OGG1 contributes to hepatocellular carcinoma by promoting cell cycle-related protein expression and enhancing DNA oxidative damage repair in tumor cells.

BACKGROUND: This study aimed to analyze the expression of 8-oxoguanine DNA glycosylase (OGG1) in patients with hepatocellular carcinoma (HCC) and its effect on prognosis by bioinformatics techniques and to determine its possible carcinogenic mechanism through data mining. METHODS: The difference in OGG1 expression between healthy people and HCC patients was searched and analyzed by TCGA and GEO databases, and the effect of OGG1 on prognosis was judged by survival analysis. Meanwhile, the possible molecular mechanism of OGG1 in the tumorigenesis and development of HCC was explored by GO analysis, KEGG analysis, immune infiltration analysis, protein-protein interaction network, promoter methylation analysis, and so forth. Quantitative polymerase chain reaction (qPCR) was used to examine the gene expression in 36 pairs of HCC tissues and adjacent tissues. RESULTS: The expression of OGG1 in HCC patients was higher than that in healthy people, and the overexpression of OGG1 might stimulate cell proliferation by increasing the activity of cell cycle-related proteins. CONCLUSION: The alteration of OGG1 was significantly correlated with the tumorigenesis and development of HCC. OGG1 is expected to be a new biomarker for evaluating the prognosis of HCC and a new target for the treatment of HCC.

[Application of TG/HDL-C Combined with Liver Function Indexes to Predict Metabolic-Associated Fatty Liver Disease].

Objective: To study the application of triglycerides to high-density lipoprotein cholesterol ratio (TG/HDL-C) combined with liver function indexes to predict metabolic-associated fatty liver disease (MAFLD). Methods: A total of 2971 outpatients diagnosed with MAFLD and 2794 healthy controls were enrolled, and their relevant data were collected. Two-sample Mann-Whitney U test and binary logistic regression analysis were conducted to study the relationship between TG/HDL-C and MAFLD and to construct combined diagnosis models of MAFLD. The area under the curve (AUC) of receiver operating characteristic (ROC) was used to pick out the optimal model. Results: The TG/HDL-C of MAFLD patients was significantly higher than that of healthy controls. In multivariate analysis, after adjusting for body mass index, systolic blood pressure, diastolic blood pressure, fasting blood glucose, triglycerides, high-density lipoprotein cholesterol, uric acid and creatinine, the odds ratio of TG/HDL-C was 2.356 (95% confidence interval [CI]: 1.028-5.400). Therefore, TG/HDL-C was an independent risk factor for MAFLD. ROC curve analysis showed that the AUC of using TG/HDL-C to predict MAFLD was 0.795 (95% CI: 0.784-0.807), and when the cut-off value was 1.09, the sensitivity was 0.679 and the specificity was 0.755. The AUC of the diagnosis model established by a combined use of TG/HDL-C, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and albumin (ALB) was 0.890 (95% CI: 0.882-0.898), and when the cut-off value was 0.47, the sensitivity and specificity were 0.792 and 0.839, respectively. Conclusion: TG/HDL-C is an independent risk factor for MAFLD. TG/HDL-C can well predict MAFLD when it is used in combination with ALT, AST, and ALB.

Lactated Ringer's solution versus normal saline in pediatric living-donor liver transplantation: A matched retrospective cohort study.

