bluuebunny/crossref_metadata_2025 huggingface dataset:
In the Acute Phase of Trypanosoma cruzi Infection, Liver Lymphoid and Myeloid Cells Display an Ambiguous Phenotype Combining Pro- and Anti-Inflammatory Markers
Authors: de Lima Pereira dos Santos Carina , Vacani-Martins Natalia , Cascabulho Cynthia Machado , Pereira Mirian Claudia de Souza , Crispe Ian Nicholas , Henriques-Pons Andrea
Published: June 2022

Multiple cell populations, cellular biochemical pathways, and the autonomic nervous system contribute to maintaining the immunological tolerance in the liver. This tolerance is coherent because the organ is exposed to high levels of bacterial pathogen-associated molecular pattern (PAMP) molecules from the intestinal microbiota, such as lipopolysaccharide endotoxin (LPS). In the case ofTrypanosoma cruziinfection, although there is a dramatic acute immune response in the liver, we observed intrahepatic cell populations combining pro- and anti-inflammatory markers. There was loss of fully mature Kupffer cells and an increase in other myeloid cells, which are likely to include monocytes. Among dendritic cells (DCs), the cDC1 population expanded relative to the others, and these cells lost both some macrophage markers (F4/80) and immunosuppressive cytokines (IL-10, TGF-β1). In parallel, a massive T cell response occured with loss of naïve cells and increase in several post-activation subsets. However, these activated T cells expressed both markers programmed cell death protein (PD-1) and cytokines consistent with immunosuppressive function (IL-10, TGF-β1). NK and NK-T cells broadly followed the pattern of T cell activation, while TCR-γδ cells appeared to be bystanders. While no data were obtained concerning IL-2, several cell populations also synthesized IFN-γ and TNF-α, which has been linked to host defense but also to tissue injury. It therefore appears thatT. cruziexerts control over liver immunity, causing T cell activationviacDC1 but subverting multiple populations of T cells into immunosuppressive pathways. In this way,T. cruziengages a mechanism of hepatic T cell tolerance that is familiar from liver allograft tolerance, in which activation and proliferation are followed by T cell inactivation.
Vitamin D Supplementation Modulates Platelet-Mediated Inflammation in Subjects With Type 2 Diabetes: A Randomized, Double-Blind, Placebo-Controlled Trial
Authors: Johny Ebin , Jala Aishwarya , Nath Bishamber , Alam Md Jahangir , Kuladhipati Indra , Das Rupam , Borkar Roshan M. , Adela Ramu
Published: June 2022

Background

Recently, our group identified increased platelet-mediated inflammation in type 2 diabetes (T2DM) patients, and it is a well-established risk factor for diabetes complications, particularly for the development of cardiovascular diseases (CVD). Furthermore, vitamin D is reported to play an important role in the modulation of platelet hyperactivity and immune function, although the effect of vitamin D on platelet-mediated inflammation is not well studied. Hence, we aimed to investigate the effect of vitamin D supplementation on platelet-mediated inflammation in T2DM patients.

Methods

After screening a total of 201 subjects, our randomized, double-blind, placebo-controlled trial included 59 vitamin-D-deficient T2DM subjects, and the participants were randomly assigned to placebo (n = 29) or vitamin D3 (n = 30) for 6 months. Serum vitamin D metabolite levels, immunome profiling, platelet activation, and platelet–immune cell aggregate formation were measured at baseline and at the end of the study. Similarly, the serum levels of inflammatory cytokines/chemokines were assessed by a multiplex assay.

Results

Six months of vitamin D supplementation increases the serum vitamin D3 and total 25(OH)D levels from the baseline (p < 0.05). Vitamin D supplementation does not improve glycemic control, and no significant difference was observed in immune cells. However, platelet activation and platelet immune cell aggregates were altered after the vitamin D intervention (p < 0.05). Moreover, vitamin D reduces the serum levels of IL-18, TNF-α, IFN-γ, CXCL-10, CXCL-12, CCL-2, CCL-5, CCL-11, and PF-4 levels compared to the baseline levels (p < 0.05). Our ex vivo experiment confirms that a sufficient circulating level of vitamin D reduces platelet activation and platelet intracellular reactive oxygen species.

Conclusion

Our study results provide evidence that vitamin D supportive therapy may help to reduce or prevent the disease progression and cardiovascular risk in T2DM patients by suppressing oxidative stress and platelet-mediated inflammation.

Clinical Trial Registration

Clinical Trial Registry of India: CTRI/2019/01/016921.
Immune Subtypes in LUAD Identify Novel Tumor Microenvironment Profiles With Prognostic and Therapeutic Implications
Authors: Wang Feng , Gao Xuan , Wang Peiyuan , He Hao , Chen Peng , Liu Zhentian , Chen Yujie , Zhou Hang , Chen Weijie , Yi Xin , Xia Xuefeng , Liu Shuoyan
Published: June 2022

