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Skin manifestations associated with systemic diseases - Part I.

The skin demonstrates what is happening in the body in many diseases, as it reflects some internal processes on the surface. In this sense, skin as an organ, goes beyond its protective and barrier functions, as it provides clues for the identification of some systemic diseases. The dermatologist then raises diagnostic hypotheses for conditions related to all systems and refers them to the appropriate specialty. With easy access to examination by trained eyes and biopsies, the skin can present specific or non specific alterations on histopathology. In the first case this combination establishes

Cancer treatment using peptides: current therapies and future prospects.

This paper discusses the role of peptides in cancer therapy with special emphasis on peptide drugs which are already approved and those in clinical trials. The potential of peptides in cancer treatment is evident from a variety of different strategies that are available to address the progression of tumor growth and propagation of the disease. Use of peptides that can directly target cancer cells without affecting normal cells (targeted therapy) is evolving as an alternate strategy to conventional chemotherapy. Peptide can be utilized directly as a cytotoxic agent through various mechanisms or

Устроенная ЦАР клеточная терапия: текущее понимание и перспективы на будущее.

Инженерная клеточная терапия химерического антигенного рецептора (CAR) представляет собой значительный прорыв в иммунотерапии, первоначально в раке и в настоящее время распространяется на различные клинические области. Хотя изначально эти платформы разрабатывались для онкологии, они все чаще адаптируются к таким ненасытным условиям, как аутоиммунные расстройства, инфекционные заболевания, фиброз, проблемы старения и трансплантация органов. В настоящем обзоре содержится подробная информация об эволюции и диверсификации методов ЦАР, включая CAR-T, CAR-NK, CA-Macrophages и CAR-NKT, а также о новы

Delivery of Drugs into Cancer Cells Using Antibody-Drug Conjugates Based on Receptor-Mediated Endocytosis and the Enhanced Permeability and Retention Effect.

Innumerable people worldwide die of cancer every year, although pharmaceutical therapy has actualized many benefits in human health. For background, anti-cancer drug development is difficult due to the multifactorial pathogenesis and complicated pathology of cancers. Cancer cells excrete hydrophobic low-molecular anti-cancer drugs by overexpressed efflux transporters such as multiple drug resistance 1 (MDR1) at the apical membrane. Mutation-driven drug resistance is also developed in cancer. Moreover, the poor distribution of drug to cancer cells is a serious problem, because patients suffer f

Etodolac improves collagen induced rheumatoid arthritis in rats by inhibiting synovial inflammation, fibrosis and hyperplasia.

Synovial hyperplasia is the main cause of chronic rheumatoid arthritis (RA), but the mechanism of synovial hyperplasia is still unclear. Etodolac (ETD) is a selective COX-2 inhibitor for relieving pain and stiffness in RA, but the disease modifying effect is still lack of evidence. Proteomics method was used to study the differential proteome of synovial tissue in collagen induced arthritis (CIA) in rats. With the help of STRING analysis, the upregulated proteins enriched in the cluster of complement and coagulation cascades and platelet degranulation were highlighted, these proteins with fibr

Translating IL-6 biology into effective treatments.

In 1973, IL-6 was identified as a soluble factor that is secreted by T cells and is important for antibody production by B cells. Since its discovery more than 40 years ago, the IL-6 pathway has emerged as a pivotal pathway involved in immune regulation in health and dysregulation in many diseases. Targeting of the IL-6 pathway has led to innovative therapeutic approaches for various rheumatic diseases, such as rheumatoid arthritis, juvenile idiopathic arthritis, adult-onset Still's disease, giant cell arteritis and Takayasu arteritis, as well as other conditions such as Castleman disease and

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Frontiers in Antibody-Drug Conjugates: Mechanisms, Design Innovations, and Clinical Applications in Targeted Cancer Therapy.

Antibody-drug conjugates (ADCs) represent a transformative class of targeted therapies designed to deliver potent cytotoxic agents specifically to tumor cells, minimizing systemic toxicity. This review provides a comprehensive overview of ADCs, detailing their mechanisms of action, design strategies, and clinical advancements. ADCs utilize monoclonal antibodies to selectively bind tumor-associated antigens, enabling the precise delivery of toxic payloads to cancer cells. The review explores the critical components of ADCs, including the antibody, linker, and payload, and highlights how these e

Osteoprotegerin and receptor activator of NF-kappaB ligand as biomarkers for bone resorption-related disorders.