BACKGROUND: In pediatric living-donor liver transplantation, lactated Ringer's solution and normal saline are commonly used for intraoperative fluid management, but the comparative clinical outcomes remain uncertain. AIMS: To compare the effect between lactated Ringer's solution and normal saline for intraoperative volume replacement on clinical outcomes among pediatric living-donor liver transplantation patients. METHODS: This single-center, retrospective trial study enrolled children who received either lactated Ringer's solution or normal saline during living-donor liver transplantation between January 2010 and August 2016. The groups with comparable clinical characteristics were balanced by propensity score matching. The primary outcome was 90-day all-cause mortality, and the secondary outcomes included early allograft dysfunction, primary nonfunction, acute renal injury, and hospital-free days (days alive postdischarge within 30 days of liver transplantation). RESULTS: We included 333 pediatric patients who met the entry criteria for analysis. Propensity score matching identified 61 patients in each group. After matching, the lactated Ringer's solution group had a higher 90-day mortality rate than the normal saline group (11.5% vs. 0.0%). Early allograft dysfunction and primary nonfunction incidences were also more frequent in the lactated Ringer's solution group (19.7% and 11.5%, respectively) than in the normal saline group (3.3% and 0.0%, respectively). In the lactated Ringer's solution group, four (6.6%) recipients developed acute renal injury within 7 days postoperatively compared with three (4.9%) recipients in the normal saline group. Hospital-free days did not differ between groups (9 days [1-13] vs. 9 days [0-12]). CONCLUSIONS: For intraoperative fluid management in pediatric living-donor liver transplantation patients, lactated Ringer's solution administration was associated with a higher 90-day mortality rate than normal saline. This finding has important implications for selecting crystalloid in pediatric living-donor liver transplantation. Further randomized clinical trials in larger cohort are necessary to confirm this finding.

Neferine inhibits LPS-ATP-induced endothelial cell pyroptosis via regulation of ROS/NLRP3/Caspase-1 signaling pathway.

BACKGROUND: Oxidative stress-induced endothelial dysfunction and pyroptosis play an important role during chronic kidney disease (CKD) progression. Neferine, which is an alkaloid ingredient from the lotus seed embryo, has many biological actions such as anti-inflammatory, anticancer and antioxidant. However, the role of neferine in endothelial cell pyroptosis and the involved mechanism remain obscure. The aim is to probe the protective effects of neferine on cell pyroptosis and the involved underlying mechanism. METHODS: After the HUVECs were primed with neferine treatment for 2 h prior to LPS and ATP exposure for 24 h, the cell proliferation was determined by BrdU; the cell LDH release was detected by LDH kits; the levels of intracellular ROS, MDA and SOD were tested by detection kits; Caspase-1 activity kit was used to determine caspase-1 activity; the contents of NLRP3, ASC, caspase-1, IL-1ß, IL-18 and GSDMD were tested by RT-PCR and western blot. RESULTS: We found that neferine could inhibit LPS-ATP-induced oxidative stress and the activation of NLRP3 inflammasome signaling, and increased the endothelial cell viability and SOD production. siRNA which mediated the knockdown of NLRP3 promoted the neferine-induced inhibition effects of cell pyroptosis. Furthermore, these neferine-induced effects were reversed by the over-expression of NLRP3. CONCLUSIONS: Our findings indicated neferine may reduce ROS by anti-oxidation and inhibit LPS-ATP-induced endothelial cell pyroptosis via blocking ROS/NLRP3/Caspase-1 signaling pathway, which provides the evidence for therapeutic effect in CKD.

Ligand-controlled regiodivergent aminocarbonylation of cyclobutanols toward 1,1- and 1,2-substituted cyclobutanecarboxamides.

Four-membered carbocycles are among the most sought-after backbones which are commonly found in biologically active molecules. However, difficulties on their producing are existing due to its highly strained ring system. On the other hand, cyclobutanols can be straightforwardly prepared and can serves as precursors for synthesizing cyclobutane derivatives. Here we report an example of regioselective aminocarbonylation of cyclobutanols in which the cyclobutane core remained intact. The method exhibits good functional group compatibility, as well as high regio- and stereoselectivity, offering new pathways for synthesizing several pharmaceuticals. Furthermore, this strategy enables the rapid installation of cyclobutane as a conformational restricted skeleton, greatly facilitating direct access to valuable drug molecules that require conformational restriction.

Palladium-Catalyzed Carbonylative Sonogashira Coupling of Aryl Thianthrenium Salts with Arylalkynes.

