Vascular Changes Research Articles

Melatonin and mesenchymal stem cells co-administration alleviates chronic obstructive pulmonary disease via modulation of angiogenesis at the vascular-alveolar unit.

Chronic obstructive pulmonary disease (COPD) is considered a severe disease mitigating lung physiological functions with high mortality outcomes, insufficient therapy, and pathophysiology pathways which is still not fully understood. Mesenchymal stem cells (MSCs) derived from bone marrow play an important role in improving the function of organs suffering inflammation, oxidative stress, and immune reaction. It might also play a role in regenerative medicine, but that is still questionable. Additionally, Melatonin with its known antioxidative and anti-inflammatory impact is attracting attention nowadays as a useful treatment. We hypothesized that Melatonin may augment the effect of MSCs at the level of angiogenesis in COPD. In our study, the COPD model was established using cigarette smoking and lipopolysaccharide. The COPD rats were divided into four groups: COPD group, Melatonin-treated group, MSC-treated group, and combined treated group (Melatonin-MSCs). We found that COPD was accompanied by deterioration of pulmonary function tests in response to expiratory parameter affection more than inspiratory ones. This was associated with increased Hypoxia induciblefactor-1α expression and vascular endothelial growth factor level. Consequently, there was increased CD31 expression indicating increased angiogenesis with massive enlargement of airspaces and thinning of alveolar septa with decreased mean radial alveolar count, in addition to, inflammatory cell infiltration and disruption of the bronchiolar epithelial wall with loss of cilia and blood vessel wall thickening. These findings were improved significantly when Melatonin and bone marrow-derived MSCs were used as a combined treatment proving the hypothesized target that Melatonin might augment MSCs aiming at vascular changes.

Choroidal thickness and retinal vascular changes in patients with lichen planus: an inflammatory disease beyond the skin.

Lichen planus (LP) is a common inflammatory condition of unknown etiology that commonly affects the skin and mucous membranes. Optical coherence tomography angiography (OCTA) is a noninvasive technique for identifying early retinal vascular impairment in systemic disease without clinical damage by imaging deep and superficial capillary networks. To assess the impacts of LP on the choroid and assess vascular changes in retinal capillary density using OCTA. This single-center prospective case-control study included 30 therapeutic-naïve LP patients and 30 age and sex-matched healthy individuals. All study subjects underwent a complete ophthalmological examination, including best-corrected visual acuity (BCVA) measurement using a Snellen chart, slit-lamp biomicroscopy, intraocular pressure (IOP) measurement, and fundus examination. They were then examined using spectral domain OCT and choroidal thickness was measured. The vessel density of the superficial and deep capillary networks was measured and assessed using OCTA. Patients had significantly thicker choroidal and retinal thickness than controls, with subfoveal, nasal, and temporal areas showing a significant difference. A significantly higher vascular density in the superficial capillary plexus, particularly in the nasal perifoveal area, was found compared to the control group. Significantly, higher vascular density in the deep capillary plexus in the parafoveal area compared to controls was reported. Significant correlations were found between visual acuity and IOP, and age, duration of disease, and severity of disease. This study is the first to reveal that LP patients exhibit choroidal changes and retinal vascular alterations compared to healthy controls.

Gross and Histopathological Dermal Changes at Sites of Snakebite – Report from Autopsy Series

