Maternal tobacco exposure during pregnancy and atopic dermatitis in offspring: A systematic review and meta-analysis.

The main purpose of this review was to examine the evidence of the relationship between active smoking or passive smoking during pregnancy and atopic dermatitis in offspring. The protocol was written following the PRISMA Checklist and was registered in the PROSPERO database (registration number CRD42022381136). We implemented a comprehensive search in PubMed, Embase and Web of Science databases to identify all potentially related articles from inception through 1 December 2022. We assessed cohort studies and case-control studies using the Newcastle-Ottawa Scale (NOS), and the Joanna Briggs Institute (JBI) critical appraisal tool to assess the quality of cross-sectional studies. Heterogeneity was investigated by using Cochrane Q tests and I2 statistics. In addition, according to the research design, population source and population size, the reasons for the heterogeneity were analysed. A total of 15 observational studies were included in this analysis. Our meta-analysis suggests that atopic dermatitis in offspring is not associated with active smoking during pregnancy (pooled OR, 0.96 [95% CI 0.86-1.07]); however, it is related to passive smoking (OR, 1.52 [95% CI 1.36-1.70]). Passive smoking during pregnancy is associated with an increased risk of eczema development in offspring. More research is needed to explore the risk of active smoking and eczema development in offspring, especially the association between measurements of pregnancy cotinine levels in maternal body fluids and AD in offspring.

Particulate matter and inflammatory skin diseases: From epidemiological and mechanistic studies.

Epidemiological and toxicological studies have confirmed that exposure to atmospheric particulate matter (PM) could affect our cardiovascular and respiratory systems. Recent studies have shown that PM can penetrate the skin and cause skin inflammation, but the evidence is limited and contradictory. As the largest outermost surface of the human body, the skin is constantly exposed to the environment. The aim of this study was to assess the relationship between PM and inflammatory skin diseases. Most epidemiological studies have provided positive evidence for outdoor, indoor, and wildfire PM and inflammatory skin diseases. The effects of PM exposure during pregnancy and inflammatory skin diseases in offspring are heterogeneous. Skin barrier dysfunction, Oxidative stress, and inflammation may play a critical role in the underlying mechanisms. Finally, we summarize some interventions to alleviate PM-induced inflammatory skin diseases, which may contribute to public health welfare. Overall, PM is related to inflammatory skin diseases via skin barrier dysfunction, oxidative stress, and inflammation. Appropriate government interventions are beneficial.

Vertical compressive bearing performance and optimization design method of large-diameter manually-excavated rock-socketed cast-in-place piles.

To study the vertical compressive bearing characteristics of large-diameter rock-socketed cast-in-place piles, eight manually-excavated rock-socketed cast-in-place piles were subjected to vertical compressive on-site load and pile stress tests. The test results showed that the load-displacement (Q-s) curves of the eight test piles were all slow-varying, and the settlement of the piles was less than 11 mm, which met the minimum engineering requirements. The unloading rebound rate was between 55 and 75%, and the elastic working properties of the piles were apparent. The pile axial force gradually decreased with depth, and the slope of the axial force distribution curve reached a minimum in the moderately weathered muddy siltstone layer while the pile side friction resistance reached its maximum value. Pile end friction increases with the increase of load. But the pile end resistance was inversely proportional to the single pile length-to-diameter (L/D) ratio and the depth of rock embedment for the pile. The percentage of pile side friction resistance under maximum load was 86%, indicating that these were characteristic friction piles. Based on the test results and the current Chinese code, the friction coefficient of the pile side soil layer η and the total resistance coefficient of the rock-socketed section ζ were introduced. A revision to the calculation equation for the vertical bearing capacity of the rock-socketed cast-in-place pile in the code was proposed, together with an optimization design method for large-diameter rock-socketed cast-in-place piles.

Intraoperative analgesic effect of intravertebral lidocaine injection during percutaneous kyphoplasty in the treatment of thoracolumbar compression fractures in elderly patients.

