A lung–joint axis in smokers with RA?
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The impact of e-cigarette use on periodontal health: a systematic review and meta-analysis
Electronic Nicotine Delivery Systems (ENDS, e-cigarettes) are a popular alternative to traditional tobacco smoking. Objective: To evaluate the effect of ENDS use on periodontal health.
SMARCB1-driven EGFR-GLI1 epigenetic alterations in lung cancer progression and therapy are differentially modulated by MEOX2 and GLI-1
Lung cancer remains the leading cause of cancer-related mortality globally, with genes such as SMARCB1, MEOX2, and GLI-1 playing significant roles in its malignancy. Despite their known involvement, the specific molecular contributions of these genes to lung cancer progression, particularly their effects on epigenetic modifications on oncogenes sequences as EGFR and GLI-1, and their influence in the response to EGFR-TKI-based therapies, have not been fully explored. Our study reveals how MEOX2 and GLI-1 are key molecular modulators of the GLI-1 and EGFR-epigenetic patterns, which in turn transcriptionally and epigenetically affect EGFR gene expression in lung cancer. Additionally, MEOX2 was found to significantly promote in vivo lung tumor progression and diminish the effectiveness of EGFR-TKI therapies. Conversely, mSWI/SNF derived subunit SMARCB1 was detected to suppress tumor growth and enhance the oncological therapeutic response in in vivo studies by inducing epigenetic modifications in the GLI-1 and EGFR genetic sequences. Furthermore, our results suggest that BRD9 may contribute to the activation of both lung cancer oncogenes GLI-1 and EGFR. Such findings suggest that SMARCB1 and MEOX2 could serve as important prognosis biomarkers and target genes in human lung cancer therapy, offering new opportunities for the development of more effective and selective treatment strategies in the field of lung malignant diseases.
Inhibition of GSK3β is synthetic lethal with FHIT loss in lung cancer by blocking homologous recombination repair
FHIT is a fragile site tumor suppressor that is primarily inactivated upon tobacco smoking. FHIT loss is frequently observed in lung cancer, making it an important biomarker for the development of targeted therapy for lung cancer. Here, we report that inhibitors of glycogen synthase kinase 3 beta (GSK3β) and the homologous recombination DNA repair (HRR) pathway are synthetic lethal with FHIT loss in lung cancer. Pharmacological inhibition or siRNA depletion of GSK3β selectively suppressed the growth of FHIT-deficient lung cancer tumors in vitro and in animal models. We further showed that FHIT inactivation leads to the activation of DNA damage repair pathways, including the HRR and NHEJ pathways, in lung cancer cells. Conversely, FHIT-deficient cells are highly dependent on HRR for survival under DNA damage stress. The inhibition of GSK3β in FHIT-deficient cells suppressed the ATR/BRCA1/RAD51 axis in HRR signaling via two distinct pathways and suppressed DNA double-strand break repair, leading to the accumulation of DNA damage and apoptosis. Small molecule inhibitors of HRR, but not NHEJ or PARP, induced synthetic lethality in FHIT-deficient lung cancer cells. The findings of this study suggest that the GSK3β and HRR pathways are potential drug targets in lung cancer patients with FHIT loss.
Cigarette smoking is associated with reduced neuroinflammation and better cognitive control in people living with HIV
People living with HIV (HIV+) are roughly twice as likely to smoke cigarettes (Smok+) as the general population. With the advent of effective antiretroviral therapies, it is increasingly important to understand the effects of chronic HIV infection and cigarette smoking on brain function and cognition since HIV+ individuals have heightened neuroinflammation and cognitive deficits even with such therapies. Based on prior studies demonstrating that smoking reduces a marker for neuroinflammation in HIV- individuals, we hypothesized that HIV+/Smok+ individuals would have less neuroinflammation and better cognitive control than HIV+/Smok- individuals. Fifty-nine participants (HIV-/Smok- [n = 16], HIV-/Smok+ [n=14], HIV+/Smok- [n = 18], and HIV+/Smok+ [n = 11]) underwent baseline eligibility tests, positron emission tomography (PET) scanning to determine levels of a marker for neuroinflammation, and assessment of cognitive control with the reverse-translated 5-choice continuous performance test (5C-CPT), with smokers having smoked to satiety prior to testing. For the PET data, a significant effect of smoking status on whole brain (WB) standardized uptake value (SUV) was found between HIV+/Smok+ and HIV+/Smok- participants (due to 18.8% lower WB SUV in the HIV+/Smok+ group). HIV+/Smok- participants exhibited a mean 13.5% higher WB SUV than HIV-/Smok- participants. For the 5C-CPT, HIV+/Smok+ participants performed significantly better than HIV+/Smok- participants (d prime), and HIV+/Smok- participants performed worse than HIV-/Smok- participants. Thus, HIV+/Smok+ individuals demonstrated lower levels of the neuroinflammation marker and better cognitive control than HIV+/Smok- individuals. Given that HIV+ individuals whose HIV is well-controlled can still have chronic neurocognitive complications, study results suggest possible paths for future research into nicotine-related treatments to prevent such complications.
Lung microbial-host interface through the lens of multi-omics
In recent years, our understanding of the microbial world within us has been revolutionized by the use of culture-independent techniques. The use of multi-omic approaches can now not only comprehensively characterize the microbial environment but also evaluate its functional aspects and its relationship with the host immune response. Advances in bioinformatics have enabled high throughput and in-depth analyses of transcripts, proteins and metabolites and enormously expanded our understanding of the role of the human microbiome in different conditions. Such investigations of the lower airways have specific challenges but as the field develops, new approaches will be facilitated. In this review, we focus on how integrative multi-omics can advance our understanding of the microbial environment and its effects on the host immune tone in the lungs.
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