Two curcumin analogs inhibited the function and protein expression of breast cancer resistance protein: in vitro and in vivo studies.

1. Two curcumin analogs, (1E,6E)-1,7-bis(3,5-diethyl-4-hydroxyphenyl)hepta-1,6-diene-3,5- dione (N17) and its prodrug ((1E,6E)-3,5-dioxohepta-1,6-diene-1,7-diyl)bis(2,6-diethyl-4,1- phenylene)bis(3-hydroxy-2-(hydroxymethyl)-2-methylpropanoate) (N17'), were evaluated as breast cancer resistance protein (BCRP) inhibitors.2. MDCKII-BCRP and MDCKII-WT were used to evaluate the modulation effects of N17 and N17' on BCRP and to explore the relevant mechanism. Sprague-Dawley rats were orally administered rosuvastatin (ROS), a probe substrate of BCRP, without and with N17' (100 mg/kg) to investigate the effect of N17' on ROS pharmacokinetics.3. In cell studies, N17 and N17' were substrates of BCRP, and they decreased the activity and protein expression of BCRP. In rat study, N17' increased the systemic exposure of ROS by 218% (p = 0.058).4. N17 and N17' are potential BCRP inhibitors and will be promising candidates for overcoming the BCRP-mediated multidrug resistance.

Upregulation of APAF1 and CSF1R in Peripheral Blood Mononuclear Cells of Parkinson's Disease.

Increased oxidative stress and neuroinflammation play a crucial role in the pathogenesis of Parkinson's disease (PD). In this study, the expression levels of 52 genes related to oxidative stress and inflammation were measured in peripheral blood mononuclear cells of the discovery cohort including 48 PD patients and 25 healthy controls. Four genes, including ALDH1A, APAF1, CR1, and CSF1R, were found to be upregulated in PD patients. The expression patterns of these genes were validated in a second cohort of 101 PD patients and 61 healthy controls. The results confirmed the upregulation of APAF1 (PD: 0.34 ± 0.18, control: 0.26 ± 0.11, p < 0.001) and CSF1R (PD: 0.38 ± 0.12, control: 0.33 ± 0.10, p = 0.005) in PD patients. The expression level of APAF1 was correlated with the scores of the Unified Parkinson's Disease Rating Scale (UPDRS, r = 0.235, p = 0.018) and 39-item PD questionnaire (PDQ-39, r = 0.250, p = 0.012). The expression level of CSF1R was negatively correlated with the scores of the mini-mental status examination (MMSE, r = -0.200, p = 0.047) and Montréal Cognitive Assessment (MoCA, r = -0.226, p = 0.023). These results highly suggest that oxidative stress biomarkers in peripheral blood may be useful in monitoring the progression of motor disabilities and cognitive decline in PD patients.

Survey of factors related to diabetic foot pruritus in the elderly in Shanghai.

The objective of the study is to explore the status quo of foot pruritus and related factors in elderly diabetics and provide a reference for targeted preventive measures. The study involved a survey using a self-designed foot pruritus assessment scale to understand the status quo of foot pruritus among 411 cases of elderly diabetics from 5 communities in Shanghai. The morbidity rate of foot pruritus in elderly diabetics in the community was 20.1%. Good self-management behaviour was the protective factor, while diabetic peripheral neuropathy, hyperlipidemia, and dry skin were risk factors (all P < 0.05). The incidence of foot pruritus in elderly diabetics was high and influenced by several factors. We recommend that self-management behaviour of patients be improved. Additionally, screening and interventions to address hyperlipidemia, diabetic peripheral neuropathy, and dry skin should be conducted regularly to prevent diabetic foot ulcers.

Design, synthesis and biological evaluation of novel pyrazinone derivatives as PI3K/HDAC dual inhibitors.

