A ferroptosis-reinforced nanocatalyst enhances chemodynamic therapy through dual H2O2 production and oxidative stress amplification.

The existence of a delicate redox balance in tumors usually leads to cancer treatment failure. Breaking redox homeostasis by amplifying oxidative stress and reducing glutathione (GSH) can accelerate cancer cell death. Herein, we construct a ferroptosis-reinforced nanocatalyst (denoted as HBGL) to amplify intracellular oxidative stress via dual H2O2 production-assisted chemodynamic therapy (CDT). Specifically, a long-circulating liposome is employed to deliver hemin (a natural iron-containing substrate for Fenton reaction and ferroptosis), ß-lapachone (a DNA topoisomerase inhibitor with H2O2 generation capacity for chemotherapy), and glucose oxidase (which can consume glucose for starvation therapy and generate H2O2). HBGL can achieve rapid, continuous, and massive H2O2 and •OH production and GSH depletion in cancer cells, resulting in increased intracellular oxidative stress. Additionally, hemin can reinforce the ferroptosis-inducing ability of HBGL, which is reflected in the downregulation of glutathione peroxidase-4 and the accumulation of lipid peroxide. Notably, HBGL can disrupt endo/lysosomes and impair mitochondrial function in cancer cells. HBGL exhibits effective tumor-killing ability without eliciting obvious side effects, indicating its clinical translation potential for synergistic starvation therapy, chemotherapy, ferroptosis therapy, and CDT. Overall, this nanocatalytic liposome may be a promising candidate for achieving potentiated cancer treatment.

Hydrogel-Based Growth Factor Delivery Platforms: Strategies and Recent Advances.

Growth factors play a crucial role in regulating a broad variety of biological processes and are regarded as powerful therapeutic agents in tissue engineering and regenerative medicine in the past decades. However, their application is limited by their short half-lives and potential side effects in physiological environments. Hydrogels are identified as having the promising potential to prolong the half-lives of growth factors and mitigate their adverse effects by restricting them within the matrix to reduce their rapid proteolysis, burst release, and unwanted diffusion. This review discusses recent progress in the development of growth factor-containing hydrogels for various biomedical applications, including wound healing, brain tissue repair, cartilage and bone regeneration, and spinal cord injury repair. In addition, the review introduces strategies for optimizing growth factor release including affinity-based delivery, carrier-assisted delivery, stimuli-responsive delivery, spatial structure-based delivery, and cellular system-based delivery. Finally, the review presents current limitations and future research directions for growth factor-delivering hydrogels.

A PD-L1xCD3 bispecific nanobody as a novel T-cell engager in treating PD-L1 overexpression melanoma.

The development of Immune checkpoint blockade(ICB) therapy and BRAF- and MEK-targeted therapies has reshaped the survival outcomes of the patients with advanced melanoma. PD-1/PD-L1 blockade was an approved strategy in melanoma treatment. Here we design a PD-L1 xCD3 nanobody as a novel bispecific T cell engager (BiTE) in treating PD-L1 overexpression melanoma. BiTE PD-L1×CD3 Nb was predicted to bind near a large acidic surface on CD3-ε similar to UCHT1-scFv antibody based on alpha-fold and molecular docking. BiTE PD-L1×CD3 Nb and anti-CD3 Nb retained the ability to activate T cells to produce TNF-α and IFN-γ in a dose-dependent manner. The IC50 value of BiTE PD-L1×CD3 Nb was 4.208µg/mL. BiTE PD-L1×CD3 Nb showed obvious cytotoxic activity on both A375WT and A375PD-L1 related to PD-L1 expression level.

Pediatric tinea capitis in Jilin Province: analyzing previous results from a new perspective.

