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BACKGROUND: While spontaneous pneumothorax has been documented in COVID-19 patients, reports on recurrent spontaneous pneumothorax due to cystic lesions in convalescent COVID-19 patients are scarce. The progression of these lung cystic lesions remains inadequately explored. CASE PRESENTATION AND LITERATURE REVIEW: An 81-year-old male, a non-smoker with a history of rheumatoid arthritis, presented with fever, cough, and expectoration for 14 days. Initially diagnosed with moderate COVID-19, he deteriorated to severe COVID-19 despite adherence to local treatment guidelines. Successive identification of three cystic lesions termed "bulla" or "pneumatocele", and one cystic lesion with air-fluid level, referred to as "pneumo-hamatocele" (PHC), occurred in his lungs. Gradual improvement followed anti-inflammatory therapy and optimal supportive care. However, on day 42, sudden worsening dyspnea prompted a computed tomography (CT) scan, confirming a right spontaneous pneumothorax and subcutaneous emphysema, likely due to PHC rupture. Discharge followed chest tube implementation for pneumothorax resolution. On day 116, he returned to the hospital with mild exertional dyspnea. Chest CT revealed recurrent right pneumothorax from a remaining cyst in the right lung. Apart from our patient, literature retrieval identified 22 COVID-19 patients with spontaneous pneumothorax due to cystic lesions, with a male predominance (95.6%; 22/23). Diagnosis of pneumothorax and lung cystic lesions occurred around day 29.5 (range: 18-35) and day 26.4 (± 9.8) since symptom onset, respectively. Except for one patient whose pneumothorax occurred on day seven of illness, all patients eventually recovered. CONCLUSIONS: Recurrent spontaneous pneumothorax secondary to lung cystic lesions may manifest in convalescent COVID-19 patients, particularly males with COVID-19 pneumonia. Chest CT around 2 to 3 weeks post-symptom onset may be prudent to detect cystic lesion development and anticipate spontaneous pneumothorax.
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COVID-19 , Neumotórax , Recurrencia , Tomografía Computarizada por Rayos X , Humanos , Neumotórax/etiología , Neumotórax/terapia , Neumotórax/diagnóstico por imagen , Masculino , COVID-19/complicaciones , COVID-19/terapia , Anciano de 80 o más Años , SARS-CoV-2 , Quistes/complicaciones , Quistes/diagnóstico por imagen , Pulmón/diagnóstico por imagen , Pulmón/patología , Enfermedades Pulmonares/diagnósticoRESUMEN
OBJECTIVE: Triple-Negative Breast Cancer (TNBC) is known for its aggressiveness and treatment challenges due to the absence of ER, PR, and HER2 receptors. Our work emphasizes the prognostic value of LCP1 (Lymphocyte cytosolic protein 1), which plays a crucial role in cell processes and immune cell activity, to predict outcomes and guide treatments in TNBC. METHODS: We explored LCP1 as a potential biomarker in TNBC and investigated the mRNA and protein expression levels of LCP1. We investigated different databases, including GTEX, TCGA, GEO, cBioPortal and Kaplan-Meier Plotter. Immunohistochemistry on TNBC and benign tumor samples was performed to examine LCP1's relationship with patient clinical characteristics and macrophage markers. We also assessed survival rates, immune cell infiltration, and drug sensitivity related to LCP1 using various bioinformatics tools. RESULTS: The results indicated that LCP1 expression was higher in TNBC tissues compared to adjacent normal tissues. However, high expression of LCP1 was significantly associated with favorable survival outcomes in patients with TNBC. Enrichment analysis revealed that genes co-expressed with LCP1 were significantly enriched in various immune processes. LCP1 showed a positive correlation with the infiltration of resting dendritic cells, M1 macrophages, and memory CD4 T cells, and a negative correlation with M2 macrophages. Further analysis suggested a link between high levels of LCP1 and increased survival outcomes in cancer patients receiving immunotherapy. CONCLUSION: LCP1 may serve as a potential diagnostic and prognostic biomarker for TNBC, which was closely associated with immune cell infiltration, particularly M1 and M2 macrophages. Our findings may provide valuable insights into immunotherapeutic strategies for TNBC patients.