PI3Ks and HDACs play essential roles in the occurrence and progression of leukemia. Herein, a series of novel pyrazin-2(1H)-one derivatives were rationally designed and synthesized as novel dual PI3K and HDAC inhibitors based on scaffold replacement and heterozygous strategies. Most of the target compounds showed potent inhibitory potency to PI3Kα and HDAC6. Especially, compound 9q displayed PI3Kα and HDAC6 inhibitory with IC50 values of 372 nM and 4.5 nM, and anti-proliferative activity against MV4-11 cells with IC50 value of 0.093 ± 0.012 µM. Further mechanistic studies revealed that 9q induced apoptosis, arrested the cell cycle in the G2/M phase, promoted the acetylation of α-tubulin, and blocked the PI3K/AKT/mTOR signal way in MV4-11 cells. All the results demonstrated that 9q was a promising lead candidate for further development of novel PI3K/HDAC dual inhibitors for leukemia treatment.

[Value of Contrast-enhanced Ultrasound Parameters in Evaluating K-W Nodule Formation in Diabetic Nephropathy].

Objective To discuss the value of contrast-enhanced ultrasound(CEUS)parameters in evaluating the formation of Kimmelstiel-Wilson(K-W)nodules in diabetic nephropathy(DN).Methods Sixty-two patients pathologically diagnosed with DN and undergoing CEUS in the First Medical Center of Chinese PLA General Hospital from March 2017 to January 2020 were assigned into two groups according to whether K-W nodules were formed.The cortical CEUS parameters and the ratios of cortical to medullary CEUS parameters were compared between the two groups.Results The 62 patients included 19 patients without K-W nodules(group A)and 43 patients with K-W nodules(group B).The median rise time(U=209,P=0.013)and fall time(U=197,P=0.007)in group B were significantly longer than those in group A.The median wash-in rate(WiR)(U=228,P=0.031)and wash-out rate(WoR)(U=229,P=0.032)in group B were significantly lower than those in group A.The median peak enhancement(PE)1/PE2(U=224,P=0.026),WiR1/WiR2(U=235,P=0.041),and WoR1/WoR2(U=230,P=0.043)ratios in group B were significantly lower than those in group A.The median FT1/FT2 ratio in group B was significantly higher than that in group A(U=227,P=0.038).Conclusion CEUS parameters can be used to quantitatively evaluate renal cortical microperfusion in DN patients with K-W nodules.

Potential value of three-dimensional ultrasonography in diagnosis of diabetic nephropathy in Chinese diabetic population with kidney injury.

BACKGROUND: To explore the potential value of three-dimensional ultrasonography (3DUS) and contrast-enhanced ultrasound (CEUS) in the diagnosis of diabetic nephropathy (DN) in Chinese diabetic patients with kidney injury. METHODS: Patients with type 2 diabetes mellitus and kidney injury in our hospital were enrolled, and the clinical characteristics as well as the laboratory data of patients were collected; 3DUS and CEUS were used to evaluate the morphological structure and blood perfusion of kidneys. Eligible patients were categorized into two groups based on renal biopsy results: DN group and non-diabetic renal diseases (NDRD) group. Correlation analysis and logistic regression analysis were applied to identify the risk factors of DN development. RESULTS: A total of 115 patients aged from 24 to 78 years old were recruited in the experiment, of which 64 patients (55.65%) and 51 patients (44.35%) were in the DN group and NDRD group, respectively. After correction to CKD stage, BMI and right kidney volume index were retained to identify patients with DN. The ROC of the logistic regression model had an AUC of 0.703 (95% CI: 0.591-0.815) and it was higher than both indicators. CONCLUSION: 3DUS has potential value in the diagnosis of diabetic nephropathy in Chinese diabetic population with kidney injury and may act as an auxiliary diagnosis for DN. More prospective and well-designed studies with larger samples are needed to verify the result.

[Application Value of Transrectal Shear Wave Elastography Mode Combined with Elastic Modulus in the Diagnosis of Prostate Cancer].

