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1.
Heliyon ; 10(17): e37080, 2024 Sep 15.
Article in English | MEDLINE | ID: mdl-39319163

ABSTRACT

The content and density of traffic signs directly affect the operation of urban road traffic and drivers. To overcome the limitations of quantitative research on the density threshold of traffic signs on urban roads, a real vehicle experiment was conducted to record the psychological characteristics of drivers. Four psychological parameters of drivers-pupil area, fixation intensity, heart rate change rate, and heart rate variability-were explored. Subsequently, principal component analysis was used to present a new index, S, divided into 5 grade scales, to represent the driving visual comfort level. The information entropy theory was applied to quantify the amount of information on road traffic signs that are included in driving tests, and a regression relationship between the traffic sign information and comfort index S was established. The visual psychological load thresholds for different comfort levels were -2.289≤S < -1.526 for very comfortable, 1.526≤S < -0.763 for relatively comfortable, -0.763≤S ≤ 0.763 for comfortable, 0.763

2.
Cell Mol Life Sci ; 81(1): 385, 2024 Sep 05.
Article in English | MEDLINE | ID: mdl-39235496

ABSTRACT

Cisplatin-induced renal tubular injury largely restricts the wide-spread usage of cisplatin in the treatment of malignancies. Identifying the key signaling pathways that regulate cisplatin-induced renal tubular injury is thus clinically important. PARVB, a focal adhesion protein, plays a crucial role in tumorigenesis. However, the function of PARVB in kidney disease is largely unknown. To investigate whether and how PARVB contributes to cisplatin-induced renal tubular injury, a mouse model (PARVB cKO) was generated in which PARVB gene was specifically deleted from proximal tubular epithelial cells using the Cre-LoxP system. In this study, we found depletion of PARVB in proximal tubular epithelial cells significantly attenuates cisplatin-induced renal tubular injury, including tubular cell death and inflammation. Mechanistically, PARVB associates with transforming growth factor-ß-activated kinase 1 (TAK1), a central regulator of cell survival and inflammation that is critically involved in mediating cisplatin-induced renal tubular injury. Depletion of PARVB promotes cisplatin-induced TAK1 degradation, inhibits TAK1 downstream signaling, and ultimately alleviates cisplatin-induced tubular cell damage. Restoration of PARVB or TAK1 in PARVB-deficient cells aggravates cisplatin-induced tubular cell injury. Finally, we demonstrated that PARVB regulates TAK1 protein expression through an E3 ligase ITCH-dependent pathway. PARVB prevents ITCH association with TAK1 to block its ubiquitination. Our study reveals that PARVB deficiency protects against cisplatin-induced tubular injury through regulation of TAK1 signaling and indicates targeting this pathway may provide a novel therapeutic strategy to alleviate cisplatin-induced kidney damage.


Subject(s)
Cisplatin , MAP Kinase Kinase Kinases , Mice, Knockout , Signal Transduction , Cisplatin/adverse effects , Cisplatin/toxicity , Animals , MAP Kinase Kinase Kinases/metabolism , MAP Kinase Kinase Kinases/genetics , Signal Transduction/drug effects , Mice , Kidney Tubules, Proximal/metabolism , Kidney Tubules, Proximal/pathology , Kidney Tubules, Proximal/drug effects , Humans , Mice, Inbred C57BL , Epithelial Cells/metabolism , Epithelial Cells/drug effects , Epithelial Cells/pathology , Ubiquitin-Protein Ligases/metabolism , Ubiquitin-Protein Ligases/genetics , Antineoplastic Agents/pharmacology , Antineoplastic Agents/adverse effects , Kidney Tubules/pathology , Kidney Tubules/metabolism , Kidney Tubules/drug effects , Adaptor Proteins, Signal Transducing
3.
J Cell Biol ; 223(11)2024 Nov 04.
Article in English | MEDLINE | ID: mdl-39283311

