Circ_0000877 accelerates proliferation and immune escape of non-small cell lung cancer cells by regulating microRNA-637/E2F2 axis.

BACKGROUND: Recently, circular RNA (circRNA) has become a vital targeted therapy gene for non-small-cell lung cancer (NSCLC) cells. CircRNA_0000877 (Circ_0000877) has been researched in diffuse large B-cell lymphoma (DLBCL). However, whether circ_0000877 regulated NSCLC cell progression is still poorly investigated. The research attempted to investigate the influence of circ_0000877 in NSCLC. METHODS: Circ_0000877 levels in NSCLC tissues and cell lines were determined applying RT-qPCR. Cell functions were evaluated by CCK-8, EdU, flow cytometry, ELISA, and western blot. Gene interactions were predicted by Cirular RNA interactome database and Target Scan website and certified by dual-luciferase reporter, RIP, and RNA pull-down assays. Finally, mice experimental model was established to explore the effects of circ_0000877 on tumor growth in vivo. RESULTS: The elevated trend of circ_0000877 expression was discovered in NSCLC tissues compared to para-carcinoma tissues. The clinicopathological data uncovered that up-regulated circ_0000877 was linked to tumor size, differentiation, and TNM stages of NSCLC patients. Knockdown of circ_0000877 inhibited the proliferation, triggered apoptosis, and prohibited immune escape in NSCLC cells. It was certified that miR-637 was directly interacted with circ_0000877 and targeted by E2F2. Overexpressed E2F2 strongly overturned the functions of circ_0000877 knockdown in NSCLC cells. Mice experimental data demonstrated that circ_0000877 knockdown suppressed tumor growth in vivo. CONCLUSION: The research demonstrated that circ_0000877 exhibited the promotive effect on NSCLC cells proliferation and immune escape by regulating miR-637/E2F2 axis.

Eosinophils in patients with lone atrial fibrillation.

BACKGROUND: Inflammation has been evidenced as a critical contributable mechanism for the atrial fibrillation (AF) onset and development. As the consistent inflammatory and oxidative marker, the effects of white blood cell (WBC) and its differential on lone atrial fibrillation (LAF) were investigated in the study. METHODS: A total of 126 patients with paroxysmal LAF who scheduled for rhythm control drug therapy and 120 age- and gender-matched subjects in sinus rhythm were included sequentially. Peripheral blood sample and clinic data were collected during the first evaluation. Recurrence of AF was evaluated by outpatient clinics and telephone visits for the following 12 months. RESULTS: Peripheral eosinophil count, neutrophil count, and left atrial diameter (LAD) were significantly higher in LAF than control. Within a follow-up of 12 months, 56 patients (44.4%) had developed AF recurrence. Patients with AF recurrence had higher eosinophil count and LAD. Univariable analyses showed a statistically significant relationship between eosinophil count (P = 0.042), LAD (P = 0.030), and AF recurrence. Multivariate logistic regression analysis showed that LAD (OR: 1.090 per 1 mm increase; 95% CI: 1.007-1.180; P = 0.032) and eosinophil (OR: 1.643 per 1 × 108 /L increase; 95% CI: 1.047-2.578; P = 0.031) were independent predictors of AF recurrence during antiarrhythmic drug therapy. CONCLUSION: Our results support the association of the WBC response and its components with the LAF. Especially, the peripheral eosinophil and LAD may play important roles in mediating inflammation and atrial remodeling in AF.

Possible involvement of fibrocytes in atrial fibrosis in patients with chronic atrial fibrillation.

