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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Changes in the syphilis reactive plasma regain (RPR) titre between diagnosis and treatment

alexandrossfakianakis shared this article with you from Inoreader Changes in the syphilis reactive plasma regain (RPR) titre between diagnosis and treatment via Clinical Infectious Diseases Advance Access Abstract Background We compared the reactive plasma regain (RPR) titre on the day of initial presentation to the day of syphilis treatment to inform clinical practice as to whether a repeat RPR test should be recommended. Methods We undertook a retrospective study between 1-March-2011 and 31-December-2020 at the Melbourne Sexual Health Centre in Australia among individuals who received syphilis serology on the day of initial presentation and the day of treatment, if it were within 14 days after initial presentation. We calculated the percentage of individuals with a four-fold or greater RPR change, stratified by the time between initial presentation and treatment, and syphilis stages. Results Of the 766 included syphilis cases, the median number of days between initial presentation and treatment was 6 (IQR = 5-7). There were 14.8% (n = 113) of cases that had a four-fold increase o r decrease between the day of initial presentation and the day of treatment. The number of cases with a 4-fold increase or decrease in RPR titre increased with increasing number of days between the day of initial presentation and day of treatment, i.e., 4.1% (n = 6) within 1-3 days after initial presentation to 25.7% (n = 27) with 10-14 days after initial presentation (ptrend < 0.0001). There was no significant difference in the number of cases with 4-fold increase or decrease in RPR between syphilis stages (p = 0.37). Conclusion Our data support the recommendation of repeating the RPR titre if the day of initial presentation and treatment are different, even when treatment is within a few days of the initial presentation. 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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Risk estimation of degenerative joint disease in temporomandibular disorder patients with different types of sagittal and coronal disc displacements: MRI and CBCT analysis

alexandrossfakianakis shared this article with you from Inoreader Risk estimation of degenerative joint disease in temporomandibular disorder patients with different types of sagittal and coronal disc displacements: MRI and CBCT analysis via Journal of Oral Rehabilitation Abstract Background Degenerative joint disease (DJD) can be associated with disc displacement (DD) in temporomandibular disorder (TMD) patients. However, the relationship between different types of DDs and DJD remains unclear. Objectives To investigate the odds ratios of different types of sagittal and coronal DDs confirmed by magnetic resonance imaging (MRI) and DJD confirmed by cone-beam computed tomography (CBCT) in TMD patients. Methods Radiographic data from 69 males and 232 females were collected for analysis. CBCT was used to diagnose DJD, with criteria including erosion, osteophytes, generalized sclerosis, and cysts in the joint. Eight types of DDs were evaluated by sagittal and coronal MRIs: NA, no abnormality; SW, sideways; ADDR, anterior with reduction; ADDR+SW; ADDNR, anterior without reduction; ADDNR+SW; single SW; PDD, posterior; PDD+SW. The odds ratios of DJD in joints with different types of DDs were determined after joint correlation, age, and gender adjustment. Results Compared with NA, the odds ratio of DJD in ADDR was 2.397 (95% CI [confidence interval]: 1.070-5.368), ADDR+SW was 4.808 (95% CI: 1.709-3.528), ADDNR was 29.982 (95% CI: 15.512-57.950), and ADDNR+SW was 25.974 (95% CI: 12.743-52.945). Erosion was significantly increased in ADDR, ADDR+SW, ADDNR and ADDNR+SW; osteophytes were significantly increased in ADDR+SW, ADDNR and ADDNR+SW; and generalized sclerosis and cysts were significantly increased in ADDNR and ADDNR+SW. There were no significant associations between single SW, PDD, PDD+SW and DJD. Conclusions ADDR, ADDR+SW, ADDNR, and ADDNR+SW were associated with DJD. ADDNR had a significantly higher prevalence of DJD than ADDR. There were no significant relationships between single SW, PDD, PDD+SW and DJD. 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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Influence of genetic polymorphisms on mechanical pain sensitivity and endogenous pain modulation of trigeminal and spinal areas

alexandrossfakianakis shared this article with you from Inoreader Influence of genetic polymorphisms on mechanical pain sensitivity and endogenous pain modulation of trigeminal and spinal areas via Journal of Oral Rehabilitation Abstract Background Previous evidence indicates significant association between genetic polymorphisms and phenotypes related to pain sensitivity in patients with temporomandibular disorders (TMD). Despite the important advances in cataloging diverse factors such as sleep disorders, anxiety and depression, the interrelated mechanisms of painful TMD etiopathogenesis still need investigation. Objectives This case-control study aimed to evaluate the influence of genetic polymorphisms (rs6296, rs6295, rs1799971, rs4680, rs4633, rs4818) and psychosocial factors on the mechanical pain sensitivity and endogenous pain modulation in women with painful TMD and asymptomatic controls. Methods We evaluated six independent variables: anxiety levels, depression, stress, sleep quality, pain catastrophizing and genetic polymorphisms, and four dependent variables: mechanical pain threshold (MPT), pressure pain threshold (PPT), wind-up ratio (WUR) and conditioned pain modulation (CPM) collected at masseter (trigeminal) and hand (spinal) areas in a sample of 95 painful TMD patients and 85 controls. A regression model was used to test the possible effect of the independent variables on dependent variables. Results The regression model was significant for MPT (F11,168 = 9.772; R2=0.390). Painful TMD diagnoses and sleep quality were associated with trigeminal MPT (B coefficient = -0.499; and B coefficient = -0.211, respectively). WUR was associated with rs6295 and rs6746030 for, respectively, the spinal and trigeminal area. Conclusion Genetic polymorphisms had a slight contribution to endogenous pain modulation as indicated by the significant association with WUR but did not contribute to mechanical pain sensitivity. On the other hand, the presence of painful TMD and the sleep quality contributed significantly to mechanical pain sensitivity. View on Web

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