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Biomarcadores de Tumor , Linfocitos Infiltrantes de Tumor , Neoplasias de la Mama Triple Negativas , Humanos , Neoplasias de la Mama Triple Negativas/inmunología , Neoplasias de la Mama Triple Negativas/mortalidad , Neoplasias de la Mama Triple Negativas/genética , Femenino , Biomarcadores de Tumor/metabolismo , Pronóstico , Linfocitos Infiltrantes de Tumor/inmunología , Regulación Neoplásica de la Expresión Génica , Macrófagos/inmunología , Macrófagos/metabolismo , Microambiente Tumoral/inmunología , Estimación de Kaplan-MeierRESUMEN
Targeting telomere maintenance has emerged as a promising strategy for hepatocellular carcinoma (HCC) treatment. However, given the duality of the telomere-telomerase axis in telomere maintenance, a comprehensive strategy is urgently needed. Herein, we develop a poly(amino acid) (D-PAAs)-based strategy for spatiotemporal codelivery of telomerase inhibitor, BIBR1523, and AKT inhibitor, isobavachalcone. By leveraging D-PAAs' modifiability, we synthesize polymer-inhibitor conjugates (PB and PI) and a folic acid-decorated tumor-targeting vector (PF). These building blocks undergo micellization to fabricate a codelivery nanomedicine (P-BI@P-FA) by exploiting D-PAAs' noncovalent assembly. P-BI@P-FA improves the pharmacokinetics, tumor selectivity, and bioavailability of small molecule inhibitors and initiates a dual telomere-specific inhibition by combining telomerase deactivation with telomere disruption. Furthermore, a hybrid tumor-targeting magnetic nanosystem is designed using D-PAAs and manganese dioxide to showcase magnetic resonance imaging capacities. Our D-PAAs-based strategy addresses the pressing need for telomere-specific HCC treatment while allowing for diagnostic application, presenting a promising avenue for nanomedicine design.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Imagen por Resonancia Magnética , Nanomedicina , Telomerasa , Telómero , Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/patología , Telomerasa/antagonistas & inhibidores , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/tratamiento farmacológico , Humanos , Nanomedicina/métodos , Telómero/metabolismo , Imagen por Resonancia Magnética/métodos , Animales , Ratones , Línea Celular Tumoral , Aminoácidos/química , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/uso terapéuticoRESUMEN
Despite the critical role of self-disturbance in psychiatric diagnosis and treatment, its diverse behavioral manifestations remain poorly understood. This investigation aimed to elucidate unique patterns of self-referential processing in affective disorders and first-episode schizophrenia. A total of 156 participants (41 first-episode schizophrenia [SZ], 33 bipolar disorder [BD], 44 major depressive disorder [MDD], and 38 healthy controls [HC]) engaged in a self-referential effect (SRE) task, assessing trait adjectives for self-descriptiveness, applicability to mother, or others, followed by an unexpected recognition test. All groups displayed preferential self- and mother-referential processing with no significant differences in recognition scores. However, MDD patients showed significantly enhanced self-referential recognition scores and increased bias compared to HC, first-episode SZ, and BD. The present study provides empirical evidence for increased self-focus in MDD and demonstrates that first-episode SZ and BD patients maintain intact self-referential processing abilities. These findings refine our understanding of self-referential processing impairments across psychiatric conditions, suggesting that it could serve as a supplementary measure for assessing treatment response in first-episode SZ and potentially function as a discriminative diagnostic criterion between MDD and BD.
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Trastorno Bipolar , Trastorno Depresivo Mayor , Esquizofrenia , Psicología del Esquizofrénico , Autoimagen , Humanos , Femenino , Masculino , Adulto , Esquizofrenia/fisiopatología , Trastorno Bipolar/psicología , Trastorno Bipolar/fisiopatología , Trastorno Depresivo Mayor/psicología , Adulto Joven , Estudios de Casos y Controles , Persona de Mediana EdadRESUMEN
Angiopterisnodosipetiolata Ting Wang tris, H.F.Chen & Y.H.Yan, a new fern of Marattiaceae, is described and illustrated. Morphologically, A.nodosipetiolata is similar to A.chingii with more than one naked pulvinus on the stipe and numerous jointed hairs on the undersides of the mature pinnae. However, the pinnae of A.nodosipetiolata are lanceolate and can reach up to 4-6 pairs, whereas they are elliptic and occur in 2-3 pairs in A.chingii. Phylogenetic and genetic distance analysis, based on the plastid genomes, also indicates that A.nodosipetiolata is not closely related to A.chingii. Currently, there are ca. 500 mature individuals in Gulinqing Nature Reserve and we suggest A.nodosipetiolata should be categorised as an Endangered (EN) species according to the criteria of IUCN.
