bluuebunny/crossref_metadata_2025 huggingface dataset:
Hyperglycemia aggravates ischemic brain damage via ERK1/2 activated cell autophagy and mitochondrial fission
Authors: Liu Ping , Yang Xiao , Niu Jianguo , Hei Changchun
Published: August 2022

Background

Hyperglycemia is one of the major risk factors for stroke and stroke recurrence, leading to aggravated neuronal damage after cerebral ischemia/reperfusion (I/R). ERK1/2 signaling pathway plays a vital role in cerebral ischemic injury. However, the role of the ERK1/2 pathway in hyperglycemia-aggravated ischemic brain damage is not clear.

Methods

Streptozotocin (STZ; 50 mg/kg)-induced diabetes (blood glucose ≥12 mmol/L) or control groups in adult Sprague-Dawley rats were further subdivided into I/R (carotid artery/vein clamping), I/R + PD98059 (I/R plus ERK1/2 inhibitor), and Sham-operated groups (n = 10 each). Neurobehavioral status (Neurological behavior scores) and the volume of the cerebral infarction (TTC staining); brain mitochondrial potential (JCI ratio test) and cell apoptosis (TUNEL assay); RAS protein expression, phosphorylated/total ERK1/2 and Drp-1 (Dynamic-related protein 1) protein levels (Western blotting); mitochondrial fusion-related proteins mitofusin-1/2 (Mfn1/2), optic atrophy (OPA-1) and mitochondrial fission 1 (Fis1), and autophagy-associated proteins Beclin-1, LC3-I/II and P62 (Western blotting and immunohistochemistry) were analyzed.

Results

The I/R + PD98059 group demonstrated better neurobehavior on the 1st (p < 0.05) and the 3rd day (p < 0.01) than the I/R group. Compared to the Sham group, cerebral ischemia/reperfusion brought about neuronal damage in the I/R group (p <0.01). However, treatment with PD98059 showed an improved situation with faster recovery of mitochondrial potential and less apoptosis of neuronal cells in the I/R + PD98059 group (p < 0.01). The I/R group had a higher-level expression of RAS and phosphorylated ERK1/2 and Drp-1 than the diabetes mellitus (DM) group (p < 0.01). The PD98059 treated group showed decreased expression of p-ERK1/2, p-Drp-1, Fis1, and Beclin-1, LC3-I/II and P62, but increased Mfn1/2 and OPA-1 than the I/R group (p < 0.01).

Conclusion

Hyperglycemia worsens cerebral ischemia/reperfusion-induced neuronal damage via ERK1/2 activated cell autophagy and mitochondrial fission.
Dyslipidemia and 10-year diabetes incidence in Japanese people: Population-based Panasonic cohort study 9
Authors: Kobayashi Genki , Okada Hiroshi , Hamaguchi Masahide , Kurogi Kazushiro , Murata Hiroaki , Ito Masato , Fukui Michiaki
Published: August 2022

Low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and LDL/HDL ratio have been associated with new-onset diabetes; however, their cut-off levels have not been determined. We clarified the association between dyslipidemia and the incidence of diabetes. People who underwent a health checkup under a program conducted by Panasonic Corporation from 2008 to 2018 were included. In total, 87,570 participants were included, of whom 5,110 developed type 2 diabetes. Cox regression analyses and time-dependent receiver operating characteristic (ROC) curves were used to evaluate the association between LDL cholesterol, HDL cholesterol, or LDL/HDL ratio and incident diabetes and to identify the cut-off values for incident diabetes. Multivariate analysis showed that LDL cholesterol, HDL cholesterol, and LDL/HDL ratio were significantly associated with the risk of incident type 2 diabetes. Further, the area under the ROC curve and optimized cut-off values for LDL cholesterol, HDL cholesterol, and LDL/HDL ratio for incident type 2 diabetes at 10 years were 0.613 and 124 mg/dl, 0.640 and 54 mg/dl, and 0.662 and 2.4 mg/dl, respectively. The LDL/HDL ratio with a cut-off value of 2.4 was a better predictor of incident diabetes within 10 years than LDL and HDL cholesterol.
Exposure to per- and polyfluoroalkyl substances (PFAS) and type 2 diabetes risk
Authors: Roth Katherine , Petriello Michael C.
Published: August 2022

Per- and polyfluoroalkyl substances (PFAS) are ubiquitous man-made chemicals found in consumer products including fabrics, food packaging, non-stick coatings, and aqueous film-forming foams. PFAS are stable and extremely resistant to degradation, resulting in high persistence throughout the environment as well as in human blood. PFAS consist of a large family of synthetic chemicals, with over 4000 distinct varieties having been identified and around 250 currently being manufactured at globally relevant levels. Numerous epidemiological studies have linked exposure to PFAS with adverse health effects ranging from immunotoxicity, cardiometabolic disease, developmental and reproductive effects, cancer, and recently type 2 diabetes. Several studies have demonstrated associations between serum PFAS concentrations and glycemic indicators of type 2 diabetes including glucose, insulin, and HOMA-IR in adolescent and adult cohorts. In addition, some studies have shown positive associations with incident type 2 diabetes and multiple PFAS. However, the link between PFAS exposure and the development of diabetes continues to be a disputed area of study, with conflicting data having been reported from various epidemiological studies. In this mini review we will summarize the current state of the literature linking PFAS to type 2 diabetes and discuss important future directions including the use of more complex mixtures-based statistical analyses.
Species selection and plantation management in enrichment planting with native timber species in the Panama Canal watershed
Authors: Marshall Abigail , Nelson Cara R. , Hall Jefferson S.
Published: August 2022

