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It is important to consider the full spectrum of complex interactions between mineral elements and biologically active substances to evaluate the development of cardiovascular disease (CVD) in animals, in addition to the classical physiological approach. This study aimed to assess changes in mineral element levels in wild and exotic animals in relation to their cardiovascular diseases. A total of 171 animals, including 128 healthy and 43 sick animals from three Russian zoos, were sampled and analyzed. For the first time, species from the canine (nine) and feline (seven) families from Moscow, Ivanovo, and Yaroslavl zoos in the Central Federal District of Russia were selected. A total of 108 samples from canines and 63 samples from feline animals were collected. Mineral element measurements were conducted on 1026 samples via a "Kvant-2A" atomic absorption spectrometer from Russia. Correlation and regression analyses were performed. CVDs were found in 10.1% of the studied animals, with a high percentage of heart muscle pathologies noted (25.8% of all CVDs). Iron (Fe) accumulated in canine and feline fur at approximately 208 and 203 mg/kg, with variations of 72.8% and 80.9%, respectively. A significant decrease in Fe and an increase in cadmium (Cd) during CVD were observed (correlations r = 0.25 and r = 0.16, respectively). The dysregulation of Fe homeostasis, increased absorption, and accumulation of Fe in the reticuloendothelial system are discussed. Finally, the mineral elements absorbed by canine and feline fur can be ranked in descending order: Fe > Zn > Cu > Pb > Cd > As. [ABSTRACT FROM AUTHOR]

Optical imaging is a powerful tool for early disease detection and effective treatment planning, but its accuracy is often compromised by the uptake of imaging materials by the mononuclear phagocyte system (MPS). Herein, we leverage multivalent host-guest interactions between cyanine dyes and ß-cyclodextrin polymers to develop supramolecular probes with enhanced stability, optical, and transport profiles for accurate in vivo imaging. These multivalent interactions not only ensure the stability of the probes but also enhance fluorescence efficiency by minimizing nonradiative decay. Our self-assembly approach effectively modulates probe size and surface properties, enabling evasion of MPS clearance and promoting prolonged bloodstream circulation, thereby improving the signal-to-background ratio for imaging. The effectiveness of our design is demonstrated by substantial advancements in the early diagnosis of acute kidney injury and by providing high-contrast imaging and precise surgical navigation across various tumor models. Our strategy not only advances optical imaging materials toward clinical translation but also establishes a versatile platform applicable to multiple imaging modalities. [ABSTRACT FROM AUTHOR]

Lung cancer is one of the major cancer types and poses challenges in its treatment, including lack of specificity and harm to healthy cells. Nanoparticle-based drug delivery systems (NDDSs) show promise in overcoming these challenges. While conventional NDDSs have drawbacks, such as immune response and capture by the reticuloendothelial system (RES), extracellular vesicles (EVs) present a potential solution. EVs, which are naturally released from cells, can evade the RES without surface modification and with minimal toxicity to healthy cells. This makes them a promising candidate for developing a lung-cancer-targeting drug delivery system. EVs isolated from vascular endothelial cells, such as human umbilical endothelial-cell-derived EVs (HUVEC-EVs), have shown anti-angiogenic activity in a lung cancer mouse model; therefore, in this study, HUVEC-EVs were chosen as a carrier for drug delivery. To achieve lung-cancer-specific targeting, HUVEC-EVs were engineered to be decorated with GE11 peptides (GE11-HUVEC-EVs) via a postinsertional technique to target the epidermal growth factor receptor (EGFR) that is overexpressed on the surface of lung cancer cells. The GE11-HUVEC-EVs were loaded with vinorelbine (GE11-HUVEC-EVs-Vin), and then characterized and evaluated in in vitro and in vivo lung cancer models. Further, we examined the binding affinity of ABCB1, encoding P-glycoprotein, which plays a crucial role in chemoresistance via the efflux of the drug. Our results indicate that GE11-HUVEC-EVs-Vin effectively showed tumoricidal effects against cell and mouse models of lung cancer. [ABSTRACT FROM AUTHOR]

Ischemia/reperfusion (I/R) is an important inducer of acute kidney injury (AKI), and triggers the generation of reactive oxygen species (ROS) and the expression of matrix metalloproteinase 2 (MMP2), exacerbating kidney damage. Given the immense potential of vitamin E (VitE) as a natural fat-soluble antioxidant in kidney protection, we designed the nanoparticles (NPs) that could dual respond to ROS and MMP2, aiming to accurately deliver VitE to renal injury cells. The NPs utilized Gel-SH as a sensitive receptor for MMP2 and diselenide as a sensitive receptor for ROS, while PEG2k modification enhanced biocompatibility and prevented phagocytosis mediated by the mononuclear phagocyte system. The amphiphilic Gel-SH and diselenide encapsulate the liposoluble VitE and self-assemble into the NPs with a hydrodynamic size of 69.92 nm. Both in vivo and in vitro experiments based on these NPs show good biocompatibility and the ability of target renal injury cells. In vivo kidney I/R injury models and in vitro cell hypoxia/reoxygenation models, the NPs have demonstrated effects in reducing oxidative stress and alleviating AKI. Notably, VitE can preferentially react with peroxyl radical (LOO•) than polyunsaturated fatty acid (PUFA), inhibiting the formation of carbon centered radical (L•), thereby blocking the chain reaction between PUFA and LOO• in ferroptosis. The NPs also inhibit the transition from AKI to chronic kidney disease, with few side effects. Thus, the NPs with dual-responsiveness to MMP2 and ROS for targeted delivery of VitE to renal injury cells exhibit remarkable effects in inhibiting ROS and the chain reactions of ferroptosis, making it a promising therapeutic agent against AKI caused by I/R. [ABSTRACT FROM AUTHOR]

The development of novel conditional gene targeting tools is allowing us to disentangle the contribution of mononuclear phagocytes to autoimmune neuroinflammation. Microglia and border-associated macrophages are not major contributors to tissue damage but are involved in controlling inflammation and promoting tissue repair (remyelination) during experimental autoimmune encephalomyelitis, a mouse model for multiple sclerosis. Conventional dendritic cells play a dual role: they maintain tolerance to central nervous system (CNS) antigens while also facilitating the reactivation and expansion of pathogenic effector T cells within the CNS. Monocyte-derived macrophages can mediate tissue damage, although emerging evidence suggests that they may also possess tissue-protective and immunoregulatory properties. With emerging single-cell technologies and conditional gene targeting, it is evident that mammalian central nervous system (CNS)-associated phagocytes play crucial yet different and even opposing roles in neuroinflammation. Our developing understanding of their individual impact can help guide the development of more specific, effective, and safe therapies for patients suffering from neuroinflammatory diseases. A healthy mammalian central nervous system (CNS) harbors a diverse population of leukocytes including members of the mononuclear phagocyte system (MPS). Exerting their specific functions, CNS tissue-resident macrophages as well as associated monocytes and dendritic cells (DCs) maintain CNS homeostasis. Under neuroinflammatory conditions, leukocytes from the systemic immune compartment invade the CNS. This review focuses on the newly discovered roles of the MPS in autoimmune neuroinflammation elicited by encephalitogenic T cells. We propose that CNS-associated DCs act as gatekeepers and antigen-presenting cells that guide the adaptive immune response while bone marrow (BM)-derived monocytes contribute to immunopathology and tissue damage. By contrast, CNS-resident macrophages primarily support tissue function and promote the repair and maintenance of CNS functions. [ABSTRACT FROM AUTHOR]

Purpose: We explore the use of intravenously delivered fluorescent perfluorocarbon (PFC) nanoemulsion tracers and multi-spectral cryo-fluorescence tomography (CFT) for whole-body tracer imaging in murine inflammation models. CFT is an emerging technique that provides high-resolution, three-dimensional mapping of probe localization in intact animals and tissue samples, enabling unbiased validation of probe biodistribution and minimizes reliance on laborious histological methods employing discrete tissue panels, where disseminated populations of PFC-labeled cells may be overlooked. This methodology can be used to streamline the development of new generations of non-invasive, cellular-molecular imaging probes for in vivo imaging. Procedures: Mixtures of nanoemulsions with different fluorescent emission wavelengths were administered intravenously to naïve mice and models of acute inflammation, colitis, and solid tumor. Mice were euthanized 24 h post-injection, frozen en bloc, and imaged at high resolution (~ 50 µm voxels) using CFT at multiple wavelengths. Results: PFC nanoemulsions were visualized using CFT within tissues of the reticuloendothelial system and inflammatory lesions, consistent with immune cell (macrophage) labeling, as previously reported in in vivo magnetic resonance and nuclear imaging studies. The CFT signals show pronounced differences among fluorescence wavelengths and tissues, presumably due to autofluorescence, differential fluorescence quenching, and scattering of incident and emitted light. Conclusions: CFT is an effective and complementary methodology to in vivo imaging for validating PFC nanoemulsion biodistribution at high spatial localization, bridging the resolution gap between in vivo imaging and histology. [ABSTRACT FROM AUTHOR]

