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BACKGROUND: Stroke represents a significant health crisis in the United States, claiming approximately 140,000 lives annually and ranking as the fifth leading cause of death. OBJECTIVE: Utilizing data from the National Health and Nutrition Examination Survey (NHANES) for 2005 to 2008, this study examines the correlation between various sleep characteristics and both stroke morbidity and all-cause mortality among U.S. adults. METHODS: We applied logistic regression, Cox regression, and subgroup analyses to a sample of 7,827 adults aged 18 and older from NHANES 2005-2008. The study focused on six sleep characteristics: duration of sleep, sleep onset latency, snoring frequency, number of awakenings, frequency of leg spasms during sleep, and daytime sleepiness, analyzing their impacts on stroke incidence and mortality rates. RESULTS: Participants had an average age of 45.80 ± 0.45 years, with females accounting for 48.13 % of the sample. Analysis revealed significant associations between sleep duration, onset latency, number of awakenings, leg spasms, and daytime sleepiness with stroke incidence. However, these associations weakened with increasing confounders. Additionally, stroke patients showed a higher likelihood of using sleep aids. The influence of sleep disturbances on stroke appeared more pronounced in females and younger demographics. An association was also noted between the number of awakenings, sleep duration, and stroke mortality rates CONCLUSIONS: The study reinforces the critical role of maintaining healthy sleep patterns in preventing strokes and enhancing stroke prognosis, emphasizing specific sleep disturbances as potential risk factors.
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The Coptidis Rhizoma and Bovis Calculus herb pair possesses clearing heat and detoxifying effects. The aim of this study was to reveal the effects and mechanisms of the herb pair in the treatment of NASH by network pharmacology and experimental verification. A network pharmacology-based approach was employed to predict the putative mechanism of the herb pair against NASH. The high-fat diet (HFD) and methionine/choline deficient (MCD) diet induced NASH models were used to evaluate efficacy and mechanism of the herb pair. Network pharmacological analysis showed that the herb pair modulated NOD-like receptor pathway. In the HFD mice, herb pair reduced body weight, blood sugar, serum ALT, AST, TBA, TC, TG and LDL-C contents, also improved the general morphology and pathological manifestations. Hepatic transcriptomics study showed that herb pair attenuated NASH by regulating NOD-like receptor signaling pathway. Western blotting showed that herb pair reduced the protein expression levels of NLRP3, cleaved Caspase-1 and cleaved IL-1ß. In the MCD mice, herb pair also reduced serum ALT, ALT and TBA levels, improved liver pathological manifestations, inhibited the protein expression levels of NLRP3, cleaved Caspase-1 and cleaved IL-1ß. Our findings proved that the Coptidis Rhizoma and Bovis Calculus herb pair attenuates NASH through suppression of NLRP3 inflammasome activation. This will demonstrate effective pharmacological evidence for the clinical application of herb pair.
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BACKGROUND: Uterine sarcoma is a rare and heterogeneous gynecological malignancy characterized by aggressive progression and poor prognosis. The current study aimed to investigate the relationship between clinicopathological characteristics and the prognosis of uterine sarcoma in Chinese patients. METHODS: In this single-center retrospective study, we reviewed the medical records of 75 patients with histologically verified uterine sarcoma treated at the First Affiliated Hospital of Xi'an Jiaotong University between 2011 and 2020. Information on clinical characteristics, treatments, pathology and survival was collected. Progression-free survival (PFS) and overall survival (OS) were visualized in Kaplan-Meier curves. Prognostic factors were identified using the log-rank test for univariate analysis and Cox-proportional hazards regression models for multivariate analysis. RESULTS: The histopathological types included 36 endometrial stromal sarcomas (ESS,48%), 33 leiomyosarcomas (LMS,44%) and 6 adenosarcomas (8%). The mean age at diagnosis was 50.2 ± 10.7 years. Stage I and low-grade accounted for the majority. There were 26 recurrences and 25 deaths at the last follow-up. The mean PFS and OS were 89.41 (95% CI: 76.07-102.75) and 94.03 (95% CI: 81.67-106.38) months, respectively. Univariate analysis showed that > 50 years, post-menopause, advanced stage, ≥ 1/2 myometrial invasion, lymphovascular space invasion and high grade were associated with shorter survival (P < 0.05). Color Doppler flow imaging positive signals were associated with shorter PFS in the LMS group (P = 0.046). The ESS group had longer PFS than that of the LMS group (99.56 vs. 76.05 months, P = 0.043). The multivariate analysis showed that post-menopause and advanced stage were independent risk factors of both PFS and OS in the total cohort and LMS group. In the ESS group, diagnosis age > 50 years and high-grade were independent risk factors of PFS, while high-grade and lymphovascular space invasion were independent risk factors of OS. CONCLUSION: In Chinese patients with uterine sarcoma, post-menopause and advanced stage were associated with a significantly poorer prognosis. The prognosis of ESS was better than that of LMS. Color Doppler flow imaging positive signals of the tumor helped to identify LMS, which needs to be further tested in a larger sample in the future.
