Potential Role Research Articles

Experimental Hydrothermal Alteration of Rhyolite and Andesite at 325 °C and 300 Bar: Implications for a Potential Role of Volcanic Glass in the Fluid Composition in the Okinawa Trough

The experimental study of water–rock reactions under high-temperature and -pressure conditions is a useful approach to constrain controlling factors of the fluid composition in a natural hydrothermal system. Previous studies have focused mainly on the mid-ocean ridge fields, and the hydrothermal alteration of intermediate-to-felsic rocks has been less emphasized despite its potential importance in the fluid chemistry in an arc/back-arc basin setting. We examined the alteration processes of fresh rhyolite and andesite rocks collected from the middle and southern Okinawa Trough, respectively, at 325 °C and 300 bar (the estimated condition at the reaction zone in the fields), especially focusing on the behavior of silica between the solid and liquid phases. The experimental fluids are characterized by the high Si concentration up to 30 mM, indicating the substantial dissolution of volcanic glass in the analyzed rocks. The high Si concentration in the fluids was presumably buffered by amorphous silica, precipitated from the fluids as a precursor of hydrothermal quartz, during the experiments. Our results emphasize a previously overlooked role of volcanic glass/amorphous silica in the fluid composition in the Okinawa Trough and are consistent with the previous model of pumice replacement mineralization for the SMS deposit formation in the trough.

Modification of 4-(4-chlorothiophen-2-yl)thiazol-2-amine derivatives for the treatment of analgesia and inflammation: synthesis and in vitro, in vivo, and in silico studies.

Inflammation is a protective response to a variety of infectious agents. To develop a new anti-inflammatory drug, we explored a pharmacologically important thiazole scaffold in this study. In a multi-step synthetic approach, we synthesized seven new thiazole derivatives (5a-5g). Initially, we examined the in vitro anti-inflammatory potentials of our compounds using COX-1, COX-2, and 5-LOX enzyme assays. After in vitro confirmation, the potential compounds were subjected to in vivo analgesic and anti-inflammatory studies. The hot plate method was used for analgesia, and carrageenan-induced inflammation was also assayed. Overall, all our compounds proved to be potent inhibitors of COX-2 compared to celecoxib (IC50 0.05μM), exhibiting IC50 values in the range of 0.76-9.01μM .Compounds 5b, 5d, and 5e were dominant and selective COX-2 inhibitors with the lowest IC50 values and selectivity index (SI) values of 42, 112, and 124, respectively. Similarly, in the COX-1 assay, our compounds were relatively less potent but still encouraging. Standard aspirin exhibited an IC50 value of 15.32μM. In the 5-LOX results, once again, compounds 5d and 5e were dominant with IC50 values of 23.08 and 38.46μM, respectively. Standard zileuton exhibited an IC50 value of 11.00μM. Based on the COX/LOX and SI potencies, the compounds 5d and 5e were subjected to in vivo analgesic and anti-inflammatory studies. Compounds 5d and 5e at concentrations of 5, 10, and 20mg/kg body weight were significant in animal models. Furthermore, we explored the potential role of compounds 5d and 5e in various phlogistic agents. Similarly, both compounds 5d and 5e were also significantly potent in the anti-nociceptive assay. The molecular docking interactions of these two compounds with the target proteins of COX and LOX further strengthened their potential for use in COX/LOX pathway inhibitions.

A step too far: Employer perspectives on in-work conditionality

This chapter explores employer perspectives on the extension of behavioural conditionality to working social security claimants (‘in-work conditionality’). As policymakers across Europe and other developed nations have pursued increasingly interventionist approaches to activating the unemployed through conditional welfare policies, the UK has gone a significant and ‘unprecedented’ step further by requiring those in receipt of in-work benefits to demonstrate their efforts to increase their working hours and/or pay. As the actors ultimately in control over the jobs people can access and progress in, understanding employer perspectives on this new policy development is critical, which, however, has so far been overlooked by policymakers and researchers. We address this omission through presenting original analysis of 84 semi-structured interviews conducted with a diverse group of employers. We find that while the UK’s Work First approach to activation has seemingly encountered little resistance from employers to date, this new Work First, Work More approach may be a step too far. We contribute theoretically by identifying a potential role for employers as latent path disruptors in policy development, and challenge the commonly-held assumption that employers are typically supportive of extensions of behavioural conditionality to social security claimants.

