Brain metastasis magnetic resonance imaging-based deep learning for predicting epidermal growth factor receptor (EGFR) mutation and subtypes in metastatic non-small cell lung cancer.

Background: The preoperative identification of epidermal growth factor receptor (EGFR) mutations and subtypes based on magnetic resonance imaging (MRI) of brain metastases (BM) is necessary to facilitate individualized therapy. This study aimed to develop a deep learning model to preoperatively detect EGFR mutations and identify the location of EGFR mutations in patients with non-small cell lung cancer (NSCLC) and BM. Methods: We included 160 and 72 patients who underwent contrast-enhanced T1-weighted (T1w-CE) and T2-weighted (T2W) MRI at Liaoning Cancer Hospital and Institute (center 1) and Shengjing Hospital of China Medical University (center 2) to form a training cohort and an external validation cohort, respectively. A multiscale feature fusion network (MSF-Net) was developed by adaptively integrating features based on different stages of residual network (ResNet) 50 and by introducing channel and spatial attention modules. The external validation set from center 2 was used to assess the performance of MSF-Net and to compare it with that of handcrafted radiomics features. Receiver operating characteristic (ROC) curves, accuracy, precision, recall, and F1-score were used to evaluate the effectiveness of the models. Gradient-weighted class activation mapping (Grad-CAM) was used to demonstrate the attention of the MSF-Net model. Results: The developed MSF-Net generated a better diagnostic performance than did the handcrafted radiomics in terms of the microaveraged area under the curve (AUC) (MSF-Net: 0.91; radiomics: 0.80) and macroaveraged AUC (MSF-Net: 0.90; radiomics: 0.81) for predicting EGFR mutations and subtypes. Conclusions: This study provides an end-to-end and noninvasive imaging tool for the preoperative prediction of EGFR mutation status and subtypes based on BM, which may be helpful for facilitating individualized clinical treatment plans.

Inhibition of ABI2 ubiquitination-dependent degradation suppresses TNBC cell growth via down-regulating PI3K/Akt signaling pathway.

Triple negative breast cancer (TNBC) is a type of cancer that lacks receptor expression and has complex molecular mechanisms. Recent evidence shows that the ubiquitin-protease system is closely related to TNBC. In this study, we obtain a key ubiquitination regulatory substrate-ABI2 protein by bioinformatics methods, which is also closely related to the survival and prognosis of TNBC. Further, through a series of experiments, we demonstrated that ABI2 expressed at a low level in TNBC tumors, and it has the ability to control cell cycle and inhibit TNBC cell migration, invasion and proliferation. Molecular mechanism studies proved E3 ligase CBLC could increase the ubiquitination degradation of ABI2 protein. Meanwhile, RNA-seq and IP experiments indicated that ABI2, acting as a crucial factor of tumor suppression, can significantly inhibit PI3K/Akt signaling pathway via the interaction with Rho GTPase RAC1. Finally, based on TNBC drug target ABI2, we screened and found that FDA-approved drug Colistimethate sodium(CS) has significant potential in suppressing the proliferation of TNBC cells and inducing cell apoptosis, making it a promising candidate for impeding the progression of TNBC.

GATA4 regulates the transcription of MMP9 to suppress the invasion and migration of breast cancer cells via HDAC1-mediated p65 deacetylation.

GATA-binding protein 4 (GATA4) is recognized for its significant roles in embryogenesis and various cancers. Through bioinformatics and clinical data, it appears that GATA4 plays a role in breast cancer development. Yet, the specific roles and mechanisms of GATA4 in breast cancer progression remain elusive. In this study, we identify GATA4 as a tumor suppressor in the invasion and migration of breast cancer. Functionally, GATA4 significantly reduces the transcription of MMP9. On a mechanistic level, GATA4 diminishes MMP9 transcription by interacting with p65 at the NF-κB binding site on the MMP9 promoter. Additionally, GATA4 promotes the recruitment of HDAC1, amplifying the bond between p65 and HDAC1. This leads to decreased acetylation of p65, thus inhibiting p65's transcriptional activity on the MMP9 promoter. Moreover, GATA4 hampers the metastasis of breast cancer in vivo mouse model. In summary, our research unveils a novel mechanism wherein GATA4 curtails breast cancer cell metastasis by downregulating MMP9 expression, suggesting a potential therapeutic avenue for breast cancer metastasis.

