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1.
Materials (Basel) ; 17(8)2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38673211

RESUMO

Medium-carbon, high-strength steels are widely used in the field of hydrogen energy because of their good mechanical properties, and they can be readily tailored by heat treatment processes such as the normalizing-tempering (N&T) and quenching-tempering (Q&T) methods. The hydrogen embrittlement (HE) susceptibility of a medium-carbon, high-strength steel was investigated utilizing microstructural characterization with scanning electron microscopy (SEM), the electron backscatter diffraction (EBSD) technique, and transmission electron microscopy (TEM). A study was also conducted on the steel's hydrogen transport behavior as affected by the N&T and Q&T treatments. The steel contained more hydrogen traps, such as dislocations, grain boundaries, lath boundaries, and carbide interfaces, after the Q&T process, which was associated with a lower HE sensitivity when comparing the two treatments. In comparison, the N&T process produced larger-size and lesser-density carbides distributed along the grain boundaries, and this resulted in a relatively higher HE susceptibility, as revealed by the slow-strain-rate tensile (SSRT) tests of the hydrogen-charged steels and by the fractographic study of the fracture surface.

2.
Acta Pharmacol Sin ; 45(7): 1366-1380, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38538717

RESUMO

Parkinson's disease (PD) is the second most common neurodegenerative disease, and its prevalence is increasing. Currently, no effective therapies for PD exist. Marine-derived natural compounds are considered important resources for the discovery of new drugs due to their distinctive structures and diverse activities. In this study, tetrahydroauroglaucin (TAG), a polyketide isolated from a marine sponge, was found to have notable neuroprotective effects on MPTP/MPP+-induced neurotoxicity. RNA sequencing analysis and metabolomics revealed that TAG significantly improved lipid metabolism disorder in PD models. Further investigation indicated that TAG markedly decreased the accumulation of lipid droplets (LDs), downregulated the expression of RUBCN, and promoted autophagic flux. Moreover, conditional knockdown of Rubcn notably attenuated PD-like symptoms and the accumulation of LDs, accompanied by blockade of the neuroprotective effect of TAG. Collectively, our results first indicated that TAG, a promising PD therapeutic candidate, could suppress the accumulation of LDs through the RUBCN-autophagy pathway, which highlighted a novel and effective strategy for PD treatment.


Assuntos
Metabolismo dos Lipídeos , Fármacos Neuroprotetores , Animais , Metabolismo dos Lipídeos/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Homeostase/efeitos dos fármacos , Poríferos/química , Camundongos , Camundongos Endogâmicos C57BL , Autofagia/efeitos dos fármacos , Masculino , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/metabolismo , Policetídeos/farmacologia , Humanos
3.
Nat Commun ; 15(1): 251, 2024 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-38177173

RESUMO

Colorful circularly polarized luminescence materials are desired for 3D displays, information security and asymmetric synthesis, in which single-emitted materials are ideal owing to self-absorption avoidance, evenly entire-visible-spectrum-covered photon emission and facile device fabrication. However, restricted by the synthesis of chiral broad-luminescent emitters, the realization and application of high-performing single-emitted full-color circularly polarized luminescence is in its infancy. Here, we disclose a single-emitted full-color circularly polarized luminescence system (spiral full-color emission generator), composed of whole-vis-spectrum emissive quantum dots and chiral liquid crystals. The system achieves a maximum luminescence dissymmetry factor of 0.8 and remains an order of 10-1 in visible region by tuning its photonic bandgap. We then expand it to a series of desired customized-color circularly polarized luminescence, build chiral devices and further demonstrate the working scenario in the photoinduced enantioselective polymerization. This work contributes to the design and synthesis of efficient chiroptical materials, device fabrication and photoinduced asymmetric synthesis.

