Matrix stiffness drives drop like nuclear deformation and lamin A/C tension-dependent YAP nuclear localization.

Extracellular matrix (ECM) stiffness influences cancer cell fate by altering gene expression. Previous studies suggest that stiffness-induced nuclear deformation may regulate gene expression through YAP nuclear localization. We investigated the role of the nuclear lamina in this process.

Modern surgical strategies in pediatric neuroblastoma: Evolving approaches and treatment principles.

Neuroblastoma, the most common extracranial solid tumor in children under the age of 5, has been described as early as the 19th century, and its complexity has continued to intrigue researchers, as well as medical and surgical specialists. At one end of the phenotypic spectrum, neuroblastoma is self-limiting with minimal to no intervention required, while on the opposite end exists the challenge of refractory disease despite aggressive management and toxic systemic treatments. The goal of this review is to describe a comprehensive surgical perspective and contemporary approach to neuroblastoma.

Periodontal disease and emerging point-of-care technologies for its diagnosis.

Periodontal disease (PD), a chronic inflammatory disorder that damages the tooth and its supporting components, is a common global oral health problem. Understanding the intricacies of these disorders, from gingivitis to severe PD, is critical for efficient treatment, diagnosis, and prevention in dental care. Periodontal biosensors and biomarkers are critical in improving oral health diagnostic skills.

Cinnamaldehyde Protects against Induced Intestinal Epithelial Barrier Dysfunction in IEC-6 Cells via the PI3K/Akt-Mediated NO/Nrf2 Signaling Pathway.

(), a Gram-negative oral pathogen, promotes and accelerates periodontitis-associated gut disorders. Intestinal epithelial barrier dysfunction is crucial in the pathogenesis of intestinal and systemic diseases. In this study, we sought to elucidate the protective role of cinnamaldehyde (CNM, an activator of Nrf2) against (W83) and -derived lipopolysaccharide (-LPS) induced intestinal epithelial barrier dysfunction via antioxidative mechanisms in IEC-6 cells.

Structural enrichment attenuates colitis-associated colon cancer.

Colorectal cancer (CRC) is a major public health concern and disproportionately impacts racial/ethnic minority populations in the US. Animal models are helpful in examining human health disparities because many stress-induced human health conditions can be recapitulated using mouse models. Azoxymethane (AOM)/ dextran sodium sulfate (DSS) treatment can be used to model colitis-associated cancers.

Targeting Oncogenic Wnt/β-Catenin Signaling in Adrenocortical Carcinoma Disrupts ECM Expression and Impairs Tumor Growth.

Adrenocortical carcinoma (ACC) is a rare but highly aggressive cancer with limited treatment options and poor survival for patients with advanced disease. An improved understanding of the transcriptional programs engaged in ACC will help direct rational, targeted therapies. Whereas activating mutations in Wnt/β-catenin signaling are frequently observed, the β-catenin-dependent transcriptional targets that promote tumor progression are poorly understood.

Rho activation drives luminal collapse and eversion in epithelial acini.

Epithelial cells lining a gland and cells grown in a soft extracellular matrix polarize with apical proteins exposed to the lumen and basal proteins in contact with the extracellular matrix. Alterations to polarity, including an apical-out polarity, occur in human cancers. Although some aberrant polarity states may result from altered protein trafficking, recent observations of an extraordinary tissue-level inside-out unfolding suggest an alternative pathway for altered polarity.

Conditioned Medium Induces Amyloidogenic Processing of the Amyloid-β Protein Precursor upon Infection of SH-SY5Y Cells.

Background: Cleavage of the amyloid-β protein precursor (AβPP) mediated by host secretase enzymes, releases several fragments including amyloid-β (Aβ and Aβ).

Objective: To determine if conditioned medium cleaved AβPP to release Aβ and Aβ.

Methods: The SH-SY5Y cell line was challenged, , with (Pg381) conditioned medium in the presence/absence of cytokines.

VBNC, previously unrecognized in the life cycle of

Bacteria are exposed to stresses during their growth and multiplication in their ecological systems to which they respond in multiple ways as expert survivalists. One such response mechanism is to convert to a viable but not culturable (VBNC) state. As the name indicates, bacteria in the VBNC state have lost their ability to grow on routine growth medium.

Porphyromonas gingivalis (W83) Infection Induces Alzheimer's Disease-Like Pathophysiology in Obese and Diabetic Mice.