Subject(s)
Uterine Neoplasms , Humans , Female , Middle Aged , Retrospective Studies , Uterine Neoplasms/pathology , Uterine Neoplasms/mortality , China/epidemiology , Adult , Prognosis , Sarcoma, Endometrial Stromal/pathology , Sarcoma, Endometrial Stromal/mortality , Sarcoma/pathology , Sarcoma/mortality , Leiomyosarcoma/pathology , Leiomyosarcoma/mortality , Aged , Adenosarcoma/pathology , Adenosarcoma/mortality , Adenosarcoma/therapy , Progression-Free SurvivalABSTRACT
Uncontrollable interfacial side reactions generated from common aqueous electrolytes, just like the hydrogen evolution reaction (HER) and dendrite growth, have severely prevented the practical application of zinc-ion batteries (ZIBs). Solid-state ZIBs are considered to be an efficient strategy by adopting high-quality solid-state electrolytes (SSEs). Here, by confining the deep eutectic electrolyte (DEE) into the nanochannels of the metal-organic framework (MOF)-PCN-222, a stable DEE@PCN-222 SSE with internal Zn2+ transport channels was obtained. A distinctive ion-transport network composed of DEE and PCN-222 in the interior of DEE@PCN-222 realizes the efficient Zn2+ conduction, contributing to a high ionic conductivity of 3.13 × 10-4 S cm-1 at room temperature, a low activation energy of 0.12 eV, and a high Zn2+ transference number of 0.76. Furthermore, experimental and theoretical investigations demonstrate that DEE@PCN-222 with its unique channel structure could homogeneously regulate the Zn2+ distribution and effectively alleviate the side reactions. Highly reversible Zn plating/stripping performance of 2476 h can be realized by the SSE. The solid-state ZIBs show a specific capacity of 306 mAh g-1 and display cycling stability of 517 cycles. This unique design concept provides a new perspective in realizing the high-safety and high-performance ZIBs.
ABSTRACT
The lack of stable solid-state electrolytes (SSEs) with high-ionic conductivity and rational design of electrode/electrolyte interfaces remains challenging for solid-state lithium batteries. Here, for the first time, a high-performance solid-state lithium-oxygen battery is developed based on the Li-ion-conducted hydrogen-bonded organic framework (LHOF) electrolyte and the core-shell HOF-DAT@CNT cathode with a few layers of HOF-DAT on surface of carbon nanotubes. Benefiting from the abundant dynamic hydrogen bonding network in LHOF-DAT SSEs, fast Li+ ion transport (2.2 × 10-4 S cm-1), a high Li+ transfer number (0.88), and a wide electrochemical window of 5.05 V are achieved. Symmetric batteries constructed with LHOF-DAT SSEs exhibit a stably cycled duration of over 1400 h, which mainly stems from the jumping sites that promote a uniformly high rate of Li+ flux and the hydrogen-bonding network structure that can relieve the structural changes during Li+ transport. LHOF-DAT SSEs-based Li-O2 batteries exhibit high specific capacity (10335 mAh g-1), and stable cycling life up to 150 cycles. Moreover, the solid-state lithium metal battery with LHOF-DAT SSEs endow good rate capability (128.8 mAh g-1 at 1 C), long-term discharge/charge stability (210 cycles). The design of LHOF-DAT SSEs opens an avenue for the development of novel SSEs-based solid-state lithium batteries.
