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1.
J Dent ; : 105260, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-39096996

RESUMEN

OBJECTIVES: The aim of this study was to predict the risk of dental implant loss by clustering features associated with implant survival rates. MATERIALS AND METHODS: Multiple clinical features from 8513 patients who underwent single implant placement were retrospectively analysed. A hybrid method integrating unsupervised learning algorithms with survival analysis was employed for data mining. Two-step cluster, univariate Cox regression, and Kaplan‒Meier survival analyses were performed to identify the clustering features associated with implant survival rates. To predict the risk of dental implant loss, nomograms were constructed on the basis of time-stratified multivariate Cox regression. RESULTS: Six clusters with distinct features and prognoses were identified using two-step cluster analysis and Kaplan‒Meier survival analysis. Compared with the other clusters, only one cluster presented significantly lower implant survival rates, and six specific clustering features within this cluster were identified as high-risk factors, including age, smoking history, implant diameter, implant length, implant position, and surgical procedure. Nomograms were created to assess the impact of the six high-risk factors on implant loss for three periods: 1) 0-120 days, 2) 120-310 days, and 3) more than 310 days after implant placement. The concordance indices of the models were 0.642, 0.781, and 0.715, respectively. CONCLUSIONS: The hybrid unsupervised clustering method, which clusters and identifies high-risk clinical features associated with implant loss without relying on predefined labels or target variables, represents an effective approach for developing a visual model for predicting implant prognosis. However, further validation with a multimodal, multicentre, prospective cohort is needed. CLINICAL SIGNIFICANCE: Visual prognosis prediction utilizing this nomogram that predicts the risk of implant loss on the basis of clustering features can assist dentists in preoperative assessments and clinical decision-making, potentially improving dental implant prognosis.

2.
J Pediatr Surg ; 2024 Jul 06.
Artículo en Inglés | MEDLINE | ID: mdl-39054116

RESUMEN

BACKGROUND: Pediatric minimally invasive surgery requires advanced technical skills. Off-the-job training (OJT), especially when using disease-specific models, is an effective method of acquiring surgical skills. To achieve effective OJT, it is necessary to provide objective and appropriate skill assessment feedback to trainees. We aimed to construct a system that automatically evaluates surgical skills based on forceps movement using deep learning (DL). METHODS: Using our original esophageal atresia OJT model, participants were tasked with performing esophageal anastomosis. All tasks were recorded for image analysis. Based on manual objective skill assessments, each participant's surgical skills were categorized into two groups: good and poor. The motion of the forceps in both groups was used as training data. Employing this training data, we constructed an automated system that recognized the movement of forceps and determined the quality of the surgical technique. RESULTS: Thirteen participants were assigned to the good skill group and 32 to the poor skill group. These cases were validated using an automated skill assessment system. This system showed a precision of 75%, a specificity of 94%, and an area under the receiver operating characteristic curve of 0.81. CONCLUSIONS: We constructed a system that automatically evaluated the quality of surgical techniques based on the movement of forceps using DL. Artificial intelligence diagnostics further revealed the procedures important for suture manipulation. LEVELS OF EVIDENCE: Level IV.

3.
J Chem Phys ; 161(3)2024 Jul 21.
Artículo en Inglés | MEDLINE | ID: mdl-39007392

RESUMEN

Silicon, renowned for its remarkable energy density, has emerged as a focal point in the pursuit of high-energy storage solutions for the next generation. Nevertheless, silicon electrodes are known to undergo significant volume expansion during the insertion of lithium ions, leading to structural deformation and the development of internal stresses, and causing a rapid decline in battery capacity and overall lifespan. To gain deeper insights into the intricacies of charge rate effects, this study employs a combination of in situ measurements and computational modeling to elucidate the cyclic performance of composite silicon electrodes. The findings derived from the established model and curvature measurement system unveil the substantial alterations in stress and deformation as a consequence of varying charge rates. Notably, the active layer experiences compressive forces that diminish as the charge rate decreases. At a charge rate of 0.2, the active layer endures a maximum stress of 89.145 MPa, providing a comprehensive explanation for the observed deterioration in cycling performance at higher charge rates. This study not only establishes a fundamental basis for subsequent stress analyses of silicon electrodes but also lays a solid foundation for further exploration of the impact of charge rates on composite silicon electrodes.

