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1.
Anim Reprod Sci ; 270: 107605, 2024 Sep 27.
Article de Anglais | MEDLINE | ID: mdl-39362062

RÉSUMÉ

Bovine embryos by in vitro fertilization have become the primary source of commercial embryo transfers globally. However, the developmental capacity of in vitro maturation (IVM) oocytes is considerably lower than that of in vivo maturation (IVO) oocytes, owing to the production of reactive oxygen species (ROS) via mitochondrial metabolism, which was higher in IVM oocytes than in IVO oocytes. To avoid the negative effects of ROS on embryo quality, folic acid (FA) was supplemented directly into the IVM medium to antagonize ROS production, however, the mechanisms remain unknown. In the present study, five levels of FA (0, 25, 50, 100, and 200 µM) were supplemented into the bovine oocyte culture medium. The maturation, cleavage, and blastocyst formation rates increased by 8.95 %, 6.94 %, and 4.36 %, respectively, in the 50 µM group compared to the 0 µM group. Moreover, 7904 differential genes were identified between 0 µM and 50 µM groups by transcriptome sequencing, and they were mainly enriched in 8 pathways. The glutathione, ROS, and Fe2+ levels in oocytes were found to be associated with ferroptosis. Our results revealed that 50 µM FA promoted the IVM of bovine oocytes and affected the expression of genes involved in the ferroptosis pathway. The downregulation of TFR1 and STEAP3 led to a decrease in intracellular Fe2+ accumulation, and the upregulation of GCL increased oocyte GSH levels, thereby reducing the production of ROS in the ferroptosis pathway. Our study provides a new insight into the molecular mechanisms by which FA promotes bovine oocyte development in vitro.

2.
Reprod Biomed Online ; 49(6): 104326, 2024 Jun 21.
Article de Anglais | MEDLINE | ID: mdl-39389002

RÉSUMÉ

RESEARCH QUESTION: Does LncRNA BANCR promote the malignant transformation of endometriosis by activating the miR-612/CPNE3 pathway? DESIGN: The expression patterns of BANCR, miR-612 and CPNE3 in normal endometrium, eutopic endometrium from endometriosis, eutopic endometrium or malignant tissues from endometriosis-associated ovarian cancer. On the basis of primary normal endometrial stromal cells (NESC) and eutopic endometrial stromal cells (EESC), the regulatory relationships between BANCR, miR-612 and CPNE3, and the potential mechanisms that promote the malignant transformation of endometriosis, were elucidated in vitro and in vivo. RESULTS: The expression levels of BANCR and CPNE3 were lowest in normal endometrium, significantly increased in eutopic endometrium (P < 0.05) and was significantly increased in eutopic endometrium (P < 0.05). During the malignant transformation of endometriosis, the expression levels of BANCR and CPNE3 were significantly upregulated (P < 0.05), whereas those of miR-612 were significantly downregulated (P < 0.05). miRNA-612 was found to target BANCR and CPNE3. The overexpression and knockdown of BANCR in NESC and EESC upregulated and downregulated the expression of CPNE3 and promoted or prevented cell proliferation and migration, respectively; these effects were reversed by miR-612 mimics and inhibitor. These changes were all statistically significant (P < 0.05). In-vivo experiments revealed that BANCR significantly increased the survival of subcutaneous endometrial cells by regulating miR-612/CPNE3 (P < 0.05). CONCLUSION: The expression of BANCR gradually increased with the progression of endometriosis during malignant transformation, and promoted the proliferation and migration of endometrial cells via the miR-612/CPNE3 pathway. BANCR may represent a novel target for monitoring the malignant transformation of endometriosis.

3.
J Control Release ; 2024 Oct 07.
Article de Anglais | MEDLINE | ID: mdl-39384152

RÉSUMÉ

Mild autophagy accompanied with immunogenic cell death (ICD) effect destructs immune-associated antigens, weakening the immune response against tumor growth. To address this dilemma, we develop a peptide-based bicomponent nanocarrier with encapsulation of a cellular hyperautophagy activator (STF-62247) for near-infrared (NIR) photo/immunotherapy to eliminate primary and metastatic breast tumors. The electrostatic-driven nanodrug (PPNPs@STF) with active-targeting and efficient endosomal escape can induce specific ICD effect upon NIR laser irradiation, and trigger autophagy to a mild activation state. Notably, the simultaneously released STF-62247 precisely promotes autophagy to an overactivated state, resulting in autophagic death of tumor cells and further boosting ICD-related antigen presentation. More importantly, the combined photo/immunotherapy of PPNPs@STF not only inhibits tumor cell proliferation, but also promotes dendritic cells (DCs)-associated immune response. In 4 T1 tumor-bearing mice, PPNPs@STF effectively inhibits growth of primary and distant tumors, and suppresses lung metastasis with a minimized side effect. This study provides a hyperautophagy activator-assisted strategy that can enhance ICD-based antitumor immune response for the treatment of metastatic breast cancer.

