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1.
IEEE Trans Biomed Eng ; PP2024 Sep 03.
Article in English | MEDLINE | ID: mdl-39226200

ABSTRACT

Perfusion index (PI), the ratio between variable pulsatile (AC) and non-pulsatile (DC) components in a photoplethysmographic (PPG) signal, is an indirect and non-invasive measure of peripheral perfusion. PI has been widely used in assessing sympathetic block success, and monitoring hemodynamics in anesthesia and intensive care. Based on the principle of dual-wavelength depolarization (DWD) of skin tissues, we propose to investigate its opportunity in quantifying the skin perfusion contactlessly. The proposed method exploits the characteristic changes in chromaticity caused by skin depolarization and chromophore absorption. The experimental results of DWD, obtained with the post occlusive reactive hyperemia test and the local cooling and heating test, were compared to the PI values obtained from the patient monitor and photoplethysmography imaging (PPGI). The comparison demonstrated the feasibility of using DWD for PI measurement. Clinical trials conducted in the anesthesia recovery room and operating theatre further showed that DWD is potentially a new metric for camera-based non-contact skin perfusion monitoring during clinical operations, such as the guidance in anesthetic surgery.

2.
Biochim Biophys Acta Mol Basis Dis ; 1871(1): 167509, 2024 Sep 12.
Article in English | MEDLINE | ID: mdl-39277057

ABSTRACT

The recurrence of glioma after treatment has remained an intractable problem for many years. Recently, numerous studies have explored the pivotal role of the mouse double minute 2 (MDM2)/p53 pathway in cancer treatment. Lysine phosphate phosphohistidine inorganic pyrophosphate phosphatase (LHPP), a newly discovered tumor suppressor, has been confirmed in numerous studies on tumors, but its role in glioma remains poorly understood. Expression matrices in The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) databases were analyzed using gene set enrichment analysis (GSEA), revealing significant alterations in the p53 pathway among glioma patients with high LHPP expression. The overexpression of LHPP in glioma cells resulted in a reduction in cell proliferation, migration, and invasive ability, as well as an increase in apoptosis and alterations to the cell cycle. The present study has identified a novel inhibitory mechanism of LHPP against glioma, both in vivo and in vitro. The results demonstrate that LHPP exerts anti-glioma effects via the MDM2/p53 pathway. These findings may offer a new perspective for the treatment of glioma in the clinic.

