RESUMEN

The evaluation of toxicity related to polychlorinated dibenzo-p-dioxins and furans (PCDD/Fs) and dioxin-like polychlorinated biphenyls (DL-PCBs) is crucial for a comprehensive risk assessment in real-world exposure scenarios. This study employed a controlled feeding experiment to investigate the metabolic effects of dioxin-like compounds (DLCs) on laying hens via feed exposure. Diets enriched with two concentrations (1.17 and 5.13 pg toxic equivalents (TEQ)/g dry weight (dw)) were administered over 14 days, followed by 28 days of clean feed. Metabolomics analyses of blood samples revealed significant metabolic variations between PCDD/Fs and DL-PCBs exposed groups and controls, reflecting the induced metabolic disruption. Distinct changes were observed in sphingosine, palmitoleic acid, linoleate, linolenic acid, taurocholic acid, indole acrylic acid, and dibutyl phthalate levels, implying possible connections between PCDD/Fs and DL-PCBs toxic effects and energy-neuronal imbalances, along with lipid accumulation and anomalous amino acid metabolism, impacting taurine metabolism. Moreover, we identified three differential endogenous metabolites-L-tryptophan, indole-3-acetaldehyde, and indole acrylic acid-as potential ligands for the aryl hydrocarbon receptor (AhR), suggesting their role in mediating PCDD/Fs and DL-PCBs toxicity. This comprehensive investigation provides novel insights into the metabolic alterations induced by PCDD/Fs and DL-PCBs in laying hens, thereby enhancing our ability to assess risks associated with their exposure in human populations.

Asunto(s)

Pollos , Animales , Dioxinas y Compuestos Similares a la Dioxina/metabolismo , Dioxinas y Compuestos Similares a la Dioxina/toxicidad , Femenino , Contaminantes Ambientales/toxicidad , Contaminantes Ambientales/metabolismo , Bifenilos Policlorados/toxicidad , Metabolómica , Metaboloma/efectos de los fármacos , Alimentación Animal/análisis , Dibenzodioxinas Policloradas/toxicidad

RESUMEN

Bisphenol A (BPA) is an industrial pollutant that can cause immune impairment. Selenium acts as an antioxidant, as selenium deficiency often accompanies oxidative stress, resulting in organ damage. This study is the first to demonstrate that BPA and/or selenium deficiency induce pyroptosis and ferroptosis-mediated thymic injury in chicken and chicken lymphoma cell (MDCC-MSB-1) via oxidative stress-induced endoplasmic reticulum (ER) stress. We established a broiler chicken model of BPA and/or selenium deficiency exposure and collected thymus samples as research subjects after 42 days. The results demonstrated that BPA or selenium deficiency led to a decrease in antioxidant enzyme activities (T-AOC, CAT, and GSH-Px), accumulation of peroxides (H2O2 and MDA), significant upregulation of ER stress-related markers (GRP78, IER 1, PERK, EIF-2α, ATF4, and CHOP), a significant increase in iron ion levels, significant upregulation of pyroptosis-related gene (NLRP3, ASC, Caspase1, GSDMD, IL-18 and IL-1ß), significantly increase ferroptosis-related genes (TFRC, COX2) and downregulate GPX4, HO-1, FTH, NADPH. In vitro experiments conducted in MDCC-MSB-1 cells confirmed the results, demonstrating that the addition of antioxidant (NAC), ER stress inhibitor (TUDCA) and pyroptosis inhibitor (Vx765) alleviated oxidative stress, endoplasmic reticulum stress, pyroptosis, and ferroptosis. Overall, this study concludes that the combined effects of oxidative stress and ER stress mediate pyroptosis and ferroptosis in chicken thymus induced by BPA exposure and selenium deficiency.

