Red Blood Cell Membrane Research Articles

Prospective Cohort Study Investigating Polyunsaturated Fatty Acids and Chronic Lung Disease in Preterm Infants.

Chronic lung disease (CLD) is a complication of prematurity. Studies examining the effects of long-chain polyunsaturated fatty acids (LC-PUFAs) on CLD are conflicting. This study investigated LC-PUFAs in the red blood cell membrane (RBCM) in preterm infants. This prospective observational study included infants with gestational age <32 weeks or birth weight <2 kg and at least one LC-PUFA measurement in the first month of life. Subjects without CLD (CON group) were compared to those with CLD (CLD group) and then by CLD severity. Seventy infants were included (CON n=29; CLD n=41). Twenty six infants had Grade 1 CLD; 12 had Grade 2 CLD; 3 had Grade 3 CLD. When the CLD group was compared to the CON group, the overall mean (95% confidence interval) RBCM% for linoleic acid (LA) was similar (CLD vs. CON 12.5% [11.7% - 13.4%] vs. 11.2% [10.2 - 12.3%] p=0.06) but the overall mean arachidonic acid (ARA) was lower (17.6% [17.1% - 18.0%] vs. 18.6% [18.1% - 19.2%], p<0.01). During weeks 1-4, LA% was similar, while ARA% was lower in weeks 2 and 3 (18.8% ± 2.2% vs. 20.0% ± 1.5%, p=0.05, 16.8% ± 2.0% vs. 18.3% ± 1.6%, p=0.01). A similar trend was noted when groups were compared by CLD severity. The CLD group had a higher overall mean ∝-linolenic acid (ALA) compared to the CON group (0.4% [0.3% - 0.4%] vs. 0.2% [0.2 % - 0.3%], p<0.01) but no difference in docosahexaenoic acid (DHA) (3.8% [3.4% - 4.1%] vs. 3.8% [3.4% - 4.3%], p=0.80). During weeks 1-4, ALA% was higher during week 1 only (0.4% ± 0.3% vs. 0.2% ± 0.1%, p<0.01), and DHA% was similar for weeks 1-4. Results were similar when groups were compared by CLD severity. In this study, low ARA status was associated with CLD.

Recent advances in cell membrane-coated porphyrin-based nanoscale MOFs for enhanced photodynamic therapy.

Porphyrins-based nanoscale metal-organic frameworks (nMOFs) has been widely utilized to kills tumor cells by generating cytotoxic reactive oxygen species (ROS). However, porphyrin based nMOFs (por-nMOFs) still face challenges such as rapid immune clearance and weak tumor targeting. Researchers have discovered that using a top-down biomimetic strategy, where nMOFs are coated with cell membranes, can promote long blood circulation, evade the reticuloendothelial system, and improve cancer cell targeting, thereby significantly enhancing the photodynamic therapy (PDT) effect of nMOFs. This review summarizes the recent work on different cell membranes-coated por-nMOFs for enhanced tumor PDT. This review details the changes in physicochemical properties, enhanced homotypic cancer cell-selective endocytosis, improved tumor tissue targeting, and increased cytotoxicity and effective in vivo tumor suppression after the nMOFs are wrapped with cell membranes. Additionally, this review compares the biological functions of various types of cell membranes, including cancer cell membranes, red blood cell membranes, aptamer-modified red blood cell membranes, and hybrid membranes from the fusion of cancer and immune cells. The review highlights the enhanced immunogenic cell death function when using hybrid membranes derived from the fusion of cancer and immune cell membranes. By summarizing the augmented PDT effects and the combined antitumor outcomes with other therapeutic modalities, this review aims to provide new insights into the biomedical applications of por-nMOFs and offer more references for the preclinical application of porphyrin-based photosensitizers.

