma through PBX3.

Long noncoding RNAs play an important regulatory role in the development and progression of tumors. Our study found that LINC00478 was upregulated in clear cell renal cell carcinoma (ccRCC), so we made an in-depth exploration into its mechanism. In Caki-2 cells, we established the oe-LINC00478 cell line overexpressing LINC00478, and established underexpressing sh-LINC00478 cell line by short hairpin RNA silencing. The abilities of oe-LINC00478 cell invasion and metastasis were significantly enhanced, and the cell proliferative potential was also improved. The cellular expressions of PBX3, CDCA8, and CDK2 were upregulated, while in the sh-LINC00478 cells, the proliferative potential and metastatic and invasive abilities were weakened. Similarly, we established the PBX3-overexpressing oe-PBX3 cell line and the PBX3-underexpressing sh-PBX3 cell line, finding that the PBX3 overexpression enhanced the metastatic and invasive abilities of Caki-2 cells. When we overexpressed LINC00478 in PBX3-knockout Caki-2-PBX3- / - cells, no significant changes were noted in the metastatic or invasive ability. Through RNA pull-down and RNA-binding protein immunoprecipitation assays, we found that LINC00478 could facilitate the transcription-translation processes of PBX3 by binding to it, thus further promoting the expression of downstream cyclins to exert its action. In animal experimentation, the oe-LINC00478 and sh-LINC00478 Caki-2 cells were separately seeded, revealing that the tumor volume was significantly larger in the oe-LINC00478 group than in the sh-LINC00478 group. This study finds that by promoting the PBX3 transcription, LINC00478 can further regulate the expressions of downstream cyclins, thereby facilitating the metastasis and invasion of ccRCC.

Lower Platelet-to-Lymphocyte Ratio Was Associated with Poor Prognosis for Newborn Patients in NICU.

Background: Platelet-to-lymphocyte ratio (PLR) is reported to be related to the outcome of intensive care unit (ICU) patients. However, little is known about their associations with prognosis in newborn patients in neonatal ICU (NICU). The aim of the present study was to investigate the prognostic significance of the PLR for newborn patients in the NICU. Methods: Data on newborn patients in the NICU were extracted from the Multiparameter Intelligent Monitoring in Intensive Care III (MIMIC III) database. The initial PLR value of blood examinations within 24 h was analyzed. Spearman's correlation was used to analyze the association of PLR with the length of hospital and ICU stays. The chi-square test was used to analyze the association of PLR with mortality rate. Multivariable logistic regression was used to determine whether the PLR was an independent prognostic factor of mortality. The area under the receiver operating characteristic (ROC) curve was used to assess the predictive ability of models combining PLR with other variables. Results: In total, 5240 patients were enrolled. PLR was negatively associated with length of hospital stay and ICU stay (hospital stay: ρ = −0.416, p < 0.0001; ICU stay: ρ = −0.442, p < 0.0001). PLR was significantly correlated with hospital mortality (p < 0.0001). Lower PLR was associated with higher hospital mortality (OR = 0.85, 95% CI = 0.75−0.95, p = 0.005) and 90-day mortality (OR = 0.85, 95% CI = 0.76−0.96, p = 0.010). The prognostic predictive ability of models combining PLR with other variables for hospital mortality was good (AUC for Model 1 = 0.804, 95% CI = 0.73−0.88, p < 0.0001; AUC for Model 2 = 0.964, 95% CI = 0.95−0.98, p < 0.0001). Conclusion: PLR is a novel independent risk factor for newborn patients in the NICU.

[Water migration and kinetics of Arecae Semen during moistening process].