BACKGROUND: In recent years, percutaneous kyphoplasty (PKP) has been increasingly used in clinical settings. OBJECTIVE: In this study, we aimed to determine the analgesic effect of intravertebral lidocaine injections in PKP. METHODS: A total of 60 patients who were treated with PKP were enrolled in this study. Lidocaine hydrochloride was chosen as the medication for the experimental group. Patients were randomly assigned into three groups using a double-blind study design: In group A (20 cases), no drugs were injected into the vertebral body during surgery; group B (20 cases) received intravertebral injection of normal saline; and in group C (20 cases), lidocaine hydrochloride was administered into the vertebral body during surgery. The age of patients, operation time, balloon dilatation pressure, balloon dilatation volume, and amount of bone cement injected were compared across the three groups. A pain visual analog scale (VAS) was used to assess pain suffered by the patients before, during, and 24 hours after the surgery. RESULTS: Age, operation time, balloon dilatation pressure, balloon dilatation volume, and amount of bone cement injected did not differ significantly among the three groups (P> 0.05). The differences in VAS scores 24 hours before and after surgery were not statistically significant (P> 0.05). Group C had lower intraoperative VAS scores than groups A and B, and the difference was statistically significant (P< 0.01). There was no statistically significant difference between group A and group B (P> 0.05). CONCLUSION: Intravertebral injections of lidocaine during PKP can successfully reduce intraoperative pain.

No Meaningful Drug-Drug Interactions Are Associated with the Coadministration of ACC007, Lamivudine, and Tenofovir Disoproxil Fumarate.

ACC007 is a new-generation nonnucleoside reverse transcriptase inhibitor (NNRTI) with favorable pharmacokinetic and safety profiles. NNRTIs are typically administered in combination with two nucleoside reverse transcriptase inhibitors as first-line recommended regimens in several guidelines. Therefore, this open-label, randomized, single-period, parallel-cohort study aimed to assess the drug-drug interactions (DDIs) and safety profiles of ACC007 in combination with tenofovir disoproxil fumarate (TDF) and lamivudine (3TC) in healthy subjects. All 24 screened subjects were randomly assigned to group A or B. On days 1 to 17, 3TC at 300 mg and TDF at 300 mg were taken orally by group A, and ACC007 at 300 mg was coadministered on days 8 to 17. On days 1 to 17, 300 mg of ACC007 was taken orally by group B, and 300 mg 3TC and 300 mg TDF were coadministered on days 8 to 17. When we compared 3TC-TDF versus 3TC-TDF-ACC007 DDIs, the geometric mean ratios (GMRs, with 90% confidence intervals [CIs] in parentheses) of the maximum concentration at steady state (Cmax,ss) and area under the concentration-time curve from 0 h to infinity (i.e., at steady state; AUCss) values for TDF were 108.14% (95.68 to 122.22%) and 89.90% (82.67 to 97.76%) (P = 0.344); for 3TC, these values were 113.48% (91.45 to 140.82%) and 95.33% (83.61 to 108.7%) (P = 0.629). When ACC007 alone was compared to the combination 3TC-TDF-ACC007, the GMRs (90% CIs) of the Cmax,ss and AUCss values for ACC007 were 89.00% (76.35 to 103.74%) and 82.57% (73.27 to 93.05%) (P = 0.375). The coadministration of 3TC-TDF-ACC007 did not significantly affect the time to maximum concentration of any of the drugs in terms of P values. ACC007 combined with 3TC-TDF was generally well tolerated during daily dosing for 17 days with no serious adverse events. Overall, ACC007 and 3TC-TDF had no significant or meaningful interactions and a favorable safety profile, which supports the use of the combination regimen.

SmCIP7, a COP1 interactive protein, positively regulates anthocyanin accumulation and fruit size in eggplant.

