bluuebunny/crossref_metadata_2025 huggingface dataset:
KL-6 as an Immunological Biomarker Predicts the Severity, Progression, Acute Exacerbation, and Poor Outcomes of Interstitial Lung Disease: A Systematic Review and Meta-Analysis
Authors: Zhang Tao , Shen Ping , Duan Chunyan , Gao Lingyun
Published: December 2021

Object

Interstitial lung disease (ILD) is a specific form of chronic fibrosing interstitial pneumonia with various etiology. The severity and progression of ILD usually predict the poor outcomes of ILD. Otherwise, Krebs von den Lungen-6 (KL-6) is a potential immunological biomarker reflecting the severity and progression of ILD. This meta-analysis is to clarify the predictive value of elevated KL-6 levels in ILD.

Method

EBSCO, PubMed, and Cochrane were systematically searched for articles exploring the prognosis of ILD published between January 1980 and April 2021. The Weighted Mean Difference (WMD) and 95% Confidence Interval (CI) were computed as the effect sizes for comparisons between groups. For the relationship between adverse outcome and elevated KL-6 concentration, Hazard Ratio (HR), and its 95%CI were used to estimate the risk factor of ILD.

Result

Our result showed that ILD patients in severe and progressive groups had higher KL-6 levels, and the KL-6 level of patients in the severe ILD was 703.41 (U/ml) than in mild ILD. The KL-6 level in progressive ILD group was 325.98 (U/ml) higher than that in the non-progressive ILD group. Secondly, the KL-6 level of patients in acute exacerbation (AE) of ILD was 545.44 (U/ml) higher than stable ILD. Lastly, the higher KL-6 level in ILD patients predicted poor outcomes. The KL-6 level in death of ILD was 383.53 (U/ml) higher than in survivors of ILD. The pooled HR (95%CI) about elevated KL-6 level predicting the mortality of ILD was 2.05 (1.50–2.78), and the HR (95%CI) for progression of ILD was 1.98 (1.07–3.67).

Conclusion

The elevated KL-6 level indicated more severe, more progressive, and predicted the higher mortality and poor outcomes of ILD.
Genetic Modification of Limbal Stem Cells to Decrease Allogeneic Immune Responses
Authors: Valdivia Emilio , Bertolin Marina , Breda Claudia , Carvalho Oliveira Marco , Salz Anna Katharina , Hofmann Nicola , Börgel Martin , Blasczyk Rainer , Ferrari Stefano , Figueiredo Constanca
Published: December 2021

Limbal stem cell (LSC) transplantation is the only efficient treatment for patients affected by LSC deficiency (LSCD). Allogeneic LSC transplantation is one of the most successful alternative for patients with bilateral LSCD. Nevertheless, the high variability of the human leukocyte antigens (HLA) remains a relevant obstacle to long-term allogeneic graft survival. This study characterized the immunologic properties of LSCs and proposed a genetic engineering strategy to reduce the immunogenicity of LSCs and of their derivatives. Hence, LSC HLA expression was silenced using lentiviral vectors encoding for short hairpin (sh) RNAs targeting β2-microglobulin (β2M) or class II major histocompatibility complex transactivator (CIITA) to silence HLA class I and II respectively. Beside the constitutive expression of HLA class I, LSCs showed the capability to upregulate HLA class II expression under inflammatory conditions. Furthermore, LSCs demonstrated the capability to induce T-cell mediated immune responses. LSCs phenotypical and functional characteristics are not disturbed after genetic modification. However, HLA silenced LSC showed to prevent T cell activation, proliferation and cytotoxicity in comparison to fully HLA-expressing LSCs. Additionally; HLA-silenced LSCs were protected against antibody-mediated cellular-dependent cytotoxicity. Our data is a proof-of-concept of the feasibility to generate low immunogenic human LSCs without affecting their typical features. The use of low immunogenic LSCs may support for long-term survival of LSCs and their derivatives after allogeneic transplantation.
Human Properdin Released By Infiltrating Neutrophils Can Modulate Influenza A Virus Infection
Authors: Varghese Praveen M. , Mukherjee Shuvechha , Al-Mohanna Futwan A. , Saleh Souad M. , Almajhdi Fahad N. , Beirag Nazar , Alkahtani Saad H. , Rajkumari Reena , Nal Rogier Beatrice , Sim Robert B. , Idicula-Thomas Susan , Madan Taruna , Murugaiah Valarmathy , Kishore Uday
Published: December 2021