Complications of delayed diagnosis and challenges: successfully managed SPTB gene variant hereditary spherocytosis with hepatocellular jaundice—a case report

BackgroundHereditary spherocytosis is a rare genetic disorder of the red blood cell membrane that is characterized by anemia, jaundice, and splenomegaly; however, in the absence of family history and with unusual clinical presentation, the diagnosis might not be made until later in life.Case presentationHere, we present a challenging case of genetically proven hereditary spherocytosis that involves the SPTB gene in a 23-year-old female patient from Ethiopia who had repeated medical visits for episodic jaundice and hepatosplenomegaly, with unusual features of conjugated hyperbilirubinemia, pancytopenia, normal reticulocyte count, and lack of family history, where the delay in diagnosis led to several complications. The patient was successfully managed with simultaneous splenectomy and cholecystectomy.ConclusionThis case underscores the importance of a thorough clinical examination, spending the time to review a case periodically without assuming the initial diagnosis is correct, and maintaining a healthy skepticism of inconsistent data to prevent misdiagnosis and mistreatment. The diagnostic delay highlights the need for increased awareness and familiarity with diagnostic modalities of hereditary spherocytosis among healthcare providers in Ethiopia.

Stomatocyte-discocyte-echinocyte transformations of erythrocyte modulated by membrane-cytoskeleton mechanical properties.

Stomatocyte-discocyte-echinocyte (SDE) transformations in human red blood cells (RBCs) have significant influences on blood dynamics and related disorders. The mechanical properties of the RBC membrane, such as shear modulus and bending elasticity, play crucial roles in determining RBC shapes. Recent biophysical findings reveal that building a comprehensive model capable of describing SDE shape transformations is a challenging problem. Based on dissipative particle dynamics, this study develops a two-component RBC model considering the detachment between the lipid bilayer and cytoskeleton, as well as the cytoskeletal reorganization during echinocyte formation. This model is validated by comparing RBCs' geometric shape and the apparent membrane tension with previous experimental measurements. Results indicate that a complete SDE sequence represented by six typical shapes can be obtained by modulating the model's mechanical and geometric parameters. Furthermore, a phase diagram based on reduced variables is obtained using principal-component analysis, demonstrating the phase transformations among SDE shapes. Our result suggests that the transformation from discocyte to stomatocyte is primarily influenced by dimensionless bending rigidity, whereas, during echinocyte formation, three key variables, i.e., dimensionless bending rigidity, targeting cytoskeleton shrinkage ratio, and connecting pattern, have joint impacts on the formation of spicules or bumps and the development of the cytoskeletal framework. The present two-component RBC model and the associated findings provide a perspective for a deeper understanding of the SDE transformation mechanism. This framework offers new insights into biological science and potential applications in the field of biomedical engineering.

New mutation in the β-spectrin gene in hereditary spherocytosis: A case report

In patients with recurrent anemia, jaundice, and splenomegaly, a thorough assessment of family history and peripheral blood smears is crucial for diagnosing hereditary spherocytosis (HS). Furthermore, gene sequencing can enhance diagnostic accuracy and facilitate the investigation of disease mechanisms at the molecular level. In this report, we present a case of HS caused by a heterozygous nonsense mutation in the SPTB gene, along with a family history of this specific mutation. A 35-year-old man was evaluated for jaundice and splenomegaly, which he had experienced since childhood. Blood tests revealed anemia, reticulocytosis, elevated indirect bilirubin levels, and an increased percentage of spherical red blood cells in the peripheral blood. His family history indicated that both his father and daughter exhibited similar clinical manifestations. Subsequently, genetic sequencing confirmed that the patient, along with his father and daughter, shared the heterozygous missense mutation c.155G > A (p.Arg52Gln) in the SPTB gene, which is absent in public population and animal sequence databases. Structural prediction analysis of the protein suggests that this mutation may lead to instability of SPTB mRNA, thereby affecting the synthesis of the spectrin protein and the integrity of the red blood cell membrane skeleton. Further research is needed to clarify the exact relationship between this mutation and the occurrence of HS.

Convergent Synthesis, Kinetics, and Computational Studies of Indole(Phenyl)Triazole Bi-Heterocycles Modified With Propanamides as Elastase Inhibitors.

