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Vitamin C Transporters and Their Implications in Carcinogenesis.

Vitamin C is implicated in various bodily functions due to its unique properties in redox homeostasis. Moreover, vitamin C also plays a great role in restoring the activity of 2-oxoglutarate and Fe2+ dependent dioxygenases (2-OGDD), which are involved in active DNA demethylation (TET proteins), the demethylation of histones, and hypoxia processes. Therefore, vitamin C may be engaged in the regulation of gene expression or in a hypoxic state. Hence, vitamin C has acquired great interest for its plausible effects on cancer treatment. Since its conceptualization, the role of vitamin C in cancer t

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… Primarily, these members are responsible for glucose transport between the extracellular space and the cells [ 61 ]. … A recent paper by Pena et al. suggested that the vast majority of vitamin C transferred from the extracellular space into cancer cells assumes the form of DHA [ 66 ]. …

Communication in the Cancer Microenvironment as a Target for Therapeutic Interventions.

The tumor microenvironment (TME) is a complex system composed of multiple cells, such as non-cancerous fibroblasts, adipocytes, immune and vascular cells, as well as signal molecules and mediators. Tumor cells recruit and reprogram other cells to produce factors that maintain tumor growth. Communication between cancerous and surrounding cells is a two-way process and engages a diverse range of mechanisms that, in consequence, can lead to rapid proliferation, metastasis, and drug resistance, or can serve as a tumors-suppressor, e.g., through tumor-immune cell interaction. Cross-talk within the

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… The most common type of signal transition to neighboring or long-distance cells is the secretion of soluble factors into the extracellular space, like cytokines, chemokines, and growth factors. Another way of cell interaction is through adhesion molecules and gap junctions. …

Extracellular matrix dysregulation in aging, calcification, and cancer diseases: insights into cellular senescence, inflammation, and novel therapeutic strategies.

This review underscores the dynamic role of the extracellular matrix (ECM) in regulating cellular behavior and maintaining tissue homeostasis, highlighting its pivotal involvement in aging, calcification, and cancer diseases. In healthy tissues, controlled ECM remodeling provides essential biochemical and mechanical cues, but dysregulation (driven by chronic inflammation, cellular senescence, and altered intercellular communication) leads to fibrosis, calcification, and the creation of a pro-tumorigenic microenvironment. Senescent cells contribute to these changes through senescence-associated

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… Once activated, collagen molecules align in a row in the extracellular space and self-assemble in a longitudinal head-to-tail fashion 60 . …

The Immune Regulatory Role of Adenosine in the Tumor Microenvironment.

Adenosine, an immunosuppressive metabolite, is produced by adenosine triphosphate (ATP) released from dying or stressed cells and is found at high levels in the tumor microenvironment of most solid tumors. It mediates pro-tumor activities by inducing tumor cell proliferation, migration or invasion, tumor tissue angiogenesis, and chemoresistance. In addition, adenosine plays an important role in regulating anti-tumor immune responses and facilitating tumor immune escape. Adenosine receptors are broadly expressed by tumor-infiltrated immune cells, including suppressive tumor-associated macrophag

Cancer Cell Metabolism in Hypoxia: Role of HIF-1 as Key Regulator and Therapeutic Target.

In order to meet the high energy demand, a metabolic reprogramming occurs in cancer cells. Its role is crucial in promoting tumor survival. Among the substrates in demand, oxygen is fundamental for bioenergetics. Nevertheless, tumor microenvironment is frequently characterized by low-oxygen conditions. Hypoxia-inducible factor 1 (HIF-1) is a pivotal modulator of the metabolic reprogramming which takes place in hypoxic cancer cells. In the hub of cellular bioenergetics, mitochondria are key players in regulating cellular energy. Therefore, a close crosstalk between mitochondria and HIF-1 underl

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… To avoid this effect, an efflux of lactate and H + to the extracellular space occurs through proton-like monocarboxylate transporters (MCTs) [ 52 , 53 ]. … Moreover, excreted lactate contributes to regulate pH homeostasis inside the cell and acidification of the extracellular space. Lactate and/or protons in the microenvironment regulate the function of immune cells and promote invasion and metastasis [ 60 ]. …

The Role of Extracellular Vesicles in Bone Metastasis.

