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Nanoparticles for Targeted Drug Delivery to Cancer Stem Cells: A Review of Recent Advances.

Cancer stem cells (CSCs) are a subpopulation of cells that can initiate, self-renew, and sustain tumor growth. CSCs are responsible for tumor metastasis, recurrence, and drug resistance in cancer therapy. CSCs reside within a niche maintained by multiple unique factors in the microenvironment. These factors include hypoxia, excessive levels of angiogenesis, a change of mitochondrial activity from aerobic aspiration to aerobic glycolysis, an upregulated expression of CSC biomarkers and stem cell signaling, and an elevated synthesis of the cytochromes P450 family of enzymes responsible for drug

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… Following washing and incubating the cells with a fresh medium, the endocytosed DOX-PSiNPs fused with the cell membrane and exocytosed to the extracellular space as exosome-sheathed DOX-PSiNPs. …

Targeting Macrophage Migration Inhibitory Factor in Acute Pancreatitis and Pancreatic Cancer.

Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine implicated in the pathogenesis of inflammation and cancer. It is produced by various cells and circulating MIF has been identified as a biomarker for a range of diseases. Extracellular MIF mainly binds to the cluster of differentiation 74 (CD74)/CD44 to activate downstream signaling pathways. These in turn activate immune responses, enhance inflammation and can promote cancer cell proliferation and invasion. Extracellular MIF also binds to the C-X-C chemokine receptors cooperating with or without CD74 to activate chemokine

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… Constitutive release of MIF from cells results in its high concentration in the extracellular space ( Lee et al., 2016 ; Lang et al., 2018 ). However, the process by which MIF is released is not fully understood. …

Comparing the Therapeutic Potential of Stem Cells and their Secretory Products in Regenerative Medicine.

Cell therapy involves the transplantation of human cells to replace or repair the damaged tissues and modulate the mechanisms underlying disease initiation and progression in the body. Nowadays, many different types of cell-based therapy are developed and used to treat a variety of diseases. In the past decade, cell-free therapy has emerged as a novel approach in regenerative medicine after the discovery that the transplanted cells exerted their therapeutic effect mainly through the secretion of paracrine factors. More and more evidence showed that stem cell-derived secretome, i.e., growth fac

ADMET-Guided Design and In Silico Planning of Boron Delivery Systems for BNCT: From Transport and Biodistribution to PBPK-Informed Irradiation Windows.

BNCT (Boron Neutron Capture Therapy) is a binary radiotherapeutic modality in which high LET (Linear Energy Transfer) particles are generated from 10B(n,α)7Li reaction, ideally within boron-loaded tumour cells, so the therapeutic outcome depends critically on the pharmacokinetics and biodistribution of boron carriers. In this review, boron-containing agents for BNCT, with a focus on ADMET (absorption, distribution, metabolism, excretion and toxicity) and model-informed design, were examined. Low-MW (low-molecular-weight) compounds, peptide conjugates, polymeric and nanostructured platforms and

New insights into non-small cell lung cancer bone metastasis: mechanisms and therapies.

Bone metastasis is a common cause of death in patients with non-small cell lung cancer (NSCLC), with approximately 30-40% of NSCLC patients eventually developing bone metastases. Bone metastasis, especially the occurrence of skeletal-related events (SREs), significantly reduces overall survival (OS) and quality of life (QoL) in patients. Although bone-targeting agents (BTAs) have been shown to reduce SREs and improve QoL in NSCLC patients with bone metastases, the prognosis for these patients remains poor. Understanding the underlying molecular pathways of bone metastasis is crucial for the de

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

Enhancing the Safety of Nanoparticles in Medicine: Highlights of Progress and Critical Objectives.

Nanoparticles have transformed drug delivery, imaging, vaccination, and precision therapeutics, but their clinical translation remains constrained by safety profiles that are inseparable from material design, biological identity, host factors, and manufacturing. This review critically evaluates recent progress, persistent limitations, and priority objectives for safer nanomedicine. Unlike reviews organized primarily by material class or isolated toxicology endpoints, we integrate physicochemical determinants, protein corona formation, immune recognition, organ disposition, preclinical models,

Localized Drug Delivery Systems: An Update on Treatment Options for Head and Neck Squamous Cell Carcinomas.