BACKGROUND: Chronic atrial fibrillation (AF) is characterized by a remodeling process with prominent atrial fibrosis. Fibrocytes, a bone marrow-derived population of fibroblast-like cells, have been placed at the center of a number of fibrosing conditions. The purpose of this study was to evaluate the contribution of fibrocytes to atrial fibrosis in patients with chronic AF and the possible mechanisms. METHODS AND RESULTS: We enrolled 22 consecutive valvular heart disease patients with chronic AF (>6 months: CAF group) and 15 valvular heart disease patients in sinus rhythm served as controls (SR group). Left atrial tissue samples were obtained during cardiac surgery. The infiltration of fibrocytes into the atrial interstitium was observed by confocal microscopy. The number of atrial fibrocytes was approximately three-fold higher in the CAF group compared with the SR controls, and positively correlated with both the atrial collagen volume fraction (r=0.713; P=0.0002) and the left atrial volume index (r=0.631; P=0.002). In the peripheral blood samples collected before the operation, approximately 2.5-fold higher percentage of circulating fibrocytes was identified in the CAF group. These fibrocytes showed a stronger proliferative capacity (≍2.5-fold) and higher level expression of collagen I and α-SMA (≍2-fold and 4-fold, respectively) compared with the SR controls. CONCLUSIONS: The results suggested that fibrocytes may be involved in atrial fibrosis in chronic AF through enhanced profibrotic characteristics.

Efficacy and tolerability of adding coenzyme A 400 U/d capsule to stable statin therapy for the treatment of patients with mixed dyslipidemia: an 8-week, multicenter, double-blind, randomized, placebo-controlled study.

BACKGROUND: Patients with mixed hyperlipidemia usually are in need of combination therapy to achieve low-density lipoprotein cholesterol (LDL-C) and triglyceride (TG) target values for reduction of cardiovascular risk. This study investigated the efficacy and safety of adding a new hypolipidemic agent, coenzyme A (CoA) to stable statin therapy in patients with mixed hyperlipidemia. METHODS: In this multi-center, 8-week, double-blind study, adults who had received ≥8 weeks of stable statin therapy and had hypertriglyceridemia (TG level at 2.3-6.5 mmol/L) were randomized to receive CoA 400 U/d or placebo plus stable dosage of statin. Efficacy was assessed by the changes in the levels and patterns of lipoproteins. Tolerability was assessed by the incidence and severity of adverse events (AEs). RESULTS: A total of 304 patients with mixed hyperlipidemia were randomized to receive CoA 400 U/d plus statin or placebo plus statin (n = 152, each group). After treatment for 8 weeks, the mean percent change in TG was significantly greater with CoA plus statin compared with placebo plus statin (-25.9% vs -4.9%, respectively; p = 0.0003). CoA plus statin was associated with significant reductions in TC (-9.1% vs -3.1%; p = 0.0033), LDL-C (-9.9% vs 0.1%; p = 0.003), and non- high-density lipoprotein cholesterol (-13.5% vs -5.7%; p = 0.0039). There was no significant difference in the frequency of AEs between groups. No serious AEs were considered treatment related. CONCLUSIONS: In these adult patients with persistent hypertriglyceridemia, CoA plus statin therapy improved TG and other lipoprotein parameters to a greater extent than statin alone and has no obviously adverse effect. TRIAL REGISTRATION: Current Controlled Trials ClinicalTrials.gov ID NCT01928342.

Effects of a mindfulness-based interventions on stress, burnout in nurses: a systematic review and meta-analysis.

Background: Stress in the healthcare environment causes negative effects in nurses such as burnout, anxiety, and depression. The COVID-19 pandemic has resulted in increased pressure on medical staff globally, highlighting the potential benefits of mindfulness-based interventions in reducing nurses' stress levels. Despite numerous studies exploring the effect of mindfulness-based training on nurses, the results remain inconclusive. Objective: To systematically evaluate the impact of mindfulness training on nurse's performance and increase the certainty of existing evidence. Methods: This study searched various databases, including EBSCO, Embase, Web of Science, PubMed, ProQuest, Scopus, Cochrane Online Library, Wanfang, SinoMed, CNKI, and VIP, for randomized controlled trials on the impact of mindfulness-based interventions for nurses up until 02 December 2022. Two investigators independently screened and extracted data from the articles, while also assessing the risk of bias. The data was analyzed using RevMan 5.4 software. Results: This review identified 15 studies out of the 2,171 records retrieved, consisting of a total of 1,165 participants who were randomized. Post-intervention analysis provided very-low certainty evidence of moderate effectiveness of mindfulness-based training in reducing stress [standardized mean difference (SMD) = -0.81; 95% confidence interval (CI) = -1.11 to -0.52], with no significant effect on anxiety (SMD = -0.30; 95% CI = -0.72 to 0.13) or depression (SMD = -0.24; 95% CI = -0.55 to 0.07). However, the training was effective in reducing burnout, as demonstrated by the lower scores for emotional exhaustion (SMD = -4.27; 95% CI = -5.94 to -2.59) and depersonalization (SMD = -2.89; 95% CI = -4.24 to -1.54) and higher scores for personal accomplishment (SMD = 2.81; 95% CI = 0.12 to 5.50). There was a sustained improvement in stress levels in the short-term (≤3 months), with delayed benefits for burnout. However, only two studies were available for later follow-ups, and there was no significant evidence of long-term effects. Conclusion: Mindfulness-based training may be a viable intervention for improving the psychological wellbeing of nurses, including reducing stress, burnout. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023387081.

