bluuebunny/crossref_metadata_2025 huggingface dataset:
Serum extracellular vesicle MicroRNAs as candidate biomarkers for acute rejection in patients subjected to liver transplant
Authors: Wang Wenjing , Li Wen , Cao Li , Wang Bo , Liu Chang , Qin Yannan , Guo Bo , Huang Chen
Published: October 2022

Acute rejection (AR) is a common and grave complication of liver transplantation (LT). The diagnosis of AR is challenging because it has nonspecific clinical features and requires invasive procedures. Since extracellular vesicles (EVs) are promising candidates as indicators for diagnosis of various diseases, this study aimed to identify serum EV microRNAs (miRNAs) as potential biomarkers for AR in patients subjected to LT. We collected clinical information and serum samples from the liver transplant recipients with and without AR (non-AR). EVs from the serum were isolated via ultracentrifugation and identified using transmission electron microscopy, nanoparticle tracking analysis, and western blotting. EV RNA was extracted and sequenced on an Illumina HiSeq 2500/2000 platform to identify differentially expressed miRNAs between the groups. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed on the target gene candidates of the differentially expressed miRNAs to test their functions in biological systems. Then, we validated 12 differentially expressed miRNAs by quantitative real-time PCR. The results demonstrated that 614 EV miRNAs were significantly altered (387 up regulated and 227 down regulated) between non-AR and AR patients. GO enrichment analysis revealed that these target genes were related to cellular processes, single-organism processes, biological regulation, metabolic processes, cells, cell parts, protein-binding processes, nucleoid binding, and catalytic activity. Furthermore, KEGG pathway analysis demonstrated that the target genes of the differentially expressed miRNAs were primarily involved in ubiquitin-mediated proteolysis, lysosomes, and protein processing in the endoplasmic reticulum. miR-223 and let-7e-5p in AR patients were significantly up-regulated compared to those in non-AR patients, whereas miR-199a-3p was significantly down-regulated, which was consistent with sequencing results. The expression of serum EV miRNAs (up-regulated: miR-223 and let-7e-5p and miR-486-3p; down regulated: miR-199a-3p, miR-148a-3p and miR-152-3p) in AR patients was significantly different from that in non-AR patients, and these miRNAs can serve as promising diagnostic biomarkers for AR in patients subjected to liver transplant.
Characterization and evolutionary diversification of the phospholipase D gene family in mosses
Authors: Zhao Jinjie , Pu Xinyuan , Li Wenfei , Li Meng
Published: October 2022

Plant phospholipase D (PLD) exerts important roles in various biological processes, such as intracellular signaling and morphological development. Our knowledge about early land plant PLDs is still underdeveloped. In this study, we identified 84 PLD genes in six mosses, i.e., Physcomitrella patens, Ceratodon purpureus, Fontinalis antipyretica, Pleurozium schreberi, Sphagnum magellanicum, and Sphagnum fallax. These PLDs were classified into four clades (I–IV). We showed that PLD underwent rapid expansion in mosses. A total of six conserved domains and two core HKD motifs were detected. Structure analysis uncovered that the moss PLDs from within a clade generally exhibited similar exon-intron organization. Cis-elements prediction and expression analyses indicated that P. patens PLDs had key roles in stress responsiveness and plant development. Particularly, about half of the P. patens PLDs (e.g., PpPLD1, PpPLD2, and PpPLD5) were differentially expressed under biotic and abiotic stresses. We also determined the expression pattern of P. patens PLD genes in various tissues and at different stages of development. Although the moss, clubmoss, liverwort, and fern PLDs evolved largely under functional constraints, we found episodic positive selection in the moss PLDs, e.g., C. purpureus PLD2 and P. patens PLD11. We infer that the evolutionary force acting on the PLDs may have facilitated moss colonization of land. Our work provides valuable insights into the diversification of moss PLD genes, and can be used for future studies of their functions.
The causal relationship between abdominal obesity and lower bone mineral density: A two-sample mendelian randomization study
Authors: Wang Xiang-xuan , Lin Kai-nan , Xu Wen-chen , Chen Hui
Published: October 2022

Aims: The purpose of this study was to assess the causal effect of abdominal obesity on bone mineral density by two-sample Mendelian randomization (MR).

Methods: Abdominal obesity was chosen as exposure in this study. Single nucleotide polymorphisms, extracted from Genome-wide association analysis (GWAS) data, which are closely associated with waist circumference (WC), hip circumference (HC), and waist-to-hip ratio (WHR) were used as instrumental variables to perform MR studies. Different site bone mineral density, such as total bone mineral density (TBMD) and forearm bone mineral density (FBMD) were chosen as outcomes. Inverse variance weighted (IVW) was used as the primary method to assess this causality.

Results: According to the IVW method (β = −0.177; 95% CI = −0.287, −0.067; p = 1.52 × 10–3), WC had a negative causal relationship with TBMD, besides, with one standard deviation (SD) higher in HC, there was a 0.195 SD decrease in TBMD (95% CI = −0.279, −0.110; p = 6.32 × 10–6), and with an increase of one SD in HC was related to a decrease of 0.312 SD in FBMD analyzed by the IVW.

