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1.
Biofactors ; 2024 Mar 22.
Article in English | MEDLINE | ID: mdl-38516823

ABSTRACT

Lactate dehydrogenase A (LDHA) is highly expressed in various tumors. However, the role of LDHA in the pathogenesis of B-cell lymphoma remains unclear. Analysis of data from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases revealed an elevated LDHA expression in diffuse large B-cell lymphoma (DLBC) tissues compared with normal tissues. Similarly, our results demonstrated a significant increase in LDHA expression in tumor tissues from the patients with B-cell lymphoma compared with those with lymphadenitis. To further elucidate potential roles of LDHA in B-cell lymphoma pathogenesis, we silenced LDHA in the Raji cells (a B-cell lymphoma cell line) using shRNA techniques. Silencing LDHA led to reduced mitochondrial membrane integrity, adenosine triphosphate (ATP) production, glycolytic activity, cell viability and invasion. Notably, LDHA knockdown substantially suppressed in vivo growth of Raji cells and extended survival in mice bearing lymphoma (Raji cells). Moreover, proteomic analysis identified feline sarcoma-related protein (FER) as a differential protein positively associated with LDHA expression. Treatment with E260, a FER inhibitor, significantly reduced the metabolism, proliferation and invasion of Raji cells. In summary, our findings highlight that LDHA plays multiple roles in B-cell lymphoma pathogenesis via FER pathways, establishing LDHA/FER may as a potential therapeutic target.

2.
BMC Geriatr ; 23(1): 698, 2023 10 27.
Article in English | MEDLINE | ID: mdl-37891456

ABSTRACT

BACKGROUND: This study aimed to construct a risk prediction model to estimate the odds of osteoporosis (OP) in elderly patients with type 2 diabetes mellitus (T2DM) and evaluate its prediction efficiency. METHODS: This study included 21,070 elderly patients with T2DM who were hospitalized at six tertiary hospitals in Southwest China between 2012 and 2022. Univariate logistic regression analysis was used to screen for potential influencing factors of OP and least absolute shrinkage. Further, selection operator regression (LASSO) and multivariate logistic regression analyses were performed to select variables for developing a novel predictive model. The area under the receiver operating characteristic curve (AUROC), calibration curve, decision curve analysis (DCA), and clinical impact curve (CIC) were used to evaluate the performance and clinical utility of the model. RESULTS: The incidence of OP in elderly patients with T2DM was 7.01% (1,476/21,070). Age, sex, hypertension, coronary heart disease, cerebral infarction, hyperlipidemia, and surgical history were the influencing factors. The seven-variable model displayed an AUROC of 0.713 (95% confidence interval [CI]:0.697-0.730) in the training set, 0.716 (95% CI: 0.691-0.740) in the internal validation set, and 0.694 (95% CI: 0.653-0.735) in the external validation set. The optimal decision probability cut-off value was 0.075. The calibration curve (bootstrap = 1,000) showed good calibration. In addition, the DCA and CIC demonstrated good clinical practicality. An operating interface on a webpage ( https://juntaotan.shinyapps.io/osteoporosis/ ) was developed to provide convenient access for users. CONCLUSIONS: This study constructed a highly accurate model to predict OP in elderly patients with T2DM. This model incorporates demographic characteristics and clinical risk factors and may be easily used to facilitate individualized prediction.


Subject(s)
Diabetes Mellitus, Type 2 , Osteoporosis , Aged , Humans , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus, Type 2/epidemiology , Retrospective Studies , Osteoporosis/diagnosis , Osteoporosis/epidemiology , Risk Factors , Cerebral Infarction
3.
Immun Inflamm Dis ; 11(9): e1013, 2023 09.
Article in English | MEDLINE | ID: mdl-37773718

