Masticatory function in growing individuals with hypohidrotic ectodermal dysplasia: A longitudinal study.

BACKGROUND: Hypohidrotic ectodermal dysplasia (HED) is a hereditary disorder with agenesis of ectodermal derivatives, causing oligodontia or anodontia. Dentures are needed to improve the patients' mastication. AIM: This study aimed at preliminarily evaluating the masticatory function changes in Chinese individuals with HED after prosthetic rehabilitation from childhood to adolescence. DESIGN: This longitudinal study enrolled 10 HED patients. Data were collected during childhood and adolescence, respectively. The healthy children and adolescents were recruited as the control group. The surface electromyography (EMG) of masseter (MM) and anterior temporalis (TA) muscles during clenching and chewing were recorded. The EMG activity, asymmetry index (As), activity index (Ac), and chewing cycle were analyzed. The masticatory efficiency was measured by spectrophotometry with subjective masticatory ability assessed by a questionnaire. RESULTS: The EMG activities and masticatory efficiency of HED patients during childhood and adolescence were mostly lower with a higher As (p < .05). The chewing process enhanced the TA activity and balanced the As of HED adolescents (p > .05). The HED adolescents showed a more prevalent TA activity (p < .05). CONCLUSION: The masticatory function of the growing HED patients was functionally inferior to the dentate individuals with a narrowed gap from childhood to adolescence.

A rare case of TFEB/6p21/VEGFA-amplified renal cell carcinoma diagnosed by whole-exome sequencing: clinicopathological and genetic feature report and literature review.

BACKGROUND: TFEB/6p21/VEGFA-amplified renal cell carcinoma (RCC) is rare and difficult to diagnose, with diverse histological patterns and immunohistochemical and poorly defined molecular genetic characteristics. CASE PRESENTATION: We report a case of a 63-year-old male admitted in 2017 with complex histomorphology, three morphological features of clear cell, eosinophilic and papillary RCC and resembling areas of glomerular and tubular formation. The immunophenotype also showed a mixture of CD10 and P504s. RCC with a high suspicion of collision tumors was indicated according to the 2014 WHO classification system; no precise diagnosis was possible. The patient was diagnosed at a different hospital with poorly differentiated lung squamous cell carcinoma one year after RCC surgery. We exploited molecular technology advances to retrospectively investigate the patient's molecular genetic alterations by whole-exome sequencing. The results revealed a 6p21 amplification in VEGFA and TFEB gene acquisition absent in other RCC subtypes. Clear cell, papillary, chromophobe, TFE3-translocation, eosinophilic solid and cystic RCC were excluded. Strong TFEB and Melan-A protein positivity prompted rediagnosis as TFEB/6p21/VEGFA-amplified RCC as per 2022 WHO classification. TMB-L (low tumor mutational load), CCND3 gene acquisition and MRE11A and ATM gene deletion mutations indicated sensitivity to PD-1/PD-L1 inhibitor combinations and the FDA-approved targeted agents Niraparib (Grade C), Olaparib (Grade C), Rucaparib (Grade C) and Talazoparib (Class C). GO (Gene Ontology) and KEGG enrichment analyses revealed major mutations and abnormal CNVs in genes involved in biological processes such as the TGF-ß, Hippo, E-cadherin, lysosomal biogenesis and autophagy signaling pathways, biofilm synthesis cell adhesion substance metabolism regulation and others. We compared TFEB/6p21/VEGFA-amplified with TFEB-translocated RCC; significant differences in disease onset age, histological patterns, pathological stages, clinical prognoses, and genetic characteristics were revealed. CONCLUSION: We clarified the patient's challenging diagnosis and discussed the clinicopathology, immunophenotype, differential diagnosis, and molecular genetic information regarding TFEB/6p21/VEGFA-amplified RCC via exome analysis and a literature review.

A smartphone-assisted colorimetric and photothermal probe for glutathione detection based on enhanced oxidase-mimic CoFeCe three-atom nanozyme in food.

