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2.
Int Immunopharmacol ; 116: 109747, 2023 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-36706592

RESUMO

Intestinal damage has long been viewed as the primary cause of sepsis-induced multiple organ dysfunction syndrome (MODS). Previous studies have demonstrated that calcitonin gene-related peptide (CGRP) exhibits anti-inflammatory and protective effects in mice exposed to endotoxin. This study investigated whether CGRP protects against sepsis-induced intestinal damage and its underlying mechanisms. Using a murine caecal ligation and puncture (CLP) model, we observed elevated serum and intestinal CGRP levels in septic mice. CGRP knockout (KO) mice showed more severe intestinal barrier damage, excessive NLRP3 inflammasome activation and higher levels of inflammation. In vitro, we used lipopolysaccharide (LPS) and adenosine triphosphate (ATP) to activate the NLRP3 inflammasome in MODE-K murine intestinal epithelial cells. CGRP inhibited NF-κB pathway activation; prevented ASC assembly and ROS accumulation; significantly decreased NLRP3, Caspase-1 p10, and IL-1ß levels and LDH release; and increased cell viability. Treatment with an IL-1ß inhibitor or CGRP suppressed p38 MAPK and ERK1/2 pathway activation and increased ZO-1 and Occludin protein levels in LPS+ATP-treated MODE-K cells. Finally, we used the CGRP upstream agonist drug rutaecarpine (RUT) to control endogenous CGRP release in mice, and this drug demonstrated good therapeutic effects on septic intestinal injury. In conclusion, our results suggest that CGRP ameliorates sepsis-induced intestinal damage, providing valuable insights for drug development.

3.
BMC Cancer ; 23(1): 108, 2023 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-36717783

RESUMO

As the dominant component of the tumor microenvironment, cancer-associated fibroblasts (CAFs), play a vital role in tumor progression. An increasing number of studies have confirmed that CAFs are involved in almost every aspect of tumors including tumorigenesis, metabolism, invasion, metastasis and drug resistance, and CAFs provide an attractive therapeutic target. This study aimed to explore the feature genes of CAFs for potential therapeutic targets and reliable prediction of prognosis in patients with gastric cancer (GC). Bioinformatic analysis was utilized to identify the feature genes of CAFs in GC by performing an integrated analysis of single-cell and transcriptome RNA sequencing using R software. Based on these feature genes, a CAF-related gene signature was constructed for prognostic prediction by LASSO. Simultaneously, survival analysis and nomogram were performed to validate the prognostic predictive value of this gene signature, and qRT-PCR and immunohistochemical staining verified the expression of the feature genes of CAFs. In addition, small molecular drugs for gene therapy of CAF-related gene signatures in GC patients were identified using the connectivity map (CMAP) database. A combination of nine CAF-related genes was constructed to characterize the prognosis of GC, and the prognostic potential and differential expression of the gene signature were initially validated. Additionally, three small molecular drugs were deduced to have anticancer properties on GC progression. By integrating single-cell and bulk RNA sequencing analyses, a novel gene signature of CAFs was constructed. The results provide a positive impact on future research and clinical studies involving CAFs for GC.


Assuntos
Fibroblastos Associados a Câncer , Neoplasias Gástricas , Humanos , Fibroblastos Associados a Câncer/metabolismo , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/genética , Transcriptoma , Prognóstico , Análise de Sequência de RNA , Microambiente Tumoral/genética
4.
Int J Bioprint ; 9(1): 638, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36636137

