Red Cell Membrane Research Articles

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 < 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 < 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.

Radioprotective potential of pomegranate peel extract against gamma irradiation-induced hazards

BackgroundWhile gamma irradiation’s damaging biological effects are well-established, the natural radioprotective agents from agricultural waste remain an underexplored area of significant potential.Aim of studyThis study was to investigate the novel use of pomegranate peel ethanol extract (PE) as a radioprotective agent against gamma radiation damage.MethodsWe pretreated Wistar rats with PE (100 mg/kg) for 14 days prior to 6 Gy gamma irradiation. We analyzed blood biochemicals, oxidative stress, and inflammatory markers. These included tests of red cell membrane integrity, lipid and protein oxidation, antioxidant enzyme levels, and cytokine profiles.ResultsThe study showed that PE demonstrated remarkable radioprotective effects across multiple parameters. Antioxidants were significantly enhanced, as evidenced by increased glutathione peroxidase activity (87.00 ± 6.11 mg/ml in PE-treated irradiated rats compared to 26.40 ± 1.21 mg/ml in irradiated controls). Oxidative damage was markedly reduced, with MDA levels dropping from 9.59 ± 0.24 nmol/ml in irradiated controls to near-control levels in PE-treated rats. Notably, PE treatment resulted in unprecedented maintenance of red blood cell membrane integrity post-irradiation. Furthermore, PE exhibited novel modulation of inflammatory cytokines, effectively reducing pro-inflammatory markers IL-6 and TNF-α while simultaneously boosting anti-inflammatory IL-4 and IL-10 levels. These multifaceted protective effects highlight PE’s potential as a comprehensive radioprotective agent.ConclusionThis study presents PE as an effective new natural radioprotective agent. Its protective effect is due to its high polyphenol content, which enhances antioxidant defenses, reduces oxidative damage, and prevents inflammation. The findings open new avenues for sustainable, cost-effective radioprotection strategies and demonstrate the potential for repurposing agricultural byproducts for critical health applications.

Cell membrane camouflaged Cu-doped mesoporous polydopamine for combined CT/PTT/CDT synergistic treatment of breast cancer

Currently, traditional monotherapy for cancer often results in indiscriminate attacks on the body, leading to the emergence of new health problems. To confront these challenges, multimodal combination therapy has become necessary. However, how to develop new smart nanomaterials through green synthesis methods, delivering drugs while simultaneously synergizing multimodal combination therapies for tumor treatment, remains a topic of great significance. In this study, a biomimetic composite nanomaterial (RM-Cu/P) composed of mesoporous polydopamine (MPDA) as the core and red blood cell membranes (RBCMs) as the shell was synthesized as a drug carrier to deliver doxorubicin (DOX) while achieving synergistic chemotherapy, photothermal and chemodynamic therapy (CT/PTT/CDT). Herein, the nanoparticles were extensively characterized to examine their morphological characteristics, elemental composition, and drug-carrying capacity. Notably, the coating of RBCM reduced the toxicity of the RM-Cu/P@DOX nanoparticles, improved their targeting ability and prolonged their circulation time in vivo. The Cu-doped nanoparticles were capable of initiating a Fenton-like reaction to generate reactive oxygen species (ROS) for CDT, while the photothermal conversion efficiency (η) reached 45.20 % under NIR laser irradiation. Subsequently, the particles were examined by in vivo and in vitro experimental studies in cytotoxicity, cellular uptake, ROS levels, lysosomal escape, and mouse tumor model to evaluate their potential application in antitumor. Compared with monotherapy, the RM-Cu/P@DOX nanoparticles had multiple-stimulation response properties under redox, pH, and NIR, which exhibited the advantage of combined trimodal therapy, resulting in remarkable synergistic antitumor efficacy. In conclusion, this innovative platform exhibited promising applications in smart drug delivery and synergistic treatment of cancer.

Design and Antimalarial Evaluation of Polydopamine-Modified Methyl Artelinate Nanoparticles.

