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1.
Proc Natl Acad Sci U S A ; 121(26): e2321710121, 2024 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-38885377

RESUMEN

Somatostatin receptor 5 (SSTR5) is an important G protein-coupled receptor and drug target for neuroendocrine tumors and pituitary disorders. This study presents two high-resolution cryogenicelectron microscope structures of the SSTR5-Gi complexes bound to the cyclic neuropeptide agonists, cortistatin-17 (CST17) and octreotide, with resolutions of 2.7 Å and 2.9 Å, respectively. The structures reveal that binding of these peptides causes rearrangement of a "hydrophobic lock", consisting of residues from transmembrane helices TM3 and TM6. This rearrangement triggers outward movement of TM6, enabling Gαi protein engagement and receptor activation. In addition to hydrophobic interactions, CST17 forms conserved polar contacts similar to somatostatin-14 binding to SSTR2, while further structural and functional analysis shows that extracellular loops differently recognize CST17 and octreotide. These insights elucidate agonist selectivity and activation mechanisms of SSTR5, providing valuable guidance for structure-based drug development targeting this therapeutically relevant receptor.


Asunto(s)
Octreótido , Receptores de Somatostatina , Receptores de Somatostatina/metabolismo , Receptores de Somatostatina/agonistas , Receptores de Somatostatina/química , Humanos , Octreótido/química , Octreótido/farmacología , Octreótido/metabolismo , Neuropéptidos/metabolismo , Neuropéptidos/química , Microscopía por Crioelectrón , Unión Proteica , Péptidos Cíclicos/química , Péptidos Cíclicos/farmacología , Péptidos Cíclicos/metabolismo , Somatostatina/metabolismo , Somatostatina/química , Somatostatina/análogos & derivados , Modelos Moleculares , Células HEK293
2.
Curr Genomics ; 25(2): 88-104, 2024 Apr 08.
Artículo en Inglés | MEDLINE | ID: mdl-38751598

RESUMEN

Objectives: This study aims to assess the prognostic implications of gene signature of the tertiary lymphoid structures (TLSs) in head and neck squamous cell carcinoma (HNSCC) and scrutinize the influence of TLS on immune infiltration. Methods: Patients with HNSCC from the Cancer Genome Atlas were categorized into high/low TLS signature groups based on the predetermined TLS signature threshold. The association of the TLS signature with the immune microenvironment, driver gene mutation status, and tumor mutational load was systematically analyzed. Validation was conducted using independent datasets (GSE41613 and GSE102349). Results: Patients with a high TLS signature score exhibited better prognosis compared to those with a low TLS signature score. The group with a high TLS signature score had significantly higher immune cell subpopulations compared to the group with a low TLS signature score. Moreover, the major immune cell subpopulations and immune circulation characteristics in the tumor immune microenvironment were positively correlated with the TLS signature. Mutational differences in driver genes were observed between the TLS signature high/low groups, primarily in the cell cycle and NRF2 signaling pathways. Patients with TP53 mutations and high TLS signature scores demonstrated a better prognosis compared to those with TP53 wild-type. In the independent cohort, the relationship between TLS signatures and patient prognosis and immune infiltration was also confirmed. Additionally, immune-related biological processes and signaling pathways were activated with elevated TLS signature. Conclusion: High TLS signature is a promising independent prognostic factor for HNSCC patients. Immunological analysis indicated a correlation between TLS and immune cell infiltration in HNSCC. These findings provide a theoretical basis for future applications of TLS signature in HNSCC prognosis and immunotherapy.

3.
Cell Discov ; 10(1): 48, 2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38710677

RESUMEN

Melanin-concentrating hormone (MCH) is a cyclic neuropeptide that regulates food intake, energy balance, and other physiological functions by stimulating MCHR1 and MCHR2 receptors, both of which are class A G protein-coupled receptors. MCHR1 predominately couples to inhibitory G protein, Gi/o, and MCHR2 can only couple to Gq/11. Here we present cryo-electron microscopy structures of MCH-activated MCHR1 with Gi and MCH-activated MCHR2 with Gq at the global resolutions of 3.01 Å and 2.40 Å, respectively. These structures reveal that MCH adopts a consistent cysteine-mediated hairpin loop configuration when bound to both receptors. A central arginine from the LGRVY core motif between the two cysteines of MCH penetrates deeply into the transmembrane pocket, triggering receptor activation. Integrated with mutational and functional insights, our findings elucidate the molecular underpinnings of ligand recognition and MCH receptor activation and offer a structural foundation for targeted drug design.