ABSTRACT

Autophagy plays a crucial role in cancer cell survival by facilitating the elimination of detrimental cellular components and the recycling of nutrients. Understanding the molecular regulation of autophagy is critical for developing interventional approaches for cancer therapy. In this study, we report that migfilin, a focal adhesion protein, plays a novel role in promoting autophagy by increasing autophagosome-lysosome fusion. We found that migfilin is associated with SNAP29 and Vamp8, thereby facilitating Stx17-SNAP29-Vamp8 SNARE complex assembly. Depletion of migfilin disrupted the formation of the SNAP29-mediated SNARE complex, which consequently blocked the autophagosome-lysosome fusion, ultimately suppressing cancer cell growth. Restoration of the SNARE complex formation rescued migfilin-deficiency-induced autophagic flux defects. Finally, we found depletion of migfilin inhibited cancer cell proliferation. SNARE complex reassembly successfully reversed migfilin-deficiency-induced inhibition of cancer cell growth. Taken together, our study uncovers a new function of migfilin as an autophagy-regulatory protein and suggests that targeting the migfilin-SNARE assembly could provide a promising therapeutic approach to alleviate cancer progression.


Subject(s)
Autophagy , Cell Adhesion Molecules , Cell Proliferation , Lysosomes , Qb-SNARE Proteins , Qc-SNARE Proteins , R-SNARE Proteins , Humans , R-SNARE Proteins/metabolism , R-SNARE Proteins/genetics , Qb-SNARE Proteins/metabolism , Qb-SNARE Proteins/genetics , Qc-SNARE Proteins/metabolism , Qc-SNARE Proteins/genetics , Lysosomes/metabolism , Cell Adhesion Molecules/metabolism , Cell Adhesion Molecules/genetics , Autophagosomes/metabolism , HeLa Cells , Cell Line, Tumor , Protein Binding , SNARE Proteins/metabolism , SNARE Proteins/genetics , Membrane Fusion , Qa-SNARE Proteins
4.
Biomark Med ; 18(15-16): 703-715, 2024.
Article in English | MEDLINE | ID: mdl-39143949

ABSTRACT

Biliary tract cancers (BTCs) have rising incidence and mortality rates. Chemotherapy's limited efficacy has led to exploring new treatments like immunotherapy. which offers modest benefits. Moreover, the identification of reliable predictive biomarkers for immune checkpoint therapy in BTCs remains elusive, hindering personalized treatment strategies. This review provides an overview of the current landscape of emerging biomarkers for immunotherapy response in BTCs. We discuss the incremental benefits of combination therapy and the evolving role of immunotherapy in managing advanced BTC. Additionally, we highlight the need for robust predictive biomarkers to optimize treatment outcomes and foster a more individualized approach to patient care. We aim to identify promising research avenues and strategies to enhance therapeutic efficacy and patient survival in BTCs.


[Box: see text].


Subject(s)
Biliary Tract Neoplasms , Biomarkers, Tumor , Immune Checkpoint Inhibitors , Immunotherapy , Humans , Biliary Tract Neoplasms/therapy , Biliary Tract Neoplasms/immunology , Biliary Tract Neoplasms/drug therapy , Immune Checkpoint Inhibitors/therapeutic use , Immunotherapy/methods , Biomarkers, Tumor/metabolism
5.
BMC Gastroenterol ; 24(1): 276, 2024 Aug 20.
Article in English | MEDLINE | ID: mdl-39164628

ABSTRACT

BACKGROUND: The association between marital status and gallbladder cancer (GBC) remains uncertain. This study aimed to verify the relationship between marital status and GBC and construct a prognostic nomogram to predict the impact of marital status on GBC patients. METHOD: GBC patients were divided into married and unmarried groups using data from the Surveillance, Epidemiology, and End Results (SEER) database. We employed competing risk analyses, propensity score matching (PSM), and Kaplan-Meier survival analyses. The relationship between marital status and GBC was then verified, and the predicted nomogram was constructed. RESULTS: A total of 3913 GBC patients were obtained from the SEER database, and an additional 76 GBC patients from Hangzhou Traditional Chinese Medicine Hospital were selected as the external validation group. The competing risk analysis revealed a significant disparity in the 5-year cumulative incidence of cancer-specific death (CSD) between the two cohorts (59.1% vs. 65.2%, p = 0.003). Furthermore, the multivariate competing hazards regression analysis identified a significant association (HR, 1.17; 95% CI, 1.04-1.31; p = 0.007) between marital status and CSD. To assess the 1-, 3-, and 5-year risks of CSD, a comprehensive competing event nomogram was constructed using factors derived from the multivariate analysis. The area under the receiver operating characteristic curve (AUC) values for the 1-, 3-, and 5-year training cohorts were 0.806, 0.785, and 0.776, respectively. In the internal validation cohort, these values were 0.798, 0.790, and 0.790, while the external validation cohort exhibited AUC values of 0.748, 0.835, and 0.883 for the corresponding time intervals. Furthermore, calibration curves demonstrated a commendable level of concordance between the observed and predicted probabilities of CSD. CONCLUSION: Marriage was a protective factor for GBC patients after taking competing risk into consideration. The proposed nomogram demonstrated exceptional predictive power.


