Risk of candidiasis associated with interleukin-17 inhibitors: Implications and management.

The application of interleukin-17 (IL-17) inhibitors, including secukinumab, ixekizumab, brodalumab, and bimekizumab, are associated with elevated risk of candidiasis. These medications interfere with the IL-17 pathway, which is essential for maintaining mucosal barriers and coordinating the immune response against Candida species. The observational data and clinical trials demonstrate the increased incidence of candidiasis in individuals treated with IL-17 inhibitors. Brodalumab and bimekizumab pose a greater risk than secukinumab in eliciting candidiasis, whereas the data regarding ixekizumab are equivocal. Higher doses and prolonged treatment duration of IL-17 inhibitors increase the risk of candidiasis by compromising the immune response against Candida species. Prior to prescribing IL-17 inhibitors, healthcare professionals should comprehensively evaluate patients' medical histories and assess their risk factors. Patients should be educated on the signs and symptoms of candidiasis to facilitate early detection and intervention. Future research should focus on identifying the risk factors associated with candidiasis in patients receiving IL-17 inhibitors. Prospective studies and long-term surveillance are required to explore the impact of specific inhibitors on the incidence and severity of candidiasis and to evaluate the effectiveness of combination therapies, such as concurrent use of IL-17 inhibitors and prophylactic antifungal agents.

Interleukin inhibitors and the associated risk of candidiasis.

Interleukins (ILs) are vital in regulating the immune system, enabling to combat fungal diseases like candidiasis effectively. Their inhibition may cause enhanced susceptibility to infection. IL inhibitors have been employed to control autoimmune diseases and inhibitors of IL-17 and IL-23, for example, have been associated with an elevated risk of Candida infection. Thus, applying IL inhibitors might impact an individual's susceptibility to Candida infections. Variations in the severity of Candida infections have been observed between individuals with different IL inhibitors, necessitating careful consideration of their specific risk profiles. IL-1 inhibitors (anakinra, canakinumab, and rilonacept), IL-2 inhibitors (daclizumab, and basiliximab), and IL-4 inhibitors (dupilumab) have rarely been associated with Candida infection. In contrast, tocilizumab, an inhibitor of IL-6, has demonstrated an elevated risk in the context of coronavirus disease 2019 (COVID-19) treatment, as evidenced by a 6.9% prevalence of candidemia among patients using the drug. Furthermore, the incidence of Candida infections appeared to be higher in patients exposed to IL-17 inhibitors than in those exposed to IL-23 inhibitors. Therefore, healthcare practitioners must maintain awareness of the risk of candidiasis associated with using of IL inhibitors before prescribing them. Future prospective studies need to exhaustively investigate candidiasis and its associated risk factors in patients receiving IL inhibitors. Implementing enduring surveillance methods is crucial to ensure IL inhibitors safe and efficient utilization of in clinical settings.

Genome-wide DNA methylation and transcription analysis in psoriatic epidermis.

Aim: To identify DNA methylation and transcription biomarkers in the psoriatic epidermis. Materials & methods: Gene transcription and DNA methylation datasets of psoriatic epidermal tissue were obtained from the Gene Expression Omnibus. Machine learning algorithm analysis and weighted gene coexpression network analysis were carried out to screen hub genes. Results: Differentially methylated and expressed genes were identified in the psoriatic epidermis. Six hub genes were selected - GZMB, CRIP1, S100A12, ISG15, CRABP2 and VNN1 - whose transcript levels showed a significant correlation with Psoriasis Area and Severity Index scores and immune infiltration. Conclusion: Psoriatic epidermis is primarily in a hypermethylated status. Epidermis-specific hub differentially methylated and expressed genes are potential biomarkers to help judge the condition of psoriasis.

LncRNA TUG1 relieves renal mesangial cell injury by modulating the miR-153-3p/Bcl-2 axis in lupus nephritis.

