Invasive fungal infections induced by Candida species are becoming an urgent threat to global health. While a series of antifungal vaccines have been developed, their efficiency is frequently compromised by the failure of immune stimulation. In this study, a novel antifungal vaccine was constructed by assembling u03B2-glucan with the Candida albicans antigen candidalysin on the surface of the genetically engineered Escherichia coli strain EcS. This co-assembly was mediated by the cell surface-exposed artificial glucan-binding protein CipC-mCherry-CipC, leading to the formation of the surface glucan nanofilm with a thickness of ~ 80 nm. Upon co-incubation with macrophages, the vaccine efficiently escapes from the lysosomes, leading to enhanced production of reactive oxygen species (ROS) and macrophage maturation. After mouse immunization, the vaccine persists longer in lymph nodes than free candidalysin or the glucan-free complex, and induces higher levels of CD4+, CD8+, TNFu03B1+/CD4+ and IFNu03B3+/CD4+ T cells in the spleen. In a murine model of invasive fungal infection, immunization with this vaccine remarkably increases the survival rate, reduces the kidney fungal burdens and attenuates inflammatory responses. This bioengineering strategy offers a potentially viable approach for developing co-assembled whole-cell vaccines and can be extended to leverage bacterial carriers for surface antigen display. The vaccine acts not only as antigens but also as adjuvants, thereby eliciting strong and specific protective immunity against invasive fungal infections.

Oxidative stress is one of the major environmental stresses that the fungal pathogen Candida albicans frequently encounters. In view of the negative regulatory effect of Ume6 on autophagy in Saccharomyces cerevisiae and the close link between autophagy and oxidative stress in mammals, we explored the regulatory effect of Ume6 on autophagy and oxidative stress in C. albicans in this study. Here, we identify the transcriptional regulator Ume6 as a key positive regulator of autophagy under oxidative stress conditions. Deletion of UME6 resulted in reduced autophagy levels under H2O2 treatment, correlating with reduced transcriptional expression of core autophagy-related genes. Although UME6 deletion alone did not alter H2O2 sensitivity, it significantly exacerbated the sensitivity of a catalase mutant, revealing a functional role for Ume6 in oxidative stress tolerance. Intriguingly, we discovered that 3-methyladenine (3-MA), a canonical autophagy inhibitor in other systems, acts as an autophagy activator in C. albicans, promoting Atg8 transport to the vacuole and enhancing autophagy levels. This 3-MA-induced autophagy alleviated oxidative stress damage, as evidenced by improved growth and protection of vacuolar membrane integrity in H2O2-treated cells. Furthermore, deletion of UME6 or nitrogen starvation reduced apoptosis under oxidative stress, including decreased Annexin-V binding, metacaspase activation, mitochondrial membrane depolarization, and mitochondrial cytochrome c release. This study uncovers the critical role of Ume6 in governing oxidative stress, autophagy, and apoptosis.

Sepsis is characterized by dysregulated inflammatory responses triggered by pathogen-associated molecular patterns (PAMPs) and remains a major cause of mortality worldwide. Although antibiotics are widely used for the treatment of sepsis-associated infections, their clinical efficacy is often limited by antimicrobial resistance and the inability to control excessive inflammatory responses. Indolicidin is a bovine-derived antimicrobial peptide with antimicrobial and immunomodulatory activities; however, its anti-inflammatory mechanisms in sepsis remain unclear. In this study, we investigated the protective effects and mechanisms of indolicidin in bacterial and fungal sepsis models. The results showed that indolicidin exhibited good biocompatibility both in vitro and in vivo. In murine models of Escherichia coli- and Candida albicans-induced sepsis, indolicidin significantly improved survival and reduced microbial burden in the kidneys. In RAW264.7 macrophages stimulated with lipopolysaccharide (LPS), a major PAMP of E. coli, indolicidin suppressed M1 polarization, reactive oxygen species production, and proinflammatory cytokine expression. Transcriptomic analyses of macrophages and infected kidney tissues revealed that indolicidin consistently downregulated inflammation-related pathways, chemokine signaling, and LPS-response pathways, including genes associated with IL-6, chemokines, and M1 macrophage markers such as CD80 and CD86. Mechanistically, indolicidin directly bound LPS, interacted with lipopolysaccharide-binding protein (LBP), and reduced the surface expression of CD14 and the TLR4/MD2 complex, indicating modulation of the TLR4 signaling pathway. Overall, this study highlights indolicidin as a dual-function peptide with antimicrobial and immunomodulatory activity and supports its potential as a therapeutic candidate against sepsis.