3.
Spine J ; 2024 Sep 28.
Article in English | MEDLINE | ID: mdl-39349258

ABSTRACT

BACKGROUND CONTEXT: Use of an anterior cervical dynamic implant (ACDI) is generally considered a non-fusion technique for treating cervical degenerative disorders. However, there is limited research focused on evaluating the long-term clinical and radiographic outcomes of ACDI. PURPOSE: To analyze the long-term clinical and radiographic outcomes of ACDI in the treatment of degenerative cervical disorders. STUDY DESIGN: A retrospective cohort study PATIENTS SAMPLE: Patients with degenerative cervical disorders who underwent anterior cervical discectomy and dynamic cervical implant (DCI) implantation between May 2012 and August 202 at our institution were included in this study. OUTCOME MEASURES: Clinical outcomes were assessed using the modified Japanese Orthopedic Association (mJOA), visual analog scale (VAS) scores and patient reported satisfaction rate. Imaging assessment parameters included intervertebral height (IH), intervertebral disc height (IDH), C2-7 range of motion (ROM), segmental ROM, the degree of DCI subsidence and anterior migration, heterotopic ossification (HO) as well as adjacent segment degeneration (ASD). METHODS: JOA and VAS scores were obtained through questionnaire. The patient reported satisfaction was rated as very satisfied, satisfied, less satisfied and dissatisfied at the final follow-up. The position of the implants, IDH and IH were evaluated on lateral radiographs. ROM at C2-7, ROM at operated level were measured on dynamic radiographs. Cervical three -dimensional computer tomography (CT) and magnetic resonance image (MRI) images were used to assess the presence of HO and ASD. The clinical and radiologic variables between the preoperative period and different follow-up time point were statistically analyzed by unpaired t-tests or chi-square tests. Statistical significance was defined as p<0.05. RESULTS: A total of 92 patients (51 males and 41 females) were included in this study. Among them, there were 36 cases of cervical spondylotic myelopathy, 26 cases of cervical radiculopathy, and 30 cases of myeloradiculopathy. The mean age was 55.1±12.6 years. The number of operated levels was single level in 57 patients, two levels in 31 patients, and three levels in 4 patients. The average follow-up period was 81.3 months (range: 35-135 months). The mean JOA scores showed a gradual increase at one month, one year, and the final follow-up (12.0±0.7,13.5±0.8, and14.4±1.1 respectively) compared to the preoperative score (9.1±0.9, p<0.01). VAS scores significantly decreased at one month, one year, and the final follow-up (4.1±0.7,2.3±0.9, and 2.0±0.8 respectively) compared to the preoperative score (7.2±l .2, p<0 .01). At the final follow-up, the patient reported satisfaction was rated as very satisfied, satisfied, less satisfied and dissatisfied (79%, 10%, 10%, 1% respectively). Revision surgery was not required for any of the patients during the follow-up period, either due to instrumentation failure or adjacent segmental diseases. In the radiographic assessment, there was a notable increase in IH and IDH after surgery compared to preoperative values (33.0±4.0mm vs 30.7±3.0mm, p<0.01 and 6.7±2.4mm vs 4.6±0.9mm, p<0.01 respectively), which gradually decreased at 1 year and the final follow-up (IH: 32.1±2.5 vs 30.9±3.5 p=0.024; IDH: 5.3±1.5 mm vs 4.3±0.6 mm, p=0.043 respectively). At the one-month postoperative follow-up, the segmental ROM exhibited a decrease compared with preoperative values (6.2±1.8° vs 7.5±2.0° p=0.044), followed by an increase at the one-year follow-up (6.2±1.8° vs 6.4±1.5° p=0 .078), but ultimately decreased at the final follow-up (6.4±1.5° vs 2.9±0.6°, p<0.01). HO was observed in approximately 81.5% of cases (75/92), while a great proportion (41.3%) of patients experienced varying degrees of prosthesis subsidence and anterior migration during the follow-up. CONCLUSION: At the long-term follow-up, a high incidence of HO, along with varying degrees of subsidence and migration of the prosthesis, were observed in most patients. As the motion preservation capability of the ACDI gradually diminishes, delayed intervertebral autofusion becomes a more likely outcome compared to motion sparing.

4.
Chem Biol Interact ; 402: 111202, 2024 Oct 01.
Article in English | MEDLINE | ID: mdl-39128802

ABSTRACT

High-grade gliomas, including glioblastoma multiforme (GBM), continue to be a leading aggressive brain tumor in adults, marked by its rapid growth and invasive nature. Aldehyde dehydrogenase 1 family, member A1 (ALDH1A1), an enzyme, plays a significant role in tumor progression, yet its function in high-grade gliomas is still poorly investigated. In this study, we evaluated ALDH1A1 levels in clinical samples of GBM. We also assessed the prognostic significance of ALDH1A1 expression in GBM and LGG (low grade glioma) patients using TCGA (The Cancer Genome Atlas) database analysis. The MTT and transwell assays were utilized to examine cell growth and the invasive capability of U87 cells, respectively. We quantitatively examined markers for cell proliferation (Ki-67 and cyclin D1) and invasion (MMP2 and 9). A Western blot test was conducted to determine the downstream signaling of ALDH1A1. We found a notable increase in ALDH1A1 expression in high-grade gliomas compared to their low-grade counterparts. U87 cells that overexpressed ALDH1A1 showed increased cell growth and invasion. We found that ALDH1A1 promotes the phosphorylation of AKT, and inhibiting AKT phosphorylation mitigates the ALDH1A1's effects on tumor growth and migration. In summary, our findings suggest ALDH1A1 as a potential therapeutic target for GBM treatment.


