Cancer cells corrupt normal epithelial cells through miR-let-7c-rich small extracellular vesicle-mediated downregulation of p53/PTEN

alexandrossfakianakis shared this article with you from Inoreader Cancer cells corrupt normal epithelial cells through miR-let-7c-rich small extracellular vesicle-mediated downregulation of p53/PTEN via International Journal of Oral Science - Issue International Journal of Oral Science, Published online: 19 July 2022; doi:10.1038/s41368-022-00192-2 Cancer cells corrupt normal epithelial cells through miR-let-7c-rich small extracellular vesicle-mediated downregulation of p53/PTEN View on Web

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TREM2‐induced activation of microglia contributes to synaptic integrity in cognitively intact aged individuals with Alzheimer's neuropathology

alexandrossfakianakis shared this article with you from Inoreader TREM2‐induced activation of microglia contributes to synaptic integrity in cognitively intact aged individuals with Alzheimer's neuropathology via Brain Pathology Efficient TREM2-phagocytic microglia underlie synaptic resilience in NDAN, removing damaged synpases, contributing to synaptic integrity and protecting from memory deficits. Abstract The existence of individuals who remain cognitively intact despite presenting histopathological signs of Alzheimer's disease (AD), here referred to as "Nondemented with AD neuropathology" (NDAN), suggests that some mechanisms are triggered to resist cognitive impairment. Exposed phosphatidylserine (ePS) represents a neuronal "eat-me" signal involved in microglial-mediated phagocytosis of damaged synapses. A possible mediator of this process is TREM2, a microglial surface receptor activated by ligands including PS. Based on TREM2 role in the scavenging function of microglia, we hypothesize that an efficient microglial phagocytosis of damaged synapses underlies synaptic resilience in NDAN, thus protecting from memory deficits. Using immunofluorescence microscopy, we performed a comparative study of human post-mortem frontal cortices of aged-matched, AD and NDAN individuals. We studied the distribution of activated microglia (IBA1, IBA1+/CD68+ cells) and phagocytic microglia-related proteins (TREM2, DAP12), demonstrating higher microglial activation and TREM2 expression in NDAN versus AD. A study of the preservation of synapses around plaques, assessed using MAP2 and βIII tubulin as dendritic and axonal markers, respectively, and PSD95 as a postsynaptic marker, revealed preserved axonal/dendritic structure around plaques in NDAN versus AD. Moreover, high levels of PSD95 around NDAN plaques and the colocalization of PSD95 with CD68 indicated a prompt removal of damaged synapses by phagocytic microglia. Furthermore, Annexin V assay on aged-matched, AD and NDAN individuals synaptosomes revealed increased levels of ePS in NDAN, confirming damaged synapses engulfment. Our results suggest a higher efficiency of TREM2-induced phagocytic microglia in removing damaged synapses, underlying synaptic resilience in NDAN individuals. View on Web

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Camrelizumab plus chemotherapy in advanced non‐squamous non‐small cell lung cancer: Treatment response, survival pattern, and safety

