bluuebunny/crossref_metadata_2025_split huggingface dataset:
Follicle-Stimulating Hormone Provokes Macrophages to Secrete IL-1β Contributing to Atherosclerosis Progression
Authors: Han Jing-li , Song Yu-xuan , Yao Wei-juan , Zhou Jing , Du Yiqing , Xu Tao 
Published: January 2023

Abstract
Abnormally high follicle-stimulating hormone (FSH) has been reported to associate with cardiovascular diseases in prostate cancer patients with specific androgen deprivation therapy and in menopausal women. All of the cardiovascular diseases were involved in atherosclerosis. However, the pathogenic mechanism of FSH-associated atherosclerosis remains uncertain. Apolipoprotein E–deficient mice were chosen to develop atherosclerosis, of which the plaques were analyzed with administration of short- and long-term FSH imitating androgen deprivation therapy–induced and menopausal FSH elevation. The study showed that short- and long-term exposure of FSH significantly accelerated atherosclerosis progression in apolipoprotein E–deficient mice, manifested as strikingly increased plaques in the aorta and its roots, increased macrophage content, reduced fibrin, and an enlarged necrotic core, suggesting a decrease in plaque stability. Furthermore, expression profiles from the Gene Expression Omnibus GSE21545 dataset revealed that macrophage inflammation was tightly associated with FSH-induced atherosclerotic progression. The human monocyte cell line THP-1 was induced by PMA and worked as a macrophage model to detect inflammatory factors and cellular functions. FSH remarkably promoted the expression of IL-1β in macrophages and strikingly increased the chemotactic migratory capacity of macrophages toward MCP-1, but the promigratory capacity of FSH was attenuated in foam cells. Overall, we revealed that FSH significantly promoted the inflammatory response and migration of macrophages, thereby provoking atherosclerosis development.
The Drosophila Toll Pathway in Innate Immunity: from the Core Pathway toward Effector Functions
Authors: Valanne Susanna , Vesala Laura , Maasdorp Matthew K , Salminen Tiina S , Rämet Mika 
Published: January 2023

Abstract
The fruit fly Drosophila melanogaster Toll signaling pathway has an evolutionarily conserved role in controlling immune responses. Whereas the microbial recognition mechanisms and the core signaling pathway leading to activation of the humoral immune response via the NF-κB transcription factors have been well established for many years, the mechanistic understanding of the effector functions at the molecular level is currently rapidly evolving. In this review, we discuss the current developments in elucidating the role of the Drosophila Toll signaling pathway in immunity. We discuss the emerging role of Toll in viral infections and sex-specific differences in immunity. Mainly, we focus on Toll pathway regulation, the effector molecules, and cellular immunity.
Spring Viremia of Carp Virus N Protein Negatively Regulates IFN Induction through Autophagy-Lysosome–Dependent Degradation of STING
Authors: Wang Xue-li , Li Zhuo-Cong , Zhang Can , Jiang Jing-Yu , Han Ke-jia , Tong Jin-Feng , Yang Xiao-Li , Chen Dan-Dan , Lu Long-Feng , Li Shun 
Published: January 2023

