Changes In Blood Vessels Research Articles

Metabolomics analysis of rat blood in atherosclerosis modelling

Introduction. Atherosclerotic changes in blood vessels are one of the main causes of death from cardiovascular diseases worldwide. The use of modern approaches to the study of the disease giving a more detailed description of its pathophysiology may open up additional opportunities for prevention, diagnosis, and treatment. Metabolomics is one of such approaches allows obtaining information on a large number of compounds, the combination of which reflects ongoing metabolic changes. The data presented in this article supplement our previously published study results. The study aimed to find the relationship between the thickness of the wall of the thoracic aorta in animals on a hyperlipidemic diet and the content of metabolites in the blood. Materials and methods. The study involved thirty male albino Wistar rats. Atherosclerosis was modelled using a diet consisting of standard feed, simple sugars and fats with the addition of vitamin D3 and Thiamazole. Liquid chromatography with tandem mass spectrometry was used for the metabolomics blood test. Histological sections of rat thoracic aortas were stained with hematoxylin and eosin for the analysis. Results. Histopathological examination of the thoracic aorta in the animals fed with the atherogenic diet revealed morphological signs of atherosclerosis with severe calcification of the vascular wall. The wall of the thoracic aorta in cases (2.61 ± 0.05 µm) was statistically thicker than in the controls (1.82 ± 0.01 µm) (p < 0.001). Correlation analysis revealed significant negative relationships between thoracic aortic wall thickness and arginine, indole and three of its derivatives, and ketodeoxycholic acid, and positive relationships with glutamate, ophthalmic acid, adenosine diphosphate, two long-chain acylcarnitines, glycocholic acid, oxidized fatty acid, and six lysoglycerophospholipids. Limitations. The study included only Wistar rats with a limited number of rodents per group. Conclusion. The relationship between metabolomic alterations in blood and thickness of the wall of the rat thoracic aorta indicates metabolic restructuring typical for atherosclerosis, resulting from oxidative stress, an ongoing inflammatory response, and lipid metabolism disorders characterized by severe calcification, endothelial dysfunction, and increased thrombosis.

Histomorphological Changes of Placental Terminal Villi and Stem Villous Blood Vessel in Normotensive and Eclamptic Mothers

Context: The placenta is a vital organ through which mother and fetus come in close contact with eachother. The important component of the placenta is chorionic villi and it is fully dependent on maternal bloodflow for getting proper oxygen supply. In eclampsia, placental insufficiency results various placental villouschanges which may lead to adverse fetal outcome. Aim: The study was done to see the histomorphologicalchanges of placental terminal villi and stem villous blood vessels in the case of eclamptic mothers. Thesefindings will guide clinicians to adopt appropriate plans for treatment and management of subsequentpregnancies. Materials and Methods: This cross-sectional study was conducted in the Department ofAnatomy, Dhaka Medical College, Dhaka, from January 2017 to December 2017. Seventy full-termplacentae (35 from normotensive and 35 from eclamptic mothers) were collected. After tissue processing,histomorphological changes were studied under a light microscope. Data were analyzed using the UnpairedStudent’s t-test. Result: Among normal pregnant and eclamptic mothers, the diameter of placental terminalvilli (70.17±3.34;50.19±3.29), the capillary of terminal villi (35.50±2.23;30.62±1.80), and luminaldiameter of stem villous blood vessel(33.63±3.95;15.63±3.67) respectively were significantly reduced incase of eclamptic mothers. Conclusion: The present study reveals significant differences in the diameter ofterminal villi and terminal villous capillaries in eclamptic mothers’ placentas. The luminal diameter of stemvillous blood vessels also showed a significant difference in the placenta of eclamptic mothers.