Biological screening combined with the synthesis of heterocyclic compounds with numerous functions is the most effective approach available for pharmacological assessment of potential future medications. In the under taken research that is presented here, 4-(1H-indol-3-yl)butanoic acid was sequentially converted into 4-(1H-indol-3-yl)butanoate, 4-(1H-indol-3-yl)butanohydrazide, and 5-[3-(1H-indol-3-yl)propyl]-1,2,4-triazole-2-thiol as a nucleophile. By treating aryl amines with 3-bromopropanoyl chloride in a series of parallel reactions, different electrophiles were created, leading to the formation of N-(aryl)-3-bromopropanamides. After that, several electrophiles were used in the nucleophilic substitution process of 5 to produce the final bi-heterocyclic derivative. The structural confirmation of all the synthesized compounds was done by IR, 1H-NMR, 13C-NMR, and CHN analysis data. The enzyme inhibitory effects of these bi-heterocyclic propanamides were evaluated against elastase, and all these molecules were identified as potent inhibitors relative to the standard oleanolic acid with IC50 value 13.453±0.015µM used. The kinetics mechanism was ascribed by evaluating the Lineweaver-Burk plots, which revealed that compound 9d inhibited elastase competitively to form an enzyme-inhibitor complex. The inhibition constant Ki calculated from Dixon plots for this compound was 0.51µM. Compound 9d's activity (IC50=0.142±0.014µM) significantly increased when a slightly bulky ethyl group was replaced for the solitary methyl group in 9c at the para-position. However, compound 9e's activity was significantly lower (IC50=38.338±0.993µM) when a more polar ethoxy group was replaced at the same para-position. This was likely because of electronic considerations. These molecules also exhibited mild cytotoxicity toward red blood cell membranes, when analyzing through hemolysis. So, these molecules might be deliberated as nontoxic medicinal scaffolds for dealing with the elastase-related ailments such as lung diseases, cyclic neutropenia, pruritic skin disease, and liver infection.

Eco-friendly synthesis of ZnO nanoparticles fabricated using Fioria vitifolia L. and their Biomedical Potentials

The present study aimed to environmentally friendly synthesis of ZnO NPs using Fioria vitifolia leaf extracts which provides a sustainable and green approach for production of NPs. The produced ZnO NPs were evaluated using various spectrum approaches (UV-vis, FTIR XRD, TEM and EDAX). The synthesized ZnO NPs was confirmed by UV-Visible spectroscopy exhibited a peak at 370 nm. SEM imaging revealed a flash-like and needle-like bottom morphology. Fourier-transform infrared spectroscopy (FTIR) analysis detected vibrations corresponding to alcohols, halides, and aromatics functional groups. TEM showed spherical-shaped NPs with an average diameter of 11 nm. XRD analysis exhibited distinct peaks at 2θ values of 31.7°, 34.3°, 36.2°, 47.4°, 56.6°, 62.8°, 66.4°, 67.9°, 69.1°, and 76.8°, corresponding to the crystallographic planes (100), (002), (101), (102), (110), (103), (200), (112), (201), (004), and (202) planes respectively. The antibacterial activity demonstrated significant zones of inhibition against E. coli (17±0.6 mm) and S. aureus (23.7±0.5 mm), and inhibition of biofilm formation in S. aureus and C. albicans. Additionally, S. mutans exhibited the highest sensitivity to the minimum inhibitory concentration (MIC) of ZnO NPs, with complete inhibition occurring at 7.5 μg/mL. Furthermore, antioxidant DPPH assays exhibited IC50 values of 42 μg/mL. Additionally, the anti-inflammatory properties of ZnO NPs of F. vitifolia were evaluated in-vitro using models utilizing the human red blood cells (HRBC) membrane stabilization method (MSM), and it was shown to have an MSM of 83.87% at 250 μg/mL. Furthermore, ZnO NPs exhibited anticancer activity against the MDA-MB-231 breast cancer cell line with an IC50 value of 35.50 μg/mL. Toxicological evaluation of FV-ZnO nanoparticles in zebrafish (Danio rerio) embryos indicated low toxicity at maximum concentration. These is first findings suggest that ZnO NPs synthesized from F. vitifolia leaf extracts possess significant antibacterial, antioxidant, anti-inflammatory, and anticancer properties. Additionally, their low toxicity in zebrafish embryos makes them suitable for further development in antimicrobial therapies with minimal side effects, offering a sustainable, biocompatible solution to tackle multidrug-resistant microbial infections.

Associations between perinatal biomarkers of maternal dairy fat intake and child cognitive development: results from the EDEN mother-child cohort.

