Visual field improvement after endoscopic transsphenoidal surgery in patients with pituitary adenoma.

Purpose: To analyze and predict the possibility of visual field (VF) recovery after endoscopic transsphenoidal surgery (ETSS) in patients with pituitary adenoma, we investigated the factors affecting the improvement of the visual field defect (VFD) and built a nomogram predictive model based on these risk factors. We further investigated specific recovery regions of VF associated with the improvement of VFD. Methods: The clinical data of patients who underwent ETSS for pituitary adenomas at a single center between the January 2021 and April 2022 were retrospectively analyzed. Univariate and multivariate analyses were used to determine the predictive factors affecting the improvement in the VF defect and specific recovery regions in patients with pituitary adenomas after ETSS. Results: We enrolled 28 patients (56 eyes) who were hospitalized at our institution. Four clinical features, including compression of the optic chiasm, preoperative mean defect (MD), diffuse defect, and duration of the visual symptom, were chosen from the least absolute shrinkage and selection operator regression analysis to establish the predictive nomogram. The nomogram's area under the curve (AUC) was 0.912, indicating a good degree of differentiation. A calibration plot was used to evaluate the predictive model's calibration, and a decision curve was used to evaluate its clinical application value. The VF defects were improved in the 270-300° range (270-300: RR = 361.00, 95% CI: 21.01-6,202.41). Conclusion: We developed a predictive nomogram model based on significant visual field improvement-associated factors after ETSS in patients with pituitary adenoma. Postoperative visual field improvement is likely to begin at 270-300° in the inferior temporal quadrant. This improvement would enable personalized counselling for individual patients by precisely predicting the visual field recovery after surgery.

Correlative factors of ocular surface lesions after allogeneic hematopoietic stem cell transplantation: A retrospective study.

Background: Ocular graft-versus-host disease (oGVHD) is one of the complications after allogeneic hematopoietic stem cell transplantation (HSCT), which impairs the quality of life and may indicate poor prognosis. In this retrospective study, the aim was to investigate the characteristics of ocular surface after HSCT, and analyze the risk factors related to the severity of ocular surface lesions. Methods: 248 post-HSCT patients were enrolled in this retrospective study. Subjects were divided into no lesion group, mild lesion group and severe lesion group, according to the severity of ocular surface lesions. The correlations between grades of ocular surface lesions and gender, age, primary disease, donor source, human leukocyte antigen (HLA) type, kinship, donor-recipient relationship, blood type, source of stem cell and systemic GVHD were analyzed. Results: The median scores of corneal epitheliopathy, lid margin lesions and meibomian gland loss were 3, 6 and 2 points, respectively. The grade of corneal epitheliopathy was related to donor source (P<0.001), kinship (P=0.033), HLA-matching (P<0.001), and systemic GVHD (P=0.007), especially oral GVHD (P<0.001) and liver GVHD (P=0.002). The grade of lid margin lesions was related to donor source (P=0.019), HLA-matching (P=0.006), and systemic GVHD (P=0.013), especially skin GVHD (P=0.019) and oral GVHD (P=0.019). The grade of meibomian gland loss was related to age (P=0.035) and gastrointestinal GVHD (P=0.007). The grade of corneal epitheliopathy after HSCT was related to the lid margin lesion score (P<0.001). Conclusions: The occurrence and development of ocular GVHD are mostly accompanied by the history of systemic GVHD. While in few cases, ocular surface lesions related to GVHD can be observed prior to the rejection of other tissues and organs. Severe corneal epitheliopathy occurs in patients with severe lid margin lesions in ocular GVHD. The lesions of corneal epithelium and lid margin are milder in HLA partially matching transplantation.

Corneal perforation associated with ocular graft-versus-host disease.

