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Calycosin (Caly), a flavonoid compound, demonstrates a variety of beneficial properties. However, the specific mechanisms behind Caly's anticancer effects remain largely unexplored. Network pharmacology was used to explore the potential targets of Caly in renal cancer. Additionally, RNA-seq sequencing was used to detect changes in genes in renal cancer cells after Caly treatment. Validation was carried out through quantitative reverse transcription-PCR and Western blot analysis. The luciferase reporter assay was applied to pinpoint the interaction site between MAZ and HAS2. Furthermore, the immunoprecipitation assay was utilized to examine the ubiquitination and degradation of MAZ. In vivo experiments using cell line-derived xenograft mouse models were performed to assess Calycosin's impact on cancer growth. Network pharmacology research suggests Caly plays a role in promoting apoptosis and inhibiting cell adhesion in renal cancer. In vitro, Caly has been observed to suppress proliferation, colony formation, and metastasis of renal cancer cells while also triggering apoptosis. Additionally, it appears to diminish hyaluronic acid synthesis by downregulating HAS2 expression. MAZ is identified as a transcriptional regulator of HAS2 expression. Calycosin further facilitates the degradation of MAZ via the ubiquitin-proteasome pathway. Notably, Caly demonstrates efficacy in reducing the growth of renal cell carcinoma xenograft tumors in vivo. Our findings indicate that Caly suppresses the proliferation, metastasis, and progression of renal cell carcinoma through its action on the MAZ/HAS2 signaling pathway. Thus, Caly represents a promising therapeutic candidate for the treatment of renal cell carcinoma.
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Atrial fibrillation (AF) has been receiving a lot of attention from scientists and clinicians because it is an extremely common clinical condition. Due to its special hemodynamic changes, AF has a high rate of disability and mortality. So far, although AF has some therapeutic means, it is still an incurable disease because of its complex risk factors and pathophysiologic mechanisms, which is a difficult problem for global public health. Age is an important independent risk factor for AF, and the incidence of AF increases with age. To date, there is no comprehensive review on aging-associated AF. In this review, we systematically discuss the pathophysiologic evidence for aging-associated AF, and in particular explore the pathophysiologic mechanisms of mitochondrial dysfunction, telomere attrition, cellular senescence, disabled macroautophagy, and gut dysbiosis involved in recent studies with aging-associated AF. We hope that by exploring the various dimensions of aging-associated AF, we can better understand the specific relationship between age and AF, which may be crucial for innovative treatments of aging-associated AF.
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Artemisia annua L. ("Qinghao" in Chinese) is a famous traditional Chinese medicinal herb and has been used to treat malaria and various tumors. Our preliminary screening indicated that the EtOAc extract of A. annua manifested activity against HepG2, Huh7, and SK-Hep-1 cell lines with inhibitory ratios of 53.2%, 52.1%, and 59.6% at 200 µg/mL, respectively. Bioassay-guided isolation of A. annua afforded 14 unusual cadinane-involved sesquiterpenoid dimers, artemannuins AâN (1-14), of which the structures were elucidated by extensive spectral analyses, ECD calculations, and single-crystal X-ray diffraction. Structurally, these compounds were classified into five different types based on the coupled modes of two monomeric sesquiterpenoids. Among them, compounds 1-9 represented the first examples of sesquiterpenoid dimers formed via the C-3âC-3' single bond of two 5(4 â 3)-abeo-cadinane sesquiterpenoid monomers, while compounds 13 and 14 were dimers fused by cadinane and humulane sesquiterpenoids via an ester bond. Methylated derivatives of 1, 4, 6, and 8 showed antihepatoma activity against HepG2, Huh7, and SK-Hep-1 cell lines with IC50 values ranging from 30.5 to 57.2 µM.
