Novel selective agents for the degradation of AR/AR-V7 to treat advanced prostate cancer.

The androgen receptor AR antagonists, such as enzalutamide and apalutamide, are efficient therapeutics for the treatment of prostate cancer (PCa). Even though they are effective at first, resistance to both drugs occurs frequently. Resistance is mainly driven by aberrations of the AR signaling pathway including AR gene amplification and the expression of AR splice variants (e.

Lymphatic microcirculation profile in the progression of hypertension in spontaneously hypertensive rats.

Objective: The contractile behavior of collecting lymphatic vessels occurs in essential hypertension in response to homeostasis, suggesting a possible role for microcirculation. We aimed to clarify the nature of the lymphatic microcirculation profile in spontaneously hypertensive rats (SHRs) and normotensive controls.

Methods: The vasomotion of collecting lymphatic vessels in eight- and thirteen-week-old SHRs and age-matched Wistar-Kyoto rats (WKYs, n = 4 per group) was visualized by intravital video and VasTrack.

Integrated pancreatic microcirculatory profiles of streptozotocin-induced and insulin-administrated type 1 diabetes mellitus.

Objective: As an integrated system, pancreatic microcirculatory disturbance plays a vital role in the pathogenesis of type 1 diabetes mellitus (T1DM), which involves changes in microcirculatory oxygen and microhemodynamics. Therefore, we aimed to release type 1 diabetic and insulin-administrated microcirculatory profiles of the pancreas.

Methods: BALB/c mice were assigned to control, T1DM, and insulin-administrated groups randomly.

Differential expression of lncRNAs in hypertension-induced pericytes.

Pericytes facilitate vessel maturation and endothelial barrier functions closely related with the pathogenesis of organ damage from cardiovascular and cerebrovascular diseases such as hypertension. We used a computational-based strategy to first screen for differentially expressed genes and lncRNAs and characterized associations between lncRNAs of microvascular pericytes and hypertension. In total, 22 lncRNAs were upregulated and 46 were downregulated in the rats afflicted with spontaneous hypertension.

Comparison of pancreatic microcirculation profiles in spontaneously hypertensive rats and Wistar-kyoto rats by laser doppler and wavelet transform analysis.

Pancreatic microcirculatory dysfunction emerged as a novel mechanism in the development of hypertension. However, the changes of pancreatic microcirculation profiles in hypertension remain unknown. Pancreatic microcirculatory blood distribution pattern and microvascular vasomotion of spontaneously hypertensive rats (SHRs) and Wistar Kyoto rats (WKYs) were determined by laser Doppler.

Pancreatic Microcirculation Profiles in the Progression of Hypertension in Spontaneously Hypertensive Rats.

Background: Emerging evidence indicates that the pancreas serves as a major source of degrading protease activities and that uncontrolled proteolytic receptor cleavage occurs under hypertensive conditions, which leading to systemic dysfunction and end-organic damage. However, changes in pancreatic microcirculation profiles during the progression of hypertension remain unknown.

Methods: Pancreatic microcirculatory blood distribution patterns and microvascular vasomotion of spontaneously hypertensive rats (SHRs) and normotensive control Wistar Kyoto rats at 5, 8, 13, and 18 weeks of age were determined.

Multimodal Device and Computer Algorithm-Based Monitoring of Pancreatic Microcirculation Profiles In Vivo.

Objectives: Pancreatic microcirculation has an essential role in orchestrating pancreatic homeostasis. Inherent complexity and technological limitation lead to interobserver variability and 1-sided microcirculatory data. Here, we introduce a multimodal device and computer algorithm-based platform for monitoring and visualizing integrated pancreatic microcirculation profiles.

Insulin protects against type 1 diabetes mellitus-induced ultrastructural abnormalities of pancreatic islet microcirculation.

Pancreatic islet microcirculation, consisting of pancreatic islet microvascular endothelial cells (IMECs) and pericytes (IMPCs), provides crucial support for the physiological function of pancreatic islet. Emerging evidence suggests that pancreatic islet microcirculation is impaired in type 1 diabetes mellitus (T1DM). Here, we investigated the potential ultrastructural protective effects of insulin against streptozotocin (STZ)-induced ultrastructural abnormalities of the pancreatic islet microcirculation in T1DM mouse model.