Large areas of the Panama Canal Watershed have been converted to monocultures of teak (Tectona grandis), a non-native timber species that is generally not providing hoped-for economic and ecological benefits of Forest Landscape Restoration. Enrichment planting offers a potential strategy for revitalizing these underperforming plantations through the addition of high-value, native species to the understory, but more information is needed to guide implementation and management in this region and other tropical areas. We assessed the performance of six promising native species (Byrsonima crassifolia, Dalbergia retusa, Dipteryx oleifera, Hyeronima alchorneoides, Platymiscium pinnatum, Terminalia amazonia) as an enrichment planting in teak plantations, and specifically considered how light availability, crowding pressure and annual fertilization affected seedling performance, we measured survival and growth for the first 30 months post-planting for ∼3,000 seedlings; half received annual fertilization and half did not. We found that growth rate did not significantly affect survival among- or within-species, except for a positive relationship for D. oleifera. Overall seedling survival was high (83%), and, while species varied widely, there was not a strong effect of light, crowding or fertilization on survival. In contrast, overall growth of species was significantly affected by these factors. Across all species growth was negatively related to crowding and positively related to light availability and fertilization. There were among-species differences; while all but one species (D. oleifera) were negatively affected by crowding, only half responded positively to light availability (D. retusa, P. pinnatum, and B. crassifolia) and fertilization (D. retusa, P. pinnatum, and T. amazonia). Our findings suggest that all study species except for B. crassifolia, which suffered unacceptably high mortality, have high potential for use in enrichment planting in Panama teak plantations. Among-species differences in response to fertilization and growing environment highlight the need for continued studies to establish specific silvicultural guidelines for species in the enrichment planting context.
Novel MEIOB variants cause primary ovarian insufficiency and non-obstructive azoospermia
Authors: Wang Yurong , Liu Ling , Tan Chen , Meng Guiquan , Meng Lanlan , Nie Hongchuan , Du Juan , Lu Guang-Xiu , Lin Ge , He Wen-Bin , Tan Yue-Qiu
Published: August 2022

Background: Infertility is a global health concern. MEIOB has been found to be associated with premature ovarian insufficiency (POI) and non-obstructive azoospermia (NOA), but its variants have not been reported in Chinese patients. The aim of this study was to identify the genetic aetiology of POI or NOA in three Han Chinese families.

Methods: Whole-exome sequencing (WES) was used to identify candidate pathogenic variants in three consanguineous Chinese infertile families with POI or NOA. Sanger sequencing was performed to validate these variants in the proband of family I and her affected family members. In vitro functional analyses were performed to confirm the effects of these variants.

Results: Two novel homozygous frameshift variants (c.258_259del and c.1072_1073del) and one novel homozygous nonsense variant (c.814C > T) in the MEIOB gene were identified in three consanguineous Han Chinese families. In vitro functional analyses revealed that these variants produced truncated proteins and affected their function.

Conclusion: We identified three novel MEIOB loss-of-function variants in local Chinese patients for the first time and confirmed their pathogenicity using in vitro functional analyses. These results extend the mutation spectrum of the MEIOB gene and have important significance for genetic counselling in these families.
Construction of a survival nomogram for gastric cancer based on the cancer genome atlas of m6A-related genes
Authors: Wang Xiaokang , Xu Kexin , Liao Xueyi , Rao Jiaoyu , Huang Kaiyuan , Gao Jianlin , Xu Gengrui , Wang Dengchuan
Published: August 2022

Objective: Based on TCGA database, a prediction model for 1-, 3-, and 5-year overall survival rates of gastric cancer (GC) patients was constructed by analyzing the critical risk factors affecting the prognosis of gastric cancer patients.

Method: Clinicopathological features as well as gene signature of GC patients were obtained from TCGA database. Patients were randomly divided into a training cohort and an internal validation cohort. Independent predictors of GC prognosis were analyzed by univariate and multivariate Cox analyses to construct nomogram. The accuracy and reliability of the model was further validated by calibration curves, ROC curves, and C-indexes, and the clinical utility of the model was analyzed by decision analysis curves.

Result: Age, sex, N stage, M stage, METTL16, RBM15, FMR1, IGFBP1, and FTO were significantly associated with the prognosis of GC patients, and these predictors were further included in the construction of nomogram. The C-indexes for the training cohort and validation set were 0.735 and 0.688, respectively. The results of the ROC curve analysis indicated that the area under the curve (AUC) exceeded 0.6 in training and validation sets at 1, 3, and 5 years.

Conclusion: We have constructed and validated a nomogram that provides individual survival condition prediction for GC patients. The prognostic model integrating gene signatures and clinicopathological characteristics would help clinicians determine the prognosis of patients with GC and develop individualized treatment plans.
Development of a prognostic model for children with neuroblastoma based on necroptosis-related genes
Authors: Jing Chu
Published: August 2022

Background: Neuroblastoma (NBL) is a rare malignant tumor of the peripheral sympathetic nervous system in children with a low overall survival rate. Recent studies have revealed the important role of necroptosis in the occurrence and development of many kinds of tumors. In this study, a prognostic model based on necroptosis-related genes was constructed for NBL.

Methods: Expression profiles and clinical information for patients with NBL were downloaded from TARGET. Data for necroptosis-related genes were extracted for Cox regression and lasso regression analyses to evaluate factors associated with prognosis and to construct a prognostic model. Data from the GEO datasets GSE62564 and GSE85047 were used for external verification. Associations between risk scores were calculated, and immune infiltration, drug sensitivity, and mutation analyses were conducted. Functional enrichment analyses of genes in the prognostic model were performed.