Multiple types of cancer have the specific ability to home to the bone microenvironment and cause metastatic lesions. Despite being the focus of intense investigation, the molecular and cellular mechanisms that regulate the metastasis of disseminated tumor cells still remain largely unknown. Bone metastases severely impact quality of life since they are associated with pain, fractures, and bone marrow aplasia. In this review, we will summarize the recent discoveries on the role of extracellular vesicles (EV) in the regulation of bone remodeling activity and bone metastasis occurrence. Indeed,

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… Extracellular Vesicles The extracellular space of the multicellular organism represents a complex environment, composed of metabolites, ions, proteins, and polysaccharides. …

Alcohol septal ablation for left ventricular outflow tract obstruction in cardiac amyloidosis: New indication for an established therapy.

Cardiac amyloidosis can occasionally demonstrate an atypical pattern of infiltration, causing asymmetric septal thickening and a left ventricular outflow tract (LVOT) gradient with systolic anterior motion (SAM) of the mitral valve resembling obstructive hypertrophic cardiomyopathy. We present a case of a 70-year-old man with cardiac light-chain amyloidosis and LVOT obstruction successfully treated with alcohol septal ablation (ASA). Following the procedure, he reported significant improvement in his heart failure symptoms as well as improvement in LVOT gradient and SAM of the mitral valve. Th

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… These deposits compress cardiomyocytes, leading to myocardial dysfunction through both stiffenings of the extracellular space and direct myocyte damage. The most common forms of amyloid that affect the heart are immunoglobulin‐derived light chains (AL) and transthyretin (TTR). …

Application of cell-derived exosomes in the hematological malignancies therapy.

Exosomes are small membrane vesicles of endocytic origin that are produced by both tumor and normal cells and can be found in physiological fluids like plasma and cell culture supernatants. They include cytokines, growth factors, proteins, lipids, RNAs, and metabolites and are important intercellular communication controllers in several disorders. According to a vast amount of research, exosomes could support or inhibit tumor start and diffusion in a variety of solid and hematological malignancies by paracrine signaling. Exosomes are crucial therapeutic agents for a variety of illnesses, such

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… In the recycling pathway, MVBs can fuse with the plasma membrane, releasing ILVs back into the extracellular space as exosomes ( Van Niel et al., 2006 ; Cocucci and Meldolesi, 2015 ). … Exosome release: when MVBs fuse with the plasma membrane, the ILVs within them are released into the extracellular space as exosomes ( Janas et al., 2015 ). …

Hypophosphatasia: Results of a Country-Wide Selective Screening Program Using NGS Technology as a First-Tier Test.

Hypophosphatasia (HPP) is a rare hereditary metabolic disorder caused by nucleotide variants (NVs) in the ALPL gene, leading to a deficiency of tissue-nonspecific alkaline phosphatase (TNSALP). HPP has a variable clinical presentation (such as impaired mineralization of bones and teeth, respiratory dysfunctions, muscle weakness, muscle and bone pain, growth deficiency, nephrocalcinosis, seizures, encephalopathy, intracranial hypertension, and intellectual disability) overlapping with other disorders which often delays a correct diagnosis. In this study, we present the results of a two-center (

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… TNSALP is a transmembrane N-glycosylated glycoprotein, anchored in the cell membrane by glycosylphosphatidylinositol anchor, facing the extracellular space. … It is predominately localized on cell surface, specifically cell plasma membrane, or can be secreted into extracellular space and circulation; in some cells (brown adipocytes) it is found anchored to mitochondrial membrane [ 8 ]. …

Exosomal miR-328 originated from pulmonary adenocarcinoma cells enhances osteoclastogenesis via downregulating Nrp-2 expression.

