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CONTEXT: Epigallocatechin-3-gallate (EGCG), the predominant catechin in green tea, has shown the potential to combat various types of cancer cells through its ability to modulate multiple signaling pathways. However, its low bioavailability and rapid degradation hinder its clinical application. OBJECTIVE: This review explores the potential of nanoencapsulation to enhance the stability, bioavailability, and therapeutic efficacy of EGCG in cancer treatment. METHODS: We searched the PubMed database from 2019 to the present, using 'epigallocatechin gallate', 'EGCG', and 'nanoparticles' as search terms to identify pertinent literature. This review examines recent nano-engineering technology advancements that encapsulate EGCG within various nanocarriers. The focus was on evaluating the types of nanoparticles used, their synthesis methods, and the technologies applied to optimize drug delivery, diagnostic capabilities, and therapeutic outcomes. RESULTS: Nanoparticles improve the physicochemical stability and pharmacokinetics of EGCG, leading to enhanced therapeutic outcomes in cancer treatment. Nanoencapsulation allows for targeted drug delivery, controlled release, enhanced cellular uptake, and reduced premature degradation of EGCG. The studies highlighted include those where EGCG-loaded nanoparticles significantly inhibited tumor growth in various models, demonstrating enhanced penetration and efficacy through active targeting mechanisms. CONCLUSIONS: Nanoencapsulation of EGCG represents a promising approach in oncology, offering multiple therapeutic benefits over its unencapsulated form. Although the results so far are promising, further research is necessary to fully optimize the design of these nanosystems to ensure their safety, efficacy, and clinical viability.
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Catequina , Nanopartículas , Neoplasias , Catequina/análogos & derivados , Catequina/administração & dosagem , Catequina/química , Catequina/farmacologia , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Animais , Disponibilidade Biológica , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Chá/químicaRESUMO
Although tumor necrosis factor receptor 2 (TNFR2) may serve a protumor role in several types of tumors, the clinical significance of TNFR2, including the diagnostic and prognostic value in tumor (T) stage 2-3 esophageal squamous cell carcinoma (ESCC), remains unclear. Therefore, the present study aimed to explore the clinical significance of TNFR2 in stage T2-3 ESCC. The present study collected the mRNA expression data of TNFR2 from two databases and confirmed the high expression of TNFR2 in ESCC tissue. TNFR2 expression in stage T2-3 ESCC tissue (n=404) was detected using immunohistochemistry and a stratified analysis was performed. For all patients with stage T2-3 ESCC, TNFR2 expression was associated with clinical stage, invasion depth and metastatic lymph nodes. Stage T3 and low differentiation was associated with an increase in the risk of lymph node metastasis, but older age was associated with a decrease. TNFR2 expression was associated with poor overall survival (OS) of all patients with stage T2-3 ESCC and stratified patients with stage T3 ESCC. Moreover, TNFR2 expression and metastatic lymph nodes were independent prognostic factors for these patients. For stratified patients aged ≤60 years, TNFR2 expression was associated with clinical stage and metastatic lymph nodes. In addition, TNFR2 expression was associated with poor OS in stratified patients with stage T2 ESCC. The presence of metastatic lymph nodes was also an independent prognostic factor for these patients. For stratified patients aged >60 years, TNFR2 expression was associated with invasion depth. TNFR2 expression was also associated with poor OS in all patients with stage T2-3 ESCC and stratified patients with stage T3 ESCC. TNFR2 expression and metastatic lymph nodes were identified as independent prognostic factors for these patients. In conclusion, TNFR2 expression is associated with progression and poor prognosis in patients with stage T2-3 ESCC as an independent prognostic factor, except in the subgroup of patients with stage T2-3 ESCC aged ≤60 years.