ABSTRACT
Chemically self-recharging zinc ion batteries (ZIBs), which are capable of auto-recharging in ambient air, are promising in self-powered battery systems. Nevertheless, the exclusive reliance on chemical energy from oxygen for ZIBs charging often would bring some obstacles in charging efficiency. Herein, we develop photo-assisted chemically self-recharging aqueous ZIBs with a heterojunction of MoS2/SnO2 cathode, which are favorable to enhancing both the charging and discharging efficiency as well as the chemical self-charging capabilities under illumination. The photo-assisted process promotes the electron transfer from MoS2/SnO2 to oxygen, accelerating the occurrence of the oxidation reaction during chemical self-charging. Furthermore, the electrons within the MoS2/SnO2 cathode exhibit a low transfer impedance under illumination, which is beneficial to reducing the migration barrier of Zn2+ within the cathode and thereby facilitating the uniform inserting of Zn2+ into MoS2/SnO2 cathode during discharging. This photo-assisted chemical self-recharging mechanism enables ZIBs to attain a maximum self-charging potential of 0.95 V within 3 hours, a considerable self-charging capacity of 202.5 mAh g-1 and excellent cycling performance in a self-charging mode. This work not only provides a route for optimizing chemical self-charging energy storage, but also broadens the potential application of aqueous ZIBs.
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A series of piperine derivatives were designed and successfully synthesized. The antitumor activities of these compounds against 293 T human normal cells, as well as MDA-MB-231 (breast) and Hela (cervical) cancer cell lines, were assessed through the MTT assay. Notably, compound H7 exhibited moderate activity, displaying reduced toxicity towards non-tumor 293 T cells while potently enhancing the antiproliferative effects in Hela and MDA-MB-231 cells. The IC50 values were determined to be 147.45 ± 6.05 µM, 11.86 ± 0.32 µM, and 10.50 ± 3.74 µM for the respective cell lines. In subsequent mechanistic investigations, compound H7 demonstrated a dose-dependent inhibition of clone formation, migration, and adhesion in Hela cells. At a concentration of 15 µM, its inhibitory effect on Hela cell function surpassed that of both piperine and 5-Fu. Furthermore, compound H7 exhibited promising antitumor activity in vivo, as evidenced by significant inhibition of tumor angiogenesis and reduction in tumor weight in a chicken embryo model. These findings provide a valuable scientific foundation for the development of novel and efficacious antitumor agents, particularly highlighting the potential of compound H7 as a therapeutic candidate for cervical cancer and breast cancer.
Subject(s)
Alkaloids , Benzodioxoles , Piperidines , Polyunsaturated Alkamides , Humans , Piperidines/pharmacology , Piperidines/chemical synthesis , Piperidines/chemistry , Benzodioxoles/pharmacology , Benzodioxoles/chemical synthesis , Polyunsaturated Alkamides/pharmacology , Polyunsaturated Alkamides/chemical synthesis , Polyunsaturated Alkamides/chemistry , Alkaloids/pharmacology , Alkaloids/chemical synthesis , Alkaloids/chemistry , Animals , Molecular Structure , Cell Line, Tumor , HeLa Cells , Chick Embryo , Cell Movement/drug effects , Antineoplastic Agents, Phytogenic/pharmacology , Antineoplastic Agents, Phytogenic/chemical synthesis , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Drug Design , Cell Proliferation/drug effectsABSTRACT
This study reports the design, synthesis, and comprehensive biological evaluation of 13 benzodioxolane derivatives, derived from the core structure of piperine, a natural product with established antitumor properties. Piperine, primarily found in black pepper, has been noted for its diverse pharmacological activities, including anti-inflammatory, antioxidant, and anticancer effects. Leveraging piperine's antitumor potential, we aimed to enhance its efficacy through structural modifications. Among the synthesized compounds, HJ1 emerged as the most potent, exhibiting a 4-fold and 10-fold increase in inhibitory effects on HeLa and MDA-MB-231 cell lines, respectively, compared to piperine. Furthermore, HJ1 demonstrated a favorable safety profile, characterized by significantly lower cytotoxicity towards the human normal cell line 293T. Mechanistic investigations revealed that HJ1 markedly inhibited clonogenicity, migration, and adhesion of HeLa cells. In vivo studies utilizing the chick embryo chorioallantoic membrane (CAM) model substantiated the robust antitumor activity of HJ1, evidenced by its ability to suppress tumor angiogenesis and reduce tumor weight. These results suggest that HJ1 holds significant promise as a lead compound for the development of novel antitumor therapies.