In this study, low-field nuclear magnetic resonance(LF-NMR) and magnetic resonance imaging(MRI) were employed to analyze the water distribution, status, and migration in the moistening process of Arecae Semen. Peleg model was adopted to study the water absorption kinetics of Arecae Semen moistened at different water temperatures(10, 30, and 50 ℃). The Arecae Semen samples soaked at different water temperatures all contained four water states: binding water T_(21), non-flowing water T_(22), free water T_(23), and unbound water T_(24). Non-flowing water had the largest increase in peak area during the moistening process, followed by free water. The peak areas of non-flowing water, free water, and total water were correlated with the water content(P<0.01). Therefore, LF-NMR can quickly and non-destructively predict the water content of Arecae Semen during moistening. The peak area of non-flowing water and the content of free water were correlated with the content of arecoline in the soaking solution(P<0.01), which indicated that the faster flow of non-flowing water and more free water corresponded to more arecoline dissolved. The MRI images showed that the water migration pathway varied at different soaking temperatures, and the moistening degree obtained by this means was consistent with that obtained based on traditional experience. The rate constant K_1 fitted by Peleg model decreased with the increase in water temperature, while the capacity constant K_2 showed an opposite trend. The Arrhenius equation fitting of K_1 with temperature showed that the activation energy of Arecae Semen in the moistening process was 32.98 kJ·mol~(-1). LF-NMR/MRI can be used to analyze the water status and content and determine the end moisturing point of Arecae Semen. Peleg model can accurately describe the water absorption properties of Arecae Semen in the moistening process. The findings of this study can guide the moistening optimization and mechanism research of other seed Chinese medicinal materials.

TVT-O vs TVT-S for female stress urinary incontinence: A systematic review and meta-analysis.

BACKGROUND: Tension-free vaginal tape obturator (TVT-O) and tension-free vaginal tape secur (TVT-S) are common surgeries for the treatment of stress urinary incontinence (SUI), several randomised controlled trials (RCTs) have compared the effects of TVT-O and TVT-S, yet the results remained inconsistent. Therefore, we attempted to conduct this systematic review and meta-analysis to analyse the role of TVT-O and TVT-S in patients with SUI. METHODS: We searched PubMed databases from inception date to Jan 15, 2020 for RCTs that compared TVT-O and TVT-S in SUI patients. Two authors independently screened and extracted data from the published articles. Summary odd ratios (OR) or mean differences (MD) with 95% confidence intervals (95% CI) were calculated for each outcome by fixed- or random-effects model. RESULTS: Seven RCTs with a total of 755 patients were identified, with 373 patients for TVT-O and 382 patients for TVT-S. TVT-O preceded TVT-S in the objective cure at 12 months (OR = 1.72, 95% CI 1.21-2.45), subjective cure (OR = 1.98, 95% CI 1.08-3.62); but TVT-S have more advantage in the incidence of postoperative thigh pain (OR = 18.94, 95% CI 7.01-51.15); no significant differences on the duration of operative procedure (OR = -1.09, 95% CI -2.37-0.18), urinary retention (OR = 0.77, 95% CI 0.36-1.62) and urinary infection (OR = 1.80, 95% CI 0.63-5.13) were found. CONCLUSIONS: TVT-O should be preferred for patients with SUI even though with higher risks of postoperative thigh pain when compared with TVT-S, more related studies are needed to identify the role of TVT-O and TVT-S for the treatment of SUI.

microRNA221 is Involved in Human Placental Development by Targeting DDIT4.

BACKGROUND/AIMS: miR221 might have an important role in human embryo development. However, little is known about the function of miR221 in the human embryo. The aim of this study was to evaluate miR221 expression in human placental tissue, and to analyze the relationship between miR221 and target genes. METHODS: The human placentas tissue samples were collected from healthy pregnant women who were willing to terminate their pregnancy. The total RNA isolation and microRNA reverse transcription quantification were performed by TaqMan microRNA assay and qRT-PCR. RESULTS: The results showed that miR221 expression was significantly higher in 55- to 71-day placenta (mean value=0.1049) than that in 38- to 54- day (the mean value=0.0133) (p<0.001). miR221 targeting genes, such as PIK3R1, CDKN1B, CDKN1C, DDIT4, and FOS, were detected in human placenta tissue, but only DDIT4 was significantly decreased with development (mean value: 0.0101 for 38∼54 days, 0.0021 for 55∼71 days, p<0.001). Further analysis showed that only DDIT4 was negatively correlated with miR221 expression (DDIT4: r=-0.396, p=0.033; PI3KR: r=0.322, p=0.089; CDKN1B: r=0.298, p=0.128; CDKN1C: r=0.198, p=0.304; FOS: r=0.171, p=0.347). CONCLUSION: These findings indicate that miR221 might play an important role in human placental development by precisely regulating the DDIT4 expression.

Apocynin Attenuates Cobalt Chloride-Induced Pheochromocytoma Cell Apoptosis by Inhibiting P38-MAPK/Caspase-3 Pathway.

