Результаты поиска

Construction of a Novel Necroptosis-Related Signature in Rat DRG for Neuropathic Pain.

BackgroundRecent studies have shown necroptosis may play a role in the development of inflammation-associated pain. However, research on the correlation between necroptosis-related genes and neuropathic pain in the dorsal root ganglia (DRG) is limited. This study aims to identify a gene signature related to necroptosis in DRG that can predict neuropathic pain.MethodsThe mRNA expression profiles associated with neuropathic pain (GSE24982 and GSE30691) were acquired from the Gene Expression Omnibus (GEO) database. The Least Absolute Shrinkage and Selection Operator (Lasso) and Support Vector Mac

Совпадение в полном тексте источника
… The expression of Toll-like receptor 4, 7 and co-receptors in neurochemical sub-populations of rat trigeminal ganglion sensory neurons . Neuroscience . 2015 ; 310 : 686 – 698 . doi: 10.1016/j.neuroscience.2015.09.069 26434622 20. Zhang H , Li Y , de Carvalho-Barbosa M , et al. … HIV protease inhibitor saquinavir inhibits toll-like receptor 4 activation by targeting receptor dimerization . Immunopharm Immunot . 2023 ; 45 ( 6 ): 754 – 760 . doi: 10.1080/08923973.2023.2239488 37485845 29. Sato A , Asano T , Okubo K , et al. …

Advances in nanotechnology-enabled adjuvants for peptide-based cancer vaccines.

Peptide-based vaccines only contain peptide epitopes and exclude unnecessary biological materials, which greatly reduces the risk of causing an undesired immune response and further improves the safety profile, garnering considerable interest in vaccine development. However, the immunogenicity induced by these peptides alone is not potent enough to elicit an effective immune response. Recently, combining the adjuvants with peptide antigens has shown promising effects to realize a satisfying immune response. In this review, we discuss the development of immunoadjuvants to enhance the safety and

Появляющаяся роль BTK Inhibitors в многоразовом склерозе: от иммунобиологии к клиническому переводу.

Множественный склероз (MS), аутоиммунное заболевание, предполагает периферическую иммунную активацию, за которой следует воспаление CNS в разрозненной форме. Несмотря на то, что высокоэффективные методы коррекции заболеваний (HO-DMT) оказались эффективными в борьбе с рецидивами у пациентов с синдромом MS, они не позволяют эффективно ориентироваться на хроническую микрогильевую активацию и удушающие повреждения у пациентов с синдромом MS. Тейросиновые ингибиторы киназы Брютона (BTKis), которые являются перорально активными и способными пересечь мозговой барьер, были признаны эффективными для мо

The emerging role of exosomes in innate immunity, diagnosis and therapy.

Exosomes, which are nano-sized transport bio-vehicles, play a pivotal role in maintaining homeostasis by exchanging genetic or metabolic information between different cells. Exosomes can also play a vital role in transferring virulent factors between the host and parasite, thereby regulating host gene expression and the immune interphase. The association of inflammation with disease development and the potential of exosomes to enhance or mitigate inflammatory pathways support the notion that exosomes have the potential to alter the course of a disease. Clinical trials exploring the role of exo

[Immunotherapy - The New Era of Oncology].

In the field of immunotherapy, essential progress was achieved over the past years partially demonstrating long lasting therapeutic responses in different tumor entities. A better understanding of the interactions between the tumor and the immune system as well as the integration of immunotherapeutic approaches into clinical routine were the foundations for this development. The different approaches intervene on multiple levels of the immune response and directly or indirectly mount the patient's own immune defense against tumor cells. Immunotherapeutic approaches are represented by cytokine t

What is new in the pathogenesis and treatment of IgA glomerulonephritis.

Recently, new findings have been clarified concerning both pathogenesis and treatment of IgA nephritis. The four hits theory has been confirmed but several genetic wide association studies have allowed finding several genes connected with the pathogenesis of the disease. All these new genes apply to each of the four hits. Additionally, new discoveries concerning the microbiota and its connection with immune system and IgA generation have allowed finding out the role of the mucosa in IgA nephropathy pathogenesis. The IgA treatment is also changed included the future possibilities. The treatment

Host impairments in patients with neoplastic diseases.