Results: Six necroptosis-related genes (i.e., CYLD, JAK1, APC, ERH, CNBP, and BAX) were selected to construct a prognostic risk model. The risk score was highly correlated with levels of infiltration of multiple immune cells and sensitivity to common antineoplastic drugs. In addition, the risk score was identified as an independent prognostic factor for patients with NBL.

Conclusion: We constructed and validated a prognostic model based on necroptosis-related genes, providing insights into the development and progression of NBL and a basis for improved management. In addition to providing a tool for clinical decision-making, these findings support the importance of necroptosis in NBL and may guide the development of therapeutic strategies targeting this process.
The putative role of gut microbiota in cancer: Cysteine is a pivotal coin
Authors: Serpa Jacinta
Published: August 2022

Tumor metabolism is mandatory for the proper adaptation of malignant cells to the microenvironment and the acquisition of crucial cellular skills supporting the systemic spread of cancer. Throughout this journey, the contribution of the gut microbiota to the bioavailability of nutrients supporting the bioenergetic and biosynthetic requirements of malignant cells is an issue. This review will focus on the role of cysteine ​​as a coin that mediates the metabolic crosstalk between microbiota and cancer. The key points enclose the way cysteine ​​can be made available by the microbiota, by degradation of more complex compounds or by de novo synthesis, in order to contribute to the enrichment of the colonic microenvironment as well to the increase of cysteine systemic bioavailability. In addition, the main metabolic pathways in cancer that rely on cysteine ​​as a source of energy and biomass will be pointed out and how the interspecific relationship with the microbiota and its dynamics related to aging may be relevant points to explore, contributing to a better understanding of cancer biology.
Kinetics of severe acute respiratory syndrome coronavirus 2 infection antibody responses
Authors: Lin Yajie , Zhu Jiajie , Liu Zongming , Li Chaonan , Guo Yikai , Wang Ying , Chen Keda
Published: August 2022

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread rapidly throughout the world, causing severe morbidity and mortality. Since the first reports of Coronavirus disease 2019 (COVID-19) in late 2019, research on the characteristics of specific humoral immunity against SARS-CoV-2 in patients with COVID-19 has made great progress. However, our knowledge of persistent humoral immunity to SARS-CoV-2 infection is limited. The existence of protective immunity after infection will affect future transmission and disease severity. Therefore, it is important to gather knowledge about the kinetics of antibody responses. In this review, we summarize the information obtained so far on the characteristics and kinetics of the SARS-CoV-2 infection of specific humoral immune response, especially in neutralizing antibodies and their relationship with disease severity. In addition, with the emergence of variants of concern, we summarize the neutralizing effect of specific humoral immunity on variants of concern after the initial SARS-CoV-2 infection and vaccination.
Lipopolysaccharide-induced interferon response networks at birth are predictive of severe viral lower respiratory infections in the first year of life
Authors: Read James F. , Serralha Michael , Mok Danny , Holt Barbara J. , Cruickshank Mark , Karpievitch Yuliya V. , Broadhurst David I. , Sly Peter D. , Strickland Deborah H. , Reinke Stacey N. , Holt Patrick G. , Bosco Anthony
Published: August 2022

Appropriate innate immune function is essential to limit pathogenesis and severity of severe lower respiratory infections (sLRI) during infancy, a leading cause of hospitalization and risk factor for subsequent asthma in this age group. Employing a systems biology approach to analysis of multi-omic profiles generated from a high-risk cohort (n=50), we found that the intensity of activation of an LPS-induced interferon gene network at birth was predictive of sLRI risk in infancy (AUC=0.724). Connectivity patterns within this network were stronger among susceptible individuals, and a systems biology approach identified IRF1 as a putative master regulator of this response. These findings were specific to the LPS-induced interferon response and were not observed following activation of viral nucleic acid sensing pathways. Comparison of responses at birth versus age 5 demonstrated that LPS-induced interferon responses but not responses triggered by viral nucleic acid sensing pathways may be subject to strong developmental regulation. These data suggest that the risk of sLRI in early life is in part already determined at birth, and additionally that the developmental status of LPS-induced interferon responses may be a key determinant of susceptibility. Our findings provide a rationale for the identification of at-risk infants for early intervention aimed at sLRI prevention and identifies targets which may be relevant for drug development.
DMGV Is a Rheostat of T Cell Survival and a Potential Therapeutic for Inflammatory Diseases and Cancers
Authors: Yang Fengyuan Mandy , Shen Liya , Fan Dengxia Denise , Chen Kuan-Hung , Lee Jongdae
Published: August 2022

Activated effector T cells (Teff) and/or compromised regulatory T cells (Treg) underlie many chronic inflammatory diseases. We discovered a novel pathway to regulate survival and expansion of Teff without compromising Treg survival and a potential therapeutic to treat these diseases. We found dimethylguanidino valeric acid (DMGV) as a rheostat for Teff survival: while cell-intrinsic DMGV generated by Alanine-Glyoxylate Aminotransferase 2 (AGXT2) is essential for survival and expansion by inducing mitochondrial ROS and regulation of glycolysis, an excessive (or exogenous) DMGV level inhibits activated Teff survival, thereby the AGXT2-DMGV-ROS axis functioning as a switch to turn on and off Teff expansion. DMGV-induced ROS is essential for glycolysis in Teff, and paradoxically DMGV induces ROS only when glycolysis is active. Mechanistically, DMGV rapidly activates mitochondrial calcium uniporter (MCU), causing a surge in mitochondrial Ca2+ without provoking calcium influx to the cytosol. The mitochondrial Ca2+ surge in turn triggers the mitochondrial Na+/Ca2+ exchanger (NCLX) and the subsequent mitochondrial Na+ import induces ROS by uncoupling the Coenzyme Q cycle in Complex III of the electron transport chain. In preclinical studies, DMGV administration significantly diminished the number of inflammatory T cells, effectively suppressing chronic inflammation in mouse models of colitis and rheumatoid arthritis. DMGV also suppressed expansion of cancer cells in vitro and in a mouse T cell leukemic model by the same mechanism. Our data provide a new pathway regulating T cell survival and a novel mode to treat autoimmune diseases and cancers.
Strong T-cell activation in response to COVID-19 vaccination in multiple sclerosis patients receiving B-cell depleting therapies
Authors: Alfonso-Dunn Roberto , Lin Jerry , Kirschner Vanessa , Lei Joyce , Feuer Grant , Malin Michaela , Liu Jiayuan , Roche Morgan , Sadiq Saud A.
Published: August 2022