Conclusion: This study showed that abdominal obesity has a negative effect on bone mineral density.
Role of the microbiome and its metabolites in ankylosing spondylitis
Authors: Song Zi-Yi , Yuan Duo , Zhang Sheng-Xiao
Published: October 2022

Ankylosing spondylitis (AS), a chronic condition that commonly influences the spine and sacroiliac joints, usually progresses to stiffness and progressive functional limitation. Its fundamental etiology and pathogenesis are likely multifactorial and remain elusive. As environmental factors, gut microbiota performs critical functions in the pathogenesis of AS through various mechanisms, including interacting with genes, enhancing intestinal permeability, activating the gut mucosa immune system, and affecting the intestinal microbiota metabolites. This review provides an overview of recent advances in investigating gut microbiota in AS pathogenesis and discusses potential methods for future therapeutic intervention.
Kynurenic acid ameliorates NLRP3 inflammasome activation by blocking calcium mobilization via GPR35
Authors: Sun Tianyin , Xie Ruiqian , He Hongbin , Xie Qianqian , Zhao Xueqin , Kang Guijie , Cheng Chen , Yin Wenwei , Cong Jingjing , Li Jing , Wang Xuefu
Published: October 2022

The inflammasome has been linked to diverse inflammatory and metabolic diseases, and tight control of inflammasome activation is necessary to avoid excessive inflammation. Kynurenic acid (KA) is a tryptophan metabolite in the kynurenine pathway. However, the roles and mechanisms of the regulation of inflammasome activation by KA have not yet been fully elucidated. Here, we found that KA suppressed caspase-1 activation and IL-1β production in macrophages by specifically inhibiting canonical and noncanonical activation of the NLRP3 inflammasome. Mechanistically, KA reduced calcium mobilization through G-protein receptor 35 (GPR35), resulting in reduced mitochondrial damage and decreased mtROS production, thus blocking NLRP3 inflammasome assembly and activation. Importantly, KA prevented lipopolysaccharide-induced systemic inflammation, monosodium urate-induced peritoneal inflammation, and high-fat diet-induced metabolic disorder. Thus, KA ameliorated inflammation and metabolic disorders by blocking calcium mobilization-mediated NLRP3 inflammasome activation via GPR35. Our data reveal a novel mechanism for KA in the modulation of inflammasome activation and suggest that GPR35 might be a promising target for improving NLRP3 inflammasome-associated diseases by regulating calcium mobilization.
Differential immunological effects of silica nanoparticles on peripheral blood mononuclear cells of silicosis patients and controls
Authors: Ganesan Nirosha , Ronsmans Steven , Hoet Peter
Published: October 2022

Silicosis is a fibrotic disease caused by the inhalation of respirable silica particles, which are typically engulfed by alveolar macrophages and subsequently induce the release of inflammatory cytokines. Various animal experimental and human studies have focused on modeling silicosis, to assess the interactions of macrophages and other cell types with silica particles. There is still, however, limited knowledge on the differential response upon silica-exposure between silicosis patients and controls. We focused on studying the responsiveness of peripheral blood mononuclear cells (PBMCs) to silica nanoparticles (SiNPs) - Ludox and NM-200 - of silicosis patients and controls. The proliferative capacity of T- CD3+and B- CD19+cells, were evaluatedviaCarboxyfluorescein succinimidyl ester (CFSE) assay. The activation status of lymphocyte subsets and response to silica were also evaluated by comparing the extent of micro-granuloma or aggregate formation with the cytokine secretion profiles between both groups of individuals. The proliferative capacity of CD19+cells was elevated in silicotic patients as opposed to controls. Subsets of regulatory T cells (CD4+CD25+and CD8+CD25+) and immunoglobulins IgM and IgG were also significantly increased in patients. The number and the size of aggregates formed were higher with SiNPs stimulation in patients compared to controls. Multivariable analysis also elucidated the role of key cytokines like interleukin-1β (IL-1β), IL-6 and interferon-gamma (IFN-γ), which were upregulated in SiNP-stimulated PBMCs of patients compared to controls. Ourex vivomodel thus has potential to provide insights into the immunological effects of silica particles in lymphocytes of silicosis patients and controls.
Innate lymphoid cells type 3 in cancer
Authors: Castillo-González Raquel , Valle-Noguera Ana , Gomez-Sánchez Maria José , Xia Pu , Cruz-Adalia Aranzazu
Published: October 2022

Cancer is a multifactorial chronic illness caused by a combination of genetic and environmental factors. A tumor is more than just a collection of cancer cells, it also contains infiltrating and resident host cells that are constantly interacting with it. Innate lymphoid cells (ILCs) have been recently found to be within the tumor and its microenvironment in close relationship with cancer cells. Although ILCs lack an antigen-specific receptor, they can respond to environmental stress signals, aiding in the fast orchestration of an early immune response. They are tissue resident cells mostly located in mucosa and first barrier organs that have been mainly studied in the defense against pathogens, lymphoid development, and tissue repair, however, current research has begun to elucidate their involvement in carcinogenesis. Nevertheless, among all ILCs, ILC3s have been found to be the most controversial in terms of tumor immunity. It has been found that they enhance anti-tumor immunity by detecting cancerous cells and helping lymphocytes infiltrate tumors. However, some recent studies have revealed that IL-23 stimulating ILC3s may promote tumor growth. In this review, we have incorporated the most recent studies on the involvement of ILC3s in cancer development to offer an overview of the role of ILC3s in cancer emphasis on their particular activity in several organs primarily in the mucosa, but also in breast, pancreas, liver, and skin, realizing that their role likely depends on the tissue microenvironment and the subtype of ILC3s.
Combined oral immunization with probiotics Entercoccus faecalis delivering surface-anchored Eimeria tenella proteins provide protective efficacies against homologous infection in chickens
Authors: Zhi Wenjing , Chen Hang , Bai Bingrong , Jia Zhipeng , Pan Xinghui , Wang Biao , Kong Rui , Liu Qiuju , Ma Chunli , Ma Dexing
Published: October 2022

