Aberrant regulation in mesangial cell proliferation, extracellular matrix (ECM) accumulation, oxidative stress, and inflammation under hyperglycemic condition contributes significantly to the ...occurrence and development of diabetic nephropathy (DN). However, the mechanisms underlying the hyperglycemia‐induced dysregulations have not been clearly elucidated. Here, we reported that high mobility group box 1 (HMGB1) was highly elevated in high glucose (HG)‐treated mesangial cells, and induced the phosphorylation, nuclear translocation, and DNA binding activity of NF‐κB via toll‐like receptor 4 (TLR4). Function assays showed that inhibition of HMGB1 mitigated HG‐induced proliferation, oxidative stress, ECM accumulation, and inflammation in mesangial cells via TLR4/NF‐κB pathway. Increasing evidence has shown that circRNA, a large class of noncoding RNAs, functions by binding with miRNAs and terminating regulation of their target genes. We further investigated whether HMGB1 is involved in circRNA–miRNA–mRNA regulatory network. First, HMGB1 was identified and confirmed to be the target of miR‐205, and miR‐205 played a protective role against HG‐induced cell injure via targeting HMGB1. Then circLRP6 was found to be upregulated in HG‐treated mesangial cells, and regulate HG‐induced mesangial cell injure via sponging miR‐205. Besides, overexpression of miR‐205 or knockdown of circLRP6 inhibited the NF‐κB signaling pathway. Collectively, these data suggest that circLRP6 regulates HG‐induced proliferation, oxidative stress, ECM accumulation, and inflammation in mesangial cells via sponging miR‐205, upregulating HMGB1 and activating TLR4/NF‐κB pathway. These findings provide a better understanding for the pathogenesis of DN.
1.
Inhibition of high mobility group box 1 (HMGB1) mitigated high glucose (HG)‐induced proliferation, oxidative stress, extracellular matrix (ECM) accumulation, and inflammation in mesangial cells via TLR4/NF‐κB pathway.
2.
HMGB1 was identified and confirmed to be the target of miR‐205, and miR‐205 played a protective role against HG‐induced cell injure via targeting HMGB1.
3.
circLRP6 regulates HG‐induced proliferation, oxidative stress, ECM accumulation, and inflammation in mesangial cells via sponging miR‐205, upregulating HMGB1 and activating TLR4/NF‐κB pathway.
From 2003 to 2005, standardised 5-year cancer survival in China was much lower than in developed countries and varied substantially by geographical area. Monitoring population-level cancer survival ...is crucial to the understanding of the overall effectiveness of cancer care. We therefore aimed to investigate survival statistics for people with cancer in China between 2003 and 2015.
We used population-based data from 17 cancer registries in China. Data for the study population was submitted by the end of July 31, 2016, with follow-up data on vital status obtained on Dec 31, 2015. We used anonymised, individual cancer registration records of patients (aged 0–99 years) diagnosed with primary, invasive cancers from 2003 to 2013. Patients eligible for inclusion had data for demographic characteristics, date of diagnosis, anatomical site, morphology, behaviour code, vital status, and last date of contact. We analysed 5-year relative survival by sex, age, and geographical area, for all cancers combined and 26 different cancer types, between 2003 and 2015. We stratified survival estimates by calendar period (2003–05, 2006–08, 2009–11, and 2012–15).
There were 678 842 records of patients with invasive cancer who were diagnosed between 2003 and 2013. Of these records, 659 732 (97·2%) were eligible for inclusion in the final analyses. From 2003–05 to 2012–15, age-standardised 5-year relative survival increased substantially for all cancers combined, for both male and female patients, from 30·9% (95% CI 30·6–31·2) to 40·5% (40·3–40·7). Age-standardised 5-year relative survival also increased for most cancer types, including cancers of the uterus (average change per calendar period 5·5% 95% CI 2·5–8·5), thyroid (5·4% 3·2–7·6), cervix (4·5% 2·9–6·2), and bone (3·2% 2·1–4·4). In 2012–15, age-standardised 5-year survival for all patients with cancer was higher in urban areas (46·7%, 95% CI 46·5–47·0) than in rural areas (33·6%, 33·3–33·9), except for patients with oesophageal or cervical cancer; but improvements in survival were greater for patients residing in rural areas than in urban areas. Relative survival decreased with increasing age. The increasing trends in survival were consistent with the upward trends of medical expenditure of the country during the period studied.
There was a marked overall increase in cancer survival from 2003 to 2015 in the population covered by these cancer registries in China, possibly reflecting advances in the quality of cancer care in these areas. The survival gap between urban and rural areas narrowed over time, although geographical differences in cancer survival remained. Insight into these trends will help prioritise areas that need increased cancer care.
National Key R&D Program of China, PUMC Youth Fund and the Fundamental Research Funds for the Central Universities, and Major State Basic Innovation Program of the Chinese Academy of Medical Sciences.