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BACKGROUND: Long-chain acyl-coenzyme A synthases (ACSLs) are responsible for the catalysis of fatty acids into their corresponding fatty acyl-CoAs. The dysregulation of ACSLs has been increasingly recognized in cancer patients. However, the function of ACSL6 in triple-negative breast cancer (TNBC) is still completely unknown. METHODS: In this study, immunohistochemistry was applied to detect ACSL6 protein expression using a TNBC tissue microarray. Additionally, the mRNA levels of ACSL6 in human normal tissues and pancancer tissues were analyzed using Genotype Tissue Expression (GTEx) datasets and The Cancer Genome Atlas (TCGA) database. The correlations between the levels of ACSL6 expression and clinical characteristics were analyzed. The survival analysis of ACSL6 in TNBC was carried out using the KaplanâMeier Plotter online tool. Associations of ACSL6 with immune infiltration analyses were conducted using the ESTIMATE, CIBERSORT, and TISIDB databases. The relationship between ACSL6 and sensitivity to drugs was analyzed from Genomics of Drug Sensitivity in Cancer (GDSC). RESULTS: The results indicated a significant increase in ACSL6 expression in TNBC tissues compared to adjacent normal tissues. However, high ACSL6 expression was significantly associated with favorable survival outcomes in TNBC patients. Enrichment analysis revealed that coexpressed genes of ACSL6 were significantly enriched in various immunity processes. ACSL6 was positively correlated with the infiltration of memory CD4 T cells, while a negative correlation was found between ACSL6 and M2 macrophages and resting dendritic cells. Further analysis revealed that high levels of ACSL6 correlated with increased survival outcomes in cancer patients who received immunotherapy. CONCLUSION: Altogether, the current findings highlight the potential value of ACSL6 as a diagnostic and prognostic marker in the treatment of TNBC.
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Cyclic nucleotide-gated ion channel (CNGC) gene regulation plays important roles in plant immune and abiotic stress response. Here, we identified 16 CNGC genes in rice (Oryza sativa). Then, we analyzed their chromosomal location, physicochemical properties, subcellular localization, gene functional interaction network, cis-acting elements, phylogenetic relationships, collinearity, expression in tissues under normal conditions and abiotic stresses, and geng-cds-haplotype (gcHap) diversity in 3010 gcHaps. As a result, OsCNGC3 (Os06g0527300) was identified as a gene different from previous report, and OsCNGC genes were found to play important roles in rice population differentiation and rice improvement. Our results revealed their very strong differentiation between subspecies and populations, important roles in response to abiotic stresses, as well as strong genetic bottleneck effects and artificial selection of gcHap diversity in the modern breeding process of Xian (indica) and Geng (japonica) populations. The results also suggested that natural variations in most rice CNGC loci are potentially valuable for improving rice productivity and tolerance to abiotic stresses. The favorable alleles at the CNGC loci should be explored to facilitate their application in future rice improvement.
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Controlling the bandwidth and directionality of thermal emission is important for a broad range of applications, from imaging and sensing to energy harvesting. Here, we propose a new, to the best of our knowledge, type of long-wavelength infrared narrowband thermal emitter that is basically composed of aperiodic Tamm plasmon polariton structures. Compared to the thermal emitter based on periodic structures, more parameters need to be considered. An inverse design algorithm instead of traditional forward methodologies is employed to do the geometric parameter optimization. Both theoretical and experimental results show that the thermal emitter exhibits a narrowband thermal emission peak at the wavelength of 8.6â µm in the normal direction. The angular response of emission properties of the thermal emitter is dependent on the emission angle. We believe that our proposed thermal emitter provides an alternative for low-cost, high-effective narrowband mid-infrared light sources and would have a great potential in many applications.