Abstract
Fish possess a powerful IFN system to defend against aquatic virus infections. Nevertheless, spring viremia of carp virus (SVCV) causes large-scale mortality in common carp and significant economic losses to aquaculture. Therefore, it is necessary to investigate the strategies used by SVCV to escape the IFN response. In this study, we show that the SVCV nucleoprotein (N protein) negatively regulates cellular IFN production by degrading stimulator of IFN genes (STING) via the autophagy-lysosome–dependent pathway. First, overexpression of N protein inhibited the IFN promoter activation induced by polyinosinic-polycytidylic acid and STING. Second, the N protein associated with STING and experiments using a dominant-negative STING mutant demonstrated that the N-terminal transmembrane domains of STING were indispensable for this interaction. Then, the N protein degraded STING in a dose-dependent and autophagy-lysosome–dependent manner. Intriguingly, in the absence of STING, individual N proteins could not elicit host autophagic flow. Furthermore, the autophagy factor Beclin1 was found to interact with the N protein to attenuate N protein–mediated STING degradation after beclin1 knockdown. Finally, the N protein remarkably weakened STING-enhanced cellular antiviral responses. These findings reveal that SVCV uses the host autophagic process to achieve immune escape, thus broadening our understanding of aquatic virus pathogenesis.
JMJD3 Is Required for Acute Pancreatitis and Pancreatitis-Associated Lung Injury
Authors: Chen Li , Zhang Xiangxian , Liu Yu , Liu Li , Liang Xiao , Yang Shengqun , Xia Qing , Jin Tao , Ma Yun , Chen Yonghua , Yuan Xia , Tie Yan , Gu Yangzhuo , Fang Chunju , Chen Siyuan , Mo Fei , Yu Ting , Hu Yuzhu , Qian Zhiyong , Peng Yong , Geng Jia , Zhou Zongguang , Wu Min , Ding Jiansheng , Yang Daoke , Wei Xiawei 
Published: January 2023

Abstract
Acute pancreatitis (AP) can be complicated by inflammatory disorders of remote organs, such as lung injury, in which Jumonji domain-containing protein 3 (JMJD3) plays a vital role in proinflammatory responses. Currently, we found that JMJD3 expression was upregulated in the pancreas and lung in an AP male mouse model, which was also confirmed in AP patients. Further experiments revealed that the upregulation of JMJD3 and proinflammatory effects were possibly exerted by mitochondrial DNA (mtDNA) or oxidized-mtDNA from tissue injury caused by AP. The release of mtDNA and oxidized-mtDNA contributed to the infiltration of inflammatory monocytes in lung injury through the stimulator of IFN genes (STING)/TLR9-NF-κB-JMJD3-TNF-α pathway. The inhibition of JMJD3 or utilization of Jmjd3-cKO mice significantly alleviated pulmonary inflammation induced by AP. Blocking mtDNA oxidation or knocking down the TLR9/STING pathway effectively alleviated inflammation. Therefore, inhibition of JMJD3 or STING/TLR9 pathway blockage might be a potential therapeutic strategy to treat AP and the associated lung injury.
Maintenance of Lineage Identity: Lessons from a B Cell
Authors: Belcheva Kalina T , Chaudhuri Jayanta 
Published: January 2023

Abstract
The maintenance of B cell identity requires active transcriptional control that enforces a B cell–specific program and suppresses alternative lineage genes. Accordingly, disrupting the B cell identity regulatory network compromises B cell function and induces cell fate plasticity by allowing derepression of alternative lineage-specific transcriptional programs. Although the B lineage is incredibly resistant to most differentiating factors, loss of just a single B lineage–specific transcription factor or the forced expression of individual non–B cell lineage transcription factors can radically disrupt B cell maintenance and allow dedifferentiation or transdifferentiation into entirely distinct lineages. B lymphocytes thereby offer an insightful and useful case study of how a specific cell lineage can maintain a stable identity throughout life and how perturbations of a single master regulator can induce cellular plasticity. In this article, we review the regulatory mechanisms that safeguard B cell identity, and we discuss how dysregulation of the B cell maintenance program can drive malignant transformation and enable therapeutic resistance.
Immunity to Cryptosporidium: Lessons from Acquired and Primary Immunodeficiencies
Authors: Cohn Ian S , Henrickson Sarah E , Striepen Boris , Hunter Christopher A 
Published: January 2023

