Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 198
Filtrar
1.
Medicine (Baltimore) ; 103(18): e37927, 2024 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-38701296

RESUMEN

BACKGROUND: The efficacy and safety of different oral ginkgo-based Chinese patent medicines (CPMs) regimens for hypertension patients were analyzed based on the network meta-analysis of the frequency framework. METHODS: We conducted a comprehensive search of PubMed, Cochrane Library, Embase, China National Knowledge Infrastructure, Wanfang, China Science and Technology Journal Database, and Chinese Biomedical Literature Database to gather data on randomized controlled trials (RCTs) evaluating the efficacy of 8 ginkgo biloba oral preparations for the treatment of hypertension. The trials included in the analysis were conducted from the inception of the databases up to September 2023. Methodological quality and risk of bias were assessed using the RoB 2.0 evaluation tool, and a reticulated meta-analysis was conducted using STATA MP 14 software. The RCTs included in this study were published studies and therefore did not require ethics committee review or patient consent. RESULTS: We ultimately included 46 RCTs covering 8 CPMs including ginkgo biloba tablet (GBT), GB capsule (GBC), ginkgo biloba drop (GBD), ginkgo biloba ketone ester drop, Fufangyinxing capsule, fufangyinxingtongmai oral liquid, Yinxingmihuan oral liquid, Yindanxinanotong softgel capsule (YDXNT). GBD + CT demonstrated the highest effectiveness in reducing systolic blood pressure (surface under the cumulative ranking [SUCRA] = 78.7%) and improving total effective rate (SUCRA = 86.7%). GBC + CT exhibited the greatest efficacy in reducing diastolic blood pressure (SUCRA = 92.6%). GBT + CT was identified as the most effective in lowering total cholesterol (TC) (SUCRA = 100%). Additionally, YDXNT + CT demonstrated notable improvements in triglyceride levels (SUCRA = 92.2%), Nitric oxide (NO) (SUCRA = 93.9%), and ET-1 (SUCRA = 67.5%). In terms of safety, 14 studies reported the occurrence of adverse reactions with a high degree of clinical heterogeneity, which was only qualitatively analyzed in this study. CONCLUSION SUBSECTIONS: We found that a combination of 8 ginkgo-based CPMs + CT was effective in hypertension compared with CT. The evidence showed that GBD + CT were the best in improving systolic blood pressure and total effective rate, GBC + CT improved diastolic blood pressure, GBT + CT were the most effective in improving TC, and YDXNT + CT was the most effective in improving TG, NO, and ET-1. Adverse effects were only analyzed qualitatively, and the number of adverse effects of CPMs treatment was relatively low compared to CT. In addition, the quality of the literature included in the study was low, and further validation through RCTs with larger sample sizes, higher quality, and more rigorously designed is needed.


Asunto(s)
Medicamentos Herbarios Chinos , Extracto de Ginkgo , Ginkgo biloba , Hipertensión , Metaanálisis en Red , Ensayos Clínicos Controlados Aleatorios como Asunto , Humanos , Antihipertensivos/uso terapéutico , Antihipertensivos/efectos adversos , Medicamentos Herbarios Chinos/uso terapéutico , Medicamentos Herbarios Chinos/efectos adversos , Hipertensión/tratamiento farmacológico , Resultado del Tratamiento
2.
iScience ; 27(6): 109901, 2024 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-38799554

RESUMEN

Non-apoptotic regulated cell death (RCD) of tumor cells profoundly affects tumor progression and plays critical roles in determining response to immune checkpoint inhibitors (ICIs). Prognosis-distinctive HCC subtypes were identified by consensus cluster analysis based on the expressions of 507 non-apoptotic RCD genes obtained from databases and literature. Meanwhile, a set of bioinformatic tools was integrated to analyze the differences of the tumor immune microenvironment infiltration, genetic mutation, copy number variation, and epigenetics alternations within two subtypes. Finally, a non-apoptotic RCDRS signature was constructed and its reliability was evaluated in HCC patients' tissues. The high-RCDRS HCC subgroup showed a significantly lower overall survival and less sensitivity to ICIs compared to low-RCDRS subgroup, but higher sensitivity to cisplatin, paclitaxel, and sorafenib. Overall, we established an RCDRS panel consisting of four non-apoptotic RCD genes, which might be a promising predictor for evaluating HCC prognosis, guiding therapeutic decision-making, and ultimately improving patient outcomes.