Subject(s)
Antineoplastic Agents , Cell Proliferation , Drug Design , Drug Screening Assays, Antitumor , Humans , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Structure-Activity Relationship , Animals , Cell Proliferation/drug effects , Molecular Structure , Benzodioxoles/pharmacology , Benzodioxoles/chemical synthesis , Benzodioxoles/chemistry , Dose-Response Relationship, Drug , Cell Line, Tumor , HeLa Cells , Cell Movement/drug effects , Chick EmbryoABSTRACT
6:2 fluorotelomer carboxylic acid (6:2 FTCA) is a perfluorooctanoic acid (PFOA) substitute, which is supposedly less accumulative and toxic than PFOA. However, 6:2 FTCA is structurally similar to PFOA, and there had already been reports about its toxicities comparable to PFOA. The aim of the current study is to assess potential effects of developmental exposure to 6:2 FTCA on the development of kidney in chicken embryo and to investigate underlying mechanism. Fertile chicken eggs were exposed to 1.25â¯mg/kg, 2.5â¯mg/kg or 5â¯mg/kg doses of 6:2 FTCA, or 2â¯mg/kg PFOA, then incubated to hatch. Serum and kidney of hatchling chickens were collected. Blood urea nitrogen (BUN) and creatinine (Cre) levels were measured with commercially available kits. Morphology of kidney was assessed with histopathology. To further reveal molecular mechanism of observed endpoints, IGF signaling molecules were assessed in the kidney samples with qRT-PCR, results indicated that IGFBP3 is a potentially crucial molecule. Lentiviruses overexpressing or silencing IGFBP3 were designed and applied to enhance/suppress the expression of IGFBP3 in developing chicken embryo for further verification of its role in the observed effects. Disrupted nephron formation, in the manifestation of decreased glomeruli number/area and increased serum BUN/Cre levels, was observed in the animals developmentally exposed to 6:2 FTCA. Correspondingly, IGF signaling molecules (IGF1, IGF1R and IGFBP3) were affected by 6:2 FTCA exposure. Meanwhile, overexpression of IGFBP3 effectively alleviated such changes, while silencing of IGFBP3 mimicked observed effects. In conclusion, developmental exposure to 6:2 FTCA is associated with disrupted chicken embryo renal development, in which IGFBP3 seems to be a remarkable contributor, suggesting potential health risks for human and other species. Further risk assessments and mechanistic works are necessary.