4.
Trends Genet ; 2024 Sep 13.
Article de Anglais | MEDLINE | ID: mdl-39277449

RÉSUMÉ

Hydrothermal vents are unique habitats like an oases of life compared with typical deep-sea, soft-sediment environments. Most animals that live in these habitats are invertebrates, and they have adapted to extreme vent environments that include high temperatures, hypoxia, high sulfide, high metal concentration, and darkness. The advent of next-generation sequencing technology, especially the coming of the new era of omics, allowed more studies to focus on the molecular adaptation of these invertebrates to vent habitats. Many genes linked to hydrothermal adaptation have been studied. We summarize the findings related to these genetic adaptations and discuss which new techniques can facilitate studies in the future.

5.
Nat Commun ; 15(1): 7801, 2024 Sep 12.
Article de Anglais | MEDLINE | ID: mdl-39266520

RÉSUMÉ

The mixed-valence compound YbB12 displays paradoxical quantum oscillations in electrical resistivity and magnetic torque in a regime with a well-developed insulating charge gap and in the absence of an electronic Fermi surface. However, signatures of such unusual fermionic quasiparticles in other bulk thermodynamic observables have been missing. Here we report the observation of a series of sharp double-peak features in the specific heat as a function of the magnetic field. The measured Hall resistivity evolves smoothly across the field values at which the characteristic anomalies appear in the thermodynamic response and rules out the possibility of conventional electrons as their origin. Our observations of thermodynamic anomalies in a bulk three-dimensional electrical insulator provide the evidence for the presence of emergent dispersing fermionic excitations within the insulating bulk, which sets the stage for further investigation of electron fractionalization in other correlated mixed-valence compounds.

6.
ACS Nano ; 18(37): 25671-25684, 2024 Sep 17.
Article de Anglais | MEDLINE | ID: mdl-39223995

RÉSUMÉ

Combined photodynamic and photothermal therapy (PDT and PTT) can achieve more superior therapeutic effects than the sole mode by maximizing the photon utilization, but there remains a significant challenge in the development of related single-molecule photosensitizers (PSs), particularly those with type I photosensitization. In this study, self-assembly of squaraine dyes (SQs) is shown to be a promising strategy for designing PSs for combined type I PDT and PTT, and a supramolecular PS (TPE-SQ7) has been successfully developed through subtle molecular design of an indolenine SQ, which can self-assemble into highly ordered H-aggregates in aqueous solution as well as nanoparticles (NPs). In contrast to the typical quenching effect of H-aggregates on reactive oxygen species (ROS) generation, our results encouragingly manifest that H-aggregates can enhance type I ROS (•OH) generation by facilitating the intersystem crossing process while maintaining a high PTT performance. Consequently, TPE-SQ7 NPs with ordered H-aggregates not only exhibit superior combined therapeutic efficacy than the well-known PS (Ce6) under both normoxic and hypoxic conditions but also have excellent biosafety, making them have important application prospects in tumor phototherapy and antibacterial fields. This study not only proves that the supramolecular self-assembly of SQs is an effective strategy toward high-performance PSs for combined type I PDT and PTT but also provides a different understanding of the effect of H-aggregates on the PDT performance.


Sujet(s)
Cyclobutanes , Phénols , Photothérapie dynamique , Photosensibilisants , Thérapie photothermique , Espèces réactives de l'oxygène , Photosensibilisants/composition chimique , Photosensibilisants/pharmacologie , Humains , Cyclobutanes/composition chimique , Cyclobutanes/pharmacologie , Phénols/composition chimique , Phénols/pharmacologie , Espèces réactives de l'oxygène/métabolisme , Souris , Animaux , Survie cellulaire/effets des médicaments et des substances chimiques , Nanoparticules/composition chimique , Antinéoplasiques/composition chimique , Antinéoplasiques/pharmacologie , Structures macromoléculaires/composition chimique , Structures macromoléculaires/pharmacologie , Structures macromoléculaires/synthèse chimique
7.
Heliyon ; 10(18): e37858, 2024 Sep 30.
Article de Anglais | MEDLINE | ID: mdl-39323799

RÉSUMÉ

Thalassemia is a hemoglobin disease characterized by reduced or complete absence of the production of the α/ß globin gene. Currently, the detection of ß-thalassemia carriers is based on differences in blood cell parameters. However, ß-thalassemia carriers cannot be distinguished from α- and ß-thalassemia co-inherited carriers based solely on hematological findings, and the differential diagnosis must rely on molecular diagnosis. We report a 32-year-old male from Yunnan Province, who had abnormal hemoglobin E without obvious anemia. A rare αCS (CD142, TAA→CAA) combined with a ßE (CD26, GAG→AAG) double heterozygous mutation was identified in the proband by PCR-reverse dot blot (PCR-RDB) and DNA sequencing. Additionally, a family lineage analysis was performed. This study complements the spectrum of rare thalassemia gene variants and is critical for clinical genetic counseling.