3.
Adv Sci (Weinh) ; 11(14): e2305204, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38327127

RESUMEN

Hepatocellular carcinoma (HCC) is a highly lethal malignant tumor, and the current non-invasive diagnosis method based on serum markers, such as α-fetoprotein (AFP), and des-γ-carboxy-prothrombin (DCP), has limited efficacy in detecting it. Therefore, there is a critical need to develop novel biomarkers for HCC. Recent studies have highlighted the potential of exosomes as biomarkers. To enhance exosome enrichment, a silicon dioxide (SiO2) microsphere-coated three-dimensional (3D) hierarchical porous chip, named a SiO2-chip is designed. The features of the chip, including its continuous porous 3D scaffold, large surface area, and nanopores between the SiO2 microspheres, synergistically improved the exosome capture efficiency. Exosomes from both non-HCC and HCC subjects are enriched using an SiO2-chip and performed RNA sequencing to identify HCC-related long non-coding RNAs (lncRNAs) in the exosomes. This study analysis reveales that LUCAT-1 and EGFR-AS-1 are two HCC-related lncRNAs. To further detect dual lncRNAs in exosomes, quantitative real time polymerase chain reaction (qRT-PCR) is employed. The integration of dual lncRNAs with AFP and DCP significantly improves the diagnostic accuracy. Furthermore, the integration of dual lncRNAs with DCP effectively monitors the prognosis of patients with HCC and detects disease progression. In this study, a liquid biopsy-based approach for noninvasive and reliable HCC detection is developed.


Asunto(s)
Carcinoma Hepatocelular , Exosomas , Neoplasias Hepáticas , ARN Largo no Codificante , Humanos , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/genética , alfa-Fetoproteínas/análisis , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/genética , Biomarcadores de Tumor/genética , Exosomas/genética , Exosomas/química , Porosidad , Dióxido de Silicio , Perfilación de la Expresión Génica
4.
bioRxiv ; 2024 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-38405864

RESUMEN

Hypothyroidism is commonly detected in patients with medulloblastoma (MB). A possible link between thyroid hormone (TH) signaling and MB pathogenicity has not been reported. Here, we find that TH plays a critical role in promoting tumor cell differentiation. Reduction in TH levels frees the TH receptor, TRα1, to bind to EZH2 and repress expression of NeuroD1, a transcription factor that drives tumor cell differentiation. Increased TH reverses EZH2-mediated repression of NeuroD1 by abrogating the binding of EZH2 and TRα1, thereby stimulating tumor cell differentiation and reducing MB growth. Importantly, TH-induced differentiation of tumor cells is not restricted by the molecular subgroup of MB. These findings establish an unprecedented association between TH signaling and MB pathogenicity, providing solid evidence for TH as a promising modality for MB treatment.

5.
Small Methods ; 8(1): e2301009, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37882328

RESUMEN

Basic and clinical cancer research requires tumor models that consistently recapitulate the characteristics of prima tumors. As ex vivo 3D cultures of patient tumor cells, patient-derived tumor organoids possess the biological properties of primary tumors and are therefore excellent preclinical models for cancer research. Patient-derived organoids can be established using primary tumor tissues, peripheral blood, pleural fluid, ascites, and other samples containing tumor cells. Circulating tumor cells acquired by non-invasive sampling feature dynamic circulation and high heterogeneity. Circulating tumor cell-derived organoids are prospective tools for the dynamic monitoring of tumor mutation evolution profiles because they reflect the heterogeneity of the original tumors to a certain extent. This review discusses the advantages and applications of patient-derived organoids. Meanwhile, this work highlights the biological functions of circulating tumor cells, the latest advancement in research of circulating tumor cell-derived organoids, and potential application and challenges of this technology.


Asunto(s)
Células Neoplásicas Circulantes , Humanos , Medicina de Precisión , Organoides/patología
6.
Zhongguo Zhen Jiu ; 43(12): 1425-1430, 2023 Dec 12.
Artículo en Inglés, Chino | MEDLINE | ID: mdl-38092542