The genomic landscape of sensitivity to arsenic trioxide uncovered by genome-wide CRISPR-Cas9 screening.

Introduction: Arsenic trioxide (ATO) is a promising anticancer drug for hematological malignancy. Given the dramatic efficacy of acute promyelocytic leukemia (APL), ATO has been utilized in other types of cancers, including solid tumors. Unfortunately, the results were not comparable with the effects on APL, and the resistance mechanism has not been clarified yet. This study intends to identify relevant genes and pathways affecting ATO drug sensitivity through genome-wide CRISPR-Cas9 knockdown screening to provide a panoramic view for further study of ATO targets and improved clinical outcomes. Methods: A genome-wide CRISPR-Cas9 knockdown screening system was constructed for ATO screening. The screening results were processed with MAGeCK, and the results were subjected to pathway enrichment analysis using WebGestalt and KOBAS. We also performed protein-protein interaction (PPI) network analysis using String and Cytoscape, followed by expression profiling and survival curve analysis of critical genes. Virtual screening was used to recognize drugs that may interact with the hub gene. Results: We applied enrichment analysis and identified vital ATO-related pathways such as metabolism, chemokines and cytokines production and signaling, and immune system responses. In addition, we identified KEAP1 as the top gene relating to ATO resistance. We found that KEAP1 expression was higher in the pan-cancer, including ALL, than in normal tissue. Patients with acute myeloid leukemia (AML) with higher KEAP1 expression had worse overall survival (OS). A virtual screen showed that etoposide and eltrombopag could bind to KEAP1 and potentially interact with ATO. Discussion: ATO is a multi-target anticancer drug, and the key pathways regulating its sensitivity include oxidative stress, metabolism, chemokines and cytokines, and the immune system. KEAP1 is the most critical gene regulating ATO drug sensitivity, which is related to AML prognosis and may bind to some clinical drugs leading to an interaction with ATO. These integrated results provided new insights into the pharmacological mechanism of ATO and potentiate for further applications in cancer treatments.

Curcumin Induces Ferroptosis in Follicular Thyroid Cancer by Upregulating HO-1 Expression.

Follicular thyroid cancer (FTC) is a highly aggressive type of endocrine malignancy. It is necessary to investigate the mechanisms of tumorigenesis and therapeutic pathways in patients with FTC. Haem oxygenase-1 (HO-1) can regulate oxidative stress and the occurrence of tumors and diseases. In this study, we discovered that HO-1 was abnormally overexpressed in FTC compared with adjacent tissues. However, the HO-1 overexpression was demonstrated to decrease cell viability and to potentially activate the ferroptosis signalling pathway. Ferroptosis is a newly identified form of oxidative cell death and is currently being targeted as a new cancer treatment. Tumorigenesis is significantly inhibited by curcumin. The present study shows that curcumin inhibits the growth of FTC by increasing the HO-1 expression, further activating the ferroptosis pathway. This study demonstrates that the HO-1-ferroptosis signalling pathway might play an important role in FTC tumorigenesis, and that curcumin inhibits the growth of FTC cells by affecting this pathway.

QCR7 affects the virulence of Candida albicans and the uptake of multiple carbon sources present in different host niches.