Pyroptosis-Derived Long Noncoding RNA Profiles Reveal a Novel Signature for Evaluating the Prognosis of Patients With Lung Adenocarcinoma.

PURPOSE: Long noncoding RNAs (lncRNAs) were recently implicated in modifying pyroptosis. Nonetheless, pyroptosis-related lncRNAs and their possible clinical relevance persist largely uninvestigated in lung adenocarcinoma (LUAD). MATERIALS AND METHODS: A sum of 921 samples were collected from three independent data sets. We obtained pyroptosis-related genes from both the Molecular Signatures Database and relevant literature sources and used four machine learning techniques, comprising stepwise Cox, ridge regression, least absolute shrinkage and selection operator, and random forest. Multiple bioinformatics approaches were used to further investigate the underlying mechanisms. RESULTS: In total, 39 differentially expressed pyroptosis genes were identified by comparing normal and tumor samples. Correlation analysis revealed 933 pyroptosis-related lncRNAs. Furthermore, univariate Cox regression determined 11 lncRNAs that exhibited stable associations with prognosis in the three cohorts, which were used to construct the pyroptosis-derived lncRNA signature. After analyzing the optimal results from four machine learning algorithms, we ultimately selected random forest to develop the pyroptosis-derived lncRNA signature. This signature was proven to be an independent prognostic factor and exhibited robust performance in three cohorts. CONCLUSION: We provided novel insight and established a pyroptosis-derived lncRNA signature for patients with LUAD, exhibiting strong predictive capabilities in both the training and validation sets.

[Genetic analysis of a fetus with Meckel syndrome due to variants of TMEM67 gene].

OBJECTIVE: To carry out prenatal diagnosis for a fetus with Meckel syndrome (MKS) and explore its genetic basis. METHODS: A pregnant woman presented at Suzhou Municipal Hospital in February 2018 was selected as the study subject. Clinical data was collected. Muscle tissue sample from the abortus and peripheral blood samples from the couple were collected. Genomic DNA was extracted and subjected to chromosomal microarray analysis (CMA) and whole exome sequencing. Candidate variant was verified by Sanger sequencing. RESULTS: The fetus was found to have microcephaly, oligohydramnios, polycystic kidneys and banana-shaped cerebellum at 18 weeks of gestation. After induction of labor, it was found to have encephalocele, renal cysts and polydactyly. CMA has found no abnormality. Whole exome sequencing revealed novel compound heterozygous variants c.296delA (p.Lys99SerfsTer6) and c.1243G>A (p.Val415Met) in the TMEM67 gene. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c.296delA variant was predicted to be pathogenic (PVS1+PM2_Supporting+PP4), whilst the c.1243G>A variant was predicted to be likely pathogenic (PM2_Supporting+PM3+PP3_Moderate+PP4). CONCLUSION: The c.296delA and c.1243G>A compound heterozygous variants of the TMEM67 gene probably underlay the MKS in this fetus.

Constructing the Optimal Classification Model for Benign and Malignant Breast Tumors Based on Multifeature Analysis from Multimodal Images.

The purpose of this study was to fuse conventional radiomic and deep features from digital breast tomosynthesis craniocaudal projection (DBT-CC) and ultrasound (US) images to establish a multimodal benign-malignant classification model and evaluate its clinical value. Data were obtained from a total of 487 patients at three centers, each of whom underwent DBT-CC and US examinations. A total of 322 patients from dataset 1 were used to construct the model, while 165 patients from datasets 2 and 3 formed the prospective testing cohort. Two radiologists with 10-20 years of work experience and three sonographers with 12-20 years of work experience semiautomatically segmented the lesions using ITK-SNAP software while considering the surrounding tissue. For the experiments, we extracted conventional radiomic and deep features from tumors from DBT-CCs and US images using PyRadiomics and Inception-v3. Additionally, we extracted conventional radiomic features from four peritumoral layers around the tumors via DBT-CC and US images. Features were fused separately from the intratumoral and peritumoral regions. For the models, we tested the SVM, KNN, decision tree, RF, XGBoost, and LightGBM classifiers. Early fusion and late fusion (ensemble and stacking) strategies were employed for feature fusion. Using the SVM classifier, stacking fusion of deep features and three peritumoral radiomic features from tumors in DBT-CC and US images achieved the optimal performance, with an accuracy and AUC of 0.953 and 0.959 [CI: 0.886-0.996], a sensitivity and specificity of 0.952 [CI: 0.888-0.992] and 0.955 [0.868-0.985], and a precision of 0.976. The experimental results indicate that the fusion model of deep features and peritumoral radiomic features from tumors in DBT-CC and US images shows promise in differentiating benign and malignant breast tumors.

