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Liposomes for the Treatment of Brain Cancer-A Review.

Due to their biocompatibility, non-toxicity, and surface-conjugation capabilities, liposomes are effective nanocarriers that can encapsulate chemotherapeutic drugs and facilitate targeted delivery across the blood-brain barrier (BBB). Additionally, strategies have been explored to synthesize liposomes that respond to internal and/or external stimuli to release their payload controllably. Although research into liposomes for brain cancer treatment is still in its infancy, these systems have great potential to fundamentally change the drug delivery landscape. This review paper attempts to consol

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… Considered the most selective barrier in the human body, the BBB is primarily composed of tightly joined endothelial cells connected by tight junctions (TJs) and adherens junctions (AJs), along with a thin layer of pericytes. … Astrocytic glia, pericytes, microglia, and neuronal processes are closely associated and surround the brain capillaries. This specialization of the endothelium of blood vessels entering the brain during development is crucial [ 42 ]. …

Facing CAR T Cell Challenges on the Deadliest Paediatric Brain Tumours.

Central nervous system (CNS) tumours comprise 25% of the paediatric cancer diagnoses and are the leading cause of cancer-related death in children. Current treatments for paediatric CNS tumours are far from optimal and fail for those that relapsed or are refractory to treatment. Besides, long-term sequelae in the developing brain make it mandatory to find new innovative approaches. Chimeric antigen receptor T cell (CAR T) therapy has increased survival in patients with B-cell malignancies, but the intrinsic biological characteristics of CNS tumours hamper their success. The location, heterogen

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… The BBB is composed of capillary endothelial, pericytes, astrocytes, neurons, and the extracellular matrix conforming to a neurovascular unit that protects the brain and maintain homeostasis [ 59 ]. … Non-tumour cells include microglial cells, endothelial cells, pericytes, fibroblasts, and immune cells. While several of these cell types are also prevalent in brain tumours, some important features distinguish the brain tumour stroma from other tissues. …

Cyclic nucleotide phosphodiesterases as drug targets.

Cyclic nucleotides are synthesized by adenylyl and/or guanylyl cyclase, and downstream of this synthesis, the cyclic nucleotide phosphodiesterase families (PDEs) specifically hydrolyze cyclic nucleotides. PDEs control cyclic adenosine-3',5'monophosphate (cAMP) and cyclic guanosine-3',5'-monophosphate (cGMP) intracellular levels by mediating their quick return to the basal steady state levels. This often takes place in subcellular nanodomains. Thus, PDEs govern short-term protein phosphorylation, long-term protein expression, and even epigenetic mechanisms by modulating cyclic nucleotide levels

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… Furthermore, a role for pericyte PDE3A in cAMP regulation relevant to angiogenesis and permeability was proposed ( Spiranec et al, 2018 ). … Activation of pericytes leads to endothelial cell leakage, worsens NO-mediated vasodilation, and is antiangiogenic. This is prevented by PDE5 inhibitor sildenafil in a pericyte-EC coculture model ( Majumder et al, 2007 ). …

Molecular and cellular mechanisms of aging in hematopoietic stem cells and their niches.

Aging drives the genetic and epigenetic changes that result in a decline in hematopoietic stem cell (HSC) functioning. Such changes lead to aging-related hematopoietic/immune impairments and hematopoietic disorders. Understanding how such changes are initiated and how they progress will help in the development of medications that could improve the quality life for the elderly and to treat and possibly prevent aging-related hematopoietic diseases. Here, we review the most recent advances in research into HSC aging and discuss the role of HSC-intrinsic events, as well as those that relate to the

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… Heterogeneity of BM MSCs and ECs Like HSCs and HPCs, MSCs in BM are also a mixture of cell populations which are enriched for MSC-stem cells (MSC-SCs) and early progenitors for adipocytes, osteoblasts, chondrocytes, pericytes and fibroblasts as demonstrated by cell surface markers, gene expression profiles … Such types of MSCs have been defined as Nestin-GFP + , CD45 − CD31 − Sca1 + CD24 + , < 10% of LepR + or Pdgfr + Sca1 + CD51 + which have the ability to generate CFU-F and mesenspheres in in vitro culture and can differentiate into all lineages of MSCs including adipocytes, osteoblasts, chondrocytes, pericytes …

The updated landscape of tumor microenvironment and drug repurposing.