Accurate retinal vessel segmentation in OCT-A images based on MsTCG-Net

Optical coherence tomography angiography (OCT-A) is a non-invasive visualization imaging technology with high-resolution that can more clearly image tiny blood vessels. Using OCT-A imaging technology, certain ophthalmic diseases can be better diagnosed by the morphological changes of retinal blood vessels. However, the task of segmenting retinal vessels is still very challenging due to the large variation in vessel size and shape and the presence of noise. In this paper, by introducing a transformer with a self-attention mechanism, we propose a novel multi-scale transformer-based channel and global attention network (MsTCG-Net) for segmentation of blood vessels in retinal OCT-A images. In MsTCG-Net, transformer-based channel joint attention (TC) block and transformer-based global joint attention (TG) block are proposed to capture multi-semantic features from spatial and channel dimension and fuse global contextual semantic features from different layers of encoder. Experimental results show that our proposed method achieves better segmentation performance than other state-of-the-art U-Net-based methods.

Accurate retinal vessel segmentation in OCT-A images based on MsTCG-Net

Optical coherence tomography angiography (OCT-A) is a non-invasive visualization imaging technology with high-resolution that can more clearly image tiny blood vessels. Using OCT-A imaging technology, certain ophthalmic diseases can be better diagnosed by the morphological changes of retinal blood vessels. However, the task of segmenting retinal vessels is still very challenging due to the large variation in vessel size and shape and the presence of noise. In this paper, by introducing a transformer with a self-attention mechanism, we propose a novel multi-scale transformer-based channel and global attention network (MsTCG-Net) for segmentation of blood vessels in retinal OCT-A images. In MsTCG-Net, transformer-based channel joint attention (TC) block and transformer-based global joint attention (TG) block are proposed to capture multi-semantic features from spatial and channel dimension and fuse global contextual semantic features from different layers of encoder. Experimental results show that our proposed method achieves better segmentation performance than other state-of-the-art U-Net-based methods.

Preliminary application of ulnar cortex transverse transport technique in treatment of upper extremity thromboangiitis obliterans

To investigate the feasibility and effectiveness of ulnar cortex transverse transport technique in treating upper extremity thromboangiitis obliterans (TAO). A retrospective analysis was conducted on the clinical data of 7 male patients with upper extremity TAO who were admitted and met the inclusion criteria between January 2019 and July 2022. The patients ranged in age from 32 to 50 years, with a mean age of 40.1 years. The disease duration ranged from 6 to 24 months, averaging 13.6 months. The smoking history ranged from 8 to 31 years, with a mean of 18.4 years. All patients presented with finger ulcers or gangrene, including 1 case affecting the thumb and index finger, 1 case affecting the index and middle fingers, 1 case affecting the middle and ring fingers, 1 case affecting only the ring finger, and 3 cases affecting the ring and little fingers. The preoperative visual analogue scale (VAS) score was 9.1±0.7. All patients underwent treatment with the ulnar cortext transverse transport technique. The wound healing time and the disappearance time of rest pain were recorded. The VAS score was used to assess the degree of hand pain before and after operation. Serum interleukin 6 (IL-6) levels were measured before operation and at 1 month after operation. Computed tomography angiography (CTA) of the affected limb was performed before operation and at 3 months after operation to evaluate changes in blood vessels. The clinical outcomes were evaluated at 1 year after operation based on the Patwa and Krishnan grading system. All 7 patients were followed up 12-17 months, with an average of 13.7 months. All patients experienced successful healing of ulcers, with wound healing time ranging from 14 to 21 days, averaging 17.3 days. During the follow-up, no complication occurred, and there was no recurrence of ulcers. The disappearance time of rest pain ranged from 8 to 15 days, averaging 12.1 days. The pre- and post-operative (1-month) serum IL-6 levels were (25.1±5.9) pg/mL and (11.9±2.9) pg/mL, respectively, with a significant difference ( t=5.363, P=0.002). CTA examination at 3 months after operation revealed partial revascularization of upper extremity arteries and establishment of collateral circulation, showing significant improvement compared to preoperative status. The VAS scores at 1, 7, 28 days, and 6 months postoperatively were 6.4±0.8, 3.7±0.8, 0.6±0.8, and 0.1±0.4, respectively, all of which significantly improved compared to preoperative scores ( P<0.05). Furthermore, the VAS scores gradually decreased over time, with significant differences observed between postoperative time points ( P<0.05). At 1 year after operation, the effectiveness of all 7 patients were evaluated as excellent based on the Patwa and Krishnan grading system. The ulnar cortex transverse transport technique can improve blood circulation in the upper limb of patients with TAO, reconstruct microcirculation, inhibit inflammation, promote ulcer healing, and alleviate limb pain.

