Albumin to globulin ratio (AGR) in systemic lupus erythematosus: correlation with disease activity.

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.

Removal of heavy metals in water-extracted solution through adsorption by palygorskite and stabilization by comilling.

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.

ILK inhibition reduces osteophyte formation through suppression of osteogenesis in BMSCs via Akt/GSK-3ß/ß-catenin pathway.

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.

Clinical characteristics and risk factors associated with bone erosion in patients with tophi.

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.

LncRNA expression profiling in exosomes derived from synovial fluid of patients with rheumatoid arthritis.

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.

A Bioimpedance Spectroscopy Interface for EIM Based on IF-Sampling and Pseudo 2-Path SC Bandpass ΔΣ ADC.

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) ΔΣ 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/√{Hz} 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.

Inhibition of ADAM9 promotes the selective degradation of KRAS and sensitizes pancreatic cancers to chemotherapy.

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.

Camera Wavelength Selection for Multi-wavelength Pulse Transit Time based Blood Pressure Monitoring.

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.

Therapeutic strategies for glaucoma and optic neuropathies.

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.

The Neuroimmune Regulation and Potential Therapeutic Strategies of Optic Pathway Glioma.

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.

Influence of Lithium Diffusion into Copper Current Collectors on Lithium Electrodeposition in Anode-Free Lithium-Metal Batteries.

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.

Improved Prediction of Knee Osteoarthritis by the Machine Learning Model XGBoost.

Objectives: The accurate prediction of osteoarthritis (OA) severity in patients can be helpful to make the proper decision of intervention. This study aims to build up a powerful model to assess predictive risk factors and severity of knee osteoarthritis (KOA) in the clinical scenario. Methods: A total of 4796 KOA cases and 1205 features were selected by feature selections from the public OA database, Osteoarthritis Initiative (OAI). Six machine learning-based models were constructed and compared for the accuracy of OA prediction. The gradient-boosting decision tree was used to identify important prediction features in the extreme gradient boosting (XGBoost) model. The performance of models was evaluated by F1-score. Results: Twenty features were determined as predictors for KOA risk and severity, including the subject characteristics, knee symptoms/risk factors and physical exam. The XGBoost model demonstrated 100% prediction accuracy for 54.7% of examined samples, and the remaining 45.3% of samples showed Kellgren and Lawrence (KL) gradings very close to the actual levels. It showed the highest prediction accuracy with an F1-score of 0.553 among the tested six models. Conclusions: We demonstrate that the XGBoost is the best model for the prediction of KOA severity in the six examined models. In addition, 20 risk features were determined as the essential predictors of KOA, including the physical exam, knee symptoms/risk factors and subject characteristics, which may be useful for the identification of high-risk KOA cases and for making appropriate treatment decisions as well.

Proteomics profiling of CD4 + T-cell-derived exosomes from patients with rheumatoid arthritis.

OBJECTIVES: Our study profiled the CD4 + T-cell-derived exosomes from patients with rheumatoid arthritis (RA) using proteomics. METHODS: Proteomic analysis of CD4 + T-cell-derived exosomes was performed by tandem mass tags (TMT) combined with LC-MS/MS. We validated the most significantly upregulated and downregulated proteins using ELISA and WB. RESULTS: The proteomic results showed that there were 3 upregulated differentially expressed proteins and 31 downregulated differentially expressed proteins in the RA group. The results indicated that dihydropyrimidinase-related protein 3 (DPYSL3) was significantly upregulated in CD4 + T-cell-derived exosomes, whereas proteasome activator complex subunit 1 (PSME1) was significantly downregulated in the RA group. Bioinformatics analysis showed that proteins were enriched in "positive regulation of gene expression", "antigen processing and presentation", "acute-phase response" and "PI3K-AKT signaling" pathways. ELISA verified that compared to the control group, the RA group showed significant upregulation of DPYSL3, and downregulation of PSME1 in CD4 + T-cell-derived exosomes. CONCLUSIONS: The proteomic analysis results of CD4 + T-cell-derived exosomes from patients with RA suggest that these differentially expressed proteins may be involved in RA pathogenesis. DPYSL3 and PSME1 may become useful biomarkers for RA.

Advances in mRNA vaccines for viral diseases.

Since the onset of the pandemic caused by severe acute respiratory syndrome coronavirus 2, messenger RNA (mRNA) vaccines have demonstrated outstanding performance. mRNA vaccines offer significant advantages over conventional vaccines in production speed and cost-effectiveness, making them an attractive option against other viral diseases. This article reviewed recent advances in viral mRNA vaccines and their delivery systems to provide references and guidance for developing mRNA vaccines for new viral diseases.

