Exosomal Proteomics: Unveiling Novel Insights into Lung Cancer.

Although significant progress has been made in early lung cancer screening over the past decade, it remains one of the most prevalent and deadliest forms of cancer worldwide. Exosomal proteomics has emerged as a transformative field in lung cancer research, with the potential to redefine diagnostics, prognostic assessments, and therapeutic strategies through the lens of precision medicine. This review discusses recent advances in exosome-related proteomic and glycoproteomic technologies, highlighting their potential to revolutionise lung cancer treatment by addressing issues of heterogeneity, integrating multiomics data, and utilising advanced analytical methods. While these technologies show promise, there are obstacles to overcome before they can be widely implemented, such as the need for standardization, gaps in clinical application, and the importance of dynamic monitoring. Future directions should aim to overcome the challenges to fully utilize the potential of exosomal proteomics in lung cancer. This promises a new era of personalized medicine that leverages the molecular complexity of exosomes for groundbreaking advancements in detection, prognosis, and treatment.

Effect of fractional laser alone or in combination on alopecia areata: A systematic review and meta-analysis.

BACKGROUND: Alopecia areata (AA) is characterized by limited non-scarring patchy alopecia, which appears as round or oval patches and is prone to recurrence, causing severe psychological burdens to patients. No specific device has been approved by the FDA for the treatment of baldness, but new treatments are being investigated and treatments such as the excimer laser, He- Ne laser, and excimer lamp have been proposed. A growing number of studies have found that fractional lasers also have great potential in the treatment of AA. METHODS: A literature search and meta-analysis using Review Manager 5.4 software to investigate the efficacy of fractional laser treatment for AA. RESULTS: Fractional laser combined with minoxidil (RR 1.32, 95% CI 1.17-1.49, p < 0.00001) or cortisol (RR 1.39, 95% CI 1.15-1.67, p = 0.00006) was more effective than either drug alone in the treatment of AA. Of course, the fractional laser alone was also effective in the treatment of AA (RR 10.33, 95% CI 2.07-51.36, p = 0.004) and more effective than cortisol alone (RR 1.86, 95% CI 1.36-2.52, p < 0.00001), and there was no effect on the occurrence of adverse effects (p = 0.49 > 0.05). When compared to other physical treatments of a comparable kind, fractional laser therapy's effectiveness was not significantly different (p = 0.15 > 0.05). CONCLUSION: Our results show that the use of fractional lasers can effectively treat alopecia areata.

Diffraction-Net: a robust single-shot holography for multi-distance lensless imaging.

Digital holography based on lensless imaging is a developing method adopted in microscopy and micro-scale measurement. To retrieve complex-amplitude on the sample surface, multiple images are required for common reconstruction methods. A promising single-shot approach points to deep learning, which has been used in lensless imaging but suffering from the unsatisfied generalization ability and stability. Here, we propose and construct a diffraction network (Diff-Net) to connect diffraction images at different distances, which breaks through the limitations of physical devices. The Diff-Net based single-shot holography is robust as there is no practical errors between the multiple images. An iterative complex-amplitude retrieval approach based on light transfer function through the Diff-Net generated multiple images is used for complex-amplitude recovery. This process indicates a hybrid-driven method including both physical model and deep learning, and the experimental results demonstrate that the Diff-Net possesses qualified generalization ability for samples with significantly different morphologies.

Differential Expression of Serum Exosomal Hsa-miR-487b-3p in Progressive Vitiligo Before and After Systemic Corticosteroid Treatment.

Background: Vitiligo is an acquired skin depigmentation disease. It can be misdiagnosed at an early stage and tend to relapse. Serum markers are essential to monitoring the progression of vitiligo. Exosomal miRNAs act as the communication mediator between melanocytes and immune cells. Our study aimed to use serum exosomal miRNAs as a reference for evaluating vitiligo progression. Methods: The miRNAs were extracted from the serum exosomes of ten progressive vitiligo patients (before and after treatment) and ten healthy individuals. We profiled miRNAs expression by RNA sequencing and screened out potential miRNAs and plotted their receiver operating characteristic (ROC) curves to explore their sensitivity and specificity as prognostic biomarkers in vitiligo progression. We examined the correlation between miRNA expression and the lesion area. Different databases were used to predict gene targets of miRNAs, which were analyzed by gene ontology and Kyoto encyclopedia of genes and genomes (KEGG). Results: Our results showed that 141 miRNAs were differentially expressed in serum exosomes of progressive vitiligo patients, and 365 miRNAs were differentially expressed in these patients after treatment compared to healthy individuals. The expression of hsa-miR-487b-3p was significantly lower in these patients compared to healthy individuals. Still, there was no difference in its levels in patients after corticosteroid treatment compared to healthy controls. ROC curve analysis (area under curve = 0.840) indicated that hsa-miR-487b-3p could serve as a biomarker for the prognosis of vitiligo progression. Its expression positively correlated with the lesion area. A total of 41 target genes of hsa-miR-487b-3p were predicted via different databases. KEGG pathways were enriched in phenylalanine metabolism, glycan degradation, and protein export. Conclusion: Serum exosomal hsa-miR-487b-3p can be a biomarker to detect vitiligo progression. The predicted target genes of hsa-miR-487b-3p were enriched in catabolism. Thus, its in progressive vitiligo may accelerate catabolism in melanocytes and cause its impairment.

