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Shuotheriids are Jurassic mammaliaforms that possess pseudotribosphenic teeth in which a pseudotalonid is anterior to the trigonid in the lower molar, contrasting with the tribosphenic pattern of therian mammals (placentals, marsupials and kin) in which the talonid is posterior to the trigonid1-4. The origin of the pseudotribosphenic teeth remains unclear, obscuring our perception of shuotheriid affinities and the early evolution of mammaliaforms1,5-9. Here we report a new Jurassic shuotheriid represented by two skeletal specimens. Their complete pseudotribosphenic dentitions allow reidentification of dental structures using serial homology and the tooth occlusal relationship. Contrary to the conventional view1,2,6,10,11, our findings show that dental structures of shuotheriids can be homologized to those of docodontans and partly support homologous statements for some dental structures between docodontans and other mammaliaforms6,12. The phylogenetic analysis based on new evidence removes shuotheriids from the tribosphenic ausktribosphenids (including monotremes) and clusters them with docodontans to form a new clade, Docodontiformes, that is characterized by pseudotribosphenic features. In the phylogeny, docodontiforms and 'holotherians' (Kuehneotherium, monotremes and therians)13 evolve independently from a Morganucodon-like ancestor with triconodont molars by labio-lingual widening their posterior teeth for more efficient food processing. The pseudotribosphenic pattern passed a cusp semitriangulation stage9, whereas the tribosphenic pattern and its precursor went through a stage of cusp triangulation. The two different processes resulted in complex tooth structures and occlusal patterns that elucidate the earliest diversification of mammaliaforms.
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Evolução Biológica , Fósseis , Mamíferos , Dente , Animais , Eutérios/anatomia & histologia , Mamíferos/anatomia & histologia , Mamíferos/classificação , Mamíferos/fisiologia , Marsupiais/anatomia & histologia , Dente Molar/anatomia & histologia , Dente Molar/fisiologia , Filogenia , Dente/anatomia & histologia , Dente/fisiologia , MastigaçãoRESUMO
The dual jaw joint of Morganucodon1,2 consists of the dentary-squamosal joint laterally and the articular-quadrate one medially. The articular-quadrate joint and its associated post-dentary bones constitute the precursor of the mammalian middle ear. Fossils documenting the transition from such a precursor to the mammalian middle ear are poor, resulting in inconsistent interpretations of this hallmark apparatus in the earliest stage of mammaliaform evolution1-5. Here we report mandibular middle ears from two Jurassic mammaliaforms: a new morganucodontan-like species and a pseudotribosphenic shuotheriid species6. The morganucodontan-like species shows many previously unknown post-dentary bone morphologies1,2 and exhibits features that suggest a loss of load-bearing function in its articular-quadrate joint. The middle ear of the shuotheriid approaches the mammalian condition in that it has features that are suitable for an exclusively auditory function, although the post-dentary bones are still attached to the dentary. With size reduction of the jaw-joint bones, the quadrate shifts medially at different degrees in relation to the articular in the two mammaliaforms. These changes provide evidence of a gradual loss of load-bearing function in the articular-quadrate jaw joint-a prerequisite for the detachment of the post-dentary bones from the dentary7-12 and the eventual breakdown of the Meckel's cartilage13-15 during the evolution of mammaliaforms.