4.
SLAS Discov ; 29(3): 100143, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38280460

RESUMO

Three-dimensional (3D) cell culture in vitro promises to improve representation of neuron physiology in vivo. This inspired development of a 3D culture platform for LUHMES (Lund Human Mesencephalic) dopaminergic neurons for high-throughput screening (HTS) of chemicals for neurotoxicity. Three culture platforms, adhesion (2D-monolayer), 3D-suspension, and 3D-shaken, were compared to monitor mRNA expression of seven neuronal marker genes, DCX, DRD2, ENO2, NEUROD4, SYN1, TH, and TUBB3. These seven marker genes reached similar maxima in all three formats, with the two 3D platforms showing similar kinetics, whereas several markers peaked earlier in 2D adhesion compared to both 3D culture platforms. The differentiated LUHMES (dLUHMES) neurons treated with ziram, methylmercury or thiram dynamically increased expression of metallothionein biomarker genes MT1G, MT1E and MT2A at 6 h. These gene expression increases were generally more dynamic in 2D adhesion cultures than in 3D cultures, but were generally comparable between 3D-suspension and 3D-u plate (low binding) platforms. Finally, we adapted 3D-suspension culture of dLUHMES and neural stem cells to 1536 well plates with a HTS cytotoxicity assay. This HTS assay revealed that cytotoxicity IC50 values were not significantly different between adhesion and 3D-suspension platforms for 31 of 34 (91%) neurotoxicants tested, whereas IC50 values were significantly different for at least two toxicants. In summary, the 3D-suspension culture platform for LUHMES dopaminergic neurons supported full differentiation and reproducible assay results, enabling quantitative HTS (qHTS) for cytotoxicity in 1536 well format with a Robust Z' score of 0.68.


Assuntos
Neurônios Dopaminérgicos , Ensaios de Triagem em Larga Escala , Ensaios de Triagem em Larga Escala/métodos , Neurônios Dopaminérgicos/efeitos dos fármacos , Neurônios Dopaminérgicos/metabolismo , Humanos , Técnicas de Cultura de Células/métodos , Diferenciação Celular/efeitos dos fármacos , Técnicas de Cultura de Células em Três Dimensões/métodos , Biomarcadores/metabolismo , Compostos de Metilmercúrio/toxicidade , Neurotoxinas/toxicidade , Linhagem Celular , Células Cultivadas
5.
Sci Adv ; 9(43): eadi9944, 2023 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-37878702

RESUMO

Endowing three-dimensional (3D) displays with flexibility drives innovation in the next-generation wearable and smart electronic technology. Printing circularly polarized luminescence (CPL) materials on stretchable panels gives the chance to build desired flexible stereoscopic displays: CPL provides unusual optical rotation characteristics to achieve the considerable contrast ratio and wide viewing angle. However, the lack of printable, intense circularly polarized optical materials suitable for flexible processing hinders the implementation of flexible 3D devices. Here, we report a controllable and macroscopic production of printable CPL-active photonic paints using a designed confining helical co-assembly strategy, achieving a maximum luminescence dissymmetry factor (glum) value of 1.6. We print customized graphics and meter-long luminous coatings with these paints on a range of substates such as polypropylene, cotton fabric, and polyester fabric. We then demonstrate a flexible textile 3D display panel with two printed sets of pixel arrays based on the orthogonal CPL emission, which lays an efficient framework for future intelligent displays and clothing.

6.
Zhongguo Gu Shang ; 36(8): 773-6, 2023 Aug 25.
Artigo em Chinês | MEDLINE | ID: mdl-37605918

RESUMO

OBJECTIVE: To explore clinical efficacy of Locking loop stitch with suture-bridge technique in repair of acute closed distal Achilles tendon rupture by using suture anchors. METHODS: From July 2019 to March 2021, 20 patients with acute closed distal Achilles tendon rupture were treated by minimally invasive suture anchor locking suture bridging repair technique. Among them, including 18 males and 2 females, aged from 19 to 52 years old with an average of(40.0±9.0) years old. Complications were observed, and recovery of ankle function was evaluated by American Orthopaedic Foot & Ankle Society(AOFAS) ankle and hindfoot function scoring system before operation and 1 year after operation. RESULTS: All patients followed up from 6 to 18 months with an average of (12.0±3.2) months. The incisions were healed at stageⅠwithout infection and skin necrosis occurred;no gastrocnemius nerve injury and deep vein thrombosis of the lower extremities occurred;and no heel pain and Achilles tendon re-rupture occurred. AOFAS scores of ankle and hindfoot increased from(59.0±4.3) before opertaion to(95.1±2.6) at 1 year after operation (t=-32.1, P<0.05). CONCLUSION: The effect of locking suture bridging with suture anchor nails to repair acute distal Achilles tendon rupture is definite, and it could reduce incidence of complications such as Achilles tendon re-rupture, nerve injury, and skin necrosis, which has advantages of small surgical trauma, reliable anastomosis method and good functional recovery, and is an ideal method for treating acute closed distal Achilles tendon rupture.


