ABSTRACT
BACKGROUND: The triglyceride glucose-body mass index (TyG-BMI index) has been suggested as a novel predictor of insulin resistance. However, its predictive value for slow coronary flow phenomenon (SCFP) in patients with ischemia and nonobstructive coronary arteries (INOCA) remains unclear. METHODS: We consecutively recruited 1625 patients with INOCA from February 2019 to February 2023 and divided them into two groups based on thrombolysis in myocardial infarction (TIMI) frame counts (TFCs): the SCFP group (n = 79) and the control group. A 1:2 age-matched case-control study was then performed. The TyG-BMI index was calculated as ln [plasma triglyceride (mg/dL) × fasting blood glucose (mg/dL)/2] × BMI. RESULTS: TyG-BMI index in the SCFP group (218.3 ± 25.2 vs 201.0 ± 26.5, P < .001) was significantly higher than in the normal controls. TyG-BMI index also increased with the number of coronary arteries involved in the SCFP. Multivariate logistic regression analysis showed that TyG-BMI, BMI, and TG were independent predictors for SCFP. Receiver operating characteristic (ROC) curve analysis showed that when the TyG-BMI index was above 206.7, the sensitivity and specificity were 88.6% and 68.5%, respectively, with an AUC of 0.809 (95% CI: 0.756-0.863, P = .027). Combined BMI with TG, the TyG-BMI index had a better predictive value for SCFP than BMI and TG (P < .001). CONCLUSION: The TyG-BMI index was an independent predictor for SCFP in INOCA patients, and it had a better predictive value than BMI and TG.
Subject(s)
Glucose , No-Reflow Phenomenon , Humans , Body Mass Index , Blood Glucose , Coronary Vessels , Triglycerides , Case-Control Studies , Biomarkers , Ischemia , No-Reflow Phenomenon/diagnostic imaging , No-Reflow Phenomenon/etiologyABSTRACT
Chemodivergent tandem radical cyclization offers exciting possibilities for the synthesis of structurally diverse cyclic compounds. Herein, we revealed a chemodivergent tandem cyclization of alkene-substituted quinazolinones under metal- and base-free conditions, this transformation is initiated by alkyl radicals produced from oxidant-induced α-C(sp3 )-H functionalization of alkyl nitriles or esters. The reaction resulted in the selective synthesis of a series of mono- and di-alkylated ring-fused quinazolinones by modulating the loading of oxidant, reaction temperature, and reaction time. Mechanistic investigations show that the mono-alkylated ring-fused quinazolinones is constructed by the key process of 1,2-hydrogen shift, whereas the di-alkylated ring-fused quinazolinones is mainly achieved through crucial steps of resonance and proton transfer. This protocol is the first example of remote second alkylation on the aromatic ring via α-C(sp3 )-H functionalization and difunctionalization achieved by association of two unsaturated bonds in radical cyclization.
ABSTRACT
In this study, the evidence map system was used to sort out the clinical research evidence on traditional Chinese medicine(TCM) treatment of vertigo and understand the evidence distribution in this field. CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase, and Web of Science were searched for the clinical randomized controlled trial(RCT) and systematic reviews/Meta-analysis on TCM treatment of vertigo in recent five years, and the evidence was analyzed and presented in the form of text and charts. The Cochrane handbook for systematic reviews of interventions was used to evaluate the quality of the clinical RCT, and the AMSTAR mea-surement tool was used to evaluate the quality of the systematic reviews/Meta-analysis. A total of 382 RCTs and eight systematic reviews/Meta-analysis were included. In recent five years, the number of published articles has been on the rise. There were many intervention measures and TCM therapies for vertigo. Outcome indicators mainly included clinical efficacy, TCM syndrome score, vertigo score, occurrence of adverse reactions, and effective rate. The overall quality of clinical RCT and systematic reviews/Meta-analysis was low. Most studies have proven the potential efficacy of TCM in treating vertigo, but there was still no clear clinical evidence of efficacy. The results show that TCM has advantages in the treatment of vertigo, but there are also problems. More high-quality studies are still lacking, suggesting that more large-sample and multi-center RCT should be conducted in the future, and the quality of relevant syste-matic reviews/Meta-analysis should be improved to fully explore the advantages of TCM in the treatment of vertigo, and provide strong support for the effectiveness and safety of TCM in the treatment of vertigo.