Healthy individuals possess an immune system comprising physical barriers, innate and acquired immunity as well as the indigenous microflora that populate the body surfaces. The immune system maintains constant vigilance over the body at the cellular level as well as at the interface between the host integument and the resident microflora. However, neoplastic diseases and their treatment often lead to impaired immunity resulting in an increased risk of infections due to viruses, bacteria, fungi, and protozoa. This chapter explores the various aspects of host impairment focusing on the componen

Human γδ T Cell Subsets and Their Clinical Applications for Cancer Immunotherapy.

Gamma delta (γδ) T cells are a minor population of T cells that share adaptive and innate immune properties. In contrast to MHC-restricted alpha beta (αβ) T cells, γδ T cells are activated in an MHC-independent manner, making them ideal candidates for developing allogeneic, off-the-shelf cell-based immunotherapies. As the field of cancer immunotherapy progresses rapidly, different subsets of γδ T cells have been explored. In addition, γδ T cells can be engineered using different gene editing technologies that augment their tumor recognition abilities and antitumor functions. In this review, we

Bone marrow microenvironment in myelodysplastic neoplasms: insights into pathogenesis, biomarkers, and therapeutic targets.

Myelodysplastic neoplasms (MDS) represent a heterogeneous group of malignant hematopoietic stem and progenitor cell (HSPC) disorders characterized by cytopenia, ineffective hematopoiesis, as well as the potential to progress to acute myeloid leukemia (AML). The pathogenesis of MDS is influenced by intrinsic factors, such as genetic insults, and extrinsic factors, including altered bone marrow microenvironment (BMM) composition and architecture. BMM is reprogrammed in MDS, initially to prevent the development of the disease but eventually to provide a survival advantage to dysplastic cells. Rec

Совпадение в полном тексте источника
… Additionally, in MDS, impaired macrophage clearance of apoptotic cells leads to the release of high-mobility group box 1 (HMGB1), which functions as a damage-associated molecular pattern (DAMP), activating Toll-Like Receptor 4 (TLR4) on BM macrophages and triggering pro-inflammatory cytokine production …

Genetic Risk Surveillance for Invasive Aspergillosis in Hematology Patients: A Prospective Observational Study.

IntroductionThe association between genetic background and the risk of invasive aspergillosis (IA) has not been addressed in Thailand. We conducted genetic risk surveillance for IA among Thai hematologic patients.MethodsWe conducted a prospective observational cohort study including moderate- to high-risk hematology patients at Ramathibodi Hospital. IA occurrence, relevant clinical data, and genetic analyses were assessed. Odds ratios (ORs) of IA were assessed for the presence of the selected single nucleotide polymorphism genotype using logistic regression.ResultsA total of 357 patients were

Совпадение в полном тексте источника
… like receptor 4, PTX3 pentraxin-3 a Logistic regression analysis with model adjusted for age group and high-risk hematologic disease SNP | Genotype | No IA, n (%) | IA, n (%) | Adjusted OR (95% CI) a | P value DC-SIGN rs4804800 | A/A | 123 (41.1) | 10 (30.3) | 1.000 | – A/G | 135 (45.2) | 17 (51.5) … Toll-like receptor 4 polymorphisms and aspergillosis in stem-cell transplantation. N Engl J Med. 2008;359:1766–1777. doi: 10.1056/NEJMoa0802629. 27. Mezger M, Steffens M, Beyer M, et al. …

Morphine-3-glucuronide upregulates PD-L1 expression via TLR4 and promotes the immune escape of non-small cell lung cancer.

