Specific Markers Research Articles

A Comparative Evaluation of Error Processing Performance and its Relationship with Cognitive Function in Patients with Alzheimer's Disease, Individuals with Mild Cognitive Impairment, and Normal Controls Using the Event-Related Potentials.

Some pathological changes occur in patients with Alzheimer's disease (AD) prior to the onset of clinical symptoms. In the present study, we aimed to investigate the potential of event-related potential (ERP) components in error processing performance as a neuromarker of mild cognitive impairment (MCI) and transition to AD and their relation with cognitive functions. We conducted an evaluation of 16 patients diagnosed with AD, 16 patients with MCI, and 15 normal controls using three subtests from the Cambridge Neuropsychological Testing Automated Battery (CANTAB). The ERP components of error processing were extracted and compared among the three groups using a modified version of the Eriksen flanker task. Additionally, we assessed the correlation between the cognitive results and the ERP components. Significant differences were observed among the three groups in terms of providing correct responses following errors and the amplitude of error-related negativity (ERN). These differences were also significant between all paired groups. Regarding other ERP components of error processing and the peak latency of ERN, no significant differences were observed among the three groups. The findings revealed that the spatial working memory and new learning were correlated with the amplitude of ERN. In the context of error processing performance, both the accuracy of responses following an error and the amplitude of ERN can be considered as indicators of MCI and its progression to AD. The present findings do not support the use of other error processing components as differential markers in the three groups.

Liposome-encapsulated progesterone efficiently suppresses B-lineage cell proliferation

Progesterone suppresses several ancient pathways in a concentration-dependent manner. Based on these characteristics, progesterone is considered a candidate anticancer drug. However, the concentration of progesterone used for therapy should be higher than the physiological concentration, which makes it difficult to develop progesterone-based anticancer drugs. We previously developed liposome-encapsulated progesterone (Lipo-P4) with enhanced anticancer effects, which strongly suppressed triple-negative breast cancer cell proliferation in humanized mice. In this study, we aimed to clarify whether Lipo-P4 effectively suppresses the proliferation of B-lineage cancer cells. We selected six B-cell lymphoma and two myeloma cell lines, and analyzed their surface markers using flow cytometry. Next, we prepared liposome-encapsulated progesterone and examined its effect on cell proliferation in these B-lineage cancer cells, three ovarian clear cell carcinoma cell lines, two prostate carcinoma cell lines, and one triple-negative breast cancer adenocarcinoma cell line. Lipo-P4 suppressed the proliferation of all cancer cell lines. All B-lineage cell lines, except for the HT line, were more susceptible than the other cell types, regardless of the expression of differentiation markers. Empty liposomes did not suppress cell proliferation. These results suggest that progesterone encapsulated in liposomes efficiently inhibits the proliferation of B-lineage cells and may become an anticancer drug candidate for B-lineage cancers.

Long non-coding RNA FGD5 antisense RNA 1 targets Baculovirus inhibitor 5 via microRNA-497-5p to alleviate calcific aortic valve disease.

Calcific aortic valve disease (CAVD) is featured by thickening and calcification of the aortic valve. Osteoblast differentiation is a crucial step in valve calcification. Long non-coding RNAs (LncRNAs) participate in the osteogenic differentiation of mesenchymal cells. However, the character of lncRNA FGD5 antisense RNA 1 (FGD5-AS1) in CAVD is uncertain. After collection of human aortic valve tissue samples, detection of FGD5-AS1, microRNA (miR)-497-5p and Baculovirus inhibitor 5 (BIRC5) was conducted. Valve mesenchymal cells were isolated from CAVD patients and induced to differentiate to osteoblasts, and transfected with FGD5-AS1, miR-497-5p and BIRC5 plasmids. Detection of the alkaline phosphatase activity was after osteogenic induction of human aortic valve interstitial cells (hAVICs); Detection of the degree of calcium nodules and osteoblast differentiation markers (RUNX2 and OPN) was conducted. After establishment of a mouse model of CAVD, detection of the thickness of aortic valve leaflets, and the degree of calcification of the valve leaflets, and evaluation of echocardiographic parameters were implemented. Experimental data manifested in CAVD patients, lncRNAFGD5-AS1 and BIRC5 were reduced, but miR-497-5p was elevated; Enhancing lncRNA FGD5-AS1 or repressing miR-497-5p mitigated CAVD by restraining osteogenic differentiation; LncRNA FGD5-AS1 sponged miR-497-5p to target BIRC5; Repressive BIRC5 turned around the therapeutic action of elevated FGD5-AS1 or depressed miR-497-5p on hAVICs; Enhancive FGD5-AS1 in vivo was available to reduce ApoE-/- mouse CAVD induced via high cholesterol diet. All in all, lncRNAFGD5-AS1 targets BIRC5 via miR-497-5p to alleviate CAVD.