OBJECTIVES: To investigate the current etiological, diagnostic, and therapeutic characteristics of tinea capitis in children in Jilin Province. METHODS: Sixty pediatric patients with tinea capitis were enrolled between August 2020 and December 2021. Data on calcofluor white (CFW) fluorescence microscopy, fungal culture, Wood's lamp examination, dermoscopy, treatment, and follow-up were collected and analyzed. RESULTS: 1. Of all the enrolled patients, 48 had a history of animal contact, mostly with cats and dogs. Fifty-one strains were isolated, of which 46 were Microsporum canis (M. canis). 2. All enrolled patients were examined using fluorescence microscopy, and 59 were positive. Forty-one cases of tinea alba were examined using Wood's lamp, and 38 were positive. Forty-two cases of tinea alba were examined using dermoscopy, and 39 demonstrated specific signs. Effective treatment manifested as a fading bright green fluorescence, decreased mycelial/spore load, reduced specific dermoscopic signs, and hair regrowth. 3. Treatment was terminated in 23 and 37 cases based on mycological and clinical cures, respectively. No recurrence occurred during follow-up. CONCLUSION: 1. M. canis is the predominant pathogen causing tinea capitis in children in Jilin Province. Animal contact is considered the main risk factor. 2. CFW fluorescence microscopy, Wood's lamp, and dermoscopy can be used to diagnose ringworms and follow-up patients. 3. Both mycological and clinical cures can be the endpoint of adequate treatment for tinea capitis.

Sulfur-Doped Organosilica Nanodots as a Universal Sensor for Ultrafast Live/Dead Cell Discrimination.

Rapid and accurate differentiation between live and dead cells is highly desirable for the evaluation of cell viability. Here, we report the application of the orange-emitting sulfur-doped organosilica nanodots (S-OSiNDs) for ultrafast (30 s), ultrasensitive (1 µg/mL), and universal staining of the dead bacterial, fungal, and mammalian cells but not the live ones, which satisfies the requirements of a fluorescent probe that can specifically stain the dead cells. We further verify that the fluorescence distribution range of S-OSiNDs (which are distributed in cytoplasm and nucleus) is much larger than that of the commercial dead/fixed cell/tissue staining dye RedDot2 (which is distributed in the nucleus) in terms of dead mammalian cell staining, indicating that S-OSiNDs possess a better staining effect of dead cells than RedDot2. Overall, S-OSiNDs can be used as a robust fluorescent probe for ultrafast and accurate discrimination between dead and live cells at a single cell level, which may find a variety of applications in the biomedical field.

Compound Heterozygous Mutations in TGM1 Causing a Severe Form of Lamellar Ichthyosis: A Case Report.

We aimed to detect the pathogenic gene mutations in a patient with lamellar ichthyosis (LI). The genomic DNA of the patient was examined using high-throughput whole-exome sequencing to identify the causative mutations. Compound heterozygous mutations of c.1187G>T (p.Arg396Leu) and c.607C>T (p.Gln203*) were found in the transglutaminase-1 gene (TGM1) on chromosome 14 of the proband. The mutations stated above have been reported to impair the function of TGM1 protein and to be pathogenic. Our data suggest that the proband carried compound heterozygous mutations of c.1187G>T(p.Arg396Leu) and c.607C>T(p.Gln203*) in TGM1, which were in the trans position and the cause of his disease. We also found some dermoscopic in this patient which may be specific in LI.

YY1-induced long non-coding RNA small nucleolar RNA host gene 8 promotes the tumorigenesis of melanoma via the microRNA-656-3p/SERPINE1 mRNA binding protein 1 axis.

Long non-coding (lnc) RNA serves a vital role in the cellular processes of carcinoma. This study aimed to explore the accurate mechanism underlying lncRNA small nucleolar RNA host gene 8 (SNHG8) in melanoma. In this study, lncRNA SNHG8 expression were upregulated in melanoma tissues and cells, and lncRNA SNHG8 knockdown reduced melanoma cell viability, migration and invasion. Moreover, lncRNA SNHG8 expression could be induced by transcription factor YY1. In addition, we found that miR-656 could directly bind to lncRNA SNHG8 and SERPINE1 mRNA binding protein 1 (SERBP1). Rescue assays indicated that miR-656 overexpression inhibited the aforementioned cellular activities in melanoma cells, which were reversed by SERBP1 overexpression. In conclusion, this work elucidated that YY1-induced upregulation of lncRNA SNHG8 boosted the development of melanoma via the miR-656-3p/SERBP1 axis, providing a novel therapeutic strategy for melanoma treatment.