alexandrossfakianakis shared this article with you from Inoreader Camrelizumab plus chemotherapy in advanced non‐squamous non‐small cell lung cancer: Treatment response, survival pattern, and safety via Journal of Clinical Pharmacy and Therapeutics This study retrospectively analysed 31 driver-gene-negative advanced non-squamous non-small cell lung cancer (NSCLC) patients who received a 21-day therapy cycle for four cycles of camrelizumab (intravenous injection, 200 mg/cycle) plus carboplatin and pemetrexed (CP) chemotherapy, followed by maintenance therapy using camrelizumab or pemetrexed or camrelizumab plus pemetrexed. Another 40 patients who underwent CP chemotherapy were retrieved as control group. Interestingly, objective response rate (ORR) was elevated in camrelizumab plus CP group compared to CP group (58.1% vs. 32.5%), while disease control rate (DCR) was of no difference between those two groups (83.9% vs. 72.5%). Camrelizumab plus CP achieved a prolonged progression-free survival (PFS) compared with CP alone (11.0 (95% CI: 9.1–12.9) months versus 7.2 (95% CI: 5.1–9.3) months), also realized an increasing overall survival (OS) trend (without statistical significance; 19.3 (95% CI: 15.4–23.2) months versu s 15.1 (95% CI: 13.9–16.3) months). Further multivariate Cox's regression analysis exhibited that camrelizumab plus CP (vs. CP) independently related to prolonged PFS and OS. Moreover, the most common adverse events related to camrelizumab plus CP were fatigue (45.2%), peripheral neuropathy (35.5%), nausea and vomiting (35.5%); furthermore, most adverse events were controllable. Collectively, camrelizumab plus chemotherapy exhibits good efficacy and manageable adverse events in treating advanced non-squamous NSCLC patients. Abstract What is known and objective Camrelizumab, a humanized monoclonal programmed cell death protein-1 antibody independently developed by China, is introduced as a treatment selection for non-small cell lung cancer (NSCLC). This study aimed to evaluate the efficacy and safety of camrelizumab plus chemotherapy in treating advanced non-squamous NSCLC patients. Methods This study retrospectively analysed 31 driver-gene-negative advanced non-squamous NSCLC patients who received a 21-day therapy cycle for four cycles of camrelizumab (intravenous injection, 200 mg/cycle) plus carboplatin and pemetrexed (CP) chemotherapy, followed by maintenance therapy using camrelizumab or pemetrexed or camrelizumab plus pemetrexed. Another 40 patients who underwent CP chemotherapy were retrieved as control group. Results and discussion The objective response rate (ORR) was elevated in camrelizumab plus CP group compared to CP group (58.1% vs. 32.5%, p = 0.031), while disease control rate (DCR) was of no difference between those two groups (83.9% vs. 72.5%, p = 0.255). Camrelizumab plus CP achieved a prolonged PFS compared with CP alone (median: 11.0 (95% CI: 9.1–12.9) months versus 7.2 (95% CI: 5.1–9.3) months, p = 0.026), also realized an increasing OS trend (without statistical significance; 19.3 (95% CI: 15.4–23.2) months versus 15.1 (95% CI: 13.9–16.3) months, p = 0.093). Further multivariate Cox's regression analysis exhibited that camrelizumab plus CP (vs. CP) independently related to prolonged PFS (p < 0.001) and OS (p = 0.027). Moreover, the most common adverse events related to camrelizumab plus CP were fatigue (45.2%), peripheral neuropathy (35.5%), nausea and vomiting (35.5%); furthermore, most a dverse events were controllable. What is new and conclusion Camrelizumab plus chemotherapy exhibits good efficacy and manageable adverse events in treating advanced non-squamous NSCLC patients. View on Web

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Therapeutic potential of recombinant human basic fibroblast growth factor on postoperative patients with chronic rhinosinusitis with nasal polyps

alexandrossfakianakis shared this article with you from Inoreader Therapeutic potential of recombinant human basic fibroblast growth factor on postoperative patients with chronic rhinosinusitis with nasal polyps via Clinical Otolaryngology Abstract Objectives To explore the effect of intranasal administration of recombinant human-basic fibroblast growth factor (rh-bFGF) on postoperative chronic rhinosinusitis with nasal polyps (CRSwNP) patients. Design A prospective, randomized, controlled, single-blinded trial. Setting and Participants 75 hospitalized patients who met the criteria of primary bilateral CRSwNP were enrolled from March 2020 to January 2021. Main outcome measures Visual analogue scale, 22 item Sino-Nasal Outcome Test, Lund-Kennedy (L-K) system, and Scanning electron microscopy and Quantitative real-time PCR. Results 75 patients with CRSwNP were randomly assigned to three groups, and 72 patients completed the 1-month medication regimen and 1 year follow-up. Rh-bFGF nasal-spray and drop application reduced general nasal VAS scores within two weeks after ESS(endoscopic sinus surgery) compared to the control group. In contrast, only rh-bFGF nasal-drops reduced SNOT-22 scores at 2 weeks and 1 year compared with the control group. A significant reduction in the endoscopic L-K score was observed in the rh-bFGF nasal-spray and drop group compared with the control group. This is primarily because rh-bFGF promotes cilia growth in the nasal mucosal epithelium after the operation, as illustrated by scanning electron microscopy and expression of CP110, Tap73 and Foxj1 mRNA. For eosinophilic CRSwNP, the general VAS score of rh-bFGF nasal-drops was more obviously reduced compared to the control group after ESS. A similar trend was observed for L-K score. Conclusions Rh-bFGF nasal-drops and sprays can quickly and effectively relieve postoperative symptoms and improve long-term prognosis of patients with CRSwNP. Moreover, rh-bFGF nasal-drops is also an effective method for postoperative patients with eosinophilic CRSwNP. View on Web