The six transcriptomic immune subtypes (ISs) (C1 - C6) were reported to have complex and different interplay between TME and cancer cells in TCGA (The Cancer Genome Atlas) pan-cancer cohort. Our study specifically explored how the consequence of interplay determines the prognosis and the response to therapy in LUAD cohorts. Clinical and molecular information of LUAD patients were from TCGA and Gene Expression Omnibus (GEO). The immune cell populations and gene/pathway enrichment analysis were performed to explore the molecular differences among the C3 IS and other ISs in the LUAD population. The proportion of C3 inflammatory IS was identified as the most common IS in both TCGA (N = 457) and GEO (N = 901) cohorts. The C3 IS was also found to be the most accurate prognostic subtype, which was associated with significantly longer OS (p <0.001) and DFS (p <0.001). The C3 IS presented higher levels of CD8 T, M1 macrophage, and myeloid dendritic cells, while lower levels of M2 macrophages and cancer-associated fibroblast cells. Moreover, the C3 subtype was enriched in the antigen process and presenting, interferon-gamma response, T cell receptor signaling, and natural killer cell-mediated cytotoxicity pathways than C1/C2. In contrast, the C1/C2 presented greater activation of pathways related to the cell cycles, DNA repair, and p53 signaling pathways. The immune-related C3 IS had a great ability to stratify the prognosis of LUAD, providing clues for further pathogenic research. This classification might help direct precision medicine screenings of LUAD patients, thus possibly improving their prognoses.
Predicting Response of Severe Aplastic Anemia to Rabbit-Antithymocyte Immunoglobulin Based Immunosuppressive Therapy Combined With Eltrombopag
Authors: Li Ruixin , Zhou Jiongtao , Liu Zhengyuan , Chen Xi , Long Qiqiang , Yang Yan , Lin Shengyun , Jia Jinsong , He Guangsheng , Li JianYong
Published: June 2022

Addition of eltrombopag (E-PAG) to intensive immunosuppressive therapy (IST) contributes to restoring hematopoiesis in patients with severe aplastic anemia (SAA). Used at relatively low doses in the East Asian population, the efficacies of E-PAG and the predictors for efficacy are not clear. We conducted a retrospective, multicenter study to analyze the efficacy and the possible predicting factors at 6 months in 58 adult SAA patients with rabbit ATG-based IST and E-PAG. The response rate and complete response rate at 6 months were 76% and 21%, respectively. The baseline reticulocyte percentage [area under a curve (AUC)=0.798, 95% confidence interval (CI) 0.640-0.956, P=0.006], absolute reticulocyte count (ARC) (AUC =0.808, 95%CI 0.647-0.970, P=0.004), red cell distribution width – coefficient of variation (RDW-CV) (AUC=0.722, 95%CI 0.494-0.950, P=0.040), and absolute lymphocyte count (ALC) (AUC=0.706, 95%CI 0.522-0.890, P=0.057) were highly predictive of response at 6 months. The tipping values of reticulocyte percentage, ARC, RDW-CV, and ALC were 0.45%, 7.36×109/L, 11.75%, and 1.06×109/L, respectively. The sensitivity and specificity of reticulocyte percentages were 81.6% and 66.7%; ARC were 86.8% and 66.7%, RDW-CV were 94.7% and 55.6%; ALC were 55.3% and 88.9%. At a median follow-up of 15.5 months, the 2-year cumulative overall survival was 92%. The baseline reticulocyte percentage, ARC, RDW-CV, and ALC were potential factors in predicting a favorable effect of rabbit-ATG based IST plus E-PAG in SAA patients of East Asia (ChiCTR2100045895).

Clinical Trial Registration

http://www.chictr.org.cn/edit.aspx?pid=125480&htm=4, identifier ChiCTR2100045895.
A BALB/c IGHV Reference Set, Defined by Haplotype Analysis of Long-Read VDJ-C Sequences From F1 (BALB/c x C57BL/6) Mice
Authors: Jackson Katherine J. L. , Kos Justin T. , Lees William , Gibson William S. , Smith Melissa Laird , Peres Ayelet , Yaari Gur , Corcoran Martin , Busse Christian E. , Ohlin Mats , Watson Corey T. , Collins Andrew M.
Published: June 2022

The immunoglobulin genes of inbred mouse strains that are commonly used in models of antibody-mediated human diseases are poorly characterized. This compromises data analysis. To infer the immunoglobulin genes of BALB/c mice, we used long-read SMRT sequencing to amplify VDJ-C sequences from F1 (BALB/c x C57BL/6) hybrid animals. Strain variations were identified in theIghmandIghg2bgenes, and analysis of VDJ rearrangements led to the inference of 278 germline IGHV alleles. 169 alleles are not present in the C57BL/6 genome reference sequence. To establish a set of expressed BALB/c IGHV germline gene sequences, we computationally retrieved IGHV haplotypes from the IgM dataset. Haplotyping led to the confirmation of 162 BALB/c IGHV gene sequences. A musIGHV398 pseudogene variant also appears to be present in the BALB/cByJ substrain, while a functional musIGHV398 gene is highly expressed in the BALB/cJ substrain. Only four of the BALB/c alleles were also observed in the C57BL/6 haplotype. The full set of inferred BALB/c sequences has been used to establish a BALB/c IGHV reference set, hosted athttps://ogrdb.airr-community.org. We assessed whether assemblies from the Mouse Genome Project (MGP) are suitable for the determination of the genes of the IGH loci. Only 37 (43.5%) of the 85 confirmed IMGT-named BALB/c IGHV and 33 (42.9%) of the 77 confirmed non-IMGT IGHV were found in a search of the MGP BALB/cJ genome assembly. This suggests that current MGP assemblies are unsuitable for the comprehensive documentation of germline IGHVs and more efforts will be needed to establish strain-specific reference sets.
Understanding the Concept of Pre-Clinical Autoimmunity: Prediction and Prevention of Systemic Lupus Erythematosus: Identifying Risk Factors and Developing Strategies Against Disease Development
Authors: Choi May Y. , Costenbader Karen H.
Published: June 2022