In higher plants, COP1 (Constitutively Photomorphogenic 1) acts as a central regulator of light-signaling networks and globally conditions the target proteins via the ubiquitin-proteasome pathway. However, the function of COP1-interacting proteins in light-regulated fruit coloration and development remains unknown in Solanaceous plants. Here, a COP1-interacting protein-encoding gene, SmCIP7, expressed specifically in the eggplant (Solanum melongena L.) fruit, was isolated. Gene-specific silencing of SmCIP7 using RNA interference (RNAi) significantly altered fruit coloration, fruit size, flesh browning, and seed yield. SmCIP7-RNAi fruits showed evident repression of the accumulation of anthocyanins and chlorophyll, indicating functional similarities between SmCIP7 and AtCIP7. However, the reduced fruit size and seed yield indicated SmCIP7 had evolved a distinctly new function. With the comprehensive application of HPLC-MS, RNA-seq, qRT-PCR, Y2H, BiFC, LCI, and dual-luciferase reporter system (DLR™), it was found that SmCIP7, a COP1 interactive protein in light signaling promoted anthocyanin accumulation, probably by regulating the transcription of SmTT8. Additionally, the drastic up-regulation of SmYABBY1, a homologous gene of SlFAS, might account for the strongly retarded fruit growth in SmCIP7-RNAi eggplant. Altogether, this study proved that SmCIP7 is an essential regulatory gene to modulate fruit coloration and development, serving as a key gene locus in eggplant molecular breeding.

Pharmacokinetics, Bioequivalence, and Safety Evaluation of Dienogest in Healthy Subjects Under Fasting and Fed Conditions.

Dienogest is effective in reducing endometriosis-related pain symptoms. This study aims to investigate and compare the pharmacokinetic profiles and safety of test formulations to reference formulations of dienogest in healthy Chinese female volunteers under fasting or fed conditions. The purpose of this single-center, randomized, open-label, 2-sequence, 2-period crossover clinical trial was to evaluate the safety and pharmacokinetic profiles of the 2 formulations under fasting and fed conditions. Additionally, 48 healthy female volunteers were selected and divided at random into the fasting and the fed group. After dosing, the venous blood was collected through indwelling catheters. Dienogest plasma concentrations were measured using liquid chromatography-tandem mass spectrometry after the plasma samples were prepared with the protein precipitation method. Under either fasting or fed conditions, the pharmacokinetic parameters (maximum observed concentration, area under the concentration-time curve [AUC] from time 0 to the last measurable concentration, and AUC from time 0 to infinity) for dienogest between the test and reference products, geometric mean ratio, and 90%CI were all within the range of 80%-125%. The 2 dienogest products were bioequivalent. Based on maximum observed concentration and AUC from time 0 to the last measurable concentration, the generic dienogest was bioequivalent to the original dienogest in this study conducted under fasting and fed conditions in healthy Chinese women (study CTR20190063 on chinadrugtrials.org.cn registry).

Lipid profile and prognosis in patients with coronary heart disease: a meta-analysis of prospective cohort studies.

BACKGROUND: This meta-analysis based on prospective cohort studies aimed to evaluate the associations of lipid profiles with the risk of major adverse cardiovascular outcomes in patients with coronary heart disease (CHD). METHODS: The PubMed, Embase, and Cochrane Library electronic databases were systematically searched for prospective cohort study published through December 2019, and the pooled results were calculated using the random-effects model. RESULTS: Twenty-one studies with a total of 76,221 patients with CHD met the inclusion criteria. The per standard deviation (SD) increase in triglyceride was associated with a reduced risk of major adverse cardiovascular events (MACE). Furthermore, the per SD increase in high-density lipoprotein cholesterol (HDL-C) was associated with a reduced risk of cardiac death, whereas patients with lower HDL-C were associated with an increased risk of MACE, all-cause mortality, and cardiac death. Finally, the risk of MACE was significantly increased in patients with CHD with high lipoprotein(a) levels. CONCLUSIONS: The results of this study suggested that lipid profile variables could predict major cardiovascular outcomes and all-cause mortality in patients with CHD.