Head and neck squamous cell carcinoma (HNSCC) is one of the most common cancers in the world, with surgery, radiotherapy, chemotherapy, and immunotherapy being the primary treatment modalities. The treatment for HNSCC has evolved over time, due to which the prognosis has improved drastically. Despite the varied treatment options, major challenges persist. HNSCC chemotherapeutic and immunotherapeutic drugs are usually administered systemically, which could affect the patient's quality of life due to the associated side effects. Moreover, the systemic administration of salivary stimulating agent

A Novel Intravesical Dextrose Injection Improves Lower Urinary Tract Symptoms on Interstitial Cystitis/Bladder Pain Syndrome.

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a painful recurrent condition characterized by the discomfort of the bladder, and current treatment options have limited effectiveness. Prolotherapy is a well-known treatment that involves the injection of non-biologic solutions to reduce pain and/or promote proliferation of soft tissue, and dextrose is the most common injectate. This study investigated the effects of dextrose prolotherapy in a rat model of IC/BPS and patients with IC/BPS. We used cyclophosphamide to induce IC/BPS in rats, and intravesical instillation of 10% dextrose sol

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… The HA was initially synthesized on the inner surface of the cell by HAS and released into the extracellular space. It improved the mobility of urothelial cells and smooth muscle cells and increased the bladder epithelium glycosaminoglycans. …

Обнаружение сфингосин-1-Фосфатных модуляторов-рецепторов в качестве потенциальных CHI3L1 Inhibitors с помощью лигандского виртуального скрининга и моделирования молекулярной динамики.

Множественный склероз характеризуется воспалением центральной нервной системы, обезвоживанием и нейронным дегенерацией. Нынешние методы диагностики и прогнозирования не являются точными, что требует использования биомаркеров для индивидуализированных методов лечения. Читинас 3-подобный 1 (CHI3L1) стал потенциальным прогнозным маркером с повышенными уровнями, связанными с серьезностью заболеваний и риском рецидива. Несмотря на его терапевтический потенциал, было выявлено несколько ингибиторов CHI3L1. На основе виртуального скрининга на основе лиганда и моделирования молекулярной динамики разреш

Case series: Odontohypophosphatasia or missed diagnosis of childhood/adult-onset hypophosphatasia? - Call for a long-term follow-up of premature loss of primary teeth.

IntroductionHypophosphatasia, a metabolic bone disease caused by a tissue-nonspecific alkaline phosphatase deficiency, leads to undermineralization of bone and/or teeth, impaired vitamin B6 metabolism, and a spectrum of disease presentation. At the mild end of the spectrum, it presents as pathologic fractures in later adulthood. Patients with isolated dental manifestations, typically presenting as premature loss of primary teeth, are classified as having odontohypophosphatasia (odontoHPP). A subset of patients diagnosed with odontoHPP in childhood can later develop extra-dental manifestations

Эволюция антиCD20 Лечения множественных склерозов: оптимизация характеристик и функций антител.

Истощение клеток B с помощью целевых агентов CD20 обычно используется для лечения множественных склерозов (MS), других аутоиммунных заболеваний и некоторых гематологов. Первоначальный очевидный успех с ритуксимабом в использовании MS и нейромиелитной оптики стимулировал развитие антиCD20 моноклональной антителной (mAb) терапии oprelizumab, atumumab и ublituximab, а также антиCD19 mAb inebilizumab. Хотя каждая из них является эффективной в плане целеопределения и истощения элементов В, структурные различия превращаются в различные механизмы действий, влияющие на поддержание истощения и безопасн

Enhancing CAR T cells function: role of immunomodulators in cancer immunotherapy.

CAR T-cell therapy is a promising immunotherapy, providing successful results for cancer patients who are unresponsive to standard and traditional therapeutic approaches. However, there are limiting factors which create a hurdle in the therapy performing its role optimally. CAR T cells get exhausted, produce active antitumor responses, and might even produce toxic reactions. Specifically, in the case of solid tumors, chimeric antigen receptor T (CAR-T) cells fail to produce the desired outcomes. Then, the need to use supplementary agents such as immune system modifying immunomodulatory agents

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… The ectodomain, also called extracellular domain, is the region containing a membranous protein located outside the CAR T cell’s cytoplasm exposed into the extracellular space. …

Bortezomib (PS-341) treatment decreases inflammation and partially rescues the expression of the dystrophin-glycoprotein complex in GRMD dogs.

