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Sci Rep ; 14(1): 10462, 2024 05 07.
Article En | MEDLINE | ID: mdl-38714885

Respiratory infections are common causes of acute exacerbation of chronic obstructive lung disease (AECOPD). We explored whether the pathogens causing AECOPD and clinical features changed from before to after the coronavirus disease 2019 (COVID-19) outbreak. We reviewed the medical records of patients hospitalized with AECOPD at four university hospitals between January 2017 and December 2018 and between January 2021 and December. We evaluated 1180 patients with AECOPD for whom medication histories were available. After the outbreak, the number of patients hospitalized with AECOPD was almost 44% lower compared with before the outbreak. Patients hospitalized with AECOPD after the outbreak were younger (75 vs. 77 years, p = 0.003) and more often stayed at home (96.6% vs. 88.6%, p < 0.001) than patients of AECOPD before the outbreak. Hospital stay was longer after the outbreak than before the outbreak (10 vs. 8 days. p < 0.001). After the COVID-19 outbreak, the identification rates of S. pneumoniae (15.3 vs. 6.2%, p < 0.001) and Hemophilus influenzae (6.4 vs. 2.4%, p = 0.002) decreased, whereas the identification rates of P. aeruginosa (9.4 vs. 13.7%, p = 0.023), Klebsiella pneumoniae (5.3 vs. 9.8%, p = 0.004), and methicillin-resistant Staphylococcus aureus (1.0 vs. 2.8%, p = 0.023) increased. After the outbreak, the identification rate of influenza A decreased (10.4 vs. 1.0%, p = 0.023). After the outbreak, the number of patients hospitalized with AECOPD was lower and the identification rates of community-transmitted pathogens tended to decrease, whereas the rates of pathogens capable of chronic colonization tended to increase. During the period of large-scale viral outbreaks that require quarantine, patients with AECOPD might be given more consideration for treatment against strains that can colonize chronic respiratory disease rather than community acquired pathogens.

COVID-19 , Hospitalization , Pulmonary Disease, Chronic Obstructive , Humans , COVID-19/epidemiology , COVID-19/complications , Pulmonary Disease, Chronic Obstructive/epidemiology , Pulmonary Disease, Chronic Obstructive/complications , Aged , Male , Female , Aged, 80 and over , SARS-CoV-2/isolation & purification , Middle Aged , Pandemics , Respiratory Tract Infections/epidemiology , Respiratory Tract Infections/virology , Disease Progression , Retrospective Studies , Streptococcus pneumoniae/isolation & purification , Streptococcus pneumoniae/pathogenicity , Haemophilus influenzae/isolation & purification
BMC Cancer ; 24(1): 569, 2024 May 07.
Article En | MEDLINE | ID: mdl-38714983

BACKGROUND: No definite conclusion has yet to be reached for immunotherapy beyond progression(IBP) of first-line immunotherapy as the second-line treatment for advanced NSCLC patients with negative driver genes. Therefore a retrospective study was conducted to evaluate the efficacy of IBP in this population and investigated whether the cycles best response and progressive mode of first-line immunotherapy could affect the results. PATIENTS AND METHODS: The clinical data of patients with advanced NSCLC whose response was evaluated as progressive disease (PD) after receiving a PD-1/PD-L1 inhibitors as first-line therapy were retrospectively collected and the patients were assigned to the IBP and non-IBP groups. The overall survival (OS), progression-free survival (PFS) were evaluated between the two groups. The survival effects of cycles best response and progressive mode of first-line immunotherapy were also evaluated. RESULTS: Between January 2019 and January 2022, a total of 121 patients was evaluated as PD after first-line immunotherapy in our institution; 53 (43.8%) patients were included in the IBP group and 68 (56.2%) patients were included in the non-IBP group. The OS and PFS were no significantly different between the two groups in whole population. Further analysis revealed the OS was prolonged with the prolongation of first-line medication cycle. The median OS was 15.4m (15.4 vs 10.8 p=0.047) 16.1m (16.1 vs 10.8 p=0.039), 16.3m (16.3 vs 10.9 p=0.029) for patients with ≥4, ≥6, ≥8 cycles in first-line immunotherapy, respectively. The advantages of OS and PFS were also seen in the subgroup of PR (best response) and oligo progression of first-line immunotherapy. CONCLUSIONS: The clinical outcomes of IBP were similar to those of non-IBP in patients with PD after first-line immnuotherapy in advanced NSCLC. But more cycles, PR as best response and oligo progression in first-line was benefit.

