Weight loss induced by a hypocaloric diet with or without fish oil supplementation re-established iron and omega-3 fatty acid homeostasis in middle-aged women with obesity: A post-hoc analysis of a randomized controlled trial.

OBJECTIVE: Middle-aged women with obesity are at increased risk of iron overload and iron disorder is known to disrupt n-3 polyunsaturated fatty acid homeostasis. We evaluated relationships between pretreatment hemoglobin and n-3 polyunsaturated fatty acid levels, and tested whether pretreatment hemoglobin contributed to inter-individual variability in weight loss with special focus on changes in body weight, iron and n-3 polyunsaturated fatty acid profiles. STUDY DESIGN: 117 middle and older aged women with obesity and more than two metabolic abnormalities were randomized to a 12-week hypocaloric diet without or with fish oil supplementation. Blood iron biomarker and erythrocyte membrane phospholipid profiles were evaluated. MAIN OUTCOME: The absolute change from baseline to week 12 in serum iron and erythrocyte n-3 polyunsaturated fatty acid levels according to pretreatment hemoglobin tertiles and fish oil supplementation. RESULTS: A Pearson correlation analysis showed that pretreatment hemoglobin levels were negatively correlated with linoleic acid (r = -0.231), α-linoleic acid (r = -0.279), and n-3 polyunsaturated fatty acid (r = -0.217) (all p < 0.05). Dietary weight loss markedly enhanced erythrocyte membrane lipids of linoleic acid, α-linoleic acid, and n-6 and n-3 polyunsaturated fatty acid only in those women with the highest pretreatment hemoglobin levels (tertile 3) (all p < 0.05). Fish oil supplementation increased bioavailable iron in women with moderate pretreatment hemoglobin levels (tertile 2) (p < 0.05) and, to a lesser extent, prevented a reduction in circulating iron in those with the lowest hemoglobin levels (tertile 1). CONCLUSION: Dietary weight loss is an effective treatment program to manage obesity-related iron and n-3 polyunsaturated fatty acid disorders, particularly for middle-aged women with obesity and iron overload.

Red blood cell membrane-camouflaged gold-core silica shell nanorods for cancer drug delivery and photothermal therapy.

Gold core mesoporous silica shell (AuMSS) nanorods are multifunctional nanomedicines that can act simultaneously as photothermal, drug delivery, and bioimaging agents. Nevertheless, it is reported that once administrated, nanoparticles can be coated with blood proteins, forming a protein corona, that directly impacts on nanomedicines' circulation time, biodistribution, and therapeutic performance. Therefore, it become crucial to develop novel alternatives to improve nanoparticles' half-life in the bloodstream. In this work, Polyethylenimine (PEI) and Red blood cells (RBC)-derived membranes were combined for the first time to functionalize AuMSS nanorods and simultaneously load acridine orange (AO). The obtained results revealed that the RBC-derived membranes promoted the neutralization of the AuMSS' surface charge and consequently improved the colloidal stability and biocompatibility of the nanocarriers. Indeed, the in vitro data revealed that PEI/RBC-derived membranes' functionalization also improved the nanoparticles' cellular internalization and was capable of mitigating the hemolytic effects of AuMSS and AuMSS/PEI nanorods. In turn, the combinatorial chemo-photothermal therapy mediated by AuMSS/PEI/RBC_AO nanorods was able to completely eliminate HeLa cells, contrasting with the less efficient standalone therapies. Such data reinforce the potential of AuMSS nanomaterials to act simultaneously as photothermal and chemotherapeutic agents.

Erythrocyte membrane n-3 PUFA are inversely associated with breast cancer risk among Chinese women.

