Ameliorative Role of Mitochondrial Therapy in Cognitive Function of Vascular Dementia Mice.

BACKGROUND: Mitochondrial dysfunction plays a vital role in the progression of vascular dementia (VaD). We hypothesized that transfer of exogenous mitochondria might be a beneficial strategy for VaD treatment. OBJECTIVE: The study was aimed to investigate the role of mitochondrial therapy in cognitive function of VaD. METHODS: The activity and integrity of isolated mitochondria were detected using MitoTracker and Janus Green B staining assays. After VaD mice were intravenously injected with exogenous mitochondria, Morris water maze and passive avoidance tests were used to detect cognitive function of VaD mice. Haematoxylin and eosin, Nissl, TUNEL, and Golgi staining assays were utilized to measure neuronal and synaptic injury in the hippocampus of VaD mice. Detection kits were performed to detect mitochondrial membrane potential (ΔΨ), SOD activity and the levels of ATP, ROS, and MDA in the brains of VaD mice. RESULTS: The results showed that isolated mitochondria were intact and active. Mitochondrial therapy could ameliorate cognitive performance of VaD mice. Additionally, mitochondrial administration could attenuate hippocampal neuronal and synaptic injury, improve mitochondrial ΔΨ, ATP level and SOD activity, and reduce ROS and MDA levels in the brains of VaD mice. CONCLUSIONS: The study reports profitable effect of mitochondrial therapy against cognitive impairment of VaD, making mitochondrial treatment become a promising therapeutic strategy for VaD.

Gliclazide Ameliorates Neuronal Injury by Attenuating Oxidative Stress in D-gal-Induced Senescent Cells and Aging Mice.

Enhancement of oxidative stress and resultant neuronal injury play important roles in initiating cognitive impairment during the aging process. Thus, attenuating oxidative injury is regarded as a profitable therapeutic strategy for age-associated cognitive impairment. Previous studies showed that gliclazide (Gli) had a protective role in neuronal injury from cerebral ischemia/reperfusion (I/R) injury. However, whether Gli has a profitable effect on age-associated cognitive impairment remains largely unclear. The present study showed that Gli held the potential to attenuate neuronal apoptosis in D-gal-induced senescent cells and aging mice. Additionally, Gli could alleviate synaptic injury and cognitive function in D-gal-induced aging mice. Further study showed that Gli could attenuate oxidative stress in D-gal-induced senescent cells and aging mice. The p38 MAPK pathway was predicted as the downstream target of Gli retarding oxidative stress using in silico analysis. Further studies revealed that Gli attenuated D-gal-induced phosphorylation of p38 and facilitated Nrf2 nuclear expression, indicating that the anti-oxidative property of Gli may be associated with the p38 MAPK pathway. The study demonstrates that Gli has a beneficial effect on ameliorating D-gal-induced neuronal injury and cognitive impairment, making this compound a promising agent for the prevention and treatment of age-associated cognitive impairment.

Circular RNAs: emerging players in brain aging and neurodegenerative diseases.

Brain aging is closely related to neurodegenerative diseases. Circular RNAs (circRNAs) are a type of conserved RNAs with covalently closed continuous loops. Emerging evidence has shown that circRNAs are implicated in the biology of brain aging and the pathology of age-related neurodegenerative diseases. Here, we summarize current studies on circRNAs associated with brain aging and neurodegenerative diseases by discussing their expression features, pathophysiological roles, and mechanisms of action. We also discuss the potential challenges of circRNA-based therapy against brain aging and neurodegenerative diseases, as well as their potential as diagnostic biomarkers of neurodegenerative diseases. The review provides insights into current progress in the functions of circRNAs in the process of brain aging and neurodegenerative diseases. © 2022 The Pathological Society of Great Britain and Ireland.

Erratum: Cx43 deficiency confers EMT-mediated tamoxifen resistance to breast cancer via c-Src/PI3K/Akt pathway: Erratum.

[This corrects the article DOI: 10.7150/ijbs.55453.].

Corrigendum: A Novel Role of Connexin 40-Formed Channels in the Enhanced Efficacy of Photodynamic Therapy.

