Dual Immunoglobulin Domain-Containing Cell Adhesion Molecule Increases Early in Renal Tubular Cell Injury and Plays Anti-Inflammatory Role.

Dual immunoglobulin domain-containing cell adhesion molecule (DICAM) is a type I transmembrane protein that presents in various cells including renal tubular cells. This study evaluated the expression and protective role of DICAM in renal tubular cell injury. HK-2 cells were incubated and treated with lipopolysaccharide (LPS, 30 µg/mL) or hydrogen peroxide (H2O2, 100 µM) for 24 h. To investigate the effect of the gene silencing of DICAM, small interfering RNA of DICAM was used. Additionally, to explain its role in cellular response to injury, DICAM was overexpressed using an adenoviral vector. DICAM protein expression levels significantly increased following treatment with LPS or H2O2 in HK-2 cells. In response to oxidative stress, DICAM showed an earlier increase (2-4 h following treatment) than neutrophil gelatinase-associated lipocalin (NGAL) (24 h following treatment). DICAM gene silencing increased the protein expression of inflammation-related markers, including IL-1ß, TNF-α, NOX4, integrin ß1, and integrin ß3, in H2O2-induced HK-2 cell injury. Likewise, in the LPS-induced HK-2 cell injury, DICAM knockdown led to a decrease in occludin levels and an increase in integrin ß3, IL-1ß, and IL-6 levels. Furthermore, DICAM overexpression followed by LPS-induced HK-2 cell injury resulted in an increase in occludin levels and a decrease in integrin ß1, integrin ß3, TNF-α, IL-1ß, and IL-6 levels, suggesting an alleviating effect on inflammatory responses. DICAM was elevated in the early stage of regular tubular cell injury and may protect against renal tubular injury through its anti-inflammatory properties. DICAM has a potential as an early diagnostic marker and therapeutic target for renal cell injury.

Anuria after kidney transplantation diagnosed as early recurrence of focal segmental glomerulosclerosis combined with acute calcineurin inhibitor nephrotoxicity: a case report and literature review.

BACKGROUND: Primary focal segmental glomerulosclerosis (FSGS) is a glomerular disease that sometimes recurs in patients after kidney transplantation (KT) and increases the risk of graft loss. Proteinuria is a common early sign of recurrent FSGS, but an abrupt decrease in urine volume is rare. Herein, we report a patient with early recurrence of FSGS with anuria following KT. CASE PRESENTATION: A 55-year-old man with end-stage kidney disease caused by primary FSGS experienced anuria on postoperative day 2 following deceased donor KT. Laboratory results revealed that serum tacrolimus trough levels were consistently elevated at the time of anuria. At first, we considered acute calcineurin inhibitor (CNI) nephrotoxicity based on graft biopsy on light microscopy, laboratory findings, and clinical courses. However, the allograft function did not recover even after discontinuation of CNI, and recurrent FSGS was diagnosed 2 weeks later on electron microscopy. A total of 13 sessions of plasmapheresis and two administrations of rituximab (375 mg/m2) were required to treat recurrent FSGS. The patient achieved a partial response, and the spot urine protein-to-creatinine ratio decreased from 15.5 g/g creatinine to 5.2 g/g creatinine. At 5 months following KT, the serum creatinine level was stable at 1.15 mg/dL. CONCLUSIONS: These findings highlight that anuria can occur in cases of early recurrence of FSGS combined with acute CNI nephrotoxicity.

Efficacy of Integrated Risk Score Using Omics-Based Biomarkers for the Prediction of Acute Rejection in Kidney Transplantation: A Randomized Prospective Pilot Study.