The relationship between erythrocyte membrane n-3 PUFA and breast cancer risk is controversial. We aimed to examine the associations of erythrocyte membrane n-3 PUFA with odds of breast cancer among Chinese women by using a relatively large sample size. A case-control study was conducted including 853 newly diagnosed, histologically confirmed breast cancer cases and 892 frequency-matched controls (5-year interval). Erythrocyte membrane n-3 PUFA were measured by GC. Logistic regression and restricted cubic spline were used to quantify the association between erythrocyte membrane n-3 PUFA and odds of breast cancer. Erythrocyte membrane α-linolenic acid (ALA), docosapentaenoic acid (DPA) and total n-3 PUFA were inversely and non-linearly associated with odds of breast cancer. The OR values (95 % CI), comparing the highest with the lowest quartile (Q), were 0·57 (0·43, 0·76), 0·43 (0·32, 0·58) and 0·36 (0·27, 0·49) for ALA, DPA and total n-3 PUFA, respectively. Erythrocyte membrane EPA and DHA were linearly and inversely associated with odds of breast cancer ((EPA: ORQ4 v. Q1 (95 % CI) = 0·59 (0·45, 0·79); DHA: ORQ4 v. Q1 (95 % CI) = 0·50 (0·37, 0·67)). The inverse associations were observed between ALA and odds of breast cancer in postmenopausal women, and between DHA and oestrogen receptor+ breast cancer. This study showed that erythrocyte membrane total and individual n-3 PUFA were inversely associated with odds of breast cancer. Other factors, such as menopause and hormone receptor status, may warrant further investigation when examining the association between n-3 PUFA and odds of breast cancer.

Effect of age and dietary habits on Red Blood Cell membrane fatty acids in a Southern Europe population (Basque Country).

The levels of blood eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are very variable and, in general, low in most of the world population. In this study, the effects of age, sex, COVID-19, and dietary habits on the lipid profile of the erythrocyte membranes were assessed in a sub-cohort of healthy population (N = 203) from a large cohort of individuals from the Basque Country, Spain, (AKRIBEA). Sex did not have an effect on RBC lipid profile. COVID-19 infected participants showed higher levels of DGLA. Oldest participants showed higher oleic acid, EPA and DHA levels. Arachidonic acid in RBC correlated positively with the intake of sunflower oil, butter, eggs, processed and red meat, whereas DHA and EPA correlated positively with oily and lean fish. Basque Country population showed lipid profiles similar to other high fish consuming countries, such as Italy and Japan. Baseline levels of the whole lipidomic profile of the RBC including SFA, MUFA and PUFA should be examined to obtain a better description of the health and nutritional status.

Competitive season effects on polyunsaturated fatty acid content in erythrocyte membranes of female football players.

BACKGROUND: An optimal and correctly balanced metabolic status is essential to improve sports performance in athletes. Recent advances in omic tools, such as the lipid profile of the mature erythrocyte membranes (LPMEM), allow to have a comprehensive vision of the nutritional and metabolic status of these individuals to provide personalized recommendations for nutrients, specifically, the essential omega-3 and omega-6 fatty acids, individuating deficiencies/unbalances that can arise from both habitual diet and sportive activity. This work aimed to study the LPMEM in professional female football players during the football season for the first time and compare it with those defined as optimal values for the general population and a control group. METHODS: An observational study was carried out on female football players from the Athletic Club (Bilbao) playing in the first division of the Spanish league. Blood samples were collected at three points: at the beginning, mid-season, and end of the season for three consecutive seasons (2019-2020, 2020-2021, and 2021-2022), providing a total of 160 samples from 40 women. The LPMEM analysis was obtained by GC-FID by published method and correlated to other individual data, such as blood biochemical parameters, body composition, and age. RESULTS: We observed a significant increase in docosahexaenoic acid (DHA) (p 0.048) and total polyunsaturated fatty acid (PUFA) (p 0.021) in the first season. In the second season, we observed a buildup in the membrane arachidonic acid (AA) (p < .001) and PUFA (p < .001) contents when high training accumulated. In comparison with the benchmark of average population values, 69% of the football players showed lower levels of omega-6 dihomo-γ-linolenic acid (DGLA), whereas 88%, 44%, and 81% of the participants showed increased values of AA, eicosapentaenoic acid (EPA), and the ratio of saturated and monounsaturated fatty acids (SFA/MUFA), respectively. Regarding relationships between blood biochemical parameters, body composition, and age with LPMEM, we observed some mild negative correlations, such as AA and SFA/MUFA ratio with vitamin D levels (coefficient = -0.34 p = .0019 and coefficient = -.25 p = .042); DGLA with urea and cortisol (coefficient = -0.27 p < .006 and coefficient = .28 p < .0028) and AA with age (coefficient = -0.33 p < .001). CONCLUSION: In conclusion, relevant variations in several fatty acids of the membrane fatty acid profile of elite female football players were observed during the competitive season and, in comparison with the general population, increased PUFA contents were confirmed, as reported in other sportive activities, together with the new aspect of DGLA diminution, an omega-6 involved in immune and anti-inflammatory responses. Our results highlight membrane lipidomics as a tool to ascertain the molecular profile of elite female football players with a potential application for future personalized nutritional strategies (diet and supplementation) to address unbalances created during the competitive season.

