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Sudanese Journal of Paediatrics 2024Multisystem inflammatory syndrome of childhood (MIS-C) is a recently described entity in pediatrics post-COVID-19 pandemic. Hemophagocytic lymphohistiocytosis (HLH) is a...
Multisystem inflammatory syndrome of childhood (MIS-C) is a recently described entity in pediatrics post-COVID-19 pandemic. Hemophagocytic lymphohistiocytosis (HLH) is a clinical syndrome caused by an unregulated proliferation of macrophages as well as T lymphocytes. Both entities can be considered overlapping, although distinct criteria for each can be found in the literature. Herein, we report a patient with MIS-C post-COVID-19 infection, complicated with HLH secondary to malaria from a blood transfusion.
PubMed: 38952618
DOI: 10.24911/SJP.106-1679595787 -
Frontiers in Oncology 2024Levels of the Wnt pathway components are abnormally altered in gastric cancer cells, leading to malignant cell proliferation, invasion and metastasis, poor prognosis and... (Review)
Review
Levels of the Wnt pathway components are abnormally altered in gastric cancer cells, leading to malignant cell proliferation, invasion and metastasis, poor prognosis and chemoresistance. Therefore, it is important to understand the mechanism of Wnt signaling pathway in gastric cancer. We systematically reviewed the molecular mechanisms of the Wnt pathway in gastric cancer development; and summarize the progression and the challenges of research on molecular agents of the Wnt pathway.
PubMed: 38952556
DOI: 10.3389/fonc.2024.1410513 -
Frontiers in Oncology 2024Erythropoietin-producing human hepatocellular (Eph) receptors stand out as the most expansive group of receptor tyrosine kinases (RTKs). Accumulating evidence suggests...
BACKGROUND
Erythropoietin-producing human hepatocellular (Eph) receptors stand out as the most expansive group of receptor tyrosine kinases (RTKs). Accumulating evidence suggests that within this expansive family, the EphA subset is implicated in driving cancer cell progression, proliferation, invasion, and metastasis, making it a promising target for anticancer treatment. Nonetheless, the extent of EphA family involvement across diverse cancers, along with its intricate interplay with immunity and the tumor microenvironment (TME), remains to be fully illuminated.
METHODS
The relationships between EphA gene expression and patient survival, immunological subtypes, and TME characteristics were investigated based on The Cancer Genome Atlas (TCGA) database. The analyses employed various R packages.
RESULTS
A significant difference in expression was identified for most EphA genes when comparing cancer tissues and non-cancer tissues. These genes independently functioned as prognostic factors spanning multiple cancer types. Moreover, a significant correlation surfaced between EphA gene expression and immune subtypes, except for EphA5, EphA6, and EphA8. EphA3 independently influenced the prognosis of papillary renal cell carcinoma (KIRP). This particular gene exhibited links with immune infiltration subtypes and clinicopathologic parameters, holding promise as a valuable biomarker for predicting prognosis and responsiveness to immunotherapy in patients with KIRP.
CONCLUSION
By meticulously scrutinizing the panorama of EphA genes in a spectrum of cancers, this study supplemented a complete map of the effect of EphA family in Pan-cancer and suggested that EphA family may be a potential target for cancer therapy.
PubMed: 38952552
DOI: 10.3389/fonc.2024.1378087 -
Frontiers in Oncology 2024B7-H3 (CD276), an immune checkpoint molecule, is overexpressed in various types of cancer and their tumor vasculature, demonstrating significant associations with... (Review)
Review
B7-H3 (CD276), an immune checkpoint molecule, is overexpressed in various types of cancer and their tumor vasculature, demonstrating significant associations with adverse clinical outcomes. In addition to its well-known immune functions, B7-H3 exhibits dual co-stimulatory/co-inhibitory roles in normal physiology and the tumor microenvironment. The non-immune functions of B7-H3 in tumor cells and the tumor vasculature, including promoting tumor cell anti-apoptosis, proliferation, invasion, migration, drug resistance, radioresistance, as well as affecting cellular metabolism and angiogenesis, have increasingly gained attention from researchers. Particularly, the co-expression of B7-H3 in both tumor cells and tumor endothelial cells highlights the higher potential and clinical utility of therapeutic strategies targeting B7-H3. This review aims to summarize the recent advances in understanding the non-immune functions of B7-H3 in tumors and provide insights into therapeutic approaches targeting B7-H3, focusing on its co-expression in tumor cells and endothelial cells. The aim is to establish a theoretical foundation and practical reference for the development and optimization of B7-H3-targeted therapies.