Subject(s)
Gallbladder Neoplasms , Kaplan-Meier Estimate , Marital Status , Nomograms , SEER Program , Humans , Gallbladder Neoplasms/mortality , Female , Male , Middle Aged , Risk Assessment/methods , Aged , Prognosis , Propensity Score , Risk Factors , China/epidemiology
6.
Front Bioeng Biotechnol ; 12: 1434465, 2024.
Article in English | MEDLINE | ID: mdl-39135947

ABSTRACT

The immune system, functioning as the body's "defense army", plays a role in surveillance, defense. Any disruptions in immune system can lead to the development of immune-related diseases. Extensive researches have demonstrated the crucial immunoregulatory role of mesenchymal stem cells (MSCs) in these diseases. Of particular interest is the ability to induce somatic cells under specific conditions, generating a new cell type with stem cell characteristics known as induced pluripotent stem cell (iPSC). The differentiation of iPSCs into MSCs, specifically induced pluripotent stem cell-derived mesenchymal stem cells (iMSCs), hold promise as a potential solution to the challenges of MSCs, potentially serving as an alternative to traditional drug therapies. Moreover, the products of iMSCs, termed induced pluripotent stem cell-derived mesenchymal stem cell-derived extracellular vesicles (iMSC-EVs), may exhibit functions similar to iMSCs. With the biological advantages of EVs, they have become the focus of "cell-free therapy". Here, we provided a comprehensive summary of the biological impact of iMSCs on immune cells, explored the applications of iMSCs and iMSC-EVs in diseases, and briefly discussed the fundamental characteristics of EVs. Finally, we overviewed the current advantages and challenges associated with iMSCs and iMSC-EVs. It is our hope that this review related to iMSCs and iMSC-EVs will contribute to the development of new approaches for the treatment of diseases.

8.
Small ; : e2400690, 2024 Aug 29.
Article in English | MEDLINE | ID: mdl-39210651

ABSTRACT

Developing flexible energy storage devices with good deformation resistance under extreme operating conditions is highly desirable yet remains very challenging. Super-elastic MXene-enhanced polyvinyl alcohol/polyaniline (AMPH) hydrogel electrodes are designed and synthesized through vertical gradient ice templating-induced polymerization. This approach allows for the unidirectional growth of polyaniline (PANI) and 2D MXene layers along the elongated arrayed ice crystals in a controlled manner. The resulting 3D unidirectional AMPH hydrogel exhibits inherent stretchability and electronic conductivity, with the ability to completely recover its shape even under extreme conditions, such as 500% tensile strain, 50% compressive strain. The presence of MXene in the hydrogel electrode enhances its resilience to mechanical compression and stretching, resulting in less variation in resistance. AMPH has a specific capacitance of 130.68 and 88.02 mF cm-2 at a current density of 0.2 and 2 mA cm-2, respectively, and retains 90% and 70% of its original capacitance at elongation of 100% and 200%, respectively. AMPH-based supercapacitors demonstrate exceptional performance in high salinity environments and wide temperature ranges (-30-80 °C). The high electrochemical activity, temperature tolerance, and mechanical robustness of AMPH-based supercapacitor endow it promising as the power supply for flexible and wearable electronic devices.

