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1.
Immunity ; 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38614091

RESUMO

A specialized population of mast cells residing within epithelial layers, currently known as intraepithelial mast cells (IEMCs), was originally observed over a century ago, yet their physiological functions have remained enigmatic. In this study, we unveil an unexpected and crucial role of IEMCs in driving gasdermin C-mediated type 2 immunity. During helminth infection, αEß7 integrin-positive IEMCs engaged in extensive intercellular crosstalk with neighboring intestinal epithelial cells (IECs). Through the action of IEMC-derived proteases, gasdermin C proteins intrinsic to the epithelial cells underwent cleavage, leading to the release of a critical type 2 cytokine, interleukin-33 (IL-33). Notably, mast cell deficiency abolished the gasdermin C-mediated immune cascade initiated by epithelium. These findings shed light on the functions of IEMCs, uncover a previously unrecognized phase of type 2 immunity involving mast cell-epithelial cell crosstalk, and advance our understanding of the cellular mechanisms underlying gasdermin C activation.

2.
Sci Total Environ ; 927: 172156, 2024 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-38588742

RESUMO

The variability and intrinsic mechanisms of oxidative stress induced by microplastics at different trophic levels in freshwater food chains are not well understood. To comprehensively assess the oxidative stress induced by polystyrene microplastics (PS-MPs) in freshwater food chains, the present study first quantified the oxidative stress induced by PS-MPs in organisms at different trophic levels using factorial experimental design and molecular dynamics methods. Then focuses on analyzing the variability of these responses across different trophic levels using mathematical statistical analysis. Notably, higher trophic level organisms exhibit diminished responses under PS-MPs exposure. Furthermore, the coexistence of multiple additives was found to mask these responses, with antioxidant plastic additives significantly influencing oxidative stress responses. Mechanism analysis using computational chemistry simulation determines that protein structure and amino acid characteristics are key factors driving PS-MPs induced oxidative stress variation in freshwater organisms at different nutrient levels. Increased hydrophobic additives induce protein helicalization and amino acid residue aggregation. This study systematically reveals the variability of biological oxidative stress response under different nutrient levels, emphasizing the pivotal role of chemical additives. Overall, this study offers crucial insights into PS-MPs' impact on oxidative stress responses in freshwater ecosystems, informing future environmental risk assessment.

3.
Int J Biol Macromol ; 266(Pt 2): 131283, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38561119

RESUMO

Glycosaminoglycan (GAG) lyases are important tools for investigating the structure of GAGs and preparing low-molecular-weight GAGs. The PL35 family, a recently established polysaccharide lyase family, should be further investigated. In this study, we discovered a new GAG lyase, CHa1, which belongs to the PL35 family. When expressed heterologously in Escherichia coli (BL21), CHa1 exhibited high expression levels and solubility. The optimal activity was observed in Tris-HCl buffer (pH 7.0) or sodium phosphate buffer (pH 8.0) at 30 °C. The specific activities towards HA, CSA, CSC, CSD, CSE, and HS were 3.81, 13.03, 36.47, 18.46, 6.46, and 0.50 U/mg protein, respectively. CHa1 digests substrate chains randomly that acting as an endolytic lyase and shows a significant preference for GlcA-containing structures, prefers larger oligosaccharides (≥UDP8) and can generate a series of oligosaccharides composed mainly of the A unit when digesting CSA. These oligosaccharides include ΔC-A, ΔC-A-A, ΔC-A-A-A, ΔC-A-A-A-A, and ΔC-A-A-A-A-A. The residues Tyr257 and His421 play crucial roles in the catalytic process, and Ser211, Asn212, Asn213, Trp214, Gln216, Lys360, Arg460 and Gln462 may participate in the binding process of CHa1. This study on CHa1 contributes to our understanding of the PL35 family and provides valuable tools for investigating the structure of GAGs.