Immunocompromised individuals, including multiple sclerosis (MS) patients on certain immunotherapy treatments, are considered susceptible to complications from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and specific vaccination regimens have been recommended for suitable protection. MS patients receiving anti-CD20 therapy (aCD20-MS) are considered especially vulnerable due to acquired B-cell depletion and impaired antibody production in response to virus infection and COVID-19 vaccination. Here, the humoral and cellular responses are analyzed in a group of aCD20-MS patients (n=43) compared to a healthy control cohort (n=34) during the first 6 months after a 2-dose cycle mRNA-based COVID-19 vaccination. Both IgG antibodies recognizing receptor binding domain (RBD) from CoV-2 spike protein and their blocking activity against RBD-hACE2 binding were significantly reduced in aCD20-MS patients, with a seroconversion rate of only 23.8%. Interestingly, even under conditions of severe B-cell depletion and failed seroconversion, a significantly higher polyfunctional IFNγ+ and IL-2+ T-cell response and strong T-cell proliferation capacity were detected compared to controls. Moreover, no difference in T-cell response was observed between forms of disease (relapsing remitting- vs progressive-MS), anti-CD20 therapy (Rituximab vs Ocrelizumab) and type of mRNA-based vaccine received (mRNA-1273 vs BNT162b2). These results suggest the generation of a partial adaptive immune response to COVID-19 vaccination in B-cell depleted MS individuals driven by a functionally competent T-cell arm. Investigation into the role of the cellular immune response is important to identifying the level of protection against SARS-CoV-2 in aCD20-MS patients and could have potential implications for future vaccine design and application.
The synovial fluid fibroblast-like synoviocyte: A long-neglected piece in the puzzle of rheumatoid arthritis pathogenesis
Authors: Mahmoud Dorra Elhaj , Kaabachi Wajih , Sassi Nadia , Tarhouni Lamjed , Rekik Sonia , Jemmali Samia , Sehli Hela , Kallel-Sellami Maryam , Cheour Elhem , Laadhar Lilia
Published: August 2022

Rheumatoid arthritis (RA) is a systemic autoimmune disease during which fibroblast-like synoviocytes (FLS) contribute to both joint inflammation and destruction. FLS represent the core component of the synovial membrane. Following inflammation of this membrane, an effusion of cell-rich synovial fluid (SF) fills the joint cavity. Unlikely, SF has been shown to contain fibroblasts with some shared phenotypic traits with the synovial membrane FLS. These cells are called SF-FLS and their origin is still unclear. They are either brought into the synovium via migration through blood vessels, or they could originate within the synovium and exist in projections of the synovial membrane. SF-FLS function and phenotype are poorly documented compared to recently well-characterized synovial membrane FLS subsets. Furthermore, no study has yet reported a SF-FLS single-cell profiling analysis. This review will discuss the origin and cellular characteristics of SF-FLS in patients with RA. In addition, recent advances on the involvement of SF-FLS in the pathogenesis of RA will be summarized. Current knowledge on possible relationships between SF-FLS and other types of fibroblasts, including synovial membrane FLS, circulating fibrocytes, and pre- inflammatory mesenchymal (PRIME) cells will also be addressed. Finally, recent therapeutic strategies employed to specifically target SF-FLS in RA will be discussed.
Screening of crosstalk and pyroptosis-related genes linking periodontitis and osteoporosis based on bioinformatics and machine learning
Authors: Liu Jia , Zhang Ding , Cao Yu , Zhang Huichao , Li Jianing , Xu Jingyu , Yu Ling , Ye Surong , Yang Luyi
Published: August 2022

Background and objective

This study aimed to identify crosstalk genes between periodontitis (PD) and osteoporosis (OP) and potential relationships between crosstalk and pyroptosis-related genes.

Methods

PD and OP datasets were downloaded from the GEO database and were performed differential expression analysis to obtain DEGs. Overlapping DEGs got crosstalk genes linking PD and OP. Pyroptosis-related genes were obtained from literature reviews. Pearson coefficients were used to calculate crosstalk and pyroptosis-related gene correlations in the PD and OP datasets. Paired genes were obtained from the intersection of correlated genes in PD and OP. PINA and STRING databases were used to conduct the crosstalk-bridge-pyroptosis genes PPI network. The clusters in which crosstalk and pyroptosis-related genes were mainly concentrated were defined as key clusters. The key clusters’ hub genes and the included paired genes were identified as key crosstalk-pyroptosis genes. Using ROC curve analysis and XGBoost screened key genes. PPI subnetwork, gene–biological process and gene-pathway networks were constructed based on key genes. In addition, immune infiltration was analyzed on the PD dataset using the CIBERSORT algorithm.