9.
Auton Neurosci ; 255: 103198, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39047501

ABSTRACT

Chronic Fatigue Syndrome (CFS) is a complex and perplexing medical disorder primarily characterized by persistent and debilitating fatigue, often accompanied by a constellation of symptoms, including weakness, dyspnea, arthromyalgia, sore throat, and disrupted sleep patterns. CFS is defined by its persistent or recurrent manifestation for a minimum duration of six months, marked by an enduring and unrelenting fatigue that remains refractory to rest. In recent decades, this condition has garnered significant attention within the medical community. While the precise etiology of CFS remains elusive, it is postulated to be multifactorial. CFS is potentially associated with various contributory factors such as infections, chronic stress, genetic predisposition, immune dysregulation, and psychosocial influences. The pathophysiological underpinnings of CFS encompass viral infections, immune system dysregulation, neuroendocrine aberrations, heightened oxidative stress, and perturbations in gut microbiota. Presently, clinical management predominantly relies on pharmaceutical interventions or singular therapeutic modalities, offering alleviation of specific symptoms but exhibiting inherent limitations. Traditional Chinese Medicine (TCM) interventions have emerged as a promising paradigm, demonstrating notable efficacy through their multimodal, multi-target, multi-pathway approach, and holistic regulatory mechanisms. These interventions effectively address the lacunae in contemporary medical interventions. This comprehensive review synthesizes recent advancements in the understanding of the etiological factors, pathophysiological mechanisms, and interventional strategies for CFS, drawing from a corpus of domestic and international literature. Its aim is to furnish valuable insights for clinicians actively involved in diagnosing and treating CFS, as well as for pharmaceutical researchers delving into innovative drug development pathways. Moreover, it seeks to address the intricate challenges confronted by clinical practitioners in managing this incapacitating condition.


Subject(s)
Fatigue Syndrome, Chronic , Medicine, Chinese Traditional , Fatigue Syndrome, Chronic/therapy , Fatigue Syndrome, Chronic/physiopathology , Humans , Medicine, Chinese Traditional/methods
10.
Prostate Int ; 12(2): 110-115, 2024 Jun.
Article in English | MEDLINE | ID: mdl-39036755

ABSTRACT

Background: Epidemiological reports indicate a potential association between androgenic alopecia (AGA) and increased prostate cancer (PC) prevalence, but conflicting reports also exist. This study aims to elucidate the causality of AGA on PC risk using Mendelian randomization (MR) analysis. Materials and methods: Two-sample MR analyses utilized public genome-wide association studies summary data for single-nucleotide polymorphisms associated with AGA. Four statistical methods were used: inverse variance weighted (IVW), MR-Egger, weighted median, and weighted mode, with IVW as the preliminary estimation method. Additionally, sensitivity analyses were conducted to address pleiotropic bias. Results: Genetically proxied AGA did not demonstrate a causal effect on PC risk (IVW P > 0.05). Consistently, complementary methods yielded results aligned with IVW. Conclusions: Our MR analysis indicates no causal relationship between genetically predicted AGA and PC risk, suggesting that observed associations in epidemiological studies may not be causal.

11.
Environ Sci Pollut Res Int ; 31(31): 44385-44400, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38954330

ABSTRACT

Animal farming wastewater is one of the most important sources of ammonia nitrogen (NH4+-N) emissions. Electro-oxidation can be a viable solution for removing NH4+-N in wastewater. Compared with other treatment methods, electro-oxidation has the advantages of i) high removal efficiency, ii) smaller size of treatment facilities, and iii) complete removal of contaminant. In this study, a previously prepared DSA (W, Ti-doped IrO2) was used for electro-oxidation of synthetic mariculture and livestock wastewater. The DSA was tested for chlorine evolution reaction (CER) activity, and the reaction kinetics was investigated. CER current efficiency reaches 60-80% in mariculture wastewater and less than 20% in livestock wastewater. In the absence of NH4+-N, the generation of active chlorine follows zero-order kinetics and its consumption follows first-order kinetics, with cathodic reduction being its main consumption pathway, rather than escape or conversion to ClO3-. Cyclic voltammetry experiments show that NH4+-N in the form of NH3 can be oxidized directly on the anode surface. In addition, the generated active chlorine combines with NH4+-N at a fast rate near the anode, rather than in the bulk solution. In electrolysis experiments, the NH4+-N removal rate in synthetic mariculture wastewater (30-40 mg/L NH4+-N) and livestock wastewater (~ 450 mg/L NH4+-N) is 112.9 g NH4+-N/(m2·d) and 186.5 g NH4+-N/(m2·d), respectively, which is much more efficient than biological treatment. The specific energy consumption (SEC) in synthetic mariculture wastewater is 31.5 kWh/kg NH4+-N, comparable to other modified electro-catalysts reported in the literature. However, in synthetic livestock wastewater, the SEC is as high as 260 kWh/kg NH4+-N, mainly due to the suppression of active chlorine generation by HCO3- and the generation of NO3- as a by-product. Therefore, we conclude that electro-oxidation is suitable for mariculture wastewater treatment, but is not recommended for livestock wastewater. Electrolysis prior to urea hydrolysis may enhance the treatment efficiency in livestock wastewater.