Asunto(s)

Compuestos de Bencidrilo , Pollos , Estrés del Retículo Endoplásmico , Ferroptosis , Fenoles , Piroptosis , Especies Reactivas de Oxígeno , Selenio , Animales , Compuestos de Bencidrilo/toxicidad , Ferroptosis/efectos de los fármacos , Piroptosis/efectos de los fármacos , Estrés del Retículo Endoplásmico/efectos de los fármacos , Selenio/deficiencia , Fenoles/toxicidad , Especies Reactivas de Oxígeno/metabolismo , Timo/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos

RESUMEN

Intra-tumor heterogeneity, i.e., the presence of diverse cell types and subpopulations within tumors, presents a significant obstacle in cancer treatment due to its negative consequences for resistance to therapy and disease recurrence. However, the mechanisms that underlie intra-tumor heterogeneity and result in the plethora of different cancer cells within a single lesion remain poorly understood. Here, we leverage the SW480 cell line as a model system to investigate the molecular and functional diversity of colon cancer cells. Through a combination of fluorescence-activated cell sorting (FACS) analysis and transcriptomic profiling, we identified three distinct subpopulations, namely resident cancer stem cells (rCSCs), migratory CSCs (mCSCs), and high-relapse cells (HRCs). These subpopulations show varying Wnt signaling levels and gene expression profiles mirroring their stem-like and functional properties. Examination of publicly available spatial transcriptomic data confirms the presence of these subpopulations in patient-derived cancers and reveals their distinct spatial distribution relative to the tumor microenvironment.

RESUMEN

Purpose: To develop a combined diagnostic model integrating the subclassification of the 2022 version of the American College of Radiology (ACR) Ovarian-Adnexal Reporting and Data System (O-RADS) with carbohydrate antigen 125 (CA125) and to validate whether the combined model can offer superior diagnostic efficacy than O-RADS alone in assessing adnexal malignancy risk. Methods: A retrospective analysis was performed on 593 patients with adnexal masses (AMs), and the pathological and clinical data were included. According to the large differences in malignancy risk indices for different image features in O-RADS category 4, the lesions were categorized into groups A and B. A new diagnostic criterion was developed. Lesions identified as category 1, 2, 3, or 4A with a CA125 level below 35 U/ml were classified as benign. Lesions identified as category 4A with a CA125 level more than or equal to 35 U/ml and lesions with a category of 4B and 5 were classified as malignant. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy, and area under the curve (AUC) of O-RADS (v2022), CA125, and the combined model in the diagnosis of AMs were calculated and compared. Results: The sensitivity, specificity, PPV, NPV, accuracy, and AUCs of the combined model were 92.4%, 96.5%, 80.2%, 98.8%, 94.1%, and 0.945, respectively. The specificity, PPV, accuracy, and AUC of the combined model were significantly higher than those of O-RADS alone (all P < 0.01). In addition, both models had acceptable sensitivity and NPV, but there were no significant differences among them (P > 0.05). Conclusion: The combined model integrating O-RADS subclassification with CA125 could improve the specificity and PPV in diagnosing malignant AMs. It could be a valuable tool in the clinical application of risk stratification of AMs.

RESUMEN

Thyroid cancer is the most frequently observed endocrine-related malignancy among which anaplastic thyroid cancer (ATC) is the most fatal subtype. The synthesis of protein is active to satisfy the rapid growth of ATC tumor, but the mechanisms regulating protein synthesis are still unknown. Our research revealed that kinetochore protein NUF2 played an essential role in protein synthesis and drove the progression of ATC. The prognosis of patients with thyroid carcinoma was positively correlated with high NUF2 expression. Depletion of NUF2 in ATC cells notably inhibited the proliferation and induced apoptosis, while overexpression of NUF2 facilitated ATC cell viability and colony formation. Deletion of NUF2 significantly suppressed the growth and metastasis of ATC in vivo. Notably, knockdown of NUF2 epigenetically inhibited the expression of magnesium transporters through reducing the abundance of H3K4me3 at promoters, thereby reduced intracellular Mg2+ concentration. Furthermore, we found the deletion of NUF2 or magnesium transporters significantly inhibited the protein synthesis mediated by the PI3K/Akt/mTOR pathway. In conclusion, NUF2 functions as an emerging regulator for protein synthesis by maintaining the homeostasis of intracellular Mg2+, which finally drives ATC progression.

