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1.
Biomed Opt Express ; 15(10): 5932-5946, 2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-39421770

RESUMEN

Optical diffraction tomography (ODT) enables label-free and morphological 3D imaging of biological samples using refractive-index (RI) contrast. To accomplish this, ODT systems typically capture multiple angular-specific scattering measurements, which are used to computationally reconstruct a sample's 3D RI. Standard ODT systems employ scanning mirrors to generate angular illuminations. However, scanning mirrors are limited to illuminating the sample from only one angle at a time. Furthermore, when operated at high speeds, these mirrors may exhibit mechanical instabilities that compromise image quality and measurement speed. Recently, newer ODT systems have been introduced that utilize digital-micromirror devices (DMD), spatial light modulators (SLMs), or LED arrays to achieve switchable angle-scanning with no physically-scanning components. However, these systems associate with power inefficiencies and/or spurious diffraction orders that can also limit imaging performance. In this work, we developed a novel non-interferometric ODT system that utilizes a fully switchable module for angle scanning composed of a DMD and microlens array (MLA). Compared to other switchable ODT systems, this module enables each illumination angle to be generated fully independently from every other illumination angle (i.e., no spurious diffraction orders) while also optimizing the power efficiency based on the required density of illumination angles. We validate the quantitative imaging capability of this system using calibration microspheres. We also demonstrate its capability for imaging multiple-scattering samples by imaging an early-stage zebrafish embryo.

2.
Ren Fail ; 46(2): 2416605, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-39440406

RESUMEN

OBJECTIVES: To evaluate the effectiveness and safety of different B cell-targeting biological agents combining with standard of care in patients with lupus nephritis (LN). METHODS: Comprehensive literature searches were conducted using PubMed, Embase, Web of Science, and Central in the Cochran Library, spanning from inception to May 20th, 2024. Randomized control trials (RCTs) comparing rituximab (RTX), belimumab, ocrelizumab, obinutuzumab, and anifrolumab in LN were selected. The primary outcomes of interest were related to complete renal remission (CRR), and partial renal remission (PRR). Additionally, we delved into safety outcomes, examining the occurrence of serious adverse events (SAEs), infections, and the discontinuation rates due to adverse events. RESULTS: A total of 6 RCTs with 1150 patients applying various B cell-targeting biological agents were included. Notably, ranking probability based on the surface under the cumulative ranking curve (SUCRA) indicated that obinutuzumab (SUCRA 85.2%) has the highest potential superiority in improving CRR, followed by belimumab, ocrelizumab. Regarding the improvement in PRR, obinutuzumab (SUCRA 83.0%) has the highest potential superiority. In terms of safety, with a focus on SAEs, infections, and the discontinuation rates due to adverse events, the results were: SUCRA-based ranking indicated that RTX (SUCRA 74.1%) had the highest probability of postponing SAEs, followed by belimumab and obinutuzumab. Concerning infection reduction, anifrolumab (SUCRA 78.7%) had the highest potential superiority. Safety events monitoring infection occurred better with RTX than with standard therapy (OR = 3.57, 95% CI 1.02, 12.66) and were statistically different. For the discontinuation rates due to adverse events, RTX (SUCRA 88.6%) demonstrated the highest potential superiority. CONCLUSIONS: Concerning the effectiveness and safety outcomes, obinutuzumab, belimumab, and RTX plus standard of care may be superior to the current standard therapy as treatments for LN. This study protocol has been registered with PROSPERO, with a registration number of CRD42024548522.


Asunto(s)
Anticuerpos Monoclonales Humanizados , Linfocitos B , Nefritis Lúpica , Metaanálisis en Red , Humanos , Nefritis Lúpica/tratamiento farmacológico , Linfocitos B/efectos de los fármacos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/efectos adversos , Ensayos Clínicos Controlados Aleatorios como Asunto , Productos Biológicos/uso terapéutico , Productos Biológicos/efectos adversos , Rituximab/uso terapéutico , Rituximab/efectos adversos , Resultado del Tratamiento , Inducción de Remisión
3.
Food Chem ; 463(Pt 4): 141525, 2024 Oct 04.
Artículo en Inglés | MEDLINE | ID: mdl-39388869

RESUMEN

In this work, a ratiometric fluorescence hydrogel nanosensor was developed by integrating a composite consisting of o-phenylenediamine (OPD), manganese dioxide nanoflakes (MnO2 NFs), and N-doped carbon dots (N-CDs) into an agarose hydrogel for sulfite detection. MnO2 NFs demonstrated intense oxidase-like activity, facilitating the conversion of non-fluorescent OPD into yellow-emissive 2,3-diaminophenazine (DAP). As a result, a significant emission peak belongs to DAP, alongside the fluorescence quenching of N-CDs through FRET. Upon interaction with sulfite, MnO2 NFs lost their oxidase-like function. This process decreased the fluorescence of DAP and restored the blue fluorescence of N-CDs, producing a typical ratiometric response, ranging from 3 nM âˆ¼ 400 µM, with a detection limit (LOD) of 3.79 nM. Employing a smartphone, the fluorescence color change demonstrated by the hydrogel sensor was translated into quantitative data (LOD: 8.44 nM). This hydrogel sensor offers an affordable, portable, and user-friendly solution for sulfite detection and food safety monitoring.

