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1.
Heliyon ; 10(17): e36480, 2024 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-39281574

RESUMEN

Objectives: The prenatal detection of placenta accreta spectrum (PAS) disorder is crucial for treatment strategy formulation. MRI descriptors may offer a more objective method for predicting PAS and clinical outcomes. The aim of this study is to investigate the predictive value of MRI examination for intraoperative blood loss in PAS cesarean section and elucidating the MRI descriptors that are more valuable for predicting intraoperative blood loss. Methods: A prospective study was carried out on 164 pregnant women diagnosed with PAS. Maternal and neonatal perioperative characteristics were systematically collected. To evaluate the relationship between maternal and perioperative characteristics and intraoperative blood loss, as well as the predictive value of MRI descriptors on intraoperative blood loss, a multivariable linear regression analysis was performed. Results: Patients were pre-grouped based on a combined ultrasound-MRI evaluation, with 108 cases (65.9 %) classified as placenta accreta, 47 cases (28.7 %) as placenta increta, and 9 cases (5.4 %) as placenta percreta. The results demonstrated that intraoperative blood loss was positively associated with partial MRI descriptors (F = 9.751, df = 15), such as placenta accreta (OR: 243.33, p = 0.006), cross-border blood vessels that pass through the uterine muscle layer (OR: 297.76, p = 0.012), interruption of hyperechoic uterus-bladder interface (bladder line) (OR: 342.59, p = 0.011), and subplacental hypervascularity (OR: 365.96, p = 0.027). Conclusions: Preoperative MRI demonstrates promising predictive capabilities in estimating intraoperative blood loss for PAS patients. Pregnant women identified as having a high risk of intraoperative bleeding based on MRI findings should undergo closer antenatal monitoring in late pregnancy, along with more comprehensive preoperative blood preparation, to better ensure maternal and fetal safety.

2.
J Transl Med ; 22(1): 820, 2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-39227917

RESUMEN

BACKGROUND: The prevalence of vascular calcification (VC) in chronic kidney disease (CKD) patients remains substantial, but currently, there are no effective pharmaceutical therapies available. BRCA1/BRCA2-containing complex subunit 36 (BRCC36) has been implicated in osteoblast osteogenic conversion; however, its specific role in VC remains to be fully elucidated. The aim of this study was to investigate the role and underlying mechanisms of BRCC36 in VC. METHODS: The association between BRCC36 expression and VC was examined in radial arteries from patients with CKD, high-adenine-induced CKD mice, and vascular smooth muscle cells (VSMCs). Western blotting, real-time polymerase chain reaction, immunofluorescence, and immunohistochemistry were used to analyse gene expression. Gain- and loss-of-function experiments were performed to comprehensively investigate the effects of BRCC36 on VC. Coimmunoprecipitation and TOPFlash luciferase assays were utilized to further investigate the regulatory effects of BRCC36 on the Wnt/ß-catenin pathway. RESULTS: BRCC36 expression was downregulated in human calcified radial arteries, calcified aortas from CKD mice, and calcified VSMCs. VSMC-specific BRCC36 overexpression alleviated calcium deposition in the vasculature, whereas BRCC36 depletion aggravated VC progression. Furthermore, BRCC36 inhibited the osteogenic differentiation of VSMCs in vitro. Rescue experiments revealed that BRCC36 exerts the protective effects on VC partly by regulating the Wnt/ß-catenin signalling pathway. Mechanistically, BRCC36 inhibited the Wnt/ß-catenin pathway by decreasing the K63-linked ubiquitination of ß-catenin. Additionally, pioglitazone attenuated VC partly through upregulating BRCC36 expression. CONCLUSIONS: Our research results emphasize the critical role of the BRCC36-ß-catenin axis in VC, suggesting that BRCC36 or ß-catenin may be promising therapeutic targets to prevent the progression of VC in CKD patients.


Asunto(s)
Ratones Endogámicos C57BL , Insuficiencia Renal Crónica , Ubiquitinación , Calcificación Vascular , Vía de Señalización Wnt , beta Catenina , Calcificación Vascular/metabolismo , Calcificación Vascular/patología , Insuficiencia Renal Crónica/metabolismo , Insuficiencia Renal Crónica/patología , Insuficiencia Renal Crónica/complicaciones , Animales , beta Catenina/metabolismo , Humanos , Masculino , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patología , Ratones , Miocitos del Músculo Liso/metabolismo , Miocitos del Músculo Liso/patología , Osteogénesis , Persona de Mediana Edad , Diferenciación Celular
3.
J Pain Res ; 17: 2645-2656, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39155955

