SARS-CoV-2 induced changes in the lungs based on autopsy cases

Context: Researchers throughout the world devote enormous efforts to reveal the peculiarities of the pathogenesis of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, however, it continues to surprise and cause the death of millions of people. Aims: This article aims to study the molecular mechanisms provoked by SARS-CoV-2, the virus-induced changes in Angiotensin-converting enzyme 2 (ACE2) functionality, in the vascular homeostasis through CD34 expression, B-cell immunity through the expression of CD20 and CD79?, and adhesion molecules through E-cadherin. Settings and Design: This was a prospective, descriptive, and observational study. Methods and Material: A total of 15 autopsies of patients deceased by COVID-19 infection, confirmed by PCR, were performed. The lungs of all patients were examined histologically and immunohistochemically for ACE2, E-cadherin, CD34, CD20, and CD79?. Results: Immunohistological analysis showed increased ACE2 expression in all lung autopsy material affected by COVID-19 infection and we found a higher intensity of ACE2 expression than that of a healthy lung. CD20 examination reveals total deficiency of B-cells in the pulmonary parenchyma and CD79? is also absent. E-Cadherin is not expressed in the basal cellular sections where the contact elements are missing. CD34 demonstrates a desquamation of the endothelial cells, which indicates a direct damage of the vascular walls. Conclusions: We found that patients who died after severe COVID-19 had high immune deficiency and impaired intercellular communication in the parenchyma and endothelium of lung tissue, leading to severe thromboembolic complications in patients with multiple diseases.

Angiotensin converting enzyme 2 alleviates infectious bronchitis virus-induced cellular inflammation by suppressing IL-6/JAK2/STAT3 signaling pathway / 生物工程学报

The goal of this study was to investigate the regulatory effect of angiotensin converting enzyme 2 (ACE2) on cellular inflammation caused by avian infectious bronchitis virus (IBV) and the underlying mechanism of such effect. Vero and DF-1 cells were used as test target to be exposed to recombinant IBV virus (IBV-3ab-Luc). Four different groups were tested: the control group, the infection group[IBV-3ab-Luc, MOI (multiplicity of infection)=1], the ACE2 overexpression group[IBV-3ab Luc+pcDNA3.1(+)-ACE2], and the ACE2-depleted group (IBV-3ab-Luc+siRNA-ACE2). After the cells in the infection group started to show cytopathic indicators, the overall protein and RNA in cell of each group were extracted. real-time quantitative polymerase chain reaction (RT-qPCR) was used to determine the mRNA expression level of the IBV nucleoprotein (IBV-N), glycoprotein 130 (gp130) and cellular interleukin-6 (IL-6). Enzyme linked immunosorbent assay (ELISA) was used to determine the level of IL-6 in cell supernatant. Western blotting was performed to determine the level of ACE2 phosphorylation of janus kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3). We found that ACE2 was successfully overexpressed and depleted in both Vero and DF-1 cells. Secondly, cytopathic indicators were observed in infected Vero cells including rounding, detaching, clumping, and formation of syncytia. These indicators were alleviated in ACE2 overexpression group but exacerbated when ACE2 was depleted. Thirdly, in the infection group, capering with the control group, the expression level of IBV-N, gp130, IL-6 mRNA and increased significantly (P < 0.05), the IL-6 level was significant or extremely significant elevated in cell supernatant (P < 0.05 or P < 0.01); the expression of ACE2 decreased significantly (P < 0.05); protein phosphorylation level of JAK2 and STAT3 increased significantly (P < 0.05). Fourthly, comparing with the infected group, the level of IBV-N mRNA expression in the ACE2 overexpression group had no notable change (P > 0.05), but the expression of gp130 mRNA, IL-6 level and expression of mRNA were elevated (P < 0.05) and the protein phosphorylation level of JAK2 and STAT3 decreased significantly (P < 0.05). In the ACE2-depleted group, there was no notable change in IBV-N (P > 0.05), but the IL-6 level and expression of mRNA increased significantly (P < 0.05) and the phosphorylation level of JAK2 and STAT3 protein decreased slightly (P > 0.05). The results demonstrated for the first time that ACE2 did not affect the replication of IBV in DF-1 cell, but it did contribute to the prevention of the activation of the IL-6/JAK2/STAT3 signaling pathway, resulting in an alleviation of IBV-induced cellular inflammation in Vero and DF-1 cells.

