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The Role of Angiogenesis in Haemophilic Arthropathy: Where Do We Stand and Where Are We Going?

Haemophilia is an inherited bleeding disorder that can lead to degenerative joint arthropathy due to recurrent bleeding episodes affecting the musculoskeletal system of the patient. The cause of bleeding can be either traumatic or spontaneous. The pathogenesis of haemophilic arthropathy is unclear as many factors like iron, inflammatory cytokines, and angiogenic factors contribute to this process. Blood into joints can deteriorate the bone to such an extent that the patient experiences pain, reduction of the range of movement, and deformity of the joint, conditions that could have a great impa

Острая ТРЕМ2 ингибиция истощает MAFB-высокую микроглию и препятствует воссоединению.

Мы изучили роль в регенерации миелоидных клеток 2 (TREM2) в мозгу. TREM2 является рецептором, который активирует микроглию, которая имеет решающее значение для удаления миелинового мусора и поощрения ремиэлизации. Предыдущие исследования в мышечной модели демиелинции, вызванной медным агентом Cuprizone (CPZ), показали, что стимуляция TREM2 с моноколональным антителом уменьшает демиелинацию, в то время как удаление гена Trem2 в мышах ухудшает ремиелионацию. Здесь мы резко заблокировали функцию TREM2 с антителом как на стадии обезвоживания, так и на стадии ремиэлирования модели CPZ и проанализир

The real-world safety of Ofatumumab: a pharmacovigilance analysis based on the FDA adverse event reporting system.

BACKGROUND: Ofatumumab is a humanized monoclonal antibody that targets CD20-positive B cells. It was approved by the FDA in 2020 for the treatment of relapsing multiple sclerosis (RMS) in adult patients, and in 2009 for the treatment of Chronic Lymphocytic Leukemia (CLL). With the escalating clinical application of Ofatumumab, comprehending its safety profile within actual healthcare environments is of considerable importance. METHODS: This study compiled a dataset derived from the FAERS database, which included real-world safety data on Ofatumumab from Q4 2009 to Q2 2024. We applied four dis

Computational study of SENP1 in cancer by novel natural compounds and ZINC database screening.

Introduction: Sentrin-specific protease 1 (SENP1) is a protein whose main function is deSUMOylation. SENP1 inhibits apoptosis, and increases angiogenesis, estrogen and androgen receptor transcription and c-Jun transcription factor, proliferation, growth, cell migration, and invasion of cancer. The in vivo and in vitro studies also demonstrated which natural compounds, especially phytochemicals, minerals, and vitamins, prevent cancer. More than 3,000 plant species have been reported in modern medicine. Natural compounds have many anti-cancerous andanti-turmeric properties such as antioxidative,

Antimitotic drugs in the treatment of cancer.

Cancer is a complex disease since it is adaptive in such a way that it can promote proliferation and invasion by means of an overactive cell cycle and in turn cellular division which is targeted by antimitotic drugs that are highly validated chemotherapy agents. However, antimitotic drug cytotoxicity to non-tumorigenic cells and multiple cancer resistance developed in response to drugs such as taxanes and vinca alkaloids are obstacles faced in both the clinical and basic research field to date. In this review, the classes of antimitotic compounds, their mechanisms of action and cancer cell res

Disorders of the Gastrointestinal System

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Skin Telocytes Could Fundament the Cellular Mechanisms of Wound Healing in Platelet-Rich Plasma Administration.

For more than 40 years, autologous platelet concentrates have been used in clinical medicine. Since the first formula used, namely platelet-rich plasma (PRP), other platelet concentrates have been experimented with, including platelet-rich fibrin and concentrated growth factor. Platelet concentrates have three standard characteristics: they act as scaffolds, they serve as a source of growth factors and cytokines, and they contain live cells. PRP has become extensively used in regenerative medicine for the successful treatment of a variety of clinical (non-)dermatological conditions like alopec

Spectrum of sublytic astrocytopathy in neuromyelitis optica.

Neuromyelitis optica is an autoimmune inflammatory disorder targeting aquaporin-4 water channels in CNS astrocytes. Histopathological descriptions of astrocytic lesions reported in neuromyelitis optica so far have emphasized a characteristic loss of aquaporin-4, with deposition of IgG and complement and lysis of astrocytes, but sublytic reactions have been underappreciated. We performed a multi-modality study of 23 neuromyelitis optica autopsy cases (clinically and/or pathologically confirmed; 337 tissue blocks). By evaluating astrocytic morphology, immunohistochemistry and AQP4 RNA transcript

Voltage-gated sodium channel as a target for metastatic risk reduction with re-purposed drugs.