RESUMO

Three-dimensional (3D) printing, which is a valuable technique for the fabrication of tissue-engineered constructs and biomedical devices with complex architectures, has brought about considerable progress in regenerative medicine, drug delivery, and diagnosis of diseases. However, because of the static and inanimate properties of conventional 3D-printed structures, it is difficult to use them in therapies for active and precise medicine, such as improved tissue regeneration, targeted or controlled drug delivery, and advanced pathophysiological monitoring. The integration of stimuli-responsive biomaterials into 3D printing provides a potential strategy for designing and building smart constructs that exhibit programmed functions and controllable changes in properties in response to exogenous and autogenous stimuli. These features make 3D-printed smart constructs the next generation of tissue-engineered products. In this review, we introduce the prevalent 3D printing techniques (with an emphasis on the differences between 3D printing and bioprinting, and biomaterials and bioink), the working principle of each technique, and the advantages of using 3D printing for the fabrication of smart constructs. Stimuli-responsive biomaterials that are widely used for 3D printing of smart constructs are categorized, followed by a summary of their applications in tissue regeneration, drug delivery, and biosensors. Finally, the challenges and future perspectives of 3D-printed smart constructs are discussed.

5.
Sci Rep ; 13(1): 743, 2023 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-36639415

RESUMO

It is of great significance to find new effective drugs for an adjuvant therapy targeting lung cancer to improve the survival rate and prognosis of patients with the disease. Previous studies have confirmed that certain Chinese herbal extracts have clear anti-tumor effects, and in our preliminary study, betulinaldehyde was screened for its potential anti-tumor effects. The current study thus aimed to confirm the anti-tumor effect of betulinaldehyde, using in vitro experiments to explore its underlying molecular mechanism. It was found that betulinaldehyde treatment significantly inhibited the viability, proliferation, and migration of A549 cells in a dose-dependent manner. In addition, betulinaldehyde inhibited the activation of Akt, MAPK, and STAT3 signaling pathways in A549 cells in a time-dependent manner. More importantly, betulinaldehyde also decreased the expression level of SQSTM1 protein, increased the expression level of LC3 II, and increased the autophagy flux in A549 cells. The pretreatment of A549 cells with the autophagy inhibitor, 3-methyladenine, could partially negate the anti-tumor effects of betulinaldehyde. These findings suggest that betulinaldehyde could significantly inhibit the oncological activity of A549 cells by regulating the intracellular autophagy level, making it a potentially effective option for the adjuvant therapy used to treat lung cancer in the future.


Assuntos
Aldeídos , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Células A549 , Apoptose , Autofagia , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Proliferação de Células , Neoplasias Pulmonares/patologia , Transdução de Sinais , Aldeídos/farmacologia
6.
J Med Chem ; 66(1): 1063-1081, 2023 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-36580346

RESUMO

Interrupting the embryonic ectoderm development (EED)-H3K27me3 interaction represents a promising strategy to allosterically inhibit polycomb repressive complex 2 (PRC2) for cancer therapy. In this work, we report the structure-based design of new triazolopyrimidine-based EED inhibitors, which structurally feature the electron-rich indole ring at the C8 position. Particularly, ZJH-16 directly binds to EED (HTRF IC50 = 2.72 nM, BLI KD = 4.4 nM) and potently inhibits the growth of KARPAS422 and Pfeiffer cells. In both cells, ZJH-16 is selectively engaged with EED and reduces H3K27 trimethylation levels. ZJH-16 inhibits the gene silencing function of PRC2 in KARPAS422 cells. ZJH-16 possesses favorable pharmacokinetic (PK) profiles with an excellent oral bioavailability (F = 94.7%). More importantly, ZJH-16 shows robust tumor regression in the KARPAS422 xenograft model after oral administration with the tumor growth inhibition reaching nearly 100%. The robust antitumor efficacy and favorable PK profiles of ZJH-16 warrant further advanced preclinical development for lymphoma treatment.