4.
J Agric Food Chem ; 72(14): 8225-8236, 2024 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-38557068

RESUMEN

As a continuous flow investigation of novel pesticides from natural quinolizidine alkaloids, the chemical compositions of the seeds of Sophora alopecuroides were thoroughly researched. Fifteen new aloperine-type alkaloids (1-15) as well as six known aloperine-type alkaloids (16-21) were obtained from the extract of S. alopecuroides. The structures of 1-21 were confirmed via HRESIMS, NMR, UV, IR, ECD calculations, and X-ray diffraction. The antiviral activities of 1-21 against tobacco mosaic virus (TMV) were detected following the improved method of half-leaf. Compared with ningnanmycin (protective: 69.7% and curative: 64.3%), 15 exhibited excellent protective (71.7%) and curative (64.6%) activities against TMV. Further biological studies illustrated that 15 significantly inhibited the transcription of the TMV-CP gene and increased the activities of polyphenol oxidase (PPO), peroxidase (POD), superoxide dismutase (SOD), and phenylalanine ammonia-lyase (PAL). The antifungal activities of 1-21 against Phytophythora capsica, Botrytis cinerea, Alternaria alternata, and Gibberella zeae were screened according to a mycelial inhibition test. Compound 13 displayed excellent antifungal activity against B. cinerea (EC50: 7.38 µg/mL). Moreover, in vitro antifungal mechanism studies displayed that 13 causes accumulation of reactive oxygen species and finally leads to mycelia cell membrane damage and cell death in vitro.


Asunto(s)
Alcaloides , Quinolizidinas , Sophora , Virus del Mosaico del Tabaco , Antifúngicos , Sophora/química , Alcaloides/química , Antivirales/farmacología , Antivirales/química , Semillas/química
6.
Food Chem ; 440: 138193, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38128427

RESUMEN

The heterocyclic amine 2-amino-1-methyl-6-phenyl-imidazolium [4, 5-B] pyridine (PhIP), commonly found in roasted meat products, is considered a potential carcinogen. This study is to explore the underlying mechanisms involved in the adsorption of PhIP by lactic acid bacteria 37X-15 and its peptidoglycan. The scanning electron microscope results suggested that the strain's adsorption on PhIP occurs on the cell wall, primarily composed of peptidoglycan. The fourier-transformed infrared spectroscopy results indicated that PhIP adsorption by both lactic acid bacteria 37X-15 and its peptidoglycan primarily involved OH and NH binding groups. Different adsorption conditions affected the adsorption rate of PhIP by peptidoglycan. The optimal values for each adsorption condition were 2 h, 37 °C, and pH 6 when the maximum adsorption rate reached. This study provides a new direction for the application of lactic acid bacteria and its peptidoglycan in food safety.


Asunto(s)
Imidazoles , Lactobacillales , Peptidoglicano , Lactobacillales/metabolismo , Adsorción , Carcinógenos/metabolismo , Piridinas
7.
Fish Physiol Biochem ; 50(2): 513-526, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38103084

RESUMEN

Peroxiredoxin1(Prx1), also known as natural killer enhancing factor A (NKEF-A), is a crucial antioxidant involving in various cellular activities and immune response against bacterial and viral infection in fish. In the present study, a full-length Prx1 cDNA sequence (TfPrx1) was firstly cloned from roughskin sculpin (Trachidermus fasciatus), which was composed of 1044 bp nucleotides encoding a peptide of 199 amino acids with a molecular weight of 22.35 kDa and a theoretical pI of 6.42, respectively. The predicted peptide was a typical 2-cys Prx containing two conserved characteristic motifs 43FYPLDFTFVCPTEI56 and 170GEVCPA175 with the two conserved peroxidatic and resolving cysteine residuals forming disulfide bond. Quantitative real-time PCR analysis showed that TfPrx1 was ubiquitously expressed in all tested tissues with the highest expression in the intestine. It could be significantly induced following LPS injection and heavy metal exposure. Recombinant TfPrx1 (rTfPrx1) displayed insulin disulfide reduction and ROS-scavenging activity in a concentration-dependent manner, and further exhibited DNA and cytoprotective effects under oxidative stress. These results suggested that TfPrx1 protein may play an important role in fish immune protection from oxidative damage.


