CD44 Expression Research Articles

Induction of a distinct macrophage population and protection from lung injury and fibrosis by Notch2 blockade.

Macrophages are pleiotropic and diverse cells that populate all tissues of the body. Besides tissue-specific resident macrophages such as alveolar macrophages, Kupffer cells, and microglia, multiple organs harbor at least two subtypes of other resident macrophages at steady state. During certain circumstances, like tissue insult, additional subtypes of macrophages are recruited to the tissue from the monocyte pool. Previously, a recruited macrophage population marked by expression of Spp1, Cd9, Gpnmb, Fabp5, and Trem2, has been described in several models of organ injury and cancer, and has been linked to fibrosis in mice and humans. Here, we show that Notch2 blockade, given systemically or locally, leads to an increase in this putative pro-fibrotic macrophage in the lung and that this macrophage state can only be adopted by monocytically derived cells and not resident alveolar macrophages. Using a bleomycin and COVID-19 model of lung injury and fibrosis, we find that the expansion of these macrophages before lung injury does not promote fibrosis but rather appears to ameliorate it. This suggests that these damage-associated macrophages are not, by themselves, drivers of fibrosis in the lung.

Histopathological characteristics of PRRS and expression profiles of viral receptors in the piglet immune system

Porcine reproductive and respiratory syndrome (PRRS) is a highly contagious viral disease that causes significant economic losses to the swine industry worldwide. PRRS virus (PRRSV) infection is a receptor-mediated endocytosis and replication process. The purpose of this study was to determine the localization and expression of four important PRRSV receptors in immunological organs of piglets. After piglets were infected with PRRSV, Hematoxylin and Eosin staining, immunofluorescence, and Western blot were used to perform histopathological examination and receptors distribution analysis. The results showed that PRRSV caused severe damage to the piglets’ immune organs, including atrophy of the thymus and swelling of lymph node. Histopathological lesions were mainly observed in the lung and lymph node and were characterized by interstitial pneumonia, collapsed follicles, exhaustion of germinal centers, and extensive hemorrhage. Immunofluorescence staining and Western blot results showed that the receptors of CD163 and NMHCII-A were mainly distributed in the thymus, hilar lymph nodes, and mesenteric lymph nodes. However, Sn and vimentin receptors were expressed at low levels in the immune organs of piglets. The distribution of the four receptors in the immune organs was more concentrated in the cortex but was more scattered in the medulla. Compared to the control group, the relative expression of the four receptors increased significantly in most immune organs after viral infection. In conclusion, our study examined the distribution and expression of four PRRSV receptors in immunological organs. We observed a significant increase in the expression of Sn, CD163, and vimentin following viral infection. These findings may provide potential targets for future antiviral reagent design or vaccine development.

Enhanced Macrophages Engulfment by Peptide‐Templated Nanoassemblies Targeting SIRPα and Suppressing Oxidative Stress for Atherosclerosis Pro‐Efferocytotic Therapy

AbstractPrompt removal of apoptotic cells via macrophage‐mediated efferocytosis is an emerging approach for atherosclerosis treatment, because these diseased cells directly contribute to vascular inflammation and secondary necrosis in plaques. Despite blocking CD47 can restore impaired efferocytosis by inhibiting “don't eat me” signals, the currently available CD47 antibody (CD47‐Ab)‐based therapy may accelerate off‐target clearance of healthy cells due to the ubiquitous expression of CD47 on viable cells. Here, a peptide‐templated nanoassembly (PTna‐1) engineered to induce synergistic enhancement of engulfment by macrophages is reported. Through self‐assembled polypeptides with multiple functional motifs, the nanoassembly can specifically target p32‐overexpressing macrophages and bind to the Ig‐V‐like domain of SIRPα but not to CD47, thereby normalizing intraplaque efferocytosis and alleviating persistent inflammation. Concurrently, disassembled PTna‐1 released manganese porphyrins with photoacoustic/magnetic resonance imaging capability to suppress oxidative stress and synergistically enhance macrophage phagocytosis through the RhoA/ROCK1 pathway. Compared with CD47‐Abs, PTna‐1 promoted a more significant reduction in lesion area and plaque stabilization without affecting the incidence of anemia in atherosclerotic mice. Proteomic analysis revealed that PTna‐1 treatment decreased the expression of inflammation‐related proteins in plaques. Overall, these peptide‐driven nanoassemblies employing a SIRPα‐specific blockade strategy provide a distinct paradigm of pro‐efferocytotic therapy for atherosclerosis.