RESUMEN

Purpose: Although pediatric epidural analgesia is a well-established technique used perioperatively. It is unclear whether a lumbar or caudal epidural is suitable for osteogenesis imperfecta (OI) patients, which may be associated with brittle bones and spine deformity. We conducted a retrospective study to investigate and compare the efficacy of the two continuous epidural techniques in pediatric patients undergoing lower extremity osteotomy surgery using a propensity score-matched analysis (PSMA). Patients and Methods: A total of 274 patients were included. Patients' age, weight, and height were adjusted using PSMA. 90 patients were matched for further analysis, with 45 patients in the lumbar epidural group (Group L) and 45 patients in the caudal epidural group (Group C). Pain scores were categorized into three grades: mild (0-3), moderate (4-6), and severe (7-10), and compared between the two groups. Additionally, operation time, operation site, blood loss, scoliosis, oral analgesic medications, and catheter or nerve-related complications were compared. Results: There were no significant differences in operation time, operation site, scoliosis, and blood loss between the two groups. The percentage of moderate to severe pain during movement was significantly higher in Group L than in Group C, with 37.5% versus 17.5% on the second-day post-operation (P=0.039). However, no statistically significant difference was observed on other days. Additionally, there was no significant difference in oral medication consumption and complications between the two groups. Conclusion: Both lumbar and caudal epidural analgesia can be effectively used postoperatively, and a caudal epidural should be considered where performing a lumbar epidural is challenging in OI pediatric patients.


Osteogenesis imperfecta (OI) is a rare genetic disorder that affects the body's connective tissues, particularly the bones and ligaments. It is caused by abnormalities in type I collagen, which leads to skeletal fragility known as "brittle bones". This fragility can cause various issues, including an increased risk of fractures from minor trauma, limb deformities, and unusual fractures such as vertebral compressions. OI patients may also experience spinal manifestations such as scoliosis and kyphosis. Lumbar epidural analgesia has been found to be effective in providing pain relief for surgeries that involve the lower extremities. Additionally, caudal epidural analgesia has also demonstrated its effectiveness in providing postoperative analgesia for surgeries that affect the lower limbs. However, there is still debate about the safety of epidural analgesia in patients with skeletal dysplasias, especially those with OI. Despite this uncertainty, our center, which was supported by the Rare Diseases Public Welfare Organization, has successfully used epidural analgesia since 2015 in the southern part of China for OI surgeries. We conducted a retrospective study to share our experiences of nine years of practice and compare lumbar epidural with caudal epidural using a propensity score matching to balance basic demographics. We also compared the presence of scoliosis. Our findings suggest that both lumbar and caudal epidural analgesia can be safely used in OI patients. In cases where lumbar punctures may pose challenges due to potential spine deformities, the caudal route can be an alternative.

4.
Artículo en Inglés | MEDLINE | ID: mdl-39159608

RESUMEN

INTRODUCTION: Renal cell carcinoma (RCC) is a common type of kidney cancer with limited treatment options and a high mortality rate. Therefore, it is essential to understand the role and mechanism of key genes in RCC development and progression. This study aimed to analyze the role of zinc fingers and homeoboxes 2 (ZHX2) in RCC and the underlying mechanism. METHODS: RNA expression was analyzed by quantitative real-time polymerase chain reaction, while protein expression was analyzed by western blotting assay and immunohistochemistry assay. Cell viability was evaluated using CCK-8 assay, and cell proliferation was assessed by EdU assay. The rate of cell apoptosis was quantified by flow cytometry. Transwell assays were conducted to analyze cell migration and invasion. The sphere formation assay was performed to assess the formation of microspheres. Additionally, m6A RNA immunoprecipitation assay and RNA immunoprecipitation assay were utilized to investigate the relationship between ZHX2 and two proteins, methyltransferase like 3 (METTL3) and insulin like growth factor 2 mRNA binding protein 1 (IGF2BP1). The stability of ZHX2 mRNA was analyzed through the Actinomycin D assay. Furthermore, a xenograft mouse model assay was conducted to analyze the effect of ZHX2 overexpression and METTL3 silencing on RCC cell tumor properties in vivo. RESULTS: ZHX2 expression was upregulated in both RCC tissues and cells when compared with healthy renal tissues and human renal cortex proximal convoluted tubule epithelial cells. Depletion of ZHX2 inhibited RCC cell proliferation, migration, invasion and spheroid-forming capacity but promoted cell apoptosis. Moreover, it was found that METTL3 mediated m6A methylation of ZHX2 and IGF2BP1 also stabilized ZHX2 through m6A methylation modification. Furthermore, ZHX2 overexpression showed a potential for attenuating the effects induced by METTL3 silencing and counteracted the inhibitory effect of METTL3 depletion on tumor formation in vivo. CONCLUSION: METTL3 and IGF2BP1-mediated m6A modification of ZHX2 promoted RCC progression. The finding suggests that ZHX2 may serve as a potential therapeutic target in RCC, providing valuable insights for future clinical interventions.