Targets Exploration of Hydroxychloroquine for Pigmentation and Cell Protection Effect in Melanocytes: The Clue for Vitiligo Treatment.

Objective: The treatment of vitiligo is often challenging to dermatologists. There is ample evidence to suggest that hydroxychloroquine (HCQ) is effective for vitiligo treatment; nonetheless, the underlying mechanism remains unknown. In the present study, we sought to uncover the molecular targets of HCQ by an integrated network-based pharmacologic and transcriptomic approach. Methods: The potential targets of HCQ were retrieved from databases based on the crystal structure. Targets related to vitiligo were screened and intersected with potential targets of HCQ. A protein-protein interaction network of the intersected targets was generated. Interactions between the targets were verified by molecular docking. Moreover, human vitiligo immortalized melanocytes (PIG3V) were evaluated after treatment with HCQ (1µg/mL) for 24h. The total RNA of PIG3V was extracted and determined by RNA-seq transcriptomics for differential gene expression analysis. Network pharmacology was then used to identify the relationships between putative targets of HCQ and differentially expressed genes. Results: Molecular docking analysis revealed four putative key targets (ACHE, PNMT, MC1R, and VDR) of HCQ played important roles in vitiligo treatment. According to the transcriptomic results, the melanosomal biogenesis-related gene BLOC1S5 was upregulated 138005.020 fold after HCQ treatment. Genes related to protein repair (MSRB3) and anti-ultraviolet (UV) effect (UVSSA) were upregulated 4.253 and 2.603 fold, respectively, after HCQ treatment. Conclusion: The expression of the BLOC1S5 gene is significantly upregulated, indicating upregulated melanosomal biogenesis after HCQ treatment. In addition, HCQ yields a protective effect on melanocytes by upregulating genes associated with damaged protein repair (MSRB3) and anti-UV effect (UVSSA). The protective effects of HCQ are mediated by binding to putative targets ACHE, PNMT, MC1R, and VDR according to network pharmacology and docking verification.

Differences in the skin microbial community between patients with active and stable vitiligo based on 16S rRNA gene sequencing.

BACKGROUND/OBJECTIVE: Recent studies have described an association between altered skin microbial community and epidemiology of skin diseases, such as vitiligo, atopic dermatitis and psoriasis. In this study, we conducted microbiological analysis on patients at different stages of vitiligo to determine whether the dysbiosis is associated with disease progression. METHODS: To characterise the skin microbes in vitiligo patients, we profiled samples collected from 40 patients with active and stable vitiligo using the Novaseq sequencer. Alpha diversity was used to measure richness and uniformity, while Beta diversity (Non-Metric Multi-Dimensional Scaling) analysis was used to show the differences. Moreover, the species differences were evaluated by LEfSe analysis and the flora gene function was predicted using Statistical Analysis of Metagenomic Profiles (STAMP). RESULTS: The alpha diversity results showed no significant differences between active vitiligo and stable vitiligo, while beta diversity and LEfSe analysis results showed the differences in community composition. Streptomyces and Streptococcus were enriched in active vitiligo compared to stable vitiligo. In addition, the flora gene function of mixed acid fermentation was more pronounced in active vitiligo, while the function of lipid IVA biosynthesis was more significant in stable vitiligo. CONCLUSION: This study has shown the differences in epidermal microbes between active vitiligo and stable vitiligo. Our results suggest that maintaining the flora balance might be a potential therapeutic target for vitiligo.

The multi-target mechanism of Cyclosporin A in the treatment of vitiligo based on network pharmacology.

Network pharmacology is an emerging discipline that designs drugs based on systems biology theory and biological system network analysis. Here, we applied network pharmacology to analyze the multi-target mechanism of Cyclosporin A in the treatment of vitiligo First, we predicted the targets of Cyclosporin A. Second, we obtained the genes related to vitiligo from the database. Third, we constructed the PPI network of the mutual genes between Cyclosporin A and vitiligo and used gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) to analyze. Finally, we verified the prediction of potential targets through a docking study with Cyclosporin A. We found that there were 15 shared target genes between Cyclosporin A and vitiligo. We analyzed these 15 genes by Cytoscape and obtained a network diagram of 885 nodes. Through screening and molecular docking, PRKDC, CUL7, CUL1, HSPA8, HSPA4, and SIRT7 were the most likely multi-target mechanism of Cyclosporin A in the treatment of vitiligo. In our study, Cyclosporin A might not only affect the repair of DNA strands by targeting PRKDC, but also affected the innate and adaptive immune function of vitiligo patients by the targets of CUL1, CUL7, and HSP70. In addition, Cyclosporin A might promote the repigmentation of vitiligo by adjusting the expression of SIRT7.