Background: Snake bite remains a significant cause of accidental death, its occurrence usually underestimated because of under reporting.Objective: To report on gross and microscopic changes at sites of snakebite in autopsy.Methods: A cross-sectional, descriptive study was conducted on thirty cadavers of snake bite for study duration of one year based on inclusion and exclusion criteria. Skin was collected from sites of bite. Gross examination was carried out on formalin fixed specimens. Microscopic examination was performed on dermal biopsy of formalin fixed paraffin embedded sections stained with haematoxylene and eosin (H&E).Results: 53.4% of deceased were in the age group of 41-50 years. Males were predominant in the study (90%) where 63.3% were agriculture workers. Lower limb bite was commonly seen (83.3%) in outdoor locales (90%). Snakes identified were cobra and viper. Death occurred within 48 hours of admission in 80% cases. Bite mark was visualised in ten cases and ulceration in three. Microscopic examination revealed normal epidermis in 53.3% cases. Abnormalities seen included acantholysis in 36.7% and ulceration in 10%cases. Dermal changes were coagulative necrosis (26.7%), fibrinoid necrosis (16.7%), haemorrhagic necrosis (20%), oedema (13.3%). Combination of changes in a particular case also observed. Vascular changes comprised of extravasation (30%), fibrinoid necrosis with microvascular damage (23.4%), vasculitis (13.3%), microvascular damage (26.7%). Perineural fibrosis, subcutaneous gangrenous and haemorrhagic fat necrosis were other observations.Conclusion: This study highlights histological profile of dermal changes by snake venom at site of bite that can enlighten its pathophysiologic effects on cutaneous tissue.International Journal of Human and Health Sciences Vol. 08 No. 02 Apr’24 Page: 132-139

Which is a real valuable screening tool for lung cancer and measure thoracic diseases, chest radiography or low-dose computed tomography?: A review on the current status of Japan and other countries.

Chest radiography (CR) has been used as a screening tool for lung cancer and the use of low-dose computed tomography (LDCT) is not recommended in Japan. We need to reconsider whether CR really contributes to the early detection of lung cancer. In addition, we have not well discussed about other major thoracic disease detection by CR and LDCT compared with lung cancer despite of its high frequency. We review the usefulness of CR and LDCT as veridical screening tools for lung cancer and other thoracic diseases. In the case of lung cancer, many studies showed that LDCT has capability of early detection and improving outcomes compared with CR. Recent large randomized trial also supports former results. In the case of chronic obstructive pulmonary disease (COPD), LDCT contributes to early detection and leads to the implementation of smoking cessation treatments. In the case of pulmonary infections, LDCT can reveal tiny inflammatory changes that are not observed on CR, though many of these cases improve spontaneously. Therefore, LDCT screening for pulmonary infections may be less useful. CR screening is more suitable for the detection of pulmonary infections. In the case of cardiovascular disease (CVD), CR may be a better screening tool for detecting cardiomegaly, whereas LDCT may be a more useful tool for detecting vascular changes. Therefore, the current status of thoracic disease screening is that LDCT may be a better screening tool for detecting lung cancer, COPD, and vascular changes. CR may be a suitable screening tool for pulmonary infections and cardiomegaly.

Young blood-mediated cerebromicrovascular rejuvenation through heterochronic parabiosis: enhancing blood-brain barrier integrity and capillarization in the aged mouse brain.

Age-related cerebromicrovascular changes, including blood-brain barrier (BBB) disruption and microvascular rarefaction, play a significant role in the development of vascular cognitive impairment (VCI) and neurodegenerative diseases. Utilizing the unique model of heterochronic parabiosis, which involves surgically joining young and old animals, we investigated the influence of systemic factors on these vascular changes. Our study employed heterochronic parabiosis to explore the effects of young and aged systemic environments on cerebromicrovascular aging in mice. We evaluated microvascular density and BBB integrity in parabiotic pairs equipped with chronic cranial windows, using intravital two-photon imaging techniques. Our results indicate that short-term exposure to young systemic factors leads to both functional and structural rejuvenation of cerebral microcirculation. Notably, we observed a marked decrease in capillary density and an increase in BBB permeability to fluorescent tracers in the cortices of aged mice undergoing isochronic parabiosis (20-month-old C57BL/6 mice [A-(A)]; 6 weeks of parabiosis), compared to young isochronic parabionts (6-month-old, [Y-(Y)]). However, aged heterochronic parabionts (A-(Y)) exposed to young blood exhibited a significant increase in cortical capillary density and restoration of BBB integrity. In contrast, young mice exposed to old blood from aged parabionts (Y-(A)) rapidly developed cerebromicrovascular aging traits, evidenced by reduced capillary density and increased BBB permeability. These findings underscore the profound impact of systemic factors in regulating cerebromicrovascular aging. The rejuvenation observed in the endothelium, following exposure to young blood, suggests the existence of anti-geronic elements that counteract microvascular aging. Conversely, pro-geronic factors in aged blood appear to accelerate cerebromicrovascular aging. Further research is needed to assess whether the rejuvenating effects of young blood factors could extend to other age-related cerebromicrovascular pathologies, such as microvascular amyloid deposition and increased microvascular fragility.