Alkynones are valuable compounds with applications in various areas. In this work, we developed an efficient carbonylation procedure for the carbonylative cross-coupling of aryl thianthrenium salts with aromatic alkynes. Various useful alkynones were produced in moderate to excellent yields under mild conditions. Notably, among the various tolerated functional groups, the bromide group can be maintained, which is ready for further coupling reactions.

Copper-catalyzed carbonylative multi-component borylamidation of alkenes for synthesizing γ-boryl amides with CO as both methylene and carbonyl sources.

A multi-component carbonylation reaction is an efficient strategy for the synthesis of valuable carbonyl compounds from simple and readily available substrates. However, there remain challenges in carbonylation reactions where two CO molecules are converted to different groups in the target product. Considering the merit of complex amides, we reported here a copper-catalyzed multi-component borylamidation for the synthesis of γ-boryl amides. This method provides access to a wide range of functional γ-boryl amides from alkenes, amines, B2pin2, and CO with good yields and excellent diastereomeric ratios. Notably, two CO molecules were converted to methylene and carbonyl groups in the target amides. A series of amines were successfully involved in the transformation, including arylamines, aliphatic amines, and hydrochloride salts of secondary aliphatic amines.

Evaluation of a concise fall risk stratification among older adults with cataracts in day surgery settings: A historically controlled study.

AIM: This study aimed to evaluate the use of a concise fall risk stratification in assessing and predicting falls compared with the Morse Falls Scale among older adults with cataracts in day surgery settings. METHODS: A historically controlled study conducted from July 2020 to June 2022 was used in a municipal ophthalmic hospital in China. The concise fall risk stratification which directly graded fall risk by multifactorial judgment was used during the intervention period, while the Morse Falls Scale which graded fall risk by scale scores was used during the control period. The fall risk levels, fall assessment time, fall rates, fall-related injuries, predictive validity, and patient satisfaction with day surgery care were extracted. Propensity score matching was performed to balance baselines. RESULTS: After matching, 4132 patients were included in the final analysis. Compared with the control group, the intervention group had significantly higher assessment results for fall risk level, a significantly shorter (by 48.15%) fall assessment time, and higher patient satisfaction. There were no differences in fall rates and fall-related injuries. Compared with the Morse Falls Scale, the concise fall risk stratification had higher sensitivity and negative predictive validity, and lower specificity and positive predictive validity, while the area under curve did not differ significantly. CONCLUSION: The use of the concise fall risk stratification reduced fall assessment time, improved patient satisfaction, and is unlikely to impact falls with an overall predictive performance comparable to that of the Morse Falls Scale for older cataract adults in day surgery settings.

[The comparison of the indoor environmental factors associated with asthma and related allergies among school-child between urban and suburban areas in Beijing].

OBJECTIVE: To study the indoor environmental factors associated with the prevalence of asthma and related allergies among school children. METHODS: A cluster sampling method was used and the ISAAC questionnaire was conducted. A total of 4612 elementary students under Grade Five of 7 schools were enrolled in the survey for the impact of indoor environmental factors on the prevalence of asthma and related allergies in several urban and suburban schools of Beijing. RESULTS: A total of 4060 sample were finally analyzed including 1992 urban and 2068 suburban. The prevalence of wheeze, allergic rhinoconjunctivitis and atopic eczema in the past 12 months was 3.1% (61/1992), 5.3% (106/1992), 1.1% (22/1992) among urban children while 1.3% (27/2068), 3.1% (65/2068), 1.0% (22/2068) among suburban children respectively. The prevalence of wheeze and allergic rhinoconjunctivitis of the past 12 months in urban were both significantly higher than that in suburban (χ(2) = 14.77, 11.93, P < 0.01). The incidences of having asthma and eczema ever among urban children (5.3% (105/1992), 29.4% (586/1992)) were significantly (χ(2) = 39.03, 147.22, P < 0.01) higher than that among suburban (1.7% (35/2068), 13.8% (285/2068)). Although the distributions of indoor environmental factors were similar in both areas, passive smoking and interior decoration had different influence on the prevalence of asthma and related allergies among school children in the two areas. The significant impact of passive smoking on having asthma ever among suburban children was observed (OR = 2.70, 95%CI = 1.17 - 6.23) while no significant result in urban (OR = 1.06, 95%CI = 0.71 - 1.58); the percentage of interior decoration was 84.0% (1673/1992) among urban children and 80.0% (1655/2068) among suburban children, there was significant impact of interior decoration on the prevalence of having eczema ever among urban children (OR = 1.57, 95%CI = 1.17 - 2.10) but no significant results were found in suburban sample (OR = 1.06, 95%CI = 0.76 - 1.48). CONCLUSION: The prevalence of asthma and related allergies among school children is much higher in urban areas than that in suburban areas and the indoor environmental factors such as passive smoking and interior decoration may differently explain the prevalence of asthma and related allergies in the two areas.