Salvianolic Acid Alleviated Blood-Brain Barrier Permeability in Spontaneously Hypertensive Rats by Inhibiting Apoptosis in Pericytes via P53 and the Ras/Raf/MEK/ERK Pathway.

Objective: To investigate the effect of salvianolic acid A (SA) on the permeability of blood-brain barrier (BBB) and brain microvascular pericyte apoptosis in spontaneously hypertensive rats (SHR).

Methods: Evans Blue was used to determine the BBB permeability in control rats and SHR. Western blotting was used to evaluate the expression levels of relevant proteins in the pericytes isolated from the differentially treated animals.

Effects of nebivolol versus other antihypertensive drugs on the endothelial dysfunction in patients with essential hypertension.

We aim to determine whether nebivolol has a better effect on endothelial dysfunction compared with other β-blockers or other classes of antihypertensive drugs. Searches of the PubMed, Embase etc. were performed to analyze all the randomized controlled trials using nebivolol to treat essential hypertension.

The circulating level of miR-122 is a potential risk factor for endothelial dysfunction in young patients with essential hypertension.

MicroRNAs are key molecules involved in the regulation of endothelial function. They are important risk factors and biomarkers for the development of hypertension related to endothelial dysfunction. However, the gene expression patterns associated with hypertension development related to endothelial dysfunction have not been fully elucidated.

Differential miRNA expression analysis of extracellular vesicles from brain microvascular pericytes in spontaneous hypertensive rats.

Objective: This study is to explore the exact roles of extracellular vesicle (EVs) miRNAs from brain microvascular pericytes in the pathogenesis of hypertension.

Results: Forty-eight significantly differentially expressed miRNAs were identified, of which 17 were found to be upregulated and 31 were found to be downregulated in brain microvascular pericytes of spontaneous hypertensive rats, compared with that of normotension Wistar Kyoto rats. The GO enrichment analysis verified that the target genes were enriched in signaling pathways and molecular functions, such as metal ion binding, nucleotide binding and ATP binding.

Integrated exosomal miRNA and transcriptome analysis of brain microvascular endothelial cells in spontaneously hypertensive rats.

Endothelial cells, which regulate arterial stiffness via endothelial-derived substances, are independently and strongly associated with hypertension. However, the exact roles of exosome miRNAs from brain endothelial cells in the development of hypertension are still not fully explored. Here, we investigated the miRNA functions systematically by examining both exosomal small RNA and mRNA of endothelial cells in Wistar Kyoto (WKY) rats versus spontaneously hypertensive rats (SHRs).

Targeting the COX2/MET/TOPK signaling axis induces apoptosis in gefitinib-resistant NSCLC cells.

MET overactivation is one of the crucial reasons for tyrosine kinase inhibitor (TKI) resistance, but the mechanisms are not wholly clear. Here, COX2, TOPK, and MET expression were examined in EGFR-activating mutated NSCLC by immunohistochemical (IHC) analysis. The relationship between COX2, TOPK, and MET was explored in vitro and ex vivo.

MicroRNA-181a protects against pericyte apoptosis via directly targeting FOXO1: implication for ameliorated cognitive deficits in APP/PS1 mice.

MicroRNAs (miRNAs) have emerged as critical regulators in the pathology of Alzheimer's disease (AD). MiR-181a is associated with hippocampal memory formation and aberrantly expressed in patients with mild cognitive impairment (MCI), however, little is known about its role and underlying mechanism involved in AD. Here, we report that miR-181a expression declines in APP/PS1 mice, synchronous with the increase in amyloid β (Aβ) level, which suggests a reverse correlation between miR-181a level and AD development.

TOPK inhibits autophagy by phosphorylating ULK1 and promotes glioma resistance to TMZ.

ULK1, the upper-most protein of the ULK1 complex, is emerging as a crucial node in autophagy induction. However, the regulation of ULK1 is not fully understood. In this study, we identified TOPK (T-LAK cell-originated protein kinase), an oncokinase, as a novel upstream kinase to phosphorylate ULK1.