Adding surfactant can improve the stability of hybrid nanofluids. However, positive or negative effects of the surfactant on the thermophysical properties of hybrid nanofluids should be further ...investigated. In the present study, effects of different surfactants, including SDS, PVP and CTAB, with various mass concentrations and temperatures on the stability of Al2O3-CuO/Water (W) and Al2O3-TiO2/Water (W) hybrid nanofluids are investigated. Results show that increment of surfactant concentration improves the stability and viscosity. Then obtained results from UV–Vis Spectrophotometer, TEM and sedimentation methods are compared, and PVP surfactant has the highest degree of stability, with the minimal sedimentation up to 25 days. At the optimum PVP surfactant concentrations of 0.005 wt% and 0.01 wt%, the maximum thermal conductivity enhancement is 12% and 14% at 60 °C for Al2O3-CuO/W and Al2O3-TiO2/W hybrid nanofluids. Therefore, adding even little amount of surfactant can improve the stability and thermal conductivity of hybrid nanofluids.
New drug discovery has been acknowledged as a complicated, expensive, time-consuming, and challenging project. It has been estimated that around 12 years and 2.7 billion USD, on average, are demanded ...for a new drug discovery
traditional drug development pipeline. How to reduce the research cost and speed up the development process of new drug discovery has become a challenging, urgent question for the pharmaceutical industry. Computer-aided drug discovery (CADD) has emerged as a powerful, and promising technology for faster, cheaper, and more effective drug design. Recently, the rapid growth of computational tools for drug discovery, including anticancer therapies, has exhibited a significant and outstanding impact on anticancer drug design, and has also provided fruitful insights into the area of cancer therapy. In this work, we discussed the different subareas of the computer-aided drug discovery process with a focus on anticancer drugs.
The development of a specific reaction of nanomaterials and reactive species is of fundamental importance for the determination of biomolecules. Here we report a novel nanoprobe for detection and ...imaging of ascorbic acid (AA) in living cells and in vivo based on the specific reaction of cobalt oxyhydroxide (CoOOH) and AA. Persistent luminescence nanoparticles (PLNPs) were used as the luminescence unit, and CoOOH nanoflakes served as the quencher. When CoOOH was modified on the surface of the PLNPs, the luminescence of the PLNPs was efficiently quenched by the CoOOH. In the presence of AA, CoOOH was reduced to Co(2+) and the luminescence of PLNPs was restored. The nanoprobe showed high selectivity and an instantaneous response. The luminescence property permits detection and imaging without external excitation, which could effectively avoid background noise and scattering of light from biological matrixes produced by in situ excitation. The current strategy provides an effective platform for monitoring and imaging reactive species in living cells and in vivo.
Background
Several lines of evidence have indicated that growth arrest-specific transcript 5 (GAS5) functions as a tumor suppressor and is aberrantly expressed in multiple cancers. GAS5 was found to ...be downregulated in gastric cancer (GC) tissues, and ectopic expression of GAS5 inhibited GC cell proliferation.
Aims
The present study aimed to explore the underlying mechanisms of GAS5 involved in GC cell proliferation.
Methods
GAS5 and miR-222 expressions in GC cell lines were estimated by quantitative real-time polymerase chain reaction. The effects of GAS5 and miR-222 on GC cell proliferation were assessed by MTT assay and 5-bromo-2-deoxyuridine (BrdU) incorporation assays. The interaction between GAS5 and miR-222 was confirmed by luciferase reporter assay and RNA immunoprecipitation assay. The protein levels of the phosphatase and tensin homolog (PTEN), phosphorylated protein kinase B (Akt) (p-Akt), Akt, phosphorylated mammalian target of rapamycin (mTOR) (p-mTOR), and mTOR were determined by western blot.
Results
GAS5 was downregulated and miR-222 was upregulated in GC cells. GAS5 directly targeted and suppressed miR-222 expression. GAS5 overexpression and miR-222 inhibition suppressed cell proliferation, increased PTEN protein level and decreased p-Akt and p-mTOR protein levels in GC cells while GAS5 knockdown and miR-222 overexpression exhibited the opposite effects. Moreover, mechanistic analyses revealed that GAS5 regulated GC cell proliferation through the PTEN/Akt/mTOR pathway by negatively regulating miR-222.
Conclusions
GAS5/miR-222 axis regulated proliferation of GC cells through the PTEN/Akt/mTOR pathway, which facilitated the development of lncRNA-directed therapy against this deadly disease.
Tumor hypoxia typically occurs inside a solid tumor with an inadequate oxygen supply, sharply reducing the therapeutic efficiency of radiotherapy and significantly increasing the risk of local tumor ...recurrence. Herein, we designed folic acid modified enzyme-like hafnium-based manganoporphyrin metal-organic framework nanoparticles (MnTCPP-Hf-FA MOF NPs) to overcome hypoxia-induced radioresistance and prevent postoperative recurrence. Hf, a high-Z element, can effectively absorb X-ray energy and convert O
2
and H
2
O into reactive oxygen species to induce cell apoptosis. The MnTCPP ligand has an enzyme-like ability to catalytically decompose endogenous H
2
O
2
into O
2
for enhancing RT in hypoxic tumors.