Subject(s)
Drugs, Chinese Herbal , Medicine, Chinese Traditional , Humans , Systematic Reviews as Topic , Treatment Outcome , Syndrome , Publications , Drugs, Chinese Herbal/therapeutic useABSTRACT
The processivity factors (PFs) of herpesviruses confer processivity to the DNA polymerase. Understanding whether the herpesvirus PFs function as monomers or multimers is important for clarifying the mechanism by which they provide the DNA polymerase with processivity. Herpes simplex virus type 1 UL42 is a monomer, whereas human cytomegalovirus UL44, Epstein-Barr virus BMRF1, and Kaposi's sarcoma-associated herpesvirus PF-8 exist as dimers. However, the oligomeric status of the pseudorabies virus (PRV) DNA polymerase PF UL42 has not been determined. Using fluorescence confocal microscopy and chemical crosslinking, we confirmed that UL42 is a monomer when expressed in vitro. Crosslinking of nuclear extracts from PRV-infected or uninfected PK-15 cells verified that UL42 exists as a monomer in vivo. Our demonstration that UL42 exists as a monomer in vitro and in vivo contributes to the further investigation of the mechanism used by UL42 to achieve processivity.
Subject(s)
DNA-Directed DNA Polymerase/metabolism , Gene Expression Regulation, Viral/physiology , Herpesvirus 1, Suid/enzymology , Pseudorabies/virology , Swine Diseases/virology , Viral Proteins/metabolism , Animals , DNA-Directed DNA Polymerase/genetics , Gene Expression Regulation, Enzymologic/physiology , Herpesvirus 1, Suid/genetics , Herpesvirus 1, Suid/metabolism , Swine , Viral Proteins/geneticsABSTRACT
AIM: Our previous studies have showed that ursodeoxycholic acid (UA) and jasminoidin (JA) effectively reduce cerebral infarct volume in mice. In this study we explored the pure synergistic mechanism of these compounds in treatment of mouse cerebral ischemia, which was defined as synergistic actions specific for phenotype variations after excluding interference from ineffective compounds. METHODS: Mice with focal cerebral ischemia were treated with UA, JA or a combination JA and UA (JU). Concha margaritifera (CM) was taken as ineffective compound. Cerebral infarct volume of the mice was determined, and the hippocampi were taken for microarray analysis. Particular signaling pathways and biological functions were enriched based on differentially expressed genes, and corresponding networks were constructed through Ingenuity Pathway Analysis. RESULTS: In phenotype analysis, UA, JA, and JU significantly reduced the ischemic infarct volume with JU being superior to UA or JA alone, while CM was ineffective. As a result, 4 pathways enriched in CM were excluded. Core pathways in the phenotype-positive groups (UA or JA) were involved in neuronal homeostasis and neuropathology. JU-contributing pathways included all UA-contributing and the majority (71.7%) of JA-contributing pathways, and 10 new core pathways whose effects included inflammatory immunity, apoptosis and nervous system development. The functions of JU group included all functions of JA group, the majority (93.1%) of UA-contributing functions, and 3 new core functions, which focused on physiological system development and function. CONCLUSION: The pure synergism between UA and JA underlies 10 new core pathways and 3 new core functions, which are involved in inflammation, immune responses, apoptosis and nervous system development.