Abstract
Cryptosporidium is a ubiquitous protozoan parasite that infects gut epithelial cells and causes self-limited diarrhea in immunocompetent individuals. However, in immunocompromised hosts with global defects in T cell function, this infection can result in chronic, life-threatening disease. In addition, there is a subset of individuals with primary immunodeficiencies associated with increased risk for life-threatening cryptosporidiosis. These patients highlight MHC class II expression, CD40–CD40L interactions, NF-κB signaling, and IL-21 as key host factors required for resistance to this enteric pathogen. Understanding which immune deficiencies do (or do not) lead to increased risk for severe Cryptosporidium may reveal mechanisms of parasite restriction and aid in the identification of novel strategies to manage this common pathogen in immunocompetent and deficient hosts.
Regulation of Cytotoxic CD8+ T Cells by the Circadian Clock
Authors: Cermakian Nicolas , Labrecque Nathalie 
Published: January 2023

Abstract
Most aspects of physiology, including immunity, present 24-h variations called circadian rhythms. In this review, we examine the literature on the circadian regulation of CD8+ T cells, which are important to fight intracellular infections and tumors. CD8+ T cells express circadian clock genes, and ∼6% of their transcriptome presents circadian oscillations. CD8+ T cell counts present 24-h rhythms in the blood and in secondary lymphoid organs, which depend on the clock in these cells as well as on hormonal rhythms. Moreover, the strength of the response of these cells to Ag presentation varies according to time of day, a rhythm dependent on the CD8+ T cell clock. The relevance of CD8+ T cell circadian rhythms is shown by the daily variations in the fight of intracellular infections. Such a circadian regulation also has implications for cancer, as well as the optimization of vaccination and immunotherapy.
ER-phagy Is Involved in the Degradation of Collagen I by IL-1β in Human Amnion in Parturition
Authors: Mi Ya-Bing , Liu Xiao-Hua , Wang Wang-Sheng , Wang Lu-Yao , Ling Li-Jun , Sun Kang , Ying Hao 
Published: January 2023

Abstract
The process of parturition is associated with inflammation within the uterine tissues, and IL-1β is a key proinflammatory cytokine involved. Autophagy is emerging as an important pathway to remove redundant cellular components. However, it is not known whether IL-1β employs the autophagy pathway to degrade collagen, thereby participating in membrane rupture at parturition. In this study, we investigated this issue in human amnion. Results showed that IL-1β levels were significantly increased in human amnion obtained from deliveries with spontaneous labor and membrane rupture, which was accompanied by decreased abundance of COL1A1 and COL1A2 protein but not their mRNA, the two components of collagen I. Consistently, IL-1β treatment of cultured primary human amnion fibroblasts reduced COL1A1 and COL1A2 protein but not their mRNA abundance along with increased abundance of autophagy activation markers, including the microtubule-associated protein L chain 3β II/I ratio and autophagy-related 7 (ATG7) in the cells. The reduction in COL1A1 and COL1A2 protein abundance induced by IL-1β could be blocked by the lysosome inhibitor chloroquine or small interfering RNA–mediated knockdown of ATG7 or ER-phagy receptor FAM134C, suggesting that FAM134C-mediated ER-phagy was involved in IL-1β–induced reduction in COL1A1 and COL1A2 protein in amnion fibroblasts. Consistently, levels of L chain 3β II/I ratio, ATG7, and FAM134C were significantly increased in human amnion obtained from deliveries with spontaneous labor and membrane rupture. Conclusively, increased IL-1β abundance in human amnion may stimulate ER-phagy–mediated COL1A1 and COL1A2 protein degradation in amnion fibroblasts, thereby participating in membrane rupture at parturition.
Complement: The Road Less Traveled
Authors: Kemper Claudia , Ferreira Viviana P , Paz Jeanne T , Holers V Michael , Lionakis Michail S , Alexander Jessy J 
Published: January 2023