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ABSTRACT: Chronic alcohol intake contributes to high mortality rates due to ethanol-induced cardiac hypertrophy and contractile dysfunction, which are accompanied by increased oxidative stress and disrupted mitophagy. Alpha-lipoic acid (α-LA), a well-known antioxidant, has been shown to protect against cardiac hypertrophy and inflammation. However, little is known about its role and mechanism in the treatment of alcoholic cardiomyopathy. Here, we evaluated the role of α-LA in alcohol-induced cardiac damage by feeding mice a 4.8% (v/v) alcohol diet with or without α-LA for 6 w. Our results suggested that chronic alcohol consumption increased mortality, blood alcohol concentrations, and serum aldehyde levels, but a-LA attenuated the elevations in mortality and aldehydes. Chronic alcohol intake also induced cardiac dysfunction, including enlarged left ventricles, reduced left ventricular ejection fraction, enhanced cardiomyocyte size, and increased serum levels of brain natriuretic peptide, lactate dehydrogenase, and creatine kinase myocardial isoenzyme. Moreover, alcohol intake led to the accumulation of collagen fiber and mitochondrial dysfunction, the effects of which were alleviated by α-LA. In addition, α-LA intake also prevented the increase in reactive oxygen species production and the decrease in mitochondrial number that were observed after alcohol consumption. Chronic alcohol exposure activated PINK1/Parkin-mediated mitophagy. These effects were diminished by α-LA intake by the activation of aldehyde dehydrogenase 2. Our data indicated that α-LA helps protect cardiac cells against the effects of chronic alcohol intake, likely by inhibiting PINK1/Parkin-related mitophagy through the activation of aldehyde dehydrogenase 2.
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Alcoholismo , Ácido Tióctico , Ratones , Animales , Ácido Tióctico/farmacología , Aldehído Deshidrogenasa Mitocondrial/metabolismo , Alcoholismo/metabolismo , Volumen Sistólico , Función Ventricular Izquierda , Miocitos Cardíacos , Etanol/toxicidad , Consumo de Bebidas Alcohólicas/efectos adversos , Consumo de Bebidas Alcohólicas/metabolismo , Aldehídos/metabolismo , Aldehídos/farmacología , Proteínas Quinasas/metabolismo , Cardiomegalia/metabolismo , Aldehído Deshidrogenasa/metabolismo , Aldehído Deshidrogenasa/farmacologíaRESUMEN
BACKGROUND: Clinical outcomes are poor if patients with acute heart failure (AHF) are discharged with residual congestion in the presence of renal dysfunction. However, there is no single indication to reflect the combined effects of the two related pathophysiological processes. We, therefore, proposed an indicator, congestion and renal index (CRI), and examined the associations between the CRI and one-year outcomes and the incremental prognostic value of CRI compared with the established scoring systems in a multicenter prospective cohort of AHF. METHODS: We enrolled AHF patients and calculated the ratio of thoracic fluid content index divided by estimated glomerular filtration rate before discharge, as CRI. Then we examined the associations between CRI and one-year outcomes. RESULTS: A total of 944 patients were included in the analysis (mean age 63.3 ± 13.8 years, 39.3% women). Compared with patients with CRI ≤ 0.59 mL/min per kΩ, those with CRI > 0.59 mL/min per kΩ had higher risks of cardiovascular death or HF hospitalization (HR = 1.56 [1.13-2.15]) and all-cause death or all-cause hospitalization (HR = 1.33 [1.01-1.74]). CRI had an incremental prognostic value compared with the established scoring system. CONCLUSIONS: In patients with AHF, CRI is independently associated with the risk of death or hospitalization within one year, and improves the risk stratification of the established risk models.
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Several diseases have been linked to the dysfunction of anoctamins. Anoctamins play a wide range of physiological roles, including cell proliferation, migration, epithelial secretion, and calcium-activated chloride channel activity. However, the function of anoctamin 10 (ANO10) in breast cancer is still unclear. ANO10 was highly expressed in bone marrow, blood, skin, adipose tissue, thyroid gland and salivary gland, while ANO10 was expressed at low levels in liver and skeletal muscle. Compared to benign breast lesions, the protein level of ANO10 was lower in malignant breast tumors. However, breast cancer patients with low ANO10 expression have favorable survival outcomes. ANO10 was negatively correlated with the infiltration of memory CD4 T cells, naïve B cells, CD8 T cells, chemokines and chemokine receptors. Furthermore, the ANO10 low expression group was more sensitive to certain chemotherapy drugs, including bleomycin, doxorubicin, gemcitabine, mitomycin and etoposide. Altogether, ANO10 is a potential biomarker that can effectively predict the prognosis of breast cancer. Our findings highlight the promising prognostic value and therapeutic target of ANO10 in breast cancer.