Enhancing sensitivity in wireless capacitive pressure sensors via highly flexible LC circuits utilizing porous polydimethylsiloxane dielectric layer

In this study, we introduce a highly flexible LC circuit-based wireless capacitive pressure sensor (CPS) that utilizes porous polydimethylsiloxane (PDMS) as a dielectric layer, demonstrating its transformative potential in tactile sensing, physiological monitoring, and flexible electronics. To optimize sensor performance, various porous PDMS thin films (100 μm) with different porosities (ranging from 0 % to 75 %) were prepared using a novel steaming method, and their properties were thoroughly analyzed using field emission scanning electron microscopy (FE-SEM) and capacitance measurements. Remarkably, the sensor with a 75 % porous PDMS film demonstrated enhanced sensitivity up to 11 times compared to the 0 % porous (pristine) PDMS film when subjected to a 300 g weight. High sensitivities of 0.046 kPa^-1, 0.036 kPa^-1, and 0.028 kPa^-1 were attained for the pressure sensor in the pressure ranges of 0–9.8 kPa, 0–19.6 kPa, and up to 29.4 kPa, respectively. Additionally, a real-time resonance frequency analysis was conducted using a network analyzer, allowing the detection of tiny pressure changes in an artificial blood vessel. Finally, the flexibility of the wireless CPS was investigated by studying various parameters, including body temperature, facial expressions such as smiling, selected speech characters (M, N, T, L), and swallowing actions.

Construction Guidelines for Optical-Electronic Expert Systems in Blood Rheology

Building specifically designed optical-electronic information processing expert systems for blood rheology bioimage analysis requires a painstaking, subtle approach. Such systems provide essential support for diagnostic operations and require an understanding of experimental properties such as the rheology of blood and bioimage analysis. To properly build these systems, guidelines are needed for improving imaging methods, image processing routines, and application of expert knowledge so the blood's rheological properties can be analyzed precisely. nformation features (information parameters) for the analysis of the biomedical images, in particular, for the assessment of the rheologic properties of the blood, are formed. Algorithm and optical-electronic expert system for the analysis of the rheological properties of the blood are suggested, they are used for the increase of the diagnostic validity which is adetermining factor in the biomedical diagnostics. The main focus of modern clinical hemorheology is the search diagnostic and prognostic criteria for various diseases and rheological correction methods violations. Changes in the rheological parameters of blood are one of the significant mechanisms of the formation of insufficient blood supply in the early stages the development of the disease. Main pathological effects violations of rheological properties in the blood can lead to micro-flow failure circulation, the extreme manifestation of which may lead to a decrease in trophism and the development of ischemic syndrome, a violation of micro-rheology and an increase in the viscosity of blood, which causes an increase in total peripheral resistance and the development of arterial hypertension syndrome, to atherosclerotic changes in blood vessels, to a violation of hemorheology, which contributes to increased thrombosis.

The Neutrophil-to-Lymphocyte Ratio in Patients with Spinal Cord Injury: A Narrative Review Study.

Background and Objectives: Traumatic spinal cord injury (SCI) is a devastating condition that occurs in two phases: primary and secondary injury. These phases contribute to changes in blood vessels and the influx of inflammatory cells such as neutrophils and lymphocytes. The biomarker known as the neutrophil-to-lymphocyte ratio (NLR) has been suggested as being highly valuable in predicting outcomes for patients with traumatic brain injury, acute ischemic stroke, and traumatic spinal cord injury. Therefore, this review study aims to investigate the prognostic value of the NLR in predicting outcomes for patients with SCI. Materials and Methods: A thorough review of relevant articles was conducted using Mesh keywords in Medline via Embase, PubMed, Google Scholar, and Scopus from 2000 to 2023. The search was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist. After reviewing the articles and applying inclusion and exclusion criteria, only relevant articles were included in the study. Results: In the initial search, 41 papers were identified. After applying exclusion criteria, only three clinical studies remained for review. It is still debatable whether the NLR can serve as a cost-effective, readily available, and independent predictive factor for both mortality and recovery outcomes in patients with traumatic spinal cord injuries. Conclusions: Our study demonstrates that NLR, a readily available and inexpensive marker, can serve as an independent predictor of both mortality and recovery outcomes in patients with traumatic spinal cord injury. To reach a conclusive decision, additional data are required.