4.
Pediatr Surg Int ; 40(1): 197, 2024 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-39017936

RESUMEN

PURPOSE: The prognostic factors of subsequent liver transplantation (LT) in patients with biliary atresia (BA) who presented with jaundice-free native liver survival were investigated. METHODS: This study retrospectively reviewed patients who underwent portoenterostomy (PE) for BA. Patients with jaundice-free native liver survival at 1 year postoperatively were divided into the autologous liver survivor and liver transplant recipient groups. Peri- and postoperative data were compared between the two groups. RESULTS: Among 97 patients with BA, 29 who received LT within 1 year after PE were excluded from the analysis. Further, 48 patients currently living with native liver and 20 who received LT after 1 year postoperatively were compared. Bile lake (BL) was the strongest risk factor of LT. The risk score was 2.38 ∗ B L s c o r e + 0.00466 ∗ T B A , and the area under the receiver operating characteristic curve was 0.83. Patients with BL and those without significantly differed in terms of the native liver survival rate. Patients with BL who presented with not only cholangitis but also gastrointestinal hemorrhage and hepatopulmonary syndrome received LT. CONCLUSION: BL can cause different pathologies. Moreover, it is an evident risk factor of subsequent LT in patients with BA who are living with native liver at 1 year after PE.


Asunto(s)
Atresia Biliar , Trasplante de Hígado , Portoenterostomía Hepática , Humanos , Atresia Biliar/cirugía , Atresia Biliar/complicaciones , Atresia Biliar/mortalidad , Estudios Retrospectivos , Femenino , Masculino , Lactante , Factores de Riesgo , Portoenterostomía Hepática/métodos , Tasa de Supervivencia/tendencias , Bilis , Pronóstico , Preescolar , Ictericia/etiología , Hígado
5.
J Ovarian Res ; 17(1): 149, 2024 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-39020428

RESUMEN

BACKGROUND: The five-year prognosis for patients with late-stage high-grade serous carcinoma (HGSC) remains dismal, underscoring the critical need for identifying early-stage biomarkers. This study explores the potential of extracellular vesicles (EVs) circulating in blood, which are believed to harbor proteomic cargo reflective of the HGSC microenvironment, as a source for biomarker discovery. RESULTS: We conducted a comprehensive proteomic profiling of EVs isolated from blood plasma, ascites, and cell lines of patients, employing both data-dependent (DDA) and data-independent acquisition (DIA) methods to construct a spectral library tailored for targeted proteomics. Our investigation aimed at uncovering novel biomarkers for the early detection of HGSC by comparing the proteomic signatures of EVs from women with HGSC to those with benign gynecological conditions. The initial cohort, comprising 19 donors, utilized DDA proteomics for spectral library development. The subsequent cohort, involving 30 HGSC patients and 30 control subjects, employed DIA proteomics for a similar purpose. Support vector machine (SVM) classification was applied in both cohorts to identify combinatorial biomarkers with high specificity and sensitivity (ROC-AUC > 0.90). Notably, MUC1 emerged as a significant biomarker in both cohorts when used in combination with additional biomarkers. Validation through an ELISA assay on a subset of benign (n = 18), Stage I (n = 9), and stage II (n = 9) plasma samples corroborated the diagnostic utility of MUC1 in the early-stage detection of HGSC. CONCLUSIONS: This study highlights the value of EV-based proteomic analysis in the discovery of combinatorial biomarkers for early ovarian cancer detection.