Results

A total of 69 crosstalk genes were obtained. 13 paired genes and hub genes TNF and EGFR in the key clusters (cluster2, cluster8) were identified as key crosstalk-pyroptosis genes. ROC and XGBoost showed that PRKCB, GSDMD, ARMCX3, and CASP3 were more accurate in predicting disease than other key crosstalk-pyroptosis genes while better classifying properties as a whole. KEGG analysis showed that PRKCB, GSDMD, ARMCX3, and CASP3 were involved in neutrophil extracellular trap formation and MAPK signaling pathway pathways. Immune infiltration results showed that all four key genes positively correlated with plasma cells and negatively correlated with T cells follicular helper, macrophages M2, and DCs.

Conclusion

This study shows a joint mechanism between PD and OP through crosstalk and pyroptosis-related genes. The key genes PRKCB, GSDMD, ARMCX3, and CASP3 are involved in the neutrophil extracellular trap formation and MAPK signaling pathway, affecting both diseases. These findings may point the way to future research.
A novel monoclonal IgG1 antibody specific for Galactose-alpha-1,3-galactose questions alpha-Gal epitope expression by bacteria
Authors: Kreft Luisa , Schepers Aloys , Hils Miriam , Swiontek Kyra , Flatley Andrew , Janowski Robert , Mirzaei Mohammadali Khan , Dittmar Michael , Chakrapani Neera , Desai Mahesh S. , Eyerich Stefanie , Deng Li , Niessing Dierk , Fischer Konrad , Feederle Regina , Blank Simon , Schmidt-Weber Carsten B. , Hilger Christiane , Biedermann Tilo , Ohnmacht Caspar
Published: August 2022

The alpha-Gal epitope (α-Gal) with the determining element galactose-α1,3-galactose can lead to clinically relevant allergic reactions and rejections in xenotransplantation. These immune reactions can develop because humans are devoid of this carbohydrate due to evolutionary loss of the enzyme α1,3-galactosyltransferase (GGTA1). In addition, up to 1% of human IgG antibodies are directed against α-Gal, but the stimulus for the induction of anti-α-Gal antibodies is still unclear. Commensal bacteria have been suggested as a causal factor for this induction as α-Gal binding tools such as lectins were found to stain cultivated bacteria isolated from the intestinal tract. Currently available tools for the detection of the definite α-Gal epitope, however, are cross-reactive, or have limited affinity and, hence, offer restricted possibilities for application. In this study, we describe a novel monoclonal IgG1 antibody (27H8) specific for the α-Gal epitope. The 27H8 antibody was generated by immunization of Ggta1 knockout mice and displays a high affinity towards synthetic and naturally occurring α-Gal in various applications. Using this novel tool, we found that intestinal bacteria reported to be α-Gal positive cannot be stained with 27H8 questioning whether commensal bacteria express the native α-Gal epitope at all.
Serum amyloid A, a host-derived DAMP in pregnancy?
Authors: Lin Yi-kai , Zhu Ping , Wang Wang-sheng , Sun Kang
Published: August 2022

Serum amyloid A (SAA) is one of the acute phase proteins released primarily from the liver in response to infection, inflammation and trauma. Emerging evidence indicates that SAA may function as a host-derived damage-associated molecular pattern (DAMP) protein to sense danger signals in pregnancy. The plasma SAA levels in maternal circulation are significantly increased in normal parturition, particularly in postpartum, as well as in gestational disorders such as premature preterm rupture of membranes, pre-eclampsia, gestational diabetes, and recurrent spontaneous abortion. It is likely that SAA acts as a non-specific DAMP molecule in response to inflammation and trauma experienced under these conditions. Notably, SAA can also be synthesized locally in virtually all gestational tissues. Within these gestational tissues, under the induction by bacterial products, pro-inflammatory cytokines and stress hormone glucocorticoids, SAA may exert tissue-specific effects as a toll-like receptor 4 (TLR4)-sensed DAMP molecule. SAA may promote parturition through stimulation of inflammatory reactionsviainduction of pro-inflammatory cytokines, chemokines, adhesion molecules and prostaglandins in the uterus, fetal membranes and placenta. In the fetal membranes, SAA may also facilitate membrane rupture through induction of matrix metalloproteases (MMPs)- and autophagy-mediated collagen breakdown and attenuation of lysyl oxidase-mediated collagen cross-linking. SAA synthesized in extravillous trophoblasts may promote their invasiveness into the endometrium in placentation. Here, we summarized the current understanding of SAA in pregnancy with an aim to stimulate in-depth investigation of SAA in pregnancy, which may help better understand how inflammation is initiated in gestational tissues in both normal and abnormal pregnancies.
Metabolic heterogeneity caused by HLA-DRB1*04:05 and protective effect of inosine on autoimmune hepatitis
Authors: Yang Fan , Zhou Leyu , Shen Yi , Zhao Shenglan , Zheng Yanyi , Men Ruoting , Fan Xiaoli , Yang Li
Published: August 2022

Autoimmune hepatitis (AIH) is an autoimmune disease caused by disruption of liver immune homeostasis. Genetic studies have revealed the predisposition of AIH with the human leukocyte antigen (HLA) region. Recently, metabolomics integrated with genomics has identified many genetic loci of biomedical interest. However, there is no related report in AIH. In the present study, we found that HLA-DRB1*04:05 was linked to the clinical features and prognosis of AIH in Chinese patients. Furthermore, our patients were divided into DRB1*04:05 positive and DRB1*04:05 negative groups and the metabolic profiling was done by HPLC/MS. We chose inosine, one of the highly altered metabolites, to explore the effect on an acute severe hepatitis murine model. The results showed that inosine treatment attenuated hepatocyte apoptosis, enhanced antioxidant ability and inhibited the activation and glycolysis of CD4+ T cell. We propose that inosine participates in the regulation of AIH through its protective effect on hepatocytes and inhibition of overactivated immune cells, which might provide a potential novel approach in treating acute form of AIH.
Magnetic fluid sealing status estimation based on acoustic emission monitoring
Authors: Chen Nuo , Li Decai , Xue Jinyu , Yin Yuan , Li Yanwen
Published: August 2022

