TuBG1 promotes hepatocellular carcinoma via ATR/P53-apoptosis and cycling pathways

Background:As reported,γ-tubulin(TuBG1)is related to the occurrence and development of various types of malignant tumors.However,its role in hepatocellular cancer(HCC)is not clear.The present study was to investigate the relationship between TuBG1 and clinical parameters and survival in HCC patients.Methods:The correlation between TuBG1 and clinical parameters and survival in HCC patients was ex-plored by bioinformatics analysis.Immunohistochemistry was used for the verification.The molecular function of TuBG1 was measured using colony formation,scratch assay,trans-well assay and flow cytometry.Gene set enrichment analysis(GSEA)was used to pick up the enriched pathways,followed by investigating the target pathways using Western blotting.The tumor-immune system interactions and drug bank database(TISIDB)was used to evaluate TuBG1 and immunity.Based on the TuBG1-related immune genes,a prognostic model was constructed and was further validated internally and externally.Results:The bioinformatic analysis found high expressed TuBG1 in HCC tissue,which was confirmed us-ing immunohistochemistry and Western blotting.After silencing the TuBG1 in HCC cell lines,more G1 arrested cells were found,cell proliferation and invasion were inhibited,and apoptosis was promoted.Furthermore,the silence of TuBG1 increased the expressions of Ataxia-Telangiectasia and Rad-3(ATR),phospho-P38 mitogen-activated protein kinase(P-P38MAPK),phospho-P53(P-P53),B-cell lymphoma-2 associated X protein(Bax),cleaved caspase 3 and P21;decreased the expressions of B-cell lymphoma-2(Bcl-2),cyclin D1,cyclin E2,cyclin-dependent kinase 2(CDK2)and CDK4.The correlation analysis of immunohistochemistry and clinical parameters and survival data revealed that TuBG1 was negatively corre-lated with the overall survival.The constructed immune prognosis model could effectively evaluate the prognosis.Conclusions:The increased expression of TuBG1 in HCC is associated with poor prognosis,which might be involved in the occurrence and development of HCC.

Role of ferroptosis in colorectal cancer

Colorectal cancer(CRC)is the second deadliest cancer and the third-most common malignancy in the world.Surgery,chemotherapy,and targeted therapy have been widely used to treat CRC,but some patients still develop resistance to these treatments.Ferroptosis is a novel non-apoptotic form of cell death.It is an iron-dependent non-apoptotic cell death characterized by the accumulation of lipid reactive oxygen species and has been suggested to play a role in reversing resistance to anticancer drugs.This review summarizes recent advances in the prognostic role of ferroptosis in CRC and the mechanism of action in CRC.

Intracranial large artery embolism due to carotid thrombosis caused by a neck massager:A case report

BACKGROUND There are few reported cases of intracranial large artery embolism due to carotid thrombosis caused by a neck massager.Herein we report such a case.CASE SUMMARY A 49-year-old woman presented with left limb weakness and dysarthria after a history of neck massage for 1 mo.Neurological examination showed left central facial paralysis and left hemiparesis with a National Institutes of Health Stroke Scale score of 12.Brain magnetic resonance imaging revealed restricted diffusion on diffusion-weighted imaging in the right parietal and temporal lobes.Computed tomography angiography(CTA)indicated M3 segment embolism of the right middle cerebral artery.Neck CTA revealed thrombosis of the bilateral common carotid arteries.Carotid ultrasound showed thrombosis in the bilateral common carotid arteries(approximately 2 cm below the proximal end of the carotid sinus),and contrast-enhanced ultrasound did not suggest enhancement.No hypertension,diabetes,heart disease,vasculitis,or thrombophilia was found after admission.After 1 wk of treatment with aspirin 200 mg and atorvastatin 40 mg,a carotid ultrasound reexamination showed that the thrombosis had significantly reduced.CONCLUSION Neck massager may cause carotid artery thrombosis.