Metabolic reprogramming and epigenetic alterations promote oral squamous cell carcinoma (OSCC). Lactate-dependent histone modification is a novel histone mark that connects the epigenetic process of lactylation to glycolytic metabolites. However, the role of histone lactylation in oral carcinogenesis remains poorly understood. In this study, the levels of histone lactylation in oral leukoplakia (OLK) and OSCC tissues were determined by immunohistochemistry. The involvement of histone lactylation in OSCC initiation was assessed by the inhibition of lactylation using glycolysis inhibitors or silencing lactate dehydrogenase A (LDHA), both in vitro and in vivo. CUT&Tag, scRNA-seq, ChIP-qPCR, and rescue experiments were conducted to explore the potential molecular mechanism of H3K18 lactylation (H3K18la) in OSCC tumorigenesis. Histone lactylation, particularly H3K18la levels were elevated in OLK and OSCC tissues. The inhibition of histone lactylation repressed the malignant phenotypes of OLK and OSCC cells in vitro. Glycolysis inhibitors blocked the formation of precancerous lesions and OSCC in the 4NQO-induced tongue carcinogenesis model. Mechanistically, H3K18la activated the transcription of thymidine kinase 1 (TK1) and increased TK1-mediated pyrimidine biosynthesis, resulting in oral carcinogenesis. TK1 downregulation inhibited the Wnt signaling pathway via RhoA. Moreover, the Wnt/β-catenin inhibitor XAV939 reduced lactate production and H3K18la levels. Here, we demonstrate that the glycolysis/H3K18la/TK1/β-catenin positive feedback loop exacerbates dysfunction in OSCC initiation. These findings reveal a novel link between epigenetic regulation and lactate-driven metabolic reprogramming, which may lead to the development of innovative lactylation treatment approaches for OSCC therapy.

Lactylation is a newly identified post-translational modification and an important biological function of lactate. Numerous pathological disorders, including cancer and autoimmune and inflammatory diseases, are regulated by lactylation. Additionally, lactylation controls several physiological processes in cells, such as the production of proteins, cytokines, metabolism, and several forms of cell death. Cell death is responsible for tissue homeostasis, immune responses, tissue repair and tissue regeneration. Recent studies have revealed a close association between lactylation and cell death, underscoring their significance in the development and course of illness. The regulation of different types of cell death by lactylation involves the modulation of key cell death proteins. Therefore, clarifying the precise function of lactylation and related cell death mechanisms is essential for targeted disease therapies. Here, we provide an overview of how lactylation regulates cellular signaling in cells undergoing apoptosis, autophagy, pyroptosis, ferroptosis, and cuproptosis. Lactylation intervention to control cell death may offer new therapeutic insights for a number of human diseases.