[This corrects the article DOI: 10.3389/fonc.2019.00595.].

MeCP2 prevents age-associated cognitive decline via restoring synaptic plasticity in a senescence-accelerated mouse model.

Age-related cognitive decline in neurodegenerative diseases, such as Alzheimer's disease (AD), is associated with the deficits of synaptic plasticity. Therefore, exploring promising targets to enhance synaptic plasticity in neurodegenerative disorders is crucial. It has been demonstrated that methyl-CpG binding protein 2 (MeCP2) plays a vital role in neuronal development and MeCP2 malfunction causes various neurodevelopmental disorders. However, the role of MeCP2 in neurodegenerative diseases has been less reported. In the study, we found that MeCP2 expression in the hippocampus was reduced in the hippocampus of senescence-accelerated mice P8 (SAMP8) mice. Overexpression of hippocampal MeCP2 could elevate synaptic plasticity and cognitive function in SAMP8 mice, while knockdown of MeCP2 impaired synaptic plasticity and cognitive function in senescence accelerated-resistant 1 (SAMR1) mice. MeCP2-mediated regulation of synaptic plasticity may be associated with CREB1 pathway. These results suggest that MeCP2 plays a vital role in age-related cognitive decline by regulating synaptic plasticity and indicate that MeCP2 may be promising targets for the treatment of age-related cognitive decline in neurodegenerative diseases.

Cx43 deficiency confers EMT-mediated tamoxifen resistance to breast cancer via c-Src/PI3K/Akt pathway.

Tamoxifen (TAM) resistance has indicated a significant challenge during endocrine therapy for hormone-sensitive breast cancer. Thus, it is significant to elucidate the molecular events endowing TAM resistance to endocrine therapy. In this study, we found that epithelial-mesenchymal transition (EMT) was an important event to confer TAM resistance, and attenuating EMT by elevating connexin (Cx) 43 expression could reverse TAM resistance. Specifically, Cx43 overexpression improved TAM sensitivity, while Cx43 depletion facilitated TAM insensitivity by modulating EMT in T47D TAM-resistant and -sensitive cells, and transplanted xenografts. Importantly, we found a novel reciprocal regulation between Cx43 and c-Src/PI3K/Akt pathway contributing to EMT and TAM resistance in breast cancer. Moreover, we identified that Cx43 deficiency was significantly correlated with poor relapse-free survival in patients undergoing TAM treatment. Therefore, Cx43 represents a prognostic marker and an attractive target for breast cancer treatments. Therapeutic strategies designed to increase or maintain Cx43 function may be beneficial to overcome TAM resistance.

Functional roles of circular RNAs in Alzheimer's disease.

Although efforts have been made to develop therapeutic approaches, the clinical management of AD maintains a major challenge. CircRNAs are highly abundant and evolutionarily conserved in neuronal tissues in mammals. Accumulating data suggest that circRNAs regulate biological and pathological processes by sponging miRNAs, binding to RBPs, modulating mRNA stability, and being translated into peptides in various diseases, serving as biomarkers and potential therapeutic targets. Growing evidence demonstrates that circRNAs have been implicated in the pathogenesis of AD. Here, we summarized current studies on circRNAs involved in AD pathology, providing a theoretical basis for the use of circRNAs in AD treatment and diagnosis.

Albumin-bilirubin score is associated with response to pegylated interferon and nucleos(t)ide analogues in chronic hepatitis B patients.