Carcinoma, Non-Small-Cell Lung , Immune Checkpoint Inhibitors , Immunotherapy , Lung Neoplasms , Humans , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/immunology , Carcinoma, Non-Small-Cell Lung/mortality , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/therapy , Carcinoma, Non-Small-Cell Lung/pathology , Immune Checkpoint Inhibitors/therapeutic use , Male , Female , Lung Neoplasms/drug therapy , Lung Neoplasms/mortality , Lung Neoplasms/pathology , Lung Neoplasms/immunology , Lung Neoplasms/genetics , Lung Neoplasms/therapy , Middle Aged , Retrospective Studies , Aged , Immunotherapy/methods , Disease Progression , Progression-Free Survival , Adult , Aged, 80 and over , B7-H1 Antigen/antagonists & inhibitors , Programmed Cell Death 1 Receptor/antagonists & inhibitors
BMC Ophthalmol ; 24(1): 208, 2024 May 07.
Article En | MEDLINE | ID: mdl-38715011

BACKGROUND: To find the relationship between the changes of retinal and choriodal structure/ vascular densities (VD) and the myopia progress. METHODS: 126 eyes of 126 age-matched young participants were divided into three groups: Emmetropia and Low Myopia (EaLM) (33 eyes), Moderate Myopia (MM) (39 eyes), and High Myopia (HM) (54 eyes). Fundus images measuring 12 × 12 mm were captured using ultra-widefield swept-source optical coherence tomography angiography (SS-OCTA). Each image was uniformly divided into nine regions: supra-temporal (ST), temporal (T), infra-temporal (IT), superior (S), central macular area (C), inferior (I), supra-nasal (SN), nasal (N), and infra-nasal (IN). Various structural parameters, including inner retina thickness (IRT), outer retina thickness (ORT), and choroid thickness (CT), were assessed, and the VD of the superficial capillary plexus (SCP), deep capillary plexus (DCP), choriocapillaries (CC), and choroid vessels (ChdV) were quantified. RESULTS: CT in upper fundus exhibited a significant reduction from EaLM to MM. Additionally, ORT (ST, S. SN, C, N, IT, I, IN), CT (ST, S, SN, T, C, N, IT, I, IN) and VDs of SCP (ST, S, C, I, IN), DCP (ST, S, T, C, I) and ChdV (T, N, I, IN) were statistically diminished in EaLM compared to HM. Furthermore, IRT (N), ORT (N, IN), CT (S, SN, T, C, IT, I) and VDs of SCP (I, IN) and DCP (I) exhibited significant decreases as MM progressed towards HM. Intriguingly, there was a notable increase in the VD of CC (ST, S, T, C, N) as myopia progressed from MM to HM. CONCLUSION: Significant changes in retinal and choroid structure and vascular density occur as moderate myopia advances to high myopia. Efforts to curb myopia progression to this stage are essential, as the failure to do so may lead to the development of corresponding retinopathy.

Choroid , Fluorescein Angiography , Myopia , Retinal Vessels , Tomography, Optical Coherence , Humans , Tomography, Optical Coherence/methods , Choroid/blood supply , Choroid/diagnostic imaging , Choroid/pathology , Male , Female , Young Adult , Myopia/physiopathology , Adult , Retinal Vessels/diagnostic imaging , Retinal Vessels/pathology , Fluorescein Angiography/methods , Retina/diagnostic imaging , Retina/pathology , Disease Progression , Adolescent , Fundus Oculi
Cell Commun Signal ; 22(1): 260, 2024 May 07.
Article En | MEDLINE | ID: mdl-38715015

The emergence of drug resistance is a substantial obstacle to the effective management of breast cancer, which is the primary cause of cancer-related deaths in women worldwide. To facilitate the development of targeted therapies that can effectively overcome drug resistance, it is crucial to possess a comprehensive comprehension of the molecular mechanisms that underpin resistance to breast cancer treatment. So far, considerable progress has been made in the field of exercise-oncology research and overcome drug resistance, specifically about breast cancer. Evidence has suggested that participation in physical activity is correlated with a decrease in reappearance and fatality rates of breast cancer patients. It has been reported that participation in physical activity can yield favorable outcomes in the prevention, treatment, and post-treatment of breast cancer. An increasing body of empirical evidence suggests that participation in physical activity can alter diverse biological mechanisms, potentially augmenting breast cancer treatments' efficacy. Comparing increased physical activity versus reduced physical activity in breast cancer patients who received chemotherapy, radiotherapy, and surgery supported the significance of exercise in comprehensive care strategies to enhance overall health and treatment efficacy. Furthermore, previous studies have reported that physical activity can enhance the efficacy of breast cancer treatments. This review provides the current literature regarding the influence of physical activity on the occurrence and progression of breast cancer.

Breast Neoplasms , Exercise , Humans , Breast Neoplasms/therapy , Breast Neoplasms/pathology , Female , Disease Progression , Treatment Outcome , Exercise Therapy , Animals
Arch Esp Urol ; 77(3): 292-302, 2024 Apr.
Article En | MEDLINE | ID: mdl-38715171