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Evolução Biológica , Orelha Média , Fósseis , Arcada Osseodentária , Mamíferos , Articulação Temporomandibular , Animais , Orelha Média/anatomia & histologia , Arcada Osseodentária/anatomia & histologia , Mamíferos/anatomia & histologia , Mamíferos/classificação , Mandíbula/anatomia & histologia , Articulação Temporomandibular/anatomia & histologiaRESUMO
BACKGROUND: Supraclavicular nodal (SCL) irradiation is commonly used for patients with high-risk breast cancer after breast surgery. The Radiation Therapy Oncology Group (RTOG) and European Society for Radiotherapy and Oncology (ESTRO) breast contouring atlases delineate the medial part of the SCL region, while excluding the posterolateral part. However, recent studies have found that a substantial proportion of SCL failures are located in the posterolateral SCL region, outside of the RTOG/ESTRO-defined SCL target volumes. Consequently, many radiation oncologists advocate for enlarging the SCL irradiation target volume to include both the medial and posterolateral SCL regions. Nevertheless, it remains uncertain whether adding the posterolateral SCL irradiation improves survival outcomes for high-risk breast cancer patients. METHODS: The SUCLANODE trial is an open-label, multicenter, randomized, phase 3 trial comparing the efficacy and adverse events of medial SCL irradiation (M-SCLI group) and medial plus posterolateral SCL irradiation (entire SCL irradiation, E-SCLI group) in high-risk breast cancer patients who underwent breast conserving-surgery or mastectomy. Patients with pathological N2-3b disease following initial surgery, or clinical stage III or pathological N1-3b if receiving neoadjuvant systemic therapy, are eligible and randomly assigned (1:1) to M-SCLI group and E-SCLI group. Stratification is by chemotherapy sequence (neoadjuvant vs. adjuvant), T stage (T3-4 vs. T1-2), N stage (N1-2 vs. N3), and ER status (positive vs. negative). Other radiation volumes are identical in the two arms, including breast/chest wall, undissected axillary lymph node, and internal mammary node. Advanced intensity modulated radiation therapy (IMRT), volumetric modulated arc therapy (VMAT), or tomotherapy techniques are recommended. Both hypofractionated and conventional fractionation schedules are permitted. The primary end point is invasive disease-free survival, and secondary end points included overall survival, SCL recurrence, local-regional recurrence, distance recurrence, safety outcome, and patient-reported outcomes. The target sample size is 1650 participants. DISCUSSION: The results of the SUCLANODE trial will provide high-level evidence regarding whether adding posterolateral SCL irradiation to medial SCL target volume provides survival benefit in patients with high-risk breast cancer. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05059379. Registered 28 September 2021, https://www. CLINICALTRIALS: gov/ct2/show/NCT05059379 .
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Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Mastectomia , Adjuvantes Imunológicos , Linfonodos , Mama , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Multicêntricos como Assunto , Ensaios Clínicos Fase III como AssuntoRESUMO
With the development of autonomous driving, there has been considerable attention on 3D object detection using LiDAR. Pillar-based LiDAR point cloud detection algorithms are extensively employed in the industry due to their simple structure and high real-time performance. Nevertheless, the pillar-based detection network suffers from significant loss of 3D coordinate information during the feature degradation and extraction process. In the paper, we introduce a novel framework with high performance, termed EFNet. The EFNet uses the Enhancing Pillar Feature Module (EPFM) to provide more accurate representations of features from two directions: pillar internal space and pillar external space. Additionally, the Head Up Module (HUM) is utilized in the detection head to integrate multi-scale information and enhance the network's information perception ability. The EFNet achieves impressive results on the nuScenes datasets, namely, 53.3% NDS and 42.4% mAP. Compared to the baseline PointPillars, EFNet improves 8% NDS and 11.9% mAP. The results demonstrate that the proposed framework can effectively improve the network's accuracy while ensuring deployability.
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BACKGROUND: Fried foods are favored for their unique crispiness, golden color and flavor, but they also face great challenge because of their high oil content, high calories and the existence of compounds such as acrylamide and polycyclic aromatic hydrocarbons. Long-term consumption of fried foods may adversely affect health. Therefore, it is necessary to explore fried foods with lower oil contents and a high quality to meet the demand. RESULTS: A method of enzyme treatment was explored to investigate the effects of maltogenic amylase (MA), transglutaminase (TG) and bromelain (BRO) on the physicochemical properties of the batter and the quality of fried spring roll wrapper (FSRW). The results showed that the MA-, TG- or BRO-treated batters had a significant shear-thinning behavior, especially with an increase in viscosity upon increasing TG contents. FSRW enhanced its fracturability from 419.19 g (Control) to 616.50 g (MA-6 U g-1), 623.49 g (TG-0.75 U g-1) and 644.96 g (BRO-10 U g-1). Meanwhile, in comparison with BRO and MA, TG-0.5 U g-1 endowed batter with the highest density and thermal stability. MA-15 U g-1 and TG-0.5 U g-1 displayed FSRW with uniform and dense pores, and significantly reduced its oil content by 18.05% and 25.02%, respectively. Moreover, compared to MA and TG, BRO-50 U g-1 improved the flavor of FSRW. CONCLUSION: MA, TG or BRO played a key role in affecting the physicochemical properties of the batter and the quality of FSRW. TG-0.5 U g-1 remarkly reduced the oil content of FSRW with a great potential in practical application. © 2024 Society of Chemical Industry.