The rational fabrication of point-of-care testing (POCT) featuring simplicity, rapidity, low cost, portability, high sensitivity and accuracy is crucial for maintaining food safety in resource-limited locations and home healthcare but remains challenging. Herein, we report a universal colorimetric-photothermal-smartphone triple-mode sensing platform for POC food-grade glutathione (GSH) detection. This simple sensing platform for GSH detection takes merits of three techniques: commercially available filter paper, thermometer and smartphone via an excellent CoFeCe-mediated oxidase-like activity. This strategy allows CoFeCe three-atom hydroxide to efficiently convert dissolved oxygen into O2·- and catalyzes 3, 3', 5, 5'-tertamethylbenzidine (TMB) to generate an oxidized TMB with remarkable color changes and photothermal effect, resulting in a colorimetric-temperature-color triple-mode signal output. The constructed sensor exhibits high sensitivity with a limit of detection of 0.092 µM for GSH detection. We expect this sensing platform can be easily modified for the determination of GSH in commercial samples with the simple testing strips.

Exome sequencing analysis of gastric primary myeloid sarcoma with monocytic differentiation with altered immunophenotype after chemotherapy: case report.

BACKGROUND: Myeloid Sarcoma with monocytic differentiation is rare and quite likely is missed by surgical pathologists. However it is frequently misdiagnosed because of its non-specific imaging and histological pattern. CASE PRESENTATION: We report the case of a 64-year-old woman with gastric primary myeloid sarcoma with monocytic differentiatio. Upper endoscopy revealed a neoplastic growth at the junction of the lesser curvature and gastric antrum. Except for a slightly increased peripheral monocyte count, no abnormalities were found on hematological and bone-marrow examination. Gastroscopic biopsy showed poorly differentiated atypical large cells with visible nucleoli and nuclear fission. Immunohistochemistry showed positive CD34, CD4, CD43, and CD56 expression, and weakly positive lysozyme expression. Immune markers for poorly differentiated adenocarcinoma, malignant melanoma, and lymphohematopoietic-system tumors were negative. The final diagnosis was myeloid sarcoma with monocytic differentiation. Chemotherapy did not shrink the tumor, so, radical surgery was performed. Although the tumor morphology did not change postoperatively, the immunophenotype did. CD68 and lysozyme expression (tumor tissue markers) changed from negative and weakly positive to strongly positive, AE1/3 expression (epithelial marker) changed from negative to positive, and CD34, CD4, CD43, and CD56 expression (common in naive hematopoietic cell-derived tumors) was greatly attenuated. Exome sequencing revealed missense mutations in FLT3 and PTPRB, which are associated with myeloid sarcoma, and in TP53, CD44, CD19, LTK, NOTCH2, and CNTN2, which are associated with lymphohematopoietic tumors and poorly differentiated cancers. CONCLUSION: We diagnosed myeloid sarcoma with monocytic differentiation after excluding poorly differentiated adenocarcinoma, common lymphohematopoietic-system tumors, epithelioid sarcoma, and malignant melanoma. We identified that the immunophenotypic of patient had alterations after chemotherapy, and FLT3 gene mutations. We hope that the above results will improve our understanding of this rare tumor.

Dual-mode biosensing platform for sensitive and portable detection of hydrogen sulfide based on cuprous oxide/gold/copper metal organic framework heterojunction.

Hydrogen sulfide (H2S) can not only be regarded as a critical gas signal transduction substance, but also its excess levels can lead to a range of diseases. Currently, the accurate analysis combined with electrochemical (EC) or photothermal (PT) technology for H2S in a complex biological system remains a significant challenge. Herein, an endogenous H2S-triggered heterojunction cuprous oxide/gold/copper metal organic framework (Cu2O/Au/HKUST-1) nanoprobe is designed for dual-mode EC- second near-infrared (NIR-II)/PT analysis in tumor cells with high sensitivity and simplicity. Dual-mode EC quantification - PT is achieved through "off-on" mode of EC and PT signals based on electronic transfer and biosynthesis via an in situ sulfuration reaction. Under the optimum conditions, the EC quantification mode for trace H2S exhibits a wide linear range and an excellent limit of detection of 0.1 µM. More importantly, the dual-mode can display the selective detection of trace H2S in living tumor cells because of the specific interaction between copper ion and H2S. These results provide a new EC-PT promising biosensing platform for noninvasive intelligent detection of H2S in living tumor cells.

