High level of C3 is associated with Th2 immune response and liver fibrosis in patients with schistosomiasis.

Long-term infection of schistosomiasis will seriously affect the liver health of patients. The serum of 334 chronic Schistosoma japonicum patients and 149 healthy volunteers was collected. Compared with heathy people, the level of C4 (complement 4) was increased, and the level of C3 (complement 3) was in an obvious skewed distribution. ELISA was performed to detect the serum cytokines, the results showed that the levels of IFN-γ (interferon-γ), IL (interleukin)-2 and TNF-α (tumour necrosis factor-α) were reduced, while the levels of Th2 cytokines (IL-4, IL-6 and IL-10) were increased. In the serum of patients with high C3, the secretion of HA (hyaluronic acid), LN (laminin), IV-C (type IV collagen) and PCIII (type III procollagen) were increased, the activation of hepatic stellate cells was promoted. Exogenous human recombinant C3 made mice liver structure of the mice damaged and collagen deposition. IFN-γ and IFN-γ/IL-4 were decreased, while HA, LN, PCIII and IV-C were increased, and the expressions of α-SMA and TGF-ß1 in liver tissues were up-regulated. However, the addition of IFN-γ partially reversed the effect of C3 on promoting fibrosis. High level of C3 is associated with Th2 immune response and liver fibrosis in patients with schistosomiasis.

Prediction of miRNA-disease associations by neural network-based deep matrix factorization.

MicroRNA(miRNA) is a class of short non-coding RNAs with a length of about 22 nucleotides, which participates in various biological processes of cells. A number of studies have shown that miRNAs are closely related to the occurrence of cancer and various human diseases. Therefore, studying miRNA-disease associations is helpful to understand the pathogenesis of diseases as well as the prevention, diagnosis, treatment and prognosis of diseases. Traditional biological experimental methods for studying miRNA-disease associations have disadvantages such as expensive equipment, time-consuming and labor-intensive. With the rapid development of bioinformatics, more and more researchers are committed to developing effective computational methods to predict miRNA-disease associations in roder to reduce the time and money cost of experiments. In this study, we proposed a neural network-based deep matrix factorization method named NNDMF to predict miRNA-disease associations. To address the problem that traditional matrix factorization methods can only extract linear features, NNDMF used neural network to perform deep matrix factorization to extract nonlinear features, which makes up for the shortcomings of traditional matrix factorization methods. We compared NNDMF with four previous classical prediction models (IMCMDA, GRMDA, SACMDA and ICFMDA) in global LOOCV and local LOOCV, respectively. The AUCs achieved by NNDMF in two cross-validation methods were 0.9340 and 0.8763, respectively. Furthermore, we conducted case studies on three important human diseases (lymphoma, colorectal cancer and lung cancer) to validate the effectiveness of NNDMF. In conclusion, NNDMF could effectively predict the potential miRNA-disease associations.

Application and prospect of BSA method based on bibliometrics in crop breeding.

In order to understand the progress and frontier in the application of BSA(bulked segregant analysis) method in crop breeding and to reflect objectively the contribution of different countries, institutions and researchers in this field at home and abroad, this study analyzed 2111 items in the WOS (Web of Science) database from 2000 to 2023 and 446 items in the CNKI (China National through Knowledge Infrastructure) database from 2003 to 2023, regarding the researches of the application of BSA in crop breeding, basing on bibliometric analysis methods using CiteSpace software including keyword co-occurrence analysis, highlight word analysis, keyword clustering analysis, clustering timeline analysis and author co-citation. The results showed that there was an consistent increasing trend in the publication number of the application of BSA in crop breeding both in the domestic and foreign journals year by year. Ranking of the top countries according to the number of publications was China, the United States and India. The Huazhong Agricultural University displayed the highest number of publications in the CNKI database, while the Chinese Academy of Agricultural Sciences was found to have the highest number of publications in the WOS database. The published articles related to the application of BSA in crop breeding abroad mainly focused on the disciplines such as plant science, agronomy, horticulture and genetics, while those in China mainly concentrated on such disciplines as plant science, plant protection, horticulture and biology. The top three authors in terms of influence in the field of appling BSA in crop breeding were Michelmore RW, Kosambi DD and Li H, while Michelmore RW, Lander ES and Li H had closer cooperations with other authors. The top three crops relating to the studies of BSA were rice(Oryza sativa), soybean(Glycine max), corn(Zea mays L.) with the hot spot traits of disease resistance and plant height domestically. The top three crops involving the studies of BSA were rice, Arabidopsis thaliana and wheat(Triticum aestivum L.) with hot spot traits of disease resistance abroad. Up to now, BSA was mainly used to localize and functionally verify the candidate genes linking target traits and the mutated genes in crops in the domestical documents, while the foreign published studies based on BSA were mainly focused on the fine mapping and functional verification of target trait genes aiming at the revelation of genetic mechanisms in crops. Research frontier analysis indicated that rice, peanuts(Arachis hypogaea L.), upland cotton(Gossypium hirsutum L.) would be the main objects of studies concerning application of BSA in crop breeding with the hot topics of crop mutants and crop metabolites in the future.