Long non-coding RNA HOTAIR modulates the progression of preeclampsia through inhibiting miR-106 in an EZH2-dependent manner.

AIMS: Preeclampsia (PE) accounts for the foremost cause of maternal and fetal mortality worldwide, whereas, there are no effective treatments for the disease yet. Long non-coding RNAs (lncRNAs) play critical roles in various human disorders, including PE. Here, we identified an up-regulated lncRNA HOTAIR, and explored its underlying mechanisms in PE. MAIN METHODS: qRT-PCR analysis was used to examine HOTAIR expression in PE tissues and cell lines. Trophoblast proliferation was examined by colony formation and 5-Ethynyl-2'-deoxyuridine (EdU) incorporation assays. Trophoblast migration and invasion was determined by transwell and wound healing assays. Bioinformatics analysis was performed to verify the regulation HOTAIR on miRNAs. The interaction between HOTAIR and EZH2 was detected using RNA immunoprecipitation assay (RIP). Chromatin immunoprecipitation (CHIP) assay was also performed to verify that the negative regulation of HOTAIR on miR-106a was dependent on the epigenetic repressor EZH2. KEY FINDINGS: HOTAIR was up-regulated in PE placenta tissues, which repressed the proliferation, migration and invasion of trophoblast cells. HOTAIR significantly repressed miR-106a expression and the reduced miR-106a level was also observed in placentas from PE patients. Additionally, miR-106a mimic enhanced the migration and invasion of trophoblast cells. Further mechanistic analyses implied that the action of HOTAIR is moderately attributable to its repression of miR-106a via association with EZH2. SIGNIFICANCE: High level of HOTAIR repressed the proliferation, migration and invasion of trophoblast cells through targeting miR-106 in an EZH2-dependent manner, which may provide new insights into the roles of HOTAIR and miR-106a as potential regulators in PE.

Vagus Nerve Stimulation for Depression: A Systematic Review.

Background: Depression is a common mental disorder worldwide. Psychological treatments and antidepressant medication are the usual treatments for depression. However, a large proportion of patients with depression do not respond to the treatments. In 2005, Vagus nerve stimulation was approved for the adjunctive long-term treatment of chronic or recurrent depression in adult patients experiencing a major depressive episode who had failed to respond to four or more adequate antidepressant treatments. However, the efficacy of VNS for treating depression remains unclear. Accordingly, we performed a systematic review to evaluate the efficacy and safety of VNS. Methods: We conducted a systematic review in accordance with the Cochrane Handbook for Systematic Reviews of Interventions. Systematic search was performed in the database of Pubmed, Embase, CENTRAL, and Web of science for identifying the suitable trials. Suicidal rate was considered as the primary outcome in this review. Result: Only two randomized sham controlled add-on studies including 255 cases (134 with VNS treatment and 121 control cases) were included in this review. None of the studies reported suicidal rate. We performed a qualitative analysis and it is suggested that there was no significant statistic difference between VNS and sham VNS on the score of 24-item Hamilton Rating Scale for Depression (HAMD24) (MD: -2.40, 95% CI: -7.90 to 3.10). Similar findings were also reported on improvement percentage of HAMD24 (MD: 1.00, 95%CI: -6.06 to 8.06), Montgomery-Asberg Depression Rating Scale (MADRS) (MD: 4.70, 95%CI: -2.98 to 12.38) and 30 item Inventory of Depressive Symptomalogy-Self-Report (IDS-SR30) (MD: 4.9, 95%CI: -1.89 to 11.69). However, a marginal difference of Beck Depression Inventory self-rating score was detected between the real and sham treatment (MD: 7.80, 95% CI: 0.34 to 15.26). Aminor effect of IDS-SR30was also found in real VNS group (RR: 2.33, 95% CI: 1.07 to 5.10). Conclusion: The efficacy and safety of VNS for depression is still unclear. Further randomized controlled trials are needed to confirm the efficacy and safety of VNS.