Subject(s)
Brain Ischemia/drug therapy , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/therapeutic use , Medicine, Chinese Traditional/methods , Systems Biology/methods , Animals , Brain Ischemia/diagnosis , Brain Ischemia/genetics , Brain Ischemia/metabolism , Data Mining , Databases, Genetic , Disease Models, Animal , Drug Combinations , Drug Synergism , Gene Expression Profiling , Gene Expression Regulation , Gene Regulatory Networks , Genomics , Male , Mice , Oligonucleotide Array Sequence Analysis , Phenotype , Protein Interaction Maps , Signal Transduction/drug effects , Systems IntegrationABSTRACT
Background: As a nutritional indicator, a lower level of geriatric nutritional risk index (GNRI) has been suggested as a predictor for poor prognosis in acute coronary syndrome (ACS). However, whether GNRI could improve the predictive value of the Global Registry of Acute Coronary Events (GRACE) score for the prognosis in elderly patients with non-ST segment elevation myocardial infarction (NSTEMI) after PCI remains unclear. Methods: A total of 446 elderly patients with NSTEMI after percutaneous coronary intervention (PCI) were consecutively enrolled. Patients were divided into major adverse cardiovascular and cerebrovascular events (MACCE) group and control group according to the occurrence of MACCE during one year follow up. The clinical parameters including GNRI were compared to investigate the predictors for MACCE. The performance after the addition of GNRI to the GRACE score for predicting MACCE was determined. Results: A total of 68 patients developed MACCE. In unadjusted analyses, the rate of MACCE was significantly higher in the 93.8Subject(s)
Geriatric Assessment
, Non-ST Elevated Myocardial Infarction
, Nutrition Assessment
, Percutaneous Coronary Intervention
, Humans
, Percutaneous Coronary Intervention/adverse effects
, Aged
, Female
, Male
, Geriatric Assessment/methods
, Prognosis
, Risk Assessment
, Risk Factors
, Aged, 80 and over
, Predictive Value of Tests
, Logistic Models
, Nutritional Status
ABSTRACT
Background: Investigation of fetal cerebral maturation (FCM) is necessary and important to provide crucial prognostic information for normal and high-risk fetuses. The study aimed to develop a valid and quantitative predictive model for assessing FCM using ultrasound and validate the model for fetuses with normal and restricted growth. Methods: This was a multicenter prospective observational study. Fetuses with normal growth recruited from a university teaching hospital (Center 1) and a municipal maternal unit (Center 2) were included in the training set and external validation set 1, respectively. The 124 growth-restricted fetuses enrolled in Center 1 were included in validation set 2. FCM was used to describe the gestational age (GA) in this study. The model was developed based on the sum of fetal cranial parameters (total fetal cranial parameters), including head circumference (HC) and depths of the insula (INS) and sylvian fissure (SF), parieto-occipital fissure (POF), and calcarine fissure (CF). A regression model, constructed based on total fetal cranial parameters and predicted GA, was established using the training set and validated using external validation set 1 and validation set 2. Results: The intra- and interobserver intraclass correlation coefficients for HC, and depths of the INS and SF, POF, and CF were >0.90. An exponential regression equation was used to predict FCM: predicted GA of FCM (weeks) =11.16 × exp (0.003 × total fetal cranial parameters) (P<0.001; adjusted R2=0.973), standard error of estimate, 0.67 weeks. The standard error of the predicted GA of FCM from the model was ±4.7 days. In the validation set 1, the mean standard error of the developed prediction model for FCM was 0.97 weeks. The predictive model showed that FCM was significantly delayed in validation set 2 (2.10±1.31 weeks, P<0.001), considering the GA per the last menstrual period. Conclusions: The predictive performance of the FCM model developed in this study was excellent, and the novel model may be a valuable investigative tool during clinical implementation.
ABSTRACT
A convenient and straightforward approach for the radical cascade cyclization/hydrolysis of CN-containing 1,6-enynes with simple ethers under metal- and base-free conditions is described. This strategy provides a variety of valuable ethers-substituted polyheterocycles via the construction of three C-C bonds, one C=O bond, and two new six-membered rings within a single procedure. The resulting products can smoothly undergo follow-up conversions to various useful scaffolds. The methodology shows excellent functional group tolerance, high step- and atom- economy, and mild reaction conditions, which can be further scaled up to gram quantity in a satisfactory yield.