Background: Candida albicans is a commensal yeast that may cause life-threatening infections. Studies have shown that the cytochrome b-c1 complex subunit 7 gene (QCR7) of C. albicans encodes a protein that forms a component of the mitochondrial electron transport chain complex III, making it an important target for studying the virulence of this yeast. However, to the best of our knowledge, the functions of QCR7 have not yet been characterized. Methods: A QCR7 knockout strain was constructed using SN152, and BALb/c mice were used as model animals to determine the role of QCR7 in the virulence of C. albicans. Subsequently, the effects of QCR7 on mitochondrial functions and use of carbon sources were investigated. Next, its mutant biofilm formation and hyphal growth maintenance were compared with those of the wild type. Furthermore, the transcriptome of the qcr7Δ/Δ mutant was compared with that of the WT strain to explore pathogenic mechanisms. Results: Defective QCR7 reduced recruitment of inflammatory cells and attenuated the virulence of C. albicans infection in vivo. Furthermore, the mutant influenced the use of multiple alternative carbon sources that exist in several host niches (GlcNAc, lactic acid, and amino acid, etc.). Moreover, it led to mitochondrial dysfunction. Furthermore, the QCR7 knockout strain showed defects in biofilm formation or the maintenance of filamentous growth. The overexpression of cell-surface-associated genes (HWP1, YWP1, XOG1, and SAP6) can restore defective virulence phenotypes and the carbon-source utilization of qcr7Δ/Δ. Conclusion: This study provides new insights into the mitochondria-based metabolism of C. albicans, accounting for its virulence and the use of variable carbon sources that promote C. albicans to colonize host niches.

Low molecular weight heparin inhibits circulating fibrocytes differentiation by modulating neuronal nitric oxide synthase and TGF-ß1/Smad pathway.

BACKGROUND/AIMS: Circulating fibrocytes (CFs) have been placed at the center of a number of fibrosing conditions. Recently, attention has been drawn to the non-anticoagulant activities of low molecular weight heparin (LH), especially its anti-fibrotic effects. The purpose of this study was to investigate the effects of LH on CFs differentiation and possible underlying mechanisms. METHODS/RESULTS: CFs were cultured from human peripheral blood mononuclear cells and identified by dual-immunofluorescence staining. Incubation with LH inhibited CFs trans-differentiation by upregulating CD34 and downregulating pro-Collagen I and a-SMA in a concentration- and time-dependent manner, all of which were detected by flow cytometry. Similar effects were observed after incubation with L-NAME, an inhibitor of NOS. NO production was measured by Griess methods and markedly decreased in CFs treated with LH. Three NOS isoforms were assessed by western blot and nNOS was the predominant isoform involved in this process. Additionally, LH and L-NAME had similar down-regulating effects on the expression of TGF-ß1 and pSmad2/3, which indicated that TGF-ß/Smad pathway might be a downstream signaling of nNOS/NO during LH treatment. CONCLUSION: These results suggested that LH could exhibit anti-fibrotic effects by inhibiting CFs transdifferentiation, in which the involvement of nNOS/NO and TGF-ß/Smad pathway were identified.

The application of genome-wide CRISPR-Cas9 screens to dissect the molecular mechanisms of toxins.

Many toxins are life-threatening to both animals and humans. However, specific antidotes are not available for most of those toxins. The molecular mechanisms underlying the toxicology of well-known toxins are not yet fully characterized. Recently, the advance in CRISPR-Cas9 technologies has greatly accelerated the process of revealing the toxic mechanisms of some common toxins on hosts from a genome-wide perspective. The high-throughput CRISPR screen has made it feasible to untangle complicated interactions between a particular toxin and its corresponding targeting tissue(s). In this review, we present an overview of recent advances in molecular dissection of toxins' cytotoxicity by using genome-wide CRISPR screens, summarize the components essential for toxin-specific CRISPR screens, and propose new strategies for future research.

Molecular Epidemiology, Antifungal Susceptibility, and Virulence Evaluation of Candida Isolates Causing Invasive Infection in a Tertiary Care Teaching Hospital.