PubMed: 38952550
DOI: 10.3389/fonc.2024.1408051 -
Frontiers in Oncology 2024The substantial heterogeneity exhibited by head and neck cancer (HNC), encompassing diverse cellular origins, anatomical locations, and etiological contributors,... (Review)
Review
The substantial heterogeneity exhibited by head and neck cancer (HNC), encompassing diverse cellular origins, anatomical locations, and etiological contributors, combined with the prevalent late-stage diagnosis, poses significant challenges for clinical management. Genomic sequencing endeavors have revealed extensive alterations in key signaling pathways that regulate cellular proliferation and survival. Initiatives to engineer therapies targeting these dysregulated pathways are underway, with several candidate molecules progressing to clinical evaluation phases, including FDA approval for agents like the EGFR-targeting monoclonal antibody cetuximab for K-RAS wild-type, EGFR-mutant HNSCC treatment. Non-coding RNAs (ncRNAs), owing to their enhanced stability in biological fluids and their important roles in intracellular and intercellular signaling within HNC contexts, are now recognized as potent biomarkers for disease management, catalyzing further refined diagnostic and therapeutic strategies, edging closer to the personalized medicine desideratum. Enhanced comprehension of the genomic and immunological landscapes characteristic of HNC is anticipated to facilitate a more rigorous assessment of targeted therapies benefits and limitations, optimize their clinical deployment, and foster innovative advancements in treatment approaches. This review presents an update on the molecular mechanisms and mutational spectrum of HNC driving the oncogenesis of head and neck malignancies and explores their implications for advancing diagnostic methodologies and precision therapeutics.
PubMed: 38952548
DOI: 10.3389/fonc.2024.1373821 -
Molecular Imaging 2024To investigate the performance of diffusion-tensor imaging (DTI) and hydrogen proton magnetic resonance spectroscopy (H-MRS) parameters in predicting the...
OBJECTIVE
To investigate the performance of diffusion-tensor imaging (DTI) and hydrogen proton magnetic resonance spectroscopy (H-MRS) parameters in predicting the immunohistochemistry (IHC) biomarkers of glioma.
METHODS
Patients with glioma confirmed by pathology from March 2015 to September 2019 were analyzed, the preoperative DTI and H-MRS images were collected, apparent diffusion coefficient (ADC) and fractional anisotropy (FA), in the lesion area were measured, the relative values relative ADC (rADC) and relative FA (rFA) were obtained by the ratio of them in the lesion area to the contralateral normal area. The peak of each metabolite in the lesion area of H-MRS image: N-acetylaspartate (NAA), choline (Cho), and creatine (Cr), and metabolite ratio: NAA/Cho, NAA/(Cho + Cr) were selected and calculated. The preoperative IHC data were collected including CD34, Ki-67, p53, S-100, syn, vimentin, NeuN, Nestin, and glial fibrillary acidic protein.
RESULTS
One predicting parameter of DTI was screened, the rADC of the Ki-67 positive group was lower than that of the negative group. Two parameters of H-MRS were found to have significant reference values for glioma grades, the NAA and Cr decreased as the grade of glioma increased, moreover, Ki-67 Li was negatively correlated with NAA and Cr.
CONCLUSION
NAA and Cr have potential application value in predicting glioma grades and tumor proliferation activity. Only rADC has predictive value for Ki-67 expression among DTI parameters.
Topics: Humans; Glioma; Male; Female; Middle Aged; Adult; Immunohistochemistry; Brain Neoplasms; Diffusion Tensor Imaging; Magnetic Resonance Imaging; Aged; Proton Magnetic Resonance Spectroscopy; Young Adult
PubMed: 38952400
DOI: 10.1177/15353508241261583 -
Heliyon Jun 2024To obtain insight into the molecular process implicated in venous malformations (VMs) and identify potential targets for treatment of VMs, this study profiled the gene...