Buzhong Yiqitang Reduces CIH-induced Pulmonary Inflammatory Injury by ACE2-Ang（1-7）-Mas Axis / 中国实验方剂学杂志

ObjectiveTo investigate the intervention effect of Buzhong Yiqitang （BZYQT） on pulmonary inflammation in mice induced by chronic intermittent hypoxia （CIH） and preliminarily elucidate its mechanism. MethodForty healthy male C57BL/6 mice aged 6-8 weeks were randomly divided into the following groups： normoxia group， model group （exposed to CIH）， and low-， medium-， and high-dose BZYQT groups. The normoxia group was exposed to a normoxic environment， while the model group and the low-， medium-， and high-dose BZYQT groups were exposed to intermittent hypoxia. In the BZYQT groups， the BZYQT （8.1， 16.2， 32.4 g·kg-1·d-1） was administered orally 30 min before placing the mice in the hypoxic chamber， while the model group and the normoxia group received an equivalent volume of normal saline. After five weeks of modeling， pulmonary function of the mice was measured using an EMKA animal lung function analyzer， and lung tissue samples were collected after the pulmonary function tests. Hematoxylin-eosin （HE） staining was performed to observe the histopathological changes in the lung tissue of each group. Enzyme-linked immunosorbent assay （ELISA） was used to measure the levels of interleukin-6 （IL-6）， interleukin-8 （IL-8）， tumor necrosis factor-α （TNF-α） in the serum， as well as angiotensin Ⅱ （Ang Ⅱ） and angiotensin-（1-7） ［Ang（1-7）］ in lung tissue. Western blot and immunohistochemistry were used to detect the protein expression of IL-6， IL-8， TNF-α， angiotensin-converting enzyme 2 （ACE2）， and mitochondrial assembly receptor （Mas）. ResultCompared with the normoxia group， the model group showed significant abnormalities in lung function （P<0.05， P<0.01）， lung tissue changes， such as thickening of alveolar walls and inflammatory cell infiltration， increased levels of IL-6， IL-8， TNF-α in the serum and Ang Ⅱ in lung tissue （P<0.01）， decreased level of Ang（1-7） （P<0.01）， increased protein expression of IL-6， IL-8， and TNF-α， and decreased protein expression of ACE2 and Mas （P<0.05， P<0.01）. Compared with the model group， the BZYQT groups showed improvement in lung function （P<0.05， P<0.01）， and HE staining of lung tissue showed approximately normal alveolar wall thickness and reduced inflammatory cell infiltration. Immunohistochemistry and Western blot analysis showed a significant decrease in the expression of inflammatory-related proteins （P<0.05， P<0.01）， and a significant increase in ACE2 and Mas protein expression （P<0.05， P<0.01）. ConclusionBZYQT can improve lung injury in mice exposed to CIH by regulating the ACE2-Ang（1-7）-Mas axis to inhibit inflammatory responses.

Research progress on the expression and distribution of severe acute respiratory syndrome coronavirus 2 receptor angiotensin-converting enzyme 2 in ocular tissues / 国际眼科杂志(Guoji Yanke Zazhi)

Since 2019,severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)posed a great threat to human health and social economy, which has brought out hundreds of millions infection and caused millions of deaths worldwide. With the increasing research on SARS-CoV-2, angiotensin-converting enzyme 2(ACE2)has been regarded as a significant functional receptor for SARS-CoV-2 invasion. ACE2 is distributed in many tissues of human body, not only expressed in lung, cardiovascular, kidney tissues, but also in conjunctiva, cornea, uvea, retina and optic nerve tissue. More and more cases of SARS-CoV-2 infection through ocular tissues have been found; however, whether ocular ACE2 plays a role in SARS-CoV-2 infection is not completely clear. Therefore, study on expression and distribution of ACE2 in the ocular tissues can not only provide an in-depth understanding of the mechanism of SARS-CoV-2 infection, but also supply a comprehensive acquaintance with the mechanism of ACE2 action in the ocular tissues. In this paper, we review recent research progress about the expression and distribution of ACE2 in ocular tissues and hope to better understand the mechanism of ACE2 in the pathophysiological processes of ocular tissues.