Background: Cancer patients experience a high incidence of concomitant infections due to the effects of chemotherapy drugs and their suppressed immune function. Infection has become a major cause and an accelerating factor of cancer-related deaths. The combined use of anticancer drugs and antibiotics can produce adverse effects, necessitating the urgent search for dual-active drugs that are effective against both cancer and bacteria. Since tubulin has a homologous protein filamenting temperature-sensitive mutant Z (FtsZ) in bacteria, tubulin inhibitors have the potential to emerge as dual-active drugs against both cancer and bacteria. Methods: A comprehensive screening of a tubulin inhibitor library, encompassing 196 compounds, was conducted to evaluate their various activities. Results: Compounds 6, 23, 33, 56, 60, and 71 exhibited both anticancer and antibacterial activities in vitro, and 23, 33, 56, and 60 displayed varying degrees of FtsZ inhibitory activity. Particularly, compound 23 stood out as the most potent, exhibiting not only the strongest anticancer activity with IC50 values of 12, 20, and 10 nM against A549, MCF-7 and Hela cells, respectively, but also the most exceptional antibacterial activity with minimum inhibitory concentration (MIC) values of 8, 8, 64, and 32 μM against Staphylococcus aureus (S. aureus), Bacillus subtilis (B. subtilis), Escherichia coli (E. coli), and Pseudomonas aeruginosa (P. aeruginosa), respectively. Furthermore, compound 23 possessed the superior FtsZ inhibitory activity, facilitating polymerization. This was evident in the remarkably elongated cell morphology of Bacillus subtilis treated with compound 23. To gain a deeper understanding of the underlying mechanisms, molecular docking studies were conducted, revealing the interaction mode between compound 23 and both tubulin and FtsZ, further elucidating its multifaceted biological activities. Conclusions: The dual-active drugs obtained in this study provide a new solution to the problem of bacterial infection in cancer patients. The revealed FtsZ as the antibacterial target provides an important theoretical basis for further optimization of such drugs.

Aim or purpose: Metabolic reprogramming and epigenetic alterations promote oral squamous cell carcinoma (OSCC). Lactate-dependent histone modification is a new type of histone mark, which links glycolysis metabolite to the epigenetic process of lactylation. The objective was to evaluate the role of histone lactylation in oral carcinogenesis. Materials and methods: The level of histone lactylation in dysplastic and cancer tissues was identified by immunohistochemistry. The participation of histone lactylation in OSCC initiation was confirmed through inhibition of histone lactylation by glycolysis inhibitors or lactate dehydrogenase A (LDHA) knockdown both in vitro and in vivo. RNA-seq, metabolomics analysis, and CUT&Tag were performed to investigate the mechanism of H3K18 lactylation (H3K18la). The candidate target genes were validated through RT-qPCR, western blot and ChIP-qPCR analyses. Next, the effects of these genes in oral carcinogenesis were confirmed by knockdown or overexpression. Results: Histone lactylation, especially H3K18la level was elevated in dysplastic and cancer tissues. The suppression of glycolytic activity by different kinds of inhibitors or LDHA knockdown decreased cell proliferation and induced cell cycle arrest in vitro. Glycolysis inhibitors blocked the formation of precancerous lesion and OSCC in 4NQO-induced tongue carcinogenesis model. Mechanistically, H3K18la was enriched at the promoters and activated the transcription of ribonucleotide reductase subunits M1 and M2, resulting in alleviation of replication stress. Conclusions: We reveal that H3K18la may play a vital role in blockage of oral carcinogenesis, thereby providing novel therapeutic targets for OSCC therapy. These findings bridge histone modifications with nucleotide metabolism, which provides novel understanding of epigenetic regulation in carcinogenesis.

BACKGROUND:Long-chain polyunsaturated fatty acid formation requires fatty acid desaturase (FADS), which is strongly linked to cancer progression. Nevertheless, it's unclear how FADS3 functions in head and neck squamous cell carcinoma (HNSCC). METHODS:HNSCC cases were retrieved from TCGA and GEO databases, and FADS members with transcriptionally differential expression were identified. Clinical survival, tumor microenvironment (TME), and potential pathogenic mechanism in HNSCC were also investigated. These results were validated using tissue staining, flow cytometry and functional studies in HNSCC cell lines. RESULTS:When comparing HNSCC to normal epithelial tissues, FADS3 expression was much higher in the former. FADS3 upregulation was correlated with poor clinical outcomes. FADS3 was an independent prognostic factor for poor overall survival in HNSCC patients. KEGG, GO, and GSEA revealed that FADS3 expression correlated with several immune-related pathways and the epithelial-mesenchymal transition (EMT). Knocking down FADS3 restrained HNSCC cell proliferation, migration, invasion, and EMT. Single-cell dataset analysis showed an association between FADS3 and TME features. Further investigation revealed that FADS3high tumor was accompanied with less CD8+ T cells in situ tissue and peripheral blood. FADS3 was positively correlated with immune-related molecules and could predict the adverse efficacy of immunotherapy. Finally, we constructed a CYTOR/hsa-let-7c-5p axis regulating FADS3 expression in HNSCC progression. CONCLUSIONS:FADS3 may represent a target for treatment in HNSCC, which is linked to prognosis, EMT, immune infiltration, and ceRNA regulatory network of HNSCC.