4.
Gynecol Oncol Rep ; 53: 101394, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38646445

RESUMO

Clear cell carcinoma is a rare and very aggressive subset of cervical cancer, with poor outcome if diagnosed at advanced stage. There are few data available on the optimal management of this histotype, and treatment recommendations that include surgery and chemoradiotherapy, are essentially based on those for squamous cell carcinoma. Here we report the case of a young patient newly diagnosed with advanced stage (FIGO IIB) clear cell carcinoma of the uterine cervix who received a window of opportunity one injection of nivolumab followed by standard chemoradiotherapy. She showed a persistent complete remission after 28 months of follow-up, but developed hypothyroidism, as a consequence of immunotherapy, and required lifelong thyroid hormone replacement.

5.
BMC Biol ; 22(1): 54, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38448930

RESUMO

BACKGROUND: Gut bacteria are beneficial to the host, many of which must be passed on to host offspring. During metamorphosis, the midgut of holometabolous insects undergoes histolysis and remodeling, and thus risks losing gut bacteria. Strategies employed by holometabolous insects to minimize this risk are obscure. How gut bacteria affect host insects after entering the hemocoel and causing opportunistic infections remains largely elusive. RESULTS: We used holometabolous Helicoverpa armigera as a model and found low Lactobacillus load, high level of a C-type lectin (CTL) gene CD209 antigen-like protein 2 (CD209) and its downstream lysozyme 1 (Lys1) in the midgut of the wandering stage. CD209 or Lys1 depletion increased the load of midgut Lactobacillus, which further translocate to the hemocoel. In particular, CD209 or Lys1 depletion, injection of Lactobacillus plantarum, or translocation of midgut L. plantarum into the hemocoel suppressed 20-hydroxyecdysone (20E) signaling and delayed pupariation. Injection of L. plantarum decreased triacylglycerol and cholesterol storage, which may result in insufficient energy and 20E available for pupariation. Further, Lysine-type peptidoglycan, the major component of gram-positive bacterial cell wall, contributed to delayed pupariation and decreased levels of triacylglycerols, cholesterols, and 20E, in both H. armigera and Drosophila melanogaster. CONCLUSIONS: A mechanism by which (Lactobacillus-induced) opportunistic infections delay insect metamorphosis was found, namely by disturbing the homeostasis of lipid metabolism and reducing 20E production. Moreover, the immune function of CTL - Lys was characterized for insect metamorphosis by maintaining gut homeostasis and limiting the opportunistic infections.


Assuntos
Microbioma Gastrointestinal , Lisina , Animais , Drosophila melanogaster , Disbiose , Bactérias , Imunidade
6.
Pharmaceutics ; 16(3)2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38543277

RESUMO

Nonsteroidal anti-inflammatory drugs (NSAIDs) are class II biopharmaceutics classification system drugs. The poor aqueous solubility of NSAIDs can lead to limited bioavailability after oral administration. Metformin (MET), a small-molecule compound, can be used in crystal engineering to modulate the physicochemical properties of drugs and to improve the bioavailability of orally administered drugs, according to the literature research and preliminary studies. We synthesized two drug-drug molecular salts (ketoprofen-metformin and phenylbutazone-metformin) with NSAIDs and thoroughly characterized them using SCXRD, PXRD, DSC, and IR analysis to improve the poor solubility of NSAIDs. In vitro evaluation studies revealed that the thermal stability and solubility of NSAIDs-MET were substantially enhanced compared with those of NSAIDs alone. Unexpectedly, an additional increase in permeability was observed. Since the structure determines the properties, the structure was analyzed using theoretical calculations to reveal the intermolecular interactions and to explain the reason for the change in properties. The salt formation of NSAIDs with MET could substantially increase the bio-absorption rate of NSAIDs, according to the in vivo pharmacokinetic findings, which provides an experimental basis for developing new antipyretic and analgesic drugs with rapid onset of action.