Dose-dependent neuroprotection of delta opioid peptide [D-Ala2, D-Leu5] enkephalin in neuronal death and retarded behavior induced by forebrain ischemia in rats.

Cerebral ischemic insult, mainly induced by cardiovascular disease, is one of the most severe neurological diseases in clinical. There's mounting evidence showing that delta opioid agonist [D-Ala2, D-Leu5] enkephalin (DADLE) has a tissue-protective effect. However, whether this property is effective to prevent neuronal death induced by forebrain ischemia is not clear. This study was aimed to investigate whether intracerebroventricular (ICV) administration of DADLE has a neuroprotective effect against forebrain ischemia in rats. We found in our study that administration of DADLE 45 min before forebrain ischemia had significant protective effect against CA1 neuronal lose. Further more, we found that DADLE had a dose-dependent protection for improving behavioral retardation revealed by Morris water maze and motor score test, while naltrindole, the antagonist of delta opioid receptor, partially abolished neuroprotective effect of DADLE, which implicated that both opioid and non-opioid systems are involved in ischemic insults and neuroprotection.

Atractylodin Induces Myosin Light Chain Phosphorylation and Promotes Gastric Emptying through Ghrelin Receptor.

Atractylodin is one of the main constituents in the rhizomes of Atractylodes lancea Thunb., being capable of treating cancer cachexia-anorexia and age-related diseases as an agonist of growth hormone secretagogue receptor (GHSR). GHSR was herein expressed in human gastric smooth muscle cells (HGSMCs) and activated by ghrelin receptor agonist L-692,585. Like L-692,585, atractylodin also increased Ca2+ and enhanced the phosphorylation of myosin light chain (MLC) through GHSR in HGSMCs. In addition, atractylodin promoted gastric emptying and MLC phosphorylation in the gastric antrum of mice also through GHSR. Collectively, atractylodin can activate GHSR in gastric smooth muscle, as a potential target in clinical practice.

[Pathogenic role of leukotriene B4 in pulmonary microvascular endothelial cell hyper- permeability induced by one lung ventilation in rabbits].

OBJECTIVE: To elucidate the pathogenic role of leukotriene B4 (LTB4) in increased pulmonary microvascular endothelial cell permeability induced by one lung ventilation (OLV) in rabbits. METHODS: Forty-eight healthy Japanese white rabbits were randomly divided into control group (group C), saline pretreatment group (group S), bestatin (a leukotriene A4 hydrolase (LTA4H) inhibitor) plus saline pretreatment group (group B), OLV group (group O), saline pretreatment plus OLV group (group SO) and bestatin plus saline pretreatment with OLV group (group BO). ELISA was used to detect LTB4 content in the lung tissues, and LTA4H and phospholipase Cεl (PLCEl) expressions were examined by Western blotting and quantitative PCR. The wet/dry weight (W/D) ratio of the lung, lung permeability index and the expressions of myosin light chain kinase (MLCK) protein and mRNA in the lung tissues were determined to evaluate the permeability of the pulmonary microvascular endothelial cells (PMVECs). The severities of lung injury were evaluated by lung histomorphological scores. RESULTS: No significant differences were found among groups C, S and B except that LTA4H expressions was significantly lower in group B than in groups C and S (P<0.05). OLV significantly increased the expressions of LTA4H (P<0.05) and resulted in LTB4 overproduction in the lungs (P<0.05) accompanied by significantly enhanced PLCE1 expression and PMVEC permeability (P<0.05). Pretreatment with bestatin, significantly reduced the expression of LTA4H and LTB4 production (P<0.05) and down-regulated the expression of PLCE1 in the lungs of the rabbits receiving OLV (P<0.05). CONCLUSION: Bestatin plays a protective role in OLV-induced rabbit lung injury by downregulating LTA4H to reduce the production of LTB4 in the lungs. LTB4 can increase PMVEC permeability by up-regulating PLCE1 expression in rabbits with OLV-induced lung injury.