The complement system is designed to recognise and eliminate invading pathogensviaactivation of classical, alternative and lectin pathways. Human properdin stabilises the alternative pathway C3 convertase, resulting in an amplification loop that leads to the formation of C5 convertase, thereby acting as a positive regulator of the alternative pathway. It has been noted that human properdin on its own can operate as a pattern recognition receptor and exert immune functions outside its involvement in complement activation. Properdin can bind directly to microbial targetsviaDNA, sulfatides and glycosaminoglycans, apoptotic cells, nanoparticles, and well-known viral virulence factors. This study was aimed at investigating the complement-independent role of properdin against Influenza A virus infection. As one of the first immune cells to arrive at the site of IAV infection, we show here that IAV challenged neutrophils released properdin in a time-dependent manner. Properdin was found to directly interact with haemagglutinin, neuraminidase and matrix 1 protein Influenza A virus proteins in ELISA and western blot. Furthermore, modelling studies revealed that properdin could bind HA and NA of the H1N1 subtype with higher affinity compared to that of H3N2 due to the presence of an HA cleavage site in H1N1. In an infection assay using A549 cells, properdin suppressed viral replication in pH1N1 subtype while promoting replication of H3N2 subtype, as revealed by qPCR analysis of M1 transcripts. Properdin treatment triggered an anti-inflammatory response in H1N1-challenged A549 cells and a pro-inflammatory response in H3N2-infected cells, as evident from differential mRNA expression of TNF-α, NF-κB, IFN-α, IFN-β, IL-6, IL-12 and RANTES. Properdin treatment also reduced luciferase reporter activity in MDCK cells transduced with H1N1 pseudotyped lentiviral particles; however, it was increased in the case of pseudotyped H3N2 particles. Collectively, we conclude that infiltrating neutrophils at the site of IAV infection can release properdin, which then acts as an entry inhibitor for pandemic H1N1 subtype while suppressing viral replication and inducing an anti-inflammatory response. H3N2 subtype can escape this immune restriction due to altered haemagglutinin and neuraminindase, leading to enhanced viral entry, replication and pro-inflammatory response. Thus, depending on the subtype, properdin can either limit or aggravate IAV infection in the host.
Receptor Interacting Protein Kinase Pathways Regulate Innate B Cell Developmental Checkpoints But Not Effector Function in Mice
Authors: Parthasarathy Raksha , Hägglöf Thomas , Hadley Jason T. , McLennan Alexandra , Mattke Aiden , Dudley Elizabeth A. , Kumagai Abigail , Dong Lily Q. , Leadbetter Elizabeth A.
Published: December 2021

Mutations in the scaffolding domain of Receptor Interacting Protein kinases (RIP) underlie the recently described human autoimmune syndrome, CRIA, characterized by lymphadenopathy, splenomegaly, and autoantibody production. While disease mechanisms for CRIA remain undescribed, RIP kinases work together with caspase-8 to regulate cell death, which is critical for normal differentiation of many cell types. Here, we describe a key role for RIP1 in facilitating innate B cell differentiation and subsequent activation. By comparing RIP1, RIP3, and caspase-8 triple deficient and RIP3, caspase-8 double deficient mice, we identified selective contributions of RIP1 to an accumulation of murine splenic Marginal Zone (MZ) B cells and B1-b cells. We used mixed bone-marrow chimeras to determine that innate B cell commitment required B cell-intrinsic RIP1, RIP3, and caspase-8 sufficiency. RIP1 regulated MZ B cell development rather than differentiation and RIP1 mediates its innate immune effects independent of the RIP1 kinase domain. NP-KLH/alum and NP-Ficoll vaccination of mice doubly deficient in both caspase-8 and RIP3 or deficient in all three proteins (RIP3, caspase-8, and RIP1) revealed uniquely delayed T-dependent and T-independent IgG responses, abnormal splenic germinal center architecture, and reduced extrafollicular plasmablast formation compared to WT mice. Thus, RIP kinases and caspase-8 jointly orchestrate B cell fate and delayed effector function through a B cell-intrinsic mechanism.
Activation of T-bet, FOXP3, and EOMES in Target Organs From Piglets Infected With the Virulent PRRSV-1 Lena Strain
Authors: Ruedas-Torres Inés , Gómez-Laguna Jaime , Sánchez-Carvajal José María , Larenas-Muñoz Fernanda , Barranco Inmaculada , Pallarés Francisco José , Carrasco Librado , Rodríguez-Gómez Irene Magdalena
Published: December 2021

Transcription factors (TFs) modulate genes involved in cell-type-specific proliferative and migratory properties, metabolic features, and effector functions. Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most important pathogen agents in the porcine industry; however, TFs have been poorly studied during the course of this disease. Therefore, we aimed to evaluate the expressions of the TFs T-bet, GATA3, FOXP3, and Eomesodermin (EOMES) in target organs (the lung, tracheobronchial lymph node, and thymus) and those of different effector cytokines (IFNG, TNFA, and IL10) and the Fas ligand (FASL) during the early phase of infection with PRRSV-1 strains of different virulence. Target organs from mock-, virulent Lena-, and low virulent 3249-infected animals humanely euthanized at 1, 3, 6, 8, and 13 days post-infection (dpi) were collected to analyze the PRRSV viral load, histopathological lesions, and relative quantification through reverse transcription quantitative PCR (RT-qPCR) of the TFs and cytokines. Animals belonging to both infected groups, but mainly those infected with the virulent Lena strain, showed upregulation of the TFs T-bet, EOMES, and FOXP3, together with an increase of the cytokine IFN-γ in target organs at the end of the study (approximately 2 weeks post-infection). These results are suggestive of a stronger polarization to Th1 cells and regulatory T cells (Tregs), but also CD4+ cytotoxic T lymphocytes (CTLs), effector CD8+ T cells, and γδT cells in virulent PRRSV-1-infected animals; however, their biological functionality should be the object of further studies.
SARS-CoV-2 Specific IgG Antibodies Persist Over a 12-Month Period in Oral Mucosal Fluid Collected From Previously Infected Individuals
Authors: Chellamuthu Prithivi , Angel Aaron N. , MacMullan Melanie A. , Denny Nicholas , Mades Aubree , Santacruz Marilisa , Lopez Ronell , Bagos Cedie , Casian Joseph G. , Trettner Kylie , Lopez Lauren , Nirema Nina , Brobeck Matthew , Kojima Noah , Klausner Jeffrey D. , Turner Fred , Slepnev Vladimir , Ibrayeva Albina
Published: December 2021

Background

Developing an understanding of the antibody response, seroprevalence, and seroconversion from natural infection and vaccination against SARS-CoV-2 will give way to a critical epidemiological tool to predict reinfection rates, identify vulnerable communities, and manage future viral outbreaks. To monitor the antibody response on a larger scale, we need an inexpensive, less invasive, and high throughput method.

