bluuebunny/crossref_metadata_2025 huggingface dataset:
The relationship between different iodine sources and nutrition in pregnant women and adults
Authors: Sun Rong , Fan Lijun , Du Yang , Liu Lanchun , Qian Tingting , Zhao Meng , Che Wenjing , Liu Peng , Sun Dianjun
Published: July 2022

Background

Different iodine supplement measures emerge along with the economy development in China. The article objectives are to compare and explore the relationship between iodine sources and nutrition of pregnant women and adults.

Methods

A total of 2,145 pregnant women and 1,660 adults were investigated by multi-stage random method. Questionnaire was used to collect basic information and the consumption of food, water, and iodine preparations. Household salt and individual urine and blood samples were collected, and thyroid function and morphology of pregnant women were measured.

Results

The median urinary iodine concentration (MUIC) of pregnant women (164.49 μg/L) was lower than adults (187.30 μg/L, p < 0.05). Iodine supplement with IS (iodized salt) was the main measure for pregnant women and adults, and the difference was mainly on the consumption of iodine preparations between pregnant women (5.19%) and adults (0.85%). Moreover, adults’ dietary iodine intake from food (100.6 μg/day), IS (140.8 μg/day), and drinking water (6.0 μg/day) was higher than those of pregnant women (86.5, 107.2, and 3.5 μg/day, respectively). Compared with iodine supplement with IS, ISFP (IS + iodine-rich food + iodine preparations) could reduce the risk of iodine deficiency for pregnant women. The MUICs for pregnant women and adults of iodine supplements with IF (iodine-rich food) and ISF (IS + iodine-rich food) were lower. For pregnant women, thyroid nodule (11.90%) and peroxidase antibody (TPOAb) positive (9.32%) were high prevalent thyroid diseases, and habitation (urban/rural), gestation, annual income, and drinking water type would affect them.

Conclusion

Pregnant women and adults had adequate iodine nutrition in four provinces. Their iodine supplement measures were different, the consumption of iodine preparations in pregnant women was higher, and their dietary iodine intake was lower than adults. ISFP was an effect measure for pregnant women to supplement iodine.
Alpha-cell paracrine signaling in the regulation of beta-cell insulin secretion
Authors: Holter Marlena M. , Saikia Mridusmita , Cummings Bethany P.
Published: July 2022

As an incretin hormone, glucagon-like peptide 1 (GLP-1) lowers blood glucose levels by enhancing glucose-stimulated insulin secretion from pancreatic beta-cells. Therapies targeting the GLP-1 receptor (GLP-1R) use the classical incretin model as a physiological framework in which GLP-1 secreted from enteroendocrine L-cells acts on the beta-cell GLP-1R. However, this model has come into question, as evidence demonstrating local, intra-islet GLP-1 production has advanced the competing hypothesis that the incretin activity of GLP-1 may reflect paracrine signaling of GLP-1 from alpha-cells on GLP-1Rs on beta-cells. Additionally, recent studies suggest that alpha-cell-derived glucagon can serve as an additional, albeit less potent, ligand for the beta-cell GLP-1R, thereby expanding the role of alpha-cells beyond that of a counterregulatory cell type. Efforts to understand the role of the alpha-cell in the regulation of islet function have revealed both transcriptional and functional heterogeneity within the alpha-cell population. Further analysis of this heterogeneity suggests that functionally distinct alpha-cell subpopulations display alterations in islet hormone profile. Thus, the role of the alpha-cell in glucose homeostasis has evolved in recent years, such that alpha-cell to beta-cell communication now presents a critical axis regulating the functional capacity of beta-cells. Herein, we describe and integrate recent advances in our understanding of the impact of alpha-cell paracrine signaling on insulin secretory dynamics and how this intra-islet crosstalk more broadly contributes to whole-body glucose regulation in health and under metabolic stress. Moreover, we explore how these conceptual changes in our understanding of intra-islet GLP-1 biology may impact our understanding of the mechanisms of incretin-based therapeutics.
Comparison of phycocyanin concentrations in Chaohu Lake, China, retrieved using MODIS and OLCI images
Authors: Wang Jie , Wang Zhi-cheng , Cui Yu-huan , Hao Shuang , Yi Hua-yang
Published: July 2022

Phycocyanin (PC) concentration is used as an indicator to characterize cyanobacteria biomass while monitoring eutrophication in inland water. Remote sensing provides useful methods for quantifying PC concentration; however, there is a shortage of datasets for the long-term monitoring of PC concentration when only a single remote sensing data is used. Therefore, PC concentrations obtained from multisource remote sensing images should be compared before integrating them for long-term monitoring. In this study, machine learning (ML) regression algorithms are used to develop PC concentration retrieval models suitable for Moderate Resolution Imaging Spectroradiometer (MODIS) and Sentinel-3 Ocean and Land Colour Instrument (OLCI) images, and their accuracies are compared. The two optimal retrieval models are applied to satellite images acquired on the same days to compare the spatial consistency of the two PC concentration retrieval results. The results show that the sensitive spectral range of PC concentration is 560–680 nm. Among the ML regression algorithms, gradient boosted tree (GBT) regression exhibits the highest PC retrieval accuracy for both the MODIS images (R2 = 0.82, RMSE = 61.9 μg/L) and OLCI images (R2 = 0.86, RMSE = 45.44 μg/L). The PC concentrations retrieved from the MODIS and OLCI images acquired in bloom and no-bloom periods have a high spatial consistency in most areas of Chaohu Lake. Their correlation coefficient also exceeds 0.7, and the average relative error reaches 0.293 μg/L. However, a large difference exists in areas with high PC concentrations, which may cause by the poor applicability of atmospheric correction algorithms and PC retrieval models in these areas. The proposed PC concentration retrieval models developed using GBT regression in this paper can expend the idea for the quantitative retrieval of other inland water quality parameters in inland water, and the conclusions should enable the effective integration of MODIS and OLCI images for the time series monitoring of PC concentrations in reservoirs and lakes.
Plant pathogens as introduced weed biological control agents: Could antagonistic fungi be important factors determining agent success or failure?
Authors: Den Breeyen Alana , Lange Claudia , Fowler Simon V.
Published: July 2022