Subject(s)
Ammonia , Livestock , Oxidation-Reduction , Waste Disposal, Fluid , Wastewater , Wastewater/chemistry , Animals , Ammonia/chemistry , Waste Disposal, Fluid/methods , Nitrogen/chemistry , Water Pollutants, Chemical/chemistry , Titanium/chemistry
12.
Environ Sci Pollut Res Int ; 31(35): 47960-47973, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39014141

ABSTRACT

The electrochemical advanced oxidation process (EAOP) has shown significant promise in the field of refractory organic wastewater treatment due to its high efficiency and environmentally friendly nature. In this study, Ti/Sb-SnO2 electrodes with varying proportions of Hf were prepared using the sol-gel method. The addition of Hf transformed the original collapsing and broken surface into a flat and regular surface. The results demonstrated that Ti/Sb-SnO2-Hf electrode doped with 6% Hf exhibited a higher oxygen evolution potential (OEP) and excellent stability. The OEP increased from 2.315 V without Hf-doping to 2.482 V, and the corresponding actual life was 321.05% higher than that without Hf. The current density (5-40 mA·cm-2), electrolyte concentration (0.02-0.2 mol·L-1), pH (3-11), and initial pollutant concentration (5-80 mg·L-1) were evaluated to confirm the tetracycline (TC) degradation characterization of Ti/Sb-SnO2-6%Hf electrodes. It was concluded that under the optimal degradation conditions, the removal rate of TC could reach 99.66% within 2 h. The degradation of TC follows first-order reaction kinetics. The oxidative degradation of TC was achieved through indirect oxidation, with ·OH playing a dominant role. TC's electrochemical oxidation degradation pathway has been proposed: Based on LC-MS results, three main pathways are speculated. During the electrocatalytic oxidation process, decarboxylation, deamidation, and ring-opening reactions occur under ·OH attack, producing intermediate compounds with m/z values of 427, 433, 350, 246, 461, 424, 330, 352, 309, 263, and 233. These intermediates are further oxidized to intermediate compounds with an m/z value of 218. This work introduces a new efficient anode electrochemical catalyst for the degradation of TC, providing a strategy for industrial applications.


Subject(s)
Electrodes , Oxidation-Reduction , Tetracycline , Titanium , Water Pollutants, Chemical , Titanium/chemistry , Tetracycline/chemistry , Water Pollutants, Chemical/chemistry , Tin Compounds/chemistry , Wastewater/chemistry , Antimony/chemistry , Waste Disposal, Fluid/methods
13.
Biochim Biophys Acta Mol Cell Biol Lipids ; 1869(7): 159535, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39033850

ABSTRACT

BACKGROUND: APOH plays an essential role in lipid metabolism and the transport of lipids in the circulation. Previous studies have shown that APOH deficiency causes fatty liver and gut microbiota dysbiosis in mouse models. However, the role and potential mechanisms of APOH deficiency in the pathogenesis of alcoholic liver disease remain unclear. METHODS: C57BL/6 WT and ApoH-/- mice were used to construct the binge-on-chronic alcohol feeding model. Mouse liver transcriptome, targeted bile acid metabolome, and 16S gut bacterial taxa were assayed and analyzed. Open-source human liver transcriptome dataset was analyzed. RESULTS: ApoH-/- mice fed with alcohol showed severe hepatic steatosis. Liver RNAseq and RT-qPCR data indicated that APOH deficiency predominantly impacts hepatic lipid metabolism by disrupting de novo lipogenesis, cholesterol processing, and bile acid metabolism. A targeted bile acid metabolomics assay indicated significant changes in bile acid composition, including increased percentages of TCA in the liver and DCA in the gut of alcohol-fed ApoH-/- mice. The concentrations of CA, NorCA, and HCA in the liver were higher in ApoH-/- mice on an ethanol diet compared to the control mice (p < 0.05). Additionally, APOH deficiency altered the composition of gut flora, which correlated with changes in the liver bile acid composition in the ethanol-feeding mouse model. Finally, open-source transcript-level data from human ALD livers highlighted a remarkable link between APOH downregulation and steatohepatitis, as well as bile acid metabolism. CONCLUSION: APOH deficiency aggravates alcohol induced hepatic steatosis through the disruption of gut microbiota homeostasis and bile acid metabolism in mice.