ABSTRACT

BACKGROUND: Influenza-related encephalopathy is a rapidly progressive encephalopathy that usually presents during the early phase of influenza infection and primarily manifests as central nervous system dysfunction. This study aimed to analyze the current research status and hotspots of influenza-related encephalopathy since 2000 through bibliometrics analysis. METHODS: The Web of Science Core Collection (WOSCC) was used to extract global papers on influenza-related encephalopathy from 2000 to 2022. Meanwhile, the VOSviewer and CiteSpace software were used for data processing and result visualization. RESULTS: A total of 561 published articles were included in the study. Japan was the country that published the most articles, with 205 articles, followed by the United States and China. Okayama University and Tokyo Medical University published the most articles, followed by Nagoya University, Tokyo University, and Juntendo University. Based on the analysis of keywords, four clusters with different research directions were identified: "Prevalence of H1N1 virus and the occurrence of neurological complications in different age groups," "mechanism of brain and central nervous system response after influenza virus infection," "various acute encephalopathy" and "diagnostic indicators of influenza-related encephalopathy." CONCLUSIONS: The research progress, hotspots, and frontiers on influenza-related encephalopathy after 2000 were described through the visualization of bibliometrics. The findings will lay the groundwork for future studies and provide a reference for influenza-related encephalopathy. Research on influenza-related encephalopathy is basically at a stable stage, and the number of research results is related to outbreaks of the influenza virus.


Subject(s)
Brain Diseases , Influenza A Virus, H1N1 Subtype , Influenza, Human , Humans , Influenza, Human/complications , Influenza, Human/epidemiology , Brain Diseases/epidemiology , Brain Diseases/etiology , Bibliometrics , Brain
4.
Brain Sci ; 13(4)2023 Apr 06.
Article in English | MEDLINE | ID: mdl-37190595

ABSTRACT

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is used as temporary cardiorespiratory support in patients with critical ailments, but very little is known about the functional cerebral changes in ECMO survivors. Degree centrality (DC), a graph-based assessment of network organization, was performed to explore the neural connectivity changes in ECMO survivors compared to controls and their correlation with cognitive and neurological measures. METHODS: This exploratory observational study was conducted from August 2020 to May 2022. ECMO survivors and controls underwent functional magnetic resonance imaging (fMRI) of the brain. We performed DC analysis to identify voxels that showed changes in whole-brain functional connectivity with other voxels. DC was measured by the fMRI graph method and comparisons between the two groups were performed. All participants underwent neuropsychological assessment (Montreal Cognitive Assessment, MoCA). Blood serum neuron-specific enolase and the Glasgow Coma Scale (GCS) were assessed in ECMO survivors. RESULTS: DC values in the right insula and right precuneus gyrus were lower in ECMO survivors and higher in the right medial superior frontal gyrus compared to controls (all p < 0.001). Decreased connectivity in the right insular and right precuneus gyrus correlated with total MoCA scores, delayed recollection, and calculation (all p < 0.05). Increased serum NSE levels, GCS score, and GCS-motor response correlated with decreased connectivity in the right insular and right precuneus gyrus and increased connectivity in the right medial superior frontal gyrus (all p < 0.05). CONCLUSIONS: We showed that both functional impairment and adaptation were observed in survivors of ECMO, suggesting that neural connectivity changes may provide insights into the mechanisms that may potentially link ECMO survivors to neurological and cognitive disorders.