Background: The incidence of invasive candidiasis is increasing worldwide. However, the epidemiology, antifungal susceptibility, and virulence of Candida spp. in most hospitals remain unclear. This study aimed to evaluate invasive candidiasis in a tertiary care hospital in Nanchang City, China. Methods: MALDI-TOF MS and 18S rDNA ITS sequencing were used to identify Candida strains. Randomly amplified polymorphic DNA analysis was used for molecular typing; biofilm production, caseinase, and hemolysin activities were used to evaluate virulence. The Sensititre™ YeastOne YO10 panel was used to examine antifungal susceptibility. Mutations in ERG11 and the hotspot regions of FKS1 of drug-resistant strains were sequenced to evaluate the possible mechanisms of antifungal resistance. Results: We obtained 110 Candida strains, which included 40 Candida albicans (36.36%), 37 C. parapsilosis (33.64%), 21 C. tropicalis (19.09%), 9 C. glabrata (8.18%), 2 C. rugose (1.82%), and 1 C. haemulonii (0.91%) isolates. At a limiting point of 0.80, C. albicans isolates could be grouped into five clusters, C. parapsilosis and C. tropicalis isolates into seven clusters, and C. glabrata isolates into only one cluster comprising six strains by RAPD typing. Antifungal susceptibility testing revealed that the isolates showed the greatest overall resistance against fluconazole (6.36%), followed by voriconazole (4.55%). All C. albicans and C. parapsilosis isolates exhibited 100% susceptibility to echinocandins (i.e., anidulafungin, caspofungin, and micafungin), whereas one C. glabrata strain was resistant to echinocandins. The most common amino acid substitutions noted in our study was 132aa (Y132H, Y132F) in the azole-resistant strains. No missense mutation was identified in the hotpot regions of FKS1. Comparison of the selected virulence factors detectable in a laboratory environment, such as biofilm, caseinase, and hemolysin production, revealed that most Candida isolates were caseinase and hemolysin producers with a strong activity (Pz < 0.69). Furthermore, C. parapsilosis had greater total biofilm biomass (average Abs620 = 0.712) than C. albicans (average Abs620 = 0.214, p < 0.01) or C. tropicalis (average Abs620 = 0.450, p < 0.05), although all C. glabrata strains were either low- or no-biofilm producers. The virulence level of the isolates from different specimen sources or clusters showed no obvious correlation. Interesting, 75% of the C. albicans from cluster F demonstrated azole resistance, whereas two azole-resistant C. tropicalis strains belonged to the cluster Y. Conclusion: This study provides vital information regarding the epidemiology, pathogenicity, and antifungal susceptibility of Candida spp. in patients admitted to Nanchang City Hospital.

Case Report and Systematic Review: Sarcomatoid Parathyroid Carcinoma-A Rare, Highly Malignant Subtype.

Background: Parathyroid carcinoma (PC) is a rare malignancy, the incidence of which is less than 1/1 million per year. Sarcomatoid parathyroid carcinoma (SaPC) is an extremely peculiar subtype; only three cases have been reported internationally. It consists of both malignant epithelial components and sarcomatoid components (mesenchymal origin) simultaneously. This "confusing" cancer exhibits higher invasiveness, and traditional surgery does not appear to achieve the expectation, which differs significantly from that of general PC. Objective: To characterize the clinicopathologic features of SaPC and explore similarities and differences between SaPC and general PC. Materials and Methods: We collected clinical data of SaPC cases from our center and literature. The SaPC case in our center was presented. To better understand the characteristics of SaPC, we also reviewed clinical information in general PC cases from our center and literature within the last 5 years, and a systematic review was performed for further comparison. Results: A 60-year-old woman was admitted for a neck mass and hoarseness. After the surgery, she was confirmed as SaPC and ultimately developed local recurrence at 3 months. Together with the reported cases from literature, four cases of SaPC (three cases from literature) and 203 cases of general PC (200 cases from literature) were reviewed. Both tumors showed obvious abnormalities in parathormone (PTH) level and gland size. Compared to general PC, SaPC has a later age of onset (60.50 ± 7.42 vs. 51.50 ± 8.29), relatively low levels of PTH (110.28 ± 59.32 vs. 1,156.07 ± 858.18), and a larger tumor size (6.00 ± 1.63 vs. 3.14 ± 0.70). For SaPC, all four cases were initially misdiagnosed as thyroid tumors (4/4). Spindle cell areas or transitional zones were common pathological features in SaPC cases (3/4). Conclusion: SaPC is a very rare pathologic subtype of PC and appears to be much more easily misdiagnosed as a thyroid tumor. Spindle cell areas or transitional zones are highly possible to be pathological features in its sarcomatoid components. Despite many similarities, there are some differences between SaPC and general PC-SaPC does not show the obvious endocrine feature but stronger aggressiveness. Surgical treatment of SaPC does relieve life-threatening symptoms and improve quality of life even with recurrence in the short term.