ObjectivePatients with cancer pain are highly dependent on morphine analgesia, but studies have shown a negative correlation between morphine demand and patient outcomes. The long-term use of morphine may result in abnormally elevated serum morphine-3-glucuronide (M3G) levels. Hence, the effects of M3G on tumor progression are worth studying.MethodsThe effects of M3G on PD-L1 expressions in human non-small cell lung cancer (NSCLC) cell lines were first evaluated. Activation of TLR4 downstream pathways after M3G treatment was then determined by Western blot. The effects of M3G on human cytotoxi

Совпадение в полном тексте источника
… Figure 1 Expression of toll-like receptor 4 (TLR4) and (GPCR)-mu opioid receptor (MOR) in human lung cancer cell lines. (A) Representative images of immunohistochemcial staining (40×) of TLR4 and MOR in human adenocarcinoma (ADC) and squamous cell carcinoma (SCC) tumor tissues. … Due MR Piekarz AD Wilson N Feldman P Ripsch MS Chavez S Neuroexcitatory effects of morphine-3-glucuronide are dependent on toll-like receptor 4 signaling J Neuroinflammation 2012 9 200 22898544 10.1186/1742-2094-9-200 PMC3519737 14. …

Preclinical Evaluation of a Lentiviral Vector for Huntingtin Silencing.

Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder resulting from a polyglutamine expansion in the huntingtin (HTT) protein. There is currently no cure for this disease, but recent studies suggest that RNAi to downregulate the expression of both normal and mutant HTT is a promising therapeutic approach. We previously developed a small hairpin RNA (shRNA), vectorized in an HIV-1-derived lentiviral vector (LV), that reduced pathology in an HD rodent model. Here, we modified this vector for preclinical development by using a tat-independent third-generation LV (pCCL) ba

The progression of HMGB1-induced autophagy in cancer biology.

Autophagy is an important process of cellular degradation and has been proven to contribute to tumorigenesis. High-mobility group box 1 (HMGB1) is an abundant nonhistone protein that has been widely reported to play a central role in the induction of autophagy. In nucleus, HMGB1 upregulates the expression of HSP27 to induce autophagy. In cytoplasm, the Beclin-1/PI3K-III complex can be activated by HMGB1 to promote autophagy. Extracellular HMGB1 binds to the receptor for advanced glycation end products to induce autophagy. Recent studies have shown that HMGB1-induced autophagy exerts multiple f

Совпадение в полном тексте источника
… HMG-B box has also been identified as a functional zone identifiable by toll-like receptor 4 (TLR-4). 21 In addition, the A box could compete with the B box since it contains a site antagonistic to the B box. 22 The C-terminal tail contains a number of glutamic and aspartic acid residues, whereas the …

Hepatocellular Carcinoma: Old and Emerging Therapeutic Targets.

Liver cancer, predominantly hepatocellular carcinoma (HCC), globally ranks sixth in incidence and third in cancer-related deaths. HCC risk factors include non-viral hepatitis, alcohol abuse, environmental exposures, and genetic factors. No specific genetic alterations are unequivocally linked to HCC tumorigenesis. Current standard therapies include surgical options, systemic chemotherapy, and kinase inhibitors, like sorafenib and regorafenib. Immunotherapy, targeting immune checkpoints, represents a promising avenue. FDA-approved checkpoint inhibitors, such as atezolizumab and pembrolizumab, s

The Rising Era of Immune Checkpoint Inhibitors in Myelodysplastic Syndromes.

Myelodysplastic syndromes (MDS) are a heterogeneous group of diseases characterized by ineffective hematopoiesis and a wide spectrum of manifestations ranging from indolent and asymptomatic cytopenias to acute myeloid leukemia (AML). MDS result from genetic and epigenetic derangements in clonal cells and their surrounding microenvironments. Studies have shown associations between MDS and other autoimmune diseases. Several immune mechanisms have been identified in MDS, suggesting that immune dysregulation might be at least partially implicated in its pathogenesis. This has led to rigorous inves

Pilot study of lithium to restore intestinal barrier function in severe graft-versus-host disease.