Assuntos
Tendão do Calcâneo , Traumatismos do Tornozelo , Traumatismos dos Tendões , Feminino , Masculino , Humanos , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Âncoras de Sutura , Tendão do Calcâneo/cirurgia , Traumatismos dos Tendões/cirurgia , Necrose
7.
Pancreatology ; 23(3): 314-320, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36878824

RESUMO

BACKGROUND: Involvement of transverse mesocolon (TM) during acute necrotizing pancreatitis(ANP) indicates that inflammation has spread from retroperitoneal space to peritoneum. Nevertheless, the impact of TM involvement, as confirmed by contrast-enhanced computed tomography (CECT), on local complications and clinical outcomes was poorly investigated. PURPOSE: This study aimed to explore the association between CECT-diagnosed TM involvement and the development of colonic fistula in a cohort of ANP patients. METHODS: This is a single-center, retrospective cohort study involving ANP patients admitted from January 2020 to December 2020. TM involvement was diagnosed by two experienced radiologists. The study subjects were enrolled consecutively and divided into two groups: TM involvement and non-TM involvement. The primary outcome was colonic fistula during the index admission. Clinical outcomes were compared between the two groups, and the association between the TM involvement and the development of colonic fistula was assessed using multivariable analysis to adjust for baseline unbalances. RESULTS: A total of 180 patients with ANP were enrolled, and 86 (47.8%) patients had TM involvement. The incidence of the colonic fistula is significantly higher in patients with TM involvement (16.3% vs. 5.3%;p = 0.017). Moreover, the length of hospital stay was 24(13,68) days in patients with TM involvement and 15(7,31) days in those not (p = 0.001). Analysis of multivariable logistic regression revealed that TM involvement is an independent risk factor for the development of colonic fistula (odds ratio: 10.253, 95% CI: 2.206-47.650, p = 0.003). CONCLUSION: TM involvement in ANP patients is associated with development of colonic fistula in ANP patients.


Assuntos
Fístula , Mesocolo , Pancreatite Necrosante Aguda , Humanos , Pancreatite Necrosante Aguda/complicações , Pancreatite Necrosante Aguda/diagnóstico por imagem , Estudos Retrospectivos , Inflamação , Fístula/complicações
8.
Cancer Med ; 12(8): 10105-10122, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36776001

RESUMO

BACKGROUND: Colorectal cancer (CRC) is a malignant tumor of the digestive system that contains high levels of immune cells. Lactic acid, a major metabolite, plays a crucial role in tumor development, maintenance, and therapeutic response. However, the prognostic potential and therapeutic biomarker potential of lactate-related genes (LRGs) in CRC patients remain to be elucidated. METHODS: We collected the mRNA expression profile and clinical data of CRC patients from the Cancer Genome Atlas (TCGA) database and the GSE59382 cohort. Univariate Cox regression, Lasso regression and multivariate Cox regression analysis were used to construct the prognosis model. Combined with the risk score and important clinicopathological features, the nomogram was established. In addition, the relationship between risk score and immune infiltration, immune checkpoint gene expression, and drug sensitivity was investigated. RESULTS: We constructed lactate-related gene signatures (LRGS) based on four LRGs, which independently predicted the prognosis of CRC. Patients with different risk scores are found to have distinct immune status, tumor mutation load, immune response, and drug sensitivity. In addition, nomogram results determined by risk scores and clinical factors have higher predictive performance. CONCLUSION: We found that LRGS is a reliable biomarker for predicting clinical outcomes, evaluating immune infiltration and efficacy, and predicting the sensitivity to drugs in patients with CRC.