The aim of the study was to analyze acoustic emission (AE) signals generated in different magnetic fluid sealing processes to estimate the status of the seal. Based on a magnetic fluid rotary sealing experimental setup, the AE sensor is respectively attached to the shell at the corresponding position of the seal, and the external pressure is applied to the magnetic fluid seal by a gas supply system. As the pressure gradually increases, the magnetic fluid sealing rings under different pole teeth are gradually broken, and processes such as pressure transfer between the seal stages occur. These processes generate different AE signals, which are collected by the sensors. The results show that the root-mean-square values of AE signals generated at the moment of sealing failure are different from those generated before and after. At the same time, by analyzing the characteristic values of AE signals generated in the whole process, we can infer the time when the rupture begins under different pole pieces and further estimate the status of the magnetic fluid seal. For the first time, this research demonstrates the experimental and data analysis procedures of AE technology for magnetic fluid seals.
Gut microbiota in women with gestational diabetes mellitus has potential impact on metabolism in pregnant mice and their offspring
Authors: Qin Shengtang , Wang Yutong , Wang Shuxian , Ning Bohan , Huai Jing , Yang Huixia
Published: August 2022

Studies have shown that gestational diabetes mellitus (GDM) is closely related to abnormalities in the gut microbiota, and the offspring of these women have an increased risk of diabetes. There is no direct evidence of whether bacteria in women with GDM colonize the intestinal tract of offspring and cause hyperglycemia. In this fecal microbiota transplantation (FMT), pregnant mouse model study, two groups of germ-free (GF) mice after FMT showed different colonization patterns of gut microbiota and phenotype. Compared with the control group (healthy-FMT), we found in the GDM-FMT group as a lower relative abundance of Akkermansia and Faecalibacterium; a lower content of short-chain fatty acids and naringenin in feces; an elevated blood glucose; an inflammatory factor expression (TNF-α, CXCL-15, and IL-6), and a hepatic fat deposition. In addition, the influence of the gut microbiota continued in offspring. The gut microbiota of the offspring of GDM-FMT mice was still different from that of the control group as a lower relative abundance of Akkermansia and Parvibacter; and a higher relative abundance of bacteria such as Oscillibacter, Romboutsia, and Harryflintia. In addition, the offspring of GDM-FMT mice had higher body weight and blood glucose levels than the control offspring.
The Inactivated gE/TK Gene-Deleted Vaccine Against Pseudorabies Virus Type II Confers Effective Protection in Mice and Pigs
Authors: Jin Yu-Lan , Yin Di , Xing Gang , Huang Yan-Ming , Fan Chun-Mei , Fan Cheng-Fei , Qiu Xiao-Huo , Dong Wei-Ren , Yan Yan , Gu Jin-Yan , Zhou Ji-Yong
Published: August 2022

The highly virulent and antigenic variant of Pseudorabies virus (PRV) that emerged from classical Bartha-K61-vaccinated pig herds has caused substantial economic losses to the swine industry in China since 2011. A safe and more effective vaccine is most desirable. In this study, a gE/TK gene-deficient PRV, namely, HD/c, was constructed based on a PRV type II DX strain isolated from a commercial vaccine-immunized farm and the HD/c-based inactivated vaccine was formulated and evaluated for its safety, immunogenicity, and protective efficacy in mice and piglets. The resulting PRV HD/c strain has a similar growth curve to the parental DX strain. After vaccination, the inactivated HD/c vaccine did not cause any visible gross pathological or histopathological changes in the tissues of mice and piglets and provided rapid and potent protection against the challenge of the classical and variant PRVs at day 21 post-vaccination in mice. A single immunization of 108.5TCID50 inactivated PRV HD/c strain-elicited robust immunity with high titer of neutralizing antibody and provided complete protection from the lethal challenge of PRV DX strain in piglets. These results indicated that the inactivated PRV HD/c vaccine with the deletion of gE/TK genes was a safe and effective PRV vaccine candidate for the control of PRV.
Therapeutic approaches to colorectal cancer via strategies based on modulation of gut microbiota
Authors: Chen Maohua , Lin Wei , Li Nan , Wang Qian , Zhu Shaomi , Zeng Anqi , Song Linjiang
Published: August 2022

Colorectal cancer (CRC) ranks third in terms of global incidence and second in terms of death toll among malignant tumors. Gut microbiota are involved in the formation, development, and responses to different treatments of CRC. Under normal physiological conditions, intestinal microorganisms protect the intestinal mucosa, resist pathogen invasion, and regulate the proliferation of intestinal mucosal cells via a barrier effect and inhibition of DNA damage. The composition of gut microbiota and the influences of diet, drugs, and gender on the composition of the intestinal flora are important factors in the early detection of CRC and prediction of the results of CRC treatment. Regulation of gut microbiota is one of the most promising new strategies for CRC treatment, and it is essential to clarify the effect of gut microbiota on CRC and its possible mechanisms to facilitate the prevention and treatment of CRC. This review discusses the role of gut microbiota in the pathogenesis of CRC, the potential of gut microbiota as biomarkers for CRC, and therapeutic approaches to CRC based on the regulation of gut microbiota. It might provide new ideas for the use of gut microbiota in the prevention and treatment of CRC in the near future and thus reduce the incidence of CRC.
Studies on the fitness characteristics of wMel- and wAlbB-introgressed Aedes aegypti (Pud) lines in comparison with wMel- and wAlbB-transinfected Aedes aegypti (Aus) and wild-type Aedes aegypti (Pud) lines
Authors: Sadanandane Candasamy , Gunasekaran Kasinathan , Panneer Devaraju , Subbarao Sarala K. , Rahi Manju , Vijayakumar Balakrishnan , Athithan Velan , Sakthivel Annamalai , Dinesh Sundaram , Jambulingam Purushothaman
Published: August 2022

