Serum fatty acid and lipoprotein subclass concentrations and their associations in prepubertal healthy Norwegian children

Introduction The lipid metabolism is one of the most important and complex processes in the body. Serum concentrations of 18 fatty acids (FAs) and 24 lipoprotein features, i.e. concentrations of lipoprotein main and subclasses and average particle size in main classes, in 195 ethnic Norwegian children from the rural Fjord region were quantified by chromatography. Objectives To assess gender differences in prepubertal children and reveal predictive FA patterns for lipoprotein features. Methods Lipoprotein features were modelled from FA profiles using multivariate regression. Results Contrary to observations for adults from the same region, gender differences in prepubertal children were generally small. However, higher concentrations of C16–C18 FAs for girls compared to boys correlated to higher concentrations of triglycerides (TG) and very low density lipoprotein (VLDL) particles and larger average size of VLDL particles. Concentrations of high density lipoprotein (HDL) and its subclass of medium particle size were higher in boys than in girls. These findings are opposite to observations in adults from the same region, but reflect that prepubertal boys are more physically active than girls. Furthermore, children possessed only half the serum levels of eicosapentaenoic acid and docosahexaenoic acid measured in adults. Since sampling was done after 12 h of fasting, these differences may reflect higher rate of utilization of these crucial FAs in children. Conclusion Good predictive models were obtained for TGs, VLDL and chylomicrons with C14–C18 FAs as major contributors. Weak predictive associations were observed for HDL and Apolipoprotein A1 (ApoA1) with C20–C24 FAs as contributors.publishedVersio

Predictive associations between serum fatty acids and lipoproteins in healthy non-obese Norwegians: implications for cardiovascular health

A battery of methods for multivariate data analysis has been used to assess the associations between concentrations of fatty acids (FAs) and lipoprotein subclasses and particle size in serum for a normolipidemic population of ethnic Norwegians living in the rural Fjord region. Significant gender differences were found in the lipoprotein and FA patterns. Predictive FA patterns were revealed for lipoprotein features of importance for cardiovascular (CV) health. Thus, the subclasses of atherogenic small and very small low density lipoprotein (LDL) particles and the same subclasses of high density lipoprotein (HDL) particles were associated with a pattern of saturated FAs and mono-unsaturated C16-C18 FAs. Eicosapentaenoic acid (EPA) and the ratio of EPA to arachidonic acid (AA) had strongest associations to features that promotes CV health: (i) large average size of HDL and LDL particles, and, (ii) small average size of very low density lipoprotein (VLDL) particles. Total concentration of HDL in both genders correlated to EPA, but docosahexaenoic acid (DHA) correlated just as strongly for women. For men, docosapentaenoic acid (DPA) showed stronger association to HDL concentration than EPA. For both genders, concentration of large LDL particles showed associations to levels of EPA, but stronger to DHA and DPA. High values of EPA/AA seem to be the strongest single biomarker for good CV health in both men and women.publishedVersio

Sonority bias in Rugao di-syllabic syllable contraction

Two analyses, vowel sonority and the linear order of pre-contraction vowels, have been proposed to account for the vowel selection between two competing vowels in Chinese syllable contraction. An experiment was run to test whether sonority and/or linear order bias the vowel selection in Rugao syllable contraction. Our results confirmed the role of vowel sonority, and did not present supporting evidence for the linear order analysis. Sonority hierarchies along the dimensions of both height and centrality exhibit the same consistent and robust pattern, providing a new perspective to look at competing vowels in vowel-related phonological processes

Intensive lifestyle intervention provides rapid reduction of serum fatty acid levels in women with severe obesity without lowering omega-3 to unhealthy levels

Serum fatty acid (FA) levels were monitored in women with severe obesity during intensive lifestyle intervention. At baseline, total FA levels and most individual FAs were elevated compared to a matching cohort of normal and overweight women (healthy controls). After 3 weeks of intensive lifestyle intervention, total level was only 11–12% higher than in the healthy controls and with almost all FAs being significantly lower than at baseline, but with levels of omega-3 being similar to the healthy controls. This is contrary to observations for patients subjected to bariatric surgery where omega-3 levels dropped to levels significantly lower than in the lifestyle patients and healthy controls. During the next 3 weeks of treatment, the FA levels in lifestyle patients were unchanged, while the weight loss continued at almost the same rate as in the first 3 weeks. Multivariate analysis revealed that weight loss and change of serum FA patterns were unrelated outcomes of the intervention for lifestyle patients. For bariatric patients, these processes were associated probably due to reduced dietary input and increased input from the patients’ own fat deposits, causing a higher rate of weight loss and simultaneous reduction of the ratio of serum eicosapentaenoic to arachidonic acid.publishedVersio

Smart mitochondria-specific anchored gold-based nanosystem for integration of tumor imaging and treatment