Assuntos
Neoplasias Colorretais , Ácido Láctico , Humanos , Bases de Dados Factuais , Análise Multivariada , Mutação , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Prognóstico
9.
J Am Chem Soc ; 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36724236

RESUMO

Nations, industries, and aspects of everyday life have undergone forgery and counterfeiting ever since the emergence of commercialization. Securing documents and products with anticounterfeit additives shows promise for authentication, allowing one to combat ever-increasing global counterfeiting. One most-used effective encryption strategy is to combine with optical-security markers on the required protection objects; however, state-of-the-art labels still suffer from imitation due to their poor complexity and easy forecasting, as a result of deterministic production. Developing advanced anticounterfeiting tags with unusual optical characters and further incorporating complex security features are desired to achieve multimodal, unbreakable authentication capacity; unfortunately, this has not yet been achieved. Here, we prepare a series of stable circularly polarized luminescence (CPL) materials, composed of toxicity-free, high-quality-emitting inorganic quantum dots (QDs) and liquid crystals, using a designed helical-coassembly strategy. This CPL system achieves a figure of merit (FM, assessing the performance of both luminescence dissymmetry and quantum yield) value of 0.39, fulfilling practical demands for anticounterfeiting applications. Based on these CPL structures, we produce a type of multimodal-responsive security materials (MRSMs) that exhibits six different stimuli-responsive modes, including light activation, polarization, temperature, voltage, pressure, and view angle. Thus, we show a proof-of-principle blockchain-like integrated anticounterfeiting system, allowing multimodal-responsive, interactive/changeable information encryption-decryption. We further encapsulate the obtained security materials into a fiber to expand our materials to work on flexible fabrics, that is, building an intelligent textile with a color-adaptable function along with environmental change.

10.
Mol Genet Genomic Med ; 11(1): e2091, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36345251

RESUMO

BACKGROUND: The incidence of acute pancreatitis (AP) is increasing over years, which brings enormous economy and health burden. However, the aetiologies of AP and underlying mechanisms are still unclear. Here, we performed a two-sample Mendelian randomization (MR) analysis to investigate the associations between all reported possible risk factors and AP using publicly available genome-wide association study summary statistics. METHODS: A series of quality control steps were taken in our analysis to select eligible instrumental single nucleotide polymorphisms which were strongly associated with exposures. To make the conclusions more robust and reliable, we utilized several analytical methods (inverse-variance weighting, MR-PRESSO method, weighted median, MR-Egger regression) that are based on different assumptions of two-sample MR analysis. The MR-Egger intercept test, radial regression and leave-one-out sensitivity analysis were performed to evaluate the horizontal pleiotropy, heterogeneities, and stability of these genetic variants on each exposure. A two-step MR method was applied to explore mediators in significant associations. RESULTS: Genetic predisposition to cholelithiasis (effect estimate: 17.30, 95% CI: 12.25-22.36, p = 1.95 E-11), body mass index (0.32, 95% CI: 0.13-0.51, p < 0.001), body fat percentage (0.57, 95% CI: 0.31-0.83, p = 1.31 E-05), trunk fat percentage (0.36, 95% CI: 0.14-0.59, p < 0.005), ever smoked (1.61, 95% CI: 0.45-2.77, p = 0.007), and limbs fat percentage (0.55, 95% CI: 0.41-0.69, p < 0.001) were associated with an increased risk of AP. In addition, whole-body fat-free mass (-0.32, 95% CI: -0.55 to -0.10, p = 0.004) was associated with a decrease risk of AP. CONCLUSION: Genetic predisposition to cholelithiasis, obesity and smoking could be causally associated with an increased risk of AP, and whole body fat-free mass could be associated with a decreased risk of AP.