Background: Periodontal disease(s) and metabolic illnesses negatively impact the quality of life and, eventually mental health.

Objective: This study investigated the effect of Porphyromonas gingivalis (W83) oral infection on the development of Alzheimer's disease (AD) pathophysiology in a wild-type obese, diabetic (db/db) mouse model.

Methods: The db/db mice were either orally infected with P.

a Strong Risk Factor for Alzheimer's Disease.

() is one of the several important bacterial pathogens associated with the sporadic Alzheimer's disease (AD). Different serotypes are either capsulated or are non-capsulated. It has been demonstrated that (non-capsulated) can reproduce the neurodegenerative AD-like changes , and a capsular (strain W83) could reproduce the cardinal hallmark lesions of AD in a wild-type mouse model.

Osteoprotegerin is sensitive to actomyosin tension in human periodontal ligament fibroblasts.

Periodontal ligament fibroblasts (PdLFs) are an elongated cell type in the periodontium with matrix and bone regulatory functions which become abnormal in periodontal disease (PD). Here we found that the normally elongated and oriented PdLF nucleus becomes rounded and loses orientation in a mouse model of PD. Using in vitro micropatterning of cultured primary PdLF cell shape, we show that PdLF elongation correlates with nuclear elongation and the presence of thicker, contractile F-actin fibers.

Fusobacteria modulate oral carcinogenesis and promote cancer progression.

Evidence suggest periodontal bacterial infection can contribute to oral cancer initiation and progression. To investigate the effects of periodontal bacteria on oral cancer cell behavior using a cell-based system and a mouse carcinogenesis model. Oral cancer cell lines were polyinfected with four periodontal bacteria.

Porphyromonas gingivalis infection alters Nrf2-phase II enzymes and nitric oxide in primary human aortic endothelial cells.

Background: Periodontal disease (PD) is known to be associated with endothelial dysfunction in patients with coronary artery and/or cardiovascular disease. In our study, we sought to explore the virulence of P. gingivalis (Pg) affecting glycogen synthase kinase 3 beta (GSK-3β)/nuclear factor (erythroid-derived 2)-like 2 (Nrf2)/tetrahydrobiopterin (BH )/ nitric oxide synthase (NOS) expression in primary human aortic endothelial cells (pHAECs).

Impaired innate immune signaling due to combined Toll-like receptor 2 and 4 deficiency affects both periodontitis and atherosclerosis in response to polybacterial infection.

Plasma membrane-associated Toll-like receptor (TLR2 and TLR4) signaling contributes to oral microbe infection-induced periodontitis and atherosclerosis. We recently reported that either TLR2 or TLR4 receptor deficiency alters recognition of a consortium of oral pathogens, modifying host responses in periodontitis and atherosclerosis. We evaluated the effects of combined TLR2-/-TLR4-/- double knockout mice on innate immune signaling and induction of periodontitis and atherosclerosis after polybacterial infection with Porphyromonas gingivalis, Treponema denticola, Tannerella forsythia and Fusobacterium nucleatum in a mouse model.

Periodontal cell mechanotransduction.

The periodontium is a structurally and functionally complex tissue that facilitates the anchorage of teeth in jaws. The periodontium consists of various cell types including stem cells, fibroblasts and epithelial cells. Cells of the periodontium are constantly exposed to mechanical stresses generated by biological processes such as the chewing motions of teeth, by flows generated by tongue motions and by forces generated by implants.

Utilization of Ultrasound Guided Tissue-directed Cellular Implantation for the Establishment of Biologically Relevant Metastatic Tumor Xenografts.

Preclinical testing of anticancer therapies relies on relevant xenograft models that mimic the innate tendencies of cancer. Advantages of standard subcutaneous flank models include procedural ease and the ability to monitor tumor progression and response without invasive imaging. Such models are often inconsistent in translational clinical trials and have limited biologically relevant characteristics with low proclivity to produce metastasis, as there is a lack of a native microenvironment.

Alternative NHEJ pathway proteins as components of MYCN oncogenic activity in human neural crest stem cell differentiation: implications for neuroblastoma initiation.

Neuroblastoma is a cancer of neural crest stem cell (NCSC) lineage. Signaling pathways that regulate NCSC differentiation have been implicated in neuroblastoma tumorigenesis. This is exemplified by MYCN oncogene targets that balance proliferation, differentiation, and cell death similarly in normal NCSC and in high-risk neuroblastoma.