An erythrocyte membrane-modified biomimetic synergistic nanosystem for cancer anti-vascular therapy and initial efficacy monitoring.

Tumor vascular disruption has become a promising strategy for cancer therapy in recent decades. Nanocomposites loaded with therapeutic materials and drugs are expected to improve the accuracy of anti-vascular therapy and minimize side effects. However, how to prolong blood circulation of therapeutic nanocomposites for enhanced accumulation in tumor vasculature and how to monitor the initial efficacy of anti-vascular therapy for early evaluation of prognosis remain unsolved. Herein, a biomimetic nanosystem consisting of erythrocyte membrane modified nanocomposites (CMNCs) is developed for cooperation to achieve anti-vascular cancer therapy and initial efficacy monitoring. By utilizing poly(lactic-co-glycolic acid) (PLGA) as the interface material, functional nanomaterials and drug molecules are successfully integrated into CMNCs. The long circulation and immune escape features of the erythrocyte membrane facilitate CMNCs loaded with photothermal agents and chemodrugs to be delivered to the tumor region for anti-vascular treatment. Furthermore, the vascular damage-induced haemorrhage and the following coagulation process is labelled by near infrared emissive CMNCs to indicate the initial therapeutic efficacy of the treatment. This work not only points to a biomimetic strategy for conquering the challenges in anti-vascular cancer therapy, but also provides insights into the biological responses of erythrocyte membrane modified nanocomposites to exploit their biomedical applications.

Long Circulating Cancer Cell-Targeted Bionic Nanocarriers Enable Synergistic Combinatorial Therapy in Colon Cancer.

Cancer nanomedicine treatment aims to achieve highly specific targeting and localization to cancer cells. Coating of nanoparticles with cell membranes endows them with homologous cellular mimicry, enabling nanoparticles to acquire new functions and properties, including homologous targeting and long circulation in vivo, and can enhance internalization by homologous cancer cells. Herein, we fused a human-derived HCT116 colon cancer cell membrane (cM) with a red blood cell membrane (rM) to fabricate an erythrocyte-cancer cell hybrid membrane (hM). Oxaliplatin and chlorin e6 (Ce6) co-encapsulated reactive oxygen species-responsive nanoparticles (NPOC) were camouflaged by hM and obtained a hybrid biomimetic nanomedicine (denoted as hNPOC) for colon cancer therapy. hNPOC exhibited prolonged circulation time and recognized homologous targeting ability in vivo since both rM and HCT116 cM proteins were maintained on the hNPOC surface. hNPOC showed enhanced homologous cell uptake in vitro and considerable homologous self-localization in vivo, producing effective synergistic chemophotodynamic therapy efficacy under irradiation with a homologous HCT116 tumor compared to that with a heterologous tumor. Together, the biomimetic hNPOC nanoparticles showed prolonged blood circulation and preferential cancer cell-targeted function in vivo to provide a bioinspired strategy for chemophotodynamic synergistic therapy of colon cancer.

Red Blood Cell Membrane Fatty Acid Composition, Dietary Fatty Acid Intake and Diet Quality as Predictors of Inflammation in a Group of Australian Adults.

Evidence suggests that diet can play a role in modulating systemic inflammation. This study aims to examine the relationship between fatty acids (FAs) (self-reported dietary intake and red blood cell (RBC) membrane fatty acid concentrations), three diet quality scores, and the plasma concentrations of inflammatory markers (interleukin-6, IL-6; tumour necrosis factor alpha, TNF-α; and C-reactive protein, CRP) in a group of Australian adults (n = 92). Data were collected on their demographic characteristics, health status, supplement intake, dietary intake, RBC-FAs and plasma inflammatory markers over a nine-month period. Mixed-effects models were used to determine the relationship between RBC-FAs, dietary intake of FAs, diet quality scores and inflammatory markers to determine which variable most strongly predicted systemic inflammation. A significant association was identified between dietary saturated fat intake and TNF-α (ß = 0.01, p < 0.05). An association was also identified between RBC membrane saturated fatty acids (SFA) and CRP (ß = 0.55, p < 0.05). Inverse associations were identified between RBC membrane monounsaturated fatty acids (MUFAs) (ß = -0.88, p < 0.01), dietary polyunsaturated fatty acids (PUFAs) (ß = -0.21, p < 0.05) and CRP, and the Australian Eating Survey Modified Mediterranean Diet (AES-MED) score and IL-6 (ß = -0.21, p < 0.05). In summary, using both objective and subjective measures of fat intake and diet quality, our study has confirmed a positive association between saturated fat and inflammation, while inverse associations were observed between MUFAs, PUFAs, the Mediterranean diet, and inflammation. Our results provide further evidence that manipulating diet quality, in particular fatty acid intake, may be useful for reducing chronic systemic inflammation.

