Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 254
Filtrar
1.
Yi Chuan ; 46(5): 398-407, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38763774

RESUMO

Idiopathic pulmonary fibrosis (IPF) is a progressive, chronic, and irreversible interstitial lung disease with unknown cause. To explore the role and regulatory mechanism of leucine-rich repeat-containing protein 15 (LRRC15) in IPF, bleomycin (BLM)-induced pulmonary fibrosis in mouse and A549 cells were constructed, and the expression of LRRC15 were detected. Then, MTT, GFP-RFP-LC3 dual fluorescent labeling system and Western blotting were used to investigate the effects of LRRC15 on cell activity and autophagy after transfection of siLRRC15, respectively. The results indicated that the expression of LRRC15 was significantly increased after the BLM treatment in mouse lung tissue and A549 cells. The designed and synthesized siLRRC15 followed by transfection into A549 cells resulted in a dramatic reduction in LRRC15 expression and partially restored the cell damage induced by BLM. Moreover, the expression of LC3-II and P62 were up-regulated, the amount of autophagosome were increased by GFP-RFP-LC3 dual fluorescent labeling assay after BLM treatment. Meanwhile, this study also showed that the key autophagy proteins LC3-II, ATG5 and ATG7 were up-regulated, P62 was down-regulated and autophagic flux were enhanced after further treatment of A549 cells with siLRRC15. The above findings suggest that LRRC15 is an indicator of epithelial cell damage and may participate in the regulation of fibrosis through autophagy mechanism in IPF. This study provides necessary theoretical basis for further elucidating the mechanism of IPF.


Assuntos
Autofagia , Bleomicina , Autofagia/efeitos dos fármacos , Humanos , Animais , Células A549 , Camundongos , Bleomicina/farmacologia , Fibrose Pulmonar Idiopática/metabolismo , Fibrose Pulmonar Idiopática/patologia , Fibrose Pulmonar Idiopática/induzido quimicamente , Fibrose Pulmonar Idiopática/genética , Proteínas Associadas aos Microtúbulos/genética , Proteínas Associadas aos Microtúbulos/metabolismo , Masculino
2.
Cell Biosci ; 14(1): 48, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38627830

RESUMO

BACKGROUND: Stress is a recognized risk factor for cognitive decline, which triggers neuroinflammation involving microglial activation. However, the specific mechanism for microglial activation under stress and affects learning and memory remains unclear. METHODS: The chronic stress mouse model was utilized to explore the relationship between microglial activation and spatial memory impairment. The effect of hippocampal hyperglycemia on microglial activation was evaluated through hippocampal glucose-infusion and the incubation of BV2 cells with high glucose. The gain-and loss-of-function experiments were conducted to investigate the role of GLUT1 in microglial proinflammatory activation. An adeno-associated virus (AAV) was employed to specifically knockdown of GLUT1 in hippocampal microglia to assess its impact on stressed-mice. RESULTS: Herein, we found that chronic stress induced remarkable hippocampal microglial proinflammatory activation and neuroinflammation, which were involved in the development of stress-related spatial learning and memory impairment. Mechanistically, elevated hippocampal glucose level post-stress was revealed to be a key regulator of proinflammatory microglial activation via specifically increasing the expression of microglial GLUT1. GLUT1 overexpression promoted microglial proinflammatory phenotype while inhibiting GLUT1 function mitigated this effect under high glucose. Furthermore, specific downregulation of hippocampal microglial GLUT1 in stressed-mice relieved microglial proinflammatory activation, neuroinflammation, and spatial learning and memory injury. Finally, the NF-κB signaling pathway was demonstrated to be involved in the regulatory effect of GLUT1 on microglia. CONCLUSIONS: We demonstrate that elevated glucose and GLUT1 expression induce microglia proinflammatory activation, contributing to stress-associated spatial memory dysfunction. These findings highlight significant interplay between metabolism and inflammation, presenting a possible therapeutic target for stress-related cognitive disorders.