RESUMEN

OBJECTIVES: To observe the effects on the glucose-lipid metabolism and the expression of zinc-α2-glycoprotein (ZAG) and glucose transporter 4 (GLUT4) in the femoral quadriceps and adipose tissue after electroacupuncture (EA) at "Pishu" (BL 20), "Weiwanxiashu" (EX-B 3), "Zusanli" (ST 36) and "Sanyinjiao" (SP 6) in the rats with diabetes mellitus type 2 (T2DM), so as to explore the effect mechanism of EA in treatment of T2DM. METHODS: Twelve ZDF male rats were fed with high-sugar and high-fat fodder, Purina #5008 for 4 weeks to induce T2DM model. After successfully modeled, the rats were randomly divided into a model group and an EA group, with 6 rats in each one. Additionally, 6 ZL male rats of the same months age were collected as the blank group. The rats in the EA group were treated with EA at bilateral "Pishu" (BL 20), "Weiwanxiashu" (EX-B 3), "Zusanli" (ST 36) and "Sanyinjiao" (SP 6), with continuous wave, 15 Hz in frequency, and 2 mA in intensity. The electric stimulation lasted 20 min each time. EA was delivered once daily, 6 times a week for 4 weeks. Separately, the levels of fasting blood glucose (FBG) was measured before modeling, before and after intervention, and the body mass of each rat was weighted before and after intervention. After intervention, the levels of the total cholesterol (TC), triacylglycerol (TG) and free fatty acid (FFA) in serum were detected using enzyme colorimetric method; and the levels of the serum insulin (INS) and ZAG were detected by ELISA. Besides, the insulin sensitivity index (HOMA-ISI) was calculated. With Western blot technique adopted, the protein expressions of ZAG and GLUT4 in the femoral quadriceps and adipose tissue were determined. RESULTS: After intervention, compared with the blank group, the levels of FBG and body mass, and the levels of serum TC, TG, FFA and INS increased (P<0.01), while HOMA-ISI decreased (P<0.01); the level of ZAG in the serum and the protein expressions of ZAG and GLUT4 in the femoral quadriceps and adipose tissue dropped (P<0.01) in the model group. In the EA group, compared with the model group, the levels of FBG and body mass, and the levels of serum TC, TG, FFA and INS were reduced (P<0.01), and HOMA-ISI increased (P<0.01); the level of ZAG in the serum and the protein expressions of ZAG and GLUT4 in the femoral quadriceps and adipose tissue increased (P<0.01, P<0.05). CONCLUSIONS: Electroacupuncture can effectively regulate glucose-lipid metabolism, improve insulin resistance and sensitivity in the rats with T2DM, which is associated with the modulation of ZAG and GLUT4 expression in the skeletal muscle and adipose tissue.


Asunto(s)
Diabetes Mellitus Tipo 2 , Electroacupuntura , Ratas , Masculino , Animales , Glucosa/metabolismo , Ratas Sprague-Dawley , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/terapia , Metabolismo de los Lípidos , Triglicéridos , Tejido Adiposo/metabolismo , Puntos de Acupuntura
7.
Huan Jing Ke Xue ; 44(12): 6823-6832, 2023 Dec 08.
Artículo en Chino | MEDLINE | ID: mdl-38098407

RESUMEN

Using diammonium hydrogen phosphate as an activator and N and P source and and bamboo chips as the carbon source, N, P co-doped activated carbon was prepared by one-step pyrolysis and used to efficiently remove La3+ in aqueous solutions. The effects of activation temperature and pH value on the adsorption performance of La3+ were analyzed, and the activation and adsorption mechanisms were explored using TG-IR, SEM-EDX, pore structure, XPS, and hydrophilicity. The results showed that diammonium hydrogen phosphate easily decomposed at a high temperature to produce ammonia and phosphoric acid, which activated the material and promoted the increase in the specific surface area and pore volume of the activated carbon. As an N and P source, the addition of diammonium hydrogen phosphate successfully achieved the N, P co-doping of activated carbon, and the introduction of N- and P-containing functional groups was the key to enhance the adsorption of La3+. Among them, graphitic nitrogen could provide interactions between La3+-π bonds, and C-P=O and C/P-O-P could provide active sites for the adsorption of La3+ through complexation and electrostatic interaction. The adsorption of La3+ on N, P co-doped activated carbons was endothermic and spontaneous, and the adsorption process conformed to the Langmuir isotherm and secondary kinetic model. Under the process conditions of an activation temperature of 900℃ and pH=6, the adsorption capacity of the N, P co-doped activated carbon was as high as 55.18 mg·g-1, which was 2.53 times higher than that of the undoped sample, and its adsorption selectivity for La3+ in the La3+/Na+and La3+/Ca2+ coexistence systems reached 93.49% and 82.49%, respectively. Additionally, the removal efficiency remained above 54% after five successive adsorption-desorption cycle experiments.