Asunto(s)

Progresión de la Enfermedad , Homeostasis , Magnesio , Carcinoma Anaplásico de Tiroides , Animales , Femenino , Humanos , Ratones , Apoptosis , Proteínas de Transporte de Catión/metabolismo , Proteínas de Transporte de Catión/genética , Proteínas de Ciclo Celular/metabolismo , Proteínas de Ciclo Celular/genética , Línea Celular Tumoral , Proliferación Celular , Regulación Neoplásica de la Expresión Génica , Magnesio/metabolismo , Ratones Desnudos , Biosíntesis de Proteínas , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal , Carcinoma Anaplásico de Tiroides/metabolismo , Carcinoma Anaplásico de Tiroides/patología , Carcinoma Anaplásico de Tiroides/genética , Neoplasias de la Tiroides/patología , Neoplasias de la Tiroides/metabolismo , Neoplasias de la Tiroides/genética , Serina-Treonina Quinasas TOR/metabolismo

RESUMEN

Fluorene-9-bisphenol (BHPF), as an alternative to bisphenol A, is now increasingly used in plastic products. The accumulation of BHPF in the water environment has posed potential safety risks to aquatic organisms. Unfortunately, the toxicity of BHPF on the physiological metabolism of aquatic animals remains unclear, especially on the molecular mechanisms of BHPF kidney toxicity and antagonizing BHPF toxicity. Quercetin (QCT), a naturally occurring flavonoid, has been reported to mitigate the toxic effects on aquatic organisms induced by a variety of environmental contaminants. It is unclear whether QCT can be a candidate for mitigating BHPF toxicity. In this study, we investigated the protective effect of QCT on BHPF-induced apoptosis and elucidated the possible mechanism of the protective effect mediated by QCT. We treated epithelioma papulosum cyprini cells (EPCs) with 20 µM of BHPF and/or 20 µM of QCT, and the results showed that BHPF significantly increased the release of reactive oxygen species (ROS) from EPCs, decreased the expression of SIRT3, and initiated endogenous apoptosis. Molecular docking provides evidence for the interaction of QCT and SIRT3. Our intervention with Honokiol (HKL) showed that QCT or HKL treatment significantly attenuated BHPF-induced mitochondrial dysfunction and mitochondrial apoptosis (mtApoptosis) in EPCs, and activated mitophagy, restoring autophagy flux. To further investigate the specific mechanism of the protective effect of QCT, we intervened with Cyclosporin A (CsA), and our results suggest that QCT activation of SIRT3-promoted regulation of mitophagy may be a therapeutic strategy to attenuate the toxic effects of BHPF on EPCs. In conclusion, our findings suggest that BHPF induces oxidative damage and mtApoptosis in EPCs and that QCT activates mitophagy and improves autophagic flux through activation of SIRT3, thereby alleviating apoptosis mediated by mitochondrial dysfunction in EPCs. Our study provides a theoretical basis for reassessing the safety of BHPF for aquatic organisms and reveals a novel detoxification mechanism against the toxic effects of BHPF.

RESUMEN

Porcine reproductive and respiratory syndrome (PRRS) significantly impacts the global swine industry. Sichuan province, a key pig breeding center in China, has limited data on the molecular epidemiology of PRRS Virus (PRRSV). To address this, 1618 suspected PRRSV samples were collected from 2021 to 2023, with a prevalence rate of 39.74% (643/1618). Phylogenetic analysis showed PRRSV-2 as dominant (95.65%, 615/643), with PRRSV-1 at 4.35% (28/643). PRRSV-2 strains were further classified into NADC30-like (74.18%), NADC34-like (11.98%), C-PRRSV (5.44%), and HP-PRRSV (4.04%). The significant change in the proportions of different lineages indicates genomic divergence. NADC30-like strains exhibited significant amino acid mutations in ORF5, aiding immune evasion. Recombination analysis revealed complex patterns, primarily involving NADC30-like strains. This study highlights the genomic divergence of PRRSV in Sichuan, with NADC30-like strains becoming predominant and emerging strains like NADC34-like showing potential for further spread.

RESUMEN

Coccidiosis is an important parasitic disease that has serious adverse effects on the global poultry industry. The mechanism by which the pathogenic factors of Eimeria tenella damage host cells is unknown. Some kinases from the rhoptry compartment can regulate apoptosis of host cells. This study focused on revealing the role and critical nodes of E. tenella rhoptry protein (EtROP) 38 in controlling the apoptosis of host cells via the P38 mitogen-activated protein kinase (MAPK) signaling pathway. The cells were treated with EtROP38 protein, siRNA p38MAPK, or both. The rate of infection, apoptosis, and the dynamic changes in the expression and activation of key factor genes of the P38MAPK signaling pathway in host cells infected with E. tenella were measured. The results showed that the addition of EtROP38 and/or knockdown of the host cells p38 gene reduced the apoptosis rate of cecal epithelial cells (CECS), decreased the mRNA expressions of p38, p53, c-myc, c-fos, and c-jun and increased the expression of p65, decreased the protein expressions of c-myc, c-fos, and c-jun, decreased the p38 protein phosphorylation level, and increased the p65 protein phosphorylation level in CECS. When E. tenella was inoculated for 4-96 h, the addition of Et ROP38 and/or host cell p38 knockdown both increased the infection rate of host cells, and this effect was more pronounced with the addition of EtROP38 with the host cell p38 knockdown. These observations indicate that E. tenella can inhibits the activation of the p38MAPK signaling pathway in host cells via EtROP38, which suppresses apoptosis in host cells.

