Potassium iodide enhances the killing effect of methylene blue mediated photodynamic therapy against F. monophora.

BACKGROUND: Chromoblastomycosis (CMB) is a chronic granulomatous fungal infection that affect the skin and subcutaneous tissues. It is clinically problematic due to limited treatment options, low cure rates, and high rates of relapse. This underscores the necessity for innovative treatment approaches. In this study, potassium iodide (KI) combined with Methylene Blue (MB) mediated antimicrobial photodynamic therapy (PDT) were assessed in the treatment of Fonsecaea monophora (F. monophora) both in vitro and in vivo. And the underlying mechanism that contributes to the efficacy of this treatment approach was investigated. METHODS: In vitro experiments were conducted using different combinations and concentrations of MB, KI, and 660 nm light (60 mW/cm2) to inhibit F. monophora. The study was carried out using colony-forming unit (CFU) counts and scanning electron microscopy (SEM). The production of singlet oxygen (1O2), free iodine (I2), hydrogen peroxide (H2O2), and superoxide anion during the KI combined MB-mediated antimicrobial PDT process was also detected. In vivo experiments were developed using a Balb/c mouse paw infection model with F. monophora and treated with PBS, 10 mM KI, 2 mM MB +100 J/cm² and 10 mM KI+2 mM MB +100 J/cm² respectively. Inflammatory swelling, fungal load and histopathological analyses of the mouse footpads were assessed. RESULTS: KI enhanced the killing effect of MB-mediated antimicrobial PDT on the conidial spores of F. monophora at the cell and infected animal model level. During the process, the main antimicrobial agents in KI combined with MB- mediated antimicrobial PDT could produce stronger toxic active species including free I2 and H2O2. CONCLUSION: KI combined with MB-mediated antimicrobial PDT could be an effective adjunct therapy for treating CBM.

Successful management of chromoblastomycosis utilizing conventional antifungal agents and imiquimod therapy.

Chromoblastomycosis (CBM), a chronic fungal infection affecting the skin and subcutaneous tissues, is predominantly caused by dematiaceous fungi in tropical and subtropical areas. Characteristically, CBM presents as plaques and nodules, often leading to scarring post-healing. Besides traditional diagnostic methods such as fungal microscopy, culture, and histopathology, dermatoscopy and reflectance confocal microscopy can aid in diagnosis. The treatment of CBM is an extended and protracted process. Imiquimod, acting as an immune response modifier, boosts the host's immune response against CBM, and controls scar hyperplasia, thereby reducing the treatment duration. We present a case of CBM in Guangdong with characteristic reflectance confocal microscopy manifestations, effectively managed through a combination of itraconazole, terbinafine, and imiquimod, shedding light on novel strategies for managing this challenging condition.

A systematic framework for identifying prognostic necroptosis-related lncRNAs and verification of lncRNA CRNDE/miR-23b-3p/IDH1 regulatory axis in glioma.

Glioma remains the most frequent malignancy of the central nervous system. Recently, necroptosis has been identified as a cell death process that mediates the proliferation and development of tumor cells. LncRNAs play a key role in the diagnosis and treatment of various diseases. However, the impact that necrosis-related lncRNAs (NRLs) have on glioma remains unclear. In our studies, we selected 9 NRLs to construct a prognostic model. Meanwhile, we assessed the survival curves of these 9 NRLs. Our findings found ADGRA1-AS1 and WAC-AS1 were protective lncRNAs, while MIR210HG, LINC01503, CRNDE, HOXC-AS1, ZIM2-AS1, MIR22HG and PLBD1-AS1 were risk lncRNAs. Specifically, 12 immune cells, 25 immune-correlated pathways, and TME score were differentially expressed in the both risk groups. Additionally, the study predicted and validated the necroptosis-related lncRNA CRNDE/miR-23b-3p/IDH1 axis. CRNDE was strongly expressed in glioma specimens and several cell lines. Inhibiting CRNDE resulted in a substantial reduction in the proliferation and migration of U-118MG and U251 cells. Furthermore, the study predicted that CRNDE may exhibit oncogenic features by adsorbing miR-23b-3p and positively regulating IDH1 expression. Overall, the study constructed a prognostic model in glioma, and predicted a lncRNA CRNDE/miR-23b-3p/IDH1 axis, which could potentially be useful for gene therapy of glioma.

JAK1/2 Inhibitor Baricitinib Improves Skin Fibrosis and Digital Ulcers in Systemic Sclerosis.