Biomimetic Gold Nanorods Modified with Erythrocyte Membranes for Imaging-Guided Photothermal/Gene Synergistic Therapy.

Pancreatic cancer (PC) is one of the most malignant cancers that develops rapidly and carries a poor prognosis. Synergistic cancer therapy strategy could enhance the clinical efficacy compared to either treatment alone. In this study, gold nanorods (AuNRs) were used as siRNA delivery vehicles to interfere with the oncogenes of KRAS. In addition, AuNRs were one of anisotropic nanomaterials that can absorb near-infrared (NIR) laser and achieve rapid photothermal therapy for malignant cancer cells. Modification of the erythrocyte membrane and antibody Plectin-1 occurred on the surface of the AuNRs, making them a promising target nanocarrier for enhancing antitumor effects. As a result, biomimetic nanoprobes presented advantages in biocompatibility, targeting capability, and drug-loading efficiency. Moreover, excellent antitumor effects have been achieved by synergistic photothermal/gene treatment. Therefore, our study would provide a general strategy to construct a multifunctional biomimetic theranostic multifunctional nanoplatform for preclinical studies of PC.

Lipidomics of the erythrocyte membrane and network pharmacology to explore the mechanism of mangiferin from Anemarrhenae rhizoma in treating type 2 diabetes mellitus rats.

Mangiferin, a natural C-glucoside xanthone, is one of the major bioactive ingredients derived from the dry rhizome of Anemarrhenae rhizome, which has been reported to exhibit various pharmacological effects, including anti-oxidant, anti-inflammatory, anti-fatty liver, anti-metabolic syndrome, and anti-diabetic. However, the precise molecular mechanisms underlying its impact on phospholipid metabolism in the erythrocyte membrane of type 2 diabetes mellitus (T2DM) remain unclear. The present research aimed to evaluate the effects of mangiferin on glucose and lipid metabolism in T2DM model rats and discuss the relationship between lipid metabolites and potential targets involved in the hypoglycemic effects by integrating lipidomics and network pharmacology method. After 8 consecutive weeks of treatment with mangiferin, the T2DM model rats exhibited significant improvements in several biochemical indices and cytokines, including fasting blood glucose (FBG) levels after 12 h of fasting, fasting insulin level (FINS), total cholesterol (T-CHO), triacylglycerols (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), homeostasis model assessment of insulin resistance (HMOA-IR), TNF-α and IL-6. A total of 22 differential lipid metabolites were selected from erythrocyte membrane phospholipids, which were closely associated with the processes of T2DM. These metabolites mainly belonged to glycerophospholipid metabolism and sphingolipid metabolism. Based on network pharmacology analysis, 22 genes were recognized as the potential targets of mangiferin against diabetes. Moreover, molecular docking analysis revealed that the targets of TNF, CASP3, PTGS2, MMP9, RELA, PLA2G2A, PPARA, and NOS3 could be involved in the modulation of inflammatory signaling pathways and arachidonic acid (AA) metabolism to improve IR and hyperglycemia. The combination of immunohistochemical staining and PCR showed that mangiferin could treat T2DM by regulating the expression of PPARγ protein and NF-κB mRNA expression to impact glycerophospholipids (GPs) and AA metabolism. The present study showed that mangiferin might alleviate IR and hyperglycemia of T2DM model rats via multiple targets and multiple pathways to adjust their phospholipid metabolism, which may be the underlying mechanism for mangiferin in the treatment of T2DM.

Biomimetic graphene oxide quantum dots nanoparticles targeted photothermal-chemotherapy for gastric cancer.