5.
J Med Chem ; 2024 Aug 19.
Artículo en Inglés | MEDLINE | ID: mdl-39158077

RESUMEN

DCN1, a critical co-E3 ligase during the neddylation process, is overactivated in many diseases, such as cancers, heart failure as well as fibrotic diseases, and has been regarded as a new target for drug development. Herein, we designed and synthesized a new class of 1,2,4-triazole-3-thione-based DCN1 inhibitors based the hit HD1 identified from high-throughput screening and optimized through numerous structure-activity-relationship (SAR) explorations. HD2 (IC50= 2.96 nM) was finally identified and represented a highly potent and selective DCN1 inhibitor with favorable PK properties and low toxicity. Amazingly, HD2 effectively relieved Ang II/TGFß-induced cardiac fibroblast activation in vitro, and reduced ISO-induced cardiac fibrosis as well as remodeling in vivo, which was linked to the inhibition of cullin 3 neddylation and its substrate Nrf2 accumulation. Our findings unveil a novel 1,2,4-triazole-3-thione-based derivative HD2, which can be recognized as a promising lead compound targeting DCN1 for cardiac fibrosis and remodeling.

6.
Drug Des Devel Ther ; 18: 3429-3441, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39105187

RESUMEN

Purpose: This study aimed to investigate patients' expectative pain of spinal anesthesia puncture and anxiety pre-anesthesia, and to examine the effect of lidocaine-prilocaine cream and remimazolam prior to spinal anesthesia puncture on pain relief and anxiety release. Methods: Patients undergoing spinal anesthesia were divided into control, lidocaine-prilocaine cream, and lidocaine-prilocaine cream with remimazolam groups. A questionnaire consisting of The Amsterdam Preoperative Anxiety and Information Scale (APAIS) and patient's concerns and Visual Analog Scale (VAS) was used to evaluate patient's anxiety and pain. The primary outcomes were differences in VAS and anxiety scores. Patient's spinal anesthesia-related concerns, advent events and hemodynamic index were also recorded. Results: The expected spinal anesthesia puncture pain was 5.34±0.27 and anxiety scores before spinal anesthesia was 10.88 ± 0.64. A statistically significant positive correlation of 31.3% was detected between VAS and APAIS scores (r = 0.313; P=0.003). The VAS score at the time of puncture decreased by 29.7% (3.78±0.40, P=0.001) in lidocaine-prilocaine cream group and 29.2% (3.75±0.39, P=0.001) in lidocaine-prilocaine cream with remimazolam group compared with the expected VAS score. Lidocaine-prilocaine cream combined with or without remimazolam reduced the percentage of moderate pain (21.4% and 31.3% vs 50.0%, P=0.0001) and increased mild pain (60.7% vs 59.4% vs 22.7%, P=0.03). Anxiety score in lidocaine-prilocaine cream group was reduced by 2.84 (8.04±0.76 vs 10.88 ± 0.46, P=0.05) when compared with pre-anesthesia. Concerns about postoperative pain (P=0.03) and fear of the needle or intervention (P=0.000) both decreased post-anesthesia among groups. Conclusion: Approximately half of the patients scheduled for spinal anesthesia experienced a moderate level of preoperative anxiety. The patient's pain expectation from the spinal anesthesia puncture was moderate, which was higher than the actual pain. Lidocaine-prilocaine cream with or without remimazolam sedative before spinal anesthesia puncture reduced the patient's pain and anxiety scores after surgery.


Asunto(s)
Anestesia Raquidea , Ansiedad , Lidocaína , Humanos , Masculino , Femenino , Ansiedad/tratamiento farmacológico , Persona de Mediana Edad , Adulto , Lidocaína/administración & dosificación , Lidocaína/farmacología , Prilocaína/administración & dosificación , Benzodiazepinas/administración & dosificación , Anestésicos Locales/administración & dosificación , Dimensión del Dolor
7.
Front Psychiatry ; 15: 1422229, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39205852

