ZnO nanoparticles impair autophagic flux and cell viability through the TRIM16-NRF2-p62 pathway in inflammatory keratinocytes.

PURPOSE: Zinc oxide nanoparticles (ZnO NPs) are widely used in sunscreen, cosmetics, and topical drugs. Most previous studies have confirmed the safety of ZnO NPs applied to normal skin; however, little is known about the safety and potential toxicity of ZnO NPs applied to inflamed skin. This study aimed to evaluate the exposure risk of ZnO NPs in the treatment of inflammatory skin diseases. METHODS: Normal human and tumor necrosis factor-α (TNF-α)-induced inflammatory keratinocytes were incubated with ZnO NPs to assess their toxic effects on cell viability and autophagy signaling pathway. Tandem mass tag (TMT)-based proteomics analysis was used to identify differentially expressed proteins following incubation of inflammatory keratinocytes with ZnO NPs. Protein expression was assessed by Western blot, and double fluorescent labeling and siRNA-knockdown further elucidated the role of the TRIM16-NRF2-p62 pathway in mediating the effects of ZnO NP. RESULTS: In TNF-α-induced inflammatory keratinocytes, ZnO NPs activated cytoprotective autophagy and mediated p62-related autophagic flux block, thereby reducing the viability of inflammatory keratinocytes. Additionally, TRIM16-NRF2 was essential in ZnO NP-mediated autophagy flux block and cell viability reduction in inflammatory keratinocytes. Inhibition of the TRIM16-NRF2 pathway reduced p62 levels, alleviated autophagy flux blockade, and slightly restored the viability of inflammatory keratinocytes. CONCLUSION: ZnO NPs activated protective cell autophagy. Blockade of autophagy flux mediated by the TRIM16-NRF2-p62 pathway led to decreased cell viability. This study provided a deeper understanding of the toxicity mechanism of ZnO NPs in inflammatory keratinocytes.

Adalimumab in Treating Refractory Livedoid Vasculopathy.

Livedoid vasculopathy is a chronic, recurrent skin disorder. It seriously affects the quality of patients' life. However, the pathogenesis has not been fully identified yet. Here, this retrospective study describes the successful use of anti-TNF-α agent adalimumab in three cases of refractory livedoid vasculopathy, which has not been reported previously. In addition, we provide some clinical evidence that adalimumab therapy is efficient in improving skin lesions and relieving the pain of livedoid vasculopathy.

Zinc Oxide Nanoparticles Prime a Protective Immune Response in Galleria mellonella to Defend Against Candida albicans.

Purpose: Zinc oxide nanoparticles (ZnO-NPs) have exerted antimicrobial properties. However, there is insufficient evaluation regarding the in vivo antifungal activity of ZnO-NPs. This study aimed to investigate the efficacy and mechanism of ZnO-NPs in controlling Candida albicans in the invertebrate Galleria mellonella. Methods: Galleria mellonella larvae were injected with different doses of ZnO-NPs to determine their in vivo toxicity. Non-toxic doses of ZnO-NPs were chosen for prophylactic injection in G. mellonella followed by C. albicans infection. Then the direct in vitro antifungal effect of ZnO-NPs against C. albicans was evaluated. In addition, the mode of action of ZnO-NPs was assessed in larvae through different assays: quantification of hemocyte density, morphology observation of hemocytes, characterization of hemocyte aggregation and phagocytosis, and measurement of hemolymph phenoloxidase (PO) activity. Results: Zinc oxide nanoparticles were non-toxic to the larvae at relatively low concentrations (≤20 mg/kg). ZnO-NP pretreatment significantly prolonged the survival of C. albicans-infected larvae and decreased the fungal dissemination and burden in the C. albicans-infected larvae. This observation was more related to the activation of host defense rather than their fungicidal capacities. Specifically, ZnO-NP treatment increased hemocyte density, promoted hemocyte aggregation, enhanced hemocyte phagocytosis, and activated PO activity in larvae. Conclusion: Prophylactic treatment with lower concentrations of ZnO-NPs protects G. mellonella from C. albicans infection. The innate immune response primed by ZnO-NPs may be part of the reason for the protective effects. This study provides new evidence of the capacity of ZnO-NPs in enhancing host immunity and predicts that ZnO-NPs will be attractive for further anti-infection applications.

Nanomaterials applied in wound healing: Mechanisms, limitations and perspectives.