Mycoparasitic interactions are common in nature, form part of the microbiota of plants, and are considered significant contributors to fungus-fungus antagonism. Mycoparasites kill plant pathogens, protect the plant from abiotic and biotic stressors, and reduce disease incidence and severity at the plant population level. Their exploitation as biocontrol agents in agriculture is well documented. However, mycoparasites may potentially affect classical fungal biocontrol agents of invasive weed species. Classical biological control, or biocontrol, of invasive weeds involves the intentional introduction of exotic, usually co-evolved plant pathogens and insects, for permanent establishment and long-term control of the target plant. Agent establishment, effectiveness, and safety are the critical elements for a successful weed biocontrol programme. Establishment and effectiveness of agents on the invasive plant often vary throughout the invaded range with about two-thirds of weed biocontrol agents failing to suppress their target weed. There are many documented reasons why weed biocontrol agents do not establish or are ineffective when they do, and the presence and accumulation of natural enemies in the invaded range is one of them. Endophyte-enriched, invasive weeds and those forming mutualistic associations with indigenous, native endophytes could explain the lack of consistency of some classical biological control introductions. However, another variable could be factored into the mix: mycoparasitism, where one fungus parasitises another, the natural enemies of the plant’s natural enemies. In this review article, we introduce the concept of invasive weed biocontrol and the history of using plant pathogens as biocontrol agents. We discuss the success and failure of fungal agent programmes and delve into the patterns of success or failure, with a focus on the potential antagonistic role of endophytes and mycoparasites.
Enhancing the diversity of self-replicating structures using active self-adapting mechanisms
Authors: Xu Wenli , Wu Chunrong , Peng Qinglan , Lee Jia , Xia Yunni , Kawasaki Shuji
Published: July 2022

Numerous varieties of life forms have filled the earth throughout evolution. Evolution consists of two processes: self-replication and interaction with the physical environment and other living things around it. Initiated by von Neumann et al. studies on self-replication in cellular automata have attracted much attention, which aim to explore the logical mechanism underlying the replication of living things. In nature, competition is a common and spontaneous resource to drive self-replications, whereas most cellular-automaton-based models merely focus on some self-protection mechanisms that may deprive the rights of other artificial life (loops) to live. Especially, Huang et al. designed a self-adaptive, self-replicating model using a greedy selection mechanism, which can increase the ability of loops to survive through an occasionally abandoning part of their own structural information, for the sake of adapting to the restricted environment. Though this passive adaptation can improve diversity, it is always limited by the loop’s original structure and is unable to evolve or mutate new genes in a way that is consistent with the adaptive evolution of natural life. Furthermore, it is essential to implement more complex self-adaptive evolutionary mechanisms not at the cost of increasing the complexity of cellular automata. To this end, this article proposes new self-adaptive mechanisms, which can change the information of structural genes and actively adapt to the environment when the arm of a self-replicating loop encounters obstacles, thereby increasing the chance of replication. Meanwhile, our mechanisms can also actively add a proper orientation to the current construction arm for the sake of breaking through the deadlock situation. Our new mechanisms enable active self-adaptations in comparison with the passive mechanism in the work of Huang et al. which is achieved by including a few rules without increasing the number of cell states as compared to the latter. Experiments demonstrate that this active self-adaptability can bring more diversity than the previous mechanism, whereby it may facilitate the emergence of various levels in self-replicating structures.
Innate Immune Training of Human Macrophages by Cathelicidin Analogs
Authors: van Dijk Albert , Anten Jennifer , Bakker Anne , Evers Noah , Hoekstra Anna T. , Chang Jung-Chin , Scheenstra Maaike R. , Veldhuizen Edwin J. A. , Netea Mihai G. , Berkers Celia R. , Haagsman Henk P.
Published: July 2022

Trained innate immunity can be induced in human macrophages by microbial ligands, but it is unknown if exposure to endogenous alarmins such as cathelicidins can have similar effects. Previously, we demonstrated sustained protection against infection by the chicken cathelicidin-2 analog DCATH-2. Thus, we assessed the capacity of cathelicidins to induce trained immunity. PMA-differentiated THP-1 (dTHP1) cells were trained with cathelicidin analogs for 24 hours and restimulated after a 3-day rest period. DCATH-2 training of dTHP-1 cells amplified their proinflammatory cytokine response when restimulated with TLR2/4 agonists. Trained cells displayed a biased cellular metabolism towards mTOR-dependent aerobic glycolysis and long-chain fatty acid accumulation and augmented microbicidal activity. DCATH-2-induced trained immunity was inhibited by histone acetylase inhibitors, suggesting epigenetic regulation, and depended on caveolae/lipid raft-mediated uptake, MAPK p38 and purinergic signaling. To our knowledge, this is the first report of trained immunity by host defense peptides.
SARS-CoV-2’s Variants of Concern: A Brief Characterization
Authors: Scovino Aline Miranda , Dahab Elizabeth Chen , Vieira Gustavo Fioravanti , Freire-de-Lima Leonardo , Freire-de-Lima Celio Geraldo , Morrot Alexandre
Published: July 2022