Protection of Veratrum nigrum L.var.ussuriense Nakai alkaloids against ischemia-reperfusion injury of the rat liver

AIM： TO investigate the protective effects and possible mechanisms of Veratrum nigrum L. var. ussuriense Nakai alkaloids （VnA） on hepatic ischemia/reperfusion （I/R） injury in rats. METHODS： Forty male Wistar rats were randomly divided into four experimental groups （n = 10 in each）： （A） Control group （the sham operation group）; （8） I/R group （pretreated with normal saline）; （C） Small-dose （10 μg/kg） VnA pretreatment group; （D） Large-dose （20 μg/kg） VnA pretreatment group. Hepatic ischemia/ reperfusion （Hepatic I/R） was induced by occlusion of the portal vein and the hepatic artery for 90 min, followed by reperfusion for 240 min. The pretreatment groups were administered with VnA intraperitoneally, 30 min before surgery, while the control group and I/R group were given equal volumes of normal saline. Superoxide dismutase （SOD） activity, myeloperoxidase （MPO） activity and nitric oxide （NO） content in the liver tissue at the end of reperfusion were determined and liver function was measured. The expression of intercellular adhesion molecule-1 （ICAM-1） and E-selectin （ES） were detected by immunohistochemical examinations and Western blot analyses. RESULTS： The results showed that hepatic I/R elicited a significant increase in the plasma levels of alanine aminotransferase （ALT： 74.53 ± 2.58 IU/L vs 1512.54 ± 200.76 IU/L, P 〈 0.01） and lactic dehydrogenase （LDH： 473.48 ± 52.17 IU/L vs 5821.53 ± 163.69 IU/L, P 〈 0.01）, as well as the levels of MPO （1.97 ± 0.11 U/g vs 2.57 ± 0.13 U/g, P 〈 0.01） and NO （69.37 ± 1.52 μmol/g protein vs 78.39 ± 2.28 μmol/g protein, P 〈 0.01） in the liver tissue, all of which were reduced by pretreatment with VnA, respectively （ALT： 1512.54 ± 200.76 IU/L vs 977.93 ± 89.62 IU/L, 909.81 ± 132.76 IU/L, P 〈 0.01, P 〈 0.01; LDH： 5821.53 ± 163.69 IU/L vs 3015.44 ± 253.01 IU/L, 2448.75 ± 169.4 IU/L, P 〈 0.01, P 〈 0.01; MPO： 2.57 ± 0.13 U/g vs 2.13 ± 0.13 U/g, 2.07 ± 0.05 U/g, P 〈 0.01, P 〈 0.01; NO： 78.39 ± 2.28 μmol/g protein vs 71.11 ± 1.73 μmol/g protein, 68.58 ± 1.95 μmol/g protein, P 〈 0.05, P 〈 0.01）. The activity of SOD （361.75 ± 16.22 U/rag protein vs 263.19 ± 12.10 U/rag protein, P 〈 0.01） in the liver tissue was decreased after I/R, which was enhanced by VnA pretreatment （263.19 ± 12.10 U/rag protein vs 299.40 ± 10.80 U/rag protein, 302.09 ＋ 14.80 U/rag protein, P 〈 0.05, P 〈 0.05）. Simultaneously, the histological evidence of liver hemorrhage, polymorphonuclear neutrophil infiltration and the overexpression of ICAM-1 and E-selectin in the liver tissue were observed, all of which were attenuated in the VnA pretreated groups. CONCLUSION： The results demonstrate that VnA pretreatment exerts significant protection against hepatic I/R injury in rats. The protective effects are possibly associated with enhancement of antioxidant capacity, reduction of inflammatory responses and suppressed expression of ICAM-1 and E-selectin.

