Feasibility and safety of percutaneous intramyocardial septal cryoablation: A canine model with 6-month follow-up.

Echocardiography-guided percutaneous intramyocardial septal radiofrequency ablation (PIMSRA, Liwen procedure) is a novel treatment option for hypertrophic obstructive cardiomyopathy (HOCM). The safety and feasibility of using this procedure for cryoablation are unknown. We aimed to investigate the feasibility and safety of echocardiography-guided percutaneous intramyocardial septal cryoablation (PIMSCA) for septal thickness reduction in a canine model. Eight canines underwent PIMSCA, and had electrocardiography, echocardiography(ECG), myocardial contrast echocardiography (MCE), serological and pathological examinations during the preoperative, immediate postoperative, and 6-month follow-up. All eight canines underwent successful cryoablation and continued to be in sinus rhythm during ablation and without malignant arrhythmias. MCE showed that the ablation area had decreased myocardial perfusion after the procedure. Troponin I levels were significantly elevated [0.010 (0.005, 0.297) ng/mL vs. 3.122 (1.152, 7.990) ng/mL, p < 0.05)]. At 6-month follow-up after the procedure, all animals were alive, with thinning of the interventricular septum (7.26 ± 0.52 mm vs. 3.86 ± 0.29 mm, p < 0.05). Echocardiography showed no significant decrease in the left ventricular ejection fractions (LVEF) (54.32 ± 2.93 % vs. 54.70 ± 2.47 %, p > 0.05) or changes by pulse-wave Doppler E/A (1.17 ± 0.43 vs. 1.07 ± 0.43, p > 0.05), E/e' (8.09 ± 1.49 vs. 10.05 ± 2.68, p > 0.05). Pathological findings proved the effectiveness of cryoablation in myocardial tissues. We observed pericardial effusions and premature ventricular complexes (PVCs) associated with the procedure. Our findings provided preliminary evidence of the safety and feasibility of PIMSCA in reducing interventricular septum, which provides a potentially new treatment option for HOCM.

Focus on the cGAS-STING Signaling Pathway in Sepsis and Its Inflammatory Regulatory Effects.

Sepsis is a severe systemic inflammatory response commonly occurring in infectious diseases, caused by infection with virulent pathogens. In the pathogenesis of sepsis, the cyclic guanosine monophosphate (GMP)-adenosine monophosphate (AMP) synthase-stimulator of interferon genes (cGAS-STING) signaling pathway serves a crucial role as a fundamental immunoregulatory mechanism. This signaling pathway activates STING upon recognizing intracellular DNA damage and pathogen-derived DNA, subsequently inducing the production of numerous inflammatory mediators, including interferon and inflammatory cytokines, which in turn trigger an inflammatory response. The aim of this paper is to explore the activation mechanism of the cGAS-STING signaling pathway in sepsis and its impact on inflammatory regulation. By delving into the mechanism of action of the cGAS-STING signaling pathway in sepsis, we aim to identify new therapeutic strategies for the treatment and prevention of sepsis.

Myocardial contractility characteristics of hypertrophic cardiomyopathy patients with and without sarcomere mutation.

Hypertrophic cardiomyopathy (HCM) patients with sarcomere mutations have an increased risk of heart failure and left ventricular (LV) systolic dysfunction. We hypothesize that sarcomere mutation carriers have abnormal myocardial contractility before LV dysfunction. Therefore, we aimed to associate myocardial contractility with identified sarcomere mutations and predict genotyped HCM patients with sarcomere mutation by three-dimensional speckle tracking imaging (3D-STI). A retrospective analysis of 117 HCM patients identified 32 genotype-positive (G +) and 85 genotype-negative (G-) patients. Genotype-positive patients had higher globe circumferential strain (GCS), globe longitudinal strain (GLS), and globe radial strain (GRS) (p < 0.05), and multivariate logistic regression revealed that these variables were associated with a positive genetic status (p < 0.05). After the propensity matches other possible influencing factors, we developed three models, named Model GCS, Model GLS, and Model GRS, which could identified genotype-positive HCM patients with excellent performance (AUC of 0.855, 0.833, and 0.870 respectively, all p < 0.001). Genotype-positive HCM patients show a higher myocardial hyper-contractility status than patients without sarcomere mutations. When combined with clinical and echocardiographic markers, the 3D-STI parameters can effectively identify the likelihood of genotype-positive HCM.