Ketoconazole is a classical antifungal drug commonly used in the clinic. With the increased use of ketoconazole in recent years, an increasing number of drug-resistant strains have emerged during clinical treatment. It is well known that fungi acquire drug resistance in multiple ways, while the molecular mechanisms underlying ketoconazole resistance remain for comprehensive exploration. In this study, we found that the expression of the small plasma membrane protein-encoding gene PMP3 was significantly down-regulated in several clinically isolated ketoconazole-resistant strains, indicating the relationship between PMP3 expression and ketoconazole resistance. By knocking out the PMP3, we found that the absence of the Pmp3 resulted in a significant increase in resistance of Candida albicans to ketoconazole, which was also confirmed in a systemic infection model in mice. We further demonstrated that various physiological properties, such as cell membrane fluidity, plasma membrane potential, permeability and ergosterol distribution were altered in the pmp3Δ/Δ mutant, which is associated with the enhanced cellular resistance to ketoconazole. In addition, overexpression rather than deletion of PMP3 alters the hyphal development and biofilm formation capacity in C. albicans. This study reveals the contribution of Pmp3 to alteration of drug resistance in fungal pathogens, which may guide the development of novel antifungal strategies.

Tubulin-targeting drugs have increasingly become the focus of anticancer drugs research. Twenty-six novel thiazole hydrazone derivatives grafted with indole were synthesized and estimated for bioactivity as potential tubulin polymerization inhibitors. Among them, compound D11 showed the most excellent inhibition against tubulin assembly (IC50 = 1.68 mu M) and in vitro growth inhibitory activity against three human cancer cell lines (IC50 = 0.46, 0.21 and 0.32 mu M, respectively for MCF-7, A549 and Hela). Moreover, it can effectively induce apoptosis, block cell cycle in G2/M phase and disrupt the cellular microtubule network. These results, along with molecular docking data, provided an important basis for further optimization of compound D11 as a potential anticancer agent.

Objectives Proteus are known as opportunistic human pathogens that can cause a variety of infections. Proteus appendicitidis is a novel Proteus species associated with appendicitis, whereas their genomic characteristics and virulence potential remain understudied. This study aims to compare the genomic features of P. appendicitidis to that of the close Proteus species, and to assess its virulence-factor encoding capacity as an emerging pathogen. Methods Genomes similar to that of P. appendicitidis HZ0627T were retrieved from the PATRIC-v3.6.10 web-server using the implanted Similar Genome Finder tool. Average nucleotide identity (ANI) between HZ0627T and the retrieved genomes was calculated using FastANI-v1.33. Core-genome sequences were extracted using Roary-v3.13.0, and core-genomic tree was constructed using FastTree-v2.1.11. Virulence-factor encoding capacity was predicted using PathoFact-v1.0. Results Two previously unclassified Proteus sp. strains were reclassified as P. appendicitidis. Strains phylogenomically close to P. appendicitidis were clustered into five species, three of which were previously categorized under P. vulgaris biogroup 3. Remarkably, Proteus genomosp. 6 was identified as the closest species to P. appendicitidis, exhibiting ANI values ranging from 94.45% to 94.95% against HZ0627T. Genome annotation revealed shared genomic features and antimicrobial resistance (AMR) genes between P. appendicitidis and its phylogenetic neighbors. Additionally, P. appendicitidis is hypothesized to share infection mechanisms with Proteus genomosp. 6, as evidenced by the encoding of numerous virulence factors implicated in cell lysis and membrane pore-formation in the genome of both species. Conclusions This study provides genomic insights of P. appendicitidis sp. nov. and its taxonomic relatives, shedding light on their evolutionary relationships, pathogenic mechanisms, and AMR profiles. The findings are significant for the development of targeted therapeutic interventions against infections caused by this emerging pathogen.