There is growing evidence that preceding the diagnosis or classification of systemic lupus erythematosus (SLE), patients undergo a preclinical phase of disease where markers of inflammation and autoimmunity are already present. Not surprisingly then, even though SLE management has improved over the years, many patients will already have irreversible disease-related organ damage by time they have been diagnosed with SLE. By gaining a greater understanding of the pathogenesis of preclinical SLE, we can potentially identify patients earlier in the disease course who are at-risk of transitioning to full-blown SLE and implement preventative strategies. In this review, we discuss the current state of knowledge of SLE preclinical pathogenesis and propose a screening and preventative strategy that involves the use of promising biomarkers of early disease, modification of lifestyle and environmental risk factors, and initiation of preventative therapies, as examined in other autoimmune diseases such as rheumatoid arthritis and type 1 diabetes.
Targeting PCSK9 Ameliorates Graft Vascular Disease in Mice by Inhibiting NLRP3 Inflammasome Activation in Vascular Smooth Muscle Cells
Authors: Zou Yanqiang , Chen Zhang , Zhang Xi , Yu Jizhang , Xu Heng , Cui Jikai , Li Yuan , Niu Yuqing , Zhou Cheng , Xia Jiahong , Wu Jie
Published: June 2022

Background

Graft vascular disease (GVD), which limits the long-term survival of patients after solid-organ transplantation, is associated with both immune responses and nonimmune factors, including dyslipidemia. Recent studies have shown that inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9), a U.S. Federal Drug Administration-approved treatment for hyperlipidemia, reduces cardiovascular events, regulates inflammatory responses, and enhances the efficacy of immune checkpoint therapy in cancer treatment through a cholesterol-independent mechanism. However, whether targeting PCSK9 is a potential therapeutic strategy for GVD remains unknown.

Methods

Serum samples and grafts were harvested from male mice undergoing abdominal aortic transplantation. The pathological alterations in the aortic grafts were detected by hematoxylin and eosin staining, Verhoeff’s Van Gieson staining, and Masson staining. Inflammatory cell infiltration and proinflammatory cytokine expression in the aortic grafts were detected by immunohistochemistry and quantitative real-time polymerase chain reaction (qRT-PCR), respectively. The regulatory effects of PCSK9 on vascular smooth muscle cell (VSMC) migration and proliferation were examined by transwell, EdU, and western blot assays. The effect of Evolocumab, a PCSK9 inhibitor, on GVD in humanized PCSK9 mice was also evaluated.

Results

PCSK9 was upregulated in the serum, grafts, and liver of mice in the allograft group subjected to abdominal aortic transplantation. Pcsk9 knockout significantly reduced vascular stenosis, the intimal hyperplasia area and collagen deposition. Pcsk9 depletion also inhibited macrophage recruitment and the mRNA expression of proinflammatory cytokines in aortic grafts. Furthermore, Pcsk9 knockout suppressed the migration and proliferation of VSMCs, which was related to the inhibition of NLRP3 inflammasome activation. Meanwhile, Evolocumab significantly ameliorated GVD in humanized PCSK9 mice.

Conclusion

PCSK9 is upregulated in a mouse model of GVD, and Pcsk9 knockout reduces vascular occlusion, suggesting that PCSK9 may be a promising target for the treatment of GVD.
Rapamycin Dampens Inflammatory Properties of Bone Marrow ILC2s in IL-33-Induced Eosinophilic Airway Inflammation
Authors: Boberg Emma , Weidner Julie , Malmhäll Carina , Calvén Jenny , Corciulo Carmen , Rådinger Madeleine
Published: June 2022

The alarmin cytokine interleukin (IL)-33 plays an important proinflammatory role in type 2 immunity and can act on type 2 innate lymphoid cells (ILC2s) and type 2 T helper (TH2) cells in eosinophilic inflammation and asthma. The mechanistic target of rapamycin (mTOR) signaling pathway drives immune responses in several inflammatory diseases, but its role in regulating bone marrow responses to IL-33 is unclear. The aim of this study was to determine the role of the mTORC1 signaling pathway in IL-33-induced bone marrow ILC2 responses and its impact on IL-33-induced eosinophilia. Wild-type mice were intranasally exposed to IL-33 only or in combination with the mTORC1 inhibitor, rapamycin, intraperitoneally. Four groups were included in the study: saline-treated (PBS)+PBS, rapamycin+PBS, PBS+IL-33 and rapamycin+IL-33. Bronchoalveolar lavage fluid (BALF), serum and bone marrow cells were collected and analyzed by differential cell count, enzyme-linked immunosorbent assay and flow cytometry. IL-33 induced phosphorylation of the mTORC1 protein rpS6 in bone marrow ILC2s both ex vivo and in vivo. The observed mTOR signal was reduced by rapamycin treatment, indicating the sensitivity of bone marrow ILC2s to mTORC1 inhibition. IL-5 production by ILC2s was reduced in cultures treated with rapamycin before stimulation with IL-33 compared to IL-33 only. Bone marrow and airway eosinophils were reduced in mice given rapamycin before IL-33-exposure compared to mice given IL-33 only. Bone marrow ILC2s responded to IL-33 in vivo with increased mTORC1 activity and rapamycin treatment successfully decreased IL-33-induced eosinophilic inflammation, possibly by inhibition of IL-5-producing bone marrow ILC2s. These findings highlight the importance of investigating specific cells and proinflammatory pathways as potential drivers of inflammatory diseases, including asthma.
RNA-Seq and 16S rRNA Analysis Revealed the Effect of Deltamethrin on Channel Catfish in the Early Stage of Acute Exposure
Authors: Yang Yibin , Zhu Xia , Huang Ying , Zhang Hongyu , Liu Yongtao , Xu Ning , Fu Guihong , Ai Xiaohui
Published: June 2022

