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"Fu, Li-Yan"
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Targeting glycolysis in non-small cell lung cancer: Promises and challenges
Metabolic disturbance, particularly of glucose metabolism, is a hallmark of tumors such as non-small cell lung cancer (NSCLC). Cancer cells tend to reprogram a majority of glucose metabolism reactions into glycolysis, even in oxygen-rich environments. Although glycolysis is not an efficient means of ATP production compared to oxidative phosphorylation, the inhibition of tumor glycolysis directly impedes cell survival and growth. This review focuses on research advances in glycolysis in NSCLC and systematically provides an overview of the key enzymes, biomarkers, non-coding RNAs, and signaling pathways that modulate the glycolysis process and, consequently, tumor growth and metastasis in NSCLC. Current medications, therapeutic approaches, and natural products that affect glycolysis in NSCLC are also summarized. We found that the identification of appropriate targets and biomarkers in glycolysis, specifically for NSCLC treatment, is still a challenge at present. However, LDHB, PDK1, MCT2, GLUT1, and PFKM might be promising targets in the treatment of NSCLC or its specific subtypes, and DPPA4, NQO1, GAPDH/MT-CO1, PGC-1α, OTUB2, ISLR, Barx2, OTUB2, and RFP180 might be prognostic predictors of NSCLC. In addition, natural products may serve as promising therapeutic approaches targeting multiple steps in glycolysis metabolism, since natural products always present multi-target properties. The development of metabolic intervention that targets glycolysis, alone or in combination with current therapy, is a potential therapeutic approach in NSCLC treatment. The aim of this review is to describe research patterns and interests concerning the metabolic treatment of NSCLC.
Journal Article
تاريخ العلاقات بين الصين وعمان
يستعرض هذا الكتاب الجوانب التاريخية والسياسية والثقافية للعلاقات بين الصين وسلطنة عمان، منذ العصور القديمة وحتى العصر الحديث، مع تركيز خاص على التبادل التجاري والبحري الذي ازدهر بين الجانبين عبر طريق الحرير البحري. يبرز الكتاب كيف شكل التواصل الحضاري بين الصين وعمان أحد أقدم النماذج للعلاقات السلمية في التاريخ، حيث ساهم البحارة العمانيون في نقل السلع والثقافات بين الشرق الأقصى والجزيرة العربية. كما يتناول العلاقات الدبلوماسية الحديثة بين البلدين، وتطورها في إطار الشراكات الاقتصادية ومبادرة الحزام والطريق، مؤكدا على الاحترام المتبادل والتعاون المتوازن بين البلدين عبر القرون.
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BMSCs differentiated into neurons, astrocytes and oligodendrocytes alleviated the inflammation and demyelination of EAE mice models
Multiple sclerosis (MS) is a complex, progressive neuroinflammatory disease associated with autoimmunity. Currently, effective therapeutic strategy was poorly found in MS. Experimental autoimmune encephalomyelitis (EAE) is widely used to study the pathogenesis of MS. Cumulative research have shown that bone marrow mesenchymal stem Cells (BMSCs) transplantation could treat EAE animal models, but the mechanism was divergent. Here, we systematically evaluated whether BMSCs can differentiate into neurons, astrocytes and oligodendrocytes to alleviate the symptoms of EAE mice. We used Immunofluorescence staining to detect MAP-2, GFAP, and MBP to evaluate whether BMSCs can differentiate into neurons, astrocytes and oligodendrocytes. The effect of BMSCs transplantation on inflammatory infiltration and demyelination in EAE mice were detected by Hematoxylin-Eosin (H&E) and Luxol Fast Blue (LFB) staining, respectively. Inflammatory factors expression was detected by ELISA and RT-qPCR, respectively. Our results showed that BMSCs could be induced to differentiate into neuron cells, astrocytes and oligodendrocyte in vivo and in vitro , and BMSCs transplanted in EAE mice were easier to differentiate than normal mice. Moreover, transplanted BMSCs reduced neurological function scores and disease incidence of EAE mice. BMSCs transplantation alleviated the inflammation and demyelination of EAE mice. Finally, we found that BMSCs transplantation down-regulated the levels of pro-inflammatory factors TNF-α, IL-1β and IFN-γ, and up-regulated the levels of anti-inflammatory factors IL-10 and TGF-β. In conclusion, this study found that BMSCs could alleviate the inflammatory response and demyelination in EAE mice, which may be achieved by the differentiation of BMSCs into neurons, astrocytes and oligodendrocytes in EAE mice.
Journal Article
Cyber-Attacks on Smart Meters in Household Nanogrid: Modeling, Simulation and Analysis
The subject of cyber-security and therefore cyber-attacks on smart grid (SG) has become subject of many publications in the last years, emphasizing its importance in research, as well as in practice. One especially vulnerable part of SG are smart meters (SMs). The major contribution of simulating a variety of cyber-attacks on SMs that have not been done in previous studies is the identification and quantification of the possible impacts on the security of SG. In this study, a simulation model of a nanogrid, including a complete household with an SM, was developed. Different cyber-attacks were injected into the SM to simulate their effects on household nanogrid. The analysis of the impacts of different cyber-attacks showed that the effects of cyber-attacks can be sorted into various categories. Integrity and confidentiality attacks cause monetary effects on the grid. While, availability attacks have monetary effects on the grid as well, they are mainly aimed at compromising the SM communication by either delaying or stopping it completely.