Effect of ACE2 on the prognosis of breast cancer and its potential mechanism / 中国药科大学学报

@#This study aims to investigate the effect of transmembrane protein angiotensin converting enzyme 2 (ACE2) on the prognosis of breast cancer and its potential mechanism.Public databases were used to analyze ACE2 expression and its relationship with clinicopathological features and prognosis of breast cancer patients, combined with in vitro experiments to analyze the mechanism of action and immune relevance of ACE2 in breast cancer.Results showed that the expression of ACE2 in breast cancer tissues was significantly lower than that in normal breast tissues, and that its expression was negatively correlated with age, M stage and N1mi stage of breast cancer patients (P < 0.05).Patients with Luminal type breast cancer with high ACE2 expression had poor prognosis, while in the triple-negative breast cancer (TNBC) subtype, ACE2 showed different prognostic significance.In addition, ACE2 is closely associated with the metabolic and immune microenvironment of tumor tissue.In vitro experiments have shown that ACE2 is lowly expressed in MDA-MB-231 cells and may inhibit cell progress by downregulating matrix metalloproteinase 2（MMP2）.The results suggest that the low expression of ACE2 in breast cancer is closely associated with patient prognosis as well as metabolic and immune microenvironment, and that ACE2 may inhibit TNBC cell progress through the MMP2 pathway.

Research progress of angiotensin converting enzyme 2 co-expression in non-small cell lung cancer and SARS-CoV-2 / 中国胸心血管外科临床杂志

@#Since the first case of corona virus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at the end of 2019, the virus has spread rapidly around the world and has become a global public health problem. In the process of this virus epidemic, compared with the general population, cancer patients are considered to be highly susceptible people, especially the lung cancer patients. Some studies have shown that angiotensin converting enzyme 2 (ACE2) may be the pathway for SARS-CoV-2 to infect the host. At the same time, ACE2 is often abnormally expressed in non-small cell lung cancer. Therefore, understanding the respective mechanisms of ACE2 in COVID-19 and non-small cell lung cancer has extremely important reference value for the study of vaccines and therapeutic drugs, and also provides meaningful guidance for the protection of patients with lung cancer during the epidemic. This article reviews the possible invasive mechanism of ACE2 in SARS-CoV-2 and its abnormal expression in non-small cell lung cancer.

Effect of ACE2 deletion on vasoconstriction reactivity of aortic segments in mice with tourniquet shock / 中国病理生理杂志

AIM:To observe the effect of angiotensin-converting enzyme 2(ACE2)deletion on vasoconstric-tion reactivity of aortic segments in ACE2 knockout(KO)mice with tourniquet shock(TS).METHODS:The 8-month-old male mice with C57BL/6 background were divided into wild-type(WT)control group,WT-TS group,KO group and KO-TS group,with 10 mice in each group,of which five were used for determination of vascular reactivity,and the other five for the other assays.The hindlimbs of the mice in WT-TS group and KO-TS group were ligated with tourniquet for 2 h and loosened for 4 h.The mice in WT group and KO group were subjected to the same treatment except for tourniquet liga-tion.The vasoconstriction reactivity of the aorta was measured on tensiometer.The morphological damage of the aorta was evaluated by vascular histopathology.Western blot was used to detect the expression of AT1,MAS,ACE and ACE2 pro-teins in aorta.The serum levels of angiotensin(Ang)Ⅱ and Ang-(1-7)were determined by enzyme-linked immunosorbent assay.RESULTS:Compared with WT group,the mice in WT-TS group had lower vascular reactivity to norepinephrine(NE)and obvious vascular lesions.The expression of ACE protein increased significantly(P＜0.01),while the expres-sion of ACE2 decreased(P＜0.05).The expression of AT1 protein in aorta decreased significantly,the expression of MAS protein increased significantly,and the AT1/MAS ratio decreased(P＜0.01).Serum Ang II level increased,serum Ang-(1-7)level decreased,and Ang Ⅱ/Ang-(1-7)ratio increased(P＜0.05).Compared with WT group,vascular reactivity in KO group increased at low concentration of NE(＜10-7 mol/L),and decreased at high concentration(＞10-7 mol/L)without vascular lesion.The expression levels of aortic AT1,MAS and ACE were all elevated(P＜0.05).The serum level of Ang Ⅱ increased(P＜0.05),but the level of Ang-(1-7)had no obvious change.Compared with KO and WT-TS groups,the aortic reactivity in KO-TS group subtracted apparently(P＜0.05),representing its curve shifting to the right obviously.The morphological damage aggravated slightly,and the expression of AT1 and ACE increased slightly in KO-TS group com-pared with WT-TS group(P＜0.05).However,the expression of MAS increased significantly in vascular tissue(P＜0.01).The serum levels of Ang Ⅱ and Ang-(1-7)further increased and decreased,respectively,and the Ang Ⅱ/Ang-(1-7)ratio increased(P＜0.01).CONCLUSION:Deficiency of ACE2 induces severe aortic hyporeactivity to NE during TS,which may be related to the increased imbalance of renin-angiotensin system in ACE2 gene knockout mice.

