Cytosolic DNA Sensors Activation Inhibits HIV Infection of Macrophages

alexandrossfakianakis shared this article with you from Inoreader Cytosolic DNA Sensors Activation Inhibits HIV Infection of Macrophages via Journal of Medical Virology Abstract Cytosolic recognition of microbial DNA in macrophages results in the activation of the interferon (IFN) dependent antiviral innate immunity. Here, we examined whether activating DNA sensors in peripheral blood monocyte-derived macrophages (MDMs) can inhibit HIV. We observed that the stimulation of MDMs with poly(dA:dT) or poly(dG:dC) (synthetic ligands for the DNA sensors) inhibited HIV infection and replication. MDMs treated with poly(dA:dT) or poly(dG:dC) expressed higher levels of both type I and type III IFNs than untreated cells. Activation of the DNA sensors in MDMs also induced the expression of the multiple intracellular anti-HIV factors, including IFN-stimulated genes (ISGs: ISG15, ISG56, Viperin, OAS2, GBP5, MxB and Tetherin) and the HIV restriction microRNAs (miR-29c, miR-138, miR-146a, miR-155, miR-198, and miR-223). In addition, the DNA sensor activation of MDM upregulated the expression of the CC chemokines (RANTES, MIP-1α, MIP-1β), the ligan ds for HIV entry coreceptor CCR5. These observations indicate that the cytosolic DNA sensors have a protective role in the macrophage intracellular immunity against HIV and that targeting the DNA sensors has therapeutic potential for immune activation-based anti-HIV treatment. This article is protected by copyright. All rights reserved. View on Web

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Impact of Serial Intralesional Steroid Injections on Idiopathic Subglottic Stenosis

alexandrossfakianakis shared this article with you from Inoreader Impact of Serial Intralesional Steroid Injections on Idiopathic Subglottic Stenosis via The Laryngoscope Objectives Serial intralesional steroid injection (SILSI) has been increasingly used to treat idiopathic subglottic stenosis (iSGS). Prior studies have shown effectiveness, but not in all patients. This multi-institutional study evaluates the effect of SILSI on time to recurrent operation, peak expiratory flow (PEF), and dyspnea. Methods Post-hoc secondary analysis of the North American Airway Collaborative data were performed to evaluate the outcomes of iSGS patients undergoing and not undergoing SILSI. The primary outcome was time to recurrent operation, evaluated using Kaplan–Meier curves and Cox regression analysis. Secondary outcomes were change in PEF and clinical chronic obstructive pulmonary disease questionnaire (CCQ) score. Within patients undergoing SILSI, demographics, time from last procedure, and PEF at initiation of SILSI were evaluated to determine the effect on recurrence. Results Two hundred and ninety patients were included, 238 undergoing endoscopic dilation alone and 52 undergoing dilation and SILSI. No differences in baseline characteristics were observed. There was no difference in time to recurrence (hazard ratio: 0.64; p = 0.183). There were no differences in PEF or CCQ across the 2.5-year study period. Among 52 patients undergoing SILSI, PEF at the time of starting SILSI did not affect recurrence (χ 2 = 0.09, p = 0.77). Conclusion Patients undergoing and not undergoing SILSI had similar times to recurrence, PEF, and CCQ. Factors predicting recurrence among patients undergoing SILSI were not identified. These results support a randomized controlled trial with a uniform SILSI protocol to quantify the effects of SILSI on objective and subjective outcomes and help determine which iSGS patients benefit most. Level of Evidence 3 Laryngoscope, 2022 View on Web