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Bromelaínas , Culinária , Transglutaminases , Transglutaminases/química , Bromelaínas/química , Viscosidade , Frutas/química , Glicosídeo Hidrolases/química , Glicosídeo Hidrolases/metabolismo , Farinha/análise , Paladar , Manipulação de Alimentos/métodosRESUMO
This study aims to investigate the relationship between the human papillomavirus (HPV) infection and the altered vaginal microecological environment of patients. Initially, HPV genotyping and microecological detection were performed in 1281 subjects in the Department of Obstetrics and Gynecology of The First Hospital of Qinhuangdao (Qinhuangdao, China). The relationship between the enzymes of vaginal microecology, that is, proline aminopeptidase and acetylglucosaminidase, and vaginal inflammatory diseases, as well as the prognosis of HPV infection, was analyzed. The experimental findings indicated a close relationship between the expression of positive prolyl aminopeptidase and trichomonas vaginitis, as well as bacterial vaginitis. In addition, the expression of acetylglucosaminidase is closely associated with trichomonas vaginitis and vulvovaginal candidiasis. Furthermore, the observations indicated that positive prolyl aminopeptidase and acetylglucosaminidase could increase the risk of various subtypes of HPV infection in patients. The receiver operating characteristic curve analysis presented that the expression of prolyl aminopeptidase and acetylglucosaminidase could offer exceptional diagnostic efficacy, indicating their association with persistent HPV infection. In summary, our results highlighted that the expression of positive prolyl aminopeptidase and acetylglucosaminidase in the vaginal microecology could be substantially correlated to the occurrence and the development of vaginal inflammatory diseases, as well as the outcome and the risk of persistent HPV infection.
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Infecções por Papillomavirus , Vaginite por Trichomonas , Feminino , Gravidez , Humanos , Infecções por Papillomavirus/epidemiologia , Acetilglucosaminidase , Vagina/microbiologia , Papillomavirus HumanoRESUMO
Dental caries is one of the most common diseases afflicting modern humans and occurs in both living and extinct non-human primates, as well as other mammalian species. Compared to other primates, less is known about the etiology or frequency of caries among the Strepsirrhini. Given the link between caries and diet, caries frequency may be informative about the dietary ecology of a given animal. Understanding rates of caries in wild populations is also critical to assessing dental health in captive populations. Here, we examine caries frequency in a sample of 36 extant strepsirrhine species (n = 316 individuals) using odontological collections of wild-, non-captive animals housed at the American Museum of Natural History by counting the number of specimens characterized by the disease. Additionally, in the context of studying caries lesions in strepsirrhines, case studies were also conducted to test if similar lesions were found in their fossil relatives. In particular, two fossil strepsirrhine species were analyzed: the earliest Late Eocene Karanisia clarki, and the subfossil lemur Megaladapis madagascariensis. Our results suggest that caries affects 13.92% of the extant individuals we examined. The frugivorous and folivorous taxa were characterized by the highest overall frequency of caries, whereas the insectivores, gummivores, and omnivores had much lower caries frequencies. Our results suggest that caries may be common among wild populations of strepsirrhines, and in fact is more prevalent than in many catarrhines and platyrrhines. These findings have important implications for understanding caries, diet, and health in living and fossil taxa.
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Cárie Dentária , Dieta , Fósseis , Strepsirhini , Animais , Cárie Dentária/epidemiologiaRESUMO
OBJECTIVES: Pituitary abscess (PA) accounts for only 0.3-0.5% of sellar masses, and the lack of specific clinical symptoms makes diagnosing PA difficult without a surgical biopsy. In clinical practice, PA is often mistaken for cystic pituitary adenoma, craniopharyngioma, and Rathke's cyst. Thus, this study aims to investigate challenges in diagnosing PA and evaluate the importance of combining intraoperative surgery with postoperative antibiotic treatment. METHODS: We conducted a retrospective analysis of 19 patients diagnosed with PA through histopathology. All patients underwent transsphenoidal surgery (TSS) for pituitary adenomas after undergoing comprehensive preoperative evaluations, including routine tests, endocrine assay, and imaging examination. Furthermore, we compared different treatments for pituitary abscess (PA) to determine the most effective approach for achieving a favorable prognosis. RESULTS: The most prevalent symptom of PA was headache, especially in the frontal-temporal and vertex regions, ranging from mild to moderate severity. Hypopituitarism-related symptoms were also frequently observed, including hypaphrodisia, cold sensitivity, fatigue, weight loss, polyuria, and amenorrhea. Twelve patients exhibited abnormalities in endocrinology examinations. Diagnosing PA correctly is challenging. In our study, none of the patients were correctly diagnosed with PA prior to surgery, and many sellar lesions were misdiagnosed. The favorable prognosis was largely attributed to surgical intervention and active postoperative antibiotic therapy. CONCLUSIONS: Given the lack of clarity in preoperative diagnosis, typical intraoperative findings and effective antibiotics treatment are more indicative of the correct diagnosis than other tests. In terms of therapy, optimal surgical intervention and active postoperative antibiotic treatment contribute to resolving the challenges posed by PA.
