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1.
Oncoimmunology ; 13(1): 2373526, 2024.
Article in English | MEDLINE | ID: mdl-38948931

ABSTRACT

Prostate cancer (PCa) is characterized as a "cold tumor" with limited immune responses, rendering the tumor resistant to immune checkpoint inhibitors (ICI). Therapeutic messenger RNA (mRNA) vaccines have emerged as a promising strategy to overcome this challenge by enhancing immune reactivity and significantly boosting anti-tumor efficacy. In our study, we synthesized Tetra, an mRNA vaccine mixed with multiple tumor-associated antigens, and ImmunER, an immune-enhancing adjuvant, aiming to induce potent anti-tumor immunity. ImmunER exhibited the capacity to promote dendritic cells (DCs) maturation, enhance DCs migration, and improve antigen presentation at both cellular and animal levels. Moreover, Tetra, in combination with ImmunER, induced a transformation of bone marrow-derived dendritic cells (BMDCs) to cDC1-CCL22 and up-regulated the JAK-STAT1 pathway, promoting the release of IL-12, TNF-α, and other cytokines. This cascade led to enhanced proliferation and activation of T cells, resulting in effective killing of tumor cells. In vivo experiments further revealed that Tetra + ImmunER increased CD8+T cell infiltration and activation in RM-1-PSMA tumor tissues. In summary, our findings underscore the promising potential of the integrated Tetra and ImmunER mRNA-LNP therapy for robust anti-tumor immunity in PCa.


Subject(s)
Adjuvants, Immunologic , Antigens, Neoplasm , Cancer Vaccines , Dendritic Cells , Prostatic Neoplasms , RNA, Messenger , Animals , Male , Prostatic Neoplasms/immunology , Prostatic Neoplasms/therapy , Prostatic Neoplasms/pathology , Prostatic Neoplasms/genetics , Prostatic Neoplasms/drug therapy , Antigens, Neoplasm/immunology , Mice , Dendritic Cells/immunology , Adjuvants, Immunologic/pharmacology , Adjuvants, Immunologic/administration & dosage , RNA, Messenger/genetics , RNA, Messenger/metabolism , RNA, Messenger/administration & dosage , Cancer Vaccines/administration & dosage , Cancer Vaccines/immunology , Humans , Mice, Inbred C57BL , Cell Line, Tumor , mRNA Vaccines , CD8-Positive T-Lymphocytes/immunology , T-Lymphocytes/immunology , T-Lymphocytes/metabolism , Immunotherapy/methods , Lymphocyte Activation/drug effects
2.
Mil Med Res ; 11(1): 40, 2024 Jun 21.
Article in English | MEDLINE | ID: mdl-38902808

ABSTRACT

Fibroblast growth factor (FGF) signaling encompasses a multitude of functions, including regulation of cell proliferation, differentiation, morphogenesis, and patterning. FGFs and their receptors (FGFR) are crucial for adult tissue repair processes. Aberrant FGF signal transduction is associated with various pathological conditions such as cartilage damage, bone loss, muscle reduction, and other core pathological changes observed in orthopedic degenerative diseases like osteoarthritis (OA), intervertebral disc degeneration (IVDD), osteoporosis (OP), and sarcopenia. In OA and IVDD pathologies specifically, FGF1, FGF2, FGF8, FGF9, FGF18, FGF21, and FGF23 regulate the synthesis, catabolism, and ossification of cartilage tissue. Additionally, the dysregulation of FGFR expression (FGFR1 and FGFR3) promotes the pathological process of cartilage degradation. In OP and sarcopenia, endocrine-derived FGFs (FGF19, FGF21, and FGF23) modulate bone mineral synthesis and decomposition as well as muscle tissues. FGF2 and other FGFs also exert regulatory roles. A growing body of research has focused on understanding the implications of FGF signaling in orthopedic degeneration. Moreover, an increasing number of potential targets within the FGF signaling have been identified, such as FGF9, FGF18, and FGF23. However, it should be noted that most of these discoveries are still in the experimental stage, and further studies are needed before clinical application can be considered. Presently, this review aims to document the association between the FGF signaling pathway and the development and progression of orthopedic diseases. Besides, current therapeutic strategies targeting the FGF signaling pathway to prevent and treat orthopedic degeneration will be evaluated.