Study on the mechanism of OSM participating in myocardial fibrosis by inhibiting TGFβ-induced EndMT of cardiac microvascular endothelial cells through SPARC/SMAD signaling.

Cardiac fibrosis constitutes a crucial element in the progression of diverse chronic cardiac conditions. Notably, a significant correlation has been observed between the endothelial-to-mesenchymal transition (EndMT) and the emergence of cardiac fibrosis. To investigate mechanisms, we employed immunofluorescence for α-SMA and CD31 analysis, Western blotting for CD34, vimentin, and SPARC overexpression. CCK8, wound healing, and transwell assay-assessed cell viability, invasion, and migration. SPARC overexpression plasmid was constructed and validated by Western blotting. Fibrosis levels were quantified via Masson staining, and collagen 1 and 3 expressions were measured using ELISA assays. Notably, in TGF-β-induced H5V cells, the downregulation of CD31 and CD34 expression, along with the upregulation of α-SMA and vimentin, suggests the induction of EndMT in cardiac fibrosis. Interestingly, OSM treatment mitigated EndMT progression, cell invasion, migration, and the expression of p-SMAD2, p-SMAD3, and SPARC in TGF-β-treated H5V cells. Further analysis revealed that OSM alleviated TGFβ-induced EndMT, invasion, and migration of cardiac microvascular endothelial cells by suppressing SPARC/SMAD signaling. Moreover, OSM therapy notably mitigated myocardial tissue fibrosis, along with a reduction in the expression of collagen 1, collagen 3, α-SMA, and CD34, while augmenting CD31 and vimentin expression in ISO-induced myocardial tissue. Additionally, OSM exhibited the ability to suppress myocardial tissue fibrosis and the expression of EndMT markers as well as SPARC/SMAD signals in ISO-induced myocardial tissue. Our comprehensive analysis unveiled that OSM contributes significantly to myocardial fibrosis modulation by inhibiting TGFβ-mediated EndMT in myocardial microvascular endothelial cells via SPARC/SMAD signaling.

Wound healing after surgical therapy for multiple myeloma: a case-control study.

The aim of this study was to observe the surgical wound healing process in patients with multiple myeloma who had undergone surgery. We collected clinical data on patients with multiple myeloma and observed wound healing following surgical therapy. Additionally, we compared the expression of angiogenesis markers in patients with and without multiple myeloma (undergoing surgical excision of other tumour tissues). In patients who had multiple myeloma bone disease, we examined several clinical features: haemoglobin levels; albumin levels; blood glucose levels; and surgery programme. We then compared expression levels of the angiogenesis markers CD31, CD34 and vascular endothelial growth factor (VEGF) in samples scraped from the skin margin of the surgical incision in 12 patients without multiple myeloma (control) and nine patients with multiple myeloma. All 61 patients with multiple myeloma observed showed no disunion, no delayed union and no infection in their wound healing. CD31 and VEGF expression was higher in the nine patients with multiple myeloma compared with the 12 control patients without. We observed no difference in CD34 expression between control and experimental groups. The results of this study suggest that patients with multiple myeloma who have undergone surgery recover well and produce higher quantities of new vessels compared with patients without multiple myeloma. This occurs through increased expression of CD31 and VEGF, angiogenic factors which promote wound healing. We did not observe higher expression of these factors contributing to increased incisional implantation metastasis.