MPDZ is associated with immune infiltration and regulates migration and invasion by switching YAP1 phosphorylation in colorectal cancer.

BACKGROUND: Multiple PDZ Domain Crumbs Cell Polarity Complex Component (MPDZ) is involved in a few human cancers. However, the features and potential mechanisms of MPDZ in progression of colorectal cancer (CRC) remains unknown. METHODS: The prognostic role of MPDZ in CRC was determined by Kaplan-Meier and univariate regression analysis. Enrichment analysis was performed to characterize crucial pathways of MPDZ. Immune infiltration and immunotherapeutic outcome were further evaluated. CCK8, EDU, transwell, and wound healing assay were used to assess the influence of MPDZ on pernicious performance of CRC cells. CD8+ T cells and CRC cells were co-cultured to explore the effect of MPDZ on the tumor microenvironment. qRT-PCR, western blot, immunoprecipitation (IP), and methylated RNA immunoprecipitation (me-RIP) were implemented in seeking for the potential mechanisms of MPDZ in CRC. RESULTS: CRC patients with elevated MPDZ expression suffered from significantly worse prognosis. Enrichment analysis revealed that MPDZ involved in pathways related to metastasis and cell cycle in CRC. In addition, MPDZ expression were related to several immunoinhibitors and had the ability to predict immunotherapy response. Finally, in vitro assays demonstrated that MPDZ knockdown inhibited migration, invasion and immune evasion of CRC cells. Mechanistically, MPDZ knockdown enhanced YAP1 phosphorylation by increased LATS1 expression. Moreover, m6A-MPDZ mRNA may be recognized and degraded by m6A recognition protein YTHDF2. CONCLUSIONS: MPDZ was critical for CRC development and could be a promising candidate for the treatment of CRC patients.

Predicting pathological complete response based on weakly and semi-supervised joint learning from breast cancer MRI.

Neoadjuvant chemotherapy (NAC) is the standard treatment for breast cancer patients. Patients achieving complete pathological response (pCR) after NAC usually have a good prognosis. However, automatic pCR prediction has been a challenging problem due to lacking well annotations in 3D MRI. Thus far, unifying different annotation information to predict the tumor's early response to NAC has not been systematically addressed. This paper proposes a weakly and semi-supervised joint learning method that integrates attentional features from multi-parametric MRI with radiomic features for predicting pCR to NAC in breast cancer patients. The attention-based multi-instance learning (MIL) is first developed to generate informative MRI bag-level features and mine key instances. The mean-teacher framework is then employed to segment tumor regions in a semi-supervised setting for extracting radiomic features. We perform experiments on 442 patients' data and show that our method achieves an AUC value of 0.85 in pCR prediction, which is superior to comparative methods. It is also shown that learning from multi-parametric MRI outperforms that of single-parameter MRI in pCR prediction.

Organic anion transporting polypeptide 3a1 is a novel influx pump for Perfluorooctane sulfonate in Sertoli cells and contributes to its reproductive toxicity.

Persistent organic pollutant perfluorooctane sulfonate (PFOS) is strongly associated with male reproductive disorders, but the related mechanisms are still not fully understood. In this study, we used in vivo and in vitro models to explore the role of organic anion transporting polypeptide 3a1 (Oatp3a1) on PFOS-induced male reproductive injury. Thirty male C57BL/6 (B6) mice were orally given PFOS (0-10 mg/kg/bw) for 28 days. Body weight, organ index, sperm count, histology, and blood-testis barrier (BTB) integrity were evaluated. Primary Sertoli cells were used to describe the related molecular mechanisms of male reproductive injury caused by PFOS. Our results showed that PFOS induced a decrease in sperm count, morphological damage to testicular Sertoli cells, and disruption of BTB. In the in vitro model, exposure to PFOS significantly increased Oatp3a1 mRNA and protein levels and decreased miR-23a-3p expression in Sertoli cells, accompanied by reduced trans-epithelial electrical resistance (TEER) value. By performing the 14C-PFOS uptake experiment, we showed that 14C-PFOS uptake in HEK293-Oatp3a1 cells was apparently higher than in HEK293-MOCK cells. Meanwhile, treating Sertoli cells with Oatp3a1 siRNA significantly decreased Oatp3a1 expression and rescued PFOS-induced decreases in TEER value. As such, the present study highlights that Oatp3a1 may play an important role in the toxic effect of PFOS on Sertoli cells, advancing our understanding of molecular mechanisms for PFOS-induced male reproductive disorders.

