Lateral Flow Assay Biotesting by Utilizing Plasmonic Nanoparticles Made of Inexpensive Metals─Replacing Colloidal Gold.

Nanoparticles (NPs) can be conjugated with diverse biomolecules and employed in biosensing to detect target analytes in biological samples. This proven concept was primarily used during the COVID-19 pandemic with gold-NP-based lateral flow assays (LFAs). Considering the gold price and its worldwide depletion, here we show that novel plasmonic NPs based on inexpensive metals, titanium nitride (TiN) and copper covered with a gold shell (Cu@Au), perform comparable to or even better than gold nanoparticles. After conjugation, these novel nanoparticles provided high figures of merit for LFA testing, such as high signals and specificity and robust naked-eye signal recognition. Since the main cost of Au NPs in commercial testing kits is the colloidal synthesis, our development with the Cu@Au and the laser-ablation-fabricated TiN NPs is exciting, offering potentially inexpensive plasmonic nanomaterials for various bioapplications. Moreover, our machine learning study showed that biodetection with TiN is more accurate than that with Au.

ZFP36L1 controls KLF16 mRNA stability in vascular smooth muscle cells during restenosis after vascular injury.

The RNA-binding zinc finger protein 36 (ZFP36) family participates in numerous physiological processes including transition and differentiation through post-transcriptional regulation. ZFP36L1 is a member of the ZFP36 family. This study aimed to evaluate the role of ZFP36L1 in restenosis. We found that the expression of ZFP36L1 was inhibited in VSMC-phenotypic transformation induced by TGF-ß, PDGF-BB, and FBS and also in the rat carotid injury model. In addition, we found that the overexpression of ZFP36L1 inhibited the proliferation and migration of VSMCs and promoted the expression of VSMC contractile genes; whereas ZFP36L1 interference promoted the proliferation and migration of VSMCs and suppressed the expression of contractile genes. Furthermore, the RNA binding protein immunoprecipitation and double luciferase reporter gene experiments shows that ZFP36L1 regulates the phenotypic transformation of VSMCs through the posttranscriptional regulation of KLF16. Finally, our research results in the rat carotid balloon injury animal model further confirmed that ZFP36L1 regulates the phenotypic transformation of VSMCs through the posttranscriptional regulation of KLF16 and further plays a role in vascular injury and restenosis in vivo.

Effect of Zr on the Microstructure and High-Temperature Phase Separation Evolution of SiOC Aerogels.

SiZrOC aerogels were synthesized through the pyrolysis of the zirconium source-doped SiOC system using zirconyl chloride octahydrate (ZrOCl2·8H2O) at temperatures ranging from 900 to 1300 °C. This study investigates the microstructure evolution and phase separation of SiOC and SiZrOC aerogels during the pyrolysis process. Upon pyrolysis, both aerogels exhibited a Si-O-C structure with a high thermal stability. The introduction of zirconium elements significantly enhanced the pore volume (3.20 cm3/g) and porosity (96.0%) and reduced the thermal conductivity (0.023 W·m-1·K-1) of the organic-inorganic precursor aerogel. Moreover, the three-dimensional pore structure was retained even under high-temperature pyrolysis conditions. SiZrOC-1100 displayed a high specific surface area of 273.52 m2/g, a high pore volume of 1.70 cm3/g, and a low thermal conductivity of 0.033 W·m-1·K-1. At high temperatures, the SiZrOC phase transformation produces tetragonal ZrO2, which inhibits the graphitization process of free carbon and the growth of SiC grains. Furthermore, the phase separation process of the SiOxCy matrix structure generated oxygen-rich SiOxC4-x units, while carbon-rich SiOxC4-x units were negligible below a pyrolysis temperature of 1200 °C. Between 900 and 1200 °C, SiZrOC is composed of amorphous SiOC, amorphous ZrO2, microcrystalline t-ZrO2, and free carbon phase. These findings provide valuable insights into the preparation of high-performance SiOC aerogels.

Trends in health service needs, utilization, and non-communicable chronic diseases burden of older adults in China: evidence from the 1993 to 2018 National Health Service Survey.