4.
Int J Biol Macromol ; 281(Pt 3): 136448, 2024 Oct 09.
Artículo en Inglés | MEDLINE | ID: mdl-39389488

RESUMEN

In this study, probiotics with superior fermentation performance were screened, and the mixed-bacteria fermentation was carried out with Auricularia auricula treated with microwave-puffed process as fermentation substrate, and the changes in nutritional quality under different storage conditions were investigated. The results showed that the acid and bile salt resistance of Lactiplantibacillus plantarum 21,801 and 21,805 reached 95 % and 75 % respectively, and the intestinal adhesion was superior; microwave puffing treatment had the highest retention rate of A. auricula polysaccharides and the lowest loss of polyphenols, and no effect on soluble protein. Mixed bacterial fermentation significantly increased the total polyphenols and total flavonoids of A. auricula (p < 0.05), and the DPPH and ABTS radical scavenging reached 48.31 % and 73.21 % respectively. Furthermore, the viable counts, DPPH radical scavenging, color, and sensory quality of fermented A. auricula remained stable when stored at 4 °C. In contrast, when stored at 25 °C for 7 days, the taste was unfavorable, undesirable odor and spoilage occurred; by 21 days, DPPH clearance rate dropped below 40 % and color changed significantly (△E > 2). In conclusion, the probiotic mixed fermentation and storage conditions had a significant effect on the biometabolic transformation of macromolecules and other substances in A. auricula.

5.
Neuropharmacology ; 262: 110193, 2024 Oct 16.
Artículo en Inglés | MEDLINE | ID: mdl-39424168

RESUMEN

Empathy for pain encompasses the processes of perceiving, understanding, and responding to the pain of others, playing a crucial role in social interaction and individual development. The increasing interest in this field has led to a surge in related publications; however, the overall quantity and quality of these works remain uncertain. To address this issue, we conducted a bibliometric analysis of research on empathy for pain. Our study meticulously examined 479 publications to provide a comprehensive analysis of bibliographic elements such as annual publication trends, authorship, country of origin, institutional affiliations, journals, and keywords. Our findings indicate that, although there has been a rise in research on empathy for pain in recent years, the volume remains insufficient and is predominantly concentrated in a few countries, authors, and institutions. Additionally, current research mainly focuses on four primary areas: perception, pain, empathy, and emotion. We assert that future research will likely explore the relationship between EEG measurements and empathy for pain to determine if such measurements can effectively quantify empathy, thereby enhancing clinical management.

6.
Huan Jing Ke Xue ; 45(9): 5149-5156, 2024 Sep 08.
Artículo en Chino | MEDLINE | ID: mdl-39323133

RESUMEN

To examine the underlying determinants of ozone (O3) in Yinchuan's urban park during varying seasons and to ascertain the role played by meteorological events and air contaminants in influencing O3 concentrations at high altitudes, data on O3, meteorological factors, and air pollutants were collected through prolonged positional observations carried out at the Ningxia Yinchuan National Urban Ecosystem Research Station. Pearson correlation analysis and a structural equation model were utilized to investigate the spatio-temporal distribution patterns, trends, and the primary factors influencing O3. The findings demonstrated a notable seasonal variability in O3 levels in Yinchuan's urban park, displaying an "unimodal type" with the O3 concentration peaking in summer (131.18 µg·m-3) and bottoming out in winter (71.45 µg·m-3). Among the meteorological factors, the highest impact on O3 was attributed to temperature and wind speed (temperature mainly through direct effects and wind speed mainly through indirect effects). Conversely, air pollutants such as NOx and SO2 greatly affected O3 primarily through direct effects. Wind speed was identified as the primary influencing factor on O3 during spring and summer, potentially contributing 29% and 24.7%, respectively. Conversely, NO2 was implicated as the primary factor during autumn and winter, with an estimated contribution of 26.6% and 29.7%, respectively. Thus, a structural equation model can efficiently reveal the primary determinants behind O3 variations throughout various seasons, which could furnish a scientifically rigorous foundation and technical aid for mitigating and managing O3 levels in high-altitude regions.