CRISPR-Cas9 identifies growth-related subtypes of glioblastoma with therapeutical significance through cell line knockdown.

BACKGROUND: Glioblastoma (GBM) is a type of highly malignant brain tumor that is known for its significant intratumoral heterogeneity, meaning that there can be a high degree of variability within the tumor tissue. Despite the identification of several subtypes of GBM in recent years, there remains to explore a classification based on genes related to proliferation and growth. METHODS: The growth-related genes of GBM were identified by CRISPR-Cas9 and univariate Cox regression analysis. The expression of these genes in the Cancer Genome Atlas cohort (TCGA) was used to construct growth-related genes subtypes (GGSs) via consensus clustering. Validation of this subtyping was performed using the nearest template prediction (NTP) algorithm in two independent Gene Expression Omnibus (GEO) cohorts and the ZZ cohort. Additionally, copy number variations, biological functions, and potential drugs were analyzed for each of the different subtypes separately. RESULTS: Our research established multicenter-validated GGSs. GGS1 exhibits the poorest prognosis, with the highest frequency of chr 7 gain & chr 10 loss, and the lowest frequency of chr 19 & 20 co-gain. Additionally, GGS1 displays the highest expression of EGFR. Furthermore, it is significantly enriched in metabolic, stemness, proliferation, and signaling pathways. Besides we showed that Foretinib may be a potential therapeutic agent for GGS1, the worst prognostic subtype, through data screening and in vitro experiments. GGS2 has a moderate prognosis, with a slightly higher proportion of chr 7 gain & chr 10 loss, and the highest proportion of chr 19 & 20 co-gain. The prognosis of GGS3 is the best, with the least chr 7 gain & 10 loss and EGFR expression. CONCLUSIONS: These results enhance our understanding of the heterogeneity of GBM and offer insights for stratified management and precise treatment of GBM patients.

Culture conditions of mouse ESCs impact the tumor appearance in vivo.

Various culture conditions by small molecules have been explored to extend pluripotency of stem cells, but their impacts on cell fate in vivo remain elusive. We systematically compared the effects of various culture conditions on the pluripotency and cell fate in vivo of mouse embryonic stem cells (ESCs) by tetraploid embryo complementation assay. Conventional ESC cultures in serum/LIF-based condition produced complete ESC mice and also the survival to adulthood at the highest rates of all other chemical-based cultures. Moreover, long-term examination of the survived ESC mice demonstrated that conventional ESC cultures did not lead to visible abnormality for up to 1.5-2 years, whereas the prolonged chemical-based cultures developed retroperitoneal atypical teratomas or leiomyomas. The chemical-based cultures exhibited transcriptomes and epigenomes that typically differed from those of conventional ESC cultures. Our results warrant further refinement of culture conditions in promoting the pluripotency and safety of ESCs in future applications.

Pan-cancer analysis of aldolase B gene as a novel prognostic biomarker for human cancers.

Aldolase B (ALDOB) gene is essential for the process of glycolysis and differentially expressed in cancers. The aims of this study were to explore the potential role of ALDOB in pan-cancer, in order to deepen the research on the pathological mechanism of cancer. Hence, we used several online tools (TIMER2, GEPIA2, UALCAN, cBioPortal, and MXPRESS) and R language to identify the correlation between the ALDOB expression and survival analysis, genetic alteration, DNA methylation, and immune cell infiltration based on The Cancer Genome Atlas project. The results showed that ALDOB was lowly expressed in pan-cancer. Survival analysis revealed that low expression of ALDOB was markedly related with poor clinical prognosis, while the genetic alteration within ALDOB changed along with the difference of overall survival (OS) and disease-free survival (DFS) prognosis in several cancers. A possible relationship between DNA methylation and ALDOB expression for several tumors was found. Besides, ALDOB expression was confirmed to be associated with tumor immune cell infiltration, especially in breast invasive carcinoma (BRCA), esophageal carcinoma (ESCA), and testicular germ cell tumors (TGCT) cases. Further, the enrichment analysis demonstrated that metabolic pathway was closely related to ALDOB expression. Our results provide a comprehensive pan-cancer analysis and suggest ALDOB could act as a promising tumor predictive biomarker for human cancer.

