Acquired Digital Fibrokeratoma: A Report of Five Cases and Review of the Literature.

Acquired digital fibrokeratoma (ADF) is rare in clinical practice and is easily misdiagnosed. Herein, 5 cases of patients (3 males and 2 females) with ADF are reported. The mean age at onset was 42.6 years, and the mean disease duration was 3 years. Four patients had ADF on the hands, and 1 patient had ADF on the foot. The clinical manifestations were all solitary, skin-colored papules, with a firm texture and smooth surface, protruding from the skin surface. In 3 patients, ADF manifested as columnar protrusions, and in 2 patients, ADF manifested as dome-shaped protrusions. For all 5 patients, the diameters of the lesions were <1 cm. Clinically, all 5 patients were misdiagnosed (ie, eccrine poroma (EP), common warts, rudimentary polydactyly, pyogenic granuloma (PG), and acral fibroma). All cases of ADF were confirmed by histopathology. The histopathological manifestations of ADF were as follows: finger-like protrusions on the skin surface; collagen fiber bundles running vertically to the epidermis seen in the dermis; and thick red-stained collagen fibers connected with the normal dermal connective tissue below. All 5 patients underwent surgical resection; the distance between the incision margin and the edge of the tumor was 2-3 mm, and the surgical depth was the deep dermis. No recurrence was observed in more than half a year of follow-up after surgery.

Folic Acid-Modified Long-Circulating Liposomes Loaded with Sulfasalazine For Targeted Induction of Ferroptosis in Melanoma.

Melanoma is a malignant tumor that originates from melanocytes. The incidence of melanoma is increasing worldwide, partially because of its insensitivity to radiotherapy or chemotherapy. Therefore, effective treatments for melanoma are urgently required. In this study, we employed folic acid-modified sulfasalazine long-circulating liposomes (FA-SSZ-Lips) to precisely target drug delivery to melanoma cells, eliciting ferroptosis effectively. The synthesized FA-SSZ-Lips were characterized as small spheres of a double-layer membrane, a particle size of 110.1 nm, and a ζ-potential of -22.8 ± 0.66 mV. FA-SSZ-Lips are effective drug carriers with SSZ-loading ratio and SSZ release rate of 6.2 ± 0.10%, and 72.63 ± 1.40%, respectively. The liposomes enhanced SSZ solubility, and the folic acid modifications increased the liposome targeting to melanoma cells. Compared with SSZ alone, FA-SSZ-Lips more strongly inhibited B16F10 cell growth, significantly disrupted the intracellular redox balance, and induced ferroptosis. After treatment, considerable differences were observed in the tumor volumes between FA-SSZ-Lips and phosphate-buffered saline control groups. The tumor growth-inhibition value of the FA-SSZ-Lips group reached 70.09%. Thus, FA-SSZ-Lips exhibited favorable antitumor effects in vitro and in vivo and are a promising strategy for melanoma treatment.

Selective thermotherapy of tumor by self-regulating photothermal conversion system.

One major challenge of photothermal therapy (PTT) is achieving thermal ablation of the tumor without damaging the normal cells and tissues. Here, we designed a self-regulating photothermal conversion system for selective thermotherapy based on self-assembling gold nanoparticles (S-AuNPs) and investigated the selectivity effect using a novel home-made in vitro selective photothermal transformation model and an in vivo skin damaging assessment model. In the in vitro selective photothermal transformation model, laser irradiation selectively increased the temperature of the internal microenvironment (pH 5.5) and resulted in an obvious temperature difference (ΔT ≥ 5 °C) with that of the external environment (pH 7.4). More importantly, in the in vivo skin damaging assessment model, S-AuNPs achieved good tumor inhibition without damaging the normal skin tissue compared with the conventional photothermal material. This work provides not only a novel validation protocol for tumor thermotherapy to achieve the biosafety of specifically killing tumor cells and normal tissue but also an evaluation methodology for other precise therapy for cancers.

Chemotherapeutic drug-induced immunogenic cell death for nanomedicine-based cancer chemo-immunotherapy.

Chemotherapy has been a conventional paradigm for cancer treatment, and multifarious chemotherapeutic drugs have been widely employed for decades with significant performances in suppressing tumors. Moreover, some of the antitumor chemotherapeutic agents, such as doxorubicin (DOX), oxaliplatin (OXA), cyclophosphamide (CPA) and paclitaxel (PTX), can also tackle tumors through the induction of immunogenic cell death (ICD) in tumor cells to trigger specific antitumor immune responses of the body and improve chemotherapy efficacy. In recent years, chemo-immunotherapy has attracted increasing attention as one of the most promising combination therapies to struggle with malignant tumors. Many effective antitumor therapies have benefited from the successful induction of ICD in tumors, which could incur the release of endogenous danger signals and tumor-associated antigens (TAAs), further stimulating antigen-presenting cells (APCs) and ultimately initiating efficient antitumor immunity. In this review, several well-characterized damage-associated molecular patterns (DAMPs) were introduced and the progress of ICD induced by representative chemotherapeutic drugs for nanomedicine-based chemo-immunotherapy was highlighted. In addition, the combination strategies involving ICD cooperated with other therapies were discussed. Finally, we shared some perspectives in chemotherapeutic drug-induced ICD for future chemo-immunotherapy. It was hoped that this review would provide worthwhile presentations and enlightenments for cancer chemo-immunotherapy.