ABSTRACT
CONTEXT: Granulosa cells (GCs) that surround oocytes in mammalian reproduction play an active role in oocyte differentiation through proliferation and energy production. AIMS: This study aimed to investigate the characteristics of the energy metabolism of ovarian GCs and the influence of GCs on the early embryonic development in polycystic ovary syndrome (PCOS). METHODS: The clinical characteristics and in vitro fertilization-embryo transfer treatment outcomes of 39 patients with PCOS and 68 patients with simple tubal factor infertility who underwent controlled ovarian hyperstimulation were analyzed and summarized. The mitochondrial function and glucose metabolism level of the GCs were determined, as well as the content of oxidative stress markers in the follicular fluid (FF) of patients with and without PCOS. KEY RESULTS: When compared to the non-PCOS group, patients with PCOS had a significantly increased number of retrieved oocytes but a significantly decreased number of high-quality embryos, available embryos, and high-quality blastocyst formation (P < 0.05). Furthermore, the mitochondrial membrane potential, adenosine triphosphate level, and mitochondrial DNA (mtDNA) copy number decreased in the GCs, whereas the levels of reactive oxygen species increased (P < 0.01). The levels of malondialdehyde and 8-oxo-deoxyguanosine (8-OHdG) in the follicular fluid (FF) of the patients with PCOS were higher than those of the control group (P < 0.05), and superoxide dismutase was increased by compensation (P < 0.05). In the PCOS group, the expressions of GLUT1, LDHA, and PFKP were lower than those in the non-PCOS group, and glucose levels were higher. CONCLUSIONS: The low oocyte competence of PCOS may be associated with mitochondrial dysfunction and abnormal glycolysis. IMPLICATIONS: This research offers explanations for the possible connections influencing human ovarian folliculogenesis.
Subject(s)
Polycystic Ovary Syndrome , Pregnancy , Female , Humans , Polycystic Ovary Syndrome/metabolism , Granulosa Cells/metabolism , Embryo Transfer , Follicular Fluid/metabolism , Obesity/metabolism , Fertilization in Vitro , Energy MetabolismABSTRACT
The combination of photo and copper catalysts has emerged as a novel paradigm in organic catalysis, which provides access to the acceleration of chemical synthesis. Herein, we describe an aminoalkylation of amino-dependent olefins with maleimides through a cooperative photo/copper catalytic system. In this report, the strategy allows the generation of a broad complex of functionalized nitrogenous molecules including oxazolidinones, 2-pyrrolidones, imidazolidinones, thiazolidinones, pyridines, and piperidines in the absence of an external photosensitizer and base. The approach is achieved through a photoinduced Cu(I)/Cu(II)/Cu(III) complex species of nitrogen nucleophiles, intermolecular radical addition, and hydrogen atom transfer (HAT) processes. The plausible mechanism is investigated by a series of control experiments and theoretical tests, including radical scavenging experiments, deuterium labeling experiments, ultraviolet-visible absorption, and cyclic voltammetry (CV) tests.
ABSTRACT
BACKGROUND: Research suggests that lowering maternal morbidities associated with gestational diabetes mellitus (GDM) can be achieved with earlier risk group identification. AIMS: Therefore, the purpose of this study was to examine potential markers for identifying first-trimester pregnant women who are at high risk for developing GDM. METHODS: This was a retrospective cohort study. The pertinent maternal clinical data were retrieved prior to 13+6 weeks of gestation, and a binary logistic regression analysis was used to identify potential GDM predictors. The predictive accuracy was evaluated using the area below the receiver operating characteristics curves. RESULTS: In comparison to the control group, the GDM group had significantly higher mean values for age, body mass index (BMI), mean fasting blood glucose (FBG), and hemoglobin (p < 0.05). The Pearson's correlation coefficients indicated that the first-trimester FBG was significantly positively correlated with the second-trimester FBG. Higher FBG and BMI values were associated with an increased risk of developing GDM (odds ratio [OR] = 3.04, 95% confidence interval [CI] = 2.03-4.55 and OR = 1.18, 95% CI = 1.12-1.25). In terms of predicting GDM, the FBG parameter demonstrated the greatest area under the curve values (0.66), followed by the BMI parameter (0.69). For GDM prediction, the cut-off value for FBG was 4.32 mM, whereas that for BMI was 23.7 kg/m2. CONCLUSIONS: The first-trimester FBG and BMI could be utilized to predict gestational diabetes.
