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Immunoregulation of follicular renewal, selection, POF, and menopause in vivo, vs. neo-oogenesis in vitro, POF and ovarian infertility treatment, and a clinical trial.

The immune system plays an important role in the regulation of tissue homeostasis ("tissue immune physiology"). Function of distinct tissues during adulthood, including the ovary, requires (1) Renewal from stem cells, (2) Preservation of tissue-specific cells in a proper differentiated state, which differs among distinct tissues, and (3) Regulation of tissue quantity. Such morphostasis can be executed by the tissue control system, consisting of immune system-related components, vascular pericytes, and autonomic innervation. Morphostasis is established epigenetically, during morphogenetic (deve…

Mineralocorticoid Receptor Antagonism Reduces Atrial Arrhythmias Post-Cardiac Surgery and Attenuates Atrial Stress Responses to Cardioplegic Arrest.

BACKGROUND: New postoperative atrial fibrillation (POAF) occurs in about 40% after cardiac surgery. Mineralocorticoid receptor antagonists ( … other cardiac preservation associated genes that show elevated expression in atrial macrophages and pericytes from chronic AF atria. CONCLUSIONS: Our studies show that preoperative MRA use is associated with 40% reduction in POAF as well as lowering long standing AF development by about 41%. Our cold cadiac preservation-reperfusion model showed that canren …

Coordinated inflammatory macrophage and vascular smooth muscle cell remodeling signatures in human atherosclerosis: An integrative single-cell and bulk transcriptomic analysis.

Atherosclerotic plaque progression is shaped by coordinated inflammatory and remodeling programs involving immune cells and vascular wall cells. Inflammatory macrophage activation and vascular smooth muscle cell (VSMC) phenotypic remodeling are central features of human atherosclerosis, but their transcriptomic relationships during plaque progression remain incompletely characterized. This study integrated single-cell and bulk transcriptomic datasets to examine highly inflammatory macrophage states, VSMC remodeling-related transcriptional programs, and candidate ligand-receptor expression patt

Impaired coagulation, liver dysfunction and COVID-19: Discovering an intriguing relationship.

Coronavirus disease 2019 (COVID-19) is, at present, one of the most relevant global health problems. In the literature hepatic alterations have been described in COVID-19 patients, and they are mainly represented by worsening of underlying chronic liver disease leading to hepatic decompensation and liver failure with higher mortality. Several potential mechanisms used by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to cause liver damage have been hypothesized. COVID-19 primary liver injury is less common than secondary liver injury. Most of the available data demonstrate how li

The effects of Vitis vinifera L. phenolic compounds on a blood-brain barrier culture model: Expression of leptin receptors and protection against cytokine-induced damage.

ETHNOPHARMACOLOGICAL RELEVANCE: The medicinal properties of grapes (Vitis vinifera L.) are well known since ancient times. Ethnobotanical gr … LS AND METHODS: For the BBB model, primary cultures of rat brain endothelial cells, glial cells and pericytes were used in co-culture. Cells were treated by tumor necrosis factor-α (TNF-α) and interleukin-1 β (IL-1β) (10 ng/ml each) to induce damage. Cell toxicity was evaluated by the measurement of impedance. The expression of leptin receptors was assessed …

Constraint-induced movement therapy enhances angiogenesis and neurogenesis after cerebral ischemia/reperfusion.

Constraint-induced movement therapy after cerebral ischemia stimulates axonal growth by decreasing expression levels of Nogo-A, RhoA, and Rho-associated kinase (ROCK) in the ischemic boundary zone. However, it remains unclear if there are any associations between the Nogo-A/RhoA/ROCK pathway and angiogenesis in adult rat brains in pathological processes such as ischemic stroke. In addition, it has not yet been reported whether constraint-induced movement therapy can promote angiogenesis in stroke in adult rats by overcoming Nogo-A/RhoA/ROCK signaling. Here, a stroke model was established by mi

Obstructive uropathy.

Chronic tubulointerstitial nephritis (TIN), characterized by tubular atrophy, interstitial fibrosis and inflammation, is a major prognostic … marrow-derived fibrocytes and the transformation of tubular epithelial cells, endothelial cells and pericytes into interstitial fibroblasts. Activated interstitial fibroblasts are responsible for the increased synthesis of extracellular matrix protein. This together with an impairment of various fibrolytic pathways leads to the increased deposition of extra …

Molecular mechanism leading to human coronary atherosclerosis assessed by proteomic analysis and RNA sequences.