OBJECTIVE
To obtain insight into the molecular process implicated in venous malformations (VMs) and identify potential targets for treatment of VMs, this study profiled the gene expression pattern in VMs, investigated alterations of syndecan-1 (SDC1) expression in VMs, and tested the hypothesis that aberrant SDC1 expression triggers abnormal angiogenesis and VM development.
METHODS
Microarray analysis was performed to identify differentially expressed genes (DEGs) on a transcriptome-wide level in VMs and conjunctive normal. Gene Ontology molecular functional analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis were carried out to establish enhancement of biological signaling pathways involved in VMs. Among the DEGs, we focused on SDC1, which is involved in matrix remodeling, cell proliferation and invasion, and angiogenesis. SDC1 expression in VMs was verified by qRT-PCR, western blotting, and immunohistochemistry. Loss-of-function of SDC1 was achieved in human umbilical vein endothelial cells (HUVECs) by siRNA to investigate the roles of SDC1 in cell migration, invasion, and angiogenesis.
RESULTS
Compared with control tissue, the transcriptome study identified 274 upregulated DEGs and 3 downregulated DEGs. The transcript and protein levels of SDC1 were significantly decreased in VMs compared with normal tissue. Inhibition of SDC1 enhanced HUVEC migration, invasion, and angiogenesis.
CONCLUSION
Our genome-wide microarray analysis suggests the involvement of numerous genes in VMs. Among them, SDC1 plays a substantial role in the process of angiogenesis and development of VMs. SDC1 may represent a potential target for a molecular therapy for VMs.
PubMed: 38952376
DOI: 10.1016/j.heliyon.2024.e32690 -
Heliyon Jun 2024DIP2B is related to cancer progression. This study investigated the roles and pathways of DIP2B in lung adenocarcinoma (LUAD).
Downregulation of DIP2B as a prognostic marker inhibited cancer proliferation and migration and was associated with immune infiltration in lung adenocarcinoma via CCND1 and MMP2.
BACKGROUND
DIP2B is related to cancer progression. This study investigated the roles and pathways of DIP2B in lung adenocarcinoma (LUAD).
METHODS
DIP2B expression and the relationship between survival time of cancer patients and DIP2B expression were analyzed. The relationship between DIP2B expression and survival time in LUAD patients was evaluated by a meta-analysis. Cox and survival analyses were used to evaluate the prognostic factors and construct a prognostic nomogram. The mechanisms and effects of DIP2B and the relationship between DIP2B expression and the immune microenvironment were investigated using bioinformatics, CCK-8, western blotting, and transwell experiments.
RESULTS
DIP2B was overexpressed in LUAD tissues. DIP2B overexpression was associated with shorter prognosis and was an unfavorable risk factor for prognosis in LUAD patients. DIP2B co-expressed genes were involved in cell division, DNA repair, cell cycle, and others. Inhibition of DIP2B expression could downregulate the proliferation, migration, and invasion of LUAD A549 and H1299 cells, which was related to the decrease in CCND1 and MMP2 protein expression. BRCA1 overexpression was associated with short prognosis, and the nomogram formed by DIP2B and BRCA1 was associated with a poor prognosis in LUAD patients. DIP2B expression correlated with immune cells (such as CD8 T cells, Tcm, and iDCs) and cell markers.
CONCLUSION
DIP2B is a potential biomarker of poor prognosis and the immune microenvironment in LUAD. Inhibition of DIP2B expression downregulated cancer cell proliferation, migration, and invasion, which might be related to the decrease in CCND1 and MMP2 protein expression. DIP2B-related nomograms might be useful tools for predicting the prognosis of LUAD patients.
PubMed: 38952374
DOI: 10.1016/j.heliyon.2024.e32025 -
Effects of oxidized LDL versus IL-1ß/TNF-ɑ/INFɣ on human gingival mesenchymal stem cells properties.Journal of Periodontal Research Jul 2024Oxidized low-density lipoprotein (oxLDL) is an important player in the course of metabolic inflammatory diseases. oxLDL was identified in the gingival crevicular fluid,...