8.
Cell Prolif ; : e13732, 2024 Sep 27.
Article de Anglais | MEDLINE | ID: mdl-39331585

RÉSUMÉ

Neurogenesis is the process of generating new neurons from neural stem cells (NSCs) and plays a crucial role in neurological diseases. The process involves a series of steps, including NSC proliferation, migration and differentiation, which are regulated by multiple pathways such as neurotrophic Trk and fibroblast growth factor receptors (FGFR) signalling. Despite the discovery of numerous compounds capable of modulating individual stages of neurogenesis, it remains challenging to identify an agent that can regulate multiple cellular processes of neurogenesis. Here, through screening of bioactive compounds in dietary functional foods, we identified a flavonoid chrysin that not only enhanced the human NSCs proliferation but also facilitated neuronal differentiation and neurite outgrowth. Further mechanistic study revealed the effect of chrysin was attenuated by inhibition of neurotrophic tropomyosin receptor kinase-B (TrkB) receptor. Consistently, chrysin activated TrkB and downstream ERK1/2 and AKT. Intriguingly, we found that the effect of chrysin was also reduced by FGFR1 blockade. Moreover, extended treatment of chrysin enhanced levels of brain-derived neurotrophic factor, as well as FGF1 and FGF8. Finally, chrysin was found to promote neurogenesis in human cerebral organoids by increasing the organoid expansion and folding, which was also mediated by TrkB and FGFR1 signalling. To conclude, our study indicates that activating both TrkB and FGFR1 signalling could be a promising avenue for therapeutic interventions in neurological diseases, and chrysin appears to be a potential candidate for the development of such treatments.

9.
J Agric Food Chem ; 72(37): 20496-20512, 2024 Sep 18.
Article de Anglais | MEDLINE | ID: mdl-39239930

RÉSUMÉ

Acute kidney injury (AKI) is characterized by a sudden decline in renal function. The inflammatory response is the fundamental pathologic alteration throughout AKI, regardless of the various causal factors. Macrophages are the main immune cells involved in the inflammatory microenvironment in AKI. Consequently, targeting macrophages might become a novel strategy for the treatment of AKI. In this study, we demonstrated that pseudoginsenoside-F11 (PF11), a distinctive component of Panax quinquefolius L., regulated macrophage function and protected renal tubular epithelial cells TCMK-1 from lipopolysaccharide (LPS) in vitro. PF11 also alleviated renal injuries in an LPS-induced AKI mouse model, decreased the levels of inflammatory cytokines, reduced macrophage inflammatory infiltration, and promoted the polarization of M1 macrophages to M2c macrophages with suppression of the nuclear factor-κB/NOD-like receptor thermal protein domain-associated protein 3/interleukin-1ß (NF-κB/NLRP3/IL-1ß) signaling pathway. To further investigate whether this nephroprotective effect of PF11 is mediated by macrophages, we performed macrophage depletion by injection of clodronate liposomes in mice. Macrophage depletion abolished PF11's ability to protect against LPS-induced kidney damage with downregulating the NF-κB/NLRP3/IL-1ß signaling pathway. In summary, this is the first study providing data on the efficacy and mechanism of PF11 in the treatment of AKI by regulating macrophage function.


Sujet(s)
Atteinte rénale aigüe , Ginsénosides , Lipopolysaccharides , Macrophages , Transduction du signal , Animaux , Humains , Mâle , Souris , Atteinte rénale aigüe/traitement médicamenteux , Atteinte rénale aigüe/induit chimiquement , Atteinte rénale aigüe/immunologie , Atteinte rénale aigüe/métabolisme , Ginsénosides/pharmacologie , Ginsénosides/administration et posologie , Interleukine-1 bêta/génétique , Interleukine-1 bêta/immunologie , Interleukine-1 bêta/métabolisme , Lipopolysaccharides/effets indésirables , Macrophages/effets des médicaments et des substances chimiques , Macrophages/immunologie , Souris de lignée C57BL , Facteur de transcription NF-kappa B/génétique , Facteur de transcription NF-kappa B/métabolisme , Facteur de transcription NF-kappa B/immunologie , Protéine-3 de la famille des NLR contenant un domaine pyrine/métabolisme , Protéine-3 de la famille des NLR contenant un domaine pyrine/génétique , Protéine-3 de la famille des NLR contenant un domaine pyrine/immunologie , Panax/composition chimique , Transduction du signal/effets des médicaments et des substances chimiques
10.
Animals (Basel) ; 14(16)2024 Aug 15.
Article de Anglais | MEDLINE | ID: mdl-39199906