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Comparative Evaluation of the Antibacterial Effect of Allium Sativum, Calcium hydroxide and Their Combination as Intracanal Medicaments in Infected Mature Anterior Teeth A Randomized Clinical Trial

alexandrossfakianakis shared this article with you from Inoreader Comparative Evaluation of the Antibacterial Effect of Allium Sativum, Calcium hydroxide and Their Combination as Intracanal Medicaments in Infected Mature Anterior Teeth A Randomized Clinical Trial via International Endodontic Journal Abstract Aim The purpose of this study was to compare the antibacterial effects of Allium Sativum (garlic extract), calcium hydroxide (Ca (OH)2), and their combination as intracanal medicaments in infected mature anterior teeth using real-time PCR. Material& Methods This prospective double-blind, controlled, parallel, superiority, randomized clinical trial was carried out on sixty-six permanent, necrotic incisors associated with asymptomatic apical periodontitis in sixty-six male patients. Patients were randomly divided into three groups (n =22) according to the intra -canal medications used. After access preparation, four microbiological samples (S) were taken using sterile absorbent paper points as follows: S1: before canal instrumentation. S2: after cleaning and shaping. The third samples (S3) and fourth samples (S4) were taken after the placement of the tested intracanal medications into their corresponding canals for 7 and 14 days, respectively. Total DNA was extracted from microbiological samples and relative quantitative real time PCR reactions were done to quantify the relative gene expression fold change (FC) for Enterococcus faecalis and Streptococcus species. At significance level p ≤ 0.05, the data were statist ically analyzed in SPSS software using Kruskal-Wallis and Freidman's tests, followed by Dunn-Bonferroni post-hoc test for pairwise comparisons. Results Both bacterial mean FC decreased significantly after mechanical instrumentation (S1 to S2) in all groups. However, no statistically significant differences were found after intra-canal medicament placement (from S2 to S3 and from S3 to S4) except in the garlic group. Garlic significantly reduced Enterococcus faecalis FC in S3 and S4 when compared to Ca (OH) 2 and Ca (OH) 2+ garlic combination. However, garlic and Ca (OH)2 reduced Streptococcus bacteria in S3 similarly. While in S4, garlic showed significantly more reduction than Ca (OH) 2. The combination of Ca (OH) 2 with garlic extract showed the least significant bacterial reduction. Conclusion within the study limitations, garlic intra-canal medicament has a comparable anti-Streptococcus efficiency to Ca (OH) 2, while it is more effective against Enterococcus faecalis species. When Ca (OH)2 and garlic are combined, their antibacterial effectiveness is reduced. Increasing the time of application for tested intracanal medicaments by more than one week has no additional antibacterial effectiveness. View on Web

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Bead‐anchored surgical templates for static computer‐assisted implant surgery (s‐CAIS) – A dental technique

alexandrossfakianakis shared this article with you from Inoreader Bead‐anchored surgical templates for static computer‐assisted implant surgery (s‐CAIS) – A dental technique via Journal of Prosthodontics Abstract This technique report describes an alternative method to stabilize surgical templates throughout full-arch static computer-assisted implant surgery (FA s-CAIS). In FA s-CAIS, remaining teeth, mucosa, existing implants, custom occlusal device, bone, or any combination thereof, could be used as an initial positioning mechanism to position surgical templates. Different anchoring mechanisms are then used to stabilize the surgical templates during surgery. In this report, a novel design of surgical templates using remaining dentition and opposing occlusal surfaces as initial positioning mechanism followed by the combination of bone block fixation screw and stainless-steel beads as secondary anchoring mechanisms is described. The advantages, limitations, and comparisons with surgical templates using other anchoring mechanisms are also discussed. This article is protected by copyright. All rights reserved View on Web