An Investigation of the Correlation Between Retinal Nerve Fiber Layer Thickness with Blood Biochemical Indices and Cognitive Dysfunction in Patients with Type 2 Diabetes Mellitus.

The study aimed to explore the correlation between retinal nerve fiber layer thickness (RNFLT) with blood biochemical indicators and cognitive dysfunction in patients with type 2 diabetes mellitus (T2DM) and the possible mechanism, thereby providing more theoretical basis for the occurrence and prevention of diabetes related complications. Eighty T2DM patients treated in our hospital from March 2022 to September 2022 were selected as the study subjects, and the clinical data of the patients were retrospectively analyzed. All patients underwent fundus fluorescein angiography (FFA) to analyze the changes in retinal blood vessels. Patients who met the inclusion criteria were divided as the diabetic retinopathy (DR) group (n=46) and simple diabetes group (n=34). The RNFLT, blood biochemical indexes and changes in cognitive functions of the patients were detected. The correlation between RNFLT with blood biochemical indexes and cognitive dysfunction was analyzed. Compared with the simple diabetes group, patients in the DR group had much lower mean, nasal, inferior and superior thicknesses (P<0.01). There existed no significant difference in blood pressure, body mass index (BMI), blood lipids (triglycerides, cholesterol, low-density lipoprotein, high-density lipoprotein) between the two groups (P>0.05). Compared with the simple diabetes group, patients in the DR group had much higher fasting blood glucose (FBG), hemoglobin A1c (HbA1c), fasting insulin (FINS), insulin resistance (HOMA-IR) index, apolipoprotein B (ApoB)/apolipoprotein A1 (ApoA1) (P<0.001). Besides, the DR group had sharply lower scores on the Mini-Mental State Examination (MMSE) scale and higher levels of the Trail Making Test-A (TMT-A) and TMT-B (P<0.001). Spearman correlation analysis confirmed that the mean RNFLT was negatively correlated with the levels of FBG, HbA1c, HOMA-IR index, TMT-A and TMT-B (P<0.05), positively correlated with the score of mini-mental state examination (MMSE) (P<0.05), and was no significant correlation with FINS and ApoB/ApoA1 (P>0.05). DR patients had significantly reduced RNFLT, elevated levels of blood glucose related indicators, and cognitive dysfunction. There existed a correlation between RNFLT and FBG, HbA1c, HOMA-IR index, TMT-A, TMT-B and MMSE.

LVI-PathNet: Segmentation-classification pipeline for detection of lymphovascular invasion in whole slide images of lung adenocarcinoma

Lymphovascular invasion (LVI) in lung cancer is a significant prognostic factor that influences treatment and outcomes, yet its reliable detection is challenging due to interobserver variability. This study aims to develop a deep learning model for LVI detection using whole slide images (WSIs) and evaluate its effectiveness within a pathologist's information system. Experienced pathologists annotated blood vessels and invading tumor cells in 162 WSIs of non-mucinous lung adenocarcinoma sourced from two external and one internal datasets. Two models were trained to segment vessels and identify images with LVI features. DeepLabV3+ model achieved an Intersection-over-Union of 0.8840 and an area under the receiver operating characteristic curve (AUC-ROC) of 0.9869 in vessel segmentation. For LVI classification, the ensemble model achieved a F1-score of 0.9683 and an AUC-ROC of 0.9987. The model demonstrated robustness and was unaffected by variations in staining and image quality. The pilot study showed that pathologists' evaluation time for LVI detecting decreased by an average of 16.95%, and by 21.5% in “hard cases”. The model facilitated consistent diagnostic assessments, suggesting potential for broader applications in detecting pathological changes in blood vessels and other lung pathologies.

Phoenixin-14 maintains the contractile type of vascular smooth muscle cells in cerebral aneurysms rats.