The increasing interest in bacteriophage technology has prompted its novel applications to treat different medical conditions, most interestingly cancer. Due to their high specificity, manipulability, nontoxicity, and nanosize nature, phages are promising carriers in targeted therapy and cancer immunotherapy. This approach is particularly timely, as current challenges in cancer research include damage to healthy cells, inefficiency in targeting, obstruction by biological barriers, and drug resistance. Some cancers are being kept at the forefront of phage research, such as colorectal cancer and HCC, while others like lymphoma, cervical cancer, and myeloma have not been retouched in a decade. Common mechanisms are immunogenic antigen display on phage coats and the use of phage as transporters to carry drugs, genes, and other molecules. To date, popular phage treatments being tested are gene therapy and phage-based vaccines using M13 and λ phage, with some vaccines having advanced to human clinical trials. The results from most of these studies have been promising, but limitations in phage-based therapies such as reticuloendothelial system clearance or diffusion inefficiency must be addressed. Before phage-based therapies for cancer can be successfully used in oncology practice, more in-depth research and support from local governments are required. [ABSTRACT FROM AUTHOR]

An oral Controlled Human Infection Model (CHIM) with wild-type S. Typhi was re-established allowing us to explore the development of immunity. In this model, ~55% of volunteers who received the challenge reached typhoid diagnosis criteria (TD), while ~45% did not (NoTD). Intestinal macrophages are one of the first lines of defense against enteric pathogens. Most organs have self-renewing macrophages derived from tissue-resident progenitor cells seeded during the embryonic stage; however, the gut lacks these progenitors, and all intestinal macrophages are derived from circulating monocytes. After infecting gut-associated lymphoid tissues underlying microfold (M) cells, S. Typhi causes a primary bacteremia seeding organs of the reticuloendothelial system. Following days of incubation, a second bacteremia and clinical disease ensue. S. Typhi likely interacts with circulating monocytes or their progenitors in the bone marrow. We assessed changes in circulating monocytes after CHIM. The timepoints studied included 0 hours (pre-challenge) and days 1, 2, 4, 7, 9, 14, 21 and 28 after challenge. TD participants provided extra samples at the time of typhoid diagnosis, and 48-96 hours later (referred as ToD). We report changes in Classical Monocytes -CM-, Intermediate Monocytes -IM- and Non-classical Monocytes -NCM-. Changes in monocyte activation markers were identified only in TD participants and during ToD. CM and IM upregulated molecules related to interaction with bacterial antigens (TLR4, TLR5, CD36 and CD206). Of importance, CM and IM showed enhanced binding of S. Typhi. Upregulation of inflammatory molecules like TNF-α were detected, but mechanisms involved in limiting inflammation were also activated (CD163 and CD354 downregulation). CM upregulated molecules to interact/modulate cells of the adaptive immunity, including T cells (HLA-DR, CD274 and CD86) and B cells (CD257). Both CM and IM showed potential to migrate to the gut as integrin α4β7 was upregulated. Unsupervised analysis revealed 7 dynamic cell clusters. Five of these belonged to CM showing that this is the main population activated during ToD. Overall, we provide new insights into the changes that diverse circulating monocyte subsets undergo after typhoid diagnosis, which might be important to control this disease since these cells will ultimately become intestinal macrophages once they reach the gut. [ABSTRACT FROM AUTHOR]

Objective: To determine the relative frequency of orbital lesions based on the site of origin and histopathology at a Tertiary care hospital (Mayo Hospital, Lahore Pakistan) from 1996 till 2022 (27 years). Methods: This descriptive case series included 2651 patients of all age groups presenting with orbital lesions who initially got enrolled at Institute of Ophthalmology Mayo Hospital, Lahore from 1996 till 2022. Of these, 583 patients left against medical advice. So, clinical data of 2068 patients were completely analyzed. Lesions were managed medically and/ or surgically. Final clinical diagnosis, with the help of histopathology, was used to classify the lesions. Results: There were 1258 (60.9%) adults and 810 (39.1%) children, 1358 (65.66%) were neoplastic while 710 (34.33%) non-neoplastic lesions. Amongst the neoplastic lesions, 405 (29.8 %) were benign and 953 (70.2%) malignant. Primary orbital lesions were 1676 (81.04%), Secondary orbital lesions were 300 (14.51%), Endocrine/ hematopoietic reticuloendothelial system lesions were 84 (4.06%) and Metastatic lesions from distant organs were 08 (0.39%). Conclusion: Retinoblastoma, rhabdomyosarcoma, optic nerve gliomata were common in children. Pleomorphic adenoma & adenocystic carcinoma of lacrimal gland, cavernous hemangioma, optic nerve meningioma, neurofibroma, schwannoma, squamous cell carcinoma of eyelid, carcinoma of maxillary antrum and lymphomas were more common in adults. [ABSTRACT FROM AUTHOR]

The mononuclear phagocyte system includes monocytes, macrophages, some dendritic cells, and multinuclear giant cells. These cell populations display marked heterogeneity depending on their differentiation from embryonic and bone marrow hematopoietic progenitors, tissue location, and activation. They contribute to tissue homeostasis by interacting with local and systemic immune and non-immune cells through trophic, clearance, and cytocidal functions. During evolution, they contributed to the innate host defense before effector mechanisms of specific adaptive immunity emerged. Mouse macrophages appear at mid-gestation and are distributed throughout the embryo to facilitate organogenesis and clear cells undergoing programmed cell death. Yolk sac, AGM, and fetal liver-derived tissue-resident macrophages persist throughout postnatal and adult life, supplemented by bone marrow-derived blood monocytes, as required after injury and infection. Nobel awards to Elie Metchnikoff and Paul Ehrlich in 1908 drew attention to cellular phagocytic and humoral immunity, respectively. In 2011, prizes were awarded to Jules Hoffmann and Bruce Beutler for contributions to innate immunity and to Ralph Steinman for the discovery of dendritic cells and their role in antigen presentation to T lymphocytes. We trace milestones in the history of mononuclear phagocyte research from the perspective of Nobel awards bearing directly and indirectly on their role in cellular immunity. [ABSTRACT FROM AUTHOR]

Gaucher's disease (GD) is a lysosomal storage disorder characterized by the storage of glucosylceramide in macrophages ("Gaucher cells"), mainly in the reticuloendothelial system. GD type 1 (GD1) is the most common phenotype that usually manifests with hepatosplenomegaly, cytopenias, and bone involvement. Skeletal manifestations are the most debilitating characteristic and result in significant morbidities. We describe a case of GD1, first presented by a nontraumatic bone fracture. The case presentation highlights the importance of considering GD among the differential diagnosis of nontraumatic fractures, avascular necrosis, and infarcts of the bones. Early diagnosis and treatment improve the course of disease and avoid irreversible sequelae. [ABSTRACT FROM AUTHOR]

The design of polymeric nanoparticles has gained significant attention for drug delivery and controlled release applications. Biocompatible and degradable polyesters have emerged as promising materials for this purpose. However, achieving precise control over the size of nanoparticles (NPs) is crucial to ensure selective delivery and avoid clearance by the reticuloendothelial system. This study investigates the impact of external parameters, including polymer concentration, sonication amplitude, and sonication time, on the preparation of polymeric NPs using starch butyrate (SB) via the single emulsification‐solvent evaporation (SE‐SE) technique with ultrasound assistance. Employing a Box–Behnken method, this study optimizes the conditions for nanoformulation, obtaining response surfaces that reveal the effects of these parameters on particle size. These findings highlight that sonication time is the most influential parameter, followed by sonication amplitude and polymer concentration. By utilizing the statistical model, this study predicts and controls the variables to achieve particle diameters ranging from 152 to 346 nm. The optimal conditions for NPs preparation involve a polymer concentration of 1 mg mL−1, 40% sonication amplitude, and a 30‐min sonication time, resulting in particle sizes of 142 nm. Furthermore, this model demonstrates the capability to develop nanoformulations with excellent size homogeneity, enhancing their attractiveness and efficacy in drug delivery applications. [ABSTRACT FROM AUTHOR]

Liposomes carrying chemotherapeutic drugs can accumulate passively in solid tumors at high levels. However, additional targeting of the liposomes towards e.g. receptors expressed on cancer cells may improve their interaction and therapeutic properties. In this study, we designed a liposomal delivery system, which utilizes the intrinsic characteristics of HER2-positive tumors to ensure efficient delivery of oxaliplatin to the cancer cells. On the liposome surface, trastuzumab, an antibody specific to the HER2 receptor, was shown to facilitate internalization by the cancer cells. A polyethylene glycol (PEG) layer on the liposome surface provides protection from mononuclear phagocyte system uptake. To optimize the interaction between liposomes and cancer cells, a protease-sensitive cleavable peptide linker was inserted at the base of each PEG. The PEG layer is then cleaved off by intra- and extracellular matrix metalloproteinases (MMPs) upon accumulation in the tumor. Our data demonstrate that the removal of PEG significantly destabilizes the liposomes and leads to substantial oxaliplatin release. The proposed beneficial effect of combining antibody-mediated internalization with MMP sensitivity was confirmed in a series of in vivo studies using ovarian cancer xenograft models. The results demonstrated that HER2-targeted MMP-sensitive liposomes have superior anticancer activity compared to non-targeted and non-cleavable liposomes. [Display omitted] • We have designed enzyme-activated liposomes targeted at HER2-positive cancers. • The liposomes are readily internalized by HER2-positive cancer cells. • In the presence of enzymes expressed by tumors, the liposomes release their cargo. • These liposomes have superior in vivo efficacy compared to control liposomes. • Our liposomes are promising as a treatment for HER2-positive cancer. [ABSTRACT FROM AUTHOR]