In vivo
experiments revealed that the MOF NPs could effectively inhibit melanoma growth and prevent tumor postoperative recurrence with only one X-ray irradiation after intravenous injection. We expect that the current study provides a versatile approach for solving the critical radioresistance issue of hypoxic tumors.
Tumor hypoxia typically occurs inside a solid tumor with an inadequate oxygen supply, sharply reducing the therapeutic efficiency of radiotherapy and significantly increasing the risk of local tumor recurrence.
Porcine respirovirus 1 (PRV1), first reported in Hong Kong, is currently widely spread in several countries. Our knowledge of the clinical significance and the pathogenicity of this virus is still ...limited. In this study, we studied the interactions between PRV1 and host innate immune responses. PRV1 exhibited strong inhibitory effects on the production of interferon (IFN), ISG15, and RIG-I induced by SeV infection. Our data generated in vitro suggest that multiple viral proteins can suppress host type I interferon production and signaling, including N, M, and P/C/V/W. The P gene products disrupt both IRF3 and NF-κB dependent type I IFN production and block type I IFN signaling pathway by sequestering STAT1 in the cytoplasm. The V protein disrupts both MDA5 signaling and RIG-I signaling through interaction with TRIM25 and RIG-I, V protein blocks RIG-I polyubiquitination, which is required for RIG-I activation. V protein also binds to MDA5, which may contribute to its inhibitory effect on MDA5 signaling. These findings indicate that PRV1 antagonizes host innate immune responses using various mechanisms, which provides important insights into the pathogenicity of PRV1.
To understand the remarkable enhancements in viscosity and thermal conductivity of nanofluids, a molecular dynamics (MD) simulation approach was used to investigate the structure and thickness of the ...interfacial layer and obtain values for radial distribution function, g(r), viscosity, and thermal conductivity of Cu/water nanofluids with volume fractions and temperatures ranging from 0.5–2 vol% and 293–333 K, respectively. The results revealed that value of g(r) was much higher in the first molecular nanolayer compared to the second layer, indicating that greater numbers of water molecules are present in the first layer, which reduces contact thermal resistance and improves thermal conductivity of nanofluids. Moreover, while value of g(r) increased with increasing Cu volume fraction and decreased with temperature, nanolayer thickness was unchanged with temperature at each volume fraction, indicating that intermolecular forces intensify in the first nanolayer. Macroscopically, viscosity and thermal conductivity of the nanofluids increased at higher volume fractions, showing increases of 71.7% and 75% for viscosity, and 41.7% and 53.3% for thermal conductivity at 0.5 and 2 vol%, respectively, compared to water at 333 K. These results, although obtained for Cu/water systems, can provide useful insights into structural and transport properties of nanofluids in general.
Drought is a global threat that affects agricultural production. Plants have evolved several adaptive strategies to cope with drought. Stomata are essential structures for plants to control water ...status and photosynthesis rate. Stomatal closure is an efficient way for plants to reduce water loss and improve survivability under drought conditions. The opening and closure of stomata depend on the turgor pressure in guard cells. Three key signaling molecules, including abscisic acid (ABA), reactive oxygen species (ROS), and calcium ion (Ca2+), play pivotal roles in controlling stomatal closure. Plants sense the water-deficit signal mainly via leaves and roots. On the one hand, ABA is actively synthesized in root and leaf vascular tissues and transported to guard cells. On the other hand, the roots sense the water-deficit signal and synthesize CLAVATA3/EMBRYO-SURROUNDING REGION RELATED 25 (CLE25) peptide, which is transported to the guard cells to promote ABA synthesis. ABA is perceived by pyrabactin resistance (PYR)/PYR1-like (PYL)/regulatory components of ABA receptor (RCAR) receptors, which inactivate PP2C, resulting in activating the protein kinases SnRK2s. Many proteins regulating stomatal closure are activated by SnRK2s via protein phosphorylation. ABA-activated SnRK2s promote apoplastic ROS production outside of guard cells and transportation into the guard cells. The apoplastic H2O2 can be directly sensed by a receptor kinase, HYDROGEN PEROXIDE-INDUCED CA2+ INCREASES1 (HPCA1), which induces activation of Ca2+ channels in the cytomembrane of guard cells, and triggers an increase in Ca2+ in the cytoplasm of guard cells, resulting in stomatal closure. In this review, we focused on discussing the signaling transduction of ABA, ROS, and Ca2+ in controlling stomatal closure in response to drought. Many critical genes are identified to have a function in stomatal closure under drought conditions. The identified genes in the process can serve as candidate genes for genetic engineering to improve drought resistance in crops. The review summarizes the recent advances and provides new insights into the signaling regulation of stomatal closure in response to water-deficit stress and new clues on the improvement of drought resistance in crops.
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