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Artemisia annua , Sesquiterpenos Policíclicos , Sesquiterpenos , Humanos , Artemisia annua/química , Sesquiterpenos Policíclicos/farmacología , Sesquiterpenos Policíclicos/química , Sesquiterpenos Policíclicos/aislamiento & purificación , Sesquiterpenos/química , Sesquiterpenos/farmacología , Sesquiterpenos/aislamiento & purificación , Estructura Molecular , Dimerización , Ensayos de Selección de Medicamentos Antitumorales , Relación Estructura-Actividad , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Relación Dosis-Respuesta a Droga , Línea Celular TumoralRESUMEN
The Chinese medical mechanism of Huanglian Jieduo Decoction on treating Alzheimer's disease(AD) characterized by "toxin damaging brain collateral" is still unclear. This study aims to explore the mechanism of Huanglian Jieduo Decoction on regulating triggering receptor expressed on myeloid cells 2(TREM2)/protein kinase B(Akt)/glycogen synthase kinase 3ß(GSK3ß) pathway to improve the cognitive deficit in APP/PS1 transgenic mice. APP/PS1 mice of approximately nine months old were randomly divided into the model group, the low, medium, and high(2.5, 5, and 10 g·kg~(-1)) groups of Huanglian Jiedu Decoction, and 0.75 mg·kg~(-1) donepezil hydrochloride group, and the C57BL/6J mice with the same age were taken as the normal group. After one month of continuous oral administration, a Morris water maze was performed to detect the learning and memory ability of mice. Hematoxylin-eosin(HE) staining was applied to observe the morphology of neuronal cells in the cortical area of mice. Immunofluorescence was used to detect the protein expressions of ß-amyloid(Aß_(1-42)), CD86, and arginase 1(Arg1). The mRNA levels of interleukin(IL)-1ß, IL-6, and IL-10 in the cortex of mice were detected by real-time fluorescence quantitative polymerase chain reaction(RT-qPCR). The protein expressions of TREM2, phosphoinositide-3 kinase(PI3K), Akt, GSK3ß, and beta-catenin(ß-catenin) in mouse cortex were determined by Western blot. The results indicated that the escape latency of the model group was significantly prolonged, and the residence time in the target quadrant and the number of crossing the platform were significantly reduced compared with the normal group. Mice in the model group had a significantly lower number of neurons in the cortex and showed nuclear pyknosis and a significant increase in the expressions of Aß_(1-42) and CD86. The mRNA levels of IL-1ß and IL-6 in tissue were significantly increased, IL-10 were increased, while Arg1 were significantly decreased. The expression of TREM2, p-PI3K(Y607), p-Akt(T308), p-GSK3ß(Ser9), and ß-catenin in the cortex were significantly down-regulated. Compared with the model group, the escape latency of the mice in the administration group was significantly shortened, and the number of crossing the platform and the residence time in the target quadrant were significantly increased. Furthermore, the number of neurons in the cortex of mice was increased, and nuclear pyknosis was improved. Aß_(1-42) deposition was decreased significantly. The mRNA levels of IL-1ß, IL-6 and CD86 were significantly decreased, while IL-10 and Arg1 levels were significantly increased. The expression of TREM2, p-PI3K(Y607), p-Akt(T308), p-GSK3ß(Ser9), and ß-catenin protein in the cortex of each administration group was significantly up-regulated compared with the model group. In conclusion, Huanglian Jiedu Decoction reduced the expression of Aß_(1-42) and neuroinflammation to a neuro-protective effect, thereby improving the learning and memory ability in APP/PS1 mice, which may be related to the TREM2/Akt/GSK3ß signaling pathway.