Assuntos
Histonas , Linfoma , Humanos , Histonas/metabolismo , Complexo Repressor Polycomb 2/metabolismo
7.
Biofabrication ; 15(2)2023 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-36538823

RESUMO

Much effort has been expended in emulating the kidney's glomerular unit because of its limitless potential in the field of drug screening and nephrotoxicity testing in clinics. Herein, we fabricate a functional bilayer glomerular microvessel-on-a-chip that recapitulates the specific arrangement of the glomerular endothelial cell, podocyte layers, and the intervening glomerular basement membrane (GBM) in a single step. Our perfusable chip allows for the co-culture of monolayer glomerular endothelium and podocyte epithelium, which display mature functional markers of glomerular cells, and their proper interactions produce GBM proteins, which are the major components of the GBMin vivo. Furthermore, we test the selective permeability capacity, a representative hallmark function of the glomerular filtration barrier. Lastly, we evaluate the response of our glomerular model to Adriamycin- and hyperglycemia-induced injury to evaluate its applicability for drug screening and glomerular disease modeling.


Assuntos
Podócitos , Humanos , Células Endoteliais/metabolismo , Membrana Basal Glomerular/metabolismo , Permeabilidade , Podócitos/metabolismo , Impressão
8.
World J Clin Cases ; 10(33): 12395-12403, 2022 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-36483827

RESUMO

BACKGROUND: Nuclear protein in testis (NUT) carcinoma is a rare aggressive malignant epithelial cell tumor, previously known as NUT midline carcinoma (NMC), characterized by an acquired rearrangement of the gene encoding NUT on chromosome 15q14. Due to the lack of characteristic pathological features, it is often underdiagnosed and misdiagnosed. A variety of methods can be used to diagnose NMC, including immunohistochemistry, karyotyping, fluorescence in situ hybridization, reverse transcription-polymerase chain reaction, and next-generation sequencing. So far, there is no standard treatment plan for NMC and the prognosis is poor, related to its rapid progression, easy recurrence, and unsatisfactory treatment outcome. CASE SUMMARY: A 58-year-old female came to our hospital with a complaint of eye swelling and pain for 8 d. The diagnosis of NMC was confirmed after postoperative pathology and genetic testing. The patient developed nausea and vomiting, headache, and loss of vision in both eyes to blindness after surgery. Magnetic resonance imaging (MRI) and positron emission tomography/computed tomography (PET/CT) performed after 1.5 mo postoperatively suggested tumor recurrence. The patient obtained remission after radiation therapy to some extent and after initial treatment with anti-angiogenic drugs and sonodynamic therapy (SDT), but cannot achieve long-term stability and eventually developed distant metastases, with an overall survival of only 17 mo. CONCLUSION: For patients with rapidly progressing sinus tumors and poor response to initial treatment, the possibility of NMC should be considered and immunohistochemical staining with anti-NUT should be performed as soon as possible, combined with genetic testing if necessary. CT, MRI, and PET/CT imaging are essential for the staging, management, treatment response assessment and monitoring of NMC. This case is the first attempt to apply heat therapy and SDT in the treatment of NMC, unfortunately, the prognosis remained poor.

9.
Commun Biol ; 5(1): 1400, 2022 12 21.
Artigo em Inglês | MEDLINE | ID: mdl-36543858

RESUMO

Posttranscriptional modification plays an important role in key embryonic processes. Adenosine-to-inosine RNA editing, a common example of such modifications, is widespread in human adult tissues and has various functional impacts and clinical consequences. However, whether it persists in a consistent pattern in most human embryos, and whether it supports embryonic development, are poorly understood. To address this problem, we compiled the largest human embryonic editome from 2,071 transcriptomes and identified thousands of recurrent embryonic edits (>=50% chances of occurring in a given stage) for each early developmental stage. We found that these recurrent edits prefer exons consistently across stages, tend to target genes related to DNA replication, and undergo organized loss in abnormal embryos and embryos from elder mothers. In particular, these recurrent edits are likely to enhance maternal mRNA clearance, a possible mechanism of which could be introducing more microRNA binding sites to the 3'-untranslated regions of clearance targets. This study suggests a potentially important, if not indispensable, role of RNA editing in key human embryonic processes such as maternal mRNA clearance; the identified editome can aid further investigations.