Asunto(s)
Perciformes , Peroxirredoxinas , Animales , Secuencia de Aminoácidos , Secuencia de Bases , Alineación de Secuencia , Peroxirredoxinas/genética , Peroxirredoxinas/química , Perciformes/genética , Peces/genética , Péptidos/genética , Disulfuros , Filogenia
8.
Molecules ; 28(24)2023 Dec 17.
Artículo en Inglés | MEDLINE | ID: mdl-38138627

RESUMEN

Anthraquinones are bioactive natural products, which are often found in medicinal herbs. These compounds exert antioxidant-related pharmacological actions including neuroprotective effects, anti-inflammation, anticancer, hepatoprotective effects and anti-aging, etc. Considering the benefits from their pharmacological use, recently, there was an upsurge in the development and utilization of anthraquinones as reactive oxygen species (ROS) regulators. In this review, a deep discussion was carried out on their antioxidant activities and the structure-activity relationships. The antioxidant mechanisms and the chemistry behind the antioxidant activities of both natural and synthesized compounds were furtherly explored and demonstrated. Due to the specific chemical activity of ROS, antioxidants are essential for human health. Therefore, the development of reagents that regulate the imbalance between ROS formation and elimination should be more extensive and rational, and the exploration of antioxidant mechanisms of anthraquinones may provide new therapeutic tools and ideas for various diseases mediated by ROS.


Asunto(s)
Antraquinonas , Antioxidantes , Humanos , Antioxidantes/farmacología , Especies Reactivas de Oxígeno , Antraquinonas/farmacología , Antraquinonas/química , Relación Estructura-Actividad
9.
Heliyon ; 9(9): e19434, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37809660

RESUMEN

Purpose: Altered gene methylation precedes altered gene expression and the onset of disease. This study aimed to develop a potential model for predicting recurrence of early to mid-stage hepatocellular carcinoma (HCC) using methylation loci. Methods: We used data from early to mid-stage HCC patients (TNM I-II) in the TCGA-LIHC dataset and lasso-cox regression model to identify an 18-DNA methylation site panel from which to calculate the riskScore of patients. The correlation of high/low riskScore with recurrence-free survival (RFS) and immune microenvironment in HCC patients was analyzed by bioinformatics. It was also validated in the GSE56588 dataset and the final dynamic nomogram was constructed. Results: The results showed that riskScore was significantly correlated with RFS in HCC patients. The differential mutated genes between the two groups of HCC patients with high/low riskScore were mainly enriched in the TP53 signaling pathway. The immune microenvironment was better in HCC patients in the low-riskScore group compared to the high-riskScore group. This was validated in the GSE56588 dataset. Based on the subgroup stratification analysis of the relationship between high/low riskScore and RFS, as well as univariate and multivariate cox analyses, the riskScore was found to be independent of clinical indicators. We found that riskScore, vascular invasion and cirrhosis status could effectively differentiate RFS in HCC patients, and we also constructed prediction model based on these three factors. The model we constructed were validated in the TCGA-LIHC database and a web calculator was built for clinical use. Conclusion: The methylation riskScore is a predictor of RFS independent of clinical factors and can be used as a marker to predict recurrence in HCC patients.

10.
World J Clin Cases ; 11(26): 6231-6239, 2023 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-37731571

RESUMEN

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most frequent cancers and the main cause of cancer-related death worldwide. Ectopic HCC, an extremely rare type of HCC, exhibits a wide range of clinical signs and radiographic features, making preoperative identification challenging. CASE SUMMARY: A 47-year-old man underwent routine abdominal color ultrasonography, which identified an asymptomatic tumor in the left upper abdomen. The patient had no history of hepatitis, did not drink alcohol, and had no family history of cancer. Abdominal contrast-enhanced computed tomography (CT) revealed a heterogeneously enhanced lesion between the spleen and stomach that had invaded the diaphragm, with blood supplied by the left inferior phrenic artery. The patient underwent laparoscopic surgery, and HCC was identified by postoperative pathology. Additionally, specific immunohistochemical staining was performed to assess the molecular biological characteristics of the HCC. The patient underwent two rounds of hepatic arterial interventional chemotherapy after surgery. Abdominal plain and enhanced magnetic resonance imaging and lung CT 3 mo postoperatively revealed no signs of local recurrence or distant metastasis. CONCLUSION: This asymptomatic ectopic HCC case described achieved an excellent result due to early detection, radical resection, and systematic surveillance.