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Enfermedad de Alzheimer , Corteza Cerebral , Medicamentos Herbarios Chinos , Glucógeno Sintasa Quinasa 3 beta , Glicoproteínas de Membrana , Ratones Endogámicos C57BL , Ratones Transgénicos , Proteínas Proto-Oncogénicas c-akt , Receptores Inmunológicos , Animales , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Glucógeno Sintasa Quinasa 3 beta/genética , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/administración & dosificación , Ratones , Corteza Cerebral/metabolismo , Corteza Cerebral/efectos de los fármacos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Proto-Oncogénicas c-akt/genética , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/genética , Receptores Inmunológicos/genética , Receptores Inmunológicos/metabolismo , Glicoproteínas de Membrana/metabolismo , Glicoproteínas de Membrana/genética , Masculino , Transducción de Señal/efectos de los fármacos , HumanosRESUMEN
Artemyriantholides A-K (1-11) as well as 14 known compounds (12-25) were isolated from Artemisia myriantha var. pleiocephala (Asteraceae). The structures and absolute configuration of compounds 2 and 8-9 were confirmed by the single crystal X-ray diï¬raction analyses, and the others were elucidated by MS, NMR spectral data and electronic circular dichroism calculations. All compounds were chemically characterized as guaiane-type sesquiterpenoid dimers (GSDs). Compound 1 was the first example of the GSD fused via C-3/C-11' and C-5/C-13' linkages, and compounds 2 and 5 were rare GSDs containing chlorine atoms. Eleven compounds showed obvious inhibitory activity in HepG2, Huh7 and SK-Hep-1 cell lines by antihepatoma assay to provide the IC50 values ranging from 7.9 to 67.1 µM. Importantly, compounds 5 and 8 exhibited the best inhibitory activity with IC50 values of 14.2 and 18.8 (HepG2), 9.0 and 11.5 (Huh7), and 8.8 and 11.3 µM (SK-Hep-1), respectively. The target of compound 5 was predicted to be MAP2K2 by a computational prediction model. The interaction between compound 5 and MAP2K2 was conducted to give docking score of -9.0 kcal/mol by molecular docking and provide KD value of 43.7 µM by Surface Plasmon Resonance assay.
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Artemisia , Artemisia/química , Humanos , Estructura Molecular , Relación Estructura-Actividad , Sesquiterpenos de Guayano/química , Sesquiterpenos de Guayano/farmacología , Sesquiterpenos de Guayano/aislamiento & purificación , Animales , Dimerización , Simulación del Acoplamiento Molecular , Sesquiterpenos/química , Sesquiterpenos/farmacología , Sesquiterpenos/aislamiento & purificación , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Línea Celular TumoralRESUMEN
Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder in children and adolescents, and its etiology and pathogenesis are still unclear. Brain is the organ with the largest oxygen consumption in human body and is easily affected by oxidative imbalance. Oxidative stress has become the key research direction for the pathogenesis of ADHD, but there is still a lack of relevant studies in China. Based on the latest research findings in China and overseas, this article reviews the clinical and experimental studies on oxidative stress in ADHD and explores the association of oxidative stress with neurotransmitter imbalance, neuroinflammation, and cell apoptosis in the pathogenesis of ADHD, so as to provide new research ideas for exploring the pathogenesis of ADHD.
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Trastorno por Déficit de Atención con Hiperactividad , Adolescente , Niño , Humanos , Trastorno por Déficit de Atención con Hiperactividad/etiología , Estrés Oxidativo , Apoptosis , Encéfalo , ChinaRESUMEN