Estimating the Prevalence and Mortality of Coronavirus Disease 2019 (COVID-19) in the USA, the UK, Russia, and India.

OBJECTIVE: The aim of this study is to apply the advanced error-trend-seasonal (ETS) framework to forecast the prevalence and mortality series of COVID-19 in the USA, the UK, Russia, and India, and the predictive performance of the ETS framework was compared with the most frequently used autoregressive integrated moving average (ARIMA) model. MATERIALS AND METHODS: The prevalence and mortality data of COVID-19 in the USA, the UK, Russia, and India between 20 February 2020 and 15 May 2020 were extracted from the WHO website. Then, the data subsamples between 20 February 2020 and 3 May 2020 were treated as the training horizon, and the others were used as the testing horizon to construct the ARIMA models and the ETS models. RESULTS: Based on the model evaluation criteria, the ARIMA (0,2,1) and ETS (M,MD,N), sparse coefficient ARIMA (0,2,(1,6)) and ETS (A,AD,M), ARIMA (1,1,1) and ETS (A,MD,A), together with ARIMA (2,2,1) and ETS (A,M,A) specifications were identified as the preferred ARIMA and ETS models for the prevalence data in the USA, the UK, Russia, and India, respectively; the ARIMA (0,2,1) and ETS (M,A,M), ARIMA (0,2,1) and ETS (M,A,N), ARIMA (0,2,1) and ETS (A,A,N), coupled with ARIMA (0,2,2) and ETS (M,M,N) specifications were selected as the optimal ARIMA and ETS models for the mortality data in these four countries, respectively. Among these best-fitting models, the ETS models produced smaller forecasting error rates than the ARIMA models in all the datasets. CONCLUSION: The ETS framework can be used to nowcast and forecast the long-term temporal trends of the COVID-19 prevalence and mortality in the USA, the UK, Russia, and India, and which provides a notable performance improvement over the most frequently used ARIMA model. Our findings can aid governments as a reference to prepare for and respond to the COVID-19 pandemic both in restricting the transmission of the disease and in lowering the disease-related deaths in the upcoming days.

Acute effects of ambient air pollution on hospital outpatients with chronic pharyngitis in Xinxiang, China.

We present results on a time-series study that analyzed the acute effects of six criteria air pollutants on hospital outpatient with chronic pharyngitis (CP) in Xinxiang, China. Data on the concentration of air pollutants and CP outpatient records were collected daily in Xinxiang, China, from January 1, 2015 to December 31, 2018. This study identified 62,823 outpatients with CP. The annual average concentrations of PM2.5, PM10, SO2, NO2, CO, and O3 are 75.7, 132.1, 33.2, 48.4, 1377, and 59.4 µg/m3, respectively. Further, a 10 µg/m3 increment in the concentration of PM10, SO2, NO2, and CO corresponds to an increase of 0.28% (95% confidence interval (CI): 0.03-0.53%), 1.10% (95% CI: 0.09-2.11%), 1.82% (95% CI: 0.84-2.80%), and 0.03% (95% CI: 0.01-0.06%) in daily CP hospital outpatients, respectively. Furthermore, results indicated that outpatients under the age of 15 are more susceptible to the air pollutants, excluding O3. Meanwhile, males might be more susceptible, and effect estimates appear slightly stronger in the cool season. Therefore, we should implement effective measures to manage air pollutants and reinforce protection of the high-risk population.

Prediction of hypertension, hyperglycemia and dyslipidemia from retinal fundus photographs via deep learning: A cross-sectional study of chronic diseases in central China.