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BACKGROUND: Organising pneumonia (OP) is one of the most common and lethal diseases in the category of interstitial pneumonia, along with lung cancer. Reprogramming of lipid metabolism is a newly recognized hallmark of many diseases including cancer, cardiovascular disorders, as well as liver fibrosis and sclerosis. Increased levels of ceramides composed of sphingosine and fatty acid, are implicated in the development of both acute and chronic lung diseases. However, their pathophysiological significance in OP is unclear. The aim of this study was to investigate the role of lipid metabolism reprogramming in OP, focusing on inflammation and fibrosis. METHODS: Comprehensive multi-omics profiling approaches, including single-cell RNA sequencing, Visium CytAssist spatial transcriptomics, proteomics, metabolomics and mass spectrometry, were employed to analyze the tissues. OP mice model was utilized and molecular mechanisms were investigated in macrophages. RESULTS: The results revealed a significant association between OP and lipid metabolism reprogramming, characterized by an abnormal expression of several genes related to lipid metabolism, including CD36, SCD1, and CES1 mainly in macrophages. CD36 deficiency in alveolar macrophages, led to an increased expression of C16/24 ceramides that accumulated in mitochondria, resulting in mitophagy or mitochondrial dysfunction. The number of alveolar macrophages in OP was significantly reduced, which was probably due to the ferroptosis signaling pathway involving GSH/SLC3A2/GPX4 through CD36 downregulation in OP. Furthermore, macrophage secretion of DPP7 and FABP4 influenced epithelial cell fibrosis. CONCLUSIONS: CD36 inhibited the ferroptosis pathway involving SLC3A2/GPX4 in alveolar macrophages of OP tissue by regulating lipid metabolism, thus representing a new anti-ferroptosis and anti-fibrosis effect of CD36 mediated, at least in part, by ceramides. HIGHLIGHTS: Our findings reveal a significant association between organising pneumonia and lipid metabolism reprogramming and will make a substantial contribution to the understanding of the mechanism of organising pneumonia in patients.
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Metabolismo dos Lipídeos , Animais , Camundongos , Metabolismo dos Lipídeos/genética , Modelos Animais de Doenças , Humanos , Pneumonia/metabolismo , Pneumonia/genética , Pneumonia/patologia , Camundongos Endogâmicos C57BL , Masculino , Pneumonia em Organização , MultiômicaRESUMO
BACKGROUND: Pancreatic adenocarcinoma (PAAD), a member of highly lethal malignant tumors, has a poor outcome and extremely poor prognosis. The transient receptor potential (TRP) superfamily, a group of nonselective cation channels, is capable of influencing cellular functions by regulating calcium homeostasis. In addition, it has been shown that TRP channels can also affect various cellular phenotypes by regulating gene transcription levels and are involved in the development of a variety of malignant tumors. AIMS: In order to find new therapeutic targets and biomarkers to improve the clinical prognosis of pancreatic cancer, we performed genetic and immunological characterization of TRP channels in PAAD, as well as related functional and prognostic analyses. METHODS AND RESULTS: We investigated the expression, genetic alterations, methylation levels, and immune infiltration levels of TRP channels in PAAD, and further also analyzed the function of TRP channels in PAAD and their prognostic value for PAAD patients. Our results suggest that TRPM8 may contribute to tumor proliferation by controlling the PI3K-AKT-mTOR signaling pathway in PAAD. CONCLUSION: After careful evaluation of the accumulated data, we concluded that TRPM8 has potential as a prognostic indicator and prospective therapeutic target in PAAD.