Distribution of COVID-19 transmission-related receptors ACE2 and TMPRSS2 in human conjunctival tissue and its significance / 中华实验眼科杂志

Objective:To investigate the expression of coronavirus disease 2019 (COVID-19) transmission-related receptors angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) in human conjunctival tissue and its clinical significance.Methods:Fifty human conjunctival tissue specimens from 50 patients including 10 normal conjunctival tissues, 15 conjunctival papilloma tissues, 15 conjunctival nevus tissues and 10 conjunctival cyst tissues were collected from June 2019 to June 2020 at Xi'an People's Hospital.Ten corneal tissue samples from 10 patients with eyes removed due to trauma were collected as control.The distribution of ACE2 and TMPRSS2 in different corneal tissues was detected by the immunohistochemistry.The expression of ACE2 and TMPRSS2 was scored and compared.Reuse of the human samples and the research protocol was approved by an Ethics Committee of Xi'an People's Hospital (No.20190022). Written informed consent was obtained from each patient.Results:ACE2 and TMPRSS2 were both expressed in normal conjunctival epithelium, epithelial cells in conjunctiva papilloma and conjunctival nevus, and cells in conjunctiva cyst wall.ACE2 was mainly distributed in the superficial and intermediate cells of conjunctival epithelium, but not in the basal cells and goblet cells.TMPRSS2 was found in different layers of cells.The positive expression rates of ACE2 and TMPRSS2 in conjunctiva were both 100%.There was no significant difference in the expression intensity of ACE2 and TMPRSS2 among normal conjunctival tissue, conjunctival papilloma, conjunctival nevus and conjunctival cyst (all at P>0.05). Weakly expressed in corneal tissues, ACE2 and TMPRSS2 were more moderately and strongly expressed in conjunctival tissues.There were significant differences in the number of differently graded ACE2 and TMPRSS2 expression between normal conjunctival tissues, conjunctival papilloma, conjunctival nevus, conjunctival cyst and corneal tissues (ACE2: Z=-3.473, -4.183, -3.970, -3.873, all at P<0.01; TMPRSS2: Z=-4.119, -4.472, -4.443, -4.147, all at P<0.001). Conclusions:COVID-19 transmission-related receptors ACE2 and TMPRSS2 are expressed in human conjunctival tissue, which provides organological evidence for ocular surface transmission of COVID-19.

Perforación intestinal causada por COVID-19 / Intestinal perforation caused by COVID-19 / Perfuração intestinal causada por COVID-19

Resumen: A medida que la pandemia por el virus SARS-CoV-2 se propaga por todo el mundo, se informan nuevas manifestaciones clínicas. Además de las manifestaciones respiratorias, se han descrito lesión renal aguda, hipercoagulabilidad, tromboembolia pulmonar y síntomas gastrointestinales. En el Hospital de Infectología del Centro Médico Nacional La Raza, en la Unidad de Cuidados Intensivos se han atendido 148 pacientes de noviembre de 2020 a noviembre de 2021 por COVID-19 de severo a crítico. Presentamos un caso de paciente con SARS-CoV-2 con perforación intestinal por congestión vascular a nivel del ciego por COVID-19 crítico.