Objective To explore the value of trans-rectal shear wave elastic mode combined with elastic modulus in the diagnosis of prostate cancer and establish a new method for the evaluation of prostate with trans-rectal shear wave elastography(SWE). Methods The typical findings of trans-rectal ultrasound(US)and SWE in 79 patients with prostate cancer(n=41)and benign prostatic hyperplasia(BPH)(n=38)confirmed by surgery or US-guided biopsy were analyzed retrospectively.Their diagnostic value were evaluated with the pathological results as the golden standards. Results Three or more malignant features detected by conventional trans-rectal US(χ 2=42.5,P<0.001)and asymmetrical SWE mode(χ 2=54.2,P<0.001)showed statistically significant difference in prostate cancer and BPH groups.The elastic modulus of Emean and Emax in the prostate cancer group were(92.8±21.5)and(114.2±29.8)kPa,which were significantly higher than those in the BPH group [(56.7±14.0)(t=-8.8,P<0.001)and(68.4±17.2)kPa(t=-8.3,P<0.001)].The receiver-operating characteristic(ROC)curve with Logistic regression showed that the elastic model combined elastic modulus had the largest area under ROC curve and the highest diagnosis efficiency of prostate cancer,with the cutoff value of 0.45.The diagnosis sensitivity,specificity,positive predictive value,negative predictive value,and accuracy of the combination were 95.1%,89.5%,90.7%,94.4%,and 92.4%,respectively. Conclusion Combination of SWE mode and elastic modulus is more valuable than elastic modulus alone in the diagnosis of prostate cancer.

Heme oxygenase 1 regulates apoptosis induced by heat stress in bovine ovarian granulosa cells via the ERK1/2 pathway.

Heat stress can inhibit follicular development in dairy cows, and thus can affect their reproductive performance. Follicular granulosa cells can synthesize estrogen, that affects the development and differentiation of follicles by apoptosis. Heme oxygenase 1 (HO-1/heat shock protein 32) plays an antiapoptotic and cytoprotective role in various cells during stress-induced apoptosis, but little is known about its definitive function in bovine (ovarian) granulosa cells (bGCs). In our study, the roles and mechanism of HO-1 on the heat stress-induced apoptosis of bGCs were studied. Our results show that the expression of HO-1 was significantly increased under heat stress. Moreover, HO-1 silencing increased apoptosis, whereas its overexpression dampened apoptosis by regulating the expression of Bax/Bcl-2 and the levels of cleaved caspase-3. In addition, HO-1 can also play a cytoprotective role by affecting estrogen levels and decomposing heme to produce biologically active metabolite carbon monoxide (CO). Meanwhile, CO significantly increased the level of HO-1, decreased Bax/Bcl-2 levels, and inhibited the activation of extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathway. The apoptosis of ovarian GCs can affect the secretion of estrogen and lead to disorder of the ovarian microenvironment, thus affecting the normal function of the ovary. Our results indicate that HO-1 acts as a cytoprotective enzyme and plays a protective role in heat-induced apoptosis of bGCs. In conclusion, HO-1 and its metabolite CO inhibit the apoptosis of bGCs induced by heat stress through the ERK1/2 pathway. The results of this study provide a valuable clue for improving the fertility of heat stressed cows in summer.

Atorvastatin Blocks Advanced Glycation End Products Induced Reduction in Macrophage Cholesterol Efflux Mediated With ATP-Binding Cassette Transporters G 1.