Synthesis and preclinical evaluation of [18F]AlF-NODA-MP-C6-CTHRSSVVC as a PET tracer for CD163-positive tumor-infiltrating macrophages

Positron emission tomography (PET) can provide information about tumor-associated macrophage (TAM) infiltration, as long as a suitable tracer is available. This study aimed to evaluate the radiolabeled peptide [18F]AlF-NODA-MP-C6-CTHRSSVVC as a potential PET tracer for imaging of the CD163 receptor, which is expressed on M2-type tumor-associated macrophages. The conjugated peptide NODA-MP-C6-CTHRSSVVC was labeled with aluminum [18F]fluoride. Tracer binding and its biodistribution were evaluated in an in vitro binding assay and in healthy BALB/c mice, respectively. In addition, different treatments with cyclophosphamide in tumor-bearing mice were used to assess whether the tracer could detect differences in CD163 expression caused by differential TAM infiltration. After 7 days of treatment, animals were injected with [18F]AlF-NODA-MP-C6-CTHRSSVVC, and a 60-min dynamic PET scan was performed, followed by an ex vivo biodistribution study. [18F]AlF-NODA-MP-C6-CTHRSSVVC was prepared in 23 ± 6 % radiochemical yield and showed approximately 50 % of specific receptor-mediated binding in an in vitro binding assay on human CD163-expressing tissue homogenates. No CD163-mediated binding of [18F]AlF-NODA-MP-C6-CTHRSSVVC was detected by PET under normal physiological conditions in healthy BALB/c mice. On the other hand, CD163-positive xenograft tumors were clearly visualized with PET and a positive correlation was found between CD163 levels and the [18F]AlF-NODA-MP-C6-CTHRSSVVC tumor-to-muscle ratio (TMR) obtained from the PET images (Pearson r = 0.76, p = 0.002). No significant differences in the CD163 protein level and in the tracer uptake between treatment groups were found in the tumors. Taken together, [18F]AlF-NODA-MP-C6-CTHRSSVVC appears a promising candidate PET tracer for M2-type TAM, as it binds specifically to CD163 in vitro and its tumor uptake correlates well with CD163 expression in vivo.

BMSCs-derived exosomes carrying miR-668-3p promote progression of osteoblasts in osteonecrosis of the femoral head: Expression of proteins CD63 and CD9

Recently, exosomes that are derived from bone marrow mesenchymal stem cells (BMSCs) have garnered considerable interest due to their significant roles in the processes of bone regeneration and repair. Among the various molecular components present within these exosomes, miR-668-3p has emerged as a pivotal microRNA that may be instrumental in modulating the function and proliferation of osteoblasts, the cells responsible for bone formation. The primary objective of this research was to examine the enhancing effects of BMSC-derived exosomes that are enriched with miR-668-3p on the advancement of osteoblasts in the context of osteonecrosis of the femoral head. Furthermore, the study aimed to analyze how the expression of specific exosomal proteins, namely CD63 and CD9, influences this biological process. To conduct the investigation, BMSCs were isolated from healthy rat models, followed by the extraction of their secreted exosomes. The subsequent phase of the study involved assessing the proliferation and differentiation of osteoblasts by introducing the exosomes enriched with miR-668-3p into an experimental setup representing osteonecrosis of the femoral head. The findings revealed that exosomes derived from BMSCs, which contained miR-668-3p, significantly enhanced the proliferation of osteoblasts as well as the expression of key osteogenic marker genes. Notably, the levels of CD63 and CD9 proteins were markedly increased in the treated groups, indicating that the mechanisms underlying this promotion might involve cell adhesion and the endocytic uptake of exosomes.