Assuntos
Edição de RNA , RNA Mensageiro Estocado , Humanos , Desenvolvimento Embrionário/genética , Éxons , RNA/metabolismo , RNA Mensageiro Estocado/metabolismo
10.
Nat Commun ; 13(1): 6534, 2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-36319625

RESUMO

Cancer vaccine, which can promote tumor-specific immunostimulation, is one of the most important immunotherapeutic strategies and holds tremendous potential for cancer treatment/prevention. Here, we prepare a series of nanoparticles composed of doxorubicin- and tyrosine kinase inhibitor-loaded and hyaluronic acid-coated dendritic polymers (termed HDDT nanoparticles) and find that the HDDT nanoparticles can convert various cancer cells to micrometer-sized vesicles (1.6-3.2 µm; termed HMVs) with ~100% cell-to-HMV conversion efficiency. We confirm in two tumor-bearing mouse models that the nanoparticles can restrain tumor growth, induce robust immunogenic cell death, and convert the primary tumor into an antigen depot by producing HMVs in situ to serve as personalized vaccines for cancer immunotherapy. Furthermore, the HDDT-healed mice show a strong immune memory effect and the HDDT treatment can realize long-term protection against tumor rechallenge. Collectively, the present work provides a general strategy for the preparation of tumor-associated antigen-containing vesicles and the development of personalized cancer vaccines.


Assuntos
Vacinas Anticâncer , Nanopartículas , Neoplasias , Camundongos , Animais , Células Dendríticas , Imunoterapia , Antígenos de Neoplasias , Neoplasias/tratamento farmacológico , Imunidade
11.
Front Plant Sci ; 13: 1049479, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36407607

RESUMO

Continuous flowering is a key horticultural trait in ornamental plants, whereas the specific molecular regulation mechanism remains largely unknown. In sweet osmanthus (Osmanthus fragrans Lour.), plants based on their flowering characteristics are divided into once-flowering (OF) habit and continuous flowering (CF) habit. Here, we first described the flowering phenology shifts of OF and CF habits in sweet osmanthus through paraffin section and microscope assay. Phenotypic characterization showed that CF plants had constant new shoot growth, floral transition, and blooming for 1 year, which might lead to a continuous flowering trait. We performed the transcriptome sequencing of OF and CF sweet osmanthus and analyzed the transcriptional activity of flowering-related genes. Among the genes, three floral integrators, OfFT, OfTFL1, and OfBFT, had a differential expression during the floral transition process in OF and CF habits. The expression patterns of the three genes in 1 year were revealed. The results suggested that their accumulations corresponded to the new shoots occurring and the floral transition process. Function studies suggested that OfFT acted as a flowering activator, whereas OfBFT was a flowering inhibitor. Yeast one-hybrid assay indicated that OfSPL8 was a common upstream transcription factor of OfFT and OfBFT, suggesting the vital role of OfSPL8 in continuous flowering regulation. These results provide a novel insight into the molecular mechanism of continuous flowering.

12.
Signal Transduct Target Ther ; 7(1): 380, 2022 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-36402752

RESUMO

Pleural and peritoneal metastasis accompanied by malignant pleural effusion (MPE) or malignant ascites (MA) is frequent in patients with advanced solid tumors that originate from the lung, breast, gastrointestinal tract and ovary. Regional delivery of CAR-T cells represents a new strategy to control tumor dissemination in serous cavities. However, malignant effusions constitute an immune-suppressive environment that potentially induces CAR-T cell dysfunction. Here, we demonstrated that the anti-tumor cytotoxicity of conventional 2nd-generation CAR-T cells was significantly inhibited by both the cellular and non-cellular components of MPE/MA, which was primarily attributed to impaired CAR-T cell proliferation and cytokine production in MPE/MA environment. Interestingly, we found that PD-L1 was widely expressed on freshly-isolated MPE/MA cells. Based on this feature, a novel PD-L1-targeting chimeric switch receptor (PD-L1.BB CSR) was designed, which can bind to PD-L1, switching the inhibitory signal into an additional 4-1BB signal. When co-expressed with a 2nd-generation CAR, PD-L1.BB CSR-modified CAR-T cells displayed superior fitness and enhanced functions in both culture medium and MPE/MA environment, causing rapid and durable eradication of pleural and peritoneal metastatic tumors in xenograft models. Further investigations revealed elevated expressions of T-cell activation, proliferation, and cytotoxicity-related genes, and we confirmed that PD-L1 scFv and 4-1BB intracellular domain, the two important components of PD-L1.BB CSR, were both necessary for the functional improvements of CAR-T cells. Overall, our study shed light on the clinical application of PD-L1.BB CSR-modified dual-targeting CAR-T cells. Based on this study, a phase I clinical trial was initiated in patients with pleural or peritoneal metastasis (NCT04684459).