Investigating the shared genetic architecture between frailty and insomnia.

Background: The epidemiological association between frailty and insomnia is well established, yet the presence of a common genetic etiology is still uncertain. Further exploration is needed to ascertain the causal relationship between frailty and insomnia. Methods: Utilizing data obtained from genome-wide association studies (GWAS) summaries, we utilized the linkage disequilibrium score regression (LDSC) to determine the genetic correlation existing between frailty and insomnia. The determination of causality was achieved through the application of two-sample Mendelian randomization. We investigated the enrichment of single nucleotide polymorphism (SNP) at various tissue types utilizing stratified LD score regression (S-LDSC) and multimarker analysis of genome annotation (MAGMA). Common risk SNPs were identified using Multi-Trait Analysis of GWAS (MTAG) and Cross-Phenotype Association (CPASSOC). We further investigated the expression profiles of risk genes in tissues using Summary-data-based Mendelian randomization(SMR) based on pooled data, to explore potential functional genes. Results: Our findings indicated a significant genetic correlation between frailty and insomnia, highlighting SNPs sharing risk (rs34290943, rs10865954), with a pronounced correlation in the localized genomic region 3p21.31. Partitioned genetic analysis revealed 24 functional elements significantly associated with both frailty and insomnia. Furthermore, mendelian randomization revealed a causal connection between frailty and insomnia. The genetic correlation between frailty and insomnia showed enrichment in 11 brain regions (S-LDSC) and 9 brain regions (MAGMA), where four functional genes (RMB6, MST1R, RF123, and FAM212A) were identified. Conclusion: This study suggests the existence of a genetic correlation and common risk genes between frailty and insomnia, contributing to a deeper comprehension of their pathogenesis and assists in identifying potential therapeutic targets.

Association of immune cell traits with Parkinson's disease: a Mendelian randomization study.

Background: Immunity and neuroinflammation play crucial roles in the pathogenesis of Parkinson's disease (PD). Nonetheless, prior investigations into the correlation between immune inflammation and PD have produced varying results. Identifying specific immune cell phenotypes that are truly associated with PD is challenging, and the causal relationship between immune cells and PD remains elusive. Methods: This study conducted a comprehensive two-sample Mendelian randomization (MR) analysis, employing five distinct analytical approaches, to clarify the causal connection between immune cell characteristics and the risk of PD. Utilizing GWAS data, we investigated the causal relationship between 731 immune cell traits and PD. These immune cell phenotypes encompass absolute cell (AC) counts, median fluorescence intensity (MFI), and relative cell (RC) counts for B cells, cDCs, mature stage T cells, monocytes, myeloid cells, TBNK (T cells, B cells, and natural killer cells), and Tregs, as well as the logistic parameter (MP) for cDCs and TBNK. Results: The inverse variance weighted (IVW) analysis indicated that Myeloid DCs (p = 0.004), HVEM expression on CD45RA- CD4+ T cells (p = 0.007), CD62L- CD86+ Myeloid DCs (p = 0.015), and HLA DR expression on monocytes (p = 0.019) were associated with a reduced risk of PD. CD14+ CD16+ monocytes (p = 0.005), HLA DR+ NK cells within CD3- lymphocytes (p = 0.023), and CD28 expression on activated & secreting Tregs (p = 0.032) were associated with an increased risk of PD. Conclusion: This study establishes a causal link between immune cell phenotype and the pathogenesis of PD, identifying several specific immune cell characteristics associated with PD. This could inspire researchers to delve into the pathogenesis of PD at the cellular subtype level, and aid in the identification of potential pharmacological protein targets for PD.

Percutaneous intramyocardial septal radiofrequency ablation after 5-year follow-up.