Prodigiosin as an antibiofilm agent against multidrug-resistant Staphylococcus aureus.

Staphylococcus aureus is known for forming bacterial biofilms that confer increased antimicrobial resistance. Combining antibiotics with antibiofilm agents is an alternative approach, but the antibiofilm ability of prodigiosin (PG), a potential antibiotic synergist, against antimicrobial-resistant (AMR) S. aureus remains to be understood. The antibiofilm activity of PG against 29 clinical AMR S. aureus strains was evaluated using crystal violet staining, and its synergistic effects with vancomycin (VAN) was confirmed using the checkerboard test. The viability and metabolic activity of biofilms and planktonic cells were also assessed. The results revealed that PG exhibited promising inhibitory activity against biofilm formation and synergistic activity with VAN. It effectively reduced the metabolic activity of biofilms and suppressed the production of exopolysaccharides, which might be attributed to the downregulation of biofilm-related genes such as sarA, agrA, and icaA. These findings suggest that PG could be used as a preventive coating or adjuvant against biofilms in clinical settings.

Regeneration mechanism of a novel high-performance biochar mercury adsorbent directionally modified by multimetal multilayer loading.

Biochar that is directly obtained by pyrolysis exhibits a low adsorption efficiency; furthermore, the process of recycling adsorbents is ineffective. To solve these problems, conventional chemical coprecipitation, sol-gel, multimetal multilayer loading and biomass pyrolysis coking processes have been integrated. After selecting specific components for structural design, a novel high-performance biochar adsorbent was obtained. The effects of the O2 concentration and temperature on the regeneration characteristics were explored. An isothermal regeneration method to repair the deactivated adsorbent in a specific atmosphere was proposed, and the optimal regeneration mode and conditions were determined. The microscopic characteristics of the regenerated samples were revealed along with the mechanism of Hg0 removal and regeneration by using temperature-programmed desorption technology and adsorption kinetics. The results show that doping multiple metals can reduce the pyrolysis reaction barrier of the modified biomass. On the modified surface of the sample, the doped metals formed aggregated oxides, and the resulting synergistic effect enhanced the oxidative activity of the biochar carriers and the threshold effect of Ce oxide. The optimal regeneration conditions (5% O2 and 600 °C) effectively coordinated the competitive relationship between the deep carbonization process and the adsorption/oxidation site repair process; in addition, these conditions provided outstanding structure-effect connections between the physico-chemical properties and Hg0 removal efficiency of the regenerated samples. Hg0 adsorption by the regenerated samples is a multilayer mass transfer process that involves the coupling of physical and chemical effects, and the surface adsorption sites play a leading role.

An Industrial Fault Diagnostic System Based on a Cubic Dynamic Uncertain Causality Graph.

This study presents an industrial fault diagnosis system based on the cubic dynamic uncertain causality graph (cubic DUCG) used to model and diagnose industrial systems without sufficient data for model training. The system is developed based on cloud native technology. It contains two main parts, the diagnostic knowledge base and the inference method. The knowledge base was built by domain experts modularly based on professional knowledge. It represented the causality between events in the target industrial system in a visual and graphical form. During the inference, the cubic DUCG algorithm could dynamically generate the cubic causal graph according to the real-time data and perform the logic and probability calculations based on the generated cubic DUCG models, visually displaying the dynamic causal evolution of faults. To verify the system's feasibility, we rebuild a fault-diagnosis model of the secondary circuit system of No. 1 at the Ningde nuclear power plant based on the new system. Twenty-four fault cases were used to test the diagnostic accuracy of the system, and all faults were correctly diagnosed. The results showed that it was feasible to use the cubic DUCG platform for fault diagnosis.

