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Gaucher disease: clinical profile and therapeutic developments.

Gaucher disease is a rare inborn error of glycosphingolipid metabolism due to deficiency of lysosomal acid β-glucocerebrosidase; the condition has totemic significance for the development of orphan drugs. A designer therapy, which harnesses the mannose receptor to complement the functional defect in macrophages, ameliorates the principal clinical manifestations in hematopoietic bone marrow and viscera. While several aspects of Gaucher disease (particularly those affecting the skeleton and brain) are refractory to treatment, enzyme (replacement) therapy has become a pharmaceutical blockbuster.

Taming renal inflammation: signaling pathways and therapeutic advances in lupus nephritis.

Lupus nephritis (LN), a serious complication of systemic lupus erythematosus (SLE), involves complex immune dysregulation that leads to chronic renal inflammation and progressive tissue damage. Despite decades of use of standard immunosuppressive therapy, treatment responses remain variable, and many patients experience relapses or develop end-stage renal disease. This review synthesizes emerging insights into the immunopathogenesis of LN, drawing on studies from single-cell transcriptomics, signaling pathway analyses and renal tissue immunology. It examines the role of both innate and adaptiv

Mesoporous Silica Nanoparticles as Drug Delivery Vehicles in Cancer.

Even though cancer treatment has improved over the recent decades, still more specific and effective treatment concepts are mandatory. Surgical removal is not always possible, metastases are challenging and chemo- and radiotherapy can not only have severe side-effects but also resistances may occur. To cope with these challenges more efficient therapies with fewer side-effects are required. One promising approach is the use of drug delivery vehicles. Here, mesoporous silica nanoparticles (MSN) are discussed as biodegradable drug carrier to improve efficacy and reduce side-effects. MSN excellen

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… Moreover, nanoparticles should be taken up predominantly and efficiently by cancer cells and evade the mononuclear phagocytic system (MPS). Once drug carriers are incorporated by the cells, endosomal escape and drug release is crucial. … The mononuclear phagocyte system: A new classification of macrophages, monocytes, and their precursor cells Bull. World Health Organ. 1972 46 845 852 4538544 PMC2480884 39. Huang X. Li L. Liu T. Hao N. Liu H. Chen D. Tang F. …

Pathophysiological Roles of the CX3CL1-CX3CR1 Axis in Renal Disease, Cardiovascular Disease, and Cancer.

CX3CL1 and its unique receptor, CX3CR1, are leukocyte migration factors and are involved in the pathogenesis and progression of many inflammatory diseases and malignancies. The CX3CL1-CX3CR1 axis induces a variety of responses, including cell proliferation, migration, invasion, and apoptosis resistance. CX3CL1 is a transmembrane protein, and proteolysis generates a soluble form. The membrane and soluble forms of CX3CL1 exhibit different functions, but both bind to the chemokine receptor CX3CR1. The CX3CL1-CX3CR1 axis is a chemokine system that has attracted attention not only as a therapeutic

Local administration of mesenchymal stromal cells is safe and modulates the immune compartment in ulcerative proctitis.

BACKGROUNDDue to their immunoregulatory and tissue regenerative features, mesenchymal stromal cells (MSCs) are a promising novel tool for the management of ulcerative proctitis (UP). Here we report on a phase IIa clinical study that evaluated the impact of local MSC therapy on UP.METHODSThirteen refractory UP patients, with an endoscopic Mayo score (EMS) of 2 or 3, were included. Seven patients received 20-40 million allogeneic MSCs (cohort 1), while 6 patients received 40-80 million MSCs (cohort 2). Adverse events (AEs) were assessed at baseline and on weeks 2, 6, 12, and 24. Clinical, endosc

Anticancer and cardio-protective effects of liposomal doxorubicin in the treatment of breast cancer.

Breast cancer (BC) is a highly prevalent disease, accounting for the second highest number of cancer-related mortalities worldwide. The anthracycline doxorubicin (DOX), isolated from Streptomyces peucetius var. caesius, is a potent chemotherapeutic drug that is successfully used to treat various forms of liquid and solid tumors and is currently approved to treat BC. DOX exerts its effects by intercalation into DNA and inhibition of topoisomerases I and II, causing damage to DNA and the formation of reactive oxygen species (ROS), resulting in the activation of caspases, which ultimately leads t

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… The PEGylation protects the liposomes from recognition by the mononuclear phagocyte system (MPS) and allows a longer circulation time in the bloodstream while reducing the exposure of free DOX circulating in the plasma. …

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Early Diagnosis of Herpes Zoster Neuralgia: A Narrative Review.