Subject(s)
Aldehyde Dehydrogenase 1 Family , Brain Neoplasms , Cell Movement , Cell Proliferation , Glioblastoma , Neoplasm Invasiveness , Retinal Dehydrogenase , Humans , Glioblastoma/pathology , Glioblastoma/metabolism , Glioblastoma/genetics , Aldehyde Dehydrogenase 1 Family/metabolism , Aldehyde Dehydrogenase 1 Family/genetics , Cell Line, Tumor , Retinal Dehydrogenase/metabolism , Retinal Dehydrogenase/genetics , Brain Neoplasms/pathology , Brain Neoplasms/metabolism , Brain Neoplasms/genetics , Proto-Oncogene Proteins c-akt/metabolism , Phosphorylation , Matrix Metalloproteinase 2/metabolism , Matrix Metalloproteinase 2/genetics , Cyclin D1/metabolism , Cyclin D1/genetics , Signal Transduction
5.
J Chin Med Assoc ; 2024 Aug 06.
Article in English | MEDLINE | ID: mdl-39105305

ABSTRACT

BACKGROUND: Synthetic mid-urethral sling surgery has long been the standard surgical treatment for stress urinary incontinence (SUI) worldwide. Using an autologous fascial sling is an alternative to reduce adverse events. We evaluated the treatment outcomes of a novel fixation method applied to the autologous transobturator fascial (TOF) sling procedure for female patients with SUI. METHODS: A retrospective study was conducted between 2017 and 2020, including 33 patients with SUI who underwent mid-urethral TOF sling surgery with the novel fixation method. We used a self-locking feature (V-LOC™) that was fixed to each side of skin layer above the obturator foramen, and the tension of the fascia sling was adjusted by manipulating the V-LOC™ suture. We analyzed all data collected through questionnaires, including Urinary Distress Inventory-Short Form (UDI-6), Incontinence Impact Questionnaire-Short Form (IIQ-7), Overactive Bladder Symptom Score (OABSS), and Clinical Global Impressions of Improvement (CGI-I). Adverse events were also recorded. RESULTS: This study included 33 female patients aged 39-79 (mean 59.76 years). Following the procedure, there was a significant reduction in the total scores of UDI-6, IIQ-7, and OABSS (preoperative 9.73±4.35, 10.21±5.79, 6.06±4.03 and postoperative 3.52±3.41, 0.85±3.67, 3.06±2.90, respectively) (p < 0.001). Further analysis of each sub-score of the questionnaires revealed significant improvement in certain symptoms. The mean total score of CGI-I was 2.00 ± 0.80. The maximum flow rate was documented for 18 patients, and no significant reduction was observed after the procedure (p = 0.804). Complications reported included voiding dysfunction in two patients (6.1 %), inguinal pain in one patient (3.0 %), and mild delayed wound healing in one patient (3.0 %). CONCLUSION: This modified TOF sling surgery with a novel fixation method by V-LOC™ suture offers feasibility and adjustability as its main advantages. Our study demonstrated significant improvements in patient outcomes.

6.
Article in English | MEDLINE | ID: mdl-38970420

ABSTRACT

Significance: Herbal medicines have a long history of comprehensive cancer treatment through various posttranslational modifications (PTMs). Recently, emerging evidence revealed that dysregulation of reactive oxygen species (ROS) and ROS-regulated signaling pathways influence cancer initiation, growth, and progression in a paradoxical role with either low levels or increasing levels of basal ROS. However, ROS-triggered modifications of target proteins in the face of ROS-mediated signal transduction are not fully understood in the anticancer therapies of herbal medicines. In this review, we briefly introduce the PTM-dependent regulations of herbal medicines, and then focus on the current ideals that targeting ROS-dependent PTMs via antioxidant and redox signaling pathways can provide a promising strategy in herbal-based anticancer effects. Recent Advances: Advanced development in highly sensitive mass spectrometry-based techniques has helped utilize ROS-triggered protein modifications in numerous cancers. Accumulating evidence has been achieved in laboratory to extensively ascertain the biological mechanism of herbal medicines targeting ROS in cancer therapy. Two general mechanisms underlining ROS-induced cell signaling include redox state and oxidative modification of target protein, indicating a new perspective to comprehend the intricate dialogues between herbal medicines and cancer cellular contexts. Critical Issues: Complex components of herbal medicines limit the benefits of herbal-based cancer therapies. In this review, we address that ROS-dependent PTMs add a layer of proteomic complexity to the cancer through altering the protein structure, expression, function, and localization. Elaborating ROS-triggered PTMs implicated in cell signaling, apoptosis, and transcriptional regulation function, and the possible cellular signaling, has provided important information about the contribution of many ROS targeting herbal therapies in anticancer effects. Continued optimization of proteomic strategies for PTM analysis in herbal medicines is also briefly discussed. Future Directions: Rigorous evaluations of herbal medicines and proteomic strategies are necessary to explore the aberrant regulation of ROS-triggered antioxidant and redox signaling contributing to the novel protein targets and herbal-associated pharmacological issues. These efforts will eventually help develop more herbal drugs as modern therapeutic agents.