7.
J Voice ; 2024 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-39306499

RESUMEN

Crying is one of the primary means by which infants communicate with their environment in the early stages of life. These cries can be triggered by physiological factors such as hunger or sleepiness, or by pathological factors such as illness or discomfort. Therefore, analyzing infant cries can assist inexperienced parents in better caring for their babies. Most studies have predominantly utilized a single-speech feature, such as Mel Frequency Cepstral Coefficients (MFCC), for classifying infant cries, while other speech features, such as Mel Spectrogram and Tonnetz, are often overlooked. In this study, we manually designed a hybrid feature set, MMT (including MFCC, Mel Spectrogram, and Tonnetz), and explored its application in infant cry classification. Additionally, we proposed a convolutional neural network based on residual connections and long short-term memory (LSTM) networks, termed ResLSTM. We compared the performance of different deep learning models using the hybrid feature set MMT and the single MFCC feature. This study utilized the Baby Crying, Dunstan Baby Language, and Donate a Cry datasets. The results indicate that the hybrid feature set MMT outperforms the single MFCC feature. The MMT combined with the ResLSTM method achieved the best performance, obtaining accuracy rates of 94.15%, 92.92%, and 95.98% on the three datasets, respectively.

8.
NPJ Precis Oncol ; 8(1): 211, 2024 Sep 27.
Artículo en Inglés | MEDLINE | ID: mdl-39333690

RESUMEN

Cellular prion protein (PrPC) has been implicated in carcinogenic through the activation of various signal pathways, however, the precise mechanisms remain elusive. In vitro studies have shown that PrPC is prone to undergo liquid-liquid phase separation (LLPS). However, it remains unknown whether PrPC contributes to LLPS-inducing cancer development. Herein, we observed an upregulation of PrPC expression in hepatitis B virus-positive hepatocellular carcinoma (HCC). Subsequent investigation revealed that HBx of HBV enhances PrPC expression in a dose-dependent manner by binding to CREB1. Furthermore, we demonstrated that PrPC undergoes LLPS and recruits TRAF2/6, TAB2/3, and TAK1 protein, thereby activating the NF-κB signaling pathway and promoting tumor progression. Notably, although unable to undergo LLPS itself, the α3 helix of PrPC is essential for its activation of the NF-κB signaling pathway during the LLPS process. Further analysis unveiled that disulfide bond formation within the C-terminal domain of PrPC is necessary for its LLPS and subsequent activation of the NF-κB signaling pathway. Additionally, our findings indicate that NF-κB activation by PrPC condensates leads to increased IL-8 expression which further promotes tumor development.

9.
BMC Surg ; 24(1): 265, 2024 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-39285467

RESUMEN

BACKGROUND: Early postoperative mobilization is important for enhanced recovery but can be hindered by orthostatic intolerance. However, study on postoperative orthostatic intolerance in thoracoscopic lung resection is limited. Thus, this investigation aims to examine the prevalence and variables contributing to orthostatic intolerance on the first day following thoracoscopic lung cancer resection. METHODS: A prospective observational study was conducted from February 01 to May 05, 2023, at the First Affiliated Hospital of Chongqing Medical University. Typically, 215 subjects subjected to thoracoscopic lung resection were enrolled in this study. Their general information, disease, and treatment information were collected, and the occurrence of orthostatic intolerance was recorded. RESULTS: Typically, 64 patients (29.77%) demonstrated orthostatic intolerance during early mobilization, and 43.75% failed to walk. The prevalence of nausea, dizziness, and impaired vision was 60.94%, 92.19%, and 25.00%, respectively, and no patient experienced syncope. The factors shown to be independently linked with orthostatic intolerance were being female (OR = 2.98, 1.53 to 5.82) and high pain level during sitting (OR = 2.69, 1.79 to 4.04). Individuals with orthostatic intolerance had a longer postoperative hospital stay with a mean of 5.42 days against 4.25 days (p = 0.003). CONCLUSIONS: Orthostatic intolerance was prevalent following thoracoscopic lung cancer resection and affected patients' capability to mobilize and prolonged postoperative hospitalization. Being female and having high pain levels during sitting were identified as independent factors for orthostatic intolerance. This suggests that more emphasis should be given to risky patients, and for these groups, we may optimize pain management to adjust the risk of emerging orthostatic intolerance, facilitating early mobilization and early postoperative rehabilitation.