Corneal perforation is a rare and serious complication of ocular graft-versus-host disease (oGVHD) patients. This study was to retrospectively report seven corneal perforation patients after allogeneic hematopoietic stem cell transplantation (HSCT). Demographic, hematologic, and ophthalmological data of patients were clarified in detail. Nine eyes of seven corneal perforation patients were clarified (Cases 3 and 6 were bilateral and the others are unilateral). All the cases had other affected GVHD organs, especially skin involvement. The duration between HSCT and corneal perforation was usually long with 21 (17-145) months as median interval, whereas the duration between oGVHD diagnosis and corneal perforation was relatively shorter with 4 (2-81) months as median interval. Most patients presented to ophthalmology department with poor visual acuity, BUT and Schirmer's test. Eyelid marginal hyperemia and irregularity were observed in most corneal perforation eyes. Keratoplasty or conjunctival flap covering (CFC) surgeries was performed after corneal perforation. After a long-term follow-up for most patients (median 21 months, range: 2-86 months), only two eyes of two patients (22.22%) had a final BCVA of 20/100 or better. Patients involved in both cutaneous GVHD and blepharitis indicate the aggressive development of oGVHD. Early diagnosis, long-term follow-up, and effective multi-disciplinary treatments for oGVHD patients are essential. Corticosteroids and immunosuppressor remain essential, whereas the use of topical corticosteroids should be carefully considered in corneal ulceration patients. In addition, appropriate surgeries should be performed to control oGVHD development in time.

Unique Barcoded Primer-Assisted Sample-Specific Pooled Testing (Uni-Pool) for Large-Scale Screening of Viral Pathogens.

Pooled testing has been widely adopted recently to facilitate large-scale community testing during the COVID-19 pandemic. This strategy allows to collect and screen multiple specimen samples in a single test, thus immensely saving the assay time and consumable expenses. Nevertheless, when the outcome of a pooled testing is positive, it necessitates repetitive retesting steps for each sample which can pose a serious challenge during a rising infection wave of increasing prevalence. In this work, we develop a unique barcoded primer-assisted sample-specific pooled testing strategy (Uni-Pool) where the key genetic sequences of the viral pathogen in a crude sample are extracted and amplified with concurrent tagging of sample-specific identifiers. This new process improves the existing pooled testing by eliminating the need for retesting and allowing the test results-positive or negative-for all samples in the pool to be revealed by multiplex melting curve analysis right after real-time polymerase chain reaction. It significantly reduces the total assay time for large-scale screening without compromising the specificity and detection sensitivity caused by the sample dilution of pooling. Our method was able to successfully differentiate five samples, positive and negative, in one pool with negligible cross-reactivity among the positive and negative samples. A pooling of 40 simulated samples containing severe acute respiratory syndrome coronavirus-2 pseudovirus of different loads (min: 10 copies/µL; max: 103 copies/µL) spiked into artificial saliva was demonstrated in eight randomized pools. The outcome of five samples in one pool with a hypothetical infection prevalence of 15% in 40 samples was successfully tested and validated by a typical Dorman-based pooling.

Two-Dimensional Cobalt-Doped Ti3C2 MXene Nanozyme-Mediated Homogeneous Electrochemical Strategy for Pesticides Assay Based on In Situ Generation of Electroactive Substances.

Common homogeneous electrochemical (HEC) sensors usually suffer from the drawbacks of high background signal, low signal-to-noise ratio, and even false positive results due to the preaddition of electroactive substances. Thus, it is necessary to develop novel HEC sensors based on in situ generation of electroactive substances to overcome these shortcomings, which, however, is underexplored. In this work, two-dimensional (2D) nanozymes, i.e., cobalt-doped 2D Ti3C2 MXene nanosheets (CMNSs), with excellent peroxidase-like properties were utilized to develop HEC sensors based on the in situ generation of electroactive substances for organophosphate pesticides (OPs) detection. The 2D CMNSs were synthesized via a template-directed wet chemical approach and displayed outstanding features of hydrophilia and water dispersibility, which could catalyze the oxidation of o-phenylenediamine (OPD) to generate significantly increased reduction current. Interestingly, the 2D CMNSs with peroxidase-like properties exhibited a unique response to thiol compounds and were thus employed as highly efficient catalysts to develop HEC sensors for OPs based on the hydrolysis of acetylthiocholine (ATCh) to form thiocholine catalyzed by acetylcholinesterase (AChE) and the inhibition of AChE activity by OPs. The recovery for OPs analysis of pakchoi extract solutions ranged from 97.4% to 103.3%. The as-proposed HEC sensor based on in situ generation of electroactive substances will provide a new way for the development of high-performance electrochemical sensors and demonstrate potential applicability for the determination of pesticide residues in real samples.