AKR1B1 Represses Glioma Cell Proliferation through p38 MAPK-Mediated Bcl-2/BAX/Caspase-3 Apoptotic Signaling Pathways.

This study aimed to investigate the regulatory role of Aldo-keto reductase family 1 member B1 (AKR1B1) in glioma cell proliferation through p38 MAPK activation to control Bcl-2/BAX/caspase-3 apoptosis signaling. AKR1B1 expression was quantified in normal human astrocytes, glioblastoma multiforme (GBM) cell lines, and normal tissues by using quantitative real-time polymerase chain reaction. The effects of AKR1B1 overexpression or knockdown and those of AKR1B1-induced p38 MAPK phosphorylation and a p38 MAPK inhibitor (SB203580) on glioma cell proliferation were determined using an MTT assay and Western blot, respectively. Furthermore, the AKR1B1 effect on BAX and Bcl-2 expression was examined in real-time by Western blot. A luminescence detection reagent was also utilized to identify the effect of AKR1B1 on caspase-3/7 activity. The early and late stages of AKR1B1-induced apoptosis were assessed by performing Annexin V-FITC/PI double-staining assays. AKR1B1 expression was significantly downregulated in glioma tissues and GBM cell lines (T98G and 8401). Glioma cell proliferation was inhibited by AKR1B1 overexpression but was slightly increased by AKR1B1 knockdown. Additionally, AKR1B1-induced p38 MAPK phosphorylation and SB203580 reversed AKR1B1's inhibitory effect on glioma cell proliferation. AKR1B1 overexpression also inhibited Bcl-2 expression but increased BAX expression, whereas treatment with SB203580 reversed this phenomenon. Furthermore, AKR1B1 induced caspase-3/7 activity. The induction of early and late apoptosis by AKR1B1 was confirmed using an Annexin V-FITC/PI double-staining assay. In conclusion, AKR1B1 regulated glioma cell proliferation through the involvement of p38 MAPK-induced BAX/Bcl-2/caspase-3 apoptosis signaling. Therefore, AKR1B1 may serve as a new therapeutic target for glioma therapy development.

Nordalbergin Exerts Anti-Neuroinflammatory Effects by Attenuating MAPK Signaling Pathway, NLRP3 Inflammasome Activation and ROS Production in LPS-Stimulated BV2 Microglia.

Microglia-associated neuroinflammation is recognized as a critical factor in the pathogenesis of neurodegenerative diseases; however, there is no effective treatment for the blockage of neurodegenerative disease progression. In this study, the effect of nordalbergin, a coumarin isolated from the wood bark of Dalbergia sissoo, on lipopolysaccharide (LPS)-induced inflammatory responses was investigated using murine microglial BV2 cells. Cell viability was assessed using the MTT assay, whereas nitric oxide (NO) production was analyzed using the Griess reagent. Secretion of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) was detected by the ELISA. The expression of inducible NO synthase (iNOS), cyclooxygenase (COX)-2, mitogen-activated protein kinases (MAPKs) and NLRP3 inflammasome-related proteins was assessed by Western blot. The production of mitochondrial reactive oxygen species (ROS) and intracellular ROS was detected using flow cytometry. Our experimental results indicated that nordalbergin ≤20 µM suppressed NO, IL-6, TNF-α and IL-1ß production; decreased iNOS and COX-2 expression; inhibited MAPKs activation; attenuated NLRP3 inflammasome activation; and reduced both intracellular and mitochondrial ROS production by LPS-stimulated BV2 cells in a dose-dependent manner. These results demonstrate that nordalbergin exhibits anti-inflammatory and anti-oxidative activities through inhibiting MAPK signaling pathway, NLRP3 inflammasome activation and ROS production, suggesting that nordalbergin might have the potential to inhibit neurodegenerative disease progression.

Aldose reductase inhibition decelerates optic nerve degeneration by alleviating retinal microglia activation.

