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The chemokines CXCL8 and CXCL12: molecular and functional properties, role in disease and efforts towards pharmacological intervention.

Chemokines are an indispensable component of our immune system through the regulation of directional migration and activation of leukocytes. CXCL8 is the most potent human neutrophil-attracting chemokine and plays crucial roles in the response to infection and tissue injury. CXCL8 activity inherently depends on interaction with the human CXC chemokine receptors CXCR1 and CXCR2, the atypical chemokine receptor ACKR1, and glycosaminoglycans. Furthermore, (hetero)dimerization and tight regulation of transcription and translation, as well as post-translational modifications further fine-tune the s

Recent Perspectives on Cardiovascular Toxicity Associated with Colorectal Cancer Drug Therapy.

Cardiotoxicity is a well-known adverse effect of cancer-related therapy that has a significant influence on patient outcomes and quality of life. The use of antineoplastic drugs to treat colorectal cancers (CRCs) is associated with a number of undesirable side effects including cardiac complications. For both sexes, CRC ranks second and accounts for four out of every ten cancer deaths. According to the reports, almost 39% of patients with colorectal cancer who underwent first-line chemotherapy suffered cardiovascular impairment. Although 5-fluorouracil is still the backbone of chemotherapy reg

Молекулярная и клеточная основа физиологических изменений беременности и ее последствий для нейрологовых и офтальмических патологий.

Беременность олицетворяет глубокие неврологические, гормональные и анатомические преобразования в материнском мозге, подготавливая их к уходу и сближению младенцев. Нейроимация свидетельствует о таких структурных изменениях, как сокращение содержания серых веществ и реорганизация белых веществ во время беременности, за которыми следует частичное послеродовое выздоровление. Эти адаптации модернизируются изменяющимися уровнями эстрадиола, прогестерона, пролактина и окситоцина, которые координируют нейропластичность и поведенческий уровень готовности. На молекулярном и клеточном уровнях гормоны б

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… Several pregnancy-associated factors, including leukemia inhibitory factor, progesterone, progesterone-induced blocking factor, and estradiol, are known to support this Th2-dominant state [ 79 ]. …

ImmunoPET in Multiple Myeloma-What? So What? Now What?

Despite constant progress over the past three decades, multiple myeloma (MM) is still an incurable disease, and the identification of new biomarkers to better select patients and adapt therapy is more relevant than ever. Recently, the introduction of therapeutic monoclonal antibodies (mAbs) (including direct-targeting mAbs and immune checkpoint inhibitors) appears to have changed the paradigm of MM management, emphasizing the opportunity to cure MM patients through an immunotherapeutic approach. In this context, immuno-positron emission tomography (immunoPET), combining the high sensitivity an

Chemotherapy-induced peripheral neuropathy in adults: a comprehensive update of the literature.

Commonly used chemotherapeutic agents in oncology/hematology practice, causing toxic peripheral neuropathy, include taxanes, platinum compounds, vinca alkaloids, proteasome inhibitors, and antiangiogenic/immunomodulatory agents. This review paper intends to put together and discuss the spectrum of chemotherapy-induced peripheral neuropathy (CIPN) characteristics so as to highlight areas of future research to pursue on the topic. Current knowledge shows that the pathogenesis of CIPN still remains elusive, mostly because there are several sites of involvement in the peripheral nervous system. In

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… A randomized, double-blinded, placebo-controlled phase II trial of recombinant human leukemia inhibitory factor (rhuLIF, emfilermin, AM424) to prevent chemotherapy-induced peripheral neuropathy. Clin Cancer Res. 2005;11(5):1890–1898. doi: 10.1158/1078-0432.CCR-04-1655. 41. …

Цереброспинный грипп и биомаркеры крови для нейроаксональных повреждений при многоразовом склерозе

После появления новых данных о том, что нейродегенеративные процессы в множестве склероза (MS) присутствуют на ранних стадиях, был проявлен активный научный интерес к биомаркерам нейро-аксональных повреждений в жидкостях организма пациентов, страдающих с склерозом. Недавно проведенные исследования позволили ввести новые потенциальные биомаркеры, но в то же время прояснили патогенетическое и клиническое значение хорошо известных. В настоящем документе рассматриваются имеющиеся данные о биомаркерах нейроаксональных повреждений в крови и цереброспинных жидкостях и освещается их связь с клинически

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… Leukemia inhibitory factor induces an antiapoptotic response in oligodendrocytes through Akt-phosphorylation and up-regulation of 14-3-3. Proteomics. 2008;8(6):1237–1247. doi: 10.1002/pmic.200700641. 184. Woodcock JM, Ma Y, Coolen C, et al. …

Evidence for reciprocal network interactions between injured hearts and cancer.

