Background. Trichosporon species have emerged as an important non-Candida spp yeast pathogen in immunocompromised patients in recent decades; however, the systemic analysis of Trichosporon epidemiology has seldom been reported. Methods. We reviewed 185 reported cases of Trichosporon fungemia from 1975 to 2014 in the English-language literature, and the epidemiology and prognostic factors of the included cases are described. Results. The number of cases reported has increased with time, especially over the past decade. During the 3 decades from 1975 to 2004, the most commonly used antifungal compounds were amphotericin B/liposomal amphotericin B; however, in recent decades (2005–2014), triazoles (especially voriconazole) have become the most widely used agents, significantly improving outcome in the reported cases. Correlation analysis revealed that negative outcome is associated with several prognostic factors, including a history of antimicrobial use, bacterial bloodstream coinfection, prophylactic/empirical antifungal therapy, Trichosporon beigelii infection, and receiving the antifungal regimen of amphotericin B/liposomal amphotericin B. In addition, a significantly greater proportion of patients with a positive outcome had fungemia without invasive tissue infection and received a voriconazole regimen or an AmB-triazole combined regimen. Significant positive outcome was also associated with patients who had recovered from neutropenia or after central venous catheter removal. Conclusions. Voriconazole can be recommended as a first-line antifungal compound to treat Trichosporon fungemia; the immune status of the host plays a crucial role in the outcome of this infection, and the removal of vascular catheters should be considered if feasible.

Background: Neutrophils rapidly accumulate in large numbers at sites of tissue damage, exhibiting not only their well-known bactericidal capabilities but also playing crucial roles in angiogenesis and tissue repair. While exosomes derived from human umbilical cord mesenchymal stem cells (HucMSC-Exo) have emerged as a promising therapeutic tool, their exact mechanisms of action remain partly elusive. We hypothesize that HucMSC-Exo treatment may modulate neutrophil phenotypes, thereby significantly influencing wound healing outcomes. Methods: HucMSC-Exo were isolated via ultracentrifugation and subsequently administered through subcutaneous injection into full-thickness cutaneous wounds in mice. To determine the impact of host neutrophils on the healing effects of HucMSC-Exo in skin injuries, strategies including neutrophil depletion and adoptive transfer were employed. Flow cytometry was used to evaluate the proportion of N2 subtype neutrophils in both normal and diabetic wounds, and the effect of HucMSC-Exo on this proportion was assessed. Furthermore, the mitochondrial metabolic reprogramming driven by HucMSC-Exo during N2 polarization was investigated through JC1 staining, ATP quantification, fatty acid uptake assays, and assessment of FAO-related genes (Cpt1b, Acadm, and Acadl). Results: Depleting host neutrophils strikingly dampened prohealing effect of HucMSC-Exo on skin injury, while adoptive transfer of bone marrow neutrophils rescued this process. During normal healing process, some neutrophils expressed N2 markers, in contrast, diabetic wounds exhibited a reduced expression of N2 markers. After treatment with HucMSC-Exo, most neutrophils increased the phosphorylation of STAT6, leading to mitochondrial metabolic reprogramming and thus acquired an N2 phenotype. These N2 neutrophils, polarized by HucMSC-Exo, boosted the release of proangiogenic factors, particularly BV8, a myeloid cell-derived proangiogenic factor, and induced angiogenesis thereby favoring tissue restoration. Conclusion: This research uniquely demonstrates the identification of N2 neutrophils in skin injury and shows that HucMSC-Exo could skew neutrophils toward N2 phenotype, enhancing our insight into how cells react to HucMSC-Exo.

We herein report a case of slowly progressive cutaneous, rhinofacial, and pulmonary mucormycosis caused by Mucor irregularis in an immunocompetent woman who was successfully managed by combined surgical debridement and antifungal therapy. Slow progression, pulmonary involvement, occurrence in an immunocompetent patient, and good prognosis are unusual features of our case.

Aims/hypothesis: The resolution of apoptotic cells (ACs) is crucial for wound healing and tissue remodeling and is often impaired by persistent inflammation. This study aimed to elucidate the impact of neutrophil extracellular traps (NETs) on diabetic wound healing by targeting the phosphoinositide 3-kinase/Ras-related C3 botulinum toxin substrate 1 (PI3K/Rac1) signaling pathway, which is pivotal for macrophage efferocytosis. Methods: A streptozotocin-induced diabetic mouse model was used to assess the impact of NETs on efferocytosis in vivo. The effects of NETs on macrophage efferocytosis and wound healing were evaluated using specific inhibitors and agonists targeting the PI3K/Rac1 pathway. In vitro, macrophages from diabetic wounds or cell lines (Raw264.7) were treated with NETs and a panel of pharmacological agents of the PI3K/Rac1 pathway to evaluate macrophage efferocytosis. Results: NETs were found to inhibit macrophage efferocytosis, resulting in delayed clearance of ACs that accumulate within the wounds. Inhibition of NET formation in diabetic mice rescued impaired efferocytosis, accompanied by reactivation of PI3K and Rac1 in macrophages. Moreover, pharmacological agents targeting the PI3K/Rac1 pathway restored NETs-induced impairment in efferocytosis, leading to rapid wound healing. Raw264.7 cells exhibited elevated activation levels of PI3K and Rac1 when co-cultured with ACs in vitro. Nevertheless, this signaling activation was inhibited when cultured in a NETs-conditioned medium, leading to attenuated efferocytosis. Conclusions/interpretation: Targeting NETs and the PI3K/Rac1 pathway emerges as a potential therapeutic strategy to enhance healing in diabetic wounds by promoting macrophage efferocytosis.

ATF3 Activates Stat3 Phosphorylation through Inhibition of p53 Expression in Skin Cancer Cells ATF3;Stat3 phosphorylation;p53 expression;skin cancer cell; Aim: ATF3, a member of the ATF/CREB family of transcription factors, has been found to be selectively induced by calcineurin/NFAT inhibition and to enhance keratinocyte tumor formation, although the precise role of ATF3 in human skin cancer and possible mechanisms remain unknown. Methods: In this study, clinical analysis of 30 skin cancer patients and 30 normal donors revealed that ATF3 was accumulated in skin cancer tissues. Functional assays demonstrated that ATF3 significantly promoted skin cancer cell proliferation. Results: Mechanically, ATF3 activated Stat3 phosphorylation in skin cancer cell through regulation of p53 expression. Moreover, the promotion effect of ATF3 on skin cancer cell proliferation was dependent on the p53-Stat3 signaling cascade. Conclusion: Together, the results indicate that ATF3 might promote skin cancer cell proliferation and enhance skin keratinocyte tumor development through inhibiting p53 expression and then activating Stat3 phosphorylation.