5.
Front Neurol ; 13: 968071, 2022.
Article in English | MEDLINE | ID: mdl-36518190

ABSTRACT

Background: To investigate the value of serum Cyclophilin A(Cyp A) in evaluating the prognosis of patients with different severity of craniocerebral injury. Methods: The clinical data of patients with craniocerebral injury treated in the Department of Emergency from July 2014 to August 2017 were collected. The patients were divided into survival group and death group, good neurological function group and poor neurological function group with 28-day prognosis and were divided into mild (13-15) group, moderate (9-12) group, and severe (3-8) group with Glasgow Coma Scale (GCS) score. Clinical parameters such as Cyp A and mortality in groups and the relationship between Cyp A and GCS score were compared and its predictive value for prognosis was analyzed with Binary Logistics regression, Cox proportional hazards model and kaplan-meier survival curve. Results: In a single-center retrospective study, 503 patients were enrolled, including 365 males and 138 females; serum Cyp A in the survival group was significantly smaller than the death group [18.7 (10.1, 51.5) ng/mL vs. 149.8 (79.5, 194.4) ng/mL, P < 0.005]. There were significant differences in mortality and Cyp A levels between patients with different severity of craniocerebral injury (P < 0.001). Serum Cyp A levels were negatively correlated with GCS scores in all patients with craniocerebral injury, mild, moderate, or severe craniocerebral injury (r = -0.844, r = -0.256, r = -0.540, r = -0.531, P < 0.001). Predictive value of Serum Cyp A level for all patients with craniocerebral injury, mild, moderate, and severe craniocerebral injury is 0.890, 0.789, 0.806, and 0.833, respectively. Logistics regression analysis showed that lactate (OR = 1.260, 95%CI: 1.023-1.551) and Cyp A (OR = 1.021, 95%CI: 1.011-1.031) were positively correlated with death (P < 0.05), Lactic acid (HR 1.115; 95%CI:1.001-1.243; P = 0.048), GCS score (HR 0.888; 95% CI: 0.794-0.993; P = 0.038), Cyp A levels (HR 1.009; 95% CI: 1.004-1.013; P < 0.001) had a significant effect on short-term mortality. Similar results were seen when neurologic function was used as the outcome. Kaplan-meier survival curve analysis found survival rate of patients with Cyp A level below the cut-off value was significantly higher. Conclusion: Serum Cyp A has a certain predictive value for the prognosis of patients with different severity of craniocerebral injury. Among them, patients with severe craniocerebral injury have the highest predictive value and mild craniocerebral injury patients have the least.

6.
Front Aging Neurosci ; 14: 786253, 2022.
Article in English | MEDLINE | ID: mdl-35832064

ABSTRACT

Purpose: Recent neuroimaging reports have shown the microstructural changes in coronary artery disease (CAD) and its correlation with cognitive dysfunction while little is known about the functional characteristics of CAD. We hypothesize that functional characteristics may give clues to underlying pathology in CAD and its link with cognitive dysfunction. Degree centrality (DC), a graph-based assessment of network organization was performed to explore the neural connectivity changes in CAD patients compared with healthy controls and their correlation with cognitive measures. Methods: Thirty CAD patients and 36 healthy controls were included in our study. All participants underwent functional magnetic resonance imaging (fMRI) of the brain. We performed DC analysis to identify voxels that showed changes in whole-brain functional connectivity with other voxels. DC was measured by the fMRI graph method and comparisons between the two groups were done. All participants underwent neuropsychological assessment (Montreal Cognitive Assessment, MoCA and Mini-Mental State Examination, MMSE). Results: Our data analysis included 30 CAD patients (59.90 ± 7.53 years) and 36 HCs (61.61 ± 6.19 years). CAD patients showed a greater prevalence of white matter lesions using the Fazekas score than healthy controls (P < 0.001). Importantly, CAD patients showed significantly lower (P < 0.001) MoCA and MMSE scores compared with healthy controls. CAD patients showed significantly decreased DC value (P < 0.001) in the right hippocampus (hippocampus_R), right lingual gyrus (lingual_R), and significantly increased DC value (P < 0.001) in the left middle frontal gyrus (Frontal_Mid_L) when compared with healthy controls respectively. DC value in the hippocampus_R significantly correlated (P < 0.00) with MMSE and MoCA scores in CAD patients. Fazekas scores in CAD patients showed a significant correlation (P < 0.001) with the DC value in the hippocampus_R. Conclusion: These findings suggest that reduced cerebral neural connectivity in CAD may contribute to their cognitive impairment and white matter microstructural damage.

