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Scientific Reports Jan 2024This study aimed to investigate the molecular mechanism of sporotrichosis and identify possible novel therapeutic targets. Total RNA was extracted from skin lesion...
This study aimed to investigate the molecular mechanism of sporotrichosis and identify possible novel therapeutic targets. Total RNA was extracted from skin lesion samples from sporotrichosis patients and used to construct a long-chain RNA transcriptome library and miRNA transcriptome library for whole transcriptome sequencing. The differentially expressed genes (DEGs) between the groups were identified, and then Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and Gene Set Enrichment Analysis enrichment analyses were performed based on the DEGs. An lncRNA-miRNA-mRNA ceRNA network was constructed. The expressions of JAK/STAT pathway-related proteins were detected in the patient and control tissues using RT-qPCR and Western blot analysis. Enrichment analysis showed that the DEGs were mainly enriched in various infectious diseases and immune response-related signaling pathways. Competing endogenous RNA network analysis was performed and identified the hub lncRNAs, miRNAs, and mRNAs. Compared with the control group, the mRNA expressions of SOCS3, IL-6, and JAK3 were significantly upregulated, while the expression of STAT3 did not change significantly. Also, the protein expressions of SOCS3, IL-6, JAK3, and STAT3, as well as phosphorylated JAK3 and STAT3, were significantly upregulated. We identified 671 lncRNA DEGs, 3281 mRNA DEGs, and 214 miRNA DEGs to be involved in Sporothrix globosa infection. The study findings suggest that the JAK/STAT pathway may be a therapeutic target for sporotrichosis.
Topics: Humans; RNA, Long Noncoding; Sporotrichosis; Exome Sequencing; Interleukin-6; Janus Kinases; Gene Regulatory Networks; Signal Transduction; STAT Transcription Factors; MicroRNAs; Transcriptome; RNA, Messenger
PubMed: 38172590
DOI: 10.1038/s41598-023-50728-7 -
PLoS Neglected Tropical Diseases Jan 2024Nutrition plays a critical and crucial role in addressing neglected tropical diseases (NTDs) and their complications, as they often contribute to malnutrition, which can...
Nutrition plays a critical and crucial role in addressing neglected tropical diseases (NTDs) and their complications, as they often contribute to malnutrition, which can worsen the impact of these conditions. Therefore, it is necessary to investigate the nutritional status of mycetoma patients, which has not been explored previously. This descriptive cross-sectional hospital-based study was conducted at the Mycetoma Research Center (MRC), University of Khartoum, Sudan. The study included 179 confirmed mycetoma patients and an equal number of age- and sex-matched normal controls. The nutritional status of the mycetoma patients was assessed and compared with that of the control group. The majority of the patients were young adults with varying educational levels, predominantly from Central Sudan. The foot was the most commonly affected part; most patients had lesions more than 10 cm in diameter. The Body Mass Index (BMI) was calculated for both study groups, revealing that 43.5% of the patients and 53.6% of controls had a normal BMI. Furthermore, 36% of patients were underweight, contrasting with only 11% in the control group. Correlation analyses indicated no significant associations between BMI and age groups, educational levels, daily meals, food quantity, and appetite in the study population (p > 0.05). Similarly, no significant differences were observed in BMI concerning disease duration and affected sites (p = 0.0577). The Kruskal-Wallis test did not reveal significant differences in BMI means among the groups. The study revealed that most participants consumed three meals daily, and the control group showed a more robust appetite and consumed more food than the patient group (p = 0.005). Nevertheless, there were no significant differences in the consumption of different food types between the patient and control groups and among different BMI categories (p = 0.025 and 0.040, respectively).
Topics: Young Adult; Humans; Nutritional Status; Mycetoma; Sudan; Cross-Sectional Studies; Body Mass Index
PubMed: 38166142
DOI: 10.1371/journal.pntd.0011726 -
Photodiagnosis and Photodynamic Therapy Feb 2024Dermatophytosis is the most common fungal infectious disease in the world, which is commonly caused by Trichophyton rubrum in China. The traditional therapies for...
Dermatophytosis is the most common fungal infectious disease in the world, which is commonly caused by Trichophyton rubrum in China. The traditional therapies for treating dermatophytosis include topical and oral antifungal agents like terbinafine, griseofulvin, and azole antifungal drugs. However, 5-aminolevulinic acid-based photodynamic therapy (ALA-PDT) as a new alternative therapy avoids the side effects and drug resistance of traditional antifungal agents. We report two cases diagnosed as kerion and tinea faciei secondary to ulcers with CARD 9 deficiency, both of whom were infected by T.rubrum. They were both successfully treated by ALA-PDT combined with antifungal drugs, providing a feasible strategy for therapeutic choice for adult kerion and ulcer treatment.