BACKGROUND AND AIM: Recently, the role of albumin-bilirubin (ALBI) score in chronic hepatitis B (CHB) has not been well-understood. We aimed to investigate the association of ALBI score with natural history of chronic HBV infection and treatment response of CHB patients. METHODS: The ALBI score in a cohort of 849 individuals including 721 chronic HBV-infected patients naïve to anti-HBV treatment in different phases and 128 healthy controls were estimated. Additionally, the dynamic changes of ALBI score of 243 hepatitis B e antigen (HBeAg)-positive CHB patients treated with pegylated interferon-alpha (PEG-IFN-α) or nucleos(t)ide analogues (NAs) were tested for 72 weeks. RESULTS: ALBI score differed among phases, with the highest score in HBeAg-positive CHB patients, followed by HBeAg-negative CHB patients, HBeAg-positive chronic HBV infection, and HBeAg-negative chronic HBV infection. Besides, CHB patients harbouring high baseline ALBI score exhibited a relatively stronger therapeutic response to PEG-IFN-α or NAs. Moreover, the rate of HBeAg and HBsAg loss in patients with ALBI grade 2 was persistently higher than that in patients with ALBI grade 1 throughout the course of treatment. Furthermore, ALBI score was an independent predictor of sustained response achievement. The combined use of ALBI score, HBeAg and ALT could enhance the predictive value of treatment response. CONCLUSIONS: ALBI score differed significantly across the natural course of chronic HBV infection and was correlated with PEG-IFN-α and NAs treatment response in HBeAg-positive CHB patients, which suggested that ALBI score could be useful as an auxiliary clinical factor to determine the initiation of therapy and predict stronger antiviral treatment response.

Identification of Potential Therapeutic Targets of Alzheimer's Disease By Weighted Gene Co-Expression Network Analysis.

Objective Alzheimer's disease (AD) is the most common cause of dementia. The pathophysiology of the disease mostly remains unearthed, thereby challenging drug development for AD. This study aims to screen high throughput gene expression data using weighted co-expression network analysis (WGCNA) to explore the potential therapeutic targets.Methods The dataset of GSE36980 was obtained from the Gene Expression Omnibus (GEO) database. Normalization, quality control, filtration, and soft-threshold calculation were carried out before clustering the co-expressed genes into different modules. Furthermore, the correlation coefficients between the modules and clinical traits were computed to identify the key modules. Gene ontology and pathway enrichment analyses were performed on the key module genes. The STRING database was used to construct the protein-protein interaction (PPI) networks, which were further analyzed by Cytoscape app (MCODE). Finally, validation of hub genes was conducted by external GEO datasets of GSE 1297 and GSE 28146.Results Co-expressed genes were clustered into 27 modules, among which 6 modules were identified as the key module relating to AD occurrence. These key modules are primarily involved in chemical synaptic transmission (GO:0007268), the tricarboxylic acid (TCA) cycle and respiratory electron transport (R-HSA-1428517). WDR47, OXCT1, C3orf14, ATP6V1A, SLC25A14, NAPB were found as the hub genes and their expression were validated by external datasets.Conclusions Through modules co-expression network analyses and PPI network analyses, we identified the hub genes of AD, including WDR47, OXCT1, C3orf14, ATP6V1A, SLC25A14 and NAPB. Among them, three hub genes (ATP6V1A, SLC25A14, OXCT1) might contribute to AD pathogenesis through pathway of TCA cycle.

Probucol, a "non-statin" cholesterol-lowering drug, ameliorates D-galactose induced cognitive deficits by alleviating oxidative stress via Keap1/Nrf2 signaling pathway in mice.

Oxidative stress plays a vital role in the initiation and progression of age-related neurodegenerative diseases. Ameliorating oxidative damage is therefore considered as a beneficial strategy for the treatment of age-related neurodegenerative disorders. Probucol (Prob), a lipid-lowering prototype agent, was reported to treat cardiovascular diseases, chronic kidney disease and diabetes mellitus. However, whether Prob has an effect on age-related neurodegenerative diseases remains unknown. In the study, it was found that Prob ameliorated D-galactose (D-gal) induced cognitive deficits and neuronal loss in the hippocampal CA1 region. Moreover, Prob alleviated ROS and MDA levels by elevating SOD, GSH-PX and HO-1 mRNA and protein expressions, and improving plasmic and cerebral SOD and GSH-PX activities in D-gal treated mice. Furthermore, Prob promoted the dissociation of Keap1/Nrf2 complex leading to the accumulation of Nrf2 in nucleus, implying that the improved anti-oxidant property of Prob is mediated by Keap1/Nrf2 pathway. The study firstly demonstrates the favorable effects of Prob against cognitive impairments in a senescent mouse model, rendering this compound a promising agent for the treatment or prevention of age-related neurodegenerative disease.

A Novel Role of Connexin 40-Formed Channels in the Enhanced Efficacy of Photodynamic Therapy.