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disclose the variants of concern (VOC) including Alpha (B.1.1.7), Beta (B.1.351), Gamma (P1), Delta (B.1.617.2), and Omicron (B.1.1.529). Its spike protein (S) present on the surface of the virus is recognized by the host cell receptor, the angiotensin-2 converting enzyme (ACE2) which promotes their entry into the cell. The mutations presented by VOCs are found in RBD and the N-terminal region of S protein. Therefore, mutations occurring in RBD can modify the biological and immunogenic characteristics of the virus, such as modifying the spike affinity for ACE2, increasing the virus transmissibility, or conferring the ability to escape the immune responses. The raise of a potential new SARS-CoV-2 variant capable of evading the host defenses at the same time maintaining its fitness justifies the importance of continued genetic monitoring of the pandemic coronavirus.
Defining Patient-Level Molecular Heterogeneity in Psoriasis Vulgaris Based on Single-Cell Transcriptomics
Authors: Liu Yale , Wang Hao , Cook Christopher , Taylor Mark A. , North Jeffrey P. , Hailer Ashley , Shou Yanhong , Sadik Arsil , Kim Esther , Purdom Elizabeth , Cheng Jeffrey B. , Cho Raymond J.
Published: July 2022

Identifying genetic variation underlying human diseases establishes targets for therapeutic development and helps tailor treatments to individual patients. Large-scale transcriptomic profiling has extended the study of such molecular heterogeneity between patients to somatic tissues. However, the lower resolution of bulk RNA profiling, especially in a complex, composite tissue such as the skin, has limited its success. Here we demonstrate approaches to interrogate patient-level molecular variance in a chronic skin inflammatory disease, psoriasis vulgaris, leveraging single-cell RNA-sequencing of CD45+ cells isolated from active lesions. Highly psoriasis-specific transcriptional abnormalities display greater than average inter-individual variance, nominating them as potential sources of clinical heterogeneity. We find that one of these chemokines, CXCL13, demonstrates significant correlation with severity of lesions within our patient series. Our analyses also establish that genes elevated in psoriatic skin-resident memory T cells are enriched for programs orchestrating chromatin and CDC42-dependent cytoskeleton remodeling, specific components of which are distinctly correlated with and against Th17 identity on a single-cell level. Collectively, these analyses describe systematic means to dissect cell type- and patient-level differences in cutaneous psoriasis using high-resolution transcriptional profiles of human inflammatory disease.
Kidney transplantation in systemic sclerosis: Advances in graft, disease, and patient outcome
Authors: Maritati Federica , Provenzano Michele , Lerario Sarah , Corradetti Valeria , Bini Claudia , Busutti Marco , Grandinetti Valeria , Cuna Vania , La Manna Gaetano , Comai Giorgia
Published: July 2022

Systemic sclerosis (SSc) is an immune-mediated rheumatic disease characterized by vascular abnormalities, tissue fibrosis, and inflammation. Renal disease occurring in patients with SSc may have a variable clinicopathological picture. However, the most specific renal condition associated with this disease is the scleroderma renal crisis (SRC), characterized by acute onset of renal failure and severe hypertension. SRC develops in about 20% of cases of SSc, especially in those patients with diffuse cutaneous disease. The prognosis of this condition is often negative, with a rapid progression to end-stage renal disease (ESRD). The advent of the antihypertensive angiotensin-converting enzyme inhibitors in 1980 was associated with a significant improvement in patients’ survival and recovery of renal function. However, the prognosis of these patients can still be improved. The dialytic condition is associated with early death, and mortality is significantly higher than among patients undergoing renal replacement therapy (RRT) due to other conditions. Patients with SRC who show no signs of renal functional recovery despite timely blood pressure control are candidates for kidney transplantation (KT). In this review, we reported the most recent advances in KT in patients with ESRD due to SSc, with a particular overview of the risk of disease recurrence after transplantation and the evolution of other disease manifestations.
Synovial Macrophages: Past Life, Current Situation, and Application in Inflammatory Arthritis
Authors: Bai Lin-Kun , Su Ya-Zhen , Wang Xue-Xue , Bai Bing , Zhang Cheng-Qiang , Zhang Li-Yun , Zhang Gai-Lian
Published: July 2022