Interactions of hepatic macrophages with local inflammatory microenvironment is the key factor promoting the development of acute liver failure (ALF). Hence, reprogramming pro-inflammatory M1 into anti-inflammatory M2 phenotype may offer a promising strategy for treating ALF by targeting inflammation. Our group found Carvedilol possessed potential anti-inflammatory property previously, which had been scarcely reported in ALF. We present a synergy strategy to induce macrophages into the phenotype M2-type anti-inflammatory macrophages with interleukin-4 (IL-4) and IL-10 at first. Then Carvedilol is loaded on the macrophage membrane-camouflaged biomimetic nano-platform (termed as M2M@CNP) to evade reticuloendothelial system (RES) and afford Carvedilol delivery to the inflammatory environment with overproduced reactive oxygen species (ROS), further prolonging its circulation and accumulation. Sustainably released Carvedilol produced anti-inflammatory, antioxidant and anti-apoptosis effects, combining local M2-type cell membranes (M2-CM) inhibited pro-inflammatory cytokines and ROS levels, which in turn promoted and amplified M1 to M2 phenotype polarization efficiency. This study offers new insights into the rational design of biomimetic nanosystems for safe and effective ALF therapy to accelerate the clinical translation. [ABSTRACT FROM AUTHOR]

Nanoparticle-based drug delivery systems have emerged as promising platforms for enhancing therapeutic efficacy while minimizing off-target effects. Among various strategies employed to optimize these systems, polyethylene glycol (PEG) modification, known as PEGylation—the covalent attachment of PEG to nanoparticles, has gained considerable attention for its ability to impart stealth properties to nanoparticles while also extending circulation time and improving biocompatibility. PEGylation extends to different drug delivery systems, in specific, nanoparticles for targeting cancer cells, where the concentration of drug in the cancer cells is improved by virtue of PEGylation. The primary challenge linked to PEGylation lies in its confirmation. Numerous research findings provide comprehensive insights into selecting PEG for various PEGylation methods. In this review, we have endeavored to consolidate the outcomes concerning the choice of PEG and diverse PEGylation techniques. [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EVs), characterized by low immunogenicity, high biocompatibility and targeting specificity along with excellent blood-brain barrier permeability, are increasingly recognized as promising drug delivery vehicles for treating a variety of diseases, such as cancer, inflammation and viral infection. However, recent findings demonstrate that the intracellular delivery efficiency of EVs fall short of expectations due to phagocytic clearance mediated by the host mononuclear phagocyte system through Fcg receptors, complement receptors as well as non-opsonic phagocytic receptors. In this text, we investigate a range of bacterial virulence proteins that antagonize host phagocytic machinery, aiming to explore their potential in engineering EVs to counteract phagocytosis. Special emphasis is placed on IdeS secreted by Group A Streptococcus and ImpA secreted by Pseudomonas aeruginosa, as they not only counteract phagocytosis but also bind to highly upregulated surface biomarkers aVb3 on cancer cells or cleave the tumor growth and metastasis-promoting factor CD44, respectively. This suggests that bacterial anti-phagocytic proteins, after decorated onto EVs using preloading or post-loading strategies, can not only improve EV-based drug delivery efficiency by evading host phagocytosis and thus achieve better therapeutic outcomes but also further enable an innovative synergistic EVbased cancer therapy approach by integrating both phagocytosis antagonism and cancer targeting or deactivation. [ABSTRACT FROM AUTHOR]

The crossing of the blood-brain barrier (BBB) for conventional anticancer drugs is still a big challenge in treating glioma. The biomimetic nanoparticle delivery system has attracted increasing attention and has a promising future for crossing the BBB. Herein, we construct a multifunctional biomimetic nanoplatform using the erythrocyte membrane (EM) with the tumor-penetrating peptide iRGD (CRGDK/RGPD/EC) as a delivery, and the inner core loaded with the chemotherapeutic drug temozolomide (TMZ). The resulting biomimetic nanoparticle has perfect biocompatibility and stealth ability, which will provide more chances to escape the reticuloendothelial system (RES) entrapment, and increase the opportunity to enter the tumor site. Moreover, the decorated iRGD has been extensively used to actively targeting and deliver therapeutic agents across the BBB into glioma tissue. We show that this biomimetic delivery of TMZ with a diameter of 22 nm efficiently slowed the growth of glioblastoma multiforme (GBM) and increased the survival rate of the 30 d from 0% to 100%. [ABSTRACT FROM AUTHOR]

Rapid uptake of nanoparticles by mononuclear phagocyte system (MPS) significantly hampers their therapeutic efficacy. Temporal MPS blockade is one of the few ways to overcome this barrier – the approach rediscovered many times under different names but never extensively used in clinic. Using meta-analysis of the published data we prove the efficacy of this technique for enhancing particle circulation in blood and their delivery to tumours, describe a century of its evolution and potential combined mechanism behind it. Finally, we discuss future directions of the research focusing on the features essential for successful clinical translation of the method. Temporal blockade of the mononuclear phagocyte system is an approach to enhance the therapeutic efficiency of nanocarrier drug-delivery systems but the broad applicability is hindered by the complexity of optimisation and management of potential side effects. Here, the authors review the development of this technique and show its efficiency using meta-analysis of the published data and discuss essential features for its successful translation to clinic. [ABSTRACT FROM AUTHOR]

Plasminogen activators, such as recombinant tissue-type plasminogen activators (rtPAs), while effective in treating thromboembolic diseases, often induce hemorrhagic complications due to non-specific enzyme activities in the systemic circulation. This study evaluated the targeting efficiency, efficacy, biodistribution, and potential toxicity of a rtPA covalently attached to chitosan-coated magnetic nanoparticles (chitosan-MNP-rtPA). The thrombolytic activity of a chitosan-MNP-rtPA was preserved by protection from an endogenous plasminogen activator inhibitor-1 (PAI-1) in whole blood and after circulation in vivo, as examined by thromboelastometry. Single-photon emission computed tomography (SPECT) demonstrated real-time retention of a 99mTc-MNP-rtPA induced by magnet application in a rat embolic model; an 80% reduction in rtPA dosage for a chitosan-MNP-rtPA with magnetic guidance was shown to restore blood flow. After treatment, iron deposition was observed in the reticuloendothelial systems, with portal edema and neutrophil infiltration in the liver at a ten-fold higher dose but not the regular dose. Nevertheless, no liver or renal toxicity was observed at this higher dose. In conclusion, the liver may still be the major deposit site of rtPA nanocomposites after targeted delivery; chitosan-coated MNPs are potentially amenable to target therapeutics with parenteral administration. [ABSTRACT FROM AUTHOR]

Histoplasmosis is commonly a self-limited fungal disease that primarily affects the lung and reticuloendothelial system. Cardiac involvement by histoplasmosis is uncommon. In this report, we provide a detailed description of severe pulmonary histoplasmosis complicated by the disease involvement of the free wall of the right ventricle. A 55-year-old female presented with cough, fevers, dyspnea, and 30-pound unintentional weight loss in 6 months. Her past medical history was significant for supraventricular tachycardia with permanent pacemaker implantation. Imaging studies revealed an intracardiac mass accompanied by mediastinal lymphadenopathy and bilateral lung nodules. Endobronchial ultrasound-guided transbronchial needle aspiration of station 4R lymph nodes revealed numerous yeast forms, morphologically consistent with Histoplasma capsulatum. The diagnosis was further corroborated by the elevated titers of serum antibodies against Histoplasma capsulatum. The right ventricular mass debulking with biopsy showed necrotizing granulomatous inflammation involving nonvalvular endocardium and myocardium of the free wall of the right ventricle. The report documents an unusual presentation of pulmonary histoplasmosis accompanied by nonvalvular endocarditis and suggests a possible association between the site of the cardiac infection and the presence of a permanent intravascular pacer device. [ABSTRACT FROM AUTHOR]