Regulation of ECP fimbriae-related genes by the transcriptional regulator RcsAB in Klebsiella pneumoniae NTUH-K2044.

Klebsiella pneumoniae is one of the major pathogens causing nosocomial infections. The regulator of capsule synthesis (Rcs) system is a complex signal transduction pathway that is involved in the regulation of virulence factors of K. pneumoniae as an important transcriptional regulator. The RcsAB box-like sequence was found to be present in the promoter-proximal regions of ykgK, one of the ECP fimbriae-related genes, which suggested the expression of ECP fimbriae may be regulated by RcsAB. The ykgK gene in K. pneumoniae has 86% similarity to the ecpR gene in Escherichia coli. Nucleotide sequence alignment revealed a similar ECP fimbriae gene cluster including six genes in K. pneumoniae, which was proved to be on the same operon in this study. The electrophoretic mobility shift assay and DNase I assay, relative fluorescence expression, ß-galactosidase activity, and relative gene expression of ykgK in the wild-type and mutant strains were performed to determine the transcriptional regulation mechanism of RcsAB on ECP fimbriae. The mutant ΔykgK and complementary strain ΔykgK/cΔykgK were constructed to complete the Galleria mellonella larvae infection experiment and biofilm formation assay. This study showed that RcsAB binds directly to the promoter region of the ykgK gene to positively regulate ECP fimbriae-related gene clusters, and then positively affect the biofilm formation.

Validation of the Microreader 40Y ID System: a Y-STR multiplex for casework and database samples.

Y-chromosome-specific short tandem repeat loci (Y-STRs) are commonly analysed in forensic science for paternity testing, familial searches, and, in sexual assault cases, to determine male DNA identity from mixed sources with high background female DNA content. The Microreader 40Y ID System is a six-dye multiplex amplification kit that contains 17 Y-STR loci from the Yfiler Plus PCR Amplification Kit and the powerplex Y23 system (DYS19, DYF385a/b, DYS389I/II, DYS390, DYS391, DYS392, DYS393, DYS437, DYS438, DYS439, DYS448, DYS456, DYS458, DYS549, DYS635(Y GATA C4), DYS643, Y GATA H4, DYS460, DYS481, DYS533, DYF387S1, DYS449, DYS518, DYS570, DYS576, and DYS627), plus six high polymorphic loci (DYS444, DYS447, DYS557, DYS596, DYS527 a/b) as well as 4 additional candidate Y-STR loci (DYS593, DYF404S1, DYS645) and a Y-Indel loci (Rs2032678), thereby providing greater efficiency, compatibility, and accuracy. The Microreader 40Y ID System can directly amplify markers from blood or saliva on filter paper or FTA cards, without template extraction or purification, and can also be used for extracted DNA templates. To verify the efficiency and accuracy of the kit, the Microreader 40Y ID System was validated by investigating sensitivity, amplification conditions, male-male and male-female mixtures, PCR inhibition, species specificity, reproducibility, and efficacy with degraded samples. The Y-STR loci were also tested using 437 male samples from Tibet, Han, and Yi. The Microreader 40Y ID System was able to compensate for some of the shortcomings of Y-STR markers in practical applications, such as cost and profile interpretation, and fully meets the domestic Y chromosome database construction specifications and requirements.

Ablation and Inhibition of the Immunoproteasome Catalytic Subunit LMP7 Attenuate Experimental Abdominal Aortic Aneurysm Formation in Mice.