Zinc finger protein 36 like 2-histone deacetylase 1 axis is involved in the bone responses to mechanical stress

The molecular mechanism underlying the promotion of fracture healing by mechanical stimuli remains unclear. The present study aimed to investigate the role of zinc finger protein 36 like 2 (ZFP36L2)-histone deacetylase 1 (HDAC1) axis on the osteogenic responses to moderate mechanical stimulation. Appropriate stimulation of fluid shear stress (FSS) was performed on MC3T3-E1 cells transduced with ZFP36L2 and HDAC1 recombinant adenoviruses, aiming to validate the influence of mechanical stress on the expression of ZFP36L2-HDAC1 and the osteogenic differentiation and mineralization. The results showed that moderate FSS stimulation significantly upregulated the expression of ZFP36L2 in MC3T3-E1 cells (p < 0.01). The overexpression of ZFP36L1 markedly enhanced the levels of osteogenic differentiation markers, including bone morphogenetic protein 2 (BMP2), runt-related transcription factor 2 (RUNX2), alkaline phosphatase (ALP), Osterix, and collagen type I alpha 1 (COL1A1) (p < 0.01). ZFP36L2 accelerated the degradation of HDAC1 by specifically binding to its 3’ UTR region, thereby fulfilling its function at the post-transcriptional regulatory gene level and promoting the osteogenic differentiation and mineralization fate of cells. Mechanical unloading notably diminished/elevated the expression of ZFP36L2/HDAC1, decreased bone mineral density and bone volume fraction, hindered the release of osteogenic-related factors and vascular endothelial growth factor in callus tissue (p < 0.01), and was detrimental to fracture healing. Collectively, proper stress stimulation plays a crucial role in facilitating osteogenesis through the promotion of ZFP36L2 and subsequent degradation of HDAC1. Targeting ZFP36L2-HDAC1 axis may provide promising insights to enhance bone defect healing.

Normal Brain and Brain Tumor ADC: Changes Resulting From Variation of Diffusion Time and/or Echo Time in Pulsed-Gradient Spin Echo Diffusion Imaging.

Increasing gradient performance on modern magnetic resonance imaging scanners has profoundly reduced the attainable diffusion and echo times for clinically available pulsed-gradient spin echo (PGSE) sequences. This study investigated how this may impact the measured apparent diffusion coefficient (ADC), which is considered an important diagnostic marker for differentiation between normal and abnormal brain tissue and for therapeutic follow-up. Diffusion time and echo time dependence of the ADC were evaluated on a high-performance 3 T magnetic resonance imaging scanner. Diffusion PGSE brain scans were performed in 10 healthy volunteers and in 10 brain tumor patients using diffusion times of 16, 40, and 70 ms, echo times of 60, 75, and 104 ms at 3 b-values (0, 100, and 1000 s/mm 2 ), and a maximum gradient amplitude of 68 mT/m. A low gradient performance system was also emulated by reducing the diffusion encoding gradient amplitude to 19 mT/m. In healthy subjects, the ADC was measured in 6 deep gray matter regions and in 6 white matter regions. In patients, the ADC was measured in the solid part of the tumor. With increasing diffusion time, a small but significant ADC increase of up to 2.5% was observed for 6 aggregate deep gray matter structures. With increasing echo time or reduced gradient performance, a small but significant ADC decrease of up to 2.6% was observed for 6 aggregate white matter structures. In tumors, diffusion time-related ADC changes were inconsistent without clear trend. For tumors with diffusivity above 1.0 μm 2 /ms, with prolonged echo time, there was a pronounced ADC increase of up to 12%. Meanwhile, for tumors with diffusivity at or below 1.0 μm 2 /ms, no change or a reduction was observed. Similar results were observed for gradient performance reduction, with an increase of up to 21%. The coefficient of variation determined in repeat experiments was 2.4%. For PGSE and the explored parameter range, normal tissue ADC changes seem negligible. Meanwhile, observed tumor ADC changes can be relevant if ADC is used as a quantitative biomarker and not merely assessed by visual inspection. This highlights the importance of reporting all pertinent timing parameters in ADC studies and of considering these effects when building scan protocols for use in multicenter investigations.