OBJECTIVE: The objective is to evaluate the 5-year follow-up results of percutaneous intramyocardial septal radiofrequency ablation (PIMSRA) for hypertrophic obstructive cardiomyopathy (HOCM), including clinical status, electrocardiographic and echocardiographic characteristics. METHODS: 27 patients (age: 44.3±15.5 years; 67% men, 33% women) with severely symptomatic HOCM who underwent PIMSRA from October 2016 to September 2017 were included. Their clinical status, resting and exercise stress echocardiography, electrocardiography and cardiac MRI (CMRI) after long-term follow-up were assessed. RESULTS: One patient died of intracerebral haemorrhage 1 year post procedurally. The New York Heart Association class, Canadian Cardiovascular Society class and exercise-induced syncopal attacks improved significantly in 26 patients (all p<0.01). Left ventricular (LV) outflow tract gradients revealed sustained reduction (resting: from 95.0 to 9.0 mm Hg, p<0.001; post exercise: from 130.5 to 21.0 mm Hg, p<0.001). The echocardiographic evaluation revealed decreased septal thickness, LV posterior wall thickness and left atrial (LA) diameter (all p<0.001). CMRI data revealed decrease in LV mass index and LA volume index and increase in LV end-diastolic volume index and stroke volume index between baseline and long-term follow-up (all p<0.05). The global longitudinal strain of LV improved from (-11.9%±3.7%) before the procedure to (-13.1%±3.9%) at the last check (p<0.001). Malignant ventricular arrhythmia and heart failure events were not observed. CONCLUSIONS: PIMSRA can effectively alleviate symptoms in patients with HOCM and improve their hemodynamics in the long term. TRIAL REGISTRATION NUMBER: NCT02888132.

A Novel Endoplasmic Reticulum-Targeted Metal-Organic Framework-Confined Ruthenium (Ru) Nanozyme Regulation of Oxidative Stress for Central Post-Stroke Pain.

Central post-stroke pain (CPSP) is a chronic neuropathic pain caused by cerebrovascular lesion or disfunction after stroke. Convincing evidence suggest that excessive reactive oxygen species (ROS), generated matrix metalloproteinase (MMPs) and neuroinflammation are largely involved in the development of pain. In this study, an effective strategy is reported for treating pain hypersensitivity using an endoplasmic reticulum (ER)-targeted metal-organic framework (MOF)-confined ruthenium (Ru) nanozyme. The Ru MOF is coated with a p-dodecylbenzene sulfonamide (p-DBSN) modified liposome with endoplasmic reticulum-targeted function. The experimental results reveals that ROS, Emmprin, MMP-2, and MMP-9 are upregulated in the brain of CPSP mice, along with the elevated expression of inflammation markers such as TNF-α and IL-6. Compared to vehicle, one-time intravenous administration of ER-Ru MOF significantly reduces mechanical hypersensitivity after CPSP for three days. Overall, ER-Ru MOF system can inhibit oxidative stress in the brain tissues of CPSP model, reduce MMPs expression, and suppress neuroinflammation response-induced injury, resulting in satisfactory prevention and effective treatment of CPSP during a hemorrhagic stroke. The ER-Ru MOF is expected to be useful for the treatment of neurological diseases associated with the vicious activation of ROS, based on the generality of the approach used in this study.

Analysis of the correlation between immune cell characteristics and insomnia: a Mendelian randomization study.

Insomnia, recognized as a prevalent sleep disorder, has garnered extensive attention within the realm of public health. Recent studies indicate a close interaction between the immune system and sleep; however, the specific mechanism remains not yet fully understood. Based on the publicly available Genome-Wide Association Study (GWAS) data, we used two-sample Mendelian randomization (MR) analyses to investigate the associations between 731 immune cell traits and insomnia risk. Five MR analysis methods and a comprehensive sensitivity analysis were used to evaluate the reliability of the results. In this study, we identified that 14 immune characteristics among four immune profiles [median fluorescence intensity (MFI), relative cell count (RC), absolute cell count (AC), and morphological parameters (MP)] demonstrated a significant causal association with insomnia. Specifically, eight immune cell characteristics were associated with an increased risk of insomnia, including CD11c+ monocyte% (P < 0.001), CD11c+ HLA DR++ monocyte% (P = 0.004), CD86+ plasmoid dendritic cell (DC) AC (P < 0.001), CD33br HLA DR+ CD14dim AC (P < 0.001), CD8dim AC (P = 0.002), CCR2 on CD14+ CD16- monocyte (P < 0.001), CD39 on monocyte (P < 0.001), and SSC-A on myeloid DC (P < 0.001). Six immune cell characteristics demonstrated protective effects against insomnia, including PB/PC %B cell (P < 0.001), CM CD4+% CD4+ (P < 0.001), T-cell AC (P < 0.001), BAFF-R on IgD- CD38br (P < 0.001), CD16-CD56 on HLA DR+ NK cells (P < 0.001), and CD14 on CD33br HLA DR+ CD14dim (P < 0.001). Our study established the correlation between immune cell characteristics and insomnia, offering a novel theoretical foundation for the concept of sleep-immune cross talk.NEW & NOTEWORTHY This study investigated the association between 731 immune cell characteristics and insomnia using Mendelian randomization, revealing that 14 immune cell characteristics across four groups of immune traits (MFI, RC, AC, and MP) have a significant and causal association with insomnia risk. Our results contribute to the understanding of the sleep-immune cross talk doctrine and offer a new theoretical basis for immune modulation in treating insomnia.