The rupture of intracranial aneurysm (IA) is the primary reason contributing to the occurrence of life-threatening subarachnoid hemorrhages. The oxidative stress-induced phenotypic transformation from the contractile phenotype to the synthetic phenotype of vascular smooth muscle cells (VSMCs) plays a pivotal role in IA formation and rupture. Our study aimed to figure out the role of phoenixin-14 in VSMC phenotypic switching during the pathogenesis of IA by using both cellular and animal models. Primary rat VSMCs were isolated from the Willis circle of male Sprague-Dawley rats. VSMCs were stimulated by hydrogen peroxide (H2O2) to establish a cell oxidative damage model. After pretreatment with phoenixin-14 and exposure to H2O2, VSMC viability, migration, and invasion were examined through cell counting kit-8 (CCK-8), wound healing, and Transwell assays. Intracellular reactive oxygen species (ROS) production in VSMCs was evaluated by using 2',7'-Dichlorofluorescin diacetate (DCFH-DA) fluorescence probes and flow cytometry. Rat IA models were established by ligation of the left common carotid arteries and posterior branches of both renal arteries. The histopathological changes of rat intracranial blood vessels were observed through hematoxylin and eosin staining. The levels of contractile phenotype markers (alpha-smooth muscle actin [α-SMA] and smooth muscle 22 alpha [SM22α]) in VSMCs and rat arterial rings were determined through real-time quantitative polymerase chain reaction (RT-qPCR) and western blot analysis. Our results showed that H2O2 stimulated the production of intracellular ROS and induced oxidative stress in VSMCs, while phoenixin-14 pretreatment attenuated intracellular ROS levels in H2O2-exposed VSMCs. H2O2 exposure promoted VSMC migration and invasion, which, however, was reversed by phoenixin-14 pretreatment. Besides, phoenixin-14 administration inhibited IA formation and rupture in rat models. The decrease in α-SMA and SM22α levels in H2O2-exposed VSMCs and IA rat models was antagonized by phoenixin-14. Collectively, phoenixin-14 ameliorates the progression of IA through preventing the loss of the contractile phenotype of VSMCs.

Retinochoroidal Vascular Changes in Long-Term Type 1 Diabetic Patients Assessed by Optic Coherence Tomography Angiography.

To study retinal and choriocapillaris (CC) alterations using optical coherence tomography angiography (OCTA) in long-term type 1 diabetic (DM1) patients without diabetic retinopathy (DR). Seventy-eight eyes from 78 well-controlled DM1 patients diagnosed at least 15 years prior and 130 eyes of 130 healthy subjects were included in a cross-sectional descriptive study. Six eyes were excluded from the DM1 group. OCTA with Deep Range Imaging (DRI)-Triton swept source (SS)-OCT was performed. Statistically significant differences were found in all areas of the superficial capillary plexus (SCP), with lower values in DM1 patients. Differences were noted in all quadrants of the deep capillary plexus (DCP) except for the central area. Significant changes in CC blood flow were only found in the center. The foveal avascular zone (FAZ) area and diameters in the SCP were significantly different, while the DCP FAZ area was similar in both groups. Disease duration and microalbuminuria correlated negatively with some SCP areas and positively with FAZ values. Anatomical evaluation revealed microaneurysms in both plexuses, FAZ modifications, and areas lacking blood perfusion. Long-term type 1 diabetic patients without DR display microvascular abnormalities affecting retinal and CC blood perfusion, along with anatomical changes in retinal blood vessels.

Forensic medical characterization of sudden death in young people with connective tissue dysplasia according to the data of the Bureau of Medical Examinations of Moscow City