Low-molecular mass protein 7 (LMP7) is a proteolytic subunit of the immunoproteasome that is involved in regulating inflammatory responses. However, the role of LMP7 in the pathogenesis of abdominal aortic aneurysm (AAA) remains unknown. In this study, ApoE knockout (KO) or LMP7/ApoE double KO (dKO) mice were infused with angiotensin II (Ang II, 1000 ng/kg per minute) for up to 28 d. We found that LMP7 expression was significantly upregulated in AAA tissues from ApoE KO mice and human patients. Moreover, Ang II infusion markedly increased the incidence and severity of AAA in ApoE KO mice, which was considerably reduced in LMP7/ApoE dKO mice. Histological alterations, including aortic wall thickening, collagen deposition, elastin fragmentation, and vascular smooth muscle cell apoptosis in AAA tissue of ApoE KO mice, were also significantly attenuated in LMP7/ApoE dKO mice. Interestingly, LMP7/ApoE dKO mice showed a marked reduction of infiltration of CD3+ T cells, especially CD4+ T cells in AAA tissues compared with ApoE KO mice. Moreover, ablation of LMP7 substantially inhibited the differentiation of CD4+ T cells into Th1 and Th17 cells by reducing the activation of multiple transcriptional factors. We also investigated the effects of an LMP7-specific inhibitor PR-957 (also known as ONX 0914) on AAA formation in ApoE KO mice. PR-957 treatment could reduce the AAA incidence and severity. In conclusion, our results provide, to our knowledge, novel evidence that ablation or pharmacological inhibition of LMP7 attenuates Ang II-induced AAA formation, and LMP7 might be a novel therapeutic target for treating AAA in humans.

Sodium butyrate ameliorates Schistosoma japonicum-induced liver fibrosis by inhibiting HMGB1 expression.

Schistosomiasis is a prevalent zoonotic parasitic disease caused by schistosomes. Its main threat to human health is hepatic granuloma and fibrosis due to worm eggs. Praziquantel remains the first choice for the treatment of schistosomiasis but has limited benefit in treating liver fibrosis. Therefore, the need to develop effective drugs for treating schistosomiasis-induced hepatic fibrosis is urgent. High-mobility group box 1 protein (HMGB1) is a potential immune mediator that is highly associated with the development of some fibrotic diseases and may be involved in the liver pathology of schistosomiasis. We speculated that HMGB1 inhibitors could have an anti-fibrotic effect. Sodium butyrate (SB), a potent inhibitor of HMGB1, has shown anti-inflammatory activity in some animal disease models. In this study, we evaluated the effects of SB on a murine schistosomiasis model. Mice were percutaneously infected with 20 ± 2 cercariae of Schistosoma japonicum. SB (500 mg/kg/day) was administered every 3 days for the entire experiment period. The activity of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), liver histopathology, HMGB1 expression, and the levels of interferon gamma (IFN-γ), transforming growth factor-ß1 (TGF-ß1), and interleukin-6 (IL-6) in serum were analyzed. SB reduced hepatic granuloma and fibrosis of schistosomiasis, reflected by the decreased levels of ALT and AST in serum and the reduced expression of pro-inflammatory and fibrogenic cytokines (IFN-γ, TGF-ß1, and IL-6). The protective effect could be attributable to the inhibition of the expression of HMGB1 and release by SB.

Intravenous lipid emulsion modifies synaptic transmission in hippocampal CA1 pyramidal neurons after bupivacaine-induced central nervous system toxicity.

Local anesthetics can cause severe toxicity when absorbed systemically. Rapid intravenous administration of lipid emulsion (LE) is the standard of care for severe local anesthetic systemic toxicity which can cause cardiovascular and central nervous system (CNS) injury. The biological mechanism by which LE alleviates CNS toxicity remains unknown and understudied. Previous research has suggested that local anesthetics cause an imbalance of excitatory and inhibitory transmission in the brain. Therefore, this study aimed to observe the effect of LE on glutamate- and GABA-induced currents in CA1 pyramidal neurons after bupivacaine-induced CNS toxicity. We further characterized post-synaptic modifications in these cells to try to elucidate the mechanism by which LE mediates bupivacaine-induced CNS toxicity. Sprague-Dawley rats received intravenous bupivacaine (1 mg kg-1  min-1 ) in either normal saline or LE (or LE without bupivacaine) for 5 min. An acute brain slice preparation and a combination of whole-cell patch clamp techniques and whole-cell recordings were used to characterize action potential properties, miniature excitatory, and inhibitory post-synaptic currents, and post-synaptic modifications of excitatory and inhibitory transmission in CA1 hippocampal pyramidal neurons. The expression level of GABAA receptors were assessed with western blotting, whereas H&E and TUNEL staining were used to assess cytoarchitecture and apoptosis levels respectively. Bupivacaine treatment significantly increased the number of observed action potentials, whereas significantly decreasing rheobase, the first interspike interval (ISI), and hyperpolarization-activated cation currents (Ih) in CA1 pyramidal neurons. LE treatment significantly reduced the frequency of miniature inhibitory post-synaptic currents and enhanced GABA-induced paired pulse ratio with 50 ms interval stimulation in bupivacaine-treated rats. Regulation of GABAA levels is a promising mechanism by which LE may ameliorate CNS toxicity after systemic absorption of bupivacaine.