Heart failure (HF) and cancer are responsible for 50% of all deaths in middle-aged people. These diseases are tightly linked, which is supported by recent epidemiological studies and case control studies, demonstrating that HF patients have a higher risk to develop cancer such as lung and breast cancer. For HF patients, a one-size-fits-all clinical management strategy is not effective and patient management represents a major economical and clinical burden. Anti-cancer treatments-mediated cardiotoxicity, leading to HF have been extensively studied. However, recent studies showed that even befo

Checking NEKs: Overcoming a Bottleneck in Human Diseases.

In previous years, several kinases, such as phosphoinositide 3-kinase (PI3K), mammalian target of rapamycin (mTOR), and extracellular-signal-regulated kinase (ERK), have been linked to important human diseases, although some kinase families remain neglected in terms of research, hiding their relevance to therapeutic approaches. Here, a review regarding the NEK family is presented, shedding light on important information related to NEKs and human diseases. NEKs are a large group of homologous kinases with related functions and structures that participate in several cellular processes such as th

Mechanism-based prediction of drug synergy via network controllability analysis of therapeutic pathways in intractable diseases.

Identifying effective drug combinations for multidrug therapies in intractable diseases remains challenging, and drug synergy depends on regulatory mechanisms. Herein, we introduce a mechanistic framework that redefines drug combination strategies into two distinct synergy paradigms-"boost" and "complement"-and present a network-based method called SYNERGIE to predict associated combinations across diseases. For diseases lacking known therapeutic targets, we introduced network controllability analysis to estimate therapeutic pathways and target molecules. SYNERGIE integrates drug-disease and d

Mesenchymal Stromal Cells: Bridging the Gaps in Hematologic Disease Therapy.

Mesenchymal stromal cells (MSCs) have demonstrated therapeutic potential in hematologic diseases by modulating immune responses, supporting hematopoiesis, and remodeling the bone marrow microenvironment. Clinically, MSCs have been explored for graft-versus-host disease and hematopoietic stem cell transplantation support, while their applications in hematologic malignancies, including acute myeloid leukemia, multiple myeloma, and myelodysplastic syndromes, remain under investigation. However, therapeutic heterogeneity, safety concerns, and standardization challenges limit their clinical transla

Chimeric Antigen Receptor T-Cells in Myasthenia Gravis: Advances, Safety Challenges, and Future Directions.

This review examines the emerging application of chimeric antigen receptor (CAR) T-cell therapy in myasthenia gravis (MG), with emphasis on safety, efficacy signals, and future therapeutic potential in treatment-refractory disease. A comprehensive literature search was conducted across PubMed, medRxiv, bioRxiv, and Google Scholar for studies published between January 1, 2010 and July 1, 2025, using the terms "CAR T-cell," "chimeric antigen receptor," and "myasthenia gravis." Eligible reports included clinical trials, case reports, case series, and mechanistic studies describing CAR T-cell ther

Biological Nanocarriers in Cancer Therapy: Cutting Edge Innovations in Precision Drug Delivery.

Cancer is a highly detrimental and fatal illness that poses a significant threat to human well-being. The pattern of cancer treatment is continuously being optimized by the advancement of old treatment approaches and the invention of novel treatment modes. Nanotechnology-based approaches are emerging as powerful candidates in the development of these advanced methods for treating tumors. This article provides a concise overview of nanotechnology for cancer or cancer nanomedicine and its applications. In light of prevalent issues, such as inadequate precision in targeting initial chemotherapy d

Лептин и Лептин Сигналинг в множестве склерозов: обзор скрипта.