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Adenocarcinoma , Biomarcadores Tumorais , Proliferação de Células , Neoplasias Pancreáticas , Canais de Cátion TRPM , Humanos , Canais de Cátion TRPM/genética , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/imunologia , Neoplasias Pancreáticas/mortalidade , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Adenocarcinoma/genética , Adenocarcinoma/patologia , Adenocarcinoma/imunologia , Proliferação de Células/genética , Prognóstico , Masculino , Feminino , Pessoa de Meia-Idade , Regulação Neoplásica da Expressão Gênica , Transdução de Sinais , Idoso , Serina-Treonina Quinases TOR/metabolismo , Linhagem Celular Tumoral , Fosfatidilinositol 3-Quinases/metabolismo , Metilação de DNARESUMO
BACKGROUND: Dysfunction of motile cilia, including respiratory cilia and sperm flagella, typically leads to primary ciliary dyskinesia and male infertility or low fertility in humans. Genetic defects of LRRC6 have been associated with primary ciliary dyskinesia and asthenozoospermia due to abnormal ultrastructure of ciliated axonemes. OBJECTIVES: To identify novel mutations of the LRRC6 gene related to multiple morphological abnormalities of the sperm flagella and male infertility and investigate the underlying molecular mechanisms involved. MATERIALS AND METHODS: The LRRC6 mutations were identified by whole exome sequencing and confirmed with Sanger sequencing. Papanicolaou staining, scanning, and transmission electron microscopy were performed to investigate the morphological and ultrastructural characteristics of spermatozoa. Further tandem mass tagging proteomics analyses were performed to explore the effect of mutations and confirmed by immunostaining and western blotting. Intracytoplasmic sperm injection was applied for the assisted reproductive therapy of males harboring biallelic LRRC6 mutations. RESULTS: In this study, we identified a novel homozygous LRRC6 mutation in a consanguineous family, characterized by asthenozoospermia and primary ciliary dyskinesia. Further Semen parameter and morphology analysis demonstrate that the novel LRRC6 mutation leads to a significant reduction in sperm flagella length, a decrease in sperm progressive motility parameters, and abnormalities of sperm ultrastructure. Specifically, the absence of outer dynein arms and inner dynein arms, and incomplete mitochondrial sheath in the flagellar mid-piece were observed by transmission electron microscopy. In addition, tandem mass tagging proteomics analysis revealed that spermatozoa obtained from patients harboring the LRRC6 mutation exhibited a significant decrease in the expression levels of proteins related to the assembly and function of dynein axonemal arms. Functional analysis revealed that this novel LRRC6 mutation disrupted the function of the leucine-rich repeat containing 6 protein, which in turn affects the expression of the dynein arm proteins and leucine-rich repeat containing 6-interacting proteins CCDC40, SPAG1, and ZMYND10. Finally, we reported a successful pregnancy through assisted reproductive technology with intracytoplasmic sperm injection in the female partner of the proband. DISCUSSION AND CONCLUSION: This study highlights the identification of a novel homozygous LRRC6 mutation in a consanguineous family and its impact on sperm progressive motility, morphology, and sperm kinetics parameters, which could facilitate the genetic diagnosis of asthenozoospermia and offer valuable perspectives for future genetic counseling endeavors.
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(Z)-alkenes are useful synthons but thermodynamically less stable than their (E)-isomers and typically more difficult to prepare. The synthesis of 1,4-hetero-bifunctionalized (Z)-alkenes is particularly challenging due to the inherent regio- and stereoselectivity issues. Herein we demonstrate a general, chemoselective and direct synthesis of (Z)-2-butene-1,4-diol monoesters. The protocol operates within a Pd-catalyzed decarboxylative acyloxylation regime involving vinyl ethylene carbonates (VECs) and various carboxylic acids as the reaction partners under mild and operationally attractive conditions. The newly developed process allows access to a structurally diverse pool of (Z)-2-butene-1,4-diol monoesters in good yields and with excellent regio- and stereoselectivity. Various synthetic transformations of the obtained (Z)-2-butene-1,4-diol monoesters demonstrate how these synthons are of great use to rapidly diversify the portfolio of these formal desymmetrized (Z)-alkenes.
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Usually, CymA is irreplaceable as the electron transport hub in Shewanella oneidensis MR-1 bidirectional electron transfer. In this work, biologically self-assembled FeS nanoparticles construct an artificial electron transfer route and implement electron transfer from extracellular into periplasmic space without CymA involvement, which present similar properties to type IV pili. Bacteria are wired up into a network, and more electron transfer conduits are activated by self-assembled transmembrane FeS nanoparticles (electron conduits), thereby substantially enhancing the ammonia production. In this study, we achieved an average NH4+-N production rate of 391.8 µg·h-1·L reactor-1 with the selectivity of 98.0% and cathode efficiency of 65.4%. Additionally, the amide group in the protein-like substances located in the outer membrane was first found to be able to transfer electrons from extracellular into intracellular with c-type cytochromes. Our work provides a new viewpoint that contributes to a better understanding of the interconnections between semiconductor materials and bacteria and inspires the exploration of new electron transfer chain components.
