Self-improving dystrophic epidermolysis bullosa with a novel heterozygous missense variant in the COL7A1 gene in a Taiwanese family.

Self-improving dystrophic epidermolysis bullosa (DEB) is a genodermatosis that is inherited autosomal dominantly or recessively, and its clinical symptoms may improve or subside spontaneously. Herein, we report a case of self-improving DEB with COL7A1 p.Gly2025Asp variant. The diagnosis was made through histopathological, electron microscopic examination, and genetic testing. The same variant is also noted on his father, who presents with dystrophic toenails without any blisters. This study highlights that idiopathic nail dystrophy could be linked to congenital or hereditary disease. Furthermore, we conducted a review of the literature on the characteristics of reported cases of self-improving DEB with a personal or family history of nail dystrophy. The results supported our findings that nail dystrophy may be the sole manifestation in some family members. We suggest that individuals suffering from idiopathic nail dystrophy may seek genetic counselling when planning pregnancy to early evaluate the potential risk of hereditary diseases.

Investigation of the keratinocyte transcriptome altered in high-glucose environment: An in-vitro model system for precision medicine.

BACKGROUND: Impaired wound healing is a serious diabetes complication compromising patients' quality of life. However, the pathogenesis of diabetic wounds (DWs) remains incompletely understood. Human epidermal keratinocyte (HEK) is the sentinel cell that initiates healing processes after the epidermal integrity has been disrupted. OBJECTIVE: This study aimed to investigate the functional roles of HEKs in wound healing and to identify candidate genes, signaling pathways and molecular signatures contributing to the DWs. METHODS: HEKs were cultured in normal or high-glucose environment, followed by scratch, to mimic the microenvironment of normal wounds and DWs. Subsequently, we performed RNA sequencing and systematically analyzed the expression profiles by bioinformatics approaches. RESULTS: High-glucose environment altered the keratinocyte transcriptome responses to wounding. In experimental model of DWs, we found that TNF, CYP24A1, NR4A3 and GGT1 were key overexpressed genes in keratinocytes and were implicated in multiple cellular responses. Further analysis showed that wounding in high-glucose environment activated G-protein-coupled receptor (GPCR) signaling, cAMP response element-binding protein (CREB) signaling, and adrenomedullin signaling in keratinocytes, while dysregulated skin development and immune responses as compared to their counterpart in normal glucose settings. CONCLUSION: This simplified in-vitro model serves as a valuable tool to gain insights into the molecular basis of DWs and to facilitate establishment of personalized therapies in clinical practice.

Lumbar paraspinal atypical spindle cell/pleomorphic lipomatous tumor: A report of a rare case.

The atypical spindle cell/pleomorphic lipomatous tumor (ASPLT) was classified as a new tumor by the World Health Organization (WHO) in 2020. The tumor is benign and commonly occurs in the limbs. Paraspinal presentations are rare. A 38-year-old man presented at our clinic complaining of sudden onset back pain. No neurological deficit was found. The magnetic resonance imaging (MRI) revealed a well-defined heterogeneous mass in the left psoas muscle, from L1 to L3 extending over the L1 and L2 neuroforamen. The tumor was totally excised. Pathology led to an ASPLT diagnosis. Clinical symptoms improved and there was no postsurgical neurological deficit. This case of ASPLT, located in an uncommon location and present an unusual cluster of symptoms, could be treated by surgical excision, usually the first-treatment strategy. Totally, removal was achieved because there was a clear morphological margin. The risk of metastatic dissemination was minimal, though there remains a nonnegligible risk of local recurrence.

Air-mattress system for ballistocardiogram-based heart rate and breathing rate estimation.

Sleep-related problems are widespread. Numerous devices for sleep monitoring are increasingly available, including smartwatches, sleep monitoring rings, etc. These devices accumulate and analyze a substantial quantity of physiological data. In this study, we develop a smart air-mattress system that can effectively aid health measurements. The proposed system adopts an air-mattress system to detect subtle changes in pressure and thereby collect micro physiological signals, including ballistocardiography (BCG) and breathing signals. The system uses ultrasonic signals to detect the subject's turning movements. To increase the signal recognition accuracy, the BCG signal is processed effectively to reduce noise interference engendered by the body movement during sleep and is processed using regression analysis for heart rate and breathing rate estimation. Accordingly, the proposed system is unconstrained and can be used to collect micro BCG signals, breathing signals, heart rate signals, and turning movements for the long-term health-care.

High expression of NLRP12 predicts poor prognosis in patients with intracranial glioma.

