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8,234 result(s) for "Zheng, Qin"
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Mitochondrial-derived damage-associated molecular patterns amplify neuroinflammation in neurodegenerative diseases
Both mitochondrial dysfunction and neuroinflammation are implicated in neurodegeneration and neurodegenerative diseases. Accumulating evidence shows multiple links between mitochondrial dysfunction and neuroinflammation. Mitochondrial-derived damage-associated molecular patterns (DAMPs) are recognized by immune receptors of microglia and aggravate neuroinflammation. On the other hand, inflammatory factors released by activated glial cells trigger an intracellular cascade, which regulates mitochondrial metabolism and function. The crosstalk between mitochondrial dysfunction and neuroinflammatory activation is a complex and dynamic process. There is strong evidence that mitochondrial dysfunction precedes neuroinflammation during the progression of diseases. Thus, an in-depth understanding of the specific molecular mechanisms associated with mitochondrial dysfunction and the progression of neuroinflammation in neurodegenerative diseases may contribute to the identification of new targets for the treatment of diseases. In this review, we describe in detail the DAMPs that induce or aggravate neuroinflammation in neurodegenerative diseases including mtDNA, mitochondrial unfolded protein response (mtUPR), mitochondrial reactive oxygen species (mtROS), adenosine triphosphate (ATP), transcription factor A mitochondria (TFAM), cardiolipin, cytochrome c , mitochondrial Ca 2+ and iron.
Reduced nicotinamide adenine dinucleotide phosphate in redox balance and diseases: a friend or foe?
The nicotinamide adenine dinucleotide (NAD + /NADH) and nicotinamide adenine dinucleotide phosphate (NADP + /NADPH) redox couples function as cofactors or/and substrates for numerous enzymes to retain cellular redox balance and energy metabolism. Thus, maintaining cellular NADH and NADPH balance is critical for sustaining cellular homeostasis. The sources of NADPH generation might determine its biological effects. Newly-recognized biosynthetic enzymes and genetically encoded biosensors help us better understand how cells maintain biosynthesis and distribution of compartmentalized NAD(H) and NADP(H) pools. It is essential but challenging to distinguish how cells sustain redox couple pools to perform their integral functions and escape redox stress. However, it is still obscure whether NADPH is detrimental or beneficial as either deficiency or excess in cellular NADPH levels disturbs cellular redox state and metabolic homeostasis leading to redox stress, energy stress, and eventually, to the disease state. Additional study of the pathways and regulatory mechanisms of NADPH generation in different compartments, and the means by which NADPH plays a role in various diseases, will provide innovative insights into its roles in human health and may find a value of NADPH for the treatment of certain diseases including aging, Alzheimer’s disease, Parkinson’s disease, cardiovascular diseases, ischemic stroke, diabetes, obesity, cancer, etc.
Structure, regulation, and biological functions of TIGAR and its role in diseases
TIGAR (TP53-induced glycolysis and apoptosis regulator) is the downstream target gene of p53, contains a functional sequence similar to 6-phosphofructose kinase/fructose-2, 6-bisphosphatase (PFKFB) bisphosphatase domain. TIGAR is mainly located in the cytoplasm; in response to stress, TIGAR is translocated to nucleus and organelles, including mitochondria and endoplasmic reticulum to regulate cell function. P53 family members (p53, p63, and p73), some transcription factors (SP1 and CREB), and noncoding miRNAs (miR-144, miR-885-5p, and miR-101) regulate the transcription of TIGAR. TIGAR mainly functions as fructose-2,6-bisphosphatase to hydrolyze fructose-1,6-diphosphate and fructose-2,6-diphosphate to inhibit glycolysis. TIGAR in turn facilitates pentose phosphate pathway flux to produce nicotinamide adenine dinucleotide phosphate (NADPH) and ribose, thereby promoting DNA repair, and reducing intracellular reactive oxygen species. TIGAR thus maintains energy metabolism balance, regulates autophagy and stem cell differentiation, and promotes cell survival. Meanwhile, TIGAR also has a nonenzymatic function and can interact with retinoblastoma protein, protein kinase B, nuclear factor-kappa B, hexokinase 2, and ATP5A1 to mediate cell cycle arrest, inflammatory response, and mitochondrial protection. TIGAR might be a potential target for the prevention and treatment of cardiovascular and neurological diseases, as well as cancers.