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Doenças da Hipófise , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Estudos Retrospectivos , Doenças da Hipófise/diagnóstico , Doenças da Hipófise/cirurgia , Doenças da Hipófise/terapia , Idoso , Neoplasias Hipofisárias/diagnóstico , Neoplasias Hipofisárias/cirurgia , Neoplasias Hipofisárias/terapia , Neoplasias Hipofisárias/patologia , Abscesso Encefálico/diagnóstico , Abscesso Encefálico/terapia , Abscesso/diagnóstico , Abscesso/terapia , Antibacterianos/uso terapêuticoRESUMO
Importance: The potential benefit of combining intracranial effective systemic therapy with radiotherapy for patients with breast cancer with brain metastases remains unclear. Objective: To assess the activity and safety of combining radiotherapy with pyrotinib and capecitabine in patients with ERBB2-positive breast cancer and brain metastases. Design, Setting, and Participants: This was a single-arm, single-center, phase 2 nonrandomized clinical trial with a safety run-in phase. Between January 2020 and August 2022, patients with ERBB2-positive breast cancer and brain metastases were enrolled. The data cutoff date was February 1, 2023. Interventions: Patients received either fractionated stereotactic radiotherapy or whole-brain radiotherapy. Treatment with pyrotinib (400 mg, once daily) and capecitabine (1000 mg/m2, twice daily, on days 1-14 of each 21-day cycle) was initiated from the first day of radiotherapy to the seventh day after the completion of radiotherapy and continued until disease progression or unacceptable toxic effects. Main Outcomes and Measures: The primary end point was 1-year central nervous system (CNS) progression-free survival (PFS) rate. Secondary end points included CNS objective response rate (ORR), PFS, overall survival (OS), safety, and changes in neurocognitive function. Results: A total of 40 female patients (median age, 50.5 years [IQR, 46-59 years]) were enrolled and received treatment, including 3 patients in safety run-in phase. With a median follow-up of 17.3 months (IQR, 10.3-26.9), the 1-year CNS PFS rate was 74.9% (95% CI, 61.9%-90.7%), and the median CNS PFS was 18.0 months (95% CI, 15.5 to not reached). The 1-year PFS rate was 66.9% (95% CI, 53.1%-84.2%), and the median PFS was 17.6 months (95% CI, 12.8-34.1). The CNS objective response rate was 85% (34 of 40). Median overall survival was not reached. The most common grade 3 or 4 treatment-related adverse event was diarrhea (7.5%). Asymptomatic radiation necrosis was identified in 4 of 67 lesions (6.0%) treated with fractionated stereotactic radiotherapy. Most patients maintained neurocognitive function, as evaluated by the Mini-Mental State Examination at different points. Conclusions and Relevance: The results of this trial suggest that radiotherapy combined with pyrotinib and capecitabine is associated with long intracranial survival benefit in patients with ERBB2-positive advanced breast cancer and brain metastases with an acceptable safety profile. This combination deserves further validation. Trial Registration: ClinicalTrials.gov Identifier: NCT04582968.
Assuntos
Acrilamidas , Aminoquinolinas , Neoplasias Encefálicas , Neoplasias da Mama , Feminino , Humanos , Pessoa de Meia-Idade , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Encéfalo/patologia , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/radioterapia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/radioterapia , Capecitabina/efeitos adversos , Receptor ErbB-2/metabolismoRESUMO
BACKGROUND: The chemokine receptor CXCR6 is critical for sustained tumor control mediated by CD8+ cytotoxic T cells (CTLs) in tumors. Previous studies have shown that ionizing radiation induces an inflamed immune contexture by upregulating CXCR6. However, the clinical significance of CXCR6 expression in triple-negative breast cancer (TNBC) and its correlation with radiotherapy remains unknown. This study aimed to clarify the prognostic value of CXCR6 and its role in the breast tumor microenvironment (TME). METHODS: The messenger RNA and protein expression of CXCR6 in human TNBC and their association with survival were analyzed. The role of CXCR6 in the immune context was investigated using a combination of single-cell RNA sequencing, bulk transcriptome sequencing data, and fluorescence-based multiplex immunohistochemistry (mIHC) techniques. RESULTS: Elevated CXCR6 expression correlated with better clinical outcomes and superior response to adjuvant radiotherapy and immunotherapy in TNBC. CXCR6 fostered an immunostimulatory microenvironment characterized by upregulated cytotoxic markers. We also found that CXCR6 plays a crucial role in regulating the differentiation of CD8+ T cells and the intercellular communication of immune cell subtypes, thus shaping the TME. CONCLUSIONS: This study highlights the emerging role of CXCR6 in shaping the TME and targeting CXCR6 may be a promising strategy for improving the effectiveness of radiotherapy and immunotherapy in TNBC.