7.
Curr Neurovasc Res ; 19(2): 131-136, 2022.
Article in English | MEDLINE | ID: mdl-35578846

ABSTRACT

OBJECTIVE: Cognitive impairment has been suggested to be associated with coronary artery disease [CAD]; however, the underlying mechanism is not fully understood. Our current study aimed to explore the brain activity in CAD patients compared to healthy controls [HCs]. METHODS: Twenty-two CAD patients and 23 HCs were enrolled in our study. A low-frequency oscillation at the voxel level in all participants based on the amplitude of low-frequency fluctuations [ALFF] was measured using resting-state functional magnetic resonance imaging. All participants underwent neuropsychological examinations [Mini-Mental State Examination, MMSE and Montreal Cognitive Assessment, MoCA] and visual acuity examination. RESULTS: CAD patients showed significantly lower ALFF values [P < 0.05] in the right precuneus gyrus [Precuneus_R], left supramarginal gyrus [Supramarginal_L], left angular gyrus [Angular_L], and left middle cingulum gyrus [Cingulum_Mid_L] than healthy controls. Lower MoCA scores in CAD patients significantly correlated with lower Supramarginal_L [P = 0.001] and Cingulate_ Mid_L [P = 0.004] ALFF values. Reduced visual acuity significantly correlated with lower Precuneus_R [P = 0.019] and Cingulate_Mid_L [P = 0.011] ALFF values in CAD patients. CONCLUSION: These findings may provide further insight into the underlying neuropathophysiology of CAD with cognitive impairment.


Subject(s)
Cognitive Dysfunction , Coronary Artery Disease , Humans , Magnetic Resonance Imaging/methods , Brain/pathology , Coronary Artery Disease/complications , Coronary Artery Disease/diagnostic imaging , Coronary Artery Disease/pathology , Cognitive Dysfunction/pathology , Neuropsychological Tests
8.
Front Cardiovasc Med ; 9: 788644, 2022.
Article in English | MEDLINE | ID: mdl-35391844

ABSTRACT

Background: Pheochromocytoma-induced cardiomyopathy is a rare but potentially life-threatening complication of pheochromocytoma. It mimics the patterns of stress-induced cardiomyopathy. In severe cases, patients can develop refractory cardiogenic shock, which might require mechanical circulatory support. Case Presentation: We presented a case of 54-year-old female who developed refractory cardiogenic shock, following an elective orthopaedic surgery complicated by cardiac arrest, requiring veno-arterial extracorporeal membrane oxygenation (VA-ECMO) support. After urgent coronary catheterisation revealed normal coronary arteries, further evaluation of the aetiology of cardiogenic shock revealed pheochromocytoma. With a diagnosis of pheochromocytoma-induced cardiomyopathy, the patient had accelerated preoperative alpha adrenergic blockade preparation for a total of 6 days and subsequently had the tumour removed under VA-ECMO support. Postoperatively, the patient recovered well and was off ECMO support and extubated a few days later.The optimal management of pheochromocytoma-induced cardiomyopathy, especially for severe cases, is still unclear. Indeed, some cases will require mechanical circulatory support to allow left ventricular function recovery. But our case also showed that it was possible to introduce alpha blockade safely whilst the patient is on VA-ECMO and has the pheochromocytoma removed with VA-ECMO support after accelerated preoperative preparation.