Ожирение - проблема, связанная с пандемией здоровья, - в настоящее время рассматривается как хроническое провокационное состояние, связанное со многими аутоиммунными заболеваниями, такими, как множественный склероз. Таким образом, адипокины, подстрекательские посредники, скрытые жировой тканью, играют важную роль в стимулировании иммунной реакции. В этом контексте ожирение, особенно в подростковом возрасте, как представляется, является одним из ключевых факторов развития множественного склероза. Лептин, главный провоспалительный адипокин, скрытый жировой тканью, был обнаружен у пациентов с мно

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… Leptin, a 146-amino acid (16 kDa) polypeptide hormone (Zhang et al., 1994 ), shares similarities with members of the long-chain helical cytokine family (including IL-6, IL-11, IL-12, Leukemia inhibitory factor (LIF), granulocyte-colony stimulating factor (G-CSF), Ciliary neurotrophic factor (CNTF), …

Histone modifications: Unveiling the epigenetic enigma of degenerative skeletal diseases.

Degenerative skeletal diseases, including osteoporosis, osteoarthritis, and intervertebral disc degeneration, are prevalent age-related conditions characterized by progressive tissue degeneration and functional decline. Histone modifications are covalent modifications of histone residues, catalyzed by specific enzymes, that modulate chromatin architecture and transcriptional activity. Accumulating evidence highlights the critical involvement of histone modifications in orchestrating disease-associated transcriptional programs. In osteoporosis, histone modifications regulate osteoblast and oste

Editorial: The Role of Complement in Health and Disease.

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Hyperprogression disease induced by Sintilimab combined with Oxaliplatin and S-1 after surgery: a case report and literature review.

ObjectiveTo investigate the risk factors, underlying mechanisms, and preventive strategies associated with hyperprogressive disease (HPD) induced by immunotherapy.MethodsWe analyzed the clinical data of a patient who developed HPD following palliative gastrectomy and received a combination therapy of Sintilimab, S-1 (tegafur, gimeracil, and oteracil potassium), and Oxaliplatin (SOX). Additionally, a literature review on tumor immunotherapy was conducted to further explore the risk factors and mechanisms of HPD.ResultsIn this case, the development of HPD was associated with a high postoperative

Combination of Novel Therapies and New Attempts in Anaplastic Thyroid Cancer.

Anaplastic thyroid cancer (ATC) is one of the most lethal human malignancies, and it is rapidly falling without any effective therapeutic options. Although radical surgery, radiotherapy, and chemotherapy are performed on patients, the curative effect is suboptimal, and the survival rate is still poor. The discovery of altered gene pathways involved in this aggressive disease has advanced, but molecular targeted drugs targeting these pathways are still in clinical trials. To date, there is no effective way to treat this disease, so it is particularly urgent to find new treatments. At present, m

Breakthroughs in Medicinal Chemistry: New Targets and Mechanisms, New Drugs, New Hopes-7.

Breakthroughs in Medicinal Chemistry [...].

Modulation of Angiogenic Processes by the Human Gammaherpesviruses, Epstein-Barr Virus and Kaposi's Sarcoma-Associated Herpesvirus.

Angiogenesis is the biological process by which new blood vessels are formed from pre-existing vessels. It is considered one of the classic hallmarks of cancer, as pathological angiogenesis provides oxygen and essential nutrients to growing tumors. Two of the seven known human oncoviruses, Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV), belong to the Gammaherpesvirinae subfamily. Both viruses are associated with several malignancies including lymphomas, nasopharyngeal carcinomas, and Kaposi's sarcoma. The viral genomes code for a plethora of viral factors, includin

Aging microenvironment and antitumor immunity for geriatric oncology: the landscape and future implications.

The tumor microenvironment (TME) has been extensively investigated; however, it is complex and remains unclear, especially in elderly patients. Senescence is a cellular response to a variety of stress signals, which is characterized by stable arrest of the cell cycle and major changes in cell morphology and physiology. To the best of our knowledge, senescence leads to consistent arrest of tumor cells and remodeling of the tumor-immune microenvironment (TIME) by activating a set of pleiotropic cytokines, chemokines, growth factors, and proteinases, which constitute the senescence-associated sec