Autophagy and its therapeutic potential in diabetic nephropathy.

Diabetic nephropathy (DN), the leading cause of end-stage renal disease, is the most significant microvascular complication of diabetes and poses a severe public health concern due to a lack of effective clinical treatments. Autophagy is a lysosomal process that degrades damaged proteins and organelles to preserve cellular homeostasis. Emerging studies have shown that disorder in autophagy results in the accumulation of damaged proteins and organelles in diabetic renal cells and promotes the development of DN. Autophagy is regulated by nutrient-sensing pathways including AMPK, mTOR, and Sirt1, and several intracellular stress signaling pathways such as oxidative stress and endoplasmic reticulum stress. An abnormal nutritional status and excess cellular stresses caused by diabetes-related metabolic disorders disturb the autophagic flux, leading to cellular dysfunction and DN. Here, we summarized the role of autophagy in DN focusing on signaling pathways to modulate autophagy and therapeutic interferences of autophagy in DN.

The protection of luteolin against diabetic cardiomyopathy in rats is related to reversing JNK-suppressed autophagy.

Increasing evidence has shown that impaired autophagy dramatically causes myocardial hypertrophy and fibrosis in the diabetic heart, ultimately leading to diabetic cardiomyopathy (DCM). Luteolin has been reported to effectively attenuate diabetic cardiovascular injury by inhibiting oxidative stress and alleviate sepsis-induced myocardial injury by enhancing autophagy. However, whether luteolin can reduce DCM through activating autophagy and the underlying mechanism remain unclear. Here, reversing the c-Jun N-terminal kinase (JNK)-suppressed autophagy pathway by which luteolin attenuates DCM was explored. Male Sprague-Dawley rats were injected with streptozotocin to induce diabetes. After 6 weeks of diabetes, rats were treated with luteolin (50, 100 and 200 mg kg-1, i.g.) for 4 weeks. Histological and functional alterations in the diabetic heart were determined using HE staining, Masson staining and echocardiography. The expressions of myocardial miR-221, JNK, and c-Jun and autophagic vesicles in diabetes were evaluated by quantitative PCR, Western blotting and electron microscopy. Luteolin significantly improved cardiac function and attenuated myocardial disorganization and fibrosis in the diabetic rat accompanying the dose-dependent down-regulation of JNK, c-Jun, miR-221 and p62, increase of LC3-II/I and autophagic vesicles, and decrease of mitochondrial swelling in the diabetic heart. These data suggest that the protection of luteolin against DCM, at least, is related to suppressing JNK/c-Jun-regulated miR-221 and the subsequent blockage of autophagy.

Myocardial mechanics of percutaneous intramyocardial septal radiofrequency ablation.

