Profibrotic Subsets of SPP1+ Macrophages and POSTN+ Fibroblasts Contribute to Fibrotic Scarring in Acne Keloidalis.

Acne keloidalis is a primary scarring alopecia characterized by longstanding inflammation in the scalp causing keloid-like scar formation and hair loss. Histologically, acne keloidalis is characterized by mixed leukocytic infiltrates in the acute stage followed by a granulomatous reaction and extensive fibrosis in the later stages. To further explore its pathogenesis, bulk RNA sequencing, single-cell RNA sequencing, and spatial transcriptomics were applied to occipital scalp biopsy specimens of lesional and adjacent no-lesional skin in patients with clinically active disease. Unbiased clustering revealed 19 distinct cell populations, including 2 notable populations: POSTN+ fibroblasts with enriched extracellular matrix signatures and SPP1+ myeloid cells with an M2 macrophage phenotype. Cell communication analyses indicated that fibroblasts and myeloid cells communicated by SPP1 signaling networks in lesional skin. A reverse transcriptomics in silico approach identified corticosteroids as possessing the capability to reverse the gene expression signatures of SPP1+ myeloid cells and POSTN+ fibroblasts. Intralesional corticosteroid injection greatly reduced SPP1 and POSTN gene expression as well as acne keloidalis disease activity. Spatial transcriptomics and immunofluorescence staining verified microanatomic specificity of SPP1+ myeloid cells and POSTN+ fibroblasts with disease activity. In summary, the communication between POSTN+ fibroblasts and SPP1+ myeloid cells by SPP1 axis may contribute to the pathogenesis of acne keloidalis.

The IFSD Score-A Practical Prognostic Model for Invasive Fungal Spondylodiscitis.

Objectives: Invasive fungal spondylodiscitis (IFSD) is rare and could be lethal in certain circumstances. The previous literature revealed limited data concerning its outcomes. This study aimed to establish a risk-scoring system to predict the one-year mortality rate of this disease. Methods: A total of 53 patients from a multi-centered database in Taiwan were included in this study. All the clinicopathological and laboratory data were retrospectively analyzed. Variables strongly related to one-year mortality were identified using a multivariate Cox proportional hazards model. A receiver operating characteristic (ROC) curve was used to express the performance of our IFSD scoring model. Results: Five strong predictors were included in the IFSD score: predisposing immunocompromised state, the initial presentation of either radiculopathy or myelopathy, initial laboratory findings of WBC > 12.0 or <0.4 103/µL, hemoglobin < 8 g/dL, and evidence of candidemia. One-year mortality rates for patients with IFSD scores of 0, 1, 2, 3, and 4 were 0%, 16.7%, 56.3%, 72.7%, and 100%, respectively. The area under the curve of the ROC curve was 0.823. Conclusions: We developed a practical scoring model with easily obtained demographic, clinical, and laboratory parameters to predict the probability of one-year mortality in patients with IFSD. However, more large-scale and international validations would be necessary before this scoring model is commonly used.

Biocompatible, Antibacterial, and Stable Deep Eutectic Solvent-Based Ionic Gel Multimodal Sensors for Healthcare Applications.

In this study, we investigated a novel approach to fabricate multifunctional ionic gel sensors by using deep eutectic solvents (DESs) as replacements for water. When two distinct DESs were combined, customizable mechanical and conductive properties were created, resulting in improved performance compared with traditional hydrogel-based strain sensors. DES ionic gels possess superior mechanical properties, transparency, biocompatibility, and antimicrobial properties, making them suitable for a wide range of applications such as flexible electronics, soft robotics, and healthcare. We conducted a comprehensive evaluation of the DES ionic gels, evaluating their performance under extreme temperature conditions (-70 to 80 °C), impressive optical transparency (94%), and biocompatibility. Furthermore, a series of tests were conducted to evaluate the antibacterial performance (Escherichia coli) of the DES ionic gels. Their wide strain (1-400%) and temperature (15-50 °C)-sensing ranges demonstrate the versatility and adaptability of DES ionic gels for diverse sensing requirements. The resulting DES ionic gels were successfully applied in human activity and vital sign monitoring, demonstrating their potential for biointegrated sensing devices and healthcare applications. This study offers valuable insights into the development and optimization of hydrogel sensors, particularly for applications that require environmental stability, biocompatibility, and antibacterial performance, thereby paving the way for future advancements in this field.