Assuntos
Neoplasias Peritoneais , Derrame Pleural Maligno , Feminino , Humanos , Antígeno B7-H1/genética , Ativação Linfocitária , Neoplasias Peritoneais/genética , Neoplasias Peritoneais/terapia , Derrame Pleural Maligno/metabolismo , Linfócitos T , Ensaios Clínicos Fase I como Assunto
13.
Plants (Basel) ; 11(21)2022 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-36365352

RESUMO

Rice (Oryza sativa) OsMADS58 is a C-class MADS box protein, and characterization of a transposon insertion mutant osmads58 suggested that OsMADS58 plays a role in stamen development. However, as no null mutation has been obtained, its role has remained unclear. Here, we report that the CRISPR knockout mutant osmads58 exhibits complex altered phenotypes, including anomalous diploid germ cells, aberrant meiosis, and delayed tapetum degeneration. This CRISPR mutant line exhibited stronger changes in expression of OsMADS58 target genes compared with the osmads58 dSpm (transposon insertion) line, along with changes in multiple pathways related to early stamen development. Notably, transcriptional regulatory circuits in young panicles covering the stamen at stages 4-6 were substantially altered in the CRISPR line compared to the dSpm line. These findings strongly suggest that the pleiotropic effects of OsMADS58 on stamen development derive from a potential role in stabilizing gene regulatory circuits during early stamen development. Thus, this work opens new avenues for viewing and deciphering the regulatory mechanisms of early stamen development from a network perspective.

14.
Mol Ecol ; 2022 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-36355347

RESUMO

Invasive species can successfully and rapidly colonize new niches and expand ranges via founder effects and enhanced tolerance towards environmental stresses. However, the underpinning molecular mechanisms (i.e., gene expression changes) facilitating rapid adaptation to harsh environments are still poorly understood. The red seaweed Gracilaria vermiculophylla, which is native to the northwest Pacific but invaded North American and European coastal habitats over the last 100 years, provides an excellent model to examine whether enhanced tolerance at the level of gene expression contributed to its invasion success. We collected G. vermiculophylla from its native range in Japan and from two non-native regions along the Delmarva Peninsula (Eastern United States) and in Germany. Thalli were reared in a common garden for 4 months at which time we performed comparative transcriptome (mRNA) and microRNA (miRNA) sequencing. MRNA-expression profiling identified 59 genes that were differently expressed between native and non-native thalli. Of these genes, most were involved in metabolic pathways, including photosynthesis, abiotic stress, and biosynthesis of products and hormones in all four non-native sites. MiRNA-based target-gene correlation analysis in native/non-native pairs revealed that some target genes are positively or negatively regulated via epigenetic mechanisms. Importantly, these genes are mostly associated with metabolism and defence capability (e.g., metal transporter Nramp5, senescence-associated protein, cell wall-associated hydrolase, ycf68 protein and cytochrome P450-like TBP). Thus, our gene expression results indicate that resource reallocation to metabolic processes is most likely a predominant mechanism contributing to the range-wide persistence and adaptation of G. vermiculophylla in the invaded range. This study, therefore, provides molecular insight into the speed and nature of invasion-mediated rapid adaption.