BACKGROUND: Renal cell carcinoma (RCC), a common and highly invasive malignant tumour, presents clinical challenges due to its propensity for easy metastasis. Inferior vena cava tumour thrombus is a common RCC complication significantly impacting patient prognosis. This study investigates C-X-C chemokine receptor type 2 (CXCR2)/Snail-1-induced epithelial-mesenchymal transition (EMT) in RCC with inferior vena cava tumour thrombus. METHODS: Tissues from 51 RCC patients were analysed for CXCR2 and Snail-1 Messenger Ribonucleic Acid (mRNA) levels using Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR). Elevated levels of both were observed in tumour and inferior vena cava tumour thrombus tissues. Using Short Hairpin RNA (shRNA) technology, we inhibited CXCR2 and Snail-1 expression to investigate their impact on EMT, invasiveness, and metastatic potential in RCC cells. RESULTS: Compared with that in the Short Hairpin RNA-Negative Control (ShNC) group, inhibition of CXCR2 and Snail-1 suppressed the degree of EMT, invasiveness, and metastatic ability of RCC cells (p < 0.01). Further mechanistic studies showed that CXCR2/Snail-1 participated in the formation and progression of RCC by regulating the extracellular signal-regulated kinase 1/2 (ERK1/2) signalling pathways. Additionally, compared with that in the ShNC group, knockdown of CXCR2 and Snail-1 significantly inhibited the expression of vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9; p < 0.01), thereby regulating the metastasis of RCC. CONCLUSIONS: Our findings suggest that CXCR2/Snail-1-induced EMT plays an important role in the formation and progression of RCC with inferior vena cava tumour thrombus. CXCR2/Snail-1 participates in the invasion and metastasis of RCC by regulating the expression of multiple signalling pathways and related genes. These results provide new insights and directions for the treatment of RCC.

Carcinoma, Renal Cell , Disease Progression , Epithelial-Mesenchymal Transition , Kidney Neoplasms , Snail Family Transcription Factors , Vena Cava, Inferior , Aged , Female , Humans , Male , Middle Aged , Carcinoma, Renal Cell/metabolism , Carcinoma, Renal Cell/pathology , Carcinoma, Renal Cell/secondary , Kidney Neoplasms/pathology , Kidney Neoplasms/metabolism , Neoplasm Invasiveness , Snail Family Transcription Factors/metabolism , Tumor Cells, Cultured , Vena Cava, Inferior/pathology
JCI Insight ; 9(9)2024 May 08.
Article En | MEDLINE | ID: mdl-38716725

IgA nephropathy (IgAN) represents the main cause of renal failure, while the precise pathogenetic mechanisms have not been fully determined. Herein, we conducted a cross-species single-cell survey on human IgAN and mouse and rat IgAN models to explore the pathogenic programs. Cross-species single-cell RNA sequencing (scRNA-Seq) revealed that the IgAN mesangial cells (MCs) expressed high levels of inflammatory signatures CXCL12, CCL2, CSF1, and IL-34 and specifically interacted with IgAN macrophages via the CXCL12/CXCR4, CSF1/IL-34/CSF1 receptor, and integrin subunit alpha X/integrin subunit alpha M/complement C3 (C3) axes. IgAN macrophages expressed high levels of CXCR4, PDGFB, triggering receptor expressed on myeloid cells 2, TNF, and C3, and the trajectory analysis suggested that these cells derived from the differentiation of infiltrating blood monocytes. Additionally, protein profiling of 21 progression and 28 nonprogression IgAN samples revealed that proteins CXCL12, C3, mannose receptor C-type 1, and CD163 were negatively correlated with estimated glomerular filtration rate (eGFR) value and poor prognosis (30% eGFR as composite end point). Last, a functional experiment revealed that specific blockade of the Cxcl12/Cxcr4 pathway substantially attenuated the glomerulus and tubule inflammatory injury, fibrosis, and renal function decline in the mouse IgAN model. This study provides insights into IgAN progression and may aid in the refinement of IgAN diagnosis and the optimization of treatment strategies.

Disease Progression , Glomerulonephritis, IGA , Macrophages , Single-Cell Analysis , Adult , Animals , Female , Humans , Male , Mice , Rats , Chemokine CXCL12/metabolism , Disease Models, Animal , Glomerular Filtration Rate , Glomerulonephritis, IGA/immunology , Glomerulonephritis, IGA/pathology , Interleukins , Macrophages/immunology , Macrophages/metabolism , Mesangial Cells/pathology , Mesangial Cells/metabolism , Mesangial Cells/immunology , Receptors, CXCR4/metabolism , Receptors, CXCR4/genetics , Rats, Wistar
Clin Exp Pharmacol Physiol ; 51(6): e13861, 2024 Jun.
Article En | MEDLINE | ID: mdl-38724488

Relevant studies have indicated the association of HCG18 with tumour occurrence and progression. In this study, we observed that PM2.5 can enhance the growth of lung adenocarcinoma cells by modulating the expression of HCG18. Further investigations, including overexpression and knockout experiments, elucidated that HCG18 suppresses miR-195, which in turn upregulates the expression of ATG14, resulting in the upregulation of autophagy. Consequently, exposure to PM2.5 leads to elevated HCG18 expression in lung tissues, which in turn increases Atg14 expression and activates autophagy pathways through inhibition of miR-195, thereby contributing to oncogenesis.