Abstract
The complement field has recently experienced a strong resurgence of interest because of the unexpected discovery of new complement functions extending complement’s role beyond immunity and pathogen clearance, a growing list of diseases in which complement plays a role, and the proliferation of complement therapeutics. Importantly, although the majority of complement components in the circulation are generated by the liver and activated extracellularly, complement activation unexpectedly also occurs intracellularly across a broad range of cells. Such cell-autonomous complement activation can engage intracellular complement receptors, which then drive noncanonical cell-specific effector functions. Thus, much remains to be discovered about complement biology. In this brief review, we focus on novel noncanonical activities of complement in its “classic areas of operation” (kidney and brain biology, infection, and autoimmunity), with an outlook on the next generation of complement-targeted therapeutics.
Therapeutic Opportunities for Immunoreceptor-Engineered T Cell Therapy for Modulation of Alloimmunity
Authors: Muralidharan Kavitha , Agarwal Divyansh , Naji Ali , Bhoj Vijay G 
Published: January 2023

Abstract
Achieving immunosuppression-free immune tolerance to an allograft is one of the central goals of transplantation. In this article, we review recent developments in the fields of T cell–based therapies and T cell engineering using chimeric Ag receptors and their potential for effective and targeted immune modulation of T and B cell activity in an effort to eliminate pre-existing alloantibodies (desensitization) and achieve long-term tolerance. Approaches that span preclinical to early clinical studies in transplantation will be reviewed, with specific emphasis on advances in T cell immunotherapy that have shown promise. Lastly, we conclude with a forward-looking discussion of how T cell–based therapies in other fields of medicine can be potentially applied to solid organ transplantation.
Neutrophil and Macrophage NADPH Oxidase 2 Differentially Control Responses to Inflammation and to Aspergillus fumigatus in Mice
Authors: Idol Rachel A , Bhattacharya Sourav , Huang Guangming , Song Zhimin , Huttenlocher Anna , Keller Nancy P , Dinauer Mary C 
Published: January 2023

Abstract
Aspergillus fumigatus is an important opportunistic fungal pathogen and causes invasive pulmonary aspergillosis in conditions with compromised innate antifungal immunity, including chronic granulomatous disease, which results from inherited deficiency of the superoxide-generating leukocyte NADPH oxidase 2 (NOX2). Derivative oxidants have both antimicrobial and immunoregulatory activity and, in the context of A. fumigatus, contribute to both fungal killing and dampening inflammation induced by fungal cell walls. As the relative roles of macrophage versus neutrophil NOX2 in the host response to A. fumigatus are incompletely understood, we studied mice with conditional deletion of NOX2. When NOX2 was absent in alveolar macrophages as a result of LysM-Cre–mediated deletion, germination of inhaled A. fumigatus conidia was increased. Reducing NOX2 activity specifically in neutrophils via S100a8 (MRP8)-Cre also increased fungal burden, which was inversely proportional to the level of neutrophil NOX2 activity. Moreover, diminished NOX2 in neutrophils synergized with corticosteroid immunosuppression to impair lung clearance of A. fumigatus. Neutrophil-specific reduction in NOX2 activity also enhanced acute inflammation induced by inhaled sterile fungal cell walls. These results advance understanding into cell-specific roles of NOX2 in the host response to A. fumigatus. We show that alveolar macrophage NOX2 is a nonredundant effector that limits germination of inhaled A. fumigatus conidia. In contrast, reducing NOX2 activity only in neutrophils is sufficient to enhance inflammation to fungal cell walls as well as to promote invasive A. fumigatus. This may be relevant in clinical settings with acquired defects in NOX2 activity due to underlying conditions, which overlap risk factors for invasive aspergillosis.
Restored Thymic Output after Androgen Blockade Participates in Antitumor Immunity
Authors: Polesso Fanny , Caruso Breanna , Hammond Scott A , Moran Amy E 
Published: January 2023

