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1.
J Oral Pathol Med ; 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38802299

RESUMO

BACKGROUND: circRNAs have been shown to participate in diverse diseases; however, their role in oral submucous fibrosis (OSF), a potentially malignant disorder, remains obscure. Our preliminary experiments detected the expression of circRNA mitochondrial translation optimization 1 homologue (circMTO1) in OSF tissues (n = 20) and normal mucosa tissues (n = 20) collected from Hunan Xiangya Stomatological Hospital, and a significant decrease of circMTO1 expression was showed in OSF tissues. Therefore, we further explored circMTO1 expression in OSF. METHODS: Target molecule expression was detected using RT-qPCR and western blotting. The migration and invasion of buccal mucosal fibroblasts (BMFs) were assessed using wound healing and Transwell assays. The interaction between miR-30c-5p, circMTO1, and SOCS3 was evaluated using dual luciferase, RNA immunoprecipitation (RIP), and RNA pull-down assays. The colocalisation of circMTO1 and miR-30c-5p was observed using fluorescence in situ hybridisation (FISH). RESULTS: circMTO1 and SOCS3 expression decreased, whereas miR-30c-5p expression increased in patients with OSF and arecoline-stimulated BMFs. Overexpression of circMTO1 effectively restrained the fibroblast-myofibroblast transition (FMT), as evidenced by the increase in expression of Coll I, α-SMA, Vimentin, and the weakened migration and invasion functions in BMFs. Mechanistic studies have shown that circMTO1 suppresses FMT by enhancing SOCS3 expression by sponging miR-30c-5p and subsequently inactivating the FAK/PI3K/AKT pathway. FMT induced by SOCS3 silencing was reversed by the FAK inhibitor TAE226 or the PI3K inhibitor LY294002. CONCLUSION: circMTO1/miR-30c-5p/SOCS3 axis regulates FMT in arecoline-treated BMFs via the FAK/PI3K/AKT pathway. Expanding the sample size and in vivo validation could further elucidate their potential as therapeutic targets for OSF.

2.
Foods ; 13(8)2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38672841

RESUMO

The consumption of edible vegetable oil is an important source of essential fatty acids and vitamin E for the human body. Guiding residents to consume scientifically and reasonably control the intake of edible oils is an important part of promoting the construction of a healthy China. Currently, Chinese residents have an insufficient understanding of the scientific consumption of edible oils, leading to an intake exceeding the dietary recommendations, resulting in excessive fat intake and increasing the risk of chronic diseases such as obesity and cardiovascular diseases. Based on the Theory of Planned Behavior (TPB) and using Structural Equation Modeling (SEM), this study analyzed the cognitive preferences and willingness to pay a premium for edible vegetable oils among urban consumers in China. The survey included 1098 Chinese urban consumers of vegetable oils. The research found that attitudes, health value, monetary value, and environmental endowment of urban residents are the main predicting factors of the intention to purchase high-quality vegetable oils. This study confirms the applicability of the Theory of Planned Behavior in the consumption of high-quality vegetable oils and provides theoretical contributions and insights for Chinese enterprises and policymakers in formulating marketing strategies for vegetable oils.

3.
World J Psychiatry ; 14(2): 266-275, 2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38464776

RESUMO

BACKGROUND: Sepsis is a serious infectious disease caused by various systemic inflammatory responses and is ultimately life-threatening. Patients usually experience depression and anxiety, which affect their sleep quality and post-traumatic growth levels. AIM: To investigate the effects of sepsis, a one-hour bundle (H1B) management was combined with psychological intervention in patients with sepsis. METHODS: This retrospective analysis included 300 patients with sepsis who were admitted to Henan Provincial People's Hospital between June 2022 and June 2023. According to different intervention methods, the participants were divided into a simple group (SG, n = 150) and combined group (CG, n = 150). H1B management was used in the SG and H1B management combined with psychological intervention was used in the CG. The changes of negative emotion, sleep quality and post-traumatic growth and prognosis were compared between the two groups before (T0) and after (T1) intervention. RESULTS: After intervention (T1), the scores of the Hamilton Anxiety scale and Hamilton Depression scale in the CG were significantly lower than those in the SG (P < 0.001). Sleep time, sleep quality, sleep efficiency, daytime dysfunction, sleep disturbance dimension score, and the total score in the CG were significantly lower than those in the SG (P < 0.001). The appreciation of life, mental changes, relationship with others, personal strength dimension score, and total score of the CG were significantly higher than those of the SG (P < 0.001). The scores for mental health, general health status, physiological function, emotional function, physical pain, social function, energy, and physiological function in the CG were significantly higher than those in the SG (P < 0.001). The mechanical ventilation time, intensive care unit stay time, and 28-d mortality of the CG were significantly lower than those of the SG (P < 0.05). CONCLUSION: H1B management combined with psychological intervention can effectively alleviate the negative emotions of patients with sepsis and increase their quality of sleep and life.