BACKGROUND: Early intervention reduces the incidence of postherpetic neuralgia (PHN). Typical shingles are easy to diagnose; however, there is no clear diagnostic method for neuralgia symptoms manifested before the onset of the rash, which can easily cause misdiagnosis. This not only increases the patient's pain, medical expenses, and mental burden, but more importantly, delays the valuable time for early treatment of shingles, and increases the probability of complications and PHN. OBJECTIVE: In this paper, the diagnostic methods of preherpetic neuralgia were summarized and analyzed, and the

Маресин-1 содействует нейрозащите и модифицирует метаболические и подстрекательские реакции в связанных с болезнями типах клеток в предклинических моделях множественного склероза.

Множественный склероз (MS) является распространенным воспалительным нейродегенеративным заболеванием у молодежи, вызывающим неврологические аномалии и расстройство. Для исследования нового терапевтического агента для MS мы наблюдали воздействие марезина 1 (MAR1) на прогрессию заболеваний в хорошо известной экспериментальной аутоиммунной энцефаломиелитной модели мыши. Лечение с помощью MAR1 ускорило воспаление, уменьшило неврологическое расстройство и запоздалое развитие заболеваний за счет уменьшения инфильтрации иммунных клеток (CD4+IL-17+ и CD4+IFN__+) в центральную нервную систему. Кроме то

Restoration of Peripheral Intermediate and Classical Monocytes Expressing HLA-DR in Patients With Lung Adenocarcinoma After Platinum-Based Chemotherapy.

Lung adenocarcinoma represents one of the lung cancer subtypes with major prevalence. Accumulating evidence indicates that the immune system plays an important role in the evolution of the neoplastic process; additionally, several reports suggest that chemotherapy has an immunomodulatory effect. In order to identify the peripheral subpopulations of leukocytes that may change after chemotherapy, we evaluated several peripheral immune subpopulations of monocytes and lymphocytes by multicolor flow cytometry. In addition, we also measured cytokines and growth factors on plasma in order to evaluate

No Effect of Vitamin C Administration on Neutrophil Recovery in Autologous Stem Cell Transplantation for Myeloma or Lymphoma: A Blinded, Randomized Placebo-Controlled Trial.

Vitamin C is an important micronutrient for various immune cells. It increases phagocytic cell function and is necessary for T and natural killer (NK) cell development. Patients in need of an autologous hematopoietic stem cell transplantation (HSCT) are often vitamin C-depleted. We therefore hypothesized that vitamin C supplementation could improve immune recovery in autologous HSCT patients. This blinded, placebo-controlled trial included 44 patients randomized to receive vitamin C or a placebo. The following outcome measures used were clinical and immunological parameters, among others: time

Amino acid metabolism in immune cells: essential regulators of the effector functions, and promising opportunities to enhance cancer immunotherapy.

Amino acids are basic nutrients for immune cells during organ development, tissue homeostasis, and the immune response. Regarding metabolic reprogramming in the tumor microenvironment, dysregulation of amino acid consumption in immune cells is an important underlying mechanism leading to impaired anti-tumor immunity. Emerging studies have revealed that altered amino acid metabolism is tightly linked to tumor outgrowth, metastasis, and therapeutic resistance through governing the fate of various immune cells. During these processes, the concentration of free amino acids, their membrane bound tr

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… Amino acid metabolism in myeloid cells Macrophages Macrophages are important innate myeloid cells and a major cell type within the mononuclear phagocyte system (MPS) [ 189 ]. …

Osteoclast Activation and Inflammatory Bone Diseases: Focusing on Receptors in Osteoclasts.

Bone homeostasis depends on the balance between osteoblast-mediated bone formation and osteoclast-mediated bone resorption. An increasing number of studies have revealed that under inflammatory conditions, osteoclast overactivation is responsible for bone loss in relevant bone diseases. Multiple signaling pathways such as receptor activator of nuclear factor-kappa B ligand (RANKL) signaling are involved in osteoclast activation. These signaling pathways rely on various receptors expressed on the surface of osteoclast progenitor cells (OPCs) or osteoclasts, which are activated by their correspo

Blocking the MIF-CD74 axis augments radiotherapy efficacy for brain metastasis in NSCLC via synergistically promoting microglia M1 polarization.

BackgroundBrain metastasis is one of the main causes of recurrence and death in non-small cell lung cancer (NSCLC). Although radiotherapy is the main local therapy for brain metastasis, it is inevitable that some cancer cells become resistant to radiation. Microglia, as macrophages colonized in the brain, play an important role in the tumor microenvironment. Radiotherapy could activate microglia to polarize into both the M1 and M2 phenotypes. Therefore, searching for crosstalk molecules within the microenvironment that can specifically regulate the polarization of microglia is a potential stra

Targeting strategies for bone diseases: signaling pathways and clinical studies.