15.
Elife ; 112022 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-36317962

RESUMO

Unbiased genetic screens implicated a number of uncharacterized genes in hearing loss, suggesting some biological processes required for auditory function remain unexplored. Loss of Kiaa1024L/Minar2, a previously understudied gene, caused deafness in mice, but how it functioned in the hearing was unclear. Here, we show that disruption of kiaa1024L/minar2 causes hearing loss in the zebrafish. Defects in mechanotransduction, longer and thinner hair bundles, and enlarged apical lysosomes in hair cells are observed in the kiaa1024L/minar2 mutant. In cultured cells, Kiaa1024L/Minar2 is mainly localized to lysosomes, and its overexpression recruits cholesterol and increases cholesterol labeling. Strikingly, cholesterol is highly enriched in the hair bundle membrane, and loss of kiaa1024L/minar2 reduces cholesterol localization to the hair bundles. Lowering cholesterol levels aggravates, while increasing cholesterol levels rescues the hair cell defects in the kiaa1024L/minar2 mutant. Therefore, cholesterol plays an essential role in hair bundles, and Kiaa1024L/Minar2 regulates cholesterol distribution and homeostasis to ensure normal hearing.


Cholesterol is present in every cell of the body. While it is best known for its role in heart health, it also plays a major role in hearing, with changes in cholesterol levels negatively affecting this sense. To convert sound waves into electrical brain signals, specialised ear cells rely on hair-like structures which can move with vibrations; cholesterol is present within these hair 'bundles', but its exact role remains unknown. Genetic studies have identified over 120 genes essential for normal hearing. Animal data suggest there may be many more ­ including, potentially, some which control cholesterol. For instance, in mice, loss of the Minar2 gene causes profound deafness. Yet exactly which role the protein that Minar2 codes for plays in the ear remains unknown. This is in part because that protein does not resemble any other related proteins, making it difficult to infer its function. To find out more, Gao et al. investigated loss of minar2 in zebrafish, showing that deleting the gene induced deafness in the animals. Without minar2, the hair bundles in ear cells were longer, thinner, and less able to sense vibrations: cholesterol could not move into these structures, causing them to dysfunction. Exposing the animals to drugs that lower or raise cholesterol levels respectively worsened or improved their hearing abilities. A recent study revealed that mutations in MINAR2 also cause deafness in humans. The findings by Gao et al. highlight the need for further research which explores the role of cholesterol and MINAR2 in hair bundle function, as this may potentially uncover cholesterol-based treatments for hearing problems.


Assuntos
Perda Auditiva , Peixe-Zebra , Animais , Camundongos , Peixe-Zebra/fisiologia , Proteínas de Peixe-Zebra/genética , Mecanotransdução Celular/fisiologia , Audição/fisiologia , Perda Auditiva/genética , Colesterol
16.
Antioxidants (Basel) ; 11(11)2022 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-36421471

RESUMO

Chenodeoxycholic acid (CDCA), a primary bile acid (BA), has been demonstrated to play an important role as a signaling molecule in various physiological functions. However, the role of CDCA in regulating intestinal epithelial cell (IEC) function remains largely unknown. Herein, porcine intestinal epithelial cells (IPEC-J2) were used as an in vitro model to investigate the effects of CDCA on IEC proliferation and explore the underlying mechanisms. IPEC-J2 cells were treated with CDCA, and flow cytometry and transcriptome analysis were adopted to investigate the effects and potential molecular mechanisms of CDCA on the proliferation of IECs. Our results indicated that adding 50 µmol/L of CDCA in the media significantly increased the proliferation of IPEC-J2 cells. In addition, CDCA treatment also hindered cell apoptosis, increased the proportion of G0/G1 phase cells in the cell cycle progression, reduced intracellular ROS, and MDA levels, and increased mitochondrial membrane potential, antioxidation enzyme activity (T-AOC and CAT), and intracellular ATP level (p < 0.05). RNA-seq results showed that CDCA significantly upregulated the expression of genes related to cell cycle progression (Cyclin-dependent kinase 1 (CDK1), cyclin G2 (CCNG2), cell-cycle progression gene 1 (CCPG1), Bcl-2 interacting protein 5 (BNIP5), etc.) and downregulated the expression of genes related to mitochondrial biogenesis (ND1, ND2, COX3, ATP6, etc.). Further KEGG pathway enrichment analysis showed that CDCA significantly enriched the signaling pathways of DNA replication, cell cycle, and p53. Collectively, this study demonstrated that CDCA could promote IPEC-J2 proliferation by regulating cell cycle progression and mitochondrial function. These findings provide a new strategy for promoting the intestinal health of pigs by regulating intestinal BA metabolism.