4.
Front Public Health ; 12: 1360940, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38532977

RESUMO

Background: The main purpose of this study is to analyze the relationship between moral sensitivity, empathy, and caring behaviors and to explore the mediating effect of empathy on moral sensitivity and caring behaviors of nursing interns. Methods: A cross-sectional survey was conducted from August to September 2022 in which 261 nursing interns from two Grade 3A Hospitals in Xi'an participated. The questionnaires used in the survey include the General Information Questionnaire (GIQ), the Moral Sensitivity Questionnaire-Revised Version translated into Chinese (MSQ R-CV), the Chinese version of the Jefferson Empathy Scale (JSE), and the Chinese version of the Caring Behavior Inventory (C-CBI). The obtained data were analyzed through descriptive statistics, a one-way analysis of variance (ANOVA), and Pearson's correlation coefficient, and the mediating effect of empathy was tested through structural equations. Results: The overall mean of moral sensitivity of nursing interns in two Grade 3A Hospitals in Xi'an is 40.84 ± 8.73, the overall mean of empathy is 100.51 ± 21.56, and the overall mean of caring behavior is (113.81 ± 21.05). Statistical analysis showed that there is a positive correlation between moral sensitivity and caring behavior of nursing interns (r = 0.376, p < 0.01), between their empathy and moral sensitivity (r = 0.336, p < 0.01), and between their empathy and caring behavior (r = 0.394, p < 0.01). The empathy of nursing interns has a mediated effect on the relationship between moral sensitivity and caring behavior. The mediated effect value was 0.14, accounting for 31.82% of the total effect. Conclusion: The moral sensitivity of nursing interns can have a direct impact on predicting the caring behavior and indirect influences their caring behaviors mediated by empathy, with the latter effect being mediated by empathy. Therefore, nursing educators and hospital administrators should adopt targeted interventions to improve the moral sensitivity and empathy of nursing interns, which can further prove to be beneficial in improving their caring behaviors, leading to enhanced quality of nursing care and reduced nurse-patient conflicts and finally to a stabilized nursing team.


Assuntos
Empatia , Princípios Morais , Humanos , Estudos Transversais , Análise de Variância , Inquéritos e Questionários
5.
Sensors (Basel) ; 24(4)2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38400236

RESUMO

Pressure sensing plays an important role in many industrial fields; conventional electronic pressure sensors struggle to survive in the harsh environment. Recently microelectromechanical systems (MEMS) fiber-optic Fabry-Perot (FP) pressure sensors have attracted great interest. Here we review the basic principles of MEMS fiber-optic FP pressure sensors and then discuss the sensors based on different materials and their industrial applications. We also introduce recent progress, such as two-photon polymerization-based 3D printing technology, and the state-of-the-art in this field, e.g., sapphire-based sensors that work up to 1200 °C. Finally, we discuss the limitations and opportunities for future development.

6.
Urology ; 187: 1-5, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38373576

RESUMO

OBJECTIVE: To evaluate the clinical efficacy of a novel negative pressure ureteroscopic lithotripsy (NP-URL) compared to standard ureteroscopic lithotripsy (S-URL) for treating ureteral stones. METHODS: A total of 284 patients diagnosed with ureteral stones and who underwent ureteroscopic lithotripsy between December 2020 and May 2022 at our hospital were included in the study. Among them, 146 cases underwent NP-URL and 138 cases underwent S-URL. The negative pressure device used in NP-URL consists of a 5F ureteric catheter and a tee joint. We evaluated the operative duration, stone-free rate, incidence of postoperative complications, stone retropulsion rate, and adjunct procedure rate between the two groups. RESULTS: The mean operative duration was significantly shorter in the NP-URL group compared to the S-URL group (30.17 ± 5.84 minutes vs 34.84 ± 6.62 minutes; P<.05). Additionally, the NP-URL group had a lower incidence of postoperative fever (1.4% vs 8.7%; P<.05), reduced stone retropulsion rate (3.4% vs 11.6%; P<.05), and a statistically lower rate of adjunct procedures (5.5% vs 14.5%, P<.05). The NP-URL group also demonstrated a higher primary stone-free rate (91.8% vs 81.9%; P<.05). However, there was no significant difference in the final stone-free rate between the NP-URL and S-URL groups (P>.05). CONCLUSION: NP-URL potentially reduces operative duration, significantly decreases the incidence of postoperative complications, and achieves better primary stone-free rates compared to S-URL.