Accumulating evidence shows that cellular and acellular components in tumor microenvironment (TME) can reprogram tumor initiation, growth, invasion, metastasis, and response to therapies. Cancer research and treatment have switched from a cancer-centric model to a TME-centric one, considering the increasing significance of TME in cancer biology. Nonetheless, the clinical efficacy of therapeutic strategies targeting TME, especially the specific cells or pathways of TME, remains unsatisfactory. Classifying the chemopathological characteristics of TME and crosstalk among one another can greatly b

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… and T cells, as well as B cells, natural killer (NK) cells, tumor-associated macrophages (TAMs), myeloid-derived suppressor cells (MDSCs), mast cells, granulocytes, dendritic cells (DCs), tumor-associated neutrophils, cancer-associated fibroblasts (CAFs), adipocytes, vascular endothelial cells, and pericytes … Adding aspirin activates the AMPK pathway and induces tumor cell apoptosis, whereas adding atenolol inhibits pericytes in breast cancer microenvironment; both increase the metformin-induced inhibition of complex I. 222 Targeting the acidic niche Metformin impairs the proliferation and colony formation …

Новый взгляд на механизмы нейродегенерации в экспериментальном аутоиммунном энцефаломелите и многоразовом склерозе: ранняя и критическая роль платец в нейро/аксональной потере.

Множественный склероз (MS) — аутоиммунное расстройство центральной нервной системы (CNS) с ограниченными возможностями лечения. Для этого заболевания характерны различия в патофизиологии между серым веществом (GM) и белым веществом (WM). Преобладающей отличительной чертой ВМ является периваскулярная доска, связанная с потерей функции мозгового барьера (ББД), инфильтрацией лимфоцитов, микроглиальной реактивностью, обезвоживанием и аксонной травмой и должным образом обработанная иммуномодулятивными препаратами. С другой стороны, механизмы, лежащие в основе ущерба ГМ, остаются неясными, что имеет

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… This includes, for example, the early role of perivascular macrophages in leukocyte infiltration, ahead of onset of clinical symptoms (Hoffmann et al. 2002 ; Polfliet et al. 2002 ), and of pericytes in facilitating macrophage entry into the CNS via the secretion of ICAM-1 and VCAM-1 and expression …

NLRP3 воспаление в нейро-воспалении и заболеваниях центральной нервной системы.

Нейроинфламмация играет важную роль в патогенезе различных заболеваний центральной нервной системы (КНС). NLRP3 является важным внутриклеточным многопротеиновым комплексом, состоящим из врожденного иммунного рецептора NLRP3, адаптационного белка ASC и протеза каспе-1. Активация NLRP3 испарения может вызвать пироптоз и высвобождение проинфламамина IL-1β и IL-18, тем самым играя центральную роль в иммунной и подстрекательской реакции. Недавние исследования показали, что воспаление NLRP3 активируется в мозгу, с тем чтобы вызвать нейроинфламму, что приводит к дальнейшим нейронным повреждениям и фу

Antibody drug conjugates in recurrent or metastatic cervical cancer: a focus on tisotumab vedotin state of art.

Cervical cancer (CC) is still characterized by a poor prognosis despite the progress made in its treatment in recent years. Although immunotherapy has improved outcomes for advanced/recurrent disease, there is a significant gap in addressing patients' needs when they progress after platinum and immunotherapy treatments. In this setting, traditional chemotherapy showed limited effectiveness. In this context, antibody-drug conjugates (ADCs) emerged as a promising tool within targeted cancer therapies. Tisotumab vedotin (TV), an ADC targeting tissue factor, represents the first ADC approved by th

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… In healthy conditions, TF is absent from blood and endothelial cells, being expressed in many extravascular cells, such as fibroblasts, pericytes, and vascular smooth muscle cells. …

Несапонин из Панакс Гинсенг поддерживает целостность мозгового барьера, подавляя NF-ИБ и p38 MAP cinase сигнализирующих путей для предотвращения развития экспериментального аутоиммунного энцефаломиэлита.

НЕСАпонинская (NS) фракция является важным активным компонентом Панакс Гинсенга, имеющей многофункциональную фармакологическую деятельность, включая нейрозащиту, иммунную регламентацию, противовоспалительные и антиоксидантные эффекты. Однако воздействие НС на множественный склероз (МС) - хроническое и аутоиммунное демиелионирующее расстройство - пока еще не доказано. Цель настоящего исследования состояла в том, чтобы продемонстрировать фармакологические действия НСУ по дисфункциям движения и соответствующие механизмы действий с использованием экспериментальной аутоиммунной энцефаломиелитной мо

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… The BBB is composed of endothelial cells, pericytes, and astrocytes, which produce a neurovascular unit with adjacent neurons [ 14 , 15 ]. Therefore, we evaluated changes in these components in LSCs from all groups ( Fig.4A–F ). …

How I treat unique and difficult-to-manage cases of CAR T-cell therapy-associated neurotoxicity.