8.
bioRxiv ; 2024 Sep 22.
Article in English | MEDLINE | ID: mdl-38826317

ABSTRACT

Cancer-associated fibroblasts (CAFs) play a key role in metabolic reprogramming and are well-established contributors to drug resistance in colorectal cancer (CRC). To exploit this metabolic crosstalk, we integrated a systems biology approach that identified key metabolic targets in a data-driven method and validated them experimentally. This process involved a novel machine learning-based method to computationally screen, in a high-throughput manner, the effects of enzyme perturbations predicted by a computational model of CRC metabolism. This approach reveals the network-wide effects of metabolic perturbations. Our results highlighted hexokinase (HK) as the crucial target, which subsequently became our focus for experimental validation using patient-derived tumor organoids (PDTOs). Through metabolic imaging and viability assays, we found that PDTOs cultured in CAF-conditioned media exhibited increased sensitivity to HK inhibition, confirming the model predictions. Our approach emphasizes the critical role of integrating computational and experimental techniques in exploring and exploiting CRC-CAF crosstalk.

9.
Mod Rheumatol ; 2024 May 30.
Article in English | MEDLINE | ID: mdl-38813667

ABSTRACT

OBJECTIVES: To compare the lumbar posterior lesions between axial spondyloarthritis (axSpA) and lumbar disc herniation (LDH) patients, then their diagnostic value and related factors were evaluated. METHODS: This cross-sectional study included axSpA patients from January 2020 to September 2023. They were classified as ankylosing spondylitis (AS) and non-radiographic axSpA (nr-axSpA) individuals. Canada-Denmark (CANDEN) magnetic resonance imaging (MRI) scoring system was used to assess the defects of the lumbar spine. Receiver operating characteristic curve analysis was utilized to determine the value of distinguishing nr-axSpA. Linear regression analyses were adopted to find the relevant factors for lumbar posterior lesions. RESULTS: Ninety-six AS, 98 nr-axSpA, and 108 LDH patients were included. The CANDEN scores were greater in axSpA patients, AS in particular. Furthermore, lumbar posterior lesions can distinguish AS, nr-axSpA, and LDH. Besides, lumbar posterior lesions were positively related to the similar MRI changes in their adjacent structures, but were inversely associated with the other abnormalities. CONCLUSIONS: Lumbar posterior lesions were more serious in axSpA patients. These alterations had value in distinguishing axSpA. Lumbar posterior defects were related to their adjacent components, and they may not fully follow the MRI changing pattern of vertebral bodies and sacroiliac joints.

10.
J Int Med Res ; 52(4): 3000605241244761, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38661083

ABSTRACT

OBJECTIVE: To investigate the role of albumin-to-globulin ratio (AGR) in systemic lupus erythematosus (SLE) and its relationship with disease activity. METHODS: This retrospective study consecutively selected patients with SLE and healthy controls. Patients were divided into three groups according to the SLE Disease Activity Index 2000 (SLEDAI-2K): group 1 (mild disease activity, SLEDAI-2K ≤ 6), group 2 (moderate disease activity, SLEDAI-2K 7-12) and group 3 (severe disease activity, SLEDAI-2K > 12). Predictors of SLE disease activity were analysed by ordinal logistical regression. RESULTS: A total of 101 Chinese patients with SLE and 75 healthy Chinese controls were included. Patients with SLE had lower AGR values than healthy individuals, and group 3 patients with SLE displayed lower AGR values than those in group 1, but similar values to group 2. AGR was inversely correlated with SLEDAI-2K (r = -0.543). Ordinal logistic regression analysis showed that lower AGR (ß = -1.319) and lower complement C4 (ß = -1.073) were independent risk factors for SLE disease activity. CONCLUSIONS: AGR was decreased in patients with SLE and may be utilized as a useful inflammatory biomarker for monitoring SLE disease activity.