7.
J Affect Disord ; 354: 603-610, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38503356

RESUMO

BACKGROUND: Previous observational studies have highlighted potential links between the consumption of processed meat and red meat (such as pork, mutton, and beef intake) and the occurrence of mental disorders. However, it is unclear whether a causal association exists. Therefore, we employed the Mendelian randomization (MR) study to investigate the causal effects of genetically predicted processed meat and red meat on mood disorders (MD), anxiety disorders (AD), and major depressive disorder (MDD). METHODS: Genetic instruments for processed and red meat were selected from the Genome-Wide Association Study (GWAS) of the UK Biobank Study. Their associations with MD (42,746 cases 254,976), AD (35,385 cases and 254,976 controls), and MDD (38,225 cases and 299,886 controls) were obtained from the FinnGen Consortium. The inverse variance weighted (IVW) method was the primary method for two-sample MR analysis. Additionally, we employed complementary analysis to assess the robustness of our MR findings (eg, MR Egger and weighted median). We also conducted multiple sensitivity analyses to investigate horizontal pleiotropy and heterogeneity. Moreover, we performed a univariate and multivariable MR (MVMR) study to evaluate these associations. RESULTS: In our univariate MR analysis, we observed that genetically predicted beef intake was associated with a reduced risk of MD [odds ratio (OR) = 0.403, 95 % confidence interval (CI) = 0.246-0.659; PIVW = 4.428 × 10-5], AD (OR = 0.443, 95 % CI = 0.267-0.734; PIVW = 1.563 × 10-3), and MDD (OR = 0.373, 95 % CI = 0.216-0.643; PIVW = 3.878 × 10-4). After adjusting for processed meat, pork, and mutton intake in the MVMR analysis, the protective association of beef intake against MD and MDD remained. However, there was no substantial evidence indicating a significant causal relationship between processed meat, pork, and mutton intake and the occurrence of mental disorders. Furthermore, our sensitivity analysis revealed no significant evidence of horizontal pleiotropy. CONCLUSION: These findings support a causal relationship between genetically predicted beef intake and reducing the risk of MD and MDD.


Assuntos
Transtorno Depressivo Maior , Transtornos Mentais , Carne Vermelha , Bovinos , Animais , Humanos , Análise da Randomização Mendeliana , Transtorno Depressivo Maior/etiologia , Transtorno Depressivo Maior/genética , Estudo de Associação Genômica Ampla , Carne , Carne Vermelha/efeitos adversos
9.
GMS J Med Educ ; 41(1): Doc10, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38504857

RESUMO

Objective: The outbreak of COVID-19 has disrupted social order and placed a heavy burden on the healthcare system. The pandemic also has an unprecedented impact on medical students. Methods: We searched PubMed for articles related to COVID-19 and medical students from January 2020 to December 2022. A total of 5358 studies were retrieved and after screening, 176 studies were finally included in this review. Results: The impact of COVID-19 on medical students is widespread and profound. First reflected in the transformation of educational models. In the early days, education model quickly shifted from offline to online. In terms of clinical exposure, most students have been suspended from internships, while in some areas with staff shortages they have the opportunity to continue clinical work. Scientific research of medical students is also difficult to carry out due to COVID-19. The epidemic has also seriously damaged students' mental health, and this impact won't simply disappear with the improvement of the epidemic situation. The career intentions of medical students may also become firmer or change due to COVID-19. International medical electives have also been negatively affected by COVID-19 due to travel restriction. Even in the postpandemic era, with the gradual resumption of work, production and school, medical students are still affected in some ways by COVID-19. Conclusion: The COVID-19 pandemic has had a profound impact on both the education of medical students and their personal development. Through COVID-19, we should reflect on what models of medical education should be developed in the future. Based on the experiences learned from COVID-19, we believe that a more flexible blended education model may be the most promising.