Tissue-directed Implantation Using Ultrasound Visualization for Development of Biologically Relevant Metastatic Tumor Xenografts.

Background: Advances in cancer therapeutics depend on reliable in vivo model systems. To develop biologically relevant xenografts, ultrasound was utilized for tissue-directed implantation of neuroblastoma (NB) cell line and patient-derived tumors in the adrenal gland, and for renal subcapsular engraftment of Ewing's sarcoma (ES).

Materials And Methods: NB xenografts were established by direct adrenal injection of luciferase-transfected NB cell lines (IMR32, SH-SY5Y, SK-N-BE2) or NB patient-derived tumor cells (UMNBL001, UMNBL002).

Cerebral Oxidative Stress and Microvasculature Defects in TNF-α Expressing Transgenic and Porphyromonas gingivalis-Infected ApoE-/- Mice.

The polymicrobial dysbiotic subgingival biofilm microbes associated with periodontal disease appear to contribute to developing pathologies in distal body sites, including the brain. This study examined oxidative stress, in the form of increased protein carbonylation and oxidative protein damage, in the tumor necrosis factor-α (TNF-α) transgenic mouse that models inflammatory TNF-α excess during bacterial infection; and in the apolipoprotein knockout (ApoE-/-) mouse brains, following Porphyromonas gingivalis gingival monoinfection. Following 2,4-dinitrophenylhydrazine derivatization, carbonyl groups were detected in frontal lobe brain tissue lysates by immunoblotting and immunohistochemical analysis of fixed tissue sections from the frontotemporal lobe and the hippocampus.

Aneurysm-Specific miR-221 and miR-146a Participates in Human Thoracic and Abdominal Aortic Aneurysms.

Altered microRNA expression is implicated in cardiovascular diseases. Our objective was to determine microRNA signatures in thoracic aortic aneurysms (TAAs) and abdominal aortic aneurysms (AAAs) compared with control non-aneurysmal aortic specimens. We evaluated the expression of fifteen selected microRNA in human TAA and AAA operative specimens compared to controls.

Chronic infection accelerates the occurrence of age-related granules in ApoE mice brains.

This study explored the origin of age-related granules in the apolipoprotein E gene knockout (ApoE) B6 background mice brains following chronic gingival infection with for 24 weeks. Intracerebral localization of was detected by fluorescence hybridization (FISH) and its protease by immunohistochemistry. The age-related granules were observed by periodic acid-Schiff (PAS), silver impregnation, and immunostaining.

Sequential colonization of periodontal pathogens in induction of periodontal disease and atherosclerosis in LDLRnull mice.

Periodontal disease (PD) and atherosclerotic vascular disease (ASVD) are both chronic inflammatory diseases with a polymicrobial etiology and have been epidemiologically associated. The purpose is to examine whether periodontal bacteria that infect the periodontium can also infect vascular tissues and enhance pre-existing early aortic atherosclerotic lesions in LDLRnull mice. Mice were orally infected with intermediate bacterial colonizer Fusobacterium nucleatum for the first 12 weeks followed by late bacterial colonizers (Porphyromonas gingivalis, Treponema denticola and Tannerella forsythia) for the remaining 12 weeks mimicking the human oral microbiota ecological colonization.

Spatio-temporal regulation of EGFR signaling by the Eps15 homology domain-containing protein 3 (EHD3).

The epidermal growth factor (EGF) receptor EGFR is a major receptor tyrosine kinase whose role in gliomagenesis is well established. We have recently identified EHD3 [Eps15 homology (EH) domain-containing protein 3], an endocytic trafficking regulatory protein, as a putative brain tumor suppressor. Here, we investigate the underlying mechanisms, by establishing a novel mechanistic and functional connection between EHD3 and the EGFR signaling pathway.

A Novel Rat Model of Polymicrobial Peri-Implantitis: A Preliminary Study.

Background: Peri-implantitis is a complex polymicrobial biofilm-induced inflammatory osteolytic gingival infection that results in orofacial implant failures. To the best knowledge of the authors, there are no preclinical in vivo studies in implant dentistry that have investigated the inflammatory response to known microbial biofilms observed in humans. The aim of this study is to develop a novel peri-implant rat model using an established model of polymicrobial periodontitis.