BACKGROUND: Sudden death is an urgent problem of modern public healthcare, with prevalence in the Russian Federation. The wide range of causes and data scarcity led to the complexity of diagnosis and interpretation of pathologic changes at autopsy. This study presents an epidemiologic analysis of the causes of sudden death in a young population. AIM: To provide a forensic medical description of cases of sudden death of young people with connective tissue dysplasia using data from forensic autopsies conducted at the Bureau of Medical Examinations of the Moscow City Health Department. MATERIALS AND METHODS: A sample study of 48 corpses of young people aged 18–44 years who died suddenly, was performed based on data from the Forensic Medical Examination Bureau of the Moscow Department of Health. The protocols for examining the corpse at the scene of the incident, medical records were analyzed comprehensively. An extended description of the external and internal examinations of corpses was performed, and materials for histological, histochemical, and immunohistochemical studies were collected. RESULTS: Cardiovascular pathologies were the main cause of sudden death in young people. In some cases, an asthenic type was established with the following signs: high stature, elongated chest with an acute epigastric angle, poorly defined subcutaneous fatty tissue, weight less than the age norm, and narrow shoulders. Pathological changes were identified in the sternum, spine, limbs, dental status, and internal organs, which corresponded to connective tissue dysplasia. A correlation was noted between sudden death in young people and asthenic skeletopathy with exposure to extreme factors such as physical stress, psychoemotional stress, and previous infectious diseases. In most cases of sudden death, pathological changes in blood vessels were diagnosed in young people. CONCLUSION: The development of a modern comprehensive scientific and methodological approach is necessary to assess pathomorphological changes in young people who died suddenly.

Limited Nerve Regeneration across Acellular Nerve Allografts (ANAs) Coincides with Changes in Blood Vessel Morphology and the Development of a Pro-Inflammatory Microenvironment.

The use of acellular nerve allografts (ANAs) to reconstruct long nerve gaps (>3 cm) is associated with limited axon regeneration. To understand why ANA length might limit regeneration, we focused on identifying differences in the regenerative and vascular microenvironment that develop within ANAs based on their length. A rat sciatic nerve gap model was repaired with either short (2 cm) or long (4 cm) ANAs, and histomorphometry was used to measure myelinated axon regeneration and blood vessel morphology at various timepoints (2-, 4- and 8-weeks). Both groups demonstrated robust axonal regeneration within the proximal graft region, which continued across the mid-distal graft of short ANAs as time progressed. By 8 weeks, long ANAs had limited regeneration across the ANA and into the distal nerve (98 vs. 7583 axons in short ANAs). Interestingly, blood vessels within the mid-distal graft of long ANAs underwent morphological changes characteristic of an inflammatory pathology by 8 weeks post surgery. Gene expression analysis revealed an increased expression of pro-inflammatory cytokines within the mid-distal graft region of long vs. short ANAs, which coincided with pathological changes in blood vessels. Our data show evidence of limited axonal regeneration and the development of a pro-inflammatory environment within long ANAs.

Anthrahydroquinone‑2,6‑disulfonate attenuates PQ‑induced acute lung injury through decreasing pulmonary microvascular permeability via inhibition of the PI3K/AKT/eNOS pathway.

In paraquat (PQ)‑induced acute lung injury (ALI)/ acute respiratory distress syndrome, PQ disrupts endothelial cell function and vascular integrity, which leads to increased pulmonary leakage. Anthrahydroquinone‑2,6‑disulfonate (AH2QDS) is a reducing agent that attenuates the extent of renal injury and improves survival in PQ‑intoxicated Sprague‑Dawley (SD) rats. The present study aimed to explore the beneficial role of AH2QDS in PQ‑induced ALI and its related mechanisms. A PQ‑intoxicated ALI model was established using PQ gavage in SD rats. Human pulmonary microvascular endothelial cells (HPMECs) were challenged with PQ. Superoxide dismutase, malondialdehyde, reactive oxygen species and nitric oxide (NO) fluorescence were examined to detect the level of oxidative stress in HPMECs. The levels of TNF‑α, IL‑1β and IL‑6 were assessed using an ELISA. Transwell and Cell Counting Kit‑8 assays were performed to detect the migration and proliferation of the cells. The pathological changes in lung tissues and blood vessels were examined by haematoxylin and eosin staining. Evans blue staining was used to detect pulmonary microvascular permeability. Western blotting was performed to detect target protein levels. Immunofluorescence and immunohistochemical staining were used to detect the expression levels of target proteins in HPMECs and lung tissues. AH2QDS inhibited inflammatory responses in lung tissues and HPMECs, and promoted the proliferation and migration of HPMECs. In addition, AH2QDS reduced pulmonary microvascular permeability by upregulating the levels of vascular endothelial‑cadherin, zonula occludens‑1 and CD31, thereby attenuating pathological changes in the lungs in rats. Finally, these effects may be related to the suppression of the phosphatidylinositol‑3‑kinase (PI3K)/protein kinase B (AKT)/endothelial‑type NO synthase (eNOS) signalling pathway in endothelial cells. In conclusion, AH2QDS ameliorated PQ‑induced ALI by improving alveolar endothelial barrier disruption via modulation of the PI3K/AKT/eNOS signalling pathway, which may be an effective candidate for the treatment of PQ‑induced ALI.