Assuntos
Colelitíase , Pancreatite , Humanos , Doença Aguda , Colelitíase/genética , Demografia , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Pancreatite/etiologia , Pancreatite/genética , Obesidade/complicações , Fumar/efeitos adversos
11.
Can Respir J ; 2022: 1485719, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36582191

RESUMO

Asthma is a chronic inflammatory disturbance of the airways in which many cells and cellular elements are involved. Wheezing, breathlessness, chest tightness, and coughing, especially at night or in the early morning, are typical symptoms of asthma. At present, inhaled corticosteroid (ICS) and long-acting ß-agonists (LABAs) are standard treatments for regular management. Oral corticosteroids (OCSs) were recommended for controlling asthma exacerbation but only for a short-term treatment because of the side effects on organs. Biologic therapies have achieved exciting and notable effects in clinical treatment but are not applicable for all phenotypes of asthma. At present, some new approaches are under exploration to lessen side effects and improve curative effects. Studies have revealed that bone marrow mesenchymal stem cells (BMMSCs) hold various curative effects in asthma and may benefit in the long term with high safety. Extracellular vesicles (EVs) enriched in body fluid were characterized as subcomponents of extracellular vesicles and delivered carriers combined with genetic messages in vivo. The therapeutic potential of exosomes has become a research hotspot in many diseases. BMMSC-derived exosomes were considered as the dominant part of BMMSCs in cell-to-cell communications and playing curative effects. Points also hold that BMMSC-Exo could interfere with airway inflammation and airway remolding in asthma via modulating the immune response, regulating gene expression, adjusting the phenotype of macrophage, etc. However, BMMSC-Exo still lacked more clinical trials for evaluating the effects on asthma, and the technology of extraction and purification still needs to be improved for wide use. This review aims to draw the relationship among asthma, BMMSC, and exosome, which may provide innovate ideas for treatment of asthma, and arouse attention about the curative potential of BMMSC-Exo.


Assuntos
Asma , Exossomos , Células-Tronco Mesenquimais , Humanos , Asma/tratamento farmacológico , Asma/metabolismo , Corticosteroides/uso terapêutico , Quimioterapia Combinada , Células-Tronco Mesenquimais/metabolismo
12.
Front Plant Sci ; 13: 991074, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36340390

RESUMO

Black shank disease caused by Phytophthora nicotianae is one of the most important diseases in tobacco worldwide and can result in a devastating loss in tobacco cultivation. Many efforts have been carried out to identify the chromosome segment from Nicotiana plumbaginifolia containing a resistance locus carrying a gene named Php; however, the Php gene has not been cloned, and knowledge of the potential mechanism of the Php gene in the resistant lines is limited. To further characterize the resistance mechanism of the Php gene, we first used the resistant line "RBST" and the susceptible cultivar "Honghuadajinyuan" (HD) to obtain the near-isogenic line RBS89 containing the Php gene from RBST. RBS89 showed high resistance to black shank disease. Transcriptomic and iTRAQ analyses were applied to explore the potential defense mechanisms in RBS89 plants in comparison with HD plants with or without inoculation. Many differentially expressed genes (DEGs) and proteins were identified, and some pathogenesis-related (PR) proteins were extensively abundant in the RBS89 plants when compared with the HD plants in response to black shank disease. Importantly, overexpression of the PR gene NtPR-1B in HD plants improved the resistance of tobacco plants to black shank disease, indicating that NtPR-1B and Php genes might have similar roles in protecting tobacco from black shank disease. However, the relationship between NtPR-1B and Php genes requires further analysis. Therefore, our study provides valuable information for breeding tobacco cultivars with black shank disease resistance and sheds light on the defense mechanism of black shank disease in tobacco for enhancing Phytophthora resistance in other Solanaceae crops.

