bluuebunny/crossref_metadata_2025 huggingface dataset:
RETRACTED: Extracellular Vesicles Carry lncRNA SNHG16 to Promote Metastasis of Breast Cancer Cells via the miR-892b/PPAPDC1A Axis
Authors: Xia Wenfei , Liu Yun , Cheng Teng , Xu Tao , Dong Menglu , Hu Xiaopeng
Published: June 2021

Breast cancer (BC) represents the most commonly diagnosed malignancy among women. Long non-coding RNAs (lncRNAs) can be transferred by extracellular vesicles (EVs) to participate in BC progression. This study demonstrated that SNHG16 expression was significantly increased in BC tissues and cells. Overexpression of SNHG16 promoted the migration, invasion, and epithelial–mesenchymal transition (EMT) of BC cells. SNHG16 was carried by EVs. Bioinformatics analysis predicted that SNHG16 regulated PPAPDC1A expression by sponging miR-892b, which was confirmed by RNA-fluorescence in situ hybridization (FISH), RT-qPCR, dual-luciferase gene reporter assay, and RNA immunoprecipitation (RIP). MDA-MB-157 and HS578T cells were transfected with pcDNA3.1-SNHG16, miR-892b-mimic, or si-PPAPDC1A for functional rescue experiments in vitro, and the cells were treated with MDA-MB-231 cell-derived EVs. The results confirmed that enhanced miR-892b expression partially eliminated the increase of migration, invasion, and EMT of BC cells mediated by SNHG16 or EVs. The lung metastasis model in nude mice was established by injecting HS578T cells via tail vein. The results showed that si-SNHG16 reduced the metastatic nodules and decreased the vimentin expression. In conclusion, EVs derived from BC cells transferred SNHG16 via the miR-892b/PPAPDC1A axis, thus promoting EMT, migration, and invasion of BC.
The Altered Anatomical Distribution of ACE2 in the Brain With Alzheimer’s Disease Pathology
Authors: Cui Huan , Su Si , Cao Yan , Ma Chao , Qiu Wenying
Published: June 2021

The whole world is suffering from the coronavirus disease 2019 (COVID-19) pandemic, induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) through angiotensin-converting enzyme 2 (ACE2). Neurological manifestations in COVID-19 patients suggested the invasion of SARS-CoV-2 into the central nervous system. The present study mapped the expression level of ACE2 in 12 brain regions through immunohistochemistry and detected ACE2 in endothelial cells and non-vascular cells. The comparison among brain regions found that pons, visual cortex, and amygdala presented a relatively high level of ACE2. In addition, this study demonstrates that the protein level of ACE2 was downregulated in the basal nucleus, hippocampus and entorhinal cortex, middle frontal gyrus, visual cortex, and amygdala of the brain with Alzheimer’s disease (AD) pathology. Collectively, our results suggested that ACE2 was expressed discriminatorily at different human brain regions, which was downregulated in the brain with AD pathology. This may contribute to a comprehensive understanding of the neurological symptoms caused by SARS-CoV-2 and provide clues for further research on the relationship between COVID-19 and AD.
The Replication Stress Response on a Narrow Path Between Genomic Instability and Inflammation
Authors: Técher Hervé , Pasero Philippe
Published: June 2021

The genome of eukaryotic cells is particularly at risk during the S phase of the cell cycle, when megabases of chromosomal DNA are unwound to generate two identical copies of the genome. This daunting task is executed by thousands of micro-machines called replisomes, acting at fragile structures called replication forks. The correct execution of this replication program depends on the coordinated action of hundreds of different enzymes, from the licensing of replication origins to the termination of DNA replication. This review focuses on the mechanisms that ensure the completion of DNA replication under challenging conditions of endogenous or exogenous origin. It also covers new findings connecting the processing of stalled forks to the release of small DNA fragments into the cytoplasm, activating the cGAS-STING pathway. DNA damage and fork repair comes therefore at a price, which is the activation of an inflammatory response that has both positive and negative impacts on the fate of stressed cells. These new findings have broad implications for the etiology of interferonopathies and for cancer treatment.
Cyclic Peptoid-Peptide Hybrids as Versatile Molecular Transporters
Authors: Herlan Claudine Nicole , Meschkov Anna , Schepers Ute , Bräse Stefan
Published: June 2021

Addressing intracellular targets is a challenging task that requires potent molecular transporters capable to deliver various cargos. Herein, we report the synthesis of hydrophobic macrocycles composed of both amino acids and peptoid monomers. The cyclic tetramers and hexamers were assembled in a modular approach using solid as well as solution phase techniques. To monitor their intracellular localization, the macrocycles were attached to the fluorophore Rhodamine B. Most molecular transporters were efficiently internalized by HeLa cells and revealed a specific accumulation in mitochondria without the need for cationic charges. The data will serve as a starting point for the design of further cyclic peptoid-peptide hybrids presenting a new class of highly efficient, versatile molecular transporters.
Parasitic Helminth-Derived microRNAs and Extracellular Vesicle Cargos as Biomarkers for Helminthic Infections
Authors: Mu Yi , McManus Donald P. , Gordon Catherine A. , Cai Pengfei
Published: June 2021