ABSTRACT
OBJECTIVE: This study was designed to investigate the expression patterns of CEACAM1 and its relationship with angiogenesis in nonneoplastic and neoplastic gastric lesions. METHODS: CEACAM1 and TGF-ß expression was detected by immunohistochemical staining and dual-labeling immunohistochemical staining in neoplastic and nonneoplastic lesions. MVD-CD31 and MVD-CD105 were counted in CEACAM1-positive areas by dual-labeling immunohistochemistry. RESULTS: There was no expression of CEACAM1 in normal gastric mucosa. In IM and GIN, CEACAM1 was mainly expressed with membranous pattern. CEACAM1 was expressed with membranous pattern in well-differentiated adenocarcinoma, with cytoplasmic pattern in poorly differentiated adenocarcinoma, and with cytoplasmic and membranous pattern mixed together in intermediately adenocarcinoma. The expression patterns of CEACAM1 showed a significant difference (P < 0.05) in nonneoplastic and neoplastic lesions. Coexpression of CEACAM1 and TGF-ß was elevated and significantly different from nonneoplastic to neoplastic lesions (P < 0.05). Moreover, CEACAM1 and TGF-ß coexpression were related to carcinoma progression (r = 0.35; P < 0.05). MVD-CD31 and MVD-CD105 showed significant differences from nonneoplastic to neoplastic lesions (P < 0.05). CONCLUSIONS: CEACAM1 has different expression patterns in nonneoplastic and neoplastic lesions. The coexpression of CEACAM1 and TGF-ß increased from nonneoplastic to neoplastic lesions and may be related with tumor progression via promoting tumorous angiogenesis.
Subject(s)
Antigens, CD/metabolism , Carcinoma in Situ/metabolism , Carcinoma in Situ/pathology , Cell Adhesion Molecules/metabolism , Intestines/pathology , Neovascularization, Pathologic/metabolism , Stomach Neoplasms/metabolism , Stomach Neoplasms/pathology , Analysis of Variance , Carcinoma in Situ/blood supply , Chi-Square Distribution , Endoglin , Gastric Mucosa/blood supply , Gastric Mucosa/metabolism , Humans , Intestinal Mucosa/metabolism , Intestines/blood supply , Metaplasia/metabolism , Microvessels/metabolism , Neoplasm Staging , Platelet Endothelial Cell Adhesion Molecule-1/metabolism , Receptors, Cell Surface/metabolism , Stomach Neoplasms/blood supply , Transforming Growth Factor beta/metabolismABSTRACT
BACKGROUND: The etiology of granulomatous lobular mastitis (GLM) remains unknown. This study aimed to detect bacteria in GLM using Nanopore sequencing and identify the relationship between GLM and Corynebacterium kroppenstedtii. METHODS AND MATERIALS: The bacterial detection on fresh samples (including breast pus and tissue) of 50 GLM patients using nanopore sequencing and culture methods. The bacterial detection rate of participants with different stages were compared and analyzed. Formalin-fixed and paraffin-embedded (FFPE) tissues from 39 patients were performed on Gram staining to identify Gram-positive bacilli (GPB) within lipid vacuoles. Moreover, the clinicopathological characteristics of GLM patients in different bacterial subgroups were also conducted. RESULTS: In 50 GLM patients, the detection rate of bacteria was 78% using nanopore sequencing method, especially in the early stage of GLM (over 80%), which was significantly higher than that using culture methods (24%, p < 0.001). The dominant bacteria were Corynebacterium species (64%), especially for the Corynebacterium kroppenstedtii. The detection rate of C. kroppenstedtii in nanopore sequencing method (56%) was higher than that in culture methods (16%, p < 0.001). Gram staining positive of bacteria in 7 patients, and 5 of them were C. kroppenstedtii. Thirty-one patients (31/39, 79.5%) exhibited typical histological structure of cystic neutrophilic granulomatous mastitis (CNGM), and eighteen patients detected with C. kroppenstedtii. CONCLUSION: Nanopore sequencing showed rapid and accurate bacteria detection over culture method in GLM patients. GLM is not sterile inflammation and closely related to C. kroppenstedtii. CNGM was associated with Corynebacterium infection, especially for C. kroppenstedtii.