3.
ArXiv ; 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38495568

RESUMO

Deciphering how genes interpret information from the concentration of transcription factors (TFs) within the cell nucleus remains a fundamental question in gene regulation. Recent advancements have unveiled the heterogeneous distribution of TF molecules in the nucleus, posing challenges to the precise decoding of concentration signals. To explore this phenomenon, we employ high-resolution single-cell imaging of a fluorescently tagged TF protein, Bicoid, in living fly embryos. We show that accumulation of Bicoid in submicron clusters preserves the spatial information of the maternal Bicoid gradient, and that cluster intensity, size, and frequency offer remarkably precise spatial cues. We further discover that various known gene targets of Bicoid activation colocalize with clusters and that for the target gene Hunchback, this colocalization is dependent on its enhancer binding affinity. Modeling information transfer through these clusters suggests that clustering offers a more rapid sensing mechanism for global nuclear concentrations than freely diffusing TF molecules detected by simple enhancers.

4.
BMC Geriatr ; 24(1): 133, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38317117

RESUMO

BACKGROUND: The COVID-19 pandemic has fueled the widespread adoption of telemedicine in healthcare, particularly in Sarawak, Malaysia. This study investigates the use and acceptance of Sarawak's inaugural multidisciplinary geriatric telemedicine service, TELEG. METHODS: This cross-sectional study took place at the Sarawak Heart Centre's geriatric department from July 1, 2021, to April 30, 2022. Convenient sampling included all TELEG-enrolled patients during this period, to achieve minimum sample size of 148. TELEG's utilization was assessed in terms of medication therapy and treatment plan optimization, as well as enhanced healthcare accessibility. Participants' acceptance of TELEG was measured using the Service User Technology Acceptability Questionnaire (SUTAQ) administered through Google Forms. Descriptive statistics percentages illustrated the proportion of participants who found TELEG moderately to highly acceptable. Associations between baseline characteristics and overall acceptance were explored through bivariate analyses, including Pearson's correlation test, independent t-test, and ANOVA. The influence of six SUTAQ dimensions on overall acceptance, multivariable linear regression using enter method was employed. Statistical significance was determined by p-values less than 0.5. RESULTS: Among 180 geriatric patients enrolled in TELEG during the study period, 149 agreed to participate. TELEG led to medication therapy optimization for 88.6% of participants, primarily involving dose adjustment (44.7%), de-prescribing (31.8%), and prescribing (15.9%). Additionally, 53.8% received treatment plan optimization, predominantly in the form of self-care education (56.3%), referrals for further treatment (33.8%), additional laboratory investigations (29.6%), and increased monitoring (26.8%). Among those educated in self-care (n = 40), dietary intake (27.5%), lower limb exercise (25.0%), and COVID-19 vaccination (12.5%) were the most common topics. All participants expressed moderate to high acceptance of TELEG (mean = 4.9, SD = 0.65, on a scale of 1 to 6). Notably, care personnel concern (B = 0.256; p < 0.001) had the most significant impact on overall acceptance. CONCLUSION: This pioneering study evaluates the utilization and user acceptance of a geriatric telemedicine service in the region, providing valuable insights to support its expansion. Follow-up surveys or interviews to gain insights into users' experiences are crucial to further enhance acceptance.


Assuntos
Pandemias , Telemedicina , Humanos , Idoso , Centros de Atenção Terciária , Malásia/epidemiologia , Estudos Transversais , Vacinas contra COVID-19 , Telemedicina/métodos
5.
Brain Behav Immun ; 115: 143-156, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37848095

RESUMO

Growing evidence suggests that neurovascular dysfunction characterized by blood-brain barrier (BBB) breakdown underlies the development of psychiatric disorders, such as major depressive disorder (MDD). Tight junction (TJ) proteins are critical modulators of homeostasis and BBB integrity. TJ protein Claudin-5 is the most dominant BBB component and is downregulated in numerous depression models; however, the underlying mechanisms remain elusive. Here, we demonstrate a molecular basis of BBB breakdown that links stress and depression. We implemented an animal model of depression, chronic unpredictable mild stress (CUMS) in male C57BL/6 mice, and showed that hippocampal BBB breakdown was closely associated with stress vulnerability. Concomitantly, we found that dysregulated Cldn5 level coupled with repression of the histone methylation signature at its promoter contributed to stress-induced BBB dysfunction and depression. Moreover, histone methyltransferase enhancer of zeste homolog 2 (EZH2) knockdown improved Cldn5 expression and alleviated depression-like behaviors by suppressing the tri-methylation of lysine 27 on histone 3 (H3K27me3) in chronically stressed mice. Furthermore, the stress-induced excessive transfer of peripheral cytokine tumor necrosis factor-α (TNF-α) into the hippocampus was prevented by Claudin-5 overexpression and EZH2 knockdown. Interestingly, antidepressant treatment could inhibit H3K27me3 deposition at the Cldn5 promoter, reversing the loss of the encoded protein and BBB damage. Considered together, these findings reveal the importance of the hippocampal EZH2-Claudin-5 axis in regulating neurovascular function and MDD development, providing potential therapeutic targets for this psychiatric illness.