Expression of CD68 and CD163 in malignant epithelial cells of oral squamous cell carcinoma: phenotypic shift or mere cell fusion

Background / purposeThe progression of epithelial to mesenchymal tissue (EMT) is a highly intricate process that facilitates the transformation of cancer cells, allowing them to changeover their characteristic epithelial properties to mesenchymal attributes. This notable change empowers the cells with enhanced mobility and the ability to migrate to distant locations. Furthermore, it is imperative to adopt the idea of macrophage tumor cell fusion to achieve comprehensive considerate of this phenomenon. Our primary objective was to conduct a thorough investigation of macrophage-restricted antigens expression, specifically CD68 and CD163, in malignant epithelial cells of oral cavity squamous cell carcinoma (OSCC) to elucidate aforementioned perceptions. Materials and methodsCD68 and CD163 immunohistochemical expression were assessed in oral squamous cell carcinoma (OSCC), encompassing both the neoplastic cells and the tumor-associated macrophages (TAMs). ResultsBoth CD68 and CD163 antigens were revealed in OSCC malignant epithelial cells in a granular cell pattern, localized in membrane and cytoplasm of tumor cells respectively as well as in the infiltrating TAMs. ConclusionThe macrophage antigens were not limited to the infiltrating tumor-associated macrophages (TAMs), but were also observed in a substantial proportion of OSCC malignant epithelial cells within the tumor parenchyma. This particular expression pattern may represent a subset of tumor cells that have undergone an epithelial to a mesenchymal phenotypic transition. In addition, fusion of macrophages with tumor cells cannot be excluded; both might be associated with increased metastatic activity of OSCC.

CD47 and Calreticulin Expression in Breast Cancer Subtypes and Anti-CD47 Inhibitory Effects in Macrophage-mediated Phagocytosis.

Macrophage-mediated cancer immune evasion is modulated by the balance between "the cluster of differentiation 47 (CD47), an anti-phagocytic signal" and "calreticulin (CALR), a pro-phagocytic signal". CD47 is highly expressed in various types of cancer. However, the expression profiles of CD47 and CALR in breast cancer, especially in different hormone receptor subtypes, and the effects of CD47 blockade in macrophage-mediated therapy are not well understood. The expression levels of CD47 and CALR were investigated in breast cancer and adjacent normal tissues using immunohistochemistry. To study the effects of CD47 blockade therapy, CD47 and CALR expression in breast cancer cell lines were determined. In vitro macrophage-mediated phagocytosis of breast cancer upon treatment with a monoclonal CD47 antibody (B6H12) were performed. CD47 and CALR were overexpressed in breast cancer tissues and their up-regulation was associated with hormone receptor subtypes. Patients with Luminal A breast cancer had higher levels of CD47, while patients with triple-negative breast cancer (TNBC) had higher levels of CALR. The levels of CD47 and CALR were also elevated in breast cancer cell lines of Luminal A (MCF-7) and TNBC (MDA-MB-231) subtypes. Interestingly, the expression ratio of surface CD47/CALR was significantly higher in MCF-7. Moreover, in vitro phagocytosis assays revealed that blockage of CD47 enhanced macrophage-mediated activity in both cancer cells with dramatically higher degrees of phagocytosis in MCF-7. The expression profiles of CD47 and CALR in breast cancer subtypes and the benefit of CD47 blocking-based immunotherapy are herein provided.

A polysaccharide from Periplaneta americana promotes macrophage M2 polarization, exhibiting anti-inflammatory and wound-healing activities