Assuntos
Litotripsia , Duração da Cirurgia , Cálculos Ureterais , Ureteroscopia , Humanos , Cálculos Ureterais/terapia , Cálculos Ureterais/cirurgia , Ureteroscopia/métodos , Masculino , Feminino , Litotripsia/métodos , Litotripsia/instrumentação , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos
9.
Arch. endocrinol. metab. (Online) ; 68: e220491, 2024. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1533663

RESUMO

SUMMARY Primary pigmented nodular adrenocortical disease (PPNAD) is a rare adrenocorticotropin hormone (ACTH)-independent Cushing's syndrome (CS). Pediatric patients with PPNAD typically have unusual skin lesions and slow growth with unknown causes. We present a case of a female Chinese patient with PPNAD caused by the germline PRKACA gene copy number gain of chromosome 19. The patient initially presented with kidney stones, short stature, and obesity. After further testing, it was discovered that the patient had diabetes, mild hypertension, low bone mass, a low ACTH level, and hypercortisolemia, and neither the low-dose or high-dose dexamethasone suppression test was able to inhibit hematuric cortisol, which paradoxically increased. PPNAD was pathologically diagnosed after unilateral adrenalectomy. Chromosome microarrays and whole exon sequencing analyses of the peripheral blood, as well as testing of sectioned adrenal tissue, showed a rise in the copy number of the duplication-containing PRKACA gene on chromosome 19p13.13p13.12, a de novo but not heritable gene defect that causes disease. The clinical signs and symptoms supported the diagnosis of Carney complex (CNC). One significant mechanism of CNC pathogenesis may be the rise in germline PRKACA copy number of chromosome 19. When assessing PPNAD patients for CNC, the possibility of PRKACA gene amplification should be considered. The effect of PRKACA gene amplification on the clinical manifestations of CNC needs to be confirmed by more cases.

10.
Biochem Pharmacol ; 220: 115991, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38135129

RESUMO

The mechanism of tumor drug resistance is complex and may involve stem cell maintenance, epithelial-mesenchymal transition, the activation of survival signaling pathways, transporter protein expression, and tumor microenvironment remodeling, all of which are linked to γ-secretase/Notch signaling. Increasing evidence has shown that the activation of the γ-secretase/Notch pathway is a key driver of cancer progression and drug resistance development and that γ-secretase inhibitors (GSIs) may be the most promising agents for reversing chemotherapy resistance of tumors by targeting the γ-secretase/Notch pathway. Here, we systematically summarize the roles in supporting γ-secretase/Notch activation-associated transformation of cancer cells into cancer stem cells, promotion of the EMT process, PI3K/Akt, MEK/ERK and NF-κB activation, enhancement of ABC transporter protein expression, and TME alteration in mediating tumor drug resistance. Subsequently, we analyze the mechanism of GSIs targeting the γ-secretase/Notch pathway to reverse tumor drug resistance and propose the outstanding advantages of GSIs in treating breast cancer drug resistance over other tumors. Finally, we emphasize that the development of GSIs for reversing tumor drug resistance is promising.


Assuntos
Secretases da Proteína Precursora do Amiloide , Neoplasias , Linhagem Celular Tumoral , Secretases da Proteína Precursora do Amiloide/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Resistencia a Medicamentos Antineoplásicos , Transdução de Sinais , Receptores Notch/metabolismo , Neoplasias/tratamento farmacológico
11.
Asian J Psychiatr ; 91: 103865, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38113699