Magnetic resonance imaging (MRI) is a routine diagnostic modality in oncology that produces excellent imaging resolution and tumor contrast without the use of ionizing radiation. However, improved contrast agents are still needed to further increase detection sensitivity and avoid toxicity/allergic reactions associated with paramagnetic metal contrast agents, which may be seen in a small percentage of the human population. Fluorine‐19 (19F)‐MRI is at the forefront of the developing MRI methodologies due to near‐zero background signal, high natural abundance of 100%, and unambiguous signal specificity. In this study, we have developed a colloidal nanoemulsion (NE) formulation that can encapsulate high volumes of the fluorous MRI tracer, perfluoro‐[15‐crown‐5]‐ether (PFCE) (35% v/v). These nanoparticles exhibit long‐term (at least 100 days) stability and high PFCE loading capacity in formulation with our semifluorinated triblock copolymer, M2F8H18. With sizes of approximately 200 nm, these NEs enable in vivo delivery and passive targeting to tumors. Our diagnostic formulation, M2F8H18/PFCE NE, yielded in vivo19F‐MR images with a high signal‐to‐noise ratio up to 100 in a tumor‐bearing mouse model at clinically relevant scan times. M2F8H18/PFCE NE circulated stably in the vasculature, accumulated in high concentration of an estimated 4–9 × 1017 19F spins/voxel at the tumor site, and cleared from most organs over the span of 2 weeks. Uptake by the mononuclear phagocyte system to the liver and spleen was also observed, most likely due to particle size. These promising results suggest that M2F8H18/PFCE NE is a favorable 19F‐MR diagnostic tracer for further development in oncological studies and potential clinical translation. [ABSTRACT FROM AUTHOR]

2-Deoxy-2-[18F]fluoro-d-glucose (FDG) uptake of the reticuloendothelial system on positron emission tomography/computed tomography (PET/CT) is known to be related to systemic inflammatory response to cancer cells in patients with diverse malignancies. This retrospective study aimed to investigate whether FDG uptake by the reticuloendothelial system had a prognostic value in predicting progression-free survival (PFS) and overall survival (OS) in 138 cholangiocarcinoma patients. Quantifying FDG uptake of the aorta, bone marrow (BM), liver, and spleen from staging FDG PET/CT images, we found significant correlations between the BM-to-aorta uptake ratio (BAR), spleen-to-aorta uptake ratio, and BM-to-liver uptake ratio with tumor stage and serum inflammatory markers. In the multivariate survival analysis, BAR was an independent predictor of PFS (p = 0.016; hazard ratio, 2.308) and OS (p = 0.030; hazard ratio, 2.645). Patients with stages III–IV of the disease and a high BAR exhibited low 1-year PFS (35.8%) and OS (60.2%) rates, while those with stages I–II of the disease and low BAR showed robust rates of 90.0% and 96.7%, respectively. BAR measured on staging FDG PET/CT might be a potential imaging biomarker offering insights into the systemic inflammatory response and predicting prognosis in cholangiocarcinoma. This study highlights BAR as a promising, independent predictor with potential for personalized prognostication and treatment strategies. [ABSTRACT FROM AUTHOR]

The use of cancer immunotherapeutics is currently increasing. Cancer vaccines, as a form of immunotherapy, are gaining much attention in the medical community since specific tumor-antigens can activate immune cells to induce an anti-tumor immune response. However, the delivery of cancer vaccines presents many issues for research scientists when designing cancer treatments and requires further investigation. Nanoparticles, synthetic liposomes, bacterial vectors, viral particles, and mammalian exosomes have delivered cancer vaccines. In contrast, the use of many of these nanotechnologies produces many issues of cytotoxicity, immunogenicity, and rapid clearance by the mononuclear phagocyte system (MPS). Plant-exosome-like nanovesicles (PELNVs) can provide solutions for many of these challenges because they are innocuous and nonimmunogenic when delivering nanomedicines. Hence, this review will describe the potential use of PELNVs to deliver cancer vaccines. In this review, different approaches of cancer vaccine delivery will be detailed, the mechanism of oral vaccination for delivering cancer vaccines will be described, and the review will discuss the use of PELNVs as improved drug delivery systems for cancer vaccines via oral administration while also addressing the subsequent challenges for advancing their usage into the clinical setting. [ABSTRACT FROM AUTHOR]

Lanthanide neodymium (Nd)‐based nanocrystals exhibit exceptional near‐infrared II (NIR‐II) fluorescence imaging properties, like narrow and multi‐peak emissions, long luminescence lifetime, and good photostability. However, long‐term accumulation in the reticuloendothelial system restrains their clinical applications due to toxicity in vivo. Here, a biodegradable hollow virus‐like neodymium oxide (Nd2O3) Nd‐nanoprobe is presented that is modified with cyclic arginine‐glycine‐aspartic acid (cRGD) pentapeptide, showing remarkable cancer‐targeting ability and NIR‐II fluorescence imaging features. The nanoprobe is biodegraded to 4–6 nm Nd2O3 nanogranules in vivo, and the pharmacokinetics of the nanoprobe demonstrated its rapid urine excretion and negligible systematic toxicity. Moreover, this nanoprobe can accurately identify malignant lesions from normal tissues in xenograft and transgenic mice models and precisely navigate breast cancer surgery under NIR‐II imaging guidance. Taken together, this Nd2O3‐based nanoprobe enables real‐time, dynamic delineation and accurate resection of cancers guided by NIR‐II fluorescence imaging with great potential for future clinical translation during breast‐conservative surgery. [ABSTRACT FROM AUTHOR]

Rabbit hemorrhagic disease (RHD) is an acute fatal disease caused by the rabbit hemorrhagic disease virus (RHDV). Since the first outbreaks of type 2 RHDV (RHDV2) in April 2020 in China, the persistence of this virus in the rabbit population has caused substantial economic losses in rabbit husbandry. Previous failures in preventing RHDV2 prompted us to further investigate the immune mechanisms underlying the virus's pathogenicity, particularly concerning the spleen, a vital component of the mononuclear phagocyte system (MPS). For this, a previous RHDV2 isolate, CHN/SC2020, was utilized to challenge naive adult rabbits. Then, the splenic transcriptome was determined by RNA-Seq. This study showed that the infected adult rabbits had 3148 differentially expressed genes (DEGs), which were associated with disease, signal transduction, cellular processes, and cytokine signaling categories. Of these, 100 upregulated DEGs were involved in inflammatory factors such as IL1α, IL-6, and IL-8. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that these DEGs were significantly enriched in the cytokine–cytokine receptor interaction signaling pathway, which may play a vital role in CHN/SC2020 infection. At the same time, proinflammatory cytokines and chemokines were significantly increased in the spleen at the late stages of infection. These findings suggested that RHDV2 (CHN/SC2020) might induce dysregulation of the cytokine network and compromise splenic immunity against viral infection, which expanded our understanding of RHDV2 pathogenicity. [ABSTRACT FROM AUTHOR]

Exosomes continue to attract interest as a promising nanocarrier drug delivery technology. They are naturally derived nanoscale extracellular vesicles with innate properties well suited to shuttle proteins, lipids, and nucleic acids between cells. Nonetheless, their clinical utility is currently limited by several major challenges, such as their inability to target tumor cells and a high proportion of clearance by the mononuclear phagocyte system (MPS) of the liver and spleen. To overcome these limitations, we developed "Smart Exosomes" that co-display RGD and CD47 p110–130 through CD9 engineering (Exo Smart ). The resultant Exo Smart demonstrates enhanced binding capacity to αvβ3 on pancreatic ductal adenocarcinoma (PDAC) cells, resulting in amplified cellular uptake in in vitro and in vivo models and increased chemotherapeutic efficacies. Simultaneously, Exo Smart significantly reduced liver and spleen clearance of exosomes by inhibiting macrophage phagocytosis via CD47 p110–130 interaction with signal regulatory proteins (SIRPα) on macrophages. These studies demonstrate that an engineered exosome drug delivery system increases PDAC therapeutic efficacy by enhancing active PDAC targeting and prolonging circulation times, and their findings hold tremendous translational potential for cancer therapy while providing a concrete foundation for future work utilizing novel peptide-engineered exosome strategies. Schematic illustration of ExoSmart enhances pancreatic cancer (PDAC) targeting while increase of evasion of mononuclear phagocyte system (MPS) clearance. (A) Diagram of ExoSmart; (B) Schematic diagram of ExoSmart working model; (C) Fluorescence imaging of liver, spleen and tumors of PDAC orthotopic mice that receive DiR stained exosomes via i.v. injection; (D) Immunofluorescence analysis of exosome in liver, spleen and tumors using anti-hemagglutinin (HA) antibody. [Display omitted] • A "Smart Exosome" that co-display RGD and CD47 p110–130 through CD9 engineering (Exo Smart ) was created. • The Exo Smart enhanced binding capacity to αvβ3 on PDAC cells, resulting in amplified cellular uptake in PDAC. • The Exo Smart significantly reduced liver and spleen clearance of exosomes by inhibiting macrophage phagocytosis. • The Exo Smart drug delivery system significantly increased PDAC therapeutic efficacy. [ABSTRACT FROM AUTHOR]