Macrophage-enriched novel functional long noncoding RNAs LRRC75A-AS1 and GAPLINC regulate polarization and innate immune responses.

Macrophages (Mφs) are functionally dynamic immune cells that bridge innate and adaptive immune responses; however, the underlying epigenetic mechanisms that control Mφ plasticity and innate immune functions are not well elucidated. To identify novel functions of macrophage-enriched lncRNAs in regulating polarization and innate immune responses. Total RNA isolated from differentiating monocyte-derived M1 and M2 Mφs was profiled for lncRNAs expression using RNAseq. Impact of LRRC75A-AS1, GAPLINC and AL139099.5 knockdown was examined on macrophage differentiation,polarization markers, phagocytosis, and antigen processing by flow cytometry and florescence microscopy. Cytokine profiles were examined by multiplex bead array and cytoskeletal signaling pathway genes were quantified by PCR-based array. Gingival biopsies were collected from periodontally healthy and diseased subjects to examine lncRNAs,M1/M2marker expression. Transcriptome profiling of M1 and M2 Mφs identified thousands of differentially expressed known and novel lncRNAs. We characterized three Mφ-enriched lncRNAs LRRC75A-AS1, GAPLINC and AL139099.5 in polarization and innate immunity. Knockdown of LRRC75A-AS1 and GAPLINC downregulated the Mφ differentiation markers and skewed Mφ polarization by decreasing M1 markers without a significant impact on M2 markers. LRRC75A-AS1 and GAPLINC knockdown also attenuated bacterial phagocytosis, antigen processing and inflammatory cytokine secretion in Mφs, supporting their functional role in potentiating innate immune functions. Mechanistically, LRRC75A-AS1 and GAPLINC knockdown impaired Mφ migration by downregulating the expression of multiple cytoskeletal signaling pathways suggesting their critical role in regulating Mφ migration. Finally, we showed that LRRC75A-AS1 and GAPLINC were upregulated in periodontitis and their expression correlates with higher M1 markers suggesting their role in macrophage polarizationin vivo. Our results show that polarized Mφs acquire a unique lncRNA repertoire and identified many previously unknown lncRNA sequences. LRRC75A-AS1 and GAPLINC, which are induced in periodontitis, regulate Mφ polarization and innate immune functions supporting their critical role in inflammation.

Transglutaminase 3 regulates cutaneous squamous carcinoma differentiation and inhibits progression via PI3K-AKT signaling pathway-mediated Keratin 14 degradation.

Cutaneous squamous carcinoma is the second most common epithelial malignancy, associated with significant morbidity, mortality, and economic burden. However, the mechanisms underlying cSCC remain poorly understood. In this study, we identified TGM3 as a novel cSCC tumor suppressor that acts via the PI3K-AKT axis. RT-qPCR, IHC and western blotting were employed to assess TGM3 levels. TGM3-overexpression/knockdown cSCC cell lines were utilized to detect TGM3's impact on epithelial differentiation as well as tumor cell proliferation, migration, and invasion in vitro. Additionally, subcutaneous xenograft tumor models were employed to examine the effect of TGM3 knockdown on tumor growth in vivo. Finally, molecular and biochemical approaches were employed to gain insight into the tumor-suppressing mechanisms of TGM3. TGM3 expression was increased in well-differentiated cSCC tumors, whereas it was decreased in poor-differentiated cSCC tumors. Loss of TGM3 is associated with poor differentiation and a high recurrence rate in patients with cSCC. TGM3 exhibited tumor-suppressing activity by regulating cell proliferation, migration, and invasion both in vitro and in vivo. As a novel cSCC tumor differentiation marker, TGM3 expression was positively correlated with cell differentiation. In addition, our results demonstrated an interaction between TGM3 and KRT14 that aids in the degradation of KRT14. TGM3 deficiency disrupts keratinocytes differentiation, and ultimately leads to tumorigenesis. Furthermore, RNA-sequence analysis revealed that loss of TGM3 enhanced EMT via the PI3K-AKT signaling pathway. Deguelin, a PI3K-AKT inhibitor, blocked cSCC tumor growth induced by TGM3 knockdown in vivo. Taken together, TGM3 inhibits cSCC tumor growth via PI3K-AKT signaling, which could also serve as a tumor differentiation marker and a potential therapeutic target for cSCC. Proposed model depicted the mechanism by which TGM3 suppress cSCC development. TGM3 reduces the phosphorylation level of AKT and degrades KRT14. In the epithelial cell layer, TGM3 exhibits a characteristic pattern of increasing expression from bottom to top, while KRT14 and pAKT are the opposite. Loss of TGM3 leads to reduced degradation of KRT14 and activation of pAKT, disrupting keratinocyte differentiation, and eventually resulting in the occurrence of low-differentiated cSCC.