BACKGROUND/AIMS: Apocynin, a nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor, has been identified as a potential neuroprotectant. In this study, we aimed to investigate the protective effect of apocynin against cobalt chloride (CoCl2)-induced pheochromocytoma (PC12) cell apoptosis. METHODS: The PC12 cell culture was pretreated with apocynin and/or SB203580 (p38 mitogen-activated protein kinase [p38-MAPK] inhibitor) at different time points prior to CoCl2 incubation. The cell viability, apoptosis rate, DAN damage, and antioxidant activity were detected using cell counting kit-8 (CCK-8), flow cytometry, enzyme-linked immunosorbent assay (ELISA), and comet assay respectively. The protein and mRNA expressions of p38-MAPK and caspase-3 in the cells were measured by qRT-PCR and Western blotting. RESULTS: Apocynin inhibited CoCl2-mediated apoptosis, reduced oxidative stress, and down-regulated the expression of p38-MAPK and caspase-3. CONCLUSIONS: Our findings show that apocynin attenuated CoCl2-induced apoptosis by potently restraining p38-MAPK-caspase-3 signaling pathway in PC12 cells, suggesting that apocynin may be a potent prophylactic reagent against CoCl2-mediated PC12 cell apoptosis.

Paeoniflorin Attenuates Inflammatory Pain by Inhibiting Microglial Activation and Akt-NF-κB Signaling in the Central Nervous System.

BACKGROUND/AIMS: Paeoniflorin (PF) is known to have anti-inflammatory and paregoric effects, but the mechanism underlying its analgesic effect remains unclear. The aim of this study was to clarify the effect of PF on Freund's complete adjuvant (CFA)-induced inflammatory pain and explore the underlying molecular mechanism. METHODS: An inflammatory pain model was established by intraplantar injection of CFA in C57BL/6J mice. After intrathecal injection of PF daily for 8 consecutive days, thermal and mechanical withdrawal thresholds, the levels of inflammatory factors TNF-α, IL-1ß and IL-6, microglial activity, and the expression of Akt-NF-κB signaling pathway in the spinal cord tissue were detected by animal ethological test, cell culture, enzyme-linked immunosorbent assay, immunofluorescence histochemistry, and western blot. RESULTS: PF inhibited the spinal microglial activation in the CFA-induced pain model. The production of proinflammatory cytokines was decreased in the central nervous system after PF treatment both in vivo and in vitro. PF further displayed a remarkable effect on inhibiting the activation of Akt-NF-κB signaling pathway in vivo and in vitro. CONCLUSION: These results suggest that PF is a potential therapeutic agent for inflammatory pain and merits further investigation.

Mir-382 Promotes Differentiation of Rat Liver Progenitor Cell WB-F344 by Targeting Ezh2.

BACKGROUND/AIMS: Liver progenitor cells (LPCs) were considered as a promising hepatocyte source of cell therapy for liver disease due to their self-renewal and differentiation capacities, while little is known about the mechanism of LPC differentiate into hepatocytes. This study aims to explore the effect of miR-382, a member of Dlk1-Dio3 microRNA cluster, during hepatic differentiation from LPCs. METHODS: In this study, we used rat liver progenitor cell WB-F344 as LPC cell model and HGF as inducer to simulate the process of LPCs hepatic differentiation, then microRNAs were quantified by qPCR. Next, WB-F344 cell was transfected with miR-382 mimics, then hepatocyte cell trait was characterized by multiple experiments, including that periodic acid schiff staining and cellular uptake and excretion of indocyanine green to evaluate the hepatocellular function, qPCR and Western Blotting analysis to detect the hepatocyte-specific markers (ALB, Ttr, Apo E and AFP) and transmission electron microscopy to observe the hepatocellular morphology. Moreover, Luciferase reporter assay was used to determine whether Ezh2 is the direct target of miR-382. RESULTS: We found that miR-382 increased gradually and was inversely correlated with the potential target, Ezh2, during WB-F344 hepatic differentiation. In addition, functional studies indicated that miR-382 increased the level of hepatocyte-specific genes. CONCLUSIONS: This study demonstrates that miR-382 may be a novel regulator of LPCs differentiation by targeting Ezh2.

Association between COMT Polymorphism Val158Met and Opioid Consumption in Patients with Postoperative Pain: A Meta-Analysis.