Targeted nanodrug delivery systems are highly anticipated for the treatment of malaria. It is known that Plasmodium can induce new permeability pathways (NPPs) on the membrane of infected red blood cells (iRBCs) for their nutrient uptake. The NPPs also enable the uptake of nanoparticles (NPs) smaller than 80 nm. Additionally, Plasmodium maintains a stable, slightly acidic, and reductive internal environment with higher glutathione (GSH) levels. Based on this knowledge, methyl artelinate (MA, a prodrug-like derivative of dihydroartemisinin) nanoparticles (MA-PCL-NPs) were developed using poly(ethylene glycol)-b-poly(ε-caprolactone) (mPEG-PCL) by a thin-film dispersion method and were further coated with polydopamine (PDA) to obtain MA-PCL@PDA-NPs with a particle size of ∼30 nm. The biomaterial PDA can be degraded in slightly acidic and reductive environments, thereby serving as triggers for drug release. MA could generate reactive oxygen species and decrease GSH levels, consequently causing parasite damage. The in vitro release experiment results indicated that the cumulative release percentage of MA from MA-PCL@PDA-NPs was considerably higher in phosphate buffer with 10 mM GSH at pH 5.5 (88.10%) than in phosphate buffer without GSH at pH 7.4 (16.98%). The green fluorescence within iRBCs of coumarin 6, the probe of NPs (C6-PCL@PDA-NPs), could be reduced significantly after adding the NPP inhibitor furosemide (p < 0.001), which demonstrated that MA-PCL@PDA-NPs could be ingested into iRBCs through NPPs. In vivo antimalarial pharmacodynamics in Plasmodium berghei K173-bearing mice showed that the inhibition ratio of MA-PCL@PDA-NPs (93.96%) was significantly higher than that of commercial artesunate injection (AS-Inj, 63.33%). The above results showed that the developed MA-PCL@PDA-NPs possessed pH-GSH dual-responsive drug release characteristics and targeting efficacy for iRBCs, leading to higher antimalarial efficacy against Plasmodium.

Novel Photo-STING Agonists Delivered by Erythrocyte Efferocytosis-Mimicking Pattern to Repolarize Tumor-Associated Macrophages for Boosting Anticancer Immunotherapy.

Immunotherapy has emerged as a highly effective therapeutic strategy for cancer treatment. Cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS)-stimulator of interferon gene (STING) pathway activation facilitates tumor-associated macrophage (TAM) polarization toward M1 phenotype, and Mn2+ are effective agents for this pathway activation. However, the high in vivo degradation rate and toxicity of Mn2+ hamper clinical application of immunotherapy. Here, this work has newly synthesized and screened manganese porphyrins for Mn2+ transport, referred to as photo-STING agonists (PSAs), and further encapsulate them into core-shell nanoparticles named Rm@PP-GA with dual specificity for tumor tissue and TAMs. Not only do PSAs achieve higher Mn2+ delivery efficiency compared to Mn2+, but they also generate reactive oxygen species under light exposure, promoting mitochondrial DNA release for cGAS-STING pathway activation. In Rm@PP-GA, globin and red blood cell membranes (Rm) are used for erythrocyte efferocytosis-mimicking delivery. Rm can effectively prolong the in vivo circulation period while globin enables PSAs to be taken up by TAMs via CD163 receptors. After Rm rupture mediated by perfluorohexane in nanoparticles under ultrasonication, drugs are specifically released for TAM repolarization. Further, dendritic cells mature, as well as T lymphocyte infiltrate, both of which favor tumor eradication. Therefore, cancer immunotherapy is optimized by novel PSAs delivered by erythrocyte efferocytosis-mimicking delivery pattern.

Ultrastable and Redispersible Zwitterionic Bottlebrush Micelles for Drug Delivery.

Bottlebrush copolymers are increasingly used for drug delivery and biological imaging applications in part due to the enhanced thermodynamic stability of their self-assemblies. Herein, we discuss the effect of hydrophilic block chemistry on the stability of bottlebrush micelles. Amphiphilic bottlebrushes with zwitterionic poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) and nonionic polyethylene glycol (PEG) hydrophilic blocks were synthesized by "grafting from" polymerization and self-assembled into well-defined spherical micelles. Colloidal stability and stability against disassembly were challenged under high concentrations of NaCl, MgSO4, sodium dodecyl sulfate, fetal bovine serum, and elevated temperature. While both types of micelles appeared to be stable in many of these conditions, those with a PMPC shell consistently surpassed their PEG analogs. Moreover, when repeatedly subjected to lyophilization/resuspension cycles, PMPC micelles redispersed with no apparent variation in size or dispersity even in the absence of a cryoprotectant; PEG micelles readily aggregated. The observed excellent stability of PMPC micelles is attributed to the low critical micelle concentration of the bottlebrushes as well as to the strong hydration shell caused by ionic solvation of the phosphorylcholine moieties. Zwitterionic micelles were loaded with doxorubicin, and higher loading capacity/efficiency, as well as delayed release, was observed with increasing side-chain length. Finally, hemocompatibility studies of PMPC micelles demonstrated no disruption to the red blood cell membranes. The growing concern regarding the immunogenicity of PEG-based systems propels the search for alternative hydrophilic polymers; in this respect and for their outstanding stability, zwitterionic bottlebrush micelles represent excellent candidates for drug delivery and bioimaging applications.