17.
Front Med (Lausanne) ; 9: 1047464, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36438027

RESUMO

Background: Rhabdomyosarcoma (RMS) is a common pleomorphic malignant soft tissue sarcoma in children and adolescents that originates from rhabdomyoblasts or mesenchymal precursor cells. Alveolar rhabdomyosarcoma (ARMS) mostly occurs in adolescents aged 10-15 years and is characterized by more aggressive behaviors and worse prognosis than other sarcomas, prone to lymphatic and hematogenous metastasis in the early stage as well as metastasizing to breast, testis, pancreas, and other parts. ARMS often occurs in the limbs and genitourinary system, however, head and neck ARMS are relatively rare when involving the nasal cavity or sinuses. The role of MRI and 18F-FDG positron emission tomography combined with computed tomography (PET/CT) remains to be established in ARMS. Case report: Case 1: An 18-year-old male was found with a left submandibular mass of approximately 1 cm in diameter 2 months ago, which gradually increased in size. CT showed multiple soft tissue masses in maxillofacial and neck regions and the lesions invaded the frontal lobe and the inner wall of the left orbital lobe. MRI showed the masses with hypointensity on T1WI, hyperintensity on T2WI, and diffusion-weighted imaging (DWI) with significant enhancement. 18F-FDG PET/CT showed multiple hypermetabolic lesions located in the maxillofacial, neck region, 3rd lumbar vertebra, and the right sacrum. A nasal endoscopic tumor biopsy and molecular testing finally helped to diagnose the ARMS. Case 2: A 14-year-old male presented with left maxillary pain with nasal congestion and left ocular swelling 15 days ago. CT demonstrated a soft tissue mass in the nasal cavity and sinuses with local protrusion into the left orbit. MRI showed the masses with a slightly low signal on T1WI, a high signal on T2WI, and DWI with significant heterogenous enhancement. 18F-FDG PET/CT showed hypermetabolic lesions in the left maxillofacial and neck regions. ARMS was finally diagnosed by a nasal endoscopic tumor biopsy and molecular testing. The patient had a recurrence of the lesion after chemotherapy and surgical resection and is currently undergoing radiation therapy. Conclusion: Nasal sinus ARMS is highly malignant with a poor prognosis. Accurate diagnosis relies not only on histopathology and immunohistochemistry examination but also on genetic detection of characteristic chromosomal translocations and fusion genes. Imaging methods, such as MRI and PET/CT can accurately assess the extent of the lesions and metastases, assist in the diagnosis of the disease and the selection of treatment regimens, provide precise localization for surgery, and help with treatment monitoring and follow-up.