Lipid droplets (LDs) are intracellular organelles that play important roles in cellular lipid metabolism; they change their sizes and numbers in response to both intracellular and extracellular signals. Changes in LD size reflect lipid synthesis and degradation and affect many cellular activities, including energy supply and membrane synthesis. Here, we focused on the function of the endoplasmic reticulum–plasma membrane tethering protein Ice2 in LD dynamics in the fungal pathogen Candida albicans (C. albicans). Nile red staining and size quantification showed that the LD size increased in the ice2Δ/Δ mutant, indicating the critical role of Ice2 in the regulation of LD dynamics. A lipid content analysis further demonstrated that the mutant had lower phosphatidylcholine levels. As revealed with GFP labeling and fluorescence microscopy, the methyltransferase Cho2, which is involved in phosphatidylcholine synthesis, had poorer localization in the plasma membrane in the mutant than in the wild-type strain. Interestingly, the addition of the phosphatidylcholine precursor choline led to the recovery of normal-sized LDs in the mutant. These results indicated that Ice2 regulates LD size by controlling intracellular phosphatidylcholine levels and that endoplasmic reticulum–plasma membrane tethering proteins play a role in lipid metabolism regulation in C. albicans. This study provides significant findings for further investigation of the lipid metabolism in fungi.

Background Topical photodynamic therapy (PDT) has demonstrated encouraging results in the treatment of oral leukoplakia (OLK). However, data on the clinical efficacy of PDT in Chinese patients with OLK are still limited. Methods Fifty patients diagnosed with OLK were enrolled, including patients with various dysplastic tissues. All patients received topical PDT with 5-aminolevulinic acid (5-ALA) as a photosensitizer. Clinical efficacy was evaluated 4 weeks after treatment. Follow-up was performed every 3 months during the first year and every 6 months during the second year. Results The overall response rate was 68% (34/50): 12% (n = 6) complete and 56% (n = 28) partial responses. Aneuploidy was reduced in the patients with dysplastic lesions. Oral pain and local ulcers developed in 52% of the patients (n = 26). Patients with a long history of OLK including hyperplasia and dysplastic lesions, as well as those with non-homogenous lesions, were more likely to develop pain and ulcer. During follow-up, the recurrence rate of hyperplasia and dysplastic lesions was 32% (n = 16) and the malignant transformation rate of dysplastic lesions was 4% (n = 2). Lesions on the buccal mucosa were associated with recurrence ( P = 0.044; OR: 0.108, 95% CI: 0.013–0.915). Conclusion Topical 5-ALA-mediated PDT is an effective treatment for OLK, particularly for homogenous leukoplakia, with few side effects. The buccal mucosa may be a protective factor that can reduce recurrence.

AIM or PURPOSE Fatty acid desaturase (FADS) is a key enzyme involved in long-chain polyunsaturated fatty acid biosynthesis and is closely associated with cancer progression. However, the role of FADS3 in head and neck squamous cell carcinoma (HNSCC) remains unclear. MATERIALS and METHOD HNSCC cases were retrieved from TCGA and GEO databases, and the transcriptionally differentially expressed members of FADS were identified. Clinical survival, tumor microenvironment, and potential pathogenic mechanism in HNSCC were also investigated. These results were validated with immunohistochemical staining in clinical specimens and functional experiments in HNSCC cell lines. RESULTS FADS3 was significantly upregulated in HNSCC tissues compared with normal epithelial tissues. FADS3 upregulation was associated with worse overall survival, progression-free interval, disease-specific survival, and disease-free interval. FADS3 was an independent prognostic factor for poor overall survival in HNSCC patients. KEGG, GO, and GSEA showed that FADS3 expression correlated with several immune-related pathways and the epithelial-mesenchymal transition (EMT) pathway. Single-cell dataset analysis indicated that FADS3 was associated with tumor microenvironment features. Additional analyses revealed that FADS3 expression was inversely related to the infiltration of immune cells, particularly CD8+ T cells. FADS3 was positively correlated with inhibitory immune markers and could predict the adverse efficacy of immunotherapy. We constructed a CYTOR/hsa-let-7c-5p axis regulating FADS3 expression in HNSCC progression. Finally, FADS3 knockdown inhibited the proliferation, migration, invasion, and EMT of HNSCC cells. CONCLUSION(S) FADS3 can be a potential therapeutic target for patients with HNSCC, which is associated with prognosis, EMT, and immune infiltration, and ceRNA regulatory network of HNSCC.