The Onerous task of managing paroxysmal nocturnal hemoglobinuria in a Low resource setting: a case report. A hematologist’s experience

Introduction: Paroxysmal nocturnal hemoglobinuria (PNH) is a form of red cell membrane defect characterized by increased sensitivity to complement-mediated cell lysis, resulting in intravascular hemolytic anemia, passage of hemoglobin-containing urine, a high risk of venous thrombosis and progression to pancytopenia.The diagnosis of PNH is based on the flow cytometric (FCM) detection of peripheral blood cell clones. Such clones lack expression of the surface molecules linked to the glycosylphosphatidylinositol (GPI) anchors. The underlying defect is a somatic mutation of the short arm of the phosphatidylinositol glycan class A gene (PIG-A). Case report: We report a case of a 34-year-old male, with recurrent hemolytic anemia and dural venous sinus thrombosis found to have PNH by flow cytometry. He is currently on anticoagulation, iron and folate supplements, intermittent steroids for hemolytic episodes as we await complement inhibitors. Conclusion: As part of the diagnostic workup for patients presenting with recurrent hemolytic anemia and thrombosis in unusual sites, clinicians should include PNH on the list of differential diagnoses. Effort should be taken to characterize the red urine reported on the urine dipstick as blood/hemoglobin by microscopy to differentiate hematuria and hemoglobinuria and order for flow cytometry as this has implications on patient management. Keywords: Thrombosis; hemolysis; complement; paroxysmal nocturia; hemoglobinuria.

A red cell membrane-camouflaged nanoreactor for enhanced starvation/chemodynamic/ion interference therapy for breast cancer

In this study, a multifunctional Cu-doped CaO2 nanoreactor loaded with GOx and camouflaged with a folic acid-modified cell membranewas developed for breast cancer treatment. The as-developed composite nanoreactor showed a synergistic effect on calcium overload to damage mitochondria, thus killing tumor cells to achieve ion interference therapy (IIT). The loaded GOx could deplete glucose to “starve” tumor cells. The H2O2 released by CaO2 decomposition and enzyme catalytic reactions from GOx could not only be highly toxic in the tumor microenvironment but also enhance the efficiency of chemodynamic therapy (CDT) with Cu2+. The red blood cell membranes modified by folic acid achieved a combination of active targeting and passive targeting, thereby enhancing the targeting ability of the as-prepared multifunctional composite nanoreactor and prolonging its retention time at the tumor sites for more than 48 h.

Anti-hypertensive, anti-inflammatory, glycemic and satiety impact of cocoa flavoured soy-based powder drink mix enriched with bioactive hydrolysates from nests of Aerodramus fuciphagus

Abstract Objectives The edible bird’s nest hydrolysates (EBNH) are renowned for their health benefits. The study aimed to determine their contributory functional effect as an ingredient in the cocoa-flavoured soy-based powder drink mix (PDM). The product’s glycemic and satiety impact were also studied. Materials and Methods The product was enriched with a reasonably low amount of spray-dried EBNH. The product’s functional effect with respect to in vitro angiotensin converting enzyme (ACE) inhibitory activity and human red blood cells membrane stabilization (RBCMS) activity were evaluated, using its water extract (90 - 95 oC). The glycemic and satiety impact were evaluated using 12 and 30 subjects, respectively, who consumed 250 mL of the product, containing 25 g of available carbohydrates. Results The enriched PDM’s ACE inhibitory activity and RBCMS activity were significantly higher (p&amp;lt;0.05) than those that were devoid of EBNH. A 240 mL (12.5% w/v) of PDM (containing by weight 3.0% EBNH, 75.44% soybean powder, 20% cocoa powder, 0.5% xanthan gum, 1.0% silicon dioxide and 0.06% sucralose) provides about 3.7 kcal/g energy. Its 250 mL meal (consistency index of 14.17 Pa.sn) is high in protein and dietary fiber. The product’s glycemic index (GI) and glycemic load (GL) are low, 24 and 6.0, respectively, raising a normal level of 2 hours postprandial blood glucose (&amp;lt;6 mmol/L) and satisfies hunger for about 2.5 hours. Conclusion The EBNH, as an ingredient, enhances the PDM’s anti-hypertensive and anti-inflammatory properties. The overall findings suggest that the formulated PDM is a wellness food product capable of promoting good human health, including for dieters and individuals with diabetes.