14.
Neurotox Res ; 40(5): 1526-1536, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35922689

RESUMO

Ferroptosis is a necrotic cell death caused by lipid oxidation that may be responsible for neural degeneration in Parkinson's disease. We assessed whether three neuronal cell lines are sensitive to killing by ferroptosis. Ferroptosis inducer erastin killed LUHMES neurons at sub-micromolar concentrations, whereas neuronal cells derived from SH-SY5Y cells or neural stem cells were at least 50-fold less sensitive. LUHMES differentiated neurons were likewise sensitive to killing by RSL3 or ML210, inhibitors of the glutathione peroxidase 4 enzyme (GPX4) that consumes GSH to detoxify lipid peroxides. Additional assays showed that erastin, RSL3, and ML210 increased lipid peroxide levels, and that LUHMES neurons were protected from both peroxide accumulation and cell death by ferrostatin-1. A possible role of iron was assessed by evaluating the effects of five metal chelators on cytotoxicity of erastin and RSL3. LUHMES neurons were protected from RSL3 by three of the chelators, 2,3-dimercapto-1-propanesulfonic acid (DMPS), deferoxiprone (DFX), and deferiprone (DFP). Collectively, these results demonstrate the vulnerability of LUHMES neurons to ferroptosis by chemical treatments that disrupt glutathione synthesis, lipid peroxide detoxification, or iron metabolism. The same vulnerabilities may occur in CNS neurons, which reportedly generate low levels of GSH and metallothioneins, limiting their ability to neutralize oxidative stresses and toxic metals. These results suggest a rationale and methods to search for environmental toxicants that may exploit these vulnerabilities and promote neurodegenerative diseases.


Assuntos
Ferroptose , Neuroblastoma , Humanos , Carbolinas/toxicidade , Quelantes , Deferiprona , Neurônios Dopaminérgicos/metabolismo , Glutationa/metabolismo , Ferro/metabolismo , Ferro/toxicidade , Peróxidos Lipídicos , Fosfolipídeo Hidroperóxido Glutationa Peroxidase , Unitiol
15.
Exp Neurol ; 358: 114208, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-35988700

RESUMO

Hypertension is a confirmed risk factor for cerebral hemorrhage in humans. Which endogenous factor directly induces hypertension-related hemorrhage is unclear. In this study, 42 hemorrhagic patients with hypertension and hyperlipidemia and 42 age-matched healthy controls were enrolled. The contents of serum semicarbazide-sensitive amine oxidase (SSAO) and formic acid (FC, FC is a final product of SSAO through the oxidation of endogenous formaldehyde, which results from the enzymatic oxidative deamination of the SSAO substrate, methylamine) were examined in the patients after stroke. Hemorrhagic areas were quantified by computer tomography. In the animal study, hemorrhagic degree was assessed by hemotoxylin & eosin or tissue hemoglobin kits. The relationship between FC and blood pressure/hemorrhagic degree was examined in wild-type mice and hSSAOTG mice fed with high-fat diets or high-fat and -salt diets. The results showed that the levels of serum FC were positively correlated with blood pressure and hemorrhagic areas in hemorrhagic patients. Transfection of microRNA-134 could enhance SSAO expression in human vascular smooth muscle cells. Consistently, after treatment with high-fat and -salt diets, hSSAOTG mice exhibited higher levels of miR134 and FC, higher blood pressure, and more severe hemorrhage than wild-type mice. Interestingly, folic acid reduced hypertension and hemorrhage in hSSAOTG mice fed with high-fat diets. These findings suggest that FC is a crucial endogenous factor for hypertension and hemorrhage.


Assuntos
Amina Oxidase (contendo Cobre) , Hipertensão , MicroRNAs , Amina Oxidase (contendo Cobre)/metabolismo , Amina Oxidase (contendo Cobre)/farmacologia , Animais , Amarelo de Eosina-(YS) , Ácido Fólico , Formaldeído/farmacologia , Formiatos , Hematoxilina , Hemorragia , Humanos , Metilaminas/metabolismo , Camundongos
16.
Medicine (Baltimore) ; 101(28): e29461, 2022 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-35839053