BACKGROUND: Lupus nephritis (LN) is one of the most common and serious complications of systemic lupus erythematosus. Our experiments aimed to evaluate the molecular mechanisms of long noncoding RNA (lncRNA) TUG1 in a human renal mesangial cell (HRMC) model of LN. METHODS: Cells were treated with lipopolysaccharide (LPS) to induce inflammatory damage. StarBase, TargetScan, and a luciferase reporter assay were used to predict and confirm the interactions between lncRNA TUG1, miR-153-3p, and Bcl-2. We determined the lncRNA TUG1 and miR-153-3p levels in LPS-induced HRMCs using quantitative reverse transcription PCR (RT-qPCR). MTT and flow cytometry analyses were used to detect HRMC proliferation and apoptosis, respectively. In addition, the expression of the apoptosis-related proteins Bax and Bcl-2 was evaluated using western blot analysis and RT-qPCR. Lastly, the secretion of inflammatory cytokines (IL-1ß, IL-6, and TNF-α) was assessed using ELISA. RESULTS: miR-153-3p directly targeted lncRNA TUG1. The level of lncRNA TUG1 was remarkably lower and miR-153-3p expression was markedly higher in LPS-treated HRMCs than in untreated cells. Transfection with TUG1-plasmid relieved LPS-induced HRMC injury, as evidenced by increased cell viability, inhibited apoptotic cells, reduced Bax expression, increased Bcl-2 level, and reduced secretion of inflammatory cytokines. Importantly, these findings were reversed by miR-153-3p mimic. We also found that miR-153-3p directly targeted Bcl-2 and negatively regulated Bcl-2 expression in HRMCs. In addition, our findings suggest that miR-153-3p inhibitor relieved LPS-induced HRMC injury via the upregulation of Bcl-2. CONCLUSION: lncRNA TUG1 alleviated LPS-induced HRMC injury through regulation of the miR-153-3p/Bcl-2 axis in LN.

Neural Networks for Hyperspectral Imaging of Historical Paintings: A Practical Review.

Hyperspectral imaging (HSI) has become widely used in cultural heritage (CH). This very efficient method for artwork analysis is connected with the generation of large amounts of spectral data. The effective processing of such heavy spectral datasets remains an active research area. Along with the firmly established statistical and multivariate analysis methods, neural networks (NNs) represent a promising alternative in the field of CH. Over the last five years, the application of NNs for pigment identification and classification based on HSI datasets has drastically expanded due to the flexibility of the types of data they can process, and their superior ability to extract structures contained in the raw spectral data. This review provides an exhaustive analysis of the literature related to NNs applied for HSI data in the CH field. We outline the existing data processing workflows and propose a comprehensive comparison of the applications and limitations of the various input dataset preparation methods and NN architectures. By leveraging NN strategies in CH, the paper contributes to a wider and more systematic application of this novel data analysis method.

IL-33-mediated activation of mast cells is involved in the progression of imiquimod-induced psoriasis-like dermatitis.

BACKGROUND: Psoriasis is a chronic inflammatory dermatosis with an unclear pathogenesis. Mast cells (MCs) can serve as a bridge between innate and adaptive immunity and are involved in the regulation of the inflammatory state and immune homeostasis in diseases. MCs constitutively express interleukin-33 receptor T1/ST2 (IL-33R). IL-33 is a potent MCs activator that is actively secreted by keratinocytes in psoriasis. However, the regulatory role of MCs in psoriasis remains uncertain. Therefore, we hypothesised that IL-33 could promote MC activation to regulate psoriasis development. METHODS: We performed experiments on wild-type (WT) and MC-deficient (Kit Wsh/Wsh) mice, established psoriasis-like mouse models using imiquimod (IMQ), and performed RNA sequencing and transcriptomic analysis of skin lesions. Exogenous administration was performed using recombinant IL-33. Validation and evaluation were performed using PSI scoring, immunofluorescence, immunohistochemistry, and qPCR. RESULTS: We observed an upregulation in the number and activation of MCs in patients with psoriasis and in IMQ-induced psoriasis-like dermatitis. Deficiency of MCs ameliorates IMQ-induced psoriatic dermatitis at an early stage. IL-33 is increased and co-localized with MCs in the dermis of psoriasis-like lesions using immunofluorescence. Compared to WT mice, IMQ-induced KitWsh/Wsh mice demonstrated a delayed response to exogenous IL-33. CONCLUSIONS: MCs are activated by IL-33 in the early stages of psoriasis and exacerbate psoriasis-associated skin inflammation. The regulation of MC homeostasis may be a potential therapeutic strategy for psoriasis. Video Abstract.