ObjectiveTo determine the exact role of sodium channel proteins in migration, invasion and metastasis and understand the possible anti-invasion and anti-metastatic activity of repurposed drugs with voltage gated sodium channel blocking properties.Material and methodsA review of the published medical literature was performed searching for pharmaceuticals used in daily practice, with inhibitory activity on voltage gated sodium channels. For every drug found, the literature was reviewed in order to define if it may act against cancer cells as an anti-invasion and anti-metastatic agent and if it w

Одноклеточная транскриптомика для иммунного профилирования цереброспинной жидкости в неврологических заболеваниях.

В ходе этого всеобъемлющего обзора мы прорабатываем значительный объем исследований по одноклеточной транскриптомике в цереброспайнальной жидкости (CSF) для понимания неврологических заболеваний с аутоиммунным, нейродегенеративным, инфекционным или онкогенным происхождением. Мы тщательно изучаем все опубликованные исследования в этих областях с особым акцентом на множественный склероз, болезнь Альцгеймера и болезнь Паркинсона. Что касается этих заболеваний, то мы анализируем результаты, связанные с иммунными клетками, проникающими в мозг, на основе вскрытого анализа тканей мозга и с использова

Implications of regulatory T cells in anti-cancer immunity: from pathogenesis to therapeutics.

Regulatory T cells (Tregs) play an essential role in maintaining immune tolerance and suppressing inflammation. However, Tregs present major hurdle in eliciting potent anti-cancer immune responses. Therefore, curbing the activity of Tregs represents a novel and efficient way towards successful immunotherapy of cancer. Moreover, there is an emerging interest in harnessing Treg-based strategies for augmenting anti-cancer immunity in different types of the disease. This review summarises the crucial mechanisms of Tregs' mediated suppression of anti-cancer immunity and strategies to suppress or to

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… In particular, it has been suggested that hypoxic stress in TME leads to ATP release into extracellular space by exocytosis or pannexin-1 channels [ 106 ]. … The accumulation of adenosine in the extracellular space is supported by HIF-mediated inhibition of the nucleoside transporter ENT-1 which impedes adenosine transport into the cell and removes it from the extracellular space [ 106 ]. …

Arctiin Inhibits Inflammation, Fibrosis, and Tumor Cell Migration in Rats With Ehrlich Solid Carcinoma.

Background and objectivesESC or Ehrlich solid carcinoma is a type of tumor originating from a spontaneous mammary adenocarcinoma in mice. It is a highly aggressive and fast-growing carcinoma that can create a solid mass when inserted under the skin. Its solid, undifferentiated form makes it an ideal model for researching cancer biology, tumor immunology, and testing various anti-cancer treatments. Additionally, arctiin has multiple beneficial properties, such as anti-proliferative, anti-oxidative, anti-adipogenic, and anti-bacterial. This study aimed to explore the potential anti-cancer benefi

Rethinking the Combination of Proton Exchanger Inhibitors in Cancer Therapy.

Microenvironmental acidity is becoming a key target for the new age of cancer treatment. In fact, while cancer is characterized by genetic heterogeneity, extracellular acidity is a common phenotype of almost all cancers. To survive and proliferate under acidic conditions, tumor cells up-regulate proton exchangers and transporters (mainly V-ATPase, Na⁺/H⁺ exchanger (NHE), monocarboxylate transporters (MCTs), and carbonic anhydrases (CAs)), that actively extrude excess protons, avoiding intracellular accumulation of toxic molecules, thus becoming a sort of survival option with many similarities

Conditioned Media-Derived Tumor Extracellular Vesicles: Bridging Molecular Insights and Therapeutic Applications in Oncology.

Tumor-derived extracellular vesicles (EVs) are major mediators of oncogenic intercellular communication. However, many studies using conditioned media (CM) recover operationally defined EV- or small EV-enriched fractions rather than biogenesis-proven exosomes. This review synthesizes evidence from CM-derived tumor EV studies and aligns their biological interpretation with current EV nomenclature, characterization, and reporting principles. We first discuss exosome biogenesis as a defined endosomal pathway and then examine how CM collection, serum handling, culture format, oxygen tension, condi

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… When MVBs fuse with the plasma membrane, ILVs are released into the extracellular space as exosomes (Figure 1 ) (Han et al. 2022 ; Mashouri et al. 2019 ). … Once released into the extracellular space, tumor‐derived EVs can interact with recipient cells and contribute to intercellular communication processes involved in tumor progression. …

Monitoring concentration and lipid signature of plasma extracellular vesicles from HR+ metastatic breast cancer patients under CDK4/6 inhibitors treatment.