Evaluation of the Anti-inflammatory Effects of Methanol Extract of Rauwofia vomitera Leaves (MERVL) Using In-vivo Based Assays

Background of the Study: The response of the body to harmful stimuli, such as tissue damage or a pathogenic infection is known as inflammation.  Rauwofia vomitera is a medicinal plant that is native to large areas of tropical Africa and it belongs to the family of Apocynaceae. It is a medicinal herb used in traditional Nigerian medicine to treat a variety of diseases, including inflammatory disorders. Aim of the Study:The present study investigated the anti-inflammatory  effects of methanol extract of Rauwofia vomitera leaves (MERVL) using  in-vivo  based assays.  Methodology: The anti-inflammatory effect of (MERVL) was ascertained using the Egg albumin -induced inflammation using in vivo assay. A total of thirty (30) adult male albino rats (130-170g) were divided into five (5) groups of six (6) rats each for the in-vivo anti-inflammatory assay. Group 1 normal; Group 2 was given 10 mg/kg body weight of Indomethacin and Groups 3, 4 and 5 were given 100, 200 and 400 mg/kg body weight of MERVL) respectively. Acute toxicity was carried out using standard method. Place and Duration of the Study: Department of Pharmacology Lab, Enugu State of University of Science and Technology Agbani Nigeria, between March 2021 and August 2021. Results: The percentage yield of the extract was 10.8%. The result of the quantitative and qualitative phytochemical screening of methanol extract of R. vomitoria leaves showed that Phenol (1590 ± 55.66) Flavonoid (1168 ± 11.43) and Tannin (1466 ± 40.73) were present in high concentration whereas, Alkaloid (549 ± 4.21) Glycoside (315 ± 61.38) and Terpenoid (162 ± 1.38) were present in moderate concentration. Saponin (1.16 ± 0.23) and Steroid (0.84 ± 0.03) were present in low concentrations. Acute toxicity tests showed no toxicity and mortality at doses up to 5000 mgkg-1. A significant (P < 0.05) reduction in the mean paw oedema was observed for all the treatment groups from 1 hour to 12 hours when compared to the normal group.  The result shown that groups treated with 100, 200 and 400 mg/kg b.w of extract inhibit the inflammation in a non-dose dependent manner with percentage mobilization of 5.7%, 14.1% and 6.2% respectively. Conclusion:  The study's results demonstrate that MERVL exhibits remarkable anti-inflammatory and anti-oxidant activities and the extract yielded a better reduction in edema and increases mobilization in leukocyte in response to agar suspension. It also demonstrates that MERVL has a modulatory effect on the vascular changes that accompany inflammation. The plant's anti-inflammatory properties could potentially result from the interaction of different photochemical substances present.  The findings suggest that, if used, the plant may serve as a source of anti-inflammatory agents.

Current research trends on the effect of diabetes mellitus on rotator cuff tendon healing/tendinopathy.