Despite responses to initial treatment of photodynamic therapy (PDT) being promising, a recurrence rate exists. Thus, finding novel therapeutic targets to enhance PDT efficacy is an urgent need. Reports indicate that connexin (Cx) 40 plays an important role in tumor angiogenesis and growth. However, it is unknown whether Cx40-composed channels have effects on PDT efficacy. The study uniquely demonstrated that Cx40-formed channels could enhance the phototoxicity of PDT to malignant cells in vitro and in vivo. Specifically, Cx40-formed channels at high cell density could increase PDT photocytotoxicity. This action was substantially restricted when Cx40 expression was not induced or Cx40 channels were restrained. Additionally, the presence of Cx40-composed channels enhanced the phototoxicity of PDT in the tumor xenografts. The above results indicate that enhancing the function of Cx40-formed channels increases PDT efficacy. The enhancement of PDT efficacy mediated by Cx40 channels was related with intracellular pathways mediated by ROS and calcium pathways, but not the lipid peroxide-mediated pathway. This work demonstrates the capacity of Cx40-mediated channels to increase PDT efficacy and suggests that therapeutic strategies designed to maintain or enhance Cx40 expression and/or channels composed by Cx40 may increase the therapeutic efficacy of PDT.

A novel role of Cx43-composed GJIC in PDT phototoxicity: an implication of Cx43 for the enhancement of PDT efficacy.

In spite of initially promising responses, 5-year recurrence after photodynamic therapy (PDT) sustains high level and an increase in PDT effectiveness is needed. It has been demonstrated that gap junctional intercellular communication (GJIC) formed by Connexin (Cx)43 could improve the transfer of "death signal" between cells, thereby causing the enhancement of cytotoxicity of chemotherapeutics and suicide gene therapy. Nevertheless, whether Cx43-composed GJIC has an effect on PDT phototoxicity remains unknown. This study showed that Cx43-formed GJIC could improve PDT phototoxicity to tumor cells in vitro and in vivo. Specifically, Cx43-formed GJIC under the condition of high cellular density could improve PDT phototoxicity in Cx43-transfected HeLa cells and Cx43-expressing U87 glioma cells. This effect was remarkably inhibited when Cx43 was not expressed or Cx43-formed GJ channels were prohibited. Additionally, the presence of Cx43-mediated GJIC could decrease the mean RTV and tumor weights of xenografts after Photofrin-PDT. The improved PDT efficacy by Cx43-composed GJIC was correlated with stress signaling pathways mediated by ROS, calcium and lipid peroxide. The present study demonstrates the presence of Cx43-composed GJIC improves PDT phototoxicity and suggests that therapeutic strategies designed to upregulate the expression of Cx43 or enhance Cx43-mediated GJIC function may increase the sensitivity of malignant cell to PDT, leading to the increment of PDT efficacy. Oppositely, factors that retard Cx43 expression or prohibit the function of Cx43-mediated GJIC may cause insensitivity of malignant cells to PDT, leading to PDT resistance.

Decreased phototoxicity of photodynamic therapy by Cx32/Cx26-composed GJIC: A "Good Samaritan" effect.