Offspring's optimal neurodevelopment depends on maternal dietary lipids supply during the perinatal period. Dairy products are an important source of fat in Western diets. This study aimed at examining the associations between maternal dairy fat intake during pregnancy, evaluated through biomarkers in perinatal biofluids (C15:0 and C17:0) and child's cognitive outcomes. Participants (N up to 1200) were French mother-child pairs from the EDEN cohort study. Biomarkers were assessed in the following biofluids: maternal red blood cells (RBC) membrane at 24 weeks' gestation, cord RBC membrane, and colostrum. Cognitive outcomes were language abilities scores at ages 2 and 3 years and overall cognitive development scores at ages 3 and 5-6 years. Associations were assessed using multiple linear regression models adjusted for factors related to family socioeconomic context, maternal lifestyle, and healthy diet score. Interaction of any breastfeeding duration on the associations with dairy fat biomarkers in colostrum was studied. Positive associations were observed between levels of C17:0 in cord RBC and C15:0 in maternal RBC with language abilities. In children breastfed for at least 6 months, C15:0 level in colostrum was positively associated with language abilities at age 3 years and overall cognitive development at ages 3 and 5-6 years whereas C17:0 level was only associated with overall cognitive development at age 3 years. Our results suggest that maternal higher intake of dairy fat during perinatal period could be potentially associated with offspring's better cognitive development. These pioneering results call for external validation to challenge their causality.

Formulation and Characterization of RBCS Coated Carboplatin Loaded Nano-Liposomal Formulation for Managing Breast Cancer.

Cell membrane-coated Nano-Liposomes (CM-NLPs) offer a promising approach that combines the advantages of both host cells and synthetic nano-liposomes (NLPs). This technique involves coating liposomes with red blood cell (RBC) membranes to enhance their functionality. In this study, novel carboplatin-loaded NLPs (CP-NLPs) were formulated using phospholipids (Soya Phosphatidyl Choline) and cholesterol through the thin-film hydration method, and optimized using a 32 full factorial design. The optimized CP-NLPs were coated with RBC membranes, resulting in the formulation "CP-RBCs-NLPs." These were characterized for particle size, zeta potential, entrapment efficiency, transmission electron microscopy (TEM), differential scanning calorimetry (DSC), protein content, in vitro drug release, cell viability, and stability. The optimized CP-RBCs-NLPs exhibited a particle size of 103.6 nm, with zeta potential values of -27.3 mV indicating good stability. The entrapment efficiency was approximately 56%, and the drug release profile showed sustained release for up to 8 h. Cytotoxicity studies in human triple-negative breast cancer (MDA-MB468) cell lines demonstrated that CP-RBCs-NLPs effectively delivered the drug into target cells, facilitating cell death due to their bilayer structure similar to cell membranes. Overall, CP-RBCs-NLPs outperformed both carboplatin-loaded conventional NLPs (CP-CNLPs) and carboplatin-conventional solution (CP-CNS), making it a superior formulation for drug delivery.

Hydrogen peroxide diffusion across the red blood cell membrane occurs mainly by simple diffusion through the lipid fraction

Hydrogen peroxide (H2O2) is an oxidant produced endogenously by several enzymatic pathways. While it can cause molecular damage, H2O2 also plays a role in regulating cell proliferation and survival through redox signaling pathways. In the vascular system, red blood cells (RBCs) are notably efficient at metabolizing H2O2. In addition to a robust antioxidant defense, we recently determined that human RBCs also have a high membrane permeability to H2O2 that is independent of aquaporin 1 or aquaporin 3. In this work, we sought to further investigate the permeation mechanism of H2O2 through the membrane of human RBCs. First, we explored the role of other erythrocytic membrane proteins in H2O2 transport, including urea transporter B and ammonia transporter Rh proteins. However, no differences were found in H2O2 permeability in RBCs lacking these proteins compared to control RBCs. We then focused on the hypothesis that H2O2 diffuses through the lipid bilayer. To test this, we studied H2O2 permeability in RBCs from patients with Gaucher disease (GD), which accumulate sphingolipids in the membrane, affecting RBC morphology and deformability. We found that RBCs from GD patients exhibited lower H₂O₂ membrane permeability. In another approach, we treated normal RBCs with hexanol, which fluidizes the lipid fraction of the RBC membrane, and observed an increase in the permeability to H2O2. In contrast, hexanol had no effect on the rate of water efflux by aquaporin 1. Together, these results support the hypothesis that H2O2 diffusion through the RBC membrane occurs primarily through the lipid fraction.