Time- and Stimulus-Dependent Characteristics of Innate Immune Cells in Organ-Cultured Human Corneal Tissue.

PURPOSE: The pattern of immune cells infiltrating the corneal stroma has been extensively studied in mice, but data on human tissue have been far less elaborate. To further characterize the number and differentiation state of resident immune cells in organ-cultured human corneal tissue, we employed a comprehensive bioinformatic deconvolution (xCell) of bulk RNA-sequencing (RNA-seq) data, immunohistochemistry (IHC), and flow cytometry (FC). METHODS: A transcriptome-based analysis of immune cell types in human corneal samples was performed. The results were validated by IHC, focusing on the identification of pro-inflammatory (M1) and regulatory (M2) macrophages. A protocol was established to identify these 2 different macrophage populations in human corneal tissue by means of FC. Subsequently, corneal samples in organ culture were differentially stimulated by IL-10, IL-4 & IL-13, or LPS and macrophage populations were evaluated regarding their response to these stimuli. Furthermore, cell survival was analyzed in correlation with time in organ culture. RESULTS: xCell-based mathematical deconvolution of bulk RNA-seq data revealed the presence of CD8 T cells, Th17 cells, dendritic cells, and macrophages as the predominant immune cell types in organ-cultured human corneal tissue. Furthermore, RNA-seq allowed the detection of different macrophage marker genes in corneal samples, including PTPRC (CD45), ITGAM (CD11b), CD14, and CD74. Our RNA-seq data showed no evidence of a relevant presence of monocytes in human corneal tissue. The presence of different macrophage subtypes was confirmed by IHC. The disintegration and subsequent FC analysis of human corneal samples showed the presence of both M1 (HLA-DR+, CD282+, CD86+, and CD284+) and M2 (CD163+ and CD206+) macrophage subtypes. Furthermore, we found that the total number of macrophages in corneal samples decreased more than the total cell count with increasing tissue culture time. Treatment with IL-10 led to higher total cell counts per cornea and to an increased expression of the M2 marker CD163 (p < 0.05) while expression levels of various M1 macrophage markers were not significantly reduced by interleukin treatment. CONCLUSIONS: Regarding different macrophage populations, untreated human corneas showed more M1 than M2 macrophages. With increasing organ culture time, these macrophages decreased. In terms of cell dynamics, adding interleukins to the organ culture medium influenced the phenotype of macrophages within the cornea as detected by FC. Modifying the immunomodulatory properties of human grafts appears a promising approach to further reduce the risk of graft rejection in patients. In this context, treatment with interleukins was more effective in upregulating M2 macrophages than in suppressing M1 macrophages in corneal tissue.

Inhibition of Autophagy Suppresses SARS-CoV-2 Replication and Ameliorates Pneumonia in hACE2 Transgenic Mice and Xenografted Human Lung Tissues.