OBJECTIVE: Echocardiography-guided Percutaneous IntraMyocardial Septal Radiofrequency Ablation (PIMSRA, Liwen procedure) is a novel treatment option for hypertrophic obstructive cardiomyopathy (HOCM). The impact of PIMSRA on myocardial mechanics is unknown. METHODS: Between October 2016 and June 2019, PIMSRA and 3-dimentional speckle tracking echocardiography were performed in 82 patients. Echocardiographic imaging, qualitative and quantitative clinical assessment were completed at baseline, immediately postprocedure and 1-year follow-up. RESULTS: There was a significant reduction in the peak left ventricular outflow tract (LVOT) gradients immediately following PIMSRA and at 1-year follow-up (resting gradients: from 83.50 (61.25) to 23.00 (41.75) mm Hg, p<0.001 and 13.50 (21.75) mm Hg, p<0.001, respectively; stress-induced gradients: from 118.25 (96.02) to 47.00 (74.50) mm Hg (1 year), p<0.001). There was an improvement in exercise time on stress echocardiography (p<0.001) and distance by 6 min walk test (p=0.034). Immediately after PIMSRA, there was a significant reduction in radial and circumferential strain in the ablated segments (p<0.001), with no change of longitudinal strain. At 1-year follow-up, the radial and circumferential strain recovered in the ablated segments. Meanwhile, left ventricular regional and global longitudinal strain had improved significantly (p<0.05). CONCLUSIONS: PIMSRA is an effective treatment for symptomatic HOCM that resulted in a sustained improvement in exercise capacity, a persistent decrease in LVOT gradient, and a measurable increase in myocardial contractile function. TRIAL REGISTRATION NUMBER: NCT04777188.

Profile of crosstalk between glucose and lipid metabolic disturbance and diabetic cardiomyopathy: Inflammation and oxidative stress.

In recent years, the risk, such as hypertension, obesity and diabetes mellitus, of cardiovascular diseases has been increasing explosively with the development of living conditions and the expansion of social psychological pressure. The disturbance of glucose and lipid metabolism contributes to both collapse of myocardial structure and cardiac dysfunction, which ultimately leads to diabetic cardiomyopathy. The pathogenesis of diabetic cardiomyopathy is multifactorial, including inflammatory cascade activation, oxidative/nitrative stress, and the following impaired Ca2+ handling induced by insulin resistance/hyperinsulinemia, hyperglycemia, hyperlipidemia in diabetes. Some key alterations of cellular signaling network, such as translocation of CD36 to sarcolemma, activation of NLRP3 inflammasome, up-regulation of AGE/RAGE system, and disequilibrium of micro-RNA, mediate diabetic oxidative stress/inflammation related myocardial remodeling and ventricular dysfunction in the context of glucose and lipid metabolic disturbance. Here, we summarized the detailed oxidative stress/inflammation network by which the abnormality of glucose and lipid metabolism facilitates diabetic cardiomyopathy.

RNA sequencing profiling of mRNAs, long noncoding RNAs, and circular RNAs in Trigeminal Ganglion following Temporomandibular Joint inflammation.

Patients with temporomandibular joint disorders (TMD) have high levels of inflammatory pain-related disability, which seriously affects their physical and mental health. However, an effective treatment is yet to be developed. Both circular RNAs (circRNAs) and long noncoding RNAs (lncRNAs) contribute to regulating pain conduction. In our current study, we report the expression profiles of circRNAs, lncRNAs, and mRNAs in the trigeminal ganglion (TG) associated with complete Freund's adjuvant (CFA)-induced TMD inflammation pain. The collected TGs from the experimental (CFA) and control (saline) groups were processed for deep RNA sequencing. Overall, 1078,909,068 clean reads were obtained. A total of 15,657 novel lncRNAs were identified, where 281 lncRNAs were differentially expressed on CFA3D and 350 lncRNAs were differentially expressed on CFA6D. In addition, a total of 55,441 mRNAs and 27,805 circRNAs were identified, where 3,914 mRNAs and 91 circRNAs were found differentially expressed, between the CFA3D and saline groups, while 4,232 mRNAs and 98 DE circRNAs were differentially expressed between the CFA6D and saline groups. Based on functional analyses, we found that the most significant enriched biological processes of the upregulated mRNAs were involved in the immunity, neuron projection, inflammatory response, MAPK signaling pathway, Ras signaling pathway, chemokine signaling pathway, and inflammatory response in TG. Further analyses of Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes pathway suggest the involvement of dysregulated genes in the pain occurrence mechanism. Our findings provide a resource for expression patterns of gene transcripts in regions related to pain. These results suggest that apoptosis and neuroinflammation are important pathogenic mechanisms underlying TMD pain. Some of the reported differentially expressed genes might be considered promising therapeutic targets. The current research study revealed the expression profiles of circRNAs, lncRNAs, and mRNAs during TMD inflammation pain and sheds light on the roles of circRNAs and lncRNAs underlying the pain pathway in the trigeminal system of TMD inflammation pain.