BACKGROUND: Aging is associated with an increased prevalence of non-communicable chronic diseases (NCDs), functional impairments, and diverse demands for health services. This study analyzed the trends in older adults' needs and utilization of health services from 1993 to 2018 in China, as well as chronic disease-related economic burdens. METHODS: The research data were collected from the six cross-sectional National Health Service Survey (NHSS), implemented every 5 years from 1993 to 2018. A multi-stage stratified random cluster sampling method has been adopted in the NHSS. The data on the older population's socio-economic characteristics, health service needs, and utilization were collected from the 6 waves National Health Service Survey (NHSS) 1993-2018. In the 2013 and 2018 NHSSs, EQ-5D-3L and visual analogue scale were used to evaluate the health condition. And the prevalence of NCDs and related Out-of-pocket (OOP) expenditures were collected. Functional dependency and impairment were collected in 2018. The Katz Activities of Daily Living scale was used to evaluate six functions, including self-feeding, dressing, bathing, transferring, toilet hygiene, and controlling bowel movements. RESULTS: The two-week morbidity rate and prevalence of NCDs showed a rapid upward trend in older adults. With the development of health system reform and universal health insurance coverage, older adults' two-week medical consultation rate increased from 25.6% in 1993 to 40.1% in 2018, and the hospitalization rate rose from 6.1% to 24.9%. The difference in health service needs and utilization between urban and rural areas decreased, and the hospitalization rate in rural areas (26.3%) exceeded that in urban areas (23.6%) for the first time in 2018. Functional independence become more severe as aged. The proportion of severe functional impairment was 6.9% and 2% in the group aged 80 or over and group 70-79 years, respectively. Regarding disability status, 32.5% had hearing problems and 31.4% had visual impairment. The highest prevalence rates of NCDs in older adults were found in hypertension (36.9%), followed by diabetes (10.6%), cerebrovascular disease (5.4%), ischemic heart disease (4.5%), and intervertebral disc disease (4.2%). The average annual OOP expenditures attributed to NCDs increased from ¥2481.8 RMB in 2013 to ¥8255.9 RMB in 2018 for older adults. About 90.7% of older adults prefer to live in the residential community, leading to the demands for preventive healthcare (30.4%), medical treatment (14.1%), and elderly education (8.6%). CONCLUSION: The elevated risks of age-related impairments and chronic morbidities, and increased demands for preventive healthcare are critical public health issues. Policymakers should strengthen primary healthcare and move towards integrated delivery to improve access and quality of care for older adults. The integration of healthcare and social security constitutes an adaptive trend in meeting the multi-level demands of an aging society.

Trends and regional variations in chronic diseases and their risk factors in China: an observational study based on National Health Service Surveys.

BACKGROUND: Over the past 25 years, the spectrum of diseases in China has rapidly changed from infectious to non-communicable diseases (NCDs). This study aimed to identify the prevalence of chronic diseases over the past 25 years in China and estimate the trends and changes in risk factors related to NCDs. METHODS: We conducted a descriptive analysis based on the National Health Service Survey (NHSS) from 1993 to 2018. The survey year (in parentheses) and its respective number of respondents were (1993) 215,163; (1998) 216,101; (2003) 193,689; (2008) 177,501; (2013) 273,688; and (2018) 256,304. In each survey, approximately half the participants were male. In addition, we estimated the trends in the prevalence and risk factors of NCDs from 1993 to 2018 and described their coefficient of variation in the provisions. RESULTS: The prevalence of NCDs has risen rapidly, from 17.0% in 1993 to 34.3% 2018. Hypertension and diabetes were the two main NCDs accounting for 53.3% in 2018. Similarly, the prevalence of hypertension and diabetes have also increased rapidly, increasing 15.1 and 27.0 times respectively from 1993 to 2018. Moreover, from 1993 to 2018, the proportion of smoking decreased from 32.0% to 24.7%, and the proportion of drinking and physical activity increased from 18.4% and 8.0% to 27.6% and 49.9%, respectively. The proportion of obesity increased from 5.4% in 2013 to 9.5% in 2018. The prevalence of NCDs in rural areas (35.2%) in 2018 was slightly higher than that in urban areas (33.5%). Changes in the prevalence of NCDs in rural were larger than those in urban. However, from 2013 to 2018, the provincial gaps for these metrics narrowed, except for that of smoking (Coefficient of Variation from 0.14 to 0.16). CONCLUSIONS: The prevalence of NCDs increased rapidly in China and was similar in urban and rural areas in 2018. Two key risk factors (drinking and obesity) increased in prevalence, while the other two (smoking and physical inactivity) decreased. These results indicate that China is facing considerable challenges in curbing chronic diseases to achieve the United Nations Sustainable Development Goals or the Healthy China 2030 goals. The government should take more active measures to change unhealthy lifestyles, improve efficiency in risk factor management, and pay more attention and allocate more health resources to rural areas.