BACKGROUND: Intracranial gliomas are the most common primary central nervous system tumors in humans, and glioblastoma multiforme is the most malignant intracranial glioma. The nucleotide-binding domain leucine-rich repeat (NLR)-containing family are crucial regulators of inflammatory and innate immune responses. NLRP12 codes for the monarch-1 protein, which regulates immune responses in humans. Data from a next-generation sequencing database indicated that NLRP12 expression is increased in glioma cells. However, the relationship between NLRP12 levels and gliomas is unclear. METHODS: To explore the role of NLRP12-related translation factors and proteins in glioma, we evaluated the clinical data and paraffin sections from glioma patients. The expression of NLRP12 was evaluated using immunohistochemical analysis, and clinical parameters were analyzed using chi-square and Kaplan-Meier survival tests. RESULTS: The degree of malignancy and prognosis highly correlated with NLRP12 levels. In addition, the siRNA-mediated downregulation of NLRP12 in glioma cell lines decreased proliferation, invasion, and migration. The levels of VEGF, N-cadherin, and cyclin D1 were downregulated after knockdown of NRLP12 in glioma cell lines, as observed using western blotting in vitro. Knockdown of NLRP12 attenuated the tumor progression in vivo. CONCLUSION: The expression of NLRP12 may be an independent prognostic factor and a potential target for the treatment of intracranial glioma.

High expression of GSKIP is associated with poor prognosis in meningioma.

Meningiomas are the most common extra-axial primary central nervous system tumors. There is no effective treatment or targeted therapy for meningioma except excision and radiotherapy. glycogen synthesis kinase 3ß interaction protein (GSKIP) is an A-kinase anchor protein that has cytosolic scaffolding function and binds to a protein kinase A and glycogen synthesis kinase 3ß to modulate different biological processes and malignant tumorigenesis through the Wnt pathway. The purpose of this study was to investigate the relationship between GSKIP expression and the clinico-pathological parameters in meningioma using immunohistochemical staining. We collected samples from 74 patients, from 2008 to 2012, in the Kaohsiung Medical University Hospital that had data on the staging and prognosis of the meningioma pathological section. Chi-square, Kaplan-Meier method, and cox regression were used to analyze the correlation between clinical parameters and immunohistochemistry staining for GSKIP. Following our immunohistochemical score, we found that higher expression of GSKIP was associated with high World Health Organization grading, recurrence, malignant transformation, and reduced overall survival time and recurrence-free survival time in meningioma. GSKIP may be a biomarker of poor prognosis and a target protein for therapy in meningioma.

Evaluation of Radioiodinated Fluoronicotinamide/Fluoropicolinamide-Benzamide Derivatives as Theranostic Agents for Melanoma.

Malignant melanoma is the most harmful type of skin cancer and its incidence has increased in this past decade. Early diagnosis and treatment are urgently desired. In this study, we conjugated picolinamide/nicotinamide with the pharmacophore of 131I-MIP-1145 to develop 131I-iodofluoropicolinamide benzamide (131I-IFPABZA) and 131I-iodofluoronicotiamide benzamide (131I-IFNABZA) with acceptable radiochemical yield (40 ± 5%) and high radiochemical purity (>98%). We also presented their biological characteristics in melanoma-bearing mouse models. 131I-IFPABZA (Log P = 2.01) was more lipophilic than 131I-IFNABZA (Log P = 1.49). B16F10-bearing mice injected with 131I-IFNABZA exhibited higher tumor-to-muscle ratio (T/M) than those administered with 131I-IFPABZA in planar γ-imaging and biodistribution studies. However, the imaging of 131I-IFNABZA- and 131I-IFPABZA-injected mice only showed marginal tumor uptake in A375 amelanotic melanoma-bearing mice throughout the experiment period, indicating the high binding affinity of these two radiotracers to melanin. Comparing the radiation-absorbed dose of 131I-IFNABZA with the melanin-targeted agents reported in the literature, 131I-IFNABZA exerts lower doses to normal tissues on the basis of similar tumor dose. Based on the in vitro and in vivo studies, we clearly demonstrated the potential of using 131I-IFNABZA as a theranostic agent against melanoma.

Noninvasive prenatal detection of hemoglobin Bart hydrops fetalis via maternal plasma dispensed with parental haplotyping using the semiconductor sequencing platform.

BACKGROUND: Thalassemia is one of the most common monogenetic diseases in the south of China and Southeast Asia. Hemoglobin Bart's hydrops fetalis syndrome was caused by a homozygous Southeast Asian deletion (-/-) in the HBA gene. Few studies have proved the potential of screen for Bart's hydrops fetalis using fetal cell-free DNA. However, the number of cases is still relatively small. Clinical trials of large samples would be needed. OBJECTIVE: In this study, we aimed to develop a noninvasive method of target-captured sequencing and genotyping by the Bayesian method using cell-free fetal DNA to identify the fetal genotype in pregnant women who are at risk of having hemoglobin Bart hydrops fetalis in a large-scale study. STUDY DESIGN: In total, 192,173 couples from 30 hospitals were enrolled in our study and 878 couples were recruited, among whom both the pregnant women and their husbands were detected to be carriers of Southeast Asian type (-/αα) of α-thalassemia. Prenatal diagnosis was performed by chorionic villus sampling, amniocentesis, or cordocentesis using gap-polymerase chain reaction considered as the golden standard. RESULTS: As a result, we found that the sensitivity and specificity of our noninvasive method were 98.81% and 94.72%, respectively, in the training set as well as 100% and 99.31%, respectively, in the testing set. Moreover, our method could identify all of 885 maternal samples with the Southeast Asian carrier and 36 trisomy samples with 100% of sensitivity in T13, T18, and T21 and 99.89% (1 of 917) and 99.88% (1 of 888) of specificity in T18 and T21, respectively. CONCLUSION: Our method opens the possibility of early screening for maternal genotyping of α-thalassemia, fetal aneuploidies in chromosomes 13/18/21, and hemoglobin Bart hydrops fetalis detection in 1 tube of maternal plasma.