Biomimetic Nano-delivery of Small-Molecule Piceatannol Modulates Tumor Stemness and Suppresses Colorectal Cancer Metastasis via Hippo/YAP1/SOX9 Signaling.

Suppressing tumor metastasis is a crucial strategy for improving survival rates in patients with colorectal cancer (CRC), with cancer stem cells (CSCs) being the primary drivers of metastasis. Current therapeutic approaches targeting CSCs are limited, and their molecular mechanisms remain unclear. To address this challenge, a biomimetic nanoparticle delivery system, CMD-BHQ3-PTL/DOX@RBCM is developed, to deliver the stem cell regulator, piceatannol (PTL). This system used carboxymethyl dextran (CMD) and Black Hole Quencher 3 (BHQ3) to encapsulate PTL and the cytotoxic drug doxorubicin (DOX) within a red blood cell membrane (RBCm), enhancing stability and biocompatibility while allowing gradual drug release under hypoxic conditions. The effects of PTL are investigated on CSCs using molecular biology experiments, plasmid construction, and high-throughput sequencing and elucidated the molecular mechanisms underlying this biomimetic nanoparticle delivery system. The therapeutic efficacy of PTL is validated at the tissue level using subcutaneous and metastatic tumor models in human and murine systems. The results demonstrated that CMD-BHQ3-PTL/DOX@RBCM effectively addressed the challenges of specificity and biocompatibility in vivo, significantly inhibiting CSC-related tumor metastasis. This inhibitory effect is closely associated with the Hippo/YAP1/SOX9 pathway. This study highlights the effectiveness of the pH-responsive biomimetic nanoparticle system CMD-BHQ3-PTL/DOX@RBCm in delivering PTL to tumor sites, with SOX9 and its upstream Hippo/YAP1 pathway playing a critical role in the underlying mechanism.

Anti –Inflammatory Activity of Propolis Trigona sp. Water Extract from North Lombok with Red Blood Cell Membrane Stability Method

Propolis is a bee product that can be used as an anti-inflammatory. Cultivation of propolis-producing bees is also carried out in North Lombok. However, propolis has not been utilized optimally by the people of North Lombok. Apart from that, testing of North Lombok propolis is still limited to the chemical content and antioxidant activity of propolis extracted with ethanol solvent. Therefore, this study aims to determine the activity and effective concentration of North Lombok propolis water extract as an anti-inflammatory using the red blood cell membrane stability method. Groups include control groups such as positive control (diclofenac sodium), negative control (distilled water), and test groups (propolis water extract concentrations of 10%, 12.5%, 15%, 17.5%, 20%, 22.5%, 25%, 27.5%, and 30%). In The first step human blood was centrifuged of human blood, and then part of the red blood cells (sediment) was taken and saline was added to obtain a red blood cell suspension. Next, mixing the test solution was carried out in the order of 0.5 ml of red blood cell suspension, then 0.5 ml of extract was added (0.1% w/v Na-diclofenac solution in the positive control, distilled water in the negative control), 1 mL of buffer solution and 2 mL of hyposaline solution, then homogenized. Each group was incubated at 37°C for 30 minutes, then centrifuged for 10 minutes at 3000 rpm. The supernatant was taken, and the absorbance was read with a UV-Vis spectrophotometer at 560 nm. Next, the percentage value of red blood cell hemolysis protection was calculated. The data obtained were tested statistically using One-way ANOVA and post-hoc (LSD) tests SPSS version 29. The results showed that propolis water extract concentrations were 10%, 12.5%, 15%, 17.5%, 20%, 22.5%, 25%, 27.5%, and 30% have anti-inflammatory activity because they can increase the stability of the red blood cell membrane with a percentage of hemolysis protection of respectively 57.92%, 59.99%, 60.99%, 61.99%, 64.31%, 69.59%, 75.07%, 79.77% and 84.45%. Propolis water extract concentrations of 10%, 12.5%, 15%, 17.5%, 20%, 22.5%, and 25% had anti-inflammatory effects that were not significantly different from the positive control (p&gt;0.05). The 27.5 % and 30% concentrations had a higher percent hemolysis protection value than the positive control (p&lt;0.05).