BACKGROUND: There is accumulating evidence that the AGEs-RAGE interaction plays an important role in accelerated atherosclerosis in diabetes. Our previous study showed that the AGEs-RAGE axis can reduce the cholesterol efflux of THP-1 macrophages through suppression of the expression of ABCG1 and that statins can inhibit the expression of RAGE. However, the role of statins in recovering the cholesterol efflux of macrophages reduced by AGEs has not been assessed.Methods and Results:ApoE-/-mice and THP-1 macrophages were both treated by AGEs or AGEs combined with anti-RAGE antibody (only in THP-1 cells), ALT711 and atorvastatin separately. Cholesterol efflux of THP-1 macrophages and murine peritoneal macrophages was tested by fluorescence microplate technique. RT-PCR and western blot analysis were used to measure the expression of RAGE and molecules included in cholesterol efflux. After co-incubating with atorvastatin and AGEs, reduction in lipid accumulation in THP-1 macrophages and improvement of lesions complexity occurred compared with treating by AGEs only. Atorvastatin increased cholesterol efflux and ABCG1 expression of macrophages, which were reduced by AGEs, and decreased the expression of RAGE at the same time. CONCLUSIONS: This study demonstrated that atorvastatin can recover the deleterious ABCG1-mediated cholesterol efflux induced by AGEs in THP-1 macrophages and murine peritoneal macrophages by downregulating RAGE expression. It may contribute to the protective action of atorvastatin in diabetic subjects with atherosclerosis.

[Effect of HPMCAS/curcumin amorphous solid dispersion in enhancing dissolution and chemical stability of curcumin].

To enhance in vitro dissolution of Cur by preparing Cur solid dispersions. The ability of HPMCAS-HF,HPMCAS-MF,HPMCAS-LF and PVPK30 to maintain supersaturated solution was investigated by supersaturation test. Amorphous solid dispersions were prepared by the solvent-evaporation method. The prepared samples were characterized using infrared spectroscopy( IR) and differential scanning calorimetry( DSC),and in vitro dissolution was investigated. DSC and IR results showed that in 1 ∶3 and 1 ∶9 solid dispersions,Cur was amorphously dispersed in the carrier,and the interaction existed between drug and carrier. The supersaturation test showed that the order of the ability of polymer to inhibit crystallization of Cur was MF>HF>LF>K30. The dissolution results showed that Cur-K30 amorphous solid dispersion had the highest drug release rate; Cur-K30 and Cur-LF amorphous solid dispersions had a quicker but not stable dissolution rate,and the drug concentration decrease after 4 h; Cur-MF and Cur-HF solid dispersions had a low dissolution,which however increased steadily,attributing to the strong ability of the polymers to inhibit the crystallization of Cur. HPMCAS could inhibit the degradation of Cur better than K30,especially MF and HF. The amorphous solid dispersions of cur significantly enhanced the dissolution of Cur and improved the chemical stability of Cur. This study can provide a basis for the rational selection of the polymer used for Cur solid dispersion.

SIRT7 depletion inhibits cell proliferation, migration, and increases drug sensitivity by activating p38MAPK in breast cancer cells.

SIRT7 is a member of the sirtuin family of proteins that are known to be associated with tumor development. However, the functional roles and molecular mechanisms underlying the function of SIRT7 in breast cancer cell survival and tumor development remain unclear. Recent studies demonstrated that SIRT7 is upregulated in breast cancer cells and tissues. In the present study, we systematically explored the roles of SIRT7 in the growth of breast cancer cells and tumors both in vitro and in vivo. Our results showed that SIRT7 plays a major role in facilitating cell survival by promoting cell proliferation and inhibiting apoptosis. SIRT7 depletion significantly inhibited cell invasion and wound healing by blocking cell cycle progression and inducing cell apoptosis. Meanwhile, SIRT7 depletion can increase the sensitivity of breast cancer cells to doxorubicin (DOX). Xenograft model studies showed that stable silencing of SIRT7 inhibited tumor growth and enhanced tumor sensitivity to DOX. Further research revealed that p38MAPK is involved in SIRT7-mediated regulation of breast cancer cell proliferation and tumor growth. Taken together, our results showed that SIRT7 plays a critical role in breast cancer cell survival, migration, and tumor growth, and increased the efficiency of DOX treatment both in vitro and in vivo. Therefore, SIRT7 is a promising therapeutic target in breast cancer treatment.