Changes of equality of medical service utilization in China between 1993 and 2018: findings from six waves of nationwide household interview survey.

BACKGROUND: Changes in China's health care system in the last three decades was remarkable. The current study aims on examine the change of equality of health care utilization in mainland China based on a nationwide household interview survey. METHODS: We used household interview data extracted from six waves of National Health Service Survey between 1993 and 2018. Changes of health care utilization were descripted. Equality of the utilization were examined with univariate meta-regression across urban and rural areas, socioeconomic development regions and income groups. RESULTS: The proportion of outpatient visits within last two weeks experienced a decrease from 17.0% in 1993 to 13.0% in 2013 and bounced back to 24.0% in 2018. The age-standardized trend remained unchanged. Hospitalization in the last 12 month increased from 2.6% in 1998 to 13.8% in 2018. The perceived unmet need of hospital admission fell from 35.9% in 1998 to 21.5% in 2018. The gaps in health care utilization between urban and rural areas, across regions and by income groups have been narrowed, implying improved equality of using medical services in the last two and a half decades. CONCLUSION: China has experienced significant increases in health care utilization over the past 25 years. Meanwhile, the unmet needs for health care decreased remarkably and the equality of health care utilization improved significantly. These results imply significant achievements in health service accessibility in China.

Study on physicochemical characteristics, solidification and utilisation of tannery sludge gasification ash.

Gasification is an attractive method for tannery sludge (TS) disposal because of its advantages: volume reduction, stabilisation, harmlessness, and energy recovery. TS reduction ash (AR) and TS oxidation ash (AO), simulated from a downdraft fixed bed gasifier (DFBG) and an updraft fixed bed gasifier (UFBG), were investigated on their physicochemical characteristics, solidification behaviour, and value-added utilisation. Results showed that the main mineral matters in AR and AO consisted of Fe-oxids and Fe-Cr compounds, and the DFBG was more suitable for TS gasification than the UFBG because of the lower content of Cr(Ⅵ) in AR. With the addition of waste glass bottles (WGB), the ash fusion temperatures (AFTs) and leaching concentrations of heavy metals in AR and AO decreased significantly, and the heavy metals in AR and AO were successfully immobilised by the wrapping effect of the molten WGB. Moreover, gasification ash, as an auxiliary material for rock wool, reduced the AFTs and viscosity coefficient of the main chemical compositions in rock wool. With the addition of AR, the occurrence of Fe-containing compounds and the extremely low risk of leaching toxicity of heavy metals were observed. The maximum addition proportion of gasification ash was dependent on the maximum content of Fe2O3 allowed in the raw materials of rock wool, and its addition ratio must be below 15%.

LncRNA-cCSC1 promotes cell proliferation of colorectal cancer through sponging miR-124-3p and upregulating CD44.

LncRNA-cCSC1 is highly expressed in colorectal cancer (CRC). The study was designed to evaluate the function and mechanism of lncRNA-cCSC1 in cell proliferation of CRC. RT-PCR was used to measure the expression levels of lncRNA-cCSC1 in CRC cell lines. CCK-8, colony formation, EdU staining, flow cytometry and Western blot were performed to examine the effect of interference with lncRNA-cCSC1 expression on cell proliferation. miR-124-3p and the target genes of miR-124-3p were investigated using bioinformatics analysis and verified by dual-luciferase reporter, RT-PCR and Western blot. Rescue experiments were carried out to confirm the role of miR-124-3p in cell proliferation of CRC. Our results showed that cell proliferation of CRC was promoted by lncRNA-cCSC1 upregulation and inhibited by lncRNA-cCSC1 downregulation. In addition, miR-124-3p is predicted to be the target of lncRNA-cCSC1 and is negatively correlated with lncRNA-cCSC1. Moreover, the addition of miR-124-3p mimics or inhibitor reversed the effects induced by lncRNA-cCSC1 overexpression or silencing on cell proliferation of CRC. Additionally, lncRNA-cCSC1 regulated the expression level of CD44, a target gene of miR-124-3p. Finally, we studied the effects of the lncRNA-cCSC1/miR-124-3p axis on CD44. These results indicate that lncRNA-cCSC1 promotes cell proliferation of CRC through sponging miR-124-3p and upregulating CD44.