Background and Objectives

Avian coccidiosis is an intestinal parasitic disease exerting a highly negative impact on the global poultry industry. The aim of the present study is to evaluate the immune protective efficacies against Eimeria tenella infection in chickens orally immunized with combined recombinant probiotics Entercoccus faecalis (E. faecalis) delivering surface-anchored E. tenella proteins.

Methods

Four kinds of novel probiotics vaccines that surface-expressing four Eimeria tenella (E. tenella) proteins EtAMA1, EtIMP1, EtMIC2 and Et3-1E were produced, respectively. The expression of four target proteins on the surface of recombinant bacteria was detected by Western blot and indirect immunofluorescence assay (IFA). Then the four kinds of recombinant E. faecalis were combined to immunize chickens via oral route in different combinations. The immunizations were performed three times at two-week intervals, and each for three consecutive days. After immunizations, chickens in each immunized group were orally challenged with E. tenella sporulated oocysts. The immune responses and protective efficacies against homologous infection were evaluated.

Results

The results showed that three or four live recombinant E. faecalis induced effective antigen-specific humoral, intestinal mucosal immune responses, stimulated peripheral T lymphocytes proliferation, and displayed partial protections against homologous challenge as measured by cecal lesions, oocyst shedding, and body weight gain (BWG). Notably, higher levels of protective efficacies were observed when the four recombinant E. faecalis delivering target proteins were combined.

Conclusion

Chickens orally administrated with three or four, especially the four combined recombinant E. faecalis stimulated specific immune responses, which provided anti-coccidial effects. This study offers an idea for future development of novel vaccines based on multi-antigens delivered by probiotic bacteria.
The role of organ-deposited IgG in the pathogenesis of multi-organ and tissue damage in systemic lupus erythematosus
Authors: Qiu Wenlin , Yu Tong , Deng Guo-Min
Published: October 2022

Systemic lupus erythematosus (SLE), often known simply as lupus, is a severe chronic autoimmune disease that is characterized by multi-organ and tissue damage and high levels of autoantibodies in serum. We have recently investigated, using animal models, the role of organ-deposited IgG autoantibodies in the pathogenesis of organ and tissue damage in SLE. We found that intra-organ injection of serum from mice with lupus (i.e., lupus mice) into healthy mice triggered inflammation in tissue and organs but that serum from other healthy mice did not, and that the severity of inflammation was related to the dose of serum injected. Immunohistochemistry showed that a large number of IgG molecules are deposited at the site of organ and tissue damage in lupus mice, and that IgG is a major contributor to the development of tissue inflammation triggered by serum from lupus mice or patients. The development of tissue inflammation induced by IgG in serum from lupus mice requires the presence of monocytes/macrophages, but not of lymphocytes or neutrophils; tumor necrosis factor (TNF)/tumor necrosis factor receptor 1 (TNFR1) and interleukin 1 (IL-1) also play essential roles in the development of tissue inflammation triggered by IgG. In addition, it has been found that TNFR1 inhibitors can suppress skin injury in lupus mice and that spleen tyrosine kinase (Syk) inhibitors, which can block the signaling transduction of IgG/Fc gamma receptors (FcγRs), can prevent and treat skin injury and kidney damage in lupus mice. We have also observed that lupus IgG might protect against bone erosion. Based on these results, we conclude that IgG plays a crucial role in the development of organ and tissue damage in SLE and in protecting bone erosion and arthritis, and we suggest that the IgG/FcγR signaling pathway is an important therapeutic target in SLE.
TNF-induced metalloproteinase-9 production is associated with neurological manifestations in HTLV-1-infected individuals
Authors: Guerra Mariele , Carvalho Natália B. , Santos Silvane , Nascimento Mauricio T. , Sá Renata , Carvalho Augusto M. , Carvalho Edgar M. , Carvalho Lucas P.
Published: October 2022

HTLV-1-infected individuals may develop a neurologic inflammatory condition known as HTLV-1-associated myelopathy (HAM/TSP), in which the high production of TNF is observed. These patients exhibit higher proviral loads, enhanced production of proinflammatory cytokines and lymphocyte proliferation in comparison to asymptomatic HTLV-1 carriers and those presenting overactive bladder (OAB-HTLV-infected). Metalloproteinases (MMPs) are known to degrade the components of the blood-brain barrier, favoring the migration of infected cells into the central nervous system. Moreover, the unbalanced production of MMPs and their inhibitors (TIMPs) has also been associated with tissue damage. The present work studied the production of MMP-9 and TIMPs in HTLV-1-infected individuals with and without neurological manifestations. HAM/TSP patients presented higher concentrations of MMP-9 in peripheral blood mononuclear cell (PBMC) culture supernatants, as well as a higher MMP-9/TIMP-3 ratio when compared to the other groups studied. MMP-9 levels positively correlated with proviral load and TNF in OAB-HTLV-infected individuals, and thein vitroneutralization of TNF significantly decreased MMP-9 levels in PBMC culture supernatants. Our findings indicate an association between MMP-9 production and the proinflammatory state associated with HTLV-1 infection, as well as HAM/TSP.
Functional variant rs12614 in CFB confers a low risk of IgA nephropathy by attenuating complement alternative pathway activation in Han Chinese
Authors: Shi Dian-Chun , Feng Shao-Zhen , Zhong Zhong , Cai Lu , Wang Meng , Fu Dong-Ying , Yu Xue-Qing , Li Ming
Published: October 2022