Development of a novel radioligand for imaging 18-kD translocator protein (TSPO) in a rat model of Parkinson's disease.

PURPOSE: The inflammation reaction in the brain may stimulate damage repair or possibly lead to secondary brain injury. It is often associated with activated microglia, which would overexpress 18-kDa translocator protein (TSPO). In this study, we successfully developed a new TSPO radioligand, [18F]-2-(4-fluoro-2-(p-tolyloxy)phenyl)-1,2-dihydroisoquinolin-3(4H)-one ([18F]FTPQ), and evaluate its potential to noninvasively detect brain changes in a rat model of Parkinson's disease (PD). PROCEDURES: The precursor (8) for [18F]FTPQ preparation was synthesized via six steps. Radiofluorination was carried out in the presence of a copper catalyst, and the crude product was purified by high-performance liquid chromatography (HPLC) to give the desired [18F]FTPQ. The rat model of PD was established by the injection of 6-OHDA into the right hemisphere of male 8-week-old Sprague-Dawley rats. MicroPET/CT imaging and immunohistochemistry (IHC) were performed to characterize the biological properties of [18F]FTPQ. RESULTS: The overall chemical yield for the precursor (8) was around 14% after multi-step synthesis. The radiofluorination efficiency of [18F]FTPQ was 60 ± 5%. After HPLC purification, the radiochemical purity was higher than 98%. The overall radiochemical yield was approximately 19%. The microPET/CT images demonstrated apparent striatum accumulation in the brains of PD rats at the first 30 min after intravenous injection of [18F]FTPQ. Besides, longitudinal imaging found the uptake of [18F]FTPQ in the brain may reflect the severity of PD. The radioactivity accumulated in the ipsilateral hemisphere of PD rats at 1, 2, and 3 weeks after 6-OHDA administration was 1.84 ± 0.26, 3.43 ± 0.45, and 5.58 ± 0.72%ID/mL, respectively. IHC revealed that an accumulation of microglia/macrophages and astrocytes in the 6-OHDA-injected hemisphere. CONCLUSIONS: In this study, we have successfully synthesized [18F]FTPQ with acceptable radiochemical yield and demonstrated the feasibility of [18F]FTPQ as a TSPO radioligand for the noninvasive monitoring the disease progression of PD.

Expressions of HLA Class II Genes in Cutaneous Melanoma Were Associated with Clinical Outcome: Bioinformatics Approaches and Systematic Analysis of Public Microarray and RNA-Seq Datasets.

Major histocompatibility complex (MHC) class II molecules, encoded by human leukocyte antigen (HLA) class II genes, play important roles in antigen presentation and initiation of immune responses. However, the correlation between HLA class II gene expression level and patient survival and disease progression in cutaneous melanoma is still under investigation. In the present study, we analyzed microarray and RNA-Seq data of cutaneous melanoma from The Cancer Genome Atlas (TCGA) using different bioinformatics tools. Survival analysis revealed higher expression level of HLA class II genes in cutaneous melanoma, especially HLA-DP and -DR, was significantly associated with better overall survival. Furthermore, the expressions of HLA class II genes were most closely associated with survival in cutaneous melanoma as compared with other cancer types. The expression of HLA class II co-expressed genes, which were found to associate with antigen processing, immune response, and inflammatory response, was also positively associated with overall survival in cutaneous melanoma. Therefore, the results indicated that increased HLA class II expression may contribute to enhanced anti-tumor immunity and related inflammatory response via presenting tumor antigens to the immune system. The expression pattern of HLA class II genes may serve as a prognostic biomarker and therapeutic targets in cutaneous melanoma.

Deduction of Novel Genes Potentially Involved in Keratinocytes of Type 2 Diabetes Using Next-Generation Sequencing and Bioinformatics Approaches.

Keratinocytes constitute the major cell type of epidermis, which participates in re-epithelialization during wound repair and the immune defense response to pathogens. The aim of the current study was to explore the differentially expressed genes and novel microRNA (miRNA) regulations that are potentially involved in diabetic keratinocytes through next-generation sequencing (NGS) and bioinformatics approaches. A total of 420 differentially expressed genes between normal and diabetic keratinocytes were identified, and systematic bioinformatics analyses indicated that these differentially expressed genes were functionally enriched in interferon-alpha signaling, viral defense response, and immune response. Additionally, the potential miR-340-3p-DTX3L interaction that has been systematically validated in miRNA prediction databases was proposed to participate in the disrupted skin homeostasis, altering the defense and immune response of diabetic skin. The findings may provide new insights into understanding the pathogenesis of epidermal pathologies in diabetic patients and targeting novel molecules to advance diabetic skin care in clinical practice.