RESUMEN

Objective: The mental health issues of individuals with coronavirus disease 2019 (COVID-19) are currently widespread. Traditional Chinese exercise (Daoyin) plays an important role in relieving patients' psychological problems. This study aims to assess the efficacy of Daoyin in mitigating mental health issues among individuals diagnosed with COVID-19. Methods: PubMed, the Cochrane library, Embase, CNKI, Wanfang, VIP database, and SinoMed were searched from their inception to October 2023. Two researchers independently selected the eligible studies. The analysis and presentation of the findings were conducted using Review Manager 5.2 software. The data were analyzed using mean difference (MD), inverse variance, and 95% confidence intervals (CIs). Results: A total of 12 studies (N = 1291) were included in this study. The results showed that Daoyin can significantly reduce the scores of the Self-Rating Anxiety Scale (SAS: MD = -13.03, 95% CI -19.56 to -6.49, P<.49,yca Self-Rating Depression Scale (SDS: MD = -11.13, 95% CI -14.56 to -7.71, P<.71,sion Pittsburgh Sleep Quality Index (PSQI: MD = -2.00, 95% CI -5.43 to 1.43, P = 0.25), Hamilton Anxiety Scale (HAMA: MD = -2.42, 95% CI -5.25 to 0.41, P = 0.09), and Hamilton Depression Scale (HAMD: MD = -11.17, 95% CI -25.5 to 3.15, P = 0.13). Conclusion: In COVID-19 patients, Daoyin can alleviate feelings of anxiety and depression, as well as improve sleep quality. The use of Daoyin has no adverse effects and side effects and can reduce the cost of medication. Therefore, Daoyin can be widely promoted. Further research is warranted to analyze the effect of Daoyin on mental health. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/#recordDetails, identifier CRD42023391845.

8.
Mech Ageing Dev ; 221: 111964, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39019118

RESUMEN

Age-related hearing loss (ARHL) is an auditory disease characterized by gradual loss of high-frequency hearing sensitivity. Excessive reactive oxygen species trigger NLRP3-inflammasome activation that may be crucial for ARHL pathogenesis. The antioxidant factor Sestrin2 (SESN2) has been reported to be involved in the remission of oxidative stress and ARHL. However, the mechanism by which SESN2 protects auditory cells in the aging mouse cochlea remains unknown. Here, we observed that ectopic overexpression of SESN2 delayed ARHL, whereas SESN2 knockdown accelerated it. Importantly, we elucidated that SESN2 exerts a hearing-protective effect by inhibiting the production of NLRP3 by acting as a mitophagy agonist. Our study proposes a new theoretical basis for SESN2 prevention of ARHL and provides a novel therapeutic strategy for maintaining SESN2 activity in the aging cochlea.


Asunto(s)
Inflamasomas , Proteína con Dominio Pirina 3 de la Familia NLR , Presbiacusia , Animales , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Ratones , Presbiacusia/metabolismo , Presbiacusia/patología , Presbiacusia/prevención & control , Inflamasomas/metabolismo , Mitofagia/fisiología , Envejecimiento/metabolismo , Cóclea/metabolismo , Cóclea/patología , Estrés Oxidativo , Sestrinas
9.
Toxicon ; 247: 107829, 2024 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-38925341

RESUMEN

Naja atra bites often result in immediate and severe illness. The venom of N. atra contains a complex mixture of toxins that can cause significant damage to the patient's skin tissue. If left untreated, this condition can progress to localized necrosis, potentially resulting in impairment or even amputation in severe cases. Despite the known effects of the venom, the exact mechanisms underlying this tissue necrosis are not fully understood. This study aimed to investigate the protein components responsible for tissue necrosis induced by N. atra venom at both the organism-wide and molecular levels. To achieve this, venom was injected into Bama miniature pigs to cause ulcers, and exudate samples were collected at various time points after injection. Label-free proteomics analysis identified 1119, 1016, 938, 864, and 855 proteins in the exudate at 6, 12, 24, 36, and 48 h post-injection, respectively. Further analysis revealed 431 differentially expressed proteins, with S100A8, MMP-2, MIF, and IDH2 identified as proteins associated with local tissue necrosis. In this study, we established a Bama miniature pig model for N. atra venom injection and performed proteomic analysis of the wound exudate, which provides important insights into the molecular pathology of snakebite-induced tissue necrosis and potential theoretical bases for clinical treatment. Proteomic data from this study can be accessed through ProteomeXchange using the identifier PXD052498.