As part of the central nervous system (CNS), retinal ganglion cells (RGCs) and their axons are the only neurons in the retina that transmit visual signals from the eye to the brain via the optic nerve (ON). Unfortunately, they do not regenerate upon injury in mammals. In ON trauma, retinal microglia (RMG) become activated, inducing inflammatory responses and resulting in axon degeneration and RGC loss. Since aldose reductase (AR) is an inflammatory response mediator highly expressed in RMG, we investigated if pharmacological inhibition of AR can attenuate ocular inflammation and thereby promote RGC survival and axon regeneration after ON crush (ONC). In vitro, we discovered that Sorbinil, an AR inhibitor, attenuates BV2 microglia activation and migration in the lipopolysaccharide (LPS) and monocyte chemoattractant protein-1 (MCP-1) treatments. In vivo, Sorbinil suppressed ONC-induced Iba1 + microglia/macrophage infiltration in the retina and ON and promoted RGC survival. Moreover, Sorbinil restored RGC function and delayed axon degeneration one week after ONC. RNA sequencing data revealed that Sorbinil protects the retina from ONC-induced degeneration by suppressing inflammatory signaling. In summary, we report the first study demonstrating that AR inhibition transiently protects RGC and axon from degeneration, providing a potential therapeutic strategy for optic neuropathies.

Revolutionizing viral disease vaccination: the promising clinical advancements of non-replicating mRNA vaccines.

The mRNA vaccine technology was developed rapidly during the global pandemic of COVID-19. The crucial role of the COVID-19 mRNA vaccine in preventing viral infection also have been beneficial to the exploration and application of other viral mRNA vaccines, especially for non-replication structure mRNA vaccines of viral disease with outstanding research results. Therefore, this review pays attention to the existing mRNA vaccines, which are of great value for candidates for clinical applications in viral diseases. We provide an overview of the optimization of the mRNA vaccine development process as well as the good immune efficacy and safety shown in clinical studies. In addition, we also provide a brief description of the important role of mRNA immunomodulators in the treatment of viral diseases. After that, it will provide a good reference or strategy for research on mRNA vaccines used in clinical medicine with more stable structures, higher translation efficiency, better immune efficacy and safety, shorter production time, and lower production costs than conditional vaccines to be used as preventive or therapeutic strategy for the control of viral diseases in the future.

Artificial intelligence system for the detection of Barrett's esophagus.

BACKGROUND: Barrett's esophagus (BE), which has increased in prevalence worldwide, is a precursor for esophageal adenocarcinoma. Although there is a gap in the detection rates between endoscopic BE and histological BE in current research, we trained our artificial intelligence (AI) system with images of endoscopic BE and tested the system with images of histological BE. AIM: To assess whether an AI system can aid in the detection of BE in our setting. METHODS: Endoscopic narrow-band imaging (NBI) was collected from Chung Shan Medical University Hospital and Changhua Christian Hospital, resulting in 724 cases, with 86 patients having pathological results. Three senior endoscopists, who were instructing physicians of the Digestive Endoscopy Society of Taiwan, independently annotated the images in the development set to determine whether each image was classified as an endoscopic BE. The test set consisted of 160 endoscopic images of 86 cases with histological results. RESULTS: Six pre-trained models were compared, and EfficientNetV2B2 (accuracy [ACC]: 0.8) was selected as the backbone architecture for further evaluation due to better ACC results. In the final test, the AI system correctly identified 66 of 70 cases of BE and 85 of 90 cases without BE, resulting in an ACC of 94.37%. CONCLUSION: Our AI system, which was trained by NBI of endoscopic BE, can adequately predict endoscopic images of histological BE. The ACC, sensitivity, and specificity are 94.37%, 94.29%, and 94.44%, respectively.

The Role of Aldose Reductase in Beta-Amyloid-Induced Microglia Activation.

The occurrence of Alzheimer's disease has been associated with the accumulation of beta-amyloid (ß-amyloid) plaques. These plaques activate microglia to secrete inflammatory molecules, which damage neurons in the brain. Thus, understanding the underlying mechanism of microglia activation can provide a therapeutic strategy for alleviating microglia-induced neuroinflammation. The aldose reductase (AR) enzyme catalyzes the reduction of glucose to sorbitol in the polyol pathway. In addition to mediating diabetic complications in hyperglycemic environments, AR also helps regulate inflammation in microglia. However, little is known about the role of AR in ß-amyloid-induced inflammation in microglia and subsequent neuronal death. In this study, we confirmed that AR inhibition attenuates increased ß-amyloid-induced reactive oxygen species and tumor necrosis factor α secretion by suppressing ERK signaling in BV2 cells. In addition, we are the first to report that AR inhibition reduced the phagocytotic capability and cell migration of BV2 cells in response to ß-amyloid. To further investigate the protective role of the AR inhibitor sorbinil in neurons, we co-cultured ß-amyloid-induced microglia with stem cell-induced neurons. sorbinil ameliorated neuronal damage in both cells in the co-culture system. In summary, our findings reveal AR regulation of microglia activation as a novel therapeutic target for Alzheimer's disease.