Subject(s)
Bile Acids and Salts , Dysbiosis , Gastrointestinal Microbiome , Lipid Metabolism , Liver Diseases, Alcoholic , Animals , Humans , Male , Mice , Bile Acids and Salts/metabolism , Disease Models, Animal , Dysbiosis/metabolism , Dysbiosis/microbiology , Dysbiosis/chemically induced , Liver/metabolism , Liver/pathology , Liver Diseases, Alcoholic/metabolism , Liver Diseases, Alcoholic/microbiology , Liver Diseases, Alcoholic/pathology , Liver Diseases, Alcoholic/genetics , Liver Diseases, Alcoholic/etiology , Mice, Inbred C57BL , Mice, Knockout
14.
Ann Hematol ; 2024 Jul 30.
Article in English | MEDLINE | ID: mdl-39078437

ABSTRACT

Neutrophil extracellular traps (NETs) represent a response mechanism in which activated neutrophils release DNA-based webs, adorned with histones and neutrophil proteases, to capture and eliminate invasive microorganisms. However, when these neutrophils become excessively activated, much more proteases associated with NETs are liberated into surrounding tissues or bloodstreams, thereby altering the cellular milieu and causing tissue damage. Recent research has revealed that NETs may play significant roles in the emergence and progression of various diseases, spanning from infections, inflammation to autoimmune disorders and cancers. In this review, we delve deeply into the intricate and complex mechanisms that underlie the formation of NETs and their profound interplay with various clinical pathologies. We aim to describe the application perspectives of NETs related proteins in specific disease diagnosis and treatment.

15.
Int J Biol Macromol ; 275(Pt 1): 133361, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38960245

ABSTRACT

Diabetic wound healing poses a substantial challenge owing to bacterial infections, insufficient angiogenesis, and excessive exudates. Currently, most of the clinical dressings used for diabetic wounds are still conventional dressings such as gauze. In this study, a three-layer Janus dressing was developed via continuous electrostatic spinning. The top-layer was composed of polylactic acid-glycolic acid and hydroxyapatite doped with silver ions and silicate. The hydrophobic top-layer prevented the adhesion of foreign bacteria. The mid-layer was composed of polyethylene glycol, polylactic acid-glycolic acid and hydroxyapatite doped with silver ions and silicate facilitated exudate absorption and bioactive ion release. The modified sub-layer containing polylactic acid-glycolic acid, hydroxyapatite doped with silver ions and silicate and sodium alginate microspheres enabled both the transport of wound exudate from the wound bed to dressing and the backflow of bioactive silver ions and silicate to the wound bed, thereby reducing infection and stimulating angiogenesis. Through in vivo and in vivo experiments, the Janus dressing showed to have antimicrobial, angiogenic, and exudate-control properties that accelerate healing in diabetic wounds. As a novel dressing, the multifunctional, self-pumping Janus wound dressing with bi-directional biofluidic transport offers a new approach to diabetic wound healing.


Subject(s)
Angiogenesis , Anti-Bacterial Agents , Bandages , Polylactic Acid-Polyglycolic Acid Copolymer , Wound Healing , Animals , Male , Mice , Angiogenesis/drug effects , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Diabetes Mellitus, Experimental , Neovascularization, Physiologic/drug effects , Polylactic Acid-Polyglycolic Acid Copolymer/chemistry , Polylactic Acid-Polyglycolic Acid Copolymer/pharmacology , Wound Healing/drug effects
16.
Oncol Res ; 32(6): 1129-1139, 2024.
Article in English | MEDLINE | ID: mdl-38827325