Asunto(s)
Venenos Elapídicos , Necrosis , Proteómica , Animales , Porcinos , Venenos Elapídicos/toxicidad , Necrosis/inducido químicamente , Porcinos Enanos , Naja naja , Mordeduras de Serpientes , Piel/efectos de los fármacos , Piel/patología , Piel/metabolismo
10.
Neuropsychiatr Dis Treat ; 20: 1309-1319, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38933097

RESUMEN

Purpose: The aim of our study was to explore the relation between serum levels of non-enzymatic antioxidants, thyroid function with the risk of non-suicidal self-injury (NSSI) in depressed adolescents. Patients and Methods: We retrospected the electronic records of 454 hospitalized patients aged 13-17 years old with a diagnosis of major depressive disorder (239 patients with NSSI and 215 subjects without NSSI), and collected their demographic and clinical information, including serum levels of total bilirubin (Tbil), uric acid (UA), free triiodothyronine (FT3), free thyroxine (FT4) and thyroid stimulating hormone (TSH). Results: The incidence of NSSI was 52.6% among depressed adolescents aged 13-17, 57.1% in female and 38.5% in male. After using the propensity scoring method to exclude the influence of age between the two groups, it was found that patients with NSSI showed lower levels of Tbil (P=0.046) and UA (P=0.015) compared with those without NSSI. Logistic regression results showed that serum UA was associated with NSSI behavior in female patients (OR=0.995, 95% CI: 0.991-0.999, P=0.014), and TSH was associated with NSSI in male participants (OR=0.499, 95% CI: 0.267-0.932, P=0.029). Conclusion: Female and male may have different pathological mechanisms of NSSI. NSSI is more likely to be related to antioxidant reaction in female adolescent patients, while more likely to be related to thyroid function in male depressed adolescent patients.

11.
Int J Gen Med ; 17: 2673-2680, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38863738

RESUMEN

Purpose: This study aims to investigate whether dexmedetomidine could prevent postoperative cognitive dysfunction and delirium in patients with lobectomy. Patients and Methods: Patients with lung cancer who underwent thoracoscopic lobectomy under general anesthesia were enrolled in this study and divided into dexmedetomidine group or control group. Propensity-score match (PSM) was used to reduce the bias and imbalance of confounding variables. After PSM, 87 patients in each group were included. Primary outcomes were postoperative cognitive function and delirium. Secondary outcomes include plasma TNF-α, IL-6, and S100 ß protein concentrations. Adverse events were also collected. Results: There were no significant differences in the demographic characteristics and hemodynamic parameters between the two groups. Compared with the control group, the MoCA scores were significantly higher (P<0.01), while the incidence of delirium (P<0.01) and the plasma TNF-α (P<0.01), IL-6 (P<0.01), and S100 ß protein (P<0.01) concentrations were significantly lower in the dexmedetomidine group at 7 days post-operatively. The incidences of adverse events were similar between the two groups. Conclusion: Dexmedetomidine could prevent postoperative cognitive dysfunction and delirium in patients with lobectomy by decreasing neuroinflammation.

12.
J Minim Invasive Gynecol ; 31(9): 795-802, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38692483

RESUMEN

OBJECTIVE: Vaginal natural orifice transluminal endoscopic surgery (vNOTES) is considered to have the advantages of completely scarless, less postoperative pain, earlier flatus, and faster postoperative recovery. However, posterior myoma are relatively difficult to operate through vNOTES in the conventional lithotomy position. Thus, we innovated the application of prone position in the removal of posterior myoma in vNOTES. The aim of this study is the comparison of myomectomy outcomes of patient for single posterior myoma in prone and lithotomy position. DESIGN: A single-center, prospective study. SETTING: A university teaching hospital. PATIENTS: A total of 81 patients with posterior myoma who underwent myomectomy in vNOTES from January 2021 to December 2022. INTERVENTIONS: The patients underwent myomectomy in vNOTES in prone or lithotomy position. MEASUREMENTS AND MAIN RESULTS: Among the patients who underwent vNOTES myomectomy, 29 (35.8%) were in the lithotomy position group, and 52 (64.2%) in the prone position group. Of note, 4 (4.9%) patients underwent a conversion to LESS during the operation-3 in the lithotomy and 1 in the prone position group. And a patient in the lithotomy position group underwent resurgery for hemostasis due to postoperative pelvic bleeding. Compared with the lithotomy position, prone position significantly shortens the operation time (12.3, 95% CI: 6.811, 17.761. p = .009) without increasing the complications and postoperative discomfort of patients. CONCLUSION: Compared to the lithotomy position, the prone position provides greater convenience for operation and exhibits a lower rate of surgical conversion during the removal of single posterior myomas via vNOTES. Further, for patients selecting vNOTES, surgeons need to conduct sufficient preoperative evaluation, timely hemostasis during surgery, and timely surgical conversion if necessary to ensure patient safety.