Revealing the Structural Intricacies of Biomembrane-Interfaced Emulsions with Small- and Ultra-Small-Angle Neutron Scattering.

Utilizing cell membranes from diverse cell types for biointerfacing has demonstrated significant advantages in enhancing colloidal stability and incorporating biological properties, tailored specifically for various biomedical applications. However, the structures of these materials, particularly emulsions interfaced with red blood cell (RBC) or platelet (PLT) membranes, remain an underexplored area. This study systematically employs small- and ultra-small-angle neutron scattering (SANS and USANS) with contrast variation to investigate the structure of emulsions containing perfluorohexane within RBC (RBC/PFH) and PLT membranes (PLT/PFH). The findings reveal that the scattering length density of RBC and PLT membranes is 1.5 × 10-6Å-2, similar to 30% (w/w) deuterium oxide. Using this solvent as a cell membrane-matching medium, estimated droplet diameters are 770nm (RBC/PFH) and 1.5µm (PLT/PFH), based on polydispersed sphere model fitting. Intriguingly, calculated patterns and invariant analysis reveal native droplet architectures featuring entirely liquid PFH cores, differing significantly from the observed bubble-droplet core system in electron microscopy. This highlights the advantage of SANS and USANS in differentiating genuine colloidal structures in complex dispersions. In summary, this work underscores the pivotal role of SANS and USANS in characterizing biointerfaced colloids and in uncovering novel colloidal structures with significant potential for biomedical applications and clinical translation.

Synthesis of 2-Phenoxyacetic Acid Analogs for Evaluation of the Anti-inflammatory Potential and Subsequent &lt;i&gt;In Silico&lt;/i&gt; Analysis

Several 2-phenoxyacetic acid derivatives and their isosteres were synthesized in moderate to high yield (57–96%) for searching newer and safer alternatives to these existing anti-inflammatory agents. The compounds were characterized by 1H-NMR, 13C-NMR and HRMS. The synthesized compounds have been subjected to in vitro anti-inflammatory activity using egg albumin denaturation and human red blood cell membrane stabilization methods. The compounds were also evaluated for their anti-inflammatory activity in the mice model. The synthesized compounds were subsequently subjected to docking analysis. The in vitro pharmacokinetic properties were analyzed by applying the pkCSM software and drug-likeness was checked by using Lipinski’s rule. Some synthesized esters and amides, like SM61, SM81, SM82, SM83, SM91 and SM101, were significantly more powerful as anti-inflammatory agents. The efficacies were correlated with their orientations in the binding pocket of the cyclooxygenase enzyme. The encouraging in vitro and in vivo activities, the optimum pharmacokinetic profile, and good drug-likeness indicated that these scaffolds could be considered for future discovery of newer nonsteroidal anti-inflammatory drugs (NSAIDs).

Enzyme-armed nanocleaner provides superior detoxification against organophosphorus compounds via a dual-action mechanism

By inhibiting acetylcholinesterase (AChE) activity, organophosphate compounds (OPs) can quickly cause severe injury to the nervous system and death, making it extremely difficult to rescue victims after OP exposure. However, it is quite challenging to construct scavengers that neutralize and eliminate these harmful chemical agents promptly in the blood circulation system. Herein, we report an enzyme-armed biomimetic nanoparticle that enables a ‘targeted binding and catalytic degradation’ action mechanism designed for highly efficient in vivo detoxification (denoted as ‘Nanocleaner’). Specifically, the resulting Nanocleaner is fabricated with polymeric cores camouflaged with a modified red blood cell membrane (RBC membrane) that is inserted with the organophosphorus hydrolase (OPH) enzyme. In such a subtle construct, Nanocleaner inherits abundant acetylcholinesterase (AChE) on the surface of the RBC membrane, which can specifically lure and neutralize OPs through biological binding. The OPH enzyme on the membrane surface breaks down toxicants catalytically. The in vitro protective effects of Nanocleaner against methyl paraoxon (MPO)-induced inhibition of AChE activity were validated using both preincubation and competitive regimens. Furthermore, we selected the PC12 neuroendocrine cell line as an experimental model and confirmed the cytoprotective effects of Nanocleaner against MPO. In mice challenged with a lethal dose of MPO, Nanocleaner significantly reduces clinical signs of intoxication, rescues AChE activity and promotes the survival rate of mice challenged with lethal MPO. Overall, these results suggest considerable promise of enzyme-armed Nanocleaner for the highly efficient removal of OPs for clinical treatment.