RESUMO

OBJECTIVE: The aim of this research was to assess the therapeutic drug monitoring (TDM) of clozapine (CLO) and norclozapine (NCLO). METHODS: TDM results of CLO and NCLO in patients obtained from the Xi'an Mental Health Center were retrospectively analyzed. RESULTS: TDM of CLO and NCLO was typically conducted only once in the majority of patients, particularly those receiving outpatient care. The CLO plasma concentrations were higher in inpatients and female patients. The interquartile (25th-75th) CLO concentrations ranged from 129.83 to 397.53 ng/mL, nearly 68.63% of the samples had subtherapeutic concentrations (<350 ng/mL). Receiver operating characteristic curve analysis showed that inpatients achieved the therapeutic level concentration of 350-600 ng/mL when their daily CLO dose was > 125 mg. CONCLUSIONS: It was surprising to find such a large number of patients with CLO levels below the therapeutic range, there is still a window of improvement for optimizing pharmacological treatments in clinical practice.


Assuntos
Antipsicóticos , Clozapina , Esquizofrenia , Humanos , Feminino , Clozapina/uso terapêutico , Esquizofrenia/tratamento farmacológico , Estudos Retrospectivos , Antipsicóticos/uso terapêutico , Monitoramento de Medicamentos/métodos
12.
Sci Rep ; 13(1): 22972, 2023 12 27.
Artigo em Inglês | MEDLINE | ID: mdl-38151518

RESUMO

This study aims to evaluate the therapeutic efficacy of a novel double-sheath negative-pressure minimally invasive percutaneous nephrolithotomy (D-mPCNL) compared to conventional minimally invasive percutaneous nephrolithotomy (C-mPCNL) for large kidney stones. A total of 132 patients diagnosed with large kidney stones in our hospital were included in the study. Among them, sixty-eight patients underwent D-mPCNL, while sixty-four underwent C-mPCNL. Parameters such as operative duration, stone-free rate, incidence of postoperative complications, and the need for auxiliary procedures were evaluated between the two groups. Compared to the C-mPCNL group, the D-mPCNL group demonstrated a significantly shorter operative time (41.97 ± 8.24 min vs. 52.30 ± 13.72 min; P < 0.000), lower rates of auxiliary procedures (5.9% vs. 17.2%; P = 0.041), and lower fever rates (2.9% vs. 14.1%; P = 0.021). The group also had a significantly higher primary stone-free rate (85.3% vs. 70.3%; P = 0.038). However, there were no statistically significant advantages in terms of the final stone-free rate, hemoglobin drops, and stone composition in the D-mPCNL group (P > 0.05). D-mPCNL is a novel surgical method that is safe and effective, reducing operative time, improving stone-free efficiency, and decreasing postoperative complications.


Assuntos
Cálculos Renais , Nefrolitotomia Percutânea , Humanos , Nefrolitotomia Percutânea/efeitos adversos , Nefrolitotomia Percutânea/métodos , Resultado do Tratamento , Tempo de Internação , Cálculos Renais/cirurgia , Cálculos Renais/complicações , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/epidemiologia
13.
Arch Endocrinol Metab ; 68: e220491, 2023 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-37988664

RESUMO

Primary pigmented nodular adrenocortical disease (PPNAD) is a rare adrenocorticotropin hormone (ACTH)-independent Cushing's syndrome (CS). Pediatric patients with PPNAD typically have unusual skin lesions and slow growth with unknown causes. We present a case of a female Chinese patient with PPNAD caused by the germline PRKACA gene copy number gain of chromosome 19. The patient initially presented with kidney stones, short stature, and obesity. After further testing, it was discovered that the patient had diabetes, mild hypertension, low bone mass, a low ACTH level, and hypercortisolemia, and neither the low-dose or high-dose dexamethasone suppression test was able to inhibit hematuric cortisol, which paradoxically increased. PPNAD was pathologically diagnosed after unilateral adrenalectomy. Chromosome microarrays and whole exon sequencing analyses of the peripheral blood, as well as testing of sectioned adrenal tissue, showed a rise in the copy number of the duplication-containing PRKACA gene on chromosome 19p13.13p13.12, a de novo but not heritable gene defect that causes disease. The clinical signs and symptoms supported the diagnosis of Carney complex (CNC). One significant mechanism of CNC pathogenesis may be the rise in germline PRKACA copy number of chromosome 19. When assessing PPNAD patients for CNC, the possibility of PRKACA gene amplification should be considered. The effect of PRKACA gene amplification on the clinical manifestations of CNC needs to be confirmed by more cases.