Mathermycin, an anti-cancer molecule that targets cell surface phospholipids.

Mathermycin, a lantipeptide isolated from marine actinomycete Marinactinospora thermotolerans, is an antibiotic that has been shown to disrupt bacterial plasma membrane. We now provide evidences that mathermycin can also disrupt cancer, but not normal, cell plasma membranes through targeting phosphatidylethanolamine (PE), which is located only in the inner leaflet of the plasma membrane in normal cells but in both the inner and outer leaflets of the membrane in tumor cells. Our data shows that mathermycin inhibits the metabolic activity and induces mainly necrotic death of all cancer cell lines with EC50 between 4.2 and 16.9 µM, while normal cell lines have EC50 between 113 and 129 µM. The cytotoxicity of mathermycin could be inhibited by exogenous PE, but not phosphoserine and phosphocholine. The formation of mathermycin-PE complexes was confirmed by in silico analysis, HPLC and MS spectrometer. Furthermore, mathermycin exhibited similar cytotoxicity toward cancer and multidrug resistant cancer cells, which could be due to its ability to inhibit mitochondrial function, as shown by our data from the Seahorse™ metabolic analyzer. This study demonstrates that mathermycin is a potentially effective class of anti-tumor chemotherapeutics that do not easily develop resistance due to a mechanism of action targeting PE.

Corrigendum to "MicroRNA-30-5p Suppresses Inflammatory Factor-Induced Endothelial Cell Injury by Targeting TCF21".

[This corrects the article DOI: 10.1155/2019/1342190.].

Contemporary trends on expenditure of hospital care on total cancer and its subtypes in China during 2008-2017.

OBJECTIVE: To describe the contemporary trends in total, inpatient, and outpatient expenditure on major subtypes of cancer in different classifications of hospitals in mainland China. METHODS: Home page of Inpatient Medical Records (HIMRs) and Hospital Annual Reports (HARs) were used to estimate hospital care expenditure on cancer. Inpatient payments and their share of cancer were calculated with the top-down method. Kriging spatial interpolation methods were used at the county level and summed at the province level. Outpatient expenditure was estimated with inpatient expenditure and the ratios of outpatient to inpatient payments in specialized cancer hospitals, stratified by province. Total expenditure on cancer was the sum of both payments. Log-linear regression was applied to estimate annual percentage change (APC) of expenditure. RESULTS: Total expenses for cancer of Chinese residents reached up to 304.84 billion Chinese Yuan (CNY) in 2017, accounting for 5.8% of the total health expenses (THE). After adjusting for consumer price index (CPI), medical expenses for cancer have increased from 63.30 billion CNY in 2008 to 249.56 billion CNY in 2017 [APC: 15.2%, 95% confidence interval (95% CI): 13.4%-17.0%]. The APC was slightly higher than THE around 2013, while was lower after 2013. During 2008-2017, the ratio of inpatient to outpatient costs for cancer decreased from 4.3:1 to 3.8:1. The inpatient payments for cancer mainly happened in grade 3 general hospitals, East China, and among lung, colorectal, and stomach cancer; while the fastest increase was found in West China, and among thyroid, prostate, and colorectal cancer. CONCLUSIONS: During 2008-2017, the rapid growth trend of medical expenses for cancer has been effectively controlled with the continuous deepening of medical reform and improvements of residents' health care. More attention should be paid to potential increases of medical costs caused by technological progress and demand release. Socialized and multi-channel insurance financing modes should be explored in the future.

An integrated PKD1-dependent signaling network amplifies IRE1 prosurvival signaling.