Background: Systemic sclerosis (SSc) is a rare disabling connective tissue disease with few available treatment options. Diffuse cutaneous systemic sclerosis (dcSSc) is associated with high mortality. A previous experiment has shown that JAK2 inhibitor can significantly improve skin fibrosis in bleomycin (BLM)-induced murine model, including reducing dermal thickening and collagen accumulation. We aimed to describe the efficacy of oral JAK1/2 inhibitor baricitinib in SSc patients, especially focusing on skin fibrosis and microvascular manifestations. Methods: We described the different effects of oral selective JAK1, JAK2, or JAK3 inhibitor treatment in a BLM-induced skin fibrosis mouse model. Furthermore, 10 adult patients with dcSSc were treated with baricitinib. We assessed the changes in modified rodman skin score (mRSS) and digital ulcer net burden at week 12 and 24 from baseline. We also compared the absolute changes in scores on the Scleroderma Health Assessment Questionnaire (SHAQ) and a total score on the St. George's Respiratory Questionnaire (SGRQ) over a 24-week period. Results: In the experimental mouse model of skin fibrosis, a JAK1 and JAK2 inhibitor ameliorated skin fibrosis, and a JAK2 inhibitor had the most obvious effect. Treatment with the JAK2 inhibitor also blunted the capillary rarefaction. We demonstrated that skin fibrosis and digital ulcers were significantly relieved in 10 SSc patients treated with baricitinib. The mRSS significantly improved at week 12 from baseline, with a mean change in mRSS of -8.3 [95% confidence interval (CI), -12.03 to -4.574; p = 0.0007] and improved greater at week 24 to -11.67 (95% CI, -16.84 to -6.496; p = 0.0008). Among the four patients with digital ulcers (DU), three were completely healed at week 24, the number of ulcers in another patient was significantly reduced, and there was no patient with new ulcers. Only one adverse event (AE) of herpes zoster was observed. Conclusions: Our results indicate that selective JAK1 and JAK2 inhibitor alleviates skin fibrosis, and oral JAK1/2 inhibitor baricitinib is a potentially effective treatment for dcSSc patients with skin fibrosis and DU. Baricitinib was well-tolerated by most patients in this study. Additional large clinical trials are needed to confirm our pilot findings. Chinese Clinical Trial Registry Number: ChiCTR2000030995.

Molecular Characteristics of Regional Chromoblastomycosis in Guangdong, China: Epidemiological, Clinical, Antifungal Susceptibility, and Serum Cytokine Profiles of 45 Cases.

Chromoblastomycosis (CBM) is a chronic disease caused by several species of dematiaceous fungi. In this study, a regional collection of 45 CBM cases was conducted in Guangdong, China, a hyper-endemic area of CBM. Epidemiology findings indicated that the mean age of cases was 61.38 ± 11.20 years, long duration ranged from 3 months to 30 years, and the gender ratio of male to female was 4.6:1. Thirteen cases (29%) declared underlying diseases. Verrucous form was the most common clinical manifestation (n = 19, 42%). Forty-five corresponding clinical strains were isolated, and 28 of them (62%) were identified as F. monophora; the remaining 17 (38%) were identified as F. nubica through ITS rDNA sequence analysis. Antifungal susceptibility tests in vitro showed low MICs in azoles (PCZ 0.015-0.25 µg/ml, VCZ 0.015-0.5 µg/ml, and ITZ 0.03-0.5 µg/ml) and TRB (0.015-1 µg/ml). Itraconazole combined with terbinafine was the main therapeutic strategy used for 31 of 45 cases, and 68% (n = 21) of them improved or were cured. Cytokine profile assays indicated upregulation of IL-4, IL-7, IL-15, IL-11, and IL-17, while downregulation of IL-1RA, MIP-1ß, IL-8, and IL-16 compared to healthy donors (p < 0.05). The abnormal cytokine profiles indicated impaired immune response to eliminate fungus in CBM cases, which probably contributed to the chronic duration of this disease. In conclusion, we investigated the molecular epidemiological, clinical, and laboratory characteristics of CBM in Guangdong, China, which may assist further clinical therapy, as well as fundamental pathogenesis studies of CBM.

Corrigendum: JAK1/2 inhibitor baricitinib improves skin fibrosis and digital ulcers in systemic sclerosis.

[This corrects the article DOI: 10.3389/fmed.2022.859330.].

Effect and safety of acupuncture for autism spectrum disorders: A protocol for systematic review and meta-analysis.