Asunto(s)
Leiomioma , Cirugía Endoscópica por Orificios Naturales , Posicionamiento del Paciente , Miomectomía Uterina , Neoplasias Uterinas , Humanos , Femenino , Estudios Prospectivos , Adulto , Neoplasias Uterinas/cirugía , Cirugía Endoscópica por Orificios Naturales/métodos , Miomectomía Uterina/métodos , Leiomioma/cirugía , Posicionamiento del Paciente/métodos , Persona de Mediana Edad , Posición Prona , Vagina/cirugía , Tempo Operativo , Resultado del Tratamiento
13.
Int J Pharm ; 657: 124159, 2024 May 25.
Artículo en Inglés | MEDLINE | ID: mdl-38701907

RESUMEN

Inhibiting the expression of tumor necrosis factor-α (TNF-α), a pro-inflammatory cytokine widely distributed in the serum and synovial fluid, is important for managing rheumatoid arthritis (RA). Despite the good therapeutic effects of TNF-α small interfering RNA (TNF-α siRNA) in RA animal models, safe and efficient siRNA delivery systems that retain stability are lacking. We introduced a novel therapy using milk-derived exosomes(mEXOs)-encapsulated TNF-α siRNA-coated cryomicroneedle (cryoMN) patch and evaluated its efficacy via local transdermal administration through acupoints in RA treatment. The loading of TNF-α siRNAs into mEXOs was achieved by sonication, the loading rate, stability, and in vitro release of mEXOs-TNF-α siRNA were determined. The cryoMNs were prepared by micromolding, morphology, drug loading, and mechanical strength of the cryoMN array were analyzed. The loading efficiency of TNF-α siRNA was up to 21% and each cryoMN contained 39.6 ± 1.29 µg of TNF-α siRNA. Frozen sections penetrated 523 ± 63 µm deep. In vitro experiments have shown that mEXOs-TNF-α siRNA cryoMNs have good biocompatibility and inhibit the proliferation of HFLS-RA cells. In vivo pharmacodynamics studies found that general conditions, changes in microcirculation indexes, synovial histopathological changes, and expression of related proteins in the synovial tissue in RA rabbits were effectively alleviated by mEXOs-TNF-α siRNA cryoMNs. Improvement of each index at acupoints was greater than that at non-acupoints. Our findings facilitate the development of cryoMNs combined with exosomes and acupoints drug delivery for the treatment of RA. The combination of exosomes and cryoMNs will enable the development of new-generation microneedle-based treatments.


Asunto(s)
Administración Cutánea , Artritis Reumatoide , Exosomas , Leche , ARN Interferente Pequeño , Factor de Necrosis Tumoral alfa , Animales , Artritis Reumatoide/terapia , ARN Interferente Pequeño/administración & dosificación , Conejos , Humanos , Leche/química , Agujas , Línea Celular , Masculino , Sistemas de Liberación de Medicamentos/métodos
14.
Cell Signal ; 120: 111211, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38705504

RESUMEN

Vascular calcification (VC) is a characteristic feature in patients with diabetes mellitus (DM) and is closely associated with the osteogenic differentiation of vascular smooth muscle cells (VSMCs). Ubiquitin-Specific Protease 10 (USP10) has been shown to regulate multiple cellular processes; however, its relationship with diabetic VC remains unclear. This study aims to elucidate the role of USP10 in VC development and the underlying regulatory mechanisms. Nε-carboxymethyl lysine (CML) was significantly increased in calcified ateries from diabetic atherosclerosis ApoE-/- mice fed with high-fat diets. CML downregulated USP10 expression in VSMCs and calcified mice coronary arteries, as assessd by Western blotting, RT-qPCR,immunofluorescence and immunohistochemistry. Loss-and gain-of-function experiments were conducted both in vitro and in vivo to verify the biological functions of USP10. Ectopic expression of USP10 mitigated the severity of VC. With regard to the mechanism, the interaction between USP10 and AMPKα was investigated through double-label immunofluorescence and Co-immunoprecipitation. In vitro ubiquitination assay revealed that USP10 was capable of mediating AMPKα ubiquitination and caused increased AMPKα phosphorylation level at Thr172. Moreover, the anticalcification effect of USP10 was reversed by pharmacological inhibition of AMPK signaling pathway. The current fundings suggest an important role of USP10 in diabetic VC progression, at least in part, via mediating the ubiquitination and activation of AMPKα. USP10 may serve as a novel therapeutic target for the treatment of diabetic VC.