Assuntos
Receptores CXCR6 , Neoplasias de Mama Triplo Negativas , Microambiente Tumoral , Humanos , Neoplasias de Mama Triplo Negativas/radioterapia , Neoplasias de Mama Triplo Negativas/imunologia , Feminino , Microambiente Tumoral/imunologia , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Prognóstico , Imunoterapia/métodos , Radioterapia AdjuvanteRESUMO
Influenced by heating, the concentration of atmospheric fine particulate matter (PM2.5) rises in autumn and winter in northern cities. In this study, Q-ACSM, AE33, and Xact 625 were used to carry out online monitoring of PM2.5 chemical components with high time resolution in Xi'an from October 25 to November 17, 2019, to analyze the characteristics of PM2.5 pollution during the transition period of the heating season. Additionally, we analyzed the sources of PM2.5 in combination with the positive matrix factorization model. The results showed that the average PM2.5 concentration during the observation period was (78.3 ± 38.5) µg·m-3, and the main chemical components were organic matter (OA), secondary inorganic ions (SIA), and dust, which accounted for 38.7%, 31.6%, and 21.2%, respectively. The average concentrations of sulfate, nitrate, and ammonium were (4.0 ± 3.1), (14.9 ± 13.7), and (5.8 ± 4.8) µg·m-3, and the average concentrations of the major metals potassium, calcium, and iron were (1.0 ± 0.4), (1.5 ± 1.1), and (1.4 ± 0.9) µg·m-3. Black carbon, chloride ions, and trace elements contributed relatively little to PM2.5 (5.7%, 1.3%, and 1.5%, respectively). In the pollution development and maintenance stage, the concentration of OA and SIA increased by 137.7% to 537.0%, whereas in the pollution dissipation stage, only the concentration of dust gradually increased. The source apportionment results showed that secondary sources, biomass burning, dust, vehicle emission, industrial emission, and coal combustion were the main sources of PM2.5 during the observation period, contributing 29.1%, 21.1%, 15.3%, 12.9%, 11.4%, and 10.2%, respectively. The contribution rate of secondary sources and biomass burning was higher in the pollution development and maintenance stage, and dust was higher in the pollution dissipation stage.
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Colorectal cancer (CRC) is the third most common cancer worldwide and the second most common cause of cancer death. Nanotherapies are able to selectively target the delivery of cancer therapeutics, thus improving overall antitumor efficiency and reducing conventional chemotherapy side effects. Mesoporous silica nanoparticles (MSNs) have attracted the attention of many researchers due to their remarkable advantages and biosafety. We offer insights into the recent advances of MSNs in CRC treatment and their potential clinical application value.
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Background: Exosomes derived from bone marrow mesenchymal stem cells (MSC-exo) have been considered as a promising cell-free therapeutic strategy for ischemic heart disease. Cardioprotective drug pretreatment could be an effective approach to improve the efficacy of MSC-exo. Nicorandil has long been used in clinical practice for cardioprotection. This study aimed to investigate whether the effects of exosomes derived from nicorandil pretreated MSC (MSCNIC-exo) could be enhanced in facilitating cardiac repair after acute myocardial infarction (AMI). Methods: MSCNIC-exo and MSC-exo were collected and injected into the border zone of infarcted hearts 30 minutes after coronary ligation in rats. Macrophage polarization was detected 3 days post-infarction, cardiac function as well as histological pathology were measured on the 28th day after AMI. Macrophages were separated from the bone marrow of rats for in vitro model. Exosomal miRNA sequencing was conducted to identify differentially expressed miRNAs between MSCNIC-exo and MSC-exo. MiRNA mimics and inhibitors were transfected to MSCs or macrophages to explore the specific mechanism. Results: Compared to MSC-exo, MSCNIC-exo showed superior therapeutic effects on cardiac functional and structural recovery after AMI and markedly elevated the ratio of CD68+ CD206+/ CD68+cells in infarcted hearts 3 days post-infarction. The notable ability of MSCNIC-exo to promote macrophage M2 polarization was also confirmed in vitro. Exosomal miRNA sequencing and both in vivo and in vitro experiments identified and verified that miR-125a-5p was an effector of the roles of MSCNIC-exo in vivo and in vitro. Furthermore, we found miR-125a-5p promoted macrophage M2 polarization by inhibiting TRAF6/IRF5 signaling pathway. Conclusion: This study suggested that MSCNIC-exo could markedly facilitate cardiac repair post-infarction by promoting macrophage M2 polarization by upregulating miR-125a-5p targeting TRAF6/IRF5 signaling pathway, which has great potential for clinical translation.