RESUMO

RATIONALE: Heparin-induced thrombocytopenia (HIT), a potentially devastating form of drug-induced thrombocytopenia, occurs in patients receiving heparin for thrombosis prevention or treatment. An isolated HIT is characterized by decreased platelet counts without thrombosis, which are atypical and difficult to clinically find. SYMPTOMS AND CLINICAL FINDINGS: A 33-year-old female patient's admission examination revealed elevated D-dimer levels. After prophylactic anticoagulation using low-molecular weight heparin, her blood platelet counts were rapidly decreased, whereas her D-dimer levels increased, followed by presentations of chest tightness, abdominal pain, and skin itching without thrombosis. After excluding all the other causes of thrombocytopenia, HIT was suspected. Her 4Ts score was 5 points, and enzyme-linked immunoassay for platelet factor 4 (PF4)/heparin antibodies was positive, indicating isolated HIT. DIAGNOSES, INTERVENTIONS, AND OUTCOMES: The patient was diagnosed with advanced lung cancer presenting with isolated HIT. We immediately stopped low-molecular weight heparin and initiated rivaroxaban for anticoagulation. We administered thrombopoietin (TPO) and avatripopal maleate tablets to increase blood platelet counts, whereas intravenous immunoglobulin (IVIG) was administered to stimulate her immune system. The patient's thrombocytopenia was successfully treated without thrombosis and bleeding complications. LESSONS: Rivaroxaban is a potential option for tumor preventive anticoagulation and HIT treatment. Early HIT identification is necessary. After identification, the 4Ts score as well as PF4/heparin antibodies should be assessed and appropriate anticoagulants selected based on patients' conditions.


Assuntos
Neoplasias Pulmonares , Trombocitopenia , Trombose , Adulto , Anticorpos , Anticoagulantes/efeitos adversos , Feminino , Heparina/efeitos adversos , Humanos , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/tratamento farmacológico , Fator Plaquetário 4 , Rivaroxabana/efeitos adversos , Trombocitopenia/diagnóstico , Trombose/complicações
17.
Obesity (Silver Spring) ; 30(7): 1357-1369, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35707874

RESUMO

OBJECTIVE: This study aimed to recapitulate the change trajectory of postoperative weight and investigate the association between postoperative hypothalamic damage and weight gain and hypothalamic obesity (HO) in patients with adult-onset craniopharyngioma. METHODS: The data of 96 patients with surgically treated primary adult-onset craniopharyngioma were retrospectively analyzed. The association between postoperative hypothalamic damage based on magnetic resonance images or endoscopic observation and postoperative weight gain and HO was determined by multivariable logistic regression. RESULTS: Forty-seven (49.0%) patients and 18 (18.8%) patients experienced clinically meaningful weight gain (≥5%) and HO at last follow-up, respectively. Postoperative weight significantly increased during the first 6 months following surgery, followed by stabilization. Both grade 2 postoperative hypothalamus damage, as evaluated by the magnetic resonance imaging classification system of Müller et al., and higher scores based on the Roth et al. hypothalamic lesion score were significantly associated with postoperative weight gain of ≥5% (p = 0.005 and p = 0.002) and with HO (p = 0.001 and p = 0.008). Additionally, bilateral hypothalamic injury as evaluated by the Hong et al. hypothalamic injury pattern based on endoscopic observation (p = 0.008) could predict postoperative weight gain ≥5%. CONCLUSIONS: Significant postoperative weight gain is common in patients with adult-onset craniopharyngioma. Postoperative hypothalamic damage can predict clinically meaningful weight gain and HO.


Assuntos
Craniofaringioma , Doenças Hipotalâmicas , Neoplasias Hipofisárias , Adulto , Índice de Massa Corporal , Craniofaringioma/complicações , Craniofaringioma/diagnóstico por imagem , Craniofaringioma/cirurgia , Humanos , Doenças Hipotalâmicas/complicações , Hipotálamo/diagnóstico por imagem , Hipotálamo/patologia , Obesidade/complicações , Obesidade/patologia , Obesidade/cirurgia , Neoplasias Hipofisárias/complicações , Neoplasias Hipofisárias/diagnóstico por imagem , Neoplasias Hipofisárias/cirurgia , Estudos Retrospectivos , Aumento de Peso
18.
Reprod Sci ; 29(8): 2391-2400, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35585293