Activation of the alternative pathway (AP) of complement is thought to play an important role in Immunoglobin A nephropathy (IgAN). Our previous study showed that rs4151657 within the complement factor B (CFB) gene increased the risk of IgAN. The protein encoded by the CFB gene is an initial factor that promotes AP activation. The aim of this study was to investigate whether other variants of CFB confer susceptibility to IgAN and elucidate their potential roles in AP activation. A total of 1,350 patients with IgAN and 1,420 healthy controls were enrolled and five tag single-nucleotide polymorphisms were selected for genotyping. The levels of key AP components, such as CFB, complement factor H and complement split product C3a, were measured by enzyme-linked immunosorbent assay. Molecular docking and molecular dynamic simulation were carried out to characterize the mutation of residues in the protein structure and the dynamic properties of wide type and mutation models of CFB protein. The allele-specific effect on CFB expression and its binding affinity to C3b were investigated through cell transfection and surface plasmon resonance analysis, respectively. We found that rs12614 significantly reduced the risk of IgAN (OR = 0.69, 95% CI = 0.52–0.91, P = 0.009), and the rs12614-T (R32W mutation) was correlated with lower CFB levels, higher serum C3 level, and less mesangial C3 deposition in patients with IgAN. The structural model showed that the R32W mutation reduced the structural stability of CFB protein. Furthermore, in vitro study revealed that rs12614-T decreased the expression of CFB and reduced its binding affinity to C3b by four-fold compared with rs12614-C. In conclusion, the rs12614-T in CFB was associated with low risk of IgAN probably by attenuating AP activation.
Long-term cellular immune response in immunocompromised unvaccinated COVID-19 patients undergoing monoclonal antibody treatment
Authors: Thümmler Laura , Konik Margarethe , Lindemann Monika , Fisenkci Neslinur , Koldehoff Michael , Gäckler Anja , Horn Peter A. , Theodoropoulos Fotis , Taube Christian , Zettler Markus , Anastasiou Olympia Evdoxia , Braß Peer , Jansen Sarah , Witzke Oliver , Rohn Hana , Krawczyk Adalbert
Published: October 2022

Immunocompromised patients are at increased risk for a severe course of COVID-19. Treatment of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection with anti-SARS-CoV-2 monoclonal antibodies (mAbs) has become widely accepted. However, the effects of mAb treatment on the long-term primary cellular response to SARS-CoV-2 are unknown. In the following study, we investigated the long-term cellular immune responses to SARS-CoV-2 Spike S1, Membrane (M) and Nucleocapsid (N) antigens using the ELISpot assay in unvaccinated, mAb-treated immunocompromised high-risk patients. Anti-SARS-CoV-2 mAb untreated though vaccinated COVID-19 immunocompromised patients, vaccinated SARS-CoV-2 immunocompromised patients without COVID-19 and vaccinated healthy control subjects served as control groups. The cellular immune response was determined at a median of 5 months after SARS-CoV-2 infection. Our data suggest that immunocompromised patients develop an endogenous long-term cellular immune response after COVID-19, although at low levels. A better understanding of the cellular immune response will help guide clinical decision making for these vulnerable patient cohorts.
Analysis of key genes in Mycobacterium ulcerans reveals conserved RNA structural motifs and regions with apparent pressure to remain unstructured
Authors: Rouse Warren B. , Gart Jessica , Peysakhova Lauren , Moss Walter N.
Published: October 2022

Buruli Ulcer is a neglected tropical disease that results in disfiguring and dangerous lesions in affected persons across a wide geographic area, including much of West Africa. The causative agent of Buruli Ulcer is Mycobacterium ulcerans, a relative of the bacterium that causes tuberculosis and leprosy. Few therapeutic options exist for the treatment of this disease beyond antibiotics in the early stages, which are frequently ineffective, and surgical removal in the later stage. In this study we analyze six genes in Mycobacterium ulcerans that have high potential of therapeutic targeting. We focus our analysis on a combined in silico and comparative sequence study of potential RNA secondary structure across these genes. The result of this work was the comprehensive local RNA structural landscape across each of these significant genes. This revealed multiple sites of ordered and evolved RNA structure interspersed between sequences that either have no bias for structure or, indeed, appear to be ordered to be unstructured and (potentially) accessible. In addition to providing data that could be of interest to basic biology, our results provide guides for efforts aimed at targeting this pathogen at the RNA level. We explore this latter possibility through the in silico analysis of antisense oligonucleotides that could potentially be used to target pathogen RNA.
Host and microbiota derived extracellular vesicles: Crucial players in iron homeostasis
Authors: Daou Yasmeen , Falabrègue Marion , Pourzand Charareh , Peyssonnaux Carole , Edeas Marvin
Published: October 2022