Efficacy and safety of anti-inflammatory agents for the treatment of major depressive disorder: a systematic review and meta-analysis of randomised controlled trials.

OBJECTIVES: To systematically review the efficacy and safety of anti-inflammatory agents for patients with major depressive disorders. METHODS: We searched the literature to identify potentially relevant randomised controlled trials (RCTs) up to 1 January 2019. The primary outcome was efficacy, measured by mean changes in depression score from baseline to endpoint. Secondary outcomes included response and remission rates and quality of life (QoL). Safety was evaluated by incidence of classified adverse events. Heterogeneity was examined using the I2 and Q statistic. Pooled standard mean differences (SMDs) and risk ratios (RRs) were calculated. Subgroup meta-analyses were conducted based on type of treatment, type of anti-inflammatory agents, sex, sponsor type and quality of studies. RESULTS: Thirty RCTs with 1610 participants were included in the quantitative analysis. The overall analysis pooling from 26 of the RCTs suggested that anti-inflammatory agents reduced depressive symptoms (SMD -0.55, 95% CI -0.75 to -0.35, I2=71%) compared with placebo. Higher response (RR 1.52, 95% CI 1.30 to 1.79, I2=29%) and remission rates (RR 1.79, 95% CI 1.29 to 2.49, I2=41%) were seen in the group receiving anti-inflammatory agents than in those receiving placebo. Subgroup analysis showed a greater reduction in symptom severity in both the monotherapy and adjunctive treatment groups. Subgroup analysis of non-steroidal anti-inflammatory drugs, omega-3 fatty acids, statins and minocyclines, respectively, disclosed significant antidepressant effects for major depressive disorder (MDD). For women-only trials, no difference in changes of depression severity was found between groups. Subanalysis stratified by sponsor type and study quality led to the same outcomes in favour of anti-inflammatory agents in both subgroups. Changes of QoL showed no difference between the groups. Gastrointestinal events were the only significant differences between groups in the treatment periods. CONCLUSIONS: Results of this systematic review suggest that anti-inflammatory agents play an antidepressant role in patients with MDD and are reasonably safe.

Efficacy and safety of calcitonin-gene-related peptide binding monoclonal antibodies for the preventive treatment of episodic migraine - an updated systematic review and meta-analysis.

BACKGROUND: Migraine is one of the most common neurological disorders that leads to disabilities. However, the conventional drug therapy for migraine might be unsatisfactory at times. Therefore, this meta-analysis aimed to evaluate the efficacy and safety of calcitonin-gene-related peptide binding monoclonal antibody (CGRP mAb) for the preventive treatment of episodic migraine, and provide high-quality clinical evidence for migraine therapy. METHODS: A systematic electronic database search was conducted to identify the potentially relevant studies. Two independent authors performed data extraction and quality appraisal. Mean difference (MD) and risk ratio (RR) were pooled for continuous and dichotomous data, respectively. The significance levels, weighted effect sizes and homogeneity of variance were calculated. RESULTS: Eleven high-quality randomized control trials that collectively included 4402 patients were included in this meta-analysis. Compared to placebo group, CGRP mAb therapy resulted in a reduction of monthly migraine days [weighted mean difference (WMD) = - 1.44, 95% CI = (- 1.68,- 1.19)] and acute migraine-specific medication days [WMD = - 1.28, 95% CI = (- 1.66,- 0.90)], with an improvement in 50% responder rate [RR = 1.51, 95% CI = (1.37,1.66)]. In addition, the adverse events (AEs) and treatment withdrawal rates due to AEs were not significantly different between CGRP mAb and placebo groups. Similar efficacy and safety results were obtained for erenumab, fremanezumab, and galcanezumab in subgroup analysis. CONCLUSIONS: The current body of evidence reveals that CGRP mAb is an effective and safe preventive treatment for episodic migraine.