Assuntos
COVID-19 , Educação Médica , Estudantes de Medicina , Humanos , COVID-19/epidemiologia , Pandemias , Surtos de Doenças
10.
Medicine (Baltimore) ; 103(11): e36871, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38489732

RESUMO

This study aimed to investigate nursing strategies for patients with non-muscle invasive bladder cancer (NMIBC) undergoing postoperative intravesical instillation. We recruited 100 NMIBC patients from January 2017 to January 2022. Participants were randomly assigned to either the research group or the control group (n = 50 each) using random number tables. The control group received routine nursing interventions, while the research group received integrated nursing interventions. We compared and analyzed various parameters, including patient satisfaction, treatment compliance, General Self-Efficacy Scale (GSES) scores, core quality of life scale scores, bladder carcinoma specificity scale scores, disease coping scores, and the incidence of complications among patients undergoing instillation treatment. The research group exhibited significantly higher satisfaction scores and treatment compliance (P < .05). Additionally, GSES, Self-Rating Anxiety Scale (SAS), and Self-Rating Depression Scale (SDS) scores were significantly improved in the research group (P < .05). Scores on each dimension of the EORTC QLQ-C30 were higher (P < .05). The research group also had lower scores for post-nursing urinary system diseases, treatment problems, future worries, and intestinal symptoms in the QLQ-BLS24 score (P < .05). Furthermore, the research group experienced fewer postoperative complications (P < .05). Nursing interventions significantly enhance the outcomes of NMIBC patients undergoing intravesical instillation treatment. These interventions effectively improve treatment compliance, alleviate negative emotions, modify coping strategies, reduce the incidence of complications, and enhance overall nursing satisfaction.


Assuntos
Neoplasias não Músculo Invasivas da Bexiga , Neoplasias da Bexiga Urinária , Humanos , Administração Intravesical , Qualidade de Vida , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/cirurgia , Neoplasias da Bexiga Urinária/patologia , Satisfação do Paciente
11.
Sci Bull (Beijing) ; 2024 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-38531718

RESUMO

Atmospheric water harvesting (AWH) is a promising solution to the water shortage problem. Current sorption-based AWH (SAWH) systems seldom obtain both wide climatic adaptability and high energy efficiency due to the lack of thermodynamic optimization. To achieve the ideal harvesting circulation in SAWH systems, the "optimal harvesting window" (OHW) design based on thermodynamic analysis was first proposed and validated by our prototype. The "OHW" theory indicates the water production rate and energy efficiency could be improved by properly reducing the adsorption temperature. As the humidity increases, the optimal adsorption temperature should be closer to the dew point of the environment. Experimental results revealed that, loaded with 3 kg widely adopted silica gel, the daily water production could reach 5.76-17.64 L/d with ultrahigh energy efficiency of 0.46-1.5 L/kWh. This prototype could also achieve optimal performance in wide climatic conditions in terms of 13-35 °C and 18%-72% RH. Lastly, the performance of photovoltaic (PV)-driven SAWH was evaluated. Results showed that a 1 m2 PV panel could generate 0.66-2 L water per day in Shanghai throughout the year, the highest in opening literature. Notably, this work introduces a promising concept that can help achieve large-scale, ultra-fast, energy-efficient AWH worldwide.

12.
Hum Genet ; 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38526745

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) is a malignant tumor with poor prognosis and high mortality. Although a large number of studies have explored its potential prognostic markers using traditional RNA sequencing (RNA-Seq) data, they have not achieved good prediction effect. In order to explore the possible prognostic signaling pathways leading to the difference in prognosis, we identified differentially expressed genes from one scRNA-seq cohort and four GEO cohorts, respectively. Then Cox and Lasso regression analysis showed that 12 genes were independent prognostic factors for PDAC. AUC and calibration curve analysis showed that the prognostic model had good discrimination and calibration. Compared with the low-risk group, the high-risk group had a higher proportion of gene mutations than the low-risk group. Immune infiltration analysis revealed differences in macrophages and monocytes between the two groups. Prognosis related genes were mainly distributed in fibroblasts, macrophages and type 2 ducts. The results of cell communication analysis showed that there was a strong communication between cancer-associated fibroblasts (CAF) and type 2 ductal cells, and collagen formation was the main interaction pathway.