8.
Int J Mol Sci ; 24(16)2023 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-37628996

RESUMEN

Oncogenic Yes-associated protein (YAP) 1 fusions have been recently identified in several cases of meningioma mostly involving pediatric patients. The meningiomas harboring YAP1-MAML2, which is the most frequent fusion subtype, exhibit activated YAP1 signaling and share similarities with NF2 (neurofibromatosis type 2 gene) mutant meningiomas. We reported a rare case of atypical intraparenchymal meningioma with YAP1-MAML2 fusion in a 20-year-old male. The patient presented with an episode of seizure without a medical history. MRI revealed a lesion in the right temporal lobe without extra-axial involvement. The radiological and morphological findings, however, were indistinctive from other intracranial diseases, e.g., vascular malformation and glioma. Immunohistochemical results confirmed the presence of abundant meningothelial cells in the tumor and indicated brain invasion, supporting the diagnosis of atypical intraparenchymal meningioma. Targeted RNA fusion analysis further identified a YAP1-MAML2 rearrangement in the tumor. Non-dural-based intraparenchymal meningiomas are uncommon, and the careful selection of specific tumor markers is crucial for an accurate diagnosis. Additionally, the detection of the fusion gene provides valuable insights into the oncogenic mechanism of meningioma.


Asunto(s)
Neoplasias Meníngeas , Meningioma , Humanos , Masculino , Adulto Joven , Niño , Adulto , Meningioma/diagnóstico por imagen , Meningioma/genética , Genes de la Neurofibromatosis 2 , Proteínas Adaptadoras Transductoras de Señales/genética , Transducción de Señal , Factores de Transcripción/genética , Neoplasias Meníngeas/diagnóstico por imagen , Neoplasias Meníngeas/genética , Transactivadores/genética
9.
Entropy (Basel) ; 25(7)2023 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-37510028

RESUMEN

The selection of offshore wind farm site (OWFS) has important strategic significance for vigorously developing offshore new energy and is deemed as a complicated uncertain multicriteria decision-making (MCDM) process. To further promote offshore wind power energy planning and provide decision support, this paper proposes a hybrid picture fuzzy (PF) combined compromise solution (CoCoSo) technique for prioritization of OWFSs. To begin with, a fresh PF similarity measure is proffered to estimate the importance of experts. Next, the novel operational rules for PF numbers based upon the generalized Dombi norms are defined, and four novel generalized Dombi operators are propounded. Afterward, the PF preference selection index (PSI) method and PF stepwise weights assessment ratio analysis (SWARA) model are propounded to identify the objective and subjective weight of criteria, separately. In addition, the enhanced CoCoSo method is proffered via the similarity measure and new operators for ranking OWFSs with PF information. Lastly, the applicability and feasibility of the propounded PF-PSI-SWARA-CoCoSo method are adopted to ascertain the optimal OWFS. The comparison and sensibility investigations are also carried out to validate the robustness and superiority of our methodology. Results manifest that the developed methodology can offer powerful decision support for departments and managers to evaluate and choose the satisfying OWFSs.

10.
Br J Pharmacol ; 180(24): 3175-3193, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37501645

RESUMEN

BACKGROUND AND PURPOSE: Osteosarcoma, a primary malignant bone tumour prevalent among adolescents and young adults, remains a considerable challenge despite protracted progress made in enhancing patient survival rates over the last 40 years. Consequently, the development of novel therapeutic approaches for osteosarcoma is imperative. Sanguinarine (SNG), a compound with demonstrated potent anticancer properties against various malignancies, presents a promising avenue for exploration. Nevertheless, the intricate molecular mechanisms underpinning SNG's actions in osteosarcoma remain elusive, necessitating further elucidation. EXPERIMENTAL APPROACH: Single-stranded DNA-binding protein 1 (SSBP1) was screened out by differential proteomic analysis. Apoptosis, cell cycle, reactive oxygen species (ROS) and mitochondrial changes were assessed via flow cytometry. Western blotting and quantitative real-time reverse transcription PCR (qRT-PCR) were used to determine protein and gene levels. The antitumour mechanism of SNG was explored at a molecular level using chromatin immunoprecipitation (ChIP) and dual luciferase reporter plasmids. KEY RESULTS: Our investigation revealed that SNG exerted an up-regulated effect on SSBP1, disrupting mitochondrial function and inducing apoptosis. In-depth analysis uncovered a mechanism whereby SNG hindered the JAK/signal transducer and activator of transcription 3 (STAT3) signalling pathway, relieved the inhibitory effect of STAT3 on SSBP1 transcription, and inhibited the downstream PI3K/Akt/mTOR signalling axis, ultimately activating apoptosis. CONCLUSIONS AND IMPLICATIONS: The study delved further into elucidating the anticancer mechanism of SNG in osteosarcoma. Notably, we unravelled the previously undisclosed apoptotic potential of SSBP1 in osteosarcoma cells. This finding holds substantial promise in advancing the development of novel anticancer drugs and identification of therapeutic targets.