Wolbachia, an intracellular maternally transmitted endosymbiont, has been shown to interfere with the replication of dengue virus inAedes aegyptimosquitoes. TheWolbachia-transinfectedAe. aegyptihas been currently released in many countries to test its effectiveness in preventing the transmission of dengue virus. ICMR-Vector Control Research Centre in collaboration with World Mosquito Program Monash University, Australia, has generated two newWolbachia-introgressedAe. aegyptiPuducherry (Pud) linesviabackcrossingAe. aegyptifemales of Australian (Aus) strains, infected withwMel andwAlbBWolbachiawith wild-typeAe. aegyptiPuducherry (Pud) males.Wolbachiainfections are known to induce a fitness cost and confer benefit on the host mosquito populations that will influence spread of theWolbachiainto native wild mosquito populations during the field release. Hence, the induced fitness cost or benefit/advantage in the two newly generatedAe. aegypti(Pud) lines was assessed in the laboratory in comparison with the wild-typeAe. aegypti(Pud) strain. In addition, maternal transmission (MT) efficiency, induced cytoplasmic incompatibility (CI), and insecticide resistance status of the two (Pud) lines were determined to assess the likely frequency ofwMel andwAlbB infections in the native wild population after field invasion. The study shows thatwMel andwAlbB infections did not induce any fitness cost on the two newly generated (Pud) lines. Rather, in terms of wing length, fecundity, egg hatch rate, and adult survival, theWolbachiaintrogression conferred fitness benefits on the (Pud) lines compared to uninfectedWolbachiafree wildAe. aegyptipopulation.wMel andwAlbB exhibited a high maternal transmission (99–100%) and induced nearly complete (98–100%) cytoplasmic incompatibility. Both the (Pud) lines were resistant to deltamethrin, malathion, DDT, and temephos, and the level of resistance was almost the same between the two lines as in the wild type. Overall, the stable association ofwMel andwAlbB established withAe. aegyptiand the reproductive advantages of the (Pud) lines encourage a pilot release in the field for population replacement potential.
Selenium-enriched Bifidobacterium longum DD98 effectively ameliorates dextran sulfate sodium-induced ulcerative colitis in mice
Authors: Hu Yongjia , Jin Xueli , Gao Fei , Lin Ting , Zhu Hui , Hou Xiao , Yin Yu , Kan Shidong , Chen Daijie
Published: August 2022

The pathogenesis of ulcerative colitis (UC) is complicated with impaired intestinal epithelial barrier and imbalanced gut microbiota. Both selenium and probiotics have shown effects in regulating intestinal flora and ameliorating UC. The objective of this study is to investigate the alleviating effects of Selenium-enriched Bifidobacterium longum DD98 (Se-B. longum DD98) on dextran sulfate sodium (DSS)-induced colitis in mice and explore the underlying mechanism. After treatment of B. longum DD98, Se-B. longum DD98, and sulfasalazine for 3 weeks, the disease severity of UC mice was decreased, with colon lengthened and pathological phenotype improved. The expression of pro-inflammatory cytokines and oxidative stress parameters were also decreased. Thus, Se-B. longum DD98 showed a stronger effect on relieving the aforementioned symptoms caused by DSS-induced colitis. Exploration of the potential mechanism demonstrated that Se-B. longum DD98 showed higher activities to suppress the inflammatory response by inhibiting the activation of the toll-like receptor 4 (TLR4), compared to B. longum DD98 and sulfasalazine. Se-B. longum DD98 also significantly improved the intestinal barrier integrity by increasing the expression of tight junction proteins including ZO-1 and occludin. 16S rDNA sequencing analyses showed that Se-B. longum DD98 improved the diversity of the intestinal flora and promoted the abundance of health-benefiting taxa including Lachnospiraceae, Lactobacillaceae, and Prevotellaceae in family level. In conclusion, compared to B. longum DD98 and sulfasalazine, Se-B. longum DD98 showed stronger therapeutic effects on DSS-induced colitis in mice and might be a promising candidate for the treatment of UC.
Efficacy of simultaneous hexavalent chromium biosorption and nitrogen removal by the aerobic denitrifying bacterium Pseudomonas stutzeri YC-34 from chromium-rich wastewater
Authors: Yang Keyin , Bu Huijun , Zhang Ying , Yu Hongxia , Huang Sining , Ke Lixia , Hong Pei
Published: August 2022