Subject(s)
Kidney , Signal Transduction , Animals , Chick Embryo , Kidney/drug effects , Signal Transduction/drug effects , Fluorocarbons/toxicity , Caprylates/toxicity , Insulin-Like Growth Factor Binding Protein 3 , Chickens , Blood Urea Nitrogen , Creatinine/bloodABSTRACT
Nanowelding is a bottom-up technique to create custom-designed nanostructures and devices beyond the precision of lithographic methods. Here, a new technique is reported based on anisotropic lubricity at the van der Waals interface between monolayer and bilayer SnSe nanoplates and a graphene substrate to achieve precise control of the crystal orientation and the interface during the welding process. As-grown SnSe monolayer and bilayer nanoplates are commensurate with graphene's armchair direction but lack commensuration along graphene's zigzag direction, resulting in a reduced friction along that direction and a rail-like, 1D movement that permits joining nanoplates with high precision. This way, molecular beam epitaxially grown SnSe nanoplates of lateral sizes 30-100 nm are manipulated by the tip of a scanning tunneling microscope at room temperature. In situ annealing is applied afterward to weld contacting nanoplates without atomic defects at the interface. This technique can be generalized to any van der Waals interfaces with anisotropic lubricity and is highly promising for the construction of complex quantum devices, such as field effect transistors, quantum interference devices, lateral tunneling junctions, and solid-state qubits.
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Temozolomide (TMZ) is a widely utilized chemotherapy treatment for patients with glioblastoma (GBM), although drug resistance constitutes a major therapeutic hurdle. Emerging evidence suggests that ferroptosis-mediated therapy could offer an appropriate alternative treatment option against cancer cells that are resistant to certain drugs. However, recurrent gliomas display robust ferroptosis resistance, although the precise mechanism of resistance remains elusive. In the present work, we report that proline rich protein 11 (PRR11) depletion significantly sensitizes GBM cells to TMZ by inducing ferroptosis. Mechanistically, PRR11 directly binds to and stabilizes dihydroorotate dehydrogenase (DHODH), which leads to glioma ferroptosis-resistant in a DHODH-dependent manner in vivo and in vitro. Furthermore, PRR11 inhibits HERC4 and DHODH binding, by suppressing the recruitment of E3 ubiquitin ligase HERC4 and polyubiquitination degradation of DHODH at the K306 site, which maintains DHODH protein stability. Importantly, downregulated PRR11 increases lipid peroxidation and alters DHODH-mediated mitochondrial morphology, thereby promoting ferroptosis and increasing TMZ chemotherapy sensitivity. In conclusion, our results reveal a mechanism via which PRR11 drives ferroptosis resistance and identifies ferroptosis induction and TMZ as an attractive combined therapeutic strategy for GBM.
Subject(s)
Dihydroorotate Dehydrogenase , Drug Resistance, Neoplasm , Ferroptosis , Glioblastoma , Temozolomide , Humans , Ferroptosis/drug effects , Ferroptosis/genetics , Glioblastoma/metabolism , Glioblastoma/drug therapy , Glioblastoma/genetics , Glioblastoma/pathology , Temozolomide/pharmacology , Drug Resistance, Neoplasm/genetics , Cell Line, Tumor , Mice , Dihydroorotate Dehydrogenase/metabolism , Animals , Gene Expression Regulation, Neoplastic/drug effects , Brain Neoplasms/drug therapy , Brain Neoplasms/metabolism , Brain Neoplasms/pathology , Brain Neoplasms/geneticsABSTRACT
Frontotemporal lobe abnormalities are linked to neuropsychiatric disorders and cognition, but the role of cellular heterogeneity between temporal lobe (TL) and frontal lobe (FL) in the vulnerability to genetic risk factors remains to be elucidated. We integrated single-nucleus transcriptome analysis in 'fresh' human FL and TL with genetic susceptibility, gene dysregulation in neuropsychiatric disease and psychoactive drug response data. We show how intrinsic differences between TL and FL contribute to the vulnerability of specific cell types to both genetic risk factors and psychoactive drugs. Neuronal populations, specifically PVALB neurons, were most highly vulnerable to genetic risk factors for psychiatric disease. These psychiatric disease-associated genes were mostly upregulated in the TL, and dysregulated in the brain of patients with obsessive-compulsive disorder, bipolar disorder and schizophrenia. Among these genes, GRIN2A and SLC12A5, implicated in schizophrenia and bipolar disorder, were significantly upregulated in TL PVALB neurons and in psychiatric disease patients' brain. PVALB neurons from the TL were twofold more vulnerable to psychoactive drugs than to genetic risk factors, showing the influence and specificity of frontotemporal lobe differences on cell vulnerabilities. These studies provide a cell type resolved map of the impact of brain regional differences on cell type vulnerabilities in neuropsychiatric disorders.