Asunto(s)
Neoplasias Óseas , Osteosarcoma , Adolescente , Humanos , Factor de Transcripción STAT3/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Proteómica , Línea Celular Tumoral , Apoptosis , Osteosarcoma/tratamiento farmacológico , Osteosarcoma/genética , Osteosarcoma/metabolismo , Neoplasias Óseas/tratamiento farmacológico , Neoplasias Óseas/genética , Neoplasias Óseas/patología , Proteínas de Unión al ADN/genética , Regiones Promotoras Genéticas , Proliferación Celular , Proteínas Mitocondriales/metabolismo
11.
Cancers (Basel) ; 15(13)2023 Jun 29.
Artículo en Inglés | MEDLINE | ID: mdl-37444514

RESUMEN

Follicular neoplasms are classified as benign or malignant depending on the presence or absence of capsular and/or vascular invasion. Due to incomplete capsular penetration or equivocal vascular invasion, the evaluation of these features can be challenging using histologic examination. In the current study, we analyzed the involvement of G-protein coupled receptor-associated sorting protein 1 (GASP-1) in the development and progression of thyroid neoplasms. Affinity-purified anti-GASP-1 polyclonal antibodies were used for routine immunohistochemistry (IHC) analysis. Thyroid tissue microarrays containing normal thyroid tissue, follicular adenoma, follicular carcinoma, papillary thyroid carcinoma, and anaplastic carcinoma were analyzed. We found that the level of GASP-1 expression can differentiate follicular adenoma from follicular carcinoma. When numerous cases were scored for GASP-1 expression by a board-certified pathologist, we found that GASP-1 expression is 7-fold higher in thyroid malignant neoplasms compared to normal thyroid tissue, and about 4-fold higher in follicular carcinoma compared to follicular adenoma. In follicular adenoma tissues, we observed the presence of many mini-glands that are enriched in GASP-1 and some mini-glands contain as few as three cells. GASP-1 IHC also possesses several advantages over the conventional H&E and can be used to identify early thyroid cancer and monitor cancer progression.

12.
Clin Chem Lab Med ; 61(12): 2216-2228, 2023 11 27.
Artículo en Inglés | MEDLINE | ID: mdl-37387637

RESUMEN

OBJECTIVES: Non-small cell lung cancer (NSCLC) accounts for more than 80 % of all lung cancers, and its 5-year survival rate can be greatly improved by early diagnosis. However, early diagnosis remains elusive because of the lack of effective biomarkers. In this study, we aimed to develop an effective diagnostic model for NSCLC based on a combination of circulating biomarkers. METHODS: Tissue-deregulated long noncoding RNAs (lncRNAs) in NSCLC were identified in datasets retrieved from the Gene Expression Omnibus (GEO, n=727) and The Cancer Genome Atlas (TCGA, n=1,135) databases, and their differential expression was verified in paired local plasma and exosome samples from NSCLC patients. Subsequently, LASSO regression was used to screen for biomarkers in a large clinical population, and a logistic regression model was used to establish a multi-marker diagnostic model. The area under the receiver operating characteristic (ROC) curve (AUC), calibration plots, decision curve analysis (DCA), clinical impact curves, and integrated discrimination improvement (IDI) were used to evaluate the efficiency of the diagnostic model. RESULTS: Three lncRNAs-PGM5-AS1, SFTA1P, and CTA-384D8.35 were consistently expressed in online tissue datasets, plasma, and exosomes from local patients. LASSO regression identified nine variables (Plasma CTA-384D8.35, Plasma PGM5-AS1, Exosome CTA-384D8.35, Exosome PGM5-AS1, Exosome SFTA1P, Log10CEA, Log10CA125, SCC, and NSE) in clinical samples that were eventually included in the multi-marker diagnostic model. Logistic regression analysis revealed that Plasma CTA-384D8.35, exosome SFTA1P, Log10CEA, Exosome CTA-384D8.35, SCC, and NSE were independent risk factors for NSCLC (p<0.01), and their results were visualized using a nomogram to obtain personalized prediction outcomes. The constructed diagnostic model demonstrated good NSCLC prediction ability in both the training and validation sets (AUC=0.97). CONCLUSIONS: In summary, the constructed circulating lncRNA-based diagnostic model has good NSCLC prediction ability in clinical samples and provides a potential diagnostic tool for NSCLC.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Exosomas , Neoplasias Pulmonares , ARN Largo no Codificante , Humanos , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Carcinoma de Pulmón de Células no Pequeñas/genética , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , ARN Largo no Codificante/genética , Exosomas/genética , Biomarcadores de Tumor/genética , Pronóstico , Regulación Neoplásica de la Expresión Génica
13.
Br J Pharmacol ; 2023 Jun 13.
Artículo en Inglés | MEDLINE | ID: mdl-37311689