Methods

Here we investigate the use of oral mucosal fluids from individuals recovered from SARS-CoV-2 infection to monitor antibody response and persistence over a 12-month period. For this cohort study, enzyme-linked immunosorbent assays (ELISAs) were used to quantify anti-Spike(S) protein IgG antibodies in participants who had prior SARS-CoV-2 infection and regularly (every 2-4 weeks) provided both serum and oral fluid mucosal fluid samples for longitudinal antibody titer analysis.

Results

In our study cohort (n=42) with 17 males and 25 females with an average age of 45.6 +/- 19.3 years, we observed no significant change in oral mucosal fluid IgG levels across the time course of antibody monitoring. In oral mucosal fluids, all the participants who initially had detectable antibodies continued to have detectable antibodies throughout the study.

Conclusions

Based on the results presented here, we have shown that oral mucosal fluid-based assays are an effective, less invasive tool for monitoring seroprevalence and seroconversion, which offers an alternative to serum-based assays for understanding the protective ability conferred by the adaptive immune response from viral infection and vaccination against future reinfections.
Evidence of SARS-CoV-2-Specific T-Cell-Mediated Myocarditis in a MIS-A Case
Authors: Vannella Kevin M. , Oguz Cihan , Stein Sydney R. , Pittaluga Stefania , Dikoglu Esra , Kanwal Arjun , Ramelli Sabrina C. , Briese Thomas , Su Ling , Wu Xiaolin , Ramos-Benitez Marcos J. , Perez-Valencia Luis J. , Babyak Ashley , Cha Nu Ri , Chung Joon-Yong , Ylaya Kris , Madathil Ronson J. , Saharia Kapil K. , Scalea Thomas M. , Tran Quincy K. , Herr Daniel L. , Kleiner David E. , Hewitt Stephen M. , Notarangelo Luigi D. , Grazioli Alison , Chertow Daniel S.
Published: December 2021

A 26-year-old otherwise healthy man died of fulminant myocarditis. Nasopharyngeal specimens collected premortem tested negative for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Histopathological evaluation of the heart showed myocardial necrosis surrounded by cytotoxic T-cells and tissue-repair macrophages. Myocardial T-cell receptor (TCR) sequencing revealed hyper-dominant clones with highly similar sequences to TCRs that are specific for SARS-CoV-2 epitopes. SARS-CoV-2 RNA was detected in the gut, supporting a diagnosis of multisystem inflammatory syndrome in adults (MIS-A). Molecular targets of MIS-associated inflammation are not known. Our data indicate that SARS-CoV-2 antigens selected high-frequency T-cell clones that mediated fatal myocarditis.
Lymphatic Reconstruction in Kidney Allograft Aggravates Chronic Rejection by Promoting Alloantigen Presentation
Authors: Lin Jinwen , Chen Ying , Zhu Huijuan , Cheng Kai , Wang Huiping , Yu Xianping , Tang Mengmeng , Chen Jianghua
Published: December 2021

Chronic rejection of the renal allograft remains a major cause of graft loss. Here, we demonstrated that the remodeling of lymphatic vessels (LVs) after their broken during transplantation contributes to the antigen presenting and lymph nodes activating. Our studies observed a rebuilt of interrupted lymph draining one week after mouse kidney transplantation, involving preexisting lymphatic endothelial cells (LECs) from both the donor and recipient. These expanding LVs also release C-C chemokine ligand 21 (CCL21) and recruit CCR7+ cells, mainly dendritic cells (DCs), toward lymph nodes and spleen, evoking the adaptive response. This rejection could be relieved by LYVE-1 specific LVs knockout or CCR7 migration inhibition in mouse model. Moreover, in retrospective analysis, posttransplant patients exhibiting higher area density of LVs presented with lower eGFR, severe serum creatinine and proteinuria, and greater interstitial fibrosis. These results reveal a rebuilt pathway for alloantigen trafficking and lymphocytes activation, providing strategies to alleviate chronic transplantation rejection.
Pharmacological Applications and Action Mechanisms of Phytochemicals as Alternatives to Antibiotics in Pig Production
Authors: Li Lexing , Sun Xueyan , Zhao Dai , Dai Hanchuan
Published: December 2021

Antibiotics are widely used for infectious diseases and feed additives for animal health and growth. Antibiotic resistant caused by overuse of antibiotics poses a global health threat. It is urgent to choose safe and environment-friendly alternatives to antibiotics to promote the ecological sustainable development of the pig industry. Phytochemicals are characterized by little residue, no resistance, and minimal side effects and have been reported to improve animal health and growth performance in pigs, which may become a promising additive in pig production. This paper summarizes the biological functions of recent studies of phytochemicals on growth performance, metabolism, antioxidative capacity, gut microbiota, intestinal mucosa barrier, antiviral, antimicrobial, immunomodulatory, detoxification of mycotoxins, as well as their action mechanisms in pig production. The review may provide the theoretical basis for the application of phytochemicals functioning as alternative antibiotic additives in the pig industry.
Th17/Treg Imbalance in Chronic Obstructive Pulmonary Disease: Clinical and Experimental Evidence
Authors: Lourenço Juliana Dias , Ito Juliana Tiyaki , Martins Milton de Arruda , Tibério Iolanda de Fátima Lopes Calvo , Lopes Fernanda Degobbi Tenorio Quirino dos Santos
Published: December 2021