Asunto(s)

Apoptosis , Pollos , Eimeria tenella , Proteínas Quinasas p38 Activadas por Mitógenos , Eimeria tenella/fisiología , Animales , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/genética , Enfermedades de las Aves de Corral/parasitología , Proteínas Protozoarias/metabolismo , Proteínas Protozoarias/genética , Coccidiosis/parasitología , Coccidiosis/veterinaria , Sistema de Señalización de MAP Quinasas , Células Epiteliales/parasitología , Ciego/parasitología , Transducción de Señal

RESUMEN

The cycloaddition reaction involving bicyclo[1.1.0]butanes (BCBs) offers a versatile and efficient synthetic platform for producing C(sp3)-rich rigid bridged ring scaffolds, which act as phenyl bioisosteres. However, there is a scarcity of catalytic asymmetric cycloadditions of BCBs to fulfill the need for enantioenriched saturated bicycles in drug design and development. In this study, an efficient synthesis of valuable azabicyclo[2.1.1]hexanes (aza-BCHs) by an enantioselective zinc-catalyzed (3+2) cycloadditions of BCBs with imines is reported. The reaction proceeds effectively with a novel type of BCB that incorporates a 2-acyl imidazole group and a diverse array of alkynyl- and aryl-substituted imines. The target aza-BCHs, which consist of α-chiral amine fragments and two quaternary carbon centers, are efficiently synthesized with up to 94% yield and 96.5:3.5 er under mild conditions. Experimental and computational studies reveal that the reaction follows a concerted nucleophilic ring-opening mechanism of BCBs with imines. This mechanism is distinct from previous studies on Lewis acid-catalyzed cycloadditions of BCBs.

RESUMEN

Poly(methyl methacrylate) (PMMA) bone cements have been widely used in orthopedics; thanks to their excellent mechanical properties, biocompatibility, and chemical stability. Barium sulfate and zirconia are usually added into PMMA bone cement to enhance the X-ray radiopacity, while the mechanical strength, radiopacity, and biocompatibility are not well improved. In this study, an insoluble and corrosion-resistant ceramic, tantalum carbide (TaC), was added into the PMMA bone cement as radiopacifies, significantly improving the mechanical, radiopaque, biocompatibility, and osteogenic performance of bone cement. The TaC-PMMA bone cement with varied TaC contents exhibits compressive strength over 100 MPa, higher than that of the commercial 30% BaSO4-PMMA bone cement. Intriguingly, when the TaC content reaches 20%, the radiopacity is equivalent to the commercial bone cement with 30% of BaSO4 in PMMA. The cytotoxicity and osteogenic performance indicate that the incorporation of TaC not only enhances the osteogenic properties of PMMA but also does not reduce cell viability. This study suggests that TaC could be a superior and multifunctional radio-pacifier for PMMA bone cement, offering a promising avenue for improving patient outcomes in orthopedic applications.

Asunto(s)

Materiales Biocompatibles , Cementos para Huesos , Osteogénesis , Polimetil Metacrilato , Tantalio , Cementos para Huesos/química , Tantalio/química , Polimetil Metacrilato/química , Osteogénesis/efectos de los fármacos , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Ensayo de Materiales , Supervivencia Celular/efectos de los fármacos , Humanos , Animales , Fuerza Compresiva , Ratones