Acute rejection (AR) is critical for long-term graft survival in kidney transplant recipients (KTRs). This study aimed to evaluate the efficacy of the integrated risk score of omics-based biomarkers in predicting AR in KTRs. This prospective, randomized, controlled, multicenter, pilot study enrolled 40 patients who recently underwent high-immunologic-risk kidney transplantation (KT). Five omics biomarkers were measured, namely, blood mRNA (three-gene signature), urinary exosomal miRNA (three-gene signature), urinary mRNA (six-gene signature), and two urinary exosomal proteins (hemopexin and tetraspanin-1) at 2 weeks and every 4 weeks after KT for 1 year. An integrated risk score was generated by summing each biomarker up. The biomarker group was informed about the integrated risk scores and used to adjust immunosuppression, but not the control group. The outcomes were graft function and frequency of graft biopsy. Sixteen patients in the biomarker group and nineteen in the control group completed the study. The mean estimated glomerular filtration rate after KT did not differ between the groups. Graft biopsy was performed in two patients (12.5%) and nine (47.4%) in the biomarker and control groups, respectively, with the proportion being significantly lower in the biomarker group (p = 0.027). One patient (6.3%) in the biomarker group and two (10.5%) in the control group were diagnosed with AR, and the AR incidence did not differ between the groups. The tacrolimus trough level was significantly lower in the biomarker group than in the control group at 1 year after KT (p = 0.006). Integrated omics biomarker monitoring may help prevent unnecessary or high-complication-risk biopsy and enables tailored immunosuppression by predicting the risk of AR in KTRs.

The Current Status and Future Perspectives of Chimeric Antigen Receptor-Engineered T Cell Therapy for the Management of Patients with Endometrial Cancer.

Endometrial cancer (EC) is a gynecological neoplasm that is increasing in occurrence and mortality rates. Although endometrial cancer in the early stages shows a relatively favorable prognosis, there is an increase in cancer-related mortality rates in the advanced or recurrent endometrial carcinoma population and patients in the metastatic setting. This discrepancy has presented an opportunity for research and development of target therapies in this population. After obtaining promising results with hematologic cancers, chimeric antigen receptor (CAR)-T cell immunotherapy is gaining acceptance as a treatment for solid neoplasms. This treatment platform allows T cells to express tumor-specific CARs on the cell surface, which are administered to the patient to treat neoplastic cells. Given that CAR-T cell therapy has shown potential and clinical benefit compared to other T cell treatment platforms, additional research is required to overcome physiological limitations such as CAR-T cell depletion, immunosuppressive tumor microenvironment, and the lack of specific target molecules. Different approaches and development are ongoing to overcome these complications. This review examines CAR-T cell therapy's current use for endometrial carcinomas. We also discuss the significant adverse effects and limitations of this immunotherapeutic approach. Finally, we consolidate signal-seeking early-phase clinical trials and advancements that have shown promising results, leading to the approval of new immunotherapeutic agents for the disease.

Re-identification and Characterization of Multidrug-Resistant Corynebacterium haemomassiliense-Like Organisms from Humans.

Recently, non-diphtheriae Corynebacterium spp. have been increasingly reported in patients. In addition, several novel species of Corynebacterium isolated from humans. Here, we report two cases of human infections caused by Corynebacterium haemomassiliense-like organisms, which had not been identified at the species level by MALDI-TOF MS analysis. They were revealed to be closely related to C. haemomassiliense, a recently described species by three housekeeping genes (16S rRNA, rpoB, and gyrA) and phenotypic features. Both strains were multidrug-resistant but susceptible to vancomycin, meropenem, and linezolid. Our report suggests that human infections by the recently described Corynebacterium species may not be limited to a specific region, in addition to difficulty of classifying the genus Corynebacterium.

Effects of C-Peptide on Dexamethasone-Induced In Vitro and In Vivo Models as a Potential Therapeutic Agent for Muscle Atrophy.