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Diagnostic performance of magnetic resonance imaging for degenerative temporomandibular joint disease

alexandrossfakianakis shared this article with you from Inoreader Diagnostic performance of magnetic resonance imaging for degenerative temporomandibular joint disease via Journal of Oral Rehabilitation Abstract Background Degenerative joint disease (DJD) of the temporomandibular joint (TMJ) is an important type of temporomandibular disorders (TMDs) potentially leading to orofacial pain and jaw dysfunction. Magnetic resonance imaging (MRI) is important in TMD diagnosis; however, its diagnostic ability for DJD remains unknown. Objective To explore the utility of MRI in diagnosing DJD according to the latest diagnostic criteria for TMD and detecting condylar bone abnormalities and their severity. Methods Overall, 122 participants were examined using cone-beam computed tomography (CBCT) and MRI. The sensitivity, specificity, and accuracy of MRI for detecting DJD and different types of TMJ condylar bone abnormalities were calculated (considering CBCT as gold standard); in addition, we tested MRI and CBCT's consistency in scoring five types of condylar bone abnormalities. Results The sensitivity and specificity of MRI for DJD were 95.3% and 43.1%, respectively.The MRI sensitivities for condylar flattening, erosion, osteophytes, sclerosis, and cysts were 98.6%, 96.2%, 79.4%, 50%, and 79.2% (specificity, 53.6%, 48.3%, 81.6%, 83.3%, and 88.2%, respectively), respectively. The consistency between MRI and CBCT in assessing the severity of condylar bone abnormalities was fair-to-moderate (kappa coefficient: 0.278-0.491). The inter-observer consistency for CBCT was good, whereas for MRI it was relatively poor. Conclusion MRI can detect DJD and condylar bone abnormalities. However, MRI could not efficiently detect the severity of condylar bone abnormalities. View on Web

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Broadly Neutralizing Antibodies for HIV Treatment: Broad in Theory, Narrow in Reality

alexandrossfakianakis shared this article with you from Inoreader Broadly Neutralizing Antibodies for HIV Treatment: Broad in Theory, Narrow in Reality via Clinical Infectious Diseases Advance Access Abstract In this viewpoint we briefly review the status of antiretroviral therapy, its unmet needs, and the role that broadly neutralizing antibodies (bNAbs) might have in the near future for the treatment of HIV. We summarize advances in the development of bNAbs as antiretroviral therapy, the results of main clinical trials of bNAbs for HIV treatment and prevention, and its role in cure trials. The limitations of broadly neutralizing antibodies are the current need for primary re sistance testing, the still unclear number of antibodies that must be combined, the lack of penetration in anatomical reservoirs and the role they might play in cure studies. We compare the advantages and disadvantages of "classical ART" and therapy based on broadly neutralizing antibodies. We conclude that broadly neutralizing antibodies still need considerable improvements before they can be considered an alternative to "classical ART". View on Web

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LANA regulates miR‐155 /GATA3 signaling axis by enhancing c‐Jun/c‐Fos interaction to promote the proliferation and migration of KSHV‐infected cells

alexandrossfakianakis shared this article with you from Inoreader LANA regulates miR‐155 /GATA3 signaling axis by enhancing c‐Jun/c‐Fos interaction to promote the proliferation and migration of KSHV‐infected cells via Journal of Medical Virology Abstract Kaposi's sarcoma (KS) is the second most common tumor in people infected with human immunodeficiency virus worldwide, but its pathogenesis is still unclear. In this study, we discovered that the expression of GATA-binding protein 3 (GATA3) was lowly expressed in KS tissues and KSHV-infected cells, while microRNA-155 (miR-155) was highly expressed in KS serum and KSHV-infected cells. miR-155 promoted the proliferation, migration and invasion of KSHV infection by targeting GATA3. Further, The KSHV-encoded protein, the Latency associated nuclear antigen (LANA), promotes the proliferation, migration and invasion of KSHV-infected cells by regulating the miR-155/GATA3 axis. Regarding the molecular mechanism, c-Jun and c-Fos interact to form a complex. LANA up-regulates the expression of c-Jun and c-Fos and enhances the formation of c-Jun/c-Fos complex. The complex binds to the -95 ~ -100 bp site of miR-155 promoter and transcriptionally activates miR-155. All in a ll, LANA enhances the c-Jun/c-Fos interaction, resulting in enhanced transcriptional regulation of miR-155 by the c-Jun/c-Fos complex, thereby downregulating GATA3 and promoting the proliferation, migration and invasion of KSHV-infected cells. The discovery of LANA/c-Jun/c-Fos/miR-155/GATA3 further refines the pathogenesis of KS, potentially opening a new avenue for developing effective drugs against KS. This article is protected by copyright. All rights reserved. View on Web