RESUMEN

Bisphenol A (BPA) is widely applied in plastic products, which will produce immunotoxicity to organisms after spilling in the environment, and become a kind of endocrine disruptor. Selenium (Se) is an essential trace element and plays an important role in maintaining redox homeostasis and immune function. BPA exposure and Se deficiency often occur together in livestock and poultry farming, however, studies on the effects of joint exposure on chicken immunotoxins have not been reported. Therefore, this study established a chicken spleen and MDCC-MSB1 cell model under the combined effects of BPA exposure or/and Se deficiency. Transcriptomic analysis showed that BPA exposure and/or Se deficiency induced differential enrichment of positive regulatory pathways such as NLRP3 inflammatory complex assembly, inflammatory response and cellular oxidative stress response. In the -Se+BPA group, pathological damage was significantly increased, Se content decreased, BPA accumulation, oxidative stress and pyroptosis. Meanwhile, the roles and mechanisms of oxidative stress and pyroptosis in BPA exposure or/and Se deficiency-induced splenic tissue injury were investigated by using IF and qRT-PCR methods. The results showed that joint BPA exposure with Se deficiency resulted in more significant changes in the above outcomes than 1 of them. The oxidative stress inhibitor NAC effectually reduced Se deficiency and BPA-induced oxidative stress and pyroptosis, further suggests that oxidative stress mediated Se deficiency or/and BPA-induced pyroptosis. This study revealed that BPA exposure and Se deficiency induced spleen pyroptosis in chickens via the ROS/NLRP3 pathway. These results provide the theoretical basis for the toxicity of BPA in poultry and enrich the toxicological mechanism of combined exposure of Se deficiency and environmental toxins.

RESUMEN

Activated Wnt/ß-catenin pathway is a key genetic event in liver cancer development. Solute carrier (SLC) transporters are promising drug targets. Here, we identify SLC13A3 as a drug-targetable effector downstream of ß-catenin in liver cancer. SLC13A3 expression is elevated in human liver cancer samples with gain of function (GOF) mutant CTNNB1, the gene encoding ß-catenin. Activation of ß-catenin up-regulates SLC13A3, leading to intracellular accumulation of endogenous SLC13A3 substrates. SLC13A3 is identified as a low-affinity transporter for glutathione (GSH). Silencing of SLC13A3 downregulates the leucine transporter SLC7A5 via c-MYC signaling, leading to leucine depletion and mTOR inactivation. Furthermore, silencing of SLC13A3 depletes GSH and induces autophagic ferroptosis in ß-catenin-activated liver cancer cells. Importantly, both genetic inhibition of SLC13A3 and a small molecule SLC13A3 inhibitor suppress ß-catenin-driven hepatocarcinogenesis in mice. Altogether, our study suggests that SLC13A3 could be a promising therapeutic target for treating human liver cancers with GOF CTNNB1 mutations.

Asunto(s)

Neoplasias Hepáticas , beta Catenina , Animales , Humanos , Masculino , Ratones , Sistema de Transporte de Aminoácidos y+/metabolismo , Sistema de Transporte de Aminoácidos y+/genética , beta Catenina/metabolismo , beta Catenina/genética , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patología , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica , Glutatión/metabolismo , Transportador de Aminoácidos Neutros Grandes 1 , Leucina/metabolismo , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , Proteínas Proto-Oncogénicas c-myc/metabolismo , Proteínas Proto-Oncogénicas c-myc/genética , Serina-Treonina Quinasas TOR/metabolismo , Vía de Señalización Wnt

RESUMEN

BACKGROUND: This study explored risk perception characteristics and influencing factors among informal caregivers of functionally dependent elderly individuals at home, aiming to improve caregivers' caregiving risk perception and coping abilities and ultimately enhance the quality of life for these individuals. METHODS: We used purposive sampling to select 22 informal caregivers from a community in Zhengzhou City, Henan Province, China, between March and September 2023 and conducted face-to-face semi-structured in-depth interviews. The data were analyzed using Colaizzi's seven-step analysis method. RESULTS: We extracted two themes, caregiving risk perception characteristics and caregiving risk perception associated factors, and eight sub-themes, perceived risk possibility, perceived risk anticipation, perceived severity of consequences, past caregiving experiences, health literacy, psychological status, caregiving burden, and family social support. CONCLUSION: There were differences in how informal caregivers perceived the risks associated with caring for functionally dependent elderly individuals at home, which various factors could influence. It was essential to provide training that covered the knowledge and skills needed for caregiving, improve caregivers' awareness of safety risks, and establish a correct perception of caregiving risks. The government must construct and refine a comprehensive framework for caregiver respite services. Simultaneously, healthcare professionals should proactively undertake health education endeavors to augment the recognition of care safety risks among informal caregivers, thereby cultivating an accurate awareness of care risk perception.