This study aimed to investigate the effects of C-peptide on C2C12 myotubes and a mouse model. Both in vitro and in vivo experiments were conducted to elucidate the role of C-peptide in muscle atrophy. Various concentrations (0, 0.01, 0.1, 1, 10, and 100 nM) of C-peptide were used on the differentiated C2C12 myotubes with or without dexamethasone (DEX). C57BL/6J mice were administered with C-peptide and DEX for 8 days, followed by C-peptide treatment for 12 days. Compared to the DEX group, C-peptide increased the fusion and differentiation indices and suppressed atrophic factor expression in C2C12 myotubes. However, 100 nM C-peptide decreased the fusion and differentiation indices and increased atrophic factor expression regardless of DEX treatment. In C57BL/6J mice, DEX + C-peptide co-treatment significantly attenuated the body and muscle weight loss and improved the grip strength and cross-sectional area of the gastrocnemius (Gas) and quadriceps (Quad) muscles. C-peptide downregulated the mRNA and protein levels of muscle degradation-related markers, particularly Atrogin-1, in Gas and Quad muscles. This study underscores the potential of C-peptides in mitigating muscle weight reduction and preserving muscle function during muscle atrophy via molecular regulation. In addition, the work presents basic data for future studies on the effect of C-peptide on diabetic muscular dystrophy.

Renal Sarcoidosis-like Reaction Induced by PD-1 Inhibitor Treatment in Non-Small Cell Lung Cancer: A Case Report and Literature Review.

Monoclonal antibodies directed against immune checkpoint proteins have been widely used to treat various cancers and have resulted in favorable clinical outcomes. Despite these beneficial properties, immune checkpoint inhibitors (ICIs) can induce side effects called immune-related adverse events, including sarcoidosis-like reactions (SLR) across multiple organs. Here, we report a case of renal SLR after ICI treatment, and we review the related literature. A 66-year-old Korean patient with non-small cell lung cancer was referred to the nephrology clinic for renal failure after the 14th pembrolizumab treatment dose. A renal biopsy revealed multiple epithelioid cell granulomas, with several lymphoid aggregates in the renal interstitium and a moderate degree of inflammatory cell infiltration in the tubulointerstitium. A moderate dose of steroid therapy was initiated, and the serum creatinine level partially recovered after four weeks of treatment. Judicious monitoring of renal SLR is, therefore, required during ICI therapy, and a timely diagnosis by renal biopsy and appropriate treatment are important.

Recurrent C3 Glomerulonephritis along with BK-Virus-Associated Nephropathy after Kidney Transplantation: A Case Report.

C3 glomerulonephritis (C3GN) is a rare cause of end-stage kidney disease and frequently recurrent in allografts following kidney transplantation (KT). Herein, we describe the case of a kidney transplant recipient who developed recurrent C3GN along with BK-virus-associated nephropathy (BKVAN) following KT. A 33-year-old man diagnosed with membranoproliferative glomerulonephritis 17 years ago underwent preemptive KT with a donor kidney from his aunt. Proteinuria gradually increased after 3 months following KT, and graft biopsy was performed 30 months after KT. Histopathological examination revealed recurrent C3GN. The dosages of triple immunosuppressive maintenance therapy agents were increased. Subsequently, serum C3 levels recovered to normal levels. However, at 33 months following KT, the BK viral load increased and graft function gradually deteriorated; a second graft biopsy was performed at 46 months following KT, which revealed BKVAN and decreased C3GN activity. The dosages of immunosuppressive agents were decreased; subsequently, BKVAN improved and graft function was maintained with normal serum C3 levels at 49 months following KT. This case indicates that C3GN is highly prone to recurrence following KT and that immunosuppressive therapy for C3GN increases the risk of BKVAN.

Lycopus lucidus Turcz Water Extract Ameliorates the Metabolic Disorder by Up-Regulated Major Urinary Protein Expression in High-Fat Diet-Induced Obesity.