Assuntos
Barreira Hematoencefálica , Transtorno Depressivo Maior , Humanos , Masculino , Camundongos , Animais , Barreira Hematoencefálica/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Histonas/metabolismo , Claudina-5/genética , Claudina-5/metabolismo , Depressão/metabolismo , Transtorno Depressivo Maior/metabolismo , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Camundongos Endogâmicos C57BL
6.
World J Clin Cases ; 11(32): 7761-7769, 2023 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-38073680

RESUMO

BACKGROUND: Perimenopausal is the period when women's ovarian function begins to decline before and after menopause. During this period, women experience a series of mental state changes, such as decreased hormone levels, decreased libido, and even female sexual dysfunction (FSD) in severe cases, which reduces their quality of life. Factors affecting the occurrence of FSD include physiological and non-physiological factors, among which physiological factors are uncontrollable. Therefore, it is particularly important to ascertain the related non-physiological factors that affect the occurrence of FSD for improving the quality of sexual life of perimenopausal women. AIM: To investigate the mediating effect of depressive mood and body image on menopausal symptoms and sexual function in perimenopausal women. METHODS: A total of 186 perimenopausal women were enrolled between January 2019 and January 2021 and divided into the FSD (134 cases) and control (52 cases) groups based on the presence and absence of FSD. Clinical data were compared between the two groups. FSD-related factors were analyzed using logistic regression analysis. Hamilton Depression Scale (HAMD), Body Image Scale (BIS), and Menopause Rating Scale (MRS) scores were compared among women with different FSD scores. The correlation of the MRS score with the BIS and HAMD scores and the mediating effect of the BIS and HAMD scores on the MRS score and female sexual function index (FSFI) were analyzed. RESULTS: The HAMD and BIS scores were higher in the FSD group than in the control group, and the difference in monthly income between the two groups was statistically significant (all P < 0.05). Monthly income of < 2000 yuan [odds ratio (OR) = 26.586, P = 0.000], BIS score (OR = 1.590, P = 0.000), and HAMD score (OR = 1.884, P = 0.000) were independent risk factors for FSD. MRS scores were positively correlated with BIS and HAMD scores (r = 0.358 and 0.244, P = 0.000 and 0.001, respectively) and negatively correlated with FSFI scores (r = -0.433, P = 0.000). Body image and depressive mood had partial mediating effects, accounting for 39.90% of the total effect. CONCLUSION: Depression and body image play mediating roles between menopausal symptoms and sexual function in perimenopausal women.

7.
Vaccine ; 41(49): 7482-7490, 2023 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-37953099

RESUMO

BACKGROUND: Hantaan virus (HTNV, Orthohantavirus hantanensae species, Hantaviridae family) is the main etiological agent responsible for hemorrhagic fever with renal syndrome (HFRS). The novel HTNV may pose a potential danger to the control and prevention of HFRS in China, which highlights the importance of vaccine development in public health management. In previous studies, our laboratory discovered and successfully isolated a new HTNV strain, HV004 strain, from Apodemus agrarius captured in an epidemic area in Hubei, China. METHODS: An initial biological and pathogenicity characterization of HTNV 76-118 (standard train), HV114 strain (a clinical isolate from Hubei province in 1986), and the novel isolate HV004 strain from the epidemic areas of Hubei province were performed in susceptible cells and in vivo. An experimental HV004 strain inactivated vaccine was prepared, and its corresponding immunogenicity was analyzed in BALB/c mice. RESULTS: HV004 strain had a similar but higher pathogenicity than HTNV 76-118 and HV114 in suckling mice. A subcutaneous vaccination (s.c.) with the inactivated HTNV vaccine adjuvanted with aluminum, followed by a challenge intraperitoneally with 106 FFU/ml HTNV, afforded full protection against an HTNV challenge. All immunized mice in every group elicited serum neutralizing antibodies with increasing dosages, which may protect mice from HTNV infection. A dose-dependent stimulation index of splenocytes was also observed in immunized mice. The percentage of IFN-γ-producing CD3+CD8+ T cells was significantly higher in the spleens of immunized mice than in those of control mice. CONCLUSIONS: These findings suggest that the inactivated HTNV vaccine may stimulate mice to produce high levels of antibodies with neutralization activity and elicit specific anti-HTNV humoral and cellular immune responses in BALB/c mice against the prevalent strain of HTNV in south central China.