RÉSUMÉ

Mastitis (MAS), endometritis (MET), and ketosis (KET) are prevalent diseases in dairy cows that result in substantial economic losses for the dairy farming industry. This study gathered 26,014 records of the health and sickness of dairy cows and 99,102 data of reproduction from 13 Holstein dairy farms in Central China; the milk protein and milk fat content from 56,640 milk samples, as well as the pedigree data of 37,836 dairy cows were obtained. The logistic regression method was used to analyze the variations in the prevalence rates of MAS, MET, and KET among various parities; the mixed linear model was used to examine the effects of the three diseases on milk production, milk quality, and reproductive traits. DMU software (version 5.2) utilized the DMUAI module in conjunction with the single-trait and two-trait animal model, as well as best linear unbiased prediction (BLUP), to estimate the genetic parameters for the three diseases, milk production, milk quality, and reproductive traits in dairy cows. The primary findings of the investigation comprised the following: (1) The prevalence rates of MAS, MET, and KET in dairy farms were 20.04%, 10.68%, and 7.33%, respectively. (2) MAS and MET had a substantial impact (p < 0.01) on milk production, resulting in significant decreases of 112 kg and 372 kg in 305-d Milk Yield (305-d MY), 4 kg and 12 kg in 305-d Protein Yield (305-d PY), and 6 kg and 16 kg in 305-d Fat Yield (305-d FY). As a result of their excessive 305-d MY, some cows were diagnosed with KET due to glucose metabolism disorder. The 305-d MY of cows with KET was significantly higher than that of healthy cows (205 kg, p < 0.01). (3) All three diseases resulted in an increase in the Interval from Calving to First Service (CTFS, 0.60-1.50 d), Interval from First Service to Conception (FSTC, 0.20-16.20 d), Calving Interval (CI, 4.00-7.00 d), and Number of Services (NUMS, 0.07-0.35). (4) The heritabilities of cows with MAS, MET, and KET were found to be low, with values of 0.09, 0.01, and 0.02, respectively. The genetic correlation between these traits ranged from 0.14 to 0.44. This study offers valuable insights on the prevention and control of the three diseases, as well as feeding management and genetic breeding.

11.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 32(4): 1078-1084, 2024 Aug.
Article de Chinois | MEDLINE | ID: mdl-39192401

RÉSUMÉ

OBJECTIVE: To investigate the anti- chronic myelogenous leukemia (CML) activity of Nur77-specific agonist Csn-B combined with imatinib by promoting Nur77 expression, and explore the potential role of its signaling pathway. METHODS: Firstly, CCK-8 and Transwell assay were used to detect the inhibitory effects of Csn-B, imatinib, and their combination on the proliferation and migration of K562 cells. Furthermore, the apoptosis rate of K562 cells treated with Csn-B, imatinib, and their combination was detected by flow cytometry. The expression levels of Nur77, Pim-1, Drp1, p-Drp1 S616, Bcl-2 and Bax in K562 cells were detected by Western blot. Finally, the expression levels of reactive oxygen species (ROS) in K562 cells treated with Csn-B, imatinib and their combination were detected by immunofluorescence assay. RESULTS: The level of Nur77 in CML patients decreased significantly compared with normal population in dataset of GSE43754 (P < 0.001). Csn-B combined with imatinib could significantly inhibit the proliferation and migration of K562 cells (both P < 0.001), and induce apoptosis (P < 0.001). Csn-B promoted Nur77 expression in K562 cells, and synergistically enhanced imatinib sensitivity when combined with imatinib. Csn-B combined with imatinib could significantly enhanced ROS levels in K562 cells and mitochondria compared with single-drug treatment (both P < 0.001). CONCLUSION: Csn-B combined with imatinib can enhance ROS expression and induce apoptosis of K562 cells through Nur77/Pim-1/Drp1 pathway.