Tape stripping and lipidomics reveal skin surface lipid abnormity in female melasma.

The skin barrier of melasma is involved in the pathogenesis of melasma. Previous studies have shown that there are differences in the expression of epidermal lipid genes in melasma, but little is known about the epidermis lipid composition of melasma. Compared with the non-lesional skin, the content of total lipids, phosphatidic acid, phosphatidylserine, and ceramide (Cer) increased significantly in the lesional skin. Multivariate data analysis indicated that 40 individual Cer lipid species were responsible for the discrimination. In terms of acyl chain length in Cer, the expressions of very long chain (VLC) (C20-C26) and ultra-long chain (ULC) (>C26) increased significantly in the lesional skin. However, Cer[AH] had negative correlations with the activation of melanocytes in the lesional skin. Some lipid species had lower expression in lesional skin with high activation of melanocytes, as well as the high darkness. The epidermal thickness of lesional skin was higher compared with the non-lesional skin. These results suggest that Cer increased significantly in the lesional skin of melasma, possibly as a compensatory mechanism to maintain skin barrier function. Between different groups of darkness and activation of melanocytes, the change of ceramides might have correlation with the pigmentation progress of melasma.

Targets of hydroxychloroquine in the treatment of rheumatoid arthritis. A network pharmacology study.

OBJECTIVE: This study was performed to investigate the multi-targets mechanism of hydroxychloroquine (HCQ) in the treatment of rheumatoid arthritis (RA). METHODS: The predicted targets of HCQ and the proteins related to RA were returned from databases. Followed by protein-protein interaction (PPI) network, the intersection of the two group of proteins was studied. Furthermore, gene ontology (GO) and KyotoEncyclopediaofGenesandGenomes (KEGG) enrichment was used to analyse these proteins in a macro perspective. Finally, the candidate targets were checked by molecular docking. RESULTS: The results suggested that HCQ in the treatment of RA was mainly associated with 4 targets that are smoothened homolog (SMO), sphingosine kinase (SPHK) 1, SPHK2 and gatty-acid amide hydrolase (FAAH), with their related 3276 proteins' network which regulate ErbB, HIF-1, NF-κB, FoxO, chemokines, MAPK, PI3K/Akt pathways and so forth. Biological process were mainly focused in the regulation of cell activation, myeloid leukocyte activation, regulated exocytosis and so forth. Molecular docking analysis showed that hydrogen bonding and π-π stacking were the main forms of chemical force. CONCLUSIONS: Our research provides protein targets affected by HCQ in the treatment of RA. SMO, SPHK1, SPHK2 and FAAH involving 3276 proteins become the multi-targets mechanism of HCQ in the treatment of RA.

The multi-targets mechanism of hydroxychloroquine in the treatment of systemic lupus erythematosus based on network pharmacology.

BACKGROUND: Network pharmacology is used with bioinformatic tools to broaden the understanding of drugs' potential targets and the intersections with key genes of particular disease. Here we applied network pharmacology to collect testable hypotheses about the multi-targets mechanism of hydroxychloroquine (HCQ) against systemic lupus erythematosus (SLE). METHODS: Firstly, we predicted the potential targets of HCQ. Secondly, we got the related genes of SLE returned from databases. Thirdly, the intersections of the potential targets (HCQ) and related genes (SLE) were analyzed with gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment. Finally, we validated our predictions of the potential targets by performing docking studies with HCQ. RESULTS: The results suggest that the efficacy of HCQ against SLE is mainly associated with the targets of cyclin-dependent kinase 2 (CDK2), estrogen receptor alpha (ESR1) and CDK1, which regulate PI3K/Akt/GSK3ß as well as interferon (IFN) signaling pathway. Biological process of the network associated with the three targets is concentrated in the inhibition of immune response, negative regulation of gene expression and regulation of immune system process. Molecular docking analysis proves that hydrogen bonding and π-π stacking are the main forms of interaction. CONCLUSIONS: Our research provides protein targets affected by HCQ in the treatment of SLE. Three key targets (CDK2, ESR1 and CDK1) involving 1766 proteins become the multi-targets mechanism of HCQ in the treatment of SLE. As well, the research also provides a new idea for introducing network pharmacology into the evaluation of the drugs with multi-targets in dermatology.