Asunto(s)
Biomarcadores de Tumor , Detección Precoz del Cáncer , Vesículas Extracelulares , Mucina-1 , Neoplasias Ováricas , Proteómica , Humanos , Femenino , Vesículas Extracelulares/metabolismo , Proteómica/métodos , Neoplasias Ováricas/sangre , Neoplasias Ováricas/diagnóstico , Neoplasias Ováricas/patología , Neoplasias Ováricas/metabolismo , Biomarcadores de Tumor/sangre , Detección Precoz del Cáncer/métodos , Persona de Mediana Edad , Mucina-1/sangre , Cistadenocarcinoma Seroso/sangre , Cistadenocarcinoma Seroso/diagnóstico , Cistadenocarcinoma Seroso/metabolismo , Cistadenocarcinoma Seroso/patología , Anciano , Clasificación del Tumor , Adulto
6.
Cell Biol Toxicol ; 40(1): 54, 2024 Jul 12.
Artículo en Inglés | MEDLINE | ID: mdl-38995476

RESUMEN

BACKGROUND: The neuropathic pain with complex networks of neuroinflammatory activation severely limits clinical therapeutic research. TNF receptor-associated factor 6 (TRAF6) is associated with multiple inflammatory diseases. However, there remains confusion about the effects and mechanisms of TRAF6 in neuropathic pain. METHODS: A chronic constriction injury (CCI) model was developed to simulate neuralgia in vivo. We overexpressed or knocked down TRAF6 in CCI mice, respectively. Activation of microglia by TRAF6, the inflammatory response, and disease progression were inspected using WB, qRT-PCR, immunofluorescence, flow cytometry, and ELISA assays. Moreover, the mechanism of M1/M2 polarization activation of microglia by TRAF6 was elaborated in BV-2 cells. RESULTS: TRAF6 was enhanced in the spinal neurons and microglia of the CCI mice model compared with the sham operation group.. Down-regulation of TRAF6 rescued the expression of Iba-1. In response to mechanical and thermal stimulation, PWT and PWL were improved after the knockdown of TRAF6. Decreased levels of pro-inflammatory factors were observed in TRAF6 knockdown groups. Meanwhile, increased microglial M1 markers induced by CCI were limited in mice with TRAF6 knockdown. In addition, TRAF6 overexpression has the precise opposite effect on CCI mice or microglia polarization. We also identifed that TRAF6 activated the c-JUN/NF-kB pathway signaling; the inhibitor of c-JUN/NF-kB could effectively alleviate the neuropathic pain induced by upregulated TRAF6 in the CCI mice model. CONCLUSION: In summary, this study indicated that TRAF6 was concerned with neuropathic pain, and targeting the TRAF6/c-JUN/NF-kB pathway may be a prospective target for treating neuropathic pain.


Asunto(s)
Microglía , FN-kappa B , Neuralgia , Transducción de Señal , Factor 6 Asociado a Receptor de TNF , Animales , Masculino , Ratones , Línea Celular , Polaridad Celular , Modelos Animales de Enfermedad , Ratones Endogámicos C57BL , Microglía/metabolismo , Neuralgia/metabolismo , FN-kappa B/metabolismo , Proteínas Proto-Oncogénicas c-jun/metabolismo , Médula Espinal/metabolismo , Médula Espinal/patología , Factor 6 Asociado a Receptor de TNF/metabolismo
7.
World J Gastrointest Oncol ; 16(7): 3331-3340, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-39072150

RESUMEN

BACKGROUND: Metastatic breast cancer originating in the gastrointestinal tract is a rare occurrence. The limited number of cases has resulted in incomplete understanding of the disease, making it challenging to differentiate from primary breast cancer. While clinical history and immunohistochemical studies can aid in distinguishing between the two, the management principles and pathogenesis of gastrointestinal metastatic breast cancer remain controversial. The scarcity of data has hampered comprehensive knowledge. Our objective is to shed light on this rare disease through our case study. CASE SUMMARY: Here, we report a case of breast metastasis from gastric cancer in a 43-year-old woman. This patient was admitted to our hospital with complaints of discomfort in the upper and middle abdomen persisting for two months, as well as black stools for over ten days. She underwent radical distal gastrectomy for gastric cancer, followed by postoperative chemotherapy. Three years later, the patient developed bilateral breast nodules. Imaging studies indicated a high probability of malignancy. She subsequently underwent a right modified radical mastectomy and excision of a left breast mass. Postoperative pathology revealed the right breast tumor was consistent with primary gastric cancer. CONCLUSION: We present a case of breast metastasis from gastric cancer to contribute to the limited foundation of research into this rare disease.

