Neuroinflammation in Alzheimer’s disease

Amyloid-β plaques and neurofibrillary tangles are the main neuropathological hallmarks in Alzheimer’s disease (AD), the most common cause of dementia in the elderly. However, it has become increasingly apparent that neuroinflammation plays a significant role in the pathophysiology of AD. This review summarizes the current status of neuroinflammation research related to AD, focusing on the connections between neuroinflammation and some inflammation factors in AD. Among these connections, we discuss the dysfunctional blood–brain barrier and alterations in the functional responses of microglia and astrocytes in this process. In addition, we summarize and discuss the role of intracellular signaling pathways involved in inflammatory responses in astrocytes and microglia, including the mitogen-activated protein kinase pathways, nuclear factor-kappa B cascade, and peroxisome proliferator–activated receptor-gamma transcription factors. Finally, the dysregulation of the control and release of pro- and anti-inflammatory cytokines and classic AD pathology (amyloid plaques and neurofibrillary tangles) in AD is also reviewed

Adiponectin exhibits proliferative and anti-apoptotic effects on ovarian cancer cells via PI3K/Akt and Raf/MEK/ERK pathways

Purpose: To elucidate the effects and the underlying mechanism of adiponectin on human ovarian cancer cells.Methods: The level of adiponectin, adiponectin receptor-1, caspase-3 and bcl-2 in the serum and ascites of the patients were measured with enzyme-linked immunosorbent assay (ELISA), qPCR and Western blotting. The human ovarian cancer cell lines (Caov3 and SKOV3) were enumerated using 3-(4,5-dimethylthiazol-2-yl)-2,5-tetrazolium bromide (MTT) assay. Western blotting was also used to determine the levels of p-Akt, p-ERK and cyclin B.Results: Serum and ascite levels of adiponectin were significantly higher in ovarian cancer patients than in healthy patients (p < 0.05). Expression of adiponectin in the serum and ascites of patients in FIGO stage IV was remarkably higher than in earlier stages (p < 0.05). The proliferative effect of adiponectin on ovarian cells was dose-dependent. Adiponectin treatment significantly increased the expression of cyclin B in Caov3 and SKOV3, and reduced the levels of caspase-3 and bcl-2. Inhibitors of PI3K and MEK pathways significantly reduced the proliferation of attenuated Caov3 and SKOV3 by up-regulating cyclin B upon adiponectin treatment (p < 0.05), and thus alleviated the inhibitory effect of adiponectin on the expressions of caspase-3 and bcl-2.Conclusion: The findings demonstrate that adiponectin promotes proliferation of the cells via the PI3K/Akt and Raf/MEK/ERK pathways, and also provide new insights into ovarian cancer treatmment.Keywords: Adiponectin, Ovarian cancer, Proliferation, Apoptosis, PI3K/Akt pathwa

Knockdown of a novel lincRNA AATBC suppresses proliferation and induces apoptosis in bladder cancer

Long intergenic noncoding RNAs (lincRNAs) play important roles in regulating various biological processes in cancer, including proliferation and apoptosis. However, the roles of lincRNAs in bladder cancer remain elusive. In this study, we identified a novel lincRNA, which we termed AATBC. We found that AATBC was overexpressed in bladder cancer patient tissues and positively correlated with tumor grade and pT stage. We also found that inhibition of AATBC resulted in cell proliferation arrest through G1 cell cycle mediated by cyclin D1, CDK4, p18 and phosphorylated Rb. In addition, inhibition of AATBC induced cell apoptosis through the intrinsic apoptosis signaling pathway, as evidenced by the activation of caspase-9 and caspase-3. The investigation for the signaling pathway revealed that the apoptosis following AATBC knockdown was mediated by activation of phosphorylated JNK and suppression of NRF2. Furthermore, JNK inhibitor SP600125 could attenuate the apoptotic effect achieved by AATBC knockdown, confirming the involvement of JNK signaling in the induced apoptosis. Moreover, mouse xenograft model revealed that knockdown of AATBC led to suppress tumorigenesis in vivo. Taken together, our study indicated that AATBC might play a critical role in pro-proliferation and anti-apoptosis in bladder cancer by regulating cell cycle, intrinsic apoptosis signaling, JNK signaling and NRF2. AATBC could be a potential therapeutic target and molecular biomarker for bladder cancer

Long Non-Coding RNA LUCAT1 Promotes Proliferation and Invasion in Clear Cell Renal Cell Carcinoma Through AKT/GSK-3β Signaling Pathway