Osseous metastases of pulmonary carcinoma and the detailed mechanisms remain unclear, and the effects of exosomes (Exos) originated from pulmonary adenocarcinoma cells in this process have received a lot of attentions. Our study revealed that the Exos secreted from A549 cells (A549-Exos) enhanced osteoclastogenesis and osseous resorption in vitro. In addition, A549-Exos showed a targeted effect on bones to enhance osseous resorption in vivo. A549-exosomal miR-328 enhanced osseous resorption via downregulating neuropilin 2 (Nrp-2) expression, and A549-Exos miR-328 inhibitors suppressed osseous

Overhauling CAR T Cells to Improve Efficacy, Safety and Cost.

Gene therapy is now surpassing 30 years of clinical experience and in that time a variety of approaches has been applied for the treatment of a wide range of pathologies. While the promise of gene therapy was over-stated in the 1990's, the following decades were met with polar extremes between demonstrable success and devastating setbacks. Currently, the field of gene therapy is enjoying the rewards of overcoming the hurdles that come with turning new ideas into safe and reliable treatments, including for cancer. Among these modalities, the modification of T cells with chimeric antigen recepto

Нацеливаюсь на иммунологический синапс в нескольких миэломах.

Иммунологический синапс, высокоорганизованный соединитель клеток, является важной основой для эффективного убийства раковых клеток с помощью Т. Однако в миеломе терапевтическое сопротивление отражает множество взаимодействующих слоев, включая синаптическое нарушение, клональную эволюцию, метаболическую перепрограммирование и пространственные неоднородные ниши костного мозга, которые могут способствовать дисфункции Т-клеток и иммунной отток. В этом обзоре иммунологический синапс в качестве потенциально изменяемого межклеточного интерфейса: мы описываем, как ниша костного мозга влияет на синапти

Оценка клинической значимости анализатора растворимой крови на миелоидных клетках 2 в неврологических болезнях.

Преобразование рецептора, выраженного на миелиоидных клетках 2 (TREM2), является одним из ключевых регуляторов микроглиальной и периферической функции миелиоидных клеток, причем его растворимая форма (STREM2) становится биомаркером нейроинфламмации. Хотя цереброспинная жидкость (CSF) sTREM2 постоянно повышается в нейродегенеративных болезнях, клиническая значимость sTREM2 крови остается неясной. Мы провели ретроспективное исследование, в котором приняли участие 547 человек: болезнь Альцгеймера (AD, n = 142), слабое когнитивное расстройство (MCI, n = 42), множественный склероз (MS, n = 105), на

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… Given that sTREM2 is released into the extracellular space following proteolytic cleavage by ADAM10/17 and meprin β from both microglia and peripheral macrophages, blood sTREM2 levels may reflect not only CNS microglial activation but also peripheral macrophage and Schwann cell activity (Carmona et al …

A Case of Light Chain Deposition Disease Leading to Acute Liver Failure and Review of Literature.

Light chain deposition disease (LCDD) is a monoclonal immunoglobulin deposition disease characterized by light chain deposition in soft tissues and viscera, causing systemic organ dysfunction with an underlying lymphoproliferative disorder. While the kidney is the most affected organ, cardiac and hepatic involvement is also seen with LCDD. Hepatic manifestation can range from mild hepatic injury to fulminant liver failure. Herein, we are presenting a case of an 83-year-old woman with a monoclonal gammopathy of undetermined significance (MGUS), who presented to our institution with acute liver

Malignant mesothelioma tumours: molecular pathogenesis, diagnosis, and therapies accompanying clinical studies.

The pathetic malignant mesothelioma (MM) is a extremely uncommon and confrontational tumor that evolves in the mesothelium layer of the pleural cavities (inner lining- visceral pleura and outer lining- parietal pleura), peritoneum, pericardium, and tunica vaginalis and is highly resistant to standard treatments. In mesothelioma, the predominant pattern of lesions is a loss of genes that limit tumour growth. Despite the worldwide ban on the manufacture and supply of asbestos, the prevalence of mesothelioma continues to increase. Mesothelioma presents and behaves in a variety of ways, making dia

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… After asbestos exposure, mesothelial cells die, releasing HMGB1 and TNF-α into the extracellular space. Mesothelial cells undergo metamorphosis when the NF-κB pathway is activated. …

Regulatory T cells and immune escape in HCC: understanding the tumor microenvironment and advancing CAR-T cell therapy.