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The application of plasmonic structure has been demonstrated to improve the performance of infrared photodetectors. However, the successful experimental realization of the incorporation of such optical engineering structure into HgCdTe-based photodetectors has rarely been reported. In this paper, we present a HgCdTe infrared photodetector with integrated plasmonic structure. The experimental results show that the device with plasmonic structure has a distinct narrowband effect with a peak response rate close to 2 A/W, which is nearly 34% higher compared with the reference device. The simulation results are in good agreement with the experiment, and an analysis of the effect of the plasmonic structure is given, demonstrating the crucial role of the plasmonic structure in the enhancement of the device performance.
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Endiandramacrocarpa, a new species of Endiandra (Lauraceae) from Yunnan Province of south-western China, is here described and illustrated, based on morphological evidence. Compared to other Endiandra species occurring in south China and the adjacent regions in Indochina, this species is mainly characterised by its much larger ellipsoidal fruits (up to 11 × 6 cm), as well as glabrous branchlets and puberulent inflorescences.
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BACKGROUND: Doxorubicin (DOX) is an effective broad-spectrum antitumor drug, but its clinical application is limited due to the side effects of cardiac damage. Astragaloside IV (AS-IV) is a significant active component of Astragalus membranaceus that exerts cardioprotective effects through various pathways. However, whether AS-IV exerts protective effects against DOX-induced myocardial injury by regulating the pyroptosis is still unknown and is investigated in this study. METHODS: The myocardial injury model was constructed by intraperitoneal injection of DOX, and AS-IV was administered via oral gavage to explore its specific protective mechanism. Cardiac function and cardiac injury indicators, including lactate dehydrogenase (LDH), cardiac troponin I (cTnI), creatine kinase isoenzyme (CK-MB), and brain natriuretic peptide (BNP), and histopathology of the cardiomyocytes were assessed 4 weeks post DOX challenge. Serum levels of IL-1ß, IL-18, superoxide dismutase (SOD), malondialdehyde (MDA) and glutathione (GSH) and the expression of pyroptosis and signaling proteins were also determined. RESULTS: Cardiac dysfunction was observed after the DOX challenge, as evidenced by reduced ejection fraction, increased myocardial fibrosis, and increased BNP, LDH, cTnI, and CK-MB levels (p < 0.05, N = 3-10). AS-IV attenuated DOX-induced myocardial injury. The mitochondrial morphology and structure were also significantly damaged after DOX treatment, and these changes were restored after AS-IV treatment. DOX induced an increase in the serum levels of IL-1ß, IL-18, SOD, MDA and GSH as well as an increase in the expression of pyroptosis-related proteins (p < 0.05, N = 3-6). Besides, AS-IV depressed myocardial inflammatory-related pyroptosis via activation of the expressions of nuclear factor E2-related factor 2 (Nrf-2) and heme oxygenase 1 (HO-1) (p < 0.05, N = 3). CONCLUSIONS: Our results showed that AS-IV had a significant protective effect against DOX-induced myocardial injury, which may be associated with the activation of Nrf-2/HO-1 to inhibit pyroptosis.
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Cardiopatías , Piroptosis , Humanos , Factor 2 Relacionado con NF-E2/metabolismo , Inflamasomas/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Interleucina-18/metabolismo , Interleucina-18/farmacología , Hemo-Oxigenasa 1 , Estrés Oxidativo , Transducción de Señal , Cardiopatías/metabolismo , Miocitos Cardíacos/metabolismo , Doxorrubicina/toxicidadRESUMEN
OBJECTIVE: To explore the clinical and genetic characteristics of a patient with hypertrophic cardiomyopathy as the initial manifestation of Mucopolysaccharidosis type â ¢ A (MPS â ¢ A). METHODS: A female patient with MPS â ¢ A who was admitted to the Affiliated Hospital of Jining Medical University in January 2022 and her family members (seven individuals from three generations) were selected as the study subjects. Clinical data of the proband were collected. Peripheral blood samples of the proband was collected and subjected to whole exome sequencing. Candidate variants were verified by Sanger sequencing. Heparan-N-sulfatase activity was determined for the disease associated with the variant site. RESULTS: The proband was a 49-year-old woman, for whom cardiac MRI has revealed significant thickening (up to 20 mm) of left ventricular wall and delayed gadolinium enhancement at the apical myocardium. Genetic testing revealed that she has harbored compound heterozygous variants in exon 17 of the SGSH gene, namely c.545G>A (p.Arg182His) and c.703G>A (p.Asp235Asn). Based on guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were predicted to be pathogenic (PM2_Supporting +PM3+PP1Strong+PP3+PP4; PS3+PM1+PM2_Supporting +PM3+PP3+PP4). Sanger sequencing confirmed that her mother was heterozygous for the c.545G>A (p.Arg182His) variant, whilst her father, sisters and her son were heterozygous for the c.703G>A (p.Asp235Asn) variant. Determination of blood leukocyte heparan-N-sulfatase activity suggested that the patient had a low level of 1.6 nmol/(g·h), whilst that of her father, elder and younger sisters and son were all in the normal range. CONCLUSION: The compound heterozygous variants of the SGSH gene probably underlay the MPS â ¢A in this patient, for which hypertrophic cardiomyopathy is an associated phenotype.