Adipose transcriptome in the scalp of androgenetic alopecia.

Previous studies have shown how adipocytes can modulate the activity of hair follicle stem cells. However, the role of adipocytes in the pathogenesis of androgenetic alopecia (AGA) remains unknown. We aimed to determine signaling pathways related to the adipose tissue changes in the human scalp with AGA through RNA-seq analysis. RNA was isolated from the adipose tissues derived from the bald (frontal) and normal (occipital) scalps of male patients with AGA (n = 4). The pooled RNA extracts from these samples were subjected to RNA sequencing, followed by differential gene expression and pathway analysis. Our gene expression analysis identified 1,060 differentially expressed genes, including 522 upregulated and 538 downregulated genes in the bald AGA scalp. Biological pathways pertaining to either adipose tissue metabolism or the hair cycle were generated in our pathway analysis. Downregulation of the peroxisome proliferator-activated receptor (PPAR) signaling pathway was noted to be significant in the bald scalp. Expression of adipogenic markers (e.g., PPARG, FABP4, PLN1, and ADIPOQ) was also decreased in the bald site. These findings imply that adipogenesis becomes downregulated in AGA, specifically within the bald scalp adipose. Our results lead to the hypothesis that PPARγ-mediated adipogenesis in the scalp adipose, via crosstalk with signaling pathways involved in hair cycling, might play a role in AGA.

Clinical application of serum biomarkers for detecting and monitoring of chronic plaque psoriasis.

Psoriasis, a chronic, multisystemic inflammatory disease affecting millions of people globally, manifests as erythematous, thick, scaly plaques on the skin. Clinical evaluation remains to be the benchmark for diagnosis and monitoring of this debilitating disease. With current advancements in targeted molecular therapy for psoriasis such as biologics, molecular detection methods may also help guide clinical decisions and therapeutic strategies through quantification of circulating biomarkers, which could reflect the underlying pathogenic events happening at a certain point of the disease course. In this review, we will discuss how biomarkers are detected in serum samples using enzyme-linked immunosorbent assay (ELISA). This review will feature candidate biomarkers supported by clinical data for psoriasis including, but not limited to, cytokines, chemokines, adipokines, and antimicrobial peptides. A better understanding of the common method used for biomarker detection would enable physicians to interpret and correlate laboratory results with the disease pathogenesis and clinical outcomes, e.g., severity assessment and/or therapeutic response. With better health outcomes as the main goal, the utility of such information to evaluate and even predict treatment response would be a major step closer towards patient-tailored management.

Aberrant expression of interleukin-17A in mast cells contributes to the pathogenesis of hidradenitis suppurativa.

BACKGROUND: Hidradenitis suppurativa (HS) significantly diminishes the quality of life for patients. Delayed diagnosis represents a significant challenge in effectively managing HS. OBJECTIVES: To identify and characterize the key mediator in HS. METHODS: Bioinformatic transcriptomic analysis was applied to identify potential candidates contributing to the disease process of HS. Skin samples from 40 patients with HS, four with psoriasis and 29 with normal skin were included. The expression of interleukin (IL)-17A was evaluated and compared among samples of normal skin, psoriatic skin and skin from different stages of HS by immunohistochemistry or dual-colour immunofluorescence. In vitro experiments and RNA sequencing analysis were also conducted to validate the expression of IL-17A and its pathogenic effect in HS. RESULTS: Transcriptomic database analyses identified IL-17 signalling as a potential contributor to HS. In HS, the predominant IL-17A+ cell population was identified as mast cells. IL-17A+ mast-cell density was significantly elevated in HS, especially in samples with advanced Hurley stages, compared with normal skin and psoriasis samples. The close contact between IL-17A+ mast cells and IL-17 receptor A (IL-17RA)-expressing keratinocytes was demonstrated, along with the significant effects of IL-17A on keratinocyte cell proliferation and HS pathogenic gene expression. Treatment with biologics (brodalumab or adalimumab) reduced the severity of the disease and the number of IL-17A+ mast cells in affected tissues. CONCLUSIONS: The presence of high-density IL-17A+ mast cells may serve as a valuable pathological marker for diagnosing HS. Moreover, developing therapeutic drugs targeting IL-17A+ mast cells may provide a new approach to treating HS.