Hemophagocytic lymphohistiocytosis (HLH), also known as hemophagocytic syndrome (HPS), is a benign histiocytosis with hyperreactive proliferation of the mononuclear phagocyte system caused by immune function abnormalities, which often occurs under the background of genetic mutations, inflammation, infection or tumors. Because the research on malignancy-associated HLH (M-HLH) is focused on hematological malignancies, reports on HLH secondary to solid tumors are rare. In this case, we report a 14-year-old girl who developed HLH during treatment for intracranial multifocal germinoma, and the disease was controlled after hormone combined with etoposide(VP-16) and other related treatments. To our knowledge, there have been no documented cases of HLH caused by intracranial multifocal germinoma. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is the second most common neurodegenerative disorder characterized by the accumulation of α-synuclein (α-syn) aggregates called Lewy bodies leading to the gradual loss of dopaminergic (DA) neurons in the substantia nigra. Although α-syn expression can be attenuated by antisense oligonucleotides (ASOs) and heteroduplex oligonucleotide (HDO) by intracerebroventricular (ICV) injection, the challenge to peripheral targeted delivery of oligonucleotide safely and effectively into DA neurons remains unresolved. Here, we designed a new DNA/DNA double-stranded (complementary DNA, coDNA) molecule with cholesterol conjugation (Chol-HDO (coDNA)) based on an α-syn-ASO sequence and evaluated its silence efficiency. Further, Chol-HDO@LMNPs, Chol-HDO-loaded, cerebrovascular endothelial cell membrane with DSPE-PEG 2000 -levodopa modification (L-DOPA-CECm)-coated nanoparticles (NPs), were developed for the targeted treatment of PD by tail intravenous injection. CECm facilitated the blood-brain barrier (BBB) penetration of NPs, together with cholesterol escaped from reticuloendothelial system uptake, as well as L-DOPA was decarboxylated into dopamine which promoted the NPs toward the PD site for DA neuron regeneration. The behavioral tests demonstrated that the nanodecoys improved the efficacy of HDO on PD mice. These findings provide insights into the development of biomimetic nanodecoys loading HDO for precise therapy of PD. The accumulation of α-synuclein (α-syn) aggregates is a hallmark of PD. Our previous study designed a specific antisense oligonucleotide (ASO) targeting human SNCA , but the traumatic intracerebroventricular (ICV) is not conducive to clinical application. Here, we further optimize the ASO by creating a DNA/DNA double-stranded molecule with cholesterol-conjugated, named Chol-HDO (coDNA), and develop a DA-targeted biomimetic nanodecoy Chol-HDO@LMNPs by engineering cerebrovascular endothelial cells membranes (CECm) with DSPE-PEG 2000 and L-DOPA. The in vivo results demonstrated that tail vein injection of Chol-HDO@LMNPs could target DA neurons in the brain and ameliorate motor deficits in a PD mouse model. This investigation provides a promising peripheral delivery platform of L-DOPA-CECm nanodecoy loaded with a new Chol-HDO (coDNA) targeting DA neurons in PD therapy. [Display omitted] [ABSTRACT FROM AUTHOR]

BACKGROUND: Myocardial infarction is one of the most serious cardiovascular diseases at present, and the existing clinical treatment options such as thrombolytic therapy, percutaneous coronary intervention and coronary artery bypass grafting cannot fully restore the myocardial damage caused by ischemia. Stem cell-derived exosomes for the treatment of myocardial infarction have been a hot research topic in recent years, but the low yield of natural-derived exosomes, the difficulty and time consuming nature of obtaining them, and the poor homing effect have limited their clinical application. In this context, the construction of artificial exosomes as an alternative to natural exosomes has become an effective strategy to solve the above problems. OBJECTIVE: To expound the research status of artificial exosomes in the treatment of myocardial infarction, and classify them into two design modes: semiartificial and full-artificial, and discuss the research progress and problems of the two modes, finally, make the evaluation and prospect of its clinical application in the future. METHODS: PubMed and CNKI were searched for relevant articles with “artificial exosomes, myocardial infarction, engineering” in Chinese, and “artificial exosome, hybrid exosome, myocardial infarction, nanoparticle, drug delivery system” in English. The focus of the search was from January 2017 to December 2022, and some of the classic forward literature was included. A preliminary selection was conducted through reading titles and abstracts. Repetitive studies, low-quality journals and irrelevant articles were excluded. Finally, 73 articles were included for review. RESULTS AND CONCLUSION: (1) By semi-artificially modifying exosomes, whether it is the modification of targeting peptides, hybridization of biofilms or the assistance of magnetic substances, traditional exosome therapies with insufficient targeting and low retention rate and easy to be cleared by the reticuloendothelial system have improved the efficiency of traditional exosome therapy for myocardial infarction. However, these strategies have problems such as unclear modification efficiency, medical ethics, and biotoxicity. (2) Fully artificial bionic exosomes have a higher degree of design freedom compared to exosome modification, which can solve the problems of high extraction and storage difficulties of exosomes of natural origin and limitations of large-scale production; however, this artificial exosome strategy still lacks reliable preclinical data support and biosafety testing, and has not yet formed a standardized process required for large-scale production; therefore, before applying to the clinic, the artificial exosome solution as an alternative to natural exosomes still needs continuous in-depth research by researchers. [ABSTRACT FROM AUTHOR]

Respiratory viral infections are one of the major causes of illness and death worldwide. Symptoms associated with respiratory infections can range from mild to severe, and there is limited understanding of why there is large variation in severity. Environmental exposures are a potential causative factor. The aryl hydrocarbon receptor (AHR) is an environment-sensing molecule expressed in all immune cells. Although there is considerable evidence that AHR signaling influences immune responses to other immune challenges, including respiratory pathogens, less is known about the impact of AHR signaling on immune responses during coronavirus (CoV) infection. In this study, we report that AHR activation significantly altered immune cells in the lungs and bone marrow of mice infected with a mouse CoV. AHR activation transiently reduced the frequency of multiple cells in the mononuclear phagocyte system, including monocytes, interstitial macrophages, and dendritic cells in the lung. In the bone marrow, AHR activation altered myelopoiesis, as evidenced by a reduction in granulocyte monocyte progenitor cells and an increased frequency of myeloid-biased progenitor cells. Moreover, AHR activation significantly affected multiple stages of the megakaryocyte lineage. Overall, these findings indicate that AHR activation modulates multiple aspects of the immune response to a CoV infection. Given the significant burden of respiratory viruses on human health, understanding how environmental exposures shape immune responses to infection advances our knowledge of factors that contribute to variability in disease severity and provides insight into novel approaches to prevent or treat disease. NEW & NOTEWORTHY Our study reveals a multifaceted role for aryl hydrocarbon receptor (AHR) signaling in the immune response to coronavirus (CoV) infection. Sustained AHR activation during in vivo mouse CoV infection altered the frequency of mature immune cells in the lung and modulated emergency hematopoiesis, specifically myelopoiesis and megakaryopoiesis, in bone marrow. This provides new insight into immunoregulation by the AHR and extends our understanding of how environmental exposures can impact host responses to respiratory viral infections. [ABSTRACT FROM AUTHOR]

Most nanomedicines require efficient in vivo delivery to elicit meaningful diagnostic and therapeutic effects. However, en route to their intended tissues, systemically administered nanoparticles often encounter delivery barriers. To describe these barriers, the term "nanoparticle blood removal pathways" (NBRP) is proposed, which summarizes the interactions between nanoparticles and the body's various cell‐dependent and cell‐independent blood clearance mechanisms. Nanoparticle design and biological modulation strategies are reviewed to mitigate nanoparticle‐NBRP interactions. As these interactions affect nanoparticle delivery, the preclinical literature from 2011–2021 is studied, and the nanoparticle blood circulation and organ biodistribution data are analyzed. The findings reveal that nanoparticle surface chemistry affects the in vivo behavior more than other nanoparticle design parameters. Combinatory biological‐PEG surface modification improves the blood area under the curve by ≈418%, with a decrease in liver accumulation of up to 47%. A greater understanding of nanoparticle‐NBRP interactions and associated delivery trends will provide new nanoparticle design and biological modulation strategies for safer, more effective, and more efficient nanomedicines. [ABSTRACT FROM AUTHOR]

Macrophages regulate metabolic homeostasis in health and disease. Macrophage colony-stimulating factor (CSF1)-dependent macrophages contribute to homeostatic control of the size of the liver. This study aimed to determine the systemic metabolic consequences of elevating circulating CSF1. Acute administration of a CSF1-Fc fusion protein to mice led to monocytosis, increased resident tissue macrophages in the liver and all major organs, and liver growth. These effects were associated with increased hepatic glucose uptake and extensive mobilization of body fat. The impacts of CSF1 on macrophage abundance, liver size, and body composition were rapidly reversed to restore homeostasis. The effects of CSF1 on metabolism were independent of several known endocrine regulators and did not impact the physiological fasting response. Analysis using implantable telemetry in metabolic cages revealed progressively reduced body temperature and physical activity with no change in diurnal food intake. These results demonstrate the existence of a dynamic equilibrium between CSF1, the mononuclear phagocyte system, and control of liver-to-body weight ratio, which in turn controls systemic metabolic homeostasis. This novel macrophage regulatory axis has the potential to promote fat mobilization, without changes in appetence, which may have novel implications for managing metabolic syndrome. NEW & NOTEWORTHY CSF1 administration expands tissue macrophages, which transforms systemic metabolism. CSF1 drives fat mobilization and glucose uptake to support liver growth. The effects of CSF1 are independent of normal hormonal metabolic regulation. The effects of CSF1 are rapidly reversible, restoring homeostatic body composition. CSF1-dependent macrophages and liver size are coupled in a dynamic equilibrium. [ABSTRACT FROM AUTHOR]