Subject(s)
Frontal Lobe , Mental Disorders , Psychotropic Drugs , Temporal Lobe , Humans , Psychotropic Drugs/pharmacology , Frontal Lobe/metabolism , Frontal Lobe/pathology , Temporal Lobe/metabolism , Temporal Lobe/pathology , Mental Disorders/genetics , Mental Disorders/metabolism , Neurons/metabolism , Receptors, N-Methyl-D-Aspartate/metabolism , Receptors, N-Methyl-D-Aspartate/genetics , Genetic Predisposition to Disease , Gene Expression Profiling , Transcriptome , Gene Expression Regulation , Schizophrenia/genetics , Schizophrenia/metabolism , Bipolar Disorder/genetics , Bipolar Disorder/metabolismABSTRACT
This paper proposes a method for classifying crystal planes based on the bond angle characteristics of quartz unit cells and constructs an etch rate model for quartz crystal planes at both macro and micro scales. By omitting oxygen atoms from the quartz cell structure, a method based on bond angle characteristics was established to partition the atomic arrangement of the crystal surface. This approach was used to analyze the etching processes of typical quartz crystal planes (R, r, m, and (0001)), approximating the etching process of crystals as a cyclic removal of certain bond angle characteristics on the crystal planes. This led to the development of an etch rate model based on micro-geometric parameters of crystal planes. Additionally, using the proposed bond angle classification method, the common characteristics of atomic configurations on the crystal plane surfaces within the X_cut type were extracted and classified into seven regions, further expanding and applying the etch rate model. The computational results of this model showed good agreement with experimental data, indicating the rationality and feasibility of the proposed method. These also provide a theoretical basis for understanding the microstructural changes during quartz-based MEMS etching processes.
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Introduction: In recent research, the expansion in the use of Mg alloys for biomedical applications has been approached by modifying their surfaces in conjunction with micro-arc oxidation (MAO) techniques which enhance their abrasion and corrosion resistance. Methods: In this study, combining laser texturing and MAO techniques to produce the dense ceramic coatings with microstructures. On the surface of the AZ31 Mg alloy, a micro-raised annulus array texture has been designed in order to increase the surface friction under liquid lubrication and to improve the operator's grip when holding the tool. For this work, the micro-morphology of the coatings was characterised, and the friction properties of the commonly used scalpel shank material 316 L, the untextured surface and the textured surface were comparatively analysed against disposable surgical gloves. Results and discussion: The results show that the Laser-MAO ceramic coating grows homogenous, the porosity decreases from 14.3% to 7.8%, and the morphology after friction indicates that the coating has good wear resistance. More specifically, the average coefficient of friction (COF) of the three types of gloves coated with Laser-MAO ceramic was higher than that of the 316 L and MAO ceramic coatings under the action of the annulus-integrated texture under the lubrication conditions of physiological saline and defatted sheep blood, which achieved the goal of increasing friction for the purpose of helping to prevent the problem of tool slippage from the hand.