Retinal fundus photography provides a non-invasive approach for identifying early microcirculatory alterations of chronic diseases prior to the onset of overt clinical complications. Here, we developed neural network models to predict hypertension, hyperglycemia, dyslipidemia, and a range of risk factors from retinal fundus images obtained from a cross-sectional study of chronic diseases in rural areas of Xinxiang County, Henan, in central China. 1222 high-quality retinal images and over 50 measurements of anthropometry and biochemical parameters were generated from 625 subjects. The models in this study achieved an area under the ROC curve (AUC) of 0.880 in predicting hyperglycemia, of 0.766 in predicting hypertension, and of 0.703 in predicting dyslipidemia. In addition, these models can predict with AUC>0.7 several blood test erythrocyte parameters, including hematocrit (HCT), mean corpuscular hemoglobin concentration (MCHC), and a cluster of cardiovascular disease (CVD) risk factors. Taken together, deep learning approaches are feasible for predicting hypertension, dyslipidemia, diabetes, and risks of other chronic diseases.

Secular Seasonality and Trend Forecasting of Tuberculosis Incidence Rate in China Using the Advanced Error-Trend-Seasonal Framework.

OBJECTIVE: Tuberculosis (TB) is a major public health problem in China, and contriving a long-term forecast is a useful aid for better launching prevention initiatives. Regrettably, such a forecasting method with robust and accurate performance is still lacking. Here, we aim to investigate its potential of the error-trend-seasonal (ETS) framework through a series of comparative experiments to analyze and forecast its secular epidemic seasonality and trends of TB incidence in China. METHODS: We collected the TB incidence data from January 1997 to August 2019, and then partitioning the data into eight different training and testing subsamples. Thereafter, we constructed the ETS and seasonal autoregressive integrated moving average (SARIMA) models based on the training subsamples, and multiple performance indices including the mean absolute deviation, mean absolute percentage error, root-mean-squared error, and mean error rate were adopted to assess their simulation and projection effects. RESULTS: In the light of the above performance measures, the ETS models provided a pronounced improvement for the long-term seasonality and trend forecasting in TB incidence rate over the SARIMA models, be it in various training or testing subsets apart from the 48-step ahead forecasting. The descriptive results to the data revealed that TB incidence showed notable seasonal characteristics with predominant peaks of spring and early summer and began to be plunging at on average 3.722% per year since 2008. However, this rate reduced to 2.613% per year since 2015 and furthermore such a trend would be predicted to continue in years ahead. CONCLUSION: The ETS framework has the ability to conduct long-term forecasting for TB incidence, which may be beneficial for the long-term planning of the TB prevention and control. Additionally, considering the predicted dropping rate of TB morbidity, more particular strategies should be formulated to dramatically accelerate progress towards the goals of the End TB Strategy.

Association of bone mineral density with lung function in a Chinese general population: the Xinxiang rural cohort study.

BACKGROUND: Bone mineral density (BMD) has been positively associated with lung function in patients diagnosed with respiratory diseases such as chronic obstructive pulmonary disease (COPD) and cystic fibrosis. However, the relationship between BMD and lung function is inconsistent in the general population. METHODS: To investigate the association between BMD and lung function in a Chinese general population, a total of 1024 adults aged 40-70 years old from Qiliying (an industrial polluted exposure area) and Langgongmiao (the reference area with non-industrial pollution) were recruited and underwent BMD and spirometry tests. RESULTS: Both BMD and lung function levels were lower in the exposed area compared to the reference area. In addition, BMD and lung function levels were also lower in females compared to males. Both Spearman and partial correlation analyses showed that BMD was positively correlated with FVC and FEV1. After adjusting linear regression analyses for potential confounding factors, every 0.1 g/cm2 drop in BMD was associated with 53.0 mL decrease in FVC and 33.5 mL decrease in FEV1. CONCLUSIONS: A reduction of BMD is associated with lower lung function in a general population from China.

Spin switching in tris(8-aminoquinoline)iron(ii)(BPh4)2: quantitative guest-losing dependent spin crossover properties and single-crystal-to-single-crystal transformation.