Subject(s)
Lupus Erythematosus, Systemic , Serum Albumin , Adult , Female , Humans , Male , Middle Aged , Biomarkers/blood , Case-Control Studies , Complement C4/metabolism , Complement C4/analysis , Logistic Models , Lupus Erythematosus, Systemic/blood , Lupus Erythematosus, Systemic/diagnosis , Retrospective Studies , Risk Factors , Serum Albumin/analysis , Serum Albumin/metabolism , Serum Globulins/analysis , Serum Globulins/metabolism , Severity of Illness Index
11.
Adv Rheumatol ; 64(1): 18, 2024 03 04.
Article in English | MEDLINE | ID: mdl-38438904

ABSTRACT

INTRODUCTION: If a large amount of urate crystals is deposited in a joint cavity for an extended period of time, bone erosion will occur and gradually cause skeletal muscle necrosis and joint deformity. The aim of this study was to describe the clinical characteristics and factors associated with bone erosion in gout patients with tophi. METHODS: A total of 210 gout patients with tophi were enrolled and divided into a bone erosion group (n = 135) and a non-bone erosion group (n = 75). Digital radiography (DR) was performed to detect bone erosion in the elbow, wrist, knee, ankle joints, interphalangeal and metatarsophalangeal joints. The clinical characteristics were recorded and compared between the two groups. Multivariate logistic regression analysis was conducted to explore the factors associated with bone erosion. RESULTS: Compared with the non-bone erosion group, the bone erosion group had an older age, longer disease duration of gout and tophi, higher level of serum creatinine (sCr), higher proportion of drinking history and ulceration, and a lower glomerular filtration rate (GFR). Univariate logistic regression analysis results showed that sex, age, body mass index (BMI), gout duration, tophi duration, GFR, white blood cell (WBC) count, sCr level, smoking history, drinking history, and presence of ulceration were associated with bone destruction. Multivariable logistic regression analysis results indicated that tophi duration, drinking history, ulceration and sCr were positively and independently related to bone erosion. CONCLUSIONS: Tophi patients with bone erosion presented different clinical characteristics. Tophi duration, drinking history, ulceration and sCr were associated with bone erosion in gout patients with tophi.


Subject(s)
Gout , Humans , Gout/complications , Risk Factors , Smoking/adverse effects , Body Mass Index , Glomerular Filtration Rate
12.
Waste Manag Res ; : 734242X241237107, 2024 Mar 18.
Article in English | MEDLINE | ID: mdl-38497604

ABSTRACT

Removing water-soluble chlorides (WSCs) through water extraction is a common pretreatment technology for recycling municipal solid waste incineration (MSWI) fly ash (FA). However, the extracted solution often contains heavy metals, the concentrations of which exceed standards for effluent. This study aims to investigate the adsorption of heavy metals by palygorskite in water-extracted solution and explore the feasibility of stabilizing heavy metals through comilling palygorskite-adsorbed heavy metals (PAHMs) with water-extracted fly ash (WFA). The experimental parameters include: two-stage water extraction with a liquid-to-solid ratio of 5, adding 0, 0.125, 0.25, 0.5, 1, 2 or 3 g of palygorskite to 100 mL of water-extracted solution, and comilling the mixture of PAHMs and WFA for 0, 0.5, 1, 2, 4, 8, 12, 24 or 96 hours. The experimental results revealed that 3 g of palygorskite in 100 mL of extracted solution could absorb Pb, Cd, Cr, Cu and Zn, meeting the effluent standards. The total amount of Pb, Cd, Cr, Cu and Zn removal rate reached 99.7%. Moreover, 98.44% of the WSCs were not adsorbed, the water extraction process for removing WSCs was not compromised. After the comilling of PAHMs and WFA, the distribution of the heavy metals in the milled blended powder was greater than 99.44%; moreover, toxicity characteristic leaching procedure concentrations were determined to conform to regulatory standards, and the sequential extraction procedure revealed that the heavy metals tended to be in stable fractions. This achieves the goal of preventing secondary pollution from heavy metals during the MSWI FA recycling process.