A miscellaneous polysaccharide, PAP55–3-1, with a molecular weight of 23.03 kDa, was isolated from Periplaneta americana through extraction with dilute alkali solution, ethanol precipitation, and column chromatography purification. Structural analysis shows that PAP55–3-1 is mainly composed of five monosaccharides: galactosamine hydrochloride, glucosamine hydrochloride, galactose, glucose and mannose. Its main glycosidic bonds are: Manp-(1→, Galp-(1→, →3)-Galp-(1→, →3,6)-Manp-(1→, →2,6)-Manp-(1→, →6)-Manp-(1→, →4)-Galp-(1→, →6-Glcp-(1→, →6)-Galp-(1→, →2)-Manp-(1 →, →3,4)-Glcp-(1→, →3,6)-Galp-(1→. In vitro experiments demonstrated that PAP55–3-1 can effectively inhibit reactive oxygen species (ROS) and O2− production following H2O2−induction. After H2O2−induction, HIF-1α (hypoxia-inducible factor) was translocated in mitochondria PAP55–3-1 increased localization of HIF-1α was located on mitochondria to maintain the stability of mitochondrial function stability, thereby effectively inhibiting H2O2-induced mitochondrial oxidative damage. Additionally, PAP55–3-1 inhibited the M1 polarization of macrophages stimulated by H2O2 and promoted the phenotype polarization of macrophages from M1 to M2, displaying anti-inflammatory and pro-repair properties. In vivo experimental results indicated that PAP55–3-1 promoted wound healing in mice. Immunohistochemical experiments revealed a reduction in CD68 expression and increase in CD206 expression in both positive and the high-dose polysaccharide group control group. This further demonstrated that PAP55–3-1 promotes the phenotype polarization of macrophages from M1 to M2, exerting anti-inflammatory and wound-healing activities.

RNA sequencing comparing centenarian and middle-aged women lymphoblastoid cell lines identifies age-related dysregulated expression of genes encoding selenoproteins, heat shock proteins, CD99, and BID.

Women typically live longer than men, and constitute the majority of centenarians. We applied RNA-sequencing (RNA-seq) of blood-derived lymphoblastoid cell lines (LCLs) from women aged 60-80 years and centenarians (100-105 years), validated the RNA-seq findings by real-time PCR, and additionally measured the differentially expressed genes in LCLs from young women aged 20-35 years. Top RNA-seq genes with differential expression between the age groups included three selenoproteins (GPX1, SELENOW, SELENOH) and three heat shock proteins (HSPA6, HSPA1A, HSPA1B), with the highest expression in LCLs from young women, indicating that young women are better protected from oxidative stress. The expression of two additional genes, BID encoding BH3-interacting domain death agonist and CD99 encoding CD99 antigen, showed unique age dependence, with similar expression levels in young and centenarian women while exhibiting higher and lower expression levels, respectively, in LCLs from women aged 60-80 years compared with the two other age groups. This age-related differential expression of BID and CD99 suggests elevated inflammation susceptibility in middle-aged women compared with either young or centenarian women. Our findings, once validated with human peripheral blood mononuclear cells and further cell types, may lead to novel healthy aging diagnostics and therapeutics.

LncRNA ZNF649-AS1 promotes trastuzumab resistance and TAM-dependent PD-L1 expression in breast cancer by regulating EXOC7 alternative splicing

BackgroundTrastuzumab resistance is a serious clinical problem in the treatment of HER2-positive breast cancer (BC). The lncRNA ZNF649-AS1 was previously found to promote HER2-positive BC trastuzumab resistance. The study aims to explore the molecular mechanism of ZNF649-AS1 in HER2-positive BC trastuzumab resistance. MethodsTumor tissue and peripheral blood samples were collected from 20 HER2-positive BC patients with trastuzumab-resistant and non-resistant, respectively. Trastuzumab-resistant BC cell lines SKBR-3-TR and BT474-TR were established. RIP was employed to confirm the binding of ZNF649-AS1, PRPF8 and exocyst complex component 7 (EXOC7). RNA expression of EXOC7-L (Full length of EXOC7) and EXOC7-S (Spliceosome of EXOC7) were detected using agarose gel electrophoresis. Expressions of macrophage markers CD68+ CD206+ were measured by flow cytometry. ResultsZNF649-AS1 expression was upregulated in HER2-positive BC trastuzumab resistance. ZNF649-AS1 downregulation inhibited trastuzumab resistance in HER2-positive BC. ZNF649-AS1 regulated EXOC7 alternative splicing by binding with PRPF8. EXOC7-S knockdown suppressed trastuzumab resistance and TAM-dependent PD-L1 expression in HER2-positive BC. EXOC7-S overexpression abolished the effects of ZNF649-AS1 knockdown on trastuzumab resistance and TAM-dependent PD-L1 expression in HER2-positive BC. ConclusionZNF649-AS1 promoted trastuzumab resistance and TAM-dependent PD-L1 expression in HER2-positive BC via promoting alternative splicing of EXOC7 by PRPF8.