[Effect of Active Ingredients of Qingxin Kaiqiao Recipe on Spatial Learning and Memory Capacities, and Expressions of Bax, Bcl-2, Caspase-3, and PAPP in Hippocampus of AD Model Rats].

Objective To observe the effects of active ingredients of Qingxin Kaiqiao Recipe (QKR) , such as saponins, volatile oils, effective compositions of polysaccharides, on expressions of Bcl-2 associated X protein (Bax) , B-cell lymphoma-2 (Bcl-2) , cysteinyl aspartate specific proteinase-3 (Caspase-3) , and ß-amyloid precursor protein (pAPP) in hippocampus of Ap1_40-induced Alzheimer's disease (AD) model rats. Methods Totally 112 male Sprague-Dawley (SD) rats were randomly divided into 7 groups, i.e., the normal control group, the sham-operation group, the model group, the Aricept group, the saponin group, the volatile oil group, the polysaccharide group, 16 in each group. The AD rat model was established by injecting Aß1₋40 from bilateral hippocampus. Equal volume of double distilled water was administered to rats by gastrogavage in the normal control group, the sham-operation group, the model group from the 2nd day after modeling, once per day for 2 successive weeks (at 10:00 am). Aricept (Donepezil Hydrochloride Tablet, 1. 67 mg/kg per day) , saponin (9 mL/kg per day) , benzene (3. 33 mL/kg per day) , and polysaccharides (8. 33 mL/kg per day) was administered to rats by gastro- gavage to the Aricept group, the saponin group, the volatile oil group, the polysaccharides group, re- spectively, once per day for 2 successive weeks (at 10:00 am). By the end of gastrogavage spatial learning and memory capacities were detected using Morris water maze (MWZ). Apoptosis in hippocam- pal CAI region was detected using TUNEL staining. Expressions of Bax, Bcl-2, Caspase-3, and PAPP were measured via Real-time fluorescent quantitative PCR, Western blot, and immunohistochemistry, respectively. Results There was no statistical difference in pre-modeling escape latency and times of crossing platforms among groups at the same time point (P >0. 05). Besides, escape latency was gradu- ally shortened as time went by. Compared with the model group, escape latency was shortened, and times of crossing platforms was significantly increased in the Aricept group and the saponin group (P < 0. 05, P <0. 01). Compared with the model group, the amount of apoptotic cells in hippocampal CA1 re- gion was obviously reduced (P <0. 05, P <0. 01) , expressions levels of Bax, Caspase-3, and pAPP were down-regulated, Bcl-2/Bax ratio was obviously elevated in the saponin group, the volatile oil group, the polysaccharide group (P <0. 05, P <0. 01). Conclusion Three active ingredients (spaonins, benzene, and polysaccharides) of QKR could improve spatial memory and learning capacities to different degrees, which might be possibly achieved by decreasing expressions of Bax, Caspase-3, PAPP in hippocampal CA1 region, elevating Bcl-2 expression, and inhibiting apoptosis in hippocampus.

Advanced glycation end products increase lipids accumulation in macrophages through upregulation of receptor of advanced glycation end products: increasing uptake, esterification and decreasing efflux of cholesterol.