13.
Mol Biol Rep ; 51(1): 421, 2024 Mar 14.
Article in English | MEDLINE | ID: mdl-38483756

ABSTRACT

BACKGROUND: Osteophyte development is a common characteristic of inflammatory skeletal diseases. Elevated osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) participates in pathological osteogenesis. Integrin-linked kinase (ILK) positively regulates the osteoblastic differentiation of osteoprogenitors, but whether the ILK blockage prevents osteophytes and its potential mechanism is still unknown. Furthermore, the low-dose tumor necrosis factor-α (TNF-α) promotes osteogenic differentiation, but a lack of study reports on the relationship between this cytokine and ILK. OSU-T315 is a small ILK inhibitor, which was used to determine the effect of ILK inhibition on osteogenesis and osteophyte formation. METHODS AND RESULTS: The osteogenesis of BMSCs was evaluated using Alizarin red S staining, alkaline phosphatase, collagen type I alpha 2 chain, and bone gamma-carboxyglutamate protein. The expression and phosphorylation of protein were assessed through western blot. Immunofluorescence was employed to display the distribution of ß-catenin. microCT, hematoxylin-eosin, and safranin O/fast green staining were utilized to observe the osteophyte formation in collagen antibody-induced arthritis mice. We found that ILK blockage significantly declined calcium deposition and osteoblastic markers in a dose- and time-dependent manner. Furthermore, it lowered osteogenesis in the TNF-α-induced inflammatory microenvironment by diminishing the effect of ILK and inactivating the Akt/ GSK-3ß/ ß-catenin pathway. Nuclear ß-catenin was descended by OSU-T315 as well. Finally, the ILK suppression restrained osteophyte formation but not inflammation in vivo. CONCLUSIONS: ILK inhibition lowered osteogenesis in TNF-α-related inflammatory conditions by deactivating the Akt/ GSK-3ß/ ß-catenin pathway. This may be a potential strategy to alleviate osteophyte development in addition to anti-inflammatory treatment.


Subject(s)
Mesenchymal Stem Cells , Osteophyte , Protein Serine-Threonine Kinases , Mice , Animals , Osteogenesis , Glycogen Synthase Kinase 3 beta/metabolism , Proto-Oncogene Proteins c-akt/metabolism , beta Catenin/metabolism , Osteophyte/metabolism , Tumor Necrosis Factor-alpha/metabolism , Mesenchymal Stem Cells/metabolism , Cell Differentiation , Cells, Cultured , Wnt Signaling Pathway
14.
IEEE Trans Biomed Circuits Syst ; 18(5): 1001-1013, 2024 Oct.
Article in English | MEDLINE | ID: mdl-38408001

ABSTRACT

This paper presents a low-noise bioimpedance (bio-Z) spectroscopy interface for electrical impedance myography (EIM) over the 1 kHz to 2 MHz frequency range. The proposed interface employs a sinusoidal signal generator based on direct-digital-synthesis (DDS) to improve the accuracy of the bio-Z reading, and a quadrature low-intermediate frequency (IF) readout to achieve a good noise-to-power efficiency and the required data throughput to detect muscle contractions. The readout is able to measure baseline and time-varying bio-Z by employing robust and power-efficient low-gain IAs and sixth-order single-bit bandpass (BP) ∆Σ ADCs. The proposed bio-Z spectroscopy interface is implemented in a 180 nm CMOS process, consumes 344.3 - 479.3 µW, and occupies 5.4 mm2 area. Measurement results show 0.7 m Ω/[Formula: see text] sensitivity at 15.625 kHz, 105.8 dB SNR within 4 Hz bandwidth, and a 146.5 dB figure-of-merit. Additionally, recording of EIM in time and frequency domain during contractions of the bicep brachii muscle demonstrates the potential of the proposed bio-Z interface for wearable EIM systems.