Inflammatory arthritis is an inflammatory disease that involves the joints and surrounding tissues. Synovial hyperplasia often presents when joints become inflamed due to immune cell infiltration. Synovial membrane is an important as well as a highly specific component of the joint, and its lesions can lead to degeneration of the joint surface, causing pain and joint disability or affecting the patients’ quality of life in severe cases. Synovial macrophages (SMs) are one of the cellular components of the synovial membrane, which not only retain the function of macrophages to engulf foreign bodies in the joint cavity, but also interact with synovial fibroblasts (SFs), T cells, B cells, and other inflammatory cells to promote the production of a variety of pro-inflammatory cytokines and chemokines, such as TNF-α, IL-1β, IL-8, and IL-6, which are involved in the pathogenic process of inflammatory arthritis. SMs from different tissue sources have differently differentiated potentials and functional expressions. This article provides a summary on studies pertaining to SMs in inflammatory arthritis, and explores their role in its treatment, in order to highlight novel treatment modalities for the disease.
Immunogenicity and safety of concomitant administration of the chinese inactivated poliovirus vaccine with the diphtheria-tetanus-acellular pertussis (DTaP) vaccine in children: A multicenter, randomized, non-inferiority, controlled trial
Authors: Sun Xiang , Xu Yan , Tang Fenyang , Xiao Yanhui , Wang Zhiguo , Wang Binbing , Zhu Xiaoping , Yang Xiaoming , Chen Haiping
Published: July 2022

Key point

Considering that vaccination with the sIPV and DTaP overlap at the ages of 3 and 4 months in China, to reduce the burden of treatment on parents and increase vaccination coverage rates, we designed a postmarket clinical study of co-administration.

Background

The Sabin-strain-based inactivated poliovirus vaccine (sIPV) and the diphtheria-tetanus-acellular pertussis vaccine (DTaP) have been licensed in China for many years. To conduct a clinical study on the safety and immunogenicity of the sIPV when administered concomitantly with the DTaP.

Methods

The study population was divided into three groups: group 1 was the sIPV+ DTaP concomitant administration group, group 2 was the sIPV inoculation group, and group 3 was the DTaP inoculation group. Blood samples were collected prevaccination and 30 days postvaccination, and serum antibody levels were detected.

Results

This study showed that the seropositive and seroconversion rates of type 1, 2 and 3 poliovirus in group 1 were higher than those in group 2, with no statistically significant difference after vaccination (P>0.05). Groups 1 and 3 also showed similar responses for all vaccine antigens except anti-FHA (97.65 (94.09-99.36) vs. 100 (97.89-100)). The geometric mean titers (GMTs) for the DTaP and sIPV among the groups were comparable, and the non-inferiority t test result was P<0.001. The number of local adverse events (AEs) reported in group 1 (29.91%) were larger than those in group 2 (12.39%) and group 3 (21.93%), among which the most common was redness. Similarly, the most common systemic AE was fever. All 5 severe AE (SAE) cases were determined by experts to be unrelated to the vaccines during the study.

Conclusions

The evidence of similar seroconversion and safety with co-administered DTaP and sIPV supports the co-administration supports the introduction of a strategy of simultaneous administration of both vaccines into routine infant immunization, and it could increase vaccination coverage and protect more infants from morbidity and mortality from these related diseases.

Clinical Trial Registration

https://clinicaltrials.gov/ct2/show/NCT04054882?term=NCT04054882&cntry=CN&draw=2&rank=1, identifier NCT04054882.
Adoptive B cell therapy for chronic viral infection
Authors: Chung Young Rock , Dangi Tanushree , Palacio Nicole , Sanchez Sarah , Penaloza-MacMaster Pablo
Published: July 2022

T cell-based therapies have been widely explored for the treatment of cancer and chronic infection, but B cell-based therapies have remained largely unexplored. To study the effect of B cell therapy, we adoptively transferred virus-specific B cells into mice that were chronically infected with lymphocytic choriomeningitis virus (LCMV). Adoptive transfer of virus-specific B cells resulted in increase in antibody titers and reduction of viral loads. Importantly, the efficacy of B cell therapy was partly dependent on antibody effector functions, and was improved by co-transferring virus-specific CD4 T cells. These findings provide a proof-of-concept that adoptive B cell therapy can be effective for the treatment of chronic infections, but provision of virus-specific CD4 T cells may be critical for optimal virus neutralization.
TGFβ limits Myc-dependent TCR-induced metabolic reprogramming in CD8+ T cells
Authors: Hope Helen Carrasco , Pickersgill Gabriella , Ginefra Pierpaolo , Vannini Nicola , Cook Graham P. , Salmond Robert J.
Published: July 2022

T cell activation is dependent upon the integration of antigenic, co-stimulatory and cytokine-derived signals and the availability and acquisition of nutrients from the environment. Furthermore, T cell activation is accompanied by reprogramming of cellular metabolism to provide the energy and building blocks for proliferation, differentiation and effector function. Transforming growth factor β (TGFβ) has pleiotropic effects on T cell populations, having both an essential role in the maintenance of immune tolerance but also context-dependent pro-inflammatory functions. We set out to define the mechanisms underpinning the suppressive effects of TGFβ on mouse CD8+ T cell activation. RNA-sequencing analysis of TCR-stimulated T cells determined that Myc-regulated genes were highly enriched within gene sets downregulated by TGFβ. Functional analysis demonstrated that TGFβ impeded TCR-induced upregulation of amino acid transporter expression, amino acid uptake and protein synthesis. Furthermore, TCR-induced upregulation of Myc-dependent glycolytic metabolism was substantially inhibited by TGFβ treatment with minimal effects on mitochondrial respiration. Thus, our data suggest that inhibition of Myc-dependent metabolic reprogramming represents a major mechanism underpinning the suppressive effects of TGFβ on CD8+ T cell activation.
Pan-caspase inhibition during normothermic machine perfusion of discarded livers mitigates ex situ innate immune responses
Authors: Raigani Siavash , Santiago John , Ohman Anders , Heaney Megan , Baptista Sofia , Coe Taylor M. , de Vries Reinier J. , Rosales Ivy , Shih Angela , Markmann James F. , Gruppuso Philip , Uygun Korkut , Sanders Jennifer , Yeh Heidi
Published: July 2022