Mitapivat-Induced Improvements in RBC Deformability and Membrane Integrity in Patients with Sickle Cell Disease Are Sustained during Extended Therapy

Mitapivat-Induced Improvements in RBC Deformability and Membrane Integrity in Patients with Sickle Cell Disease Are Sustained during Extended Therapy

Phytochemical Profiling and Pharmacological Evaluation of Methanolic Leaf Extract of C. digyna for Cytotoxic, Anti‐inflammatory, Antioxidant, Antiarthritic, and Analgesic Activities

ABSTRACTCaesalpinia digyna (Family: Fabaceae) is traditionally used in Ayurvedic medicine for various medicinal purposes, including as a treatment for wounds, leprosy, skin diseases, fever, diabetes, etc. Although the root and stem of this plant have a significant medicinal value, there was little research on the leaves of this plant. This study aimed to investigate the qualitative phytochemical profile and evaluate the in vitro cytotoxic, anti‐inflammatory, antioxidant, and antiarthritic activities, as well as the in vivo anti‐inflammatory and analgesic activities, of C. digyna leaf extract. The methanolic extract of C. digyna leaves was prepared using an ultrasonic‐assisted extraction process. In vitro and in vivo anti‐inflammatory activities were evaluated using the hypotonicity‐induced hemolysis and carrageenan‐induced paw edema methods, respectively. Additionally, the extract was assessed for in vitro DPPH (1, 1‐diphenyl‐2‐picrylhydrazyl) free radical scavenging, antiarthritic (protein denaturation), and in vivo analgesic (acetic acid‐induced writhing and tail immersion) activities. Brine shrimp lethality bioassay (BSLB) showed moderate cytotoxic activity (LC50 = 2.25 μg/mL) compared with the standard vincristine sulfate (LC50 = 1.61 μg/mL). In vitro, anti‐inflammatory activity exhibited 85.13% (IC50 value = 2.51 μg/mL) inhibition of Human Red Blood Cell (HRBC) membrane lysis at a concentration of 2000 μg/mL whereas in vivo anti‐inflammatory study exerted its maximum effect (p &lt; 0.05) at 400 mg/kg bw dose. This extract also showed significant antioxidant (IC50 = 0.218 μg/mL), antiarthritic (83.61% inhibition) activity, and moderate analgesic effect (p &lt; 0.05) in both methods. These research findings indicated that C. digyna leaves extract has potent antioxidant, analgesic, and anti‐inflammatory effects which can be used as a supplementary medication for inflammatory pain‐relieving factors. In future, finding the mechanism involved in these effects could have significant impact on clinical science.

Autoimmune haemolytic anaemias.

Adult autoimmune haemolytic anaemias (AIHAs) include different subtypes of a rare autoimmune disease in which autoantibodies targeting autoantigens expressed on the membrane of autologous red blood cells (RBCs) are produced, leading to their accelerated destruction. In the presence of haemolytic anaemia, the direct antiglobulin test is the cornerstone of AIHA diagnosis. AIHAs are classified according to the isotype and the thermal optimum of the autoantibody into warm (wAIHAs), cold and mixed AIHAs. wAIHAs, the most frequent type of AIHAs, are associated with underlying conditions in ~50% of cases. In wAIHA, IgG autoantibody reacts with autologous RBCs at 37 °C, leading to antibody-dependent cell-mediated cytotoxicity and increased phagocytosis of RBCs in the spleen. Cold AIHAs include cold agglutinin disease (CAD) and cold agglutinin syndrome (CAS) when there is an underlying condition. CAD and cold agglutinin syndrome are IgM cold antibody-driven AIHAs characterized by classical complement pathway-mediated haemolysis. The management of wAIHAs has long been based around corticosteroids and splenectomy and on symptomatic measures and non-specific cytotoxic agents for CAD. Rituximab and the development of complement inhibitors, such as the anti-C1s antibody sutimlimab, have changed the therapeutic landscape of AIHAs, and new promising targeted therapies are under investigation.

Biomimetic Modification of siRNA/Chemo Drug Nanoassemblies for Targeted Combination Therapy in Breast Cancer.