9.
Exp Ther Med ; 23(4): 304, 2022 Apr.
Article in English | MEDLINE | ID: mdl-35340874

ABSTRACT

Periodontitis is a common chronic inflammatory oral disease. The objective of periodontal treatment is to control infection whilst regenerating damaged periodontal tissue. The present study aimed to determine the potential effects of pterostilbene (PTE), a representative stilbene compound, on the proliferation and differentiation of human periodontal ligament stem cells (hPDLSCs). Different concentrations (1, 5, 10 and 20 µM) of PTE were applied to hPDLSCs, after which Cell Counting Kit-8 and western blotting assays were performed to examine the protein levels of Ki67, PCNA, p-IκBα, IκBα, Bcl-2, Bax, cleaved caspase3. The effect of PTE on the release of inflammatory factors, including IL-1ß, IL-6 and IL-10 was assessed by RT-qPCR. The apoptosis of TNF-α-induced hPDLSCs was evaluated by TUNEL assay and western blotting. Additionally, the role of PTE in hPDLSC mineralization was evaluated using alizarin red staining. The expression levels of mineralization indices, including RUNX2 and ALP were subsequently determined using western blotting. Subsequently, the target of PTE was predicted using TargetNet database and AutoDock v4.2 software and verified using western blotting. The results of the present study revealed that PTE promoted the proliferation of hPDLSCs in a concentration-dependent manner. Furthermore, PTE treatment decreased the release of inflammatory factors and alleviated the apoptosis of TNF-α-induced hPDLSCs. PTE was also demonstrated to promote the formation of mineral nodules in TNF-α-induced hPDLSCs. The Targetnet database, along with molecular docking, indicated that histone deacetylases (HDACs) were the probable targets of PTE upstream of regulating periodontitis. The results of western blotting implied that TNF-α significantly increased expression levels of HDAC2, 4, 6 and 8, whilst PTE treatment markedly decreased HDAC4, 6 and 8 expression in a concentration-dependent manner compared with the TNF-α group, which further confirmed these conclusions. In summary, results of the present study revealed that PTE promoted TNF-α-induced hPDLSC proliferation and differentiation, whilst alleviating inflammation and apoptosis. PTE also inhibited the expression of HDACs, which may be involved in the mechanism of periodontitis.

12.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-750741

ABSTRACT

Objective @#To explore the clinical effect of composite resin inlays in repairing large areas of primary molar defects after root canal treatment to provide a reference for the restoration of carious primary molars.@*Methods@#Thirty-eight primary molars of 32 children were selected as the research objects. Indirect restoration with composite resin inlays was performed after root canal therapy. The clinical efficacy was evaluated in terms of five indices, including restoration retention, marginal integrity, gingival status, anatomical morphology and secondary caries, according to the modified USHPS evaluation criteria, at 6, 12 and 18 months after restoration.@*Results @#During the 18-month follow-up period, 36 of the 38 teeth were successfully restored, and all the evaluated items reached grade A or B. Six months after the repair, one prosthesis had fallen off, resulting in a success rate of 97.37% (37/38). The success rate remained 97.37% (37/38) 12 months after the repair; 18 months after the repair, another prosthesis had failed(Marginal integrity and anatomical morphology were grade C), reducing the success rate to 94.74% (36/38). There was no significant difference in the success rate of resin inlay repair at 6, 12 or 18 months (χ2=0.518, p=0.772).@*Conclusion@#Composite resin inlay restoration is an alternative method for repairing primary molars with large defects after root canal treatment.

13.
Exp Ther Med ; 16(4): 3317-3324, 2018 Oct.
Article in English | MEDLINE | ID: mdl-30233678

ABSTRACT

Mixed lineage kinase-4 (MLK-4) is an important member of the mixed-lineage family of kinases that regulates the extracellular signal-regulated kinases and c-Jun N-terminal kinase (JNK) signaling pathways. The functions and mechanisms of MLK-4 in cancer initiation and progression have not been well understood. The present study investigated the expression, function and regulatory mechanism of MLK-4 in gastric carcinoma cells. Biochemical data indicated that normal MLK-4 was downregulated, which exerted dominant negative effects on gastric carcinoma cell viability, migration and invasion. The experimental data demonstrated that MLK-4 supplement abrogated activity of these mutants and induced inhibitory effects on gastric carcinoma cell viabilty, migration and invasion in vitro and in vivo. In addition, to determine the regulatory mechanism of MLK-4, its signaling pathway was assessed in gastric carcinoma cancer cells by regulating MLK-4. The present observations indicated that restoring MLK-4 activity by supplemental MLK-4 reduced gastric carcinoma cell colony formation in vitro and suppressed tumor viability, migration and invasion in vivo. The results of the present study indicated that MLK-4 may be a potential protein for targeting gastric carcinoma by suppressing kinases, which may lead to reduction of JNK signaling and enhance therapeutic efficacy in gastric carcinoma.