Despite a century of research on obesity, metabolic disorders and their complications, including dyslipidemia, insulin resistance, and fatty liver disease remain a serious global health problem. Lycopus lucidus Turcz (LT) is a traditional medicine used for its anti-inflammatory properties that has not been evaluated for its efficacy in improving obesity. In this study, mice were fed a normal diet (n = 10) or obesity was induced with a high-fat diet (HFD, n = 20, 60% kcal from fat) for 4 weeks. The HFD mice were then divided into two groups, one of which received LT supplementation with water extract for 13 weeks [HFD (n = 10) or HFD with LT water extract (n = 10, 1.5%)]. LT reduced body and adipose tissue weight by elevating energy expenditure by increasing fatty oxidation in epididymal white adipose tissue (eWAT) and muscle. LT ameliorated dyslipidemia and hepatic steatosis by restricting lipogenesis. Additionally, LT normalized the impaired glucose homeostasis by diet-induced obesity to improve pancreatic islet dysfunction with increasing hepatic major urinary protein expression. Moreover, LT attenuated the inflammation and collagen accumulation in the liver and eWAT. In conclusion, these results suggest that LT can treat obesity-related metabolic disorders such as adiposity, dyslipidemia, hepatic steatosis, insulin resistance, and inflammation.

SARS-CoV-2 spike S1 subunit protein-mediated increase of beta-secretase 1 (BACE1) impairs human brain vessel cells.

Increasing evidence suggests incomplete recovery of COVID-19 patients, who continue to suffer from cardiovascular diseases, including cerebral vascular disorders (CVD) and neurological symptoms. Recent findings indicate that some of the damaging effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, especially in the brain, may be induced by the spike protein, leading to the disruption of the initial blood-brain barrier (BBB). SARS-CoV-2-infected cells and animals exhibit age-dependent pathogenesis. In this study, we identified endothelial BACE1 as a critical mediator of BBB disruption and cellular senescence induced by the SARS-CoV-2 spike S1 subunit protein. Increased BACE1 in human brain microvascular endothelial cells (HBMVEC) decreases the levels of tight junction proteins, including ZO-1, occludin, and claudins. Moreover, BACE1 overexpression leads to the accumulation of p16 and p21, typical hallmarks of cellular senescence. Our findings show that the SARS-CoV-2 spike S1 subunit protein upregulated BACE1 expression in HBMVECs, causing endothelial leakage. In addition, the SARS-CoV-2 spike S1 subunit protein induced p16 and p21 expression, indicating BACE1-mediated cellular senescence, confirmed by ß-Gal staining in HBMVECs. In conclusion, this study demonstrated that BACE1-mediated endothelial cell damage and senescence may be linked to CVD after COVID-19 infection.

Pixel Image Analysis and Its Application with an Alcohol-Based Liquid Scintillator for Particle Therapy.

We synthesized an alcohol-based liquid scintillator (AbLS), and we implemented an auxiliary monitoring system with short calibration intervals using AbLS for particle therapy. The commercial liquid scintillator used in previous studies did not allow the user to control the chemical ratio and its composition. In our study, the chemical ratio of AbLS was freely controlled by simultaneously mixing water and alcohol. To make an equivalent substance to the human body, 2-ethoxyethanol was used. There was no significant difference between AbLS and water in areal density. As an application of AbLS, the range was measured with AbLS using an electron beam in an image analysis that combined AbLS and a digital phone camera. Given a range-energy relationship for the electron expressed as areal density, the electron beam range (cm) in water can be easily estimated. To date, no literature report for the direct comparison of a pixel image analysis and Monte Carlo (MC) simulation has been published. Furthermore, optical tomography of the inverse problem was performed with AbLS and a mobile phone camera. Analyses of optical tomography images provide deeper insight into Radon transformation. In addition, the human phantom, which is difficult to compose with semiconductor diodes, was easily implemented as an image acquisition and analysis system.

The Spectrum of Light Emitted by LED Using a CMOS Sensor-Based Digital Camera and Its Application.