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Masking ability of resin composites: Effect of the layering strategy and substrate color

alexandrossfakianakis shared this article with you from Inoreader Masking ability of resin composites: Effect of the layering strategy and substrate color via Journal of Esthetic and Restorative Dentistry Abstract Objective To evaluate the effect of layering strategy and substrate color on the masking ability of resin composites. Materials and Methods A1-shaded specimens from Charisma Diamond and Filtek Z350XT were produced using different layering strategies. Color measurements were made by a reflectance spectrophotometer over A2, C2, A3.5, C3, C4 substrates. Color differences were calculated and interpreted by the 50%:50% perceptibility and acceptability visual thresholds. Data was analyzed by Kruskal–Wallis and Dunn post hoc test. Chi-square test was used to determine the association between masking ability, and independent variables. Results Color differences were significantly lower on A2 and C2 in comparison with C4 for the majority of the layering strategies. Acceptable matches were observed on most of the combinations over A2. Moderately unacceptable mismatches were observed in most of the combinations over C2 and A3.5. Clearly unacceptable mismatches were observed on the C3 and C4. The ΔE 00 color shifts were predominantly influenced by ΔL 00 for all layering strategies and substrate colors. Conclusion Masking ability was affected by the layering strategy and substrate color. Acceptable masking was associated with A2 and C2, and with layering strategy composed of 0.5 mm enamel opacity and 1.0 mm dentin opacity thicknesses, using the Filtek Z350XT. Clinical Significance Resin composites—shade A1—applied by different layering strategies with a final thickness of 1.5 mm were able to mask mild and moderately discolored substrates. Severely discolored substrates were not masked effectively. View on Web

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The malignant property of circHIPK2 for angiogenesis and chemoresistance in non-small cell lung cancer

alexandrossfakianakis shared this article with you from Inoreader The malignant property of circHIPK2 for angiogenesis and chemoresistance in non-small cell lung cancer via ScienceDirect Publication: Experimental Cell Research Publication date: Available online 19 July 2022 Source: Experimental Cell Research Author(s): Mingming Ren, Xiang Song, Jieting Niu, Guojie Tang, Zhen Sun, Yanguang Li, Fanyi Kong View on Web

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Orthopedic Surgery Causes Gut Microbiome Dysbiosis and Intestinal Barrier Dysfunction in Prodromal Alzheimer Disease Patients: A Prospective Observational Cohort Study

alexandrossfakianakis shared this article with you from Inoreader Orthopedic Surgery Causes Gut Microbiome Dysbiosis and Intestinal Barrier Dysfunction in Prodromal Alzheimer Disease Patients: A Prospective Observational Cohort Study via Annals of Surgery - Most Popular Articles Objective: To investigate gut microbiota and intestinal barrier function changes after orthopedic surgery in elderly patients with either normal cognition (NC) or a prodromal Alzheimer disease phenotype (pAD) comprising either subjective cognitive decline (SCD) or amnestic mild cognitive impairment (aMCI). Background: Homeostatic disturbances induced by surgical trauma and/or stress can potentially alter the gut microbiota and intestinal barrier function in elderly patients before and after orthopedic surgery. Methods: In this prospective cohort study, 135 patients were subject to preoperative neuropsychological assessment and then classified into: NC (n=40), SCD (n=58), or aMCI (n=37). Their gut microbiota, bacterial endotoxin (lipopolysaccharide), tight junction (TJ) protein, and inflammatory cytokines in blood were measured before surgery and on postsurgical day 1, 3, and 7 (or before discharge). Results: The short-chain fatty acid (SCFA)-producing bacteria were lower while the gram-negative bacteria, lipopolysaccharide and TJ were higher preoperatively in both the SCD and aMCI (pAD) groups compared with the NC group. After surgery, a decrease in SCFA-producing bacteria, and an increase in both gram-negative bacteria and plasma claudin were significant in the pAD groups relative to the NC group. SCFA-producing bacteria were negatively correlated with TJ and cytokines in pAD patients on postsurgical day 7. Furthermore, surgery-induced perioperative metabolic stress and inflammatory responses were associated with gut microbiota alterations. Conclusions: Surgery exacerbates both preexisting microbiota dysbiosis and intestinal barrier dysfunction in pAD patients, all of which may be associated with systemic inflammation and, in turn, may lead to further cognitive deterioration. View on Web

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