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Amônia , Shewanella , Amônia/metabolismo , Transporte de Elétrons , Shewanella/metabolismo , Elétrons , Eletrodos , Fontes de Energia BioelétricaRESUMO
This work investigates wireless covert communication in a multi-sensor asymmetric noise scenario. We adopt KL (Kullback-Leibler) divergence as the covertness constraint metric and mutual information as the transmission rate metric. To accurately approximate KL divergence and mutual information in covert communication, we employ the Taylor series expansion technique. Analytical expressions for KL divergence and mutual information in covert communication are derived, and we optimize the amplitude gain and phase angles based on these analytical expressions. Our findings underscore the importance of phase angle selection in covert communication within asymmetric noise systems. We propose an effective method for optimizing the transmission amplitude gain and phase angles in scenarios with asymmetric noise. Numerical results validate the effectiveness and superiority of our proposed method.
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Although polymeric anion exchange resins can remove phosphonates, they lack selectivity for target phosphonates and are susceptible to interference by anions and other substances. Here, we developed a novel strategy via confining MIL-101(Fe)-NH2 inside commercial resins IRA-900 for high-efficient and precise phosphonate removal, accompanying with the improvement of the stability and recovery of MIL-101(Fe)-NH2. The obtained nanocomposite MIL-101(Fe)-NH2@IRA-900 (MFNI) exhibited significantly enhanced phosphonate removal in the presence of competing anions (Cl-, SO42-, NO3- and CO32-) and natural organic matter (humic acid) at high concentrations (2-4 times of phosphonate concentration). Moreover, MFNI displayed the highest phosphonate adsorption capacity (12.9 mg P/g) and the fastest adsorption kinetics (120 min) than hydrated ferric oxides modified IRA-900 (HFOI) (6.7 mg P/g, 180 min), MIL-101(Fe)-NH2 (7.6 mg P/g, 240 min) and IRA-900 (5.6 mg P/g, 360 min). Such higher adsorption affinity and anti-interference ability came from the synergistic effect of the host IRA-900 (hydrogen-bond interaction and electrostatic attraction) and the embedded MIL-101(Fe)-NH2 (ligand exchange). The depleted MFNI could be regenerated with a binary NaOH-NaCl solution and reused without significant loss of capacity. Column adsorption runs by using MFNI indicated the fresh MFNI could achieve 100 % removal of PPOA in 10.5 h continuously feeding, which offered the possibility of achieving potential large-scale applications. In general, a new MOF-confined design approach was practiced to achieve selective elimination of phosphates and to improve the stability and recovery of MOF.
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Dissimilatory nitrate reduction to ammonium (DNRA) has been found to occur in some anammox bacteria species, and the DNRA metabolites (nitrite and ammonium) can further be removed to nitrogen from water. However, the activation of DNRA pathway of anammox bacteria is usually limited by the access to electron donors. Herein, we constructed a photosensitized hybrid system combining anammox bacteria (Candidatus Kuenenia stuttgartiensis and Candidatus Brocadia anammoxidans) with CdS nanoparticles semiconductor for energy-efficient NO3- removal. Such photosensitized anammox-CdS hybrid systems achieved NO3- removal with an average efficiency of 88% (the maximum of 91%) and a N2 selectivity of 72%, only with photoexcited electrons as donors. The DNRA-anammox metabolism of anammox bacteria was proved to responsible for NO3- removal via inward extracellular electron transfer channel. The greatly up-regulated genes encoding c-type cytochrome proteins (5 or 11 hemes) in the outer membrane, c-type cytochrome protein (4 hemes) and electron transport protein RnfA-E in the inner membrane, ferredoxin (2Fe-2S) in the cytoplasm and c-type cytochrome bc1 in anammoxosome membrane were supposed to play key roles in the inward extracellular electron transfer pathway. This work provides a novel insight into the design of the biotic-abiotic hybrid photosynthetic systems, and opens a new strategy for light-driven NO3- removal from the perspective of light energy input.