Sujet(s)
Apoptose , Prolifération cellulaire , Mésilate d'imatinib , Leucémie myéloïde chronique BCR-ABL positive , Membre-1 du groupe A de la sous-famille-4 de récepteurs nucléaires , Protéines proto-oncogènes c-pim-1 , Humains , Mésilate d'imatinib/pharmacologie , Membre-1 du groupe A de la sous-famille-4 de récepteurs nucléaires/métabolisme , Leucémie myéloïde chronique BCR-ABL positive/métabolisme , Leucémie myéloïde chronique BCR-ABL positive/traitement médicamenteux , Apoptose/effets des médicaments et des substances chimiques , Cellules K562 , Prolifération cellulaire/effets des médicaments et des substances chimiques , Protéines proto-oncogènes c-pim-1/métabolisme , Dynamines , Transduction du signal , Espèces réactives de l'oxygène/métabolisme , Mouvement cellulaire
12.
Adv Ther ; 41(10): 3792-3806, 2024 Oct.
Article de Anglais | MEDLINE | ID: mdl-39207666

RÉSUMÉ

INTRODUCTION: Concomitant gallbladder and common bile duct (CBD) stones, known as cholecystocholedocholithiasis, are clinically prevalent. There is currently no consensus on sequential versus simultaneous management approaches, and, if simultaneous, which approach to adopt. This meta-analysis evaluates the safety and efficacy of one-stage laparoscopic cholecystectomy (LC) with intraoperative endoscopic retrograde cholangiopancreatography (ERCP) versus two-stage ERCP followed by LC for treating concomitant gallbladder and CBD stones. METHODS: A comprehensive literature search was conducted in five databases, PubMed, Embase, Web of Science, VIP, and Wanfang, for all randomized controlled trials (RCTs), cohort and retrospective studies published up to February 2024. Data extraction was performed independently by two reviewers. The primary outcomes were CBD stone clearance rate and postoperative complications morbidity. Secondary outcomes included conversion to other procedures and length of hospital stay. Statistical analyses were performed using R (v.4.3.2) with weighted mean differences and odds ratios (ORs) calculated for continuous and dichotomous variables, respectively, with 95% confidence intervals (CIs). RESULTS: A total of 17 studies involving 2120 patients have been included, with 898 patients receiving single-stage and 1222 patients undergoing two-stage treatment. Of these studies, 9 were RCTs and 8 were retrospective cohort study. The one-stage group demonstrated superior outcomes in terms of CBD stone clearance (OR = 2.07, p = 0.0004), overall morbidity (OR = 0.35, p < 0.0001), post-operative pancreatitis (OR = 0.49, p = 0.006), conversion to other procedures (OR = 0.38, p = 0.0006), and length of hospital stay (MD = - 2.6456, 95% CI - 3.5776; - 1.7136, p < 0.0001). No significant differences were observed in post-operative cholangitis (OR = 0.44, p = 0.12), post-operative bleeding (OR = 0.76, p = 0.47), or bile leakage (OR = 1.28, p = 0.54). CONCLUSION: For patients with concomitant gallbladder and CBD stones, the one-stage approach combining ERCP and LC appears safer and more effective, with advantages including higher stone clearance rates, reduced postoperative complications (particularly pancreatitis), shorter hospital stays, fewer residual stones, and decreased need for additional procedures. However, additional high-quality clinical trials are needed to establish the optimal treatment approach for various patient scenarios.


Sujet(s)
Cholangiopancréatographie rétrograde endoscopique , Cholécystectomie laparoscopique , Humains , Cholécystectomie laparoscopique/méthodes , Cholécystectomie laparoscopique/effets indésirables , Cholangiopancréatographie rétrograde endoscopique/méthodes , Calculs biliaires/chirurgie , Complications postopératoires/épidémiologie , Durée du séjour/statistiques et données numériques , Lithiase cholédocienne/chirurgie , Résultat thérapeutique , Soins peropératoires/méthodes
13.
J Affect Disord ; 365: 213-221, 2024 Nov 15.
Article de Anglais | MEDLINE | ID: mdl-39154980

RÉSUMÉ

BACKGROUND: The excessive secretion of glucocorticoids resulting from the overactivation of the hypothalamic-pituitary-adrenal axis is a crucial factor in the pathogenesis of depression. RIPK3 plays a significant role in apoptosis and necroptosis. Glucocorticoids have been implicated in directly regulating the expression of RIPK3, leading to apoptosis and necroptosis of osteoblasts. This suggests that RIPK3 may contribute to cell death induced by glucocorticoids. However, the precise involvement of RIPK3 in glucocorticoid-induced depression remains poorly understood. METHODS: In this study, a mouse model of depression was established by repeated corticosterone injections to examine the impact of RIPK3 knockdown on depression-like behavior. Additionally, a corticosterone-induced HT22 injury model was also established to investigate the role of RIPK3 in corticosterone-induced neuronal cell death and underlying mechanisms. RESULTS: Our findings demonstrate that hippocampal RIPK3 knockdown effectively ameliorated depression-related symptoms and restored synaptic plasticity impairment caused by corticosterone. Furthermore, treatment with the RIPK3 inhibitor GSK872 in vitro successfully mitigated corticosterone-induced HT22 cell death. Additionally, the administration of a free radical scavenger alleviated neuronal death and effectively suppressed the expression of corticosterone-induced RIPK3. LIMITATIONS: The limitation of this study is that only the changes of RIPK3 in the hippocampus of depressed male animals were studied. CONCLUSIONS: These results suggest that corticosterone may induce RIPK3-dependent neuronal cell death and impair synaptic plasticity through the generation of high levels of oxidative stress, ultimately leading to depression-like behavior.