14.
PLoS One ; 13(9): e0202620, 2018.
Article in English | MEDLINE | ID: mdl-30231052

ABSTRACT

This study aimed to evaluate the efficacy and safety of dexmedetomidine versus any other treatment without dexmedetomidine in patients who have undergone cardiac surgery. Electronic databases including PubMed, Embase, and Cochrane Library were systematically searched without limitations of language and publication time. Randomized controlled trials (RCTs) aiming to evaluate the efficacy and safety of dexmedetomidine versus any other treatment without dexmedetomidine in patients that have undergone cardiac surgery were selected. Endpoints such as hemodynamic indexes and adverse events in eligible studies were extracted by two researchers, independently. The data was analyzed using RevMan 5.3 and Stata 11.0 software. A total of 18 RCTs met the inclusion criteria, involving 1730 patients. Compared to control (any treatment without dexmedetomidine), dexmedetomidine showed a pooled mean difference (MD) of -14.46 [95% confidence interval(CI): -24.69, -4.23; p<0.01] for systolic arterial pressure, a standardized mean difference (SMD) of -1.74 for mean arterial blood pressure (95% CI: -2.80, -0.68; P < 0.01), -2.12 (95%CI: -3.23, -1.00; p<0.01) for heart rate, and combined odds ratio (OR) of 0.22 (95%CI: 0.11, 0.44; p<0.01) for tachycardia, 3.44 (95%CI: 1.95, 5.96; p<0.01) for bradycardia, 0.74 (95%CI: 0.49, 1.12; p>0.05) for atrial fibrillation, and 0.99 (95%CI: 0.51, 1.90; p>0.05) for hypotension. In addition, dexmedetomidine could reduce time of surgery and stay in intensive care units, improve delirium with good safety. Our study shows clinical application of dexmedetomidine in cardiac surgery patients can reduce risks of abnormal hemodynamics with good safety.


Subject(s)
Analgesics, Non-Narcotic/therapeutic use , Cardiac Surgical Procedures/methods , Dexmedetomidine/therapeutic use , Analgesics, Non-Narcotic/adverse effects , Dexmedetomidine/adverse effects , Hemodynamics , Humans , Intensive Care Units , Operative Time , Postoperative Complications/epidemiology , Randomized Controlled Trials as Topic
15.
Medicine (Baltimore) ; 97(22): e10787, 2018 Jun.
Article in English | MEDLINE | ID: mdl-29851786

ABSTRACT

INTRODUCTION: This case study is concerning the meticulous observation of the moving process and track of 2 ingested needles using interval x-ray radiography, trying to localize the foreign bodies and reduce unnecessary exploration of digestive tract. CASE PRESENTATION: An unusual case of a 1-year, 9-month-old female baby, with incarcerated hernia perforation caused by sewing needles with sharp ends, was reported herein. The patient had swallowed 2 sewing needles. One needle was excreted uneventfully after 8 days. On the contrary, the other needle stabbed the ileocecal junction wall into the right side of inguinal hernia sac after 9 days, and the patient received successful operation management. Interval x-ray confirmed that 1 needle-like foreign body moving down in 8 days until excretion along with feces. However, the other pierced into the incarcerated hernia. Preoperative x-ray radiography successfully monitored the moving process and tract of the sewing needles. Considering the penetrating-migrating nature of the foreign bodies, once the sharp-pointed objects were located, they should be removed as the mortality and risk of related complications may be increased. CONCLUSION: Interval x-ray radiography represents a meticulous preoperative monitoring method of the moving process and tract of needle-like foreign bodies. Interval x-ray with real-time images accurately detecting the moving foreign bodies could be help to reduce the unnecessary exploration of digestive tract and subsequently prevent possible complications. Based on the basic findings from the interval x-ray, treatment choices of endoscopic removal and surgical intervention may be attempted.


