Результаты поиска

Pharmaceutical Chaperones and Proteostasis Regulators in the Therapy of Lysosomal Storage Disorders: Current Perspective and Future Promises.

Different approaches have been utilized or proposed for the treatment of lysosomal storage disorders (LSDs) including enzyme replacement and hematopoietic stem cell transplant therapies, both aiming to compensate for the enzymatic loss of the underlying mutated lysosomal enzymes. However, these approaches have their own limitations and therefore the vast majority of LSDs are either still untreatable or their treatments are inadequate. Missense mutations affecting enzyme stability, folding and cellular trafficking are common in LSDs resulting often in low protein half-life, premature degradatio

Clinical innovations and future directions of nanoparticles in the treatment of psychiatric and neurological disorders.

Nanoparticles (NPs) provide a versatile toolkit for psychiatry and neurology by leveraging tunable size, surface chemistry, and payload control to overcome long-standing barriers in central nervous system (CNS) therapy. Lipid, polymeric, inorganic, and hybrid NPs can be engineered to traverse the blood-brain barrier (BBB) via receptor/transporter pathways, target specific cell types, and deliver sustained or stimuli-responsive release. Beyond drug delivery, NPs improve imaging, enable gene/RNA therapeutics, and support anti-inflammatory and neuroprotective strategies, advancing precision medic

Targeting B cells in IgA nephropathy: from pathogenic insight to therapeutic horizon.

Immunoglobulin A nephropathy (IgAN) remains the most common primary glomerulonephritis globally. Advances in mucosal immunology have illuminated the role of dysregulated B cell activity, galactose-deficient IgA1 (Gd-IgA1) and Gd-IgA1-specific antibody formation in driving disease pathogenesis. Therapeutic targeting of the mucosal immune system and, more specifically, B cell survival and differentiation pathways have entered late-stage development, offering a mechanistically guided approach to disease modification. Targeting of the gut-associated lymphoid tissue of the terminal ileum, B cell ac

Glycoprotein Non-Metastatic Protein B: An Emerging Biomarker for Lysosomal Dysfunction in Macrophages.

Several diseases are caused by inherited defects in lysosomes, the so-called lysosomal storage disorders (LSDs). In some of these LSDs, tissue macrophages transform into prominent storage cells, as is the case in Gaucher disease. Here, macrophages become the characteristic Gaucher cells filled with lysosomes laden with glucosylceramide, because of their impaired enzymatic degradation. Biomarkers of Gaucher cells were actively searched, particularly after the development of costly therapies based on enzyme supplementation and substrate reduction. Proteins selectively expressed by storage macrop

Совпадение в полном тексте источника
… Brady and colleagues used GBA isolated from human placentas which was being modified in its N-glycans to favor mannose receptor-mediated uptake by macrophages following intravenous administration [ 59 ]. …

Clusterin and pentraxin 3 are markers of severity during febrile neutropenia in adults with haematological malignancies receiving intensive chemotherapy.

The identification of predictive biomarkers of severity can improve patient management because febrile neutropenia can be associated with significant morbidity and mortality. We prospectively studied pentraxin 3 (PTX3), a soluble innate immunity receptor, and clusterin (CLU), a chaperone protein that binds extracellular histones during sepsis, in patients experiencing febrile neutropenia after intensive treatment for haematological malignancies. One hundred and forty-three adult patients were included, with 158 episodes of neutropenia analysed. Febrile neutropenia was observed in 119 patients

A year in pharmacology: new drugs approved by the US Food and Drug Administration in 2021.

The second year of the COVID-19 pandemic had no adverse effect on the number of new drug approvals by the US Food and Drug Administration (FDA). Quite the contrary, with a total of 50 new drugs, 2021 belongs to the most successful FDA years. We assign these new drugs to one of three levels of innovation: (1) first drug against a condition ("first-in-indication"), (2) first drug using a novel molecular mechanism ("first-in-class"), and (3) "next-in-class", i.e., a drug using an already exploited molecular mechanism. We identify 21 first-in-class, 28 next-in-class, and only one first-in-indicati

Potential Targeting Mechanisms for Bone-Directed Therapies.

Bone development is characterized by complex regulation mechanisms, including signal transduction and transcription factor-related pathways, glycobiological processes, cellular interactions, transportation mechanisms, and, importantly, chemical formation resulting from hydroxyapatite. Any abnormal regulation in the bone development processes causes skeletal system-related problems. To some extent, the avascularity of cartilage and bone makes drug delivery more challenging than that of soft tissues. Recent studies have implemented many novel bone-targeting approaches to overcome drawbacks. Howe

Совпадение в полном тексте источника
… Besides the other two units binding to collagen collectively, the type 2 unit of fibronectin collagen-binding domain is present in mannose receptors and MMP-2. Interestingly, fibronectin binds to denatured collagens [ 77 , 78 ]. …

Alendronate-coated long-circulating liposomes containing 99mtechnetium-ceftizoxime used to identify osteomyelitis.