Asunto(s)
Ambulación Precoz , Neoplasias Pulmonares , Intolerancia Ortostática , Neumonectomía , Complicaciones Posoperatorias , Humanos , Femenino , Masculino , Estudios Prospectivos , Persona de Mediana Edad , Neoplasias Pulmonares/cirugía , Intolerancia Ortostática/etiología , Intolerancia Ortostática/epidemiología , Neumonectomía/efectos adversos , Neumonectomía/métodos , Anciano , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Cirugía Torácica Asistida por Video/métodos , Cirugía Torácica Asistida por Video/efectos adversos , Prevalencia , Adulto , Tiempo de Internación/estadística & datos numéricos
10.
Virol J ; 21(1): 231, 2024 Sep 27.
Artículo en Inglés | MEDLINE | ID: mdl-39334422

RESUMEN

PURPOSE: Peginterferon alfa-2b (Peg-IFN α-2b) has demonstrated superior efficacy over nucleos(t)ide analogs (NAs) in the treatment of chronic hepatitis B (CHB), particularly among patients with low levels of hepatitis B surface antigen (HBsAg). This study aims to determine whether patients with ultra-low HBsAg levels (< 200 IU/mL) can achieve significantly higher clinical cure rates with abbreviated courses of Peg-IFN α-2b therapy. METHODS: In this retrospective analysis, CHB patients with HBsAg levels below 200 IU/mL were categorized into a Peg-IFN α-2b group and a control group. The Peg-IFN α-2b group received Peg-IFN α-2b for a minimum of 24 weeks, with the possibility of early discontinuation upon achieving HBsAg clearance, and were followed through week 48. The control group remained untreated for hepatitis B virus (HBV), and was observed for 24 weeks. HBsAg clearance rates were compared between groups. Univariate and multivariate logistic regression analyses were employed to identify factors associated with HBsAg clearance . RESULTS: By week 24, the HBsAg clearance rate in the Peg-IFN α-2b group was notably 52.1% (38/73), contrasting sharply with the mere 1.3% (1/77) observed in the control group. Within the Peg-IFN α-2b group, a substantial 97.3% (71/73) of patients noted a reduction in HBsAg levels. Besides, the decision to continue or discontinue treatment after the 24-week mark had no significant impact on the HBsAg clearance rate at week 48. Multivariable analysis pinpointed baseline HBsAg levels (OR = 0.984, p = 0.001) and the presence of fatty liver (OR = 5.960, p = 0.033) as independent predictors of HBsAg clearance. CONCLUSION: Our findings confirm that a 24-week course of Peg-IFN α-2b yields robust efficacy in CHB patients with ultra-low HBsAg levels. Prolonging treatment beyond the 24-week threshold is deemed unnecessary. Both baseline HBsAg level and the presence of fatty liver emerged as significant predictors for HBsAg clearance.


Asunto(s)
Antivirales , Antígenos de Superficie de la Hepatitis B , Hepatitis B Crónica , Interferón alfa-2 , Interferón-alfa , Polietilenglicoles , Proteínas Recombinantes , Humanos , Hepatitis B Crónica/tratamiento farmacológico , Estudios Retrospectivos , Proteínas Recombinantes/uso terapéutico , Proteínas Recombinantes/administración & dosificación , Masculino , Polietilenglicoles/uso terapéutico , Polietilenglicoles/administración & dosificación , Antígenos de Superficie de la Hepatitis B/sangre , Femenino , Interferón-alfa/uso terapéutico , Antivirales/uso terapéutico , Adulto , Interferón alfa-2/uso terapéutico , Interferón alfa-2/administración & dosificación , Persona de Mediana Edad , Resultado del Tratamiento , Virus de la Hepatitis B/efectos de los fármacos , Adulto Joven
11.
Heliyon ; 10(16): e36341, 2024 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-39262948

RESUMEN

In field hydraulic fracturing operation of shale gas development, the high pressure and large displacement liquid-particle two-phase fracturing fluid can be forced to change direction many times through high-pressure double-elbow, and be transported from the outlet pipeline of the fracturing pump to the main pipeline. The high-pressure double-elbow is prone to be affected by erosion wear and Fluid-Structure Interaction (FSI), resulting in perforation and fracture, posing a potential safety threat to field operation. In this study, we conducted the erosion wear experiments on 35CrMo steel used for high-pressure double-elbow in shale-gas fracturing. The erosion rates under different impact angles and flow velocities were obtained, and proposed a novel model of erosion prediction for high-pressure double-elbow. Then the numerical investigation was employed to conduct a comprehensive analysis of erosion wear, structural stress and deformation by the coupling of Computational Fluid Dynamics (CFD) and Finite Element Analysis (FEA). The effects of structural parameters such as connection straight pipe length, pipe inner diameter and fluid turning direction were discussed. The results indicate that with the increase of connection straight pipe length, the flow erosion decreases first then varies little, and the deformation gradually increases. Slight erosion wear but large structural stress and deformation in major inner diameter pipe. And the minimum degree of erosion and flow-induced deformation present with the fluid turning direction of double-elbow as 0°. The study can provide references for the design, installation and detection of high-pressure double-elbow and ensure safety in the process of shale gas fracturing.