Downregulation of CTRP1 Reduces Radio-resistance in Glioblastoma Cells by Inhibiting the Expression of CD133 after X-ray and Carbon Ion Irradiation

Downregulation of CTRP1 Reduces Radio-resistance in Glioblastoma Cells by Inhibiting the Expression of CD133 after X-ray and Carbon Ion Irradiation

One-step construction of silver nanoparticles immersed hydrogels by triple-helix β-glucans and the application in infectious wound healing

Hydrogels composed of polysaccharides and silver nanoparticles (AgNPs) are widely recognized for their application in wound dressings, particularly for healing wounds prone to infection. Traditional methods for preparing AgNP-immersed hydrogels are often complex, costly, and may lead to sustained cytotoxicity. To address these challenges, we developed a biocompatible, one-step green reduction strategy to generate AgNPs within hydrogels using a triple-helix β-glucan (PCPA) derived from Poria cocos, a renowned Chinese traditional herb. PCPA serves as a reducing agent, converting silver ions into AgNPs while its triple-helix conformation prevents AgNP aggregation. The resulting hydrogel (PAg-G) is injectable and contains uniformly distributed AgNPs. PAg-G exhibits broad-spectrum antimicrobial activity and enhanced bioactivity. The in vivo studies on S.aureus-infected SD rats demonstrated that PAg-G accelerates wound healing within 12 days by down-regulating inflammatory factors such as IL-6 and TNF-α, and up-regulating VEGF and CD31 expression, promoting neovascularization in wound tissues. This innovative one-step construction of AgNP-immersed hydrogels offers a promising approach for the development of antimicrobial hydrogels, especially for treating bacterial-infected wounds.

CD34 and Ki-67 Immunoexpression in Periapical Granulomas: Implications for Angiogenesis and Cellular Proliferation

Background/Objectives: The main mechanism of the formation of granulation tissue is the progression of an infection from the tooth to the periapical bone. At this level, the immune system tries to localize and annihilate the microorganism’s injury. Ki-67 is a protein directly associated with the cell proliferation rate, while CD34 is a biomarker involved in angiogenesis, and studies suggest that they both have a positive correlation with the intensity of the local inflammatory infiltrate. This study will determine the immunoexpression of CD34 and Ki-67 in periapical granulomas and assess their impact on the growth and development of this tissue, as well as consider their roles in the proliferative process and aggressiveness of evolution. Methods: In the present study, 35 periapical granulomas obtained after a tooth extraction were included. The specimens were analyzed via histopathology and immunohistochemistry. Results: A positive reaction for the Ki-67 antibody was observed in 32 (86.5%) of the 35 periapical granuloma cases included in our study. We identified the overexpression of Ki-67 and CD34 and further calculated the Ki-67 index to evaluate and correlate the proliferation potential and angiogenesis with regard to the presence of an inflammatory infiltrate. Conclusions: These findings suggest that the persistence of an inflammatory environment directly influences Ki-67 and CD34 expression, sustaining the proliferative capacity of cells and abnormal angiogenesis. This study is the first to evaluate the presence of the CD34+ and Ki-67+ proliferating vessels in periapical granulomas.