The imbalance between pro- and anti-inflammatory immune responses mediated by Th17 and Treg cells is deeply involved in the development and progression of inflammation in chronic obstructive pulmonary disease (COPD). Several clinical and experimental studies have described the Th17/Treg imbalance in COPD progression. Due to its importance, many studies have also evaluated the effect of different treatments targeting Th17/Treg cells. However, discrepant results have been observed among different lung compartments, different COPD stages or local and systemic markers. Thus, the data must be carefully examined. In this context, this review explores and summarizes the recent outcomes of Th17/Treg imbalance in COPD development and progression in clinical, experimental and in vitro studies.
A Global Red List for Hydrothermal Vent Molluscs
Authors: Thomas Elin A. , Molloy Aoife , Hanson Nova B. , Böhm Monika , Seddon Mary , Sigwart Julia D.
Published: December 2021

With the accelerating development of direct and indirect anthropogenic threats, including climate change and pollution as well as extractive industries such as deep-sea mining, there is an urgent need for simple but effective solutions to identify conservation priorities for deep-sea species. The International Union for Conservation of Nature (IUCN) Red List of Threatened Species is an effective and well-recognized tool to promote the protection of species and presents an opportunity to communicate conservation threats to industry, policy makers, and the general public. Here, we present the Vent Red List for molluscs: a complete global assessment of the extinction risk of all described molluscs endemic to hydrothermal vents, a habitat under imminent threat from deep-sea mining. Of the 184 species assessed, 62% are listed as threatened: 39 are Critically Endangered, 32 are Endangered, and 43 are Vulnerable. In contrast, the 25 species that are fully protected from deep-sea mining by local conservation measures are assessed as Least Concern, and a further 45 species are listed as Near Threatened, where some subpopulations face mining threats while others lie within protected areas. We further examined the risk to faunas at specific vent sites and biogeographic regions using a relative threat index, which highlights the imperiled status of vent fields in the Indian Ocean while other vent sites within established marine protected areas have a high proportion of species assessed as Least Concern. The Vent Red List exemplifies how taxonomy-driven tools can be utilized to support deep-sea conservation and provides a precedent for the application of Red List assessment criteria to diverse taxa from deep-sea habitats.
Low Transcriptomic Plasticity of Antarctic Giant Isopod Glyptonotus antarcticus Juveniles Exposed to Acute Thermal Stress
Authors: González-Aravena Marcelo , Rondon Rodolfo , Font Alejandro , Cárdenas César A. , Toullec Jean-Yves , Corre Erwan , Paschke Kurt
Published: December 2021

The Western Antarctic Peninsula (WAP) is among the areas of the planet showing some of the most significant increases in air and water temperature. It is projected that increasing temperature will modulate coastal ecosystems at species ecological performance and molecular composition. The main way that the organisms can cope with large thermal variation is by having a reversible phenotypic plasticity, which provides the organisms with a compensatory physiological response when facing challenging conditions. The giant Antarctic isopod Glyptonotus antarcticus is one of most common species in Antarctic waters. This species has a larval development inside of the maternal marsupium, where juveniles have a short period to acclimate to environmental conditions after birth. In this sense, we hypothesize that juveniles exposed to unusual temperature increases even for short periods, would not respond adequately showing a narrow phenotypic plasticity. We experimentally assessed if early juveniles of G. antarcticus have the molecular plasticity when exposed to increased temperature at 5°C during 1, 6, 12 and 24 h. Sequenced libraries were compared between control (0°C) and each experimental treatment to detect differentially expressed transcripts. The main molecular pathways affected by thermal stress were antioxidant, proteases, endopeptidases and ubiquination transcripts which were up-regulated and mitochondrial respiratory chain, cuticle, cytoskeleton and a molt transcript which were down-regulated. Regarding the HSP transcript, only 3 were up-regulated at least in two points of the stress kinetic, without classical Hsp70 and Hsp90 transcripts. This study shows that juveniles of G. antarcticus do not show molecular phenotypic plasticity to cope with acute short-term heat stress, even for one or few hours of exposure with an absence of an eco-physiological capacity to respond. This may have consequences at the ecological population level, showing a reduced individual ability to survive decreasing population recruitment.
Assessing the Viability of the Sarasota Bay Community of Bottlenose Dolphins
Authors: Lacy Robert C. , Wells Randall S. , Scott Michael D. , Allen Jason B. , Barleycorn Aaron A. , Urian Kim W. , Hofmann Suzanne
Published: December 2021

Population models, such as those used for Population Viability Analysis (PVA), are valuable for projecting trends, assessing threats, guiding environmental resource management, and planning species conservation measures. However, rarely are the needed data on all aspects of the life history available for cetacean species, because they are long-lived and difficult to study in their aquatic habitats. We present a detailed assessment of population dynamics for the long-term resident Sarasota Bay common bottlenose dolphin (Tursiops truncatus) community. Model parameters were estimated from 27 years of nearly complete monitoring, allowing calculation of age-specific and sex-specific mortality and reproductive rates, uncertainty in parameter values, fluctuation in demographic rates over time, and intrinsic uncertainty in the population trajectory resulting from stochastic processes. Using the Vortex PVA model, we projected mean population growth and quantified causes of variation and uncertainty in growth. The ability of the model to simulate the dynamics of the population was confirmed by comparing model projections to observed census trends from 1993 to 2020. When the simulation treated all losses as deaths and included observed immigration, the model projects a long-term mean annual population growth of 2.1%. Variance in annual growth across years of the simulation (SD= 3.1%) was due more to environmental variation and intrinsic demographic stochasticity than to uncertainty in estimates of mean demographic rates. Population growth was most sensitive to uncertainty and annual variation in reproduction of peak breeding age females and in calf and juvenile mortality, while adult survival varied little over time. We examined potential threats to the population, including increased anthropogenic mortality and impacts of red tides, and tested resilience to catastrophic events. Due to its life history characteristics, the population was projected to be demographically stable at smaller sizes than commonly assumed for Minimum Viable Population of mammals, but it is expected to recover only slowly from any catastrophic events, such as disease outbreaks and spills of oil or other toxins. The analyses indicate that well-studied populations of small cetaceans might typically experience slower growth rates (about 2%) than has been assumed in calculations of Potential Biological Removal used by management agencies to determine limits to incidental take of marine mammals. The loss of an additional one dolphin per year was found to cause significant harm to this population of about 150 to 175 animals. Beyond the significance for the specific population, demographic analyses of the Sarasota Bay dolphins provide a template for examining viability of other populations of small cetaceans.
Changes of Dry Eye Related Markers and Tear Inflammatory Cytokines After Upper Blepharoplasty
Authors: Zhao Songjiao , Song Nan , Gong Lan
Published: December 2021