13.
Shock ; 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38526135

RESUMO

BACKGROUND: Postresuscitation cardiac dysfunction is a significant contributor to early death following cardiopulmonary resuscitation (CPR). Therapeutic hypothermia (TH) mitigates myocardial dysfunction due to cardiac arrest (CA); however, the underlying mechanism remains unclear. Sirtuin 3 (Sirt3) was found to affect autophagic activity in recent research, motivating us to investigate its role in the cardioprotective effects of TH in the treatment of CA. METHODS: Sprague-Dawley rats were used to establish an in vivo CA/CPR model and treated with a selective Sirt3 inhibitor or vehicle. Survival rate, myocardial function, autophagic flux, and Sirt3 expression and activity were evaluated. H9C2 cells were subjected to oxygen-glucose deprivation/reoxygenation (OGD/R) injury in vitro. The cells were transfected with Sirt3-siRNA and treated with the autophagy inhibitor chloroquine or the PI3K inhibitor LY294002, and cell viability and autophagic flux were assessed. RESULTS: Rats exhibited decreased survival and impaired cardiac function after CA/CPR, which were alleviated by TH. Mechanistically, TH restored Sirt3 expression and autophagic flux which were impaired by CA/CPR. Sirt3 inactivation diminished the capacity of TH to restore autophagic flux and partially abolished the improvements in myocardial function and survival. An in vitro study further showed that TH-induced restoration of disrupted autophagic flux by OGD/R was attenuated by pretreatment with Sirt3-siRNA, and this attenuation was partially rescued by the inhibition of PI3K/Akt/mTOR signaling cascades. CONCLUSIONS: Sirt3 mediates the cardioprotective effect of TH by restoring autophagic flux via the PI3K/Akt/mTOR pathway. These findings suggest the potential of Sirt3 as a therapeutic target for CA.

15.
Sci Rep ; 14(1): 5073, 2024 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-38429378

RESUMO

Vitamin C played pleiotropic roles in critical illness and vitamin C insufficiency was predictive of the development of multiple organ failure. Currently, the prevalence of vitamin C insufficiency in Chinese critically ill patients is rarely determined and there are no established bedside tools to predict hypovitaminosis C. To develop a nomogram to identify patients with high risk of hypovitaminosis C, we performed a bi-center prospective cohort study at two ICUs of the first and sixth medical center in PLA General Hospital, Beijing, China from May 6th to July 31st, 2021 We identified 322 eligible patients. 62.4% patients were hypovitaminosis C. 7 features, including source of infection, the level of serum albumin, age, male gender, sepsis, vascular disease, and wasting of vitamin C by the kidney, were selected using LASSO algorithm and therefore included in the nomogram. In the testing set, our model showed moderate discrimination ability with areas under the curve of 0.75 [0.64-0.84]. Variable importance evaluated by SHAP value highlighted two novel important predictors, i.e., abdominal infection and the level of serum albumin. In conclusion, we first reported a high burden of vitamin C insufficiency in Chinese adult patient in the ICU. We also constructed a prediction model to timely identify patients with high risk of hypovitaminosis C, which allows the clinicians to choose appropriate candidates for Vitamin C repletion in clinical practice or clinical trials.


Assuntos
Deficiência de Vitaminas , Estado Terminal , Adulto , Humanos , Masculino , Estudos Prospectivos , Vitaminas , Ácido Ascórbico , Algoritmos , Hospitais Gerais , Unidades de Terapia Intensiva , Albumina Sérica , Cuidados Críticos
16.
World J Clin Cases ; 12(5): 995-1003, 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38414609