Ultra-broadband metamaterial absorbers from long to very long infrared regime
Broadband metamaterials absorbers with high absorption, ultrathin thickness and easy configurations are in great demand for many potential applications. In this paper, we first analyse the coupling resonances in a Ti/Ge/Ti three-layer absorber, which can realise broadband absorption from 8 to 12 μm. Then we experimentally demonstrate two types of absorbers based on the Ti/Ge/Si3N4/Ti configuration. By taking advantage of coupling surface plasmon resonances and intrinsic absorption of lossy material Si3N4, the average absorptions of two types of absorbers achieve almost 95% from 8 to 14 μm (experiment result: 78% from 6.5 to 13.5 μm). In order to expand the absorption bandwidth, we further propose two Ti/Si/SiO2/Ti absorbers which can absorb 92% and 87% of ultra-broadband light in the 14–30 μm and 8–30 μm spectral range, respectively. Our findings establish general and systematic strategies for guiding the design of metamaterial absorbers with excellent broadband absorption and pave the way for enhancing the optical performance in applications of infrared thermal emitters, imaging and photodetectors.Ultra-broadband metamaterials absorbers with high absorption, ultrathin thickness and easy configurations are designed and demonstrated, which pave the way for enhancing the optical performance in applications of infrared thermal emitters, imaging and photodetectors.
The value of kidney injury molecule 1 in predicting acute kidney injury in adult patients: a systematic review and Bayesian meta-analysis
Introduction The aim of the study was to systematically review relevant studies to evaluate the diagnostic value of urinary kidney injury molecule 1 (uKIM-1) for acute kidney injury (AKI) in adults. Method We searched PubMed and Embase for literature published up to November 1st, 2019 and used the Quality Assessment Tool for Diagnosis Accuracy Studies (QUADAS-2) to assess the quality. Then, we extracted useful information from each eligible study and pooled sensitivity, specificity, and area under the curve (AUC) values. Results A total of 14 studies with 3300 patients were included. The estimated sensitivity of urinary KIM-1 (uKIM-1) in the diagnosis of AKI was 0.74 (95% CrI 0.62–0.84), and the specificity was 0.84 (95% CrI, 0.76–0.90). The pooled diagnostic odds ratio (DOR) was 15.22 (95% CrI, 6.74–42.20), the RD was 0.55 (95% CrI 0.43–0.70), and the AUC of uKIM-1 in diagnosing AKI was 0.62 (95% CrI 0.41–0.76). The results of the subgroup analysis showed the influence of different factors. Conclusion Urinary KIM-1 is a good predictor for AKI in adult patients with relatively high sensitivity and specificity. However, further research and clinical trials are still needed to confirm whether and how uKIM-1 can be commonly used in clinical diagnosis.
Natural Products as Anticancer Agents: Current Status and Future Perspectives
Natural products have been an invaluable and useful source of anticancer agents over the years. Several compounds have been synthesized from natural products by modifying their structures or by using naturally occurring compounds as building blocks in the synthesis of these compounds for various purposes in different fields, such as biology, medicine, and engineering. Multiple modern and costly treatments have been applied to combat cancer and limit its lethality, but the results are not significantly refreshing. Natural products, which are a significant source of new therapeutic drugs, are currently being investigated as potential cytotoxic agents and have shown a positive trend in preclinical research and have prompted numerous innovative strategies in order to combat cancer and expedite the clinical research. Natural products are becoming increasingly important for drug discovery due to their high molecular diversity and novel biofunctionality. Furthermore, natural products can provide superior efficacy and safety due to their unique molecular properties. The objective of the current review is to provide an overview of the emergence of natural products for the treatment and prevention of cancer, such as chemosensitizers, immunotherapeutics, combinatorial therapies with other anticancer drugs, novel formulations of natural products, and the molecular mechanisms underlying their anticancer properties.