Sujet(s)
Corticostérone , Dépression , Modèles animaux de maladie humaine , Régulation négative , Hippocampe , Plasticité neuronale , Neurones , Receptor-Interacting Protein Serine-Threonine Kinases , Animaux , Receptor-Interacting Protein Serine-Threonine Kinases/métabolisme , Receptor-Interacting Protein Serine-Threonine Kinases/génétique , Souris , Plasticité neuronale/effets des médicaments et des substances chimiques , Plasticité neuronale/physiologie , Dépression/métabolisme , Mâle , Neurones/effets des médicaments et des substances chimiques , Hippocampe/effets des médicaments et des substances chimiques , Hippocampe/métabolisme , Comportement animal/effets des médicaments et des substances chimiques , Souris de lignée C57BL , Mort cellulaire/effets des médicaments et des substances chimiques , Apoptose/effets des médicaments et des substances chimiques
14.
Medicine (Baltimore) ; 103(31): e39153, 2024 Aug 02.
Article de Anglais | MEDLINE | ID: mdl-39093744

RÉSUMÉ

BACKGROUND: WD repeat domain 43 (WDR43) is a protein component that encodes WD-repeats and is involved in ribosome biogenesis. However, little is known about the role of WDR43 in cancer prognosis and immune modulation. METHODS: In this study, we analyzed the expression and prognostic significance of WDR43 in pan-cancer using the Cancer Genome Atlas, the Genotype-Tissue Expression, and the Human Protein Atlas. We also examined the differential expression of WDR43 in liver hepatocellular carcinoma (LIHC) and adjacent tissues of 48 patients using immunohistochemistry. Additionally, we investigated the correlation between WDR43 and clinical characteristics, gene alterations, tumor mutation burden, microsatellite instability, mismatch repair, tumor microenvironment, immune infiltrating cells, and immune-related genes using bioinformatics methods. Gene set enrichment analysis was conducted, and potential biological mechanisms were identified. RESULTS: Immunohistochemistry staining showed that WDR43 was overexpressed in LIHC among 48 patients. Upregulation of WDR43 was associated with unfavorable prognosis, including overall survival in various types of cancer such as LIHC, uterine corpus endometrial cancer, head and neck squamous cell carcinoma, and pancreatic adenocarcinoma. Differential expression of WDR43 was significantly correlated with microsatellite instability, mismatch repair, and immune cell infiltration. Gene ontology annotation analysis revealed that these genes were significantly enriched in immune-related functions, including immune response, immune regulation, and signaling pathways. CONCLUSION: We conducted a thorough investigation of the clinical features, phases of tumor development, immune infiltration, gene mutation, and functional enrichment analysis of WDR43 in various types of cancer. This research offers valuable insight into the significance and function of WDR43 in clinical therapy.


Sujet(s)
Marqueurs biologiques tumoraux , Femelle , Humains , Mâle , Adulte d'âge moyen , Marqueurs biologiques tumoraux/génétique , Marqueurs biologiques tumoraux/métabolisme , Carcinome hépatocellulaire/génétique , Carcinome hépatocellulaire/immunologie , Carcinome hépatocellulaire/anatomopathologie , Carcinome hépatocellulaire/mortalité , Régulation de l'expression des gènes tumoraux , Immunohistochimie , Tumeurs du foie/génétique , Tumeurs du foie/immunologie , Tumeurs du foie/anatomopathologie , Tumeurs du foie/mortalité , Lymphocytes TIL/immunologie , Instabilité des microsatellites , Tumeurs/immunologie , Tumeurs/génétique , Tumeurs/anatomopathologie , Pronostic , Microenvironnement tumoral/immunologie , Microenvironnement tumoral/génétique
15.
Small ; : e2403869, 2024 Aug 05.
Article de Anglais | MEDLINE | ID: mdl-39101346