RESUMO

BACKGROUND: A solitary fibrous tumor (SFT) is often located in the pleura, while SFT of the pancreas is extremely rare. Here, we report a case of SFT of the pancreas and discuss imaging, histopathology, and immunohistochemistry for accurate diagnosis and treatment. CASE SUMMARY: A 54-year-old man presented to our hospital with pancreatic occupancy for over a month. There were no previous complaints of discomfort. His blood pressure was normal. Blood glucose, tumor markers, and enhanced computed tomography (CT) suggested a malignant tumor. Because the CT appearance of pancreatic cancer varies, we could not confirm the diagnosis; therefore, we performed endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB). Pathology and immunohistochemistry were consistent with SFT of the pancreas. The postoperative pathology and immunohistochemistry were consistent with the puncture results. The patient presented for a follow-up examination one month after discharge with no adverse effects. CONCLUSION: Other diseases must be excluded in patients with a pancreatic mass that cannot be diagnosed. CT and pathological histology have diagnostic value for pancreatic tumors. Endoscopic puncture biopsy under ultrasound can help diagnose pancreatic masses that cannot be diagnosed preoperatively. Surgery is an effective treatment for SFT of the pancreas; however, long-term follow-up is strongly recommended because of the possibility of malignant transformation of the tumor.

17.
Nature ; 627(8004): 586-593, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38355797

RESUMO

Over half of hepatocellular carcinoma (HCC) cases diagnosed worldwide are in China1-3. However, whole-genome analysis of hepatitis B virus (HBV)-associated HCC in Chinese individuals is limited4-8, with current analyses of HCC mainly from non-HBV-enriched populations9,10. Here we initiated the Chinese Liver Cancer Atlas (CLCA) project and performed deep whole-genome sequencing (average depth, 120×) of 494 HCC tumours. We identified 6 coding and 28 non-coding previously undescribed driver candidates. Five previously undescribed mutational signatures were found, including aristolochic-acid-associated indel and doublet base signatures, and a single-base-substitution signature that we termed SBS_H8. Pentanucleotide context analysis and experimental validation confirmed that SBS_H8 was distinct to the aristolochic-acid-associated SBS22. Notably, HBV integrations could take the form of extrachromosomal circular DNA, resulting in elevated copy numbers and gene expression. Our high-depth data also enabled us to characterize subclonal clustered alterations, including chromothripsis, chromoplexy and kataegis, suggesting that these catastrophic events could also occur in late stages of hepatocarcinogenesis. Pathway analysis of all classes of alterations further linked non-coding mutations to dysregulation of liver metabolism. Finally, we performed in vitro and in vivo assays to show that fibrinogen alpha chain (FGA), determined as both a candidate coding and non-coding driver, regulates HCC progression and metastasis. Our CLCA study depicts a detailed genomic landscape and evolutionary history of HCC in Chinese individuals, providing important clinical implications.


Assuntos
Carcinoma Hepatocelular , Genoma Humano , Sequenciamento de Nucleotídeos em Larga Escala , Neoplasias Hepáticas , Mutação , Sequenciamento Completo do Genoma , Humanos , Ácidos Aristolóquicos/metabolismo , Carcinogênese , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/virologia , China , Cromotripsia , Progressão da Doença , DNA Circular/genética , População do Leste Asiático/genética , Evolução Molecular , Genoma Humano/genética , Vírus da Hepatite B/genética , Mutação INDEL/genética , Fígado/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/virologia , Mutação/genética , Metástase Neoplásica/genética , Fases de Leitura Aberta/genética , Reprodutibilidade dos Testes
18.
Poult Sci ; 103(3): 103377, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38301496