BACKGROUND AND OBJECTIVE: Photodynamic therapy (PDT) has been widely used to treat malignant tumors. Our previous studies indicated that connexin (Cx) 32- and Cx26-composed gap junctional intercellular communication (GJIC) could improve the phototoxicity of PDT. However, the role of heterotypic Cx32/Cx26-formed GJIC in PDT phototoxicity is still unknown. Thus, the present study was aimed to investigate the effect of Cx32/Cx26-formed GJIC on PDT efficacy. METHODS: CCK8 assay was used to detect cell survival after PDT. Western blot assay was utilized to detect Cx32/Cx26 expression. "Parachute" dye-coupling assay was performed to measure the function of GJ channels. The intracellular Ca2+ concentrations were determined using flow cytometer. ELISA assay was performed to detect the intracellular levels of PGE2 and cAMP. RESULTS: The present study demonstrates there is a Cx32/Cx26-formed GJIC-dependent reduction of phototoxicity when cells were exposure to low concentration of Photofrin. Such a protective action is missing at low cell density due to the lack of GJ coupling. Under high-cell density condition, where there is opportunity for the cells to contact each other and form GJ, suppressing Cx32/Cx26-formed GJIC by either inhibiting the expression of Cx32/Cx26 or pretreating with GJ channel inhibitor augments PDT phototoxicity after cells were treated with at 2.5 µg/ml Photofrin. The above results suggest that at low Photofrin concentration, the presence of Cx32/Cx26-formed GJIC may decrease the phototoxicity of PDT, leading to the insensitivity of malignant cells to PDT treatment. The GJIC-mediated PDT insensitivity was associated with Ca2+ and prostaglandin E2 (PGE2 ) signaling pathways. CONCLUSION: The present study provides a cautionary note that for tumors expressing Cx32/Cx26, the presence of Cx32/Cx26-composed GJIC may cause the resistance of tumor cells to PDT. Oppositely, treatment strategies designed to downregulate the expression of Cx32/Cx26 or restrain the function of Cx32/Cx26-mediated GJIC may increase the sensitivity of malignant cell to PDT. Lasers Surg. Med. 51:301-308, 2019. © 2019 Wiley Periodicals, Inc.

Association of serum total cholesterol with pegylated interferon-α treatment in HBeAg-positive chronic hepatitis B patients.

BACKGROUND: Recent studies suggest that serum lipids are associated with pegylated interferon-alpha (PEG-IFN-α) treatment response in chronic hepatitis C patients. However, the role of serum lipids in influencing the outcome of HBV treatment is not well understood. This study aims to investigate the association of serum lipids with the response to interferon-alpha treatment for chronic hepatitis B (CHB) patients. METHODS: We dynamically measured 11 clinical serum lipid parameters of 119 hepatitis B e antigen (HBeAg)-positive CHB patients, including 53 patients who achieved sustained response (SR) and 66 patients who achieved non-response (NR) induced by PEG-IFN-α treatment for 48 weeks. RESULTS: The dynamic analysis showed that the baseline serum total cholesterol (TCHO) level was higher in the NR group than that in the SR group (P=0.004). Moreover, the correlation analysis demonstrated a significant positive correlation between TCHO and hepatitis B surface antigen (HBsAg) at baseline (P=0.009). In addition, CHB patients with high baseline TCHO levels exhibited higher HBV DNA, HBsAg, HBeAg and hepatitis B e antibody (HBeAb) levels during early treatment periods (weeks 0, 4, 12 and 24) than those with the low TCHO levels. Furthermore, the logistic regression analysis identified that baseline serum TCHO was a risk factor for NR achievement (OR=4.94; P=0.047). CONCLUSIONS: Our results indicated that serum TCHO was associated with PEG-IFN-α therapeutic response in HBeAg-positive CHB patients which suggested that serum TCHO could be useful as an auxiliary clinical factor to predict poor efficacy of PEG-IFN-α therapy.

Identification of Differentially Expressed Profiles of Alzheimer's Disease Associated Circular RNAs in a Panax Notoginseng Saponins-Treated Alzheimer's Disease Mouse Model.

Circular RNAs (circRNAs) play vital roles in AD pathogenesis. Thus, developing therapeutic candidates targeting circRNA may provide a novel therapeutic strategy for AD treatment. Our previous studies showed that Panax notoginseng saponins (PNS) could significantly prohibit the pathological progress of AD. However, the mechanisms by which PNS attenuates AD progression is still unclear. The present study shows that PNS may exhibit an ability to modulate the expression of AD-associated circRNAs. Specifically, PNS treatment leads to five circRNAs upregulation and two circRNAs downregulation, indicating that the therapeutic effect of PNS against AD may be associated with its role in the regulation of circRNA expression. Next, mmu_circRNA_013636 and mmu_circRNA_012180 were selected and GO and KEGG analyses were performed to further investigate the biological functions and potential mechanisms of these circRNAs. The results showed that the selected circRNAs were involved in AD-associated biological process and pathways, suggesting that these circRNAs may participate in AD pathogenesis. Collectively, our study indicates that the therapeutic effects of PNS on AD may be through modulating the expression of AD associated circRNAs and suggests that PNS is a potential circRNA-targeted agent against AD, which may provide useful resources for developing potential candidates targeting circRNAs against AD.