Golden retriever muscular dystrophy (GRMD) is a genetic myopathy corresponding to Duchenne muscular dystrophy (DMD) in humans. Muscle atrophy is known to be associated with degradation of the dystrophin-glycoprotein complex (DGC) via the ubiquitin-proteasome pathway. In the present study, we investigated the effect of bortezomib treatment on the muscle fibers of GRMD dogs. Five GRMD dogs were examined; two were treated (TD- Treated dogs) with the proteasome inhibitor bortezomib, and three were control dogs (CD). Dogs were treated with bortezomib using the same treatment regimen used for multip

The pleiotropic effects of erythropoietin in infection and inflammation.

Erythropoietin (EPO) is a multi-functional cytokine, which exerts erythropoietic effects but also carries anti-apoptotic and immune-modulatory activities upon binding to two distinct receptors which are expressed on erythroid, parenchymal and immune cells, respectively. Whereas EPO ameliorates hemolytic anemia in malaria or trypanosomiasis and improves the course of autoimmune diseases such as inflammatory bowel disease or autoimmune encephalomyelitis, it deleteriously inhibits macrophage functions in Salmonella infection in animal models. Thus, the specific modulation of extra-erythropoietic

ANMCO position paper 'Hypertrophic cardiomyopathy: from diagnosis to treatment'.

Hypertrophic cardiomyopathy (HCM) is a non-rare genetic cardiomyopathy, with an estimated prevalence of 1:500, characterized by an increase in the left ventricular wall thickness in the absence of increased loading conditions. The hypertrophy is mostly asymmetric and predominantly affects the basal septum and anterior wall. Left ventricular outflow tract obstruction, at rest or after provocative tests, is detected in many patients and represents the primary cause of reduced functional capacity, as well as an independent predictor of sudden cardiac death and advanced heart failure. Until ∼1 yea

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… Phenocopies of hypertrophic cardiomyopathy: differential diagnosis and treatment of cardiac amyloidosis Cardiac amyloidosis is linked to the deposition of amyloid fibres in the myocardial extracellular space: the alteration of the substrate leads to progressive dysfunction of ventricular diastole and …

Cardiac amyloidosis: evolving pathogenesis, multimodal diagnostics, and principles of treatment.

Amyloidosis is a protein deposition disorder in which insoluble fibril structures accumulate in the bodily tissues damaging the organ function. Cardiac amyloidosis is a severe but under-reported medical condition characterized by the accumulation of amyloid in the extracellular area of the myocardium, which results in thickening and stiffening of ventricular walls. Cardiac amyloidosis has recently gained much attention with its slowly surging incidence. With this study, we seek to comprehensively compile the pathophysiology and clinical picture of cardiac amyloidosis subtypes, extending a clin

Роль врожденных иммунных клеток в множественном склерозе.

Множественный склероз (MS) — хроническое аутоиммунное, воспалительное и нейродегенеративное заболевание, затрагивающее центральную нервную систему (КНС). MS ассоциируется со сложным взаимодействием между нейродегенеративными и воспалительными процессами, в основном связанными с патогенными Т и В клетками. Однако все большее количество доклинических и клинических данных свидетельствует о том, что врожденный иммунитет играет ключевую роль в поощрении и развитии НР. В этой связи в настоящее время изучаются доклинические и клинические исследования, ориентированные на различные врожденные иммунные

Multifunctionality of Calebin A in inflammation, chronic diseases and cancer.

Chronic diseases including cancer have high case numbers as well as mortality rates. The efficient treatment of chronic diseases is a major ongoing medical challenge worldwide, because of their complexity and many inflammatory pathways such as JNK, p38/MAPK, MEK/ERK, JAK/STAT3, PI3K and NF-κB among others being implicated in their pathogenesis. Together with the versatility of chronic disease classical mono-target therapies are often insufficient. Therefore, the anti-inflammatory as well as anti-cancer capacities of polyphenols are currently investigated to complement and improve the effect of

A Review on the Molecular Mechanisms of Action of Natural Products in Preventing Bone Diseases.

The drugs used for treating bone diseases (BDs), at present, elicit hazardous side effects that include certain types of cancers and strokes, hence the ongoing quest for the discovery of alternatives with little or no side effects. Natural products (NPs), mainly of plant origin, have shown compelling promise in the treatments of BDs, with little or no side effects. However, the paucity in knowledge of the mechanisms behind their activities on bone remodeling has remained a hindrance to NPs' adoption. This review discusses the pathological development of some BDs, the NP-targeted components, an