Isoprene: An Antioxidant to Guard Plants against Stress

Isoprene, a lipophilic and unstable compound with the chemical formula C5H8, is transported to plant chloroplasts via the 2-C-methyl-d-erythritol 4-phosphate (MEP) pathway, which relies on photosynthesis. Although only about 20% of terrestrial plants can synthesize isoprene, those that emit it are more adaptable to oxidative and thermal stresses. To shed light on the still-elusive protective mechanism of isoprene, numerous investigations have been conducted. Isoprene has been shown to react with and quench various reactive oxygen species (ROS) such as singlet oxygen (1O2). Its reduced state and conjugated double bonds suggest that it functions as an antioxidant, although this has yet to be conclusively proven. Despite its low abundance relative to other molecules in plant tissues, recent research has explored several potential roles for isoprene including acting as a scavenger of ROS by serving as an antioxidant; strengthening cell membranes; modulating genomic, proteomic and metabolomic profiles; signaling stress responses among neighboring plants compared with other volatile organic compounds (VOCs); regulating metabolic fluxes of hormones produced through the MEP pathway; or even functioning as a free developmental hormone. Future prospective studies, such as identifying the specific receptors for VOCs along with transcription factors (TFs) and other regulatory proteins participating in the signaling pathways and also metabolomic, transcriptomic and physiological analyses could help in comprehending VOC-induced defense responses in plants under stress conditions.

Construction of a ferroptosis and hypoxia-related gene signature in cervical cancer to assess tumour immune microenvironment and predict prognosis

Background This study aimed to investigate the potential role of ferroptosis/hypoxia-related genes in cervical cancer to improve early management and treatment of cervical cancer. Methods All data were downloaded from public databases. Ferroptosis/hypoxia-related genes associated with cervical cancer prognosis were selected to construct a risk score model. The relationship between risk score and clinical features, immune microenvironment and prognosis were analysed. Results Risk score model was constructed based on eight signature genes. Drug prediction analysis showed that bevacizumab and cisplatin were related to vascular endothelial growth factor A. Risk score, as an independent prognostic factor of cervical cancer, had a good survival prediction effect. The two groups differed significantly in degree of immune cell infiltration, gene expression, tumour mutation burden and somatic variation. Conclusions We developed a novel prognostic gene signature combining ferroptosis/hypoxia-related genes, which provides new ideas for individual treatment of cervical cancer.

Advancing In-Depth N-Terminomics Detection with a Cleavable 2-Pyridinecarboxyaldehyde Probe.

Proteolysis, an irreversible post-translational modification catalyzed by proteases, plays a crucial role in various biological processes. Exploring abnormally hydrolyzed proteins in pathological tissues is a valuable approach for elucidating the mechanisms underlying disease development. Herein, we have developed a cleavable 2-pyridinecarboxyaldehyde probe (2PCA-Probe) that enables efficient and in-depth N-terminomics detection, addressing limitations of previous methods. Furthermore, we unexpectedly discovered a new marker capable of identifying N-terminal chemical labeling with the 2PCA-Probe and elucidated the reaction mechanism. Using this probe, we identified 4686 N-terminal peptides in colorectal cancer and adjacent tissues, significantly expanding the depth of the N-terminome and revealing the potential role of abnormal protein hydrolysis in colorectal cancer development.

Construction and validation of m6A-related diagnostic model for psoriasis.