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Exhaled Breath Aerosol Shedding by Highly Transmissible Versus Prior SARS-CoV-2 Variants

alexandrossfakianakis shared this article with you from Inoreader Exhaled Breath Aerosol Shedding by Highly Transmissible Versus Prior SARS-CoV-2 Variants via Clinical Infectious Diseases Advance Access Abstract Background Aerosol inhalation is recognized as the dominant mode of SARS-CoV-2 transmission. Three highly transmissible lineages evolved during the pandemic. One hypothesis to explain increased transmissibility is that natural selection favors variants with higher rates of viral aerosol shedding. However, the extent of aerosol shedding of successive SARS-CoV-2 variants is unknown. We aimed to measure the infectivity and rate of SARS-CoV-2 shedding into exhaled breath aerosol (EBA) by individuals during the Delta and Omicron waves and compared those rates with those of prior SARS-CoV-2 variants from our previously published work. Methods COVID-19 cases (n = 93, 32 vaccinated and 20 boosted) were recruited to give samples, including 30-minute breath samples into a Gesundheit-II exhaled breath aerosol sampler. Samples were quantified for viral RNA using RT-PCR and cultured for virus. Results Alpha (n = 4), Delta ( n = 3), and Omicron (n = 29) cases shed significantly more viral RNA copies into exhaled breath aerosols than cases infected with ancestral strains and variants not associated with increased transmissibility (n = 57). All Delta and Omicron cases were fully vaccinated and most Omicron cases were boosted. We cultured virus from the EBA of one boosted and three fully vaccinated cases. Conclusions Alpha, Delta, and Omicron independently evolved high viral aerosol shedding phenotypes, demonstrating convergent evolution. Vaccinated and boosted cases can shed infectious SARS-CoV-2 via EBA. These findings support a dominant role of infectious aerosols in transmission of SARS-CoV-2. Monitoring aerosol shedding from new variants and emerging pathogens can be an important component of future threat assessments and guide interventions to prevent transmission. View on Web

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Src family kinase targeting in head and neck tumor cells using SU6656, PP2 and dasatinib

alexandrossfakianakis shared this article with you from Inoreader Src family kinase targeting in head and neck tumor cells using SU6656, PP2 and dasatinib via Head & Neck Abstract Background We have recently shown a frequent upregulation of Src-family kinases (SFK) in head and neck squamous cell carcinoma (HNSCC). Here we tested, if SFK targeting is effective especially in HNSCC cells with upregulated SFK signaling. Methods The impact of SFK inhibitors SU6656, PP2 and dasatinib on three HNSCC cell lines with different SFK activity levels was analyzed using proliferation and colony formation assays, Western blot and functional kinomics. Results Proliferation was blocked by all inhibitors in a micro-molar range. With respect to cell kill, dasatinib was most effective, while SU6656 showed moderate and PP2 minor effects. Cellular signaling was affected differently, with PP2 having no effect on SFK signaling while dasatinib probably has non-SFK specific effects. Only SU6656 showed clear SFK specific effects on signaling. Conclusion The results demonstrate potential benefit of SFK inhibition in HNSCC but they also highlight challenges due to non-specificities of the different drugs. View on Web