Autophagy is thought to be involved in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, how SARS-CoV-2 interferes with the autophagic pathway and whether autophagy contributes to virus infection in vivo is unclear. In this study, we identified SARS-CoV-2-triggered autophagy in animal models, including the long-tailed or crab-eating macaque (Macaca fascicularis), human angiotensin-converting enzyme 2 (hACE2) transgenic mice, and xenografted human lung tissues. In Vero E6 and Huh-7 cells, SARS-CoV-2 induces autophagosome formation, accompanied by consistent autophagic events, including inhibition of the Akt-mTOR pathway and activation of the ULK-1-Atg13 and VPS34-VPS15-Beclin1 complexes, but it blocks autophagosome-lysosome fusion. Modulation of autophagic elements, including the VPS34 complex and Atg14, but not Atg5, inhibits SARS-CoV-2 replication. Moreover, this study represents the first to demonstrate that the mouse bearing xenografted human lung tissue is a suitable model for SARS-CoV-2 infection and that autophagy inhibition suppresses SARS-CoV-2 replication and ameliorates virus-associated pneumonia in human lung tissues. We also observed a critical role of autophagy in SARS-CoV-2 infection in an hACE2 transgenic mouse model. This study, therefore, gives insights into the mechanisms by which SARS-CoV-2 manipulates autophagosome formation, and we suggest that autophagy-inhibiting agents might be useful as therapeutic agents against SARS-CoV-2 infection. IMPORTANCE Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused a global pandemic with limited therapeutics. Insights into the virus-host interactions contribute substantially to the development of anti-SARS-CoV-2 therapeutics. The novelty of this study is the use of a new animal model: mice xenografted with human lung tissues. Using a combination of in vitro and in vivo studies, we have obtained experimental evidence that induction of autophagy contributes to SARS-CoV-2 infection and improves our understanding of potential therapeutic targets for SARS-CoV-2.

Different Innate Immune Responses in BALB/c and C57BL/6 Strains following Corneal Transplantation.

PURPOSE: To investigate immunological differences and the role of CD38+/F4/80 + M1 macrophages in C57BL/6J- and BALB/c-recipient mouse corneal transplantation models. METHODS: Allogeneic transplantation was performed crosswise in BALB/c mice and C57BL/6J mice; syngeneic transplantation was performed in both strains. Anterior chamber depth (ACD) was measured before and central corneal thickness (CCT) was measured both before and after transplantation. In vivo graft rejection was monitored using anterior eye segment optical coherence tomography (ASOCT) evaluating the CCT and grading of corneal oedema using a well-established clinical score (CS). Histology of corneal grafts was performed 18 or 21 days after surgery. Immunohistochemistry with anti-F4/80 antibody and anti-CD38 antibody was used for detecting M1 macrophages within the grafts. RESULTS: High CS and CCT values after allogeneic transplantation persisted in both BALB/c (n = 18) and C57BL/6J recipients (n = 20). After syngeneic transplantation, CS and CCT values increased in both models in the early phase after surgery due to the surgical trauma. Surprisingly, in the syngeneic C57BL/6J model, high CCT values persisted. Furthermore, anterior synechiae developed in C57BL/6 recipients after both syngeneic and allogeneic transplantation, whereas BALB/c recipients showed almost no synechiae - even though C57/BL6J animals tended to have a deeper anterior chamber (281 ± 11 pixels [mean ± SD]) compared with BALB/c animals of the same age (270 ± 9 pixels [mean ± SD]). Immunohistochemistry revealed numerous CD38+/F4/80 + M1 macrophages in grafts of C57BL/6J recipients following both syngeneic and allogeneic transplantation. However, in BALB/c-recipient mice only sparse M1 macrophages were detectable (CD38 + M1 macrophages relative to all F4/80 + cells: 75 vs. 17% [after allogeneic transplantation] and 66 vs. 17% [after syngeneic transplantation]; p < 0.05). CONCLUSIONS: Allogeneic corneal transplants are rejected in BALB/c as well as C57BL/6J mice, but tissue alterations with anterior synechiae are more pronounced in C57BL/6J recipients. Following syngeneic transplantation, C57BL/6J-recipient animals show a persistent graft swelling with increased numbers of CD38+/F4/80 + M1 macrophages in grafted tissue, in contrast to the common model using BALB/c-recipient mice. Our data strongly suggest that strain-dependent differences convey different innate immune responses in BALB/c and C57BL/6J strains. Accordingly, in murine keratoplasty experiments, the mouse line of both donor and recipient animals must be carefully considered. C57BL/6J-recipient mice might be particularly suited to study corneal graft rejection in a clinical setting considered "high risk."