AIMS
Oxidized low-density lipoprotein (oxLDL) is an important player in the course of metabolic inflammatory diseases. oxLDL was identified in the gingival crevicular fluid, denoting possible associations between oxLDL-induced inflammation and periodontal disease. The current investigation compared for the first-time direct effects of oxLDL to a cytokine cocktail of IL-1ß/TNF-ɑ/INF-γ on gingival mesenchymal stem cells' (G-MSCs) attributes.
METHODS
Human third passage G-MSCs, isolated from connective tissue biopsies (n = 5) and characterized, were stimulated in three groups over 7 days: control group, cytokine group (IL-1β[1 ng/mL], TNF-α[10 ng/mL], IFN-γ[100 ng/mL]), or oxLDL group (oxLDL [50 μg/mL]). Next Generation Sequencing and KEGG pathway enrichment analysis, stemness gene expression (NANOG/SOX2/OCT4A), cellular proliferation, colony-formation, multilinear potential, and altered intracellular pathways were investigated via histochemistry, next-generation sequencing, and RT-qPCR.
RESULTS
G-MSCs exhibited all mesenchymal stem cells' characteristics. oxLDL group and cytokine group displayed no disparities in their stemness markers (p > .05). Next-generation-sequencing revealed altered expression of the TXNIP gene in response to oxLDL treatment compared with controls (p = .04). Following an initial boosting for up to 5 days by inflammatory stimuli, over 14 day, cellular counts [median count ×10 (Q25/Q75)] were utmost in control - [2.6607 (2.0804/4.5357)], followed by cytokine - [0.0433 (0.0026/1.4215)] and significantly lowered in the oxLDL group [0.0274 (0.0023/0.7290); p = .0047]. Osteogenic differentiation [median relative Ca content(Q25/Q75)] was significantly lower in cytokine - [0.0066 (0.0052/0.0105)] compared to oxLDL - [0.0144 (0.0108/0.0216)] (p = .0133), with no differences notable for chondrogenic and adipogenic differentiation (p > .05).
CONCLUSIONS
Within the current investigation's limitations, in contrast to cytokine-mediated inflammation, G-MSCs appear to be minimally responsive to oxLDL-mediated metabolic inflammation, with little negative effect on their differentiation attributes and significantly reduced cellular proliferation.
PubMed: 38952262
DOI: 10.1111/jre.13319 -
European Journal of Translational... Jul 2024Azoospermia, or the complete absence of sperm in the ejaculate, affects about 1% of men worldwide and is a significant fertility challenge. This study investigates...
Azoospermia, or the complete absence of sperm in the ejaculate, affects about 1% of men worldwide and is a significant fertility challenge. This study investigates Linc00513, a long non-coding RNA, and its potential role in regulating the TGF-β signaling pathway, a key player in spermatogenesis, in the context of azoospermia. We show that Linc00513 expression is significantly lower in testicular tissues from azoospermic patients than in HS1 controls. Linc00513 interacts directly with microRNA-7 (miR-7) via complementary base pairing, acting as a competing endogenous RNA (ceRNA). This interaction effectively inhibits miR-7's inhibitory action on the TGF-β receptor 1 (TGFBR1), a critical component of the TGF-β signaling cascade. Downregulating Linc00513 reduces TGFBR1 repression and increases TGF-β signaling in azoospermic testes. Functional assays with spermatogonial cell lines support these findings. Silencing Linc00513 leads to increased cell proliferation and decreased apoptosis, similar to TGF-β inhibition. Overexpression of miR-7 inhibits the effects of Linc00513 on TGF-β signaling. Our study sheds new light on how Linc00513, miR-7, and the TGF-β signaling pathway interact in azoospermia. Linc00513 regulates TGFBR1 expression and thus influences spermatogonial cell fate by acting as a miR-7 ceRNA. These findings identify a potential therapeutic target for azoospermia treatment, paving the way for future research into restoring fertility in affected individuals.
PubMed: 38952199
DOI: 10.4081/ejtm.2024.12516