11.
Food Sci Anim Resour ; 43(5): 805-825, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37701743

RESUMEN

This experiment aims to investigate the impact of probiotic feed on growth performance, carcass traits, plasma lipid biochemical parameters, intramuscular fat and triglyceride content, fatty acid composition, mRNA expression levels of genes related to lipid metabolism, and the activity of the enzyme in Sunit sheep. In this experiment, 12 of 96 randomly selected Sunit sheep were assigned to receive the basic diet or the basic diet supplemented with probiotics. The results showed that supplementation with probiotics significantly increased the loin eye area, and decreased plasma triglycerides and free fatty acids, increasing the content of intramuscular fat and triglycerides in the muscle and improving the composition of the fatty acids. The inclusion of probiotics in the diet reduced the expression of adenosine 5'-monophosphate-activated protein kinase alpha 2 (AMPKα2) mRNA and carnitine palmitoyltransferase 1B (CPT1B) mRNA, while increasing the expression of acetyl-CoA carboxylase alpha (ACCα) mRNA, sterol regulatory element-binding protein-1c (SREBP-1c) mRNA, fatty acid synthase mRNA, and stearoyl-CoA desaturase 1 mRNA. The results of this study indicate that supplementation with probiotics can regulate fat deposition and improves the composition of fatty acids in Sunit sheep through the signaling pathways AMPK-ACC-CPT1B and AMPK-SREBP-1c. This regulatory mechanism leads to an increase in intramuscular fat content, a restructuring of muscle composition of the fatty acids, and an enhancement of the nutritional value of meat. These findings contribute to a better understanding of the food science of animal resources and provide valuable references for the production of meat of higher nutritional value.

12.
Life Sci ; 331: 122060, 2023 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-37652155

RESUMEN

AIMS: Microbial infection is the main factor that induces mastitis. Staphylococcus aureus (S. aureus) is a major pathogen associated with mastitis. The purpose of this study was to investigate the effects of diosmetin on S. aureus-induced mastitis. MATERIALS AND METHODS: The mice were divided into six groups: control group, S. aureus group, diosmetin (12.5, 25, 50 mg/kg) + S. aureus groups, and diosmetin (50 mg/kg) + S. aureus + EX-527 (10 mg/kg) group. S. aureus was injected into the mammary gland to establish a mouse mastitis model. Diosmetin was administered 1 h before S. aureus treatment. KEY FINDINGS: Our results showed that diosmetin significantly alleviated the pathological changes of mammary gland induced by S. aureus. Diosmetin alleviated myeloperoxidase (MPO) activity, and the release of TNF-α and IL-1ß, and nuclear factor kappa-B (NF-κB) activation. Moreover, diosmetin inhibited malondialdehyde (MDA) and Fe2+ levels induced by S. aureus. Diosmetin upregulated ATP, glutathione (GSH) production and glutathione peroxidase 4 (GPX4) expression, which were decreased by S. aureus. Furthermore, the expression of Sirtuin 1 (SIRT1), nuclear factor erythroid2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) was upregulated by diosmetin. In addition, the inhibitory effects of diosmetin on S. aureus-induced inflammation and ferroptosis were prevented by the SIRT1 inhibitor EX-527. SIGNIFICANCE: In conclusion, the data indicated that diosmetin suppressed S. aureus-induced mastitis by attenuating inflammation and ferroptosis.


Asunto(s)
Ferroptosis , Mastitis , Staphylococcus aureus Resistente a Meticilina , Infecciones Estafilocócicas , Femenino , Humanos , Animales , Ratones , Sirtuina 1 , Staphylococcus aureus , Mastitis/tratamiento farmacológico , Inflamación , Modelos Animales de Enfermedad , Glutatión , Infecciones Estafilocócicas/tratamiento farmacológico
13.
Nature ; 621(7979): 635-641, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37524305