Salidroside Attenuates Doxorubicin-Induced Cardiac Dysfunction Partially Through Activation of QKI/FoxO1 Pathway.

Doxorubicin (DOX) is an effective chemotherapy. However, its usage has been associated with adverse effects. Salidroside (SAL) is an antioxidative drug, which confers protective effects against several diseases. Salidroside can attenuate cardiac dysfunction induced by DOX. Quaking (QKI) is identified as a protective factor that can inhibit cardiotoxicity medicated by DOX through the regulation of cardiac circular RNA expression. The present study investigated the role of QKI on the protective effect of SAL in the DOX-induced cardiotoxicity model. Results indicated that SAL attenuated DOX-induced adverse effects, including cardiac dysfunction, weight loss, and reactive oxygen species (ROS) production, and decreased the expression of BAX, caspase 3, and FoxO1. Also, it increased the Mn-SOD2 and QKI expression in vivo and in vitro. Furthermore, QKI knockdown suppressed anti-cardiotoxicity mediated by SAL. In conclusion, the results of the current study show that salidroside attenuates doxorubicin-induced cardiac dysfunction through activation of QKI/FoxO1 pathway.

Corneal tissue induces transcription of metallothioneins in monocyte-derived human macrophages.

PURPOSE: Immune reactions following corneal transplantation are the most common cause of transplant failure. However, the underlying mechanisms of corneal graft rejection are not yet fully understood but increasing evidence points to a crucial role of the innate immune system in this context. Using a human in vitro model, we aimed to assess the response of human macrophages to stimulation with human corneal tissue and whether corneal endothelial cells (CEC) have immune-modulating properties. METHODS: Human monocytes were isolated from peripheral blood mononuclear cells and differentiated into monocyte-derived macrophages (MDM). A standardized protocol was used for disaggregation of human corneas into fragments of defined sizes. MDMs were stimulated using processed corneal material with or without CEC. Lipopolysaccharide (LPS) or interferon-gamma (IFNγ) served as controls. RNA sequencing was applied to analyze the impact of differential stimulation of MDMs on their transcriptional profile. RNA sequencing results were validated using digital PCR. RESULTS: The transcriptional profile of MDMs was significantly modulated by the type of stimulus used for MDM activation as well as by the individual MDM donor. LPS- or IFNγ-stimulation resulted in distinct transcriptional alterations compared to unstimulated MDMs including an upregulation of various cytokines such as CCL3, 4, 5, 19 or CXCL9. Corneal tissue induced the differential expression of 45 genes when compared to unstimulated MDMs, with several metallothioneins (MTs) among the upregulated factors (MT1A, MT1E, MT1F, MT1G, MT1H, MT1L, MT1M, MT1X, MT2A). This effect was independent of the presence or absence of CEC. PCR validation confirmed induction of 3 different metallothioneins (MT1G, MT1H and MT2A) in MDMs stimulated by corneal tissue. CONCLUSIONS: The MDM in vitro model proved to be a robust tool to study the effects of LPS, IFNγ and corneal tissue homogenates on the transcriptional activity of MDM. Human macrophages showed a distinct upregulation of various MTs when challenged with human corneal allogen with or without corneal endothelium, which might have an immune-modulatory effect. As a general observation, it appears that in MDM-based studies a significant donor-dependent effect on the transcriptional profile of MDMs needs to be considered and adjusted before downstream analysis.

Carbonic Anhydrase 4 serves as a Clinicopathological Biomarker for Outcomes and Immune Infiltration in Renal Cell Carcinoma, Lower Grade Glioma, Lung Adenocarcinoma and Uveal Melanoma.