BACKGROUND: Previous reports have suggested that advanced glycation end products (AGEs) participate in the pathogenesis of diabetic macroangiopathy. Our previous study have found that AGEs can increase the lipid droplets accumulation in aortas of diabetic rats, but the current understanding of the mechanisms remains incomplete by which AGEs affect lipids accumulation in macrophages and accelerate atherosclerosis. In this study, we investigated the role of AGEs on lipids accumulation in macrophages and the possible molecular mechanisms including cholesterol influx, esterification and efflux of macrophages. METHODS: THP-1 cells were incubated with PMA to differentiate to be macrophages which were treated with AGEs in the concentration of 300 µg/ml and 600 µg/ml with or without anti-RAGE (receptor for AGEs) antibody and then stimulated by oxidized-LDL (oxLDL) or Dil-oxLDL. Lipids accumulation was examined by oil red staining. The cholesterol uptake, esterification and efflux were detected respectively by fluorescence microscope, enzymatic assay kit and fluorescence microplate. Quantitative RT-PCR and Western blot were used to measure expression of the moleculars involved in cholesterol uptake, synthesis/esterification and efflux. RESULTS: AGEs increased lipids accumulation in macrophages in a concentration-dependent manner. 600 µg/ml AGEs obviously upregulated oxLDL uptake, increased levels of cholesterol ester in macrophages, and decreased the HDL-mediated cholesterol efflux by regulating the main molecular expression including CD36, Scavenger receptors (SR) A2, HMG-CoA reductase (HMGCR), ACAT1 and ATP-binding cassette transporter G1 (ABCG1). The changes above were inversed when the cells were pretreated with anti-RAGE antibody. CONCLUSIONS: The current study suggest that AGEs can increase lipids accumulation in macrophages by regulating cholesterol uptake, esterification and efflux mainly through binding with RAGE, which provide a deep understanding of mechanisms how AGEs accelerating diabetic atherogenesis.

[Study on the Mechanism of Three Kinds Extracts of Qingxin Kaiqiao Recipe in Improving Learning and Memory Capabilities of AD Rats].

OBJECTIVE: To explore the mechanism of three kinds extracts (saponins, volatile components, polysaccharide components) of Qingxin Kaiqiao Recipe (QKR) in improving learning and memory capabilities of Alzheimer's disease (AD) rats. METHODS: A controlled comparison method was used. Totally 56 male SD rats were randomly divided into seven groups, i.e., the normal control group, the sham-operation group, the model group, the Aricept group, the saponin group, the benzene group, and the polysaccharide group, 8 in each group. AD rat model was established by bilateral hippocampus injection of Aß1-40 (2 µL, 2.5 µg/µL). The next day after modeling rats in the saponin group, the benzene group, and the polysaccharide group, the saponin group, the Aricept group were intragastrically administered with saponin (at the daily dose of 9 mL/kg, 2.1 g/mL) , benzene (at the daily dose of 3.33 mL/kg, 5.7 g/mL) , polysaccharide (at the daily dose of 8.33 mL/kg, 2.28 g/mL), Aricept (at the daily dose of 1.67 mg/kg), respectively, once a day for 2 consecutive weeks from 10 am every day. Equal volume of normal saline was intragastrically administered to rats in the normal control group and the model group. Learning and memory capabilities were detected using water maze 2 weeks later. Expression levels of synaptotagmin-1 (Syt-1), interleukin-1ß (IL-1ß), glia fibrillary acidic protein (GFAP), and ß-amyloid precursor protein (ßAPP) in the cortex and hippocampus of AD rats were detected using immunohistochemistry. RESULTS: Learning and memory capabilities could be improved by three kinds extracts of QKR. There was no statistical difference in the escape latency between the polysaccharide group and the model group (P >0. 05). The escape lacency was shortened in the rest treatment groups (P < 0.05). The escape latency was obviously prolonged in three kinds extracts of QKR groups, when compared with the Aricept group (P < 0.05, P < 0.01). Compared with the model group, times for crossing platforms were significantly increased in the saponin group and the Aricept group (P < 0.05). Compared with the Aricept group, average times for crossing platforms were significantly lessened in three kinds extracts of QKR groups (P < 0.01). Compared with the sham-operation group, expression levels of Syt-1, IL-1ß, GFAP, and ßAPP in the cortex and hippocampus were increased in the model group (P < 0.01). Compared with the model group, the expression of cortical Syt-1 increased in the saponin group and the benzene group; the expression of cortical IL-1ß increased in the benzene group and the polysaccharide group; the expression of hippocampal GFAP increased in the three kinds extracts of QKR groups; expression levels of Syt-1, IL-1ß, GFAP, and ß-APP in the cortex and hippocampus decreased in the rest treatment groups (all P < 0.05, P < 0.01). Compared with the Aricept group, expression levels of Syt-1, IL-1ß, GFAP, and ßAPP in the cortex and hippocampus were significantly increased in three kinds extracts of QKR groups (P < 0.05, P < 0.01). CONCLUSION: Three kinds extracts of QKR might play roles in anti-AD possibly by decreasing expression levels of Syt-1, IL-1ß, GFAP, and ßAPP in the cortex and hippocampus.