The role of extracellular ATP in regulating the functional activity of cells

A search and analysis of scientific articles presented in the databases PubMed, ScienceDirect, Elsevier, eLibrary for 2000–2024 was carried out. The selection criterion was the presence in the articles of information on the concentration of extracellular ATP in normal and pathological tissues, the mechanisms of purinergic regulation of cell functioning, and the expression of CD73 and CD39 ectonucleotidases on cells, which regulate proinflammatory extracellular ATP catabolism to immunosuppressive adenosine. Modern data are presented on the role of extracellular ATP in the regulation of cell functioning under normal and pathological conditions, during inflammation and the formation of cellular and humoral immune responses, as well as on the study of the mechanisms of purinergic signaling from extracellular ATP in the development of targeted drugs for various diseases, including neoplasms, neurodegenerative and autoimmune pathologies.

MiR-126 accelerates renal injury induced by UUO via inhibition PI3K/ IRS-1/ FAK signaling induced M2 polarization and endocytosis in macrophages

To investigate the role and molecular mechanism of miR-126 in unilateral ureteral occlusion (UUO). We used bioinformatics to analyse miRNAs specifically expressed in UUO. The mouse model of UUO was established using RAW264.7 cells cultured in vitro and in vivo. The mice were divided into control group, miR-126-NC (negative control) group and miR-126-KD (knockdown) group. Then the relative expression of miR-126 was detected by quantitative reverse transcription-polymerase chain reaction (qRT-PCR), the renal fibrosis was detected by Masson staining, and the protein expression of CD68, collagen I and collagen III in the kidney was detected by immunofluorescence assay. Immunohistochemistry detects α-SMA expression. Moreover, Western blotting was performed to measure the expressions of p-PI3K, CD163, CD206, CD86, iNOS, IL-1β, p-FAK, p-Rac-1, p-IRS-1 and MMP9. The relative fluorescence intensity of F-actin and p-FAK was detected by immunofluorescence assay, and the phagocytosis ability of macrophages was determined by phagocytosis assay with fluorescent microspheres. Bioinformatics analysis reveals miR-126-specific overexpression in UUO. Successful transfection of miR-126-NC and miR-126-KD was confirmed by RT-PCR. The selective reduction of miR-126 was validated by Masson, immunohistochemistry and immunofluorescence staining to decrease the area of UUO-induced renal fibrosis and to lower the expression of CD68, α-SMA, collagen I, and collagen III. The reduction of iNOS expression may also be achieved with selective knockdown of miR-126, as verified by cell tests. enhances the phagocytic ability of macrophages and the expression of p-PI3K, CD206, p-FAK, F-actin, p-Rac-1, p-IRS-1 and MMP9. MiR-126 can inhibit the PI3K signaling pathway, promote M1 macrophage polarization, and suppress the activation of FAK and Rac-1, thus accelerating the progression of UUO.

Exploring the clinicopathological characteristics of submucosal tumor-like esophageal squamous cell carcinoma and the diagnostic significance of endoscopic ultrasound: a comprehensive analysis.

Completely intramural growth submucosal squamous cell carcinoma of the esophagus, also known as SMT-like esophageal squamous cell carcinoma (ESCC), represents a rare and distinct form of esophageal cancer. Its white light endoscopic manifestations resemble those of esophageal subepithelial lesions, and biopsy pathology is often negative, leading to potential oversight or misdiagnosis. This study aimed to comprehensively summarize the clinicopathological and endoscopic ultrasound (EUS) characteristics of patients with SMT-like ESCC while also evaluating the immunohistochemical expression of these patient. This study collected clinical data, including demographic and clinicopathological data, as well as EUS findings, from six patients with SMT-like ESCC. Immunohistochemical analysis was also conducted on tumor tissues to assess the expression of CK7, CK19, CK20, TTF-1, SMA, S-100, Melan-A, CD117, Mucin (MUC) 2, and MUC5. In EUS, SMT-like ESCC is characterized by nonuniform hypoechoic lesions with indistinct borders, often exhibiting a burr or serrated appearance. Most of these lesions involved multiple levels. Cytological specimens obtained through EUS-guided fine needle aspiration (EUS-FNA) revealed suspected squamous cell carcinoma with positive expression of CK5/6, P40, and P63, further confirming the diagnosis of ESCC. Additionally, four patients exhibited CK7+/CK20- immune-expression profiles, and all patients had positive CK19 expression. TTF-1, SMA, S-100, Melan-A, CD117, MUC2, and MUC5 were negative. Combining EUS with EUS-FNA is a valuable approach for diagnosing and differentiating SMT-like ESCC. Furthermore, the characteristic CK7+/CK20- immune profile suggested a potential origin from the esophageal submucosa glands.

