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An understanding of mitochondria and its role in targeting nanocarriers for diagnosis and treatment of cancer.

Nanotechnology has changed the entire paradigm of drug targeting and has shown tremendous potential in the area of cancer therapy due to its specificity. In cancer, several targets have been explored which could be utilized for the better treatment of disease. Mitochondria, the so-called powerhouse of cell, portrays significant role in the survival and death of cells, and has emerged as potential target for cancer therapy. Direct targeting and nanotechnology based approaches can be tailor-made to target mitochondria and thus improve the survival rate of patients suffering from cancer. With thi

miRNAs and lncRNAs as Novel Therapeutic Targets to Improve Cancer Immunotherapy.

Immunotherapy is presently one of the most promising areas of investigation and development for the treatment of cancer. While immune checkpoint-blocking monoclonal antibodies and chimeric antigen receptor (CAR) T-cell-based therapy have recently provided in some cases valuable therapeutic options, the goal of cure has not yet been achieved for most malignancies and more efforts are urgently needed. Noncoding RNAs (ncRNA), including microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), regulate several biological processes via selective targeting of crucial molecular signaling pathways. Recent

Advances in chimeric antigen receptor T-cell therapy for B-cell non-Hodgkin lymphoma.

B-cell non-Hodgkin lymphoma (B-NHL) is a group of heterogeneous disease which remains incurable despite developments of standard chemotherapy regimens and new therapeutic agents in decades. Some individuals could have promising response to standard therapy while others are unresponsive to standard chemotherapy or relapse after autologous hematopoietic stem-cell transplantation (ASCT), which indicates the necessity to develop novel therapies for refractory or relapsed B-NHLs. In recent years, a novel cell therapy, chimeric antigen receptor T-cell therapy (CAR-T), was invented to overcome the li

Consensus Recommendations for the Diagnosis and Management of X-Linked Hypophosphatemia in Belgium.

X-linked hypophosphatemia (XLH) is the most common genetic form of hypophosphatemic rickets and osteomalacia. In this disease, mutations in the PHEX gene lead to elevated levels of the hormone fibroblast growth factor 23 (FGF23), resulting in renal phosphate wasting and impaired skeletal and dental mineralization. Recently, international guidelines for the diagnosis and treatment of this condition have been published. However, more specific recommendations are needed to provide guidance at the national level, considering resource availability and health economic aspects. A national multidiscip

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

High-Dose Intravenous Immunoglobulins in the Treatment of Severe Acute Viral Pneumonia: The Known Mechanisms and Clinical Effects.

The current outbreak of viral pneumonia, caused by novel coronavirus SARS-CoV-2, is the focus of worldwide attention. The WHO declared the COVID-19 outbreak a pandemic event on Mar 12, 2020, and the number of confirmed cases is still on the rise worldwide. While most infected individuals only experience mild symptoms or may even be asymptomatic, some patients rapidly progress to severe acute respiratory failure with substantial mortality, making it imperative to develop an efficient treatment for severe SARS-CoV-2 pneumonia alongside supportive care. So far, the optimal treatment strategy for

Targeting Tumor Microenvironment for Cancer Therapy.

Cancer development is highly associated to the physiological state of the tumor microenvironment (TME). Despite the existing heterogeneity of tumors from the same or from different anatomical locations, common features can be found in the TME maturation of epithelial-derived tumors. Genetic alterations in tumor cells result in hyperplasia, uncontrolled growth, resistance to apoptosis, and metabolic shift towards anaerobic glycolysis (Warburg effect). These events create hypoxia, oxidative stress and acidosis within the TME triggering an adjustment of the extracellular matrix (ECM), a response

The Relevance of Mass Spectrometry Analysis for Personalized Medicine through Its Successful Application in Cancer "Omics".

Mass spectrometry (MS) is an essential analytical technology on which the emerging omics domains; such as genomics; transcriptomics; proteomics and metabolomics; are based. This quantifiable technique allows for the identification of thousands of proteins from cell culture; bodily fluids or tissue using either global or targeted strategies; or detection of biologically active metabolites in ultra amounts. The routine performance of MS technology in the oncological field provides a better understanding of human diseases in terms of pathophysiology; prevention; diagnosis and treatment; as well a

Acute and Chronic Respiratory Failure in Cancer Patients

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mTOR Cross-Talk in Cancer and Potential for Combination Therapy.

The mammalian Target of Rapamycin (mTOR) pathway plays an essential role in sensing and integrating a variety of exogenous cues to regulate cellular growth and metabolism, in both physiological and pathological conditions. mTOR functions through two functionally and structurally distinct multi-component complexes, mTORC1 and mTORC2, which interact with each other and with several elements of other signaling pathways. In the past few years, many new insights into mTOR function and regulation have been gained and extensive genetic and pharmacological studies in mice have enhanced our understandi

Preclinical Evaluation of a Lentiviral Vector for Huntingtin Silencing.

Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder resulting from a polyglutamine expansion in the huntingtin (HTT) protein. There is currently no cure for this disease, but recent studies suggest that RNAi to downregulate the expression of both normal and mutant HTT is a promising therapeutic approach. We previously developed a small hairpin RNA (shRNA), vectorized in an HIV-1-derived lentiviral vector (LV), that reduced pathology in an HD rodent model. Here, we modified this vector for preclinical development by using a tat-independent third-generation LV (pCCL) ba

Lost in Translation (LiT): IUPHAR Review 6.