Assuntos
Doenças Transmissíveis , Vírus Hantaan , Infecções por Hantavirus , Febre Hemorrágica com Síndrome Renal , Orthohantavírus , Camundongos , Animais , Febre Hemorrágica com Síndrome Renal/prevenção & controle , Febre Hemorrágica com Síndrome Renal/epidemiologia , Virulência , Vacinas de Produtos Inativados , Linfócitos T CD8-Positivos , Anticorpos Antivirais , Infecções por Hantavirus/prevenção & controle
8.
ACS Omega ; 8(45): 42540-42547, 2023 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-38024748

RESUMO

The application of an inhibitor to the remaining coal in the goaf not only prevents spontaneous combustion of the coal seam in the mining area but also greatly enhances the capacity of coal to adsorb CO2. To investigate the mechanism by which inhibitors improve the CO2 adsorption capacity of the coal seam in the goaf, we conducted swelling experiments, infrared spectroscopy, scanning electron microscopy, and X-ray diffraction analyses to examine the microstructural changes in the adsorption of CO2 before and after inhibition. The results indicate that after inhibition, the number of hydrogen bonds between coal macromolecules decreased, and the samples exhibited approximately 5% swelling. This swelling of the coal macromolecular structure and the increased distance between coal particles create additional space for CO2 sequestration, which is a critical factor contributing to the enhanced CO2 adsorption capacity of coal. The mineral composition of coal consists of 75.6% kaolinite, and inhibition leads to a reduction in kaolinite content by 0.8-7.9%. After inhibition, the swelling and disintegration of kaolinite cause uneven stress, resulting in changes to the pore structure. Closed pores filled with kaolinite transform into open pores, and the original pores crack, forming new pores and pore channels. The dissolution of kaolinite particles increases the porosity of the coal, further facilitating gas adsorption. Among the three inhibitors tested, the most effective in enhancing CO2 sequestration by bituminous coal in the mining area was the urea solution. This study holds significant importance in improving the CO2 sequestration capacity of residual coal in goaves.

9.
Eur J Transl Clin Med ; 6(1): 9-13, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37693941

RESUMO

Pregnancy increases metabolic demand for insulin and may lead to the exhaustion of intraportally transplanted islets and post-gestational hyperglycemia. To prevent these complications, we implemented preemptive insulin supplementation during two subsequent pregnancies in an insulin-independent islet transplant recipient. This strategy resulted in optimal blood glucose control during the pregnancies, the preservation of the optimal islet graft function and the postpartum maintenance of long-term insulin independence.

10.
bioRxiv ; 2023 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-37645833

RESUMO

Genetic interactions have long informed our understanding of the coordinated proteins and pathways that respond to DNA damage in mammalian cells, but systematic interrogation of the genetic network underlying that system has yet to be achieved. Towards this goal, we measured 147,153 pairwise interactions among genes implicated in PARP inhibitor (PARPi) response. Evaluating genetic interactions at this scale, with and without exposure to PARPi, revealed hierarchical organization of the pathways and complexes that maintain genome stability during normal growth and defined changes that occur upon accumulation of DNA lesions due to cytotoxic doses of PARPi. We uncovered unexpected relationships among DNA repair genes, including context-specific buffering interactions between the minimally characterized AUNIP and BRCA1-A complex genes. Our work thus establishes a foundation for mapping differential genetic interactions in mammalian cells and provides a comprehensive resource for future studies of DNA repair and PARP inhibitors.