We introduced a digital photo image analysis in color space to estimate the spectrum of fluor components dissolved in a liquid scintillator sample through the hue and wavelength relationship. Complementary metal oxide semiconductor (CMOS) image sensors with Bayer color filter array (CFA) technology in the digital camera were used to reconstruct and decode color images. Hue and wavelength are closely related. To date, no literature has reported the hue and wavelength relationship measurements, especially for blue or close to the UV region. The non-linear hue and wavelength relationship in the blue region was investigated using a light emitting diode source. We focused on this wavelength region, because the maximum quantum efficiency of the bi-alkali photomultiplier tube (PMT) is around 430 nm. It is necessary to have a good understanding of this wavelength region in PMT-based experiments. The CMOS Bayer CFA approach was sufficient to estimate the fluor emission spectrum in the liquid scintillator sample without using an expensive spectrophotometer.

Investigation of the Hue-Wavelength Response of a CMOS RGB-Based Image Sensor.

In this study, a non-linear hue-wavelength (H-W) curve was investigated from 400 to 650 nm. To date, no study has reported on H-W relationship measurements, especially down to the 400 nm region. A digital camera mounted with complementary metal oxide semiconductor (CMOS) image sensors was used. The obtained digital images of the sample were based on an RGB-based imaging analysis rather than multispectral imaging or hyperspectral imaging. In this study, we focused on the raw image to reconstruct the H-W curve. In addition, several factors affecting the digital image, such as exposure time or international organization for standardization (ISO), were investigated. In addition, cross check of the H-W response using laser was performed. We expect that our method will be useful as an auxiliary method in the future for obtaining the fluor emission wavelength information.

Novel Plant Extract Ameliorates Metabolic Disorder through Activation of Brown Adipose Tissue in High-Fat Diet-Induced Obese Mice.

Obesity is characterized by excessive body fat accumulation due to unbalanced energy intake and expenditure. Potential therapeutic targets for anti-obesity include the inhibition of white adipose tissue (WAT) hypertrophy and hyperplasia and the activation of brown adipose tissue (BAT). Not only the activation of BAT but also the browning of WAT have gained increasing attention in research fields as an alternative method in the prevention and treatment of obesity. Here, we investigated possible mechanisms underlying the anti-obesity effect of Phlomis umbrosa Turcz. root ethanol extract (PUE) in an obesogenic animal model. PUE treatment can reduce diet-induced obesity and modulate obesity-associated metabolic disorders, including insulin resistance, hepatic steatosis, and inflammation. In the liver, PUE improved hepatic steatosis by suppressing hepatic lipogenesis and lipid absorption while increasing biliary sterol excretion and hepatic fatty acid oxidation compared to the high-fat group. Moreover, PUE increased energy expenditure and regulated fecal lipid excretion, leading to reduced body weight gain. In particular, PUE remarkably activated the browning of subWAT via upregulation of the browning-related protein and gene expression and promoted BAT activation. In conclusion, these findings provide the potential therapeutic usefulness into the effects of PUE in the treatment of obesity and metabolic disorders. Furthermore, it suggests that PUE treatment can regulate energy metabolism via activating BAT and browning subWAT.

Overexpression of translationally controlled tumor protein ameliorates metabolic imbalance and increases energy expenditure in mice.