Abstract: As the SARS-CoV-2 virus pandemic spreads around the world, new clinical manifestations are being reported. In addition to respiratory manifestations, acute kidney injury, hypercoagulability, pulmonary thromboembolism, and gastrointestinal symptoms have been described. The Hospital de Infectología del Centro Médico Nacional La Raza, in the Intensive Care Unit, has treated 148 patients from November 2020 to November 2021 for COVID-19 from severe to critical. We present the case of a patient with SARS-CoV-2, with intestinal perforation due to vascular congestion at the level of the cecum in a critical COVID-19 patient.

Resumo: À medida que a pandemia do vírus SARS-CoV-2 se espalha pelo mundo, novas manifestações clínicas estão sendo relatadas. Além das manifestações respiratórias, foram descritos lesão renal aguda, hipercoagulabilidade, tromboembolismo pulmonar e sintomas gastrointestinais. O Hospital de Infectologia do Centro Médico Nacional «La Raza¼, na Unidade de Terapia Intensiva, tratou 148 pacientes de novembro de 2020 a novembro de 2021 para COVID-19 de estado grave a crítico. Apresentamos o caso de um paciente com SARS-CoV-2, com perfuração intestinal por congestão vascular ao nível do ceco em um paciente em estado crítico com COVID-19.

Angiotensin-converting enzyme 2 particapates in ozone-induced lung inflammation and airway remodeling in mice / 南方医科大学学报

OBJECTIVE@#To investigate the roles of angiotensin-converting enzyme 2 (ACE2) in ozone-induced pulmonary inflammation and airway remodeling in mice.@*METHODS@#Sixteen wild-type (WT) C57BL/6J mice and 16 ACE2 knock-out (KO) mice were exposed to either filtered air or ozone (0.8 ppm) for 3 h per day for 5 consecutive days. Masson's staining and HE staining were used to observe lung pathologies. Bronchoalveolar lavage fluid (BALF) was collected and the total cell count was determined. The total proteins and cytokines in BALF were determined by BCA and ELISA method. The transcription levels of airway remodeling-related indicators in the lung tissues were detected using real-time quantitative PCR. The airway resistance of the mice was measured using a small animal ventilator with methacholine stimulation.@*RESULTS@#Following ozoneexposure ACE2 KO mice had significantly higher lung pathological scores than WT mice (P < 0.05). Masson staining results showed that compared with ozone-exposed WT mice, ozone-exposed ACE2 KO mice presented with significantly larger area of collagen deposition in the bronchi [(19.62±3.16)% vs (6.49±1.34)%, P < 0.05] and alveoli [(21.63±3.78)% vs (4.44±0.99)%, P < 0.05]. The total cell count and total protein contents in the BALF were both higher in ozone-exposed ACE2 KO mice than in WT mice, but these differences were not statistically significant (P > 0.05). The concentrations of IL-6, IL-1β, TNF-α, CXCL1/KC and MCP-1 in the BALF were all higher in ozone-exposed ACE2 KO mice than in ozone-exposed WT mice, but only the difference in IL-1β was statistically significant (P < 0.05). The transcription levels of MMP-9, MMP-13, TIMP 4, COL1A1, and TGF-β in the lung tissues were all significantly higher in ozone-exposed ACE2 KO mice (P < 0.01). No significant difference was found in airway resistance between ozone-exposed ACE KO mice and WT mice after challenge with 0, 10, 25, or 100 mg/mL of methacholine.@*CONCLUSION@#ACE2 participates in ozone-induced lung inflammation and airway remodeling in mice.