The long non-coding RNA PTTG3P promotes cell growth and metastasis via up-regulating PTTG1 and activating PI3K/AKT signaling in hepatocellular carcinoma.

BACKGROUND: Dysfunctions of long non-coding RNA (lncRNAs) have been associated with the initiation and progression of hepatocellular carcinoma (HCC), but the clinicopathologic significance and potential role of lncRNA PTTG3P (pituitary tumor-transforming 3, pseudogene) in HCC remains largely unknown. METHODS: We compared the expression profiles of lncRNAs in 3 HCC tumor tissues and adjacent non-tumor tissues by microarrays. In situ hybridization (ISH) and quantitative real-time polymerase chain reaction (qRT-PCR) were applied to assess the level of PTTG3P and prognostic values of PTTG3P were assayed in two HCC cohorts (n = 46 and 90). Artificial modulation of PTTG3P (down- and over-expression) was performed to explore the role of PTTG3P in tumor growth and metastasis in vitro and in vivo. Involvement of PTTG1 (pituitary tumor-transforming 1), PI3K/AKT signaling and its downstream signals were validated by qRT-PCR and western blot. RESULTS: We found that PTTG3P was frequently up-regulated in HCC and its level was positively correlated to tumor size, TNM stage and poor survival of patients with HCC. Enforced expression of PTTG3P significantly promoted cell proliferation, migration, and invasion in vitro, as well as tumorigenesis and metastasis in vivo. Conversely, PTTG3P knockdown had opposite effects. Mechanistically, over-expression of PTTG3P up-regulated PTTG1, activated PI3K/AKT signaling and its downstream signals including cell cycle progression, cell apoptosis and epithelial-mesenchymal transition (EMT)-associated genes. CONCLUSIONS: Our findings suggest that PTTG3P, a valuable marker of HCC prognosis, promotes tumor growth and metastasis via up-regulating PTTG1 and activating PI3K/AKT signaling in HCC and might represent a potential target for gene-based therapy.

Comprehensive analysis of differentially expressed profiles of Alzheimer's disease associated circular RNAs in an Alzheimer's disease mouse model.

Circular RNAs (circRNAs), a novel kind of non-coding RNA, have received increasing attention for their involvement in pathogenesis of Alzheimer's disease (AD); however, few studies have reported in the characterization and function of AD associated circRNAs. Here the expression profiles of circRNAs in 5- and 10-month-old SAMP8 mice were identified using circRNA microarray and found that 85 dysregulated circRNAs were observed in 10-month-old SAMP8 versus control mice and 231 circRNAs exhibited differential expression in 10-month-old SAMP8 versus 5-month-old SAMP8. One most significantly dysregulated circRNA, mmu_circRNA_017963, was select for Gene Oncology (GO) and pathway analysis. The results showed that mmu_circRNA_017963 was strongly related with autophagosome assembly, exocytosis, apoptotic process, transport and RNA splicing and highly associated with synaptic vesicle cycle, spliceosome, glycosaminoglycan and SNARE interactions in vesicular transport pathways. Collectively, this study was the first to describe circRNAs expression in different ages of SAMP8 and will contribute to the understanding of the regulatory roles of circRNAs in AD pathogenesis and provide a valuable resource for the diagnosis and therapy of AD.

Diagnostic value of preoperative inflammatory markers in patients with glioma: a multicenter cohort study.