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The influence of apical periodontitis on circulatory inflammatory mediators in peripheral blood: a prospective case‐control study

alexandrossfakianakis shared this article with you from Inoreader The influence of apical periodontitis on circulatory inflammatory mediators in peripheral blood: a prospective case‐control study via International Endodontic Journal Abstract Aim To explore the influence of apical periodontitis (AP) on inflammatory markers in blood of otherwise healthy individuals and to depict the inflammatory profile of the healing after dental extraction. Methodology This is a prospective case-control intervention study, during which, individuals with a diagnosis of AP of one affected tooth were included, along with a control group matched for age and gender. A broad panel of blood inflammatory mediators were examined longitudinally in all subjects during 6 visits. In the case of the AP subjects, the tooth with AP was extracted at the third visit. Results were analyzed by linear regression analyses and linear mixed model analyses. Results A total of 53 subjects were included in the study, 27 with AP and 26 without. Fifteen females and 12 males were included in the AP group, and 14 females and 12 males in the control group. At baseline, G-CSF (P<0.001), IL-1β (P=0.03) and IL-4 (P=0.01) were significantly lower in AP subjects than in controls. Comparison of the differences between baseline and the last visit, i.e., three months after the tooth extraction, showed a significant reduction in IL-10 (P=0.03) and IL-12p70 (P=0.01). Conclusions The immunologic profile of chronic AP in one tooth and its healing profile reveals a systemic low-grade inflammation through compensatory immunosuppression. A larger lesion or multiple lesions could disrupt the balance that the system is trying to maintain, resulting in loss of homeostasis. View on Web

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Subgingival host‐microbiome metatranscriptomic changes following scaling and root planning in Grade II/III Periodontitis

alexandrossfakianakis shared this article with you from Inoreader Subgingival host‐microbiome metatranscriptomic changes following scaling and root planning in Grade II/III Periodontitis via Journal of Clinical Periodontology Abstract Aims To assess the effects of scaling and root planning (SRP) on the dynamics of gene expression by the host and the microbiome in subgingival plaque samples. Methods Fourteen periodontitis patients were closely monitored in the absence of periodontal treatment for 12 months. During this period, comprehensive periodontal examination and subgingival biofilm sample collection were performed bi-monthly. After 12 months, clinical attachment level (CAL) data was compiled and analyzed using linear mixed models (LMM) fitted to longitudinal CAL measurements for each tooth site. LMM classified sites as stable (S), progressing (P), or fluctuating (F). After 12 month visit, subjects received SRP and at 15 months they received comprehensive examination and supportive periodontal therapy (SPT). Those procedures were repeated at the 18 month visit, when patients were also sampled. Each patient contributed with one S, one P and one F site collected at 12 and 18 month visits. Samples were analyzed using Dual RNA-Sequencing to capture host and bacterial transcriptomes simultaneously. Results Microbiome and host response behavior were specific to the site's progression classification (i.e., S, P or F). Microbial profiles of pre and post-treatment samples exhibited specific microbiome changes, with progressing sites showing the most significant changes. Among them, P. gingivalis was reduced after treatment, while F. nucleatum showed an increase in proportion. Transcriptome analysis of the host response showed that IL-17, TNF signaling pathways, and neutrophil extracellular trap (NETs) formation were the primary immune response activities impacted by periodontal treatment. Conclusion Scaling and root planing resulted in a significant "rewiring" of host and microbial activities in the progressing sites, while in stable and fluctuating sites, the restructuring of the microbiome was minor. This article is protected by copyright. All rights reserved. View on Web

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‘Pillow technique’ to improve lip support in the context of zygoma implant rehabilitation

alexandrossfakianakis shared this article with you from Inoreader 'Pillow technique' to improve lip support in the context of zygoma implant rehabilitation via International Journal of Oral and Maxillofacial Surgery via MedWorm.com This study proposes a simple, off-the-shelf ancillary method for application in the dental rehabilitation of severe maxillary atrophy with zygoma implants, allowing simultaneous improvement of lip support in cases with a moderate lack of premaxillary projection. Three consecutive patients with an atrophic maxilla were evaluated retrospectively. All were treated with a fixed rehabilitation over four zygomatic implants and the pillow technique. The study variables included radiological assessment of the premaxilla volume, upper lip and perinasal soft tissue changes, clinical complications, and subjective evaluation of functional and aesthetic patient satisfaction based on a visual analogue scale. (Source: International Journal of Oral and Maxillofacial Surgery) View on Web

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