Objectives: To investigate the changes of dry eye-related clinical manifestations, ocular surface parameters, and tear inflammatory cytokines after upper blepharoplasty.

Methods: Forty eyes of 20 who underwent upper blepharoplasty were divided into either the group with or the group without preexisting dry eye before upper blepharoplasty. Ocular Surface Disease Index (OSDI), Schirmer I test, tear meniscus height, lipid layer thickness, non-invasive tear break-up time (NIKBUT), fluorescein tear film break-up time (FBUT), corneal fluorescein staining, meibum expression, lid margin changes, and tear inflammatory cytokines were assessed preoperatively and at 1, 3, and 6 months postoperatively. Correlations between inflammatory cytokines and dry eye-related parameters were determined.

Results: The OSDI scores increased significantly at 1 month (p = 0.040) and subsequently decreased to the preoperative levels at 6 months postoperatively in subjects with dry eye. First (f)-NIKBUT and FBUT were significantly shortened at 1, 3, and 6 months postoperatively in subjects with dry eye (f-NIKBUT: p <0.001, p = 0.010, p = 0.042; FBUT: p = 0.002, p = 0.005, p = 0.037, respectively), but were only shortened at 1 month (p = 0.028, p = 0.005) and returned to baseline levels at 6 months postoperatively in subjects without preexisting dry eye. A significant increasing trend of interleukin (IL)-6 was found in both dry eye and subjects without preexisting dry eye (p = 0.016, p = 0.008), while IL-8 and tumor necrosis factor alpha (TNF-α) were only found to be increased in subjects with dry eye postoperatively (p = 0.031, p = 0.031). The levels of IL-8 and TNF-α were positively correlated with OSDI scores (p = 0.046, p = 0.043, respectively) and negatively correlated with f-NIKBUT and FBUT (p = 0.026, p = 0.006, respectively).

Conclusions: Upper blepharoplasty might increase the release of tear inflammatory cytokines and tear film instability that contribute to the development of postoperative dry eye in the early postoperative period and the changes most relieved in 6 months. Preexisting dry eye is a higher risk factor for worse and persistent ocular surface damage after upper blepharoplasty.
Inflammation and Fibrogenesis in MAFLD: Role of the Hepatic Immune System
Authors: Torre Pietro , Motta Benedetta Maria , Sciorio Roberta , Masarone Mario , Persico Marcello
Published: December 2021

Metabolic (dysfunction)-associated fatty liver disease (MAFLD) is the definition recently proposed to better circumscribe the spectrum of conditions long known as non-alcoholic fatty liver disease (NAFLD) that range from simple steatosis without inflammation to more advanced liver diseases. The progression of MAFLD, as well as other chronic liver diseases, toward cirrhosis, is driven by hepatic inflammation and fibrogenesis. The latter, result of a “chronic wound healing reaction,” is a dynamic process, and the understanding of its underlying pathophysiological events has increased in recent years. Fibrosis progresses in a microenvironment where it takes part an interplay between fibrogenic cells and many other elements, including some cells of the immune system with an underexplored or still unclear role in liver diseases. Some therapeutic approaches, also acting on the immune system, have been probed over time to evaluate their ability to improve inflammation and fibrosis in NAFLD, but to date no drug has been approved to treat this condition. In this review, we will focus on the contribution of the liver immune system in the progression of NAFLD, and on therapies under study that aim to counter the immune substrate of the disease.
Epidemiological Indicators of SARS-CoV-2 (COVID-19) and Vaccination Effectiveness on the Report of Positive Cases in the Colombian Army
Authors: Duque Maria Clara , Correa-Cárdenas Camilo A. , Londoño-Méndez Sebastián , Oliveros Carolina , Pérez Julie , Daza Carlos D. , Albarracin Lorena , Márquez Elizabeth K. , Alvarado Maria T. , Ortíz Frank De Los Santos , Romero Yanira , Gutierrez-Riveros Sergio , Méndez Claudia
Published: December 2021

The description of the epidemiological indicators of SARS-CoV-2 (COVID-19), such as the mortality rate (MR), the case fatality rate (CFR), and the attack rate (AR), as well as the geographical distribution and daily case reports, are used to evaluate the impact that this virus has had within the Colombian Army and its health system. As military forces around the world represent the force that defends sovereignty, independence, the integrity of the national territory, and the constitutional order, while maintaining migration controls in blocked border areas during this critical pandemic times, they must carry out strict epidemiological surveillance to control the situation among the servicemen. Up to date, the Colombian Army has faced a very high attack rate (AR = 8.55%) due, among others, to living conditions where active military personnel share bedrooms, bathrooms, and dining facilities, which facilitate the spread of the virus. However, being a mainly young and healthy population, the MR was 1.82 deaths/1,000 ha, while the CFR = 2.13% indexes consistently low if compared with those values reported for the national population. In addition, the effectiveness of vaccination is shown in daily cases of COVID-19, where, for the third peak, the active military population presented a decrease of positive patients compared to the dynamics of national transmission and the total population of the military forces (active, retired, and beneficiaries).
Physical Exercise vs. Metformin to Improve Delivery- and Newborn-Related Outcomes Among Pregnant Women With Overweight: A Network Meta-Analysis
Authors: Pascual-Morena Carlos , Cavero-Redondo Iván , Álvarez-Bueno Celia , Martínez-Hortelano José Alberto , Reina-Gutiérrez Sara , Saz-Lara Alicia , Núñez de Arenas-Arroyo Sergio , Martínez-Vizcaíno Vicente
Published: December 2021

Background: Overweight/obesity is associated with the risk of delivery- and newborn-related complications in pregnancy. Interventions such as exercise or metformin could reduce the risk of these complications.