Background: Recent research reported that mononuclear phagocyte system (MPS) can contribute to immune defense but the classification of head and neck squamous cell carcinoma (HNSCC) patients based on MPS-related multi-omics features using machine learning lacked. Methods: In this study, we obtain marker genes for MPS through differential analysis at the single-cell level and utilize "similarity network fusion" and "MoCluster" algorithms to cluster patients' multi-omics features. Subsequently, based on the corresponding clinical information, we investigate the prognosis, drugs, immunotherapy, and biological differences between the subtypes. A total of 848 patients have been included in this study, and the results obtained from the training set can be verified by two independent validation sets using "the nearest template prediction". Results: We identified two subtypes of HNSCC based on MPS-related multi-omics features, with CS2 exhibiting better predictive prognosis and drug response. CS2 represented better xenobiotic metabolism and higher levels of T and B cell infiltration, while the biological functions of CS1 were mainly enriched in coagulation function, extracellular matrix, and the JAK-STAT signaling pathway. Furthermore, we established a novel and stable classifier called "getMPsub" to classify HNSCC patients, demonstrating good consistency in the same training set. External validation sets classified by "getMPsub" also illustrated similar differences between the two subtypes. Conclusions: Our study identified two HNSCC subtypes by machine learning and explored their biological difference. Notably, we constructed a robust classifier that presented an excellent classifying prediction, providing new insight into the precision medicine of HNSCC. [ABSTRACT FROM AUTHOR]

Various nanomaterials have been studied for their biomedical application in recent years. Among them, nanocomposites have a prominent medical application in the prevention, diagnosis, and treatment of various diseases. Nanocomposites are made up of polymeric matrix layers composed of synthetic or natural polymers like chitosan, polyethylene glycol, etc. Polymer nanocomposites are inorganic nanoparticles dispersed in a polymer matrix. There are two types of polymeric nanocomposites which include natural and synthetic polymer nanocomposites. These nanocomposites have various biomedical applications, such as medical implants, wound healing, wound dressing, bone repair and replacement, and dental filling. Polymeric nanocomposites have a wide range of biomedical applications due to their high stability, non-immunogenic nature, sustained drug delivery, non-toxic, and can escape reticuloendothelial system uptake along with drug bioavailability improvement. In this review, we have discussed various types of natural and synthetic polymer nanocomposites and their biomedical applications. [ABSTRACT FROM AUTHOR]

The immune system's role in tumor growth and spread has led to the importance of activating immune function in tumor therapy. We present a strategy using an M1-type macrophage membrane-camouflaged ferrous-supply-regeneration nanoplatform (M1mDDTF) to synergistically reinforce immunogenic cell death (ICD) and transform tumor-associated macrophages (TAMs) against tumors. The M1mDDTF nanoparticles consist of doxorubicin-loaded dendritic mesoporous silica nanoparticles chelated with FeIII-tannic acid (FeIIITA) and coated with M1-type macrophage membranes. In the acidic tumor microenvironment, FeIIITA releases Fe2+ and generates ·OH, aided by near infrared irradiation for enhanced doxorubicin release. Furthermore, the M1mDDTF nanoplatform not only directly kills tumor cells but stimulates ICD, which can increase the proportion of CD86+ CD80+ cells and promote dendritic cell maturation. Particularly, the M1mDDTF nanoplatform can also promote the gradual polarization of TAMs into the M1-type and promote tumor cell killing. This study demonstrates the safety and multifunctionality of M1mDDTF nanoparticles, highlighting their potential for clinical tumor treatment. Malignant tumors are a global concern and a major cause of death. Nanoparticles' passive targeting is ineffective and hindered by reticuloendothelial system clearance. Therefore, enhancing nanoparticle accumulation in tumors while minimizing toxicity is a challenge. Coating nanoparticles with cell membranes enhances biocompatibility, immune evasion, and specific targeting. This approach has led to the development of numerous cell membrane-mimicking nanomaterials with remarkable properties and functions. This study developed an M1-type macrophage membrane-camouflaged ferrous-supply-regeneration nanoplatform, boosting immunogenic cell death and transforming tumor-associated macrophages. Tannic acid in the tumor microenvironment reduced Fe3+ to Fe2+, generating ·OH. M1mDDTF nanosystem induced M1-type macrophage polarization, inhibiting tumor growth and triggering immune cell death. Safe and versatile, these M1mDDTF nanoparticles hold promise for clinical tumor treatment. [Display omitted] [ABSTRACT FROM AUTHOR]

Background Leprosy, sometimes referred to as Hansen's disease, is a chronic granulomatous infection caused by bacteria that predominantly impacts the peripheral nerves but may additionally harm the eyes, muscles, bones, skin, the mucous membrane of the mouth, upper respiratory tract, reticuloendothelial system, eyeballs, and the testicles. The factors that predispose to illness development must be recognized. Poverty, undernutrition, food scarcity, insufficient food supply, and a lack of food diversity are the most obvious risk factors. Objective To determine the relationship between body mass index (BMI) and leprosy type. Methods This is an analytical cross-sectional study design involving 30 subjects with leprosy. Clinical examination and history-taking were carried out and the BMI was taken into account. Results It was discovered that this study's leprosy subjects were more likely to be male, with 20 male subjects (66.6%) and 10 female subjects (33.3%). 11 patients (36.6%) of the study group's participants were beyond the age of 47. The correlation between the BMI value and the type of leprosy has a positive direction of 0.123 with very low relationship criteria and there's no relationship between body mass index and leprosy type (p=0.069). Conclusion No association between body mass index and leprosy type. [ABSTRACT FROM AUTHOR]

Micelles have been extensively used in biomedicine as potential carriers of hydrophobic fluorescent dyes. Their small diameters can potentially enable them to evade recognition by the reticuloendothelial system, resulting in prolonged circulation. Nevertheless, their lack of stability in physiological environments limits the imaging utility of micelles. In particular, when a dye sensitive to water, such as IR‐1061, is encapsulated in the micelle core, the destabilized structure leads to interactions between water and dye, degrading the fluorescence. In this study, we investigated a method to improve micelle stability utilizing the electrical effect of gadolinium (Gd3+) and tetraazacyclododecane tetraacetic acid (DOTA), introduced into the micelles. Three micellar structures, one containing a poly(lactic‐co‐glycolic acid)‐block‐poly(ethylene glycol) (PLGA‐b‐PEG) block copolymer, and two other structures, including PLGA‐b‐PEG with DOTA or Gd‐DOTA introduced at the boundary of PLGA and PEG, were prepared with IR‐1061 in the core. Structures that contained DOTA at the border of the PLGA core and PEG shell exhibited much higher fluorescence intensity than probes without DOTA. With Gd3+ ions at the DOTA center, fluorescence stability was enhanced remarkably in physiological environments. Most interesting is the finding that fluorescence is enhanced with increased Gd‐DOTA concentrations. In conclusion, we found that overall fluorescence and stability are improved by introducing Gd‐DOTA at the boundary of the PLGA core and PEG shell. Improving micelle stability is crucial for further biomedical applications of micellar probes such as bimodal fluorescence and magnetic resonance imaging. [ABSTRACT FROM AUTHOR]

Microglia, the resident macrophages of the central nervous system (CNS), play a critical role in CNS homeostasis and neuroinflammation. Pexidartinib (PLX3397), a colony-stimulating factor 1 (CSF1) receptor inhibitor, is widely used to deplete microglia, offering flexible options for both long-term depletion and highly versatile depletion-repopulation cycles. However, the potential impact of PLX3397 on peripheral (immune) cells remains controversial. Until now, the microglia-specificity of this type of compounds has not been thoroughly evaluated, particularly in the context of peripherally derived neuroinflammation. Our study addresses this gap by examining the effects of PLX3397 on immune cells in the brain, liver, circulation and bone marrow, both in homeostasis and systemic inflammation models. Intriguingly, we demonstrate that PLX3397 treatment not only influences the levels of tissue-resident macrophages, but also affects circulating and bone marrow immune cells beyond the mononuclear phagocyte system (MPS). These alterations in peripheral immune cells disrupt the response to systemic inflammation, consequently impacting the phenotype irrespective of microglial depletion. Furthermore, we observed that a lower dose of PLX3397, which does not deplete microglia, demonstrates similar (non-)MPS effects, both in the periphery and the brain, but fails to fully replicate the peripheral alterations seen in the higher doses, questioning lower doses as a ‘peripheral control’ strategy. Overall, our data highlight the need for caution when interpreting studies employing this compound, as it may not be suitable for specific investigation of microglial function in the presence of systemic inflammation. [ABSTRACT FROM AUTHOR]