Zuogui Wan modulates macrophage polarization and promotes osteogenic differentiation through regulation of CD51-positive bone marrow mesenchymal stem cells

Background Zuogui Wan (ZGW) is a traditional herbal formula used to treat chronic kidney and bone diseases. Previous research has shown that ZGW slows down the aging process of bone marrow mesenchymal stem cells (BMSCs) and improves bone metabolism. However, its role in treating postmenopausal osteoporosis (PMOP) has not yet been fully investigated. Therefore, we investigated the therapeutic effects of ZGW and its potential mechanisms in an ovariectomy (OVX)-induced osteoporosis rat model. Results We observed significant improvements in bone loss and the osteoporotic phenotype in OVX rats treated with ZGW. These findings were confirmed with micro-computed tomography (micro-CT) and histomorphological analysis. We also discovered that ZGW reversed the macrophage imbalance, which in turn inhibited osteoclast differentiation and bone resorption. Furthermore, RNA-Seq results revealed the active expression of CD51 in BMSCs before and after ZGW therapy, which is associated with macrophage polarization and osteoblastic differentiation. The results also showed that ZGW decreased CD51 + BMSCs levels, which is closely related to the inhibition of osteoblast differentiation and promotion of osteoclast resorption. Conclusions Our study demonstrated that ZGW may improve postmenopausal osteoporosis by restoring macrophage polarization and down-regulating CD51 + BMSCs. In addition, ZGW promoted osteoblast formation and inhibited osteoclast resorption.

Integrated multi-level omics profiling of disulfidptosis identifis SPAG4 as an innovative immunotherapeutic target in glioblastoma

ObjectiveTo investigate the association between disulfidptosis-related genes (DFRGs) and patient prognosis, while concurrently identifying potential therapeutic targets in glioblastoma (GBM).MethodsWe retrieved RNA sequencing data and clinical characteristics of GBM patients from the TCGA database. We found there was a total of 6 distinct clusters in GBM, which was identified by the t-SNE and UMAP dimension reduction analysis. Prognostically significant genes in GBM were identified using the limma package, coupled with univariate Cox regression analysis. Machine learning algorithms were then applied to identify central genes. The CIBERSORT algorithm was utilized to assess the immunological landscape across different GBM subtypes. In vitro and in vivo experiments were conducted to investigate the role of SPAG4 in regulating the proliferation, invasion of GBM, and its effects within the immune microenvironment.Results23 genes, termed DFRGs, were successfully identified, demonstrating substantial potential for establishing a prognostic model for GBM. Single cell analysis revealed a significant correlation between DFRGs and the progression of GBM. Utilizing individual risk scores derived from this model enabled the stratification of patients into two distinct risk groups, revealing significant variations in immune infiltration patterns and responses to immunotherapy. Utilizing the random survival forests algorithm, SPAG4 was identified as the gene with the highest prognostic significance within our model. In vitro studies have elucidated SPAG4’s significant role in GBM pathogenesis, potentially through the regulation of fatty acid metabolism pathways. Our in vivo investigations using a subcutaneous xenograft model have confirmed SPAG4’s influence on tumor growth and its capacity to modulate the immune microenvironment. Advanced research hints that SPAG4 might achieve immune evasion by increasing CD47 expression, consequently reducing phagocytosis.ConclusionsThese findings highlight SPAG4 as a potential GBM therapeutic target and emphasize the complexity of the immune microenvironment in GBM progression.