RÉSUMÉ

Cancer metastasis poses significant challenges in current clinical therapy. Osthole (OST) has demonstrated efficacy in treating cervical cancer and inhibiting metastasis. Despite these positive results, its limited solubility, poor oral absorption, low bioavailability, and photosensitivity hinder its clinical application. To address this limitation, a glutathione (GSH)-responded nano-herb delivery system (HA/MOS@OST&L-Arg nanoparticles, HMOA NPs) is devised for the targeted delivery of OST with cascade-activatable nitric oxide (NO) release. The HMOA NPs system is engineered utilizing enhanced permeability and retention (EPR) effects and active targeting mediated by hyaluronic acid (HA) binding to glycoprotein CD44. The cargoes, including OST and L-Arginine (L-Arg), are released rapidly due to the degradation of GSH-responsive mesoporous organic silica (MOS). Then abundant reactive oxygen species (ROS) are produced from OST in the presence of high concentrations of NAD(P)H quinone oxidoreductase 1 (NQO1), resulting in the generation of NO and subsequently highly toxic peroxynitrite (ONOO-) by catalyzing guanidine groups of L-Arg. These ROS, NO, and ONOO- molecules have a direct impact on mitochondrial function by reducing mitochondrial membrane potential and inhibiting adenosine triphosphate (ATP) production, thereby promoting increased apoptosis and inhibiting metastasis. Overall, the results indicated that HMOA NPs has great potential as a promising alternative for the clinical treatment of cervical cancer.

16.
Cogn Neurodyn ; 18(4): 1563-1574, 2024 Aug.
Article de Anglais | MEDLINE | ID: mdl-39104704

RÉSUMÉ

Autism spectrum disorder (ASD) is a general neurodevelopmental disease characterized by unusual social communication and rigid, repetitive behavior patterns. The purpose of this study was to investigate the effects of ASD on the alteration of neural oscillatory patterns and synaptic plasticity, which commonly supported a wide range of basic and higher memory activities. Accordingly, a prenatal valproic acid (VPA) exposure rat model was established for studying autism. The behavioral experiments showed that the social orientation declined and the memory ability was significantly impaired in VPA rats, which was closely associated with the synaptic plasticity deficits. Neural oscillation is the rhythmic neuron-activity, and the pathological characteristics and neurological changes in autism may be peeped at the neural oscillatory analysis. Interestingly, neural oscillatory analysis showed that prenatal VPA exposure reduced the low-frequency power but increased high-frequency gamma (HG) power in the hippocampus CA1 area. Meanwhile, the coherence and synchronization between CA3 and CA1 were abnormally increased in the VPA group, especially in theta and HG rhythms. Furthermore, the cross-frequency coupling strength of theta-LG in the CA1 and CA3 → CA1 pathway was significantly attenuated, but the theta-HG coupling strength was increased. Additionally, prenatal VPA exposure inhibited the expression of SYP and NR2B but enhanced the expression of PSD-95 along with decreased synaptic plasticity. The neural oscillatory patterns in VPA-induced offspring were disturbed with the intensity and direction of neural information flow disordered, which are consistent with the changes in synaptic plasticity, suggesting that the decline in synaptic plasticity is the underlying mechanism.

17.
Adv Mater ; 36(40): e2406987, 2024 Oct.
Article de Anglais | MEDLINE | ID: mdl-39194411

RÉSUMÉ

Radiative cooling technology, which is renowned for its ability to dissipate heat without energy consumption, has garnered immense interest. However, achieving high performance, multifunctionality, and smart integration while addressing challenges such as film thickness and enhancing anisotropic light reflection remains challenging. In this study, a core-shell composite nanofiber, PVDF@PEI, is introduced and designed primarily from a symmetry-breaking perspective to develop highly efficient radiative cooling materials. Using a combination of solvent-induced phase separation (EIPS) inverse spinning and (aggregation) self-assembly methods (EISA or EIAA) and coaxial electrostatic spinning (ES), superconformal surface anisotropic porous nanofiber membranes are fabricated. These membranes exhibit exceptional thermal stability (up to 210 °C), high hydrophobicity (contact angle of 126°), robust UV protection (exceeding 99%), a fluorescence multiplication effect (with a 0.6% increase in fluorescence quantum efficiency), and good breathability. These properties enable the material to excel in a wide range of application scenarios. Moreover, this material achieved a remarkable daytime cooling temperature of 8 °C. The development of this fiber membrane offers significant advancements in the field of wearables and the multifunctionality of materials, paving new paths for future research and innovation.