RESUMEN

Class B G-protein-coupled receptors (GPCRs), including glucagon-like peptide 1 receptor (GLP1R) and parathyroid hormone 1 receptor (PTH1R), are important drug targets1-5. Injectable peptide drugs targeting these receptors have been developed, but orally available small-molecule drugs remain under development6,7. Here we report the high-resolution structure of human PTH1R in complex with the stimulatory G protein (Gs) and a small-molecule agonist, PCO371, which reveals an unexpected binding mode of PCO371 at the cytoplasmic interface of PTH1R with Gs. The PCO371-binding site is totally different from all binding sites previously reported for small molecules or peptide ligands in GPCRs. The residues that make up the PCO371-binding pocket are conserved in class B GPCRs, and a single alteration in PTH2R and two residue alterations in GLP1R convert these receptors to respond to PCO371. Functional assays reveal that PCO371 is a G-protein-biased agonist that is defective in promoting PTH1R-mediated arrestin signalling. Together, these results uncover a distinct binding site for designing small-molecule agonists for PTH1R and possibly other members of the class B GPCRs and define a receptor conformation that is specific only for G-protein activation but not arrestin signalling. These insights should facilitate the design of distinct types of class B GPCR small-molecule agonist for various therapeutic indications.


Asunto(s)
Imidazolidinas , Receptores Acoplados a Proteínas G , Compuestos de Espiro , Humanos , Arrestina/metabolismo , Sitios de Unión , Subunidades alfa de la Proteína de Unión al GTP Gs/metabolismo , Imidazolidinas/farmacología , Ligandos , Péptidos/farmacología , Conformación Proteica , Receptor de Hormona Paratiroídea Tipo 1/agonistas , Receptor de Hormona Paratiroídea Tipo 1/clasificación , Receptor de Hormona Paratiroídea Tipo 1/metabolismo , Receptores Acoplados a Proteínas G/agonistas , Receptores Acoplados a Proteínas G/clasificación , Receptores Acoplados a Proteínas G/metabolismo , Transducción de Señal/efectos de los fármacos , Compuestos de Espiro/farmacología , Diseño de Fármacos
14.
J Cell Mol Med ; 27(16): 2321-2327, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37328960

RESUMEN

Mastitis refers to the inflammation in the mammary gland caused by various reasons. Protocatechuic acid (PCA) exerts anti-inflammatory effect. However, no studies have shown the protective role of PCA on mastitis. We investigated the protective effect of PCA on LPS-induced mastitis in mice and elucidated its possible mechanism. LPS-induced mastitis model was established by injection of LPS into the mammary gland. The pathology of mammary gland, MPO activity and inflammatory cytokine production were detected to evaluate the effects of PCA on mastitis. In vivo, PCA significantly attenuated LPS-induced mammary pathological changes, MPO activity, TNF-α and IL-1ß production. In vitro, the production of inflammatory cytokines TNF-α and IL-1ß was significantly reduced by PCA. Furthermore, LPS-induced NF-κB activation was also inhibited by PCA. In addition, PCA was found to activate pregnane X receptor (PXR) transactivation and PCA dose-dependently increased the expression of PXR downstream molecule CYP3A4. In addition, the inhibitory effect of PCA on inflammatory cytokine production was also reversed when PXR was knocked down. In conclusion, the protective effects of PCA on LPS-induced mastitis in mice through regulating PXR.


Asunto(s)
Lipopolisacáridos , Mastitis , Femenino , Humanos , Animales , Ratones , Receptor X de Pregnano , Lipopolisacáridos/toxicidad , Factor de Necrosis Tumoral alfa/genética , Mastitis/inducido químicamente , Mastitis/tratamiento farmacológico , Citocinas
15.
J Anim Sci ; 1012023 Jan 03.
Artículo en Inglés | MEDLINE | ID: mdl-37085268

RESUMEN

Mastitis is a relatively common disease in rabbit does. The aim of this study was to investigate a relationship between the severity of clinical signs and pathological observations and to analyze differentially expressed genes (DEGs) in the mammary gland with mastitis versus healthy mammary gland. The result showed that rectal temperatures of the rabbits with both mild mastitis and severe mastitis were higher than that of control. Cell counting results showed that the somatic cell count (SCC) only in milk of the rabbit with severe mastitis was significantly higher than that in the control group. However, the number of heterophils in the histological sections of mammary glands with mild mastitis was significantly higher than that of control. A total of 1,096 DEGs between the control and mastitis mammary glands was identified by RNA-sequencing (RNA-seq). Gene ontology (GO) showed that most of up-regulated genes were enriched in terms such as response to stimulus, signal transduction, and cell communication. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that these genes were mostly enriched in the pathways such as Rap1 signaling pathway, proteoglycans in cancer, and PI3K-Akt signaling pathway. However, the downregulated genes were mainly enriched in metabolic processes and significantly involved in metabolic pathways. The data provides useful information to further dissect the molecular genetic mechanisms underlying rabbit mastitis, which is a prerequisite for designing effective intervention strategies.