As an adaption to their complex lifecycles, helminth parasites garner a unique repertoire of genes at different developmental stages with subtle regulatory mechanisms. These parasitic worms release differential components such as microRNAs (miRNAs) and extracellular vesicles (EVs) as mediators which participate in the host-parasite interaction, immune regulation/evasion, and in governing processes associated with host infection. MiRNAs are small (~ 22-nucleotides) non-coding RNAs that regulate gene expression at the post-transcriptional level, and can exist in stable form in bodily fluids such as serum/plasma, urine, saliva and bile. In addition to reports focusing on the identification of miRNAs or in the probing of differentially expressed miRNA profiles in different development stages/sexes or in specific tissues, a number of studies have focused on the detection of helminth-derived miRNAs in the mammalian host circulatory system as diagnostic biomarkers. Extracellular vesicles (EVs), small membrane-surrounded structures secreted by a wide variety of cell types, contain rich cargos that are important in cell-cell communication. EVs have attracted wide attention due to their unique functional relevance in host-parasite interactions and for their potential value in translational applications such as biomarker discovery. In the current review, we discuss the status and potential of helminth parasite-derived circulating miRNAs and EV cargos as novel diagnostic tools.
Framing Good Food: Communicating Value of Community Food Initiatives in the Midst of a Food Crisis
Authors: Knezevic Irena
Published: June 2021

Community-embedded food initiatives exist in market economies, but make more-than-market contributions. They challenge the dominant, industrialized food system, while generating non-monetary benefits in their communities. Yet food policy, regulation, and public spending in much of the world is still framed by the values of market economy. Revenue, yield, and technological advancements remain key formal measurements of the wellbeing of food systems. Community-embedded food initiatives like small local businesses and non-profit organizations, are often committed to advancing social and environmental benefits of non-industrialized food, and they call for clearer recognition of their more-than-market contribution to community wellbeing. The Nourishing Communities network has worked with such initiatives for more than a decade, undertaking community-engaged research with practitioners across sectors. The network has found that these initiatives are impeded by a communication conundrum. On the one hand, they are expected (by funders, governments, and other institutions) to demonstrate their value using market-economy measurements and translating what they do into “social returns on investment.” On the other hand, many of those initiatives need non-market terminology to express the values that they espouse and generate. To balance these needs, Gibson-Graham’s framing of “diverse economies” can potentially offer a pathway to better communication and thus more accurate valuing of the work of such initiatives. Their notion of diverse economies offers endless opportunities to frame community food work as valuable in ways that go beyond market-economy measurements. As such, the diverse economies framing offers new possibilities for alternative food, and for more general discussions of social reform.
From Clinical Clues to Final Diagnosis: The Return of Detective Work to Clinical Medicine in Cardiac Amyloidosis
Authors: Sabbour Hani , Hasan Khwaja Yousuf , Al Badarin Firas , Alibazoglu Haluk , Rivard Andrew L. , Romany Ingy , Perlini Stefano
Published: June 2021

Cardiac amyloidosis is frequently misdiagnosed, denying patients the opportunity for timely and appropriate management of the disease. The purpose of this review and case studies is to raise awareness of the diagnostic “red flags” associated with cardiac amyloidosis and the currently available non-invasive strategies for diagnosis. The review focuses on the identification of one of the two main types of cardiac amyloidosis, transthyretin amyloid cardiomyopathy, and non-invasive tools to distinguish this from light-chain amyloidosis. A diagnostic algorithm centered around the use of non-invasive imaging and laboratory analysis is presented. The algorithm generates four differential diagnoses for patients presenting with signs and symptoms consistent with cardiac amyloidosis. Case examples are presented, representing the four potential outcomes of diagnosis using the algorithm. The review provides a guide on how to recognize the often-overlooked presentations of this disease in clinical practice. Non-invasive imaging techniques and diagnostic tools that do not require the involvement of a specialty center have allowed for the improved diagnosis of cardiac amyloidosis. Timely diagnosis of this life-threatening disease is essential for optimal management and it is imperative that clinicians have a high index of suspicion for patients presenting with “red flag” symptoms.
NRF2-Related Epigenetic Modifications in Cardiac and Vascular Complications of Diabetes Mellitus
Authors: Wang Jie , Xiao Mengjie , Wang Jie , Wang Shudong , Zhang Jingjing , Guo Yuanfang , Tang Yufeng , Gu Junlian
Published: June 2021

Diabetes mellitus (DM) is a highly prevalent chronic disease that is accompanied with serious complications, especially cardiac and vascular complications. Thus, there is an urgent need to identify new strategies to treat diabetic cardiac and vascular complications. Nuclear factor erythroid 2-related factor 2 (NRF2) has been verified as a crucial target for the prevention and treatment of diabetic complications. The function of NRF2 in the treatment of diabetic complications has been widely reported, but the role of NRF2-related epigenetic modifications remains unclear. The purpose of this review is to summarize the recent advances in targeting NRF2-related epigenetic modifications in the treatment of cardiac and vascular complications associated with DM. We also discuss agonists that could potentially regulate NRF2-associated epigenetic mechanisms. This review provides a better understanding of strategies to target NRF2 to protect against DM-related cardiac and vascular complications.
Distinguishing Benign and Malignant Thyroid Nodules and Identifying Lymph Node Metastasis in Papillary Thyroid Cancer by Plasma N-Glycomics
Authors: Zhang Zejian , Reiding Karli R. , Wu Jianqiang , Li Zepeng , Xu Xiequn
Published: June 2021

Background

Biomarkers are needed for patient stratification between benign thyroid nodules (BTN) and thyroid cancer (TC) and identifying metastasis in TC. Though plasma N-glycome profiling has shown potential in the discovery of biomarkers and can provide new insight into the mechanisms involved, little is known about it in TC and BTN. Besides, several studies have indicated associations between abnormal glycosylation and TC. Here, we aimed to explore plasma protein N-glycome of a TC cohort with regard to their applicability to serve as biomarkers.