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Introduction: Mitochondrial fission process 1 (MTFP1) is an inner mitochondrial membrane (IMM) protein implicated in the development and progression of various tumors, particularly lung squamous cell carcinoma (LUSC). This study aims to provide a more theoretical basis for the treatment of LUSC. Methods: Through bioinformatics analysis, MTFP1 was identified as a novel target gene of HIF1A. MTFP1 expression in LUSC was examined using The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and Proteomics Data Commons (PDC) databases. The Kaplan-Meier plotter (KM plotter) database was utilized to evaluate its correlation with patient survival. Western blot and chromatin immunoprecipitation (ChIP) assays were employed to confirm the regulatory relationship between MTFP1 and HIF1A. Additionally, cell proliferation, colony formation, and migration assays were conducted to investigate the mechanism by which MTFP1 enhances LUSC cell proliferation and metastasis. Results: Our findings revealed that MTFP1 overexpression correlated with poor prognosis in LUSC patients(P < 0.05). Moreover, MTFP1 was closely associated with hypoxia and glycolysis in LUSC (R = 0.203; P < 0.001, R = 0.391; P < 0.001). HIF1A was identified as a positive regulator of MTFP1. Functional enrichment analysis demonstrated that MTFP1 played a role in controlling LUSC cell proliferation. Cell proliferation, colony formation, and migration assays indicated that MTFP1 promoted LUSC cell proliferation and metastasis by activating the glycolytic pathway (P < 0.05). Conclusions: This study establishes MTFP1 as a novel HIF1A target gene that promotes LUSC growth by activating the glycolytic pathway. Investigating MTFP1 may contribute to the development of effective therapies for LUSC patients, particularly those lacking targeted oncogene therapies.
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Overexpression of human CD200 (hCD200) in porcine endothelial cells (PECs) has been reported to suppress xenogeneic immune responses of human macrophages against porcine endothelial cells. The current study aimed to address whether the above-mentioned beneficial effect of hCD200 is mediated by overcoming the molecular incompatibility between porcine CD200 (pCD200) and hCD200 receptor or simply by increasing the expression levels of CD200 without any molecular incompatibility across the two species. We overexpressed hCD200 or pCD200 using lentiviral vectors with V5 marker in porcine endothelial cells and compared their suppressive activity against U937-derived human macrophage-like cells (hMCs) and primary macrophages. In xenogeneic coculture of porcine endothelial cells and human macrophage-like cells or macrophages, hCD200-porcine endothelial cells suppressed phagocytosis and cytotoxicity of human macrophages to a greater extent than pCD200-porcine endothelial cells. Secretion of tumor necrosis factor-α, interleukin-1ß, and monocyte chemoattractant protein-1 from human macrophages and expression of M1 phenotypes (inducible nitric oxide synthase, dectin-1, and CD86) were also suppressed by hCD200 to a greater extent than pCD200. Furthermore, in signal transduction downstream of CD200 receptor, hCD200 induced Dok2 phosphorylation and suppressed IκB phosphorylation to a greater extent than pCD200. The above data supported the possibility of a significant molecular incompatibility between pCD200 and human CD200 receptor, suggesting that the beneficial effects of hCD200 overexpression in porcine endothelial cells could be mediated by overcoming the molecular incompatibility across the species barrier rather than by simple overexpression effects of CD200.
Subject(s)
Antigens, CD , Endothelial Cells , Macrophages , Transplantation, Heterologous , Animals , Humans , Antigens, CD/immunology , Antigens, CD/metabolism , Antigens, CD/genetics , Swine , Macrophages/immunology , Macrophages/metabolism , Transplantation, Heterologous/methods , Endothelial Cells/immunology , Phagocytosis , Orexin Receptors/genetics , Orexin Receptors/metabolism , Orexin Receptors/immunology , Coculture TechniquesABSTRACT
PURPOSE OF REVIEW: Vascular dementia (VaD) is the second most prevalent type of dementia after Alzheimer's disease.Hypercholesterolemia may increase the risk of dementia, but the association between cholesterol and cognitive function is very complex. From the perspective of peripheral and brain cholesterol, we review the relationship between hypercholesterolemia and increased risk of VaD and how the use of lipid-lowering therapies affects cognition. RECENT FINDINGS: Epidemiologic studies show since 1980, non-HDL-C levels of individuals has increased rapidly in Asian countries.The study has suggested that vascular risk factors increase the risk of VaD, such as disordered lipid metabolism. Dyslipidemia has been found to interact with chronic cerebral hypoperfusion to promote inflammation resulting in cognitive dysfunction in the brain.Hypercholesterolemia may be a risk factor for VaD. Inflammation could potentially serve as a link between hypercholesterolemia and VaD. Additionally, the potential impact of lipid-lowering therapy on cognitive function is also worth considering. Finding strategies to prevent and treat VaD is critical given the aging of the population to lessen the load on society. Currently, controlling underlying vascular risk factors is considered one of the most effective methods of preventing VaD. Understanding the relationship between abnormal cholesterol levels and VaD, as well as discovering potential serum biomarkers, is important for the early prevention and treatment of VaD.