11.
Chem Sci ; 14(23): 6393-6398, 2023 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-37325142

RESUMO

A highly enantioselective cobalt-catalyzed desymmetrizing reductive cyclization of alkynyl cyclodiketones has been developed. Under mild reaction conditions by employing HBpin as a reducing agent and ferrocene-based PHOX as a chiral ligand, a series of polycyclic tertiary allylic alcohols bearing contiguous quaternary stereocenters are achieved in moderate to excellent yields with excellent enantioselectivities (up to 99%). Broad substrate scope and high functional group compatibility are observed in this reaction. A CoH-catalyzed pathway involving alkyne hydrocobaltation followed by nucleophilic addition to the C[double bond, length as m-dash]O bond is proposed. Synthetic transformations of the product are conducted to demonstrate the practical utilities of this reaction.

12.
Heliyon ; 9(5): e16068, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37215773

RESUMO

Although many models are available to predict prognosis of heart failure patients, most tools combining survival analysis are based on proportional hazard model. Non-linear machine learning algorithms would overcome the limitation of the time-independent hazard ratio assumption and provide more information in readmission or mortality prediction among heart failure patients. The present study collected the clinical information of 1796 hospitalized heart failure patients surviving during hospitalization in a Chinese clinical center from December 2016 to June 2019. A traditional multivariate Cox regression model and three machine learning survival models were developed in derivation cohort. Uno's concordance index and integrated Brier score in validation cohort were calculated to evaluate the discrimination and calibration of different models. Time-dependent AUC and Brier score curves were plotted to assess the performance of models at different time phases.

14.
J Aging Phys Act ; 31(1): 89-95, 2023 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-35894957

RESUMO

This descriptive cross-sectional mixed methods study conducted in Singapore aimed to describe community-dwelling older adults' differences in physical activity (PA) based on perceived safety to exercise, barriers to PA, and preferred modes of PA during a pandemic. Out of 268 older adults, 25.4% felt unsafe to exercise during the pandemic. More participants who felt unsafe were aged 75 years and older (72.1% vs. 57.0%, p = .028) and lacked formal education (54.4% vs. 37.0%, p = .040). Barriers included difficulties exercising with masks, family concerns, and exercise center closures. Those who felt unsafe were significantly more likely to exercise at home and had significantly shorter duration of exercise and walks per week (2.72 vs. 4.50 hr, p = .002). Perceived barriers and exercise preferences should be considered when developing programs to improve older adults' PA during pandemics.


Assuntos
COVID-19 , Pandemias , Humanos , Idoso , Pandemias/prevenção & controle , Vida Independente , Estudos Transversais , Singapura/epidemiologia , COVID-19/prevenção & controle , Exercício Físico
15.
Chin J Integr Med ; 29(3): 213-223, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36044114

RESUMO

OBJECTIVE: To evaluate the apoptosis and cycle arrest effects of Oldenlandia diffusa flavonoids on human gastric cancer cells, determine the action mechanisms in association with the mitochondrial dependent signal transduction pathway that controls production of reactive oxygen species (ROS), and evaluate the pharmacodynamics of a mouse xenotransplantation model to provide a reference for the use of flavonoids in prevention and treatment of gastric cancer. METHODS: Flavonoids were extracted by an enzymatic-ultrasonic assisted method and purified with D-101 resin. Bioactive components were characterized by high-performance liquid chromatography. Cell lines MKN-45, AGS, and GES-1 were treated with different concentrations of flavonoids (64, 96, 128, 160 µg/mL). The effect of flavonoids on cell viability was evaluated by MTT method, and cell nuclear morphology was observed by Hoechst staining. The apoptosis rate and cell cycle phases were measured by flow cytometry, the production of ROS was detected by laser confocal microscope, the mitochondrial membrane potential (MMP) were observed by fluorescence microscope, and the expression of apoptotic proteins related to activation of mitochondrial pathway were measured by immunoblotting. MKN-45 cells were transplanted into BALB/c nude mice to establish a xenograft tumor model. Hematoxylin and eosin staining was used to reveal the subcutaneous tumor tissue. The tumor volume and tumor weight were measured, the expression levels of proliferation markers proliferating cell nuclear antigen (PCNA) and Ki-67 were detected by immunohistochemistry, and the expression levels of CA72-4 were measured by enzyme linked immunosorbent assay. RESULTS: Oldenlandia diffusa flavonoids inhibited proliferation of MKN-45 and AGS human gastric cancer cells, arrested the cell cycle in G1/S phase, induced accumulation of ROS in the process of apoptosis, and altered MMP. In addition, flavonoids increased Apaf-1, Cleaved-Caspase-3, and Bax, and decreased Cyclin A, Cdk2, Bcl-2, Pro-Caspase-9, and Mitochondrial Cytochrome C (P<0.05). The MKN-45 cell mouse xenotransplantation model further clarified the growth inhibitory effect of flavonoids towards tumors. The expression levels of PCNA and Ki-67 decreased in each flavonoid dose group, the expression level of CA72-4 decreased (P<0.05). CONCLUSION: Flavonoids derived from Oldenlandia diffusa can inhibit proliferation and induce apoptosis of human gastric cancer cells by activating the mitochondrial controlled signal transduction pathway.


