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CD100/Plexin-B1 interactions sustain proliferation and survival of normal and leukemic CD5+ B lymphocytes.

Growth and survival of chronic B-cell tumors are favored by the malignant cell's capacity to respond to selected microenvironmental stimuli provided by nontumoral bystander cells. To investigate which mechanisms operate in these crosstalks and whether they are malignancy-related or reproduce the mechanisms used by normal B cells we have studied the expression and functional role of semaphorin CD100 (now called Sema4D) in chronic lymphocytic leukemia (CLL) cells and normal CD5+ B cells. We demonstrate here that (1) leukemic and normal CD5+ B lymphocytes uniformly express CD100; (2) the CD100 hi

Expression of the dihydropyrimidinase related protein 2 (DRP-2) in Down syndrome and Alzheimer's disease brain is downregulated at the mRNA and dysregulated at the protein level.

Deteriorated migration, axonal pathfinding and wiring of the brain is a main neuropathological feature of Down Syndrome (DS). Information on the underlying mechanisms is still limited, although basic functions of a series of growth factors, cell adhesion molecules, guidance factors and chemoattractants for brain histogenesis have been reported. We used proteomics to detect differences in protein expression between control, DS and Alzheimer's disease brains: In five individual brain regions of 9 individuals of each group we performed two dimensional electrophoresis with MALDI--identification of

Immunomodulatory cytoskeleton of bionic periosteum affects mitochondrial dynamics to promote osteogenesis.

PURPOSE: Periosteum is a key regulatory hub in the immune microenvironment of bone repair and the mitochondrial dynamics of bone marrow mesenchymal stem cells (BMSCs) directly determine the osteogenic efficiency; therefore, how to promote bone healing through the immunomodulation of mitochondrial dynamics is a key challenge. METHODS: Inspired by the natural periosteum, we designed a bionic periosteum that integrates topology and controlled Semaphorin 3 A (Sema3A) release. Hyaluronic acid-coated Sema3A granular microsols spontaneously formed a nucleus-sheath structure under a high-voltage elec

Impact of Sema3A Interference on Cerebellum-Dependent Motor Associative Learning and Memory.

Semaphorin 3A (Sema3A), a known axon chemorepulsive protein during development, is localised in perineuronal nets (PNNs) in the adult brain. PNNs are condensed aggregates of extracellular matrix molecules surrounding specific types of neurons, which regulate neuroplasticity and memory. However, the role of PNN-associated Sema3A in these processes remains unclear. To address this topic, we investigated the contribution of Sema3A to cerebellum-dependent learning and memory in adult mice using the eyeblink conditioning (EBC) paradigm. We interfered with Sema3A signalling by employing: (i) a molec

Sema7A is crucial for resolution of severe inflammation.

Endogenous mediators regulating acute inflammatory responses in both the induction and resolution phases of inflammatory processes are pivotal in host defense and tissue homeostasis. Recent studies have identified neuronal guidance proteins characterized in axonal development that display immunomodulatory functions. Here, we identify the neuroimmune guidance cue Semaphorin 7A (Sema7A), which appears to link macrophage (MΦ) metabolic remodeling to inflammation resolution. Sema7A orchestrated MΦ chemotaxis and chemokinesis, activated MΦ differentiation and polarization toward the proresolving M2

The linkage of cell cycle and DNA replication with growth difference in female Chinese tongue sole (Cynoglossus semilaevis): Analysis from transcriptomic study and WGCNA.

In addition to the typical sexual size dimorphism, considerable size differences within the female population of the Chinese tongue sole (Cynoglossus semilaevis) have become a further bottleneck of the improvement of sole aquaculture. To identify the internal mechanism, transcriptomic analysis and weighted gene co-expression network analysis (WGCNA) were employed simultaneously. Transcriptomic analyses of brain, pituitary gland, liver, gonad, and muscle tissues from two female groups with size differences identified 109, 698, 1325, 2299, and 2141 differentially expressed genes (DEGs), respecti

A conceptual framework linking immunology, pathology, and clinical features in primary membranous nephropathy.

Primary membranous nephropathy is a leading cause of adult nephrotic syndrome. The field took a major step forward with the identification of phospholipase A2 receptor (PLA2R) as a target antigen in the majority of cases and with the ability to measure circulating autoantibodies to PLA2R. Since then, the existence of additional target antigens such as thrombospondin type-1 domain-containing 7A, exostosin 1 and 2, neural EGFL like 1, and semaphorin 3B has been demonstrated. The ability to detect and monitor levels of circulating autoantibodies has opened a new window onto the humoral aspect of

miR-155 overexpression is followed by downregulation of its target gene, NFE2L2, and altered pattern of VEGFA expression in the liver of melanoma B16-bearing mice at the premetastatic stage.