Subject(s)
Fibroblast Growth Factors , Osteoarthritis , Signal Transduction , Humans , Fibroblast Growth Factors/physiology , Fibroblast Growth Factors/metabolism , Signal Transduction/physiology , Osteoarthritis/physiopathology , Fibroblast Growth Factor-23 , Intervertebral Disc Degeneration/physiopathology , Osteoporosis/physiopathology , Osteoporosis/etiology , Sarcopenia/physiopathology , Aging/physiology , Animals
3.
World J Clin Cases ; 12(16): 2911-2916, 2024 Jun 06.
Article in English | MEDLINE | ID: mdl-38899298

ABSTRACT

BACKGROUND: Transarterial chemoembolization (TACE) is a standard treatment for intermediate-stage hepatocellular carcinoma (HCC). The complications of TACE include biliary tract infection, liver dysfunction, tumor lysis syndrome, biloma, partial intestinal obstruction, cerebral lipiodol embolism, etc. There are few reports about tracheal fistula induced by TACE. CASE SUMMARY: A 42-year-old man came to our hospital with cough and expectoration for 1 month after TACE for HCC. Laboratory test results showed abnormalities of albumin, hemoglobin, prothrombin time, C-reactive protein, D-dimer, and prothrombin. Culture of both phlegm and liver pus revealed growth of Citrobacter flavescens. Computed tomography showed infection in the inferior lobe of the right lung and a low-density lesion with gas in the right liver. Liver ultrasound showed that there was a big hypoechoic liquid lesion without blood flow signal. Drainage for liver abscess by needle puncture under ultrasonic guidance was performed. After 1 month of drainage and anti-infection therapy, the abscess in the liver and the infection in the lung were reduced obviously, and the symptom of expectoration was relieved. CONCLUSION: Clinicians should be alert to the possibility of complications of liver abscess and tracheal fistula after TACE for HCC. Drainage for liver abscess by needle puncture under ultrasonic guidance could relieve the liver abscess and tracheal fistula.

4.
World J Clin Cases ; 12(15): 2614-2620, 2024 May 26.
Article in English | MEDLINE | ID: mdl-38817231

ABSTRACT

BACKGROUND: The stent embedded in the esophageal mucosa is one of the complications after stenting for esophageal stricture. We present a case of stent adjustment with the aid of a transparent cap after endoscopic injection of an esophageal varices stent. CASE SUMMARY: A 61-year-old male patient came to the hospital with discomfort of the chest after the stent implanted for the stenosis because of endoscopic injection of esophageal varices. The gastroscopy was performed, and the stent embedded into the esophageal mucosa. At first, we pulled the recycling line for shrinking the stent, however, the mucosa could not be removed from the stent. Then a forceps was performed to remove the mucosa in the stent, nevertheless, the bleeding form the mucosa was obvious. And then, we used a transparent cap to scrape the mucosa along the stent, and the mucosa were removed successfully without bleeding. CONCLUSION: A transparent cap helps gastroscopy to remove the mucosa embedded in the stent after endoscopic injection of the esophageal varices stent.

5.
Development ; 151(20)2024 Oct 15.
Article in English | MEDLINE | ID: mdl-38646855

ABSTRACT

Ecdysone-induced protein 93 (E93), known as the 'adult-specifier' transcription factor in insects, triggers metamorphosis in both hemimetabolous and holometabolous insects. Although E93 is conserved in ametabolous insects, its spatiotemporal expression and physiological function remain poorly understood. In this study, we first discover that, in the ametabolous firebrat Thermobia domestica, the previtellogenic ovary exhibits cyclically high E93 expression, and E93 mRNA is broadly distributed in previtellogenic ovarioles. E93 homozygous mutant females of T. domestica exhibit severe fecundity deficiency due to impaired previtellogenic development of the ovarian follicles, likely because E93 induces the expression of genes involved in ECM (extracellular matrix)-receptor interactions during previtellogenesis. Moreover, we reveal that in the hemimetabolous cockroach Blattella germanica, E93 similarly promotes previtellogenic ovarian development. In addition, E93 is also essential for vitellogenesis that is necessary to guarantee ovarian maturation and promotes the vitellogenesis-previtellogenesis switch in the fat body of adult female cockroaches. Our findings deepen the understanding of the roles of E93 in controlling reproduction in insects, and of E93 expression and functional evolution, which are proposed to have made crucial contributions to the origin of insect metamorphosis.