Opsonization plays a pivotal role in hindering controlled drug release from nanoformulations due to macrophage‐mediated nanoparticle destruction. While first and second‐generation delivery systems, such as lipoplexes (50–150 nm) and quantum dots, hold immense potential in revolutionizing disease treatment through spatiotemporal controlled drug delivery, their therapeutic efficacy is restricted by the selective labeling of nanoparticles for uptake by reticuloendothelial system and mononuclear phagocyte system via various molecular forces, such as electrostatic, hydrophobic, and van der Waals bonds. This review article presents novel insights into surface‐modification techniques utilizing macromolecule‐mediated approaches, including PEGylation, di‐block copolymerization, and multi‐block polymerization. These techniques induce stealth properties by generating steric forces to repel micromolecular‐opsonins, such as fibrinogen, thereby mitigating opsonization effects. Moreover, advanced biological methods, like cellular hitchhiking and dysopsonic protein adsorption, are highlighted for their potential to induce biological camouflage by adsorbing onto the nanoparticulate surface, leading to immune escape. These significant findings pave the way for the development of long‐circulating next‐generation nanoplatforms capable of delivering superior therapy to patients. Future integration of artificial intelligence‐based algorithms, integrated with nanoparticle properties such as shape, size, and surface chemistry, can aid in elucidating nanoparticulate‐surface morphology and predicting interactions with the immune system, providing valuable insights into the probable path of opsonization. Significance statement: This review article meticulously compiles an extensive body of knowledge, encompassing state‐of‐the‐art surface modification techniques and innovative biological camouflage strategies. These insights collectively propel the progression of next‐generation drug delivery platforms. By elucidating the underlying mechanisms, detailing achievements, and recognizing inherent limitations of these methodologies, the article provides essential guidance to researchers, clinicians, and pharmaceutical developers, facilitating well‐informed decision‐making. Moreover, the incorporation of empirical data pertaining to clinical trials, patent landscape, and commercially available formulations augments the pragmatic utility of this review. It emerges as an indispensable resource for those endeavoring to bridge the chasm between scientific innovation and tangible therapeutic outcomes. In conclusion, this review signifies a transformative contribution poised to reshape the landscape of drug delivery, holding promising prospects for substantial enhancements in patient outcomes in the immediate future. [ABSTRACT FROM AUTHOR]

Acute liver injury (ALI) has the potential to compromise hepatic function rapidly, with severe cases posing a considerable threat to human health and wellbeing. Conventional treatments, such as the oral administration of antioxidants, can inadvertently lead to liver toxicity and other unwanted side effects. Mesenchymal stromal cells (MSCs) can target therapeutic agents directly to inflammatory sites owing to their homing effect, and they offer a promising avenue for the treatment of ALI. However, the efficacy and feasibility of these live cell products are hampered by challenges associated with delivery pathways and safety concerns. Therefore, in this work, MSC membranes were ingeniously harnessed as protective shells to encapsulate synthesized PLGA nanoparticle cores (PLGA/MSCs). This strategic approach enabled nanoparticles to simulate endogenous substances and yielded a core–shell nano-biomimetic structure. The biomimetic nanocarrier remarkably maintained the homing ability of MSCs to inflammatory sites. In this study, cryptotanshinone (CPT)-loaded PLGA/MSCs (CPT@PLGA/MSC) were prepared. These nanoparticles can be effectively internalized by LO2 cells. They reduced cellular oxidative stress and elevated inflammatory levels. In vivo results suggested that, after intravenous administration, CPT@PLGA/MSCs significantly reduced uptake by the reticuloendothelial system and immune recognition compared to PLGA nanoparticles without MSC membrane coatings, subsequently resulting in their targeted and enhanced accumulation in the liver. The effectiveness of CPT@PLGA/MSCs in alleviating carbon tetrachloride-induced oxidative stress and inflammation in a mouse model was unequivocally demonstrated through comprehensive histological examination and liver function tests. This study introduces a pioneering strategy with substantial potential for ALI treatment. [ABSTRACT FROM AUTHOR]

Liposomes are versatile carriers that can encapsulate various drugs; however, for delivery to the brain, they must be modified with a targeting ligand or other modifications to provide blood–brain barrier (BBB) permeability, while avoiding rapid clearance by reticuloendothelial systems through polyethylene glycol (PEG) modification. BBB-penetrating peptides act as brain-targeting ligands. In this study, to achieve efficient brain delivery of liposomes, we screened the functionality of eight BBB-penetrating peptides reported previously, based on high-throughput quantitative evaluation methods with in vitro BBB permeability evaluation system using Transwell, in situ brain perfusion system, and others. For apolipoprotein E mimetic tandem dimer peptide (ApoEdp), which showed the best brain-targeting and BBB permeability in the comparative evaluation of eight peptides, its lipid conjugate with serine–glycine (SG)5 spacer (ApoEdp-SG-lipid) was newly synthesized and ApoEdp-modified PEGylated liposomes were prepared. ApoEdp-modified PEGylated liposomes were effectively associated with human brain capillary endothelial cells via the ApoEdp sequence and permeated the membrane in an in vitro BBB model. Moreover, ApoEdp-modified PEGylated liposomes accumulated in the brain 3.9-fold higher than PEGylated liposomes in mice. In addition, the ability of ApoEdp-modified PEGylated liposomes to localize beyond the BBB into the brain parenchyma in mice was demonstrated via three-dimensional imaging with tissue clearing. These results suggest that ApoEdp-SG-lipid modification is an effective approach for endowing PEGylated liposomes with the brain-targeting ability and BBB permeability. [ABSTRACT FROM AUTHOR]

This article presents a case study of a female infant who experienced various complications after being delivered prematurely due to the mother's acute malaria. The infant developed cutaneous lesions, which were later diagnosed as congenital self-healing reticulohistiocytosis (CSHR). CSHR is a rare variant of Langerhans cell histiocytosis (LCH) characterized by the absence of systemic symptoms and spontaneous involution. The article discusses the histopathology, clinical presentation, and differential diagnoses of CSHR, as well as the long-term follow-up recommended for patients with this condition. [Extracted from the article]

Iron oxide nanoparticles (IONP) are showing promise in many biomedical applications. One of these- magnetic hyperthermia- utilizes externally applied alternating magnetic fields and tumor-residing magnetic nanoparticles to generate localized therapeutic temperature elevations. Magnetic hyperthermia is approved in Europe to treat glioblastoma and is undergoing clinical assessment in the United States to treat prostate cancer. In this study, we performed biodistribution and histological analysis of a new IONP (RCL-01) in Wistar rats. These nanoparticles are currently undergoing clinical assessment in locally advanced pancreatic ductal adenocarcinoma to determine the feasibility of magnetic hyperthermia treatment in this disease. The study presented here aimed to determine the fate of these nanoparticles in vivo and whether this results in organ damage. Wistar rats were injected intravenously with relatively high doses of IONP (30 mgFe/kg, 45 mgFe/kg and 60 mgFe/kg) and compared to a vehicle control to determine the accumulation of iron in organs and whether this resulted in histological changes in these tissues. Dose-dependent increases of iron were observed in the liver, spleen and lungs of IONP-treated animals at 7 days postinjection; however, this did not result in significant histological changes in these tissues. Immunofluorescent imaging determined these nanoparticles are internalized by macrophages in tissue, suggesting they are readily phagocytosed by the reticuloendothelial system for eventual recycling. Notably, no changes in iron or dextran staining were found in the kidneys across all treatment groups, providing evidence for potential renal clearance. [ABSTRACT FROM AUTHOR]

Timely diagnosis and appropriate antitumoral treatments remain of utmost importance, since cancer remains a leading cause of death worldwide. Within this context, nanotechnology offers specific benefits in terms of cancer therapy by reducing its adverse effects and guiding drugs to selectively target cancer cells. In this comprehensive review, we have summarized the most relevant novel outcomes in the range of 2010–2023, covering the design and application of nanosystems for cancer therapy. We have established the general requirements for nanoparticles to be used in drug delivery and strategies for their uptake in tumor microenvironment and vasculature, including the reticuloendothelial system uptake and surface functionalization with protein corona. After a brief review of the classes of nanovectors, we have covered different classes of nanoparticles used in cancer therapies. First, the advances in the encapsulation of drugs (such as paclitaxel and fisetin) into nanoliposomes and nanoemulsions are described, as well as their relevance in current clinical trials. Then, polymeric nanoparticles are presented, namely the ones comprising poly lactic-co-glycolic acid, polyethylene glycol (and PEG dilemma) and dendrimers. The relevance of quantum dots in bioimaging is also covered, namely the systems with zinc sulfide and indium phosphide. Afterwards, we have reviewed gold nanoparticles (spheres and anisotropic) and their application in plasmon-induced photothermal therapy. The clinical relevance of iron oxide nanoparticles, such as magnetite and maghemite, has been analyzed in different fields, namely for magnetic resonance imaging, immunotherapy, hyperthermia, and drug delivery. Lastly, we have covered the recent advances in the systems using carbon nanomaterials, namely graphene oxide, carbon nanotubes, fullerenes, and carbon dots. Finally, we have compared the strategies of passive and active targeting of nanoparticles and their relevance in cancer theranostics. This review aims to be a (nano)mark on the ongoing journey towards realizing the remarkable potential of different nanoparticles in the realm of cancer therapeutics. [ABSTRACT FROM AUTHOR]