Access to liver transplantation is limited by a significant organ shortage. The recent introduction of machine perfusion technology allows surgeons to monitor and assess ex situ liver function prior to transplantation. However, many donated organs are of inadequate quality for transplant, though opportunities exist to rehabilitate organ function with adjunct therapeutics during normothermic machine perfusion. In this preclinical study, we targeted the apoptosis pathway as a potential method of improving hepatocellular function. Treatment of discarded human livers during normothermic perfusion with an irreversible pan-caspase inhibitor, emricasan, resulted in significant mitigation of innate immune and pro-inflammatory responses at both the transcriptional and protein level. This was evidenced by significantly decreased circulating levels of the pro-inflammatory cytokines, interleukin-6, interleukin-8, and interferon-gamma, compared to control livers. Compared to emricasan-treated livers, untreated livers demonstrated transcriptional changes notable for enrichment in pathways involved in innate immunity, leukocyte migration, and cytokine-mediated signaling. Targeting of unregulated apoptosis may represent a viable therapeutic intervention for immunomodulation during machine perfusion.
Early detection of soluble CD27, BTLA, and TIM-3 predicts the development of nosocomial infection in pediatric burn patients
Authors: Penatzer Julia A. , Alexander Robin , Simon Shan , Wolfe Amber , Breuer Julie , Hensley Josey , Fabia Renata , Hall Mark , Thakkar Rajan K.
Published: July 2022

Thermal injury induces concurrent inflammatory and immune dysfunction, which is associated with adverse clinical outcomes. However, these effects in the pediatric population are less studied and there is no standard method to identify those at risk for developing infections. Our goal was to better understand immune dysfunction and identify soluble protein markers following pediatric thermal injury. Further we wanted to determine which early inflammatory, soluble, or immune function markers are most predictive of the development of nosocomial infections (NI) after burn injury. We performed a prospective observational study at a single American Burn Association-verified Pediatric Burn Center. A total of 94 pediatric burn subjects were enrolled and twenty-three of those subjects developed a NI with a median time to diagnosis of 8 days. Whole blood samples, collected within the first 72 hours after injury, were used to compare various markers of inflammation, immune function, and soluble proteins between those who recovered without developing an infection and those who developed a NI after burn injury. Within the first three days of burn injury, innate and adaptive immune function markers (ex vivo lipopolysaccharide-induced tumor necrosis factor alpha production capacity, and ex vivo phytohemagglutinin-induced interleukin-10 production capacity, respectively) were decreased for those subjects who developed a subsequent NI. Further analysis of soluble protein targets associated with these pathways displayed significant increases in soluble CD27, BTLA, and TIM-3 for those who developed a NI. Our findings indicate that suppression of both the innate and adaptive immune function occurs concurrently within the first 72 hours following pediatric thermal injury. At the same time, subjects who developed NI have increased soluble protein biomarkers. Soluble CD27, BTLA, and TIM-3 were highly predictive of the development of subsequent infectious complications. This study identifies early soluble protein makers that are predictive of infection in pediatric burn subjects. These findings should inform future immunomodulatory therapeutic studies.
Prognostic implications of preoperative systemic inflammatory markers in oral squamous cell carcinoma, and correlations with the local immune tumor microenvironment
Authors: Ruiz-Ranz Marta , Lequerica-Fernández Paloma , Rodríguez-Santamarta Tania , Suárez-Sánchez Faustino J. , López-Pintor Rosa M. , García-Pedrero Juana M. , de Vicente Juan C.
Published: July 2022

Purpose

The aim of this study was to investigate the prognostic significance of preoperative inflammatory markers in peripheral blood of patients with oral squamous cell carcinoma (OSCC), and to establish correlations with the infiltrate of macrophages and lymphocytes in the local immune tumor microenvironment (TME).

Materials and Methods

Neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), lymphocyte-monocyte ratio (LMR), and systemic immune-inflammation index (SII) were retrospectively evaluated in a cohort of 348 OSCC patients, and correlated with overall (OS) and disease-specific survival (DSS). Immunohistochemical analysis of tumoral and stromal infiltration of CD8+, CD4+, FOXP3+ and CD20+ lymphocytes and CD68+ and CD163+ macrophages was performed in a subset of 119 OSCC patient samples, and correlations further assessed.

Results

NLR, SII, and LMR were significantly associated with a poorer OS in univariate analysis; however, only NLR remained a significant independent predictor in the multivariate analysis (HR = 1.626, p = 0.04). NLR and SII were inversely and significantly correlated with stromal infiltration of CD8+, CD4+, and CD20+ lymphocytes. Moreover, a significant correlation between LMR was also found to significantly associate with stromal infiltration of CD8+, CD4+, and CD20+ lymphocytes, stromal CD68+ and CD163+ macrophages, and also tumoral infiltration of CD4+ and CD20+ lymphocytes.