Rotator cuff tendon tears are a leading cause of shoulder pain. They are challenging to treat, and tendon-bone healing has a high failure rate despite successful surgery. Tendons connect the muscles and bones, which make them important for the body's overall mobility and stability. Metabolic diseases, including diabetes or high blood pressure, can affect the healing process after repair of a damaged tendon. With a global incidence of 9.3%, diabetes is considered as a significant risk factor for rotator cuff tendon healing because it causes structural, inflammatory, and vascular changes in the tendon. However, the mechanisms of how diabetes affects tendon healing remain unknown. Several factors have been suggested, including glycation product accumulation, adipokine dysregulation, increased levels of reactive oxygen species, apoptosis, inflammatory cytokines, imbalanced matrix-metalloproteinase-to-tissue-inhibitor ratio, and impaired angiogenesis and differentiation of the tendon sheath. Despite the effects of diabetes on tendon function and healing, few treatments are available to improve recovery in these patients. This review summarizes the current literature on the pathophysiological changes of the tendon in diabetes and hyperlipidemia. Preclinical and clinical evidence regarding the association between diabetes and tendon healing is presented. Moreover, current approaches to improve tendon healing in patients with diabetes are reviewed.

Anatomical Vascular Differences and Leishmania-Induced Vascular Morphological Changes Are Associated with a High Parasite Load in the Skin of Dogs Infected with Leishmania infantum

Canine visceral leishmaniasis (CVL), caused by the protozoan Leishmania infantum, affects several organs, including the skin. Dogs are considered the major domestic reservoir animals for leishmaniasis, and through their highly parasitized skin, they can serve as a source of infection for sandfly vectors. Therefore, studies of the skin parasite–host relationship can contribute to the understanding of the infectious dissemination processes of parasites in the dermis and help to identify targets for diagnosis and treatment. Thus, the aim of this study was to evaluate the association of anatomical vascular differences and Leishmania-induced vascular morphological changes with clinical signs and parasite load by analyzing the ear and abdominal skin from dogs naturally infected with L. infantum. Paired samples of ear and abdominal skin from L. infantum-positive dogs (n = 26) were submitted for histological and immunohistochemistry analyses. The ear skin samples showed a more intense and more diffusely distributed granulomatous inflammatory reaction, a higher number and larger diameter of blood vessels, increased parasite load, higher expression of VEGF+ (vascular endothelial growth factor) and MAC 387+ (calprotectin) recently infiltrating cells, and more intense collagen disruption compared to the abdominal skin samples. Intracellular amastigotes were observed in blood vessels and inside endothelial cells and were diffusely distributed throughout the dermis in the ear skin samples. The NOS2/MAC387+ cell ratio was lower in the ear skin samples than in those of the abdomen, suggesting that in the ear dermis, the inflammatory infiltrate was less capable of producing NO and thereby control the parasite load. Together, these findings indicate how parasites and immune cells are distributed in the skin and suggest an important role for dermal vascularization in cellular influx and thereby in parasite dissemination through the skin of naturally infected dogs.

High Spatiotemporal Resolution Radial Encoding Single-Vessel fMRI.

High-field preclinical functional MRI (fMRI) is enabled the high spatial resolution mapping of vessel-specific hemodynamic responses, that is single-vessel fMRI. In contrast to investigating the neuronal sources of the fMRI signal, single-vessel fMRI focuses on elucidating its vascular origin, which can be readily implemented to identify vascular changes relevant to vascular dementia or cognitive impairment. However, the limited spatial and temporal resolution of fMRI is hindered hemodynamic mapping of intracortical microvessels. Here, the radial encoding MRI scheme is implemented to measure BOLD signals of individual vessels penetrating the rat somatosensory cortex. Radial encoding MRI is employed to map cortical activation with a focal field of view (FOV), allowing vessel-specific functional mapping with 50×50 µm2 in-plane resolution at a 1 to 2 Hz sampling rate. Besides detecting refined hemodynamic responses of intracortical micro-venules, the radial encoding-based single-vessel fMRI enables the distinction of fMRI signals from vessel and peri-vessel voxels due to the different contribution of intravascular and extravascular effects.