Cutaneous Mycobacterium chelonae in a Patient with Sjogren's Syndrome.

A case of cutaneous Mycobacterium chelonae infection in a patient with Sjogren's syndrome (SS) was misdiagnosed as sporotrichosis. A 56-year-old female patient was admitted to another hospital. Based on results of the histopathological examination and secretion culture obtained at the other hospital, the patient was diagnosed with sporotrichosis and received antifungal therapy. After treatment failure, the patient was admitted to our hospital, and a histopathological examination and secretion culture were performed again. The secretion culture revealed the presence of Mycobacterium chelonae. The antinuclear antibody test suggested SS, and the patient was treated with antibiotics and corticosteroids.

Lycodine type alkaloids from Lycopodiastrum casuarinoides with cytotoxic and cholinesterase inhibitory activities.

A chemical investigation on the 70% EtOH extract of the aerial parts of Lycopodiastrum casuarinoides led to the isolation of six novel lycodine type alkaloids, lycocasuarines A-F (1-6). The structures of the isolated compounds were established based on 1D and 2D (1H1H COSY, HMQC, and HMBC) NMR spectroscopy, in addition to high resolution mass spectrometry. The isolated alkaloids were tested in vitro for cytotoxic potentials against seven malignant melanoma cell lines as well as acetylcholinesterase (AChE) and butyrocholinesterase (BuChE) inhibitory activities. As a result, alkaloids 1 and 3 exhibited significant cytotoxic activities against all the tested tumor cell lines with IC50 values <10 µM and the inhibitory activities for AchE (0.94 ±â€¯0.15 and 0.24 ±â€¯0.03 µM, respectively) and BuchE (1.82 ±â€¯0.12 and 7.31 ±â€¯0.42 µM, respectively).

Dacryocystitis due to sporothrix inoculated vis an unusual mode: Case report.

RATIONALE: Sporotrichosis is the most common subcutaneous mycosis. It is caused by the dimorphic fungus Sporothrix schenckii. Ocular sporotrichosis is uncommon and has been rarely reported. PATIENT CONCERNS: We describe a 34-year-old female who presented with a nodule increasing in size near the medial angle of the left eye. Originally, she was misdiagnosed with a dacryocyst space-occupying lesion, and the lesion was removed by surgery. DIAGNOSES: Findings of fungal structures in the histopathological examination contributed to the diagnosis of Sporothrix dacryocystitis. Further culture of conjunctival secretions and contact lens storage solution was positive for Sporothrix. INTERVENTIONS: She was treated with oral itraconazole, 200 mg by mouth twice daily. OUTCOMES: After 3 months of treatment with oral itraconazole, culture of the conjunctival secretions was negative. LESSONS: It is of paramount importance to clinically suspect mycosis, even in unusual locations or in the absence of the typical epidemiological history.

Changes of serum trace elements level in patients with alopecia areata: A meta-analysis.

Abnormalities of serum trace elements are involved in the etiology and pathogenesis of alopecia areata (AA); however, the results of published studies are controversial. The purpose of the present study is to investigate the alterations of serum level of trace elements and AA using a meta-analysis approach. We searched all articles indexed in PubMed, Embase and Science Citation Index published up to 30 April 2016 concerning the association between serum level of zinc, copper, iron/ferritin, selenium or magnesium and AA. Ten eligible articles involving 764 subjects were identified. Overall, pooled analysis indicated that patients with AA had a lower serum level of zinc (P < 10-4 ) and selenium (P < 10-4 ) than the healthy controls. However, there was no significant difference between the AA patients and controls in the levels of serum copper (P = 0.81), serum iron (P = 0.36), serum ferritin (P = 0.37) and serum magnesium (P = 0.07). This meta-analysis suggests that low serum levels of zinc and selenium seem to be important risk factors for AA.