Abstract
The thymus is a hormone-sensitive organ, which involutes with age in response to production of sex steroids. Thymic involution leads to a decrease in the generation of recent thymic emigrants (RTEs), resulting in a reduced response to immune challenges such as cancer. Interestingly, the standard of care for prostate cancer patients is androgen deprivation therapy (ADT), which leads to thymic regeneration and an increase in thymic output. It remains unknown whether these newly produced T cells can contribute to the antitumor immune response. This study defines the kinetics of thymic regeneration in response to ADT in mice, determining that thymic epithelial cell proliferation is critical for the increase in RTE output. Using a mouse model to track RTE in vivo, we demonstrate that these newly generated RTEs can traffic to tumors, where they become activated and produce effector cytokines at levels similar to more mature T cells. Collectively, these data suggest that RTEs produced from ADT-induced thymic regeneration could be harnessed for the antitumor immune response.
Effect of serial plasma exchange sessions with albumin replacement on ABO antibody titers
Authors: Hassan Mohamed S. , Zaki Mahmoud M. , El Said Tamer W. , Abdelaziz Haitham E. , Al-Semrawy Mahmoud S.M. , Elsayed Hebatallah N. , Abdelmegied Shaimaa Z. 
Published: January 2023

Background
Donor shortage in kidney transplantation stimulates trails of live-related transplants across the ABO antibody barrier. Successful desensitization was achieved by repeated plasmapheresis with intensified immunosuppression. This study estimates the effect of serial sessions of plasma exchange on different blood group antibody titers.

Patients and methods
This is a pilot study that included 25 prescribed plasma exchange treatments with albumin replacement for miscellaneous indications. Patients using plasma as a replacement during sessions, positive direct and indirect antiglobulin test and AB blood group were excluded. Blood group antibody titers were measured by the gel card method before starting plasma exchange and after each session for five sessions.

Results
The study included a total of 25 patients, 12 (48%) had A1 blood group, eight (32%) had blood group B, and five (20%) had blood group O. The baseline anti-(A) and anti-(B) antibody titers before plasma exchange were median (interquartile range) 128.00 (192) and 64 (64) with significant reduction after five sessions with median (interquartile range) 1 (4) and 2 (1), respectively, with P value less than 0.001. Anti-(A) and anti-(B) antibody titer percent reduction from baseline to fifth session were mean±SD=99.04 ± 0.72 and =97.93 ± 0.99%, respectively. Anti-(A) and anti-(B) antibody titers were negatively correlated with patient's age (r=0.731, P=0.005; r=0.793, P<0.001, respectively). Patients with age less than 50 (n=13) years have higher anti-(A) and anti-(B) antibodies compared with patients with age more than 50 years (N=12) with P value less than 0.001. Also, on comparing patients on immunosuppressive drugs with patients not on immunosuppressive drugs as regards baseline antibody titers before exchange sessions and after five plasma exchange sessions, there was no significant difference in anti-(B) while anti-(A) titer was higher in patients without immunosuppressive drugs with P valueless than 0.05 and on fifth session, P value of 0.01.

Conclusion
Serial plasma exchange sessions with albumin replacement is an effective method for ABO antibody titer reduction. Baseline titers seem to be affected by age and adjuvant immunosuppressive therapy.
The effect of cryopreserved and noncryopreserved stem cells on the outcome of autologous stem-cell transplantation in multiple myeloma patients
Authors: Uysal Ayşe , Erkurt Mehmet A. , Kuku İrfan , Kaya Emin , Berber İlhami , Sarıcı Ahmet , Biçim Soykan , Hidayet Emine , Kaya Ahmet , Merter Mustafa 
Published: January 2023

Background
The CD34+ stem cells are either noncryopreserved (non-CP) or cryopreserved (CP) in autologous stem-cell transplantation (ASCT). Some retrospective studies have shown that engraftment failure and engraftment rate are similar in CP cells and infusion reactions are lower in CP cells due to the absence of dimethyl sulfoxide.

Objective
In this study, we presented our clinical experience comparing the outcomes and safety of ASCT with CP and non-CP stem cells.

Patients and methods
A total of 163 patients were enrolled between January 2019 and June 2021. Duration of neutrophil/platelet engraftment, rates of infusion-related reactions, febrile neutropenia, and duration of hospitalization were compared between the CP and non-CP groups.