Effect of Modified Chaihu Shugansan and Its Disassembled Formulas on ACE2- Ang （Ⅰ-Ⅶ）-MasR Axis in Rats with Myocardial Ischemia and Depression / 中国实验方剂学杂志

ObjectiveTo observe the effects of modified Chaihu Shugansan（CHSG） and its disassembled formulas on angiotensin-converting enzyme 2 （ACE2）-angiotensin （Ⅰ-Ⅶ） ［Ang （Ⅰ-Ⅶ）］-mitochondrial assembly receptor （MasR） axis in hyperlipidemic rats with myocardial ischemia and depression， and to explore the underlying mechanism of its prevention and treatment of myocardial ischemia and depression. MethodA total of 108 male SD rats were randomly divided into a normal group， a model group， a modified CHSG group （11.7 g·kg-1）， a Quyu Huatan disassembled formula group （4.05 g·kg-1）， a Shugan Xingqi disassembled formula group （3.15 g·kg-1）， a Jianpi Yangxue disassembled formula group （4.5 g·kg-1）， a fluoxetine group （0.001 8 g·kg-1）， a trimetazidine group （0.005 4 g·kg-1）， and a simvastatin group （0.001 8 g·kg-1）， with 12 rats in each group. The hyperlipidemia model with myocardial ischemia and depression was induced with a high-fat diet combined with injection of isoproterenol （ISO） and chronic unpredictable mild stress （CUMS） in rats in the model group and groups with drug intervention for eight weeks. The rats in each group with drug intervention were treated correspondingly by gavage from the first day of modeling， while those in the normal group and the model group received the same amount of normal saline. The behavioral changes of rats in each group were observed by open field test and forced swimming test. Left ventricular fractional shortening （LVFS） and left ventricular ejection fraction （LVEF） were measured by echocardiography. The serum levels of total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein cholesterol （LDL-C）， and high-density lipoprotein cholesterol （HDL-C） were detected by the enzyme-labeled apparatus. Hematoxylin-eosin （HE） staining was used to observe the histomorphological changes of the heart. The serum levels of angiotensin Ⅱ （AngⅡ）， ACE2， and Ang（Ⅰ-Ⅶ） were detected by enzyme-linked immunosorbent assay （ELISA）. The protein and mRNA expression of ACE2 and MasR in the hippocampus and the heart was detected by real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot. ResultCompared with the normal group， the model group showed reduced movement time， distance， and average speed in the central area of the open field （P<0.01）， prolonged immobility time of rats in the forced swimming test （P<0.01）， decreased LVFS and LVEF （P<0.01）， inflammatory exudation and disorderly arranged fiber in heart tissues， elevated serum levels of TC， LDL-C， AngⅡ， ACE2 and Ang（Ⅰ-Ⅶ）， diminished HDL-C （P<0.01）， dwindled mRNA and protein expression of ACE2 in the hippocampus and the heart and MasR in the hippocampus， and up-regulated mRNA and protein expression of MasR in the heart （P<0.01）. Compared with the model group， the modified CHSG group displayed increased movement time， distance， and average speed in the center area of the open field （P<0.01）， shortened immobility time in the forced swimming test （P<0.01）， increased LVFS and LVEF （P<0.01）， relieved heart injury， reduced serum levels of TC， LDL-C， AngⅡ， ACE2， and Ang（Ⅰ-Ⅶ）， elevated level of HDL-C （P<0.01）， up-regulated mRNA and protein expression of ACE2 in the hippocampus and the heart and MasR in the hippocampus， and down-regulated mRNA and protein expression of MasR in the heart （P<0.01）. Each disassembled formula could improve the above indexes to a certain extent （P<0.05， P<0.01）， but the effect of the whole formula was optimal. ConclusionThe modified CHSG and its disassembled formulas have the effects of resisting depression， improving myocardial injury， and reducing blood lipid. Due to the synergistic effects of stasis-resolving/phlegm-eliminating drugs， liver-smoothing/Qi-moving drugs， and spleen-tonifying/blood-nourishing drugs in the formula， the modified CHSG is superior to each disassembled formula in efficacy. Its mechanism may be related to the activation of the ACE2-Ang （Ⅰ-Ⅶ）-MasR axis.