Systemic evaluation of platelet and leukocyte activation and interaction in a rat model of pulmonary arterial hypertension.

OBJECTIVES: Thrombosis and inflammation are associated with the pathogenesis of pulmonary arterial hypertension (PAH). However, there are no solid data supporting the involvement of platelet and leukocyte activation and interaction in PAH. The present study thus investigated the activation and interaction of circulating platelets and leukocytes in a rat model of monocrotaline (MCT)-induced pulmonary hypertension. METHODS: Mean pulmonary arterial pressure (mPAP) was monitored in rats (n = 24) before and 2, 3 and 7 weeks after MCT (60 mg/kg)injection. In parallel, activation of circulating platelets and leukocytes and platelet-leukocyte aggregates were measured by whole-blood flow cytometry. RESULTS: Two weeks after MCT injection, mPAP had increased significantly, i.e. from 11.25 ± 0.92 mm Hg at baseline to 15.71 ± 1.66 mm Hg (p < 0.05), and it had increased even further at week 7 (26.83 ± 3.29 mm Hg; p < 0.01). Fibrinogen binding of circulating platelets had increased from the basal level of 1.45 ± 0.61 to 4.08 ± 1.59% 3 weeks after MCT injection (p < 0.01). Platelet responsiveness to ADP was also significantly enhanced. CD11b expression of circulating neutrophils was elevated; i.e. mean fluorescence intensity increased from 1.67 ± 0.38 before MCT injection to 2.37 ± 0.31 3 weeks after MCT injection (p < 0.01), and N-formyl-methionyl-leucyl-phenylalanine (1 × 10⁻7M) stimulation induced more marked elevation of neutrophil CD11b expression in MCT-treated animals. Circulating platelet-neutrophil aggregates were already increased 2 weeks after MCT treatment (14.93 ± 4.22%; p < 0.01) compared to baseline (6.01 ± 2.91%) and remained elevated at 3 weeks (15.19 ± 4.78%; p < 0.01). CONCLUSIONS: MCT-induced PAH in rats is associated with increased platelet and leukocyte activation and platelet-leukocyte interaction in vivo, which may play an important role in the pathogenesis of PAH.

Effects of Losartan on expression of connexins at the early stage of atherosclerosis in rabbits.

AIM: to investigate effects of Losartan on expression of connexin 40 and 43 (Cx40 and Cx43), in arteries at the early stage of atherosclerosis in a rabbit model. METHODS: A total of 28 male New Zealand white rabbits were divided into following groups: control group, high fat diet group, and Losartan group (10 mg/kg/day). Losartan was administrated in food for two weeks. Iliac arteries were obtained for immunohistochemistry, transmission electron microscopy, Western blot, and reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS: Transmission electron microscopy revealed abundant gap junctions between neointimal smooth muscle cells (SMCs), which were markedly reduced by treatment. RT-PCR and Western blot assay showed that the mRNA and protein expression of Cx40 and Cx43 were elevated in the neointimal area at the early stage of atherosclerosis. The mRNA and protein expression of Cx43 were significantly down-regulated by losartan treatment but those of Cx40 were not markedly changed. CONCLUSION: Cx40 and Cx43 in the neointimal SMCs were up-regulated at the early stage of atherosclerosis. Losartan (an angiotensin-converting enzyme inhibitor) could reduce neointima proliferation and down-regulate the elevated protein expression of Cx43, suggesting the rennin-angiotensin system (RAS) plays an important role in the remodeling of gap junction between ventricular myocytes under pathological conditions.

Protein Acetylation/Deacetylation: A Potential Strategy for Fungal Infection Control.