Transcriptomic responses of peripheral blood mononuclear cells to cyclosporin and etanercept in a female infant with juvenile generalized pustular psoriasis.

Generalized pustular psoriasis (GPP) is a rare but severe form of psoriasis. An early onset of the diseases is correlated with mutations among IL36RN, CARD14, AP1S3, MPO and SERPINA3 genes. Systemic biological agents including anti-TNF-α, anti-IL-17, anti-IL-12/IL-23, anti-IL1R, anti-IL1ß and anti-IL-36R act as novel treatment methods for GPP. Herein we report a female infant clinically diagnosed with GPP since she was 10-month-old. Results of whole-exome sequencing (WES) and Sanger sequencing revealed a reported heterozygous IL36RN (c.115+6T>C) and another reported heterozygous SERPINA3 frame-shifting variant (c.1247_1248del). Initial cyclosporin treatment for the patient led to a partial remission of the symptoms. However, the patient reached nearly total remission of pustules and erythema after anti-TNF-α inhibitor etanercept treatment. Results of further RNA sequencing (RNA-seq) done on peripheral blood mononuclear cells correlated with the clinical responses, showing that cyclosporin suppressed a portion of the neutrophil-related genes, while most genes associated with neutrophil activation, neutrophil-mediated immunity and degranulation were downregulated by the subsequent etanercept treatment. We report this case to demonstrate WES and RNA-seq in combination could come in handy in reaching a precise diagnosis and in evaluating or even predicting the molecular alterations underlying clinical treatment effectiveness.

Complications of Full-Endoscopic Lumbar Discectomy versus Open Lumbar Microdiscectomy: A Systematic Review and Meta-Analysis.

OBJECTIVE: Endoscopic lumbar discectomy has been an alternative for treating lumbar disc herniation. Evidence-based study for the benefit zone of full-endoscopic lumbar discectomy (FELD) is necessary. The study compared the complication risks between the FELD and open discectomy or microdiscectomy. METHODS: The literature search was from 4 online databases for randomized controlled trials (RCTs) and cohort studies. The meta-analysis of different study designs was conducted separately. Complication rates were considered primary outcomes, and the recurrence and revision rates were considered secondary outcomes. RESULTS: Six RCTs and thirteen cohort studies met the eligibility criteria. The meta-analysis was conducted separately. From the pooled RCT meta-analysis, the overall complication rates of FELD and open discectomy/microdiscectomy were 5.5% and 10.4%, respectively. The moderate-quality evidence suggested that FELD had a lower risk of overall complications (risk ratio [RR] = 0.55, 95% confidence interval [CI] = 0.31-0.98). There was no significant difference in specific complications and recurrence. The analysis of cohort studies revealed no significant difference in overall complications, but there was significant heterogeneity in the results. The risk of dural injury was significantly lower for FELD (RR = 0.46, 95% CI = 0.22-0.96). The pooled meta-analysis from cohort studies suggested a higher risk of transient dysesthesia (RR = 3.70, 95% CI = 1.54-8.89), residual fragment (RR = 5.29, 95% CI = 2.67-10.45), and revision surgeries (RR = 1.53, 95% CI = 1.12-2.08) for FELD. CONCLUSIONS: The current evidence showed a lower risk of overall complications for FELD. The quality of evidence was moderate to low, and the risk of bias from the primary literature should be concerned.