AIM: Atrial fibrillation (AF) is a progressive disease from paroxysmal to persistent, and persistent AF (PerAF) had worse prognosis. AF has potential link with inflammation, but it is not clear whether PerAF or paroxysmal AF (ParAF) is more closely related to inflammation. On the basis of inhibiting myocardial physiological uptake, 18F-fluorodeoxyglucosepositron emission tomography/computed tomography (18F-FDG PET/CT) is an established imaging modality to detect cardiac inflammation. We aimed to decipher the association between AF and atrial inflammatory activity by 18F-FDG PET/CT. METHODS: Thirty-five PerAF patients were compared to age and sex matched ParAF group with baseline 18F-FDG PET/CT scans prior to radiofrequency catheter ablation (RFCA) in the prospective case-control study. High-fat and low-carbohydrate diet and prolonged fast (HFLC+Fast) was applied to all AF patients before PET/CT. Then 22 AF patients with positive right atrial (RA) wall FDG uptake (HFLC+Fast) were randomly selected and underwent HFLC+Fast+heparin the next day. The CHA2DS2-VASc score was calculated to evaluate the risk of stroke. Clinical data, ECG, echocardiography, and atrial 18F-FDG uptake were compared. RESULTS: PerAF patients had significantly higher probability of RA wall positive FDG uptake and higher SUVmax than ParAF group [91.4% VS. 28.6%, P < 0.001; SUVmax: 4.10(3.20-4.90) VS. 2.60(2.40-3.10), P < 0.001]. Multivariate logistic regression analyses demonstrated that RA wall SUVmax was the independent influencing factor of PerAF (OR = 1.80, 95%CI 1.02-3.18, P = 0.04). In 22 AF patients with RA wall positive FDG uptake (HFLC+Fast), the "HFLC+Fast+Heparin" method did not significantly change RA wall FDG uptake evaluated by either quantitative analysis or visual analysis. High CHA2DS2-VASc score group had higher RA wall 18F-FDG uptake [3.35 (2.70, 4.50) vs, 2.8 (2.4, 3.1) P = 0.01]. CONCLUSIONS: RA wall FDG positive uptake was present mainly in PerAF. A higher RA wall 18F-FDG uptake was an independent influencing factor of PerAF. RA wall FDG uptake based on 18F-FDG PET/CT may indicate pathological inflammation. TRIAL REGISTRATION: http://www.chictr.org.cn , ChiCTR2000038288.
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Fibrilación Atrial , Humanos , Fibrilación Atrial/diagnóstico por imagen , Fibrilación Atrial/complicaciones , Estudios de Casos y Controles , Fluorodesoxiglucosa F18 , Heparina , Inflamación/diagnóstico por imagen , Inflamación/complicaciones , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Tomografía Computarizada por Rayos X , Masculino , FemeninoRESUMEN
PURPOSE OF REVIEW: Acute coronary syndrome (ACS) and non-alcoholic fatty liver disease (NAFLD) are two clinically common disease entities that share numerous risk factors. This review aimed to discuss the impacts of NAFLD on ACS. RECENT FINDINGS: In an era of improved control of traditional risk factors, the substantial burden of cardiometabolic abnormalities has caused widespread concern. NAFLD is considered the hepatic component of metabolic syndrome, which can exert an impact on human health beyond the liver. Accumulating studies have demonstrated that NAFLD is closely related to cardiovascular disease, especially coronary artery disease. Interestingly, although recent data have suggested an association between NAFLD and the incidence and outcomes of ACS, the results are not consistent. In this review, we comprehensively summarized evidence and controversies regarding whether NAFLD is a contributor to either the development of ACS or worse outcomes in patients with ACS. The potential pathophysiological and molecular mechanisms involved in the impacts of NAFLD on ACS were also elucidated.
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Síndrome Coronario Agudo , Síndrome Metabólico , Enfermedad del Hígado Graso no Alcohólico , Humanos , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Síndrome Coronario Agudo/epidemiología , Factores de RiesgoRESUMEN
Artemeriosides A-F (1-6), six novel sesquiterpenoids containing a 6'-O-crontonyl ß-glucopyranoside, were isolated from Artemisia annua L. Their structures were determined by spectral data including HRESIMS, IR, UV, 1D and 2D NMR, and ECD calculations. Compounds 1-6 represented the first examples of natural sesquiterpenoid substituted by 6'-O-crontonyl ß-glucopyranoside. By antihepatoma assay, compounds 1 and 2 demonstrated inhibitory effect against both HepG2 and SK-Hep-1 cells with inhibitory ratios of 77.0%, 88.8%, and 86.8%, 83.9% at 200.0 µM, and compound 1 showed inhibitory activity against Huh7 cells with inhibitory ratio of 56.8%.