Protein acetylation is a universal post-translational modification that fine-tunes the major cellular processes of many life forms. Although the mechanisms regulating protein acetylation have not been fully elucidated, this modification is finely tuned by both enzymatic and non-enzymatic mechanisms. Protein deacetylation is the reverse process of acetylation and is mediated by deacetylases. Together, protein acetylation and deacetylation constitute a reversible regulatory protein acetylation network. The recent application of mass spectrometry-based proteomics has led to accumulating evidence indicating that reversible protein acetylation may be related to fungal virulence because a substantial amount of virulence factors are acetylated. Additionally, the relationship between protein acetylation/deacetylation and fungal drug resistance has also been proven and the potential of deacetylase inhibitors as an anti-infective treatment has attracted attention. This review aimed to summarize the research progress in understanding fungal protein acetylation/deacetylation and discuss the mechanism of its mediation in fungal virulence, providing novel targets for the treatment of fungal infection.

Morphological and molecular identification of four new resupinate species of Lyomyces (Hymenochaetales) from southern China.

Four new wood-inhabiting fungal species, Lyomyces bambusinus, L. cremeus, L. macrosporus and L. wuliangshanensis, are proposed based on a combination of morphological and molecular evidence. Lyomyces bambusinus is characterized by resupinate basidiomata with colliculose to tuberculate hymenial surface and broadly ellipsoid, hyaline, slightly thick-walled, smooth basidiospores. Lyomyces cremeus is characterised by resupinate basidiomata with smooth, cream hymenial surface and ellipsoid, hyaline, thin-walled to slightly thick-walled basidiospores. Lyomyces macrosporus is characterized by pruinose basidiomata with reticulate hymenial surface, presence of three kinds of cystidia and larger basidiospores (6.7-8.9 × 4.4-5.4 µm). Lyomyces wuliangshanensis is characterized by coriaceous basidiomata and ellipsoid, hyaline, slightly thick-walled, smooth basidiospores. The phylogenetic analyses based on molecular data of the internal transcribed spacer (ITS) region sequences revealed that the four new species belonged to Lyomyces. Lyomyces bambusinus grouped with L. sambuci. Lyomyces cremeus clade was sister to a clade comprised of L. microfasciculatus. Lyomyces macrosporus was sister to L. allantosporus. Lyomyces wuliangshanensis was closely related to L. mascarensis.

Protective effect of citicoline on random flap survival in a rat mode.

BACKGROUND: Medical therapy for flap survival has been extensively investigated. In this study, we explored the effect of citicoline (CDP-choline, CDPC), used for clinical treatment of cerebral trauma, on random skin flap survival in rats. MATERIALS AND METHODS: Sixty rats were divided into three groups: low-dose (CDPC-L), high-dose (CDPC-H), and control. The CDPC-L and CDPC-H groups were intraperitoneally injected with 100 mg/kg and 300 mg/kg CDPC every day, respectively; the control group was injected with an equivalent volume of normal saline. The survival region was assessed on the 7th day after the flap operation. The microvascular density and neutrophil density were measured by hematoxylin and eosin staining. Lead angiography was used to detect angiogenesis, and laser Doppler was used to detect blood perfusion. Expression levels of vascular endothelial growth factor (VEGF), interleukin (IL)-1ß, IL-6, tumor necrosis factor (TNF)-α, Toll-like receptor (TLR) 4, and nuclear factor kappa B (NF-κB) were detected by immunohistochemistry. Malondialdehyde and superoxide dismutase were used to determine the lipid peroxidation level. RESULTS: The average survival region of the flap was significantly larger in the CDPC-H group than in CDPC-L and control groups, with less ischemic necrosis. VEGF expression, microvascular density, angiogenesis, blood perfusion, and superoxide dismutase in the flap were higher in the CDPC-H group than in the CDPC-L and control groups. In addition, levels of neutrophil density, IL-1ß, IL-6, TNF-α, TLR4, NF-κB, and malondialdehyde decreased significantly in the CDPC-H group. CONCLUSION: High-dose CDPC injection after a random flap operation is beneficial for flap survival.

Resveratrol Inhibits the Tumorigenesis of Follicular Thyroid Cancer via ST6GAL2-Regulated Activation of the Hippo Signaling Pathway.