Objective: To estimate and compare the effects of different types of exercise interventions (i.e., aerobic, resistance, combined exercise) and metformin on delivery- and newborn-related outcomes among pregnant women with overweight/obesity.

Methods: MEDLINE, Scopus, Web of Science, Cochrane Library databases and the gray literature were searched from inception to September 2021. This systematic review was registered in PROSPERO (CDR: 42019121715). Randomized controlled trials (RCTs) of metformin or an exercise intervention aimed at preventing cesarean section, preterm birth, macrosomia, or birth weight among pregnant women with overweight/obesity were included. Random effects meta-analyses and frequentist network meta-analyses (NMA) were conducted for each outcome.

Results: Fifteen RCTs were included. In the NMA, metformin reduced the risk of cesarean section (RR = 0.66, 95% CI: 0.46, 0.95), combined exercise reduced the risk of macrosomia (RR = 0.37, 95% CI: 0.14, 0.95), and aerobic exercise reduced birth weight (mean difference = −96.66 g, 95% CI: −192.45, −0.88). In the subgroup among pregnant women with obesity, metformin reduced the risk of cesarean section (RR = 0.66, 95% CI: 0.45, 0.97).

Conclusions: Combined exercise could reduce the risk of macrosomia in pregnant women with overweight, whereas metformin could reduce the risk of cesarean section in pregnant women with obesity. However, previous evidence suggests a larger effect of physical exercise in other outcomes for this population group. Therefore, the medicalization of healthy pregnant women with obesity is not justified by the current evidence.

Systematic Review Registration: PROSPERO: CRD42019121715; https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42019121715
Copper/Zinc-Modified Palygorskite Protects Against Salmonella Typhimurium Infection and Modulates the Intestinal Microbiota in Chickens
Authors: Zhang Chaozheng , Yao Dawei , Su Zenan , Chen Huan , Hao Pan , Liao Yun , Guo Yiwen , Yang Deji
Published: December 2021

Palygorskite (Pal), a clay nanoparticle, has been demonstrated to be a vehicle for drug delivery. Copper has antibacterial properties, and zinc is an essential micronutrient for intestinal health in animals and humans. However, whether copper/zinc-modified Pal (Cu/Zn-Pal) can protect chickens from Salmonella enterica subsp. enterica serovar Typhimurium (S. Typhimurium) infection remains unclear. In this study, three complexes (Cu/Zn-Pal-1, Cu/Zn-Pal-2, and Cu/Zn-Pal-3) were prepared, and Cu/Zn-Pal-1 was shown to be the most effective at inhibiting the growth of S. Typhimurium in vitro, whereas natural Pal alone had no inhibitory effect. In vivo, Cu/Zn-Pal-1 reduced S. Typhimurium colonization in the intestine of infected chickens and relieved S. Typhimurium-induced organ and intestinal mucosal barrier damage. Moreover, this reduction in Salmonella load attenuated intestinal inflammation and the oxidative stress response in challenged chickens. Additionally, Cu/Zn-Pal-1 modulated the intestinal microbiota in infected chickens, which was characterized by the reduced abundance of Firmicutes and the increased abundance of Proteobacteria and Bacteroidetes. Our results indicated that the Cu/Zn-Pal-1 complex may be an effective feed supplement for reducing S. Typhimurium colonization of the gut.
Genetically Modified Sugarcane Intercropping Soybean Impact on Rhizosphere Bacterial Communities and Co-occurrence Patterns
Authors: Wei Beilei , Zhang Jinlian , Wen Rushuang , Chen Tingsu , Xia Ningshao , Liu Yue , Wang Ziting
Published: December 2021

Strategies involving genes in the dehydration-responsive element binding (DREB) family, which participates in drought stress regulation, and intercropping with legumes are becoming prominent options in promoting sustainable sugarcane cultivation. An increasing number of studies focusing on root interactions in intercropping systems, particularly involving transgenic crops, are being conducted to better understand and thus, harness beneficial soil microbes to enhance plant growth. We designed experiments to investigate the characteristics of two intercropping patterns, soybean with wild-type (WT) sugarcane and soybean with genetically modified (GM) Ea-DREB2B-overexpressing sugarcane, to assess the response of the rhizosphere microbiota to the different cropping patterns. Bacterial diversity in the rhizosphere microbial community differed between the two intercropping pattens. In addition, the biomass of GM sugarcane that intercropped with soybean was significantly improved compared with WT sugarcane, and the aboveground biomass and root biomass of GM soybean intercropping sugarcane increased by 49.15 and 46.03% compared with monoculture. Furthermore, a beneficial rhizosphere environment for the growth of Actinobacteria was established in the systems intercropped with GM sugarcane. Improving the production mode of crops by genetic modification is a key strategy to improving crop yields and provides new opportunities to further investigate the effects of intercropping on plant roots and soil microbiota. Thus, this study provides a basis for selecting suitable sugarcane–soybean intercropping patterns and a theoretical foundation for a sustainable sugarcane production.
Blastocystis One Health Approach in a Rural Community of Northern Thailand: Prevalence, Subtypes and Novel Transmission Routes
Authors: Jinatham Vasana , Maxamhud Sadiya , Popluechai Siam , Tsaousis Anastasios D. , Gentekaki Eleni
Published: December 2021