Assuntos
Doenças do Córtex Suprarrenal , Síndrome de Cushing , Humanos , Criança , Feminino , Doenças do Córtex Suprarrenal/genética , Doenças do Córtex Suprarrenal/diagnóstico , Doenças do Córtex Suprarrenal/patologia , Síndrome de Cushing/genética , Adrenalectomia/efeitos adversos , Hidrocortisona , Hormônio Adrenocorticotrópico , Subunidades Catalíticas da Proteína Quinase Dependente de AMP Cíclico
14.
Neuro Endocrinol Lett ; 44(7): 427-431, 2023 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-37874555

RESUMO

INTRODUCTION: Acute thyrotoxic myopathy (ATM) is a rare and potentially lethal complication of thyrotoxicosis. The typical clinical symptoms of ATM are characterized by bulbar paralysis. Reports of the successful treatment of ATM are sporadic due to its low incidence. However, no English literature has reported Chinese patients with ATM and neck pain. Here, we report for the first time a Chinese patient with ATM and neck pain who recovered through large doses of systemic glucocorticoids and one intrathyroidal steroid injection. CASE REPORT: A 23-year-old woman visited our hospital with a two-year history of progressive weakness of her bulbar muscles, hoarseness, cough when swallowing, dysphagia, and a one-month history of recurrent painful swelling of the thyroid gland. She was diagnosed with ATM, chronic thyrotoxic myopathy (CTM), and Graves' ophthalmopathy (GO) due to Graves' disease (GD). After she was treated with a combination of low-dose glucocorticoids, antithyroid drugs (ATDs), propranolol, and ultrasound-guided percutaneous intrathyroidal injection of glucocorticoids, her bulbar paralysis, proximal myopathy, and neck pain simultaneously improved without recurrence during follow-up. To our knowledge, this is the first case report of a patient with ATM, CTM, GD, GO and neck pain treated by administering a combination of low-dose glucocorticoids, one intrathyroidal steroid injection and antithyroid agents. CONCLUSIONS: Clinicians should consider ATM and intervene with aggressive glucocorticoid therapy, and this is the key to reversing the progression of ATM when a patient has bulbar paralysis and thyrotoxic symptoms. Our case report references the clinical diagnosis and treatment of such cases.


Assuntos
Paralisia Bulbar Progressiva , Doença de Graves , Oftalmopatia de Graves , Doenças Musculares , Tireotoxicose , Humanos , Feminino , Adulto Jovem , Adulto , Paralisia Bulbar Progressiva/complicações , Paralisia Bulbar Progressiva/tratamento farmacológico , Cervicalgia/etiologia , Cervicalgia/complicações , Tireotoxicose/complicações , Tireotoxicose/tratamento farmacológico , Tireotoxicose/diagnóstico , Doença de Graves/complicações , Doença de Graves/tratamento farmacológico , Antitireóideos/uso terapêutico , Glucocorticoides/uso terapêutico , Doenças Musculares/complicações , Doenças Musculares/tratamento farmacológico , Esteroides/uso terapêutico
15.
Endocr Connect ; 12(11)2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37682119

RESUMO

Introduction: Chronic thyrotoxic myopathy (CTM) is a common, easily neglected complication of hyperthyroidism. There are currently no standard diagnostic criteria for CTM, and the ultrasonic characteristics of CTM-affected skeletal muscle remain unclear. Herein, we aimed to evaluate hyperthyroid patients for CTM by ultrasound and identify ultrasonic muscle parameter cutoffs for CTM diagnosis. Materials and methods: Each participant underwent ultrasonography. The original (muscle thickness (MT), pennation angle (PA), and cross-sectional area (CSA)) and corrected (MT/height (HT), MT/body mass index (BMI), CSA/HT, and CSA/BMI) parameters of the vastus lateralis and vastus medialis (VM) were evaluated. The diagnostic effectiveness of ultrasound for predicting CTM was determined using receiver operating characteristic (ROC) curve analysis. Our study included 203 participants: 67 CTM patients (18 males, 49 females), 67 non-CTM patients (28 males, 39 females) and 69 healthy controls (20 males, 49 females). Results: The CTM group had lower muscular ultrasonic and anthropometric parameters, higher thyroid hormone and thyroid-stimulating hormone receptor antibody (TRAb) levels, and a longer duration of hyperthyroidism than the non-CTM group (P < 0.05). The VM-PA, VM-CSA, VM-CSA/HT, and VM-CSA/BMI were lower in females than in males (P < 0.05). Free thyroxine (FT4) and TRAb both showed significant negative correlations with VM-MT, VM-MT/HT, VM-CSA, and VM-CSA/HT (P < 0.05). VM-MT/BMI and VM-CSA/HT, respectively, best predicted male and female CTM (AUC = 0.84, 0.85; cutoff ≤ 0.07, < 4.01). Conclusion: Ultrasound measurement of muscular parameters, especially in the VM, is a valid and feasible way of diagnosing and characterizing possible CTM in hyperthyroidism.