BACKGROUND/OBJECTIVES: Translationally controlled tumor protein (TCTP) exhibits numerous biological functions. It has been shown to be involved in the regulation of glucose. However, its specific role in metabolism has not yet been clearly elucidated. Here, we aimed to assess the effect of TCTP overexpression on metabolic tissues and systemic energy metabolism. SUBJECTS/METHODS: We investigated whether TCTP can ameliorate the metabolic imbalance that causes obesity using TCTP-overexpressing transgenic (TCTP TG) mice. The mice were subjected to biochemical, morphological, physiological and protein expression studies to define the role of TCTP in metabolic regulation in response to normal chow diet (NCD) compared to high-fat diet (HFD) conditions, and cold environment. RESULTS: We found that TCTP TG mice show improved metabolic homeostasis under both of NCD and HFD conditions with simultaneous enhancements in glucose tolerance and insulin sensitivity. In particular, we found coincident increases in energy expenditure with significant upregulation of uncoupling protein 1 (UCP1) in the brown adipose tissue (BAT). Moreover, TCTP overexpressing mice exhibit significantly enhanced adaptive thermogenesis of BAT in response to cold exposure. CONCLUSIONS: Overexpression of TCTP ameliorated systemic metabolic homeostasis by stimulating UCP1-mediated thermogenesis in the BAT. This suggests that TCTP may function as a modulator of energy expenditure. This study suggests TCTP may serve as a therapeutic target for obesity and obesity-associated metabolic disorders including type 2 diabetes.

Declining trend of preemptive kidney transplantation and impact of pretransplant dialysis: a Korean nationwide prospective cohort study.

We evaluated the temporal trend of preemptive kidney transplantation (KT) and the effect of pretransplant dialysis duration on post-transplant outcomes. This was a nationwide cohort study of the first-time 3392 living donor KT (LDKT) recipients (2014-2019). The annual changes in proportion of preemptive KT, factors associated with preemptive KT, and post-transplant outcomes were analyzed. Preemptive KT was performed in 816 (24.1%) patients. Annual trend analysis revealed gradual decrease in preemptive KT over time (P = 0.042). Among the underlying causes of preemptive KT, the proportion of diabetes increased and that of glomerulonephritis decreased during the study period. Glomerulonephritis as the primary renal disease was a predictor of preemptive KT. Patients with pretransplant dialysis >6 months showed increased graft failure risk than preemptive KT in the subdistribution of hazard model for competing risk (adjusted hazard ratio [aHR], 2.53; 95% confidence interval [CI], 1.09-5.87; P = 0.031) and in propensity score-matched analysis (aHR, 2.45; 95% CI, 1.02-5.92; P = 0.034); however, pretransplant dialysis ≤6 months showed comparable graft survival with preemptive KT in both analyses. Preemptive KT declined over successive years, associated with an increase in diabetes and a decrease in glomerulonephritis as underlying causes of KT. Short period of dialysis less than 6 months does not affect graft survival compared with preemptive KT; however, longer dialysis decreases graft survival.

Notch1-mediated inflammation is associated with endothelial dysfunction in human brain microvascular endothelial cells upon particulate matter exposure.

Exposure to atmospheric particulate matter (PM) is an emerging risk factor for the pathogenesis of several diseases in humans, including cerebrovascular diseases. However, the mechanisms underlying PM-induced endothelial dysfunction are currently unclear. In this study, we examined how PM leads to endothelial dysfunction in human brain microvascular endothelial cells (HBMECs). We demonstrated that PM10 exposure (up to 25 µg/mL) increase Notch1 cleavage, and it regulates endothelial dysfunction through NICD-mediated inflammation and senescence. PM10-induced NICD signaling causes increased expression of interleukin-1 beta (IL-1ß) and enhances characteristics of cellular senescence, which leads to increased endothelial permeability in HBMECs. Knockdown of Notch1 by siRNA blocks PM10-induced endothelial dysfunction via the suppression of inflammation and senescence. Furthermore, we found that Notch1-mediated inflammation accelerates endothelial senescence, which eventually leads to endothelial dysfunction. Altogether, our data suggest that Notch1 and NICD are potential target regulators for the prevention of cerebrovascular endothelial dysfunction induced by ambient air pollutants such as PM.

Estimation of Fluor Emission Spectrum through Digital Photo Image Analysis with a Water-Based Liquid Scintillator.