8.
J Med Case Rep ; 18(1): 282, 2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38886731

RESUMEN

BACKGROUND: Iatrogenic pseudoaneurysms arising from the internal carotid artery subsequent to carotid endarterectomy are exceptionally infrequent. Herein, we present a case detailing an internal carotid artery pseudoaneurysm that manifested subsequent to a hybrid carotid endarterectomy and endovascular therapy intervention. Our approach to managing this condition involved a novel technique wherein thrombin was directly injected into the luminal cavity of the pseudoaneurysm under the guidance of a C-arm. CASE PRESENTATION: A 66-year-old male patient of Chinese ethnicity exhibited a 4-month history of headache and a 20-day history of gait disturbance. Digital subtraction angiography revealed occlusion in the cervical region of the left carotid artery. Following a hybrid surgical procedure, the patient reported mild pain and bruising surrounding the incision site of the left internal carotid artery endarterectomy. Subsequent angiography identified the presence of a carotid artery pseudoaneurysm. Utilizing C-arm guidance, thrombin was then directly injected into the luminal cavity of the pseudoaneurysm, resulting in complete healing during follow-up. CONCLUSION: For the management of pseudoaneurysms arising post carotid endarterectomy, the direct injection of thrombin into the aneurysm cavity under the guidance of a C-arm is deemed both safe and efficacious.


Asunto(s)
Traumatismos de las Arterias Carótidas , Arteria Carótida Interna , Endarterectomía Carotidea , Enfermedad Iatrogénica , Trombina , Humanos , Masculino , Endarterectomía Carotidea/efectos adversos , Trombina/administración & dosificación , Trombina/uso terapéutico , Anciano , Traumatismos de las Arterias Carótidas/etiología , Traumatismos de las Arterias Carótidas/cirugía , Aneurisma Falso/etiología , Aneurisma Falso/diagnóstico por imagen , Aneurisma Falso/cirugía , Resultado del Tratamiento , Angiografía de Substracción Digital
9.
Animals (Basel) ; 14(11)2024 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-38891675

RESUMEN

A total of 320 1-day-old broilers were randomly divided into five groups. The control group (CON) received a basal diet, while the FAP4, FAP2, and FAP1 groups were provided with the basal diet supplemented with 4%, 2%, and 1% fermented Astragalus powder, respectively. The unfermented Astragalus powder (UAP2) group was fed the basal diet supplemented with 2% UAP. Each group contained eight replicates of eight chicks each. The results revealed that the final BW and ADG in the FAP 1 and FAP2 were higher than those in the UAP2 and CON groups, while reducing F/G from day 14 to day 42. On day 42, the thymus index in the UAP and FAP groups as well as the bursa index in the FAP4 group showed significant increases compared to those in the CON group. Supplementation with 2% FAP elevated serum IgA levels in broilers on day 28 and day 42, and it also increased serum IgG levels on day 42. Furthermore, supplementation with 2% FAP elevated serum albumin (ALB) levels in broilers, while supplementation with 4% FAP increased serum (glucose) GLU levels in broilers on day 28. The serum biochemical parameters and pathological observation of the liver and kidney in the groups did not show any adverse effects on broilers' health. In addition, the serum total antioxidant capacity (T-AOC) level significantly increased in the FAP4 and FAP2 groups on day 28, and the malondialdehyde (MDA) level in both serum and liver tissue decreased in the FAP2 group on day 28 and day 42. Compared to the CON group, 2% FAP and 2% UAP supplementation reduced the relative abundance of Bacteroides and supplementation with 2% FAP increased the relative abundance of Alistipes on day 42. In conclusion, the dietary supplementation of FAP can enhance the growth performance, immune function, and antioxidant capacity and regulate microflora in broilers, of which 2% FAP is more effective. It indicates FAP exhibits significant application potential as a promising feed additive for broilers.