MicroRNAs are involved in the control of tumour progression and in metastatic cascade dynamics. However, the role of microRNAs in distant organ reorganization at the premetastatic stage is less clear, although the process of premetastatic niche formation is a crucial event according to modern concepts of tumour dissemination. The role of the present study was to investigate the expression levels of miR-155, miR-21, miR-205 and miR-let7b, as well as that of their target genes, in target organs of melanoma metastasis at the premetastatic stage. The expression levels of both the pro-oncogenic miR

NRP1 and NRP2 cooperate to regulate gangliogenesis, axon guidance and target innervation in the sympathetic nervous system.

The sympathetic nervous system (SNS) arises from neural crest (NC) cells during embryonic development and innervates the internal organs of vertebrates to modulate their stress response. NRP1 and NRP2 are receptors for guidance cues of the class 3 semaphorin (SEMA) family and are expressed in partially overlapping patterns in sympathetic NC cells and their progeny. By comparing the phenotypes of mice lacking NRP1 or its ligand SEMA3A with mice lacking NRP1 in the sympathetic versus vascular endothelial cell lineages, we demonstrate that SEMA3A signalling through NRP1 has multiple cell-autonomo

LIN-39 and the EGFR/RAS/MAPK pathway regulate C. elegans vulval morphogenesis via the VAB-23 zinc finger protein.

Morphogenesis represents a phase of development during which cell fates are executed. The conserved hox genes are key cell fate determinants during metazoan development, but their role in controlling organ morphogenesis is less understood. Here, we show that the C. elegans hox gene lin-39 regulates epidermal morphogenesis via its novel target, the essential zinc finger protein VAB-23. During the development of the vulva, the egg-laying organ of the hermaphrodite, the EGFR/RAS/MAPK signaling pathway activates, together with LIN-39 HOX, the expression of VAB-23 in the primary cell lineage to con

Conditional inactivation of the NBS1 gene in the mouse central nervous system leads to neurodegeneration and disorganization of the visual system.

Nijmegen breakage syndrome (NBS) is a genomic instability disease caused by hypomorphic mutations in the NBS1 gene encoding the Nbs1 (nibrin) protein. Nbs1 is a component of the Mre11/Rad50/Nbs1 (MRN) complex that acts as a sensor of double strand breaks (DSBs) in the DNA and is critical for proper activation of the broad cellular response to DSBs. Conditional disruption of the murine ortholog of the human NBS1, Nbs1, in the CNS of mice was previously reported to cause microcephaly, severe cerebellar atrophy and ataxia. Here we report that conditional targeted disruption of the murine NBS1 gen

The dichotomous impacts of Semaphorin3E deficiency on exacerbating airway hyperresponsiveness, remodelling, and inflammation in type-2 low and type-2 high asthma models.

Semaphorin3E has shown promise in alleviating the severity of asthma in preclinical studies; however, its role in the chronic features of type 2-low asthma remains unclear. Therefore, we aimed to investigate the role of Sema3E in a mouse model of severe asthma that exhibits a mix of granulocytic inflammation with neutrophils dominance and compared the results with those from the type-2 high eosinophilic asthma model. Sema3E knockout (KO) and wild-type (WT) mice were subjected to type-2 low and type-2 high regimens using house dust mite (HDM) combined with cyclic-di-GMP or HDM alone, respective

A Comprehensive Prognostic Analysis of Tumor-Related Blood Group Antigens in Pan-Cancers Suggests That SEMA7A as a Novel Biomarker in Kidney Renal Clear Cell Carcinoma.

Blood group antigen is a class of heritable antigenic substances present on the erythrocyte membrane. However, the role of blood group antigens in cancer prognosis is still largely unclear. In this study, we investigated the expression of 33 blood group antigen genes and their association with the prognosis of 30 types of cancers in 31,870 tumor tissue samples. Our results revealed that blood group antigens are abnormally expressed in a variety of cancers. The high expression of these antigen genes was mainly related to the activation of the epithelial-mesenchymal transition (EMT) pathway. Hig

Characterization of non-alpha retinal ganglion cell injury responses reveals a possible block to restoring ipRGC function.

Visual impairment caused by retinal ganglion cell (RGC) axon damage or degeneration affects millions of individuals throughout the world. While some progress has been made in promoting long-distance RGC axon regrowth following injury, it remains unclear whether RGC axons can properly reconnect with their central targets to restore visual function. Additionally, the regenerative capacity of many RGC subtypes remains unknown in part due to a lack of available genetic tools. Here, we use a new mouse line, Sema6ACreERT2, that labels On direction-selective RGCs (oDSGCs) and characterize the surviva

miR-15b-5p ameliorated high glucose-induced podocyte injury through repressing apoptosis, oxidative stress, and inflammatory responses by targeting Sema3A.