BACKGROUND AND AIMS: Atherosclerosis results from cellular and extracellular changes in the arterial wall, preceded by molecular shifts that … ines in mitochondrial energy biosynthesis proteins, evidence of vascular unit activation (including pericytes), and neurovascular and neuroimmune modulation (all FDR P < .01). These early changes preceded the expected immune cell recruitment and innate immune response characteristic of atherosclerotic plaque formation. Analysis of transcriptional regulatory …

[Molecular mechanisms of vasculogenesis and angiogenesis. What regulates vascular growth?].

The basic mechanisms governing how endothelial cells, periendothelial cells, matrix molecules and blood constituents interact with each other are discussed. The many insights gained from this basic knowledge are being extended to further understand physiological and pathological features of vascular sprouting and maintenance. Understanding these basic principles that drive angiogenesis and vasculogenesis will lead to a more specific therapy of many disorders in ophthalmology and other fields, such as arteriosclerosis, tumor growth, myocardial ischemia and tissue repair.

Scavenging acrolein with 2-HDP preserves neurovascular integrity in a rat model of diabetic retinal disease.

AIMS/HYPOTHESIS: Diabetic retinal disease (DRD) is characterised by progressive neurovascular unit (NVU) dysfunction, often occurring before visible microvascular damage. Our previous studies suggested that the accumulation of acrolein (ACR)-derived protein adducts on retinal Müller cells and neuronal proteins may contribute to NVU dysfunction in diabetes, although this has yet to be directly tested. In this study, we evaluated the effects of the novel ACR-scavenging drug 2-hydrazino-4,6-dimethylpyrimidine (2-HDP) on retinal NVU dysfunction in experimental diabetes and explored its potential f

Characterization and angiogenic potential of CD146+ endometrial stem cells.

BACKGROUND: The human endometrium, lining the inner uterus, regenerates over 400 times uniquely during a woman's reproductive life. Endometrial stem cells (eSCs) enrich the tissue, resulting in a dense vascular network, significant angiogenic potential, and effective regeneration power. Being of natural angiogenic properties and proven effective in the treatment of vascular disorders, eSCs can be considered safe, reliable, and superior to other post-natal stem cells. Cluster of Differentiation 146 (CD146) has emerged as a pivotal marker associated with pericytes and endothelial cells for promo…

Neural deletion of Tgfbr2 impairs angiogenesis through an altered secretome.

Simultaneous generation of neural cells and that of the nutrient-supplying vasculature during brain development is called neurovascular coupling. We report on a transgenic mouse with impaired transforming growth factor β (TGFβ)-signalling in forebrain-derived neural cells using a Foxg1-cre knock-in to drive the conditional knock-out of the Tgfbr2. Although the expression of FOXG1 is assigned to neural progenitors and neurons of the telencephalon, Foxg1(cre/+);Tgfbr2(flox/flox) (Tgfbr2-cKO) mutants displayed intracerebral haemorrhage. Blood vessels exhibited an atypical, clustered appearance we

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

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… It was found that pericytes are directly involved in the process of angiogenesis as increasing pericyte coverage via Ang-2 inhibition can potentially represent an antiangiogenic tumour therapy [ 22 , 23 ]. … In order to protect them, PDGF stimulates pericytes, which migrate to the place of the angiogenesis and embrace the vessels with dendritic processes, forming a stabilising coat. The presence of pericytes is considered a sign of maturity. …

Compound Danshen Dripping Pills retards the progression of cerebral cavernous malformations via strengthening vascular integrity and ameliorating inflammatory response.

BACKGROUND: Cerebral cavernous malformations (CCMs) are characterized by abnormal clusters of dilated, thin-walled capillaries in the brain that are prone to bleeding, which give rise to a range of neurological symptoms including seizures and stroke. Current therapeutic strategies are restricted to surgical resection, highlighting the requirement for effective and efficient treatments. OBJECTIVE: In this study, we investigated the therapeutic potential of Compound Danshen Dripping Pills (CDDP) as a traditional Chinese medicine (TCM) against the progression of CCMs. METHODS: Ultra-performance

Single-Cell Multiomics Integration Reveals Cell Trajectories and Regulatory Networks in Breast Cancer Progression.

BACKGROUND: Breast cancer is a molecularly heterogeneous disease encompassing distinct subtypes with divergent prognoses and therapeutic responses. Despite extensive bulk genomic characterization, the single-cell transcriptional trajectories, chromatin regulatory landscapes, and intercellular communication networks that drive breast cancer progression from luminal to mesenchymal states remain incompletely understood. Emerging evidence implicates gut microbiome dysbiosis as a systemic modulator of breast cancer risk, immune regulation, and treatment response; however, its coordinated characteri

Defining the Role of Oral Pathway Inhibitors as Targeted Therapeutics in Arteriovenous Malformation Care.