Adenocarcinoma of Lung , Autophagy-Related Proteins , Autophagy , Disease Progression , Lung Neoplasms , MicroRNAs , Particulate Matter , MicroRNAs/genetics , MicroRNAs/metabolism , Humans , Adenocarcinoma of Lung/genetics , Adenocarcinoma of Lung/pathology , Adenocarcinoma of Lung/metabolism , Autophagy-Related Proteins/genetics , Autophagy-Related Proteins/metabolism , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Lung Neoplasms/metabolism , Particulate Matter/adverse effects , Autophagy/genetics , Gene Expression Regulation, Neoplastic , Vesicular Transport Proteins/genetics , Vesicular Transport Proteins/metabolism , Cell Proliferation/genetics , A549 Cells , Cell Line, Tumor , Adaptor Proteins, Vesicular Transport
Clin Exp Pharmacol Physiol ; 51(7): e13868, 2024 Jul.
Article En | MEDLINE | ID: mdl-38745265

Cervical cancer (CC) is a gynaecological malignancy tumour that seriously threatens women's health. Recent evidence has identified that interferon regulatory factor 5 (IRF5), a nucleoplasm shuttling protein, is a pivotal transcription factor regulating the growth and metastasis of various human tumours. This study aimed to investigate the function and molecular basis of IRF5 in CC development. IRF5, protein phosphatase 6 catalytic subunit (PPP6C) and methyltransferase-like 3 (METTL3) mRNA levels were evaluated by quantitative real-time (qRT)-polymerase chain reaction (PCR). IRF5, PPP6C, METTL3, B-cell lymphoma 2 and Bax protein levels were detected using western blot. Cell proliferation, migration, invasion, angiogenesis and apoptosis were determined by using colony formation, 5-ethynyl-2'-deoxyuridine (EdU), transwell, tube formation assay and flow cytometry assay, respectively. Glucose uptake and lactate production were measured using commercial kits. Xenograft tumour assay in vivo was used to explore the role of IRF5. After JASPAR predication, binding between IRF5 and PPP6C promoter was verified using chromatin immunoprecipitation and dual-luciferase reporter assays. Moreover, the interaction between METTL3 and IRF5 was verified using methylated RNA immunoprecipitation (MeRIP). IRF5, PPP6C and METTL3 were highly expressed in CC tissues and cells. IRF5 silencing significantly inhibited cell proliferation, migration, invasion, angiogenesis and glycolytic metabolism in CC cells, while induced cell apoptosis. Furthermore, the absence of IRF5 hindered tumour growth in vivo. At the molecular level, IRF5 might bind with PPP6C to positively regulate the expression of PPP6C mRNA. Meanwhile, IRF5 was identified as a downstream target of METTL3-mediated m6A modification. METTL3-mediated m6A modification of mRNA might promote CC malignant progression by regulating PPP6C, which might provide a promising therapeutic target for CC treatment.

Cell Proliferation , Disease Progression , Interferon Regulatory Factors , Methyltransferases , Up-Regulation , Uterine Cervical Neoplasms , Humans , Female , Uterine Cervical Neoplasms/genetics , Uterine Cervical Neoplasms/pathology , Uterine Cervical Neoplasms/metabolism , Methyltransferases/genetics , Methyltransferases/metabolism , Interferon Regulatory Factors/genetics , Interferon Regulatory Factors/metabolism , Cell Line, Tumor , Animals , Cell Proliferation/genetics , Mice , Gene Expression Regulation, Neoplastic , Apoptosis/genetics , Cell Movement/genetics , Mice, Nude , Neoplasm Invasiveness , Neovascularization, Pathologic/genetics , Neovascularization, Pathologic/pathology , Neovascularization, Pathologic/metabolism
Harefuah ; 163(5): 298-304, 2024 May.
Article He | MEDLINE | ID: mdl-38734943

INTRODUCTION: Glaucoma is a progressive optic neuropathy and is the leading cause of preventable irreversible blindness worldwide. Glaucoma causes progressive visual field loss and can have significant implications on the patient's quality of life. Lowering intraocular pressure (IOP) is the only treatment proven to prevent vision loss from glaucoma. It is achieved using medication, laser treatment and surgery. The treatment paradigm of glaucoma has been one whereby surgical intervention has been left for advanced cases due to a variety of reasons, mainly concerning safety and long term success. The past two decades have seen a paradigm shift towards earlier IOP lowering interventions using a wide array of different technologies in the laser and surgical spaces. This review aims to understand the background to this paradigm shift, its necessity, and its potential impact on the vision and life of glaucoma patients.