Optical coherence tomography angiography changes in patients with hemoglobinopathy

Aim: The aim of this study is to evaluate retinal vascular changes in patients with sickle cell disease (SCD) and beta-thalassemia with optical coherence tomography angiography (OCT-A). Methods: For this purpose, 98 patients with SCD, 75 patients with beta-thalassemia, and 100 healthy controls in Mersin University Hospital between January 1, 2020, and November 1, 2021, were included in this study. OCT-A imaging was performed with ZEISS AngioPlex OCT angiography (Carl Zeiss Meditec, Dublin, CA, USA). Results: All OCT-A parameters (FAZ area, perimeter, circularity, vessel, and perfusion density) were found to be statistically significantly different in both patients with thalassemia and patients with sickle cell disease when compared to the controls. Conclusions: In conclusion, retinopathy related to both hemoglobinopathy subgroups can be diagnosed and followed up with OCT-A. It was also found that OCT-A parameters are affected before the development of clinically detectable retinopathy.

Evaluation of macular vessel density with OCTA in patients undergoing inferior oblique muscle surgery

Aims: To evaluate pre- and postoperative macular vascular density changes in patients undergoing inferior oblique muscle surgery using optical coherence tomography angiography (OCTA). Methods: 28 eyes of 16 patients who underwent inferior oblique muscle surgery were included in the study. Measurements were taken preoperatively (T0) and one day (PO1), 15 days (PO15) and 6 weeks (PO6w) after surgery. The vessel densities of the superficial capillary plexus (SCP), deep capillary plexus (DCP) and choriocapillaris (CCL) were measured by OCTA. Results: This study included 28 eyes of 16 patients. The mean age of the patients was 8.07±5.5 years (4-23 years). SCP and DCP mean vascular densities decreased significantly at PO1 and PO15 compared to T0, but increased at PO6w, reaching their initial levels. Mean CCL levels were lower at PO1 compared to all other measurements and reached their preop values at PO6w. Conclusion: The inferior oblique muscle insertion is known to be close to the macula and surgical interventions for this muscle may cause changes in macular vascular density. In our study, macular vascular density decreased in all parameters at PO1 compared to T0, but almost reached its preop levels at PO6w.

Krüppel-like factors: potential roles in blood-brain barrier dysfunction and epileptogenesis.

Epilepsy is a chronic and debilitating neurological disorder, known for the occurrence of spontaneous and recurrent seizures. Despite the availability of antiseizure drugs, 30% of people with epilepsy experience uncontrolled seizures and drug resistance, evidencing that new therapeutic options are required. The process of epileptogenesis involves the development and expansion of tissue capable of generating spontaneous recurrent seizures, during which numerous events take place, namely blood-brain barrier (BBB) dysfunction, and neuroinflammation. The consequent cerebrovascular dysfunction results in a lower seizure threshold, seizure recurrence, and chronic epilepsy. This suggests that improving cerebrovascular health may interrupt the pathological cycle responsible for disease development and progression. Krüppel-like factors (KLFs) are a family of zinc-finger transcription factors, encountered in brain endothelial cells, glial cells, and neurons. KLFs are known to regulate vascular function and changes in their expression are associated with neuroinflammation and human diseases, including epilepsy. Hence, KLFs have demonstrated various roles in cerebrovascular dysfunction and epileptogenesis. This review critically discusses the purpose of KLFs in epileptogenic mechanisms and BBB dysfunction, as well as the potential of their pharmacological modulation as therapeutic approach for epilepsy treatment.

Quantification of vascular changes in macular telangiectasia type 2 with AngioTool software.