SLAM Family Receptors in B Cell Chronic Lymphoproliferative Disorders.

The signaling lymphocytic activation molecule (SLAM) receptor family (SLAMF) consists of nine glycoproteins that belong to the CD2 superfamily of immunoglobulin (Ig) domain-containing molecules. SLAMF receptors modulate the differentiation and activation of a wide range of immune cells. Individual SLAMF receptors are expressed on the surface of hematopoietic stem cells, hematopoietic progenitor cells, B cells, T cells, NK cells, NKT cells, monocytes, macrophages, dendritic cells, neutrophils, and platelets. The expression of SLAMF receptors was studied during normal B cell maturation. Several SLAMF receptors were also detected in cancer cell lines of B-lymphoid origin and in pathological B cells from patients with B cell chronic lymphoproliferative disorders (B-CLPD), the most frequent hematological malignancies in adults. This review summarizes current knowledge on the expression of SLAMF receptors and their adaptor proteins SAP and EAT-2 in B-CLPD. Several SLAMF receptors could be regarded as potential diagnostic and differential diagnostic markers, prognostic factors, and targets for the development of novel drugs for patients with B-CLPD.

Effect of graphene oxide/ poly-L-lactic acid composite scaffold on the biological properties of human dental pulp stem cells

BackgroundTissue engineering has attracted recent attention as a promising bone repair and reconstruction approach. Dental pulp stem cells (DPSCs) are pluripotent and can differentiate into bone cells with the correct environment and substrate. Therefore, suitable scaffold materials are essential for fabricating functional three-dimensional (3D) tissue and tissue regeneration. Composite scaffolds consisting of biodegradable polymers are very promising constructs. This study aims to verify the biological function of human DPSCs seeded onto composite scaffolds based on graphene oxide (GO) and poly-L-lactic acid (PLLA).MethodsThe surface morphology was observed under scanning electron microscopy (SEM). Chemical composition was evaluated with Fourier transform infrared (FTIR) spectroscopy. The biocompatibility of GO/PLLA scaffolds was assessed using phalloidin staining of cytoskeletal actin filaments, live/dead staining, and a CCK-8 assay. The effect of GO/PLLA scaffolds on cell osteogenic differentiation was detected through ALP staining, ALP activity assays, and alizarin red S staining, complemented by quantitative real-time PCR (qRT-PCR) analysis.ResultsOur data showed that GO and PLLA are successfully integrated and the GO/PLLA scaffolds exhibit favorable bioactivity and biocompatibility towards DPSCs. Additionally, it was observed that the 0.15% GO/PLLA scaffold group promoted DPSC proliferation and osteogenic differentiation by forming more calcium nodules, showing a higher intensity of ALP staining and ALP activity, and enhancing the expression levels of differentiation marker genes RUNX2 and COL1.ConclusionsThese results demonstrate that the GO/PLLA scaffold is a feasible composite material suitable for cell culture and holds promising applications for oral bone tissue engineering.