As a derivative of 2-picolylamine, which contains rich protons favouring hydrogen bond formation to assemble a variety of valuable spin crossover (SCO) compounds, 8-aminoquinoline (aqin) will be a good candidate for constructing new mononuclear bistable state compounds. With the guidance of this view, two solvated compounds [Fe(aqin)3](BPh4)2·2(CH3CN) (1·2CH3CN) and [Fe(aqin)3](BPh4)2·1.5(CH3COCH3) (2·1.5CH3COCH3) were synthesized. The structural characterization and magnetic studies demonstrate that this strategy has been successful. Single-crystal diffraction reveals that both the mononuclear compounds have facial (fac-)-configuration cations, which form hydrogen bonds using -NH2 groups with solvent molecules (acetonitrile or acetone). Subsequent magnetic measurement shows the highly sensitive solvent-dependent occurrence of a spin transition above room temperature for both compounds. Interestingly, for compound 1·2CH3CN, in the successively repeated heating and cooling process, by monitoring the loss of solvent molecules by TGA, the shifting of the spin transition curve is found to be linearly dependent on the fraction of the residual solvent content. Additionally, the desolvated sample can re-solvate with CH3CN and recover the magnetic response reproducibly. Furthermore, after losing the acetonitrile molecules, the single-crystal-to-single-crystal transformation occurred to give 1.

Acute effects of air pollution on type II diabetes mellitus hospitalization in Shijiazhuang, China.

Air pollution has been considered as an important contributor to diabetes development. However, the evidence is fewer in developing countries where air pollution concentrations were much higher. In this study, we conduct a time-series study to investigate the acute adverse effect of six air pollutants on type II diabetes mellitus (T2DM) hospitalization in Shijiazhuang, China. An over-dispersed passion generalized addictive model adjusted for weather conditions, day of the week, and long-term and seasonal trends was used. Finally, a 10-µg/m3 increase of fine particulate matter (PM2.5), inhalable particulate matter (PM10), sulfur dioxide (SO2), nitrogen dioxide (NO2), and carbon monoxide (CO) corresponded to 0.53% (95% confidence interval = 0.22-0.83), 0.32% (95% CI = 0.10-0.55), 0.55% (95% CI = 0.04-1.07), 1.27% (95% CI = 0.33-2.22), and 0.04% (95% CI = 0.02-0.06) increment of T2DM hospitalization, respectively. The effects of PM2.5, PM10, and CO were robust when adjusted for co-pollutants. The associations appeared to be a little stronger in the cool season than in the warm season. And stronger associations were found in male and elderly (≥ 65 years) than in female and younger people (35-65 years). Our results contribute to the limited data in the scientific literature on acute effects of air pollution on type II diabetes mellitus in developing countries. MAIN FINDINGS: This is the first adverse effect evidence of air pollution on T2DM in Shijiazhuang, a severely polluted city in China. Males were more vulnerable than females in severe pollution.

Targeting intracellular MMPs efficiently inhibits tumor metastasis and angiogenesis.

Treatment for metastatic cancer is a great challenge throughout the world. Commonly, directed inhibition of extracellular matrix metalloproteinases (MMPs) secreted by cancer cells can reduce metastasis. Here, a novel nanoplatform (HPMC NPs) assembled from hyaluronic acid (HA)-paclitaxel (PTX) prodrug and marimastat (MATT)/ß-casein (CN) complexes was established to cure a 4T1 metastatic cancer model via targeting CD44 and intracellular, rather than extracellular, MMPs. Methods: HPMC NPs were prepared by assembling the complexes and prodrug under ultrasonic treatment, which the interaction between them was evaluated by förster resonance energy transfer, circular dichroism and fluorescence spectra. The developed nanoplatform was characterized via dynamic light scattering and transmission electron microscopy, and was evaluated in terms of MMP-sensitive release and stability. Subsequently, the cellular uptake, trafficking, and in vitro invasion were studied by flow cytometry, confocal laser microscopy and transwell assay. MMP expression and activity was determined by western blotting and gelatin zymography. Finally, the studies of biodistribution and antitumor efficacy in vivo were performed in a mouse 4T1 tumor breast model, followed by in vivo safety study in normal mouse. Results: The interaction between the prodrug and complexes is strong with a high affinity, resulting in the assembly of these two components into hybrid nanoparticles (250 nm). Compared with extracellular incubation with MATT, HPMC NP treatment markedly reduced the expression (100%) and activity (50%) of MMPs in 4T1 cells and in the tumor. HPMC NPs exhibited 1.4-fold tumor accumulation, inhibited tumor-growth by >8-fold in volume with efficient apoptosis and proliferation, and suppressed metastasis (>5-fold) and angiogenesis (>3-fold). Overall, HPMC NPs were efficient in metastatic cancer therapy. Conclusions: According to the assembly of polymer prodrug and protein-drug complexes, this study offers a new strategy for constructing nanoparticles for targeted drug delivery, biomedical imaging, and combinatorial treatment. Importantly, via inhibition of intracellular MMPs, metastasis and angiogenesis can be potently blocked, benefiting the rational design of nanomedicine for cancer treatment.