Following the accumulation of improperly folded proteins in the endoplasmic reticulum (ER), a condition known as ER stress in this compartment triggers an adaptive signaling pathway referred to as the unfolded protein response (UPR). The UPR aims at restoring ER homeostasis; if the ER stress cannot be resolved, apoptosis is triggered. However, the mechanisms responsible for regulating the balance between cell life and death decisions that occur after exposure to ER stress remain unclear. Protein kinase D1 (PKD1) has been reported to initiate protective signaling against oxidative stress or ischemia, two conditions that impinge on the induction of ER stress. In addition, the high levels of expression of PKD1, observed in highly proliferative cancers and tumors with poor prognosis, contribute to enhanced resistance to chemotherapy. In this study, we show that the ER stress inducers tunicamycin and thapsigargin lead to the activation of PKD1 in human prostate cancer PC-3 cells and in hepatoma HepG2 cells through a PKCδ-dependent mechanism. Moreover, our data indicate that PKD1 is required for the stabilization of inositol-requiring enzyme 1 (IRE1) and the subsequent regulation of its activity. PKD1 activation contributes to the phosphorylation of mitogen-activated protein kinase phosphatase 1, resulting in decreased IRE1-mediated c-Jun N-terminal kinase activation. This study unveils the existence of a novel PKD1-dependent prosurvival mechanism that is activated upon ER stress and selectively enhances IRE1 prosurvival signaling.

Hypoxic ER stress suppresses ß-catenin expression and promotes cooperation between the transcription factors XBP1 and HIF1α for cell survival.

Hypoxia occurs in many human solid tumors and activates multiple cellular adaptive-response pathways, including the unfolded protein response (UPR) in the endoplasmic reticulum (ER). Wnt/ß-catenin signaling plays a critical role in tumorigenesis, and ß-catenin has been shown to enhance hypoxia-inducible factor 1α (HIF1α)-activated gene expression, thereby supporting cell survival during hypoxia. However, the molecular interplay between hypoxic ER stress, Wnt/ß-catenin signaling, and HIF1α-mediated gene regulation during hypoxia remains incompletely understood. Here, we report that hypoxic ER stress reduces ß-catenin stability, which, in turn, enhances the activity of spliced X-box-binding protein 1 (XBP1s), a transcription factor and signal transducer of the UPR, in HIF1α-mediated hypoxic responses. We observed that in the RKO colon cancer cell line, which possesses a Wnt-stimulated ß-catenin signaling cascade, increased ER stress during hypoxia is accompanied by a reduction in low-density lipoprotein receptor-related protein 6 (LRP6), and this reduction in LRP6 decreased ß-catenin accumulation and impaired Wnt/ß-catenin signaling. Of note, ß-catenin interacted with both XBP1s and HIF1α, suppressing XBP1s-mediated augmentation of HIF1α target gene expression. Furthermore, Wnt stimulation or ß-catenin overexpression blunted XBP1s-mediated cell survival under hypoxia. Together, these results reveal an unanticipated role for the Wnt/ß-catenin pathway in hindering hypoxic UPR-mediated responses that increase cell survival. Our findings suggest that the molecular cross-talks between hypoxic ER stress, LRP6/ß-catenin signaling, and the HIF1α pathway may represent an unappreciated mechanism that enables some tumor subtypes to survive and grow in hypoxic conditions.

Role of constitutive nitric oxide synthases in the dynamic regulation of the autophagy response of keratinocytes upon UVB exposure.

Ultraviolet B (UVB) radiation induces autophagy responses, which play a role in the regulation of the oncogenic processes of irradiated cells. However, the mechanism of autophagy responses post-UVB irradiation remains to be fully elucidated. Previous studies indicate that UVB radiation induces the activation and uncoupling of constitutive nitric oxide synthases (cNOS), which produce nitric oxide and peroxynitrite; both have been shown to regulate autophagy responses. In this study, the UVB-induced autophagy responses were analysed in cell line- and UVB dose-dependent manners, and the role of cNOS in UVB-induced autophagy responses was also studied. Our data showed that UVB induces both autophagosome formation and degradation, and that cNOS is involved in the regulation of autophagy responses post UVB exposure. Both nitric oxide and peroxynitrite, the two products that are produced in cells immediately after UVB exposure, could upregulate autophagy in a dose-dependent manner. Furthermore, cNOS is involved in the UVB-induced downregulation of SQSTM1/p62, a scaffold protein used as a reporter of the autophagy response. However, the cNOS-mediated reduction of SQSTM1/p62 is autophagy-independent post UVB irradiation. Our results indicated that autophagy responses post UVB exposure are a dynamic balance of autophagosome formation and degradation, with cNOS playing a role in the regulation of the balance.

MicroRNA-30-3p Suppresses Inflammatory Factor-Induced Endothelial Cell Injury by Targeting TCF21.