RESUMEN

BACKGROUND AND PURPOSE: Chaperone-mediated autophagy (CMA) is a selective type of autophagy targeting protein degradation and maintains high activity in many malignancies. Inhibition of the combination of HSC70 and LAMP2A can potently block CMA. At present, knockdown of LAMP2A remains the most specific method for inhibiting CMA and chemical inhibitors against CMA have not yet been discovered. EXPERIMENTAL APPROACH: Levels of CMA in non-small cell lung cancer (NSCLC) tissue samples were confirmed by tyramide signal amplification dual immunofluorescence assay. High-content screening was performed based on CMA activity, to identify potential inhibitors of CMA. Inhibitor targets were determined by drug affinity responsive target stability-mass spectrum and confirmed by protein mass spectrometry. CMA was inhibited and activated to elucidate the molecular mechanism of the CMA inhibitor. KEY RESULTS: Suppression of interactions between HSC70 and LAMP2A blocked CMA in NSCLC, restraining tumour growth. Polyphyllin D (PPD) was identified as a targeted CMA small-molecule inhibitor through disrupting HSC70-LAMP2A interactions. The binding sites for PPD were E129 and T278 at the nucleotide-binding domain of HSC70 and C-terminal of LAMP2A, respectively. PPD accelerated unfolded protein generation to induce reactive oxygen species (ROS) accumulation by inhibiting HSC70-LAMP2A-eIF2α signalling axis. Also, PPD prevented regulatory compensation of macroautophagy induced by CMA inhibition via blocking the STX17-SNAP29-VAMP8 signalling axis. CONCLUSIONS AND IMPLICATIONS: PPD is a targeted CMA inhibitor that blocked both HSC70-LAMP2A interactions and LAMP2A homo-multimerization. CMA suppression without increasing the regulatory compensation from macroautophagy is a good strategy for NSCLC therapy.

14.
Virus Genes ; 59(4): 541-553, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37243920

RESUMEN

The critical Epstein‒Barr virus (EBV)-encoded latent membrane protein 1 (LMP-1) and BamHI fragment H rightward open reading frame 1 (BHRF-1) genes affect EBV-mediated malignant transformation and virus replication during EBV infection. Therefore, these two genes are considered ideal targets for EBV vaccine development. However, gene mutations in LMP-1 and BHRF-1 in different cohorts may affect the biological functions of EBV, which would seriously hinder development of personalized vaccines for EBV. In the present study, by performing nested polymerase chain reaction (nested PCR) and DNA sequence techniques, we analyzed the nucleotide variability and phylogeny of LMP-1 containing a 30 bp deletion region (del-LMP-1) and BHRF-1 in EBV-infected patients (N = 382) and healthy persons receiving physical examination (N = 98; defined as the control group) in Yunnan Province, China. Three BHRF-1 subtypes were identified in this study: 79V88V, 79L88L, and 79V88L, with mutation frequencies of 58.59%, 24.24%, and 17.17%, respectively. Compared with the control group, the distribution of BHRF-1 subtypes of the three groups showed no significant difference, suggesting that BHRF-1 is highly conserved in EBV-related samples. In addition, a short fragment of del-LMP-1 was found in 133 cases, and the nucleotide variation rate was 87.50% (133/152). For del-LMP-1, a significant distribution in three groups was detected, as characterized by a high mutation rate. In conclusion, our study illustrates gene variability and mutations of EBV-encoded del-LMP-1 and BHRF-1 in clinical samples. Highly mutated LMP-1 might be associated with various types of EBV-related diseases, indicating that BHRF-1 combined with LMP-1 may be used as an ideal target for development of EBV personalized vaccines.