Effects of enzymatic hydrolysate of locust bean gum on digestibility, intestinal morphology and microflora of broilers.

To investigate the effects of different levels of enzymatic hydrolysate of dietary locust bean gum on nutrient digestibility, intestinal morphology and microflora of broilers, a total of 768 one-day-old Arbor Acres (AA) broiler chicks were randomly divided into 6 treatments with 8 replicates per treatment and 16 birds per replicate. The treatments were as follows: (1) CON, basal diet; (2) ANT, basal diet +62.5 mg/kg flavomycin; (3) LBG, basal diet +0.1% locust bean gum; (4) ELBG-0.1, basal diet +0.1% enzymatic hydrolysate of LBG; (5) ELBG-0.2, basal diet +0.2% enzymatic hydrolysate of LBG; and (6) ELBG-0.3, basal diet +0.3% enzymatic hydrolysate of LBG. The digestibilities of ether extract, crude protein and dry matter were increased (p < .01) in broilers fed the ELBG-0.3 diet compared with the CON and LBG diets on day 21. Duodenal villus height and the ratio of the villus height to crypt depth were greater (p < .01) in broilers fed the ELBG-0.3 diet than the CON, ANT and LBG diets. Jejunum villus height was higher (p < .05) in broilers fed the ELBG-0.2 and ELBG-0.3 diets than the CON diet. The number of caecal Escherichia coli was reduced (p = .01) in broilers fed the ELBG-0.2 and ELBG-0.3 diets compared with the CON diet. The number of caecal Lactobacilli was greater (p < .05) in broilers fed the ELBG-0.3 diet than the CON and ANT diets. In summary, the addition of 0.3% locust bean enzymatic hydrolysate can increase the surface area of intestinal villi and the number of beneficial bacteria, inhibit the proliferation of harmful bacteria, maintain the balance of intestinal microflora and improve the digestibility of nutrients.

Chemokine (C-X-C motif) receptor 2 blockade by SB265610 inhibited angiotensin II-induced abdominal aortic aneurysm in Apo E-/- mice.

Inflammation plays a critical role in the development of abdominal aortic aneurysm (AAA). Chemokine receptor CXCR2 mediates inflammatory cell chemotaxis in several diseases. However, the role of CXCR2 in AAA and the underlying mechanisms remain unknown. In this study, we found that the CXCR2 expressions in AAA tissues from human and angiotensin II (Ang II)-infused apolipoprotein E knockout (Apo E-/-) mice were significantly increased. The pharmacological inhibition of CXCR2 (SB265610) markedly reduced Ang II-induced AAA formation. Furthermore, SB265610 treatment significantly reduced collagen deposition, elastin degradation, the metal matrix metalloprotease expression and accumulation of macrophage cells. In conclusion, these results showed CXCR2 plays a pathogenic role in AAA formation. Inhibition of CXCR2 pathway may represent a novel therapeutic approach to treat AAA.

Hybridizing the "Sandwich" and "Chimney" Techniques in the Endovascular Repair of Coarctation of the Aortic Arch and Postcoarctation Ectasia Concomitant with a Left Subclavian Artery Aneurysm.

Coarctation of aorta is a rare congenital malformation and is usually accompanied by other cardiac or vascular lesions. In this case, we describe a 51-year-old patient who presented with coarctation of the aortic arch and postcoarctation ectasia concomitant with a left subclavian artery aneurysm. Endovascular therapy included the deployment of an inverted wedge-shaped covered stent inserted by a long "chimney" stent and another cylinder-covered stent, forming a "sandwich"-like configuration. The symptoms were alleviated after surgery, and no perioperative or stent-graft-related complications were observed at a 2-year follow-up.

An association of spleen volume and aortic diameter in patients and in mice with abdominal aortic aneurysm.