OBJECTIVE Glioma is the most common form of brain tumor and has high lethality. The authors of this study aimed to elucidate the efficiency of preoperative inflammatory markers, including neutrophil/lymphocyte ratio (NLR), derived NLR (dNLR), platelet/lymphocyte ratio (PLR), lymphocyte/monocyte ratio (LMR), and prognostic nutritional index (PNI), and their paired combinations as tools for the preoperative diagnosis of glioma, with particular interest in its most aggressive form, glioblastoma (GBM). METHODS The medical records of patients newly diagnosed with glioma, acoustic neuroma, meningioma, or nonlesional epilepsy at 3 hospitals between January 2011 and February 2016 were collected and retrospectively analyzed. The values of NLR, dNLR, PLR, LMR, and PNI were compared among patients suffering from glioma, acoustic neuroma, meningioma, and nonlesional epilepsy and healthy controls by using nonparametric tests. Correlations between NLR, dNLR, PLR, LMR, PNI, and tumor grade were analyzed. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic significance of NLR, dNLR, PLR, LMR, PNI, and their paired combinations for glioma, particularly GBM. RESULTS A total of 750 patients with glioma (Grade I, 81 patients; Grade II, 208 patients; Grade III, 169 patients; Grade IV [GBM], 292 patients), 44 with acoustic neuroma, 271 with meningioma, 102 with nonlesional epilepsy, and 682 healthy controls were included in this study. Compared with healthy controls and patients with acoustic neuroma, meningioma, or nonlesional epilepsy, the patients with glioma had higher values of preoperative NLR and dNLR as well as lower values of LMR and PNI, whereas PLR was higher in glioma patients than in healthy controls and patients with nonlesional epilepsy. Subgroup analysis revealed a positive correlation between NLR, dNLR, PLR, and tumor grade but a negative correlation between LMR, PNI, and tumor grade in glioma. For glioma diagnosis, the area under the curve (AUC) obtained from the ROC curve was 0.722 (0.697-0.747) for NLR, 0.696 (0.670-0.722) for dNLR, 0.576 (0.549-0.604) for PLR, 0.760 (0.738-0.783) for LMR, and 0.672 (0.646-0.698) for PNI. The best diagnostic performance was obtained with the combination of NLR+LMR and dNLR+LMR, with AUCs of 0.777 and 0.778, respectively. Additionally, NLR (AUC 0.860, 95% CI 0.832-0.887), dNLR (0.840, 0.810-0.869), PLR (0.678, 0.641-0.715), LMR (0.837, 0.811-0.863), and PNI (0.740, 0.706-0.773) had significant predictive value for GBM compared with healthy controls and other disease groups. As compared with the Grade I-III glioma patients, the GBM patients had an AUC of 0.811 (95% CI 0.778-0.844) for NLR, 0.797 (0.763-0.832) for dNLR, 0.662 (0.622-0.702) for PLR, 0.743 (0.707-0.779) for LMR, and 0.661(0.622-0.701) for PNI. For the paired combinations, NLR+LMR demonstrated the highest accuracy. CONCLUSIONS The NLR+LMR combination was revealed as a noninvasive biomarker with relatively high sensitivity and specificity for glioma diagnosis, the differential diagnosis of glioma from acoustic neuroma and meningioma, GBM diagnosis, and the differential diagnosis of GBM from low-grade glioma.

Fraction n-Butanol of Radix Notoginseng Protects PC12 Cells from Aß25-35-Induced Cytotoxicity and Alleviates Cognitive Deficits in SAMP8 Mice by Attenuating Oxidative Stress and Aß Accumulation.

Chinese medicine has been used for Alzheimer's disease (AD) treatment for thousands of years with more effective and fewer side effects. Therefore, developing effective potential candidates from Chinese medicine against AD would be considered as critical and efficient therapy for AD treatment. This study was designed to evaluate the neuronal protective effect of fraction n-butanol (NB) of Radix Notoginseng on Aß25-35-induced PC12 cells, explore the effect of the tested fraction on spatial learning and memory, and characterize the impacts of fraction NB on antioxidant enzymes, Aß production, and APP and BACE1 expressions. The results revealed that fraction NB could promote proliferation of PC12 cells and protect and rescue PC12 cells from Aß25-35-induced cell death. Moreover, fraction NB could improve spatial learning and memory impairments of senescence-accelerated prone8 (SAMP8) mice and attenuate oxidative stress and reduce the production of Aß by inhibiting the expressions of APP and BACE1 in the brains of SAMP8 mice. The result of single dose acute toxicity assay showed that fraction NB had a mild toxicity in vivo. The pronounced actions against AD and in vivo low toxicity of fraction NB suggest that fraction NB may be a useful alternative to the current AD treatment.