Methods

Plasma protein N-glycomes of TC, BTN, and matched healthy controls (HC) were obtained using a robust quantitative strategy based on MALDI-TOF MS and included linkage-specific sialylation information.

Results

Plasma N-glycans were found to differ between BTN, TC, and HC in main glycosylation features, namely complexity, galactosylation, fucosylation, and sialylation. Four altered glycan traits, which were consecutively decreased in BTN and TC, and classification models based on them showed high potential as biomarkers for discrimination between BTN and TC (“moderately accurate” to “accurate”). Additionally, strong associations were found between plasma N-glycans and lymph node metastasis in TC, which added the accuracy of predicting metastasis before surgery to the existing method.

Conclusions

We comprehensively evaluated the plasma N-glycomic changes in patients with TC or BTN for the first time. We determined several N-glycan biomarkers, some of them have potential in the differential diagnosis of TC, and the others can help to stratify TC patients to low or high risk of lymph node metastasis. The findings enhanced the understanding of TC.
Challenges in Cytology Specimens With Hürthle Cells
Authors: Thodou Eleni , Canberk Sule , Schmitt Fernando
Published: June 2021

In fine-needle aspirations (FNA) of thyroid, Hürthle cells can be found in a broad spectrum of lesions, ranging from non-neoplastic conditions to aggressive malignant tumors. Recognize them morphologically, frequently represents a challenging for an adequately diagnosis and are associated with a significant interobserver variability. Although the limitations of the morphologic diagnosis still exist, the interpretation of the context where the cells appear and the recent advances in the molecular knowledge of Hürthle cells tumors are contributing for a more precise diagnosis. This review aims to describe the cytology aspects of all Hürthle cells neoplastic and non-neoplastic thyroid lesions, focusing on the differential diagnosis and reporting according to The Bethesda System for Reporting Thyroid Cytology (TBSRTC). New entities according to the latest World Health Organization (WHO) classification are included, as well as an update of the current molecular data.
Identification and Comparative Analysis of Long Non-coding RNAs in High- and Low-Fecundity Goat Ovaries During Estrus
Authors: Li Yaokun , Xu Xiangping , Deng Ming , Zou Xian , Zhao Zhifeng , Huang Sixiu , Liu Dewu , Liu Guangbin
Published: June 2021

The ovary is the most important reproductive organ in goats and directly affects the fecundity. Long non-coding RNAs (lncRNAs) are involved in the biological process of oocyte maturation. However, in the context of reproduction in goats, few studies have explored the regulation of lncRNAs. Therefore, we herein used the ovaries of high and low fecundity Leizhou black goats to identify differentially expressed lncRNAs (DElncRNAs) by high-throughput RNA sequencing; moreover, we analyzed the target genes of lncRNAs by functional annotation to explore the role of DElncRNAs in ovarian development. Twenty DElncRNAs were identified, of which six were significantly upregulated and 14 were significantly downregulated in high fecundity goats. Gene Ontology analyses suggested that MSTRG.3782 positively influences the expression of the corresponding gene API5, exerting regulative effects on the development of follicles, through which litter size might show variations. The target gene KRR1 of ENSCHIT00000001883 is significantly enriched in cell components, and ENSCHIT00000001883 may regulate cell growth and thus affect follicular development. Further, as per Kyoto Encyclopedia of Genes and Genomes pathway analyses, MSTRG.2938 was found to be significantly enriched, and we speculate that MSTRG.2938 could regulate ribosomal biogenesis in the pre-snoRNP complex as well as cell transformation in eukaryotes. Quantitative real-time PCR results were consistent with sequencing data. To conclude, our research results indicate that some lncRNAs play a key role in regulating follicle development and cell growth during goat’ s ovarian development.
Transcriptional Profiling of Monocytes Deficient in Nuclear Orphan Receptors NR4A2 and NR4A3 Reveals Distinct Signalling Roles Related to Antigen Presentation and Viral Response
Authors: Phelan David E. , Shigemura Masahiko , Aldhafiri Sarah , Mota Catarina , Hall Thomas J. , Sznajder Jacob I. , Murphy Evelyn P. , Crean Daniel , Cummins Eoin P.
Published: June 2021

The nuclear receptor sub-family 4 group A (NR4A) family are early response genes that encode proteins that are activated in several tissues/cells in response to a variety of stressors. The NR4A family comprises NR4A1, NR4A2 and NR4A3 of which NR4A2 and NR4A3 are under researched and less understood, particularly in the context of immune cells. NR4A expression is associated with multiple diseases e.g. arthritis and atherosclerosis and the development of NR4A-targetting molecules as therapeutics is a current focus in this research field. Here, we use a combination of RNA-sequencing coupled with strategic bioinformatic analysis to investigate the down-stream effects of NR4A2 and NR4A3 in monocytes and dissect their common and distinct signalling roles. Our data reveals that NR4A2 and NR4A3 depletion has a robust and broad-reaching effect on transcription in both the unstimulated state and in the presence of LPS. Interestingly, many of the genes affected were present in both the unstimulated and stimulated states revealing a previously unappreciated role for the NR4As in unstimulated cells. Strategic clustering and bioinformatic analysis identified both distinct and common transcriptional roles for NR4A2 and NR4A3 in monocytes. NR4A2 notably was linked by both bioinformatic clustering analysis and transcription factor interactome analysis to pathways associated with antigen presentation and regulation of MHC genes. NR4A3 in contrast was more closely linked to pathways associated with viral response. Functional studies further support our data analysis pointing towards preferential/selective roles for NR4A2 in the regulation of antigen processing with common roles for NR4A2 and NR4A3 evident with respect to cell migration. Taken together this study provides novel mechanistic insights into the role of the enigmatic nuclear receptors NR4A2 and NR4A3 in monocytes.
Resveratrol Alleviates Levodopa-Induced Dyskinesia in Rats
Authors: Zheng Chang-Qing , Fan Hong-Xia , Li Xiao-Xian , Li Jing-Jie , Sheng Shuo , Zhang Feng
Published: June 2021