RESUMO

Steroid-producing cells contain key cytochrome P450 enzymes, such as side-chain cleavage (P450-SCC) and 17α-hydroxylase (17α-OH). They are required for steroid hormone synthesis and considered antigens associated with Addison's disease and autoimmune primary ovarian insufficiency (POI). We studied an animal model for human autoimmune POI in mice with autoimmune oophoritis induced by neonatal thymectomy performed at day 3 (TX3). We previously identified an oocyte-specific protein as a major antigen inciting autoimmune oophoritis in mice. In this study, we characterized ovarian steroid-producing cell antigens. Using indirect immunofluorescence staining, we tested immune reactions in mouse ovarian and adrenal tissue sections with sera from TX3 female mice. More than half of the TX3 mice (8 of 15) produced antibodies reacting with both ovarian and adrenal steroid-producing cells, including some that reacted to oocytes as well. We produced recombinant proteins for the three key steroidogenic enzymes 17α-OH, P450-SSC, and 3ß-hydroxysteroid dehydrogenase (3ß-HSD) and tested their immune reactions with individual mouse sera. By immunoblotting, all mouse sera that reacted with the steroid-producing cells (n = 8) were shown to react with the P450-SCC, but not with the 17α-OH or 3ß-HSD recombinant proteins. The sham-operated mouse sera and TX3 mouse sera negative for steroid-producing cells did not react with the P450-SCC recombinant protein. Our findings indicate that the P450-SCC is a specific and unique major antigen within the ovarian steroid-producing cells. Given their similarity of predicted antigenicity, we assume that P450-SCC acts in human autoimmune POI as it does in mouse autoimmune oophoritis.


Assuntos
Doença de Addison , Insuficiência Ovariana Primária , Animais , Autoantígenos , Enzima de Clivagem da Cadeia Lateral do Colesterol , Feminino , Humanos , Camundongos , Ooforite , Poliendocrinopatias Autoimunes , Proteínas Recombinantes , Esteroide 17-alfa-Hidroxilase , Esteroides
19.
ACS Nano ; 16(4): 5515-5528, 2022 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-35352555

RESUMO

Nearly half of pregnancies worldwide are unintended mainly due to failure of contraception, resulting in negative effects on women's health. Male contraception techniques, primarily condoms and vasectomy, play a crucial role in birth control, but cannot be both highly effective and reversible at the same time. Herein, an ultrasound (US)-induced self-clearance hydrogel capable of real-time monitoring is utilized for in situ injection into the vas deferens, enabling effective contraception and noninvasive recanalization whenever needed. The hydrogel is composed of (i) sodium alginate (SA) conjugated with reactive oxygen species (ROS)-cleavable thioketal (SA-tK), (ii) titanium dioxide (TiO2), which can generate a specific level of ROS after US treatment, and (iii) calcium chloride (CaCl2), which triggers the formation of the hydrogel. For contraception, the above mixture agents are one-time injected into the vas deferens, which can transform from liquid to hydrogel within 160 s, thereby significantly physically blocking the vas deferens and inhibiting movability of sperm. When fertility is needed, a noninvasive remedial ultrasound can make TiO2 generate ROS, which cleaves SA-tK to destroy the network of the hydrogel. Owing to the recanalization, the refertility rate is restored to 100%. Meanwhile, diagnostic ultrasound (D-US, 22 MHz) can monitor the occlusion and recanalization process in real-time. In summary, the proposed hydrogel contraception can be a reliable, safe, and reversible male contraceptive strategy that addresses an unmet need for men to control their fertility.


Assuntos
Hidrogéis , Sêmen , Gravidez , Masculino , Feminino , Humanos , Espécies Reativas de Oxigênio , Anticoncepção/métodos , Ultrassonografia
20.
World J Diabetes ; 13(2): 126-128, 2022 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-35211249

RESUMO

Patients with inflammatory bowel disease (IBD) are reported to have an increased risk of diabetes. IBD therapies may also modulate blood glucose substantially. These observations are indicative of mechanistic connection(s) between IBD and diabetes.

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