Iron is a double-edged sword. It is vital for all that’s living, yet its deficiency or overload can be fatal. In humans, iron homeostasis is tightly regulated at both cellular and systemic levels. Extracellular vesicles (EVs), now known as major players in cellular communication, potentially play an important role in regulating iron metabolism. The gut microbiota was also recently reported to impact the iron metabolism process and indirectly participate in regulating iron homeostasis, yet there is no proof of whether or not microbiota-derived EVs interfere in this relationship. In this review, we discuss the implication of EVs on iron metabolism and homeostasis. We elaborate on the blooming role of gut microbiota in iron homeostasis while focusing on the possible EVs contribution. We conclude that EVs are extensively involved in the complex iron metabolism process; they carry ferritin and express transferrin receptors. Bone marrow-derived EVs even induce hepcidin expression in β-thalassemia. The gut microbiota, in turn, affects iron homeostasis on the level of iron absorption and possibly macrophage iron recycling, with still no proof of the interference of EVs. This review is the first step toward understanding the multiplex iron metabolism process. Targeting extracellular vesicles and gut microbiota-derived extracellular vesicles will be a huge challenge to treat many diseases related to iron metabolism alteration.
Transcriptional response of the xerotolerant Arthrobacter sp. Helios strain to PEG-induced drought stress
Authors: Hernández-Fernández Gabriel , Galán Beatriz , Carmona Manuel , Castro Laura , García José Luis
Published: October 2022

A new bacterial strain has been isolated from the microbiome of solar panels and classified as Arthrobacter sp. Helios according to its 16S rDNA, positioning it in the “Arthrobacter citreus group.” The isolated strain is highly tolerant to desiccation, UV radiation and to the presence of metals and metalloids, while it is motile and capable of growing in a variety of carbon sources. These characteristics, together with observation that Arthrobacter sp. Helios seems to be permanently prepared to handle the desiccation stress, make it very versatile and give it a great potential to use it as a biotechnological chassis. The new strain genome has been sequenced and its analysis revealed that it is extremely well poised to respond to environmental stresses. We have analyzed the transcriptional response of this strain to PEG6000-mediated arid stress to investigate the desiccation resistance mechanism. Most of the induced genes participate in cellular homeostasis such as ion and osmolyte transport and iron scavenging. Moreover, the greatest induction has been found in a gene cluster responsible for biogenic amine catabolism, suggesting their involvement in the desiccation resistance mechanism in this bacterium.
CircDDX17 enhances coxsackievirus B3 replication through regulating miR-1248/NOTCH receptor 2 axis
Authors: Liu Tingjun , Li Yuhan , Chen Shengjie , Wang Lulu , Liu Xiaolan , Yang Qingru , Wang Yan , Qiao Xiaorong , Tong Jing , Deng Xintao , Shao Shihe , Wang Hua , Shen Hongxing
Published: October 2022

Coxsackievirus B3 (CVB3) was one of the most common pathogens to cause viral myocarditis. Circular RNAs as novel non-coding RNAs with a closed loop molecular structure have been confirmed to be involved in virus infectious diseases, but the function in CVB3 infection was not systematically studied. In this study, we identified that hsa_circ_0063331 (circDDX17) was drastically decreased after CVB3 infection by circRNA microarray. In vivo and in vitro, when cells or mice were infected with CVB3, the expression of circDDX17 was significantly reduced, as demonstrated by quantitative real-time PCR assays. Additionally, circDDX17 enhanced CVB3 replication by downregulating the expression of miR-1248 in HeLa and HL-1 cells, and miR-1248 regulated CVB3 replication through interacting with the gene coding for NOTCH Receptor 2 (NOTCH2), and NOTCH2 could upregulate methyltransferase-like protein 3 (METTL3). Taken together, this study suggested that circDDX17 promoted CVB3 replication and regulated NOTCH2 by targeting miR-1248 as a miRNAs sponge.
Neural and behavioral alterations of a real-time interpersonal distance (IPD) development process in differing social status interactions
Authors: Huang Xinxin , Izumi Shin-Ichi , Suzukamo Yoshimi
Published: October 2022

Background

Evidence showed neural changes in interpersonal distance (IPD) interaction, and neural activities are affected by relationships (such as friends or strangers). Behavior studies proved that social status strongly affects IPD between two persons. However, how the differing social status impacts neural alterations in the IPD interactions remains unknown.

Objectives

The teacher-student relationship is a typical representation of the difference in social status. The present study aims to investigate the IPD performance and brain processes underlying real-time differing social status during the development process from teacher-student interactions.

Materials and methods

We designed three within-subject experiments corresponding to the inclusion, control, and affection stages of IPD. Altogether, 38 valid healthy participants participated in three experiments with a teacher (differing social status condition, DS condition) and a peer student (peer social status condition, PS condition) separately. This study employed functional near-infrared spectroscopy (fNIRS) and modified real-time stop-distance paradigms to record IPD performance and neural processes.