Blastocystis is the most commonly found eukaryote in the gut of humans and other animals. This protist is extremely heterogeneous genetically and is classified into 28 subtypes (STs) based on the small subunit ribosomal RNA (SSU rRNA) gene. Numerous studies exist on prevalence of the organism, which usually focus on either humans or animals or the environment, while only a handful investigates all three sources simultaneously. Consequently, understanding of Blastocystis transmission dynamics remains inadequate. Our aim was to explore Blastocystis under the One Health perspective using a rural community in northern Thailand as our study area. We surveyed human, other animal and environmental samples using both morphological and molecular approaches. Prevalence rates of Blastocystis were 73% in human hosts (n = 45), 100% in non-human hosts (n = 44) and 91% in environmental samples (n = 35). Overall, ten subtypes were identified (ST1, ST2, ST3, ST4 ST5, ST6, ST7, ST10, ST23, and ST26), eight of which were detected in humans (ST1, ST2, ST3, ST4, ST5, ST7, ST10, and ST23), three in other animals (ST6, ST7, and ST23), while seven (ST1, ST3, ST6, ST7, ST10, ST23, and ST26) were found in the environment. In our investigation of transmission dynamics, we assessed various groupings both at the household and community level. Given the overall high prevalence rate, transmission amongst humans and between animals and humans are not as frequent as expected with only two subtypes being shared. This raises questions on the role of the environment on transmission of Blastocystis. Water and soil comprise the main reservoirs of the various subtypes in this community. Five subtypes are shared between humans and the environment, while three overlap between the latter and animal hosts. We propose soil as a novel route of transmission, which should be considered in future investigations. This study provides a thorough One Health perspective on Blastocystis. Using this type of approach advances our understanding on occurrence, diversity, ecology and transmission dynamics of this poorly understood, yet frequent gut resident.
Actinobacteria From Desert: Diversity and Biotechnological Applications
Authors: Xie Feiyang , Pathom-aree Wasu
Published: December 2021

Deserts, as an unexplored extreme ecosystem, are known to harbor diverse actinobacteria with biotechnological potential. Both multidrug-resistant (MDR) pathogens and environmental issues have sharply raised the emerging demand for functional actinobacteria. From 2000 to 2021, 129 new species have been continuously reported from 35 deserts worldwide. The two largest numbers are of the members of the genera Streptomyces and Geodermatophilus, followed by other functional extremophilic strains such as alkaliphiles, halotolerant species, thermophiles, and psychrotolerant species. Improved isolation strategies for the recovery of culturable and unculturable desert actinobacteria are crucial for the exploration of their diversity and offer a better understanding of their survival mechanisms under extreme environmental stresses. The main bioprospecting processes involve isolation of target actinobacteria on selective media and incubation and selection of representatives from isolation plates for further investigations. Bioactive compounds obtained from desert actinobacteria are being continuously explored for their biotechnological potential, especially in medicine. To date, there are more than 50 novel compounds discovered from these gifted actinobacteria with potential antimicrobial activities, including anti-MDR pathogens and anti-inflammatory, antivirus, antifungal, antiallergic, antibacterial, antitumor, and cytotoxic activities. A range of plant growth-promoting abilities of the desert actinobacteria inspired great interest in their agricultural potential. In addition, several degradative, oxidative, and other functional enzymes from desert strains can be applied in the industry and the environment. This review aims to provide a comprehensive overview of desert environments as a remarkable source of diverse actinobacteria while such rich diversity offers an underexplored resource for biotechnological exploitations.
Seed Endophytic Bacteria of Pearl Millet (Pennisetum glaucum L.) Promote Seedling Development and Defend Against a Fungal Phytopathogen
Authors: Kumar Kanchan , Verma Anand , Pal Gaurav , Anubha  , White James F. , Verma Satish K.
Published: December 2021

Seed endophytic bacteria (SEB) are primary symbionts that play crucial roles in plant growth and development. The present study reports the isolation of seven culturable SEB including Kosakonia cowanii (KAS1), Bacillus subtilis (KAS2), Bacillus tequilensis (KAS3), Pantoea stewartii (KAS4), Paenibacillus dendritiformis (KAS5), Pseudomonas aeruginosa (KAS6), and Bacillus velezensis (KAS7) in pearl millet seeds. All the isolates were characterized for their plant growth promoting activities. Most of the SEB also inhibited the growth of tested fungal phytopathogens in dual plate culture. Removal of these SEB from seeds compromised the growth and development of seedlings, however, re-inoculation with the SEB (Kosakonia cowanii, Pantoea stewartii, and Pseudomonas aeruginosa) restored the growth and development of seedlings significantly. Fluorescence microscopy showed inter and intracellular colonization of SEB in root parenchyma and root hair cells. Lipopeptides were extracted from all three Bacillus spp. which showed strong antifungal activity against tested fungal pathogens. Antifungal lipopeptide genes were also screened in Bacillus spp. After lipopeptide treatment, live-dead staining with fluorescence microscopy along with bright-field and scanning electron microscopy (SEM) revealed structural deformation and cell death in Fusarium mycelia and spores. Furthermore, the development of pores in the membrane and leakages of protoplasmic substances from cells and ultimately death of hyphae and spores were also confirmed. In microcosm assays, treatment of seeds with Bacillus subtilis or application of its lipopeptide alone significantly protected seedlings from Fusarium sp. infection.
Association of the Serum Levels of the Nucleocapsid Antigen of SARS-CoV-2 With the Diagnosis, Disease Severity, and Antibody Titers in Patients With COVID-19: A Retrospective Cross-Sectional Study
Authors: Yokoyama Rin , Kurano Makoto , Nakano Yuki , Morita Yoshifumi , Ohmiya Hiroko , Kishi Yoshiro , Okada Jun , Qian Chungen , Xia Fuzhen , He Fan , Zheng Liang , Yu Yi , Mizoguchi Miyuki , Higurashi Yoshimi , Harada Sohei , Jubishi Daisuke , Okamoto Koh , Moriya Kyoji , Kodama Tatsuhiko , Yatomi Yutaka
Published: December 2021