To compare AngioTool (AT) vascular parameters (VP) between MacTel2 eyes and normal eyes. Secondary outcome measures were to correlate VP with BCVA and to analyze VP between various grades of Simple MacTel Classification. This is a retrospective study. SD OCTA images of the superficial vascular complex (SVC) and deep capillary complex (DVC) were exported into Image J and AT. The explant area (EA), vessel area (VA), vessel percentage area (VPA), total number of junctions (TNJ), junction density (JD), total vessel length (TVL), average vessel length (AVL), total number of endpoints (TNE) and mean E lacunarity (MEL) were studied. Group 1 had 120 MacTel2 eyes. Group 2 had 60 age-matched normal eyes. All VP were significantly different between the two groups except EA and TNE in both complexes. None of the VP had a correlation with BCVA. Interquadrant analysis (IQA) in SVC and DVC showed statistical significance in VPA, AVL and JD and in AVL, TNE, JD, VPA respectively. Post hoc analysis in SVC and DVC showed statistical significance in TNJ, JD, TVL and AVL between grade 1 and grade 3, and in VA, VPA, TNJ, JD, TVL and MEL between grade 0 and grade 3 respectively. VP were affected in MacTel2 eyes. VP did not correlate with BCVA. Occurrence of pigmentation is an important event in the progression of disease. AT may provide quantitative markers to measure disease progression.

Choroidal manifestations of non-ocular sarcoidosis: an enhanced depth imaging OCT study

BackgroundAlthough choroidal thickening was reported as a sign of active inflammation in ocular sarcoidosis, there has been no research on the choroidal changes in non-ocular sarcoidosis (defined as systemic sarcoidosis without overt clinical signs of ocular involvement). Therefore, this study aimed to investigate choroidal structural changes in patients with non-ocular sarcoidosis.MethodsThis retrospective case–control study was conducted at Asan Medical Center, a tertiary referral center. We evaluated 30 eyes with non-ocular sarcoidosis and their age- and spherical equivalent-matched healthy control eyes. The subfoveal choroidal thickness, area ratio (Sattler layer-choriocapillaris complex [SLCC] area to Haller layer [HL] area), and choroidal vascularity index (CVI, luminal area to choroidal area) were analyzed using enhanced depth imaging in optical coherence tomography. Systemic and ocular factors associated with the choroidal thickness were investigated.ResultsCompared with the healthy control group, the non-ocular sarcoidosis group had significantly thicker subfoveal choroid (total and all sublayers [SLCC and HL]) and lower area ratio. There were no significant differences in the CVIs at all sublayers between groups. In the non-ocular sarcoidosis group, eyes under oral steroid treatment had thinner choroid than eyes under observation. In the control group, eyes with older age and more myopic spherical equivalent had thinner choroidal thickness.ConclusionTotal and all sublayers of the subfoveal choroid were significantly thicker without significant vascularity changes in non-ocular sarcoidosis eyes than in healthy control eyes. The degree of choroidal thickening was disproportionally greater at HL than at SLCC. These characteristic choroidal changes may be the subclinical manifestations in non-ocular sarcoidosis.

Effects of a Global Rab27a Null Mutation on Murine PVAT and Cardiovascular Function.

RAB27A, a modulator of secretion, is expressed within vessels and perivascular adipose tissue. We hypothesized that loss of RAB27A would alter cardiovascular function. Body weight of Rab27aash mice was measured from 2 to 18 months of age, along with glucose resorption at 6 and 12 months of age and glucose sensitivity at 18 months of age. Body weight and cellular and molecular features of perivascular adipose tissue and aortic tissue were examined in a novel C57BL/6J Rab27a null strain. Analyses included morphometric quantification and proteomic analyses. Wire myography measured vasoreactivity, and echocardiography measured cardiac function. Comparisons across ages and genotypes were evaluated via 2-way ANOVA with multiple comparison testing. Significance for myography was determined via 4-parameter nonlinear regression testing. Genome-wide association data linked rare human RAB27A variants with body mass index and glucose handling. Changes in glucose tolerance were observed in Rab27aash male mice at 18 months of age. In WT (wild-type) and Rab27a null male mice, body weight, adipocyte lipid area, and aortic area increased with age. In female mice, only body weight increased with age, independent of RAB27A presence. Protein signatures from male Rab27a null mice suggested greater associations with cardiovascular and metabolic phenotypes compared with female tissues. Wire myography results showed Rab27a null males exhibited increased vasoconstriction and reduced vasodilation at 8 weeks of age. Rab27a null females exhibited increased vasoconstriction and vasodilation at 20 weeks of age. Consistent with these vascular changes, male Rab27a null mice experienced age-related cardiomyopathy, with severe differences observed by 21 weeks of age. Global RAB27A loss impacted perivascular adipose tissue and thoracic aorta proteomic signatures, altered vasocontractile responses, and decreased left ventricular ejection fraction in mice.