Assuntos
Oldenlandia , Neoplasias Gástricas , Humanos , Animais , Camundongos , Oldenlandia/metabolismo , Antígeno Nuclear de Célula em Proliferação , Flavonoides/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Camundongos Nus , Antígeno Ki-67 , Linhagem Celular Tumoral , Apoptose , Extratos Vegetais/farmacologia , Caspases , Proliferação de Células
16.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-969997

RESUMO

The development status of the first 11 inheritance studios of acupuncture and moxibustion academic schools is summarized. Aiming at the current problems, it is suggested to establish qualitative and quantitative evaluation standards and establish a fair and reasonable evaluation system, build a systematic scientific theory and excavate the inherent laws of the schools, implement standardized management of the schools and protect the personalized characteristics of the schools, open outpatient clinic of acupuncture and moxibustion schools and promote the characteristic diagnosis and treatment technology, to promote the inheritance and development of acupuncture and moxibustion academic schools.


Assuntos
Moxibustão , Terapia por Acupuntura , Instituições Acadêmicas
17.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-969975

RESUMO

Qilu acupuncture and moxibustion has promoted the formation and development of traditional Chinese medicine, which has a special historical position. By systematically collecting, sorting out and summarizing the characteristic acupuncture methods and academic ideas of several Qilu acupuncturists since the founding of the People's Republic of China, the understanding of the advantages and characteristics of Qilu modern acupuncture methods is deepened, aiming to exploring the inheritance and development pattern of Qilu acupuncture methods in the new era.


Assuntos
Humanos , Terapia por Acupuntura , Moxibustão , Acupuntura , Medicina Tradicional Chinesa , China
18.
Chinese Journal of Pathology ; (12): 447-453, 2023.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-985699

RESUMO

Objective: To investigate the clinicopathological features and immunohistochemical phenotypes of gastric SMARCA4-deficient undifferentiated carcinoma, and to discuss the daily diagnostics of this entity and analyze its prognosis. Methods: The cases of gastric SMARCA4-deficient undifferentiated carcinoma diagnosed at the Department of Pathology, Peking University Cancer Hospital, China from January 2010 to August 2022 were collected. The histological sections were reviewed, the immunohistochemical results and clinicopathological features were analyzed, and relevant literature was reviewed. Results: Pure foci of undifferentiated carcinoma were seen in 7 cases, and 1 case was accompanied by a moderately differentiated tubular adenocarcinoma component. Undifferentiated carcinoma foci showed similar sheet-like or solid diffuse growth pattern, medium-sized tumor cells characterized by 1-2 nucleoli, and abundant cytoplasm and rhabdoid appearance. The average patient age was 65±8 years. Six patients were male and 2 were female. Immunohistochemical staining showed that undifferentiated carcinoma of all 8 tumors were negative for SMARCA4 (BRG1). Among 7 patients who underwent SMARCA2 (BRM) and SMARCB1 (INI1) staining, 4 cases showed loss of BRM expression, 2 cases showed weakly positive staining, and 1 case was diffusely positive, but all 7 cases were diffusely strong positive for INI1. The neuroendocrine marker, synaptophysin, was weakly positive in 5 cases, while CgA and CD56 were negative in 8 cases. Ki-67 index was more than 70%. Two cases were mismatch repair deficient and showed the loss of MLH1/PMS2 expression, while 1 case showed only MSH2 loss. PD-L1 staining showed that combined positive score (CPS)≥1 in 4 cases (CPS ranging from 1 to 55) and CPS<1 in the other 3 cases. Four patients had clinical stage Ⅳ disease. Two of them died within 3 months after diagnosis. Conclusions: Gastric SMARCA4-deficient undifferentiated carcinoma/rhabdoid carcinoma is a rare group of highly malignant tumors with a poor prognosis. Loss of the core subunit of SWI/SNF complex may be associated with the development of dedifferentiated histological pattern and aggressive tumor progression, which may be more frequently accompanied with mismatch repair deficiency.