Comparative analysis of microbial composition and functional characteristics in dental plaque and saliva of oral cancer patients

BackgroundThe oral cavity is home to various ecological niches, each with its own unique microbial composition. Understanding the microbial communities and gene composition in different ecological niches within the oral cavity of oral cancer (OC) patients is crucial for determining how these microbial populations contribute to disease progression.MethodsIn this study, saliva and dental plaque samples were collected from patients with OC. Metagenomic sequencing was employed to analyze the microbial community classification and functional composition of the different sample groups.ResultsThe results of the study revealed significant differences in both the function and classification of microbial communities between saliva and dental plaque samples. The diversity of microbial species in saliva was found to be higher compared to that in plaque samples. Notably, Actinobacteria were enriched in the dental plaque of OC patients. Furthermore, the study identified several inter-group differential marker species, including Prevotella intermedia, Haemophilus parahaemolyticus, Actinomyces radius, Corynebacterium matruchitii, and Veillonella atypica. Additionally, 1,353 differential genes were annotated into 23 functional pathways. Interestingly, a significant correlation was observed between differentially labeled species and Herpes simplex virus 1 (HSV-1) infection, which may be related to the occurrence and development of cancer.ConclusionsSignificant differences in the microbial and genetic composition of saliva and dental plaque samples were observed in OC patients. Furthermore, pathogenic bacteria associated with oral diseases were predominantly enriched in saliva. The identification of inter-group differential biomarkers and pathways provide insights into the relationship between oral microbiota and the occurrence and development of OC.

Disturbed flow regulates protein disulfide isomerase A1 expression via microRNA-204.

Redox processes can modulate vascular pathophysiology. The endoplasmic reticulum redox chaperone protein disulfide isomerase A1 (PDIA1) is overexpressed during vascular proliferative diseases, regulating thrombus formation, endoplasmic reticulum stress adaptation, and structural remodeling. However, both protective and deleterious vascular effects have been reported for PDIA1, depending on the cell type and underlying vascular condition. Further understanding of this question is hampered by the poorly studied mechanisms underlying PDIA1 expression regulation. Here, we showed that PDIA1 mRNA and protein levels were upregulated (average 5-fold) in the intima and media/adventitia following partial carotid ligation (PCL). Our search identified that miR-204-5p and miR-211-5p (miR-204/211), two broadly conserved miRNAs, share PDIA1 as a potential target. MiR-204/211 was downregulated in vascular layers following PCL. In isolated endothelial cells, gain-of-function experiments of miR-204 with miR mimic decreased PDIA1 mRNA while having negligible effects on markers of endothelial activation/stress response. Similar effects were observed in vascular smooth muscle cells (VSMCs). Furthermore, PDIA1 downregulation by miR-204 decreased levels of the VSMC contractile differentiation markers. In addition, PDIA1 overexpression prevented VSMC dedifferentiation by miR-204. Collectively, we report a new mechanism for PDIA1 regulation through miR-204 and identify its relevance in a model of vascular disease playing a role in VSMC differentiation. This mechanism may be regulated in distinct stages of atherosclerosis and provide a potential therapeutic target.

The Impact of Phenotype of Inflammatory Bowel Diseases, Inflammation Activity and Therapy on Mucosal Mature Cd83+ Dendritic Cell.

Background: Crohn's disease (CD) and ulcerative colitis (UC) are well-defined phenotypes of chronic inflammatory bowel diseases (IBDs). A mechanism of inflammation in these diseases is partially controlled by the intestinal dendritic cell (DC). In this study, we observed a mature CD83+ DC in colonic bioptic samples, and its correlation with disease phenotype and activity. Methods: The study included 219 subjects: 100 with UC, 44 with CD and 75 healthy subjects. Colonic biopsy specimens were incubated with the primary antibody Anti-CD83. Intraepithelial CD83+ DCs were counted per 100 enterocytes. The presence of CD83+ DC was analysed according to the type of IBD, histopathologic inflammation activity and treatment outcome. Results: The presence of mature CD83+ DCs (0, ≥1) differed according to disease types of IBD (p = 0.001), histologic inflammation activity (p = 0.049) and applied therapy (p = 0.001). The odds for CD83+ DC presence were 5.2 times higher in the CD group than in the control/UC group. The odds for CD83+ DC presence were 2.6 times higher in subjects without inflammation or chronic inflammation than with acute inflammation. They were also 3.7 times higher in subjects without therapy. The cut-off value 0.5 CD83+ DC (Rock analysis area = 0.699; SE 0.046; p < 0.001; 95% CI: 0.609-0.788) had been assessed as a differentiation marker between UC and CD. Conclusion: Presence of CD83+ DC could be used as a possible parameter in distinction between UC and CD, as well as a predictor of inflammation activity and treatment outcome.