Metal-Organic Framework with Structural Flexibility Responding Specifically to Acetylene and Its Adsorption Behavior.

Flexible metal-organic frameworks (MOFs) are one kind of stimuli-responsive materials that exhibit reversible structural transformations in response to external stimuli. Exploring and understanding the stimuli response behavior of flexible MOFs is challenging, as it involves weak host-guest interaction. We report here the unique flexibility of MOF Zn(int)(Ad) (TIF-A1, Hint = isonicotinic acid, Had = adenine) induced by acetylene adsorption. TIF-A1 is rigid toward most gas molecules, while only C2H2 can induce the flexibility of TIF-A1. C2H2-loaded TIF-A1 is characterized by single-crystal X-ray diffraction and molecular modeling. It is revealed that the flexibility of TIF-A1 originates from the strong interaction between acetylene and the framework, which pushes the rotation of the int ligand and the expansion of the framework simultaneously. This work is helpful in deeply understanding the flexibility of MOFs and guides exploring new flexible MOFs in the future.

Percutaneous Intramyocardial Septal Radiofrequency Ablation in Patients With Drug-Refractory Hypertrophic Obstructive Cardiomyopathy.

Importance: Patients with hypertrophic obstructive cardiomyopathy (HOCM) and drug-refractory symptoms and outflow gradients have limited nonsurgical treatment options. The feasibility of percutaneous intramyocardial septal radiofrequency ablation (PIMSRA) has been reported previously; however, procedural and medium-term outcomes are unknown. Objective: To describe the safety and medium-term outcomes of PIMSRA in a large patient cohort with drug-refractory HOCM. Design, Setting, and Participants: This was a single-arm, open-label study of PIMSRA in patients with drug-refractory HOCM. Patients presenting to the Xijing Hospital in Xi'an, China, between October 2016 to June 2020 with hypertrophic cardiomyopathy. Of 1314 patients presenting with HOCM, 244 fulfilled inclusion criteria of severe resting/provoked outflow gradients of 50 mm Hg or higher, and symptoms of New York Heart Association functional class of II or higher refractory to maximum tolerated medications. After discussion among the heart team, 40 patients underwent surgical or alcohol septal reduction therapy and 4 required treatment of significant coronary artery disease. Interventions: PIMSRA performed in patients. Main Outcomes and Measures: The primary outcome was 30-day major adverse clinical events: death, emergency surgery, severe effusion requiring intervention, procedure-related stroke, bleeding, and stroke. Secondary outcomes included 30-day technical success and 90-day improvement in outflow obstruction. Results: The mean (SD) age of 200 patients was 46.9 (14.0) years, and 125 (62.5%) were men. Resting or provoked left ventricular outflow tract gradients were 50 mm Hg or higher. The median (IQR) follow-up for all patients was 19 (6-50) months. Thirty-day major adverse clinical events rate was 10.5% (n = 21): there were 2 in-hospital/30-day deaths (1.0%), 7 patients (3.5%) with pericardial effusion requiring mini-thoracotomy, 12 patients (6%) with pericardial effusion requiring pericardiocentesis, and no bleeding or strokes. Other periprocedural complications included permanent right bundle branch block in 5 patients (2.5%), resuscitated ventricular fibrillation in 2 (1.0%), and septal branch aneurysm in 2 (1.0%). There were no permanent pacemaker implantations. At follow-up, maximum septal thickness was reduced from a mean (SD) of 24.0 (5.1) mm to 17.3 (4.4) mm (P < .001), and left ventricular outflow tract gradient was decreased from a mean (SD) of 79.0 (53.0) mm Hg to 14.0 (24.0) mm Hg (P < .001). Overall, 190 patients (96%) with HOCM were in New York Heart Association functional class I or II at last follow-up. Conclusions and Relevance: This study found that PIMSRA in patients with drug-refractory HOCM may be an effective procedure for relief of left ventricular outflow tract obstruction and symptoms with acceptable complication rates. These results are encouraging and support the design of a randomized clinical trial against well-established septal reduction therapies.