BACKGROUND: Autism spectrum disorder (ASD) is a complex neurodevelopmental condition, which is characterized by impairment in social interaction or communication and lack of flexibility of imagination and behavior. Acupuncture is one of the most common modality of Traditional Chinese medicine (TCM) and has been used to treat various disease in clinical practice for more than 2000 years in China by correcting disharmony and dysregulation of body. It has sometimes been used as a treatment aimed at improving ASD symptoms and outcomes, but its clinical effectiveness and safety has not been rigorously reviewed. We will plan to conduct a systematic review and meta-analysis to summarize the current evidence on the effects and safety of acupuncture for ASD. METHODS: The following databases will be searched: PubMed, the Cochrane Library, Embase, Wanfang Data, China National Knowledge Infrastructure, SinoMed, and VIP. Randomised controlled trials will be included to evaluate the effect and safety of acupuncture on patients with ASD. The primary outcome will be the core features of ASD. The risk of bias will be assessed by the Cochrane risk of bias tool. We will conduct a meta-analysis and sensitivity analysis, as well as a subgroup analysis if high heterogeneity is present, using Revman 5.3. We will use funnel plots to identify potential reporting biases. The Grading of Recommendations Assessment, Development and Evaluation will be used to evaluate the quality of evidence. RESULTS: This study will be to assess the effect and safety of acupuncture for ASD. CONCLUSIONS: This study will assess the effect of acupuncture for ASD and provide reliable evidence for the choice of treatments. ETHICS AND DISSEMINATION: The protocol will not need ethical approval because no issues of participant privacy exist. The results of this systematic review will provide evidence about the effect and safety of acupuncture for ASD. The results will be disseminated through peer review.

Urinary Metabonomic Profiling Discriminates Between Children with Autism and Their Healthy Siblings.

BACKGROUND Autism spectrum disorder (ASD) is a complicated neuropsychiatric disease that displays significant heterogeneity. The diagnosis of ASD is currently primarily dependent upon descriptions of clinical symptoms, and it remains urgent to find biological markers for the detection and diagnosis of autism. The current study applied the urinary metabolic profiling approach to characterize metabolic phenotypes in ASD. MATERIAL AND METHODS Urine was obtained from children with ASD and their matched healthy siblings. Samples were analyzed using 1H NMR-based methods designed to measure a broad range of metabolites. Partial least-square-discriminant analysis (PLS-DA) was used to develop models to identify metabonomic variations that can be used to distinguish between individuals with ASD and their unaffected siblings. RESULTS A significant difference was observed between the metabolomic profiles of children with ASD and that of their healthy siblings. An increase in the levels of tryptophan, hippurate, glycine, and creatine, and a decrease in trigonelline, melatonin, pantothenate, serotonin, and taurine were observed compared to the control group. We conclude that several metabolic pathways are affected by autism, which suggests that a gut-brain link may be important in the pathophysiology of ASD. CONCLUSIONS 1H NMR-based metabonomic analysis of the urine can determine perturbations of specific metabolic pathways related to ASD and help identify a characteristic metabolic fingerprint to better understand the disease and its causes.

Untargeted Metabolomic Profiling Using UHPLC-QTOF/MS Reveals Metabolic Alterations Associated with Autism.

Autism spectrum disorder (ASD) is a clinical spectrum of neurodevelopment disorder characterized by deficits in social communication and social interaction along with repetitive/stereotyped behaviors. The current diagnosis for autism relies entirely on clinical evaluation and has many limitations. In this study, we aim to elucidate the potential mechanism behind autism and establish a series of potential biomarkers for diagnosis. Here, we established an ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry- (UHPLC-QTOF/MS-) based metabonomic approach to discriminate the metabolic modifications between the cohort of autism patients and the healthy subjects. UHPLC-QTOF/MS analysis revealed that 24 of the identified potential biomarkers were primarily involved in amino acid or lipid metabolism and the tryptophan kynurenine pathway. The combination of nicotinamide, anthranilic acid, D-neopterin, and 7,8-dihydroneopterin allows for discrimination between ASD patients and controls, which were validated in an independent autism case-control cohort. The results indicated that UHPLC-QTOF/MS-based metabolomics is capable of rapidly profiling autism metabolites and is a promising technique for the discovery of potential biomarkers related to autism.

Phaeohyphomycosis due to Exophiala spinifera greatly improved by ALA-PDT: A case report.

An 80-year-old women complained of painful erythema, papules, nodules on her right wrist for 9 months. Granuloma and inflammatory infiltrates with septate fungal hyphae were observed in pathological sections. Growth of demaciatious fungus on SDA was confirmed to be Exophiala spinifera by microscopic appearance and ITS rDNA sequencing. The diagnosis of phaeohyphomycosis due to E. spinifera was established. The patient had a poor response to oral itraconazole (200 mg/d) combining with terbinafine (250 mg/d) for 6 weeks. Then, following three courses of ALA-PDT, used as adjuvant therapy, skin lesions greatly improved and remained stable after 3 months follow-up. The case suggests that ALA-PDT is an effective adjuvant treatment option for patients with recalcitrant local subcutaneous fungal infection.