Tumor acidity and near-infrared light responsive drug delivery MoS2-based nanoparticles for chemo-photothermal therapy.

The rational design of tumor microenvironment (TME)- multifunctional stimuli-responsive nanocomposites is appealing for effective cancer treatment. However, multidrug resistance remains an obstacle to construct responsive oncotherapy. Herein, a novel MoS2/PDA-TPP nanocomposite loaded with chemotherapy drug of doxorubicin (DOX) is designed for TME dual-response and synergistically enhanced anti-tumor therapy based on the tumor-specific mitochondria accumulation ability and photothermal (PTT) therapy. In detail, the designed MoS2/PDA-TPP nanoplatform can act as a pH-responsive dissociation to endow fast release of DOX under an acidic TME and simultaneously improve the efficiency of PTT. Moreover, the mechanism shows that MoS2/PDA-TPP trigger mitochondrial-dependent apoptosis by producing reactive oxygen species (ROS) and reducing mitochondrial membrane potential (MMP). Most importantly, during PTT procedure, hyperthermia up to 50 °C can effectively induce tumor cell death without causing severe inflammation to adjacent tissues. Tumor targeting double stimulation response of nanocomposites is a novel idea to overcome drug resistance, which will provide a more effective strategy for solving practical problems.

SR-B1 and CD10 combined immunoprofile for differential diagnosis of metastatic clear cell renal cell carcinoma and clear cell carcinoma of the ovary.

Both clear cell renal carcinoma (ccRCC) and clear cell carcinoma of the ovary (CCOC) have a clear cytoplasmic morphological feature, hence it is difficult to identify metastatic ccRCC and CCOC by morphology alone. At present, there are no effective immunohistochemical markers to distinguish between these two tumors. Studies have shown that the clear cytoplasm of ccRCC is mainly caused by cholesterol-rich lipids in the cytoplasm, while that of CCOC is due to the accumulation of cytoplasmic glycogen. OBJECTIVE: to hypothesize that the scavenger receptor class B-type 1 (SR-B1) protein responsible for HDL cholesterol uptake may be differentially expressed in ccRCC and CCOC, and high CD10 expression in the renal tubular epithelium may assist in distinguishing between ccRCC and CCOC. METHODS: effective immunohistochemical markers were applied in 90 cases of renal clear cell carcinoma and 31 cases of ovarian cancer to distinguish between the two types of tumors. RESULT: SR-B1 and CD10 expression is significantly higher in ccRCC than CCOC. Both SR-B1 and CD10 exhibited focal weak-medium intensity staining in CCOC, and their staining extent and intensity were significantly lower than ccRCC. The sensitivity and specificity of SR-B1 for identifying ccRCC were 74.4% and 83.9%, respectively. The sensitivity and specificity of CD10 for identifying CCOC were 93.3% and 80.6%, respectively. The combined SR-B1( +) CD10( +) immunoprofile supports the diagnosis of ccRCC with a specificity of 93.5%. The combined SR-B1(-) CD10(-) immunoprofile supports the diagnosis of CCOC with a specificity of 93.3%. CONCLUSIONS: our findings demonstrate that the combination of SR-B1 and CD10 immunoprofiling is a valuable tool for differential diagnosis of ccRCC and CCOC.

Facial Morphological Changes Following Denture Treatment in Children with Hypohidrotic Ectodermal Dysplasia.