10.
Appl Opt ; 63(14): 3929-3943, 2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38856357

RESUMEN

In order to extract smooth and accurate strain fields from the noisy displacement fields obtained by digital image correlation (DIC), a point interpolation meshless (PIM) method with a radial basis function (RBF) is introduced for full-field strain calculation, which overcomes the problems of slow calculation speed and unstable matrix inverse calculation of the element-free Galerkin method (EFG). The radial basis point interpolation method (RPIM) with three different radial basis functions and the moving least squares (MLS) and pointwise least squares (PLS) methods are compared by analyzing and validating the strain fields with high-strain gradients in simulation experiments. The results indicate that the RPIM is nearly 80% more computationally efficient than the MLS method when a larger support domain is used, and the efficiency of the RPIM is nearly 26% higher than that of the MLS method when a smaller support domain is used; the strain calculation accuracy is slightly lower than that of the MLS method by 0.3-0.5%, but the stability of the calculation is significantly improved. In contrast with the PLS method, which is easily affected by the noise and the size of the strain calculation window, the RPIM is insensitive to the displacement noise and the size of the support domain and can obtain a similar calculation accuracy. The RPIM with multiquadric (MQ) radial basis functions performs well in balancing the computational accuracy and efficiency and is insensitive to shape parameters. The application cases show that the method can effectively compute the strain field at the crack tip, validating its applicability to the study of the plastic region at the crack tip. In conclusion, the proposed RPIM-based method provides an accurate, practical, and robust approach for full-field strain measurements.

12.
J Hazard Mater ; 474: 134826, 2024 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-38852248

RESUMEN

Phenylpropanoid biosynthesis plays crucial roles in the adaptation to cadmium (Cd) stress. Nevertheless, few reports have dabbled in physiological mechanisms of such super pathway regulating Cd accumulation in plants. Herein, by integrating transcriptomic, histological and molecular biology approaches, the present study dedicated to clarify molecular mechanism on how rice adapt to Cd stress via phenylpropanoid biosynthesis. Our analysis identified that the enhancement of phenylpropanoid biosynthesis was as a key response to Cd stress. Intriguingly, POD occupied a significant part in this process, with the number of POD related genes accounted for 26/29 of all upregulated genes in phenylpropanoid biosynthesis. We further used SHAM (salicylhydroxamic acid, the POD inhibitor) to validate that POD exhibited a negative correlation with the Cd accumulation in rice tissues, and proposed two intrinsic molecular mechanisms on POD in contributing to Cd detoxification. One strategy was that POD promoted the formation of lignin and CSs both in endodermis and exodermis for intercepting Cd influx. In detail, inhibited POD induced by external addition of SHAM decreased the content of lignin by 50.98-66.65 % and delayed percentage of the DTIP-CS to root length by 39.17-104.51 %. The other strategy was expression of transporter genes involved in Cd uptake, including OsIRT1, OsIRT2, OsZIP1 and OsZIP, negatively regulated by POD. In a word, our findings firstly draws a direct link between POD activity and the Cd accumulation, which is imperative for the breeding of rice with low-Cd-accumulating capacity in the future.


Asunto(s)
Cadmio , Oryza , Oryza/metabolismo , Oryza/genética , Cadmio/toxicidad , Cadmio/metabolismo , Regulación de la Expresión Génica de las Plantas/efectos de los fármacos , Peroxidasa/metabolismo , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Lignina/metabolismo , Contaminantes del Suelo/metabolismo , Contaminantes del Suelo/toxicidad
14.
Biomolecules ; 14(6)2024 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-38927136