Subject(s)
Cholesterol , Dementia, Vascular , Hypercholesterolemia , Humans , Dementia, Vascular/etiology , Dementia, Vascular/epidemiology , Dementia, Vascular/metabolism , Hypercholesterolemia/complications , Hypercholesterolemia/epidemiology , Risk Factors , Cholesterol/metabolism , Cholesterol/bloodABSTRACT
Ovarian cancer (OV) poses a significant challenge in clinical settings due to its difficulty in early diagnosis and treatment resistance. FOXP4, belonging to the FOXP subfamily, plays a pivotal role in various biological processes including cancer, cell cycle regulation, and embryonic development. However, the specific role and importance of FOXP4 in OV have remained unclear. Our research showed that FOXP4 is highly expressed in OV tissues, with its elevated levels correlating with poor prognosis. We further explored FOXP4's function through RNA sequencing and functional analysis in FOXP4-deficient cells, revealing its critical role in activating the Wnt signaling pathway. This activation exacerbates the malignant phenotype in OV. Mechanistically, FOXP4 directly induces the expression of protein tyrosine kinase 7 (PTK7), a Wnt-binding receptor tyrosine pseudokinase, which causes abnormal activation of the Wnt signaling pathway. Disrupting the FOXP4-Wnt feedback loop by inactivating the Wnt signaling pathway or reducing FOXP4 expression resulted in the reduction of the malignant phenotype of OV cells, while restoring PTK7 expression reversed this effect. In conclusion, our findings underscore the significance of the FOXP4-induced Wnt pathway activation in OV, suggesting the therapeutic potential of targeting this pathway in OV treatment.
Subject(s)
Forkhead Transcription Factors , Ovarian Neoplasms , Receptor Protein-Tyrosine Kinases , Wnt Signaling Pathway , Animals , Female , Humans , Mice , beta Catenin/metabolism , Cell Adhesion Molecules/metabolism , Cell Adhesion Molecules/genetics , Cell Line, Tumor , Cell Proliferation , Forkhead Transcription Factors/metabolism , Forkhead Transcription Factors/genetics , Gene Expression Regulation, Neoplastic , Mice, Nude , Ovarian Neoplasms/pathology , Ovarian Neoplasms/metabolism , Ovarian Neoplasms/genetics , Receptor Protein-Tyrosine Kinases/metabolism , Receptor Protein-Tyrosine Kinases/geneticsABSTRACT
BACKGROUND: Sarcopenia and knee osteoarthritis are common age-related diseases that have become important public health issues worldwide. Few studies have reported the association between muscle mass loss and knee osteoarthritis. This may be due to the high level of heterogeneity between studies stemming from different definitions of muscle mass loss. METHODS: The systematic searches were carried out in PubMed and Web of Science from the inception of the databases until 13 January 2023, by two independent researchers. Pooled odds ratios (ORs) for overall and subgroup analyses were obtained using either a random effects model (I2 >50%) or fixed effects model (I2 ≤50%) in Stata. RESULTS: Of the 1,606 studies identified, we ultimately included 12 articles on the association between muscle mass and knee osteoarthritis (prospective: n = 5; cross-sectional: n = 7). Low-quality evidence indicated that low muscle mass index and sarcopenic obesity increase the odds of knee osteoarthritis (low muscle mass index OR: 1.36, 95% CI: 1.13-1.64; sarcopenic obesity OR: 1.78, 95% CI: 1.35-2.34). However, no association was observed between general sarcopenia or low muscle mass with knee osteoarthritis. CONCLUSION: This systematic review and meta-analysis revealed that low muscle mass index and sarcopenic obesity were associated with an increased risk of developing knee osteoarthritis.