RESUMEN

Di(2-ethylhexyl) phthalate (DEHP) is a plasticizer that can damage various organizations and physiques through oxidative stress. Quercetin (Que) is a rich polyphenol flavonoid with good anti-inflammatory and antioxidant effects. However, the protection mechanism of Que against DEHP exposure-induced IPEC-J2 cell injury and the implication of autophagy, apoptosis and immunity are still unclear. In this experiment, we looked into the toxicity regime of DEHP exposure on IPEC-J2 cells and the antagonistic function of Que on DEHP. In the experiment, 135 µM DEHP and/or 80 µM Que were used to treat the IPEC-J2 cells for 24h. Experiments indicated that DEHP exposure can cause increased reactive oxygen species (ROS) levels leading to oxidative stress, decreased CAT, T-AOC and GSH-Px activities, increased MDA and H2O2 accumulation, activated the ASK1/JNK signalling pathway, and further increases in the levels of apoptosis markers Bax, Caspase3, Caspase9, and Cyt-c, while reduced the Bcl-2 expression. DEHP also increased the expression of genes linked to autophagy (ATG5, Beclin1, LC3), while decreasing the expression of P62. Additionally, DEHP exposure led to elevated levels of IL1-ß, IL-6, MCP-1, and TNF expression. When exposed to Que alone, there were no significant changes in cellular oxidative stress level, ASK1/JNK signalling pathway expression level, apoptosis, autophagy and cellular immune function. The combination of DEHP and Que treatment remarkably decreased the proportion of autophagy and apoptosis, and recovered cellular immunity. In summary, Que can attenuate DEHP-induced apoptosis and autophagy in IPEC-J2 cells by regulating the ROS/ASK1/JNK signalling pathway and improving the immune dysfunction of IPEC-J2 cells.

Asunto(s)

Apoptosis , Autofagia , Dietilhexil Ftalato , MAP Quinasa Quinasa Quinasa 5 , Sistema de Señalización de MAP Quinasas , Estrés Oxidativo , Quercetina , Especies Reactivas de Oxígeno , Apoptosis/efectos de los fármacos , Animales , Autofagia/efectos de los fármacos , Dietilhexil Ftalato/toxicidad , Quercetina/farmacología , Especies Reactivas de Oxígeno/metabolismo , MAP Quinasa Quinasa Quinasa 5/metabolismo , Estrés Oxidativo/efectos de los fármacos , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Línea Celular , Porcinos , Plastificantes/toxicidad

RESUMEN

BACKGROUND: Laparoscopic and robotic-assisted techniques have gained popularity, and endometrial cancer (EC) remains a significant health problem among women. OBJECTIVE: Minimally invasive surgical (MIS) therapy options for early endometrial cancer will be evaluated for their effectiveness and safety is the aim of this paper. We also investigate the differences in oncologic outcomes between MIS and open surgery (OS) for individuals with early-stage EC. The patient was diagnosed with early-stage EC and treated with laparoscopic surgery and was the focus of a retrospective analysis. 162 patients with early EC were analyzed, with diagnoses occurring between 2002 and 2022. METHODS: The patients were fragmented into two groups, one for OS and another for laparoscopic procedures. The total tumor excision and recurrence rates were identical across the two methods, indicating similar oncologic results. Rates of complications were likewise comparable across the two groups. RESULTS: The quality of life ratings of patients with robotic-assisted surgery was higher than those with laparoscopic surgery. Sixty-two (62.2%) of the 162 patients in this research had OS, whereas Fifty-six (57.8%) had MIS. The probability of recurrence of EC from stages III to IV was significanitly higher in women who had OS. CONCLUSION: Minimally invasive procedures were shown to be effective in treating early-stage EC, and while these findings provide support for their usage, larger multicenter randomized controlled studies are required to verify these results and further examine possible long-term advantages. Patients with early-stage EC, regardless of histologic type, had superior survival rates with MIS compared to OS.