Intravenous Polymyxin B as Adjunctive Therapy to High-Dose Tigecycline for the Treatment of Nosocomial Pneumonia Due to Carbapenem-Resistant Acinetobacter baumannii and Klebsiella pneumoniae: A Propensity Score-Matched Cohort Study.

Although the combination of polymyxin and tigecycline is widely used in treating carbapenem-resistant bacterial infections, the benefit of this combination is still uncertain. To assess whether adding polymyxin B to the high-dose tigecycline regimen would result in better clinical outcomes than the high-dose tigecycline therapy in patients with pneumonia caused by carbapenem-resistant Klebsiella pneumoniae and Acinetobacter baumannii, we conducted a propensity score-matched cohort study in a single center between July 2019 and December 2021. Of the 162 eligible patients, 102 were included in the 1:1 matched cohort. The overall 14-day mortality in the matched cohort was 24.5%. Compared with high-dose tigecycline, the combination therapy was not associated with better clinical outcomes, and showed similar 14-day mortality (OR, 0.72, 95% CI 0.27-1.83, p = 0.486), clinical cure (OR, 1.09, 95% CI 0.48-2.54, p = 0.823), microbiological cure (OR, 0.96, 95% CI 0.39-2.53, p = 0.928) and rate of nephrotoxicity (OR 0.85, 95% CI 0.36-1.99, p = 0.712). Subgroup analyses also did not demonstrate any statistical differences. Based on these results, it is reasonable to recommend against adding polymyxin B to the high-dose tigecycline regimen in treating pneumonia caused by carbapenem-resistant K. pneumoniae and A. baumannii.

Circ_0048856 competes with ABCC1 for miR-193a-5p/miR-98-5p binding sites to promote the cisplatin resistance and tumorigenesis in lung cancer.

Although cisplatin (DDP)-based therapy is the most predominant chemotherapeutic strategy used for lung cancer, drug resistance usually occurs after several cycle use of it. Circular RNAs (circRNAs) are found to be involved in the chemoresistance in lung cancer. Hence, this study aimed to clarify the role and mechanism of circ_0048856 in lung cancer tumorigenesis and DDP resistance. The levels of circ_0048856, miR-193a-5p, miR-98-5p and ABCC1 (ATP Binding Cassette Subfamily C Member 1) were determined by qRT-PCR and western blotting. In vitro assays were conducted by cell counting kit-8 assay, 5-ethynyl-2'-deoxyuridine (EDU) assay, flow cytometry and transwell assay, respectively. The binding interaction was verified using dual-luciferase reporter assay and RIP assay. In vivo experiment was performed by the establishment of murine xenograft model. Circ_0048856 was highly expressed in DDP-resistant lung cancer tissues and cells. Functionally, circ_0048856 silencing re-sensitized DDP-resistant lung cancer cells to DDP, as well as suppressed cell growth and invasion in lung cancer in vitro and in vivo. Mechanistically, circ_0048856 acted as the sponge for miR-193a-5p or miR-98-5p, which targeted ABCC1. Furthermore, rescue experiments showed that inhibition of miR-193a-5p or miR-98-5p reversed the effects of circ_0048856 knockdown on lung cancer cells. Besides that, overexpression of miR-193a-5p or miR-98-5p suppressed cell tumorigenesis and reduced DDP resistance in lung cancer, which were attenuated by ABCC1 up-regulation. Circ_0048856 knockdown suppressed tumor growth and reduced DDP resistance in lung cancer by miR-193a-5p/ABCC1 or miR-98-5p/ABCC1 axis, indicating a novel strategy for efficient application of DDP in lung cancer.

Whole-genome identification and construction of the lncRNA-mRNA co-expression network in patients with actinic keratosis.