β-Citronellol: a potential anti-inflammatory and gastro-protective agent-mechanistic insights into its modulatory effects on COX-II, 5-LOX, eNOS, and ICAM-1 pathways through in vitro, in vivo, in silico, and network pharmacology studies.

The current study aimed to evaluate the anti-inflammatory, anti-oxidant, and pronounced gastro-protective activities of β- Citronellol using in vitro, in vivo assays and in silico approaches. In vitro assays, denaturation of bovine serum albumin, egg protein, and human Red Blood Cells (RBCs) membrane stabilization were performed, using Piroxicam as standard. For in vivo assessment, Histamine (0.1ml from 1% w/v) and Formaldehyde (0.1ml from 2% v/v) were used to mediate inflammation. In silico molecular docking and network pharmacology were employed to probe the possible target genes mediating gastroprotective effect of β-Citronellol at 25, 50, and 100mg/kg, using indomethacin-induced (25mg/kg i.p) gastric ulcer in rats. Moreover, Gastric tissues were evaluated for morphological, histopathological, and bio-chemical analysis of PGE2, COX-I, COX-II, 5-LOX, eNOS, ICAM-1, oxygen-free radical scavengers (SOD, CAT), and oxidative stress marker (MDA). β-Citronellol prevented denaturation of proteins and RBCs membrane stabilization with maximum effect observed at 6,400µg/mL. Citronellol decreased rat's paw edema. Network pharmacology and docking studies revealed gastro-protective potential of Citronellol possibly mediated through arachidonic acid pathways by targeting COX-I, COX-II, PGE2, and 5-LOX. Citronellol reduced the ulcer indices, and histopathological changes. Further, β-Citronellol (50 and 100mg/kg) increased gastric PGE2, COX-1, and eNOS; while suppressing COX-2, 5-LOX and ICAM-1. Citronellol markedly enhanced the oxidative balance in isolated rat stomach tissues. The anti-inflammatory, anti-oxidant, and gastro-protective effects of β-Citronellol against indomethacin-induced gastric ulcer model in rats through mediating COX-I, COX-II, PGE2, 5-LOX, eNOS, and ICAM-1 inflammatory markers.

Multi-step synthesis, kinetics and in silico explorations of indole-Phenyl-1,2,4-triazole Bi-heterocyclic hybrids unified with 3-substituted benzamides as elastase inhibitors

In the present research work, a library of unique indole-phenyltriazole hybrids comprising 3-substituted-benzamide moiety was synthesized through convergent multi-step strategy. The structural confirmation of all synthesized molecules was corroborated by IR, 1H NMR, 13C MMR, EI-MS and CHN analysis data. The results of in vitro inhibitory potential of novel benzamides against elastase enzyme revealed that all molecules were potent inhibitors and 10d was most active compound among them having IC50 value of (0.197 ± 0.027 µM), relative to the standard (13.421 ± 0.016 µM). The Kinetics mechanism analyzed by Lineweaver-Burk plots which exposed that 10d inhibited this enzyme competitively by forming an enzyme-inhibitor complex. The inhibition constant Ki determined from Dixon plot for compound 10d was 0.85 µM. Moreover, cytotoxicity of these compounds was also profiled by hemolytic activity and it was observed that almost all these benzamides compounds displayed low cytotoxicity. These molecules also exhibited mild cytotoxicity toward red blood cell membrane. In addition, the in silico computational explorations fully supported the in vitro enzyme inhibitory results. The binding energy ranges from -7.1 to -9.1 kcal/mol, which showed that compound possessed good interaction tendencies to the pancreatic elastase target protein. So, it was anticipated from the experimental results and computational investigations of the current research that these derivatives might lead to further research gateways for obtaining better and safe nontoxic medicinal scaffolds for dealing with the elastase related ailments such as lungs diseases, pruritic skin disease and liver infection.