The development and progression of tumors are characterized by intricate biological processes. Monotherapy not only struggles to achieve effective treatment but also tends to precipitate a series of issues, including multidrug resistance and limited antitumor effect. Consequently, it is imperative to adopt a synergistic multitherapy approach to enhance the efficacy of tumor treatment. The integration of chemotherapy drug with oligonucleotide drug for combinational treatment has shown significant promise in improving tumor therapeutic efficiency. However, the effective in vivo codelivery of oligonucleotide drugs and chemotherapy drugs faces substantial challenges such as poor stability of oligonucleotide drugs during the circulation time, limited tumor accumulation, and uncertain delivery ratios of different payloads. To overcome these obstacles, we have engineered cyclic Arg-Gly-Asp (cRGD)-modified red blood cell membrane (RBCm)-coated multidrug nanocomplexes, which were self-assembled from the Polo-like kinase 1 siRNA (siPlk1) and an irreversible tyrosine kinase inhibitor neratinib targeted to human epidermal growth factor receptor 2 (HER2) overexpressed in breast cancer. Through electrostatic and amphiphilic interactions between the positively charged neratinib and negatively charged siPlk1, we have successfully fabricated uniform multidrug nanoparticles. The cRGD-modified red blood cell membranes coated on the surface of the multidrug nanoparticles could enhance drug stability in circulation and tumor accumulation. This targeted combinational therapy significantly enhanced the antitumor efficiency in HER2-positive breast cancer in vitro and in vivo.

Effect of Moderate Beer Intake on the Lipid Composition of Human Red Blood Cell Membranes.

Background/Objectives: Growing evidence suggests that erythrocyte membrane lipids are subject to changes during their lifespan. Factors such as the type of dietary intake and its composition contribute to the changes in red blood cell (RBC) membranes. Due to the high antioxidant content of beer, we aimed to investigate the effect of moderate beer consumption on the lipid composition of RBCs membranes from healthy overweight individuals. Methods: We conducted a four-weeks, prospective two-arm longitudinal crossed-over study, where participants (n = 36) were randomly assigned to alcohol-free beer group or traditional beer group. The lipids of RBCs membranes were assessed at the beginning and the end of the intervention by thin-layer chromatography. Results: Four-weeks of alcohol-free beer promoted changes in fatty acids (FA), free cholesterol (FC), phosphatidylethanolamine (PE) and phosphatidylcholine (PC) (p < 0.05). Meanwhile, traditional beer intake led to changes in FA, FC, phospholipids (PL), PE and PC (p < 0.05). The observed alterations in membrane lipids were found to be independent of sex and BMI as influencing factors. Conclusions: The lipid composition of erythrocyte membranes is distinctly but mildly influenced by the consumption of both non-alcoholic and conventional beer, with no effects on RBC membrane fluidity.

Biomimetic nanoparticles with red blood cell membranes for enhanced photothermal and immunotherapy for tumors.

The alarming escalation in cancer incidence and mortality has thrust into spotlight the quest for groundbreaking therapeutic strategies. Our research delves into the potential of RDIR780, a novel class of biomimetic nanoparticles cloaked in red blood cell membranes, to significantly enhance their in vivo persistence and therapeutic potency. Through an exhaustive suite of experiments, we have charted the therapeutic horizons of RDIR780 in the realms of tumor photothermal synergistic immunotherapy and targeted drug delivery. Preliminary in vitro cellular assays have revealed that RDIR780 not only achieves remarkable uptake by tumor cells but also triggers swift tumor cell death under the influence of laser irradiation. Subsequent in vivo fluorescence imaging studies have corroborated the nanoparticles' propensity for tumor-specific accumulation, thereby bolstering the case for precision medicine. The results of the precise imaging techniques of therapeutic trials conducted on mice with implanted tumors have underscored the profound impact of RDIR780 when synergized with an anti-PD-L1 antibody. This synergistic approach has shown to fairly eradicate tumor growth, marking a significant stride in the battle against cancer. This pioneering endeavor not only lays down a formidable groundwork for the evolution of long-circulating photothermal therapeutic nanoparticles but also heralds a new era of transformative clinical interventions.