Subject(s)
Foreign Bodies/diagnostic imaging , Foreign-Body Migration/diagnostic imaging , Hernia, Inguinal/complications , Intestinal Perforation/complications , Eating , Female , Foreign Bodies/complications , Foreign Bodies/surgery , Foreign-Body Migration/complications , Foreign-Body Migration/surgery , Hernia, Inguinal/pathology , Humans , Ileum/pathology , Infant , Intestinal Perforation/pathology , Needles , Radiography/methods , Treatment Outcome , Ultrasonography/methods
16.
J Surg Res ; 204(2): 452-459, 2016 08.
Article in English | MEDLINE | ID: mdl-27565082

ABSTRACT

This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). This article has been retracted at the request of the Editor-in-Chief and authors, as portions of the clinical data used were inaccurate. Specifically, more than 500 cases of the total 1882 cases of hernia patients presented in the paper were actually hydrocele of tunica vaginalis, not hernia. The authors sincerely apologize for these errors.


Subject(s)
Hernia, Inguinal/surgery , Herniorrhaphy/methods , Adolescent , Child , Child, Preschool , China/epidemiology , Female , Humans , Infant , Male , Postoperative Complications/epidemiology , Retrospective Studies , Treatment Outcome
17.
Biochem Biophys Res Commun ; 478(1): 330-336, 2016 09 09.
Article in English | MEDLINE | ID: mdl-26828267

ABSTRACT

The AGC kinase family is important cell proliferation and survival. Dysregulation of this family contributes to gastric cancer progression. Here, we evaluated the potential activity of AT13148, a first-in-class multi-AGC kinase inhibitor, against gastric cancer cells. Our results showed that AT13148 exerted potent cytotoxic and anti-proliferative activities against a panel human gastric cancer cell lines (HGC-27, AGS, SNU-601, N87 and MKN-28), possibly via inducing cancer cell apoptotic death. Apoptosis inhibition by the Caspase blockers dramatically attenuated AT13148-caused cytotoxicity against gastric cancer cells. Intriguingly, same AT13148 treatment was not cytotoxic/pro-apoptotic to the non-cancerous human gastric epithelial GEC-1 cells. At the signaling level, AT13148 treatment in gastric cancer cells dramatically suppressed activation of multiple AGC kinases, including Akt (at p-Thr-308), p70S6 kinase (p70S6K), glycogen synthase kinase 3ß (GSK-3ß) and p90 ribosomal S6 kinase (RSK). Our in vivo studies demonstrated that daily oral gavage of AT13148 at well-tolerated doses significantly inhibited HGC27 xenograft tumor growth in nude mice. AGC activity was also dramatically decreased in AT13148-administrated HGC27 tumors. Therefore, targeting AGC kinases by AT13148 demonstrates superior anti-gastric cancer activity both in vitro and in vivo. The preclinical results of this study support the progression of this molecule into future evaluation as a valuable anti-gastric cancer candidate.


Subject(s)
2-Hydroxyphenethylamine/analogs & derivatives , Apoptosis/drug effects , Cell Survival/drug effects , Protein Kinases/metabolism , Pyrazoles/administration & dosage , Stomach Neoplasms/drug therapy , Stomach Neoplasms/metabolism , 2-Hydroxyphenethylamine/administration & dosage , Administration, Oral , Animals , Antineoplastic Agents/administration & dosage , Cell Line, Tumor , Dose-Response Relationship, Drug , Female , Humans , Mice , Mice, Inbred BALB C , Mice, Nude , Protein Kinase Inhibitors/administration & dosage , Stomach Neoplasms/pathology , Treatment Outcome
18.
Front Med ; 9(3): 388-91, 2015 Sep.
Article in English | MEDLINE | ID: mdl-26085469