Conclusions

Preoperative NLR, SII, and LMR may serve as valuable systemic markers to predict OSCC patient survival, with NLR emerging as an independent predictor of poor OS. Moreover, strong significant correlations were exclusively observed between systemic inflammatory markers and the local stromal infiltration of lymphocytes in the TME.
Targeting ETosis by miR-155 inhibition mitigates mixed granulocytic asthmatic lung inflammation
Authors: Kim Ji Young , Stevens Patrick , Karpurapu Manjula , Lee Hyunwook , Englert Joshua A. , Yan Pearlly , Lee Tae Jin , Pabla Navjot , Pietrzak Maciej , Park Gye Young , Christman John W. , Chung Sangwoon
Published: July 2022

Asthma is phenotypically heterogeneous with several distinctive pathological mechanistic pathways. Previous studies indicate that neutrophilic asthma has a poor response to standard asthma treatments comprising inhaled corticosteroids. Therefore, it is important to identify critical factors that contribute to increased numbers of neutrophils in asthma patients whose symptoms are poorly controlled by conventional therapy. Leukocytes release chromatin fibers, referred to as extracellular traps (ETs) consisting of double-stranded (ds) DNA, histones, and granule contents. Excessive components of ETs contribute to the pathophysiology of asthma; however, it is unclear how ETs drive asthma phenotypes and whether they could be a potential therapeutic target. We employed a mouse model of severe asthma that recapitulates the intricate immune responses of neutrophilic and eosinophilic airway inflammation identified in patients with severe asthma. We used both a pharmacologic approach using miR-155 inhibitor-laden exosomes and genetic approaches using miR-155 knockout mice. Our data show that ETs are present in the bronchoalveolar lavage fluid of patients with mild asthma subjected to experimental subsegmental bronchoprovocation to an allergen and a severe asthma mouse model, which resembles the complex immune responses identified in severe human asthma. Furthermore, we show that miR-155 contributes to the extracellular release of dsDNA, which exacerbates allergic lung inflammation, and the inhibition of miR-155 results in therapeutic benefit in severe asthma mice. Our findings show that targeting dsDNA release represents an attractive therapeutic target for mitigating neutrophilic asthma phenotype, which is clinically refractory to standard care.
Endoplasmic reticulum stress in innate immune cells - a significant contribution to non-alcoholic fatty liver disease
Authors: Zhou Liangliang , Shen Haiyuan , Li Xiaofeng , Wang Hua
Published: July 2022

Liver disease and its complications affect millions of people worldwide. NAFLD (non-alcoholic fatty liver disease) is the liver disease associated with metabolic dysfunction and consists of four stages: steatosis with or without mild inflammation (NAFLD), non-alcoholic steatohepatitis (NASH), fibrosis, and cirrhosis. With increased necroinflammation and progression of liver fibrosis, NAFLD may progress to cirrhosis or even hepatocellular carcinoma. Although the underlying mechanisms have not been clearly elucidated in detail, what is clear is that complex immune responses are involved in the pathogenesis of NASH, activation of the innate immune system is critically involved in triggering and amplifying hepatic inflammation and fibrosis in NAFLD/NASH. Additionally, disruption of endoplasmic reticulum (ER) homeostasis in cells, also known as ER stress, triggers the unfolded protein response (UPR) which has been shown to be involved to inflammation and apoptosis. To further develop the prevention and treatment of NAFLD/NASH, it is imperative to clarify the relationship between NAFLD/NASH and innate immune cells and ER stress. As such, this review focuses on innate immune cells and their ER stress in the occurrence of NAFLD and the progression of cirrhosis.
MiR-365-3p is a negative regulator in IL-17-mediated asthmatic inflammation
Authors: Wang Weijia , Li Ying , Fan Jiaqi , Qu Xiaoyan , Shang Dong , Qin Qiaohong , Xu Tun , Hamid Qutayba , Dang Xiaomin , Chang Ying , Xu Dan
Published: July 2022

Background

Interleukin-17, the major proinflammatory cytokine secreted by Th17 cells, makes essential contribution to pathogenesis of severe asthma, while the detailed mechanisms, especially the involvement of microRNAs which are also important participants in asthma progression, remains largely unclear.

Methods

In this study, we established a house dust mite (HDM) extract-induced murine asthmatic models and the miRNA expression in the lung tissues of mice were profiled by miRNA microarray assay. The effect of miR-365-3p on IL-17-mediated inflammation was examined by qRT-PCR and immunoblotting analysis. The involvement of ARRB2 as target gene of miR-365-3p was verified by overexpression or RNA interference.

Results

HDM extract-induced asthmatic inflammation was proved to be IL17-mediated and miR-365-3p was screened out to be the only miRNA exclusively responsive to IL-17. miR-365-3p, whose expression was significantly downregulated upon IL-17 stimulation, was demonstrated to exert remarkable anti-inflammatory effect to decrease IL-17-provoked inflammatory cytokines (KC/IL-8 and IL-6) in both airway epithelial cells and macrophages of murine and human origins, verifying its universal antagonizing activity against IL-17-initiated inflammation across the two species. ARRB2 was characterized as the key target of miR-365-3p to negate IL-17-induced inflammatory cytokines.