Purpose: The purpose of this study was to characterize the facial morphology of Chinese children with hypohidrotic ectodermal dysplasia (HED) and quantify facial changes after prosthetic treatment. Methods: 3-D facial images of 12 HED children were taken and their facial morphology was compared against 28 healthy controls. Facial changes due to denture placement were also quantified. Group differences were quantified and visualized by superimposing the average faces with robust Procrustes superimposition. Partial least square regression was used to investigate the effects of group membership (HED or controls, pre- and posttreatment) on facial morphology. Results: HED patients had a more prominent forehead, depressed nasal region, depressed zygomatic zone, flat cheeks, and protuberant lips and chin compared with controls. The strongest differences were localized in the middle and lower face, especially in the cheeks and zygomatic and chin regions (P<0.05). Pre- and post-treatment comparisons showed the chin retruded (P<0.05). Statistical facial differences between the posttreatment patients and the controls were localized in the perinasal area and submental region (P<0.05). Conclusions: The facial morphology of Chinese children with hypohidrotic ectodermal dysplasia differs significantly from healthy children, creating a more concave facial profile. Posttreatment facial changes provide a better understanding of dentures' role in improving facial appearance.

MicroRNA-31 weakens cisplatin resistance of medulloblastoma cells via NF-κB and PI3K/AKT pathways.

BACKGROUND: Medulloblastoma (MB) is a malignant intracranial tumor. Cisplatin is a broad-spectrum antitumor drug. It is important to study the cisplatin resistance of MB cells for the treatment of MB. In this article, we preliminarily studied the cisplatin resistance of microRNA (miR)-31 and the possible mechanism in DAOY and UW228 cells, laying a theoretical foundation for clinical treatment of MB. METHODS: Following anti-miR-31 and pre-miR-31 transfections, cell viability, BrdU, CyclinD1, and apoptosis levels of DAOY and UW228 cell were detected by CCK8, BrdU, and western blot. Meanwhile, migration, invasion, and western blot assay were respectively used to detect the functions of miR-31 migration and invasion. miR-31 levels were changed by cell transfection and detected by RT-qPCR. Furthermore, the related-proteins of pathways were also detected by western blot. RESULTS: Anti-miR-31 increased DAOY and UW228 cells viability, BrdU+ numbers, and expression of CyclinD1. The migration/invasion rate and expression levels of MMP-9 and vimentin after anti-miR-31 transfection were increased. Furthermore, anti-miR-31 enhanced cells' cisplatin resistance and triggered PI3K/AKT and NF-κB pathways. Pre-miR-31 played opposite roles and promoted the apoptosis. CONCLUSION: miR-31 regulated cell growth, migration, invasion and cisplatin resistance of MB cells via PI3K/AKT and NF-κB pathways.

Comparative analysis of gene expression profiles in children with type 1 diabetes mellitus.

Type 1 diabetes (T1D) is an autoimmune disease that is typically diagnosed in children. The aim of the present study was to identify potential genes involved in the pathogenesis of childhood T1D. Two datasets of mRNA expression in children with T1D were obtained from the Gene Expression Omnibus (GEO). Differentially expressed genes (DEGs) in children with T1D were identified. Functional analysis was performed and a protein­protein interaction (PPI) network was constructed, as was a transcription factor (TF)­target network. The expression of selected DEGs was further assessed using reverse transcription­quantitative polymerase chain reaction (RT­qPCR) analysis. Electronic validation and diagnostic value analysis of the identified DEGs [cytokine inducible SH2 containing protein (CISH), SR­related CTD associated factor 11 (SCAF11), estrogen receptor 1 (ESR1), Rho GTPase activating protein 25 (ARHGAP25), major histocompatibility complex, class II, DR ß4 (HLA­DRB4) and interleukin 23 subunit α (IL23A)] was performed in the GEO dataset. Compared with the normal control group, a total of 1,467 DEGs with P<0.05 were identified in children with T1D. CISH and SCAF11 were determined to be the most up­ and downregulated genes, respectively. Heterogeneous nuclear ribonucleoprotein D (HNRNPD; degree=33), protein kinase AMP­activated catalytic subunit α1 (PRKAA1; degree=11), integrin subunit α4 (ITGA4; degree=8) and ESR1 (degree=8) were identified in the PPI network as high­degree genes. ARHGAP25 (degree=12), HNRNPD (degree=10), HLA­DRB4 (degree=10) and IL23A (degree=9) were high­degree genes identified in the TF­target network. RT­qPCR revealed that the expression of HNRNPD, PRKAA1, ITGA4 and transporter 2, ATP binding cassette subfamily B member was consistent with the results of the integrated analysis. Furthermore, the results of the electronic validation were consistent with the bioinformatics analysis. SCAF11, CISH and ARHGAP25 were identified to possess value as potential diagnostic markers for children with T1D. In conclusion, identifying DEGs in children with T1D may contribute to our understanding of its pathogenesis, and such DEGs may be used as diagnostic biomarkers for children with T1D.