Follicular thyroid carcinoma (FTC) is a common endocrine malignancy with highly aggressive features. In this study, next-generation sequencing technology was used to identify aberrant expression of sialyltransferase (ST) family members in FTC. Aberrant high expression of alpha-2,6-sialyltransferase 2 (ST6GAL2) was demonstrated to promote tumorigenesis of FTC in vitro and in vivo. Furthermore, ST6GAL2 promoted tumorigenesis by inactivating the Hippo signaling pathway. Resveratrol is a native compound extracted from Vitis species, and many studies have confirmed its protective cardiovascular and antineoplastic effects. Here we found that resveratrol can inhibit the tumorigenesis of FTC by suppressing the expression of ST6GAL2, further activating the Hippo pathway. In summary, this study revealed the role of the ST6GAL2-Hippo signaling pathway in FTC tumorigenesis and indicated that resveratrol, a commonly found antineoplastic compound, could inhibit tumorigenesis of FTC by regulating the abovementioned pathways.

Impairment of monocyte-derived dendritic cells in idiopathic pulmonary arterial hypertension.

BACKGROUND AND AIM: With the development of immunology, the role of immune inflammation in idiopathic pulmonary arterial hypertension (IPAH) has attracted interest. Recently, it was discovered that dendritic cells, which are key players in immune inflammation, are implicated in the pathogenesis of IPAH. To elucidate the role of dendritic cells in human IPAH, we compared the changes in the number and immunological function of monocyte-derived dendritic cells (MoDCs) from the peripheral blood of patients with IPAH and healthy controls. METHODS: The numbers of MoDC subsets (including plasmacytoid dendritic cells (pDCs) and myeloid dendritic cells (mDCs)) in circulating peripheral blood mononuclear cells (PBMCs) was analyzed by flow cytometry, and the concentrations of interleukin (IL)-12, IL-10, and tumor necrosis factor-alpha were measured by enzyme-linked immunosorbent serologic assay kits. The morphology, phenotypic expression, and the ability to stimulate T cell proliferation of MoDCs, cultured from PBMCs in vitro with granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-4, was analyzed by microscopy, flow cytometry, and MTT assay. RESULTS: The results of the study are as follows: (1) The number of circulating mDCs was lower in IPAH patients than in controls (0.07 +/- 0.01% to 0.14 +/- 0.02%; p < 0.05). (2) IL-12 levels were higher in IPAH patients than in controls (p < 0.05). (3) MoDCs showed higher expression of CD1a (53.34 +/- 7.43% to 19.29 +/- 7.37%; p < 0.05), and lower expression of costimulatory molecule CD86 (64.54 +/- 5.93% to 87.04 +/- 4.82%; p < 0.05), and less ability to simulate T cell proliferation (when the ratio is 1:10) compared to the controls. CONCLUSIONS: The study shows that it is possible to obtain typical DCs by culturing PBMCs from patients with IPAH with GM-CSF and IL-4, and it demonstrates that patients with IPAH have a significant change in the number of mDC and a marked immune deficiency of MoDCs.

[Clinical study of idiopathic dilated cardiomyopathy complicated by left ventricular aneurysm].

OBJECTIVE: To examine the hemodynamic and electrophysiological influence of left ventricular aneurysm (LVA) formation in patients with idiopathic dilated cardiomyopathy (IDCM). METHODS: All hospital records were retrospectively reviewed from IDCM patients admitted to our hospital between 2003 and 2008. Patients with coronary angiography evidenced ischemic cardiomyopathy were excluded. IDCM patients with LVA (I + L) diagnosed by left ventriculography were enrolled. Twelve age-, gender- and left-ventricular-diameter- matched patients with IDCM without LVA served as control group (I - L). RESULTS: Six out of 998 patients with IDCM were confirmed to have LVA (0.60%). The LV peak-systolic pressure was higher in the I + L group than in I - L group [ (130 +/- 10) mm Hg (1 mm Hg = 0.133 kPa) vs. (117 +/-9) mm Hg, P < 0.05]. The LV end-diastolic volume was significantly larger in the I + L group than in I-L group[ (272 +/- 57) ml vs. (207 +/- 60) ml, P < 0.05]. The LV ejection fraction was slightly lower in the I + L group than in I - L group [ (27 +/- 9)% vs. (35 +/- 6)%, P = 0. 09]. Ventricular arrhythmia occurred more frequently in I + L group than in I - L group. CONCLUSION: LVA formation in IDCM was a rare phenomenon. IDCM patients with LVA seem to have higher LV peak-systolic pressure, larger end-diastolic volume, worse LV systolic function and more frequent ventricular arrhythmia than those without LVA.