12.
Mater Today Bio ; 28: 101200, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39221207

RESUMEN

Triple-negative breast cancer (TNBC) is characterized by higher recurrence rate and mortality. Thermally-mediated ablation via photothermal therapy (PTT) demonstrates considerable promise for the eradication of breast cancer. Nonetheless, the efficacy of PTT is impeded by the thermal tolerance of tumor cells, which is attributed to the augmented expression of heat shock proteins (HSPs). These proteins, which function as ATP-dependent molecular chaperones, confer protection to cancer cells against the cytotoxic heat generated during PTT. Glycolysis is an important way for breast cancer cells to produce ATP, which can promote the occurrence and development of lung metastasis of breast cancer. Therefore, inhibiting glycolysis may diminish the expression of HSPs, curtail the growth of breast cancer, and prevent its metastasis. Glycolytic metabolism plays a pivotal role in the ATP biosynthesis within breast cancer cells, facilitating the progression and dissemination of pulmonary metastases. Consequently, targeting glycolysis presents a strategic approach to HSP expression, the proliferation of breast cancer, and impede its metastatic spread. Herein, we designed an indocyanine green (ICG) and cryptotanshinone (CTS) loaded hyaluronic acid (HA) coated Zeolitic Imidazolate Framework-8 (ZIF-8) drug delivery system. The drug delivery system had excellent photothermal properties, which could reach temperature sufficient for photothermal ablation of tumor cells. (ICG + CTS)@HA-ZIF-8 also showed pH-responsive drug release, enhancing the sustained release of ICG and CTS to extend their systemic circulation duration. Moreover, the HA modification of ZIF-8 served to augment its targeting capabilities both in vitro and in vivo, leveraging the enhanced permeation and retention (EPR) effect, as well as active tumor targeting via the CD44 receptor pathway, resulting in a higher drug concentration and a better therapeutic effect in tumor. (ICG + CTS)@HA-ZIF-8 could downregulate the expression of glycolysis-related protein pyruvate kinase-M2 (PKM2), thereby inhibiting the glycolysis process, further suppressing tumor cell energy metabolism, downregulating the expression of HSPs, overcoming tumor cell heat resistance, and improving PTT effect. It exhibited a notable suppressive impact on both the proliferation and migration of breast cancer cells, potentially offering innovative insights for the visualized PTT in breast cancer treatment.

13.
Orphanet J Rare Dis ; 19(1): 360, 2024 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-39350127

RESUMEN

The diagnosis of fibrodysplasia ossificans progressiva is missed or delayed because of its insidious precursors, especially in uncharacteristic cases. Fibrodysplasia ossificans progressiva, which mostly displayed the mutation c.617G > A, p.R206H, is characterized by congenital malformation of the great toe and progressive extra-skeletal ossification of ligaments, tendons and muscles. The mutation c.774G > C, p.R258S (HGVS: NC_000002.11:g.158626896 C > G) in activin A receptor type I is an infrequent etiology of fibrodysplasia ossificans progressiva and can present different clinical features. Awareness of these multiple clinical features will help endocrinologists in the early diagnosis of fibrodysplasia ossificans progressiva. We report a case of fibrodysplasia ossificans progressiva with the activin A receptor type I mutation c.774G > C, p.R258S, which was diagnosed before its ossifying period.


Asunto(s)
Receptores de Activinas Tipo I , Miositis Osificante , Humanos , Receptores de Activinas Tipo I/genética , Mutación , Miositis Osificante/diagnóstico , Miositis Osificante/tratamiento farmacológico , Miositis Osificante/genética
14.
Neuropharmacology ; 261: 110168, 2024 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-39332670

RESUMEN

Placebo analgesia is observed in both humans and animals. Given the complexity of placebo analgesia involving a variety of neurobiological, psychological, and psychosocial processes, further investigation into its underlying mechanisms is essential. Gut microbiota has been implicated in the responsivity of placebo analgesia, but its precise role remains unknown and warrants further investigations. Here, we conducted a conditioning training model with chronic inflammatory pain induced by complete Freund's adjuvant (CFA) in mice, associating parecoxib with different cues. Hierarchical clustering analysis of placebo analgesia behaviors was employed to classify mice into responders and non-responders phenotypes. Approximately 40% of CFA mice undergoing conditioning training exhibited placebo analgesia. Notably, placebo analgesia responders displayed reduced anxiety-like behaviors. 16S rRNA results revealed a distinct composition of gut microbiota composition among the control, placebo analgesia non-responders and responders groups. Notably, levels of Escherichia Shigella and Klebsiella in the gut were increased considerably in the placebo analgesia responders as compared to both control and non-responders groups. In conclusion, placebo analgesia responders demonstrated marked analgesia, reduced anxiety-like behaviors, and increased levels of Escherichia-Shigella and Klebsiella, implying a potential linkage between gut microbiota and placebo analgesia.