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Artemisia annua , Artemisia , Sesquiterpenos , Estructura Molecular , Sesquiterpenos/farmacología , Sesquiterpenos/química , Espectroscopía de Resonancia Magnética , Artemisia/químicaRESUMEN
Artemisia annua, also known as "Qinghao" in Chinese, is a famous traditional Chinese medicine and has been used for the treatment of malaria and various tumors. In this study, three novel sesquiterpenoid-flavonol hybrids, artemannuols A-C (1-3), were isolated and elucidated by extensive spectral data and ECD calculations. Structurally, artemannuols A-C (1-3) are the first examples of sesquiterpenoid-flavonol hybrids fused by an ether bond, among which artemannuols A and B (1 and 2) are composed of bisabolane-type sesquiterpenoid and flavonol moieties, and artemannuol C (3) is composed of humulane-type sesquiterpenoid and flavonol moieties. The antihepatoma assay suggested that compounds 1-3 showed inhibitory effects against HepG2, Huh7, and SK-Hep-1 cell lines with IC50 values in the range of 32.7 to 70.4 µM.
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Artemisia annua , Sesquiterpenos , Sesquiterpenos/farmacología , Sesquiterpenos/química , Línea CelularRESUMEN
Fe-catalyzed difunctionalization of aryl titanates via double C-H activation has been developed, where aryl titanates were arylated via ortho C-H activation, followed by ipso electrophilic trapping of the C-Ti bond. The ortho C-H arylation should be promoted by a 1,2-Fe/Ti synergistic heterobimetallic arylene intermediate and represents an ortho C-H ferration directed by a readily transformable C-Ti group. Common benzamides, esters, and nitriles function as arylating reagents, which involves another ortho C-H activation directed by these functionalities.
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Regioselective difunctionalization of arenes remains a long-standing challenge in organic chemistry. We report a novel and general Fe/Ti synergistic methodology for regioselective synthesis of various polysubstituted arenes through either E/E' or Nu/E ortho difunctionalizations of arenes. Preliminary results showed that an unprecedented 1,2-Fe/Ti heterobimetallic arylene intermediate bearing two distinct C-M bonds is essential to the regioselective difunctionalization.
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Atrial fibrillation (AF) is one of the most common cardiac arrhythmias, but its pathogenesis is still poorly understood. Catheter ablation is one of the most effective treatments for AF, but recurrence after ablation remains a challenge. There has been much research into the association of AF recurrence with several factors, including genetics. Over the past decade or so, significant advances have been made in the genetic architecture of atrial fibrillation. Genome-wide association studies (GWAS) have identified over 100 loci for genetic variants associated with atrial fibrillation. However, there is relatively little information on the systematic assessment of the genes related to AF recurrence after ablation. In this review article, we highlight the value of genetic polymorphisms in atrial fibrillation recurrence after catheter ablation and their potential mechanisms in the recurrence process to enhance our understanding of atrial fibrillation recurrence and contribute to individualized treatment strategies for patients with AF.
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Five new furanobutenolide-derived C19-norcembranoid diterpenes, sinudenoids A-E (1-5, respectively), were isolated from the soft coral Sinularia densa. Sinudenoid A (1) possesses an uncommon 5/5/11-fused tricyclic ring system. Sinudenoids B-D (2-4, respectively) share the same tetracyclic 5/5/6/6 ring system but represent two kinds of new skeletons. Sinudenoid E (5) is the second compound with the rare 8/8 bicyclic carbon core. A plausible biosynthesis pathway for compounds 1-6 is proposed. Compound 5 exhibits strong anti-inflammatory activity in the zebrafish model.
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Antozoos , Diterpenos , Animales , Pez Cebra , Diterpenos/farmacología , Diterpenos/metabolismo , Antiinflamatorios , Carbono , Estructura MolecularRESUMEN
Three new neoflavonoids, named (1S,8R,9S)-1,5-dihydroxy-4,12-dimethoxy-8-vinyl-tricyclo[7.3.1.02,7]trideca-2,4,6,11-tetraen-10-one (1), 2,5,2',5'-tetrahydroxy-4-methoxybenzophenone (2) and 2,5,3'-trihydroxy-4-methoxybenzophenone (3), were isolated from the heartwood of Dalbergia melanoxylon. Their structures were established by spectroscopic methods, including UV, IR, HRMS, 1 D and 2 D-NMR. Compounds 1-3 were evaluated for inhibitory activity against three fungal strains Candida albicans, Mucor ramosissimus, Saccharomycopsis fermentans and seven bacterial strains Shigella dysenteriae, Salmonella enteri, Bacillus cereus, Staphylococcus epidermidis, Bacillus sphaericus, Staphylococcus aureus, Escherichia coli using the broth dilution method. However, none of compounds 1-3 showed potential antimicrobial activities in vitro.