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Cardiomiopatía Hipertrófica , Mucopolisacaridosis III , Femenino , Humanos , Medios de Contraste , Pueblos del Este de Asia , Gadolinio , Mutación , Linaje , Masculino , Persona de Mediana EdadRESUMEN
In this work, we experimentally demonstrate a new type of compact, low-cost, visible microbolometer based on metal-insulator-metal (MIM) planar subwavelength thin films, which exploits resonant absorption for spectral selectivity without additional filters and has the advantages of compact design, simple structure, cost-efficiency, and large format fabrication. The experimental results show that a proof-of-principle microbolometer exhibits spectrally selective properties in the visible frequency range. At a resonant absorption wavelength of 638 nm, a responsivity of about 10 mV W-1 is achieved at room temperature at a bias current of 0.2 mA, which is about one order of magnitude higher than that of the control device (a bare Au bolometer). Our proposed approach provides a viable solution for the development of compact and inexpensive detectors.
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Background: Currently, targeting immune checkpoint molecules holds great promise for triple-negative breast cancer (TNBC). However, the expression landscape of immune checkpoint genes (ICGs) in TNBC remains largely unknown. Method: Herein, we systematically investigated the ICGs expression patterns in 422 TNBC samples. We evaluated the ICGs molecular typing based on the ICGs expression profile and explored the associations between ICGs molecular subtypes and tumor immune characteristics, clinical significance, and response to immune checkpoint inhibitors (ICIs). Results: Two ICGs clusters and two ICGs-related gene clusters were determined, which were involved in different survival outcomes, biological roles and infiltration levels of immune cells. We established a quantification system ICGs riskscore (named IRS) to assess the ICGs expression patterns for individuals. TNBC patients with lower IRS were characterized by increased immune cell infiltration, favorable clinical outcomes and high sensitivity to ICIs therapy. We also developed a nomogram model combining clinicopathological variables to predict overall survival in TNBC. Genomic feature analysis revealed that high IRS group presented an increased tumor mutation burden compared with the low IRS group. Conclusion: Collectively, dissecting the ICGs expression patterns not only provides a new insight into TNBC subtypes but also deepens the understanding of ICGs in the tumor immune microenvironment.
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Neoplasias de la Mama Triple Negativas , Humanos , Pronóstico , Nomogramas , Relevancia Clínica , Genómica , Proteínas de Punto de Control Inmunitario , Microambiente TumoralRESUMEN
SRY-box transcription factor 11 (SOX11), as a member of the SOX family, is a transcription factor involved in the regulation of specific biological processes and has recently been found to be a prognostic marker for certain cancers. However, the roles of SOX11 in cancer remain controversial. Our study aimed to explore the various aspects of SOX11 in pan-cancer. The expression of SOX11 was investigated by the Genotype Tissue-Expression (GTEX) dataset and the Cancer Genome Atlas (TCGA) database. The protein level of SOX11 in tumor tissues and tumor-adjacent tissues was verified by human pan-cancer tissue microarray. Additionally, we used TCGA pan-cancer data to analyze the correlations among SOX11 expression and survival outcomes, clinical features, stemness, microsatellite instability (MSI), tumor mutation burden (TMB), mismatch repair (MMR) related genes and the tumor immune microenvironment. Furthermore, the cBioPortal database was applied to investigate the gene alterations of SOX11. The main biological processes of SOX11 in cancers were analyzed by Gene Set Enrichment Analysis (GSEA). As a result, aberrant expression of SOX11 has been implicated in 27 kinds of cancer types. Aberrant SOX11 expression was closely associated with survival outcomes, stage, tumor recurrence, MSI, TMB and MMR-related genes. In addition, the most frequent alteration of the SOX11 genome was mutation. Our study also showed the correlations of SOX11 with the level of immune infiltration in various cancers. In summary, our findings underline the multifaceted role and prognostic value of SOX11 in pan-cancer.