Results

For IPD performance, significantly larger IPD gaps were shown in the DS condition than in the PS condition, and IPD feedback affected IPD performance. For neural alterations, activated frontopolar area (FPA, BA10), dorsolateral prefrontal cortex (DLPFC, BA9/BA46), and Broca’s area (BA45) were observed across the IPD stages. Importantly, brain activation shifts with the development of IPD. In addition, results showed that differences in Oxy-Hb changes were located in the FPA (BA10), DLPFC (BA9/BA46), and Broca’s area (BA45) between the DS and PS conditions across IPD stages. Additionally, negative correlations were found between Oxy-Hb changes and IPD performance.

Conclusion

We propose prefrontal cortex (PFC) and Broca’s area involvement in IPD interactions, initially focusing on evaluation and action periods, and later on IPD-evaluation processes after feedback. In addition, a difference in Oxy-Hb activities implies the complexity of relationships and social status in IPD interactions.
Dorsomedial prefrontal cortex activation disrupts Pavlovian incentive motivation
Authors: Halbout Briac , Hutson Collin , Wassum Kate M. , Ostlund Sean B.
Published: October 2022

The dorsomedial prefrontal cortex (dmPFC) is known to make important contributions to flexible, reward-motivated behavior. However, it remains unclear if the dmPFC is involved in regulating the expression of Pavlovian incentive motivation, the process through which reward-paired cues promote instrumental reward-seeking behavior, which is modeled in rats using the Pavlovian-instrumental transfer (PIT) task. The current study examined this question using a bidirectional chemogenetic strategy in which inhibitory (hM4Di) or excitatory (hM3Dq) designer G-protein coupled receptors were virally expressed in dmPFC neurons, allowing us to later stimulate or inhibit this region by administering CNO prior to PIT testing. We found that dmPFC inhibition did not alter the tendency for a reward-paired cue to instigate instrumental reward-seeking behavior, whereas dmPFC stimulation disrupted the expression of this motivational influence. Neither treatment altered cue-elicited anticipatory activity at the reward-delivery port, indicating that dmPFC stimulation did not lead to more widespread motor suppression. A reporter-only control experiment indicated that our CNO treatment did not have non-specific behavioral effects. Thus, the dmPFC does not mediate the expression of Pavlovian incentive motivation but instead has the capacity to exert pronounced inhibitory control over this process, suggesting that it is involved in adaptively regulating cue-motivated behavior.
Bioinformatics analysis constructs potential ferroptosis-related ceRNA network involved in the formation of intracranial aneurysm
Authors: Zhu Huaxin , Tan Jiacong , Wang Zhihua , Wu Zhiwu , Zhou Wu , Zhang Zhixiong , Li Meihua , Zhao Yeyu
Published: October 2022

Background

Intracranial aneurysm (IA) causes more than 80% of nontraumatic subarachnoid hemorrhages (SAHs). The mechanism of ferroptosis involved in IA formation remains unclear. The roles played by competitive endogenous RNA (ceRNA) regulation networks in many diseases are becoming clearer. The goal of this study was to understand more fully the ferroptosis-related ceRNA regulation network in IA.

Materials and methods

To identify differentially expressed genes (DEGs), differentially expressed miRNAs (DEMs), and differentially expressed lncRNAs (DELs) across IA and control samples, the GEO datasets GSE122897 and GSE66239 were downloaded and analyzed with the aid of R. Ferroptosis DEGs were discovered by exploring the DEGs of ferroptosis-related genes of the ferroptosis database. Potentially interacting miRNAs and lncRNAs were predicted using miRWalk and StarBase. Enrichment analysis was also performed. We utilized the STRING database and Cytoscape software to identify protein-protein interactions and networks. DAB-enhanced Prussian blue staining was used to detect iron in IA tissues.

Results

Iron deposition was evident in IA tissue. In all, 30 ferroptosis DEGs, 5 key DEMs, and 17 key DELs were screened out for constructing a triple regulatory network. According to expression regulation of DELs, DEMs, and DEGs, a hub triple regulatory network was built. As the functions of lncRNAs are determined by their cellular location, PVT1-hsa-miR-4644-SLC39A14 ceRNA and DUXAP8-hsa-miR-378e/378f-SLC2A3 ceRNA networks were constructed.

Conclusion

CeRNA (PVT1-hsa-miR-4644-SLC39A14 and DUXAP8-hsa-miR-378e/378f-SLC2A3) overexpression networks associated with ferroptosis in IA were established.
An overview of the evidence to guide decision-making in acupuncture therapies for early recovery after acute ischemic stroke
Authors: Wang Liuding , Chi Xiansu , Lyu Jian , Xu Zhenmin , Fu Guojing , Liu Yue , Liu Shaojiao , Qiu Wenran , Liu Hongxi , Liang Xiao , Zhang Yunling
Published: October 2022

Background

Acupuncture is a proven technique of traditional Chinese medicine (TCM) for ischemic stroke. The purpose of this overview was to summarize and evaluate the evidence from current systematic reviews (SRs) of acupuncture for early recovery after acute ischemic stroke (AIS).

Methods

We performed a comprehensive search for SRs of acupuncture for AIS in seven electronic databases up to May 23, 2022. Two reviewers independently selected SRs, extracted data, evaluated the methodological quality using the Assessment of Multiple Systematic Reviews 2 (AMSTAR 2), and rated evidence certainty using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE).