An Anti-VEGF-B Antibody Reduces Abnormal Tumor Vasculature and Enhances the Effects of Chemotherapy

The vascular endothelial growth factors (VEGFs) and their receptors (VEGFRs) are key regulators of blood vessel formation, including in tumors, where their deregulated function can promote the production of aberrant, leaky blood vessels, supporting tumor development. Here we investigated the VEGFR1 ligand VEGF-B, which we demonstrate to be expressed in tumor cells and in tumor stroma and vasculature across a range of tumor types. We examined the anti-VEGF-B-specific monoclonal antibody 2H10 in preclinical xenograft models of breast and colorectal cancer, in comparison with the anti-VEGF-A antibody bevacizumab. Similar to bevacizumab, 2H10 therapy was associated with changes in tumor blood vessels and intra-tumoral diffusion consistent with normalization of the tumor vasculature. Accordingly, treatment resulted in partial inhibition of tumor growth, and significantly improved the response to chemotherapy. Our studies indicate the importance of VEGF-B in tumor growth, and the potential of specific anti-VEGF-B treatment to inhibit tumor development, alone or in combination with established chemotherapies.

Crosstalk between endothelial cells and dermal papilla entails hair regeneration and angiogenesis during aging

IntroductionTissues maintain their function through interaction with microenvironment. During aging, both hair follicles and blood vessels (BV) in skin undergo degenerative changes. However, it is elusive whether the changes are due to intrinsic aging changes in hair follicles or blood vessels respectively, or their interactions. ObjectiveTo explore how hair follicles and blood vessels interact to regulate angiogenesis and hair regeneration during aging. MethodsSingle-cell RNA-sequencing (scRNA-seq) analyses were used to identify the declined ability of dermal papilla (DP) and endothelial cells (ECs) during aging. CellChat and CellCall were performed to investigate interaction between DP and ECs. Single-cell metabolism (scMetabolism) analysis and iPATH were applied to analyze downstream metabolites in DP and ECs. Hair-plucking model and mouse cell organoid model were used for functional studies. ResultsDuring aging, distance and interaction between DP and ECs are decreased. DP interacts with ECs, with decreased EDN1-EDNRA signaling from ECs to DP and CTF1-IL6ST signaling from DP to ECs during aging. ECs-secreted EDN1 binds to DP-expressed EDNRA which enhances Taurine (TA) metabolism to promote hair regeneration. DP-emitted CTF1 binds to ECs-expressed IL6ST which activates alpha-linolenic acid (ALA) metabolism to promote angiogenesis. Activated EDN1-EDNRA-TA signaling promotes hair regeneration in aged mouse skin and in organoid cultures, and increased CTF1-IL6ST-ALA signaling also promotes angiogenesis in aged mouse skin and organoid cultures. ConclusionsOur finding reveals reciprocal interactions between ECs and DP. ECs releases EDN1 sensed by DP to activate TA metabolism which induces hair regeneration, while DP emits CTF1 signal received by ECs to enhance ALA metabolism which promotes angiogenesis. Our study provides new insights into mutualistic cellular crosstalk between hair follicles and blood vessels, and identifies novel signaling contributing to the interactions of hair follicles and blood vessels in normal and aged skin.