BACKGROUND: To investigate the potential mechanism of splenic enlargement in Ang II/APOE model and the associations between the spleen volume and the indices of abdominal aortic aneurysm (AAA) in human. METHODS: To investigate the changes of spleen volume on AAA formation, apolipoprotein E knockout (Apo E-/-) mice were treated with Ang II (1000 ng/kg/min) up to 28 days to generate AAA. We used Magnetic Resonance Imaging (MRI), liquid measurement, H&E and immunohistochemistry to analyze the morphological or pathological changes of spleen. To investigate the changes of spleen volume in human, a retrospective case-control study involving 30 male AAA patients and 25 male controls were performed. Spleen volume was measured on computed tomography images. Univariate analysis and multivariable sequential logistic regression analyses were used to analyze the association between spleen volume and maximal diameter (Dmax). RESULTS: In Ang II/APOE model, we found splenic enlargement in mice with AAA compared with the sham group. Histopathological investigations revealed hypertrophies of splenic follicles and increased populations of CD3+ T cells. In clinic cohort study, univariate analysis revealed higher values in large AAA (Dmax > 5.5 cm,n = 15) compared with the small (Dmax < 5.5 cm,n = 15) for spleen volume (230.6 ± 64.5 cm3 vs. 170.0 ± 32.8 cm3; P = 0.0030). Regression analysis revealed a statistically significant positive linear correlation of spleen volume and Dmax of AAA (r = 0.3611;P = 0.0423). CONCLUSIONS: Mimicking the splenic pathology observed in murine AAA model, there is a strong positive correlation between spleen volume and the Dmax in male AAA patients. As Dmax is a valuable predictor of AAA rupture, the spleen enlargement may be another indicator.

Effect of Bortezomib on Angiotensin â ¡-induced Abdominal Aortic Aneurysm in ApoE-/- Mice.

Objective To investigate the role of proteasome inhibitor bortezomib (BTZ) in inflammatory response in abdominal aortic aneurysm (AAA) formation induced by angiotensin Ⅱ (Ang Ⅱ). Methods Ang Ⅱ-induced ApoE-/- mice AAA models were established. Forty male ApoE-/- mice (8-10-week-old) were randomly and equally divided into four groups:Sham group,BTZ group,Ang Ⅱ group,and Ang Ⅱ+BTZ group.HE staining,immunohistochemical staining,and flow cytometry were used to analyze the inflammatory response. Real-time quantitative polymerase chain reaction (qPCR) was used to analyze the mRNA expression of intercellular cell adhesion molecule-1 (ICAM-1). Western blotting was used to analyze the activation of nuclear factor κB signaling (NF-κB). Results The mean maximum suprarenal aortic diameter (Dmax) of Sham group,BTZ group,Ang Ⅱ group,and Ang Ⅱ+BTZ group were (1.00±0.01),(0.99±0.01),(1.50±0.13),and (1.20±0.04)mm,respectively (F=8.959,P=0.000). The Dmax of Ang Ⅱ group was significantly larger than those of Sham group (P=0.000) and Ang Ⅱ+BTZ group (P=0.015). The incidence of AAA in Ang Ⅱ group,Ang Ⅱ+BTZ group,and Sham group were 60%,17%,and 0,respectively. HE staining revealed that the abdominal aortic wall thickening was more severe in Ang Ⅱ group than in Sham group and Ang Ⅱ+BTZ group,similar with the infiltration of inflammatory cells. Immunohistochemical staining demonstrated that the CD3+T lymphocyte count was significantly higher in Ang Ⅱ group than in Sham group (107.9±15.9 vs. 0,P=0.000) and Ang Ⅱ+BTZ group (107.9±15.9 vs. 0.8±0.5,P=0.000). Flow cytometry also demonstrated that the proportion of the CD3+T lymphocytes of the Ang Ⅱ group [(13.50±0.69)%] was significantly higher than that in the Ang Ⅱ+BTZ group [(10.40±0.78)%] at week 1 (t=3.009,P=0.040),and the proportion of the CD3+T lymphocytes of the Ang Ⅱ group [(22.70±0.93)%] was significantly higher than that in the Ang Ⅱ+BTZ group [(15.10±0.97)%] at week 4 (t=5.654,P=0.005). The qPCR analysis showed that the mRNA expression of ICAM-1 was significantly up-regulated in Ang Ⅱ group than in Sham group (1.93±0.54 vs. 1.00±0.15,P=0.011) and Ang Ⅱ+BTZ group (1.93±0.54 vs. 0.83±0.08,P=0.009). Western blot analysis showed a lower phosphorylation level of inhibitor of NF-κB in the Ang Ⅱ group compared with the Sham group or Ang Ⅱ+BTZ group,accompanied with an increased phosphorylation level of p65. Conclusion Proteasome inhibitor BTZ can attenuate AAA formation partially by regulating T lymphocytes infiltration through regulating the mRNA expression of ICAM-1 regulated by the activation of NF-κB signaling pathway.