RESUMEN

Diabetic kidney disease (DKD) is a common microvascular complication of diabetes and the main cause of end-stage renal disease around the world. Mitochondria are the main organelles responsible for producing energy in cells and are closely involved in maintaining normal organ function. Studies have found that a high-sugar environment can damage glomeruli and tubules and trigger mitochondrial dysfunction. Meanwhile, animal experiments have shown that DKD symptoms are alleviated when mitochondrial damage is targeted, suggesting that mitochondrial dysfunction is inextricably linked to the development of DKD. This article describes the mechanisms of mitochondrial dysfunction and the progression and onset of DKD. The relationship between DKD and mitochondrial dysfunction is discussed. At the same time, the progress of DKD treatment targeting mitochondrial dysfunction is summarized. We hope to provide new insights into the progress and treatment of DKD.


Asunto(s)
Nefropatías Diabéticas , Mitocondrias , Nefropatías Diabéticas/metabolismo , Nefropatías Diabéticas/tratamiento farmacológico , Nefropatías Diabéticas/patología , Humanos , Mitocondrias/metabolismo , Mitocondrias/efectos de los fármacos , Animales
15.
Pediatr Surg Int ; 40(1): 149, 2024 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-38829446

RESUMEN

PURPOSE: The surgical indication of thoracoscopic primary repair for esophageal atresia with tracheoesophageal fistula is under debate. The current study aimed to investigate the outcome of thoracoscopic primary repair for esophageal atresia with tracheoesophageal fistula in patients weighing < 2000 g and those who underwent emergency surgery at the age of 0 day. METHODS: The surgical outcomes were compared between patients weighing < 2000 g and those weighing > 2000 g at surgery and between patients who underwent surgery at the age of 0 day and those who underwent surgery at age ≥ 1 day. RESULTS: In total, 43 patients underwent thoracoscopic primary repair for esophageal atresia with tracheoesophageal fistula. The surgical outcomes according to body weight were similar. Patients who underwent surgery at the age of 0 day were more likely to develop anastomotic leakage than those who underwent surgery at the age of ≥ 1 day (2 vs. 0 case, p = 0.02). Anastomotic leakage was treated with conservative therapy. CONCLUSION: Thoracoscopic primary repair is safe and useful for esophageal atresia with tracheoesophageal fistula even in newborns weighing < 2000 g. However, emergency surgery at the age of 0 day should be cautiously performed due to the risk of anastomotic leakage.


Asunto(s)
Atresia Esofágica , Toracoscopía , Fístula Traqueoesofágica , Humanos , Fístula Traqueoesofágica/cirugía , Fístula Traqueoesofágica/complicaciones , Atresia Esofágica/cirugía , Atresia Esofágica/complicaciones , Recién Nacido , Toracoscopía/métodos , Masculino , Femenino , Estudios Retrospectivos , Resultado del Tratamiento , Recién Nacido de Bajo Peso , Fuga Anastomótica/cirugía
16.
Phytomedicine ; 132: 155329, 2024 Jun 08.
Artículo en Inglés | MEDLINE | ID: mdl-38853123