Effectiveness and safety of over-the-scope clip in closing perforations after duodenal surgery

BACKGROUND Endoscopic resection of duodenal subepithelial lesions(SELs)is a difficult procedure with a high risk of perforation.At present,dealing with perforation after endoscopic resection of duodenal SELs is still considered a great challenge.AIM To evaluate the effectiveness and safety of an over-the-scope clip(OTSC)in the treatment of perforation post-endoscopic resection of duodenal SELs.METHODS From May 2015 to November 2019,18 patients with perforation following endoscopic resection of duodenal SELs were treated with OTSCs.Data comprising the rate of complete resection,closure of intraprocedural perforation,delayed bleeding,delayed perforation,and postoperative infection were extracted.RESULTS The rate of complete removal of duodenal SELs and successful closure of the perforation was 100%.The median perforation size was 1 cm in diameter.Seventeen patients had minor intraoperative bleeding,while the remaining 1 patient had considerable amount of bleeding during the procedure.Seven patients had postoperative abdominal infections,of which 1 patient developed an abscess in the right iliac fossa and another patient developed septic shock.All 18 patients recovered and were discharged.No delayed bleeding or perforation was reported.The mean time taken to resume normal diet after the procedure was 6.5 d.The mean postoperative hospital stay was 9.5 d.No residual or recurrent lesions were detected during the follow-up period(15-66 mo).CONCLUSION Closing a perforation after endoscopic resection of duodenal SELs with OTSCs seems to be an effective and reasonably safe therapeutic method.

Prophylaxis with carnosol attenuates liver injury induced by intestinal ischemia/reperfusion

AIM： To investigate the possible protective effects of carnosol on liver injury induced by intestinal ischemia reperfusion （I/R）. METHODS： Rats were divided randomly into three experimental groups： sham, intestinal I/R and carnosol treatment （n = 18 each）. The intestinal I/R model was established by clamping the superior mesenteric artery for 1 h. In the carnosol treatment group, surgery was performed as in the intestinal I/R group, with intraperitoneal administration of 3 mg/kg carnosol 1 h before the operation. At 2, 4 and 6 h after reperfusion, rats were killed and blood, intestine and liver tissue samples were obtained. Intestine and liver histology was investigated. Serum levels of aspartate aminotransferase （AST）, alanine aminotransferase （ALT） and interleukin （IL）-6 were measured. Liver tissue superoxide dismutase （SOD） and myeloperoxidase （IvIPO） activity were assayed. The liver intercellular adhesion molecule-1 （ICAM-1） and nuclear factor κB （NF-κB） were determined by immunohistochemical analysis and western blot analysis. RESULTS： Intestinal I/R induced intestine and liver injury, characterized by histological changes, as well as a significant increase in serum AST and ALT levels. The activity of SOD in the liver tissue decreased after I/R, which was enhanced by carnosol pretreatment. In addition, compared with the control group, carnosol markedly reduced liver tissue MPO activity and serum IL-6 level, which was in parallel with the decreased level of liver ICAI-1 and NF-κB expression. CONCLUSION： Our results indicate that carnosol pretreatment attenuates liver injury induced by intestinal I/R, attributable to the antioxidant effect and inhibition of the NF-κB pathway.

The mTORC1 signaling network underlying the pathogenesis and treatment of depression: new insights into rapid-acting antidepressant therapies

Depression is a devastating mental disorder and major depressive disorder(MDD) that afflicts 16% of the global population at some point in their lives.Currently available classical antide.pressants(SSRIs,SNRIs,TCAs and MOIs),require a minimum of 2–4 weeks of continuous treat.ment to elicit therapeutic relief in depressed patients and are associated with high rates of non-respon.siveness,and limited duration of efficacy.Therefore,faster-acting antidepressant therapies are need.ed,particularly for patients at risk for suicide for current therapies for depression.Although the molecu.lar mechanisms underlying the pathogenesis of depression are still largely unclear,previous studies have suggested that modulators of mammalian target of rapamycin complex 1(mTORC1) signaling may have beneficial neuroprotective and antidepressant effects.Here,we review recent advances in understanding mTORC1 signaling in depression and potential therapeutic strategies resulting from modulation of the mTORC1 signaling network.We also highlight recent studies considered to support mTORC1 signaling modulation as a rapid-acting antidepressant therapy(e.g.ketamine,scopolamine,GLYX-13,(2R,6 R)-HNK,Ro-256891 etc.) and discuss future research directions.Studies on prospec.tive next-generation rapid-acting antidepressant therapies should focus on developing more selective glutamate receptors(e.g.α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors(AMPARs)agonists or activators) that activate the mTORC1 signaling pathway free of ketamine's adverse effects.