Podocyte damage is a hallmark of diabetic nephropathy (DN). Accumulating evidence indicates that microRNAs play important roles in the DN pathogenesis. This study aimed to explore the possible roles and underlying mechanisms of miR-15b-5p on high glucose (HG)-triggered podocyte injury. We observed that miR-15b-5p declined dramatically in a time-dependent manner in podocytes exposed to HG. In addition, miR-15b-5p restored cell proliferation in HG-induced podocytes. Meanwhile, forced expression of miR-15b-5p apparently restrained HG-triggered apoptosis of podocytes, concomitant with downregulate

Комплексный подход к дифференцированию системного лейкоцита от других аутоиммунных заболеваний, вызываемых оптическим невритом.

Системная волчанка (SLE) представляет собой сложное аутоиммунное заболевание со значительной заболеваемостью и смертностью. Ранняя диагностика имеет решающее значение для эффективного управления. В качестве потенциальных первых признаков SLE появились окулярные проявления, в частности оптический нейрит (ON). В этом систематическом обзоре литературы анализируются 23 исследования, включая восемь ретроспективных исследований, пять межсекторальных исследований, два групповых исследования, четыре тематических доклада, один обзор описательной части и три систематического обзора литературы, в целях и

Совпадение в аннотации оригинала
Systemic lupus erythematosus (SLE) is a complex autoimmune disease with significant morbidity and mortality. Early diagnosis is crucial for … ple vertebral bodies. Dermatological manifestations, genetic factors, and blood biomarkers, such as semaphorins and complement levels, also offer diagnostic insights. This systematic review underscores the importance of integrating clinical, laboratory, and radiologic imaging data for precise diagnosis and differentiation of SLE, NMOSD, and MS when encounteri …

Tendon pain - what are the mechanisms behind it?

OBJECTIVES: Management of chronic tendon pain is difficult and controversial. This is due to poor knowledge of the underlying pathophysiolog … blocking promotors of nerve ingrowth, such as NGF, and promoting inhibitors of nerve ingrowth, like semaphorins, as well as blocking glutamate-NMDA-receptor pathways, which are prominent in chronic tendon pain.

Soluble Neuropilin-1 Response to Hypoglycemia in Type 2 Diabetes: Increased Risk or Protection in SARS-CoV-2 Infection?

INTRODUCTION: Neuropilin-1(NRP1) is a cofactor that enhances SARS-CoV-2 coronavirus cell infectivity when co-expressed with angiotensin-conv … AGT), ACE2, soluble NRP1(sNRP1), NRP1 ligands (Vascular endothelial growth factor, VEGF and Class 3 Semaphorins, SEM3A) and NRP1 proteolytic enzyme (A Disintegrin and Metalloproteinase 9, ADAM9). RESULTS: Baseline RAS overactivity was present with REN elevated and AGT decreased in T2D (p<0.05); ACE2 was unchanged. Baseline sNRP1, VEGF and ADAM9 did not diffe …

Decreased expression of neuropilin-1 as a novel key factor contributing to peripheral microvasculopathy and defective angiogenesis in systemic sclerosis.

OBJECTIVES: In systemic sclerosis (SSc), vascular involvement is characterised by vascular endothelial growth factor (VEGF)-A/VEGF receptor (VEGFR) system disturbances. Neuropilin-1 (NRP1), a receptor for both class-3 semaphorins (Sema3s) and VEGF-A, is required for optimal VEGF-A/VEGFR-2 signalling. Here, we investigated the possible involvement of Sema3A/NRP1 axis in SSc. METHODS: Circulating Sema3A and soluble NRP1 (sNRP1) were measured in patients with SSc and controls. NRP1 and Sema3A expression in skin biopsies was evaluated by immunofluorescence and western blotting. NRP1 expression wa…

CHD7, the gene mutated in CHARGE syndrome, regulates genes involved in neural crest cell guidance.

Heterozygous loss of function mutations in CHD7 (chromodomain helicase DNA-binding protein 7) lead to CHARGE syndrome, a complex development … Interestingly, many misregulated genes are involved in neural crest cell and axon guidance such as semaphorins and ephrin receptors. By performing knockdown experiments for Chd7 in Xenopus laevis embryos, we found abnormalities in the expression pattern of Sema3a, a protein involved in the pathogenesis of Kallmann syndrome, in vivo. In addition, we detected …