Atherosclerosis is one of the leading causes of mortality worldwide. Growing evidence suggested that miRNAs contributed to the progression of atherosclerosis. miR-30-5p was found involved in various diseases. However, the role of miR-30-5p in regulation of atherosclerosis is not known. Here, we aim to investigate the effects of miR-30-5p on regulating the progression of atherosclerosis. The expression levels of miR-30-5p in serum collected from atherosclerosis patients and normal healthy people were analyzed by qRT-PCR. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway bioinformatics were carried out to reveal the possible signaling pathways involved in the mode of action of miR-30-5p. A potential target gene of miRNA-30-5p was searched and examined by a luciferase reporter assay. ELISA, Western blot, proliferation, and flow cytometry assays were performed to assess the biological functional role of miR-30-5p in vitro. Also, an in vitro monocyte-endothelial cell coculture model was used to study the functional role of miR-30-5p in atherosclerosis. We found that miR-30-5p was significantly decreased in serum samples from atherosclerosis patients compared with control subjects. GO and KEGG analysis results showed that miR-30-5p is highly associated with genetic profile of cardiovascular disease. TCF21 was verified as a target gene of miR-30-5p. Overexpression of miR-30-5p in THP-1 not only protected endothelial cell viability but also inhibited endothelial cell apoptosis, and similar results were observed in cells with that of TCF21 knocked down. Moreover, miR-30-5p decreased the expression levels of lactate dehydrogenase (LDH) and tumor necrosis factor-α (TNF-α) and reduced reactive oxygen species (ROS) accumulation. NF-κB and MAPK/p38 pathways played an indispensable role in the protection ability of miR-30-5p against atherosclerosis. Our results reveal that miR-30-5p suppresses the progression of atherosclerosis through targeting TCF21 in vitro. Therefore, the miR-30-5p-TCF21-MAPK/p38 signaling pathway may be a potential biomarker or therapeutic target in atherosclerosis.

Constraining Dark Matter Models with a Light Mediator at the PandaX-II Experiment.

We search for nuclear recoil signals of dark matter models with a light mediator in PandaX-II, a direct detection experiment in the China Jinping underground laboratory. Using data collected in 2016 and 2017 runs, corresponding to a total exposure of 54 ton day, we set upper limits on the zero-momentum dark matter-nucleon cross section. These limits have a strong dependence on the mediator mass when it is comparable to or below the typical momentum transfer. We apply our results to constrain self-interacting dark matter models with a light mediator mixing with standard model particles, and set strong limits on the model parameter space for the dark matter mass ranging from 5 GeV to 10 TeV.

ERK1/2 and JNK signaling synergistically modulate mitogenic effect of fibroblast growth factor 2 on liver cell.

Proliferation of the adult hepatocyte population represents a central feature of tissue regeneration after liver injury and resection. This process could be driven by a diverse range of mitogens, such as hepatocyte growth factor (HGF) and fibroblast growth factor (FGF). Among FGF family, FGF2 is closely related to wound repair and cell proliferation. FGF2 does function in the process of angiogenesis in regenerating liver, while fewer reports are concerned with the impact and underlying mechanism of FGF2 on liver cell proliferation. To this end, an immortalized human normal hepatocyte L02 and mouse primary hepatocytes were exposed to FGF2 in this study. We demonstrate that FGF2 significantly enhances liver cell proliferation. Treatment with FGF2 obviously increases the phosphorylation level of extracellular signal-regulated kinases 1 and 2 (ERK1/2) and c-Jun N-terminal kinase (JNK). Activity inhibition or expression down-regulation prove that both ERK1/2 and JNK signaling are required for FGF2-mediated effect on liver cell proliferation. Interestingly, interfering of ERK1/2 signaling results in marked decrease of JNK activation under FGF2 treatment, and JNK signaling is also involved in regulation of FGF2-induced ERK1/2 activation, suggesting that cross-talk between ERK1/2 and JNK signaling is important for FGF2 mitogenic activity. Both ERK1/2 and JNK signal via CREB to function in proliferation impact of FGF2 on liver cells. Taken together, this study reveals that ERK and JNK pathways synergistically regulate FGF2-induced liver cell proliferation via phosphorylating CREB, which will contribute to the understanding of FGF2 impact on liver cell proliferation and liver regeneration.