Conclusion

Taken together, our data supported the notion that miR-365-3p, which was diminished by IL-17 in murine and human asthmatic pathogenesis, functioned as an essential negative mediator in IL-17-stimuated inflammatory response by targeting ARRB2, which would shed new light to the understanding and therapeutics thereof of asthmatic inflammation.
Effectiveness and tolerability of different therapies in preventive treatment of MOG-IgG-associated disorder: A network meta-analysis
Authors: Wang Xiaofei , Kong Lingyao , Zhao Zhengyang , Shi Ziyan , Chen Hongxi , Lang Yanlin , Lin Xue , Du Qin , Zhou Hongyu
Published: July 2022

Background

Immunotherapy has been shown to reduce relapses in patients with myelin oligodendrocyte glycoprotein antibody-associated disorder (MOG-AD); however, the superiority of specific treatments remains unclear.

Aim

To identify the efficacy and tolerability of different treatments for MOG-AD.

Methods

Systematic search in Pubmed, Embase, Web of Science, and Cochrane Library databases from inception to March 1, 2021, were performed. Published articles including patients with MOG-AD and reporting the efficacy or tolerability of two or more types of treatment in preventing relapses were included. Reported outcomes including incidence of relapse, annualized relapse rate (ARR), and side effects were extracted. Network meta-analysis with a random-effect model within a Bayesian framework was conducted. Between group comparisons were estimated using Odds ratio (OR) or mean difference (MD) with 95% credible intervals (CrI).

Results

Twelve studies that compared the efficacy of 10 different treatments in preventing MOG-AD relapse, including 735 patients, were analyzed. In terms of incidence of relapse, intravenous immunoglobulins (IVIG), oral corticosteroids (OC), mycophenolate mofetil (MMF), azathioprine (AZA), and rituximab (RTX) were all significantly more effective than no treatment (ORs ranged from 0.075 to 0.34). On the contrary, disease-modifying therapy (DMT) (OR=1.3, 95% CrI: 0.31 to 5.0) and tacrolimus (TAC) (OR=5.9, 95% CrI: 0.19 to 310) would increase the incidence of relapse. Compared with DMT, IVIG significantly reduced the ARR (MD=−0.85, 95% CrI: −1.7 to −0.098). AZA, MMF, OC and RTX showed a trend to decrease ARR, but those results did not reach significant differences. The combined results for relapse rate and adverse events, as well as ARR and adverse events showed that IVIG and OC were the most effective and tolerable therapies.

Conclusions

Whilst DMT should be avoided, IVIG and OC may be suited as first-line therapies for patients with MOG-AD. RTX, MMF, and AZA present suitable alternatives.
Immunomodulatory roles of selenium nanoparticles: Novel arts for potential immunotherapy strategy development
Authors: Chen Gengshi , Yang Fen , Fan Shuhao , Jin Hua , Liao Kangsheng , Li Xuemeng , Liu Gan-Bin , Liang Jing , Zhang Junai , Xu Jun-Fa , Pi Jiang
Published: July 2022

Current chemotherapy strategies used in clinic appear with lots of disadvantages due to the low targeting effects of drugs and strong side effects, which significantly restricts the drug potency, causes multiple dysfunctions in the body, and even drives the emergence of diseases. Immunotherapy has been proved to boost the body’s innate and adaptive defenses for more effective disease control and treatment. As a trace element, selenium plays vital roles in human health by regulating the antioxidant defense, enzyme activity, and immune response through various specific pathways. Profiting from novel nanotechnology, selenium nanoparticles have been widely developed to reveal great potential in anticancer, antibacterial, and anti-inflammation treatments. More interestingly, increasing evidence has also shown that functional selenium nanoparticles can be applied for potential immunotherapy, which would achieve more effective treatment efficiency as adjunctive therapy strategies for the current chemotherapy. By directly interacting with innate immune cells, such as macrophages, dendritic cells, and natural killer cells, selenium nanoparticles can regulate innate immunity to intervene disease developments, which were reported to boost the anticancer, anti-infection, and anti-inflammation treatments. Moreover, selenium nanoparticles can also activate and recover different T cells for adaptive immunity regulations to enhance their cytotoxic to combat cancer cells, indicating the potential of selenium nanoparticles for potential immunotherapy strategy development. Here, aiming to enhance our understanding of the potential immunotherapy strategy development based on Se NPs, this review will summarize the immunological regulation effects of selenium nanoparticles and the application of selenium nanoparticle-based immunotherapy strategies. Furthermore, we will discuss the advancing perspective of selenium nanoparticle-based potential immunotherapy as a kind of novel adjunctive therapy to enhance the efficiency of current chemotherapies and also introduce the current obstacles for the development of selenium nanoparticles for potential immunotherapy strategy development. This work is expected to promote the future research on selenium nanoparticle-assisted immunotherapy and finally benefit the more effective disease treatments against the threatening cancer and infectious and chronic diseases.
Interleukin-6 inhibition in the treatment of autoinflammatory diseases
Authors: Koga Tomohiro , Kawakami Atsushi
Published: July 2022