With growing indications for chimeric antigen receptor (CAR) T-cell therapy, toxicity profiles are evolving. There is an urgent and unmet need of approaches to optimally manage emerging adverse events that extend beyond the standard paradigm of cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome (ICANS). Although management guidelines exist for ICANS, there is little guidance on how to approach patients with neurologic comorbidities, and how to manage rare neurotoxicity presentations, such as CAR T-cell therapy-related cerebral edema, severe motor complications

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… In a recent study, single-cell sequencing analyses demonstrated CD19 expression on human brain mural cells, including pericytes and vascular smooth muscle cells, and it was proposed that an on-target off-tumor effect may contribute to the neurotoxicity observed with CD19 CAR T cells. 66 However, it is …

Macrophage miR-149-5p induction is a key driver and therapeutic target for BRONJ.

Bisphosphonate-related (BP-related) osteonecrosis of the jaw (BRONJ) is one of the severe side effects of administration of BPs, such as zoledronic acid (ZA), which can disrupt the patient's quality of life. Although the direct target of skeletal vasculature and bone resorption activity by BPs has been phenomenally observed, the underlying mechanism in BRONJ remains largely elusive. Thus, it is urgently necessary to discover effective therapeutic targets based on the multifaceted underlying mechanisms in the development of BRONJ. Here, we determined the inhibitory role of ZA-treated macrophage

Mechanisms and management of CAR T toxicity.

Chimeric antigen receptor (CAR) T cell therapies have dramatically improved treatment outcomes for patients with relapsed or refractory B-cell acute lymphoblastic leukemia, large B-cell lymphoma, follicular lymphoma, mantle cell lymphoma, and multiple myeloma. Despite unprecedented efficacy, treatment with CAR T cell therapies can cause a multitude of adverse effects which require monitoring and management at specialized centers and contribute to morbidity and non-relapse mortality. Such toxicities include cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, neuro

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… When human brain vascular pericytes were exposed in vitro to IFN-ɣ and TNF-α, pericyte secretion of IL-6 and VEGF was observed which further increased blood-brain barrier disruption. …

Revisiting the standards of cancer detection and therapy alongside their comparison to modern methods.

In accordance with the World Health Organization data, cancer remains at the forefront of fatal diseases. An upward trend in cancer incidence and mortality has been observed globally, emphasizing that efforts in developing detection and treatment methods should continue. The diagnostic path typically begins with learning the medical history of a patient; this is followed by basic blood tests and imaging tests to indicate where cancer may be located to schedule a needle biopsy. Prompt initiation of diagnosis is crucial since delayed cancer detection entails higher costs of treatment and hospita

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… CAFs may derive from myeloid precursor cells, normal fibroblasts that have acquired genetic mutations, epithelial cells that have undergone epithelial-to-mesenchymal transition, mesenchymal stem cells, or less commonly pericytes and smooth muscle cells[ 68 ]. … In addition, no sufficient exclusion criteria exist among various mesenchymal lineages (such as pericytes or adipocytes), the correlation with specific cancer types/locations is unclear, and few experimental studies have been performed. …

In Vivo Bone Tissue Engineering Strategies: Advances and Prospects.

Reconstruction of critical-sized bone defects remains a tremendous challenge for surgeons worldwide. Despite the variety of surgical techniques, current clinical strategies for bone defect repair demonstrate significant limitations and drawbacks, including donor-site morbidity, poor anatomical match, insufficient bone volume, bone graft resorption, and rejection. Bone tissue engineering (BTE) has emerged as a novel approach to guided bone tissue regeneration. BTE focuses on in vitro manipulations with seed cells, growth factors and bioactive scaffolds using bioreactors. The successful clinical

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… incorporation of the GF in the scaffold Use of the angiogenic cell cultures | Direct delivery of endothelial cells into the implantation site (scaffold-based or scaffold free techniques) Hypoxia-induced vascularization | Promoting the proliferation and sprouting of endothelial cells Recruitment of pericytes … The outer fibrous layer contains highly organized and directional collagen fibers (Sharpey’s fibers), and a smaller number of cells, mostly fibroblasts and pericytes [ 225 , 226 ]. …

The evolving roles of Wnt signaling in stem cell proliferation and differentiation, the development of human diseases, and therapeutic opportunities.