Morbidity and mortality of cardiovascular diseases (CVDs) are exceedingly high worldwide. Researchers have found that the occurrence and development of CVDs are closely related to intestinal microecology. Imbalances in intestinal microecology caused by changes in the composition of the intestinal microbiota will eventually alter intestinal metabolites, thus transforming the host physiological state from healthy mode to pathological mode. Trimethylamine N-oxide (TMAO) is produced from the metabolism of dietary choline and L-carnitine by intestinal microbiota, and many studies have shown that this important product inhibits cholesterol metabolism, induces platelet aggregation and thrombosis, and promotes atherosclerosis. TMAO is directly or indirectly involved in the pathogenesis of CVDs and is an important risk factor affecting the occurrence and even prognosis of CVDs. This review presents the biological and chemical characteristics of TMAO, and the process of TMAO produced by gut microbiota. In particular, the review focuses on summarizing how the increase of gut microbial metabolite TMAO affects CVDs including atherosclerosis, heart failure, hypertension, arrhythmia, coronary artery disease, and other CVD-related diseases. Understanding the mechanism of how increases in TMAO promotes CVDs will potentially facilitate the identification and development of targeted therapy for CVDs.

Magnetic nanoparticles (MNPs) are becoming important DNA nanocarriers for genetic engineering of industrial fungi. However, the biological effect of MNPs on industrial fungi remains unknown. In this study, we prepared three kinds of magnetic nanoparticles with different sizes (i.e., 10 nm, 20 nm, and 200 nm) to investigate their impact on the growth and sporulation of the important industrial fungus Aspergillus niger. Transmission electron microscopy, X-ray diffraction analysis and Zeta potential analysis revealed that the three kinds of MNPs, including MNP10, MNP20 and MNP200, had uniform size distribution, regular Fe3O4 X-ray diffraction (XRD) patterns and similar Zeta potentials. Interestingly, although the three kinds of MNPs did not obviously inhibit growth of the fungus, the MNP20 at 500 mg/L strongly attenuated sporulation, leading to a remarkable decrease in spore numbers on culturing plates. Further investigation showed that MNP20 at the high concentration led to drastic chitin accumulation in the cell wall, indicating cell wall disruption of the MNP20-treated fungal cells. Moreover, the MNPs did not cause unusual iron dissolution and reactive oxygen species (ROS) accumulation, and the addition of ferrous ion, ferric ion or the reactive oxygen species scavenger N-acetyl-L-cysteine (NAC) had no impact on the sporulation of the fungus, suggesting that both iron dissolution and ROS accumulation did not contribute to attenuated sporulation by MNP20. This study revealed the size-dependent effect of MNPs on fungal sporulation, which was associated with MNP-induced cell wall disruption.

Oral lichen planus (OLP) is a localized autoimmune disease of the oral mucosa, with an incidence of up to 2%. Although corticosteroids are the first-line treatment, they cause several adverse effects. Quercetin, a naturally occurring compound, has fewer side-effects and provides long-term benefits. Besides, it has powerful anti‑inflammatory activities. Here, we combined network pharmacology with experimental verification to predict and verify the key targets of quercetin against OLP. First, 66 quercetin-OLP common targets were analyzed from various databases. The protein–protein interaction (PPI) network was constructed. Topology analysis and MCODE cluster analysis of common targets were conducted to identify 12 key targets including TP53, IL-6 and IFN-γ and their connections. Gene functions and key signaling pathways, including reactive oxygen species metabolism, IL-17 pathway and AGE-RAGE pathway, were enriched by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Then, in vitro experiments showed that quercetin interfered with Th1/Th2 balance by acting on IL-6 and IFN-γ to modulate the immune system in treating OLP. Quercetin considerably affected the apoptosis and migration of T lymphocytes in OLP patients. Our study reveals the potential therapeutic targets and signaling pathways of quercetin associated with OLP, and establishes the groundwork for future clinical applications.