Osteoclastic bone diseases represent a significant health burden, especially in an aging population, due to imbalances in bone homeostasis that result in postmenopausal osteoporosis, inflammatory arthritis, malignancy-induced bone disease and secondary metabolic conditions, which result in fragility fractures, disability and death. Although advances in imaging and pharmacology have enhanced management, existing diagnostic strategies have poor sensitivity in detecting early-stage pathological changes or fracture risk. The NF-kappaB/receptor activator of NF-kappaB ligand (RANKL)/osteoprotegerin

The Effects of Artificial Sweeteners on Intestinal Nutrient-Sensing Receptors: Dr. Jekyll or Mr. Hyde?

The consumption of artificial and low-calorie sweeteners (ASs, LCSs) is an important component of the Western diet. ASs play a role in the pathogenesis of metabolic syndrome, dysbiosis, inflammatory bowel diseases (IBDs), and various inflammatory conditions. Intestinal nutrient-sensing receptors act as a crosstalk between dietary components, the gut microbiota, and the regulation of immune, endocrinological, and neurological responses. This narrative review aimed to summarize the possible effects of ASs and LCSs on intestinal nutrient-sensing receptors and their related functions. Based on the

Derivation and elimination of uremic toxins from kidney-gut axis.

Uremic toxins are chemicals, organic or inorganic, that accumulate in the body fluids of individuals with acute or chronic kidney disease and impaired renal function. More than 130 uremic solutions are included in the most comprehensive reviews to date by the European Uremic Toxins Work Group, and novel investigations are ongoing to increase this number. Although approaches to remove uremic toxins have emerged, recalcitrant toxins that injure the human body remain a difficult problem. Herein, we review the derivation and elimination of uremic toxins, outline kidney-gut axis function and relati

Mathematical reconstruction of the metabolic network in an in-vitro multiple myeloma model.

It is increasingly apparent that cancer cells, in addition to remodelling their metabolism to survive and proliferate, adapt and manipulate the metabolism of other cells. This property may be a telling sign that pre-clinical tumour metabolism studies exclusively utilising in-vitro mono-culture models could prove to be limited for uncovering novel metabolic targets able to translate into clinical therapies. Although this is increasingly recognised, and work towards addressing the issue is becoming routinary much remains poorly understood. For instance, knowledge regarding the biochemical mechan

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… Citrullination of histone H3 drives IL-6 production by bone marrow mesenchymal stem cells in MGUS and multiple myeloma . Leukemia . 2017 ; 31 ( 2 ): 373 – 381 . doi: 10.1038/leu.2016.187 27400413 PMC5292682 31 Gnaiger E , Fasching M , Gradl L , Gradl P . …

Polymyalgia rheumatica: An update (Review).

Polymyalgia rheumatica (PMR) is a chronic inflammatory disease which affects the connective vascular tissue, characterized by pain accompanied by morning stiffness, predominantly of the neck muscles, hip and shoulder girdle. Usually, patients with this disease are >50 years of age and biological inflammatory syndrome is present with an increase in both the erythrocyte sedimentation rate and C-reactive protein levels, aspects similar to giant cell arteritis. The aim of the present review was to depict the current pathogenic hypothesis, diagnostic and treatment approach for patients with PMR, an

Boron Chemicals in Drug Discovery and Development: Synthesis and Medicinal Perspective.

A standard goal of medicinal chemists has been to discover efficient and potent drug candidates with specific enzyme-inhibitor abilities. In this regard, boron-based bioactive compounds have provided amphiphilic properties to facilitate interaction with protein targets. Indeed, the spectrum of boron-based entities as drug candidates against many diseases has grown tremendously since the first clinically tested boron-based drug, Velcade. In this review, we collectively represent the current boron-containing drug candidates, boron-containing retinoids, benzoxaboroles, aminoboronic acid, carboran

Pathogenic Role of FGFR3 Autoantibodies in Small Fiber Neuropathy.