Psoriasis is a chronic immune-mediated inflammatory disease. N6-methyladenosine (m6A) is involved in numerous biological processes in both normal and diseased states. Herein, we aimed to explore the potential role of m6A regulators in the diagnosis of psoriasis and predict molecular mechanisms by which m6A regulators impact psoriasis. GSE30999 (170 human skin tissue samples) and GSE13355 (180 human skin tissue samples) were downloaded as the training analysis dataset and validation dataset respectively. M6A-related genes were obtained from the literature and their expression levels in GSE30999 samples were measured to identify M6A-related DEGs between psoriasis lesions (LS) and non-lesional lesions (NL). We identified m6A-related DEGs using differential expression analysis and assessed their interactions through correlation analysis and network construction. A logistic regression analysis followed by LASSO optimization was employed to select m6A-related DEGs for the construction of a diagnostic model. The performance of the model was validated using support vector machine (SVM) methodology with sigmoid kernel function and extensive cross-validation. Additionally, the correlation between m6A-related DEGs and immune cell infiltration was analyzed, as well as the association of these DEGs with psoriasis subtypes. Functional analysis of the m6A-related DEGs included the construction of regulatory networks involving miRNAs, transcription factors (TFs), and small-molecule drugs. The m6A modification patterns were also explored by examining the gene expression differences between psoriasis subtypes and their enriched biological pathways. Finally, the expression of significant m6A regulators involved in the diagnostic model was examined by RT-qPCR. In this study, ten optimal m6A-related DEGs were identified, including FTO, IGF2BP2, METTL3, YTHDC1, ZC3H13, HNRNPC, IGF2BP3, LRPPRC, YTHDC2, and HNRNPA2B1. A diagnostic model based on these m6A-related DEGs was constructed, demonstrating high diagnostic accuracy with an area under the curve (AUC) in GSE30999 and GSE13355 of 0.974 and 0.730, respectively. Meanwhile, the expression level of m6A regulators verified by RT-qPCR was consistent with the results in GSE30999. The infiltration of activated mast cells and NK cells was significantly associated with all ten m6A-related DEGs in psoriasis. Among them, YTHDC1, HNRNPC, and FTO were targeted by most miRNAs and were regulated by nine related TFs. Therefore, patients may benefit from dorsomorphin and cyclosporine therapy. Between the two subgroups, 1,592 DEGs were identified, including LRPPRC and METTL3. These DEGs were predicted to be involved in neutrophil activation, cytokine-cytokine receptor interactions, and chemokine signaling pathways. A diagnostic model based on ten m6A-related DEGs in patients with psoriasis was constructed, which may provide early diagnostic biomarkers and therapeutic targets for psoriasis.

Work Overload, Work–Life Balance and Auditors' Turnover Intention: The Moderating Role of Motivation

AbstractAuditor turnover remains a persistent concern for regulatory bodies and auditing firms. Past research on auditors’ turnover intention has explored various factors influencing auditors’ turnover intention, including job satisfaction, organisational commitment, work overload and work–life balance. However, the potential role of motivation in mitigating the adverse effects of work overload and work–life imbalance has been overlooked. Our study addresses this gap in the existing literature by revealing the crucial role of motivation and identifying differences between Big4 and Non‐Big4 firms. Using questionnaire data from 301 auditors, analysed using structural equation modelling, we find that work overload is positively but indirectly related to turnover intention via work–life balance. Additionally, organisational commitment (job satisfaction) is directly (indirectly) and negatively related to turnover intention. Moreover, and considering that, due to work overload, a lack of work–life balance can be responsible for increasing auditors’ turnover intention, our study suggests that motivation can mitigate this effect. Finally, our study suggests that work–life balance can directly reduce turnover intention for Big4 firms, while for Non‐Big4 firms this reduction can only occur via organisational commitment (a channel that is weaker for Big4 firms).