Oral lichen planus (OLP) is a chronic inflammatory oral mucosal disease. Cytokines are closely associated with OLP development. In addition to immune cells, fibroblasts have been reported to induce regional inflammation. MicroRNA(miR)-155-5p is reportedly increased significantly in OLP and is known to regulate inflammation. This study aimed to investigate the role of miR-155-5p in fibroblasts of OLP lesions. Normal mucosal fibroblasts (NFs) and OLP associated-fibroblasts (OLP AFs) were isolated from the oral mucosa of 15 healthy controls and 30 OLP patients. We detected the expression of miR-155-5p and fibroblast activation protein alpha (FAP-α) using quantitative RT-PCR and analyzed their correlation. Interleukin (IL)-6 and IL-8 levels were determined using ELISA. Expression of suppressor of cytokine signaling (SOCS) 1 was analyzed by western blotting. A dual-luciferase reporter assay was performed to investigate the interaction between miR-155-5p and SOCS1. MiR-155-5p and FAP-α were significantly increased and positively correlated in OLP AFs. Overexpression of miR-155-5p in OLP AFs augmented IL-6 and IL-8 release and decreased SOCS1 expression, whereas knockdown of miR-155-5p in OLP AFs decreased IL-6 and IL-8 release. The expression of SOCS1 was downregulated in OLP AFs, and SOCS1 silencing augmented IL-6 and IL-8 production in OLP AFs. Furthermore, miR-155-5p inhibited SOCS1 expression by directly targeting its 3′-UTR in OLP AFs. MiR-155-5p regulates the secretion of IL-6 and IL-8 by downregulating the expression of SOCS1 in activated OLP AFs. Our results provide novel insights into the pathogenesis of OLP and identify a potential new target for OLP therapy.

Cerebrovascular diseases (CVDs) are among the most serious diseases with high mortality and disability rates. The prevalent diagnosis and treatment methods of CVDs include imaging and interventional therapy. With the development of nanotechnology, large numbers of nanomaterials have been applied to the diagnosis and treatment of CVDs, mainly including carbon nanotubes, quantum dots, fullerenes, and dendrimers. In this review, the applications of nanomaterials in the field of diagnosis and treatment of CVDs, mainly including drug target delivery, imaging, therapy, endovascular treatment, and angiogenesis, are summarized. The applications of nanomaterials in the field of CVD are almost in the laboratory, and more effort is needed for clinical translation. The aim of this review is to provide useful information for future research and equipment development.

Tumor necrosis factor-α inducible protein-8 (TIPE2), initially recognized as a negative immune regulator, exerts an important role in suppressing the progression of numerous cancers. In our previous investigation, we found that TIPE2 expression displayed a decrease or absence in gastric tumor tissue, and the overexpression of TIPE2 suppressed the growth of gastric cancer tumors and cells, demonstrating that TIPE2 could be a potential medicinal target for gastric cancer treatment. However, it’s seldomly reported that several medicinal agents or candidates targeted TIPE2 for treating diseases, including gastric cancer. To identify the candidate targeting TIPE2 to fight against gastric cancer, several extractions from traditional natural medicinal plants with anti-tumor functions were employed to screen the active compounds according to bioassay-guided isolation. Interestingly, gracillin, a component from the ethyl acetate extraction of Rhizoma Paridis, was identified to induce the expression of TIPE2 and inhibit the cell proliferation in gastric cancer BGC-823 cells. Furthermore, the underlying mechanisms that restrain gastric cancer were evaluated by clone formation, EdU staining, flow cytometry, and other assays. Meanwhile, the role of TIPE2 in the anti-tumor effect of gracillin was elucidated via the use of siTIPE2 RNA. It was determined that gracillin could fight against gastric cancer cells by inhibiting the cell proliferation participated by the PI3K/AKT pathway and cell cycle arrest, suppressing the EMT pathway-regulating cell migration, and inducing bcl2-associated mitochondrial apoptosis. Additionally, TIPE2 maybe contribute to the benefits of gracillin. These results of the present study are an important step toward the medicinal development of gracillin, and are also of use in understanding the effect of TIPE2 as a potential tumor target.