19F magnetic resonance imaging (MRI) is a powerful molecular imaging technique that enables high‐resolution imaging of deep tissues without background signal interference. However, the use of nanoparticles (NPs) as 19F MRI probes has been limited by the immediate trapping and accumulation of stiff NPs, typically of around 100 nm in size, in the mononuclear phagocyte system, particularly in the liver. To address this issue, elastic nanomaterials have emerged as promising candidates for improving delivery efficacy in vivo. Nevertheless, the impact of elasticity on NP elimination has remained unclear due to the lack of suitable probes for real‐time and long‐term monitoring. In this study, we present the development of perfluorocarbon‐encapsulated polymer NPs as a novel 19F MRI contrast agent, with the aim of suppressing long‐term accumulation. The polymer NPs have high elasticity and exhibit robust sensitivity in 19F MRI imaging. Importantly, our 19F MRI data demonstrate a gradual decline in the signal intensity of the polymer NPs after administration, which contrasts starkly with the behavior observed for stiff silica NPs. This innovative polymer‐coated NP system represents a groundbreaking nanomaterial that successfully overcomes the challenges associated with long‐term accumulation, while enabling tracking of biodistribution over extended periods. [ABSTRACT FROM AUTHOR]

Targeted drug delivery systems are highly desirable for their ability to release drugs specifically at targeted sites. Among these systems, active targeting is considered the most promising. However, the nanomaterials commonly used for constructing the targeting moiety of multifunctional drug delivery vehicles have several disadvantages that limit their applications, such as low biocompatibility, susceptibility to elimination by the mononuclear phagocyte system, and difficulty in modification. Sialic acid, a natural ligand, is often present as the terminal sugar of glycans on glycoproteins or glycolipids on the cell surface. As an endogenous substance, it is highly biocompatible, has a clear molecular structure, and is easy to chemically modify. Sialic acid-functionalized nanoparticles can carry drugs that target cells expressing receptors (sialic acid-binding immunoglobulin-like lectin or selectin receptors) for the treatment of diseases. In the present review, we presented current literature on sialic acid-decorated nanoparticle-based targeted drug delivery systems that bind to “sialic acid-binding immunoglobulin-like lectin or selectin receptors” for therapeutic effects in tumors or inflammation. We also discussed chemical modification strategies for natural sialic acid ligands to improve binding affinity and selectivity to receptors. [ABSTRACT FROM AUTHOR]

Background: Soft tissue can be defined as non-epithelial extraskeletal tissue of the body exclusive of the reticuloendothelial system, glia, and supporting tissues of different parenchymal organs. These tumors are a highly heterogeneous group and are classified into benign, intermediate, and malignant forms according to the adult tissue they resemble. They can occur in all sites of the body. Aims and Objectives: The present study was undertaken to assess the histopathological pattern of various soft-tissue tumors. Materials and Methods: This is a prospective observational study for a period of 2 years, in which 152 soft-tissue tumors were analyzed and classified primarily as per the WHO classification. The age-wise, sex-wise, and site-wise distribution and the histopathological spectrum of soft-tissue tumors were studied. Results: A total of 152 soft-tissue tumors were included in the study, of which 90.79% were benign tumors, 5.92% were malignant, 2.63% were intermediate grade tumors, and 0.66% was of uncertain malignant potential. Maximum number of patients belonged to the 41-50-year age group. Males constitute 53.29% cases and females, 46.71% with a male-to-female ratio of 1.14:1. Lipoma was the most common soft-tissue tumor in the present study. Conclusion: Overall soft-tissue tumors are a rare category of tumors with benign tumors vastly outnumbering malignant tumors. The diagnosis of soft-tissue tumors needs a meticulous approach and team effort. Proper examination of the gross specimen and careful sampling of the tumor is required for the correct diagnosis. Hematoxylin- and Eosin-stained sections remain very important for the diagnosis of soft-tissue tumors along with immunohistochemistry and molecular markers. [ABSTRACT FROM AUTHOR]

Sickle cell disease (SCD) is a hereditary hemoglobinopathy characterized by painful vaso-occlusive crises (VOC) and chronic hemolysis. The mononuclear phagocyte system is pivotal to SCD pathophysiology, but the mechanisms governing monocyte/macrophage differentiation remain unknown. This study examined the influence of hemolysis on circulating monocyte trajectories in SCD. We discovered that hemolysis stimulated CSF-1 production, partly by endothelial cells via Nrf2, promoting classical monocyte (CMo) differentiation into blood patrolling monocytes (PMo) in SCD mice. However, hemolysis also upregulated CCL-2 through IFN-I, inducing CMo transmigration and differentiation into tissue monocyte-derived macrophages. Blocking CMo transmigration by anti-P selectin antibody in SCD mice increased circulating PMo, corroborating that CMo-to-tissue macrophage differentiation occurs at the expense of CMo-to-blood PMo differentiation. We observed a positive correlation between plasma CSF-1/CCL-2 ratios and blood PMo levels in patients with SCD, underscoring the clinical significance of these two opposing factors in monocyte differentiation. Combined treatment with CSF-1 and anti-P selectin antibody more effectively increased PMo numbers and reduced stasis compared with single-agent therapies in SCD mice. Altogether, these data indicate that monocyte fates are regulated by the balance between two heme pathways, Nrf2/CSF-1 and IFN-I/CCL-2, and suggest that the CSF-1/CCL-2 ratio may present a diagnostic and therapeutic target in SCD. [ABSTRACT FROM AUTHOR]

[Display omitted] • "PEGylation" has emerged as a boon for improving the anticancer effect by delivering nanoparticle payload to the tumor tissue or inside the tumour cells. • The designed Docetaxel (DOC) loaded PEGylated SLNs overcome the aqueous solubility issue and improvement of the biopharmaceutics of DOC. • DOC-loaded PEGylated SLNs exhibited better cell cytotoxicity and cellular uptake on PC-3 cells. • DOC-loaded PEGylated SLNs showed enhanced bioavailability and prolonged blood circulation via systemic administration in healthy male Wistar rats. • Briefly, DOC-loaded PEGylated SLNs will be a promising approach for the management of prostate cancer. Docetaxel (DOC) is a potent anticancer molecule widely used to treat various cancers. However, its therapeutic efficacy as a potential anticancer agent has been limited owing to poor aqueous solubility, short circulation time, rapid reticuloendothelial system uptake, and high renal clearance, which consecutively showed poor bioavailability. In the present investigation, we developed polyethylene glycol (PEG) decorated solid lipid nanoparticles (SLN) using the solvent diffusion method to increase the biopharmaceutical properties of DOC. PEG monostearate (SA-PEG 2000) was initially synthesized and characterized using various analytical techniques. Afterwards, DOC-loaded SLN was synthesized with and without SA-PEG 2000 and systematically characterized for in-vitro and in-vivo properties. Spherical-shaped SA-PEG 2000 -DOC SLN showed hydrodynamic diameter and zeta potential of 177 nm and −13 mV, respectively. During the in-vitro release study DOC-loaded SLN showed a controlled release of approximately 54.35 % ± 5.46 within 12 h with Higuchi release kinetics in the tumor microenvironment (pH 5.5). In an in-vitro cytotoxicity study, SA-PEG 2000 -DOC SLN showed significantly lower IC 50 values (p < 0.001) compared to DOC-SLN and DOC alone against prostate cancer cell lines (PC-3). Similarly, an in-vitro cellular uptake study showed a significant increase in intracellular DOC concentration for SA-PEG 2000 -DOC SLN. Additionally, in in-vivo studies, PEGylated SLN of DOC showed around 2- and 15-fold increase in the maximum concentration of drug (Cmax) and area under the curve (AUC), respectively, as compared to plain DOC solution due to the unique hydrophilicity and hydrophobicity balance and electrical neutrality of specially designed PEG architect. The biological half-life (t 1/2) and mean residence time (MRT) was found to increase from 8.55 and 11.43 to 34.96 and 47.68 h, respectively, with SA-PEG 2000 -DOC SLN. Moreover, the bio-distribution study indicates high DOC concentration in the plasma which signifies the more pronounced blood residence time of SA-PEG 2000 -DOC SLN. In a nutshell, SA-PEG 2000 -DOC SLN was found to be a promising and efficient drug delivery platform for the management of Metastatic Prostate cancer. [ABSTRACT FROM AUTHOR]