Results

Seven SRs were included. The overall methodological quality of SRs was critically low. As for GRADE, 3 outcomes had moderate-quality evidence, 14 had low-quality evidence, and 12 had very low-quality evidence. Moderate-quality evidence demonstrated that initiating acupuncture therapies within 30 days of AIS onset significantly improves neurological function and the total effective rate of patients. Low-quality evidence showed that for patients within 2 weeks of AIS onset Xingnao Kaiqiao acupuncture (XNKQ Ac) could reduce disability rate and might reduce mortality. Regarding the safety of acupuncture therapies, low-quality evidence showed that there was no difference in the incidence of adverse reactions between the 2 groups, and very-low quality evidence showed that acupuncture did not promote hemorrhagic conversion.

Conclusions

In the acute and early recovery phases after AIS onset, acupuncture is a promising therapeutic strategy to improve the curative effect of current treatments, especially in the recovery of neurological function. Patients in the acute phase might receive XNKQ Ac, and patients in the early recovery phase might receive EA1, CA, or SA. However, considering the current certainty of evidence, a solid recommendation warrants further exploration.

Systematic review registration:https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022335426.
Repairing sciatic nerve injury with self-assembling peptide nanofiber scaffold-containing chitosan conduit
Authors: Shen Xuezhen , Qu Feng , Pei Yilun , Lei Simeng , Xia Suhang , Liang Jing , Li Shan , Sun Xun , Liu Liang
Published: October 2022

Background

An increasing number of nerve guide scaffolds have been used to replace the “gold-standard” autologous nerve graft for repairing peripheral nerve defects, but nerve regeneration is usually far from complete.

Methods

Here, we designed and prepared two functionalized self-assembling peptides (SAP) with the IKVAV and KLT sequences, which were derived from the combination of laminin and VEGF, respectively. Their mixtures were also obtained to combine the effects of neuroprotective and neurotrophic and proangiogenic factors.

Results

The beneficial effect of peptide gels on nerve regeneration was evaluated in vitro using Schwann cells (SCs). As a useful intraluminal filling, a three-dimensional (3D) functionalized self-assembling peptide (SAP) nanofiber hydrogel was formed in the hollow lumen of chitosan conduits under physiological conditions. In vivo, the combination of the two functionalized SAP gels containing a chitosan nerve conduit significantly accelerated nerve healing and enhanced morphological repair.

Conclusion

Based on the current findings, the combined application of two functionalized SAP gels with chitosan nerve conduit is a promising therapy for the engineering of peripheral nerve regeneration.
Transcranial direct current stimulation modulates working memory and prefrontal-insula connectivity after mild-moderate traumatic brain injury
Authors: Quinn Davin K. , Story-Remer Jacqueline , Brandt Emma , Fratzke Violet , Rieger Rebecca , Wilson John Kevin , Gill Darbi , Mertens Nickolas , Hunter Michael , Upston Joel , Jones Thomas R. , Richardson Jessica D. , Myers Orrin , Arciniegas David B. , Campbell Richard , Clark Vincent P. , Yeo Ronald A. , Shuttleworth C. William , Mayer Andrew R.
Published: October 2022

Background: Persistent posttraumatic symptoms (PPS) may manifest after a mild-moderate traumatic brain injury (mmTBI) even when standard brain imaging appears normal. Transcranial direct current stimulation (tDCS) represents a promising treatment that may ameliorate pathophysiological processes contributing to PPS.

Objective/Hypothesis: We hypothesized that in a mmTBI population, active tDCS combined with training would result in greater improvement in executive functions and post-TBI cognitive symptoms and increased resting state connectivity of the stimulated region, i.e., left dorsolateral prefrontal cortex (DLPFC) compared to control tDCS.

Methods: Thirty-four subjects with mmTBI underwent baseline assessments of demographics, symptoms, and cognitive function as well as resting state functional magnetic resonance imaging (rsfMRI) in a subset of patients (n = 24). Primary outcome measures included NIH EXAMINER composite scores, and the Neurobehavioral Symptom Inventory (NSI). All participants received 10 daily sessions of 30 min of executive function training coupled with active or control tDCS (2 mA, anode F3, cathode right deltoid). Imaging and assessments were re-obtained after the final training session, and assessments were repeated after 1 month. Mixed-models linear regression and repeated measures analyses of variance were calculated for main effects and interactions.

Results: Both active and control groups demonstrated improvements in executive function (EXAMINER composite: p < 0.001) and posttraumatic symptoms (NSI cognitive: p = 0.01) from baseline to 1 month. Active anodal tDCS was associated with greater improvements in working memory reaction time compared to control (p = 0.007). Reaction time improvement correlated significantly with the degree of connectivity change between the right DLPFC and the left anterior insula (p = 0.02).