Survey on Predicting the Risk of Heart Attack Through Retinal Eye Images Analysis

Cardiovascular diseases (CVDs) remain a leading cause of global morbidity and mortality. Early detection and intervention are crucial for improving patient outcomes and reducing the burden on healthcare systems. Recent research suggests a potential link between retinal vascular changes and cardiovascular health. Retinal images offer a non-invasive means to assess microvascular abnormalities, making them an attractive source of data for predictive modeling. This project focuses on developing a machine learning model, specifically using Recurrent Neural Networks (RNNs), to analyze retinal images and detect patterns indicative of heart diseases. RNNs are well-suited for processing sequential data, making them suitable for capturing temporal dependencies in the retinal images and improving the predictive accuracy of the model.

Paracentral acute middle maculopathy and cotton wool spots in a patient with ocular migraine: A case report.

In this study, we report paracentral acute middle maculopathy (PAMM) and cotton wool spots (CWS) in a patient with ocular migraine. A 74-year-old man presented with persistent paracentral scotoma in the right eye that began a week prior. His visual acuity was 20/25 in the right eye and 20/40 in the left. Dilated fundoscopy revealed CWS in the right eye. Spectral-domain optical coherence tomography (SD-OCT) showed hyper-reflective bands in the inner nuclear layer corresponding to parafoveal lesions seen on near-infrared imaging in the right eye consistent with the diagnosis of PAMM. Further laboratory studies were unremarkable, and a transthoracic echocardiogram and a carotid ultrasound were unrevealing. The patient was started on brimonidine three times daily in both eyes. The patient reported subjective improvement in the paracentral scotoma and the absence of ocular migraine symptoms at two-month follow-up. We conclude from this case that PAMM and CWS can occur simultaneously in ocular migraine, and we suggest that retinal vascular changes associated with ocular migraine may contribute to ischemia underlying both entities. Additionally, we suggest a potential therapy in brimonidine due to its proposed beneficial effects on retinal vasculature and neuroprotection.

Evaluating Vascular Depth-Dependent Changes in Multi-Wavelength PPG Signals Due to Contact Force.

Photoplethysmography (PPG) is a non-invasive method used for cardiovascular monitoring, with multi-wavelength PPG (MW-PPG) enhancing its efficacy by using multiple wavelengths for improved assessment. This study explores how contact force (CF) variations impact MW-PPG signals. Data from 11 healthy subjects are analyzed to investigate the still understudied specific effects of CF on PPG signals. The obtained dataset includes simultaneous recording of five PPG wavelengths (470, 525, 590, 631, and 940 nm), CF, skin temperature, and the tonometric measurement derived from CF. The evolution of raw signals and the PPG DC and AC components are analyzed in relation to the increasing and decreasing faces of the CF. Findings reveal individual variability in signal responses related to skin and vasculature properties and demonstrate hysteresis and wavelength-dependent responses to CF changes. Notably, all wavelengths except 631 nm showed that the DC component of PPG signals correlates with CF trends, suggesting the potential use of this component as an indirect CF indicator. However, further validation is needed for practical application. The study underscores the importance of biomechanical properties at the measurement site and inter-individual variability and proposes the arterial pressure wave as a key factor in PPG signal formation.