Osteomyelitis is a progressive destruction of bones caused by microorganisms. Inadequate or absent treatment increases the risk of bone growth inhibition, fractures, and sepsis. Among the diagnostic techniques, functional images are the most sensitive in detecting osteomyelitis in its early stages. However, these techniques do not have adequate specificity. By contrast, radiolabeled antibiotics could improve selectivity, since they are specifically recognized by the bacteria. The incorporation of these radiopharmaceuticals in drug-delivery systems with high affinity for bones could improve the

Serial low doses of sorafenib enhance therapeutic efficacy of adoptive T cell therapy in a murine model by improving tumor microenvironment.

Requirements of large numbers of transferred T cells and various immunosuppressive factors and cells in the tumor microenvironment limit the applications of adoptive T cells therapy (ACT) in clinic. Accumulating evidences show that chemotherapeutic drugs could act as immune supportive instead of immunosuppressive agents when proper dosage is used, and combined with immunotherapy often results in better treatment outcomes than monotherapy. Controversial immunomodulation effects of sorafenib, a multi-kinases inhibitor, at high and low doses have been reported in several types of cancer. However,

Mycobiota и Antifungal Antibodies как новые целевые показатели для диагностики и прогнозирования болезней человека.

Человеческое тело колонизируется различными микроорганизмами, при этом наиболее активно изучаются бактерии. Однако грибы, которые в совокупности известны как «микобиота», все чаще признаются в качестве составных компонентов микробиоты, населяющей почти все мукосальные поверхности. Комменсальные грибы оказывают влияние на иммунитет хост-приемника, как и бактерии, и способствуют выполнению других важных функций, включая метаболизм. В этом новом понимании грибы рассматриваются как потенциальные биомаркеры для диагностики и прогнозирования различных заболеваний. В этом обзоре мы изучаем двойную ро

A year in pharmacology: new drugs approved by the US Food and Drug Administration in 2023.

With 54 new drugs and seven cellular and gene therapy products, the approvals by the US Food and Drug Administration (FDA) recovered 2023 from the 2022 dent back to the levels of 2020-2021. As in previous years of this annual review, we assign these new drugs to one of three levels of innovation: first drug against a condition ("first-in-indication"), first drug using a novel molecular mechanism ("first-in-class"), and "next-in-class," i.e., a drug using an already exploited molecular mechanism. We identify four (7%) "first-in-indication," 22 (36%) "first-in-class," and 35 (57%) "next-in-class

Recent Advances in Cancer Vaccines: Challenges, Achievements, and Futuristic Prospects.

Cancer is a chronic disease, and it can be lethal due to limited therapeutic options. The conventional treatment options for cancer have numerous challenges, such as a low blood circulation time as well as poor solubility of anticancer drugs. Therapeutic cancer vaccines emerged to try to improve anticancer drugs' efficiency and to deliver them to the target site. Cancer vaccines are considered a viable therapeutic technique for most solid tumors. Vaccines boost antitumor immunity by delivering tumor antigens, nucleic acids, entire cells, and peptides. Cancer vaccines are designed to induce lon

Совпадение в полном тексте источника
… Innate cells express many receptors, such as Toll-like receptors (TLRs), nucleotide-binding oligomerization domain receptors, and mannose receptors, on their surface. TLR agonists initiate immunological stimulation and boost vaccination efficacy [ 80 ]. …

The Role of Macrophage in the Pathogenesis of Osteoporosis.

Osteoporosis is a systemic disease with progressive bone loss. The bone loss is associated with an imbalance between bone resorption via osteoclasts and bone formation via osteoblasts. Other cells including T cells, B cells, macrophages, and osteocytes are also involved in the pathogenesis of osteoporosis. Different cytokines from activated macrophages can regulate or stimulate the development of osteoclastogenesis-associated bone loss. The fusion of macrophages can form multinucleated osteoclasts and, thus, cause bone resorption via the expression of IL-4 and IL-13. Different cytokines, endoc

Совпадение в полном тексте источника
… Interleukin-13 induces human monocyte/macrophage fusion and macrophage mannose receptor expression J. Immunol. 1997 158 3385 3390 9120298 39. DeFife K.M. Jenney C.R. Colton E. Anderson J.M. Cytoskeletal and adhesive structural polarizations accompany il-13-induced human macrophage fusion J. …

The GH-IGF-SST system in hepatocellular carcinoma: biological and molecular pathogenetic mechanisms and therapeutic targets.