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Compostos de Amônio , Nitratos , Nitratos/metabolismo , Transporte de Elétrons , Elétrons , Oxirredução , Oxidação Anaeróbia da Amônia , Bactérias/metabolismo , Compostos de Amônio/metabolismo , Citocromos/metabolismo , Nitrogênio/metabolismo , Desnitrificação , Reatores Biológicos/microbiologiaRESUMO
AIMS: The intestinal biota, known for its colonization of the human intestine and its modulation of host pathophysiological responses through the immune and endocrine systems, has gained substantial interest in recent years due to its notable correlation with diabetes and stroke. METHODS: In order to examine this association, a comparative study was conducted on the intestinal biota and blood samples obtained from mouse models and type 2 diabetic patients with and without stroke complications. Advanced techniques, such as high-throughput sequencing and enzyme-linked immunosorbent assay were employed to identify the differences in the intestinal biota and blood indices of mouse models and patients. RESULTS: At the phylum level, the dominant gut bacteria identified in patients with diabetes mellitus and stroke were Firmicutes, Bacteroidetes, and Proteobacteria. It was noteworthy that the relative abundance of Bacteroides at the genus level was significantly diminished in the DB-PT group (photothrombotic diabetes mice) as compared to the DB group (diabetesmice). This result was consistent with observations in human samples. Additionally, significant variations were detected in lipid proteins, specifically APOA4, in diabetic patients with and without stroke. CONCLUSIONS: Stroke can diminish the abundance and diversity of intestinal biota, potentially correlating with lipid proteins in patients with diabetes.
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This study investigated the removal performance of ofloxacin (OFL) by a novel electro-Fenton enhanced microfiltration membrane. The membranes used in this study consisted of metal-organic framework derived porous carbon, carbon nanotubes and Fe2+, which were able to produce hydroxyl radicals (â¢OH) in-situ via reducing O2 to hydrogen peroxide. Herein, membrane filtration with bias not only concentrated the pollutants to the level that could be efficiently treated by electro-Fenton but also confined/retained the toxic intermediates within the membrane to ensure a prolonged contact time with the oxidants. After validated by experiments, the applied bias of -1.0 V, pH of 3 and electrolyte concentration of 0.1 M were the relatively optimum conditions for OFL degradation. Under these conditions, the average OFL removal rate could be reach 75% with merely 5% membrane flux loss after 4 cycles operation by filtrating 1 mg/L OFL. Via decarboxylation reaction, piperazinyl ring opening, dealkylation and ipso substitution reaction, etc., OFL could be gradually and efficiently degraded to intermediate products and even to CO2 by â¢OH. Moreover, the oxidation reaction was preferred to following first-order reaction kinetics. This research verified a possibility for antibiotic removal by electro-enhanced microfiltration membrane.
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Nanotubos de Carbono , Poluentes Químicos da Água , Ofloxacino , Porosidade , Antibacterianos , Oxidantes , Peróxido de Hidrogênio , OxirreduçãoRESUMO
Amidst the "double carbon" target, China is vigorously promoting the transformation of the electricity and coal markets and carbon markets widely regarded as an effective policy tool for managing carbon emissions. Leveraging sample data from January 3, 2017, to December 16, 2022, this study investigates the risk spillover effects among China's power, coal, and carbon markets via rolling window technology and the DY spillover index. The empirical results indicate a significant long-term two-way asymmetric spillover effect among these markets. Specifically, the Guangdong carbon market acts as both an exporter and receiver of risky fluctuations across the two sample periods. The coal market primarily exhibits a net risk spillover effect on the Guangdong and Hubei carbon markets. Furthermore, the aggregate spillover index reveals that the volatility spillover effects of the power, coal, and carbon markets are significantly amplified by extreme risk events. The rise and volatility of coal prices under the influence of these extreme risk events may lead to government intervention in the power sector, which in turn has an impact on the coal market. These findings underscore the time-varying nature of risk spillovers among markets and have important implications for risk management and the construction of diversified energy markets.