18.
Immun Inflamm Dis ; 12(7): e1301, 2024 Jul.
Article de Anglais | MEDLINE | ID: mdl-38967361

RÉSUMÉ

OBJECTIVE: Acute pancreatitis (AP) stands as a frequent cause for clinical emergency hospital admissions. The X-box binding protein 1 (XBP1) was found to be implicated in pancreatic acinar cell apoptosis. The objective is to unveil the potential mechanisms governed by XBP1 and SIRT6 in the context of AP. METHODS: Caerulein-treated human pancreatic duct epithelial (HPDE) cells to establish an in vitro research model. The levels and regulatory role of SIRT6 in the treated cells were evaluated, including its effects on inflammatory responses, oxidative stress, apoptosis, and endoplasmic reticulum stress. The relationship between XBP1 and SIRT6 was explored by luciferase and ChIP experiments. Furthermore, the effect of XBP1 overexpression on the regulatory function of SIRT6 on cells was evaluated. RESULTS: Caerulein promoted the decrease of SIRT6 and the increase of XBP1 in HPDE cells. Overexpression of SIRT6 slowed down the secretion of inflammatory factors, oxidative stress, apoptosis level, and endoplasmic reticulum stress in HPDE cells. However, XBP1 negatively regulated SIRT6, and XBP1 overexpression partially reversed the regulation of SIRT6 on the above aspects. CONCLUSION: Our study illuminates the role of XBP1 in downregulating SIRT6 in HPDE cells, thereby promoting cellular injury. Inhibiting XBP1 or augmenting SIRT6 levels holds promise in preserving cell function and represents a potential therapeutic avenue in the management of AP.


Sujet(s)
Apoptose , Régulation négative , Cellules épithéliales , Conduits pancréatiques , Pancréatite , Sirtuines , Protéine-1 liant la boite X , Humains , Sirtuines/métabolisme , Sirtuines/génétique , Cellules épithéliales/métabolisme , Protéine-1 liant la boite X/métabolisme , Protéine-1 liant la boite X/génétique , Pancréatite/métabolisme , Pancréatite/anatomopathologie , Conduits pancréatiques/métabolisme , Conduits pancréatiques/anatomopathologie , Stress du réticulum endoplasmique , Stress oxydatif , Lignée cellulaire , Céruléine/toxicité
19.
Wideochir Inne Tech Maloinwazyjne ; 19(1): 1-10, 2024 Mar.
Article de Anglais | MEDLINE | ID: mdl-38974765

RÉSUMÉ

Introduction: The Pfannenstiel incision is often used in gynecological Cesarean section; however, there is limited research on the use of the Pfannenstiel incision for specimen extraction in laparoscopic surgery for the treatment of colorectal cancer. Aim: To evaluate the safety of using the Pfannenstiel incision for specimen extraction in laparoscopic surgery for colorectal cancer patients. Material and methods: PubMed, Embase, Web of Science, Cochrane Library, CNKI, VIP and WanFangData were searched for studies published up to March 10, 2023; a random-effects model (RCT) and a fixed-effect model were used to evaluate the safety. Operative time, length of extraction skin incision, overall complications, superficial wound infection, organ/space surgical site infection and incisional hernia were evaluated. Results: A total of 5 studies were included in this research. There were no significant advantages in operation time, length of the incision, overall complications, superficial wound infection and organ/space surgical site in the Pfannenstiel group compared to the no Pfannenstiel group. However, the Pfannenstiel incision has a tendency to increase the length of the incision (SMD = 0.05; 95% CI = -0.22 to 0.33; p = 0.71) and the results of the remaining five (operative time,overall complications,incisional hernia, incisional infection and organ/space surgical site infection) are slightly skewed toward the Pfannenstiel incision. It is worth mentioning that incisional hernia (IH) may have an advantage in the Pfannenstiel group compared to the no Pfannenstiel group. Four studies were not at clear risk of bias and two studies were at risk of bias. Conclusions: Our study concludes that the Pfannenstiel incision has a good safety record and it is a good option for extracting specimens during laparoscopic surgery for colon cancer. The Pfannenstiel incision used for laparoscopic surgical specimen extraction has a significantly lower incidence of incisional hernia over no Pfannenstiel.

20.
ACS Nano ; 2024 Jul 15.
Article de Anglais | MEDLINE | ID: mdl-39007545

RÉSUMÉ

The development of cost-efficient, long-lifespan, and all-climate sodium-ion batteries is of great importance for advancing large-scale energy storage but is plagued by the lack of suitable cathode materials. Here, we report low-cost Na-rich Mn-based Prussian blue analogues with superior rate capability and ultralong cycling stability over 10,000 cycles via structural optimization with electrochemically inert Ni atoms. Their thermal stability, all-climate properties, and potential in full cells are investigated in detail. Multiple in situ characterizations reveal that the outstanding performances benefit from their highly reversible three-phase transformations and trimetal (Mn-Ni-Fe) synergistic effects. In addition, a high sodium diffusion coefficient and a low volume distortion of 2.3% are observed through in situ transmission electron microscopy and first-principles calculations. Our results provide insights into the structural engineering of Prussian blue analogues for advanced sodium-ion batteries in large-scale energy storage applications.

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