17.
Mil Med Res ; 10(1): 25, 2023 06 05.
Artigo em Inglês | MEDLINE | ID: mdl-37271807

RESUMO

BACKGROUND: Globally, despite prostate cancer (PCa) representing second most prevalent malignancy in male, the precise molecular mechanisms implicated in its pathogenesis remain unclear. Consequently, elucidating the key molecular regulators that govern disease progression could substantially contribute to the establishment of novel therapeutic strategies, ultimately advancing the management of PCa. METHODS: A total of 49 PCa tissues and 43 adjacent normal tissues were collected from January 2017 to December 2021 at Zhongnan Hospital of Wuhan University. The advanced transcriptomic methodologies were employed to identify differentially expressed mRNAs in PCa. The expression of aspartoacylase (ASPA) in PCa was thoroughly evaluated using quantitative real-time PCR and Western blotting techniques. To elucidate the inhibitory role of ASPA in PCa cell proliferation and metastasis, a comprehensive set of in vitro and in vivo assays were conducted, including orthotopic and tumor-bearing mouse models (n = 8 for each group). A combination of experimental approaches, such as Western blotting, luciferase assays, immunoprecipitation assays, mass spectrometry, glutathione S-transferase pull-down experiments, and rescue studies, were employed to investigate the underlying molecular mechanisms of ASPA's action in PCa. The Student's t-test was employed to assess the statistical significance between two distinct groups, while one-way analysis of variance was utilized for comparisons involving more than two groups. A two-sided P value of less than 0.05 was deemed to indicate statistical significance. RESULTS: ASPA was identified as a novel inhibitor of PCa progression. The expression of ASPA was found to be significantly down-regulated in PCa tissue samples, and its decreased expression was independently associated with patients' prognosis (HR = 0.60, 95% CI 0.40-0.92, P = 0.018). Our experiments demonstrated that modulation of ASPA activity, either through gain- or loss-of-function, led to the suppression or enhancement of PCa cell proliferation, migration, and invasion, respectively. The inhibitory role of ASPA in PCa was further confirmed using orthotopic and tumor-bearing mouse models. Mechanistically, ASPA was shown to directly interact with the LYN and inhibit the phosphorylation of LYN as well as its downstream targets, JNK1/2 and C-Jun, in both PCa cells and mouse models, in an enzyme-independent manner. Importantly, the inhibition of LYN activation by bafetinib abrogated the promoting effect of ASPA knockdown on PCa progression in both in vitro and in vivo models. Moreover, we observed an inverse relationship between ASPA expression and LYN activity in clinical PCa samples, suggesting a potential regulatory role of ASPA in modulating LYN signaling. CONCLUSION: Our findings provide novel insights into the tumor-suppressive function of ASPA in PCa and highlight its potential as a prognostic biomarker and therapeutic target for the management of this malignancy.


Assuntos
MicroRNAs , Neoplasias da Próstata , Animais , Humanos , Masculino , Camundongos , Amidoidrolases/uso terapêutico , MicroRNAs/uso terapêutico , Próstata/patologia , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia
18.
Clin Exp Dermatol ; 48(10): 1145-1148, 2023 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-37227921

RESUMO

Urticarial vasculitis (UV) is a small vessel leucocytoclastic vasculitis, which often needs to be distinguished from urticaria and other dermatoses. Treatment of UV in children is challenging because of the unsatisfying efficacy of antihistamines and the safety concern of long-term systemic corticosteroids or immunosuppressive agents. As a classic biological agent widely used in chronic spontaneous urticaria, omalizumab might also be a potential therapeutic option in the treatment of children with UV. This report presented four children, aged 4-6 years, with glucocorticoid-unresponsive UV successfully treated by omalizumab, thus providing evidence that omalizumab can be used to treat UV with good efficacy and tolerability in the paediatric population.