Asunto(s)
Microbioma Gastrointestinal , Klebsiella , Microbioma Gastrointestinal/fisiología , Microbioma Gastrointestinal/efectos de los fármacos , Animales , Ratones , Masculino , Klebsiella/efectos de los fármacos , Analgesia/métodos , Ratones Endogámicos C57BL , Efecto Placebo , Ansiedad/microbiología , Adyuvante de Freund , Shigella/efectos de los fármacos , Dolor Crónico/microbiología , Dolor Crónico/psicología , Inflamación
15.
Anim Biosci ; 2024 Aug 26.
Artículo en Inglés | MEDLINE | ID: mdl-39210800

RESUMEN

Objective: This study was designed to reveal the role of nuclear poly(A) binding protein 1 (PABPN1) in the proliferation of preadipocytes, and to reveal the relationship between PABPN1 and cAMP response element (CRE)-binding protein (CREB) in the regulation of preadipocyte proliferation. Methods: Vectors overexpressing and siRNAs against PABPN1/CREB were transiently transfected into both porcine preadipocytes and mouse 3T3-L1 cells. Preadipocyte proliferation was measured with CCK-8, EdU, real-time quantitative PCR, Western blotting, and flow cytometry analyses. Additionally, the transcriptional regulation of CREB on PABPN1 were analyzed with dual-luciferase reporter gene and EMSA assays. Results: Overexpression of PABPN1 inhibits, and knockdown of PABPN1 promotes, the proliferation of both porcine preadipocytes and 3T3-L1 cell lines. PABPN1 overexpression increased, while knockdown decreased, the cell population in the G0/G1 phase. These indicates that PABPN1 repressed preadipocyte proliferation by inhibiting cell cycle progress. Additionally, it was revealed that CREB regulated the expression of PABPN1 through binding to the promoter and that CREB inhibited preadipocyte proliferation by repressed cell cycle progress. Furthermore, we showed that PABPN1 functions as a downstream gene of CREB to regulate the proliferation of preadipocytes. Conclusion: PABPN1 inhibits preadipocyte proliferation by suppressing the cell cycle. We also found that CREB could promote PABPN1 expression by binding to a motif in the promoter. Further analysis confirmed that PABPN1 functions as a downstream gene of CREB to regulate the proliferation of preadipocytes. These results suggest that the CREB/PABPN1 axis plays a role in the regulation of preadipocyte proliferation, which will contribute to further revealing the mechanism of fat accumulation.

16.
Int J Biol Macromol ; 278(Pt 4): 134798, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39153678

RESUMEN

Histone lysine demethylase (KDM), AlkB homolog (ALKBH), and Ten-Eleven Translocation (TET) proteins are members of the 2-Oxoglutarate (2OG) and ferrous iron-dependent oxygenases, each of which harbors a catalytic domain centered on a double-stranded ß-helix whose topology restricts the regions directly involved in substrate binding. However, they have different catalytic functions, and the deeply structural biological reasons are not yet clear. In this review, the catalytic domain features of the three protein families are summarized from both sequence and structural perspectives. The construction of the phylogenetic tree and comparison of the structure show ten relatively conserved ß-sheets and three key regions with substantial structural differences. We summarize the relationship between three key regions of remarkable differences and the substrate compatibility of the three protein families. This review facilitates research into substrate-selective inhibition and bioengineering by providing new insights into the catalytic domains of KDM, ALKBH, and TET proteins.


Asunto(s)
Dominio Catalítico , Ácidos Cetoglutáricos , Ácidos Cetoglutáricos/metabolismo , Ácidos Cetoglutáricos/química , Humanos , Modelos Moleculares , Filogenia , Especificidad por Sustrato , Hierro/química , Hierro/metabolismo , Animales , Histona Demetilasas/química , Histona Demetilasas/metabolismo , Secuencia de Aminoácidos
17.
Ecotoxicol Environ Saf ; 283: 116793, 2024 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-39094453