[Effect of naringin of Drynaria Rhizome, a Chinese medical component of Zhuanggu Jianxi Recipe containing serum on caveolin-p38MAPK signal pathway in IL-1ß induced rabbit degenerated chondrocytes].

OBJECTIVE: To observe the effect of naringin of Drynaria Rhizome, a Chinese medical component of Zhuanggu Jianxi Recipe (ZJR) containing serum on caveolin-p38MAPK signal factors (such as caveolin-1, p-p38, p-ATF-2, IL-1ß, and TNF-α) in IL-1ß induced rabbit degenerated chondrocytes, and further to explore its mechanism for protecting articular cartilages. METHODS: Naringin of Drynaria Rhizome was obtained and analyzed by HPLC-TOF/MS. Four weeks old New Zealand rabbits were killed and their bilateral knee joints were isolated aseptically. CDs were isolated and then cultured in vitro. The second generation of CDs were used for later experiment. The effect of naringin on CDs proliferation was detected by MTT assay. The effect of naringin on the expression of IL-1ß-induced collagen II in CDs was detected by immunohistochemical method. The effect of naringin on caveolin-1, p-p38, and p-ATF-2 protein in IL-1ß-induced CDs was detected by Western blot. The effect of naringin on mRNA expression of IL-1ß and TNF-α in IL-1ß-induced CDs was detected by RT-PCR. RESULTS: The appearance time of naringin in flow graphs of naringin standard solution and ZJR containing serum was 23.5 min, and the molecular weight ranged between 581.0 and 581.5 m/z. Naringin could promote the proliferation of CDs, and inhibit the effect of IL-1ß on collagen II in CDs. Compared with the model group, naringin could reduce the expression of caveolin-1, p-p38, p-ATF-2, IL-1ß, and TNF-α in IL-1ß induced CDs (P < 0.05), which was approximate to the level of the normal group. CONCLUSIONS: Naringin could not only promote the proliferation of CDs, but also protect IL-1ß-induced CDs. Its mechanism might be associated with decreasing the expression of caveolin-1, p-p38, and p-ATF-2 proteins, inhibiting caveolin-p38MAPK signal pathway, and further reducing mRNA expression of IL-1ß and TNF-α in the downstream of caveolin-p38MAPK signal pathway.

The highly selective and sensitive fluorescence probe for detection of copper (II) ions and its bioimaging in vitro and vivo.

We designed and developed the probe W-3 for detection of Cu2+. The results showed probe can selectively detect Cu2+, accompanied by noticeable color change. The probe can detect the Cu2+ in water samples and drinks based on absorption detection. In addition, the combination of portable test paper and the smartphone platform obtained great convenience for on-site and visual detection of Cu2+, with satisfactory sensitivity and reliability. More importantly, the fluorescence probe W-3 can be used for the detection of Cu2+ in cells and mice. Therefore, the W-3 provided potential chemical tools for detecting Cu2+ in vitro and vivo.

Multifunctional fluorescence probe for simultaneous detection of viscosity, polarity, and ONOO- and its bioimaging in vitro and vivo.