Systemic Immune-Inflammation Index Is Associated With Increased Urinary Albumin Excretion: A Population-Based Study
Systemic immune-inflammation index (SII) is a novel inflammatory marker, and inflammation has been reported to be related with renal damage. We aimed to investigate the possible relationship between SII and albuminuria. The present cross-sectional study was conducted among adults with complete data about SII and urinary albumin-to-creatinine ratio (ACR) in 2005-2018 National Health and Nutrition Examination Survey (NHANES). SII was calculated as the platelet count × neutrophil count/lymphocyte count. Albuminuria was defined as ACR >30mg/g. Weighted multivariable regression analysis and subgroup analysis were conducted to explore the independent relationship between SII and albuminuria. A total of 36,463 individuals were included in our analysis; 9.56% participants were categorized as having albuminuria overall and increased with the higher SII tertiles (tertile 1, 7.83%; tertile 2, 8.49%; tertile 3, 12.13%; p for trend <0.0001). Multivariable logistic regression showed that a higher SII level was associated with increased likelihood of albuminuria independently (OR = 1.31; 95% CI, 1.17-1.48, p<0.0001) after full adjustment. Subgroup analysis and interaction test showed that there was no significant dependence of gender, age, body mass index, hypertension, diabetes, non-alcoholic fatty liver disease, and estimated glomerular filtration rate (eGFR) on this positive association (all p for interaction >0.05). SII was positively associated with increased urinary albumin excretion in US adults. Further large-scale prospective studies are still needed to analyze the role of SII in albuminuria.
A novel TaqMan probe-based pentaplex qPCR assay for the simultaneous detection of five pathogenic protozoans
The emergence of coinfection with Toxoplasma gondii , Neospora caninum , Eimeria stiedai , Giardia lamblia , and Trypanosoma evansi is an important problem that endangers human health, animal quality and public sanitary security. These pathogenic protozoans play important roles in establishment of similar clinical signs of diseases in humans, pigs, sheep, and rabbits, including fever, diarrhea, hepatitis, encephalitis, and reproductive disorders. Therefore, a rapid and specific diagnostic method to simultaneously detect these five pathogens is urgently required. Here, we developed a TaqMan-probe-based quantitative real-time polymerase chain reaction (qPCR) for the simultaneous detection of these five pathogens for the first time. Specific primers and probes were designed targeting the G3PDH gene of Toxoplasma gondii , the NC5 gene of Neospora caninum , the ADF gene of Eimeria stiedai , the GDH gene of Giardia lamblia , the COX1 gene of Trypanosoma evansi , and a TaqMan-probe-based pentaplex qPCR assay capable of simultaneously detecting these five pathogens was developed. The assay showed strong specificity, with no cross-reactivity detected against nucleic acids from other control pathogens. The assay demonstrated high sensitivity, with the lower limit of quantification (LLOQ) of 10 copies per reaction for the recombinant plasmid standards pTgG3PDH, pNcNC5, pEsADF, pGlGDH, pTeCOX1, and the limit of detection (LOD) as low as 1.1 copies. The standard curves exhibited excellent linearity (correlation coefficient values of 0.996, 0.996, 0.996, 0.992, and 0.996, respectively) and high amplification efficiencies (95.534%, 96.203%, 107.818%, 100.851%, and 104.487%, respectively). The assay also exhibited excellent repeatability and reproducibility, with inter- and intra-assay coefficient of variation (CV) ranging from 0.07% to 2.13%. The anti-interference test showed that high-concentration nucleic acids did not interfere with low-concentration nucleic acids, thus ensuring excellent detection results even in complex samples. Among 210 clinical samples, the assay detected Toxoplasma gondii in 2.38%, Neospora caninum in 2.38%, Eimeria stiedai in 10%, and Giardia lamblia in 36.19%. The coinfection rates were 8.1% for Eimeria stiedai & Giardia lamblia . This TaqMan-probe-based pentaplex qPCR assay offers a rapid, sensitive, and specific tool for the simultaneous detection of Toxoplasma gondii , Neospora caninum , Eimeria stiedai , Giardia lamblia , and Trypanosoma . It is of great significance to safeguard human health.
SARS-CoV-2 membrane glycoprotein M antagonizes the MAVS-mediated innate antiviral response
A novel SARS-related coronavirus (SARS-CoV-2) has recently emerged as a serious pathogen that causes high morbidity and substantial mortality. However, the mechanisms by which SARS-CoV-2 evades host immunity remain poorly understood. Here, we identified SARS-CoV-2 membrane glycoprotein M as a negative regulator of the innate immune response. We found that the M protein interacted with the central adaptor protein MAVS in the innate immune response pathways. This interaction impaired MAVS aggregation and its recruitment of downstream TRAF3, TBK1, and IRF3, leading to attenuation of the innate antiviral response. Our findings reveal a mechanism by which SARS-CoV-2 evades the innate immune response and suggest that the M protein of SARS-CoV-2 is a potential target for the development of SARS-CoV-2 interventions.