Glaucoma , Intraocular Pressure , Laser Therapy , Quality of Life , Humans , Glaucoma/therapy , Glaucoma/surgery , Intraocular Pressure/physiology , Laser Therapy/methods , Blindness/etiology , Blindness/prevention & control , Visual Fields/physiology , Disease Progression , Optic Nerve Diseases/etiology , Optic Nerve Diseases/therapy
Sci Rep ; 14(1): 10568, 2024 05 08.
Article En | MEDLINE | ID: mdl-38719877

Early diagnosis and treatment of pre- and early-stage osteoarthritis (OA) is important. However, the cellular and cartilaginous changes occurring during these stages remain unclear. We investigated the histological and immunohistochemical changes over time between pre- and early-stage OA in a rat model of traumatic injury. Thirty-six male rats were divided into two groups, control and OA groups, based on destabilization of the medial meniscus. Histological and immunohistochemical analyses of articular cartilage were performed on days 1, 3, 7, 10, and 14 postoperatively. Cell density of proteins associated with cartilage degradation increased from postoperative day one. On postoperative day three, histological changes, including chondrocyte death, reduced matrix staining, and superficial fibrillation, were observed. Simultaneously, a compensatory increase in matrix staining was observed. The Osteoarthritis Research Society International score increased from postoperative day seven, indicating thinner cartilage. On postoperative day 10, the positive cell density decreased, whereas histological changes progressed with fissuring and matrix loss. The proteoglycan 4-positive cell density increased on postoperative day seven. These findings will help establish an experimental model and clarify the mechanism of the onset and progression of pre- and early-stage traumatic OA.

Cartilage, Articular , Disease Models, Animal , Disease Progression , Immunohistochemistry , Osteoarthritis , Animals , Cartilage, Articular/pathology , Cartilage, Articular/metabolism , Male , Rats , Osteoarthritis/pathology , Osteoarthritis/metabolism , Chondrocytes/metabolism , Chondrocytes/pathology , Rats, Sprague-Dawley , Proteoglycans/metabolism
Cancer Imaging ; 24(1): 59, 2024 May 08.
Article En | MEDLINE | ID: mdl-38720384

BACKGROUND: To develop a magnetic resonance imaging (MRI)-based radiomics signature for evaluating the risk of soft tissue sarcoma (STS) disease progression. METHODS: We retrospectively enrolled 335 patients with STS (training, validation, and The Cancer Imaging Archive sets, n = 168, n = 123, and n = 44, respectively) who underwent surgical resection. Regions of interest were manually delineated using two MRI sequences. Among 12 machine learning-predicted signatures, the best signature was selected, and its prediction score was inputted into Cox regression analysis to build the radiomics signature. A nomogram was created by combining the radiomics signature with a clinical model constructed using MRI and clinical features. Progression-free survival was analyzed in all patients. We assessed performance and clinical utility of the models with reference to the time-dependent receiver operating characteristic curve, area under the curve, concordance index, integrated Brier score, decision curve analysis. RESULTS: For the combined features subset, the minimum redundancy maximum relevance-least absolute shrinkage and selection operator regression algorithm + decision tree classifier had the best prediction performance. The radiomics signature based on the optimal machine learning-predicted signature, and built using Cox regression analysis, had greater prognostic capability and lower error than the nomogram and clinical model (concordance index, 0.758 and 0.812; area under the curve, 0.724 and 0.757; integrated Brier score, 0.080 and 0.143, in the validation and The Cancer Imaging Archive sets, respectively). The optimal cutoff was - 0.03 and cumulative risk rates were calculated. DATA CONCLUSION: To assess the risk of STS progression, the radiomics signature may have better prognostic power than a nomogram/clinical model.

Disease Progression , Magnetic Resonance Imaging , Nomograms , Sarcoma , Humans , Sarcoma/diagnostic imaging , Sarcoma/surgery , Sarcoma/pathology , Male , Female , Middle Aged , Retrospective Studies , Magnetic Resonance Imaging/methods , Adult , Aged , Machine Learning , Prognosis , Young Adult , Soft Tissue Neoplasms/diagnostic imaging , Soft Tissue Neoplasms/surgery , Soft Tissue Neoplasms/pathology , ROC Curve , Radiomics
Clin Respir J ; 18(5): e13765, 2024 May.
Article En | MEDLINE | ID: mdl-38721812

LINC00857 is frequently dysregulated in varying cancers, which in turn exerts carcinogenic effects; however, its DNA methylation status in promoter region and molecular mechanisms underlying the progression of lung adenocarcinoma (LUAD) remain rarely understood. Through bioinformatics analysis, we examined the expression state and methylation site of LINC00857 in LUAD and further investigated the properties of LINC00857 as a competitive endogenous RNA in the cancer progression. The current study revealed that the overexpression of LINC00857 in LUAD tissue and cells was mainly caused by the hypomethylation of the promoter region. LINC00857 knockdown prominently reduced cell proliferation, impeded cell migration and invasion, and restrained lymph node metastasis, with enhancing radiosensitivity. The effects of LINC00857 on tumor growth were also investigated in nude mice models. Subsequently, the downstream factors, miR-486-5p and NEK2, were screened, and the putative regulatory axis was examined. Overall, the regulatory effect of methylation-mediated LINC00857 overexpression on miR-486-5p/NEK2 axis may be a new mechanism for LUAD progression.