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Carbono , Carvão Mineral , Carbono/análise , China , Dióxido de Carbono/análise , EletricidadeRESUMO
BACKGROUND: The genotype-phenotype relationships between TUBB8 variants and female infertility are difficult to clearly define due to the complex inheritance patterns and the highly heterogeneous phenotypes. This study aims to identify novel TUBB8 variants and relevant phenotypes in more infertile females. METHODS: A total of 35 females with primary infertility were recruited from two reproductive centers and investigated for identifying variants in TUBB8. Pedigree analysis, in-silico analysis and molecular remodeling were performed to assess their clinical significance. The effects of the variants on human oocytes and embryos as well as HeLa cells were analyzed by morphological observations, immunostaining and Western blot. RESULTS: We totally identified five novel variants (p.G13R, p.Y50C, p.T136I, p.F265V and p.T366A) and five previously reported variants (p.I4L, p.L42V, p.Q134*, p.V255M and p.V349I) in TUBB8 from 9 unrelated females with primary infertility. These variants were rare and highly conserved among different species, and were inherited in autosomal dominant/recessive patterns, or occurred de novo. In vitro functional assays in HeLa cells revealed that exogenous expression of mutant TUBB8 proteins caused different degrees of microtubule structural disruption. The existence of these pathogenic TUBB8 variants finally induced oocyte maturation arrest or morphological abnormalities, fertilization failure, cleavage failure, embryonic development defects and implantation failure in the affected females. CONCLUSION: These findings enriched the variant spectrum of TUBB8 gene and could contribute to optimize genetic counselling and clinical management of females with primary infertility.
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Infertilidade Feminina , Tubulina (Proteína) , Gravidez , Humanos , Feminino , Células HeLa , Mutação , Tubulina (Proteína)/genética , Tubulina (Proteína)/metabolismo , Oócitos/metabolismo , Infertilidade Feminina/genética , Infertilidade Feminina/metabolismoRESUMO
OBJECTIVE: To investigate the anti-liver cancer effects and aspartic acid (Asp)-related action mechanism of Euphorbia fischeriana Steud. (Lang Du, LD). METHODS: The mice model of liver cancer was established by injection of H22 cells. After 5 days, mice were randomly divided into model group, sorafenib group (20 mg/kg), LD high-dose (LDH, 1.36 g/kg) group, LD medium-dose (LDM, 0.68 g/kg) group, and LD low-dose (LDL, 0.34 g/kg) group, 10 mice each group. Drugs were intragastrically administered to the mice once daily for 10 days, respectively. Body weight, tumor size and tumor weight were recorded. Hepatic index was calculated. Pathological changes of liver cancer tissues were evaluated by hematoxylin and eosin staining and TUNEL staining. Liquid chromatography-mass spectrometer was used to analyze different metabolites between the model and LDH groups. RESULTS: After LD treatment, tumor weight, tumor size and hepatic index were reduced compared with the model group. Necrocytosis and karyorrhexis of tumor cells were found. Moreover, 61 differential metabolites (18 up-regulated, 43 down-regulated) were affirmed and 20 pathways of KEGG (P<0.05) were gotten. In addition, Bel-7402, HepG2 and H22 cell viabilities were significantly increased after adding Asp into the medium. And then, the cell proliferation effect induced by Asp was ameliorated by LD. CONCLUSION: The anti-liver cancer efficacy of LD extract was validated in H22 mice model, and inhibition of Asp level might be the underlying mechanism.
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BACKGROUND: Benign paroxysmal positional vertigo (BPPV) is the most prevalent form of peripheral vertigo, with vascular lesions being one of its suspected causes. The older adults are particularly vulnerable to BPPV. Cerebral small vessel disease (CSVD), on the other hand, is a clinical condition that results from damage of cerebral small vessels. Vascular involvement resulting from age-related risk factors and proinflammatory state may act as the underlying factor linking both BPPV and CSVD. AIM: The objective of this study is to explore the potential correlation between BPPV and CSVD by examining whether individuals aged 50 and older with BPPV exhibit a greater burden of CSVD. MATERIALS AND METHODS: This retrospective study included patients aged 50 years and older who had been diagnosed with BPPV. A control group consisting of patients diagnosed with idiopathic facial neuritis (IFN) during the same time period was also included. The burden of cerebral white matter hyperintensities (WMHs) was evaluated using the Fazekas scale. An ordinal regression analysis was conducted to investigate the potential correlation between BPPV and WMHs. RESULTS: The study included a total of 101 patients diagnosed with BPPV and 116 patients with IFN. Patients with BPPV were found to be significantly more likely (OR = 2.37, 95% CI 1.40-4.03, p = 0.001) to have a higher Fazekas score compared to the control group. Brain infarctions, hypertension, and age were all identified as significant predictors of white matter hyperplasia on MRI, with OR of 9.9 (95% CI 4.21-24.84, P<0.001), 2.86 (95% CI 1.67-5.0, P<0.001), and 1.18 (95% CI 1.13-1.22, P<0.001) respectively. CONCLUSION: Our findings suggest that vascular impairment caused by age-related risk factors and proinflammatory status may be contributing factors to the development of BPPV in individuals aged 50 and above, as we observed a correlation between the suffering of BPPV and the severity of WMHs.