The evolutionarily conserved Wnt signaling pathway plays a central role in development and adult tissue homeostasis across species. Wnt proteins are secreted, lipid-modified signaling molecules that activate the canonical (β-catenin dependent) and non-canonical (β-catenin independent) Wnt signaling pathways. Cellular behaviors such as proliferation, differentiation, maturation, and proper body-axis specification are carried out by the canonical pathway, which is the best characterized of the known Wnt signaling paths. Wnt signaling has emerged as an important factor in stem cell biology and is

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… Isl1, in turn, mediates proinsulin production and processing via the regulation of PCSK1, PCSK2, SLC30A8, MAFA, PDX1, and NKX6.1. 317 Inactivation of TCF7L2 in the pancreatic pericytes of transgenic mice led to poor glucose tolerance as a result of β-cell dysfunction and impaired glucose-stimulated insulin … These findings were accompanied by the discovery that TCF7L2-dependent pericytic expression of secreted factors such as BMP4 promoted β-cell function. …

Angioprevention of Urologic Cancers by Plant-Derived Foods.

The number of cancer cases worldwide keeps growing unstoppably, despite the undeniable advances achieved by basic research and clinical practice. Urologic tumors, including some as prevalent as prostate, bladder or kidney tumors, are no exceptions to this rule. Moreover, the fact that many of these tumors are detected in early stages lengthens the duration of their treatment, with a significant increase in health care costs. In this scenario, prevention offers the most cost-effective long-term strategy for the global control of these diseases. Although specialized diets are not the only way to

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… Consequently, the detachment of pericytes and degradation of basement membrane and extracellular matrix (ECM) takes place. Then, other angiogenic factors promote endothelial cell proliferation and migration to initiate a new sprout. … In parallel, mesenchymal cells differentiate into smooth muscle cells and pericytes that participate in the subsequent stabilization of the new blood vessel. …

Histone Modifier KANSL2 является практически осуществимым биомаркером в Мультимиломе.

Эпигенетические отклонения являются ключевыми движущими силами множественной миеломы, однако адресная терапия, использующая эпигенетические изменения, еще не установлена. Объединяя клинические и молекулярные наборы пациентов с множественной миеломой с непредвзятым генетическим экраном в vivo, мы определили подгруппу 2 (KANSL2) КАТ8, регулирующую комплекс NSL, как гистонную послетрансляционную модификацию, связанную с онкогене. Высокое выражение KANSL2 было связано с неблагоприятным прогнозом у пациентов с множественной миеломой. Генетические модели &quot; наживы &quot; и &quot; потери функцион

Научные достижения в отношении роли остеобластов и их производных в разработке, повторении и удалении метастаза злокачественных опухолей костей: обзор повествования.

Злоумышленные опухоли костей, включая первичные опухоли костей, такие, как остеосаркома (OS), саркома Евинга (ES) и множественная миелома, а также вторичные опухоли костей от рака простаты и груди, создают значительный риск смертности. Остеобласт (OBs) и их производные играют важнейшую роль в развитии, повторении и метастазе этих опухолей. ОБ пропагандируют события, связанные с метастазом, включая остеокластную дифференциацию и распространение. Их производные, включая внеклеточные везикли и цитокины, модулярируют реконструкцию костей и развитие опухоли по различным сигнальным путям. Недавние и

Molecular events in the jaw vascular unit: A traditional review of the mechanisms involved in inflammatory jaw bone diseases.

Inflammatory jaw bone diseases are common in stomatology, including periodontitis, peri-implantitis, medication-related osteonecrosis of the jaw, radiation osteomyelitis of the jaw, age-related osteoporosis, and other specific infections. These diseases may lead to tooth loss and maxillofacial deformities, severely affecting patients' quality of life. Over the years, the reconstruction of jaw bone deficiency caused by inflammatory diseases has emerged as a medical and socioeconomic challenge. Therefore, exploring the pathogenesis of inflammatory diseases associated with jaw bones is crucial fo

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… CXCL12 triggers the expansion of mature Myh11 + CXCR4 + pericytes that differentiate into osteoblasts and contribute to bone formation [ 109 ] . …

Implications of Angiogenesis Involvement in Arthritis.

Angiogenesis, the growth of new blood vessels, is essential in the pathogenesis of joint inflammatory disorders such as rheumatoid arthritis (RA) and osteoarthritis (OA), facilitating the invasion of inflammatory cells and increase in local pain receptors that contribute to structural damage and pain. The angiogenic process is perpetuated by various mediators such as growth factors, primarily vascular endothelial growth factor (VEGF) and hypoxia-inducible factors (HIFs), as well as proinflammatory cytokines, various chemokines, matrix components, cell adhesion molecules, proteases, and others.

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… Lastly, blood vessels are stabilized by pro-angiogenic factors such as Ang1, followed by incorporation of pericytes into the newly formed basement membrane to facilitate the blood flow process (see Figure 1 ). 3. …