Adenocarcinoma of Lung , Cell Proliferation , DNA Methylation , Disease Progression , Gene Expression Regulation, Neoplastic , Lung Neoplasms , MicroRNAs , RNA, Long Noncoding , Up-Regulation , MicroRNAs/genetics , MicroRNAs/metabolism , Humans , Animals , Mice , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Lung Neoplasms/metabolism , Adenocarcinoma of Lung/genetics , Adenocarcinoma of Lung/pathology , Adenocarcinoma of Lung/metabolism , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Cell Proliferation/genetics , NIMA-Related Kinases/genetics , NIMA-Related Kinases/metabolism , Cell Line, Tumor , Mice, Nude , Cell Movement/genetics , Male
Int J Biol Sci ; 20(7): 2440-2453, 2024.
Article En | MEDLINE | ID: mdl-38725860

Glioblastoma is the prevailing and highly malignant form of primary brain neoplasm with poor prognosis. Exosomes derived from glioblastoma cells act a vital role in malignant progression via regulating tumor microenvironment (TME), exosomal tetraspanin protein family members (TSPANs) are important actors of cell communication in TME. Among all the TSPANs, TSPAN6 exhibited predominantly higher expression levels in comparison to normal tissues. Meanwhile, glioblastoma patients with high level of TSPAN6 had shorter overall survival compared with low level of TSPAN6. Furthermore, TSPAN6 promoted the malignant progression of glioblastoma via promoting the proliferation and metastatic potential of glioblastoma cells. More interestingly, TSPAN6 overexpression in glioblastoma cells promoted the migration of vascular endothelial cell, and exosome secretion inhibitor reversed the migrative ability of vascular endothelial cells enhanced by TSPAN6 overexpressing glioblastoma cells, indicating that TSPAN6 might reinforce angiogenesis via exosomes in TME. Mechanistically, TSPAN6 enhanced the malignant progression of glioblastoma by interacting with CDK5RAP3 and regulating STAT3 signaling pathway. In addition, TSPAN6 overexpression in glioblastoma cells enhanced angiogenesis via regulating TME and STAT3 signaling pathway. Collectively, TSPAN6 has the potential to serve as both a therapeutic target and a prognostic biomarker for the treatment of glioblastoma.

Glioblastoma , STAT3 Transcription Factor , Signal Transduction , Tetraspanins , Glioblastoma/metabolism , Glioblastoma/pathology , Glioblastoma/genetics , Humans , STAT3 Transcription Factor/metabolism , Tetraspanins/metabolism , Tetraspanins/genetics , Cell Line, Tumor , Brain Neoplasms/metabolism , Brain Neoplasms/pathology , Brain Neoplasms/genetics , Animals , Cell Proliferation/genetics , Exosomes/metabolism , Cell Cycle Proteins/metabolism , Cell Cycle Proteins/genetics , Cell Movement/genetics , Disease Progression , Intracellular Signaling Peptides and Proteins/metabolism , Intracellular Signaling Peptides and Proteins/genetics , Mice
Pancreas ; 53(5): e450-e465, 2024 May 01.
Article En | MEDLINE | ID: mdl-38728212

BACKGROUND AND OBJECTIVES: Pancreatic cancer is one of the most lethal malignancies. Even though many substantial improvements in the survival rates for other major cancer forms were made, pancreatic cancer survival rates have remained relatively unchanged since the 1960s. Even more, no standard classification system for pancreatic cancer is based on cellular biomarkers. This review will discuss and provide updates about the role of stem cells in the progression of PC, the genetic changes associated with it, and the promising biomarkers for diagnosis. MATERIALS AND METHODS: The search process used PubMed, Cochrane Library, and Scopus databases to identify the relevant and related articles. Articles had to be published in English to be considered. RESULTS: The increasing number of studies in recent years has revealed that the diversity of cancer-associated fibroblasts is far greater than previously acknowledged, which highlights the need for further research to better understand the various cancer-associated fibroblast subpopulations. Despite the huge diversity in pancreatic cancer, some common features can be noted to be shared among patients. Mutations involving CDKN2, P53, and K-RAS can be seen in a big number of patients, for example. Similarly, some patterns of genes and biomarkers expression and the level of their expression can help in predicting cancer behavior such as metastasis and drug resistance. The current trend in cancer research, especially with the advancement in technology, is to sequence everything in hopes of finding disease-related mutations. CONCLUSION: Optimizing pancreatic cancer treatment requires clear classification, understanding CAF roles, and exploring stroma reshaping approaches.

Biomarkers, Tumor , Carcinoma, Pancreatic Ductal , Disease Progression , Pancreatic Neoplasms , Humans , Pancreatic Neoplasms/genetics , Pancreatic Neoplasms/pathology , Pancreatic Neoplasms/therapy , Carcinoma, Pancreatic Ductal/genetics , Carcinoma, Pancreatic Ductal/pathology , Carcinoma, Pancreatic Ductal/therapy , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Mutation , Cancer-Associated Fibroblasts/metabolism , Cancer-Associated Fibroblasts/pathology , Neoplastic Stem Cells/metabolism , Neoplastic Stem Cells/pathology
Sci Immunol ; 9(95): eadi4191, 2024 May 10.
Article En | MEDLINE | ID: mdl-38728412