Although recent advances have been made in improving the efficacy of photodynamic therapy, efficient therapeutic approaches based on reactive oxygen species (ROS) are needed, particularly mitochondria-specific targeting of nanomaterials that can alter the internal environment of organelles. Herein, we report the facile synthesis of mitochondria-specific anchored nano-complexes (AG-CNP) comprised of a skeleton of gold and carbon atoms for cancer therapy. Compared to the effects of gold nanoclusters (Au NCs), AG-CNP shows enhanced fluorescence imaging effects, which can be used for tumor monitoring. AG-CNP targets the mitochondria and increases ROS damage in cancer cells. After treatment with AG-CNP, the tumor inhibition rate reaches 70.94%, which is 25.98% and 36.91% higher than that of free doxorubicin (DOX) and gemcitabine (Gem), respectively. Studying the mechanism of AG-CNP inhibiting cancer shows that AG-CNP can promote tumor cells to produce excessive ROS by overexpressing P53 and increasing the number of apoptotic cancer cells, which is caused by overexpression of Caspase1 that was closely related to cell apoptosis. AG-CNP is a promising anticancer drug that targets the mitochondria in vivo to trigger excessive ROS production in tumor cells and inhibit tumor growth.X.Y., L.Z., and L.D. contributed equally to this work. This work was supported by the National Natural Science Foundation of China (21371115, 22003038, 81922037, and 11575107), the Shanghai University-Universal Medical Imaging Diagnostic Research Foundation (19H00100), Shanghai Biomedical Science and Technology Support Project (19441903600), Guangdong Basic and Applied Basic Research Foundation (Nos. 2021A1515110657 and 2022A1515010056), Shenzhen Science and Technology Program (Grant No. RCBS20210609104513023)

Design strategies of tumor-targeted delivery systems based on 2D nanomaterials

Conventional chemotherapy and radiotherapy are nonselective and nonspecific for cell killing, causing serious side effects and threatening the lives of patients. It is of great significance to develop more accurate tumor-targeting therapeutic strategies. Nanotechnology is in a leading position to provide new treatment options for cancer, and it has great potential for selective targeted therapy and controlled drug release. 2D nanomaterials (2D NMs) have broad application prospects in the field of tumor-targeted delivery systems due to their special structure-based functions and excellent optical, electrical, and thermal properties. This review emphasizes the design strategies of tumor-targeted delivery systems based on 2D NMs from three aspects: passive targeting, active targeting, and tumor-microenvironment targeting, in order to promote the rational application of 2D NMs in clinical practice.This work was supported by the Guangdong Basic and Applied Basic Research Foundation (Nos. 2021A1515110657 and 2022A1515010056), Shenzhen Science and Technology Program (Grant No. RCBS20210609104513023), National Natural Science Foundation of China (No. 81922037), and Shanghai Biomedical Science and Technology Support Project (No. 19441903600)

A multifunctional photoacoustic/fluorescence dual-mode-imaging gold-based theranostic nanoformulation without external laser limitations

Theranostics is a new type of biomedical technology that organically combines the diagnosis and therapy of diseases. Among molecular imaging techniques, the integration of photoacoustic (PA) and fluorescence (FL) imaging modes with high sensitivity and imaging depth provides precise diagnostic outcomes. Gold nanorods (Au NRs) are well-known contrast agents for PA imaging and photothermal therapy. However, their high toxicity, poor biocompatibility, rapid clearance, and the need for an external laser source limit their application. Therefore, modification of Au NRs with carbon-based nanomaterials (CBNs) is done to obtain a multifunctional dual-mode gold-based nanoformulation (mdGC), which preforms dual-mode imaging of PA and FL. The results show that mdGC promotes tumor cell apoptosis and exhibits good antitumor performance through the mitochondria-mediated apoptotic pathway by increasing the production of intracellular reactive oxygen species, reducing mitochondrial membrane potential, and regulating the expression of apoptosis-related genes. The targeting rate of mdGC to tumor tissue is up to 20.71 ± 1.94% ID g-1; the tumor growth inhibition rate is as high as 80.44% without external laser sources. In general, mdGC is a potential multifunctional diagnostic and therapy integrated nanoformulation.J.Z., X.Y., and C.L. contributed equally to this study. This study was supported by the National Natural Science Foundation of China (81922037, 11575107, 21371115, and 22003038), the Shanghai UniversityUniversal Medical Imaging Diagnostic Research Foundation (19H00100), and Shanghai Biomedical Science and Technology Support Project (19441903600)

Organelle-specific anchored delivery system stretching a reversal of tumor hypoxia microenvironment to a combinational chemo-photothermal therapy

Direct delivery to an organelle-specific point can boost the efficacy of therapy procedures to new heights. Among other subcellular organelles, mitochondria generate ATP as intracellular powerhouse, and are associated with multiple aspects of tumorigenesis and tumor development. Here, a mitochondrial anchored biomimetic nanoplatform (CZACN) is designed and its reversal of tumor hypoxia microenvironment underlying the mitochondria-located chemo-photothermal therapy is studied. After shuttling into cancer cells, therapeutic payloads including cisplatin (CDDP) and Au nanozymes are controllably released in the ATP-overexpressed mitochondria. CDDP generates O2â ¢â , forms H2O2 for a chemical fuel in the next reaction, and damages mitochondrial DNA. Meanwhile, the catalase-like Au nanozymes catalyze the produced hydrogen peroxide for oxygen supply to relieve hypoxic tumor microenvironment, offering cytotoxic singlet oxygen against cancer cells under NIR treatment. As a result of cancer-cell self-recognition, mitochondria-targeted therapy, and photothermal conversion ability, the fabricated CZACNs obtained 89.2 ± 3.70% of tumor growth inhibition under NIR irradiation and constrained the dose-limiting toxicity of CDDP, as well. These findings reinforce the synergistic effect of organelle-specific navigation and in situ oxygen self-sufficiency for combinational chemo-photothermal therapy.X.C., X.Y., and L.Z. contributed equally to this work. This work has been supported by the National Natural Science Foundation of China (22003038, 81922037, and 11575107), the Shanghai University-Universal Medical Imaging Diagnostic Research Foundation (19H00100), Shanghai Biomedical Science and Technology Support Project (19441903600), the Program for Changjiang Scholars and Innovative Research Team in University (IRT13078). The authors would like to thank the workers from Shiyanjia Lab (www.shiyanjia.com) for the ICP-OES analysis