Asunto(s)
Mastitis , Transcriptoma , Femenino , Conejos , Animales , Perfilación de la Expresión Génica/veterinaria , Fosfatidilinositol 3-Quinasas/genética , RNA-Seq/veterinaria , Mastitis/veterinaria
16.
Front Med (Lausanne) ; 10: 1167676, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37081842

RESUMEN

Background: Breast cancer (BC) is the most common malignant disease worldwide. Although the survival rate is improved in recent years, the prognosis is still bleak once recurrence and metastasis occur. It is vital to investigate more efficient biomarkers for predicting the metastasis and relapse of BC. DYNLT1 has been reported that participating in the progression of multiple cancers. However, there is still a lack of study about the correlation between DYNLT1 and BC. Methods: In this study, we evaluated and validated the expression pattern and prognostic implication of DYNLT1 in BC with multiple public cohorts and BC tumor microarrays (TMAs) of paraffin-embedded tissues collected from the Affiliated Hospital of Jining Medical University. The response biomarkers for immune therapy, such as tumor mutational burden (TMB), between different DYNLT1 expression level BC samples were investigated using data from the TCGA-BRCA cohort utilizing public online tools. In addition, colony formation and transwell assay were conducted to verify the effects of DYNLT1 in BC cell line proliferation and invasion. Results: The results demonstrated that DYNLT1 overexpressed in BC and predicted poor relapse-free survival in our own BC TMA cohort. In addition, DYNLT1 induced BC development by promoting MDA-MB-231 cell proliferation migration, and metastasis. Conclusion: Altogether, our findings proposed that DYNLT1 could be a diagnostic and prognostic indicator in BC.

17.
Hum Pathol ; 136: 84-95, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-37019411

RESUMEN

The pathogenesis and treatment of papillary thyroid cancer with desmoid-type fibromatosis (PTC-DTF), a rare subtype of papillary thyroid carcinoma characterized by a mixed epithelial-mesenchymal structure, are still ill-defined. Previous reports on PTC-DTF have had limited follow-up and recurrence has been rarely reported. To better understand this condition, we conducted a thorough analysis of five cases of PTC-DTF from our institute, including clinical and pathological examinations, imaging, immunohistochemistry, and molecular analysis. We also reviewed relevant literature. The mean age of the patients was 51.8 years, with three women and two men included in the group. Ultrasound often showed a hypoechogenic and well-defined nodule in the thyroid gland, except for one individual who had distant lung metastases detected by PET-CT. The nodules ranged in width from 0.5 to 5.0 cm and were excised in each case. Following surgery, 131I therapy was used in two cases. The overall number of PTC-DTF cases has risen from the previously reported 55 to 60, with females being the most commonly affected and ranging in age from 19 to 82. Most masses underwent a thyroidectomy, and approximately half of the patients had lymph node metastases. Histologically, PTC-DTFs were composed of a predominant stromal component (65%-90%) and an intervening epithelial component. These spindle cells were arranged in parallel with abundant cytoplasm and vacuole-like nucleus but there wasn't evident atypia. The carcinoma cells were positively stained for CK and TTF-1 by immunohistochemistry, whereas mesenchymal cells were positive for SMA and displayed nuclear immunoreactivity for ß-catenin. BRAF, NRAS, and CTNNB1 mutations were identified in the epithelial and mesenchymal components through molecular testing, respectively. Perhaps because the mesenchyme harbors aberrant nuclear ß-catenin expression, PTC-DTF is more aggressive and prone to invasion and distant recurrence, as shown by our case 2, which is the first case to be reported thus far. PTC-DTF is typically treated with surgery, but clinicians may occasionally consider more holistic treatment plans that involve radioactive iodine and endocrine therapy.