Subject(s)
Metamorphosis, Biological , Ovary , Reproduction , Animals , Female , Reproduction/genetics , Metamorphosis, Biological/genetics , Ovary/metabolism , Gene Expression Regulation, Developmental , Vitellogenesis/genetics , Insect Proteins/metabolism , Insect Proteins/genetics , Transcription Factors/metabolism , Transcription Factors/genetics , Drosophila Proteins/metabolism , Drosophila Proteins/genetics
6.
Phys Rev Lett ; 132(15): 150401, 2024 Apr 12.
Article in English | MEDLINE | ID: mdl-38683009

ABSTRACT

Quantum many-body scars are nonthermal excited eigenstates of nonintegrable Hamiltonians, which could support coherent revival dynamics from special initial states when scars form an equally spaced tower in the energy spectrum. For open quantum systems, engineering many-body scarred dynamics by a controlled coupling to the environment remains largely unexplored. Here, we provide a general framework to exactly embed quantum many-body scars into the decoherence-free subspaces of Lindblad master equations. The dissipative scarred dynamics manifest persistent periodic oscillations for generic initial states, and can be practically utilized to prepare scar states with potential quantum metrology applications. We construct the Liouvillian dissipators with the local projectors that annihilate the whole scar towers, and utilize the Hamiltonian part to rotate the undesired states out of the null space of dissipators. We demonstrate our protocol through several typical models hosting many-body scar towers and propose an experimental scheme to observe the dissipative scarred dynamics based on digital quantum simulations and resetting ancilla qubits.

7.
Mater Horiz ; 11(13): 3178-3186, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38666445

ABSTRACT

We create high-aspect-ratio dynamic poly-regional surface topographies in a coating of a main-chain liquid crystal oligomer network (LCON). The topographies form at the topological defects in the director pattern organized in an array which are controlled by photopatterning of the alignment layer. The defect regions are activated by heat and/or light irradiation to form reversible topographic structures. Intrinsically, the LCON is rubbery and sensitive to temperature changes, resulting in shape transformations. We further advanced such system to make it light-responsive by incorporating azobenzene moieties. Actuation reduces the molecular order of the LCON coating that remains firmly adhered to the substrate which gives directional shear stresses around the topological defects. The stresses relax by deforming the surfaces by forming elevations or indents, depending on the type of defects. The formed topographies exhibit various features, including two types of protrusions, ridges and valleys. These poly-regional structures exhibit a large modulation amplitude of close to 60%, which is 6 times larger than the ones formed in liquid crystal networks (LCNs). After cooling or by blue light irradiation, the topographies are erased to the initial flat surface. A finite element method (FEM) model is adopted to simulate structures of surface topographies. These dynamic surface topographies with multilevel textures and large amplitude expand the application range, from haptics, controlled cell growth, to intelligent surfaces with adjustable adhesion and tribology.

8.
Epigenetics ; 19(1): 2341578, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38615330

ABSTRACT

Long non-coding RNAs (lncRNAs) have been shown to be involved in the regulation of skeletal muscle development through multiple mechanisms. The present study revealed that the lncRNA SOX6 AU (SRY-box transcription factor 6 antisense upstream) is reverse transcribed from upstream of the bovine sex-determining region Y (SRY)-related high-mobility-group box 6 (SOX6) gene. SOX6 AU was significantly differentially expressed in muscle tissue among different developmental stages in Xianan cattle. Subsequently, knockdown and overexpression experiments discovered that SOX6 AU promoted primary skeletal muscle cells proliferation, apoptosis, and differentiation in bovine. The overexpression of SOX6 AU in bovine primary skeletal muscle cells resulted in 483 differentially expressed genes (DEGs), including 224 upregulated DEGs and 259 downregulated DEGs. GO functional annotation analysis showed that muscle development-related biological processes such as muscle structure development and muscle cell proliferation were significantly enriched. KEGG pathway analysis revealed that the PI3K/AKT and MAPK signaling pathways were important pathways for DEG enrichment. Notably, we found that SOX6 AU inhibited the mRNA and protein expression levels of the SOX6 gene. Moreover, knockdown of the SOX6 gene promoted the proliferation and apoptosis of bovine primary skeletal muscle cells. Finally, we showed that SOX6 AU promoted the proliferation and apoptosis of bovine primary skeletal muscle cells by cis-modulation of SOX6 in cattle. This work illustrates our discovery of the molecular mechanisms underlying the regulation of SOX6 AU in the development of beef.