Asunto(s)
Proteínas Quinasas Activadas por AMP , Aterosclerosis , Lisina , Ubiquitina Tiolesterasa , Calcificación Vascular , Animales , Ubiquitina Tiolesterasa/metabolismo , Ubiquitina Tiolesterasa/genética , Calcificación Vascular/metabolismo , Calcificación Vascular/patología , Ratones , Aterosclerosis/metabolismo , Aterosclerosis/patología , Lisina/metabolismo , Lisina/análogos & derivados , Proteínas Quinasas Activadas por AMP/metabolismo , Masculino , Ubiquitinación , Ratones Endogámicos C57BL , Humanos , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patología , Miocitos del Músculo Liso/metabolismo , Miocitos del Músculo Liso/patología , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Experimental/patología
15.
Sci Total Environ ; 926: 171949, 2024 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-38537817

RESUMEN

In this study, the feasibility of tracing the origin of yak meat in Xizang Autonomous Region based on stable isotope combined with multivariable statistics was researched. The δ13C, δ15N, δ2H and δ18O in yak meat were determined by stable isotope ratio mass spectrometry, and the data were analyzed by analysis of variance, fisher discriminant analysis (FDA), back propagation (BP) neural network and orthogonal partial least squares discrimination analysis (OPLS-DA). The results showed that the δ13C, δ15N, δ2H and δ18O had significant differences among different origins (P < 0.05). The overall original correct discrimination rate of fisher discriminant analysis was 89.7 %, and the correct discrimination rate of cross validation was 88.2 %. The correct classification rate of BP neural network based on training set was 93.38 %, and the correct classification rate of BP neural network based on test set was 89.83 %. The OPLS-DA model interpretation rate parameter R2Y was 0.67, the model prediction rate parameter Q2 was 0.409, which could distinguish yak meat from seven different producing areas in Xizang Autonomous Region. The results showed that the origin of yak meat in Xizang Autonomous Region can be traced based on stable isotope combined with multivariate statistics.


Asunto(s)
Isótopos , Carne , Animales , Bovinos , Isótopos/análisis , Espectrometría de Masas/métodos , Carne/análisis , Análisis Discriminante
16.
Curr Res Food Sci ; 8: 100676, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38303999

RESUMEN

In recent years, the problem of food adulteration has become increasingly rampant, seriously hindering the development of food production, consumption, and management. The common analytical methods used to determine food authenticity present challenges, such as complicated analysis processes and time-consuming procedures, necessitating the development of rapid, efficient analysis technology for food authentication. Spectroscopic techniques, ambient ionization mass spectrometry (AIMS), electronic sensors, and DNA-based technology have gradually been applied for food authentication due to advantages such as rapid analysis and simple operation. This paper summarizes the current research on rapid food authenticity analysis technology from three perspectives, including breeds or species determination, quality fraud detection, and geographical origin identification, and introduces chemometrics method adapted to rapid analysis techniques. It aims to promote the development of rapid analysis technology in the food authenticity field.

17.
Eur J Obstet Gynecol Reprod Biol ; 295: 143-149, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38359635

RESUMEN

OBJECTIVE: Vaginal natural orifice transluminal endoscopic surgery (vNOTES) is widely recognized for its potential benefits, including reducing post-surgical pain and leaving no discernible scarring. However, the anatomical specificity of the vNOTES approach may elevate the risk of nearby organ damage, such as the rectum and bladder. Thus, this study aims to demonstrate the safety and relative merits of vNOTES over transumbilical laparoendoscopic single-site surgery (LESS). METHODS: The Longitudinal Vaginal Natural Orifice Transluminal Endoscopic Surgery Study (LovNOTESS), which was conducted in Chengdu, China. A total of 110 patients who underwent myomectomy in vNOTES or LESS from January 2021 to December 2022. This study prospectively collected and compared perioperative and follow-up data of the two groups. RESULTS: In the vNOTES group, patients had shorter postoperative anal exhaust time, lower pain medications use rate, shorter hospital stay but higher intraoperative conversion rate, and higher postoperative fever rate. vNOTES decreased the anal exhaust time by approximately 8.7 h (95 %CI: -16.182, -1.262, p = 0.007). Moreover, vNOTES reduces pain medication use risk by 73.1 % (OR: 0.269, 95 %CI: 0.172, 0.318, p = 0.016). CONCLUSION: Relative to LESS, vNOTES can make patients mitigate postoperative discomfort, accelerate the recovery of gastrointestinal function, curtail hospitalization duration, and enable a more rapid return to daily activities in myomectomy. However, vNOTES has a higher risk of surgical conversion and adjacent organ injury. Therefore, larger scale prospective studies are needed to prove its security and promote the widespread application of vNOTES in myomectomy.