Subject(s)
Corynebacterium Infections , Granulomatous Mastitis , Nanopore Sequencing , Corynebacterium/genetics , Corynebacterium Infections/diagnosis , Corynebacterium Infections/drug therapy , Female , HumansABSTRACT
Granulomatous lobular mastitis (GLM), also known as idiopathic granulomatous mastitis (IGM), is a chronic inflammatory lesion of the breast. The incidence of GLM has been increasing in recent years, especially among young women. The etiologies of GLM have not been fully elucidated but are associated with autoimmunity and bacterial infection. Bacteria, especially Corynebacterium species, play important roles in GLM. In this article, we review research progress regarding the bacteriology of GLM attained with the application of several new high-throughput detection techniques. Accurate detection might be important for deepening our understanding of the pathogenesis of GLM and hold promise for personalized GLM therapy.
Subject(s)
Granulomatous Mastitis , Bacteria , Breast , Female , Granulomatous Mastitis/diagnosis , Granulomatous Mastitis/epidemiology , Granulomatous Mastitis/therapy , HumansABSTRACT
OBJECTIVE: To explore the network control mechanism of the calcium signaling pathway in cerebral ischemic injury after intervention by the main components of Qingkailing (see text), i.e. Baicalin, Jasminoidin and their combination. METHODS: Thirty mice were randomly divided into 5 groups, a baicalin group, a Jasminoidin group, a baicalin plus Jasminoidin group, a nimodipine group, and a model group (n = 6). The global cerebral ischemia-reperfusion mouse model was established. The mice were administrated respectively by injection of baicalin, Jasminoidin, mixture of baicalin and Jasminoidin, and nimodipine into the caudal vein, with the model group given no any drug. Three hours after operation, the brain was removed and sectioned. After calculation of cerebral ischemic area by 2,3,5-triphenyltetrazolium staining, the percentage of infarct volume was calculated. The total RNA of the mouse brain tissue was extracted to obtain the whole genome expression profile, and the differentially expressed genes related to the calcium signaling pathway was analyzed with Bayesian network structures. RESULTS: Compared with the model group, the ischemic area was significantly reduced in the baicalin group, the Jasminoidin group, the Baicalin plus Jasminoidin group (all P < 0.05). The ischemic area in the baicalin plus Jasminoidin group was smaller than the other three groups (all P < 0.01). In the gene regulatory network structures of calcium signaling pathway, the average length and equitability were the highest in the baicalin plus Jasminoidin group, followed by the nimodipine group. CONCLUSION: Compared with a single component, combination of Baicalin and Jasminoidin can more obviously intervene in the overall expression of calcium signaling pathway, and the mechanism is related with the aggregation characteristic of the gene expression network.
Subject(s)
Brain Ischemia/drug therapy , Calcium Signaling/drug effects , Drugs, Chinese Herbal/therapeutic use , Animals , Brain Ischemia/metabolism , Brain Ischemia/pathology , Flavonoids/therapeutic use , Iridoids/therapeutic use , Male , Mice , Nimodipine/therapeutic useABSTRACT
OBJECTIVE: To investigate a Met-controlled allosteric module (AM) of neural generation as a potential therapeutic target for brain ischemia. METHODS: We selected Markov clustering algorithm (MCL) to mine functional modules in the related target networks. According to the topological similarity, one functional module was predicted in the modules of baicalin (BA), jasminoidin (JA), cholic acid (CA), compared with I/R model modules. This functional module included three genes: Inppl1, Met and Dapk3 (IMD). By gene ontology enrichment analysis, biological process related to this functional module was obtained. This functional module participated in generation of neurons. Western blotting was applied to present the compound-dependent regulation of IMD. Co-immunoprecipitation was used to reveal the relationship among the three members. We used IF to determine the number of newborn neurons between compound treatment group and ischemia/reperfusion group. The expressions of vascular endothelial growth factor (VEGF) and matrix metalloproteinase 9 (MMP-9) were supposed to show the changing circumstances for neural generation under cerebral ischemia. RESULTS: Significant reduction in infarction volume and pathological changes were shown in the compound treatment groups compared with the I/R model group (P<0.05). Three nodes in one novel module of IMD were found to exert diverse compound-dependent ischemic-specific excitatory regulatory activities. An anti-ischemic excitatory allosteric module (AME) of generation of neurons (AME-GN) was validated successfully in vivo. Newborn neurons increased in BJC treatment group (P<0.05). The expression of VEGF and MMP-9 decreased in the compound treatment groups compared with the I/R model group (P<0.05). CONCLUSIONS: AME demonstrates effectiveness of our pioneering approach to the discovery of therapeutic target. The novel approach for AM discovery in an effort to identify therapeutic targets holds the promise of accelerating elucidation of underlying pharmacological mechanisms in cerebral ischemia.