Epitranscriptomic mechanisms of N6-methyladenosine methylation regulating mammalian hypertension development by determined spontaneously hypertensive rats pericytes.

Pericytes maintain homeostatic functions in the blood-brain barrier. N6-methyladenosine (mA) is critical for various biological processes, but the role of mRNA mA methylation in hypertension has not been fully elucidated. The mA methylation levels of Wistar Kyoto rat pericytes and spontaneously hypertensive rat pericytes were detected via mA high-throughput sequencing.

Intraspinal administration of interleukin-7 promotes neuronal apoptosis and limits functional recovery through JAK/STAT5 pathway following spinal cord injury.

It has been previously reported that the blockade of interleukin-7 receptor (IL-7R) promotes functional recovery following spinal cord injury (SCI), however, the direct function and molecular mechanism of IL-7 involved in this pathogenic process are unclear. Here, we report that, contrary to IL-7R blockade, the intraspinal administration of IL-7 limits functional recovery following SCI. In addition, IL-7 treatment promotes neuronal apoptosis in spinal cord lesions, which may be attributed to exacerbated focal inflammatory response, as shown by increased accumulation of activated microglia/macrophage and production of proinflammatory mediators.

Exosomes Derived From Pericytes Improve Microcirculation and Protect Blood-Spinal Cord Barrier After Spinal Cord Injury in Mice.

Spinal cord injury (SCI) often leads to severe and permanent paralysis and places a heavy burden on individuals, families, and society. Until now, the therapy of SCI is still a big challenge for the researchers. Transplantation of mesenchymal stem cells (MSCs) is a hot spot for the treatment of SCI, but many problems and risks have not been resolved.

Systemic microcirculation dysfunction after low thoracic spinal cord injury in mice.

Background: Spinal cord injury (SCI) disturbs the autonomic nervous system and induces dysfunction or failure of multiple organs. The systemic microcirculation disturbance that contributes to the complications associated with SCI remains to be clarified.

Methods: We used male mice (29-32 g) and modified weight-drop injury at T10 to evaluate the systemic microcirculation dysfunction during the first 2 weeks after SCI.

Effects of tumor necrosis factor-α-induced exosomes on the endothelial cellular behavior, metabolism and bioenergetics.

Objective: To investigate the effects of TNF-α-induced exosomes release on the biological behavior, metabolism, and bioenergetics of HUVECs.

Methods: Exosomes were isolated from conditioned media of HUVECs by ultracentrifugation after treatment with or without TNF-α. HUVECs were treated with or without TNF-α, or different concentrations of exosomes isolated from conditioned media with or without TNF-α induction (T and C , respectively).

Endothelial Cells Promote Calcification in Aortic Smooth Muscle Cells from Spontaneously Hypertensive Rats.

Background/aims: Vascular calcification and hypertension are intimately linked, and the progression of hypertension is closely correlated with endothelial dysfunction. However, the role of endothelial cells (ECs) in vascular calcification of hypertension remains unclear. Therefore, the present study explored the effects of ECs on calcification of smooth muscle cells (SMCs) from aortas of spontaneously hypertensive rats (SHR).

Transcriptomic profile analysis of brain microvascular pericytes in spontaneously hypertensive rats by RNA-Seq.

Background: Changes in the structure and function of micro-vessels is the pathogenic basis of organ damage in cardiovascular and cerebrovascular diseases. Microcirculation is primarily affected in hypertension, resulting in increased vascular resistance. Pericytes are contractile cells that are embedded in the basement membrane of capillaries, and regulate endothelial cell membrane maturation, capillary blood flow, cell debris removal, and stability of endothelial cells.

A comparison of the cutaneous microvascular properties of the Spontaneously Hypertensive and the Wistar-Kyoto rats by Spectral analysis of Laser Doppler.

This work was aimed to study skin blood perfusion, vasomotion and vascular responses of the Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) in different stages of age using spectral. Laser-Doppler flowmetry (LDF) was used to examine the ears and limbs of WKY (12 and 48 weeks old) and SHR (12 and 48 weeks old). The skin blood flow oscillations (SBFOs) were studied by wavelet spectral analysis of LDF tracings.