Since the proposal of Paul Ehrlich's magic bullet concept over 100 years ago, tremendous advances have occurred in targeted therapy. From the initial selective antibody, antitoxin to targeted drug delivery that emerged in the past decades, more precise therapeutic efficacy is realized in specific pathological sites of clinical diseases. As a highly pyknotic mineralized tissue with lessened blood flow, bone is characterized by a complex remodeling and homeostatic regulation mechanism, which makes drug therapy for skeletal diseases more challenging than other tissues. Bone-targeted therapy has b

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… CD47 on hematopoietic stem cells (HSCs) serves as a ‘marker of self’ that binds to CD172α (S1RPα) on phagocytes to reduce depletion from mononuclear phagocyte system during homing A recent study showed that Lactobacillus rhamnosus (LR, a type of probiotic) supplementation effectively restored bone loss … However, liver distribution was still the highest among the tissues, suggesting that depletion from the mononuclear phagocyte system (MPS) is still a major consumption for the drug delivery system. …

Nanoparticle Strategies for Bone Metastasis Immunotherapy: Targeting, Immune Reprogramming and Combination Therapy.

Bone metastases remain one of the most clinically devastating complications of advanced cancer, particularly in breast, prostate, and lung malignancies, where they drive pain, fractures, hypercalcemia, and progressive functional decline. Their management is further complicated by a highly immunosuppressive bone microenvironment characterized by osteoclast-driven bone destruction, myeloid cell dominance, impaired antigen presentation, and weak effector T-cell infiltration, all of which limit the activity of conventional immunotherapies. In this setting, nanoparticles are emerging not merely as

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… Stealth Coatings PEGylation creates a hydrated steric barrier that prevents opsonin adsorption and subsequent uptake by the Mononuclear Phagocyte System (MPS), hence prolonging systemic half-life and enhancing tissue distribution [ 63 , 64 , 65 ]. … Leukocyte and macrophage membranes incorporate chemokine receptors and adhesion molecules that facilitate evasion of the mononuclear phagocyte system and target inflamed or neoplastic regions [ 70 , 71 , 72 ]. …

Nanotechnology-Driven Cancer Therapies for Precision Oncology: Advances and Clinical Outlook.

Cancer continues to pose a global health challenge, with conventional therapies often limited by non-specific toxicity, drug resistance, and an inadequate therapeutic index. Nanotechnology offers transformative opportunities by enabling targeted drug delivery, improved pharmacokinetics, and integrated diagnostic-therapeutic platforms (termed nanotheranostics). This review highlights key nanocarrier systems including liposomes, polymeric nanoparticles, dendrimers, inorganic nanostructures, carbon-based materials, extracellular vesicles, and hybrid platforms with a focus on human studies and cli

Перенос Митохондрии для ремонта миелина.

Обезвоживание является общей характеристикой нейро-воспалительных и дегенеративных заболеваний центральной нервной системы (КНС), таких, как множественный склероз (МС). Часто это связано с нарушениями межклеточной связи, биоэнергетики и метаболического баланса в сочетании с митохондриальной дисфункцией в таких клетках, как олигодендроциты, нейроны, астроциты и микроглиа. Несмотря на то, что нынешние методы лечения MS сосредоточены на иммуномодуляции, они не могут остановить или обратить вспять прогресс демиэлизации. Последние достижения подчеркивают межклеточный митохондриальный обмен в качест

Disorders of the Gastrointestinal System

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Targeted Delivery Strategies for Multiple Myeloma and Their Adverse Drug Reactions.

Currently, multiple myeloma (MM) is a prevalent hematopoietic system malignancy, known for its insidious onset and unfavorable prognosis. Recently developed chemotherapy drugs for MM have exhibited promising therapeutic outcomes. Nevertheless, to overcome the shortcomings of traditional clinical drug treatment, such as off-target effects, multiple drug resistance, and systemic toxicity, targeted drug delivery systems are optimizing the conventional pharmaceuticals for precise delivery to designated sites at controlled rates, striving for maximal efficacy and safety, presenting a promising appr

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… Encapsulation of PEGylated liposomes enables evasion of clearance by the mononuclear phagocyte system. … Moreover, research indicates that these nanoparticles can elude phagocytosis by the mononuclear phagocyte system, thereby extending circulation time. Hence, biomimetic delivery strategies may herald a novel approach to targeted drug delivery. Polymers are ideal carriers in gene therapy. …