The XPO1 inhibitor selinexor ameliorates bleomycin-induced pulmonary fibrosis in mice via GBP5/NLRP3 inflammasome signaling

Pulmonary fibrosis is an irreversible and progressive lung disease with limited treatments available. Selinexor (Sel), an orally available, small-molecule, selective inhibitor of XPO1, exhibits notable antitumor, anti-inflammatory and antiviral activities. However, its potential role in treating pulmonary fibrosis is unknown. C57BL/6J mice were used to establish a pulmonary fibrosis model by intratracheal administration of bleomycin (BLM). Subsequently, Sel was administered intraperitoneally. Our data demonstrated that Sel administration ameliorated BLM-induced pulmonary fibrosis by increasing mouse body weights; reducing H&E staining, Masson staining scores, and shadows in mouse lung computed tomography (CT) images, decreasing the total cell and neutrophil counts in the lung and bronchoalveolar lavage fluid (BALF); and decreasing the levels of TGF-β1. We next confirmed that Sel reduced the deposition of extracellular matrix (ECM) components in the lungs of BLM-induced pulmonary fibrosis mice. We showed that collagen I, alpha-smooth muscle actin (α-SMA), and hydroxyproline levels and the mRNA levels of Col1a1, Eln, Fn1, Ctgf, and Fgf2 were reduced. Mechanistically, tandem mass tags (TMT)- based quantitative proteomics analysis revealed a significant increase in GBP5 in the lungs of BLM mice but a decrease in that of BLM + Sel mice; this phenomenon was confirmed by western blotting and RT-qPCR. NLRP3 inflammasome signaling was significantly enriched in both the BLM group and BLM + Sel group based on GO and KEGG analyses of differentially expressed proteins between the groups. Furthermore, Sel reduced the expression of NLRP3, cleaved caspase 1, and ASC in vivo and in vitro, and decreased the levels of IL-1β, IL-18, and IFN-r in lung tissue and BALF. SiRNA-GBP5 inhibited NLRP3 signaling in vitro, and overexpression of GBP5 inhibited the protective effect of Sel against BLM-induced cellular injury. Taken together, our findings indicate that Sel ameliorates BLM-induced pulmonary fibrosis by targeting GBP5 via NLRP3 inflammasome signaling. Thus, the XPO1 inhibitor – Sel might be a potential therapeutic agent for pulmonary fibrosis.

Effect of Potassium Permanganate on Staphylococcal Isolates Derived from the Skin of Patients with Atopic Dermatitis.

In atopic dermatitis (AD), Staphylococcus aureus frequently colonizes lesions, leading to superinfections that can then lead to exacerbations. The presence of biofilm-producing isolates has been associated with worsening of the disease. Potassium permanganate is used as a topical treatment of infected eczema, blistering conditions, and wounds. Little is known of its effects against microbes in AD skin. The aim of this study was to explore antibacterial and antibiofilm properties of potassium permanganate against staphylococcal isolates derived from AD skin. Viable count and radial diffusion assays were used to investigate antibacterial effects of potassium permanganate against planktonic staphylococcal isolates. The antibiofilm effects were assessed using biofilm assays and scanning electron microscopy. The Staphylococcus aureus isolates were completely killed when exposed to 0.05% of potassium permanganate. In concentrations of 0.01%, potassium permanganate inhibited bacterial biofilm formation. Eradication of established staphylococcal biofilm was observed in concentrations of 1%. Electron microscopy revealed dense formations of coccoidal structures in growth control and looser formations of deformed bacteria when exposed to potassium permanganate. This suggests antibacterial and antibiofilm effects of potassium permanganate against staphylococcal isolates derived from AD skin, when tested in vitro, and a potential role in the treatment of superinfected AD skin.

The GaKAN2, a KANADI transcription factor, modulates stem trichomes in Gossypium arboreum.