Arteriovenous malformations (AVMs) are vascular malformations that are prone to rupturing and can cause significant morbidity and mortality in relatively young patients. Conventional treatment options such as surgery and endovascular therapy often are insufficient for cure. There is a growing body of knowledge on the genetic and molecular underpinnings of AVM development and maintenance, making the future of precision medicine a real possibility for AVM management. Here, we review the pathophysiology of AVM development across various cell types, with a focus on current and potential druggable

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… Mouse models demonstrate the increased diameter of bAVM vessels with a loss of surrounding pericytes [ 74 ]. … These findings were corroborated by human immunofluorescence models that found reductions in pericyte number and density in bAVM tissue compared to temporal lobe tissue, reduced pericyte coverage in ruptured bAVMs, and a correlation between reduced pericyte number with microhemorrhage severity and blood …

Escaping Antiangiogenic Therapy: Strategies Employed by Cancer Cells.

Tumor angiogenesis is widely recognized as one of the "hallmarks of cancer". Consequently, during the last decades the development and testing of commercial angiogenic inhibitors has been a central focus for both basic and clinical cancer research. While antiangiogenic drugs are now incorporated into standard clinical practice, as with all cancer therapies, tumors can eventually become resistant by employing a variety of strategies to receive nutrients and oxygen in the event of therapeutic assault. Herein, we concentrate and review in detail three of the principal mechanisms of antiangiogenic

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… Another mechanism of antiangiogenic therapy resistance involves an increase in pericyte coverage. … In ovarian and esophageal cancer xenografts bevacizumab increases pericyte coverage of vessels [ 115 ], as mentioned previously pericytes play a major role in EC maintenance and resistance to VEGFR inhibitors. …

Пути к прогрессивной инвалидности при множественном склерозе: роль глиальных клеток в хроническом воспалении CNS.

Множественный склероз (MS) является наиболее распространенным неинфекционным воспалительным заболеванием CNS, характеризующимся прогрессивным нейродегенерацией и точечными демиелинированными повреждениями. Традиционно считается аутоиммунным заболеванием, MS движет атака иммунной системы на CNS Myelin, что приводит к кумулятивной инвалидности. Однако традиционные методы борьбы с воспламенением часто не позволяют предотвратить постепенное ухудшение состояния, особенно при отсутствии открытого воспаления, что подчеркивает необходимость более глубокого понимания его патогенеза. Недавние исследован

Mechanisms of cytokine release syndrome and neurotoxicity of CAR T-cell therapy and associated prevention and management strategies.

Chimeric antigen receptor (CAR) T-cell therapy has yielded impressive outcomes and transformed treatment algorithms for hematological malignancies. To date, five CAR T-cell products have been approved by the US Food and Drug Administration (FDA). Nevertheless, some significant toxicities pose great challenges to the development of CAR T-cell therapy, most notably cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Understanding the mechanisms underlying these toxicities and establishing prevention and treatment strategies are important. In this r

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… Cytokines have access to pericytes, inducing pericyte stress and consequent VEGF and IL-6 release to further activate endothelial cells. CD19 CAR T-cells trigger CD19-positive pericyte depletion. … IFN-γ can also inhibit the platelet-derived growth factor receptor β (PDGFRβ) signaling pathway, which is crucial for the proliferation and migration of pericytes, inducing pericyte stress and disrupting their regulatory role in the BBB [ 77 , 78 ]. …

Вирус Эпштейн-Барр, витамин D и иммунная реакция: связи с последствиями множественного склероза.

Множественный склероз (MS) — аутоиммунное заболевание центральной нервной системы (CNS) без какого-либо окончательного запуска. Однако эпидемиологические исследования показывают, что важными факторами риска являются такие экологические факторы, как инфекция вируса Эпштейн-Барр (ЭБВ) и низкий уровень витамина D (вид D) у генетически предрасположенных лиц. Одно из ведущих предложений заключается в том, что EBV приводит в действие MS с помощью таких механизмов, как молекулярная имитация, где активированные автоматически реактивные B и T лимфоциты ошибочно нацелены на самоантигены. В соответствии

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… These cells are surrounded by pericytes and astrocytes, responsible for controlling the cellular exchange between blood and CNS ( 124 ). Pericytes are mural cells involved in sustaining BBB integrity and remyelination of the CNS lesions in MS. … Pericytes in multiple sclerosis. In: Birbrair A, editor. Pericyte Biology in Disease. Springer International Publishing, Cham: (2019). p. 167–87. 128. Dehghani L, Meamar R, Etemadifar M, Sheshde ZD, Shaygannejad V, Sharifkhah M, et al. …