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Exossomos , Células-Tronco Mesenquimais , MicroRNAs , Infarto do Miocárdio , Ratos , Animais , Nicorandil/metabolismo , Fator 6 Associado a Receptor de TNF/metabolismo , Exossomos/metabolismo , Infarto do Miocárdio/patologia , Células-Tronco Mesenquimais/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Transdução de Sinais , Macrófagos/metabolismo , Fatores Reguladores de Interferon/metabolismoRESUMO
SUMMARY: We evaluated the role and mechanism of acteoside in the regulation of memory impairment induced by chronic unpredictable mild stress (CUMS). CUMS was used to induce depression in rats and the successful establishment of CUMS model were verified by forced swimming test and sucrose preference test. The Y-maze test and novel object recognition test assessed memory functions. The structural changes in the cortex and hippocampus were observed by hematoxylin and eosin (HE) staining. Immunofluorescence staining and western blotting determined the protein levels. Y-maze test and novel object recognition test showed that there was memory performance impairment in rats of CUMS group, which was improved by the acteoside treatment. HE staining showed that CUMS exposure damaged the structure in the cortex and hippocampus, while the acteoside treatment alleviated the structural changes. Compared with the control group, the levels of BNDF and CREB in the cortex and hippocampus of the CUMS group were significantly decreased. Acteoside significantly reversed the expressions of these proteins in CUMS rats. Meanwhile, compared with the control group, the levels of p-mTOR and p- P70S6K in the cortex and hippocampus of the CUMS group were significantly increased, and these changes were significantly reversed by acteoside. Nevertheless, the effect of acteoside on mTOR signaling was markedly blocked by rapamycin, a specific inhibitor of mTOR signaling. Acteoside can attenuate memory impairment and ameliorate neuronal damage and synaptic plasticity in depression rats probably via inhibiting the mTOR signaling pathway. Acteoside may serve as a novel reagent for the prevention of depression.
Evaluamos el papel y el mecanismo del acteoside en la regulación del deterioro de la memoria inducido por estrés leve crónico impredecible (ELCI). Se utilizó ELCI para inducir depresión en ratas y el establecimiento exitoso del modelo ELCI se verificó mediante una prueba de natación forzada y una prueba de preferencia de sacarosa. La prueba del laberinto en Y y la prueba de reconocimiento de objetos novedosos evaluaron las funciones de la memoria. Los cambios estructurales en la corteza y el hipocampo se observaron mediante tinción con hematoxilina y eosina (HE). La tinción por inmunofluorescencia y la transferencia Western determinaron los niveles de proteína. La prueba del laberinto en Y y la prueba de reconocimiento de objetos novedosos mostraron que había un deterioro del rendimiento de la memoria en ratas del grupo ELCI, que mejoró con el tratamiento con acteósidos. La tinción con HE mostró que la exposición a ELCI dañó la estructura de la corteza y el hipocampo, mientras que el tratamiento con actósidos alivió los cambios estructurales. En comparación con el grupo de control, los niveles de BNDF y CREB en la corteza y el hipocampo del grupo ELCI disminuyeron significativamente. Acteoside revirtió significativamente las expresiones de estas proteínas en ratas ELCI. Mientras tanto, en comparación con el grupo control, los niveles de p-mTOR y p-P70S6K en la corteza y el hipocampo del grupo ELCI aumentaron significativamente, y estos cambios fueron revertidos significativamente ELCI por el acteoside. Sin embargo, el efecto del acteoside sobre la señalización de mTOR fue notablemente bloqueado por la rapamicina, un inhibidor específico de la señalización de mTOR. El acteoside puede atenuar el deterioro de la memoria y mejorar el daño neuronal y la plasticidad sináptica en ratas con depresión, probablemente mediante la inhibición de la vía de señalización mTOR. Acteoside puede servir como un reactivo novedoso para la prevención de la depresión.