Subject(s)
Phosphatidylinositol 3-Kinases , RNA, Long Noncoding , Cattle , Animals , Phosphatidylinositol 3-Kinases/genetics , DNA Methylation , Muscle Development/genetics , Apoptosis , Cell Differentiation
9.
Pest Manag Sci ; 2024 Apr 27.
Article in English | MEDLINE | ID: mdl-38676657

ABSTRACT

BACKGROUND: Cockroaches are widely acknowledged as significant vectors of pathogenic microorganisms. The Periplaneta fuliginosa densovirus (PfDNV) infects the smoky-brown cockroach P. fuliginosa and causes host mortality, which identifies the PfDNV as a species-specific and environmentally friendly biopesticide. However, although the biochemical characterization of PfDNV has been extensively studied, the immune response against PfDNV remains largely unclear. RESULTS: Here, we investigated the replication of PfDNV and its associated pathological phenotype in the foregut and hindgut. Consequently, we dissected and performed transcriptome sequencing on the foregut, midgut, and hindgut separately. We revealed the up-regulation of immune response signaling pathway c-Jun N-terminal kinase (JNK) and apoptosis in response to viral infection. Furthermore, knockdown of the JNK upstream gene Ben resulted in a decrease in virus titer and delayed host mortality. CONCLUSION: Taken together, our findings provide evidence that the Ben-JNK signaling plays a crucial role in PfDNV infection, leading to excessive apoptosis in intestinal tissues and ultimately resulting in the death of the host. Our results indicated that the host response to PfDNV fosters viral infection, thereby increasing host lethality. This underscores the potential of PfDNV as a viable, environmentally friendly biopesticide. © 2024 Society of Chemical Industry.

10.
Environ Sci Pollut Res Int ; 31(22): 31818-31842, 2024 May.
Article in English | MEDLINE | ID: mdl-38639909

ABSTRACT

Building envelope features (BEFs) have attracted more and more attention as they have a significant impact on flow structure and pollutant dispersion within street canyons. This paper conducted CFD numerical models validated by wind-tunnel experiments, to explore the effects of the BEFs on characteristics of the airflow and pollutant distribution inside a symmetric street canyon under perpendicular incoming flow. Three different BEFs (balconies, overhangs, and wing walls) and their locations and continuity/discontinuity structures were considered. For each canyon with various BEFs, the air exchange rate (ACH), airflow patterns, and pollutant distributions were evaluated and compared in detail. The results show that compared to the regular canyon, the BEFs will reduce the ACH of the canyon, but increase the disturbances (the proportion of ACH') inside the canyon. The BEFs on the leeward wall have the least influence on the in-canyon airflow and pollutant distributions, followed by that on the windward wall. Then when the BEFs are on both walls, the ventilation capacity of the canyon is weakened greatly, and the pollutant concentration in the ground center is increased significantly, especially near the windward side. Moreover, the discontinuity BEFs will weaken the effect of the continuity BEFs on the in-canyon flow and dispersion, specifically, the discontinuity BEFs reduced the region of high pollutant concentration distributions. These findings can help optimize the BEFs design to enhance ventilation and mitigate traffic pollution.


Subject(s)
Air Movements , Air Pollutants , Wind , Environmental Monitoring , Models, Theoretical , Ventilation
11.
GigaByte ; 2024: gigabyte111, 2024.
Article in English | MEDLINE | ID: mdl-38434930

ABSTRACT

The basic analysis steps of spatial transcriptomics require obtaining gene expression information from both space and cells. The existing tools for these analyses incur performance issues when dealing with large datasets. These issues involve computationally intensive spatial localization, RNA genome alignment, and excessive memory usage in large chip scenarios. These problems affect the applicability and efficiency of the analysis. Here, a high-performance and accurate spatial transcriptomics data analysis workflow, called Stereo-seq Analysis Workflow (SAW), was developed for the Stereo-seq technology developed at BGI. SAW includes mRNA spatial position reconstruction, genome alignment, gene expression matrix generation, and clustering. The workflow outputs files in a universal format for subsequent personalized analysis. The execution time for the entire analysis is ∼148 min with 1 GB reads 1 × 1 cm chip test data, 1.8 times faster than with an unoptimized workflow.