Conventional dendritic cells (DCs) are essential mediators of antitumor immunity. As a result, cancers have developed poorly understood mechanisms to render DCs dysfunctional within the tumor microenvironment (TME). After identification of CD63 as a specific surface marker, we demonstrate that mature regulatory DCs (mregDCs) migrate to tumor-draining lymph node tissues and suppress DC antigen cross-presentation in trans while promoting T helper 2 and regulatory T cell differentiation. Transcriptional and metabolic studies showed that mregDC functionality is dependent on the mevalonate biosynthetic pathway and its master transcription factor, SREBP2. We found that melanoma-derived lactate activates SREBP2 in tumor DCs and drives conventional DC transformation into mregDCs via homeostatic or tolerogenic maturation. DC-specific genetic silencing and pharmacologic inhibition of SREBP2 promoted antitumor CD8+ T cell activation and suppressed melanoma progression. CD63+ mregDCs were found to reside within the lymph nodes of several preclinical tumor models and in the sentinel lymph nodes of patients with melanoma. Collectively, this work suggests that a tumor lactate-stimulated SREBP2-dependent program promotes CD63+ mregDC development and function while serving as a promising therapeutic target for overcoming immune tolerance in the TME.

Dendritic Cells , Lactic Acid , Mice, Inbred C57BL , Signal Transduction , Sterol Regulatory Element Binding Protein 2 , Dendritic Cells/immunology , Animals , Mice , Humans , Sterol Regulatory Element Binding Protein 2/immunology , Lactic Acid/metabolism , Signal Transduction/immunology , Melanoma/immunology , Melanoma/pathology , Disease Progression , Immune Tolerance/immunology , Female , Cell Line, Tumor , Tumor Microenvironment/immunology , Melanoma, Experimental/immunology , Melanoma, Experimental/pathology
J Infect Dev Ctries ; 18(4): 618-626, 2024 Apr 30.
Article En | MEDLINE | ID: mdl-38728647

INTRODUCTION: Hepatitis B virus (HBV) infection is a global epidemic that can lead to several liver diseases, seriously affecting people's health. This study aimed to investigate the clinical potential of serum ß-klotho (KLB) as a promising biomarker in HBV-related liver diseases. METHODOLOGY: This study enrolled 30 patients with chronic hepatitis B (CHB), 35 with HBV-related cirrhosis, 66 with HBV-related hepatocellular carcinoma (HCC), and 48 healthy individuals. ELISA measured the levels of serum KLB in the four groups. We then compared the differences in serum KLB levels among the groups and analyzed the relationship between serum KLB and routine clinical parameters. RESULTS: The concentrations of serum KLB levels were increased sequentially among the healthy subjects, the HBV-related CHB group, the HBV-related cirrhosis group, and the HBV-related HCC group (p < 0.05). Expression of KLB was positively correlated with alpha-fetoprotein (AFP), total bilirubin, direct bilirubin, alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl-transferase, alkaline phosphatase, total bile acid, serum markers for liver fibrosis, ascites, cirrhosis, splenomegaly, and model for end-stage liver disease sodium, while negatively correlated with platelet count, albumin, and prothrombin activity (p < 0.05). In addition, serum KLB has better sensitivity in diagnosing HCC than AFP, and serum KLB combined with AFP has higher sensitivity and specificity than AFP alone in diagnosing HCC. CONCLUSIONS: Serum KLB level is associated with the severity of HBV-related liver diseases and has important diagnostic value for HCC. Therefore, it could be a predictive biomarker for monitoring disease progression.

Biomarkers , Carcinoma, Hepatocellular , Hepatitis B, Chronic , Klotho Proteins , Humans , Male , Female , Biomarkers/blood , Middle Aged , Adult , Hepatitis B, Chronic/blood , Hepatitis B, Chronic/complications , Carcinoma, Hepatocellular/blood , Carcinoma, Hepatocellular/diagnosis , Carcinoma, Hepatocellular/virology , Glucuronidase/blood , Liver Neoplasms/blood , Liver Neoplasms/diagnosis , Liver Neoplasms/virology , Liver Cirrhosis/blood , Liver Cirrhosis/diagnosis , Liver Cirrhosis/virology , Disease Progression , Enzyme-Linked Immunosorbent Assay , Aged
Medicine (Baltimore) ; 103(19): e38169, 2024 May 10.
Article En | MEDLINE | ID: mdl-38728450

We investigated the correlation of orthostatic hypotension (OH) in Parkinson disease (PD) with the disease course and severity, and its possible impact on quality of life. 171 PD patients were recruited and divided into the PD-NOH (n = 91) and PD-OH groups (n = 80). Clinical data were collected. The severity and quality of life of PD patients were evaluated. The impact of disease severity was analyzed using logistic regression analysis. The ROC curve was plotted. There were significant differences (P < .05) between PD-NOH and PD-OH groups in terms of the disease course, non-motor symptoms (somnipathy), Hoehn&Yahr stage, LEDD score, RBDSQ score, PDQ-39 score, MMSE score, MoCA, MDS-UPDRS Part III scores during off- and on-periods, and NMSS score. Hoehn&Yahr stage (OR 4.950, 95% CI 1.516-16.157, P = .008) was closely associated with the risk of OH in PD. PDQ-39 score (OR 1.079, 95% CI 1.033-1.127, P = .001) in PD patients with OH further decreased. Patients with PD-OH experienced severe impairment in 4 dimensions of quality of life, including motor function, cognitive function, physical discomfort, and activities of daily living. Different clinical symptoms of PD-OH were positively correlated with PDQ39 subscales. The area under the ROC curve of the Hoehn&Yahr stage in predicting the occurrence of OH was 0.679 (95% CI 0.600-0.758), and that of the Hoehn&Yahr stage combined with levodopa equivalent dose, and MDS-UPDRS Part III score during off-period was 0.793 (95% CI 0.727-0.862). Higher Hoehn&Yahr stage is associated with increased risk of OH in PD patients, and deteriorated quality of life of PD patients. Patients with different OH symptoms are affected in different dimensions of their quality of life. The Hoehn & Yahr stage can independently predict the risk of OH in PD patients.