Conclusion: Anodal tDCS improved reaction time on an online working memory task in a mmTBI population, and decreased connectivity between executive network and salience network nodes. These findings generate important hypotheses for the mechanism of recovery from PPS after mild-moderate TBI.
CDK2 regulates aminoglycoside-induced hair cell death through modulating c-Jun activity: Inhibiting CDK2 to preserve hearing
Authors: Tao Litao , Segil Neil
Published: October 2022

Sensory hair cell death caused by the ototoxic side effects of many clinically used drugs leads to permanent sensorineural hearing loss in patients. Aminoglycoside antibiotics are widely used and well-known for their ototoxicity, but the molecular mechanisms of aminoglycoside-induced hair cell death are not well understood. This creates challenges in our attempts to alleviate or prevent such adverse side effects. Here, we report a regulatory role of CDK2 in aminoglycoside-induced hair cell death. Utilizing organotypic cultures of cochleae from neonatal mice, we show that blocking CDK2 activity by either pharmaceutical inhibition or by Cdk2 gene knockout protects hair cells against the ototoxicity of gentamicin—one of the most commonly used aminoglycoside antibiotics—by interfering with intrinsic programmed cell death processes. Specifically, we show that CDK2 inhibition delays the collapse of mitochondria and the activation of a caspase cascade. Furthermore, at the molecular level, inhibition of CDK2 activity influences proapoptotic JNK signaling by reducing the protein level of c-Jun and suppressing the gentamicin-induced upregulation of c-Jun target genes Jun and Bim. Our in vivo studies reveal that Cdk2 gene knockout animals are significantly less sensitive to gentamicin ototoxicity compared to wild-type littermates. Altogether, our work ascertains the non-cell cycle role of CDK2 in regulating aminoglycoside-induced hair cell apoptosis and sheds lights on new potential strategies for hearing protection against ototoxicity.
Targeting FGL2 in glioma immunosuppression and malignant progression
Authors: Ma Xiaoyu , Zhu Hongtao , Cheng Lidong , Chen Xin , Shu Kai , Zhang Suojun
Published: October 2022

Glioblastoma (GBM) is the most malignant type of glioma with the worst prognosis. Traditional therapies (surgery combined with radiotherapy and chemotherapy) have limited therapeutic effects. As a novel therapy emerging in recent years, immunotherapy is increasingly used in glioblastoma (GBM), so we expect to discover more effective immune targets. FGL2, a member of the thrombospondin family, plays an essential role in regulating the activity of immune cells and tumor cells in GBM. Elucidating the role of FGL2 in GBM can help improve immunotherapy efficacy and design treatment protocols. This review discusses the immunosuppressive role of FGL2 in the GBM tumor microenvironment and its ability to promote malignant tumor progression while considering FGL2-targeted therapeutic strategies. Also, we summarize the molecular mechanisms of FGL2 expression on various immune cell types and discuss the possibility of FGL2 and its related mechanisms as new GBM immunotherapy.
Laparoscopic resection is not superior to endoscopic resection for relative small gastric gastrointestinal stromal tumors: A propensity score-matched study
Authors: Li De-Liang , Zhou Yang-Yang , Zhang Ji-Yu , Liu Dan , Zhao Li-Xia , Liu Bing-Rong
Published: October 2022

Background and Aim

Endoscopic resection (ER) and laparoscopic resection (LAP) have been recommended for the treatment of gastric gastrointestinal stromal tumors (GISTs) less than 2 cm. However, the therapeutic approach for gastric GISTs between 2 and 5 cm in diameter is still under debate. In this retrospective study, we aimed to evaluate the feasibility, efficacy, and safety of ER for gastric GISTs (2–5 cm) compared with LAP.

Methods

From January, 2011 to January, 2018, 197 patients with GISTs at our institution with tumor diameter between 2 and 5 cm were included in our study. Clinical baseline characteristics, histopathological results, and perioperative outcomes were collected and compared in all the patients. Propensity score matching (PSM) methods were used to balance baseline characteristics.

Results

There was no significant difference in age (p = 0.246), gender (p = 0.572), tumor location (p = 0.333), pathological risk classification (p = 0.543), Ki-67 index (p = 0.212), and follow-up time (p = 0.831) in the ER and LAP groups. However, significance difference was found in times to liquid diet intake (4.45 ± 1.2 vs. 5.40 ± 1.5 days, p = 0.013) and hospital stays (7.72 ± 1.1 vs. 10.01 ± 1.3 days, p < 0.001). During the follow-up period, there was one recurrence in the ER group vs. two recurrences in the LAP group. After PSM, the tumor size was balanced between the two groups with 49 patients in each group. The times to liquid diet intake (4.18 ± 1.3 vs. 5.16 ± 1.6 days, p = 0.042) and hospital stay days (7.12 ± 1.1 vs. 9.94 ± 1.3, p < 0.0001) were still short in the ER group.

Conclusions

ER is more associated with a quick postoperative recovery than LAP. ER could be an alternative approach for gastric GISTs (2–5 cm). However, the long-term follow-up outcomes are still unclear and random control trials are needed.
Stereotactic partial breast irradiation in primary breast cancer: A comprehensive review of the current status and future directions
Authors: Takanen Silvia , Pinnarò Paola , Farina Ilaria , Sperati Francesca , Botti Claudio , Vici Patrizia , Soriani Antonella , Marucci Laura , Sanguineti Giuseppe
Published: October 2022

In selected low-risk breast cancer patients, accelerated partial breast irradiation (APBI) may represent an alternative option to the whole breast irradiation to reduce the volume of irradiated breast and total treatment duration. In the last few years, preliminary data from clinical trials showed that stereotactic partial breast radiotherapy may have the advantage to be less invasive compared to other APBI techniques, with preliminary good results in terms of local toxicity and cosmesis: the use of magnetic resonance, fiducial markers in the tumor bed, and new breast devices support both a precise definition of the target and radiation planning.

Systematic review registration

https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021257856, identifier CRD42021257856.