Dyskinesia is a serious complication of Parkinson’s disease during levodopa (L-DOPA) treatment. The pathophysiology of L-DOPA-induced dyskinesia (LID) is complex and not fully illuminated. At present, treatment of dyskinesia is quite limited. Recent studies demonstrated neuroinflammation plays an important role in development of LID. Thus, inhibition of neuroinflammation might open a new avenue for LID treatment. Resveratrol (RES) is the most well-known polyphenolic stilbenoid and verified to possess a large variety of biological activities. DA neurotoxicity was assessed via behavior test and DA neuronal quantification. The movement disorders of dyskinesia were detected by the abnormal involuntary movements scores analysis. Effects of RES on glial cells-elicited neuroinflammation were also explored. Data showed that RES attenuated dyskinesia induced by L-DOPA without affecting L-DOPA’s anti-parkinsonian effects. Furthermore, RES generated neuroprotection against long term treatment of L-DOPA-induced DA neuronal damage. Meanwhile, RES reduced protein expression of dyskinesia molecular markers, ΔFOS B and ERK, in the striatum. Also, there was a strong negative correlation between DA system damage and ΔFOS B level in the striatum. In addition, RES inhibited microglia and astroglia activation in substantia nigra and subsequent inflammatory responses in the striatum during L-DOPA treatment. RES alleviates dyskinesia induced by L-DOPA and these beneficial effects are closely associated with protection against DA neuronal damage and inhibition of glial cells-mediated neuroinflammatory reactions.
Highly Sensitized Patients Are Well Served by Receiving a Compatible Organ Offer Based on Acceptable Mismatches
Authors: Heidt Sebastiaan , Haasnoot Geert W. , van der Linden-van Oevelen Marissa J. H. , Claas Frans H. J.
Published: June 2021

Highly sensitized kidney patients accrue on the transplant waiting list due to their broad immunization against non-self Human Leucocyte Antigens (HLA). Although challenging, the best option for highly sensitized patients is transplantation with a crossmatch negative donor without any additional therapeutic intervention. The Eurotransplant Acceptable Mismatch (AM) program was initiated more than 30 years ago with the intention to increase the chance for highly sensitized patients to be transplanted with such a compatible donor. The AM program allows for enhanced transplantation to this difficult to transplant patient group by allocating deceased donor kidneys on the basis of a match with the recipient’s own HLA antigens in combination with predefined acceptable antigens. Acceptable antigens are those HLA antigens towards which the patients has never formed antibodies, as determined by extensive laboratory testing. By using this extended HLA phenotype for allocation and giving priority whenever a compatible donor organ becomes available, organ offers are made for roughly 80% of patients in this program. Up till now, more than 1700 highly sensitized patients have been transplanted through the AM program. Recent studies have shown that the concept of acceptable mismatches being truly immunologically acceptable holds true for both rejection rates and long-term graft survival. Patients that were transplanted through the AM program had a similar rejection incidence and long-term graft survival rates identical to non-sensitized patients transplanted through regular allocation. However, a subset of patients included in the AM program does not receive an organ offer within a reasonable time frame. As these are often patients with a rare HLA phenotype in comparison to the Eurotransplant donor population, extension of the donor pool for these specific patients through further European collaboration would significantly increase their chances of being transplanted. For those patients that will not benefit from such strategy, desensitization is the ultimate solution.
High Glucose Enhances Cytotoxic T Lymphocyte-Mediated Cytotoxicity
Authors: Zhu Jie , Yang Wenjuan , Zhou Xiangda , Zöphel Dorina , Soriano-Baguet Leticia , Dolgener Denise , Carlein Christopher , Hof Chantal , Zhao Renping , Ye Shandong , Schwarz Eva C. , Brenner Dirk , Prates Roma Leticia , Qu Bin
Published: June 2021

Cytotoxic T lymphocytes (CTLs) are key players to eliminate tumorigenic or pathogen-infected cells using lytic granules (LG) and Fas ligand (FasL) pathways. Depletion of glucose leads to severely impaired cytotoxic function of CTLs. However, the impact of excessive glucose on CTL functions still remains largely unknown. Here we used primary human CD8+ T cells, which were stimulated by CD3/CD28 beads and cultured in medium either containing high glucose (HG, 25 mM) or normal glucose (NG, 5.6 mM). We found that in HG-CTLs, glucose uptake and glycolysis were enhanced, whereas proliferation remained unaltered. Furthermore, CTLs cultured in HG exhibited an enhanced CTL killing efficiency compared to their counterparts in NG. Unexpectedly, expression of cytotoxic proteins (perforin, granzyme A, granzyme B and FasL), LG release, cytokine/cytotoxic protein release and CTL migration remained unchanged in HG-cultured CTLs. Interestingly, additional extracellular Ca2+ diminished HG-enhanced CTL killing function. Our findings suggest that in an environment with excessive glucose, CTLs could eliminate target cells more efficiently, at least for a certain period of time, in a Ca2+-dependent manner.
Proteomic and Biological Analysis of an In Vitro Human Endothelial System in Response to Drug Anaphylaxis
Authors: Yuste-Montalvo Alma , Fernandez-Bravo Sergio , Oliva Tamara , Pastor-Vargas Carlos , Betancor Diana , Goikoetxea María José , Laguna José Julio , López Juan Antonio , Alvarez-Llamas Gloria , Cuesta-Herranz Javier , Martin-Lorenzo Marta , Esteban Vanesa
Published: June 2021