12.
Neurochem Int ; 175: 105718, 2024 May.
Article in English | MEDLINE | ID: mdl-38490487

ABSTRACT

Alzheimer's disease (AD) is the most common cause of dementia in the elderly. Recent evidence suggests that gamma-aminobutyric acid B (GABAB) receptor-mediated inhibition is a major contributor to AD pathobiology, and GABAB receptors have been hypothesized to be a potential target for AD treatment. The aim of this study is to determine how GABAB regulation alters cognitive function and brain activity in an AD mouse model. Early, middle and late stage (8-23 months) amyloid precursor protein (APP) and presenilin 1 (PS1) transgenic mice were used for the study. The GABAB agonist baclofen (1 and 2.5 mg/kg, i. p.) and the antagonist phaclofen (0.5 mg/kg, i. p.) were used. Primarily, we found that GABAB activation was able to improve spatial and/or working memory performance in early and late stage AD animals. In addition, GABAB activation and inhibition could regulate global and local EEG oscillations in AD animals, with activation mainly regulating low-frequency activity (delta-theta bands) and inhibition mainly regulating mid- and high-frequency activity (alpha-gamma bands), although the regulated magnitude at some frequencies was reduced in AD. The cognitive improvements in AD animals may be explained by the reduced EEG activity in the theta frequency band (2-4 Hz). This study provides evidence for a potential therapeutic effect of baclofen in the elderly AD brain and for GABAB receptor-mediated inhibition as a potential therapeutic target for AD.


Subject(s)
Alzheimer Disease , Amyloid beta-Protein Precursor , Humans , Mice , Animals , Aged , Amyloid beta-Protein Precursor/genetics , Amyloid beta-Protein Precursor/metabolism , Mice, Transgenic , Baclofen/pharmacology , Presenilin-1/genetics , Receptors, GABA-B , Alzheimer Disease/drug therapy , Alzheimer Disease/metabolism , gamma-Aminobutyric Acid , Cognition , Electroencephalography , Disease Models, Animal
13.
PLoS One ; 19(3): e0299273, 2024.
Article in English | MEDLINE | ID: mdl-38452128

ABSTRACT

PURPOSE: This study aims to evaluate the efficacy and satisfaction of using a multi-angle laser device (MLD) for C-arm fluoroscopy to assist novice learners during lumbar spine surgery. METHODS: Forty novice learners were randomly assigned to Group A using an MLD-equipped C-arm or Group B using a traditional C-arm. Both groups performed X-ray fluoroscopy on a lumbar spine model in supine and rotated positions. Time, number of shots, and deviation from the target were compared. A questionnaire was used to assess the learning experience. RESULTS: Group A required less time (13.66 vs. 25.63 min), and fewer shots (15.05 vs. 32.50), and had a smaller deviation (22.9% vs. 61.5%) than Group B (all p<0.05). The questionnaire revealed higher scores in Group A for comfort, efficiency, and knowledge mastery (all p<0.05). CONCLUSION: The MLD significantly improves novice learning of C-arm fluoroscopy during lumbar spine surgery.


Subject(s)
Lumbar Vertebrae , Surgery, Computer-Assisted , Fluoroscopy , Lumbar Vertebrae/diagnostic imaging , Lumbar Vertebrae/surgery , Surveys and Questionnaires , Humans
14.
Front Neurosci ; 18: 1357269, 2024.
Article in English | MEDLINE | ID: mdl-38516315

ABSTRACT

Introduction: Chronic lower back pain (cLBP), frequently attributed to lumbar disk herniation (LDH), imposes substantial limitations on daily activities. Despite its prevalence, the neural mechanisms underlying lower back pain remain incompletely elucidated. Functional magnetic resonance imaging (fMRI) emerges as a non-invasive modality extensively employed for investigating neuroplastic changes in neuroscience. In this study, task-based and resting-state fMRI methodologies are employed to probe the central mechanisms of lower back pain. Methods: The study included 71 chronic lower back pain patients (cLBP group) due to LDH and 80 age, gender, and education-matched healthy volunteers (HC group). The subjects are mainly middle-aged and elderly individuals. Visual Analog Scale (VAS), Oswestry Disability Index (ODI), and Japanese Orthopedic Association Scores (JOA) were recorded. Resting-state and task-based fMRI data were collected. Results/discussion: No significant differences were observed in age, gender, and education level between the two groups. In the cLBP group during task execution, there was diffuse and reduced activation observed in the primary motor cortex and supplementary motor area. Additionally, during resting states, notable changes were detected in brain regions, particularly in the frontal lobe, primary sensory area, primary motor cortex, precuneus, and caudate nucleus, accompanied by alterations in Amplitude of Low Frequency Fluctuation, Regional Homogeneity, Degree Centrality, and functional connectivity. These findings suggest that chronic lower back pain may entail reduced excitability in sensory-motor areas during tasks and heightened activity in the sensory-motor network during resting states, along with modified functional connectivity in various brain regions.