Liver cancer, which most commonly manifests as hepatocellular carcinoma (HCC), is the sixth most common cancer in the world. In HCC, the immune system plays a crucial role in the growth and proliferation of tumor cells. HCC achieve immune escape through the tumor microenvironment, which significantly promotes the development of this cancer. Here, this article introduces and summarizes the functions and effects of regulatory T cells (Tregs) in the tumor microenvironment, highlighting how Tregs inhibit and regulate the functions of immune and tumor cells, cytokines, ligands and receptors, etc, t

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… However, research has shown that following cellular damage, intracellular ATP is released into the extracellular space through vesicle exocytosis and membrane transporters. CD39 on the surface of Treg cells then metabolizes ATP into ADP and AMP, and CD73 subsequently converts AMP into adenosine. …

Pathogenesis and kidney prognosis of renal amyloidosis.

Light chain (AL), serum amyloid A (AA), transthyretin (ATTR), leukocyte cell derived chemotaxin 2 (ALECT2), and fibrinogen Aa (AFib) amyloidosis are some of the most common types of protein-deposition disorders involving the kidney. Each amyloidogenic protein differs in its origin and little is known about the exact mechanisms that govern renal tropism and tissue injury for each amyloid subtype. While amyloidogenic precursor protein is different in each subtype of amyloidosis, its aggregation into fibrils depositing in target organs and leading to disruption of tissue architecture and progress

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… The amyloidogenic light chains undergo partial digestion preferentially in the mature lysosomal compartment where enzymatic activity (such as with cathepsin B) and the acidic environment stimulates fibrillogenesis prior to exocytosis into the extracellular space [ 21 , 24 , 26 – 28 ]. … 24460740 Teng J, Turbat-Herrera EA, Herrera GA (2014) Extrusion of amyloid fibrils to the extracellular space in experimental mesangial AL-amyloidosis: transmission and scanning electron microscopy studies and correlation with renal biopsy observations. …

Применение мезенхимальных ячеек и их эксзоом в нейродегенеративных заболеваниях и лизосомных заболеваниях.

Мезенхимальные стромальные клетки (МСЦ) стали перспективной терапевтической платформой для расстройств центральной нервной системы, включая нейродегенеративные заболевания и лизосомные расстройства хранения (ЛСД). В настоящем обзоре рассматриваются механизмы КБМ, связанные с активностью паракрина, иммуномодуляцией, воздействием антиоксидантов, регулированием с помощью ТФЭБ, а также с ферментатической перекрестной корректировкой в ЛСД, хотя и критически оцениваются проблемы перевода. Мы проводим сравнительный анализ источников КБМ, административных маршрутов, дозирующих режимов и характеристик

Роль олигодендроцитов в нейродегенеративных болезнях: разрушение слоев.

Нейродегенеративные заболевания (НБ), включая болезнь Альцгеймера, болезнь Паркинсона, амиотропический боковой склероз/моторный нейрон, и множественный склероз, характеризуются постепенной утратой нейронной структуры и функции, что приводит к серьезным когнитивным, моторным и поведенческим расстройствам. Они представляют собой серьезную и растущую проблему, обусловленную их растущей распространенностью и воздействием на глобальные системы здравоохранения. Общественные и эмоциональные последствия для пациентов, лиц, обеспечивающих уход, и инфраструктуры здравоохранения значительны. Несмотря на

Потенциал CfDNA в качестве биомаркера: возможности и проблемы, связанные с нейродегенеративными заболеваниями.

Нейродегенеративные расстройства, включая болезнь Альцгеймера (AD), болезнь Паркинсона (PD), множественный склероз (MS) и амиотропический боковой склероз (ALS), характеризуются постепенным и постепенным дегенерацией нейронов. Показатели распространенности и распространенности этих заболеваний с возрастом значительно возрастают. Поскольку продолжительность жизни во многих странах продолжает увеличиваться, ожидается, что в обозримом будущем число таких случаев возрастет. Ранняя и точная диагностика, наряду с надлежащим наблюдением, по-прежнему сопряжена с трудностями. Высокая неоднородность нейр