RESUMEN

Biomass-related airborne fine particulate matter (PM2.5) is an important risk factor for chronic obstructive pulmonary disease (COPD). Macrophage polarization has been reported to be involved in PM2.5-induced COPD, but the dynamic characteristics and underlying mechanism of this process remain unclear. Our study established a PM2.5-induced COPD mouse model and revealed that M2 macrophages predominantly presented after 4 and 6 months of PM2.5 exposure, during which a notable increase in MMP12 was observed. Single cell analysis of lung tissues from COPD patients and mice further revealed that M2 macrophages were the dominant macrophage subpopulation in COPD, with MMP12 being involved as a hub gene. In vitro experiments further demonstrated that PM2.5 induced M2 polarization and increased MMP12 expression. Moreover, we found that PM2.5 increased IL-4 expression, STAT6 phosphorylation and nuclear translocation. Nuclear pSTAT6 then bound to the MMP12 promoter region. Furthermore, the inhibition of STAT6 phosphorylation effectively abrogated the PM2.5-induced increase in MMP12. Using a coculture system, we observed a significantly reduced level of E-cadherin in alveolar epithelial cells cocultured with PM2.5-exposed macrophages, while the decrease in E-cadherin was reversed by the addition of an MMP12 inhibitor to the co-culture system. Taken together, these findings indicated that PM2.5 induced M2 macrophage polarization and MMP12 upregulation via the IL-4/STAT6 pathway, which resulted in alveolar epithelial barrier dysfunction and excessive extracellular matrix (ECM) degradation, and ultimately led to COPD progression. These findings may help to elucidate the role of macrophages in COPD, and suggest promising directions for potential therapeutic strategies.


Asunto(s)
Interleucina-4 , Macrófagos , Metaloproteinasa 12 de la Matriz , Material Particulado , Enfermedad Pulmonar Obstructiva Crónica , Factor de Transcripción STAT6 , Regulación hacia Arriba , Enfermedad Pulmonar Obstructiva Crónica/inducido químicamente , Metaloproteinasa 12 de la Matriz/metabolismo , Animales , Material Particulado/toxicidad , Factor de Transcripción STAT6/metabolismo , Ratones , Macrófagos/efectos de los fármacos , Humanos , Masculino , Ratones Endogámicos C57BL , Modelos Animales de Enfermedad , Transducción de Señal/efectos de los fármacos , Contaminantes Atmosféricos/toxicidad
18.
Medicine (Baltimore) ; 103(34): e39373, 2024 Aug 23.
Artículo en Inglés | MEDLINE | ID: mdl-39183392

RESUMEN

Hepatic viral infections and breast cancer (BC) constitute major global health challenges, yet the interconnection between these hepatic infections and BC continues to be ambiguous. Conducting a comprehensive evaluation of the link between hepatitis virus infection and the incidence of BC and leveraging data from the National Health and Nutrition Examination Survey covering the period from 1999 to March 2022, we utilized logistic regression and subgroup analysis, among other methodologies, to execute a cross-sectional investigation. The univariate logistic regression analysis elucidates that individuals classified as non-Hispanic White exhibit a markedly higher incidence of BC at 2.620 (95% confidence interval [CI], 1.117-7.676; P = .045); moreover, advanced age at 1.063 (95% CI, 1.036-1.093; P < .001), elevated educational attainment at 1.962 (95% CI, 1.17-3.366; P = .012), and higher income levels at 2.835 (95% CI, 1.303-7.439; P = .017) emerge as significant predisposing factors for BC. In contrast, a greater number of live births significantly diminishes the risk of BC, reducing the incidence to 81.1% with each additional birth. Pertaining to hepatitis and vaccination status, our analysis distinctly demonstrates that only hepatitis B at 0.110 (95% CI, 0.018-0.353; P = .002) bears a significant inverse relationship with BC risk, suggesting a protective effect. The multivariate logistic regression analysis further reveals a negative association between hepatitis B infection and BC incidence, whereas hepatitis B vaccination shows a positive correlation with the disease incidence. After adjusting for all covariates, model 3 delineates odds ratios (95% CI) as follows: 0.14 (0.02-0.50; P = .009) and 1.92 (0.99-3.62; P = .046). Our investigation uncovers that within the general populace, there exists an inverse correlation between hepatitis B infection and BC incidence; in addition, the administration of the hepatitis B virus vaccine is potentially positively associated with the prevalence of BC.


Asunto(s)
Neoplasias de la Mama , Hepatitis B , Encuestas Nutricionales , Humanos , Femenino , Neoplasias de la Mama/epidemiología , Incidencia , Hepatitis B/epidemiología , Hepatitis B/prevención & control , Persona de Mediana Edad , Estados Unidos/epidemiología , Adulto , Estudios Transversales , Factores de Riesgo , Modelos Logísticos , Anciano
19.
Medicine (Baltimore) ; 103(34): e39426, 2024 Aug 23.
Artículo en Inglés | MEDLINE | ID: mdl-39183429