15.
Micromachines (Basel) ; 15(3)2024 Mar 16.
Article in English | MEDLINE | ID: mdl-38542647

ABSTRACT

This study reveals the pronounced density of oxygen vacancies (Vo) at the back channel of back-channel-etched (BCE) a-InGaZnO (a-IGZO) thin-film transistors (TFTs) results from the sputtered deposition rather than the wet etching process of the source/drain metal, and they are distributed within approximately 25 nm of the back surface. Furthermore, the existence and distribution depth of the high density of Vo defects are verified by means of XPS spectra analyses. Then, the mechanism through which the above Vo defects lead to the instability of BCE a-IGZO TFTs is elucidated. Lastly, it is demonstrated that the device instability under high-humidity conditions and negative bias temperature illumination stress can be effectively alleviated by etching and thus removing the surface layer of the back channel, which contains the high density of Vo defects. In addition, this etch method does not cause a significant deterioration in the uniformity of electrical characteristics and is quite convenient to implement in practical fabrication processes. Thus, a novel and effective solution to the device instability of BCE a-IGZO TFTs is provided.

16.
Nanomaterials (Basel) ; 14(4)2024 Feb 12.
Article in English | MEDLINE | ID: mdl-38392720

ABSTRACT

Electrowetting with a dielectric layer is commonly preferred in practical applications. However, its potential is often limited by factors like the properties of the dielectric layer and its breakdown, along with the complexity of the deposition method. Fortunately, advancements in 3D inkjet printing offer a more adaptable solution for making patterned functional layers. In this study, we used a negative photoresist (HN-1901) to create a new dielectric layer for an electrowetting display on a 3-inch ITO glass using a Dimatix DMP-2580 inkjet printer. The resulting devices performed better due to their enhanced resistance to dielectric breakdown. We meticulously investigated the physical properties of the photoresist material and printer settings to achieve optimal printing. We also controlled the uniformity of the dielectric layer by adjusting ink drop spacing. Compared to traditional electrowetting display devices, those with inkjet-printed dielectric layers showed significantly fewer defects like bubbles and electrode corrosion. They maintained an outstanding response time and breakdown resistance, operating at an open voltage of 20 V. Remarkably, these devices achieved faster response times of ton 22.3 ms and toff 14.2 ms, surpassing the performance of the standard device.

17.
Biochim Biophys Acta Rev Cancer ; 1879(2): 189086, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38342420

ABSTRACT

Metabolic associated fatty liver disease (MAFLD) is a significant risk factor for the development of hepatocellular carcinoma (HCC). Hepatic stellate cells (HSCs), as key mediators in liver injury response, are believed to play a crucial role in the repair process of liver injury. However, in MAFLD patients, the normal metabolic and immunoregulatory mechanisms of HSCs become disrupted, leading to disturbances in the local microenvironment. Abnormally activated HSCs are heavily involved in the initiation and progression of HCC. The metabolic disorders and abnormal activation of HSCs not only initiate liver fibrosis but also contribute to carcinogenesis. In this review, we provide an overview of recent research progress on the relationship between the abnormal metabolism of HSCs and the local immune system in the liver, elucidating the mechanisms of immune imbalance caused by abnormally activated HSCs in MAFLD patients. Based on this understanding, we discuss the potential and challenges of metabolic-based and immunology-based mechanisms in the treatment of MAFLD-related HCC, with a specific focus on the role of HSCs in HCC progression and their potential as targets for anti-cancer therapy. This review aims to enhance researchers' understanding of the importance of HSCs in maintaining normal liver function and highlights the significance of HSCs in the progression of MAFLD-related HCC.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Non-alcoholic Fatty Liver Disease , Humans , Carcinoma, Hepatocellular/pathology , Hepatic Stellate Cells/metabolism , Hepatic Stellate Cells/pathology , Liver Neoplasms/pathology , Non-alcoholic Fatty Liver Disease/pathology , Tumor Microenvironment
18.
Biochem Genet ; 2024 Feb 20.
Article in English | MEDLINE | ID: mdl-38376578