Anti-LAN Antibodies: Clinical Implications and Case Presentation

Abstract Introduction/Objective The LAN system, originating from the 901 Series of High Incidence antigens, transitioned to a recognized System in 2012. The LAN antigen, situated on ABCB6, a multipass membrane protein associated with porphyrin transport, plays a crucial role in heme synthesis. Functionally, LAN acts as an ATP-binding cassette transporter on the red blood cell membrane. Comprising a single antigen, LAN exhibits elevated expression in various tissues including the heart, skeletal muscles, fetal liver, mitochondrial membrane, eye, and Golgi apparatus. Notably, LAN shows no specific association with any particular geographic or ethnic group. Resistant to Ficin/Papain, Trypsin, α-Chymotrypsin, and 0.2M DTT, LAN antibodies primarily consist of IgG and necessitate IAT for detection. While Anti-LAN has been implicated in Hemolytic Transfusion Reactions (HTRs), its involvement in Hemolytic Disease of the Fetus and Newborn (HDFN) remains infrequent. LAN-negative blood is exceedingly rare, often requiring Monocyte Monolayer Assay Testing (MMA) for clinical assessment. Methods/Case Report Case Presentation: An 81-year-old female with a medical history including seizure disorder, hypertension (HTN), hyperlipidemia (HLD), gastroesophageal reflux disease (GERD), small bowel obstruction, and high-grade de-differentiated metastatic retroperitoneal liposarcoma presented for preoperative evaluation. A type and screen ordered as part of outpatient preoperative assessments revealed a positive antibody screen. Further investigation traced the origin of the anti-LAN antibody to an external facility since 2017. Antibody identification indicated the reactivity of the patient’s plasma with all cells (1+ AHG in PEG), excluding the auto control. Utilizing rare frozen antisera anti-LAN, the patient was phenotyped for LAN, yielding a LAN-negative status. Subsequent testing with three rare frozen LAN-negative group O cells aimed to exclude clinically significant antibodies. Differential adsorption, employing a comprehensive baseline RBC phenotype record obtained from the external facility, ruled out anti-E, anti-K, and anti-Fyb, thereby confirming Anti-LAN specificity. Results (if a Case Study enter NA) NA Conclusion The exceptional rarity of LAN-negative blood underscores the high prevalence of reactivity to Anti-LAN antibodies, exceeding 99% in most populations. In select cases, autologous transfusion may emerge as a viable management strategy. Consequently, the patient’s surgical procedure has been deferred, with no immediate requirement for blood products.

Comparison of Essential Oils of Schinus molle L. Leaves Growing in Different Regions of Algeria in Terms of Their Chemical Compositions and Various Biological Activities

ABSTRACTThis preliminary study investigated the chemical composition and biological properties of essential oils derived from Schinus molle L. leaves obtained from three specific regions in Algeria: Algiers (SMA), Djelfa (SMD), and Mascara (SMM). Gas chromatography (GC) and Gas chromatography–Mass Spectrometry (GC–MS) analyses confirmed the presence of 52 compounds (100.0%) in SMA essential oil, 50 compounds (100.0%) in SMD, and 72 compounds (100.0%) in SMM essential oils. The main components of SMA oil were camphene (31.82%), limonene (14.71%), and p‐cymene (9.25%). In SMD and SMM oils, α‐phellandrene (14.25% and 12.70%), limonene (13.02% and 11.90%), and germacrene D (10.62% and 10.15%) were the major components, respectively. The antioxidant characteristics were evaluated using five methods: β‐carotene‐linoleic acid, DPPH, ABTS+, CUPRAC, and Metal chelating assays. The results revealed a moderate to low anti‐oxidant effect, with SMA essential oils exhibiting the highest activity. A moderate inhibitory effect against acetylcholinesterase (AChE), butyrylcholinesterase (BChE), α‐glucosidase, α‐amylase, urease, and tyrosinase was observed, indicating anti‐enzymatic activity. Nevertheless, all samples had higher IC50 values for both antioxidant and anti‐enzymatic activities than 200 μg/mL. It was determined that regional differences in the locations where S. molle grows showed both qualitative and quantitative differences in essential oil components. This difference was also detected in the biological activities of the essential oils. The anti‐inflammatory capacities of the three samples were assessed using Human Red Blood Cell (HRBC) membrane stabilisation and egg albumin denaturation techniques. The results showed effective anti‐inflammatory activity in all three samples. The antimicrobial efficacy was evaluated using a range of tests, such as anti‐quorum sensing, violacein inhibition, anti‐swimming, and anti‐swarming assays, demonstrating moderate activity. No toxic effects were observed at the tested dosages when assessing cytotoxicity against a healthy cell line (CCD18‐Co). This thorough examination provides valuable insights into the chemical composition and bioactive properties of essential oils derived from S. molle. These findings indicate the possible use of these essential oils in the food, medicinal, and cosmetic industries.