Extracellular vesicles (EVs) are cell-derived small membrane structures that transport various molecules. They have emerged as potential circulating biomarkers for monitoring responses to cancer therapies. This study aimed to comprehensively characterize plasma-carried EVs in hormone receptor-positive (HR+) metastatic breast cancer (MBC) patients treated with first-line CDK4/6 inhibitors (iCDK4/6) combined with endocrine therapy. MBC patients were classified into three groups based on their response to therapy: resistant, intermediate or sensitive. In a prospective cohort, we monitored the con

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… INTRODUCTION Extracellular vesicles (EVs) are lipid bilayer nanoparticles ranging from 40 to 1000 nm in size, released by all cells into the extracellular space and present in various body fluids, including urine, saliva and blood (Colombo et al., 2014 ; Costa‐Silva et al., 2015 ; Fujita et al., 2016 …

Диагностика амиотропического бокового склероза: до настоящего времени.

Амиотрофический боковой склероз (ALS) — прогрессивное нейродегенеративное заболевание, характеризующееся постепенной потерей верхних и нижних моторных нейронов и их путей, обычно без воздействия на экстракулярные и сфинктерные мышцы. Причины этого заболевания пока не известны. Это цепь последующих событий, заканчивающихся запрограммированной клеточной смертью в селективных нейронных поднаселениях. Прогнозы на выживание довольно коротки с медианой 2 в адрес 4 Годы. Выживание может быть продлено на основе оперативной диагностики, подтипа ALS и надлежащего управления с помощью поддерживающего леч

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… They develop due to excessive apoptotic death of neurons, which probably occurs due to the accumulation of abnormal protein aggregates in the cytoplasm or nucleus of the cell, but also in the extracellular space [ 2 ]. Oxidative stress plays an important role [ 3 ]. … This protein can be prion-like propagated via the extracellular space by vesicular exocytosis between individual neurons or remotely through the corticospinal pathway [ 32 ]. …

Механистическая взаимосвязь между множественной миеломой и тяжелой SARS-CoV-2 Инфекция: терапевтическое обещание месенхимальных стволовых ячеек с внешней клеткой.

Пациенты с множественной миеломой (ММ) демонстрируют глубокое иммунное регулирование, предвосхищая их до тяжелых результатов после SARS-CoV-2 инфекция. Текущие данные свидетельствуют о наличии общих иммунопатологических механизмов, связывающих ММ и COVID-19, с уделением особого внимания interleukin-6 (В тыс.IL-6) ось как общий усилитель воспаления, а не как единственный движитель болезни. Для ММ характерна исходная провоспалительная среда, частично обусловленная: IL-6, которая еще больше усиливается в течение SARS-CoV-2 Инфекция, приводящая к эскалации цитокина, дополняет активацию, коагулопат

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… They form through inward budding of late endosomal membranes, leading to the formation of intraluminal vesicles within multivesicular bodies, which are subsequently released into the extracellular space following fusion with the plasma membrane [ 68 ]. …

Exosomes to exosome-functionalized scaffolds: a novel approach to stimulate bone regeneration.

Bone regeneration is a complex biological process that relies on the orchestrated interplay of various cellular and molecular events. Bone tissue engineering is currently the most promising method for treating bone regeneration. However, the immunogenicity, stable and cell quantity of seed cells limited their application. Recently, exosomes, which are small extracellular vesicles released by cells, have been found to effectively address these problems and better induce bone regeneration. Meanwhile, a growing line of research has shown the cargos of exosomes may provide effective therapeutic an

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… The mature endosomes evolve into multivesicular bodies, which ultimately fuse with the cell membrane under the action of Rab enzymes and are released into the extracellular space via exocytosis, thus forming exosomes. …

An Updated Comprehensive Review on Diseases Associated with Nephrotic Syndromes.

There have been exciting advances in our knowledge of primary glomerular diseases and nephrotic syndromes in recent years. Beyond the histological pattern from renal biopsy, more precise phenotyping of the diseases and the use of modern nephrogenetics helps to improve treatment decisions and sometimes also avoid unnecessary exposure to potentially toxic immunosuppression. New biomarkers have led to easier and more accurate diagnoses and more targeted therapeutic decisions. The treatment landscape is becoming wider with a pipeline of promising new therapeutic agents with more sophisticated appr

Diagnosis and treatment of cystic lung disease.

Cystic lung disease (CLD) is a group of lung disorders characterized by the presence of multiple cysts, defined as air-filled lucencies or low-attenuating areas, bordered by a thin wall (usually < 2 mm). The recognition of CLDs has increased with the widespread use of computed tomography. This article addresses the mechanisms of cyst formation and the diagnostic approaches to CLDs. A number of assessment methods that can be used to confirm CLDs are discussed, including high-resolution computed tomography, pathologic approaches, and genetic/ serologic markers, together with treatment modalities

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… Amyloidosis Amyloidosis is an extremely rare and heterogeneous group of disorders characterized by the deposition of a specific protein (amyloid) in extracellular spaces in an abnormal fibrillary fashion. …