ABSTRACT

Circular RNAs (circRNAs) have been recognized as pivotal regulators in tumorigenesis, yet the biological functions as well as molecular mechanisms of the majority of circRNAs in hepatocellular carcinoma (HCC) remain elusive. We sought to unveil the expression profile and biological role of circMYBL2 in HCC. Initial microarray analyses were conducted to probe the expression profile of circMYBL2 in HCC cells, and qRT‒PCR analysis was then performed in HCC cell lines and tissues, revealing significant upregulation of circMYBL2. Subsequent experiments were conducted to evaluate the biological function of circMYBL2 in HCC progression. Furthermore, bioinformatics analysis, qRT‒PCR analysis, luciferase reporter assays, and western blot analysis were employed to investigate the interplay among circMYBL2, miR-1205, and E2F1. CircMYBL2 was found to exhibit marked upregulation in tumor tissues as well as HCC cell lines. Elevated expression of circMYBL2 increased the proliferation and migration of HCC cells, whereas circMYBL2 knockdown elicited contrasting effects. Mechanistically, our results indicated that circMYBL2 promoted E2F1 expression and facilitated HCC progression by sponging miR-1205. Our findings revealed that circMYBL2 contributed to HCC progression through the circMYBL2/miR-1205/E2F1 axis, suggesting the potential of circMYBL2 as a novel target for HCC treatment or a prognostic biomarker for HCC.


Subject(s)
Carcinoma, Hepatocellular , Disease Progression , E2F1 Transcription Factor , Gene Expression Regulation, Neoplastic , Liver Neoplasms , RNA, Circular , Humans , Mice , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/metabolism , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation/genetics , E2F1 Transcription Factor/genetics , E2F1 Transcription Factor/metabolism , Liver Neoplasms/pathology , Liver Neoplasms/genetics , Liver Neoplasms/metabolism , MicroRNAs/genetics , Prognosis , RNA, Circular/genetics
17.
Cancer Lett ; 597: 217043, 2024 Aug 10.
Article in English | MEDLINE | ID: mdl-38876386

ABSTRACT

HER2-positive cancer is a prevalent subtype of malignancy with poor prognosis, yet current targeted therapies, like Trastuzumab and pyrotinib, have resulted in remission in patients with HER2-positive cancer. This study provides a novel approach for immunotherapy based on a hydroxyapatite (HA) gene delivery system producing a bispecific antibody for HER2-positive cancer treatment. An HA nanocarrier has been synthesized by the classical hydrothermal method. Particularly, the HA-nanoneedle system was able to mediate stable gene expression of minicircle DNA (MC) encoding a humanized anti-CD3/anti-HER2 bispecific antibody (BsAbHER2) in vivo. The produced BsAbs exhibited a potent killing effect not only in HER2-positive cancer cells but also in patient-derived organoids in vitro. This HA-nanoneedle gene delivery system features simple large-scale preparation and clinical applicability. Hence, the HA-nanoneedle gene delivery system combined with minicircle DNA vector encoding BsAbHER2 reported here provides a potential immunotherapy strategy for HER2-positive tumors.


Subject(s)
Antibodies, Bispecific , CD3 Complex , Durapatite , Gene Transfer Techniques , Receptor, ErbB-2 , Humans , Receptor, ErbB-2/immunology , Receptor, ErbB-2/genetics , Antibodies, Bispecific/pharmacology , Animals , CD3 Complex/immunology , CD3 Complex/genetics , Organoids/immunology , Cell Line, Tumor , Female , Mice , Xenograft Model Antitumor Assays , Genetic Therapy/methods
18.
Sci Rep ; 14(1): 12800, 2024 06 04.
Article in English | MEDLINE | ID: mdl-38834591

ABSTRACT

This study aims to observe the hemostatic and anti-inflammatory effects of intravenous administration of tranexamic acid (TXA) in dual segment posterior lumbar interbody fusion (PLIF). The data of 53 patients with lumbar disease treated with double-segment PLIF were included in this study. The observation group was received a single-dose intravenous of TXA (1 g/100 mL) 15 min before skin incision after general anesthesia. The control group was not received TXA. The observation indicators included postoperative activated partial prothrombin time (APTT), thrombin time (PT), thrombin time (TT), fibrinogen (FIB), platelets (PLT), and postoperative deep vein thrombosis in the lower limbs, surgical time, intraoperative bleeding volume, postoperative drainage volume, transfusion rate, postoperative hospital stay, red blood cell (RBC), hemoglobin (HB), hematocrit (HCT), C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) on the 1st, 4th, 7th, and last tested day after surgery. All patients successfully completed the operation, and there was no deep vein thrombosis after operation. There was no statistically significant difference in postoperative APTT, PT, TT, FIB, PLT, surgical time, and postoperative hospital stay between the two groups (p > 0.05). The intraoperative bleeding volume, postoperative drainage volume, and transfusion rate in the observation group were lower than those in the control group, and the differences were statistically significant (p < 0.05). There was no statistically significant difference in RBC, HB, HCT, CRP, and ESR between the two groups on the 1st, 4th, 7th, and last tested day after surgery (p > 0.05). Intravenous administration of TXA in dual segment PLIF does not affect coagulation function and can reduce bleeding volume, postoperative drainage volume, and transfusion rate. Moreover, it does not affect the postoperative inflammatory response.