Journal Article
Luteolin Attenuates Hypertension via Inhibiting NF-κB-Mediated Inflammation and PI3K/Akt Signaling Pathway in the Hypothalamic Paraventricular Nucleus
Background: Luteolin is widely distributed among a number of vegetal species worldwide. The pharmacological effects of luteolin are diverse and amongst antioxidant, free radical scavenging, and anti-inflammatory activities. Preliminary study showed that luteolin can ameliorate hypertension. However, the precise mechanism needs further investigation. There is no evidence that luteolin affects the paraventricular nucleus of the hypothalamus (PVN), a brain nucleus associated with a critical neural regulator of blood pressure. Our main aim was to explore the effect of luteolin on the PI3K/Akt/NF-κB signaling pathway within the PVN of hypertensive rats. Methods: spontaneously hypertensive rats (SHRs) and corresponding normotensive control rats, the Wistar Kyoto (WKY) rats were divided into four groups and subsequently treated for 4 weeks with bilateral PVN injections of either luteolin (20 µg/0.11 µL, volume: 0.11 µL/h) or vehicle (artificial cerebrospinal fluid). Results: luteolin infusion to the PVN significantly decreased some hemodynamic parameters including the mean arterial pressure (MAP), heart rate (HR), circulating plasma norepinephrine (NE) and epinephrine (EPI). Additionally, there was a decrease in the expressions of the phosphatidylinositol 3-kinase (p-PI3K) and phosphorylated protein kinase-B (p-AKT), levels of reactive oxygen species (ROS), NAD(P)H oxidase subunit (NOX2, NOX4) in the PVN of SHRs. Meanwhile, the expression of inflammatory cytokines and the activity of nuclear factor κB (NF-κB) p65 in the PVN of SHRs were lowered. Furthermore, immunofluorescence results showed that injection of luteolin in the PVN reduced the expression of tyrosine hydroxylase (TH), and increased that of superoxide dismutase (SOD1) and the 67-kDa isoform of glutamate decarboxylase (GAD67) in the PVN of SHRs. Conclusion: Our novel findings revealed that luteolin lowered hypertension via inhibiting NF-κB-mediated inflammation and PI3K/Akt signaling pathway in the PVN.
Journal Article
Population-attributable fractions of risk factors for all-cause dementia in China rural and urban areas: a cross-sectional study
BackgroundThe prevalence of dementia in China, particularly in rural areas, is consistently increasing; however, research on population-attributable fractions (PAFs) of risk factors for dementia is scarce.MethodsWe conducted a cross-sectional survey, namely, the China Multicentre Dementia Survey (CMDS) in selected rural and urban areas from 2018 to 2020. We performed face-to-face interviews and neuropsychological and clinical assessments to reach a consensus on dementia diagnosis. Prevalence and weighted PAFs of eight modifiable risk factors (six classical: less childhood education, hearing impairment, depression, physical inactivity, diabetes, and social isolation, and two novels: olfactory decline and being unmarried) for all-cause dementia were estimated.ResultsOverall, CMDS included 17,589 respondents aged ≥ 65 years, 55.6% of whom were rural residents. The age- and sex-adjusted prevalence for all-cause dementia was 9.11% (95% CI 8.96–9.26), 5.19% (5.07–5.31), and 11.98% (11.8–12.15) in the whole, urban, and rural areas of China, respectively. Further, the overall weighted PAFs of the eight potentially modifiable risk factors were 53.72% (95% CI 52.73–54.71), 50.64% (49.4–51.89), and 56.54% (55.62–57.46) in the whole, urban, and rural areas of China, respectively. The eight risk factors’ prevalence differed between rural and urban areas. Lower childhood education (PAF: 13.92%) and physical inactivity (16.99%) were primary risk factors in rural and urban areas, respectively.ConclusionsThe substantial urban–rural disparities in the prevalence of dementia and its risk factors exist, suggesting the requirement of resident-specific dementia-prevention strategies.