BACKGROUND/AIMS: Several factors influencing postoperative pain and the effect of opioid analgesics have been investigated on an individual level. The aim of this study was to clarify the impact of catecholamine-O-methyltransferase (COMT) gene Val158Met on opioid consumption in postoperative patients. METHODS: A systematic review and meta-analysis of the literature up to September 30, 2017, were performed by using PubMed, Cochrane Library, ISI Web of Science, and Chinese National Knowledge Infrastructure (CNKI) database. The meta-analysis examined all studies involving the association between genetic polymorphisms of COMT Val158Met and opioid consumption during the acute postoperative period. RESULTS: Of the 153 identified studies, 23 studies were retrieved for systematic review and 10 studies were retrieved for meta-analysis. However, it was impossible to conduct meta-analysis on the association between COMT Val158Met polymorphism and postoperative pain because of heterogeneity of the data. Overall, meta-analysis showed that COMT Val/Met carriers consumed less opioid for analgesia within the first 24 hours after surgery (SMD = 0.14, 95% CI = [0.03, 0.25], P = 0.01) but not within 48 hours (SMD = 0.14, 95% CI = [0.08, 0.36], P = 0.21). There was no significant difference in opioid consumption between Val/ Val and Met/Met patients. CONCLUSION: Patients with Val/Met but not Met/Met allele variant consumed less opioid, though larger and better-designed studies are required to obtain an exclusive conclusion about the correlation between postoperative pain and COMT Val158Met polymorphism.

Ethylenediaminetetraacetic Acid Inhibits Vibrio Vulnificus-Induced Dendritic Cell Apoptosis by Lowering [Ca2+]i.

BACKGROUND/AIMS: Vibrio vulnificus (V. vulnificus) is a Gram-negative marine bacterium that can cause life-threatening primary septicemia, especially in the innate immune system. But how V. vulnificus affects and acts on dendritic cells (DC) is not well understood. The aim of the present study is to investigate [Ca2+]i change and the expression of the mTor-STAT3-Bcl-2 signaling pathway in V. vulnificus B2-induced DC apoptosis, and explore the protective effect of ethylenediaminetetraacetic acid (EDTA) against DC apoptosis in a V. vulnificus B2 and DC2.4 cell coculture infection model, using EDTA as an intervenient. METHODS: The apoptosis rate, [Ca2+]i, and the expression of STAT3, m-Tor and Bcl-2 were detected by cytometry, Fluo-8-AM and Western blotting respectively. RESULTS: The results demonstrated that EDTA inhibited the increase of [Ca2+]i, upregulated the expression of m-Tor-STAT3-Bcl-2 signaling pathway, and protected DC against V. vulnificus B2-induced apoptosis. CONCLUSIONS: EDTA inhibits V. Vulnificus-induced DC apoptosis by lowering [Ca2+]i via m-Tor-STAT3-Bcl-2 signaling pathway.

Role of Calcium Sensing Receptor in Streptozotocin-Induced Diabetic Rats Exposed to Renal Ischemia Reperfusion Injury.

BACKGROUND/AIMS: Renal ischemia/reperfusion (I/R) injury (RI/RI) is a common complication of diabetes, and it may be involved in altering intracellular calcium concentrations at its onset, which can result in inflammation, abnormal lipid metabolism, the production of reactive oxygen species (ROS), and nitroso-redox imbalance. The calcium-sensing receptor (CaSR) is a G-protein coupled receptor, however, the functional involvement of CaSR in diabetic RI/ RI remains unclear. The present study was intended to investigate the role of CaSR on RI/RI in diabetes mellitus (DM). METHODS: The bilateral renal arteries and veins of streptozotocin (STZ)-induced diabetic rats were subjected to 45-min ischemia followed by 2-h reperfusion with or without R-568 (agonist of CaSR) and NPS-2143 (antagonist of CaSR) at the beginning of I/R procedure. DM without renal I/R rats served as control group. The expressions of CaSR, calmodulin (CaM), and p47phox in the renal tissue were analyzed by qRT-PCR and Western blot. The renal pathomorphology, renal function, oxidative stress, inflammatory response, and calcium disorder were evaluated by detection of a series of indices by hematoxylin-eosin (HE) staining, transmission electron microscope (TEM), commercial kits, enzyme-linked immunosorbent assay (ELISA), and spectrophotofluorometry, respectively. RESULTS: Results showed that the expressions of CaSR, CaM, and p47phox in I/R group were significantly up-regulated as compared with those in DM group, which were accompanied by renal tissue injury, increased calcium, oxidative stress, inflammation, and nitroso-redox imbalance. CONCLUSION: These results suggest that activation of CaSR is involved in the induction of damage of renal tubular epithelial cell during diabetic RI/RI, resulting in lipid peroxidation, inflammatory response, nitroso-redox imbalance, and apoptosis.