Anaphylaxis is a life-threatening systemic hypersensitivity reaction. During anaphylaxis, mediator release by effector cells causes endothelial barrier breakdown, increasing vascular permeability and leakage of fluids, which may lead to tissue edema. Although endothelial cells (ECs) are key players in this context, scant attention has been paid to the molecular analysis of the vascular system, and further analyses of this cell type are necessary, especially in humans. The protein expression pattern of human microvascular ECs was analyzed in response to sera from anaphylactic patients (EC-anaphylaxis) and sera from non-allergic subjects (EC-control) after 2 hours of contact. Firstly, a differential quantitative proteomic analysis of the protein extracts was performed by mass spectrometry using an isobaric labeling method. Second, the coordinated behavior of the identified proteins was analyzed using systems biology analysis (SBA). The proteome of the EC-anaphylaxis system showed 7,707 proteins, of which 1,069 were found to be significantly altered between the EC-control and EC-anaphylaxis groups (p-value < 0.05). Among them, a subproteome of 47 proteins presented a high rate of change (|ΔZq| ≥ 3). This panel offers an endothelial snapshot of the anaphylactic reaction. Those proteins with the highest individual changes in abundance were hemoglobin subunits and structural support proteins. The interacting network analysis of this altered subproteome revealed that the coagulation and complement systems are the main biological processes altered in the EC-anaphylactic system. The comprehensive SBA resulted in 5,512 functional subcategories (biological processes), 57 of which were significantly altered between EC-control and EC-anaphylaxis. The complement system, once again, was observed as the main process altered in the EC system created with serum from anaphylactic patients. Findings of the current study further our understanding of the underlying pathophysiological mechanisms operating in anaphylactic reactions. New target proteins and relevant signaling pathways operating in thein vitroendothelial-serum system have been identified. Interestingly, our results offer a protein overview of the micro-EC-anaphylaxis environment. The relevance of the coagulation, fibrinolytic, contact and complement systems in human anaphylaxis is described. Additionally, the untargeted high-throughput analysis used here is a novel approach that reveals new pathways in the study of the endothelial niche in anaphylaxis.
Current Understanding of IL-37 in Human Health and Disease
Authors: Su Zhangci , Tao Xiaoan
Published: June 2021

IL-37 is a recently discovered cytokine in the IL-1 family exerting broad protective effects on inflammatory diseases, autoimmune diseases, and cancer. Immune and non-immune cells produce the IL-37 precursor upon pro-inflammatory stimuli. Intracellularly, caspase-1 cleaves and activates IL-37, and its mature form binds to Smad3; this complex translocates into the nucleus where it suppresses cytokine production, consequently reducing inflammation. Extracellularly, IL-37 forms a complex with IL-18Rα and IL-1R8 (formerly TIR8 or SIGIRR) that transduces anti-inflammatory signals by the suppression of NF-κB and MAPK and the activation of Mer-PTEN-DOK pathways. During inflammation, IL-37 suppresses the expression of several pro-inflammatory cytokine in favor to the expression of the anti-inflammatory ones by the regulation of macrophage polarization, lipid metabolism, inflammasome function, TSLP synthesis and miRNAs function. Moreover, IL-37 not only regulates the innate and acquired immunity, but also improves aging-associated immunosenescence. Furthermore, IL-37 exerts an inhibitory effect on tumor angiogenesis and metastasis, and progression. Finally, IL-37 may have a potential ability to reduce excessive inflammation since it is aberrantly expressed in patients with inflammatory diseases, autoimmune diseases, and cancer, thus, it may be used as a marker for different types of diseases. Therefore, this review provides an updated view of the role of IL-37 in human health and disease, and discusses the potential of IL-37 as a therapeutic target and biomarker in inflammatory diseases, autoimmune diseases, and cancer.
Understanding Fatigue in Sjögren’s Syndrome: Outcome Measures, Biomarkers and Possible Interventions
Authors: Mæland Elisabeth , Miyamoto Samira T. , Hammenfors Daniel , Valim Valeria , Jonsson Malin V.
Published: June 2021

Sjögren’s syndrome (SS) is an autoimmune disease affecting the salivary and lacrimal glands. Symptoms range from dryness to severe extra-glandular disease involving manifestations in the skin, lungs, nervous system, and kidney. Fatigue occurs in 70% of patients, characterizing primary SS (pSS) and significantly impacting the patient’s quality of life. There are some generic and specific instruments used to measure fatigue in SS. The mechanisms involved with fatigue in SS are still poorly understood, but it appears fatigue signaling pathways are more associated with cell protection and defense than with pro-inflammatory pathways. There are no established pharmacological treatment options for fatigue in pSS. So far, exercise and neuromodulation techniques have shown positive effects on fatigue in pSS. This study briefly reviews fatigue in pSS, with special attention to outcome measures, biomarkers, and possible treatment options.
Conversion of Anergic T Cells Into Foxp3- IL-10+ Regulatory T Cells by a Second Antigen Stimulus In Vivo
Authors: Thomann Anna Sophie , Schneider Theresa , Cyran Laura , Eckert Ina Nathalie , Kerstan Andreas , Lutz Manfred B.
Published: June 2021