Immunophenotyping of blood and bone marrow cells as a way to search for differentiation syndrome risk factors in acute promyelocytic leukemia

Background. Differentiation syndrome (DS) is a potentially fatal complication of therapy for acute promyelocytic leukemia (APL) with an incidence of up to 48 %. To date, no reliable DS risk factors have been found, with the exception of leukocytosis at the APL onset.Aim. To determine the risk factors associated with DS in patients with APL during induction therapy with arsenic trioxide (ATO) and tretinoin (ATRA).Materials and methods. The study included 39 patients with APL, 29 (74.4 %) of them were classified as low-risk according to ELN (European Leukemia Net), 10 (25.6 %) were classified as high-risk. At the disease onset, cytological and molecular (chimeric transcript PML::RARα, FLT3-ITD mutation) bone marrow studies were performed, the expression of 28 differentiation antigens by blood and bone marrow blast cells was determined (markers of early precursors, myeloid and lymphoid differentiation, cell adhesion molecules, chemokine receptors, integrins, selectin), body mass index (BMI) and the leukocytes number dynamics during induction course were assessed. All patients received ATRA and ATO therapy. Patients from the high-risk group at the onset received 1–3 injections of idarubicin (12 mg/m2) and dexamethasone (8–10 mg/m2 2 times a day) to prevent DS until leukocytosis reduced. In cases of DS, dexamethasone was prescribed at a dose of 10 mg/m2 2 times a day; in cases of severe DS, the induction course was interrupted.Results. Of the 39 patients, 12 (30.8 %) were diagnosed with DS: 20 % of high-risk patients (2/10) and 34.5 % of low-risk patients (10/29). There was no statistically significant association of leukocytosis more than 10 × 109 /L at onset, microgranular morphology of blast cells, bcr3-variant PML::RARα, FLT3-ITD mutation with DS. In multivariate analysis, the probability of DS was associated with BMI ≥30 kg/m2 and mean fluorescence intensity of CD38 antigen by blast cells, regardless of risk group. based on the results of the ROC-analysis, the threshold value of mean CD38 fluorescence intensity was set at 25,000 cu, if exceeded, DS is highly likely to develop.Conclusion. the high incidence of DS among low-risk patients is probably due to the lack of prophylactic glucocorticosteroids administration for the development of leukocytosis during ATRA and ATO therapy. BMI ≥30 kg/m2 and mean CD38 fluorescence intensity more than 25,000 cu were identified as statistically significant DS risk factors.

TPG-functionalized PLGA/PCL nanofiber membrane facilitates periodontal tissue regeneration by modulating macrophages polarization via suppressing PI3K/AKT and NF-κB signaling pathways

Traditional fibrous membranes employed in guided tissue regeneration (GTR) in the treatment of periodontitis have limitations of bioactive and immunomodulatory properties. We fabricated a novel nTPG/PLGA/PCL fibrous membrane by electrospinning which exhibit excellent hydrophilicity, mechanical properties and biocompatibility. In addition, we investigated its regulatory effect on polarization of macrophages and facilitating the regeneration of periodontal tissue both in vivo and in vitro. These findings showed the 0.5%TPG/PLGA/PCL may inhibit the polarization of RAW 264.7 into M1 phenotype by suppressing the PI3K/AKT and NF-κB signaling pathways. Furthermore, it directly up-regulated the expression of cementoblastic differentiation markers (CEMP-1 and CAP) in periodontal ligament stem cells (hPDLSCs), and indirectly up-regulated the expression of cementoblastic (CEMP-1 and CAP) and osteoblastic (ALP, RUNX2, COL-1, and OCN) differentiation markers by inhibiting the polarization of M1 macrophage. Upon implantation into a periodontal bone defect rats model, histological assessment revealed that the 0.5%TPG/PLGA/PCL membrane could regenerate oriented collagen fibers and structurally intact epithelium. Micro-CT (BV/TV) and the expression of immunohistochemical markers (OCN, RUNX-2, COL-1, and BMP-2) ultimately exhibited satisfactory regeneration of alveolar bone, periodontal ligament. Overall, 0.5%TPG/PLGA/PCL did not only directly promote osteogenic effects on hPDLSCs, but also indirectly facilitated cementoblastic and osteogenic differentiation through its immunomodulatory effects on macrophages. These findings provide a novel perspective for the development of materials for periodontal tissue regeneration.