GaKAN2, a member of the KANADI family, was found to be widely expressed in the cotton tissues and regulates trichome development through complex pathways. Cotton trichomes are believed to be the defense barrier against insect pests. Cotton fiber and trichomes are single-cell epidermal extensions with shared regulatory mechanisms. Despite several studies underlying mechanism of trichome development remains elusive. The KANADI is one of the key transcription factors (TFs) family, regulating Arabidopsis trichomes growth. However, the function of KANADI genes in cotton remains unknown. In the current study genome-wide scanning, transcriptomic analysis, gene silencing, subcellular localization, and yeast two-hybrid techniques were employed to decipher the function of KANADI TFs family genes in cotton crop. A total of 7 GaKAN genes were found in the Gossypium arboreum. Transcriptomic data revealed that these genes were significantly expressed in stem and root. Moreover, GaKAN2 was widely expressed in other tissues also. Subsequently, we selected GaKAN2 to validate the function of KANADI genes. Silencing of GaKAN2 resulted in a 24.99% decrease in single-cell trichomes and an 11.33% reduction in internodal distance, indicating its potential role in regulating trichomes and plant growth. RNA-Seq analysis elucidated that GaSuS and GaERS were the downstream genes of GaKAN2. The transcriptional activation and similarity in silencing phenotype between GaKAN2 and GaERS suggested that GaKAN2 regulates trichomes development through GaERS. Moreover, KEGG analysis revealed that a significant number of genes were enriched in the biosynthesis of secondary metabolites and plant hormone signal transduction pathways, thereby suggesting that GaKAN2 regulates the stem trichomes and plant growth. The GFP subcellular localization and yeast transcriptional activation analysis elucidated that GaKAN2 was located in the nucleus and capable of regulating the transcription of downstream genes. This study elucidated the function and characteristics of the KANADI gene family in cotton, providing a fundamental basis for further research on GaKAN2 gene in cotton plant trichomes and plant developmental processes.

Treatment of Fascial Pain with Glucopuncture

Over the last decade, clinicians worldwide discovered that fascia plays an important role in musculoskeletal posture, balance and tensegrity. Most physicians are not fully aware that the fascial system also contains a lot of nociceptors. This may explain its potential role in vague musculoskeletal pain syndromes. However, treating fascial pain effectively is not an easy task. Recently, it has been postulated that glucopuncture – a technique which applies multiple regional injections with dextrose 5% - can regulate pain originating from fascial dysfunction. The mode of action is probably related to ATP and TRPV1. Especially the superficial layer of fascia is an interesting target for regional injections when dealing with a patient with vague pain patterns. It is particularly interesting for sports injuries, neuralgia and chronic nonrheumatic musculoskeletal pain. The major advantage of glucopuncture over steroid injections is the interesting safety profile of dextrose 5%. The disadvantages of dextrose versus steroids is that multiple injections and multiple sessions are required. The latter is particularly the case when dealing with chronic myofascial pain. It is hypothesized that glucopuncture has a very interesting balance between efficacy versus side effects. More research in this field may confirm our preliminary findings. And we hope to spread this message worldwide, especially in low-income communities.

Paulownia trees as a sustainable solution for CO2 mitigation: assessing progress toward 2050 climate goals

Due to the progressive climate change on our planet, scientists are interested in solving this issue since it threatens not only certain regions or countries but also the world’s ecosystems and economies. Therefore, minimizing carbon dioxide (CO2) emissions and reducing atmospheric levels are global priorities. Thus, it is necessary at this moment to develop an appropriate approach to reduce or stabilize CO2 levels in the atmosphere. However, CO2 capture projects are long-term, low-profitable, and high-risk environmental projects. Consequently, it is necessary to find an appropriate and sustainable CO2 capture approach that is efficient in reducing atmospheric CO2 levels while having a safe impact on the environment. Although carbon (C) is the key basic component used to produce biological compounds by photosynthetic organisms in terrestrial plants, the C pathway is a key factor affecting the capture of CO2 by photosynthetic organisms. Among photosynthetic organisms, Paulownia, a multipurpose tree, is popular around the world for its timber and its potential role in CO2 sequestration. Paulownia spp. belongs to the Paulowniaceae family and comprises a group of trees. These trees are primarily found in southeastern Asia, particularly in China, and have been intentionally grown for more than two millennia due to their ornamental, cultural, and medicinal value. The number of Paulownia species varies depending on taxonomic classification, ranging from 6 to 17. Among them, Paulownia tomentosa, Paulownia elongata, Paulownia fortunei, and Paulownia catalpifolia are the most widely recognized and favored species. The present review provides a comprehensive technical-economic scenario for the capture of one million tons of CO2 by Paulownia trees (as a terrestrial plant model, grown on 2,400 ha−1). P. tomentosa can be utilized in agroforestry systems to mitigate greenhouse gas (GHG) emissions within urban cities and emphasize the carbon storage potential of agroforestry. In conclusion, Paulownia trees as an environmental mass project showed great encouragement to investors and governments to expand these types of projects to achieve global climate goals by 2050.