RESUMEN

Obturator hernia (OH) is a rare and dangerous disease that can lead to life-threatening consequences, and pelvic computed tomography (CT) is widely used for its diagnosis. There is no consensus regarding the surgical approach and repair methods. Retrospective analysis of the clinical and follow-up data of 15 cases of incarcerated hernias patients admitted to the Department of General Surgery, affiliated to Taicang Affiliated Hospital of Soochow University, from January 2011 to December 2022. OH could be precisely diagnosed with pelvic CT scan, except for occult OH and non-strangulated OH. Thirteen patients underwent emergency surgery, with a total complication rate of 76.9% and no mortality. Ten patients underwent open surgery, and 3 patients underwent laparoscopic surgery, which had advantages in terms of total cost and postoperative hospital stay (P < .05). Emergency patients all underwent simple peritoneal closure, and hernial sac excision was simultaneously performed in 6 of them. A recurrence (7.7%) was detected at 38 months after the first operation. There was no statistically significant difference between the 2 tissue repair methods in terms of recurrent rate. Pelvic CT can be used as a gold standard for the diagnosis of incarcerated OH, but it has limited value in occult OH and non-strangulated OH. Laparoscopic surgery is recommended for patients with a short onset time and no abdominal physical signs. Tissue repair is sufficient for incarcerated OH and hernial sac excision may be unnecessary.


Asunto(s)
Hernia Obturadora , Herniorrafia , Laparoscopía , Tomografía Computarizada por Rayos X , Humanos , Hernia Obturadora/cirugía , Hernia Obturadora/diagnóstico por imagen , Hernia Obturadora/complicaciones , Hernia Obturadora/diagnóstico , Masculino , Femenino , Estudios Retrospectivos , Anciano , Laparoscopía/métodos , Persona de Mediana Edad , Estudios de Seguimiento , Herniorrafia/métodos , Anciano de 80 o más Años , Recurrencia , Tiempo de Internación/estadística & datos numéricos , Complicaciones Posoperatorias/epidemiología , Adulto , Resultado del Tratamiento
20.
Front Endocrinol (Lausanne) ; 15: 1217250, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39104815

RESUMEN

Background: Gallbladder mixed neuroendocrine-non-neuroendocrine neoplasm generally consists of a gallbladder neuroendocrine tumor and a non-neuroendocrine component. The World Health Organization (WHO) in 2019 established a guideline requiring each component, both neuroendocrine and non-neuroendocrine, to account for a minimum of 30% of the tumor mass. Methods: Patients after surgery resection and diagnosed at microscopy evaluation with pure gallbladder neuroendocrine carcinoma (GBNEC), gallbladder mixed adeno-neuroendocrine carcinoma (GBMANEC, GBNEC≥30%), and gallbladder carcinoma mixed with a small fraction of GBNEC (GBNEC <30%) between 2010 and 2022 at West China Hospital of Sichuan University were collated for the analyses. Demographic features, surgical variables, and tumor characteristics were evaluated for association with patients' overall and recurrence-free survival (OS and RFS). Results: The study included 26 GBNEC, 11 GBMANEC, 4 gallbladder squamous-cell carcinoma (GBSCC), and 7 gallbladder adenocarcinoma (GBADC) mixed with a small fraction of GBNEC. All patients had stage III or higher tumors (AJCC8th edition). The majority of included patients (79.17%) underwent curative surgical resection (R0), with only ten patients having tumoral resection margins. In the analysis comparing patients with GBNEC percentage (GBNEC≥30% vs. GBNEC<30%), the basic demographics and tumor characteristics of most patients were comparable. The prognosis of these patients was also comparable, with a median OS of 23.65 months versus 20.40 months (P=0.13) and a median RFS of 17.1 months versus 12.3 months (P=0.24). However, patients with GBADC or GBSCC mixed with GBNEC <30% had a statistically significant decreased OS and RFS (both P<0.0001)) compared with GBNEC and GBMANEC. Patients with GBNEC who exhibited advanced tumor stages and lymphovascular invasion had a higher risk of experiencing worse overall survival (OS) and recurrence-free survival (RFS). However, a 30% GBNEC component was not identified as an independent risk factor. Conclusion: Patients with GBNEC were frequently diagnosed at advanced stages and their prognosis is poor. The 30% percentage of the GBNEC component is not related to the patient's survival.


Asunto(s)
Carcinoma Neuroendocrino , Neoplasias de la Vesícula Biliar , Humanos , Neoplasias de la Vesícula Biliar/patología , Neoplasias de la Vesícula Biliar/mortalidad , Neoplasias de la Vesícula Biliar/cirugía , Femenino , Masculino , Persona de Mediana Edad , Pronóstico , Carcinoma Neuroendocrino/patología , Carcinoma Neuroendocrino/mortalidad , Carcinoma Neuroendocrino/cirugía , Carcinoma Neuroendocrino/diagnóstico , Anciano , Adulto , Estudios Retrospectivos , Adenocarcinoma/patología , Adenocarcinoma/mortalidad , Adenocarcinoma/cirugía , Tasa de Supervivencia
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