Identification and validation of a novel ubiquitination-related gene UBE2T in Ewing's sarcoma.

Background: Ewing's sarcoma (ES) is one of the most prevalent malignant bone tumors worldwide. However, the molecular mechanisms of the genes and signaling pathways of ES are still not well sufficiently comprehended. To identify candidate genes involved in the development and progression of ES, the study screened for key genes and biological pathways related to ES using bioinformatics methods. Methods: The GSE45544 and GSE17618 microarray datasets were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified, and functional enrichment analysis was performed. A protein-protein interaction (PPI) network was built, and key module analysis was performed using STRING and Cytoscape. A core-gene was gained and was validated by the validation dataset GSE67886 and immunohistochemistry (IHC). The diagnostic value and prognosis evaluation of ES were executed using, respectively, the ROC approach and Cox Regression. Results: A total of 187 DEGs, consisting of 56 downregulated genes and 131 upregulated genes, were identified by comparing the tumor samples to normal samples. The enriched functions and pathways of the DEGs, including cell division, mitotic nuclear division, cell proliferation, cell cycle, oocyte meiosis, and progesterone-mediated oocyte maturation, were analyzed. There were 149 nodes and 1246 edges in the PPI network, and 15 hub genes were identified according to the degree levels. The core gene (UBE2T) showed high expression in ES, validated by using GSE67886 and IHC. The ROC analysis revealed UBE2T had outstanding diagnostic value in ES (AUC = 0.75 in the training set, AUC = 0.90 in the validation set). Kaplan-Meier (analysis of survival rate) and Cox Regression analyses indicated that UBE2T was a sign of adverse results for sufferers with ES. Conlusion: UBE2T was a significant value biomarker for diagnosis and treatment of ES, thereby presenting a novel potential therapeutic target for ES as well as a new perspective for assessing the effect of treatment and prognostic prediction.

[Research progress on the modulation mechanism of electroacupuncture for learning and memory impairment after ischemic stroke].

Electroacupuncture may play a role in treatment of learning and memory impairment after ischemic stroke by regulating phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) signaling pathway, cyclic adenosine monophosphate (cAMP)-dependent protein kinase A (PKA)/cAMP response element binding protein (CREB) signaling pathway, nerve growth factor (NGF)/tyrosine kinase-A (TrkA) signaling pathway, Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway, Notch signaling pathway, erythropoietin-producing hepatocyte (Eph)/ephrin signaling pathway. The interactions among these pathways should be further explored in treatment of learning and memory impairment after ischemic stroke.

Additional ratios of hydrolysates from lignocellulosic digestate at different hydrothermal temperatures influencing anaerobic digestion performance.

Hydrothermal treatment (HT) is envisaged as a promising technology to treat the lignocellulosic biomass. HT temperature is an important parameter influencing the hydrolysate compositions such as organic compounds and potential inhibitors, and therefore affect the subsequential anaerobic digestion (AD) process. Herein, HT-AD was employed to treat the wheat straw-derived digestate. The HT temperature of 190 °C was proved to be the best performance with a higehst reducing sugar yield (45.05 mg g-1) in the hydrolysate and a highest methane yield (120.8 mL gTS-1) from the AD of the hydrolysate, which was 42.5% higher than the methane yield in the control without the hydrolysate addition (84.8 mL gTS-1). 3-Furaldehyde was the dominant organic in the hydrolysates. The HT temperature of 210 °C led to the presence of AD inhibitory moieties (e.g., phenols and furans) in the hydrolysate, resulting in a low methane yield. Although the treatments with the addition of 100% hydrolysate outperformed those of 50% hydrolysate in the methane yields in the late stage, the latter had higher methane yields in the first stage, suggesting that the additional ratios of hydrolysates should be carefully considered in AD, especially the detrimental effects of inhibitors and adaptability issues of AD consortia. The MiSeq sequencing showed that the hydrolysis/acidogenesis was dominant in the first stage, while methanogenesis became dominant in the late stage with the acetoclastic/hydrogenotrophic methanogens (Methanosarcina and Methanobacterium) enriched in the hydrolysate-feeding reactors. These findings demonstrated that a integration of HT-AD was a promising approach for the digestate valorization and to reduce the potential carbon emission from waste treatments.