In this paper, we performed a feasibility study of using a water-based liquid scintillator (WbLS) for conducting imaging analysis with a digital camera. The liquid scintillator (LS) dissolves a scintillating fluor in an organic base solvent to emit light. We synthesized a liquid scintillator using water as a solvent. In a WbLS, a suitable surfactant is needed to mix water and oil together. As an application of the WbLS, we introduced a digital photo image analysis in color space. A demosaicing process to reconstruct and decode color is briefly described. We were able to estimate the emission spectrum of the fluor dissolved in the WbLS by analyzing the pixel information stored in the digital image. This technique provides the potential to estimate fluor components in the visible region without using an expensive spectrophotometer. In addition, sinogram analysis was performed with Radon transformation to reconstruct transverse images with longitudinal photo images of the WbLS sample.

Paricalcitol Improves Hypoxia-Induced and TGF-ß1-Induced Injury in Kidney Pericytes.

Recently, the role of kidney pericytes in kidney fibrosis has been investigated. This study aims to evaluate the effect of paricalcitol on hypoxia-induced and TGF-ß1-induced injury in kidney pericytes. The primary cultured pericytes were pretreated with paricalcitol (20 ng/mL) for 90 min before inducing injury, and then they were exposed to TGF-ß1 (5 ng/mL) or hypoxia (1% O2 and 5% CO2). TGF-ß1 increased α-SMA and other fibrosis markers but reduced PDGFRß expression in pericytes, whereas paricalcitol reversed the changes. Paricalcitol inhibited the TGF-ß1-induced cell migration of pericytes. Hypoxia increased TGF-ß1, α-SMA and other fibrosis markers but reduced PDGFRß expression in pericyte, whereas paricalcitol reversed them. Hypoxia activated the HIF-1α and downstream molecules including prolyl hydroxylase 3 and glucose transporter-1, whereas paricalcitol attenuated the activation of the HIF-1α-dependent molecules and TGF-ß1/Smad signaling pathways in hypoxic pericytes. The gene silencing of HIF-1α vanished the hypoxia-induced TGF-ß1, α-SMA upregulation, and PDGFRß downregulation. The effect of paricalcitol on the HIF-1α-dependent changes of fibrosis markers was not significant after the gene silencing of HIF-1α. In addition, hypoxia aggravated the oxidative stress in pericytes, whereas paricalcitol reversed the oxidative stress by increasing the antioxidant enzymes in an HIF-1α-independent manner. In conclusion, paricalcitol improved the phenotype changes of pericyte to myofibroblast in TGF-ß1-stimulated pericytes. In addition, paricalcitol improved the expression of fibrosis markers in hypoxia-exposed pericytes both in an HIF-1α-dependent and independent manner.

Altered COVID-19 receptor ACE2 expression in a higher risk group for cerebrovascular disease and ischemic stroke.

Coronavirus disease 2019 (COVID-19) is a worldwide pandemic. It has a high transmission rate among humans, and is a threat to global public health. However, there are no effective prophylactics or therapeutics available. It is necessary to identify vulnerable and susceptible groups for adequate protection and care against this disease. Recent studies have reported that COVID-19 has angiotensin-converting enzyme 2 (ACE2) as a functional receptor, which may lead to the development of severe cerebrovascular diseases (CVD), including strokes, in patients with risk factors for CVD such as diabetes and smoking. Thus, the World Health Organization (WHO) advised caution against COVID-19 for smokers and patients with underlying clinical symptoms, including cardiovascular diseases. Here, we observed ACE2 expression in the brain of rat middle cerebral artery occlusion (MCAO) model and evaluated the effects of cigarette smoke extract (CSE) and diabetes on ACE2 expression in vessels. We showed that the levels of ACE2 expression was increased in the cortex penumbra after ischemic injuries. CSE treatment significantly elevated ACE2 expression in human brain vessels. We found that ACE2 expression was upregulated in primary cultured human blood vessels with diabetes compared to healthy controls. This study demonstrates that ACE2 expression is increased in ischemic brains and vessels exposed to diabetes or smoking, makes them vulnerable to COVID-19 infection.