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Vertigem Posicional Paroxística Benigna , Doenças de Pequenos Vasos Cerebrais , Humanos , Pessoa de Meia-Idade , Idoso , Vertigem Posicional Paroxística Benigna/diagnóstico , Vertigem Posicional Paroxística Benigna/etiologia , Estudos Retrospectivos , Fatores de Risco , Fatores Etários , Doenças de Pequenos Vasos Cerebrais/complicações , Doenças de Pequenos Vasos Cerebrais/diagnóstico por imagemRESUMO
Breast cancer is a prevalent malignant tumor, posing a significant threat to women's health globally due to its increasing incidence and tendency to affect younger patients. Protein tyrosine phosphatases (PTPs) are a class of enzymes that have emerged as potential targets for various tumors, including breast cancer, because they can modulate oncogenic tyrosine kinases, which are both tumor-suppressive and oncogenic. The regulation of tyrosine phosphorylation levels is crucial for cell proliferation and differentiation. Although the clinical biomarker potential of PTPs is not fully explored, there is evidence to suggest that they may serve as clinical biomarkers and therapeutic targets for breast cancer. We found that increased expression levels of PTPN11 and PTPN3 were associated with a higher risk of death in patients with breast cancer, while PTPN11 and PTPN18 are significantly associated with overall survival in patients with estrogen receptor-positive (ER+) breast cancer. Meanwhile, PTPN11 expression was found to be negatively associated with survival in patients with ER+ breast cancer. Furthermore, PTPN11 exposes a metabolic vulnerability to breast cancer metastasis via dysregulated ceramide metabolism. Therefore, we speculate that PTPN11 has the potential to serve as a therapeutic target for breast cancer by regulating lipid metabolism reprogramming.
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Neoplasias da Mama , Segunda Neoplasia Primária , Humanos , Feminino , Neoplasias da Mama/genética , Proteínas Tirosina Quinases , Metabolismo dos Lipídeos , Ceramidas , Tirosina , Proteínas Tirosina Fosfatases não Receptoras , Proteína Tirosina Fosfatase não Receptora Tipo 11/genética , Melanoma Maligno CutâneoRESUMO
Allicin exhibits various pharmacological activities and has been suggested to be beneficial in the treatment of stroke. However, the underlying mechanisms are largely unknown. Here, we confirmed that allicin protected the brain from cerebral injury, which could be ascribed to its antiapoptotic and antiinflammatory effects, as well as the regulation of lipid metabolism, using proteomics and metabolomics analysis. Our results suggested that allicin could significantly ameliorate behavioral characteristics, cerebral infarct area, cell apoptosis, inflammatory factors, and lipid metabolic-related factors (arachidonic acid, 15-hydroperoxy-eicosatetraenoic acid (15S-HPETE), palmitoylcarnitine, and acylcarnitine) by recalibrating astrocyte homeostasis in mice with photothrombotic stroke (PT). In astrocytes, allicin significantly increased glutathione peroxidase 1 (GPX1) levels and inhibited the arachidonic acid-related pathway, which was also observed in the brains of mice with PT. Allicin was proven to inhibit hypoxia-induced astrocyte apoptosis by increasing GPX1 expression, activating proto-oncogene tyrosine-protein kinase Src (Src)- protein kinase B (AKT)-extracellular signal-regulated kinase (ERK) phosphorylation, and decreasing lipid peroxidation. Thus, we concluded that allicin significantly prevented and ameliorated ischemic stroke by increasing GPX1 levels to complete the complex physiological process.