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Dalbergia , Antibacterianos/farmacología , Candida albicans , Escherichia coli , Espectroscopía de Resonancia Magnética , Pruebas de Sensibilidad Microbiana , Staphylococcus aureusRESUMEN
Seven undescribed neoflavonoids, named melanoxylonins A-G, were isolated from the heartwood of Dalbergia melanoxylon, and all the non-toxic isolates were evaluated for their cardioprotective effect against ischemia/reoxygenation (I/R) injury in H9c2 cells. Of these, melanoxylonin A-D containing the 8-OH group showed better potent cardioprotective effects than the other four congeners. Molecular docking studies confirmed the capacity of melanoxylonin D to interact with the myeloperoxidase (MPO) protein. These results indicated that the potential cardioprotective effects of melanoxylonin D in H9c2 cells with I/R injury may be imparted through suppression of MPO. These results may provide a new medicinal usage of D. melanoxylon.
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Dalbergia , Simulación del Acoplamiento MolecularRESUMEN
Steep canyons surrounded by high mountains resulting from large-scale landslides characterize the study area located in the southeastern part of the Tibetan Plateau. A total of 1766 large landslides were identified based on integrated remote sensing interpretations utilizing multisource satellite images and topographic data that were dominated by 3 major regional categories, namely, rockslides, rock falls, and flow-like landslides. The geographical detector method was applied to quantitatively unveil the spatial association between the landslides and 12 environmental factors through computation of the q values based on spatially stratified heterogeneity. Meanwhile, a certainty factor (CF) model was used for comparison. The results indicate that the q values of the 12 influencing factors vary obviously, and the dominant factors are also different for the 3 types of landslides, with annual mean precipitation (AMP) being the dominant factor for rockslide distribution, elevation being the dominant factor for rock fall distribution and lithology being the dominant factor for flow-like distribution. Integrating the results of the factor detector and ecological detector, the AMP, annual mean temperature (AMT), elevation, river density, fault distance and lithology have a stronger influence on the spatial distribution of landslides than other factors. Furthermore, the factor interactions can significantly enhance their interpretability of landslides, and the top 3 dominant interactions were revealed. Based on statistics of landslide discrepancies with respect to diverse stratification of each factor, the high-risk zones were identified for 3 types of landslides, and the results were contrasted with the CF model. In conclusion, our method provides an objective framework for landslide prevention and mitigation through quantitative, spatial and statistical analyses in regions with complex terrain.