Internal and external factors cause various types of wounds on the skin. Infections, nonhealing chronic wounds, and aesthetic and functional recovery all cause challenges for clinicians. The development of nanotechnology in biomedicine has brought many new materials, methods and therapeutic targets for the treatment of wounds, which are believed to have great prospects. In this work, the nanomaterials applied in different stages to promote wound healing and systematically expounded their mechanisms were reviewed. Then, the difficulties and defects of the present research and suggested methods for improvement were pointed out. Moreover, based on the current application status of nanomaterials in wound treatment, some new ideas for subsequent studies were proposed and the feasibility of intelligent healing by real-time monitoring, precision regulation, and signal transmission between electronic signals and human nerve signals in the future were discussed. This review will provide valuable directions and spark new thoughts for researchers.

Successful treatment of a patient with recurrent infection of Chromobacterium violaceum.

BACKGROUND: Chromobacterium violaceum (C. violaceum) is a Gram-negative saprophytic bacterium that is widespread in tropical and subtropical environments, and belongs to conditional pathogenic bacteria. Human infection with C. violaceum is rare, and this can be fatal when the diagnosis and treatment are delayed, especially recurrent infection patients. Since clinicians lack the knowledge for C. violaceum, rapid diagnosis and early appropriate antimicrobial treatment remains challenging. CASE PRESENTATION: A 15-year-old male student was hospitalized for dark abscess, pustules, severe pain in both legs, and fever for 11 days. There were pustules with gray-white pus and red infiltrating plaques on the back, and the subcutaneous nodules could be touched in front of both tibias, with scab, rupture and necrotic tissue of the lower limb. The patient's condition rapidly progressed. Therefore, next-generation sequencing (NGS), pustular secretion and blood culture were concurrently performed. The final diagnosis for this patient was C. violaceum infection by NGS. However, no bacterial or fungal growth was observed in the pustular secretion and blood culture. After 4 weeks of treatment, the patient was discharged from the hospital without any complications associated with C. violaceum infection. CONCLUSION: Rapid diagnosis and early appropriate antimicrobial treatment is the key to the successful treatment of C. violaceum infection, especially in patients with sepsis symptoms. This case highlights that NGS is a promising tool for the rapid diagnosis of C. violaceum infection, preventing the delayed diagnosis and misdiagnosis of C. violaceum infection in patients who tested negative for pustular secretion and blood culture.

Rare cases of PAMI syndrome in both father and son with the same missense mutation in PSTPIP1 gene and literature review.

PSTPIP1-associated myeloid-related proteinaemia inflammatory (PAMI) syndrome has been described as a rare and distinct clinical phenotype of PSTPIP1-associated inflammatory diseases. We report PSTPIP1 mutation in both father and son who have leukopenia and acne-like lesions. Through whole-exome sequencing on blood DNA, it is found a heterozygous mutation of PSTPIP1 gene c.748G>A on the father and son. The diagnosis of PAMI is made based on DNA sequencing results and clinical characteristics of typical lesions, leukopenia, and the markedly increased serum S100A8/A9 (calprotectin).

Pre-exposure to Candida glabrata protects Galleria mellonella against subsequent lethal fungal infections.

Commensal fungi are an important part of human microbial community, among which Candida albicans and Candida glabrata are two common opportunistic pathogens. Unlike the high pathogenicity of C. albicans, C. glabrata is reported to show low pathogenicity to the host. Here, by using a Galleria mellonella infection model, we were able to confirm the much lower virulence of C. glabrata than C. albicans. Interestingly, pre-exposure to live C. glabrata (LCG) protects the larvae against subsequent various lethal fungal infections, including C. albicans, Candida tropicalis, and Cryptococcus neoformans. Inconsistently, heat-inactivated C. glabrata (HICG) pre-exposure can only protect against C. albicans or C. tropicalis re-infection, but not C. neoformans. Mechanistically, LCG or HICG pre-exposure enhanced the fungicidal activity of hemocytes against C. albicans or C. tropicalis. Meanwhile, LCG pre-exposure enhanced the humoral immunity by modulating the expression of fungal defending proteins in the cell-free hemolymph, which may contribute to the protection against C. neoformans. Together, this study suggests the important role of C. glabrata in enhancing host immunity, and demonstrates the great potential of G. mellonella model in studying the innate immune responses against infections.

Bilateral asymmetrical herpes-zoster with Ramsay hunt syndrome in an immunocompetent adult.

BACKGROUND: Bilateral herpes zoster (BHZ) is an atypical presentation of herpes zoster (HZ), with few cases reported before. Ramsay Hunt syndrome (RHS) is an uncommon complication of VZV infection. Cases of BHZ with RHS in immunocompetent adults have been reported rarely. CASE PRESENTATION: We described an immunocompetent adult who suffered from left-sided thoracic herpes zoster and contralateral RHS simultaneously, and summarizes the characteristics of BHZ. CONCLUSIONS: Cases of BHZ with RHS in immunocompetent adults have not been reported previously. Antivirus - glucocorticoid combination therapy showed a good effect in this case.