Background/Aims: Long non-coding RNAs (lncRNAs) have emerged as new regulators and biomarkers in several cancers. However, few lncRNAs have been well characterized in clear cell renal cell carcinoma (ccRCC). Methods: We investigated the lncRNA expression profile by microarray analysis in 5 corresponding ccRCC tissues and adjacent normal tissues. Lung cancer–associated transcript 1 (LUCAT1) expression was examined in 90 paired ccRCC tissues by real-time PCR and validated by The Cancer Genome Atlas (TCGA) database. Kaplan-Meier analysis was used to examine the prognostic value of LUCAT1 and CXCL2 in ccRCC patients. Loss and gain of function were performed to explore the effect of LUCAT1 on proliferation and invasion in ccRCC cells. Western blotting was performed to evaluate the underlying mechanisms of LUCAT1 in ccRCC progression. Chemokine stimulation assay was performed to investigate possible mechanisms controlling LUCAT1 expression in ccRCC cells. Enzyme-linked immunosorbent assays were performed to determine serum CXCL2 in ccRCC patients and healthy volunteers. Receiver operating characteristic curve analysis was performed to examine the clinical diagnostic value of serum CXCL2 in ccRCC. Results: We found that LUCAT1 was significantly upregulated in both clinical ccRCC tissues (n = 90) and TCGA ccRCC tissues (n = 448) compared with normal tissues. Statistical analysis revealed that the LUCAT1 expression level positively correlated with tumor T stage (P < 0.01), M stage (P < 0.01), and TNM stage (P < 0.01). Overall survival and disease-free survival time were significantly shorter in the high-LUCAT1-expression group than in the low-LUCAT1-expression group (log-rank P < 0.01). LUCAT1 knockdown inhibited ccRCC cell proliferation and colony formation, induced cell cycle arrest at G1 phase, and inhibited cell migration and invasion. Overexpression of LUCAT1 promoted proliferation, migration, and invasion of ccRCC cells. Mechanistic investigations showed that LUCAT1 induced cell cycle G1 arrest by regulating the expression of cyclin D1, cyclin-dependent kinase 4, and phosphorylated retinoblastoma transcriptional corepressor 1. Moreover, LUCAT1 promoted proliferation and invasion in ccRCC cells partly through inducing the phosphorylation of AKT and suppressing the phosphorylation of GSK-3β. We also revealed that chemokine CXCL2, upregulated in ccRCC, induced LUCAT1 expression and might be a diagnostic and prognostic biomarker in ccRCC. Conclusions: LUCAT1 was upregulated in ccRCC tissues and renal cancer cell lines, and significantly correlated with malignant stage and poor prognosis in ccRCC. LUCAT1 promoted proliferation and invasion in ccRCC cells through the AKT/GSK-3β signaling pathway. We also revealed that LUCAT1 overexpression was induced by chemokine CXCL2. These findings indicate that the CXCL2/LUCAT1/AKT/GSK-3β axis is a potential therapeutic target and molecular biomarker for ccRCC

Cloning, Characterization, and Functional Expression of Phospholipase D α

Phospholipase D (PLD) plays a key role in adaptive responses of postharvest fruits. A cDNA clone of banana (Musa acuminate L.) PLDα (MaPLDα) was obtained by RT-PCR in this study. The MaPLDα gene contains a complete open reading frame (ORF) encoding a 92-kDa protein composed of 832 amino acid residues and possesses a characteristic C2 domain and two catalytic H×K×××D (abbr. HKD) motifs. The two HKD motifs are separated by 341 amino acid residues in the primary structure. Relatively higher PLD activity and expression of MaPLDα mRNA were detected in developing tissues compared to senescent or mature tissues in individual leaves, flower, stem, and fruit organs, respectively. The expression profile of PLDα mRNA in postharvest banana fruits at different temperatures was determined, and the MaPLDα mRNA reached the highest expression peak on day 5 at 25°C and on day 7 at 12°C. The results provide useful information for maintaining postharvest quality and extending the storage life of banana fruit

Construction and verification of a predictive model for depression risk of patients with somatization symptoms

BackgroundPatients with somatization symptoms are at elevated risk of depression, yet underdiagnosis persists due to cultural tendencies (e.g., in China) to express psychological distress via physical complaints. Existing predictive models lack integration of sociocultural and physiological factors, particularly in non-Western populations.ObjectiveTo develop a culturally tailored risk-prediction model for depression in patients with somatization symptoms, emphasizing early identification and personalized intervention.MethodsA prospective cohort study included 200 somatization patients (SSS≥38, PHQ-2<3) from a Chinese hospital (May 2020–August 2022). LASSO regression identified predictors from 18 variables, followed by multivariate logistic regression to construct a nomogram. Model performance was assessed via ROC-AUC, calibration curves, Hosmer-Lemeshow test, and decision curve analysis (DCA). Internal validation used 200 bootstrap resamples.ResultsFive independent predictors were identified: advanced age (OR=1.11, 95% CI: 1.02–1.20), poor self-rated health (OR=2.07, 95% CI: 1.04–4.30), lack of co-residence with children (OR=1.63, 95% CI: 1.10–2.42), low income (OR=1.45, 95% CI: 1.05–2.01), and self-medication (OR=1.32, 95% CI: 1.01–1.73). The nomogram demonstrated strong discrimination (AUC=0.810, 95% CI: 0.728–0.893) and calibration (Hosmer-Lemeshow p=0.32). DCA confirmed clinical utility: at threshold probabilities >5%, the model provided higher net benefit than “treat-all” or “treat-none” strategies.ConclusionThis model integrates sociocultural (e.g., family structure) and behavioral factors to predict depression risk in somatizing patients, particularly in East Asian contexts. It offers a practical tool for clinicians to prioritize high-risk individuals, reducing diagnostic delays and healthcare burdens. Future multicenter studies should validate its generalizability and incorporate biomarkers (e.g., inflammatory markers) to enhance mechanistic insights

Predictive control strategy for multi-agent relay tracking systems with time delays

This paper investigates the multi-agent systems for target tracking applications, in which the target is cooperatively relay tracked by multiple agents based on the Voronoi diagram. The relay tracking scheme is effective and reduces the tracking time of a target. However, the existence of time delays results in inaccurate determination of boundaries of Voronoi cells. Thus, the replacement of tracking agent is no longer optimal, which consequently affects the tracking time. In order to solve this issue, a predictive controller is proposed for the relay tracking system with time delays. Moreover, the boundaries of Voronoi cells are determined with the predictive values of agents’ information. In order to analyze the stability of the system, an impulse-time-dependent Lyapunov function is designed. Then, the orthogonal polynomials based inequality is applied and the average dwell time switching technique is adopted to solve the difficulty of stability analysis of the overall relay tracking system caused by the agent replacements of time-delay agents. Finally, the effectiveness and advantages of the proposed predictive control method for relay target tracking system with time delays are illustrated by comparative simulations. </jats:p