Assuntos
Masculino , Feminino , Humanos , Carcinoma/patologia , Adenocarcinoma , Neoplasias Colorretais , Diferenciação Celular , Neoplasias Gástricas , Biomarcadores Tumorais , DNA Helicases , Proteínas Nucleares , Fatores de Transcrição
19.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1008802

RESUMO

Terpenoids are important secondary metabolites of plants that possess both pharmacological activity and economic value. Terpene synthases(TPSs) are key enzymes in the synthesis process of terpenoids. In order to investigate the TPS gene family members and their potential functions in Schizonepeta tenuifolia, this study conducted a systematic analysis of the TPS gene family of S. tenuifolia based on the whole genome data of S. tenuifolia using bioinformatics methods. The results revealed 57 StTPS members identified from the genome database of S. tenuifolia. The StTPS family members encoded 285-819 amino acids, with protein molecular weights ranging from 32.75 to 94.11 kDa, all of which were hydrophilic proteins. The StTPS family members were mainly distributed in the cytoplasm and chloroplasts, exhibiting a random and uneven physical localization pattern. Phylogenetic analysis showed that the StTPS genes family were divided into six subgroups, mainly belonging to the TPS-a and TPS-b subfamilies. Promoter analysis predicted that the TPS gene family members could respond to various stressors such as light, abscisic acid, and methyl jasmonate(MeJA). Transcriptome data analysis revealed that most of the TPS genes were expressed in the roots of S. tenuifolia, and qRT-PCR analysis was conducted on genes with high expression in leaves and low expression in roots. Through the analysis of the TPS gene family of S. tenuifolia, this study identified StTPS5, StTPS18, StTPS32, and StTPS45 as potential genes involved in sesquiterpene synthesis of S. tenuifolia. StTPS45 was cloned for the construction of an prokaryotic expression vector, providing a reference for further investigation of the function and role of the TPS gene family in sesquiterpene synthesis.


Assuntos
Filogenia , Terpenos/metabolismo , Proteínas de Plantas/metabolismo , Lamiaceae/genética , Sesquiterpenos
20.
Chem Biodivers ; 19(11): e202200459, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36328758

RESUMO

Turpiniae Folium, the dried leaves of Turpinia arguta Seem., is a kind of historic traditional Chinese medicine. Here, based on our previous study, we extracted the Turpiniae Folium polysaccharides (TFP) and isolated three polysaccharide fractions from TFP. Then, TFP and one of the major polysaccharide fractions (TFP-1a) were identified through HPLC, HPGPC, and ATR-FTIR. Furthermore, the evaluations of their antioxidative, anti-inflammatory activities and inhibitory effect on angiotensin II-induced vascular smooth muscle cells (VSCMs) proliferation in vitro were conducted. Both TFP and TFP-1a showed strong hydroxyl radical scavenging, DPPH radical scavenging, and Fe2+ chelating activities, and exerted strong anti-inflammatory activity. Moreover, TFP and TFP-1a also possessed a strong inhibitory effect on Ang II-induced VSCMs proliferation. On these premises, we inferred that TFP and TFP-1a could be potential and promising natural antioxidants, anti-inflammatory agents, and implicated to treat cardiovascular disease.


Assuntos
Antioxidantes , Músculo Liso Vascular , Antioxidantes/farmacologia , Polissacarídeos/farmacologia , Anti-Inflamatórios/farmacologia , Folhas de Planta
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...