RESUMEN

BACKGROUND: Currently, there are many drugs available for the treatment of type 2 diabetes mellitus (T2DM), but most of them cause various side effects due to the need for long-term use. As a traditional Chinese medicine, Gegen Qinlian Decoction (GQD) has shown good efficacy and low side effects in the treatment of T2DM in both clinical and basic research. Based on relevant traditional Chinese medicine theories, dried ginger is innovatively added the formula of traditional GQD to create a modified GQD. This modification reduces the side effects of traditional GQD while exerting its therapeutic effect on T2DM. Previous studies have found that the modified GQD can regulate endoplasmic reticulum stress in the liver, inhibit hepatic gluconeogenesis, protect pancreatic islet ß cells, and control blood sugar levels by inhibiting the FXR/neuronal ceramide signaling pathway. GQD can also regulate the intestinal microbiota to achieve therapeutic and protective effects in various gastrointestinal diseases. However, there is no research exploring whether the modified GQD achieves its therapeutic mechanism for T2DM by regulating the intestinal microbiota. PURPOSE: To explore the mechanism of modified GQD in the treatment of T2DM based on multi-omics, focusing on its effect on the "intestinal flora bile acid TGR5'' axis. METHODS: The T2DM model was established using db/db mice, which were randomly divided into a model group, metformin group, high-dose GQD group, medium-dose GQD group, low-dose GQD group, while m/m mice were used as blank control. The drug intervention lasted for 12 weeks, during which the general conditions, oral glucose tolerance (OGT), blood glucose, and lipid-related indexes were recorded. Additionally, the fasting insulin (FINS), c-peptide, GLP-1 in serum, and cAMP in the ileum were measured by ELISA assay. Furthermore, the composition, abundance, and function of the intestinal microbiota were determined by macro genome sequencing, while bile acid was detected by targeted metabonomics. For histological evaluation, HE staining was used to observe the pathological changes of the ileum and pancreas, and the ultrastructure of the ileum and pancreas was observed by transmission electron microscopy. Apoptosis in the ileum tissue was detected by Tunel staining. Moreover, the mRNA and protein expressions of TGR5, PKA, CREB, PC1/3, GLP-1, and their phosphorylation levels in the ileum were detected by qPCR, immunohistochemistry, and Western blot; The expression of INS in the pancreas was also evaluated using immunohistochemistry. Finally, double immunofluorescence staining was used to detect the co-localization expression of TGR5 and GLP-1, NeuroD1, and GLP-1 in the ileum. RESULTS: The modified GQD was found to significantly reduce blood glucose, improve oral glucose tolerance, and blood lipid levels, as well as alleviate the injury of the ileum and pancreas in T2DM mice. Furthermore, modified GQD was found to effectively regulate intestinal flora, improve bile acid metabolism, activate the TRG5/cAMP/PKA/CREB signal pathway, and stimulate GLP-1 secretion. CONCLUSION: GQD can regulate the "intestinal flora-bile acid-TGR5" axis and has a therapeutic effect on T2DM in mice.

17.
Neurotox Res ; 42(4): 31, 2024 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-38935306

RESUMEN

Endoplasmic reticulum (ER) stress and oxidative stress (OS) are often related states in pathological conditions including Parkinson's disease (PD). This study investigates the role of anti-oxidant protein paraoxonase 2 (PON2) in ER stress and OS in PD, along with its regulatory molecule. PD was induced in C57BL/6 mice using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP) treatment and in SH-SY5Y cells using 1-methyl-4-phenylpyridinium. PON2 was found to be poorly expressed in the substantia nigra pars compacta (SNc) of PD mice, and its overexpression improved motor coordination of mice. Through the evaluation of tyrosine hydroxylase, dopamine transporter, reactive oxygen species (ROS), and C/EBP homologous protein (CHOP) levels and neuronal loss in mice, as well as the examination of CHOP, glucose-regulated protein 94 (GRP94), GRP78, caspase-12, sarco/endoplasmic reticulum calcium ATPase 2, malondialdehyde, and superoxide dismutase levels in SH-SY5Y cells, we observed that PON2 overexpression mitigated ER stress, OS, and neuronal apoptosis both in vivo and in vitro. Forkhead box A1 (FOXA1) was identified as a transcription factor binding to the PON2 promoter to activate its transcription. Upregulation of FOXA1 similarly protected against neuronal loss by alleviating ER stress and OS, while the protective roles were abrogated by additional PON2 silencing. In conclusion, this study demonstrates that FOXA1-mediated transcription of PON2 alleviates ER stress and OS, ultimately reducing neuronal apoptosis in PD.