The impact of high concentrations of heavy metals and the loss of functional microorganisms usually affect the nitrogen removal process in wastewater treatment systems. In the study, a unique auto-aggregating aerobic denitrifier (Pseudomonas stutzeri strain YC-34) was isolated with potential applications for Cr(VI) biosorption and reduction. The nitrogen removal efficiency and denitrification pathway of the strain were determined by measuring the concentration changes of inorganic nitrogen during the culture of the strain and amplifying key denitrification functional genes. The changes in auto-aggregation index, hydrophobicity index, and extracellular polymeric substances (EPS) characteristic index were used to evaluate the auto-aggregation capacity of the strain. Further studies on the biosorption ability and mechanism of cadmium in the process of denitrification were carried out. The changes in tolerance and adsorption index of cadmium were measured and the micro-characteristic changes on the cell surface were analyzed. The strain exhibited excellent denitrification ability, achieving 90.58% nitrogen removal efficiency with 54 mg/L nitrate-nitrogen as the initial nitrogen source and no accumulation of ammonia and nitrite-nitrogen. Thirty percentage of the initial nitrate-nitrogen was converted to N2, and only a small amount of N2O was produced. The successful amplification of the denitrification functional genes, norS, norB, norR, and nosZ, further suggested a complete denitrification pathway from nitrate to nitrogen. Furthermore, the strain showed efficient aggregation capacity, with the auto-aggregation and hydrophobicity indices reaching 78.4 and 75.5%, respectively. A large amount of protein-containing EPS was produced. In addition, the strain effectively removed 48.75, 46.67, 44.53, and 39.84% of Cr(VI) with the initial concentrations of 3, 5, 7, and 10 mg/L, respectively, from the nitrogen-containing synthetic wastewater. It also could reduce Cr(VI) to the less toxic Cr(III). FTIR measurements and characteristic peak deconvolution analysis demonstrated that the strain had a robust hydrogen-bonded structure with strong intermolecular forces under the stress of high Cr(VI) concentrations. The current results confirm that the novel denitrifier can simultaneously remove nitrogen and chromium and has potential applications in advanced wastewater treatment for the removal of multiple pollutants from sewage.
Designing a synthetic microbial community devoted to biological control: The case study of Fusarium wilt of banana
Authors: Prigigallo Maria Isabella , Gómez-Lama Cabanás Carmen , Mercado-Blanco Jesús , Bubici Giovanni
Published: August 2022

Fusarium oxysporum f. sp. cubense (Foc) tropical race 4 (TR4) is threatening banana production because of its increasing spread. Biological control approaches have been widely studied and constitute interesting complementary measures to integrated disease management strategies. They have been based mainly on the use of single biological control agents (BCAs). In this study, we moved a step forward by designing a synthetic microbial community (SynCom) for the control of Fusarium wilt of banana (FWB). Ninety-six isolates of Pseudomonas spp., Bacillus spp., Streptomyces spp., and Trichoderma spp. were obtained from the banana rhizosphere and selected in vitro for the antagonism against Foc TR4. In pot experiments, a large community such as SynCom 1.0 (44 isolates with moderate to high antagonistic activity) or a small one such as SynCom 1.1 (seven highly effective isolates) provided similar disease control (35% symptom severity reduction). An in vitro study of the interactions among SynCom 1.1 isolates and between them and Foc revealed that beneficial microorganisms not only antagonized the pathogen but also some of the SynCom constituents. Furthermore, Foc defended itself by antagonizing the beneficial microbes. We also demonstrated that fusaric acid, known as one of the secondary metabolites of Fusarium species, might be involved in such an interaction. With this knowledge, SynCom 1.2 was then designed with three isolates: Pseudomonas chlororaphis subsp. piscium PS5, Bacillus velezensis BN8.2, and Trichoderma virens T2C1.4. A non-simultaneous soil application of these isolates (to diminish cross-inhibition) delayed FWB progress over time, with significant reductions in incidence and severity. SynCom 1.2 also performed better than two commercial BCAs, BioPak® and T-Gro. Eventually, SynCom 1.2 isolates were characterized for several biocontrol traits and their genome was sequenced. Our data showed that assembling a SynCom for biocontrol is not an easy task. The mere mixtures of antagonists (e.g., SynCom 1.0 and 1.1) might provide effective biocontrol, but an accurate investigation of the interactions among beneficial microorganisms is needed to improve the results (e.g., SynCom 1.2). SynCom 1.2 is a valuable tool to be further developed for the biological control of FWB.
Cell-free supernatant of Bacillus velezensis suppresses mycelial growth and reduces virulence of Botrytis cinerea by inducing oxidative stress
Authors: Zhao Huanlan , Liu Kui , Fan Yezhen , Cao Jiacan , Li Huanghuan , Song Wu , Liu Yongsheng , Miao Min
Published: August 2022

As a notorious pathogenic fungus, Botrytis cinerea has been reported to infect more than 1400 species of plants and cause postharvest gray mold of numerous economic fruits, leading to substantial economic losses. Traditional chemical fungicides in pathogen control have potential issues regarding environmental pollution, disease resistance and human health. More safety and efficacious prevention technique of postharvest gray mold are in urgent demand. This study aims to investigate the potential function and mechanism of Bacillus velezensis to control gray mold for harvested fruits. The results showed that the cell-free supernatant (CFS) generated from B. velezensis strain A4 was able to inhibit spore germination, germ tube elongation and hyphal growth of B. cinerea in vitro, and impair the pathogenicity of B. cinerea on the four tested fruits. Further analysis demonstrated that CFS significantly reduced the expression of genes associated with growth and pathogenicity and weakened the ability of B. cinerea spores to penetrate plant cell walls in a dose-dependent manner. Moreover, the CFS destroyed the membrane of hyphae, resulting in exosmosis of cell contents and caused hyphal cells to accumulate excessive reactive oxygen species (ROS), leading to hyphal oxidative damage. Our findings indicate that B. velezensis CFS can damage B. cinerea mycelial cells by promoting excessive accumulation of ROS to realize its biological control function.