Background: Actinic keratosis (AK) is a common premalignant lesion induced by chronic exposure to ultraviolet radiation and may develop into invasive cutaneous squamous carcinoma (cSCC). The identification of specific biomarkers in AK are still unclear. Long non-coding RNAs (lncRNAs), as transcripts of more than 200 nucleotides, significantly involving in multiple biologic processes, especially in the development of tumors. Methods: In our study, we obtained data from RNA-sequencing analysis using two AK lesion tissues and three normal cutaneous tissues to comparatively analyze the differentially expressed (DE) lncRNAs and messenger RNAs (mRNAs). Firstly, we used microarray analyses to identify DE lncRNAs and DE mRNAs. Secondly, we performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis to analyze the primary function and find out significant pathways of these DE mRNA and lncRNAs. Finally, we used the top ten DE lncRNAs to construct a lncRNA-mRNA co-expression network. Results: Our results showed that there were a total of 2,097 DE lncRNAs and 2,043 DE mRNAs identified. GO and KEGG analysis and the lncRNA-mRNA co-expression network (using the top 10 DE lncRNAs comprises 130 specific co-expressed mRNAs to construct) indicated that lncRNA uc011fnr.2 may negatively regulate SCIMP and Toll-like receptor 4 (TLR4) and play an important role in Janus kinase-signal transducer and activator of transcription 3 (JAK-STAT3) signaling pathway of AK. Conclusions: lncRNA uc011fnr.2 may play an important role in JAK-STAT3 signaling pathway of AK by modulating SCIMP, TLR4 and IL-6. Further research is required to validate the value of lncRNA uc011fnr.2 in the progression of AK.

Landscape of circulating metabolic fingerprinting for keloid.

Background: Keloids are a fibroproliferative disease characterized by unsatisfactory therapeutic effects and a high recurrence rate. Objective: This study aimed to investigate keloid-related circulating metabolic signatures. Methods: Untargeted metabolomic analysis was performed to compare the metabolic features of 15 keloid patients with those of paired healthy volunteers in the discovery cohort. The circulating metabolic signatures were selected using the least absolute shrinkage. Furthermore, the selection operators were quantified using multiple reaction monitoring-based target metabolite detection methods in the training and test cohorts. Results: More than ten thousand metabolic features were consistently observed in all the plasma samples from the discovery cohort, and 30 significantly different metabolites were identified. Four differentially expressed metabolites including palmitoylcarnitine, sphingosine, phosphocholine, and phenylalanylisoleucine, were discovered to be related to keloid risk in the training and test cohorts. In addition, using linear and logistic regression models, the respective risk scores for keloids based on a 4-metabolite fingerprint classifier were established to distinguish keloids from healthy volunteers. Conclusions: In summary, our findings show that the characteristics of circulating metabolic fingerprinting manifest phenotypic variation in keloid onset.

Generalized Nodules in an Older Adult Man.

A man in his 60s presented with an 8-month history of pruritic papulonodular lesions on his extremities and trunk, with no significant improvement with steroids and antihistamines. What is your diagnosis?

Effects of transthoracic device closure on ventricular septal defects and reasons for conversion to open-heart surgery: A meta-analysis.

Transthoracic device closure (TTDC) is thought to be a promising technology for the repair of ventricular septal defects (VSDs). However, there is considerable controversy regarding the efficacy and safety of TTDC. The present study aimed to compare the benefits and safety of TTDC with those of conventional open-heart surgery (COHS) and analyze the associated factors causing complications, conversion to COHS and reoperation. Electronic database searches were conducted in PubMed, EMBASE, Cochrane Library, Clinicaltrials.gov and several Chinese databases. A total of 5 randomized controlled trials (RCTs), 7 cohort studies, 13 case-control studies, 129 case series and 13 case reports were included. Compared to COHS, TTDC exhibited superior efficacy with a significantly lower risk of post-operative arrhythmia; however, no significant differences in other outcomes were identified. Meta-regression analysis showed that perimembranous VSDs (pmVSDs), a smaller VSD, a smaller occluder, and a median or subxiphoid approach lowered the relative risk of several post-operative complications, conversion to COHS and reoperation. The current evidence indicates that TTDC is associated with a lower risk of post-operative arrhythmia and is not associated with an increased risk of complications. PmVSDs, a smaller VSD and occluder, and a median or subxiphoid approach correlate with better outcomes when using TTDC.