Asunto(s)
Infecciones por Virus de Epstein-Barr , Vacunas , Humanos , China , Infecciones por Virus de Epstein-Barr/genética , Infecciones por Virus de Epstein-Barr/patología , Herpesvirus Humano 4/genética , Mutación , Nucleótidos , Proteínas de la Matriz Viral/genética , Proteínas Virales/genética
15.
Chem Biol Drug Des ; 102(2): 316-331, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37156601

RESUMEN

Celastrol has been identified as a potential candidate for anticancer drug development. In this study, 28 novel celastrol derivatives with C-6 sulfhydryl substitution and 20-substitution were designed and synthesized, and their antiproliferative activity against human cancer cells and non-malignant human cells was evaluated, with cisplatin and celastrol being used as controls. The results showed that most of the derivatives had enhanced in vitro anticancer activity compared to the parent compound celastrol. Specifically, derivative 2f demonstrated the most potent inhibitory potential and selectivity against HOS with an IC50 value of 0.82 µM. Our study provides new insights into the structure-activity relationship of celastrol and suggests that compound 2f may be a promising drug candidate for the treatment of osteosarcoma.


Asunto(s)
Antineoplásicos , Triterpenos , Humanos , Estructura Molecular , Triterpenos/farmacología , Antineoplásicos/farmacología , Ensayos de Selección de Medicamentos Antitumorales , Relación Estructura-Actividad , Proliferación Celular , Relación Dosis-Respuesta a Droga , Línea Celular Tumoral , Diseño de Fármacos
16.
Am J Case Rep ; 24: e939095, 2023 Apr 03.
Artículo en Inglés | MEDLINE | ID: mdl-37010984

RESUMEN

BACKGROUND Acute aortic occlusion (AAO) is a rare emergency with high mortality. The typical clinical presentation is the sudden appearance of pain, paralysis, sensory disturbances, and mottling of the lower extremities. The etiology of AAO can be broadly classified into 3 categories: in situ thrombosis, arterial embolism, and occlusion of grafts. AAO is a rare consequence of myocardial infarction in the era of anticoagulation therapy, as part of the management of acute coronary syndrome (ACS). CASE REPORT We report the case of a 65-year-old woman who presented with acute lower extremity pain and weakness after a myocardial infarction 2 weeks earlier. She was on standardized antiplatelet therapy, a high blood D-dimer level was found during a visit to the Emergency Department, a left ventricular mural thrombus was detected using bedside ultrasound, and computed tomography angiography revealed thrombotic occlusion of the abdominal aorta. AAO disease was diagnosed, but the patient refused further treatment and died after 7 days of follow-up. CONCLUSIONS In recent years, anticoagulation has become part of the standard of care for patients with myocardial infarction or atrial fibrillation, which has led to a lower incidence of arterial embolism leading to AAO than in situ thrombosis. Depending on the type of occlusion, there are also differences in the surgical approach. A computed tomography angiography of the abdomen should be performed on all patients in whom AAO cannot be ruled out. Timely diagnosis and prompt surgical intervention are essential to preventing mortality.


Asunto(s)
Arteriopatías Oclusivas , Embolia , Infarto del Miocardio , Trombosis , Femenino , Humanos , Anciano , Aorta Abdominal/diagnóstico por imagen , Trombosis/complicaciones , Trombosis/diagnóstico por imagen , Embolia/complicaciones , Embolia/terapia , Infarto del Miocardio/complicaciones , Arteriopatías Oclusivas/complicaciones , Arteriopatías Oclusivas/diagnóstico , Abdomen
17.
Heliyon ; 9(2): e13675, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36873156