Topics: Adult; Humans; Antifungal Agents; Aminolevulinic Acid; Ulcer; Photochemotherapy; Photosensitizing Agents; Tinea Capitis; Arthrodermataceae
PubMed: 38145772
DOI: 10.1016/j.pdpdt.2023.103954 -
Journal of Clinical Immunology Dec 2023Inborn errors of the IL-17A/F-responsive pathway lead to chronic mucocutaneous candidiasis (CMC) as a predominant clinical phenotype, without other significant clinical...
PURPOSE
Inborn errors of the IL-17A/F-responsive pathway lead to chronic mucocutaneous candidiasis (CMC) as a predominant clinical phenotype, without other significant clinical manifestations apart from mucocutaneous staphylococcal diseases. Among inborn errors affecting IL-17-dependent immunity, autosomal recessive (AR) IL-17RC deficiency is a rare disease with only three kindreds described to date. The lack of an in vitro functional evaluation system of IL17RC variants renders its diagnosis difficult. We sought to characterize a 7-year-old Japanese girl with CMC carrying a novel homozygous duplication variant of IL17RC and establish a simple in vitro system to evaluate the impact of this variant.
METHODS
Flow cytometry, qPCR, RNA-sequencing, and immunoblotting were conducted, and an IL17RC-knockout cell line was established for functional evaluation.
RESULTS
The patient presented with oral and mucocutaneous candidiasis without staphylococcal diseases since the age of 3 months. Genetic analysis showed that the novel duplication variant (Chr3: 9,971,476-9,971,606 dup (+131bp)) involving exon 13 of IL17RC results in a premature stop codon (p.D457Afs*16 or p.D457Afs*17). Our functional evaluation system revealed this duplication to be loss-of-function and enabled discrimination between loss-of-function and neutral IL17RC variants. The lack of response to IL-17A by the patient's SV40-immortalized fibroblasts was restored by introducing WT-IL17RC, suggesting that the genotype identified is responsible for her clinical phenotype.
CONCLUSIONS
The clinical and cellular phenotype of the current case of AR IL-17RC deficiency supports a previous report on this rare disorder. Our newly established evaluation system will be useful for the diagnosis of AR IL-17RC deficiency, providing accurate validation of unknown IL17RC variants.
Topics: Female; Humans; Infant; Child; Candidiasis, Chronic Mucocutaneous; Interleukin-17; Candidiasis; Fibroblasts; Base Sequence
PubMed: 38129603
DOI: 10.1007/s10875-023-01601-9 -
Frontiers in Microbiology 2023The emergence of ophidiomycosis (or snake fungal disease) in snakes has prompted increased awareness of the potential effects of fungal infections on wild reptile...
The emergence of ophidiomycosis (or snake fungal disease) in snakes has prompted increased awareness of the potential effects of fungal infections on wild reptile populations. Yet, aside from , little is known about other mycoses affecting wild reptiles. The closely related genus has been associated with dermatomycosis in snakes and tuataras in captive collections, and was recently identified as the cause of skin infections in non-native wild panther chameleons () in Florida, USA. Here we describe five cases of spp. associated with skin lesions in wild snakes in North America and one additional case from a captive snake from Connecticut, USA. In addition to demonstrating that wild Nearctic snakes can serve as a host for these fungi, we also provide evidence that the genus is widespread in wild snakes, with cases being identified in Louisiana (USA), Minnesota (USA), Virginia (USA), and British Columbia (Canada). Phylogenetic analyses conducted on multiple loci of the fungal strains we isolated identified in Louisiana and Virginia; the remaining strains from Minnesota and British Columbia did not cluster with any of the described species of , although the strains from British Columbia appear to represent a single lineage. Finally, we designed a pan- real-time PCR assay targeting the internal transcribed spacer region 2. This assay successfully detected DNA of all described species of and the two potentially novel taxa isolated in this study and did not cross-react with closely related fungi or other fungi commonly found on the skin of snakes. The assay was 100% sensitive and specific when screening clinical (skin tissue or skin swab) samples, although full determination of the assay's performance will require additional follow up due to the small number of clinical samples ( = 14 from 11 snakes) available for testing in our study. Nonetheless, the PCR assay can provide an important tool in further investigating the prevalence, distribution, and host range of spp. and facilitate more rapid diagnosis of spp. infections that are otherwise difficult to differentiate from other dermatomycoses.