RESUMEN

Anaplastic thyroid cancer (ATC), an aggressive malignancy with virtually 100% disease-specific mortality, has long posed a formidable challenge in oncology due to its resistance to conventional treatments and the severe side effects associated with current regimens such as doxorubicin chemotherapy. Consequently, there was urgent need to identify novel candidate compounds that could provide innovative therapeutic strategies for ATC. Ophiopogonin D' (OPD'), a triterpenoid saponin extracted, yet its roles in ATC has not been reported. Our data demonstrated that OPD' potently inhibited proliferation and metastasis of ATC cells, promoting cell cycle arrest and apoptosis. Remarkably, OPD' impeded growth and metastasis of ATC in vitro and in vivo, displaying an encouraging safety profile. Regulator of G-protein signalling 4 (RGS4) expression was significantly up-regulated in ATC compared to normal tissues, and this upregulation was suppressed by OPD' treatment. Mechanistically, we elucidated that the transcription factor JUN bound to the RGS4 promoter, driving its transactivation. However, OPD' interacted with JUN, attenuating its transcriptional activity and thereby disrupting RGS4 overexpression. In summary, our research revealed that OPD' bound with JUN, which in turn resulted in the suppression of transcriptional activation of RGS4, thereby eliciting cell cycle arrest and apoptosis in ATC cells. These findings could offer promise in the development of high-quality candidate compounds for treatment in ATC.

Asunto(s)

Apoptosis , Proliferación Celular , Proteínas RGS , Saponinas , Transducción de Señal , Espirostanos , Carcinoma Anaplásico de Tiroides , Humanos , Carcinoma Anaplásico de Tiroides/tratamiento farmacológico , Carcinoma Anaplásico de Tiroides/metabolismo , Carcinoma Anaplásico de Tiroides/patología , Saponinas/farmacología , Proteínas RGS/metabolismo , Proteínas RGS/genética , Proliferación Celular/efectos de los fármacos , Animales , Línea Celular Tumoral , Transducción de Señal/efectos de los fármacos , Apoptosis/efectos de los fármacos , Espirostanos/farmacología , Ratones , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Puntos de Control del Ciclo Celular/efectos de los fármacos , Proteínas Proto-Oncogénicas c-jun/metabolismo , Ratones Desnudos , Neoplasias de la Tiroides/tratamiento farmacológico , Neoplasias de la Tiroides/patología , Neoplasias de la Tiroides/metabolismo , Neoplasias de la Tiroides/genética , Ensayos Antitumor por Modelo de Xenoinjerto , Metástasis de la Neoplasia

RESUMEN

Emergence heterogeneity caused by epicotyl dormancy contributes to variations in seedling quality during large-scale breeding. However, the mechanism of epicotyl dormancy release remains obscure. We first categorized the emergence stages of Chinese cork oak (Quercus variabilis) using the BBCH-scale. Subsequently, we identified the key stage of the epicotyl dormancy process. Our findings indicated that cold stratification significantly released epicotyl dormancy by increasing the levels of gibberellic acid 3 (GA3) and GA4. Genes associated with GA biosynthesis and signaling also exhibited altered expression patterns. Inhibition of GA biosynthesis by paclobutrazol (PAC) treatment severely inhibited emergence, with no effect on seed germination. Different concentrations (50 µM, 100 µM, and 200 µM) of GA3 and GA4+7 treatments of germinated seeds demonstrated that both can promote the emergence, with GA4 exhibiting a more pronounced effect. In conclusion, this study provides valuable insights into the characterization of epicotyl dormancy in Chinese cork oak and highlights the critical role of GA biosynthesis in seedling emergence. These findings serve as a basis for further investigations on epicotyl dormancy and advancing large-scale breeding techniques.

Asunto(s)

Germinación , Giberelinas , Latencia en las Plantas , Reguladores del Crecimiento de las Plantas , Quercus , Quercus/metabolismo , Quercus/fisiología , Quercus/crecimiento & desarrollo , Giberelinas/metabolismo , Reguladores del Crecimiento de las Plantas/metabolismo , Plantones/crecimiento & desarrollo , Plantones/metabolismo , Regulación de la Expresión Génica de las Plantas , Pueblos del Este de Asia , Triazoles