Direct use of chemotherapy drugs in the treatment of gastric cancer often leads to systemic side effects and unsatisfied therapeutic efficacy due to the lack of tumour-targeting ability. The excellent properties of nanoparticles make them good tools to provide more options for the targeted delivery of chemotherapeutic drugs. Herein, we developed a novel nanomedicine (GOQD-ICG-CS-6@HM nanoparticles, GIC@HM NPs), which employed graphene oxide quantum dots (GOQDs) to co-load photosensitizer indocyanine green (ICG) and chemotherapeutic drug gamabufotalin (CS-6) as the core and wrapped with the hybrid membrane (erythrocyte membrane and gastric cancer cell membrane, HM) on its surface. This nanomedicine possesses the functions of photothermal therapy and chemotherapy, making it a good choice for the treatment of gastric cancer. The results showed that the bionic-coated hybrid membrane not only improves the biocompatibility of the nanomedicine, and prolong its circulating half-life, but also delivers the drug to the tumour site precisely and improves the efficiency of drug utilisation. In vitro and in vivo studies further showed that GIC@HM NPs exhibited combinational effects on tumour therapy while displaying no obvious side effects on normal tissue. To sum up, the newly developed GIC@HM NPs provide a safer, more efficient, and more precise method for gastric cancer treatment.

Erythrocyte Membrane Docosahexaenoic Acid (DHA) and Lipid Profile in Preterm Infants at Birth and Over the First Month of Life: A Comparative Study with Infants at Term.

An observational comparative study was designed to assess the fatty acids profile in erythrocyte membrane phospholipids of 30 preterm neonates (<32 weeks gestation) at birth and after 1 month of life versus a convenience sample of 10 infants born at term. The panel of fatty acids included the families and components of saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs), and n-6 and n-3 polyunsaturated fatty acids (PUFAs) as well as enzyme activity indexes and fatty acids ratios. At birth, the comparison of fatty acid families between preterm and term neonates showed a significantly higher content of SFAs and n-6 PUFAs, and a significantly lower content of MUFAs and n-3 PUFAs in the preterm group. After 30 days of life, significantly higher levels of n-6 PUFAs and significantly lower levels of n-3 PUFAs among preterm neonates persisted. At 30 days of birth, n-6 PUFA/n-3 PUFA and arachidonic acid (ARA) ARA/DHA remained significantly elevated, and DHA sufficiency index significantly decreased in the preterm group. The pattern of n-3 PUFA deficiency at birth and sustained for the first month of life would support the need of milk banking fortified with DHA and the use of DHA supplementation in breastfeeding mothers.

Synergistic chemotherapy and phototherapy based on red blood cell biomimetic nanomaterials.

Novel drug delivery systems (DDSs) have become the mainstay of research in targeted cancer therapy. By combining different therapeutic strategies, potential DDSs and synergistic treatment approaches are needed to effectively deal with evolving drug resistance and the adverse effects of cancer. Nowadays, developing and optimizing human cell-based DDSs has become a new research strategy. Among them, red blood cells can be used as DDSs as they significantly enhance the pharmacokinetics of the transported drug cargo. Phototherapy, as a novel adjuvant in cancer treatment, can be divided into photodynamic therapy and photothermal therapy. Phototherapy using erythropoietic nanocarriers to mimic the unique properties of erythrocytes and overcome the limitations of existing DDSs shows excellent prospects in clinical settings. This review provides an overview of the development of photosensitizers and research on bio-nano-delivery systems based on erythrocytes and erythrocyte membranes that are used in achieving synergistic outcomes during phototherapy/chemotherapy.

Red blood cell membrane nanoparticles for tumor phototherapy.

Non-invasive phototherapy includes photodynamic therapy (PDT) and photothermal therapy (PTT), and has garnered special interest in anti-tumor therapy. However, traditional photosensitizers or photothermal agents are faced with major challenges, including easy recognition by immune system, rapid clearance from blood circulation, and low accumulation in target sites. Combining the characteristics of natural cell membrane with the characteristics of photosensitizer or photothermal agent is an important technology to achieve the ideal therapeutic effect of cancer. Red cell membrane (RBMs) coated can disguise phototherapy agents as endogenous substances, thus constructing a new nano bionic therapeutic platform, resisting blood clearance and prolonging circulation time. At present, a variety of phototherapy agents based on Nano-RBMs have been isolated or designed. In this review, firstly, the basic principles of Nano-RBMs and phototherapy are expounded respectively. Then, the latest progress of Nano-RBMs for PDT, PTT and PDT/PTT applications in recent five years has been introduced respectively. Finally, the problems and challenges of Nano-RBMs in the field of phototherapy are put forward.