Pharmacological Signatures of the Exenatide Nanoparticles Complex Against Myocardial Ischemia Reperfusion Injury.

BACKGROUND/AIMS: Myocardial ischemia/reperfusion (I/R) injury (MI/RI) is a critical cause of death in patients with heart disease. However, the pharmaco-therapeutical outcome for MI/RI remains unsatisfactory. Innovative approaches for enhancing drug sensitivity and recovering myocardial function in MI/RI treatment are urgently needed. The purpose of this study was to evaluate the protective effects of exenatide-loaded poly(L-lysine)-poly(ethylene glycol)-poly(L-lysine) (PLL-PEG-PLL) nanoparticles (NPs) against MI/RI. METHODS: The size of PLL-PEG-PLL NPs and the loading and release rates of exenatide were determined. The in vitro NP cytotoxicity was evaluated using newborn rat cardiomyocytes. Rats pretreated with free exenatide or exenatide/PLL-PEG-PLL polyplexes were subjected to 0.5-h ischemia and 2-h reperfusion in the left anterior descending coronary artery. The histopathologic lesions were assessed using hematoxylin-eosin staining. The general physiological indices, including blood pressure (BP), heart rate (HR), the left ventricular ejection fraction (LVEF) and end-diastolic pressure (LEVDP), and the left ventricular pressure maximal rate of rising (dp/dtmax), were monitored using a non-invasive blood pressure analyzer and color Doppler echocardiography. The antioxidative activity in the myocardial tissue was measured. The myocardial enzymatic activity was further estimated by determining the serum levels of creatine kinase (CK), lactate dehydrogenase (LDH), cardiac troponin T (cTnT), and glucagon-like peptide-1 (GLP-1), as well as the expression of GLP-1R in the myocardial tissue. RESULTS: Exenatide preconditioning attenuated the oxidative stress injury and promoted the myocardial function in I/R-induced myocardial injury, while the application of block copolymer PLL-PEG-PLL as a potential exenatide nanocarrier with sustained release significantly enhanced the bioavailability of exenatide. CONCLUSION: The block copolymer PLL-PEG-PLL may function as a potent exenatide nanocarrier for augmenting pharmacotherapy against MI/RI with unprecedented clinical benefits. Further study is needed to better clarify the underlying mechanisms.

Physiological Signatures of Dual Embryonic Origins in Mouse Skull Vault.

BACKGROUND/AIMS: The mammalian skull vault is a highly regulated structure and consists of several membrane bones of different tissue origins (e.g. neural crest derived frontal bone and mesoderm derived parietal bone). Although membrane bones form through intramembranous ossification, neural crest derived frontal bone has superior osteoblast activity and bone regeneration ability, triggering a novel conception for craniofacial reconstruction and bone regeneration called endogenous calvarial regeneration. However, a comprehensive landscape of the genes and signaling pathways involved in this process is not clear. METHODS: Transcriptome analysis within the two bone elements is firstly performed to determine the physiological signatures of differential gene expressions in mouse skull vault. RESULTS: Frontal bone tissues and parietal bone tissues maintain tissue origin through special gene expression similar to neural crest vs mesoderm tissue, and physiological functions between these two tissues are also found in differences related to proliferation, differentiation and extracellular matrix production and clustered signaling pathways. CONCLUSION: Our data provide novel insights into the potential gene regulatory network in regulating the development of neural crest-derived frontal bone and mesoderm-derived parietal bone.

Anterior wrist and medial malleolus: the optimal sites for tissue selection in electric death through hand-to-foot circuit pathway.