Deltamethrin (Del) is a widely used pyrethroid insecticide and a dangerous material that has brought serious problems to the healthy breeding of aquatic animals. However, the toxicological mechanisms of Del on channel catfish remain unclear. In the present study, we exposed channel catfish to 0, 0.5, and 5 μg/L Del for 6 h, and analyzed the changes in histopathology, trunk kidney transcriptome, and intestinal microbiota composition. The pathological analyses showed that a high concentration of Del damaged the intestine and trunk kidney of channel catfish in the early stage. The transcriptome analysis detected 32 and 1837 differentially expressed genes (DEGs) in channel catfish trunk kidneys after exposure to 0.5 and 5 μg/L Del, respectively. Moreover, the KEGG pathway and GO enrichment analyses showed that the apoptosis signaling pathway was significantly enriched, and apoptosis-related DEGs, including cathepsin L, p53, Bax, and caspase-3, were also detected. These results suggested that apoptosis occurs in the trunk kidney of channel catfish in the early stage of acute exposure to Del. We also detected some DEGs and signaling pathways related to immunity and drug metabolism, indicating that early exposure to Del can lead to immunotoxicity and metabolic disorder of channel catfish, which increases the risk of pathogenic infections and energy metabolism disorders. Additionally, 16S rRNA gene sequencing showed that the composition of the intestinal microbiome significantly changed in channel catfish treated with Del. At the phylum level, the abundance of Firmicutes, Fusobacteria, and Actinobacteria significantly decreased in the early stage of Del exposure. At the genus level, the abundance of Romboutsia, Lactobacillus, and Cetobacterium decreased after Del exposure. Overall, early exposure to Del can lead to tissue damage, metabolic disorder, immunotoxicity, and apoptosis in channel catfish, and affect the composition of its intestinal microbiota. Herein, we clarified the toxic effects of Del on channel catfish in the early stage of exposure and explored why fish under Del stress are more vulnerable to microbial infections and slow growth.
A Bibliometric Analysis of the Innate Immune DNA Sensing cGAS-STING Pathway from 2013 to 2021
Authors: Shi Xuan , Wang Sheng , Wu Yutong , Li Quanfu , Zhang Tong , Min Keting , Feng Di , Liu Meiyun , Wei Juan , Zhu Lina , Mo Wei , Xiao Zhuoran , Yang Hao , Chen Yuanli , Lv Xin
Published: June 2022

Background and aims

Cyclic guanosine monophosphate (GMP)-adenosine monophosphate (AMP) (cGAMP) synthase (cGAS) and stimulator of interferon genes (STING) are key components of the innate immune system. This study aims to evaluate the research of cGAS-STING pathway and predict the hotspots and developing trends in this field using bibliometric analysis.

Methods

We retrieved publications from Science Citation Index Expanded (SCI-expanded) of Web of Science Core Collection (WoSCC) in 1975-2021 on 16 March 2022. We examined the retrieved data by bibliometrix package in R software, VOSviewer and CiteSpace were used for visualizing the trends and hotspots of research on the cGAS-STING pathway.

Results

We identified 1047 original articles and reviews on the cGAS-STING pathway published between 1975 and 2021. Before 2016, the publication trend was increasing steadily, but there was a significant increase after 2016. The United States of America (USA) produced the highest number of papers (Np) and took the highest number of citations (Nc), followed by China and Germany. The University of Texas System and Frontiers in Immunology were the most prolific affiliation and journal respectively. In addition, collaboration network analysis showed that there were tight collaborations among the USA, China and some European countries, so the top 10 affiliations were all from these countries and regions. The paper published by Sun LJ in 2013 reached the highest local citation score (LCS). Keywords co-occurrence and co-citation cluster analysis revealed that inflammation, senescence, and tumor were popular terms related to the cGAS-STING pathway recently. Keywords burst detection suggested that STING-dependent innate immunity and NF-κB-dependent broad antiviral response were newly-emerged hotspots in this area.

Conclusions

This bibliometric analysis shows that publications related to the cGAS-STING pathway tend to increase continuously. The research focus has shifted from the mechanism how cGAS senses dsDNA and cGAMP binds to STING to the roles of the cGAS-STING pathway in different pathological state.
Satellite-Based Lagrangian Model Reveals How Upwelling and Oceanic Circulation Shape Krill Hotspots in the California Current System
Authors: Messié Monique , Sancho-Gallegos Diego A. , Fiechter Jerome , Santora Jarrod A. , Chavez Francisco P.
Published: June 2022

In the California Current System, wind-driven nutrient supply and primary production, computed from satellite data, provide a synoptic view of how phytoplankton production is coupled to upwelling. In contrast, linking upwelling to zooplankton populations is difficult due to relatively scarce observations and the inherent patchiness of zooplankton. While phytoplankton respond quickly to environmental forcing, zooplankton grow slower and tend to aggregate into mesoscale “hotspot” regions spatially decoupled from upwelling centers. To better understand mechanisms controlling the formation of zooplankton hotspots, we use a satellite-based Lagrangian method where variables from a plankton model, forced by wind-driven nutrient supply, are advected by near-surface currents following upwelling events. Modeled zooplankton distribution reproduces published accounts of euphausiid (krill) hotspots, including the location of major hotspots and their interannual variability. This satellite-based modeling tool is used to analyze the variability and drivers of krill hotspots in the California Current System, and to investigate how water masses of different origin and history converge to form predictable biological hotspots. The Lagrangian framework suggests that two conditions are necessary for a hotspot to form: a convergence of coastal water masses, and above average nutrient supply where these water masses originated from. The results highlight the role of upwelling, oceanic circulation, and plankton temporal dynamics in shaping krill mesoscale distribution, seasonal northward propagation, and interannual variability.
InSEA Project: Initiatives in Supporting the Consolidation and Enhancement of the EMSO Infrastructure and Related Activities
Authors: De Santis Angelo , Chiappini Massimo , Marinaro Giuditta , Guardato Sergio , Conversano Fabio , D’Anna Giuseppe , Di Mauro Domenico , Cardin Vanessa , Carluccio Roberto , Rende Sante Francesco , Giordano Raffaele , Rossi Lorenzo , Simeone Francesco , Giacomozzi Emanuele , Fertitta Gioacchino , Costanza Antonio , Donnarumma GianPaolo , Riccio Rosario , Siena Giuseppe , Civitarese Giuseppe
Published: June 2022