Intracellular microenvironment (viscosity and polarity) and peroxynitrite ions (ONOO-) are involved in maintaining cell morphology, cell function, and signaling so that it is crucial to explore their level changes in vitro and vivo. In this work, we designed and synthesized a mitochondria-targeted fluorescence probe XBL for monitoring the dynamic changes of viscosity, polarity, and ONOO- based on TICT and ICT mechanism. The fluorescence spectra showed obvious changes for polarity at 500 nm as well as ONOO- and viscosity at 660 nm, respectively. The XBL can image simultaneously viscosity, polarity, and ONOO- in cells, and the results showed excess ONOO- leaded to the increase of viscosity in mitochondrial. The ferroptosis process was accompanied by increase of intracellular viscosity and ONOO- levels (or decrease of polarity), which allowed us to better understand the relevant physiological and pathological processes. The XBL can distinguish normal cells and cancerous cells by the fluorescence intensity changes in green and red channels, and image viscosity in inflamed mice. Thus, XBL can provided the chemical tool to understand the physiological and pathological mechanisms of disease by simultaneous detection of viscosity, polarity and ONOO-.

Development of the near-infrared fluorescence probe for detection of ONOO- and its application in vitro and vivo.

Diabetes has become one of the most common endocrine and metabolic diseases threatening human health, which can induce mitochondrial dysfunction and exacerbate the excessive production of reactive oxygen species (ROS). Among them, ONOO- level fluctuation was closely related to diabetes. Hence, it is of great significance to develop a near-infrared fluorescence probe for visualizing ONOO- level fluctuations in diabetes. In this paper, we constructed a fluorescence probe YBL with dicyano-isophorone derivative as fluorophore and diphenyl phosphate as ONOO- response site, which can detect ONOO- with the low detection limit (39.8 nM) and exhibit excellent selectivity and sensitivity. The probe YBL has been applied to monitor intracellular ONOO- level fluctuations. Meanwhile, the image results showed that high sugar promoted the increase of ONOO- level in cells. More important, the probe YBL can be used for imaging in mice, and the results showed that content of ONOO- was increased in diabetic mice. Therefore, the probe YBL provided a tool for understanding diabetes progression by imaging ONOO-.

A fluorescence probe with targeted mitochondria for detecting hydrogen peroxide in vitro and in diabetic mice.

We designed and prepared probe W-1 for the detection of H2O2. W-1 showed excellent selectivity for H2O2 and was accompanied by colorimetric signal changes. The excellent linear relationship between fluorescence intensity and H2O2 concentration (0-100 µM) provided favorable conditions for its quantitative detection. In addition, the combination of portable test strips with a smartphone platform provided great convenience for on-site visual detection of H2O2. Moreover, W-1 possessed targeting mitochondria property and could be applied to image the exogenous and endogenous H2O2 in cells to distinguish normal cells and cancer cells. Lastly, W-1 was used for monitoring the H2O2 fluctuation of the diabetic process in mice, and the results showed an increase in H2O2 levels in diabetes. Therefore, the probe provided a tool for understanding the pathological and physiological mechanisms of diabetes by imaging H2O2.

[Preparation and characteristic analysis of ractopamine molecularly imprinted polymers].

A molecularly imprinted polymers (MIPs) of Ractopamine (RCT) was prepared by thermal polymerization method, and the adsorptive characters of the MIPs was investigated with ultraviolet spectrophotometric method. The results showed that RCT had the maximum absorbance value at the wavelength of 272 nm, the regression equation of RCT was y = 7.354 1x + 0.001 0, R2 = 0.999 9, and the average adsorption rate of MIPs was 83.4%. According to the adsorption kinetics, the adsorption time should be controlled within 10 minutes. Infrared spectrum analysis indicated that the MIPs was formed by hydrogen bonds between RCT and functional monomer methacrylic acid, the MIPs of RCT recognized RCT and combined with it exclusively via hydrogen bonds. The investigation is very useful and important for establishing RCT detection methods based on molecularly imprinted technology.