[Congenital hemolytic anemias due to erythrocyte membrane and enzyme defects]. / Kongenitale hämolytische Anämien durch Membran- und Enzymdefekte der Erythrozyten.

Erythrocyte membrane and enzyme defects are the most common cause of congenital hemolytic anemias in the Central European population. Diagnostics include erythrocyte morphology, special biochemical tests such as osmotic fragility (AGLT) and EMA. For enzymopenic hemolytic anemias, cost-effective biochemical analysis remains the gold standard, supplemented by molecular genetic diagnostics when appropriate. Therapeutically, near complete splenectomy reduces hemolysis significantly for spherocytosis. The residual spleen at least provides a considerable phagocytic function and better response to immunisation and by inference possibly better protection against severe post-splenectomy infection. For pyruvate kinase deficiency, which is not so rare, a new molecular therapy (Mitapivat) is currently being introduced. In G6PD deficiency, there are very few drugs that cause hemolytic crisis. Sudden onset of hemoglobinuria is an early important hallmark of severe hemolytic crisis in G6PD deficiency and these patients should be hospitalized. Aplastic crises in the setting of parvovirus B19 infection occur in all congenital hemolytic anemias. Transfusion is not preventable in most cases. Iron-excreting treatment is required in the rare patients in need of chronic transfusion.

Recent advances in erythrocyte membrane-camouflaged nanoparticles for the delivery of anti-cancer therapeutics.

INTRODUCTION: Red blood cell (or erythrocyte) membrane-camouflaged nanoparticles (RBC-NPs) not only have a superior circulation life and do not induce accelerated blood clearance but also possess special functions, which offers great potential in cancer therapy. AREAS COVERED: This review focuses on the recent advances of RBC-NPs for delivering various agents to treat cancers in light of their vital role in improving drug delivery. Meanwhile, the construction and in vivo behavior of RBC-NPs are discussed to provide an in-depth understanding of the basis of RBC-NPs for improved cancer drug delivery. EXPERT OPINION: Although RBC-NPs are quite prospective in delivering anti-cancer therapeutics, they are still in their infancy stage and many challenges need to be overcome for successful translation into the clinic. The preparation and modification of RBC membranes, the optimization of coating methods, the scale-up production and the quality control of RBC-NPs, and the drug loading and release should be carefully considered in the clinical translation of RBC-NPs for cancer therapy.

Erythrocyte Membrane-Enveloped Salvianolic Acid B Nanoparticles Attenuate Cerebral Ischemia-Reperfusion Injury.

Purpose: Ischemic stroke is the second leading cause of death and the third leading cause of disability worldwide. Salvianolic acid B (SAB), a water-soluble phenolic acid derived from the traditional Chinese medicine Salvia miltiorrhiza, exerted protective effects on cerebral ischemia-reperfusion injury. However, the efficacy of SAB is seriously hindered by poor blood brain barrier (BBB) permeability and short biological half-life in plasma. Brain targeted biomimetic nanoparticle delivery systems offer much promise in overcoming these limitations. Methods: A brain targeted biomimetic nanomedicine (RR@SABNPs) was developed, which comprised of SAB loaded bovine serum albumin nanoparticles and functionalized red blood cell membrane (RBCM) with Arg-Gly-Asp (RGD). The characterization parameters, including particle size, zeta potential, morphology, Encapsulation Efficiency (EE), Drug Loading (DL), release behavior, stability, and biocompatibility, were investigated. Moreover, the middle cerebral artery occlusion/reperfusion (MCAO/R) mouse model was used to assess the therapeutic efficacy of RR@SABNPs on ischemic stroke. Finally, the reactive oxygen species (ROS) levels and mitochondrial membrane potential (MMP) were detected by DHE and JC­1 staining in oxygen-glucose deprivation/reperfusion (OGD/R) and H2O2 injured PC12 cells. Results: RR@SABNPs exhibited spheric morphology with core-shell structures and good stability and biocompatibility. Meanwhile, RR@SABNPs can significantly prolong SAB circulation time by overcoming the reticuloendothelial system (RES) and actively targeting ischemic BBB. Moreover, RR@SABNPs had comprehensive protective effects on MCAO/R model mice, manifested as a reduced infarct volume and improved neurological and sensorimotor functions, and significantly scavenged excess ROS and maintained MMP. Conclusion: The designed brain targeted biomimetic nanomedicine RR@SABNPs can significantly prolong the half-time of SAB, deliver SAB into the ischemic brain and exhibit good therapeutic effects on MCAO/R model mice.