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BACKGROUND: Tribulus terrestris L. (TT) was initially documented in Shen-Nong-Ben-Cao-Jing and has been used for thousands of years in China as a herb to calm liver, dispel melancholy and wind, promote blood circulation, improve eyesight, and relieve itching. Moreover, it was also used to treat breast cancer in ancient China. However, the pharmacological activities of TT extract on breast cancer have received little attention. PURPOSE: In this study, we investigated the anti-breast cancer effects and possible mechanisms of action of this herbal drug. METHODS: Network pharmacology analysis the study of network pharmacology was done to analyze the possibility of TT's anti-breast cancer effect. And then, molecular docking between TT7/TT8 and vascular endothelial growth factor receptor 2 (VEGFR2) were performed by Autodock software as well as the related protein expressions were analyzed by western blot to verify this effect. In vivo experiment: The mouse model of breast cancer was established by injection of 4T1 cells. Then drugs were intragastrically administered to the mice once daily for fourteen days. Body weight, tumor size, and tumor weight were recorded at the end of the experiment. Moreover, tumor inhibitory rate was calculated. Finally, pathological changes and apoptosis of breast cancer tissues were respectively evaluated by HE and Hoechst staining. Proteomics and metabonomics analyses: The tumor tissues were chosen to perform conjoint analysis. Firstly, differential proteins and metabolites were found. Furthermore, the functional analyses of them were analyzed by software. At the last, immunofluorescent staining of SGPP1, SPHK1 and p-SPHK1 in tumor tissue were done. RESULTS: 12 active ingredients of TT, 127 targets of active ingredients, 15,253 targets of breast cancer, 1,225 targets of Ru yan, and 123 overlapping genes were obtained in the network pharmacology study. There was firm conjunction between TT7/TT8 and VEGFR2. Besides, tumor size and weight were markedly reduced in TT groups compared to the model group. The tumor inhibitory rate was more than 26% in TTM group. After drug treatment, many adipocytes and cracks between tumor and apoptosis were discovered. The western blot results showed that TT aqueous extract lowered the levels of VEGFR2, ERK1/2, p-ERK1/2 (Thr202, Tyr204) and Bcl2, while increasing the levels of Bax and the ratio of Bax/Bcl2. Furthermore, 495 differential proteins and 76 differential metabolites were found between TTM and model groups with the sphingolipid metabolism pathway being enriched. At last, TT treatment significantly reduced the levels of SGPP1, SPHK1 and p-SPHK1 in tumor tissue. CONCLUSIONS: In conclusion, TT demonstrates therapeutic effects in a mouse model of breast cancer, and its mechanism of action involves the regulations of sphingolipid metabolism signaling pathways. This study lends credence to the pharmacological potential of TT extract as a breast cancer therapy.
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Neoplasias , Tribulus , Animais , Camundongos , Simulação de Acoplamento Molecular , Fator A de Crescimento do Endotélio Vascular , Proteína X Associada a bcl-2 , Transdução de Sinais , Apoptose , EsfingolipídeosRESUMO
Generally, anaerobic ammonium oxidation (anammox) converts nitrite (NO2-) and ammonium (NH4+) to nitrogen gas (N2) but generates some nitrate (NO3-) (equivalent to 11% of inlet total nitrogen (TN)). Although it reported that anammox bacteria could degrade NO3- via dissimilatory nitrate reduction to ammonium (DNRA) pathway using the intracellular carbon as the electron donor, it is still unclear the specific electron transfer mechanism in this intracellular carbon-dependent DNRA inside anammox bacteria, and whether the sole anammox bacteria could achieve higher TN removal efficiency more than the theoretical maximum of 89%. In this study, transcriptome analysis and metabolic inhibitor experiments demonstrated that NADH generated from the decomposition of the intracellular carbon (glycogen) supplied electrons for the NO3-conversion; the electrons were transferred from NADH to nitrate reductase (Nar) and nitrite reductase forming ammonium (NrfA) from ubiquinone (UQ) and complex III, respectively. Combining the intracellular carbon-dependent DNRA with normal anammox process, an average TN removal efficiency of 95% was achieved by the sole anammox bacteria in a sequencing batch reactor. Fluorescent in situ hybridization (FISH) images and real-time fluorescence quantitative PCR (qPCR) results illustrated anammox bacteria could survive and proliferate in the SBR. Our work improved the understanding of the electron transfer mechanism inside anammox bacteria, and further exploit its potential in nitrogen pollutants removal.