Salidroside promotes angiogenesis after cerebral ischemia in mice through Shh signaling pathway

AimsThe purpose of this study was to explore the impacts of salidroside on vascular regeneration, vascular structural changes and long-term neurological recuperation following cerebral ischemia and its possible mechanism. Main methodsFrom Day 1 to Day 28, young male mice with middle cerebral artery blockage received daily doses of salidroside and measured neurological deficits. On the 7th day after stroke, the volume of cerebral infarction was determined using TTC and HE staining. Microvascular density, astrocyte coverage, angiogenesis and the expression of the Shh signaling pathway were detected by IF, qRTPCR and WB at 7, 14 and 28 days after stroke. Changes in blood flow, blood vessel density and diameter from stroke to 28 days were measured by the LSCI and TPMI. Key findingsCompared with the dMACO group, the salidroside treatment group significantly promoted the recovery of neurological function. Salidroside was found to enhance cerebral blood flow perfusion and reduce the infarct on the 7th day after stroke. From the 7th to the 28th day after stroke, salidroside treatment boosted the expression of CD31, CD31+/BrdU+, and GFAP in the cortex around the infarction site. On the 14th day after stroke, salidroside significantly enhanced the width and density of blood vessels. Salidroside increased the expression of histones and genes in the Shh signaling pathway during treatment, and this effect was weakened by the Shh inhibitor Cyclopamine. SignificanceSalidroside can restore nerve function, improve cerebral blood flow, reduce cerebral infarction volume, increase microvessel density and promote angiogenesis via the Shh signaling pathway.

The Essential Role of PGF2α/PTGFR in Molding Endometrial Breakdown and Vascular Dynamics, Regulated by HIF-1α in a Mouse Menstrual-like Model.

In women of childbearing age, extensive decidualization, shedding and remodeling of the endometrium during the menstrual cycle are fundamental for successful pregnancy. The role of prostaglandins (PGs) in menstruation has long been proposed in humans, and the rate-limiting enzyme cyclooxygenase was shown to play a key role in endometrial breakdown and shedding in a mouse menstrual-like model in our previous study. However, the specific types of PGs involved and their respective roles remain unclear. Therefore, our objective was to investigate the mechanism through which PGs regulate endometrial disintegration. In this study, the microscopy was observed by HE; the protein levels of prostaglandins E1 (PGE1), prostaglandins E2 (PGE2), prostaglandin F2α (PGF2α) and Prostaglandin I2 (PGI2) were detected by ELISA; the mRNA level of Pfgfr2, Vascular Endothelial Growth Factor(Vegf), Angiostatin and Hypoxia inducible factor-1α (Hif1α) were examined by real-time PCR; PTGFR Receptor (PTGFR), VEGF, Angiostatin and HIF-1α protein levels were investigated by western blotting; the locations of protein were observed by Immunohistochemistry; HIF-1α binding PTGFR promoter was detected by Chromatin Immunoprecipitation (ChIP) and real-time PCR. We found that the concentrations of PGE1, PGE2, and PGF2α all increased significantly during this process. Furthermore, Ptgfr mRNA increased soon after Progesterone (P4) withdrawal, and PTGFR protein levels increased significantly during abundant endometrial breakdown and shedding processes. PTGFR inhibitors AL8810 significantly suppressed endometrial breakdown and shedding, promoted Angiostatin expression, and reduced VEGF-A expressions and vascular permeability. And HIF-1α and PTGFR were mainly located in the luminal/gland epithelium, vascular endothelium, and pre-decidual zone. Interestingly, HIF-1α directly bound to Ptgfr promoter. Moreover, a HIF-1α inhibitor 2-methoxyestradiol (2ME) significantly reduced PTGFR expression and suppressed endometrial breakdown which was in accord with PTGFR inhibitor's effect. Similar changes occurred in human stromal cells relevant to menstruation in vitro. Our study provides evidence that PGF2α/PTGFR plays a vital role in endometrial breakdown via vascular changes that are regulated by HIF-1α during menstruation.