Background: Carbonic anhydrase 4 (CA4) maintains homeostasis of carbon dioxide and bicarbonate. It is suggested to be a potential prognostic biomarker, while the correlations between CA4 and different cancers are indistinct. Methods: Differential mRNA expression of CA4 among different cancers and corresponding normal tissues was compared based on datasets on the Cancer Genome Atlas (TCGA) platforms. Then, survival analysis was performed using Tumor-immune system interactionsplatform and TCGA cohort on the basis of distinct comparison expression of CA4 in five kinds of tumors. In addition, molecular penal analysis and functional annotations of CA4-related genes was elaborated. The correlation between CA4 mRNA expression and tumor immune microenvironment were analyzed in detail. Results: Compared with adjacent normal tissues, CA4 mRNA expressions were found significantly lower in various tumors. Moreover, decreased expression of CA4 was significantly related to worse overall survival (OS) and progression-free survival (PFS) in kidney renal clear cell carcinoma (KIRC), brain lower grade glioma (LGG), lung adenocarcinoma (LUAD) and uveal melanoma (UVM), and worse OS of prostate adenocarcinoma (PRAD) (p<0.05). Cox regression analyses indicated that CA4 was a significant prognostic biomarker in KIRC, LGG, LUAD and UVM. Moreover, CA4 showed markedly relationship with tumor immune environment and diverse immune infiltration signatures in KIRC, LGG, LUAD and UVM. Conclusions: Our study revealed that CA4 was a potential biomarker for aggressive progression and poor prognosis in KIRC, LGG, LUAD, PRAD and UVM, correlated with immune infiltration in various tumor environments. These results suggested that CA4 possibly served as a promising prognostic and immune infiltration biomarker in many cancers.

Inhibition of TRPA1 Promotes Cardiac Repair in Mice After Myocardial Infarction.

Recent studies have shown that TRPA1, a nonselective cation channel with high permeability to calcium, is expressed in many tissues of the cardiovascular system and is involved in the pathogenesis of many cardiovascular diseases. However, the role of TRPA1 in cardiac repair after myocardial infarction (MI) has not been clearly defined. The aim of this study was to confirm whether inhibition of TRPA1 could attenuate MI-induced cardiac ischemia injury. The C57BL/6 mice were subjected to ligation of the left anterior descending coronary artery and treated with TRPA1-specific inhibitor HC-030031 (HC) for 4 weeks. Echocardiography was performed to assess cardiac function. The results showed that HC significantly attenuated MI-induced cardiac dysfunction 4 weeks after MI. Similarly, HC reduced cardiac fibrosis and cell apoptosis after MI and significantly increased angiogenesis in the border zone of the infarct. In vitro, we found that HC promoted the proliferation and migration of human umbilical vein endothelial cells (HUVECs). Importantly, HC treatment decreased phosphatase and tensin homolog expression and augmented the expression of phosphorylated Akt in the myocardium post MI and HUVECs. However, treatment of HUVECs with a PI3K inhibitor, LY294002, before HC administration almost completely abolished HC-induced migration in HUVECs. In conclusion, we demonstrate that the inhibition of TRPA1 promotes angiogenesis after MI, thereby alleviating myocardial ischemia injury via mechanisms involving inhibition of phosphatase and tensin homolog expression and subsequent activation of the PI3K/Akt signaling.

Construction and immunological evaluation of recombinant adenovirus vaccines co-expressing GP3 and GP5 of EU-type porcine reproductive and respiratory syndrome virus in pigs.

Porcine reproductive and respiratory syndrome virus (PRRSV) keeps causing economic damages in the swine sector across the globe. There has been emergence of the European (EU) genotype of porcine reproductive and respiratory syndrome virus (Genotype-I PRRSV) in China in recent years. The presently available vaccines cannot unable to provide safeguard against PRRSV infection completely. This study was aimed to construct recombinant adenovirus expressing the ORF3 and ORF5 genes of the EU-type PRRSV strain. Then, the recombinant adenovirus vaccines for EU-type PRRSV (rAd-E3518, rAd-E35, rAd-E3 and rAd-E5) which we constructed and evaluated were constructed and identified by western blot and PCR. All recombinant adenovirus vaccines were evaluated for humoral and cellular responses and EU-type PRRSV challenge in pigs. The results showed that the group of rAd-E3518+Quil A developed higher GP3 and GP5 specific antibody responses compared to the group of rAd-E3518. The majority of the neutralizing antibody titers were higher than 1:16 (P<0.05), the fusion of IL-18 has increased significantly PRRSV-stimulated secretion of IFN-γ and IL-4 in porcine serum, the group of rAd-E3518+Quil A produced highest T-lymphocytes (CD3+CD4+ and CD3+CD8+ T cells) proliferative in peripheral blood of pigs. The animals were challenged with the EU-type PRRSV strain and the viral load was detected in the several tissues, the viral load of rAd-E3518 and rAd-E3518+Quil A were lower than the wild-type adenovirus group. Our findings provide evidence to confirm that the recombinant adenovirus vaccine can protect pigs from EU-PRRSV infection.

