Αρχειοθήκη ιστολογίου

Τετάρτη 26 Οκτωβρίου 2022

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

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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.

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Hit and Run oncogeneses in Head and Neck Cancers requires greater investigation

alexandrossfakianakis shared this article with you from Inoreader

Abstract

Head and neck cancers are unique in so far that 2 major oncogenic viruses, EBV and HPV infect adjacent anatomy and cause nasopharyngeal and oropharyngeal cancers respectively. Dominant recognised carcinogens are alcohol and tobacco but some head and neck cancers have been found to have mixed carcinogens (including betel leaf, areca nuts, slaked lime, viruses, etc) involved in their oncogenesis and conversely, groups of patients with unknown or less dominant carcinogens involved in their development. These cancers may have had viral involvement in the past but then lost most of their viral nucleic acids (be they DNA and/or RNA) below a detection threshold, thus rendering them virus-negative. Some of these virus-negative tumours appear to have mutagenic signatures associated with virus-positive cancers i.e. from the APOBEC defence mechanism which is known to mutate viral nucleic acids as well as cause collateral damage to host DNA, with subsequent development of strongly viral prejudiced mutational signatures. These mechanisms are likely to be less efficient at oncogenesis than traditional direct EBV and HPV oncogenes driving mutagenesis, thus accounting for the smaller frequencies of these cancers found. More profound investigations of these unusual tumours are warranted to dissect out these mechanistic pathways.

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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

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.

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

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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)
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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

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.

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