PubMed: 38125577
DOI: 10.3389/fmicb.2023.1302586 -
Indian Journal of Pathology &... 2023
Topics: Humans; Blastomycosis; Cryptococcosis; Neoplasms
PubMed: 38084563
DOI: 10.4103/ijpm.ijpm_320_22 -
Journal de Mycologie Medicale Mar 2024Exophiala dermatitidis is a relatively common environmental black yeast with a worldwide distribution that rarely causes fungal infection. Here, we report a case of a... (Review)
Review
Concurrent infection of Exophiala dermatitidis and Angiostrongylus cantonensis in central nervous system of a child with inherited CARD9 deficiency: A case report and literature review.
Exophiala dermatitidis is a relatively common environmental black yeast with a worldwide distribution that rarely causes fungal infection. Here, we report a case of a 6-year-old girl with central nervous system (CNS) encephalitis caused by E. dermatitidis and Angiostrongylus cantonensis. E. dermatitidis was identified by both cerebrospinal fluid culture and metagenomic next-generation sequencing (mNGS). Angiostrongylus cantonensis infection was confirmed by an enzyme linked immunosorbent assay (ELISA). Whole exome sequencing showed that this previously healthy girl carried a homozygous CARD9 mutation for c.820dupG (p.D274Gfs*61) that underlies invasive fungal and parasite infections. We chose glucocortieoid pulse therapy and anti-infective therapy based on the initial results of laboratory examination and cranial MRI images. With the aggravation of the disease and the evidence of the subsequent etiologic test, the combination of antifungal antiparasitic treatments (voriconazole, fluorocytosine and amphotericin B) were actively used. Unfortunately, the girl finally died due to severe systemic infection. mNGS performs a potential value for diagnosing rare CNS infections, and autosomal recessive CARD9 deficiency should be considered in patient with fatal invasive fungal infections.
Topics: Child; Animals; Female; Humans; Angiostrongylus cantonensis; Central Nervous System; Candidiasis, Chronic Mucocutaneous; Exophiala; CARD Signaling Adaptor Proteins
PubMed: 38042015
DOI: 10.1016/j.mycmed.2023.101455 -
Frontiers in Immunology 2023Dermatophytosis is a common superficial infection caused by dermatophytes, a group of pathogenic keratinophilic fungi. Apart from invasion against skin barrier, host... (Review)
Review
Dermatophytosis is a common superficial infection caused by dermatophytes, a group of pathogenic keratinophilic fungi. Apart from invasion against skin barrier, host immune responses to dermatophytes could also lead to pathologic inflammation and tissue damage to some extent. Therefore, it is of great help to understand the pathogenesis of dermatophytes, including fungal virulence factors and anti-pathogen immune responses. This review aims to summarize the recent advances in host-fungal interactions, focusing on the mechanisms of anti-fungal immunity and the relationship between immune deficiency and chronic dermatophytosis, in order to facilitate novel diagnostic and therapeutic approaches to improve the outcomes of these patients.
Topics: Humans; Arthrodermataceae; Dermatomycoses; Virulence; Tinea; Immunity
PubMed: 38022599
DOI: 10.3389/fimmu.2023.1285887 -
Journal of Clinical Microbiology Dec 2023Dermatophyte infections (a.k.a. ringworm, tinea) affect an estimated 20%-25% of the world's population. In North America, most dermatophytoses are caused by or species...
Dermatophyte infections (a.k.a. ringworm, tinea) affect an estimated 20%-25% of the world's population. In North America, most dermatophytoses are caused by or species complexes. Severe and antifungal-resistant dermatophytoses are a growing global public health problem. A new species of the species complex, , has recently emerged and is notable for the severe infections it causes, its propensity for antifungal resistance, and its global spread. In this issue of the , C. F. CaƱete-Gibas, J. Mele, H. P. Patterson, et al. (J Clin Microbiol 61:e00562-23, 2023, https://doi.org/10.1128/JCM.00562-23) summarize the results of speciation and AFST performed on North American dermatophyte isolates received at a fungal diagnostic reference laboratory. Within their collection, 18.6% of isolates were resistant to terbinafine (a first-line oral antifungal for dermatophytoses), and similar proportions of and demonstrated terbinafine resistance. The authors also found that has been present in North America since at least 2017. These findings highlight the importance of increased surveillance efforts to monitor trends in severe and antifungal-resistant dermatophytoses and the need for antifungal stewardship efforts, the success of which is contingent upon improving laboratory capacity for dermatophyte speciation and AFST.
Topics: Humans; Terbinafine; Antifungal Agents; Arthrodermataceae; Tinea; Microbial Sensitivity Tests; Trichophyton; Drug Resistance, Fungal
PubMed: 38014979
DOI: 10.1128/jcm.00903-23 -
Anais Brasileiros de Dermatologia 2024
Review
Topics: Child; Humans; Erythema Nodosum; Tinea Capitis; Trichophyton
PubMed: 38007316
DOI: 10.1016/j.abd.2023.02.009