The InSEA project (“Initiatives in Supporting the consolidation and enhancement of the EMSO research infrastructure consortium (ERIC) and related Activities”) has the objective, as the full name of the project indicates, to consolidate and strengthen the infrastructures concerning the EMSO (“European Multidisciplinary Seafloor and water column Observatory”) ERIC (European Research Infrastructure Consortium) and all those technical-scientific activities related to it. In particular, the project is upgrading localized and distributed marine infrastructures, laboratories, observatories and spatial measurement activities in Southern Italian seas to support those activities of surveys in fixed time series points of observation of EMSO ERIC. The project is developing according to six implementation Objectives of Research (OR) that involve four National research Institutions: INGV, ISPRA, OGS and Anton Dohrn Zoological Station of Naples. The paper illustrates with more details the relevant objectives of the InSEA project and its most significant implementation phases.
Changing Trends of Adverse Pregnancy Outcomes With Maternal Pre-pregnancy Body Mass Index: A Join-Point Analysis
Authors: Hu Rong , Yin Huifen , Li Xiaotian
Published: June 2022

Objective

Adverse pregnancy outcomes have been related to obesity and thinness; however, the changing trends of the specific outcome with pre-pregnancy BMI remain unknown. The aim of this study was to investigate the change in risk trends of specific adverse outcomes for different pre-pregnancy BMI and analyze the recommended BMI range for pre-pregnancy counseling.

Methods

Data were extracted from the medical records of 39 public hospitals across 14 provinces in China from 2011 to 2012. The eligibility criteria were singleton birth with delivery week ≥28 weeks. Join-point analysis was adopted to explore changing trends with pre-pregnancy BMI and calculate slopes and join points of different pregnancy complications.

Results

A total of 65,188 women were eligible for analysis. There were three categories of trend style. Continuously increasing trends were linear for intrahepatic cholestasis of pregnancy, postpartum hemorrhage, and low 1-min Apgar score, and non-linear for cesarean delivery with one join point of BMI 23, hypertension disorder in pregnancy with two join points of BMI 20 and 28, gestational diabetes mellitus with one join point of BMI 22, and macrosomia with one join point of BMI 19. The trend was continuously and linearly decreasing for anemia. The bidirectional trends were downward and upward for premature rupture of the membrane with join BMI 22, preterm premature rupture of the membrane with join BMI 22, placenta abruption with join BMI 23, preterm birth with join BMI 19, and low birth weight with join BMI 19.

Conclusions

The changes in the trends of specific outcomes differed with pre-pregnancy BMI. Our results suggested that a pre-pregnancy BMI ranging between 19 and 23 may help reduce the risk of poor maternal and neonatal outcomes.
Performances of Corneal Topography and Tomography in the Diagnosis of Subclinical and Clinical Keratoconus
Authors: Nicula Cristina Ariadna , Bulboacă Adriana Elena , Nicula Dorin , Nicula Ariadna Patricia , Horvath Karin Ursula , Bolboacă Sorana D.
Published: June 2022

Aim

The purpose of the study was to assess the efficacy of topographical and tomographical indices given by the Pentacam (pachymetric, tomopetric, and aberometric) in clinical and subclinical keratoconus (KCN) diagnosis.

Material and Methods

In this observational analytic retrospective study, patients with abnormal findings in topography and tomography maps but with no signs on clinical examination (subclinical KCN group, sKCN), patients with clinical keratoconus (KCN group), and healthy subjects (Control group) were evaluated.

Results

The KCN group proved significantly different (p < 0.001) values of the investigated parameters than the Control group. Eleven out of 28 investigated parameters proved significantly different in the sKCN group compared to controls (p < 0.001). Two topographic measurements, namely I-S (cut-off = 1.435, a large value indicates the presence of KCN) and CCT (cut-off = 537, a small value indicates the presence of KCN), showed AUCs equal to 1 [0.999 to 1]. Six other Pentacam measurements, including Back maximum keratometry (Back Kmax) proved to be excellent parameters for case-finding and screening. In distinguishing sKCN from normal eyes, Pentacam index of vertical asymmetry (IVA), inferior-superior difference (I-S) value, thinnest point (TP), Belin Ambrosio Enhanced Ectasia Display (BAD_D) and root mean square total (RMS total) performed best.

Conclusions

In distinguishing sKCN from normal eyes, Back Kmax, IVA, I-S, and RMS total values demonstrated higher accuracy and utility. Six indices, namely ISV, IVA, KISA, PRC, RMS-HOA, and Back Kmax demonstrate excellent utility in case-finding and screening for clinical KCN.
Targeted Temperature Management for Cardiac Arrest Due to Non-shockable Rhythm: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Authors: Zhu Yi-Bing , Yao Yan , Ren Yu , Feng Jing-Zhi , Huang Hui-Bin
Published: June 2022

Background

Targeted temperature management (TTM) is recommended in adult patients following cardiac arrest (CA) with any rhythm. However, as to non-shockable (NSR) CA, high-quality evidence of TTM supporting its practices remains uncertain. Thus, we aimed to conduct a systematic review and meta-analysis with randomized controlled trials (RCTs) to explore the efficacy and safety of TTM in this population.

Methods

We searched PubMed, Embase, and Cochrane library databases for potential trials from inception through Aug 25, 2021. RCTs evaluating TTM for CA adults due to NSR were included, regardless of the timing of cooling initiation. Outcome measurements were mortality and good neurological function. We used the Cochrane bias tools to evaluate the quality of the included studies. Heterogeneity, subgroup analyses, and sensitivity analysis were investigated to test the robustness of the primary outcomes.