Salidroside prevents tumor necrosis factor-α-induced vascular inflammation by blocking mitogen-activated protein kinase and NF-κB signaling activation.

Vascular inflammation is a key factor in the pathogenesis of atherosclerosis. Salidroside is an important active ingredient extracted from the root of the Rhodiola rosea plant, which has been reported to have antioxidative, anti-cancer, neuroprotective and cardioprotective effects. However, the effects of salidroside on vascular inflammation have not been clarified. The purpose of the present study was to investigate the protective effects of salidroside against tumor necrosis factor (TNF)-α-induced vascular inflammation in cardiac microvascular endothelial cells (CMECs), a specific cell type derived from coronary micro-vessels. Over a 24-h period, salidroside did not exert any significant cytotoxicity up to a dose of 100 µM. Additionally, salidroside decreased the expression levels of the cell adhesion molecule vascular cell adhesion molecule-1 (VCAM-1) in TNF-α-stimulated CMECs, thus suppressing monocyte-to-CMEC adhesion. Salidroside also decreased the production of inflammatory cytokines such as interleukin (IL)-1ß, IL-6 and monocyte chemotactic protein 1 (MCP-1) in TNF-α-induced CMECs, as well as suppressing TNF-α-activated mitogen-activated protein kinase (MAPK) and NF-κB activation. Since MAPKs and NF-κB both serve notable roles in regulating the expression of VCAM-1, IL-1ß, IL-6 and MCP-1, the present study provided a preliminary understanding of the mechanism underlying the protective effects of salidroside. Overall, salidroside alleviated vascular inflammation by mediating MAPK and NF-κB activation in TNF-α-induced CMECs. These results indicated that salidroside may have potential applications as a therapeutic agent against vascular inflammation and atherosclerosis.

CT-based radiomic signatures for prediction of pathologic complete response in esophageal squamous cell carcinoma after neoadjuvant chemoradiotherapy.

The objective of this study was to build models to predict complete pathologic response (pCR) after neoadjuvant chemoradiotherapy (nCRT) in esophageal squamous cell carcinoma (ESCC) patients using radiomic features. A total of 55 consecutive patients pathologically diagnosed as having ESCC were included in this study. Patients were divided into a training cohort (44 patients) and a testing cohort (11 patients). The logistic regression analysis using likelihood ratio forward selection was performed to select the predictive clinical parameters for pCR, and the least absolute shrinkage and selection operator (LASSO) with logistic regression to select radiomic predictors in the training cohort. Model performance in the training and testing groups was evaluated using the area under the receiver operating characteristic curves (AUC). The multivariate logistic regression analysis identified no clinical predictors for pCR. Thus, only radiomic features selected by LASSO were used to build prediction models. Three logistic regression models for pCR prediction were developed in the training cohort, and they were able to predict pCR well in both the training (AUC, 0.84-0.86) and the testing cohorts (AUC, 0.71-0.79). There were no differences between these AUCs. We developed three predictive models for pCR after nCRT using radiomic parameters and they demonstrated good model performance.

TLR4 Activation Promotes the Progression of Experimental Autoimmune Myocarditis to Dilated Cardiomyopathy by Inducing Mitochondrial Dynamic Imbalance.