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BACKGROUND: Excessive extracellular matrix (ECM) deposition in pancreatic ductal adenocarcinoma (PDAC) severely limits therapeutic drug penetration into tumors and is associated with poor prognosis. Collagen is the most abundant matrix protein in the tumor ECM, which is the main obstacle that severely hinders the diffusion of chemotherapeutic drugs or nanomedicines. METHODS: We designed a collagenase-functionalized biomimetic drug-loaded Au nanoplatform that combined ECM degradation, active targeting, immune evasion, near-infrared (NIR) light-triggered drug release, and synergistic antitumor therapy and diagnosis into one nanoplatform. PDAC tumor cell membranes were extracted and coated onto doxorubicin (Dox)-loaded Au nanocages, and then collagenase was added to functionalize the cell membrane through lipid insertion. We evaluated the physicochemical properties, in vitro and in vivo targeting, penetration and therapeutic efficacy of the nanoplatform. RESULTS: Upon intravenous injection, this nanoplatform efficiently targeted the tumor through the homologous targeting properties of the coated cell membrane. During penetration into the tumor tissue, the dense ECM in the PDAC tissues was gradually degraded by collagenase, leading to a looser ECM structure and deep penetration within the tumor parenchyma. Under NIR irradiation, both photothermal and photodynamic effects were produced and the encapsulated chemotherapeutic drugs were released effectively, exerting a strong synergistic antitumor effect. Moreover, this nanoplatform has X-ray attenuation properties that could serve to guide and monitor treatment by CT imaging. CONCLUSION: This work presented a unique and facile yet effective strategy to modulate ECM components in PDAC, enhance tumor penetration and tumor-killing effects and provide therapeutic guidance and monitoring.
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Nanopartículas , Neoplasias Pancreáticas , Fotoquimioterapia , Humanos , Nanopartículas/química , Doxorrubicina/farmacología , Liberación de Fármacos , Neoplasias Pancreáticas/tratamiento farmacológico , Matriz Extracelular , Línea Celular Tumoral , Fototerapia/métodosRESUMEN
Background: Plasma heat shock protein 90 alpha (Hsp90α) has been suggested as a novel biomarker for the diagnosis and prognosis of cancer. Carcinoembryonic antigen (CEA) and carbohydrate antigen199 (CA199) are traditional tumor biomarkers for colorectal cancer (CRC). Previous studies have shown that Hsp90α and the combination of Hsp90α and CEA are optimal biomarkers for CRC at an early stage. However, research on the use of Hsp90α alone or in combination with CEA and/or CA199 in diagnosing CRC development, particularly liver metastasis, is limited. This study sought to investigate the value of Hsp90α alone or in combination with CEA/CA199 in diagnosing CRC liver metastasis. Methods: The clinical data of 472 CRC patients were retrospectively analyzed, which were confirmed by clinical manifestations and a histopathological examination associated with an imaging diagnosis. The levels of Hsp90α, and CEA, and CA199 were assessed by enzyme-linked immunoassays and electrochemiluminescence immunoassays. Liver metastasis was diagnosed by imaging or pathology of the liver. Logistic regression models were used to analyze associations between Hsp90α, CEA, and CA199, and liver metastasis in CRC. The areas under the curves (AUCs) were used to compare the utility of Hsp90α, CEA, and CA199 in the diagnosis of CRC liver metastasis (CRLM). Additionally, we compared the diagnostic utility of the models, including the Hsp90α plus 1 of the other serum markers, and a combination of the 3 serum makers. Results: The plasma levels of Hsp90α, CEA, and CA199 were positively associated with a higher risk of CRLM [odds ratios (OR) ranging from 1.36-2.72]. The AUCs of CEA, CA199, and Hsp90α for CRLM were 0.80, 0.69, and 0.55, respectively. The AUCs for the combination of Hsp90α and CEA, combination of Hsp90α and CA199, combinations of Hsp90α, CEA, and CA199 were 0.75, 0.66, 0.76, respectively. The combination of Hsp90α, CEA, and CA199 did not improve the diagnostic utility for liver metastasis in CRC. Conclusions: The level of Hsp90α was elevated in CRC and was associated with CRLM. Thus, the Hsp90α is a potential biomarker for CRLM. CEA has the largest diagnostic utility for CRLM. Adding Hsp90α to CEA/CA199 did not improve their diagnostic utility for CRLM.