Subject(s)
Brain Ischemia , Gene Regulatory Networks , Proto-Oncogene Proteins c-met , Algorithms , Animals , Brain Ischemia/drug therapy , Gene Ontology , Markov Chains , Matrix Metalloproteinase 9 , Rodentia , Vascular Endothelial Growth Factor AABSTRACT
Liver cancer is thought as the most common human malignancy worldwide, and hepatocellular carcinoma (HCC) accounts for nearly 90% liver cancer. Due to its poor early diagnosis and limited treatment, HCC has therefore become the most lethal malignant cancers in the world. Recently, molecular targeted therapies showed great promise in the treatment of HCC, and novel molecular therapeutic targets is urgently needed. KIF15 is a microtubule-dependent motor protein involved in multiple cell processes, such as cell division. Additionally, KIF15 has been reported to participate in the growth of various types of tumors; however, the relation between KIF15 and HCC is unclear. Herein, our study investigated the possible role of KIF15 on the progression of HCC and found that KIF15 has high expression in tumor samples from HCC patients. KIF15 could play a critical role in the regulation of cell proliferation of HCC, which was proved by in vitro and in vivo assays. In conclusion, this study confirmed that KIF15 could be a novel therapeutic target for the treatment of HCC.
Subject(s)
Biomarkers, Tumor/analysis , Carcinoma, Hepatocellular/pathology , Kinesins/metabolism , Liver Neoplasms/pathology , Adult , Aged , Animals , Cell Proliferation/physiology , Disease Progression , Female , Heterografts , Humans , Kinesins/analysis , Male , Mice , Mice, Inbred BALB C , Mice, Nude , Middle AgedABSTRACT
OBJECTIVE: A meta-analysis was conducted on the clinical efficacy and safety of Wenxin granules and propafenone for the therapy of atrial premature beats (APBs). METHODS: A randomized controlled trial (RCT) of Wenxin granules and propafenone in the therapy of APB was systematically searched until June 1, 2019. Meta-analysis was conducted with review manager (RevMan) 5.3. For the evaluation of methodological quality for randomized controlled trials, the Cochrane tool was used to assess the risk of bias. For the evaluation of the evidence quality, the online GRADEpro GDT was used. RESULTS: Eleven RCTs with 1149 participants were included in this study. It has been identified that Wenxin granules combined with propafenone have better clinical efficacy than the use of propafenone alone in the treatment of APB (OR = 3.89, 95% CI (2.03, 7.44), P < 0.0001, low-dose propafenone; OR = 4.24, 95% CI (1.32, 13.60), P = 0.02, high-dose propafenone). There is no difference in clinical efficacy between the Wenxin granules alone and high-dose propafenone in the treatment of APB (OR = 1.17, 95% CI (0.65, 2.11), P = 0.60), and Wenxin granules alone are superior to the low-dose propafenone in the treatment of APB (OR = 2.56, 95% CI (1.34, 4.89), P = 0.004). Wenxin granules combined with propafenone can reduce the incidence of sinus bradycardia caused by propafenone (OR = 0.15, 95% CI (0.03, 0.70), P = 0.02). There was no significant difference between Wenxin granules combined with propafenone and propafenone alone in causing the atrioventricular block, dizziness, xerostomia, gastrointestinal symptoms, and tongue paresthesia. There was no significant difference between Wenxin granules alone and propafenone alone in causing dizziness, xerostomia, gastrointestinal symptoms, tongue paresthesia, frequent premature ventricular contractions, and prolongation of R-R interval. CONCLUSION: Very low-quality evidence showed that Wenxin granules may be superior to low-dose propafenone in the treatment of APB. Wenxin granules may reduce the incidence of sinus bradycardia caused by propafenone. Limited by the quality of included RCTs, the conclusions of this study still need further verification.