Subject(s)
Dielectric Spectroscopy , Electric Impedance , Humans , Dielectric Spectroscopy/instrumentation , Dielectric Spectroscopy/methods , Signal Processing, Computer-Assisted/instrumentation , Equipment Design , Myography/instrumentation , Myography/methods , Muscle, Skeletal/physiology , Signal-To-Noise Ratio
15.
Int Immunopharmacol ; 130: 111735, 2024 Mar 30.
Article in English | MEDLINE | ID: mdl-38412675

ABSTRACT

OBJECTIVE: To identify the long non-coding RNA (lncRNA) expression profiling in exosomes derived from synovial fluid of rheumatoid arthritis (RA) patients, and carry out bioinformatics analysis on target genes of differentially expressed lncRNAs. METHODS: Exosomes were isolated from synovial fluid via ultracentrifugation. RNAs were extracted from exosomes by using HiPure Liquid RNA/miRNA kits, followed by lncRNA sequencing. Differentially expressed lncRNAs in RA were screened, and bioinformatics analysis of their target genes was carried out. qRT-PCR was used to verify the lncRNA expression levels. RESULTS: Compared with osteoarthritis (OA), 347 lncRNAs were found differentially expressed in RA. Compared with gout, 805 lncRNAs were found differentially expressed in RA. Compared with both OA and gout, 85 lncRNAs were found specially expressed in RA (65 were upregulated (including ENST00000433825.1)). Functional analysis of target genes of the specially expressed lncRNAs revealed significant enrichment of "autophagy" and "mTOR signaling pathway". The qRT-PCR results indicated that ENST00000433825.1 was highly expressed in RA, compared with both OA and gout (P < 0.05), which matched the lncRNA sequencing results. Correlation analysis showed that the level of ENST00000433825.1 in RA patients was significantly and positively correlated with the level of C-reactive protein (CRP) (P < 0.001). CONCLUSIONS: The lncRNA expression profiling in exosomes derived from synovial fluid of RA was significantly different from OA and gout. ENST00000433825.1 was highly and uniquely expressed in RA and significantly and positively correlated with CRP, which might provide a diagnostic and therapeutic biomarker for RA.


Subject(s)
Arthritis, Rheumatoid , Exosomes , Gout , Osteoarthritis , RNA, Long Noncoding , Humans , RNA, Long Noncoding/genetics , Synovial Fluid/metabolism , Exosomes/genetics , Exosomes/metabolism , Arthritis, Rheumatoid/genetics , Arthritis, Rheumatoid/metabolism , Osteoarthritis/genetics , Osteoarthritis/metabolism
16.
Nat Cancer ; 5(3): 400-419, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38267627

ABSTRACT

Kirsten rat sarcoma virus (KRAS) signaling drives pancreatic ductal adenocarcinoma (PDAC) malignancy, which is an unmet clinical need. Here, we identify a disintegrin and metalloproteinase domain (ADAM)9 as a modulator of PDAC progression via stabilization of wild-type and mutant KRAS proteins. Mechanistically, ADAM9 loss increases the interaction of KRAS with plasminogen activator inhibitor 1 (PAI-1), which functions as a selective autophagy receptor in conjunction with light chain 3 (LC3), triggering lysosomal degradation of KRAS. Suppression of ADAM9 by a small-molecule inhibitor restricts disease progression in spontaneous models, and combination with gemcitabine elicits dramatic regression of patient-derived tumors. Our findings provide a promising strategy to target the KRAS signaling cascade and demonstrate a potential modality to enhance sensitivity to chemotherapy in PDAC.


Subject(s)
Carcinoma, Pancreatic Ductal , Pancreatic Neoplasms , Humans , Proto-Oncogene Proteins p21(ras) , Cell Proliferation , Pancreatic Neoplasms/drug therapy , Carcinoma, Pancreatic Ductal/drug therapy , Gemcitabine , Membrane Proteins/metabolism , ADAM Proteins/metabolism , ADAM Proteins/therapeutic use
17.
Article in English | MEDLINE | ID: mdl-38083039

ABSTRACT

Multi-wavelength pulse transmit time (MV-PTT) is a potential tool for remote blood pressure (BP) monitoring. It uses two wavelengths, typically green (G) and near-infrared (NIR), that have different skin penetration depths to measure the PTT between artery and arterioles of a single site of the skin for BP estimation. However, the impact of wavelength selection for MV-PTT based BP calibration is unknown. In this paper, we explore the combination of different wavelengths of camera photoplethysmography for BP measurement using a modified narrow-band camera centered at G-550/R-660/NIR-850 nm, especially focused on the comparison between G-R (full visible) and G-NIR (hybrid). The experiment was conducted on 17 adult participants in a dark chamber with their BP significantly changed by the protocol of ice water stimulation. The experimental results show that the MV-PTT obtained by G-NIR has a higher correlation with BP, and the fitted model has lower MAE in both the systolic pressure (5.78 mmHg) and diastolic pressure (6.67 mmHg) than others. It is confirmed that a hybrid wavelength of visible (G) and NIR is still essential for accurate BP calibration due to their difference in skin penetration depth that allows proper sensing of different skin layers for this measurement.