Intra- and peri-tumoral radiomics for predicting the sentinel lymph node metastasis in breast cancer based on preoperative mammography and MRI.

Purpose: This study aims to investigate values of intra- and peri-tumoral regions in the mammography and magnetic resonance imaging (MRI) image for prediction of sentinel lymph node metastasis (SLNM) in invasive breast cancer (BC). Methods: This study included 208 patients with invasive BC between Spe. 2017 and Apr. 2021. All patients underwent preoperative digital mammography (DM), digital breast tomosynthesis (DBT), dynamic contrast-enhanced MRI (DCE-MRI) and diffusion-weighted MRI (DWI) scans. Radiomics features were extracted from manually outlined intratumoral regions, and automatically dilated peritumoral tumor regions in each modality. The least absolute shrinkage and selection operator (LASSO) regression was used to select key features from each region to develop radiomics signatures (RSs). Area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, specificity and negative predictive value (NPV) were calculated to evaluate performance of the RSs. Results: Intra- and peri-tumoral regions of BC can provide complementary information on the SLN status. In each modality, the Com-RSs derived from combined intra- and peri-tumoral regions always yielded higher AUCs than the Intra-RSs or Peri-RSs. A total of 10 and 11 features were identified as the most important predictors from mammography (DM plus DBT) and MRI (DCE-MRI plus DWI), respectively. The DCE-MRI plus DWI generated higher AUCs compared with DM plus DBT in the training (AUCs, DCE-MRI plus DWI vs. DM plus DBT, 0.897 vs. 0.846) and validation (AUCs, DCE-MRI plus DWI vs. DM plus DBT, 0.826 vs. 0.786) cohort. Conclusions: Radiomics features from intra- and peri-tumoral regions can provide complementary information to identify the SLNM in both mammography and MRI. The DCE-MRI plus DWI generated lower specificity, but higher AUC, accuracy, sensitivity and negative predictive value compared with DM plus DBT.

Betaine supplementation alleviates dextran sulfate sodium-induced colitis via regulating the inflammatory response, enhancing the intestinal barrier, and altering gut microbiota.

Inflammatory bowel disease (IBD) is a multifaceted and recurrent immune disorder that occurs in the gastrointestinal tract. Betaine is a natural compound that exerts beneficial anti-inflammatory effects. However, the role of betaine in protecting IBD is still unclear. Therefore, the aim of our study was to investigate the anti-inflammatory effect of betaine in dextran sulfate sodium (DSS)-induced colitis. The results showed that betaine greatly increased the body weight and decreased the disease activity index score of DSS-treated mice. Furthermore, betaine effectively downregulated the protein levels of pro-inflammatory cytokines (IL-1ß, IL-6, and TNFα) and upregulated tight junction proteins (occludin and ZO-1) in the mice. Additionally, betaine exposure remarkably restricted the DSS-induced phosphorylation of IκB and NF-κB p65 in mice. Similarly, betaine pretreatment improved the inflammatory response and intestinal barrier of Caco-2 cells. Betaine altered the gut microbiota composition, markedly decreasing the relative abundance of Firmicutes and Proteobacteria and considerably increasing the relative abundance of Bacteroidota and Campylobacterota in DSS-induced mice. In conclusion, betaine could attenuate colitis via regulating the inflammatory response, enhancing the intestinal barrier, and altering gut microbiota and is conducive to developing new drugs for treating human diseases.

Serum adenosine deaminase activity and acute cerebral infarction: a retrospective case-control study based on 7913 participants.

BACKGROUND: Adenosine deaminase (ADA) is a key enzyme that catalyzes the deamination of adenosine into inosine, which eventually decomposes into uric acid (UA). A body of papers have reported that adenosine and UA are closely related to cerebrovascular events. However, the association between serum ADA activity and acute cerebral infarction (ACI) remains unclear. METHODS: 7913 subjects were enrolled, including 3968 ACI patients and 3945 controls, in this study. An automatic biochemistry analyzer was used to determine serum activity. RESULTS: Serum ADA activity was found that was significantly decreased in patients with ACI (10.10 ± 3.72 U/L) compared to those without ACI (11.07 ± 2.85 U/L, p < 0.001). After Logistic regression analysis, ADA concentrations were negatively correlated with ACI (OR = 1.161, 95% CI: 1.140-1.183, p < 0.001). Smoking and alcohol consumption decreased serum ADA concentrations in patients with ACI, whereas diabetes and hypertension had the opposite effect. CONCLUSIONS: Serum ADA concentrations in patients with ACI are markedly decreased, suggesting that the decreased ADA concentrations may be involved in the pathogenesis of ACI. We hypothesized that decreased ADA activity may be an adaptive mechanism to maintain adenosine levels and protect against ischemic brain injury.