T cell anergy is a common mechanism of T cell tolerance. However, although anergic T cells are retained for longer time periods in their hosts, they remain functionally passive. Here, we describe the induction of anergic CD4+T cellsin vivoby intravenous application of high doses of antigen and their subsequent conversion into suppressive Foxp3-IL-10+Tr1 cells but not Foxp3+Tregs. We describe the kinetics of up-regulation of several memory-, anergy- and suppression-related markers such as CD44, CD73, FR4, CD25, CD28, PD-1, Egr-2, Foxp3 and CTLA-4 in this process. The conversion into suppressive Tr1 cells correlates with the transient intracellular CTLA-4 expression and required the restimulation of anergic cells in a short-term time window. Restimulation after longer time periods, when CTLA-4 is down-regulated again retains the anergic state but does not lead to the induction of suppressor function. Our data require further functional investigations but at this stage may suggest a role for anergic T cells as a circulating pool of passive cells that may be re-activated into Tr1 cells upon short-term restimulation with high and systemic doses of antigen. It is tentative to speculate that such a scenario may represent cases of allergen responses in non-allergic individuals.
Light Regulation of Phytoplankton Growth in San Francisco Bay Studied Using a 3D Sediment Transport Model
Authors: Wang Zhengui , Chai Fei , Xue Huijie , Wang Xiao Hua , Zhang Yinglong J. , Dugdale Richard , Wilkerson Frances
Published: June 2021

In San Francisco Bay (SFB), light availability is largely determined by the concentration of suspended particulate matter (SPM) in the water column. SPM exhibits substantial variation with time, depth, and location. To study how SPM influences light and phytoplankton growth, we coupled a sediment transport model with a hydrodynamic model and a biogeochemical model. The coupled models were used to simulate conditions for the year of 2011 with a focus on northern SFB. For comparison, two simulations were conducted with ecosystem processes driven by SPM concentrations supplied by the sediment transport model and by applying a constant SPM concentration of 20 mg l–1. The sediment transport model successfully reproduced the general pattern of SPM variation in northern SFB, which improved the chlorophyll-a simulation resulting from the biogeochemical model, with vertically integrated primary productivity varying greatly, from 40 g[C] m–2year–1over shoals to 160 g[C] m–2year–1in the deep channel. Primary productivity in northern SFB is influenced by euphotic zone depth (Ze). Our results show thatZein shallow water regions (<2 m) is mainly determined by water depth, whileZein deep water regions is controlled by SPM concentration. As a result,Zehas low (high) values in shallow (deep) water regions. Large (small) differences in primary productivity exist between the two simulations in deep (shallow) water regions. Furthermore, we defined a new parameterFlightfor “averaged light limitation” in the euphotic zone. The averaged chlorophyll-a concentration in the euphotic zone andFlightshare a similar distribution such that both have high (low) values in shallow (deep) water regions. Our study demonstrates that light is a critical factor in regulating the phytoplankton growth in northern SFB, and a sediment transport model improves simulation of light availability in the water column.
COVID-19 and Influenza Co-infection: A Systematic Review and Meta-Analysis
Authors: Dadashi Masoud , Khaleghnejad Saeedeh , Abedi Elkhichi Parisa , Goudarzi Mehdi , Goudarzi Hossein , Taghavi Afsoon , Vaezjalali Maryam , Hajikhani Bahareh
Published: June 2021

Background and Aim: Co-infection of COVID-19 with other respiratory pathogens which may complicate the diagnosis, treatment, and prognosis of COVID-19 emerge new concern. The overlap of COVID-19 and influenza, as two epidemics at the same time can occur in the cold months of the year. The aim of current study was to evaluate the rate of such co-infection as a systematic review and meta-analysis.

Methods: A systematic literature search was performed on September 28, 2019 for original research articles published in Medline, Web of Science, and Embase databases from December 2019 to September 2020 using relevant keywords. Patients of all ages with simultaneous COVID-19 and influenza were included. Statistical analysis was performed using STATA 14 software.

Results: Eleven prevalence studies with total of 3,070 patients with COVID-19, and 79 patients with concurrent COVID-19 and influenza were selected for final evaluation. The prevalence of influenza infection was 0.8% in patients with confirmed COVID-19. The frequency of influenza virus co-infection among patients with COVID-19 was 4.5% in Asia and 0.4% in the America. Four prevalence studies reported the sex of patients, which were 30 men and 31 women. Prevalence of co-infection with influenza in men and women with COVID-19 was 5.3 and 9.1%, respectively. Eight case reports and 7 case series with a total of 123 patients with COVID-19 were selected, 29 of them (16 men, 13 women) with mean age of 48 years had concurrent infection with influenza viruses A/B. Fever, cough, and shortness of breath were the most common clinical manifestations. Two of 29 patients died (6.9%), and 17 out of 29 patients recovered (58.6%). Oseltamivir and hydroxychloroquine were the most widely used drugs used for 41.4, and 31% of patients, respectively.