Specific morphological changes may be absent in some cases of electrocution shocked by the voltage of 220 V or lower. In this study, we attempted to demonstrate that the anterior wrist and medial malleolus were the optimal sites with promising and significant changes in electric death through the hand-to-foot circuit pathway. We established an electric shock rat model and observed histopathologic changes in the anterior wrist and medial malleolus. The results showed that the current intensities in the left anterior wrist and right medial malleolus were remarkably higher than those in the other sites, and the nuclei long/short (L/S) axis ratios of the arterial endotheliocyte and the skeletal muscle cell in these two areas were significantly higher than those in other parts of the body. These findings suggested that the anterior wrist and/or medial malleolus soft tissues as the narrowest parts of the limbs could be used as promising and useful sites for the assessment of electrical shock death, especially in forensic pathologic evaluation.

Chelerythrine Attenuates Renal Ischemia/Reperfusion-induced Myocardial Injury by Activating CSE/H2S via PKC/NF-κB Pathway in Diabetic Rats.

BACKGROUND/AIMS: Chelerythrine (CHE), a benzophenanthridine alkaloid, is a potent, selective, and cell-permeable protein kinase C (PKC) inhibitor. The purpose of the present study was to evaluate the effect of CHE on myocardial recovery after renal ischemia/reperfusion (I/R)-induced myocardial injury (RI/RMI) in a streptozocin (STZ)-induced diabetic rat model. METHODS: Diabetes mellitus (DM) rats preconditioned with CHE and D, L-propargylglycine (PAG) were subjected to renal I/R. The extent of cardiac morphologic lesions and the biochemical markers of cardiorenal function and oxidative stress were detected utilizing hematoxylin-eosin staining, commercial kits, and enzyme-linked immunoassay, respectively. The expressions of cystathionine-γ-lyase (CSE), PKC-α, PKC-ß2, and nuclear factor-kappa B (NF-κB) in the rat myocardial tissue were measured utilizing western blotting. RESULTS: Renal I/R treatment resulted in myocardial injury. CHE-preconditioning promoted the recovery from myocardial damage by ameliorating the biochemical parameters of myocardial injury, reducing oxidative stress, increasing the H2S level, up-regulating the expression of CSE, and down-regulating the expressions of PKC-α, PKC-ß2, and NF-κB. CONCLUSION: These findings suggest that CHE-pretreatment may exert a protective effect on the myocardium against RI/RMI by activating endogenous CSE/H2S via PKC/NF-κB pathway in STZ-induced diabetic rats. Further studies are needed defining underlying mechanisms.

Activation of Nrf2/HO-1 Pathway by Glycogen Synthase Kinase-3ß Inhibition Attenuates Renal Ischemia/Reperfusion Injury in Diabetic Rats.

BACKGROUND/AIMS: Diabetes mellitus can exacerbate renal ischemia-reperfusion (I/R) injury (RI/RI). The aim of the present study was to evaluate the protective effect of GSK-3ß inhibition (TDZD-8) on I/R-induced renal injury through the Nrf2/HO-1 pathway in a streptozocin (STZ)-induced diabetic rat model. METHODS: STZ-induced diabetic rats preconditioned with TDZD-8 and ZnPP were subjected to renal I/R. The extent of renal morphologic lesions. Renal function was assessed from blood urea nitrogen (BUN) and serum creatinine (Scr), as determined utlizing commercial kits. Oxidative stress and inflammatory activity in the kidney tissue was estimated from levels of malondialdehyde (MDA), interleukin-10 (IL-10), tumor necrosis factor-α (TNF-α), and nitric oxide (NO), as well as the activities of superoxide dismutase (SOD) and glutathione (GSH) using qRT-PCR and ELISA. The expressions of Nrf2, HO-1, Bcl-2 and NF-κB in the renal tissue were measured by qRT-PCR and western blotting. RESULTS: I/R-induced renal inflammation was reduced significantly by TDZD-8 pretreatment. Preconditioning with TDZD-8 suppressed NF-κB expression and enhanced Bcl-2 expression in the renal tissue. The upregulated level of malondialdehyde (MDA), and reduced activities of superoxide dismutase (SOD) and glutathione (GSH) in I/R-shocked rats were markedly restored by TDZD-8 pretreatment. Furthermore, pretreatment with TDZD-8 enhanced activation of the Nrf2/HO-1 pathway in the renal tissue of diabetic RI/RI rats. CONCLUSION: These findings suggest that preconditioning with TDZD-8 may protect the kidney from I/R-induced damage via the activation of the Nrf2/HO-1 pathway in STZ-induced diabetic rats. Further detailed studies are needed to further clarify the underlying mechanisms.