Autoinflammatory diseases are characterized by abnormalities that prevent innate immune cells from producing autoantibodies. While interleukin (IL)-6 is not directly associated with inflammasomes, like IL-1β or IL-18, it plays an important role in the pathogenesis of autoinflammatory diseases. Studies of autoinflammatory diseases, such as familial Mediterranean fever, cryopyrin-associated periodic syndrome, and tumor necrosis factor receptor-associated periodic syndrome, have shown IL-6 to be a promising therapeutic target. It has also been suggested that inhibition of IL-6 may have a therapeutic effect on amyloidosis, which is frequently associated with these chronic inflammatory diseases. In this study, we discuss the most recent research on the role of IL-6 in autoinflammatory diseases and its potential as a therapeutic target in their treatment.
Molecular Phylogeny of the Genus Nipponnemertes (Nemertea: Monostilifera: Cratenemertidae) and Descriptions of 10 New Species, With Notes on Small Body Size in a Newly Discovered Clade
Authors: Hookabe Natsumi , Kajihara Hiroshi , Chernyshev Alexei V. , Jimi Naoto , Hasegawa Naohiro , Kohtsuka Hisanori , Okanishi Masanori , Tani Kenichiro , Fujiwara Yoshihiro , Tsuchida Shinji , Ueshima Rei
Published: July 2022

Nemerteans, or ribbon worms, have been reported from intertidal to hadal depths, often showing bathymetrically wide distribution in genus levels. Although current nemertean systematics practices require to provide DNA sequences and infer phylogenetic relationships with suitable molecular markers, previous molecular systematics on nemerteans are mostly biased toward shallow-water species. Members in the genus Nipponnemertes occur worldwide, from tropical to polar waters and intertidal to bathyal waters. Molecular phylogenetic studies are scarce for the genus; only six shallow-water species of 18 species in the genus were subject to molecular phylogeny. Thus, Nipponnemertes is one candidate that needs to be assessed by genetic approaches. In this study, we performed molecular phylogenetic analyses using 59 specimens in 23 species based on partial sequences of two mitochondrial (16S rRNA and cytochrome c oxidase subunit I) and three nuclear gene markers (18S rRNA, 28S rRNA, and histone H3). Our extensive sampling from intertidal to bathyal waters in the Northwest Pacific significantly updated the fauna of Nipponnemertes in this region from four to 17 species. We herein establish 10 new species and provide an updated species list concisely summarizing all the congeners known from the world. Our phylogenetic tree indicated three major lineages within the genus (herein referred to as “Clade A, B, and C”), each presumably characterized by the combination of morphological characters in the head region. Members in Clade A are: Nipponnemertes pulchra (Johnston, 1837), Nipponnemertes ogumai (Yamaoka, 1947), and several unidentified congeners, characterized by having demarcated head without cephalic patches; members in Clade B are: Nipponnemertes crypta sp. nov., Nipponnemertes jambio sp. nov., Nipponnemertes neonilae sp. nov., and Nipponnemertes ojimaorum sp. nov., species having demarcated head with cephalic patches; members in Clade C are: Nipponnemertes ganahai sp. nov., Nipponnemertes kozaensis sp. nov., Nipponnemertes lactea sp. nov., Nipponnemertes notoensis sp. nov., Nipponnemertes ornata sp. nov., Nipponnemertes sugashimaensis sp. nov., and two unidentified forms collected off Jogashima (Japan) and Guam (USA), species with non-demarcated head lacking cephalic patches. Furthermore, we discuss the evolution of remarkably small body size retained among Clade C.
Dinoflagellate cysts production, excystment and transport in the upwelling off Cape Blanc (NW Africa)
Authors: Zonneveld Karin A. F. , Grotheer Hendrik , Versteegh Gerard J. M.
Published: July 2022

To extend the understanding of dinoflagellate cysts production, excystment and vertical/lateral transport in the water column, we compared upper water cyst export production with cysts associations and concentrations in the subsurface nepheloid layer, bottom nepheloid layer and deeper water column during active upwelling off Cape Blanc (NW Africa) in August 2020. Export production was collected by two drifting trap surveys; DTS1 in an active upwelling cell for 4 days and DTS2 in an offshore drifting upwelling filament for 2 days. Subsurface, bottom nepheloid layers and deeper waters were sampled by in-situ pumps along two transects perpendicular to the shelf break. During DTS1, light limitation hampered phytoplankton production which might have influenced cyst production negatively due to up- and downward movement of water masses. Cyst export production increased at the rim of the upwelling cell. For DTS2, upwelling filament cyst export production was up to 3 times lower than that of DTS1. Echinidinium delicatum had highest relative and absolute abundances in the active upwelling, Echinidinium zonneveldiae and Bitectatodinium spongium in the upwelling filament, and Impagidinium spp. and cysts of Gymnodinium microreticulatum/nolleri at the most distal stations. Comparison of concentrations of cysts with and without cell contents showed that the majority of cysts hatched before reaching deeper waters and displayed a dormancy period of less than 6 days. About 5% of the living cysts reached deeper waters and/or the ocean floor. Living cysts were transported offshore in the upwelling filament. In case ships exchange ballast waters in the studied region, they will take up laterally transported living cysts. Upon release of the ballast waters in the port of arrival, these cysts have the potential to become “invader species” that can threaten economy and/or health. Lateral transport of cysts was observed in the bottom nepheloid layer and in deeper waters (800 - 1200m depth) with a maximal extension of about 130km off the shelf break. Therefore, sediments in the region will contain a mixture of regionally and locally produced dinoflagellate cysts. This insight contributes to the improvement of environmental reconstructions of the Cape blanc upwelling system based on downcore cyst associations.