Effect of Astragalus injection on inflammatory mediators in patients with viral myocarditis: A systematic review and meta-analysis.

BACKGROUND: To explore the therapeutic effect and mechanism of Astragalus injection on viral myocarditis, we conducted a systematic review and meta-analysis to identify the influence of Astragalus injection on inflammatory mediators and overall efficiency in patients undergoing viral myocarditis. METHODS: EMBASE, Cochrane Library, PubMed, Chinese Biomedical Literature, Chinese National Knowledge Infrastructure (CNKI), and Wanfang databases were searched to screen randomized controlled trials (RCTs) published before July 3, 2022. The quality of participating studies was assessed by the Cochrane Collaboration Risk of Bias tool. The calculation of qualitative data used a risk ratio (RR) with a 95% confidence interval (95% CI), and quantitative data had standardized mean differences (SMDs) with a 95% CI. The heterogeneity among trials was quantified with Cochran's Q test and the I2 statistic. Confounding factors were estimated by sensitivity analysis, meta-regression, and subgroup analysis. The publication bias of participating articles was evaluated by funnel plot and Egger's test. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) system was recommended for assessing the strength of evidence. RESULTS: Nineteen available studies were included in our present meta-analysis, all of which were conducted in China. The outcomes expose that Astragalus injection dramatically decreased the levels of pro-inflammatory TNF-α (SMD=-2.271, 95% CI=-2.802 to -1.739, p<0.001, I2=90.6%), IL-6 (SMD=-1.501, 95% CI=-1.872 to -1.130, p<0.001, I2=83.2%), IL-17 (SMD=-3.194, 95% CI=-4.569 to -1.818, p<0.001, I2=88.9%), 1L-8 (SMD=-6.133, 95% CI=-9.938 to -2.328, p = 0.002, I2=97%), 1L-1 (SMD=-1.814, 95% CI=-2.557 to -1.070, p<0.001, I2=92.1%), CRP (SMD=-2.020, 95% CI=-3.107 to -0.932, p<0.001, I2=92.7%), and IFN-γ (SMD=-1.512, 95% CI=-2.771 to -0.253, p = 0.019, I2=92%) and increased the total effective rate of treatment (RR=1.225, 95% CI=1.17 to 1.29, p<0.001, I2=0.0%) in patients with viral myocarditis. CONCLUSION: Astragalus injection can play a therapeutic role in patients with viral myocarditis through immunomodulatory effects. Outcomes were treated with caution due to significant heterogeneity among studies. Large-scale RCTs should be performed to support these conclusions.

Acute ammonia stress-induced oxidative and heat shock responses modulated by transcription factors in Litopenaeus vannamei.

The present study aimed to examine the effects of short-term exposure to ammonia on stress and oxidative responses in shrimp (Litopenaeus vannamei) and to determine whether the antioxidant system related to the regulatory role of transcription factors and stress proteins was activated. Shrimp were exposed ammonia-N at four concentrations: 0 (control), 5, 10, and 15 mg/L, for 48 h. The hepatopancreas was sampled to measure the levels of glutathione (GSH), malondialdehyde (MDA), nitric oxide (NO); the activities of superoxide dismutase (SOD), catalase (CAT), nitric oxide synthase (NOS); and the expression levels of GSH-px (encoding glutathione peroxidase), GST (encoding glutathione-S-transferase), HSP70 (encoding heat shock protein 70), HSP90 (encoding heat shock protein 90), p53, RELISH, and AKIRIN. We observed that exposure to a high ammonia content increased the abundance of oxidative factors (MDA, CAT, SOD, NOS, and NO), reduced the levels of GSH, and upregulated the mRNA expression levels of antioxidant genes (GSH-px and GST), stress-related genes (HSP70 and HSP90), and transcription factor genes (p53, RELISH, and AKIRIN). These results indicated that ammonia induced oxidative stress and inflammation. Both enzymatic and nonenzymatic antioxidant defense systems are involved, which might be regulated by HSPs, as well as certain transcription factors, such as p53 and nuclear factor kappa B (NF-κB), thus mounting an adaptive response to help rebalance redox homoeostasis.