Protective effects of a green tea polyphenol, epigallocatechin-3-gallate, against sevoflurane-induced neuronal apoptosis involve regulation of CREB/BDNF/TrkB and PI3K/Akt/mTOR signalling pathways in neonatal mice.

Epigallocatechin-3-gallate (EGCG), a polyphenol in green tea, is an effective antioxidant and possesses neuroprotective effects. Brain-derived neurotrophic factor (BDNF) and cyclic AMP response element-binding protein (CREB) are crucial for neurogenesis and synaptic plasticity. In this study, we aimed to assess the protective effects of EGCG against sevoflurane-induced neurotoxicity in neonatal mice. Distinct groups of C57BL/6 mice were given EGCG (25, 50, or 75 mg/kg body weight) from postnatal day 3 (P3) to P21 and were subjected to sevoflurane (3%; 6 h) exposure on P7. EGCG significantly inhibited sevoflurane-induced neuroapoptosis as determined by Fluoro-Jade B staining and terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL). Increased levels of cleaved caspase-3, downregulated Bad and Bax, and significantly enhanced Bcl-2, Bcl-xL, xIAP, c-IAP-1, and survivin expression were observed. EGCG induced activation of the PI3K/Akt pathway as evidenced by increased Akt, phospho-Akt, GSK-3ß, phospho-GSK-3ß, and mTORc1 levels. Sevoflurane-mediated downregulation of cAMP/CREB and BDNF/TrkB signalling was inhibited by EGCG. Reverse transcription PCR analysis revealed enhanced BDNF and TrkB mRNA levels upon EGCG administration. Improved performance of mice in Morris water maze tests suggested enhanced learning and memory. The study indicates that EGCG was able to effectively inhibit sevoflurane-induced neurodegeneration and improve learning and memory retention of mice via activation of CREB/BDNF/TrkB-PI3K/Akt signalling.

[Masticatory performance and assessment of life quality of children with ectodermal dysplasia after prosthetic rehabilitation].

OBJECTIVE: To evaluate masticatory performance and life quality of children with ectodermal dysplasia (ED) after prosthetic rehabilitation. METHODS: Six children with ED received denture restoration and 18 healthy children were involved in this study. The surface electromyography (EMG) of masseter (MM) and anterior temporalis (TA) during clenching and chewing movement were recorded. The EMG amplitude, area, asymmetry index of total and activity index of MM/TA were compared at each stage. The masticatory efficiency was measured with spectrophotometer. The life quality was assessed using visual analogue scale questionnaire. RESULTS: The EMG amplitude of MM and TA during chewing in ED Group were 41.7% and 45.6% of the control group respectively, the area were 35.9% and 36.0% respectively. Significant difference in asymmetry index of total during clenching was observed between the two groups (P < 0.05) but not during chewing (P > 0.05). The differences of activity index of MM/TA during clenching and chewing between the two groups were not detected (P > 0.05). The masticatory efficiency of ED group was 67.2% of the control group. The score of chewing function in children with ED after prosthetic rehabilitation was three times higher than before, and no difference was present between the two groups (P > 0.05). CONCLUSIONS: Early prosthetic rehabilitation can significantly improve the masticatory performance and life quality of children with ED.