Sensory neuronopathies (SNN) and small fiber neuropathies (SFN) are debilitating disorders associated with neuropathic pain, yet their underlying mechanisms remain poorly understood. Autoantibodies against fibroblast growth factor receptor 3 define a subset of patients with consistent reports of neuropathic pain harboring a distinct clinical phenotype characterized by small-fiber and non-length-dependent neuropathy, suggesting dorsal root ganglia (DRG) dysfunction. FGFR3-autoantibody-positive sera (FGFR3-AbS) bind to sensory neurons within dorsal root ganglia (DRG). The target of autoantibodie

Cryoglobulinemia: An update on classification, pathophysiology, clinical presentation, and management.

Cryoglobulinemia (CG) is defined by the presence of serum immunoglobulins that precipitate below 37°C and redissolve upon rewarming. It is classified into three types based on immunoglobulin composition. Type I, a rare form, involves monoclonal IgM or IgG and is linked to lymphoproliferative disorders. Types II and III are known as mixed CG (MC): Type II consists of polyclonal IgG and monoclonal IgM with rheumatoid factor (RF) activity, whereas Type III includes polyclonal IgG and polyclonal IgM with RF activity. MC is predominantly associated with hepatitis C virus (HCV) infection and involve

Cardiovascular Biomarkers in Cardio-Oncology: Antineoplastic Drug Cardiotoxicity and Beyond.

Serum biomarkers represent a reproducible, sensitive, minimally invasive and inexpensive method to explore possible adverse cardiovascular effects of antineoplastic treatments. They are useful tools in risk stratification, the early detection of cardiotoxicity and the follow-up and prognostic assessment of cancer patients. In this literature review, we aim at describing the current state of knowledge on the meaning and the usefulness of cardiovascular biomarkers in patients with cancer; analyzing the intricate relationship between cancer and cardiovascular disease (especially HF) and how this

Преодоление препятствий: развитие клеточной терапии в области аутоиммунной борьбы с заболеваниями.

Аутоиммунные заболевания возникают в результате дисрегламента в иммунной системе, что приводит к агрессивному нападению на ткани самого организма. Патогенез этих условий является многофакторным, охватывающим сложные взаимосвязи между генетическими предрасположениями, экологическими детерминантами и гормональными колебаниями. Диапазон аутоиммунных заболеваний является широким и оказывает воздействие на множество систем органов, при этом можно привести такие примечательные примеры, как ревматуидный артрит (RA), системный волчан (SLE), множественный склероз (MS), псориаз и витилиго. Несмотря на з

CAR-T cell therapy: A new dawn in the treatment of autoimmune disease.

Autoimmune diseases (AIDs) are a class of diseases caused by autoimmune intolerance, which can be divided into systemic and organ-specific diseases. AIDs affect approximately 10% of the global population and rank among the leading causes of disability and mortality. At present, immunosuppressive agents are the first choice for the treatment of AIDs. B-cell-targeted therapies-particularly CD20 monoclonal antibodies-have brought new hope for systemic AIDs, yet a subset of patients still respond poorly. As a rapidly developing cellular immunotherapy technology, Chimeric antigen receptor T cell (C

Unveiling the Role of CCL3: A Driver of CIPN in Colon Cancer Patients?

Cancer neuroscience is an emerging field revealing how malignancies interact with the nervous system to shape disease progression and symptom burden. In colorectal cancer (CRC), increasing evidence suggests a direct interplay between tumor cells and peripheral sensory neurons, contributing not only to cancer progression but also to chemotherapy-induced side effects such as peripheral neuropathy. Chemokines, particularly CCL3, appear to be key players in this bidirectional communication. This literature review aims to critically examine the role of CCL3 in CRC and chemotherapy-induced periphera

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… Citrullination of CXCL8 by peptidylarginine deiminase alters receptor usage, prevents proteolysis, and dampens tissue inflammation. J. Exp. Med. 2008;205:2085–2097. doi: 10.1084/jem.20080305. 39. Nishikawa G., Kawada K., Nakagawa J., Toda K., Ogawa R., Inamoto S., Mizuno R., Itatani Y., Sakai Y. …