Change of Serum Angiopoietin-like Protein 2 and Its Significance in Patients with Arteriosclerotic Occlusion.

Objective To investigated the changes of angiopoietin-like protein 2(Angptl2) in patients with arteriosclerotic occlusion (ASO). Methods A total of 140 subjects including 75 ASO patients (ASO group) and 65 healthy subjects (control group) were enrolled in this study. Angptl2 and adiponectin were evaluated by using enzyme-linked immunosorbent assay. Biochemical data and high sensitive C reactive protein were measured and recorded as well. Results Compared to the control group,the ASO group presented with significantly higher level of plasma Angptl2 [(13.55±9.17) µg/L vs. (9.04±4.79) µg/L,P=0.010]. Plasma Angptl2 level of critical limb ischemia subjects was significantly higher than that of intermittent claudication subjects [(17.01±10.20)µg/L vs. (10.53±6.97) µg/L,P=0.003]. The best diagnostic cutoff value of Angptl2 was 13.67 µg/L,with a sensitivity of 60.34% and a specificity of 81.25%. In addition,type 2 diabetes mellitus patients with ASO exhibited significantly higher serum Angptl2 levels [(18.67±9.84)µg/L] than those without ASO [(13.01±3.47) µg/L] (P=0.021). In ASO group,serum Angptl2 levels were negatively correlated with ankle brachial index (r=-0.244,P=0.035). Conclusion The plasma level of Angptl2 increases in ASO patients. Its level is remarkably increased when the disease progressions to critical limb ischemia. Angptl2 can be a potential biological marker of disease progression.

Bicyclol induces cell cycle arrest and autophagy in HepG2 human hepatocellular carcinoma cells through the PI3K/AKT and Ras/Raf/MEK/ERK pathways.

BACKGROUND: Bicyclol, a novel synthetic antihepatitis drug, is widely known to protect against liver injury. However, few reports have focused on the possible effect of bicyclol on anti-proliferation and autophagy induction in cancer cells, particularly hepatocellular carcinoma cells. METHODS: In this study, we investigated the antitumor efficacy of Bicyclol in HepG2 cells and the mechanism of cell growth inhibition. Cell proliferation was analyzed by MTT assay, and the cell cycle and apoptosis were assessed by flow cytometry. And we transfected the cells with the GFP-RFP-LC3 vector to detect the autophagy flux in the cells. Mechanisms of bicyclol-induced cell growth inhibition were probed by western blot analysis. RESULTS: Bicyclol effectively inhibited HepG2 cell proliferation in a dose- and time-dependent manner. In addition, we found that bicyclol inhibited cell cycle progression at G1 phase and induced autophagy in HepG2 cells, which implied that the significant decrease in cell proliferation was mainly induced by autophagy and inhibition of cell proliferation. Furthermore, western blot showed that bicyclol inhibited phosphorylation of Akt and ERK, down-regulated the expressions of cyclin D1, cyclin E2, CDK2, CDK4, p-Rb and p-mTOR. Moreover, AKT or ERK knockdown by siRNA enhanced bicyclol-induced autophagy and inhibition of cell proliferation. CONCLUSION: These results suggest that bicyclol has potent anti-proliferative activity against malignant human hepatoma cells via modulation of the PI3K/AKT pathway and the Ras/Raf/MEK/ERK pathway, and indicate that bicyclol is a potential liver cancer drug worthy of further research and development.