Asunto(s)
Recuperación Mejorada Después de la Cirugía , Laparoscopía , Cirugía Endoscópica por Orificios Naturales , Miomectomía Uterina , Femenino , Humanos , Miomectomía Uterina/efectos adversos , Vagina/cirugía , Cirugía Endoscópica por Orificios Naturales/efectos adversos , Dolor Postoperatorio/etiología , Dolor Postoperatorio/prevención & control , Dolor Postoperatorio/cirugía , Laparoscopía/efectos adversos , Estudios Retrospectivos
18.
Front Microbiol ; 15: 1348405, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38389533

RESUMEN

Several animal models have been used to assist the development of vaccines and therapeutics since the COVID-19 outbreak. Due to the lack of binding affinity of mouse angiotensin-converting enzyme II (ACE2) to the S protein of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), increasing the susceptibility of mice to SARS-CoV-2 infection was considered in several ways. Here, we generated a COVID-19 mouse model expressing human ACE2 (hACE2) under the control of the CAG promoter. Overexpression of hACE2 did not pose a significant effect on weight growth. After SARS-CoV-2 inoculation, mice showed obvious viral replication and production of inflammation within 7 days, with a gradual decrease in body weight until death. Virological testing found that the virus can replicate in the respiratory system, small intestine, and brain. Additionally, this mouse model was applied to compare two antibody drug candidates, the anti-RBD antibody (MW06) and the mouse CD24-conjugated anti-RBD antibody (mCD24-MW06). Differences in antiviral effects between these two antibodies can be demonstrated in this mouse model when a challenge dose that invalidates the anti-RBD antibody treatment was used. This study provided a new mouse model for studying SARS-CoV-2 pathogenesis and evaluating potential interventions.

19.
Int J Mol Sci ; 25(4)2024 Feb 12.
Artículo en Inglés | MEDLINE | ID: mdl-38396874

RESUMEN

Aurora kinase B (AURKB) overexpression promotes tumor initiation and development by participating in the cell cycle. In this study, we focused on the mechanism of AURKB in hepatocellular carcinoma (HCC) progression and on AURKB's value as a diagnostic and prognostic biomarker in HCC. We used data from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) to analyze AURKB expression in HCC. We found that the expression levels of AURKB in HCC samples were higher than those in the corresponding control group. R packages were used to analyze RNA sequencing data to identify AURKB-related differentially expressed genes (DEGs), and these genes were found to be significantly enriched during the cell cycle. The biological function of AURKB was verified, and the results showed that cell proliferation was slowed down and cells were arrested in the G2/M phase when AURKB was knocked down. AURKB overexpression resulted in significant differences in clinical symptoms, such as the clinical T stage and pathological stage. Kaplan-Meier survival analysis, Cox regression analysis, and Receiver Operating Characteristic (ROC) curve analysis suggested that AURKB overexpression has good diagnostic and prognostic potential in HCC. Therefore, AURKB may be used as a potential target for the diagnosis and cure of HCC.


Asunto(s)
Aurora Quinasa B , Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Aurora Quinasa B/genética , Aurora Quinasa B/metabolismo , Biomarcadores de Tumor/metabolismo , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/genética , Ciclo Celular , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/genética
20.
Heliyon ; 10(2): e24945, 2024 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-38312673

RESUMEN

Objective: We aimed to determine the safety of Vaginal natural orifice transluminal endoscopic surgery (vNOTES) in terms of the Enhanced Recovery after Surgery (ERAS) concept for tubal pregnancy surgery and provide a detailed process of vNOTES for tubal pregnancy surgery, including experience and key points for surgeons performing this procedure. Methods: The Longitudinal Vaginal Natural Orifice Transluminal Endoscopic Surgery Study (LovNOTESS), which was conducted in Chengdu, China. A total of 219 patients who underwent tubal ectopic pregnancy surgery between September 2021 and March 2022. The patients underwent salpingectomy or salpingostomy using transumbilical laparoendoscopic single-site surgery (LESS) or vNOTES, according to their preferences. This study prospectively collected perioperative and one-year follow-up data on tubal pregnancy outcomes after vNOTES and compared them with those after LESS. Results: The vNOTES group showed a shorter surgical duration, hospitalization duration, and postoperative exhaust time and a lower analgesic medication usage rate, but it showed a higher surgical conversion rate. The vNOTES approach reduced the postoperative exhaust time by approximately 9 h (95% confidence interval [CI]: -11.93, -5.57 h, p < .001) and the risk of postoperative analgesic drug use by 77% (odds ratio, 0.23; 95% CI: 0.10, 0.61, p = .023). Conclusion: vNOTES can shorten the exhaust time and duration of hospitalization, reduce postoperative pain, and avoid surface surgical scars in tubal pregnancy surgeries, consistent with the ERAS concept. However, more comprehensive preoperative evaluation of patients who choose vNOTES is required to reduce the occurrence of intraoperative conversion.Trial registration: ChiCTR2100053483.

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