Comparison of Zirconia Implant Surface Modifications for Optimal Osseointegration.

Zirconia ceramic implants are commercially available from a rapidly growing number of manufacturers. Macroscopic and microscopic surface design and characteristics are considered to be key determining factors in the success of the osseointegration process. It is, therefore, crucial to assess which surface modification promotes the most favorable biological response. The purpose of this study was to conduct a comparison of modern surface modifications that are featured in the most common commercially available zirconia ceramic implant systems. A review of the currently available literature on zirconia implant surface topography and the associated bio-physical factors was conducted, with a focus on the osseointegration of zirconia surfaces. After a review of the selected articles for this study, commercially available zirconia implant surfaces were all modified using subtractive protocols. Commercially available ceramic implant surfaces were modified or enhanced using sandblasting, acid etching, laser etching, or combinations of the aforementioned. From our literature review, laser-modified surfaces emerged as the ones with the highest surface roughness and bone-implant contact (BIC). It was also found that surface roughness could be controlled to achieve optimal roughness by modifying the laser output power during manufacturing. Furthermore, laser surface modification induced a very low amount of preload microcracks in the zirconia. Osteopontin (OPN), an early-late osteogenic differentiation marker, was significantly upregulated in laser-treated surfaces. Moreover, surface wettability was highest in laser-treated surfaces, indicating favorable hydrophilicity and thus promoting early bone forming, cell adhesion, and subsequent maturation. Sandblasting followed by laser modification and sandblasting followed by acid etching and post-milling heat treatment (SE-H) surfaces featured comparable results, with favorable biological responses around zirconia implants.

Diagnostic Accuracy of Cancer in Pleural Effusion: A Combination Serum Tumor Markers and Cytology

Abstract Background: Cytological examination of body effusion has an essential role in different tumor staging and research of malignancy. Objectives: It is to study the diagnostic effect of serum tumor markers in differentiation between benign and malignant pleural effusion. Materials and Methods: A retrospective research was done on 39 patients (28 male and 11 female with an age range of 50–77 years old). All samples undergo diagnostic thoracocentesis. The cutoff values of serum tumor markers (CEA &lt; 5 ng/mL; CA125 &lt;35 U/mL; CA19-9 &lt; 37 U/mL; and CA15-3 &lt; 31 U/mL). Results: Thirty-nine cases, resulting in 26 (67%) benign pleural effusions and 13 (33%) malignant pleural effusions, mean ± SD of age was higher malignant pleural effusion than benign type. The sensitivity of cytology was 33%. Malignant pleural effusion tended to have higher serum marker tumor concentrations. A comparison association between benign and malignant pleural effusion revealed statistically significant only in CEA. Most areas under the curve had moderate values that ranged between 0.6 for CA125, CA15.3, and other combined tumor markers, except for CEA, which had a good AUC (0.799). The best efficacy of a single tumor marker is CEA with a cutoff value of 2.05 ng/mL; at this cutoff value, the sensitivity, specificity, and accuracy were 69.2%, 88.5%, and 82.1%, respectively. Conclusion: Single serum tumor markers showed moderate sensitivity and low specificity; their combination does not result in to increase level of sensitivity and specificity to a good and dependent level for diagnosis of the malignant pleural effusion. Cytology and serum tumor markers have aided role in diagnosis. Thoracoscopy and pleural biopsy remain dependent diagnostic tools for malignant pleural effusion.

Expression of semaphorin-3A in the joint and role in osteoarthritis.

Osteoarthritis (OA) is characterised by the deterioration of cartilage in the joints and pain. We hypothesise that semaphorin-3A (sema-3A), a chemorepellent for sensory nerves, plays a role in joint degradation and pain. We used the mechanical joint loading (MJL) model of OA to investigate sema-3A expression in the joint and examine its association with the development of OA and pain. We also analyse its effect on chondrocyte differentiation using the ATDC5 cell line. We demonstrate that sema-3A is present in most tissues in the healthy joint and its expression increases in highly innervated tissues, such as cruciate ligaments, synovial lining and subchondral bone, in loaded compared to nonloaded control joints. In contrast, sema-3A expression in cartilage was decreased in the severe OA induced by the application of high loads. There was a significant increase in circulating sema-3A, 6 weeks after MJL compared to the nonloaded mice. mRNA for sema-3A and its receptor Plexin A1 were upregulated in the dorsal root ganglia of mice submitted to MJL. These increases were supressed by zoledronate, an inhibitor of bone pain. Sema-3A was expressed at all stages of Chondrocyte maturation and, when added exogenously, stimulated expression of markers of chondrocyte differentiation. This indicates that sema-3A could affect joint tissues distinctively during the development of OA. In highly innervated joint tissues, sema-3A could control innervation and/or induce pain-associated neuronal changes. In cartilage, sema-3A could favour its degeneration by modifying chondrocyte differentiation.