Results

A total of 14 RCTs with 4,009 adults were eligible for the final analysis. All trials had a low to moderate risk of bias. Of the included trials, six compared NSR patients with or without TTM, while eight compared pre-hospital to in-hospital TTM. Pooled data showed that TTM was not associated with improved mortality (Risk ratio [RR] 1.00; 95% CI, 0.944–1.05; P = 0.89, I2 = 0%) and good neurological outcome (RR 1.18; 95% CI 0.90–1.55; P = 0.22, I2 = 8%). Similarly, use of pre-hospital TTM resulted in neither an improved mortality (RR 0.99, 95% CI 0.97–1.03; I2 = 0%, P = 0.32) nor favorable neurological outcome (RR 1.13, 95% CI 0.93–1.38; I2 = 0%, P = 0.22). These results were further confirmed in the sensitivity analyses and subgroup analyses.

Conclusions

Our results showed that using the TTM strategy did not significantly affect the mortality and neurologic outcomes in CA survival presenting initial NSR.
High-Flow Nasal Cannula Oxygen Therapy: Physiological Mechanisms and Clinical Applications in Children
Authors: Nolasco Santi , Manti Sara , Leonardi Salvatore , Vancheri Carlo , Spicuzza Lucia
Published: June 2022

High-flow nasal cannula (HFNC) oxygen therapy has rapidly become a popular modality of respiratory support in pediatric care. This is undoubtedly due to its ease of use and safety, which allows it to be used in a wide variety of settings, ranging from pediatric intensive care to patients' homes. HFNC devices make it possible to regulate gas flow and temperature, as well as allowing some nebulized drugs to be administered, features very useful in children, in which the balance between therapeutic effectiveness and adherence to treatment is pivotal. Although the physiological effects of HFNC are still under investigation, their mechanisms of action include delivery of fixed concentration of oxygen, generation of positive end-expiratory pressure, reduction of the work of breathing and clearance of the nasopharyngeal dead space, while providing optimal gas conditioning. Nevertheless, current evidence supports the use of HFNC mainly in moderate-to-severe bronchiolitis, whereas for asthma exacerbations and breath sleeping disorders there is a lack of randomized controlled trials comparing HFNC to continuous positive airway pressure (CPAP) and non-invasive ventilation (NIV), which are essentials for the identification of response and non-response predictors. In this regard, the development of clinical guidelines for HFNC, including flow settings, indications, and contraindications is urgently needed.
Gut Microbes Reveal Pseudomonas Medicates Ingestion Preference via Protein Utilization and Cellular Homeostasis Under Feed Domestication in Freshwater Drum, Aplodinotus grunniens
Authors: Song Changyou , Wen Haibo , Liu Guangxiang , Ma Xueyan , Lv Guohua , Wu Ningyuan , Chen Jianxiang , Xue Miaomiao , Li Hongxia , Xu Pao
Published: June 2022

With strong demand for aquatic products, as well as a rapid decrease in global fishery resources and capture fisheries, domesticating animals to provide more high-quality proteins is meaningful for humans. Freshwater drum (Aplodinotus grunniens) is widely distributed in the wild habitats of North America. However, the research on A. grunniens and the feed domestication with diets composed of artificial compounds remains unclear. In this study, a 4-month feeding domestication experiment was conducted with A. grunniens larvae to evaluate the underlying mechanism and molecular targets responsible for alternations in the ingestion performance. The results indicated that a significant increase in the final body weight was exhibited by the feed domesticated group (DOM, 114.8 g) when compared to the group that did not ingest the feed (WT, 5.3 g) as the latest version we raised From the result, the final body weight exhibited significant increase between unfavorable with the feed (WT, 5.3 g) and feed domesticated group (DOM, 114.8 g). In addition, the enzyme activity of digestive enzymes like amylase, lipase, and trypsin was increased in DOM. Genes related to appetite and perception, such as NPY4R, PYY, and LEPR, were activated in DOM. 16s rRNA gene sequencing analysis revealed that Pseudomonas sp. increased from 58.74% to 89.77% in DOM, which accounts for the dominant upregulated microbial community at the genus level, followed by Plesiomonas. Analogously, Mycobacterium, Methylocystis, and Romboutsia also accounted for the down-regulated microbes in the diversity. Transcriptome and RT-PCR analysis revealed that feed domestication significantly improved protein digestion and absorption, inhibited apoptosis by AGE-RAGE signaling, and activated extracellular matrix remodeling by relaxin signaling. Integrated analysis of the microbiome and host transcriptome revealed that Pseudomonas-mediated ingestion capacity, protein utilization, and cellular homeostasis might be the underlying mechanism under feed domestication. These results indicate Pseudomonas and its key genes relating to food ingestion and digestion could serve as the molecular targets for feed domestication and sustainable development in A. grunniens.
Characterization of Catechol-1,2-Dioxygenase (Acdo1p) From Blastobotrys raffinosifermentans and Investigation of Its Role in the Catabolism of Aromatic Compounds
Authors: Meier Anna , Worch Sebastian , Hartmann Anja , Marzec Marek , Mock Hans-Peter , Bode Rüdiger , Kunze Gotthard , Matthes Falko
Published: June 2022