Conclusion: Although a low proportion of COVID-19 patients have influenza co-infection, however, the importance of such co-infection, especially in high-risk individuals and the elderly, cannot be ignored. We were unable to report the exact rate of simultaneous influenza in COVID-19 patients worldwide due to a lack of data from several countries. Obviously, more studies are needed to evaluate the exact effect of the COVID-19 and influenza co-infection in clinical outcomes.
Wide Distribution and Specific Resistance Pattern to Third-Generation Cephalosporins of Enterobacter cloacae Complex Members in Humans and in the Environment in Guadeloupe (French West Indies)
Authors: Pot Matthieu , Reynaud Yann , Couvin David , Ducat Célia , Ferdinand Séverine , Gravey François , Gruel Gaëlle , Guérin François , Malpote Edith , Breurec Sébastien , Talarmin Antoine , Guyomard-Rabenirina Stéphanie
Published: June 2021

Species belonging to Enterobacter cloacae complex have been isolated in numerous environments and samples of various origins. They are also involved in opportunistic infections in plants, animals, and humans. Previous prospection in Guadeloupe (French West Indies) indicated a high frequency of E. cloacae complex strains resistant to third-generation cephalosporins (3GCs) in a local lizard population (Anolis marmoratus), but knowledge of the distribution and resistance of these strains in humans and the environment is limited. The aim of this study was to compare the distribution and antibiotic susceptibility pattern of E. cloacae complex members from different sources in a “one health” approach and to find possible explanations for the high level of resistance in non-human samples. E. cloacae complex strains were collected between January 2017 and the end of 2018 from anoles, farm animals, local fresh produce, water, and clinical human samples. Isolates were characterized by the heat-shock protein 60 gene-fragment typing method, and whole-genome sequencing was conducted on the most frequent clusters (i.e., C-VI and C-VIII). The prevalence of resistance to 3GCs was relatively high (56/346, 16.2%) in non-human samples. The associated resistance mechanism was related to an AmpC overproduction; however, in human samples, most of the resistant strains (40/62) produced an extended-spectrum beta-lactamase. No relation was found between resistance in isolates from wild anoles (35/168) and human activities. Specific core-genome phylogenetic analysis highlighted an important diversity in this bacterial population and no wide circulation among the different compartments. In our setting, the mutations responsible for resistance to 3GCs, especially in ampD, were diverse and not compartment specific. In conclusion, high levels of resistance in non-human E. cloacae complex isolates are probably due to environmental factors that favor the selection of these resistant strains, and this will be explored further.
Multinuclei Occurred Under Cryopreservation and Enhanced the Pathogenicity of Melampsora larici-populina
Authors: Zheng Wei , Peng Zijia , Peng Shaobing , Yu Zhongdong , Cao Zhimin
Published: June 2021

Melampsora larici-populina is a macrocyclic rust, and the haploid stage with two nuclei and the diploid of mononuclear sequentially occur annually. During the preservation of dry urediniospores at −80°C, we found that one isolate, ΔTs06, was different from the usual wild-type isolate Ts06 at −20°C because it has mixed polykaryotic urediniospores. However, the other spores, including the 0, I, III, and IV stages of a life cycle, were the same as Ts06. After five generations of successive inoculation and harvest of urediniospores from the compatible host Populus purdomii, the isolate ΔTs06 steadily maintained more than 20% multiple nucleus spores. To test the pathogenesis variation of ΔTs06, an assay of host poplars was applied to evaluate the differences between ΔTs06 and Ts06. After ΔTs06 and Ts06 inoculation, leaves of P. purdomii were used to detect the expression of small secreted proteins (SSPs) and fungal biomasses using quantitative real-time PCR (qRT-PCR) and trypan blue staining. ΔTs06 displayed stronger expression of five SSPs and had a shorter latent period, a higher density of uredinia, and higher DNA mass. A transcriptomic comparison between ΔTs06 and Ts06 revealed that 3,224 were differentially expressed genes (DEGs), 55 of which were related to reactive oxygen species metabolism, the Mitogen-activated protein kinase (MAPK) signaling pathway, and the meiosis pathway. Ten genes in the mitotic and meiotic pathways and another two genes associated with the “response to DNA damage stimulus” all had an upward expression, which were detected by qRT-PCR in ΔTs06 during cryopreservation. Gas chromatography–mass spectrometry (GC-MS) confirmed that the amounts of hexadecanoic acid and octadecadienoic acid were much more in ΔTs06 than in Ts06. In addition, using spectrophotometry, hydrogen peroxide (H2O2) was also present in greater quantities in ΔTs06 compared with those found in Ts06. Increased fatty acids metabolism could prevent damage to urediniospores in super-low temperatures, but oxidant species that involved H2O2 may destroy tube proteins of mitosis and meiosis, which could cause abnormal nuclear division and lead to multinucleation, which has a different genotype. Therefore, the multinuclear isolate is different from the wild-type isolate in terms of phenotype and genotype; this multinucleation phenomenon in urediniospores improves the pathogenesis and environmental fitness of M. larici-populina.
A MexR Mutation Which Confers Aztreonam Resistance to Pseudomonas aeruginosa
Authors: Ma Zhenzhen , Xu Congjuan , Zhang Xinxin , Wang Dan , Pan Xiaolei , Liu Huimin , Zhu Guangbo , Bai Fang , Cheng Zhihui , Wu Weihui , Jin Yongxin
Published: June 2021