Naoxintong capsule remodels gut microbiota and ameliorates early-stage atherosclerosis in apolipoprotein E-deficient mice

BackgroundNaoxintong capsule (NXT) is a compound traditional Chinese medicine prescription with demonstrated effect for the treatment of cardiovascular and cerebrovascular diseases including atherosclerosis (AS). However, the pharmacological mechanisms of NXT in ameliorating early-stage AS are still unclear, especially regarding the role of gut microbiota. PurposeThis study is aiming to evaluate the therapeutic effect of NXT against early-stage AS, and further illustrate the potential correlations among AS, gut microbiota, and NXT. MethodsThirty-two male ApoE knockout mice (C57BL/6 background) were fed with a high cholesterol diet (HCD) for 4 weeks to establish an early-stage AS model. NXT in two different dosages and simvastatin (Simv) were than administrated for another 8 weeks. Lipid metabolism indicators and inflammation levels were measured with corresponding assay kits. Changes in blood vessels, liver lesions, and intestinal barrier proteins were evaluated with different staining methods. Furthermore, the gut microbiota structure was analyzed using 16S rRNA sequencing technology, while GC–MS was utilized to determine the fecal contents of short-chain fatty acids (SCFAs). ResultsAdministration of NXT significantly ameliorated obesity, hyperlipidemia, systemic inflammation, vasculopathy, liver injury, and intestinal barrier disorder in AS mice. Administration of NXT also significantly regulated the gut microbiota disturbance and increased the total contents of fecal SCFAs in AS mice. Furthermore, acetic acid content and the relative abundance of Faecalibacterium in feces were proposed as potential therapeutic biomarkers of NXT for AS treatment as indicated via the correlation analysis. ConclusionThis study demonstrated that NXT could effectively treat early-stage AS induced by HCD in mice. NXT regulated the gut microbiota and metabolites, maintained intestinal homeostasis, and improved the systemic inflammatory response. These findings may provide robust experimental support for the clinical use of NXT for AS treatment.

On viscoelastic blood in a locally narrow artery with magnetic field: application of distributed-order time fractional Maxwell model

Purpose. The study of hemorheology of heterogeneous vessels is of importance for the therapy of cardiovascular diseases. The present paper aims to investigate the effects of the height parameter of the stenosis, the Reynolds number, the relaxation time and the Hartmann number on the blood flow by applying distributed order time fractional Maxwell model. Methodology. Distributed order time fractional Maxwell constitutive fluid model is used to simulate viscoelastic blood flowing in a narrowing blood vessel with uniform magnetic field. The continuity and momentum equations are established in two-dimensional cylindrical coordinate system for calculation. With vorticity-stream function method, the finite difference technique, combined with the fractional derivative L1 interpolation approximation, is utilized to obtain numerical solutions of velocity and wall shear stress. The effectiveness of the numerical method is verified. Outcomes. It reveals the choice of relaxation time in the governing equation has an influence on the results. The numerical results show that an appropriate increase of Reynolds number can reduce the possibility of vessel damage. Furthermore, when the height parameter of the stenosis increases, the damage to the vessel wall is getting serious. Besides, the wall shear stress along the blood vessel increases with the increase of the magnetic field, but the wall shear stress in the narrowest part of the blood vessel changes little.

Dental pulp stones and their correlation with metabolic diseases.

Dental pulp calcifications or pulp stones are calcified structures found in dental pulp, mostly around or enclosing a blood vessel. The formation of these calcifications begins with concentric layers of calcified tissue within which remnants of necrotic and calcified cells may be present. The calcifications of thrombi in blood vessels, called phleboliths, may also serve as nidi for denticles. In metabolic diseases such as diabetes, hypertension or poor periodontal health, there are obvious changes in blood vessels and vascularization. In our study, we observed histopathological sections of dental pulp and correlated systemic diseases such as diabetes and hypertension with poor periodontal health and dental pulp stones. The aim of our study was to evaluate the histopathology of dental pulp stones, their distribution among various age groups and sexes and to identify any correlations between pulp stone formation and systemic diseases such as type II diabetes and hypertension. Samples from 100 patients with metabolic diseases such as type II diabetes and hypertension were collected. The pulp was extirpated from the teeth that were undergoing root canal treatment, and the teeth were extracted. The collected pulp sample was fixed in 10% formaline neutral buffer, subjected to routine histopathological procedures and stained with haematoxylin and eosin. The pulp of teeth extracted for orthodontic treatment was considered a control for patients with no metabolic disease. There was a definite relationship between increased pulp stones and metabolic diseases such as type II diabetes and hypertension; likewise, poor periodontal health was significantly related to pulp stones.