Hepatocellular carcinoma (HCC) is the sixth most common malignancy worldwide. Different signalling pathways have been identified to be implicated in the pathogenesis of HCC; among these, GH, IGF and somatostatin (SST) pathways have emerged as some of the major pathways implicated in the development of HCC. Physiologically, GH-IGF-SST system plays a crucial role in liver growth and development since GH induces IGF1 and IGF2 secretion and the expression of their receptors, involved in hepatocytes cell proliferation, differentiation and metabolism. On the other hand, somatostatin receptors (SSTRs

Вирус Эпштейн-Барр BALF0/1 подрывает пути кавеолина и ERAD, чтобы охватить комплексы рецепторов клеток B для разложения.

Вирус Эпштейн-Барр (ЭБВ) устанавливает стойкую инфекцию, вызывает инфекционный мононуклеоз, является одним из основных пусковых факторов множественного склероза и способствует возникновению множественных раковых заболеваний. Тем не менее, знания о том, как вирус реконструирует клетки В для поддержки литического воспроизведения, остаются неполными. Ранее мы обнаружили, что EBV литическое воспроизведение приводит к избирательному истощению комплексов рецепторов клеток В (КРВ), состоящих из иммуноглобулина, а также цепочек сигнализации CD79A и CD79B. Здесь мы использовали протеомные и биохимическ

Medicinal Mushrooms: Bioactive Compounds, Use, and Clinical Trials.

Medicinal mushrooms have important health benefits and exhibit a broad spectrum of pharmacological activities, including antiallergic, antibacterial, antifungal, anti-inflammatory, antioxidative, antiviral, cytotoxic, immunomodulating, antidepressive, antihyperlipidemic, antidiabetic, digestive, hepatoprotective, neuroprotective, nephroprotective, osteoprotective, and hypotensive activities. The growing interest in mycotherapy requires a strong commitment from the scientific community to expand clinical trials and to propose supplements of safe origin and genetic purity. Bioactive compounds of

Emerging Modes of Treatment of IgA Nephropathy.

IgA nephropathy is the most common primary glomerulonephritis with potentially serious outcome leading to end stage renal disease in 30 to 50% of patients within 20 to 30 years. Renal biopsy, which might be associated with risks of complications (bleeding and others), still remains the only reliable diagnostic tool for IgA nephropathy. Therefore, the search for non-invasive diagnostic and prognostic markers for detection of subclinical types of IgA nephropathy, evaluation of disease activity, and assessment of treatment effectiveness, is of utmost importance. In this review, we summarize treat

Transforming tumor microenvironments: nanotechnology and gene therapy in cellular signaling and epigenetic insight into chemo-resistance.

Chemoresistance remains the primary cause of cancer treatment failure, yet current understanding remains fragmented across isolated mechanistic studies. This review provides a unified framework linking tumor microenvironment (TME) signaling, epigenetic reprogramming, and nanotherapeutic intervention as an integrated axis driving and potentially reversing chemoresistance. We systematically examine how TME components: hypoxia (HIF-1α pathway), acidosis, cancer-associated fibroblasts (TGF-β/PDGF signaling), and immune cells (NF-κB-mediated immunosuppression) activate signaling cascades that direc

Совпадение в полном тексте источника
… Nanoparticles can be functionalized with mannose to target macrophage mannose receptors or other ligands to preferentially accumulate in TAMs [ 165 , 166 ]. …

Structure and function of therapeutic antibodies approved by the US FDA in 2025.

In 2025, the 50th anniversary of the invention of hybridoma technology, the United States Food and Drug Administration (US FDA) approved a total of 44 new molecular entities (NMEs), of which 10 were therapeutic antibody-based molecules. Additionally, the US FDA approved 31 small molecules (of which one was a peptide), and 3 new nonantibody therapeutic proteins, but no new chimeric antigen receptor (CAR)-T-cell therapeutics. Of the new antibody-based biologics, two were antibody-drug conjugates, one was a T-cell engager-bispecific antibody, two were Fc-modified, half-life extended antibodies, a

Biologics and Non-Biologics Immunosuppressive Treatments for IgA Nephropathy in Both Adults and Children.

Immunoglobulin A nephropathy represents the most prevalent cause of glomerulonephritis worldwide and may lead to renal failure in a relevant number of cases in both paediatric and adult subjects. Although their pathogenesis is still largely unclear, evidence of immune abnormalities provides the background for the use of immunosuppressive drugs, such as corticosteroids, calcineurin inhibitors, and antiproliferative and alkylating agents. Unfortunately, these treatments fail to achieve a sustained remission in a significant percentage of affected patients and are burdened by significant toxiciti