[Effect of nicotine on the proliferation and cell apoptosis of oral squamous cell carcinoma SCC15 cells].

OBJECTIVE: To investigate the role of nicotine on the proliferation and cell apoptosis in SCC15 oral squamous cell carcinoma cells. METHODS: The growth, apoptosis, reactive oxygen species (ROS) level and nuclear factor kappalight-chain-enhancer of activated B cell (NF-κB) DNA binding activity were detected in SCC15 oral cancer cell using methly thiazolyl tetrazolium assay, flow cytometry, enzyme linked immunosorbent assay. RESULTS: In SCC15 cells treated with nicotine for 48 h at different concentrations (0.1, 1, 10 µmol/L) ROS level was (98.24 ± 0.04)%, (98.50 ± 0.06)%, (98.61 ± 0.07)%, respectively, which were significantly higher than in control groups [(96.01 ± 0.58)%, P = 0.000] and the A value for cell growth was 2.19 ± 0.08, 2.20 ± 0.11 and 2.38 ± 0.08, respectively, which were significantly higher than in control groups (1.93 ± 0.13) (P < 0.05). Only 1 µmol/L nicotine induced significantly higher cell apoptosis than in other groups (P = 0.000). Cell growth was inhibited in SCC15 cells treated with 1 µmol/L nicotine for 72 h, which had statistically significant difference compared with control (P = 0.022). Cell apoptosis rate in 1 µmol/L nicotine treated groups for 24 h was significantly higher than 48 h and 72 h (P = 0.000). NF-κB expression in the nucleus were increased in SCC15 cells treated with 1 µmol/L nicotine for 24, 48 and 72 h and the A value for NF-κB DNA binding activity was 1.509, 1.093 and 0.746, respectively, which were higher than in control group (0.544). CONCLUSIONS: Nicotine induced SCC15 cell growth and apoptosis, which maybe by NF-κB signal pathway activated in oral cancer cells.

Protective effects of the delta opioid peptide [D-Ala2, D-Leu5]enkephalin in an ex vivo model of ischemia/reperfusion in brain slices.

INTRODUCTION: The delta opioid peptide [D-Ala2, D-Leu5]enkephalin (DADLE) plays a key role in neuronal protection against both hypoxic and ischemic conditions. However, the cellular mechanisms of action of DADLE under these conditions remain unclear. METHODS: Ischemia was simulated with perfusing the brain slices with glucose-free artificial cerebrospinal fluid. Apoptosis was examined using an in situ cell death detection kit and expressed as the percentage of positively labeled neurons relative to total number of neurons. PCR was performed by adding cDNA, 5 pm dNTP, 1 µL Taqase, and primers. PCR products were separated with electrophoresis, stained with ethidium bromide, and visualized under ultraviolet light. AIMS: To investigate the potential effects of DADLE in an ex vivo model of cerebral ischemia/reperfusion. RESULTS: DADLE attenuated lactic dehydrogenase release and neuronal apoptosis in a concentration-dependent manner. The protective effects of DADLE were attenuated by representative selective delta2, but not delta1 opioid antagonists. Treatment with PD98059, a selective inhibitor of ERK kinase (MEK), also blocked the protective effect of DADLE as well as ERK phosphorylation induced by DADLE. CONCLUSIONS: Endogenous opioid peptides could promote cell survival via delta2 opioid receptors, possibly through the downstream MEK-ERK pathway.