Bilayer Membrane Composed of Mineralized Collagen and Chitosan Cast Film Coated With Berberine-Loaded PCL/PVP Electrospun Nanofiber Promotes Bone Regeneration.

Bone defects are difficult to repair and reconstruct as bone regeneration remains technically challenging, with exogenous factors required to accelerate this process. Biodegradable synthetic scaffolds are promising materials for stimulating bone tissue repair. In this study, we investigated whether a bilayer membrane that includes mineralized collagen (MC) and chitosan (CS) delivering berberine (BER)-a typical Chinese herbal monomer-could promote bone healing in a rat model. An MC/CS cast film was coated with polycaprolactone (PCL)/polyvinylpyrrolidone (PVP) electrospun nanofibers loaded with BER, yielding the BER@PCL/PVP-MC/CS bilayer membrane. The 3-dimensional structure had nanofibers of uniform diameter and showed good hydrophilicity; the bilayer membrane showed favorable mechanical properties. BER@PCL/PVP-MC/CS enhanced the proliferation and attachment of MC3T3-E1 cells in vitro and induced bone regeneration when implanted into a rat femoral bone defect. These findings provide evidence that BER@PCL/PVP-MC/CS has clinical potential for effective bone repair.

Dual Modal Imaging-Guided Drug Delivery System for Combined Chemo-Photothermal Melanoma Therapy.

PURPOSE: Malignant melanoma is one of the most devastating types of cancer with rapid relapse and low survival rate. Novel strategies for melanoma treatment are currently needed to enhance therapeutic efficiency for this disease. In this study, we fabricated a multifunctional drug delivery system that incorporates dacarbazine (DTIC) and indocyanine green (ICG) into manganese-doped mesoporous silica nanoparticles (MSN(Mn)) coupled with magnetic resonance imaging (MRI) and photothermal imaging (PI), for achieving the superior antitumor effect of combined chemo-photothermal therapy. MATERIALS AND METHODS: MSN(Mn) were characterized in terms of size and structural properties, and drug loading and release efficiency MSN(Mn)-ICG/DTIC were analyzed by UV spectra. Photothermal imaging effect and MR imaging effect of MSN(Mn)-ICG/DTIC were detected by thermal imaging system and 3.0 T MRI scanner, respectively. Then, the combined chemo-phototherapy was verified in vitro and in vivo by morphological evaluation, ultrasonic and pathological evaluation. RESULTS: The as-synthesized MSN(Mn) were characterized as mesoporous spherical nanoparticles with 125.57±5.96 nm. MSN(Mn)-ICG/DTIC have the function of drug loading-release which loading ratio of ICG and DTIC could reach to 34.25±2.20% and 50.00±3.24%, and 32.68±2.10% of DTIC was released, respectively. Manganese doping content could reach up to 65.09±2.55 wt%, providing excellent imaging capability in vivo which the corresponding relaxation efficiency was 14.33 mM-1s-1. And outstanding photothermal heating ability and stability highlighted the potential biomedical applicability of MSN(Mn)-ICG/DTIC to kill cancer cells. Experiments by A375 melanoma cells and tumor-bearing mice demonstrated that the compound MSN(Mn)-ICG/DTIC have excellent biocompatibility and our combined therapy platform delivered a superior antitumor effect compared to standalone treatment in vivo and in vitro. CONCLUSION: Our findings demonstrate that composite MSN(Mn)-ICG/DTIC could serve as a multifunctional platform to achieve a highly effective chemo-photothermal combined therapy for melanoma treatment.

Toll-like receptor-mediated innate immunity against herpesviridae infection: a current perspective on viral infection signaling pathways.

BACKGROUND: In the past decades, researchers have demonstrated the critical role of Toll-like receptors (TLRs) in the innate immune system. They recognize viral components and trigger immune signal cascades to subsequently promote the activation of the immune system. MAIN BODY: Herpesviridae family members trigger TLRs to elicit cytokines in the process of infection to activate antiviral innate immune responses in host cells. This review aims to clarify the role of TLRs in the innate immunity defense against herpesviridae, and systematically describes the processes of TLR actions and herpesviridae recognition as well as the signal transduction pathways involved. CONCLUSIONS: Future studies of the interactions between TLRs and herpesviridae infections, especially the subsequent signaling pathways, will not only contribute to the planning of effective antiviral therapies but also provide new molecular targets for the development of antiviral drugs.