Engineered Red Blood Cell Membrane-Coating Salidroside/Indocyanine Green Nanovesicles for High-Efficiency Hypoxic Targeting Phototherapy of Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) presents special biological behavior and clinicopathological characteristics and leads to a worse prognosis than other types of breast cancer. The development of an effective therapeutic method is significant to improve the survival rate of TNBC cancer patients. In this work, an engineered red blood cell membrane (RBCm)-coating salidroside/indocyanine green nanovesicle (ARISP) is successfully prepared for hypoxic targeting phototherapy of TNBC. Salidroside in ARISP effectively ameliorates hypoxia-induced tumorigenesis by downregulating the expression of hypoxia-inducible factor 1α (HIF-1α), which increases the killing effect of reactive oxygen species on tumor cells during photodynamic therapy (PDT) using the photosensitizer indocyanine green. Besides, ARISP has an anti-LDLR modified RBCm-coating that extends its circulation time in the blood and escapes from immune surveillance and enhances hypoxia-targeted cellular uptake via the overexpressed LDLR receptor in hypoxic tumor sites. Moreover, guided by near-infrared fluorescence imaging and photoacoustic imaging, ARISP can eliminate tumors via high-efficiency phototherapy and inhibit lung and liver metastasis in TNBC models. Cytotoxicity assay of ARISP indicates the excellent biocompatibility with normal cells and tissues. This study provides fulfilling insights into the anticancer mechanism of reducing HIF-1α for enhanced PDT and has a promising therapeutic potential for TNBC treatment.

Epicatechin exerts dual action to shield sickling and hydroxyurea-induced myelosuppression: Implication in sickle cell anemia management.

Hydroxyurea (HU) is the key drug to treat Sickle cell anemia (SCA). However, its treatment is associated with the liability of myelosuppression. The present study aimed to investigate the potential of epicatechin as a supplementation therapy for the symptomatic management of SCA under HU therapy. A panel of experiments were performed at first to observe epicatechin's effect on sickling and hemolytic behaviour using SCA patient's blood (ex vivo). Thereafter, the effect of HU in the presence or absence of epicatechin was investigated on cytokine inhibition in rat splenocytes (ex vivo) as well as alterations in hematological parameters and kidney function tests in rats (in vivo). Then, any effect of epicatechin on pharmacokinetic modulation of HU in rats was elucidated along with the underlying mechanism using a battery of in vitro and in vivo models. Epicatechin exhibited potent action on anti-sickling, polymerization inhibition, and erythrocyte membrane stability. It did not show any inherent hemolytic activity and reduced TNF-α level during concomitant administration with HU. Based on hematological changes in rats, epicatechin treatment aided to the beneficial effect of HU and prevented the treatment-linked disadvantageous effects of HU like neutropenia. The plasma exposure of HU was significantly augmented in rats upon simultaneous oral administration of epicatechin with HU. Down-regulation of Oatp1b2 and catalase possibly contributed to the pharmacokinetic interaction of HU. Epicatechin is found to be a promising candidate and should be explored at a reduced dose level of HU towards offsetting the dose-dependent myelosuppressive effect of HU under the frame of supplementation therapy in SCA.

Reprint of: Is Vitamin E the Only Lipid-Soluble, Chain-Breaking Antioxidant in Human Blood Plasma and Erythrocyte Membranes?

The concentrations of lipid-soluble, chain-breaking antioxidants in human plasma and in erythrocyte ghosts have been determined for the first time by an inhibited autoxidation method. The results are very similar to the concentrations of vitamin E measured for the same blood components by the HPLC method. It is concluded that vitamin E, which is largely present as α-tocopherol, is the only significant lipid-soluble, chain-breaking type of antioxidant present in human blood. The concentration of vitamin E in the plasma lipids divided by the concentration of vitamin E in the ghost membrane lipids is approximately a constant despite the large differences in vitamin E-intake and in plasma lipid concentrations in different individuals. Vitamin E/lipid ratios for plasma and ghosts were larger for subjects taking a supplement of α-to- copherol acetate of 100 IU per week, compared to nonsupplemented subjects (based on data from a limited number of subjects). A larger supplement of 2800 IU per week did not significantly increase the vitamin E/lipid ratios.