GSK-3beta Inhibitor Induces Expression of Nrf2/TrxR2 Signaling Pathway to Protect against Renal Ischemia/Reperfusion Injury in Diabetic Rats.

BACKGROUND/AIMS: Diabetes mellitus (DM) can lead to renal damage and dysfunction, and exacerbate renal ischemia/reperfusion injury (RI/RI). The aim of this study was to investigate the protective effect of GSK-3ß inhibitor TDZD-8 against RI/RI through Nrf2/TrxR2 signaling pathway in a rat DM model. METHODS: A DM rat model was established by a single injection of streptozocin. Diabetic rats were pretreated with TDZD-8 (1 mg/kg bw) or TDZD-8+auranofin (10 nmol/L, 5ml/kg bw), and then subjected to 45-min ischemia and 24-h reperfusion. Rats were equally randomized into four groups: a Sham-operated group, a RI/RI group, a TDZD-8 group, and a TDZD-8+auranofin group. Serum levels of BUN and Scr were measured. SOD activity, MDA content, and Nrf2, TrxR2 and caspase-3 expressions in rat kidney tissues were determined. RESULTS: Renal function was improved, oxidative stress and cell apoptosis were reduced, and the expression of Nrf2 and TrxR2 was up-regulated in TDZD-8 treated rats as compared with those in auranofin treated rats. CONCLUSION: TDZD-8 may exert its protective effect against RI/RI by regulating the Nrf2/TrxR2 signaling pathway in the kidney tissue in DM.

No association between fiber intake and prostate cancer risk: a meta-analysis of epidemiological studies.

BACKGROUND: The findings of epidemiologic studies on the association between fiber intake and prostate cancer risk remain conflicting. We aimed to examine this association by conducting a meta-analysis of epidemiological studies. METHODS: Relevant studies were identified by PubMed (1966 to March 2015) and Embase (1974 to March 2015) database search through March 2015. We included epidemiological studies that reported relative risks (RRs) or odds ratios (ORs) with 95% confidence intervals (CIs) for the association between dietary fiber intake and prostate cancer risk. Random effects models were used to calculate the summary risk estimates. RESULTS: For the highest compared with the lowest dietary fiber intake, a significantly decreased risk with prostate cancer was observed in case-control studies (OR = 0.82; 95% CI, 0.68-0.96), but not in cohort studies (RR = 0.94; 95% CI, 0.77-1.11). The combined risk estimate of all studies was 0.89 (95% CI, 0.77, 1.01). A significant heterogeneity was observed across studies (p = 0.005). There was no evidence of significant publication bias based on Begg's funnel plot (p = 0.753) or Egger's test (p = 0.946). CONCLUSIONS: This meta-analysis suggests the absence of evidence for association between dietary fiber intake and prostate cancer risk.

Citrus fruit intake and incidence of renal cell carcinoma: A meta-analysis of observational studies.

Observational studies on the association between citrus fruit intake and risk of renal cell carcinoma (RCC) have reported inconsistent results. We quantitatively assessed this association by conducting a meta-analysis. PubMed and Embase databases search was conducted including relevant studies published up to January, 2020. We included epidemiological studies that reported relative risks (RRs) or odds ratios (ORs) with 95% confidence intervals (CIs) for the association between citrus fruit intake and RCC risk. A total of eight epidemiological studies consisting of five cohort and three case-control studies were included. The overall analysis showed a significantly reduced risk of RCC for high intake of citrus fruit (OR = 0.84, 95% CI 0.73-0.95). No heterogeneity was detected among the included studies (p = 0.497 for heterogeneity; I2 = 0). There was no significant publication bias by Begg's test (p = 0.266) or Egger's test (P = 0.578). A statistically significant association between citrus fruit intake and RCC was observed in case-control studies (OR = 0.84, 95% CI 0.71-0.98), while no association was observed in cohort studies (OR = 0.84, 95% CI 0.64-1.05). In addition, the dose-response analysis indicated that the RCC risk reduced by 13% (95%CI 1.0%-27%, p = 0.04 for heterogeneity) for each 100 grams per day increment of citrus fruit intake. In summary, our findings suggest an inverse association between citrus fruit intake and RCC incidence.