Subject(s)
Spinal Fusion , Tranexamic Acid , Humans , Tranexamic Acid/administration & dosage , Female , Male , Middle Aged , Spinal Fusion/methods , Spinal Fusion/adverse effects , Case-Control Studies , Aged , Lumbar Vertebrae/surgery , Administration, Intravenous , Anti-Inflammatory Agents/administration & dosage , Anti-Inflammatory Agents/pharmacology , Hemostatics/administration & dosage , Hemostatics/pharmacology , Adult , Blood Loss, Surgical/prevention & control , Antifibrinolytic Agents/administration & dosage , Antifibrinolytic Agents/therapeutic use
19.
Curr Biol ; 34(13): 2907-2920.e5, 2024 Jul 08.
Article in English | MEDLINE | ID: mdl-38906143

ABSTRACT

Protected areas conserve biodiversity and ecosystem functions but might impede local economic growth. Understanding the global patterns and predictors of different relationships between protected area effectiveness and neighboring community economic growth can inform better implementation of the Kunming-Montreal Global Biodiversity Framework. We assessed 10,143 protected areas globally with matched samples to address the non-random location of protected areas. Our results show that protected areas resist human-induced land cover changes and do not limit nightlight increases in neighboring settlements. This result is robust, using different matching techniques, parameter settings, and selection of covariates. We identify four types of relationships between land cover changes and nightlight changes for each protected area: "synergy," "retreat," and two tradeoff relationships. About half of the protected areas (47.5%) retain their natural land cover and do so despite an increase of nightlights in the neighboring communities. This synergy relationship is the most common globally but varies between biomes and continents. Synergy is less frequent in the Amazon, Southeast Asia, and some developing areas, where most biodiversity resides and which suffer more from poverty. Smaller protected areas and those with better access to cities, moderate road density, and better baseline economic conditions have a higher probability of reaching synergy. Our results are promising, as the expansion of protected areas and increased species protection will rely more on conserving the human-modified landscape with smaller protected areas. Future interventions should address local development and biodiversity conservation together to achieve more co-benefits.


Subject(s)
Biodiversity , Conservation of Natural Resources , Economic Development , Conservation of Natural Resources/methods , Ecosystem , Humans
20.
Poult Sci ; 103(8): 103877, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38843563

ABSTRACT

This study aims to provide new insight on the association between the development of wooden breast myopathy and mitochondrial and glycolytic activity under oxidative stress. Myopathic muscle had higher oxidative stress together with altered glycolytic metabolism and tricarboxylic acid (TCA) cycle. This was evidenced by significantly elevated antioxidant enzyme activities (catalase, superoxide dismutase, and glutathione peroxidase), decreased citrate synthase activity and postmortem glycolytic potential with increasing wooden breast severity. In addition, affected muscles also exhibited higher initial and ultimate pH values as well as reduced total glucose and lactate contents. Citrate synthase activity was negatively correlated to antioxidant enzyme activities. Taken together, we propose that the development of the wooden breast lesion is a chronic process that may be related to the failure of muscle fibers to defend against the excessively generated oxidative products promoted by mitochondrial damage accompanied by impaired TCA cycle. Furthermore, there was a positive correlation between citrate synthase activity and glycolytic potential, which suggests that the wooden breast condition is linked to the overall altered energy metabolism of the muscle, including the oxidative phosphorylation and glycolytic pathways.


Subject(s)
Chickens , Energy Metabolism , Poultry Diseases , Animals , Poultry Diseases/metabolism , Antioxidants/metabolism , Pectoralis Muscles/metabolism , Muscular Diseases/veterinary , Muscular Diseases/metabolism , Oxidative Stress , Glycolysis , Male , Biomarkers/metabolism , Citric Acid Cycle/physiology , Citrate (si)-Synthase/metabolism
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