Gallic acid, protocatechuic acid, catechol, and pyrogallol are only a few examples of industrially relevant aromatics. Today much attention is paid to the development of new microbial factories for the environmentally friendly biosynthesis of industrially relevant chemicals with renewable resources or organic pollutants as the starting material. The non–conventional yeast, Blastobotrys raffinosifermentans, possesses attractive properties for industrial bio-production processes such as thermo- and osmotolerance. An additional advantage is its broad substrate spectrum, with tannins at the forefront. The present study is dedicated to the characterization of catechol-1,2-dioxygenase (Acdo1p) and the analysis of its function in B. raffinosifermentans tannic acid catabolism. Acdo1p is a dimeric protein with higher affinity for catechol (KM = 0.004 ± 0.001 mM, kcat = 15.6 ± 0.4 s–1) than to pyrogallol (KM = 0.1 ± 0.02 mM, kcat = 10.6 ± 0.4 s–1). It is an intradiol dioxygenase and its reaction product with catechol as the substrate is cis,cis-muconic acid. B. raffinosifermentans G1212/YIC102-AYNI1-ACDO1-6H, which expresses the ACDO1 gene under the control of the strong nitrate-inducible AYNI1 promoter, achieved a maximum catechol-1,2-dioxygenase activity of 280.6 U/L and 26.9 U/g of dry cell weight in yeast grown in minimal medium with nitrate as the nitrogen source and 1.5% glucose as the carbon source. In the same medium with glucose as the carbon source, catechol-1,2-dioxygenase activity was not detected for the control strain G1212/YIC102 with ACDO1 expression under the regulation of its respective endogenous promoter. Gene expression analysis showed that ACDO1 is induced by gallic acid and protocatechuic acid. In contrast to the wild-type strain, the B. raffinosifermentans strain with a deletion of the ACDO1 gene was unable to grow on medium supplemented with gallic acid or protocatechuic acid as the sole carbon source. In summary, we propose that due to its substrate specificity, its thermal stability, and its ability to undergo long-term storage without significant loss of activity, B. raffinosifermentans catechol-1,2-dioxygenase (Acdo1p) is a promising enzyme candidate for industrial applications.
Variations in the Gut Microbiota in Breast Cancer Occurrence and Bone Metastasis
Authors: Wenhui Yu , Zhongyu Xie , Kai Chen , Zhaopeng Cai , Jinteng Li , Mengjun Ma , Zepeng Su , Yunshu Che , Peng Wang , Yanfeng Wu , Huiyong Shen
Published: June 2022

Breast cancer is the most common cancer in women and the second most common cancer overall. Although advancements in the early diagnosis and therapy of breast cancer have occurred in recent years, the prognosis of breast cancer bone metastasis remains poor and this type of cancer is rarely cured. The gut microbiota is indispensable for internal homeostasis and regulates various biological processes. Understanding the gut microbiota profiles in normal controls (NCs), breast cancer patients with no metastasis (BNs), and breast cancer patients with bone metastasis (BMs) may shed light on the development of diagnostic and therapeutic targets for breast cancer and bone metastasis. We comprehensively analyzed the gut microbiota from NCs, BNs, and BMs and found that the community diversity decreased in the order of NCs, BNs, and BMs. Streptococcus, Campylobacter and Moraxellaceae showed higher abundances in BNs and BMs than in NCs. The lack of Megamonas and Akkermansia in the BM compared with those in the NC and BN groups was considered related to bone metastasis. Additionally, based on the distinct gut microbiota profiles, we predicted that lipid transportation and metabolism, as well as folate biosynthesis, participate in breast cancer occurrence and that steroid hormone biosynthesis influences bone metastasis. Our study demonstrated that variations in gut microbiota are associated with breast cancer occurrence and bone metastasis, providing attractive targets to develop therapeutic and diagnostic methods.
Genome Mining Approach Reveals the Occurrence and Diversity Pattern of Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR-Associated Systems in Lactobacillus brevis Strains
Authors: Panahi Bahman , Majidi Mohammad , Hejazi Mohammad Amin
Published: June 2022

Clustered regularly interspaced short palindromic repeats (CRISPR) together with their CRISPR-associated (Cas) genes are widely distributed in prokaryotes that provide an adaptive defense mechanism against foreign invasive DNA. There is relatively little knowledge about the CRISPR-Cas diversity and evolution in Lactobacillus brevis strains. Therefore, in this study, a genome-mining approach was employed to investigate the diversity and occurrence of the CRISPR-Cas system in 83 L. brevis strains. Moreover, trans-activating CRISPR RNA (tracrRNA) and protospacer adjacent motif (PAM) as pivotal elements for the successful targeting and inference of phages by the subtype II CRISPR-Cas systems were surveyed. Finally, evolutionary paths of L. brevis strains under selective pressure from foreign invasive DNA such as plasmids and phages of studied strains were surveyed using acquisition and deletion events analysis of spacers. A total of 127 confirmed CRISPRs were identified, which were distributed in 69 strains. Among strains with confirmed CRISPRs, 35 strains only contained one CRISPR locus, 23 strains contained two CRISPR loci, and 12 strains contained three to six CRISPR loci. L. brevis strains frequently harbor more than one CRISPR system. Analysis of confirmed CRISPR arrays showed that 31 out of 127 confirmed CRISPRs included Cas genes which were categorized as one of the II-A, II-C, and I-E subtypes. Analysis of subtype II-A spacers reflected divergent evolution for 18 strains into 16 unique groups. Additional analysis of spacer sequences also confirmed the implication of characterizing CRISPR-Cas systems in targeting of phages and plasmids. The current study highlighted the potential of utilizing CRISPR spacer polymorphism in genotyping lactobacillus strains. Moreover, it provides deep insights into the occurrence, diversity, and functional impacts of the CRISPR-Cas system in L. brevis strains.
Riboflavin Attenuates Influenza Virus Through Cytokine-Mediated Effects on the Diversity of the Gut Microbiota in MAIT Cell Deficiency Mice
Authors: Li Ying , Shi Chun-Wei , Zhang Yu-Ting , Huang Hai-Bin , Jiang Yan-Long , Wang Jian-Zhong , Cao Xin , Wang Nan , Zeng Yan , Yang Gui-Lian , Yang Wen-Tao , Wang Chun-Feng
Published: June 2022