ABSTRACT

We report here the rare case of a 61-year-old man with multiple organ dysfunction caused by an aspirin overdose (4 g orally). The patient presented with a fever that reached 39.2 °C, a peptic ulcer, and massive upper gastrointestinal bleeding. His blood test results were as follows: white blood cell count, 1.8 × 10(9)/L; absolute lymphocytes, 0.4 × 10(9)/L; absolute neutrophils, 1.2 × 10(9)/L; and electrolyte disturbances. A computed tomography (CT) scan showed evidence of bilateral inferior pulmonary infection and acute pancreatitis. Thick dark bile with visible floccule was drawn via a percutaneous transhepatic cholangiodrainage (PTCD). Klebsiella pneumoniae was detected in microbiological bile tests. Two years later, the patient died of chronic liver failure.


Subject(s)
Aspirin/administration & dosage , Aspirin/toxicity , Chemical and Drug Induced Liver Injury/diagnosis , Drug Overdose/complications , Liver Failure/diagnosis , Humans , Male , Middle Aged , Tomography, X-Ray Computed
19.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 23(1): 88-93, 2015 Feb.
Article in Chinese | MEDLINE | ID: mdl-25687052

ABSTRACT

OBJECTIVE: This study was to investigate the therapeutic effectiveness and side effect of decitabine combined with modified CAG regimen for relapse or refractory patients with acute myeloid leukemia. METHODS: Ten patients suffered from relapsed or refractory acute myeloid leukemia from January 2013 to July 2013 were analyzed retrospectively, and the clinical characteristics, therapeutic effectiveness, side effect were observed. Among 10 patients 7 patients were males and 3 patients were females, the ratio of male to female was 7:3, median age was 45 (17-61) years. RESULTS: After treatment by using decitabine combined with modified CAG regimen, 7 patients achived complete remission, 1 patient achived partial remission, 2 patient did not achieve remission, the overall remission rate was 80% (8/10), the median time of white blood cell count recovery was 18.5 (5-28) days, median time of platelet level recovery was 19 (12-29) days. The main side effects of treatment were myelosuppression. There was no new lung infection in all cases, one case died of exacerbation of primary lung infection after therapy. CONCLUTION: The treatment of decitabine combined with modified CAG regimen for relapsed and refractory AML shows high response rate, low side effects, so it worthy to further clinical study.


Subject(s)
Leukemia, Myeloid, Acute , Aclarubicin , Adolescent , Adult , Antineoplastic Combined Chemotherapy Protocols , Azacitidine/analogs & derivatives , Cytarabine , Decitabine , Female , Granulocyte Colony-Stimulating Factor , Humans , Male , Middle Aged , Recurrence , Remission Induction , Retrospective Studies , Treatment Outcome , Young Adult
20.
Oncol Lett ; 10(6): 3832-3836, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26788217

ABSTRACT

The aim of the present study was to investigate the expression of neuritin in gastric cancer tissues, in order to explore the association between the expression of neuritin and the occurrence and development of gastric cancer. Tissue specimens were collected from 58 patients with gastric cancer. Immunohistochemistry, western blot analysis and reverse transcription-polymerase chain reaction (RT-PCR) were used to determine the expression of neuritin in the gastric cancer and corresponding adjacent normal gastric tissues. The expression rate of neuritin in gastric cancer tissues was 96.55% (56/58), demonstrating no statistically significant difference from the expression rate in the adjacent normal tissues (94.83%) (P>0.05). However, the rate of strong neuritin expression in gastric cancer tissues (82.76%) was significantly increased compared with the rate in the adjacent normal tissues (15.52%) (P<0.05). Neuritin expression exhibited no correlation with the gender or age of patients, tumor-node-metastasis staging, tumor depth, presence of lymph node metastasis, histological or pathological type of the tumor or presence of distant metastasis (P>0.05). As determined by RT-PCR and western blot analysis, the mRNA expression of neuritin in gastric cancer tissues was markedly increased compared with the expression in the adjacent normal tissues. In conclusion, neuritin is highly expressed in gastric cancer tissues, suggesting that neuritin may act as a novel potential target for the treatment of gastric cancer.

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