A Review of Stem Cell Attributes Derived from the Oral Cavity

Oral cavity stem cells (OCSCs) have been the focus of intense scientific efforts due to their accessibility and stem cell properties. The present work aims to compare the different characteristics of 6 types of dental stem cells derived from the oral cavity: dental pulp stem cells (DPSC), stem cells from human exfoliated deciduous teeth (SHED), periodontal ligament stem cells (PDLSC), stem cells from the apical papilla (SCAP), bone marrow mesenchymal stem cells (BMSC), and gingival mesenchymal stem cells (GMSC). Using immunofluorescence and real-time polymerase chain reaction techniques, we analysed the cells for stem cell, differentiation, adhesion, and extracellular matrix markers; the ability to proliferate in vitro; and multilineage differentiation potential. Markers such as vimentin, CD44, alkaline phosphatase, CD146, CD271, CD49f, Oct 3/4, Sox 9, FGF7, nestin, and BMP4 showed significant differences in expression levels, highlighting the heterogeneity and unique characteristics of each cell type. At the same time, we confirmed that all cell types successfully differentiated into osteogenic, chondrogenic, or adipose lineages, with different readiness. In conclusion, our study reveals the distinct properties and potential applications of various dental-derived stem cells. These findings contribute to a deeper understanding of OCSCs and their significance in future clinical applications.

Soluble Biomarkers of Cerebrovascular Pathologies.

Vascular contributions to cognitive impairment and dementia (VCID) is an all-encompassing term that describes cognitive impairment due to cerebrovascular origins. With the advancement of imaging and pathological studies, we now understand that VCID is often comorbid with Alzheimer disease. While researchers in the Alzheimer disease field have been working for years to establish and test blood-based biomarkers for Alzheimer disease diagnosis, prognosis, clinical therapy discovery, and early detection, blood-based biomarkers for VCID are in their infancy and also face challenges. VCID is heterogeneous, comprising many different pathological entities (ischemic, or hemorrhagic), and spatial and temporal differences (acute or chronic). This review highlights pathways that are aiding the search for sensitive and specific blood-based cerebrovascular dysfunction markers, describes promising candidates, and explains ongoing initiatives to discover blood-based VCID biomarkers.

Electrical Impedance Spectroscopy Quantifies Skin Barrier Function in Organotypic In Vitro Epidermis Models

3 D human epidermal equivalents (HEEs) are a state-of-the-art organotypic culture model in pre-clinical investigative dermatology and regulatory toxicology. Here, we investigated the utility of electrical impedance spectroscopy (EIS) for non-invasive measurement of HEE epidermal barrier function. Our setup comprised a custom-made lid fit with 12 electrode pairs aligned on the standard 24-transwell cell culture system. Serial EIS measurements for seven consecutive days did not impact epidermal morphology and readouts showed comparable trends to HEEs measured only once. We determined two frequency ranges in the resulting impedance spectra: a lower frequency range termed EISdiff correlated with keratinocyte terminal differentiation independent of epidermal thickness and a higher frequency range termed EISSC correlated with stratum corneum thickness. HEEs generated from CRISPR/Cas9 engineered keratinocytes that lack key differentiation genes FLG, TFAP2A, AHR or CLDN1 confirmed that keratinocyte terminal differentiation is the major parameter defining EISdiff. Exposure to pro-inflammatory psoriasis- or atopic dermatitis-associated cytokine cocktails lowered the expression of keratinocyte differentiation markers and reduced EISdiff. This cytokine-associated decrease in EISdiff was normalized after stimulation with therapeutic molecules. In conclusion, EIS provides a non-invasive system to consecutively and quantitatively assess HEE barrier function and to sensitively and objectively measure barrier development, defects and repair.