Results
Fifty five (33.7%) received CP cells, 108 (66.3%) received non-CP cells. The median dose of CD34+ cells was similar in both groups (P=0.755). The median duration of neutrophil and platelet engraftment was not statistically significantly different in CP and non-CP groups (P=0.896 and 0.183, respectively). No statistical difference was observed in the median duration of hospitalization between the two groups [CP: 16 (13–26) vs. non-CP: 15 (11–31) days, P=0.124]. The febrile neutropenia rate was higher in the CP group, but there was no statistical difference between the two groups (CP: 56.4% vs. non-CP, 48.1%, P=0.301). The rates of infusion-related reaction such as nausea, vomiting, and rash were higher in the CP group (21.8 vs. 12%), with no statistically significant difference (P=0.159).

Conclusion
Non-CP cells have similar outcomes to CP cells and lower toxicity than CP cells, which are safe and effective in ASCT.
Comparative diagnostic utility of different urinary biomarkers during pre-albuminuric stages of non-hypertensive type 2 diabetic nephropathy
Authors: Mahapatra Himansu Sekhar , Kulshreshtha Bindu , Goyal Parul , Chitkara Anubhuti , Kumari Anamika , Arora Arpita , Sekhar Venkatesan , Gupta Yadunandan Prasad 
Published: January 2023

Background & objectives:
Activation of renin-angiotensin system and tubulointerstitial damage might be seen in pre-albuminuria stage of diabetic nephropathy (DN). Here, diagnostic utility of four urinary biomarkers [Angiotensinogen (Angio), Interleukin (IL)-18, Neutrophil Gelatinase-Associated Lipocalin (NGAL) and Cystatin] during pre-albuminuria stages of non-hypertensive type 2 diabetes patients was studied.

Methods:
A total of 952 type 2 diabetes mellitus (T2DM) patients were screened for nephropathy [estimated glomerular filtration rate (eGFR) ≥120 ml/min and albumin–creatinine ratio (ACR) ≥30], and 120 patients were followed up for one year. At one year, they were classified into hyperfiltration (43), normoalbuminuria (29) and microalbuminuria (48) groups. Another 63 T2DM patients without nephropathy were included as controls. Hypertension, patients on angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, eGFR <60 ml/min/1.73 m2 and all proteinuric conditions were excluded. All were subjected to testing for urine protein, ACR, HbA1C, eGFR, along with urinary biomarkers (IL-18, cystatin-C, NGAL and AGT). Comparative analysis of all the diagnostic tests among different subgroups, correlation and logistic regression was done.

Results:
Urinary IL-18/Cr, cystatin/creatinine (Cr) and AGT/Cr levels were higher in groups of hyperfiltration (13.47, 12.11 and 8.43 mg/g), normoalbuminuria (9.24, 11.74 and 9.15 mg/g) and microalbuminuria (11.59, 14.48 and 10.24 mg/g) than controls (7.38, 8.39 and 1.26 mg/g), but NGAL/Cr was comparable. The area under receiver operating characteristic curve (AUC) and sensitivity of AGT to detect early CKD were higher than ACR and eGFR (0.91 and 90.4%, 0.6 and 40% and 0.6 and 37%, respectively). AUC values of other biomarkers, namely IL-18/Cr, cystatin/Cr and NGAL/Cr, were 0.65, 0.64 and 0.51, respectively. Angio/Cr and IL-18/Cr showed correlation with log albuminuria (r=0.3, P=0.00, and r=0.28, P=0.00, respectively). NGAL showed correlation with log eGFR (r=0.28 P=0.00). Multivariate logistic analysis showed that odds ratio of developing nephropathy was 7.5 times with higher values of log Angio/Cr.

Interpretation & conclusions:
Urinary AGT showed a higher diagnostic value than ACR and eGFR followed by IL-18 and cystatin to diagnose DN during pre-albuminuric stages.