Background: Several types of laboratory tests for COVID-19 have been established to date; however, the clinical significance of the serum SARS-CoV-2 nucleocapsid (N) antigen levels remains to be fully elucidated. In the present study, we attempted to elucidate the usefulness and clinical significance of the serum N antigen levels.

Methods: We measured the serum N antigen levels in 391 serum samples collected from symptomatic patients with a confirmed diagnosis of COVID-19 and 96 serum samples collected from patients with non-COVID-19, using a fully automated chemiluminescence immunoassay analyzer.

Results: Receiver operating characteristic analysis identified the optimal cutoff value of the serum N antigen level (cutoff index, based on Youden’s index) as 0.255, which yielded a sensitivity and specificity for the diagnosis of COVID-19 of 91.0 and 81.3%, respectively. The serum N antigen levels were significantly higher in the patient groups with moderate and severe COVID-19 than with mild disease. Moreover, a significant negative correlation was observed between the serum N antigen levels and the SARS-CoV-2 IgG antibody titers, especially in patients with severe COVID-19.

Conclusion: Serum N antigen testing might be useful both for the diagnosis of COVID-19 and for obtaining a better understanding of the clinical features of the disease.
A Case Report: Genetically Distinct Severe Acute Respiratory Syndrome Coronavirus-2 Variant Causing Reinfection
Authors: Hossain Mohammad Enayet , Rahman Md. Mahfuzur , Alam Md. Shaheen , Sarmin Monira , Karim Yeasir , Hasan Mehedi , Hoque Ananya Ferdous , Hasan Md. Mahmudul , Rahman Mohammed Ziaur , Chisti Mohammod Jobayer , Rahman Mustafizur
Published: December 2021

Background: The emergence of novel variants has been a great deal of international concern since the recently published data suggest that previous infections with SARS-CoV-2 may not protect an individual from new variants. We report a patient had two distinct episodes of COVID-19 with different variants of SARS-CoV-2.

Methods: The nasopharyngeal samples collected from the two episodes were subjected to whole-genome sequencing and comparative genome analysis.

Results: The first infection presented with mild symptoms, while the second infection presented with severe outcomes which occurred 74 days after the patient recovered from the first episode. He had elevated C-reactive protein, ferritin, and bilateral consolidation as a sign of acute infection. Genome analysis revealed that the strains from the first and second episodes belonged to two distinct Nexstrain clades 20B and 20I and Pangolin lineages B.1.1.25 and B.1.1.7, respectively. A total of 36 mutations were observed in the episode-2 strain when compared with the reference strain Wuhan-Hu-1. Among them, eight mutations were identified in the receptor-binding domain (RBD).

Conclusion: Our findings concern whether the immunity acquired by natural infection or mass vaccination could confer adequate protection against the constantly evolving SARS-CoV-2. Therefore, continuous monitoring of genetic variations of SARS-CoV-2 strains is crucial for interventions such as vaccine and drug designs, treatment using monoclonal antibodies, and patient management.
Oral Microbiota Is Associated With Immune Recovery in Human Immunodeficiency Virus-Infected Individuals
Authors: Xie Yirui , Sun Jia , Hu Caiqin , Ruan Bing , Zhu Biao
Published: December 2021

The role of the oral microbiota in HIV-infected individuals deserves attention as either HIV infection or antiretroviral therapy (ART) may have effect on the diversity and the composition of the oral microbiome. However, few studies have addressed the oral microbiota and its interplay with different immune responses to ART in HIV-infected individuals. Salivary microbiota and immune activation were studied in 30 HIV-infected immunological responders (IR) and 34 immunological non-responders (INR) (≥500 and < 200 CD4 + T-cell counts/μl after 2 years of HIV-1 viral suppression, respectively) with no comorbidities. Metagenome sequencing revealed that the IR and the INR group presented similar salivary bacterial richness and diversity. The INR group presented a significantly higher abundance of genus Selenomonas_4, while the IR group manifested higher abundances of Candidatus_Saccharimonas and norank_p_Saccharimonas. Candidatus_Saccharimonas and norank_p_Saccharimonas were positively correlated with the current CD4 + T-cells. Candidatus_Saccharimonas was positively correlated with the markers of adaptive immunity CD4 + CD57 + T-cells, while negative correlation was found between norank _p_Saccharimonas and the CD8 + CD38 + T-cells as well as the CD4/CD8 + HLADR + CD38 + T-cells. The conclusions are that the overall salivary microbiota structure was similar in the immunological responders and immunological non-responders, while there were some taxonomic differences in the salivary bacterial composition. Selenomona_4, Candidatus_Saccharimonas, and norank _p_Saccharimonas might act as important factors of the immune recovery in the immunodeficiency patients, and Candidatus_Saccharimonas could be considered in the future as screening biomarkers for the immune responses in the HIV-infected individuals.