Asunto(s)
Apoptosis , Arildialquilfosfatasa , Chaperón BiP del Retículo Endoplásmico , Estrés del Retículo Endoplásmico , Factor Nuclear 3-alfa del Hepatocito , Ratones Endogámicos C57BL , Estrés Oxidativo , Animales , Humanos , Masculino , Ratones , Apoptosis/efectos de los fármacos , Apoptosis/fisiología , Arildialquilfosfatasa/metabolismo , Arildialquilfosfatasa/genética , Línea Celular Tumoral , Estrés del Retículo Endoplásmico/fisiología , Estrés del Retículo Endoplásmico/efectos de los fármacos , Factor Nuclear 3-alfa del Hepatocito/metabolismo , Factor Nuclear 3-alfa del Hepatocito/genética , Neuronas/metabolismo , Neuronas/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Estrés Oxidativo/fisiología
18.
ACS Appl Mater Interfaces ; 16(26): 33316-33324, 2024 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-38887818

RESUMEN

Silicon is considered as the most felicitous anode material candidate for lithium-ion batteries on account of abundant availability, suitable operating potential, and high specific capacity. Nevertheless, drastic volume expansion during the cycle impedes its practical utilization. Herein, Si and MnO2 (Si-MO) constructed the binder-free intertwined electrode that is reported to effectively improve upon the cycling stability of Si-based materials. The Si-based electrode without a binder has good electrical conductivity, strong adhesion to the substrate, and ample space for mitigating volume expansion. The incorporation of MnO2 establishes a multiphase interface, which mitigates the electrode volume expansion, and supports the electrode structure. Furthermore, MnO2 (∼1230 mAh g-1 theoretical capacity) synergistically enhances the overall capacity of the composite electrodes. Consequently, the Si-MO composite electrode exhibits a reversible specific capacity of 1300 mAh g-1 at 420 mA g-1 and remarkable cycling performance with a specific capacity of 830 mAh g-1 after 500 cycles. In particular, a reversible specific capacity of 837 mAh g-1 at 4200 mA g-1 is achieved and remains stable during 200 cycles. This work provides a potentially feasible way to achieve the Si-based anode commercialization for LIBs.

20.
Skin Res Technol ; 30(7): e13785, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38932455

RESUMEN

PURPOSE: The etiology of alopecia areata (AA) in relation to serum lipids remains unclear, thereby prompting our intention to do Mendelian study on this subject. DESIGN: Two-sample Mendelian randomization (MR) analysis was performed in the study. The inverse variance-weighted method was used as the primary method. METHODS: In our study, we integrated a set of 123 single-nucleotide polymorphisms (SNPs) into our analysis. These SNPs have been extensively studied and are known to exhibit associations with serum lipids. We sourced these SNPs from a variety of relevant studies and consortia that specifically focus on lipid-related research, such as the MRC Integrative Epidemiology Unit. These carefully curated SNPs were then utilized as instrumental variables in our analysis, allowing us to explore and evaluate the causal relationships between these genetic variants and serum lipids. By incorporating this comprehensive set of SNPs, we aimed to enhance the precision and robustness of our findings, shedding light on the intricate interplay between genetics and serum lipids. RESULTS: In the MR analysis, a higher total lipid concentration in large low-density lipoprotein (LDL) particles (odds ratio [OR] = 1.502; 95% confidence interval [CI] = 1.086-1.953; p = 0.006), a greater ratio of cholesteryl esters to total lipids in chylomicrons and extremely large very LDL (VLDL) particles (OR = 2.174; 95% CI = 1.300-2.500; p = 0.010), and a greater ratio of cholesterol to total lipids in chylomicrons and extremely large VLDL particles (OR = 2.363;95% CI = 1.556-4.438; p = 0.004), were genetically predicted to be causally associated with an increased risk of AA, while patients with a higher triglyceride to total lipids ratio in chylomicrons and extremely large VLDL particles had a lower risk of AA (OR = 0.481; 95% CI = 0.191-1.270; p = 0.002). CONCLUSION: This study found that serum lipids may be causally implicated in AA.


Asunto(s)
Alopecia Areata , Lípidos , Análisis de la Aleatorización Mendeliana , Polimorfismo de Nucleótido Simple , Alopecia Areata/genética , Alopecia Areata/sangre , Alopecia Areata/epidemiología , Humanos , Lípidos/sangre , Predisposición Genética a la Enfermedad/genética
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