A comprehensive retrospective analysis of interfascial plane blocks and peripheral nerve blocks at a tertiary research hospital: Single center experience

Aim: This study aimed to analyze regional anesthesia practices at a tertiary research hospital as a single center during a one-year period (January 2022 to January 2023).Materials: Data on over 2,000 nerve blocks were retrospectively reviewed, including: type of nerve block performed (peripheral nerve vs. fascial plane, location of block (upper vs. lower extremity), purpose of block (anesthesia or analgesia) and outcomes.Method: Data was analyzed to assess trends in block utilization, identify preferred block types and locations, and compare the use of peripheral nerve blocks versus fascial plane blocks for anesthesia and analgesia. Additionally, the potential opioid-sparing benefits of fascial plane blocks were evaluated.Results: The analysis revealed a notable shift towards fascial plane blocks (61%) compared to peripheral nerve blocks (39%). Lower extremity blocks were more common (56%), with sciatic, saphenous, and femoral nerve blocks being the most frequently used. In the upper extremity (44%), infraclavicular and interscalene brachial plexus blocks dominated. Interestingly, fascial plane blocks were primarily employed for analgesia, while peripheral nerve blocks served both anesthetic and analgesic purposes. The study identified opioid-sparing advantages associated with fascial plane blocks, highlighting their potential role in multimodal pain management strategies.Conclusions: Based on these findings, areas for improvement in regional anesthesia practices were identified. Educational programs will be adjusted accordingly. Future research will delve deeper into patient characteristics, block selection rationale, and incorporate patient-reported outcomes alongside opioid consumption and pain scores. This study serves as a foundation for future enhancements in regional anesthesia practices, aiming to optimize patient care and outcomes.

Evaluation of possible role of fluoride in pathogenesis of oral submucous fibrosis: A pilot study.

Oral submucous fibrosis (OSMF) is a potentially malignant disorder. Although areca nut chewing is an established risk factor, its low prevalence among nut chewers indicates additional factors likely facilitates pathogenesis. We recently demonstrated high fluoride levels in smokeless tobacco products and hypothesized a potential pathological role of fluoride in OSMF. Further exploring this novel role, this study compared fluoride levels in tissue, serum, and saliva samples from OSMF patients and healthy controls. The ethically approved study included 25 clinically confirmed OSMF patients and 25 healthy matched controls. OSMF cases underwent buccal mucosal incisional biopsy, while controls had buccal mucosa tissue sampling during third molar removal. Fasting venous blood and unstimulated saliva were collected. Fluoride levels were analysed using ion chromatography and expressed as median (IQR). OSMF cases showed significantly higher fluoride concentrations compared with controls in tissue biopsies (30.1 vs. 0 mg/kg, p < 0.0001), serum (0.4 vs. 0 mg/L, p = 0.005) and saliva (1.3 vs. 0 mg/L, p < 0.0001). Majority (68%) of controls had undetectable fluoride levels across all samples. Tissue fluoride weakly correlated with OSMF severity (r = -0.158, p = 0.334). The preliminary findings demonstrated increased tissue fluoride levels in OSMF patients compared with healthy controls. Along with a previous study showing high fluoride content in smokeless tobacco products, these findings provided early evidence suggesting fluoride could play a contributory role in OSMF pathogenesis. Further large-scale investigation is warranted to definitively establish whether the association between fluoride exposure and OSMF is indicative of causation.