ABSTRACT

Diabetic nephropathy (DN) threatens the survival quality of patients, with complex pathogenesis. Circular RNA (circRNA) dysregulation occurs in DN development. This work aimed to investigate the role of circ-Luc7l in DN cell models and related molecular mechanisms. The expression of circ-Luc7l, microRNA (miR)-205-5p, and transforming growth factor-beta receptor 1 (Tgfbr1) was examined by real-time quantitative PCR (RT-qPCR). Cell viability and proliferation were detected by Cell Counting Kit-8 (CCK-8) assay and EdU assay. The expression of extracellular matrix (ECM)-related markers and Tgrbr1 protein was measured by Western blot. The binding between miR-205-5p and circ-Luc7l or Tgfbr1 was validated by dual-luciferase reporter assay, RNA immunoprecipitation (RIP) assay, or RNA pull-down assay. Experimental animal models were established to elucidate the function of circ-Luc7l in vivo. Circ-Luc7l expression was notably enhanced in high glucose (HG)-treated mesangial cells. Knockdown of circ-Luc7l attenuated HG-induced cell proliferation, inflammation, and ECM accumulation in vitro and relieved inflammation and ECM accumulation of kidneys of diabetic mice in vivo. Circ-Luc7l targeted miR-205-5p, and miR-205-5p inhibition rescued the depletion effects of circ-Luc7l knockdown on cell proliferation, inflammation, and ECM accumulation. MiR-205-5p bound to Tgfbr1 whose expression was negatively regulated by circ-Luc7l. Tgfbr1 overexpression also rescued the depletion effects of circ-Luc7l knockdown on cell proliferation, inflammation, and ECM accumulation. In HG conditions, increased circ-Luc7l upregulated Tgfbr1 expression via targeting miR-205-5p to induce DN progression.

19.
BMJ Open ; 14(2): e077941, 2024 Feb 20.
Article in English | MEDLINE | ID: mdl-38382963

ABSTRACT

INTRODUCTION: The lumbar puncture (LP) technique is widely used for diagnostic and therapeutic purposes. In recent years, the paramedian approach technique (PAT) has gained increasing interest due to its advantages over the conventional midline approach technique (MAT) that has been traditionally employed in clinical practice for LP. However, there have been inconsistent discussions regarding the efficacy of different LP techniques. Based on digital virtual human and computer simulation techniques, a new approach called computerised modified PAT (CMPAT) was proposed. Therefore, the aim of this study is to discuss a randomised controlled trial (RCT) protocol to investigate and compare the effects of CMPAT and MAT in patients undergoing LP. METHODS AND ANALYSIS: We will conduct a prospective, multicentre RCT. The study will recruit 84 patients aged 18-99 years who require LP. Participants will be randomly assigned to either the CMPAT treatment group (group A) or the MAT treatment group (group B). The primary outcome measure will be the number of needle insertion attempts required for a successful LP. Secondary outcomes will include the puncture success rate, pain assessment in the back, head, and legs, and the occurrence of complications. The measurement of these secondary outcomes will be taken during the procedure, as well as at specific time points: 30 min, 6 hours, 1 day, 3 days, 7 days, 2 weeks and 4 weeks after the procedure. Pain levels will be assessed using a Numerical Rating Scale. ETHICS AND DISSEMINATION: Ethical approval (2022YF052-01) has been obtained from the Ethics Committee of Fujian Medical University Union Hospital, Fuzhou, China. The research findings will be published in an international peer-reviewed scientific journal and presented at scientific conferences. TRIAL REGISTRATION NUMBER: ChiCTR2300067937.


Subject(s)
Spinal Puncture , Humans , China , Randomized Controlled Trials as Topic , Treatment Outcome , Adolescent , Young Adult , Adult , Middle Aged , Aged , Aged, 80 and over , Multicenter Studies as Topic , Prospective Studies
20.
Oncol Lett ; 27(2): 76, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38192678

ABSTRACT

[This retracts the article DOI: 10.3892/ol.2018.9512.].

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