Mitochondrial dynamic imbalance associates with several cardiovascular diseases. However, the role of mitochondrial dynamics in TLR4 activation-mediated dilated cardiomyopathy (DCM) progress remains unknown. A model of experimental autoimmune myocarditis (EAM) was established in BALB/c mice on which TLR4 activation by LPS-EB or TLR4 inhibition by LPS-RS was performed to induce chronic inflammation for 5 weeks. TLR4 activation promoted the transition of EAM to DCM as demonstrated by increased cardiomyocyte apoptosis, myocardial fibrosis, ventricular dilatation, and declined heart function. TLR4 inhibition mitigated the above DCM changes. Transmission electron microscope study showed that mitochondria became fragmented, also with damaged crista in ultrastructure in EAM mice. TLR4 activation aggravated the above mitochondrial aberration, and TLR4 inhibition alleviated it. The mitochondrial dynamic imbalance and damage in DCM development were mainly associated with OPA1 downregulation, which may be caused by elevated TNF-α level and ROS stress after TLR4 activation. Furthermore, OMA1/YME1L abnormal degradation was involved in the OPA1 dysfunction, and intervening OMA1/YME1L in H9C2 significantly alleviated mitochondrial fission, ultrastructure damage, and cell apoptosis induced by TNF-α and ROS. These data indicate that TLR4 activation resulted in OPA1 dysfunction, promoting mitochondrial dynamic imbalance and damage, which may involve in the progress of EAM to DCM.

The emerging role of interleukin-37 in cardiovascular diseases.

INTRODUCTION: Interleukin (IL)-37 is a newly identified member of the IL-1 family, and shows a growing role in a variety of diseases. This review aims at summarizing and discussing the role of IL-37 in cardiovascular diseases. METHODS: Data for this review were identified by searches of MEDLINE, Embase, and PubMed using appropriate search terms. RESULTS: IL-37 is a newly identified cytokine belonging to the IL-1 family and is expressed in inflammatory immune cells and several parenchymal cells. It has potent anti-inflammatory and immunosuppressive properties, with two mechanisms underlying this function. IL-37 is produced as a precursor and then cleaved into mature form in the cytoplasm by caspase-1, translocating to nucleus and suppressing the transcription of several pro-inflammatory genes by binding SMAD-3. Besides, IL-37 can be secreted extracellularly, and binds to IL-18Ra chain and recruits Toll/IL-1R (TIR)-8 for transducing anti-inflammatory signaling. IL-37 is upregulated in an inducible manner and negatively regulates signaling mediated by TLR agonists and pro-inflammatory cytokines. The cytokine has been shown to inhibit both innate and adaptive immunological responses, exert antitumor effects, and act as a prognostic marker in a variety of autoimmune diseases. CONCLUSIONS: Recent studies have suggested that IL-37 plays a role in cardiovascular diseases. In this review, we provide an overview of the cytokine biology, discuss recent advances made in unraveling its cardio-protective effects, and suggest guidelines for future research.

Outbreak of Marek's disease in a vaccinated broiler breeding flock during its peak egg-laying period in China.

BACKGROUND: Outbreaks of Marek's disease (MD), caused by Marek's disease virus (MDV), primarily occur in 10-12-week-old hens. CASE PRESENTATION: We report a case of MD in a breeding flock of 24-30-week-old vaccinated broilers in China. The clinical signs in the affected chickens appeared at 24 weeks, and the incidence of tumours peaked at 30 weeks. The morbidity and mortality of the hens were 5 % and 80 %, respectively. Hematoxylin-eosin staining of the tissues showed the typical characteristics of MD. MDV infection was confirmed in the hens with an agar gel diffusion precipitation assay for the MD antigen in the feather follicle epithelium. An MDV strain, designated AH1410, was isolated from the blood lymphocytes. Sequence analyses of the pp38, meq, and gB genes revealed that strain AH1410 had molecular features consistent with a virulent, previously identified MDV. CONCLUSION: Our data provide evidence that not only is MDV becoming more virulent, but that the period of its onset in chickens is expanding. These findings provide the basis the molecular surveillance and further study of virulent MDV mutants and control strategies for MD in China.