RESUMO

Ovarian follicle development depends on the proliferation and differentiation of granulosa cells and is a complex biological process. The Wnt/ß-catenin signaling pathway can regulate ovarian follicle development, and ß-catenin, encoded by catenin beta 1 (CTNNB1), is the core component of this pathway. Although several studies of the mechanisms by which the Wnt/ß-catenin pathway regulates cell proliferation in humans and mammals have reported, it remains unclear how ß-catenin functions in poultry. To investigate the function of ß-catenin in laying hens' follicle development, we evaluated the effect of CTNNB1 on cell cycle, proliferation, and apoptosis in ovarian granulosa cells (GCs) isolated from laying hens. We demonstrated that CTNNB1 significantly affected the expression of cyclin D1 (CCND1) and v-myc avian myelocytomatosis viral oncogene homolog (c-Myc) (P < 0.01 and P < 0.05), key genes related to cell cycle and proliferation, to promote cell cycle progression from G1 to S phase, and thus accelerate granulosa cell proliferation. CTNNB1 did not however affect apoptosis or the expression of related genes baculoviral IAP repeat containing 5 (BIRC5) and BCL2 apoptosis regulator (Bcl-2). Overexpression of transcription factor 7-like 2 (TCF4) resulted in increased expression of CCND1, accelerated cell cycle progression, and granulosa cell proliferation. Direct physical interaction between ß-catenin and TCF4 was demonstrated by immunofluorescence and coimmunoprecipitation. The proliferation of granulosa cells was inhibited by silencing CCND1; overexpression of TCF4 in CCND1-silenced cells restored their proliferation rate to normal levels. These results indicate that the interaction of TCF4 and ß-catenin promotes CCND1 expression which in turn accelerates the cell cycle process of laying hen hierarchical follicular granulosa cells.


Assuntos
Galinhas , beta Catenina , Humanos , Animais , Feminino , beta Catenina/genética , Galinhas/genética , Apoptose , Proliferação de Células , Células da Granulosa , Mamíferos , Fator de Transcrição 4/genética
19.
Eur Geriatr Med ; 2024 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-38349508

RESUMO

PURPOSE: Frailty is reportedly associated with postoperative adverse outcomes and may increase the risk of post-surgical pain. Our study aimed to explore whether frailty was an independent risk factor for pain after total knee arthroplasty (TKA) in older patients. METHODS: Included in this prospective observational study were patients aged 65 or older who underwent primary TKA. Frailty of the patients was assessed before surgery using the comprehensive geriatric assessment-frailty index and pain was evaluated before and after surgery using the Numerical Rating Scale. RESULTS: Of the 164 patients including 125 females with a mean age of 71.4 ± 4.6 years, 51 patients were identified as being frail. Patients with chronic post-surgical pain had a significantly higher frailty index than those without chronic post-surgical pain, which was the same in patients with acute post-surgical pain. After adjusting for other confounding factors, frailty was shown to be an independent risk factor for both acute (OR: 13.23, 95% CI 3.73-46.93, P < 0.001) and chronic post-surgical pain (OR: 4.24, 95% CI 1.29-14.00, P = 0.02). The area under the receiver operating characteristic curve for frailty predicting chronic post-surgical pain was 0.73 (P < 0.001, 95% CI 0.65-0.81). CONCLUSIONS: Our findings demonstrated that preoperative frailty in older patients was a predictor of acute and chronic post-surgical pain after TKA, suggesting that frailty assessment should become a necessary procedure before operations, especially in older patients.

20.
J Mol Cell Biol ; 2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38389254

RESUMO

Although the dynamic instability of microtubules (MTs) is fundamental to many cellular functions, quiescent MTs with unattached free distal ends are commonly present and play important roles in various events to power cellular dynamics. However, how these free MT tips are stabilized remains poorly understood. Here, we report that centrosome and spindle pole protein 1 (CSPP1) caps and stabilizes both plus and minus ends of static MTs. Real-time imaging of laser-ablated MTs in live cells showed deposition of CSPP1 at the newly generated MT ends, whose dynamic instability was concomitantly suppressed. Consistently, MT ends in CSPP1-overexpressing cells were hyper-stabilized, while those in CSPP1-depleted cells were much more dynamic. This CSPP1-elicited stabilization of MTs was demonstrated to be achieved by suppressing intrinsic MT catastrophe and restricting the polymerization. Importantly, CSPP1-bound MTs were resistant to MCAK-mediated depolymerization. These findings delineate a previously uncharacterized CSPP1 activity that integrates MT end capping to orchestrate quiescent MTs.

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