Effectiveness and safety of endoscopic resection for duodenal gastrointestinal stromal tumors:A single center analysis

BACKGROUND Endoscopic resection for duodenal gastrointestinal stromal tumors(GISTs)is still considered a great challenge with a high risk of complications,including perforation,bleeding,tumor rupture,and residual tumor.AIM To assess the effectiveness and safety of endoscopic resection for duodenal GISTs.METHODS Between January 2010 and January 2022,11 patients with duodenal GISTs were treated with endoscopic resection.Data were extracted for the incidence of complete resection,bleeding,perforation,postoperative infection,recurrence,and distant metastasis.RESULTS The incidence of successful complete resection of duodenal GISTs was 100%.Three cases(27.3%)had suspected positive margins,and the other 8 cases(72.7%)had negative vertical and horizontal margins.Perforation occurred in all 11 patients.The success rate of perforation closure was 100%,while 1 patient(9.1%)had suspected delayed perforation.All bleeding during the procedure was managed by endoscopic methods.One case(9.1%)had delayed bleeding.Postoperative infection occurred in 6 patients(54.5%),including 1 who developed septic shock and 1 who developed a right iliac fossa abscess.All 11 patients recovered and were discharged.The mean hospital stay was 15.3 d.During the follow-up period(14-80 mo),duodenal stenosis occurred in 1 case(9.1%),and no local recurrence or distant metastasis were detected.CONCLUSION Endoscopic resection for duodenal GISTs appears to be an effective and safe minimally invasive treatment when performed by an experienced endoscopist.

Level of proinsulin in association with cardiovascular risk factors and sleep snoring

AIM: To explore the relationship between the level of proinsulin with cardiovascular risk factors and sleep snoring.METHODS: Based on the random stratified sampling principle, 1 193 Chinese residents in Pizhou City, Jiangsu Province (530 males and 663 females, aged 35-59 years with an average age of 46.69 years) were recruited. Their sleep snoring habits were investigated. Biotin-avidin based double mAbs ELISA was used to detect specific insulin and proinsulin, and a risk factor score was established to evaluate the individuals according to the number of their risk factors.RESULTS: The results of Spearman correlation analysis and covariate ANOVA analysis after age and sex were controlled, indicated that not only the level of proinsulin (r = 0.156, P = 0.000, F= 5.980 P = 0.000), but also cardiovascular risk factors score (r = 0.194, P = 0.000,F= 11.135, P = 0.000) significantly associated with the frequency of sleep snoring, and the significant relationship between true insulin and frequency of sleep snoring was only shown in the covariate ANOVA analysis (F = 2.868,P = 0.022). The result of multivariate stepwise logistic regression after age, sex, body mass index, waist circumference and true insulin were controlled showed that proinsulin (division by interval of quartile) was an independent risk factor for sleep snoring (OR = 1.220,95%CI: 1.085-1.373, P = 0.001).CONCLUSION: The interaction of cardiovascular risk factors clustering, high proinsulin level and sleep breathing disorder may be a syndrome, which has not been recognized in human beings so far.