Therapy for Pseudomonas aeruginosa infections is hard due to its high natural and acquirable antibiotic resistance. After colonization in the hosts, P. aeruginosa commonly accumulates genomic mutations which confer them antibiotic resistance and better adaptations to the host environment. Deciphering the mechanisms of antibiotic resistance development in the clinical setting may provide critical insights into the design of effective combinatory antibiotic therapies to treat P. aeruginosa infections. In this work, we demonstrate a resistance mechanism to aztreonam of a clinical isolate (ARP36) in comparison with a sensitive one (CSP18). RNAseq and genomic DNA resequencing were carried out to compare the global transcriptional profiles and in the clinical setting genomic profiles between these two isolates. The results demonstrated that hyperexpression of an efflux pump MexAB-OprM caused by a R70Q substitution in MexR, contributed to the increased resistance to aztreonam in the isolate ARP36. Simulation of mexR of ARP36 by gene editing in CSP18 conferred CSP18 an ARP36-like susceptibility to the aztreonam. The R70Q substitution prevented MexR from binding to the intergenic region between mexR and mexAB-oprM operon, with no impact on its dimerization. The presented experimental results explain for the first time why the clinically relevant R70Q substitution in the MexR derepresses the expression of mexAB-oprM in P. aeruginosa.
One-Pot Microwave-Assisted Synthesis of Carbon Dots and in vivo and in vitro Antimicrobial Photodynamic Applications
Authors: Romero María Paulina , Alves Fernanda , Stringasci Mirian Denise , Buzzá Hilde Harb , Ciol Heloísa , Inada Natalia Mayumi , Bagnato Vanderlei Salvador
Published: June 2021

Graphical Abstract

Brief description of the procedures carried out in this study. In vivo and in vitro antibacterial photodynamic therapy (aPDT) studies, where aPDT mediated by C-DOTS and blue LED light against S. aureus was evaluated.
A Novel Device-Integrated Drug Delivery System for Local Inhibition of Urinary Tract Infection
Authors: Stærk Kristian , Grønnemose Rasmus Birkholm , Palarasah Yaseelan , Kolmos Hans Jørn , Lund Lars , Alm Martin , Thomsen Peter , Andersen Thomas Emil
Published: June 2021

Background:Catheter-associated urinary tract infection (CAUTI) is a frequent community-acquired infection and the most common nosocomial infection. Here, we developed a novel antimicrobial catheter concept that utilizes a silicone-based interpenetrating polymer network (IPN) as balloon material to facilitate a topical slow-release prophylaxis of antibacterial agents across the balloon to the urinary bladder.

Methods:The balloon material was achieved by modifying low shore hardness silicone tubes with a hydrogel interpenetrating polymer in supercritical CO2using the sequential method. Release properties and antibacterial efficacy of the IPN balloon treatment concept was investigatedin vitroand in a porcine CAUTI model developed for the study. In the latter, Bactiguard Infection Protection (BIP) Foley catheters were also assessed to enable benchmark with the traditional antimicrobial coating principle.

Results:UropathogenicEscherichia coliwas undetectable in urinary bladders and on retrieved catheters in the IPN treatment group as compared to control that revealed significant bacteriuria (>105colony forming units/ml) as well as catheter-associated biofilm. The BIP catheters failed to preventE. colicolonization of the bladder but significantly reduced catheter biofilm formation compared to the control.

Conclusion:The IPN-catheter concept provides a novel, promising delivery route for local treatment in the urinary tract.
Function Characterization of Endogenous Plasmids in Cronobacter sakazakii and Identification of p-Coumaric Acid as Plasmid-Curing Agent
Authors: Ji Xuemeng , Lu Ping , Hu Yaozhong , Xue Juan , Wu Jing , Zhang Bowei , Zhang Yan , Dong Lu , Lv Huan , Wang Shuo
Published: June 2021

Virulence traits and antibiotic resistance are frequently provided by genes located on plasmids. However, experimental verification of the functions of these genes is often lacking due to a lack of related experimental technology. In the present study, an integrated suicide vector was used to efficiently and specifically delete a bacterial endogenous plasmid in Cronobacter sakazakii. The pESA3 plasmid was removed from C. sakazakii BAA-894, and we confirmed that this plasmid contributes to the invasion and virulence of this strain. In addition, the pGW1 plasmid was expunged from C. sakazakii GZcsf-1, and we confirmed that this plasmid confers multidrug resistance. We further screened plasmid-curing agents and found that p-coumaric acid had a remarkable effect on the curing of pESA3 and pGW1 at sub-inhibitory concentrations. Our study investigated the contribution of endogenous plasmids pESA3 and pGW1 by constructing plasmid-cured strains using suicide vectors and suggested that p-coumaric acid can be a safe and effective plasmid-curing agent for C. sakazakii.
Effects of Lactic Acid Bacteria on Microbial Metabolic Functions of Paper Mulberry Silage: A BIOLOG ECO Microplates Approach
Authors: Wang Xuekai , Cao Xinxin , Liu Han , Guo Linna , Lin Yanli , Liu Xiaojing , Xiong Yi , Ni Kuikui , Yang Fuyu
Published: June 2021

Lactic acid bacteria occupy an important position in silage microorganisms, and the effects of exogenous lactic acid bacteria on silage quality have been widely studied. Microbial metabolism has been proved as an indicator of substrate utilization by microorganisms. Paper mulberry is rich in free carbohydrate, amino acids, and other components, with the potential to be decomposed and utilized. In this study, changes in the microbial metabolism characteristics of paper mulberry silage with Lactiplantibacillus plantarum (LP) and Lentilactobacillus buchneri (LB) were studied along with a control (CK) using BIOLOG ECO microplates. The results showed that average well-color development (AWCD), Shannon diversity, Shannon evenness, and Simpson diversity exhibited significant temporal trends. LB and LP responded differently in the early ensiling phase, and the AWCD of LB was higher than LP at 7 days. Principal component analysis revealed that CK, LB, and LP samples initially clustered at 3 days and then moved into another similar cluster after 15 days. Overall, the microplates methodology applied in this study offers important advantages, not least in terms of accuracy.