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Sistemas de Información Geográfica , Ríos , TibetRESUMEN
Background: Interleukin-9 (IL9) plays a critical role in immunity and the pathogenesis of endometrial cancer (EC), especially endometrioid EC (EEC). This study aimed to identify the IL9+ immune cell subsets and their pleiotropic functions and establish an optimized prognostic nomogram towards the promotion of personalized treatment of EEC. Methods: 1,417 EC patients were involved in the present study. 143 patients from the tertiary gynecology centers in Shanghai between 2013 and 2019 were recruited, and the study protocol was approved by the Institutional Review Board (IRB) of Shanghai First Maternity and Infant Hospital. The genomic data of the other 1,274 patients were extracted from the TCGA and the MSKCC datasets, respectively. Immune and stromal scores were calculated using the ESTIMATE R tool, and the tumor infiltration of immune cells was analyzed using the TIMER platform. Metascape and GEPIA datasets were used for bioinformatic analysis. P < 0.05 was considered statistically significant. All statistical analyses were performed with GraphPad Prism and R studio. Results: 552 genes that were correlated with leukocyte infiltration, lymphocyte activation, and regulation of innate immune response were up-regulated in the high immune score group. More IL9+ cell infiltration was detected in the highly and moderately differentiated EC (p = 0.04). High IL9+ lymphocyte infiltration was related to a better overall survival (p = 0.0027). IL9 positive cell clusters included ILC2s, Vδ2 γδT cells, mast cells, macrophages, and Th9 cells. Parameters such as FIGO stage, IL9 score, Vδ2 + γδT cell infiltration, classification of differentiation, and diabetes mellitus were assigned a weighted number of points in the nomogram for a specific predicted 3-, 5- and 10-year overall survival (OS). IL9-IL9R axis played a vital role in EEC, IL9R positive cell subgroups were also identified, and the related function was analyzed in the present study. Additionally, PR (Progesterone Receptor, or PGR) expression was relevant to a higher density of IL9+ lymphocyte infiltration. However, PGRMC1 (Progesterone Receptor Membrane Component 1) was negatively relevant to IL9R (p = 4.26e-8). Conclusion: We observed a significant infiltration of IL9+ cells and the overrepresentation of IL-9R in tissue specimens of patients in EC cases. The nomogram incorporating the IL9 could accurately predict individualized survival probability in EEC. Additionally, this study not only established a prognostic nomogram but also assist in the firmer understanding of the relevance of the IL9-IL9R axis and IL9-producing cells in EC immunity.
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Neoplasias Endometriales/inmunología , Neoplasias Endometriales/mortalidad , Interleucina-9/inmunología , Leucocitos/inmunología , Activación de Linfocitos , Nomogramas , Supervivencia sin Enfermedad , Neoplasias Endometriales/genética , Neoplasias Endometriales/patología , Femenino , Humanos , Interleucina-9/genética , Leucocitos/patología , Proteínas de la Membrana/genética , Proteínas de la Membrana/inmunología , Persona de Mediana Edad , Receptores de Progesterona/genética , Receptores de Progesterona/inmunología , Tasa de SupervivenciaRESUMEN
Pancreatic ductal adenocarcinoma (PDAC) is an incurable cancer resistant to traditional treatments, although a limited number of early-stage patients can undergo radical resection. Immunotherapies for the treatment of haematological malignancies as well as solid tumours have been substantially improved over the past decades, and impressive results have been obtained in recent preclinical and clinical trials. However, PDAC is likely the exception because of its unique tumour microenvironment (TME). In this review, we summarize the characteristics of the PDAC TME and focus on the network of various tumour-infiltrating immune cells, outlining the current advances in PDAC immunotherapy and addressing the effect of the PDAC TME on immunotherapy. This review further explores the combinations of different therapies used to enhance antitumour efficacy or reverse immunodeficiencies and describes optimizable immunotherapeutic strategies for PDAC. The concordant combination of various treatments, such as targeting cancer cells and the stroma, reversing suppressive immune reactions and enhancing antitumour reactivity, may be the most promising approach for the treatment of PDAC. Traditional treatments, especially chemotherapy, may also be optimized for individual patients to remodel the immunosuppressive microenvironment for enhanced therapy.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma Ductal Pancreático/tratamiento farmacológico , Inmunoterapia/métodos , Neoplasias Pancreáticas/tratamiento farmacológico , Microambiente Tumoral/inmunología , Animales , Carcinoma Ductal Pancreático/inmunología , Carcinoma Ductal Pancreático/patología , Humanos , Neoplasias Pancreáticas/inmunología , Neoplasias Pancreáticas/patología , Microambiente Tumoral/efectos de los fármacos , Neoplasias PancreáticasRESUMEN
The previously reported Fe-catalyzed ortho C-H arylation of benzamides relied on bi- or tridentate amide groups and specific iron ligands and was sensitive to steric hindrance. By using new mixed titanates, our present protocol accommodates various weakly coordinating benzamides and tolerates high steric hindrance and sensitive functional groups only under the catalysis of FeCl3 and TMEDA. A wide range of privileged condensed ring compounds can thus be facilely accessed.