真核起始因子4E对小鼠动脉粥样硬化发生、发展的炎症调节作用

目的探讨真核起始因子4E(eIF4E)在小鼠动脉粥样硬化发生、发展过程中的炎症调节作用。方法分别用200 ng/μl脂多糖(LPS)和20 ng/μl白细胞介素-4(IL-4)诱导RAW264.7细胞12 h后提取mRNA,24 h后提取蛋白,采用实时荧光定量聚合酶链反应(qRT-PCR)和Western blotting检测eIF4E mRNA和蛋白在M1型和M2型巨噬细胞中的表达变化。复制ApoE^-/-动脉粥样硬化小鼠模型,检测小鼠腹主动脉eIF4E mRNA和蛋白表达变化;组织免疫荧光检测eIF4E在主动脉根部中分别与M1型和M2型巨噬细胞中的共表达。结果M1型巨噬细胞eIF4E mRNA和蛋白表达高于M2型巨噬细胞(P<0.05)。在ApoE^-/-小鼠动脉粥样硬化模型中,ApoE^-/-小鼠腹主动脉eIF4E mRNA和蛋白表达高于C57BL/6J小鼠(P<0.05);eIF4E与CD86的共定位表达高于eIF4E与CD206的共定位表达。结论eIF4E在动脉粥样硬化的发展过程中主要在M1型巨噬细胞中起作用,进而对动脉粥样硬化产生影响。

Research progress of miRNA in diabetic cardiomyopathy

Diabetic cardiomyopathy is one of the main causes of death of diabetic patients and seriously endangers human health.MiRNA is a type of endogenous non-coding RNA with a length of 18-25 nucleotides.It can regulate gene expression and plays an important role in the development of diabetic cardiomyopathy.This article will review the pathogenesis of diabetic cardiomyopathy and the important role of miRNA in its pathogenesis in order to provide a reference for future research.

Development in the application of laser-induced breakdown spectroscopy in recent years:A review

Laser-induced breakdown spectroscopy(LIBS)has been widely studied due to its unique advantages such as remote sensing,real-time multi-elemental detection and none-to-little damage.With the efforts of researchers around the world,LIBS has been developed by leaps and bounds.Moreover,in recent years,more and more Chinese LIBS researchers have put tremendous energy in promoting LIBS applications.It is worth mentioning that the application of LIBS in a specific field has its special application background and technical difficulties,therefore it may develop in different stages.A review summarizing the current development status of LIBS in various fields would be helpful for the development of LIBS technology as well as its applications especially for Chinese LIBS community since most of the researchers in this field work in application.In the present work,we summarized the research status and latest progress of main research groups in coal,metallurgy,and water,etc.Based on the current research status,the challenges and opportunities of LIBS were evaluated,and suggestions were made to further promote LIBS applications.

The Role of Osteoclasts in Psoriatic Arthritis

Psoriatic arthritis (PsA) is a chronic immune-mediated inflammatory disease related to psoriasis involving bone and cartilage. It is a heterogeneous disorder with a variety of clinical manifestations, which can include peripheral arthritis, axial spondylitis, enthesitis, skin and nail disease, dactylitis, uveitis, osteitis, inflammatory bowel disease. The distinctive feature of PsA is enthesitis. The characteristic bone erosion at the bone-pannus junction in PsA is mediated by osteoclasts, which are multinucleated giant cells derived from hematopoietic stem cells. Although the pathological mechanism of osteoclasts in PsA is mainly related to the destruction of the diseased joint, the exact pathogenesis of PsA is complex and the factors involved in initiation and termination of osteoclast need to be further explored. Much attention has been paid to the importance of osteoclast in psoriasis arthritis for decades. Based on the role of osteoclasts in PsA, our review discusses the formation and characteristics of multinucleated osteoclasts in PsA, summarizes current developments in osteoclast-related pathways in PsA including classical receptor activator of nuclear factor-κB-receptor activator of nuclear factor-κB ligand-osteoprotegerin pathway and immunomodulatory factors, as well as their advances and corresponding treatment. At present, the molecular and signal pathway that interacts with osteoclasts in the pathogenesis of PSA has not been fully elucidated, therefore more detailed studies are expected in the near future.