Assuntos
Antialérgicos , Urticária Crônica , Urticária , Vasculite Leucocitoclástica Cutânea , Vasculite , Criança , Humanos , Omalizumab/uso terapêutico , Urticária/tratamento farmacológico , Urticária Crônica/tratamento farmacológico , Imunossupressores/uso terapêutico , Antialérgicos/uso terapêutico , Vasculite Leucocitoclástica Cutânea/tratamento farmacológico
19.
Curr Med Sci ; 43(2): 274-283, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36913109

RESUMO

OBJECTIVE: Intrauterine growth restriction followed by postnatal catch-up growth (CG-IUGR) increases the risk of insulin resistance-related diseases. Low-density lipoprotein receptor-related protein 6 (LRP6) plays a substantial role in glucose metabolism. However, whether LRP6 is involved in the insulin resistance of CG-IUGR is unclear. This study aimed to explore the role of LRP6 in insulin signaling in response to CG-IUGR. METHODS: The CG-IUGR rat model was established via a maternal gestational nutritional restriction followed by postnatal litter size reduction. The mRNA and protein expression of the components in the insulin pathway, LRP6/ß-catenin and mammalian target of rapamycin (mTOR)/S6 kinase (S6K) signaling, was determined. Liver tissues were immunostained for the expression of LRP6 and ß-catenin. LRP6 was overexpressed or silenced in primary hepatocytes to explore its role in insulin signaling. RESULTS: Compared with the control rats, CG-IUGR rats showed higher homeostasis model assessment for insulin resistance (HOMA-IR) index and fasting insulin level, decreased insulin signaling, reduced mTOR/S6K/ insulin receptor substrate-1 (IRS-1) serine307 activity, and decreased LRP6/ß-catenin in the liver tissue. The knockdown of LRP6 in hepatocytes from appropriate-for-gestational-age (AGA) rats led to reductions in insulin receptor (IR) signaling and mTOR/S6K/IRS-1 serine307 activity. In contrast, LRP6 overexpression in hepatocytes of CG-IUGR rats resulted in elevated IR signaling and mTOR/S6K/IRS-1 serine307 activity. CONCLUSION: LRP6 regulated the insulin signaling in the CG-IUGR rats via two distinct pathways, IR and mTOR-S6K signaling. LRP6 may be a potential therapeutic target for insulin resistance in CG-IUGR individuals.


Assuntos
Retardo do Crescimento Fetal , Resistência à Insulina , Insulina , Proteína-6 Relacionada a Receptor de Lipoproteína de Baixa Densidade , Proteínas Quinases S6 Ribossômicas , Animais , Feminino , Humanos , Ratos , beta Catenina/genética , Retardo do Crescimento Fetal/genética , Retardo do Crescimento Fetal/metabolismo , Insulina/metabolismo , Resistência à Insulina/genética , Proteína-6 Relacionada a Receptor de Lipoproteína de Baixa Densidade/genética , Receptor de Insulina/genética , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismo
20.
J Infect Public Health ; 16(3): 418-421, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36731244

RESUMO

Multisystem inflammatory syndrome adult type (MIS-A) is a rare type of post-acute COVID-19 syndrome which more frequently occurred in younger population. Here we present a 78-year-old Chinese female, the oldest case reported, diagnosed with MIS-A who had severe SARS-CoV-2 infection. She was diagnosed with severe COVID-19 and experienced an unexpected sudden hemodynamic collapse in the recovery period within three weeks. Her platelet count was sharply dropped, accompanied with sustained cardiac, kidney and liver injury. She was diagnosed with MIS-A according to criteria established by Center of Disease Control and Prevention. Though her condition was improved under administrating with high dose of methylprednisolone and intravenous immunoglobulin, methylprednisolone was unable to withdraw till two weeks as her partial pressure of oxygen/fraction of inspiration oxygen ratio and platelet count dropped on the heels of decreasing dosage. Unfortunately, the patient's condition gradually deteriorated with the development of severe nosocomial pneumonia. We presented this rare case in order to emphasize that MIS-A could occur in the elderly and the management of this population might be more difficult as the condition of the elderly with SARS-CoV-2 infection and MIS-A might be more severe.


Assuntos
COVID-19 , Humanos , Adulto , Idoso , Feminino , China/epidemiologia , SARS-CoV-2 , Metilprednisolona/uso terapêutico , Oxigênio
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