RESUMEN

Chronic stress leads to social avoidance and anhedonia in susceptible individuals, a phenomenon that has been observed in both human and animal models. Nevertheless, the underlying molecular mechanisms underpinning stress susceptibility and resilience remain largely unclear. There is growing evidence that epigenetic histone deacetylase (HDAC) mediated histone acetylation is involved in the modulation of depressive-related behaviors. We hypothesized that histone deacetylase 5 (HDAC5), which is associated with stress-related behaviors and antidepressant response, may play a vital role in the susceptibility to chronic stress. In the current study, we detected the levels of HDAC5 and acetylation of histone 4 (H4) in the hippocampus subsequent to chronic social defeat stress (CSDS) in C57BL/6J mice. We found that CSDS induces a notable increase in HDAC5 expression, concomitant with a reduction in the acetylation of histone H4 at lysine 12 (H4K12) in the hippocampus of susceptible mice. Meanwhile, intrahippocampal infusion of HDAC5 shRNA or HDAC inhibitor suberoylanilide hydroxamic acid (SAHA) both reversed the depression susceptibility in susceptible mice that subjected to CSDS. Furthermore, HDAC5 overexpression was sufficient to induce depression susceptibility following microdefeat stress, accompanied by a significant reduction in H4K12 level within the hippocampus of mice. Additionally, the Morris water maze (MWM) results indicated that neither CSDS nor HDAC5 exerted significant effects on spatial memory function in mice. Taken together, these investigations indicated that HDAC5-modulated histone acetylation is implicated in regulating the depression susceptibility, and may be serve as potential preventive targets for susceptible individuals.

Asunto(s)

Hipocampo , Histona Desacetilasas , Histonas , Ratones Endogámicos C57BL , Derrota Social , Estrés Psicológico , Animales , Estrés Psicológico/metabolismo , Hipocampo/metabolismo , Acetilación , Histonas/metabolismo , Histona Desacetilasas/metabolismo , Masculino , Depresión/metabolismo , Inhibidores de Histona Desacetilasas/farmacología , Ratones , Vorinostat/farmacología , Susceptibilidad a Enfermedades/metabolismo , Modelos Animales de Enfermedad

RESUMEN

Background: Cinnamomum camphora is a commercially important tree species in China, and it's also a common native tree in the forests of southern China. However, literature on the impact of Cinnamomum camphora essential oil (CCEO) on human psychophysiological activity is scarce. Hence, the primary objective of this study was to examine the effect of exposure to CCEO on the functioning of the human autonomic nervous system, electroencephalographic (EEG) activity, and emotional state. Methods: Forty-three healthy university students participated. The data collected included heart rate (HR), blood pressure (BP), pulse rate, blood oxygen saturation (SpO2), electroencephalographic (EEG) activity, and the results of the Profile of Mood States (POMS) test. Results: A drop in diastolic pressure (DBP) and pulse rate was also noticed after participants inhaled CCEO. Furthermore, EEG studies have demonstrated notable reductions in absolute beta (AB), absolute gamma (AG), absolute high beta (AHB), and relative gamma (RG) power spectra during exposure to CCEO. Conversely, the relative theta (RT) and power spectra values showed a significant increase. Additionally, the finding from POMS indicated that the fragrance evoked positive emotions and suppressed negative feelings. Conclusion: The results suggest that exposure to CCEO may promote mental and physical relaxation, facilitate cognitive processes such as memory and attention, and enhance mood states.

RESUMEN

Pseudorabies virus is a major pathogen in the pig industry, causing substantial economic losses. The emergence of pseudorabies virus variant strains in China has led to extensive spread, raising concerns about their potential impact. However, the differences in pathogenicity between the classical strains and the variant strains of genotype II are not well understood. In this study, we isolated three pseudorabies virus strains to evaluate their replication characteristics and to examine the differences in virulence genes among various subgenotypes strains. Additionally, a piglet infection model was utilized to investigate the clinical features of infection, tissue tropism, and the inflammatory responses induced by these strains. Our results showed that the genotype II variant strains (MS, XJ, LS, and CZ) had significantly larger plaque sizes and higher replication capacities than the genotype II classical strain Fa. The animal experiments revealed significant differences in pathogenicity among the pseudorabies virus subgenotype strains, with the variant strains showing higher mortality rates, more severe clinical symptoms, increased nasal virus shedding, and a more robust inflammatory response compared to the genotype II classical strain. There were also notable differences in tissue tropism among the strains. In terms of tissue viral loads, the genotype II variant strains did not exhibit a significant advantage over the genotype I classical strain. Furthermore, our findings indicate that antibodies against the genotype II classical strains have a reduced neutralizing capacity against the genotype II variant strains. On the other hand, antibodies against the genotype II variant strains displayed similar neutralizing abilities against both classical and variant strains. Overall, these findings offer important insights into the distinctions among pseudorabies virus subgenotypes and their implications for the clinical control of pseudorabies virus infections in pig farming.