Liquid biopsy utilizing miRNA in patients with advanced breast cancer treated with cyclin‑dependent kinase 4/6 inhibitors.

Cyclin-dependent kinase 4/6 inhibitors (CDK4/6is) are the mainstay of treatment of hormone receptor+/human epidermal growth factor receptor 2-patients with advanced breast cancer (ABC). Despite improvements in overall survival, most patients experience disease progression. Biomarkers derived from a liquid biopsy are appealing for their potential to detect resistance to treatment earlier than computed tomography imaging. However, clinical data concerning microRNAs (miRNAs/miRs) in the context of CDK4/6is are lacking. Thus, the present study assessed the use of miRNAs in patients with ABC treated with CDK4/6is. Patients treated for ABC with CDK4/6is between June and August 2022 were eligible. miRNA expression analyses were performed using a TaqMan™ low-density miRNA array. A total of 80 consecutive patients with ABC treated with CDK4/6is at Maria Sklodowska-Curie National Research Institute of Oncology (Gliwice, Poland) were assessed, with 14 patients diagnosed with progressive disease at the time of sampling, 55 patients exhibited clinical benefit from CDK4/6i treatment and 11 patients were at the beginning of CDK4/6i treatment. Patients with disease progression had significantly higher levels of miR-21 (P=0.027), miR-34a (P=0.011), miR-193b (P=0.032), miR-200a (P=0.027) and miR-200b (P=0.003) compared with patients who benefitted from CDK4/6i treatment. Significantly higher levels of miR-34a expression were observed in patients with progressive disease than in patients beginning treatment (P=0.031). The present study demonstrated the potential innovative role of circulating miRNAs during CDK4/6i treatment. Plasma-based expression of miR-21, -34a, -193b, -200a and -200b effectively distinguished patients with ABC who responded to CDK4/6i treatment from patients who were resistant. However, longitudinal studies are required to verify the predictive and prognostic potential of miRNA.

Tumor microenvironment characteristics and prognostic role of m6A modification in lung squamous cell carcinoma

BackgroundIt has recently been determined that N6-methyladenosine (m6A) RNA methylation regulators have prominent effects on several cancers. However, the potential role of m6A modification in lung squamous cell carcinoma (LUSC) remains unclear. MethodsWe evaluated the modification pattern of m6A and studied the biological function of m6A regulators in LUSC. Then, we constructed the m6Ascore to predict the prognosis of LUSC and analyzed the relationship between the m6Ascore and tumor mutation burden, immune cell infiltration, and immunotherapy. ResultIn the unsupervised consensus cluster analysis, three different m6Aclusters were identified, which correspond to an immune activation state, a moderate immune activation state, and an immune tolerance state. Forty-two genes related to the m6A phenotype were used to construct the m6Ascore; subsequently, multiple validations of the m6Ascore were carried out to determine the relationship between the score and immune cell infiltration and response to CTLA-4/PD-1 inhibitor treatment. Further analysis revealed that the m6Ascore could effectively predict the prognosis of LUSC and that the m6A phenotype-related genes, FAM162A and LOM4, might be potential biomarkers. ConclusionThese findings highlight the potential role of m6A modification in the prognosis, TME, and immunotherapy of LUSC and have profound implications for developing more effective personalized treatment strategies for LUSC.