Journal Article
Puerarin Alleviates Blood Pressure via Inhibition of ROS/TLR4/NLRP3 Inflammasome Signaling Pathway in the Hypothalamic Paraventricular Nucleus of Salt-Induced Prehypertensive Rats
Background: Puerarin is an isoflavone compound isolated from the roots of a leguminous plant, the wild kudzu. Various functional activities of this compound in multiple diseases have been reported. However, the effect and mechanism of puerarin in improving blood pressure remain non-elucidated. Purpose: The current study was designed to assess the preventive effects of puerarin on the onset and progression of hypertension and to verify the hypothesis that puerarin alleviates blood pressure by inhibiting the ROS/TLR4/NLRP3 inflammasome signaling pathway in the hypothalamic paraventricular nucleus (PVN) of salt-induced prehypertensive rats. Methods: Male Dahl salt-sensitive rats were fed low NaCl salt (3% in drinking water) for the control (NS) group or 8% (HS) to induce prehypertension. Each batch was divided into two group and treated by bilateral PVN microinjection with either artificial cerebrospinal fluid or puerarin through a micro-osmotic pump for 6 weeks. The mean arterial pressure (MAP) was recorded, and samples were collected and analyzed. Results: We concluded that puerarin significantly prevented the elevation of blood pressure and effectively alleviated the increase in heart rate caused by high salt. Norepinephrine (NE) in the plasma of salt-induced prehypertensive rats also decreased upon puerarin chronic infusion. Additionally, analysis of the PVN sample revealed that puerarin pretreatment decreased the positive cells and gene level of TLR4 (Toll-like receptor 4), NLRP3, Caspase-1 p10, NOX2, MyD88, NOX4, and proinflammatory cytokines in the PVN. Puerarin pretreatment also decreased NF-κBp65 activity, inhibited oxidative stress, and alleviated inflammatory responses in the PVN. Conclusion: We conclude that puerarin alleviated blood pressure via inhibition of the ROS/TLR4/NLRP3 inflammasome signaling pathway in the PVN, suggesting the therapeutic potential of puerarin in the prevention of hypertension.
Journal Article
Central blockade of NLRP3 reduces blood pressure via regulating inflammation microenvironment and neurohormonal excitation in salt-induced prehypertensive rats
Background
Inflammation has been implicated in the development of cardiovascular disease. We determined whether nod-like receptor with pyrin domain containing 3 (NLRP3) involved in the process of prehypertension, central blockade of NLRP3 decreased inflammation reaction, regulated neurohormonal excitation, and delayed the progression of prehypertension.
Methods
Prehypertensive rats were induced by 8% salt diet. The rats on high-salt diet for 1 month were administered a specific NLRP3 blocker in the hypothalamic paraventricular nucleus (PVN) for 4 weeks. ELISA, western blotting, immunohistochemistry, and flow cytometry were used to measure NLRP3 cascade proteins, pro-inflammation cytokines (PICs), chemokine ligand 2 (CCL2), C-X-C chemokine receptor type 3 (CXCR3), vascular cell adhesion molecule 1 (VCAM-1), neurotransmitters, and leukocytes count detection, respectively.
Results
NLRP3 expression in PVN was increased significantly in prehypertensive rats, accompanied by increased number of microglia, CD4
+
, CD8
+
T cell, and CD8
+
microglia. Expressions of PICs, CCL2, CXCR3, and VCAM-1 significantly increased. The balance between 67-kDa isoform of glutamate decarboxylase (GAD67) and tyrosine hydroxylase (TH) was damaged. Plasma norepinephrine (NE) in prehypertensive rats was increased and gamma-aminobutyric acid (GABA) was reduced. NLRP3 blockade significantly decreased blood pressure, reduced PICs, CCL2, VCAM-1 expression in PVN, and restored neurotransmitters. Blood pressure and inflammatory markers were upregulated after termination of central blockage NLRP3.
Conclusions
Salt-induced prehypertension is partly due to the role of NLRP3 in PVN. Blockade of brain NLRP3 attenuates prehypertensive response, possibly via downregulating the cascade reaction triggered by inflammation and restoring the balance of neurotransmitters.
Journal Article
Resveratrol in the Hypothalamic Paraventricular Nucleus Attenuates Hypertension by Regulation of ROS and Neurotransmitters
Background: The hypothalamic paraventricular nucleus (PVN) is an important nucleus in the brain that plays a key role in regulating sympathetic nerve activity (SNA) and blood pressure. Silent mating-type information regulation 2 homolog-1 (sirtuin1, SIRT1) not only protects cardiovascular function but also reduces inflammation and oxidative stress in the periphery. However, its role in the central regulation of hypertension remains unknown. It is hypothesized that SIRT1 activation by resveratrol may reduce SNA and lower blood pressure through the regulation of intracellular reactive oxygen species (ROS) and neurotransmitters in the PVN. Methods: The two-kidney one-clip (2K1C) method was used to induce renovascular hypertension in male Sprague-Dawley rats. Then, bilaterally injections of vehicle (artificial cerebrospinal fluid, aCSF, 0.4 μL) or resveratrol (a SIRT1 agonist, 160 μmol/L, 0.4 μL) into rat PVN were performed for four weeks. Results: PVN SIRT1 expression was lower in the hypertension group than the sham surgery (SHAM) group. Activated SIRT1 within the PVN lowered systolic blood pressure and plasma norepinephrine (NE) levels. It was found that PVN of 2K1C animals injected with resveratrol exhibited increased expression of SIRT1, copper-zinc superoxide dismutase (SOD1), and glutamic acid decarboxylase (GAD67), as well as decreased activity of nuclear factor-kappa B (NF-κB) p65 and NAD(P)H oxidase (NOX), particularly NOX4. Treatment with resveratrol also decreased expression of ROS and tyrosine hydroxylase (TH). Conclusion: Resveratrol within the PVN attenuates hypertension via the SIRT1/NF-κB pathway to decrease ROS and restore the balance of excitatory and inhibitory neurotransmitters.
Journal Article