Translational medicine is a roller coaster with occasional brilliant successes and a large majority of failures. Lost in Translation 1 ('LiT1'), beginning in the 1950s, was a golden era built upon earlier advances in experimental physiology, biochemistry and pharmacology, with a dash of serendipity, that led to the discovery of many new drugs for serious illnesses. LiT2 saw the large-scale industrialization of drug discovery using high-throughput screens and assays based on affinity for the target molecule. The links between drug development and university sciences and medicine weakened, but t

The 48th Annual Meeting of the European Society for Blood and Marrow Transplantation: Physicians - Oral Sessions (O009-O155).

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Breathing new life into T-cell receptor-engineered T-cell therapy in solid tumors: enhancing strategies to expand the universality of precision therapy.

Adoptive T-cell transfer therapy (ACT) has significantly propelled the advancement of tumor immunotherapy. Among various strategies targeting solid tumors, the T-cell receptor (TCR)-engineered T-cell (TCR-T cell) therapy has emerged as a highly promising approach, exhibiting an expanded therapeutic window across diverse patient populations and superior tumoricidal activity in certain solid malignancies compared with chimeric antigen receptor T cell (CAR-T) and tumor-infiltrating T cells/lymphocyte (TIL) therapies. However, its clinical efficacy remains constrained. In this paper, we introduce

Immune Checkpoint Inhibitors and Immunomodulators for Cancer Immunotherapy: Insights Into Resistance and Therapeutic Strategies.

Cancer immunotherapy has redefined cancer treatment. However, the molecular and cellular basis of immune evasion and therapeutic resistance remains incompletely understood. Early immune checkpoint inhibitors have delivered significant clinical benefit, but their efficacy and durability remain limited in many patients. These limitations have driven the exploration of next-generation immune checkpoints and additional regulatory pathways that shape tumor-immune interactions. Recent advances have broadened the immune checkpoint landscape and revealed new targets. These targets operate within inter

The Multifaceted Nature of GLP-1: Molecular Mechanisms and Signaling Pathways in Metabolic and Neurodegenerative Diseases.

The aim of this article is to present the current state of knowledge regarding the use of GLP-1 agonists in the treatment of type 2 diabetes, obesity, and other potential clinical indications, including neurodegenerative conditions. The article describes the characteristics of the diseases discussed, with particular emphasis on the pathophysiological mechanisms and the impact of metabolic disorders on the course of the diseases. In addition, the specific role of GLP-1 receptor agonists and their mechanisms of action leading to improved clinical outcomes were discussed, including their impact o

The evolving landscape of CAR T cell therapy in children and young adults with B cell acute lymphoblastic leukemia.

Chimeric antigen receptor (CAR) T cells have demonstrated remarkable ability to render multiple relapsed and refractory patients into a deep and often durable remission. Since initial FDA approval of tisagenlecleucel in 2017, real-world data have shown the benefit of this therapy, even among historically complex populations, such as infants, children with Down syndrome, and those with extramedullary leukemia. Despite the success of CAR T cell therapy, nearly half of patients tend to show relapsed disease, demanding ongoing advancements. Furthermore, the incorporation of the bispecific T cell e

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… Bai Z., Woodhouse S., Zhao Z., Arya R., Govek K., Kim D., Lundh S., Baysoy A., Sun H., Deng Y., et al. Single-cell antigen-specific landscape of CAR T infusion product identifies determinants of CD19-positive relapse in patients with ALL. Sci. Adv. 2022;8 doi: 10.1126/sciadv.abj2820. 97. …

Osteocytes in the Metastatic Bone Niche: Mechanistic Pathways and Therapeutic Targets.

Osteocytes, once viewed mainly as passive bone-embedded cells, are now recognized as active regulators of the metastatic bone niche. Emerging evidence indicates that these cells integrate mechanical, inflammatory, and tumor-derived cues to influence metastatic seeding, dormancy, reactivation, and lesion progression in bone. This review synthesizes current understanding of osteocyte contributions to skeletal metastasis. We discuss core signaling axes, including osteocyte-derived RANKL/OPG balance, Wnt antagonists (sclerostin/DKK1), mechanotransduction pathways (Piezo1 signaling and connexin-43

" Глаза как окно к нейродегенерации: окисляющий стресс " , " Оптическая уязвимость нерва " и " Стержневой обзор биомаркеров-а " .

Нейродегенеративные заболевания представляют собой серьезное и растущее бремя для здоровья населения мира, характеризующееся постепенной нейронной дисфункцией, аксонной дегенерацией и необратимой потерей нейронных тканей. Все больше фактов указывает на окислительный стресс как на один из нескольких взаимодействующих патогенных механизмов в болезни Альцгеймера, болезни Паркинсона, амиотропического бокового склероза и нескольких оптических нейропот. Все больше внимания уделяется оси мозга и сетчатки, поскольку сетчатка и зрительный нерв делятся структурными, метаболическими и молекулярными харак

Tumour Cell Size Control and Its Impact on Tumour Cell Function.

Cell size is an important component of cell morphological characteristics. It reflects the characteristics of the cell type, nutritional status, growth stage and physiological function. The cell size of cells of the same type tends to be homogeneous and stable. However, in tumour cells, mutations in cell cycle genes and cytoskeletal genes and overexpression of the corresponding signalling pathways often lead to large variations in tumour cell size. Tumour cells regulate cell size and growth and proliferation through multiple signalling pathways, such as PI3K/Akt/mTOR, Myc and Hippo pathways, w