18.
Cyborg Bionic Syst ; 2022: 9852853, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36285306

RESUMO

The rapid development of medical micromotors draws a beautiful blueprint for the noninvasive or minimally invasive diagnosis and therapy. By combining stimuli-sensitive hydrogel materials, micromotors are bestowed with new characteristics such as stimuli-responsive shape transformation/morphing, excellent biocompatibility and biodegradability, and drug loading ability. Actuated by chemical fuels or external fields (e.g., magnetic field, ultrasound, light, and electric field), hydrogel-based stimuli-responsive (HBSR) micromotors can be utilized to load therapeutic agents into the hydrogel networks or directly grip the target cargos (e.g., drug-loaded particles, cells, and thrombus), transport them to sites of interest (e.g., tumor area and diseased tissues), and unload the cargos or execute a specific task (e.g., cell capture, targeted sampling, and removal of blood clots) in response to a stimulus (e.g., change of temperature, pH, ion strength, and chemicals) in the physiological environment. The high flexibility, adaptive capacity, and shape morphing property enable the HBSR micromotors to complete specific medical tasks in complex physiological scenarios, especially in confined, hard-to-reach tissues, and vessels of the body. Herein, this review summarizes the current progress in hydrogel-based medical micromotors with stimuli responsiveness. The thermo-responsive, photothermal-responsive, magnetocaloric-responsive, pH-responsive, ionic-strength-responsive, and chemoresponsive micromotors are discussed in detail. Finally, current challenges and future perspectives for the development of HBSR micromotors in the biomedical field are discussed.

19.
Anal Chem ; 94(45): 15856-15863, 2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-36315837

RESUMO

Semiconductor metal-organic frameworks (MOFs) and heterojunctions have gained increasing attention in many fields, yet their full potential remains largely unexplored. Advanced optobioelectronics are envisioned to create more opportunities for innovative biomedical applications. This study reports a UiO-66-NH2 (U6N)/CdS quantum dots (QDs)-gated organic photoelectrochemical transistor (OPECT) and its application toward energy-transfer-based sensitive microRNA-166a (miRNA-166a) detection assisted by duplex-specific nuclease (DSN)-enabled target recycling. Specifically, a U6N/CdS QDs photoanode was fabricated and shown to be efficiently gating a poly(3,4-ethylenedioxythiophene) doped with poly(styrene sulfonate) (PEDOT/PSS) channel, while the DSN-enabled release of Au-reporters and hybridization upon the U6N/CdS QDs photoanode could significantly inhibit the photoanode response via an energy transfer process and thus modulate the device response, permitting novel dual-amplified optobioelectronic miRNA-166a detection with a low detection limit of 1.0 fM. This work not only features the DSN-amplified miRNA detection via an OPECT route but also unveils the potential of semiconductor MOF heterojunctions for futuristic optobioelectronics.


Assuntos
Técnicas Biossensoriais , Nanopartículas Metálicas , Estruturas Metalorgânicas , MicroRNAs , Pontos Quânticos , MicroRNAs/genética , Transferência de Energia , Endonucleases , Limite de Detecção , Técnicas Eletroquímicas
20.
Sensors (Basel) ; 22(19)2022 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-36236542

RESUMO

In recent years, much research has been conducted on time series based human activity recognition (HAR) using wearable sensors. Most existing work for HAR is based on the manual labeling. However, the complete time serial signals not only contain different types of activities, but also include many transition and atypical ones. Thus, effectively filtering out these activities has become a significant problem. In this paper, a novel machine learning based segmentation scheme with a multi-probability threshold is proposed for HAR. Threshold segmentation (TS) and slope-area (SA) approaches are employed according to the characteristics of small fluctuation of static activity signals and typical peaks and troughs of periodic-like ones. In addition, a multi-label weighted probability (MLWP) model is proposed to estimate the probability of each activity. The HAR error can be significantly decreased, as the proposed model can solve the problem that the fixed window usually contains multiple kinds of activities, while the unknown activities can be accurately rejected to reduce their impacts. Compared with other existing schemes, computer simulation reveals that the proposed model maintains high performance using the UCI and PAMAP2 datasets. The average HAR accuracies are able to reach 97.71% and 95.93%, respectively.


Assuntos
Atividades Humanas , Dispositivos Eletrônicos Vestíveis , Simulação por Computador , Humanos , Aprendizado de Máquina , Probabilidade
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