Subject(s)
Blood Pressure Determination , Pulse Wave Analysis , Adult , Humans , Blood Pressure/physiology , Blood Pressure Determination/methods , Heart Rate/physiology , Monitoring, Physiologic
18.
Brain Sci ; 13(10)2023 Oct 07.
Article in English | MEDLINE | ID: mdl-37891793

ABSTRACT

Optic pathway glioma (OPG) is one of the causes of pediatric visual impairment. Unfortunately, there is as yet no cure for such a disease. Understanding the underlying mechanisms and the potential therapeutic strategies may help to delay the progression of OPG and rescue the visual morbidities. Here, we provide an overview of preclinical OPG studies and the regulatory pathways controlling OPG pathophysiology. We next discuss the role of microenvironmental cells (neurons, T cells, and tumor-associated microglia and macrophages) in OPG development. Last, we provide insight into potential therapeutic strategies for treating OPG and promoting axon regeneration.

19.
Mol Aspects Med ; 94: 101219, 2023 12.
Article in English | MEDLINE | ID: mdl-37839232

ABSTRACT

Glaucoma is a neurodegenerative eye disease that causes permanent vision impairment. The main pathological characteristics of glaucoma are retinal ganglion cell (RGC) loss and optic nerve degeneration. Glaucoma can be caused by elevated intraocular pressure (IOP), although some cases are congenital or occur in patients with normal IOP. Current glaucoma treatments rely on medicine and surgery to lower IOP, which only delays disease progression. First-line glaucoma medicines are supported by pharmacotherapy advancements such as Rho kinase inhibitors and innovative drug delivery systems. Glaucoma surgery has shifted to safer minimally invasive (or microinvasive) glaucoma surgery, but further trials are needed to validate long-term efficacy. Further, growing evidence shows that adeno-associated virus gene transduction and stem cell-based RGC replacement therapy hold potential to treat optic nerve fiber degeneration and glaucoma. However, better understanding of the regulatory mechanisms of RGC development is needed to provide insight into RGC differentiation from stem cells and help choose target genes for viral therapy. In this review, we overview current progress in RGC development research, optic nerve fiber regeneration, and human stem cell-derived RGC differentiation and transplantation. We also provide an outlook on perspectives and challenges in the field.


Subject(s)
Glaucoma , Neurodegenerative Diseases , Optic Nerve Diseases , Humans , Animals , Glaucoma/drug therapy , Glaucoma/pathology , Retinal Ganglion Cells/pathology , Optic Nerve Diseases/therapy , Optic Nerve Diseases/pathology , Disease Progression , Neurodegenerative Diseases/pathology , Disease Models, Animal
20.
Small ; 19(43): e2306829, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37661360

ABSTRACT

The development of "anode-free" lithium-metal batteries with high energy densities is, at present, mainly limited by the poor control of the nucleation of lithium directly on the copper current collector, especially in conventional carbonate electrolytes. It is therefore essential to improve the understanding of the lithium nucleation process and its interactions with the copper substrate. In this study, it is shown that diffusion of lithium into the copper substrate, most likely via the grain boundaries, can significantly influence the nucleation process. Such diffusion makes it more difficult to obtain a great number of homogeneously distributed lithium nuclei on the copper surface and thus leads to inhomogeneous electrodeposition. It is, however, demonstrated that the nucleation of lithium on copper is significantly improved if an initial chemical prelithiation of the copper surface is performed. This prelithiation saturates the copper surface with lithium and hence decreases the influence of lithium diffusion via the grain boundaries. In this way, the lithium nucleation can be made to take place more homogenously, especially when a short potentiostatic nucleation pulse that can generate a large number of nuclei on the surface of the copper substrate is applied.

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