USP18-deficiency in cervical carcinoma is crucial for the malignant behavior of tumor cells in an ERK signal-dependent manner.

Ubiquitin-specific peptidase (USP)18 belongs to the USP family, and is involved in cleaving and removing ubiquitin or ubiquitin-like molecules from their target molecules. Recently, increasing evidence has suggested that USP18 is constitutively expressed in different types of human tumors, and ectopic expression or downregulation of USP18 expression may contribute to tumorigenesis. However, the role of USP18 in uterine cervical cancer (UCC) remains unclear. Thus, the present study aimed to investigate USP18 expression in a human tissue microarray constructed using UCC and non-cancer cervical tissues, and to determine the potential role and molecular mechanism by which USP18 is implicated in the tumor biology of human UCC HeLa cells. Microarray analysis demonstrated that USP18 protein expression was downregulated in tumor tissues compared with in normal tissues. In addition, in vitro analysis revealed that USP18-knockdown markedly promoted the proliferation, colony formation, migration and aggressiveness of HeLa cells. Mechanistic analysis demonstrated that USP18-knockdown increased the levels of Bcl-2, STAT3 and phosphorylated-ERK in HeLa cells. Notably, USP18 silencing-induced malignant phenotypes were interrupted following exogenous administration of the ERK1/2 inhibitor PD98059. Overall, the results of the present study suggested that USP18 may be a potent inhibitor involved in UCC tumor-associated biological behaviors, which are associated with the ERK signaling pathway.

Up-regulation of CXCL8 expression is associated with a poor prognosis and enhances tumor cell malignant behaviors in liver cancer.

CXCL8, a member of CXC chemokines, was constitutively expressed in many types of human cancers, and its overexpression has been shown to play a critical role in promoting tumorigenesis. The purpose of the present study was to determine CXCL8 expression in a commercial human liver tissue microarray, and elucidate the effects and underlying mechanisms by which CXCL8 is involved in the malignant progression of human liver cancer. Our data showed that high level expression of CXCL8 in tissues with liver cancer was identified as compared with non-cancer tissues, and its up-regulation was closely associated with clinical stage and tumor infiltration. In vitro, exogenous CXCL8 at concentrations of 10, 20 or 40 ng/ml obviously stimulated the proliferation abilities of HepG2 cells. Coupled with this, 10, 20 or 40 ng/ml of exogenous CXCL8 also triggered a significant elevation in HepG2 cells migration. Additionally, overexpression of CXCL8 in HepG2 cells also resulted in increased cell proliferation and migration capacities. Finally, Western blotting analysis showed that overexpression of CXCL8 increased the expression of ERK, p-ERK and survivin, decreased the expression of caspase-3 and BAX at protein level.

A taxonomic study of the genus Macromotettixoides (Tetrigidae, Metrodorinae) with descriptions of two new species and two newly discovered males.

Fifteen species of Macromotettixoides are systematically researched in this paper. Two new species (M. tuberculata Mao, Li Han, sp. n. and M. truncata Mao, Li Han, sp. n.) and two newly discovered males (M. curvimarginus (Zheng Xu) and M. longling Deng) are introduced with descriptions and illustrations. An updated identification key to all known species of the genus is given.

Comparative analysis of the effect of protein Z4 from barley malt and recombinant Pichia pastoris on beer foam stability: Role of N-glycosylation and glycation.

This study aimed to elaborate the effect of N-glycosylation and glycation of protein Z4 from barley malt and recombinant Pichia pastoris on beer foam stability. The malt protein Z4 and recombinant protein Z4 showed similar N-glycosylation patterns while recombinant protein Z4 was glycosylated at a higher degree. In the simulated mashing and boiling, malt protein Z4 and deglycosylated malt protein Z4 preferred to glycate with glucose and maltose while recombinant protein Z4 and deglycosylated recombinant protein Z4 showed preference towards fructose. The addition of protein Z4 and protein Z4-saccharide complexes in finished beer showed that the addition of glycosylated protein Z4 only slightly enhanced the beer foam stability while the addition of glycated protein Z4 and protein Z4 with both glycation and glycosylation could significantly increase the beer foam stability. Therefore, glycation instead of N-glycosylation of protein Z4 played important roles in maintaining beer foam stability.