RESUMEN

As an empirical medicine of traditional Chinese medicine, Fuzhengjiedu Granules have shown an effect against COVID-19 in clinical and inflammatory animal models. It is formulated with eight herbs, including Aconiti Lateralis Radix Praeparata, Zingiberis Rhizoma, Glycyrrhizae Radix Et Rhizoma, Lonicerae Japonicae Flos, Gleditsiae Spina, Fici Radix, Pogostemonis Herba, and Citri Reticulatae Pericarpium. This study established a high-performance liquid chromatography-triple quadrupole mass spectrometry (HPLC-QQQ-MS/MS) method by simultaneously determining 29 active compounds in the granules with significant content differences. Separation by gradient elution using acetonitrile and water (0.1% formic acid) as mobile phases was performed on a Waters Acquilty UPLC T3 column (2.1 mm × 100 mm, 1.7 µm). A triple quadrupole mass spectrometer, operating in positive and negative ionization modes, was used for multiple reaction monitoring to detect the 29 compounds. All calibration curves showed good linear regression (r2 > 0.998). RSDs of precision, reproducibility, and stability of active compounds were all lower than 5.0%. The recovery rates were 95.4-104.9%, with RSDs< 5.0%. This method was successfully used to analyze the samples, and the results showed that 26 representative active components from 8 herbs were detected in the granules. While aconitine, mesaconitine, and hypaconitine were not detected, indicating that the existing samples were safe. The granules had the maximum and minimum content of hesperidin (27.3 ± 0.375 mg/g) and benzoylaconine (38.2 ± 0.759 ng/g). To conclude, a fast, accurate, sensitive, and reliable HPLC-QQQ-MS/MS method was established, which can simultaneously detect 29 active compounds that have a considerable difference in the content of Fuzhengjiedu Granules. This study can be used to control the quality and safety of Fuzhengjiedu Granules and provide a basis and guarantee for further experimental research and clinical application.

18.
Comput Struct Biotechnol J ; 21: 677-687, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36659923

RESUMEN

Early diagnosis and progression assessment are critical for the timely detection and treatment of gastric cancer (GC) patients. Identification of diagnostic biomarkers for early detection of GC represents an unmet clinical need, and how these markers further influence GC progression is explored rarely. We performed dynamic gene screening based on high-throughput data analysis from patients with precancerous lesions and early gastric cancer (EGC) and identified a 10-gene panel by the lasso regression model. This panel demonstrated good diagnostic performance in TCGA (AUC = 0.95, sensitivity = 86.67 %, specificity = 90.63 %) and GEO (AUC = 0.84, sensitivity = 91.67 %, specificity = 78.13 %) cohorts. Moreover, three GC subtypes were clustered based on this panel, in which cluster 2 (C2) demonstrated the highest tumor progression level with a high expression of 10 genes, showing a decreased tumor mutation burden, significantly enriched epithelial-mesenchymal transition hallmark and increased immune exclusion/exhausted features. Finally, the cell localization of these panel genes was explored in scRNA-seq data based on more than 40,000 cells. The 10-gene panel is expected to be a new clinical early detection signature for GC and may aid in progression assessment and personalized treatment of patients.

19.
Granul Comput ; : 1-23, 2023 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38625159

RESUMEN

The major objective of the current investigation is to build an integrated multiple criteria group decision-making (MCGDM) methodology based on combined compromise solution (CoCoSo) and spherical fuzzy set for determining the optimal solar power station. To begin with, an innovative spherical fuzzy score function is brought forward to strengthen the efficiency of the comparison for spherical fuzzy number (SFN). Secondly, several newly operational laws for SFN are defined and some novel aggregation operation based on them are propounded. The corresponding excellent properties of the novel operators are also explored at length. Further, the spherical fuzzy method on the removal effects of criteria (MEREC) technique is presented by the proposed score function to work out the importance of the criteria. Lastly, an MCGDM approach is propounded based on improved spherical fuzzy CoCoSo to obtain the ranking of the solar power station locations. The feasibility and practicability of the proposed SF-MEREC-CoCoSo method are investigated through the comparison study with the extant methods. The sensibility analysis is also executed to discuss the robustness and stability of the propounded methodology.

20.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-990377

RESUMEN

With the acceleration of the aging process of the population in China, the utilization rate and transfer rate of ICU have significantly increased. More and more ICU survivors have post intensive care syndrome. If they cannot be intervened in time, the quality of life of patients will be seriously affected, and at the same time, the readmission rate will increase, impacting the scarce medical resources. Critical care recovery center have been established abroad for early identification and intervention of post intensive care syndrome. This paper intended to analyze the construction theory and operation mode of foreign critical care recovery center, summarize foreign experience, and put forward corresponding suggestions in combination with China′s national conditions, so as to provide reference for the construction of ritical care recovery center in China, with a view to providing long-term rehabilitation care services for patients with post intensive care syndrome in China.

SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...