Influenza is a serious respiratory disease that continues to threaten global health. Mucosa-associated invariant T (MAIT) cells use T-cell receptors (TCRs) that recognize microbial riboflavin derived intermediates presented by the major histocompatibility complex (MHC) class I-like protein MR1. Riboflavin synthesis is broadly conserved, but the roles or mechanisms of riboflavin in MR1–/– mouse influenza infection are not well understood. In our study, immunofluorescence techniques were applied to analyze the number and distribution of viruses in lung tissue. The amount of cytokine expression was assessed by flow cytometry (FCM), ELISA, and qPCR. The changes in the fecal flora of mice were evaluated based on amplicon sequencing of the 16S V3-V4 region. Our study showed that MAIT cell deficiency increased mortality and that riboflavin altered these effects in microbiota-depleted mice. The oral administration of riboflavin inhibited IL-1β, IL-17A, and IL-18 production but significantly increased the expression of IFN-γ, TNF-α, CCL2, CCL3, and CCL4 in a mouse model. The analysis of the mouse flora revealed that riboflavin treatment significantly increased the relative abundance of Akkermansia and Lactobacillus (p < 0.05) and decreased that of Bacteroides. In contrast, MR1–/– mice exhibited a concentrated aggregation of Bacteroides (p < 0.01), which indicated that MAIT cell deficiency reduced the diversity of the bacterial population. Our results define the functions of MAIT cells and riboflavin in resistance to influenza virus and suggest a potential role for riboflavin in enhancing MAIT cell immunity and the intestinal flora diversity. Gut populations can be expanded to enhance host resistance to influenza, and the results indicate novel interactions among viruses, MAIT cells, and the gut microbiota.
KCNN4 is a Potential Biomarker for Predicting Cancer Prognosis and an Essential Molecule that Remodels Various Components in the Tumor Microenvironment: A Pan-Cancer Study
Authors: Chen Shaohua , Su Xiaotao , Mo Zengnan
Published: June 2022

Objectives: Potassium Calcium-Activated Channel Subfamily N Member 4 (KCNN4) is a member of the KCNN family. Studies have revealed that KCNN4 is implicated in various physiological processes as well as promotes the malignant phenotypes of cancer cells. However, little is known about its associations with survival outcomes across varying cancer types.

Methods: Herein, we systematically explored the prognostic value of KCNN4 in the pan-cancer dataset retrieved from multiple databases. Next, we performed correlation analysis of KCNN4 expression with tumor mutational burden (TMB) and microsatellite instability (MSI), and immune checkpoint genes (ICGs) to assess its potential as a predictor of immunotherapy efficacy. Afterwards, patients were divided into increased-risk group and decreased-risk group based on the contrasting survival outcomes in various cancer types. Furthermore, the underlying mechanisms of the distinctive effects were analyzed using ESTIMATE, CIBERSORT algorithms, and Gene Set Enrichment Analysis (GSEA) analysis.

Results: KCNN4 expression levels were aberrant in transcriptomic and proteomic levels between cancer and normal control tissues in pan-cancer datasets, further survival analysis elucidated that KCNN4 expression was correlated to multiple survival data, and clinical annotations. Besides, KCNN4 expression was correlated to TMB and MSI levels in 14 types and 12 types of pan-cancers, respectively. Meanwhile, different types of cancer have specific tumor-infiltrating immune cell (TICs) profiles.

Conclusions: Our results revealed that KCNN4 could be an essential biomarker for remodeling components in the tumor microenvironment (TME), and a robust indicator for predicting prognosis as well as immunotherapy response in pan-cancer patients.
Membrane Lipids in the Thyroid Comparing to Those in Non-Endocrine Tissues Are Less Sensitive to Pro-Oxidative Effects of Fenton Reaction Substrates
Authors: Stępniak Jan , Rynkowska Aleksandra , Karbownik-Lewińska Małgorzata
Published: June 2022

Iron is an essential microelement for the proper functioning of many organs, among others it is required for thyroid hormone synthesis. However, its overload contributes to the increased formation of reactive oxygen species via Fenton chemistry (Fe2++H2O2→Fe3++˙OH + OH−), and it is potentially toxic. Individual organs/tissues are affected differently by excess iron. The excessive absorption of iron with subsequent deposition in various organs is associated with diseases such as hemochromatosis. Such an iron deposition also occurs in the thyroid gland where it can disturb thyroid hormone synthesis. In turn, melatonin is an effective antioxidant, which protects against oxidative damage. This study aims to check if lipid peroxidation resulting from oxidative damage to membrane lipids, is caused by Fenton reaction substrates, and if protective effects of melatonin differ between the thyroid and various non-endocrine porcine tissues (liver, kidney, brain cortex, spleen, and small intestine). To mimic the conditions of iron overload, Fe2+ was used in extremely high concentrations. Homogenates of individual tissues were incubated together with Fenton reaction substrates, i.e., FeSO4 (9.375, 18.75, 37.5, 75, 150, 300, 600, 1,200, 1,800, 2,100, 2,400, 3,000, 3,600, 4,200, and 4,800 µM)+H2O2 (5 mM), either without or with melatonin (5 mM). The concentration of malondialdehyde+4-hydroxyalkenals (MDA+4-HDA), as the LPO index, was evaluated by a spectrophotometrical method. Fenton reaction substrates increased concentrations of LPO products in all chosen tissues. However, in the thyroid, compared to non-endocrine tissues, the damaging effect was generally weaker, it was not observed for the two lowest concentrations of iron, and the LPO peak occurred with higher concentrations of iron. Melatonin reduced experimentally induced LPO in all examined tissues (without differences between them), and these protective effects did not depend on iron concentration. In conclusion, membrane lipids in the thyroid compared to those in non-endocrine tissues are less sensitive to pro-oxidative effects of Fenton reaction substrates, without differences regarding protective effects of melatonin.