Nanoplatform Assembled from a CD44-Targeted Prodrug and Smart Liposomes for Dual Targeting of Tumor Microenvironment and Cancer Cells.

The tumor microenvironment (TME) plays a critical role in tumor initiation, progression, invasion, and metastasis. Therefore, a therapy that combines chemotherapeutic drugs with a TME modulator could be a promising route for cancer treatment. This paper reports a nanoplatform self-assembled from a hyaluronic acid (HA)-paclitaxel (PTX) (HA-PTX) prodrug and marimastat (MATT)-loaded thermosensitive liposomes (LTSLs) (MATT-LTSLs) for the dual targeting of the TME and cancer cells. Interestingly, the prodrug HA-PTX can self-assemble on both positively and negatively charged liposomes, forming hybrid nanoparticles (HNPs, 100 nm). Triggered by mild hyperthermia, HA-PTX/MATT-LTSLs HNPs rapidly release their payloads into the extracellular environment, and the released HA-PTX quickly enters 4T1 cells through a CD44-HA affinity. The HNPs possess promoted tumor accumulation (1.6-fold), exhibit deep tumor penetration, and significantly inhibit the tumor growth (10-fold), metastasis (100%), and angiogenesis (10-fold). Importantly, by targeting the TME and maintaining its integrity via inhibiting the expression and activity of matrix metalloproteinases (>5-fold), blocking the fibroblast activation by downregulating the TGF-ß1 expression (5-fold) and suppressing the degradation of extracellular matrix, the HNPs allow for significant metastasis inhibition. Overall, these findings indicate that a prodrug of an HA-hydrophobic-active compound and liposomes can be self-assembled into a smart nanoplatform for the dual targeting of the TME and tumor cells and efficient combined treatment; additionally, the co-delivery of MATT and HA-PTX with the HNPs is a promising approach for the treatment of metastatic cancer. This study creates opportunities for fabricating multifunctional nanodevices and offers an efficient strategy for disease therapy.

Comparative investigation for hypoglycemic effects of polysaccharides from four substitutes of Lonicera japonica in Chinese medicine.

The polysaccharide fractions were obtained from flower buds of the four substitutes of Lonicera japonica, L. macranthoides (LMPB), L. hypoglauca (LHPB), L. fulvotomentosa (LFPB) and L. confuse (LCPB), and their hypoglycemic effects were investigated. In study, streptozocin (STZ)-induced diabetic rats were orally administrated once daily with LMPB, LHPB, LFPB and LCPB (each 800 mg/kg) for 42 days. Reduction for food and water intake (p < 0.05, p < 0.01) and levels of sugar and insulin (p < 0.01, p < 0.05) in blood, as well as elevation for contents of liver and skeletal muscle glycogen (p < 0.05) and concentrations of hepatic pyruvate kinase and hexokinase (p < 0.01, p < 0.05) were observed. Together with significant decline of total cholesterol (TC, 45.8 51.0%, p < 0.05), total triglyceride (TG, 50.6-53.8%, p < 0.01), low-density lipoprotein-cholesterin (LDL-C, 71.2-76.3%, p < 0.01) and very-low-density lipoprotein-cholesterin (VLDL-C, 45.2-50.0%, p < 0.01), the significant rise of high-density lipoprotein-cholesterin (HDL-C, 21.6-24.3%, p < 0.05) were also demonstrated. Consequently, the four polysaccharide fractions displayed notable hypoglycemic effects, similar to that of the polysaccharide fraction from L. japonica (LJP), so that they can be also considered as ingredients of functional foods for type-2 diabetes mellitus (T2DM).