Low-Dose 4-Hydroxy-2-Nonenal (HNE) Reperfusion Therapy Displays Cardioprotective Effects in Mice After Myocardial Infarction That Are Abrogated by Genipin.

BACKGROUND Revascularization is a successful therapeutic strategy for myocardial infarction. However, restoring coronary blood flow can lead to ischemia-reperfusion (I/R) injury. Low-dose 4-hydroxy-2-nonenal (HNE) therapy appears to play a key role in myocardial tolerance to I/R injury. We hypothesized that the positive effects of HNE on myocardial I/R injury may be UCP3-dependent. MATERIAL AND METHODS Adult male wild-type (WT) or UCP3 knockout (UCP3-/-) mice were pre-treated with the UCP inhibitor genipin or saline 1 h before ischemia and underwent 30-min coronary artery ligation followed by 24-h reperfusion. Mice were treated with intravenous HNE (4 mg/kg) or saline 5 min before reperfusion. Echocardiography was conducted to measure left ventricular end-diastolic posterior wall thickness (LVPWd), end-diastolic diameter (LVEDD), and fractional shortening (FS). Infarct size was measured by TTC staining. qRT-PCR and Western blotting were used to assess the expression of UCP3, UCP2, and the apoptosis markers cytochrome C and cleaved caspase-3. RESULTS HNE improved survival at 24 h post-MI in wild-type mice (p<0.05) but not in UCP3-/- mice. HNE preserved LVEDD and FS in WT mice (p<0.05) but not in UCP3-/- mice. HNE reduced infarct size in WT mice (p<0.05) but not in UCP3-/- mice. HNE upregulated UCP3 expression (p<0.05) but did not affect UCP2 expression. HNE reduced apoptosis marker expression in WT mice (p<0.05) but not in UCP3-/- mice. HNE's positive effects were abrogated by genipin in an UCP3-dependent manner. CONCLUSIONS Low-dose HNE reperfusion therapy attenuates murine myocardial I/R injury in an UCP3-dependent manner. These effects are abrogated by genipin in an UCP3-dependent manner.

The role of cold-inducible RNA binding protein in cell stress response.

Cold-inducible RNA binding protein (CIRP) was discovered after the cells were exposed to a moderate cold shock because its production was induced. Other cellular stresses such as ultraviolet light radiation and hypoxia also could increase its expression. Under stress conditions, CIRP could up regulate its own expression by self-transcriptional activation of alternative promoters. After relocating into cytoplasm from nucleus, CIRP assists cells in adapting to novel environmental conditions via stabilizing specific mRNAs and facilitating their translation. It not only participates in anti-apoptosis processes under mild hypothermia condition, but also protects cells from ultraviolet radiation and hypoxia induced senescence process. This article focuses on the possible mechanisms of its inducible expression, cytoprotective functions and carcinogenesis. In addition, extracellular CIRP has been shown to be a novel danger-associated molecular patter (DAMP) member and is able to induce inflammatory response. Finally, based on the distinct roles of CIRP in intracellular and extracellular conditions, a possible model of CIRP-mediated cell fate has been proposed.

The role of lipid raft translocation of prohibitin in regulation of Akt and Raf-protected apoptosis of HaCaT cells upon ultraviolet B irradiation.

Prohibitin (PHB) plays a role in regulation of ultraviolet B light (UVB)-induced apoptosis of human keratinocytes, HaCaT cells. The regulatory function of PHB appears to be associated with its lipid raft translocation. However, the detailed mechanism for PHB-mediated apoptosis of these keratinocytes upon UVB irradiation is not clear. In this report, we determined the role of lipid raft translocation of PHB in regulation of UVB-induced apoptosis. Our data show that upon UVB irradiation PHB is translocated from the non-raft membrane to the lipid rafts, which is correlated with a release of both Akt and Raf from membrane. Overexpression of Akt and/or Raf impedes UVB-induced lipid raft translocation of PHB. Immunoprecipitation analysis indicates that UVB alters the interactions among PHB, Akt, and Raf. Reduced expression of PHB leads to a decreased phosphorylation of Akt and ERK, as well as a decreased activity of Akt, and increased apoptosis of the cells upon UVB irradiation. These results suggest that PHB regulates UVB-induced apoptosis of keratinocytes via a mechanism that involves detachment from Akt and Raf on the plasma membrane, and sequential lipid raft translocation.