Immune regulation and the tumor microenvironment in anti-PD-1/PDL-1 and anti-CTLA-4 therapies for cancer immune evasion: A bibliometric analysis

ABSTRACT This study aims to conduct a bibliometric analysis, employing visualization tools to examine literature pertaining to tumor immune evasion related to anti-CTLA-4 and anti-PD-1/PD-L1 therapy from 1999 to 2022. A special emphasis is placed on the interplay between tumor microenvironment, signaling pathways, immune cells and immune evasion, with data sourced from the Web of Science core collection (WoSCC). Advanced tools, including VOSviewer, Citespace, and Scimago Graphica, were utilized to analyze various parameters, such as co-authorship/co-citation patterns, regional contributions, journal preferences, keyword co-occurrences, and significant citation bursts. Out of 4778 publications reviewed, there was a marked increase in research focusing on immune evasion, with bladder cancer being notably prominent. Geographically, China, the USA, and Japan were the leading contributors. Prestigious institutions like MD Anderson Cancer Center, Harvard Medical School, Fudan University, and Sun Yat Sen University emerged as major players. Renowned journals in this domain included Frontiers in Immunology, Cancers, and Frontiers in Oncology. Ehen LP and Wang W were identified as prolific authors on this topic, while Topalian SL stood out as one of the most cited. Research current situation is notably pivoting toward challenges like immunotherapy resistance and the intricate signaling pathways driving drug resistance. This bibliometric study seeks to provide a comprehensive overview of past and current research trends, emphasizing the potential role of tumor microenvironment, signaling pathways and immune cells in the context of immune checkpoint inhibitors (ICIs) and tumor immune evasion.

Human Papilloma Virus Positive Oropharyngeal Squamous Cell Carcinoma and the Immune System: Pathogenesis, Immunotherapy and Future Perspectives.

Oropharyngeal squamous cell carcinoma (OPSCC), a subset of head and neck squamous cell carcinoma (HNSCC), involves the palatine tonsils, soft palate, base of tongue, and uvula, with the ability to spread to adjacent subsites. Personalized treatment strategies for Human Papillomavirus-associated squamous cell carcinoma of the oropharynx (HPV+OPSCC) are yet to be established. In this article, we summarise our current understanding of the pathogenesis of HPV+OPSCC, the intrinsic role of the immune system, current ICI clinical trials, and the potential role of small molecule immunotherapy in HPV+OPSCC.

Beyond pillbox: a national cross-sectional study on the attitudes, practices, and knowledge of community pharmacists regarding complementary and alternative medicine

BackgroundWhile community pharmacists are uniquely positioned to promote the safe and effective use of complementary and alternative medicine, their potential role remains largely untapped. The objective of this study was to assess the knowledge, attitudes, and practices related to complementary and alternative medicine products among community pharmacists in the United Arab Emirates and explore the correlates of knowledge in the study sample.MethodsUsing a stratified random sampling frame, a national survey of community pharmacists was conducted in the United Arab Emirates. In a face-to-face interaction, participants completed a multi-component questionnaire consisting of four sections: sociodemographic and general characteristics; knowledge of complementary and alternative medicine products and usage; attitudes towards complementary and alternative medicine and practices related to complementary and alternative medicine. Based on participants’ answers, scores were calculated with higher scores indicating more positive knowledge, attitudes, and practices.Results373 community pharmacists participated in the study (response rate: 83%). For the knowledge questions, more than 50% of community pharmacists correctly answered the functions of complementary and alternative medicine, however lower percentages were noted for the side effects and drug interactions questions. Most community pharmacists had positive attitudes towards complementary and alternative medicine, except for particular aspects such as efficacy, where 40% agreed that complementary and alternative medicine is only effective in treating minor complaints. As for practices, while more than 70% of participants counseled patients on complementary and alternative medicine use, only 47% reported the toxic effects when encountered. Multiple linear regressions showed that community pharmacists working in independent pharmacies, those with fewer years of experience, and those who did not receive complementary and alternative medicine education during their academic degree had lower knowledge scores (p < 0.05).ConclusionsThe findings of this study showed that community pharmacists in the United Arab Emirates have good knowledge of complementary and alternative medicine functions and generally positive attitudes and practices, with few gaps identified in each. Together, these findings provide critical evidence for the development of targeted interventions to promote the role of community pharmacists towards safe and effective complementary and alternative medicine use in the country.