Hypotension, Orthostatic , Parkinson Disease , Quality of Life , Severity of Illness Index , Humans , Parkinson Disease/complications , Parkinson Disease/psychology , Parkinson Disease/physiopathology , Hypotension, Orthostatic/etiology , Hypotension, Orthostatic/epidemiology , Male , Female , Aged , Middle Aged , Disease Progression
Medicine (Baltimore) ; 103(19): e38138, 2024 May 10.
Article En | MEDLINE | ID: mdl-38728500

INTRODUCTION: Systemic therapy is recommended for patients with advanced hepatocellular carcinoma (aHCC). However, drug resistance occurs over time when patients receive systemic therapy, resulting in cancer progression. Due to the lack of relevant clinical trials, optimizing subsequent treatments after cancer progression remains elusive. PATIENT CONCERNS: A 52-year-old male patient presented with epigastric discomfort and fatigue for almost 1 month with a past history of chronic hepatitis B virus infection for 30 years. DIAGNOSIS: Based on the patient's performance status, tumor status assessed by computed tomography, liver function, he was diagnosed with HCC at BCLC stage C. INTERVENTIONS AND OUTCOMES: He first received transarterial chemoembolization (TACE) combined with sintilimab and lenvatinib as first-line treatment and experienced 10-month progression-free survival. After cancer progression, the patient participated in a clinical trial of ABSK-011, a novel fibroblast growth factor receptor 4 inhibitor, with a frustrating result. Then, the patient underwent TACE and received sintilimab plus lenvatinib again. Surprisingly, the tumor had a partial response, and the patient's serum alpha-fetoprotein returned to normal. LESSONS: The combined treatment of TACE plus systemic therapy might be an appropriate subsequent treatment.

Carcinoma, Hepatocellular , Chemoembolization, Therapeutic , Disease Progression , Liver Neoplasms , Phenylurea Compounds , Quinolines , Humans , Male , Carcinoma, Hepatocellular/therapy , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/pathology , Liver Neoplasms/therapy , Liver Neoplasms/drug therapy , Liver Neoplasms/pathology , Middle Aged , Quinolines/therapeutic use , Chemoembolization, Therapeutic/methods , Phenylurea Compounds/therapeutic use , Phenylurea Compounds/administration & dosage , Antibodies, Monoclonal, Humanized/therapeutic use , Antibodies, Monoclonal, Humanized/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/therapeutic use
Zhonghua Gan Zang Bing Za Zhi ; 32(4): 370-374, 2024 Apr 20.
Article Zh | MEDLINE | ID: mdl-38733194

Authoritative guidelines at home and abroad typically classify chronic hepatitis B virus (HBV) infection into four stages. However, in clinical practice, a considerable number of patients do not meet the guidelines for staging and are called "indeterminate phase" chronic HBV- infected patients. Studies have shown that patients in the indeterminate phase account for about 30%-50% of chronic HBV infection, have significant liver histological changes or even cirrhosis in a large proportion, and are at a higher risk of HCC and death if they do not receive antiviral therapy. Preliminary research shows that patients in the indeterminate phase who receive antiviral treatment have a good virological response and a remarkable reduced HCC risk. To this end, the 2022 publication "Expert Opinions on Expanding Antiviral Treatment for Chronic Hepatitis B" recommends aggressive treatment for patients with an indeterminate phase who have undergone more than a year of follow-up. However, there is still a lack of unified standards to refine the classification, as well as a lack of effective and rapid non-invasive diagnostic methods to identify patients in the indeterminate phase who are at risk for disease progression. This article aims to review the researches on the proportion, clinical characteristics, disease progression, and treatment benefits to further explore how to better manage indeterminate-phase chronic HBV-infected patients.

Antiviral Agents , Hepatitis B virus , Hepatitis B, Chronic , Humans , Hepatitis B, Chronic/diagnosis , Hepatitis B, Chronic/drug therapy , Antiviral Agents/therapeutic use , Hepatitis B virus/genetics , Disease Progression , Liver Cirrhosis/diagnosis , Liver Cirrhosis/etiology , Liver Neoplasms/diagnosis , Liver Neoplasms/therapy , Carcinoma, Hepatocellular/diagnosis , Carcinoma, Hepatocellular/therapy