Resveratrol and caloric restriction prevent hepatic steatosis by regulating SIRT1-autophagy pathway and alleviating endoplasmic reticulum stress in high-fat diet-fed rats.

BACKGROUND: Studies have demonstrated that resveratrol (a natural polyphenol) and caloric restriction activate Sirtuin-1 (SIRT1) and induce autophagy. Furthermore, autophagy is induced by the SIRT1-FoxO signaling pathway and was recently shown to be a critical protective mechanism against non-alcoholic fatty liver disease (NAFLD) development. We aimed to compare the effects of resveratrol and caloric restriction on hepatic lipid metabolism and elucidate the mechanism by which resveratrol supplementation and caloric restriction alleviate hepatosteatosis by examining the molecular interplay between SIRT1 and autophagy. METHODS AND RESULTS: Eight-week-old male Wistar rats (40) were divided into four groups: the STD group, which was fed a standard chow diet; the HFD group, which was fed a high-fat diet; HFD-RES group, which was fed a high-fat diet plus resveratrol (200 mg/kg.bw); and the HFD-CR group, which was fed a high-fat diet in portions containing 70% of the mean intake of the HFD group rats. The groups were maintained for 18 weeks. Metabolic parameters, Oil Red O and hematoxylin-eosin staining of the liver, and the mRNA and protein expression of SIRT1, autophagy markers and endoplasmic reticulum(ER) stress-associated genes in the liver were assessed after the 18-week treatment. We found that resveratrol (200 mg/kg bw) and caloric restriction (30%) partially prevented hepatic steatosis and hepatocyte ballooning, increased the expression of SIRT1 and autophagy markers while decreasing ER stress markers in the liver and alleviated lipid metabolism disorder. Moreover, caloric restriction provided superior protection against HFD-induced hepatic fatty accumulation compared with resveratrol and the effects were associated with decreased total energy intake and body weight. CONCLUSION: We conclude that the SIRT1-autophagy pathway and decreased ER stress are universally required for the protective effects of moderate caloric restriction (30%) and resveratrol (a pharmacological SIRT1 activator) supplementation against HFD-induced hepatic steatosis.

Hypoglycemic and hypolipidemic effects of a polysaccharide from flower buds of Lonicera japonica in streptozotocin-induced diabetic rats.

Hyperglycemia and dyslipidemia are classic features for diabetes mellitus (DM). In this study, one fraction of the crude polysaccharides extracted from Lonicera japonica flower buds (LJP) were investigated for its hypolipidaemic and hypoglycaemic activities by means of streptozotocin (STZ)-induced diabetic rats. Interestingly, after orally administrated with 800mg/kg body weight (B.W.) LJP for 42 days, the food and water intake and the levels of sugar and insulin in blood for the diabetic rats were drastically decreased, while the contents of liver and skeletal muscle glycogen and the concentrations of hepatic pyruvate kinase and hexokinase were obviously increased (p<0.01 or p<0.05). The levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein-cholesterin (LDL-C) and very-low-density lipoprotein-cholesterin (VLDL-C) were significantly descended, while high-density lipoprotein-cholesterin (HDL-C) was significantly ascended (p<0.01 or p<0.05). In addition, the oxidant stress in liver was restored as well. The results suggested that LJP could be considered as an ingredient of functional foods for diabetes, and this is the first report about the hypoglycemic and hypolipidemic effects of the polysaccharides extracted from Lonicera japonica.