UNLABELLED: Severe intestinal graft-vs-host disease (GVHD) after allogeneic hematopoietic cell transplantation (HCT) causes mucosal ulceration and induces innate and adaptive immune responses that amplify and perpetuate GVHD and the associated barrier dysfunction. Pharmacological agents to target mucosal barrier dysfunction in GVHD are needed. We hypothesized that induction of Wnt signaling by lithium, an inhibitor of glycogen synthase kinase (GSK3), would potentiate intestinal crypt proliferation and mucosal repair and that inhibition of GSK3 in inflammatory cells would attenuate the deregula

NDP52 и его новая роль в патогенезе.

Автофагика - это процесс, способствующий выживанию, который регулирует деградацию и обновление клеточных компонентов, что делает его важнейшим механизмом для клеточного гомеостазиза. Существуют выборочные формы автофагии, характерные для ряда субстратов, таких, как патогены (бактерии или вирусы), белковые агрегаты или излишние/поврежденные органеллы. Эти процессы включают в себя в качестве ключевых игроков автофагичные рецепторы, которые связывают груз, подлежащий деградации, с автофагическим оборудованием. Среди них NDP52 (известный также как КАКПО2) был охарактеризован как «бридж» между авто

Systemic Sclerosis Associated Interstitial Lung Disease: New Directions in Disease Management.

A subgroup of patients with systemic sclerosis (SSc) develop interstitial lung disease (ILD), characterized by inflammation and progressive scarring of the lungs that can lead to respiratory failure. Although ILD remains the major cause of death in these individuals, there is no consensus statement regarding the classification and characterization of SSc-related ILD (SSc-ILD). Recent clinical trials address the treatment of SSc-ILD and the results may lead to new disease-altering therapies. In this review, we provide an update to the diagnosis, management and treatment of SSc-ILD.

Совпадение в полном тексте источника
… Toll-like receptor 4 signaling augments transforming growth factor-beta responses: a novel mechanism for maintaining and amplifying fibrosis in scleroderma . Am J Pathol. ( 2013 ) 182 : 192 – 205 . 10.1016/j.ajpath.2012.09.007 23141927 PMC3538029 12. Al-Sheikh H Ahmad Z Johnson SR . … Toll-like receptor-4 signaling drives persistent fibroblast activation and prevents fibrosis resolution in scleroderma . Adv Wound Care . ( 2017 ) 6 : 356 – 69 . 10.1089/wound.2017.0732 29062592 PMC5649394 17. Kang H . Role of microRNAs in TGF-β signaling pathway-mediated pulmonary fibrosis . …

Targeting dorsal root ganglia for chemotherapy-induced peripheral neuropathy: from bench to bedside.

Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating condition affecting an increasing number of cancer survivors worldwide. However, insights into its pathophysiology and availability of effective therapies remain lacking. Dorsal root ganglia (DRG) have been studied as a key component of chemotherapeutic drug toxicity and a potential therapeutic target for CIPN treatment. This comprehensive review aims to synthesize, summarize, and correlate the results of both preclinical and clinical studies relevant to the pathophysiology and management of CIPN in relation to the DRG. Design

Совпадение в полном тексте источника
… ROS, reactive oxygen species; TLR4, Toll-like receptor 4; TNF-α, tumor necrosis factor alpha. … Dorsal root ganglion toll-like receptor 4 signaling contributes to oxaliplatin-induced peripheral neuropathy. Pain 2022; 163: 923–935. 97. Gu H, Wang C, Li J, et al. …

Выборочное ингибирование TLR2 стимулирует созревание олигодендроглиевых клеток потомства до олигодендроцитов.

Важно описать новые технологии для преодоления барьера и поощрения ремиелионации, поскольку многие аксоны остаются демиелиномированными в CNS пациентов с множественным склерозом (MS). Недавние исследования показывают, что LR2 является негативным регулятором созревания олигодендроглиевых клеток потомства (OPC) до олигодендроцитов (OLs) и что TLR2 присутствует в хронических повреждениях MS человека. Однако до недавнего времени не существовало конкретного ингибитора TLR2. Поэтому мы создали пептид, соответствующий TLR2-interacting Домена MyD88 (TIDM), которая конкретно препятствует TLR2, но не др