Asunto(s)
Carcinoma Papilar , Fibromatosis Agresiva , Neoplasias de la Tiroides , Masculino , Humanos , Femenino , Persona de Mediana Edad , Cáncer Papilar Tiroideo/terapia , Cáncer Papilar Tiroideo/patología , Neoplasias de la Tiroides/diagnóstico por imagen , Neoplasias de la Tiroides/terapia , Neoplasias de la Tiroides/genética , beta Catenina/genética , Fibromatosis Agresiva/diagnóstico por imagen , Fibromatosis Agresiva/terapia , Radioisótopos de Yodo/uso terapéutico , Tomografía Computarizada por Tomografía de Emisión de Positrones , Carcinoma Papilar/cirugía , Carcinoma Papilar/genética
18.
Ultrason Sonochem ; 95: 106366, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-36965310

RESUMEN

The study evaluated the effect of an ultrasound-assisted treatment on the structural and functional properties of sheep bone collagen (SBC). The type and distribution of SBC were analyzed by proteome (shotgun) technology combined with liquid chromatography-tandem mass spectrometry. Compared with pepsin extraction, the ultrasound-assisted treatment significantly increased the collagen extraction rate by 17.4 pp (P < 0.05). The characteristic functional groups and structural integrity of collagen extracted by both methods were determined via Fourier transform infrared spectroscopy, ultraviolet absorption spectroscopy, and fluorescence spectroscopy. Circular dichroism spectra revealed that the ultrasound-assisted pretreatment reduced α-helix content by 1.6 pp, ß-sheet content by 21.9 pp, and random coils content by 28.4 pp, whereas it increased ß-turn content by 51.9 pp (P < 0.05), compared with pepsin extraction. Moreover, ultrasound-assisted treatment collagen had superior functional properties (e.g., solubility, water absorption, and oil absorption capacity) and foaming and emulsion properties, compared with pepsin extraction. Furthermore, the relative content of type I collagen in ultrasound-assisted extracted SBC was highest at 79.66%; only small proportions of type II, VI, X, and XI collagen were present. Peptide activity analysis showed that SBC had potential antioxidant activity, dipeptidyl peptidase 4 inhibitory activity, and angiotensin-converting enzyme inhibitory activity; it also had anticancer, antihypertensive, anti-inflammatory, and immunomodulatory effects.


Asunto(s)
Colágeno , Pepsina A , Animales , Ovinos , Colágeno/química , Fenómenos Químicos , Solubilidad
19.
Genet Test Mol Biomarkers ; 27(3): 74-80, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36989525

RESUMEN

Introduction: Developmental dysplasia of the hip (DDH) is one of the most common diseases in the pediatric orthopedics, with an incidence of 1-5%. Genetic factors are the bases of the pathogenesis of DDH, but the pathogenic variants and pathogenesis of DDH are still unknown. There are no key accurate diagnostic or prognostic molecular markers for DDH. The purpose of our study was to screen for genetic variant associated with DDH and explore its pathogenesis. Materials and Methods: The genetic variation of DDH was tested by variant NGS-based exome analyses, verified by the Sanger sequencing. Results: A four-generation family in which DDH was present in three generations was recruited. A novel heterozygous missense variant c.629C>T (p.(Ala210Val)) in exon 7/8 of the parathyroid hormone 1 receptor (PTH1R) gene was identified through screening of two affected and one unaffected family members. The candidate variant was validated in all available family members with all three affected members being positive for the PTH1R variant. Conclusion: Our results are highly supportive of PTH1R as a novel candidate gene for DDH and demonstrated that the combination of pedigree information and next-generation sequencing is an effective method for identifying pathogenic variants associated with DDH.


Asunto(s)
Displasia del Desarrollo de la Cadera , Receptor de Hormona Paratiroídea Tipo 1 , Mutación Missense , Displasia del Desarrollo de la Cadera/genética , Humanos , Receptor de Hormona Paratiroídea Tipo 1/genética , Secuenciación de Nucleótidos de Alto Rendimiento , Exoma , Linaje , Masculino , Femenino
20.
Nat Commun ; 14(1): 586, 2023 Feb 03.
Artículo en Inglés | MEDLINE | ID: mdl-36737480

RESUMEN

HP's Multi Jet Fusion is a powder bed fusion 3D printing technology that utilizes a carbon-based radiation absorber in combination with a near infrared (NIR) light source to facilitate the fusion of polymer powder in a layer-by-layer fashion to generate 3D parts. Most available carbon-based and NIR radiation absorbers have an intrinsic dark color, which as a result will only produce black/gray and dark colored parts. However, there are many applications that require variable color, including prosthetics, medical models, and indicators, among others. To create white, bright colored, and translucent parts with MJF, a visibly transparent and colorless radiation absorber is required. In this paper, we designed an activating fusing agent (AFA) that contains a red, strong NIR absorbing dye that turns colorless after harvesting irradiation energy during the MJF 3D printing process and provide a bright colored part when working with other color agents.

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