ABSTRACT
Coinfection with porcine circovirus type 2 (PCV2) and Mycoplasma hyorhinis (Mhr) can induce more-severe disease than a single infection with either. We evaluated the efficacy of a new vaccine combining inactivated PCV2 and Mhr, in a model of PCV2 and Mhr infection. Twenty-five 35-day-old PCV2- and Mhr-free pigs were randomly divided into five groups, with five pigs in each group. The pigs in groups 1 and 2 were vaccinated with the combined vaccine and then challenged with Mhr or PCV2, respectively. The pigs in groups 3 and 4 were not vaccinated and then challenged with PCV2 or Mhr, respectively, and group 5 was used as the unvaccinated unchallenged control. Two weeks after booster immunization via the intramuscular route, all the pigs except those in control group 5 were challenged with PCV2 or Mhr. All the pigs were euthanized 28 days after challenge. The pigs in vaccinated groups 1 and 2 showed a significant increase in weight after challenge with PCV2 or Mhr (P < 0.001), with an average daily gain (ADG) of 0.315 kg compared with unvaccinated groups 3 and 4 (0.279 kg). Mhr was isolated from the unvaccinated pig lungs after Mhr challenge, whereas it was not isolated from the vaccinated pigs. No PCV2 or Mhr was detected with PCR or histochemical staining in vaccinated groups 1 and 2. A statistical analysis showed that the PCV2 and Mhr combined vaccine providing protected against PCV2 infection causing viremia and inguinal lymphadenopathy (5 pigs protected out 5) or against Mhr infection causing fiber inflammation (4 pigs out 5). Thus, we have developed an effective combined vaccine for the prevention and control of PCV2 or Mhr infections in swine herds, this will help reduce prevalence of PCV2 and Mhr coinfections.
Subject(s)
Bacterial Vaccines/immunology , Circoviridae Infections/veterinary , Mycoplasma Infections/veterinary , Swine Diseases/prevention & control , Viral Vaccines/immunology , Animals , Antibodies, Viral/blood , Bacterial Vaccines/administration & dosage , Circoviridae Infections/prevention & control , Circovirus/classification , Circovirus/immunology , Coinfection/microbiology , Coinfection/veterinary , Coinfection/virology , Immunization, Secondary , Injections, Intramuscular , Mycoplasma Infections/prevention & control , Mycoplasma hyorhinis/immunology , Swine , Swine Diseases/immunology , Swine Diseases/virology , Vaccines, Combined/administration & dosage , Vaccines, Combined/immunology , Vaccines, Inactivated/administration & dosage , Vaccines, Inactivated/immunology , Viral Vaccines/administration & dosageABSTRACT
Curcumin is a major active component isolated from Curcuma longa. Previously, we have reported its significant antidepressant effect. However, the mechanisms underlying the antidepressant effects are still obscure. In the present study, we explored the effect of curcumin against glutamate excitotoxicity, mainly focusing on the neuroprotective effects of curcumin on the expression of Brain-Derived Neurotrophic Factor (BDNF), which is deeply involved in the etiology and treatment of depression. Exposure of rat cortical neurons to 10 microM glutamate for 24 h caused a significant decrease in BDNF level, accompanied with reduced cell viability and enhanced cell apoptosis. Pretreatment of neurons with curcumin reversed the BDNF expression and cell viability in a dose- and time-dependent manner. However, K252a, a Trk receptor inhibitor which is known to inhibit the activity of BDNF, could block the survival-promoting effect of curcumin. In addition, the up-regulation of BDNF levels by curcumin was also suppressed by K252a. Taken together, these results suggest that the neuroprotective effect of curcumin might be mediated via BDNF/TrkB signaling pathway.