Neutralization of SARS-CoV-2 pseudovirus using ACE2-engineered extracellular vesicles

The spread of coronavirus disease 2019 (COVID-19) throughout the world has resulted in stressful healthcare burdens and global health crises. Developing an effective measure to protect people from infection is an urgent need. The blockage of interaction between angiotensin-converting enzyme 2 (ACE2) and S protein is considered an essential target for anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) drugs. A full-length ACE2 protein could be a potential drug to block early entry of SARS-CoV-2 into host cells. In this study, a therapeutic strategy was developed by using extracellular vesicles (EVs) with decoy receptor ACE2 for neutralization of SARS-CoV-2. The EVs embedded with engineered ACE2 (EVs-ACE2) were prepared; the EVs-ACE2 were derived from an engineered cell line with stable ACE2 expression. The potential effect of the EVs-ACE2 on anti-SARS-CoV-2 was demonstrated by both in vitro and in vivo neutralization experiments using the pseudovirus with the S protein (S-pseudovirus). EVs-ACE2 can inhibit the infection of S-pseudovirus in various cells, and importantly, the mice treated with intranasal administration of EVs-ACE2 can suppress the entry of S-pseudovirus into the mucosal epithelium. Therefore, the intranasal EVs-ACE2 could be a preventive medicine to protect from SARS-CoV-2 infection. This EVs-based strategy offers a potential route to COVID-19 drug development.

El impacto de CoViD-19 en la hipertensión arterial pulmonar

La enfermedad por coronavirus 2019 (CoViD-19) está causada por el virus del síndrome respiratorio agudo severo por coronavirus 2 (SARS-CoV-2), siendo particularmente perjudicial para los pacientes con enfermedad cardiovascular subyacente, y provocando una causa de morbilidad y mortalidad significativas en todo el mundo. Este virus lleva a una neumopatía, al tiempo que causa lesiones agudas de miocardio y daño crónico al sistema cardiovascular. Como consecuencia del daño del parénquima pulmonar y de la circulación pulmonar alterada, puede desarrollarse hipertensión pulmonar (HP), con su respectiva consecuencia. La fisiopatología de este tipo de HP es compleja y multifactorial, considerándose factores potenciales para las alteraciones de la circulación pulmonar. En estudios recientes, la prevalencia evidenciada de HP en pacientes con CoViD-19 es de alrededor del 12%, pero su evolución aún no está clara. La pandemia de CoViD-19 ha tenido un impacto significativo en todos los aspectos de la HP, desde el diagnóstico y manejo hasta la observación de un mayor riesgo de muerte en pacientes con hipertensión arterial pulmonar (HAP). En una encuesta de 77 centros de atención médica integral de HAP, la incidencia de infección por CoViD-19 fue de 2,1 casos por cada 1000 pacientes con HAP, similar a la incidencia de infección por CoViD-19 en la población general. Si bien, esta pandemia ha alterado el estándar de atención médica de rutina y de manejo agudo, particularmente, en aquellos pacientes con HAP, los riesgos asociados con CoViD-19 son significativos, presentándose nuevos desafíos en el cuidado de pacientes con HP. Dado que los pacientes con HAP han demostrado tener peores resultados en el ámbito de esta pandemia, es esencial trabajar de manera proactiva para disminuir el riesgo de infección por CoViD-19, mientras se continúa brindando un alto nivel de atención médica. El impacto de CoViD-19 en la prestación de atención médica y en la sociedad en general requirió que se establecieran nuevos protocolos para el tratamiento de HAP para disminuir el riesgo de exposición o transmisión de CoViD-19. De manera similar, ha habido una disminución en las pruebas de pacientes estables. Actualmente, la forma en que brindamos la atención médica se evidencia en un aumento de las visitas de telemedicina, una menor exposición a los entornos de atención médica para los pacientes y los profesionales de la salud, ayudando a nuestra necesidad continua de brindar servicios a los pacientes dentro del entorno de CoViD-19 y adaptándonos a una forma diferente de interactuar, ampliando nuestra comprensión de la mejor manera de cuidar a nuestros pacientes.

Coronavirus disease 2019 (CoViD-19) causes severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), being particularly harmful for patients with underlying cardiovascular disease, and causing a cause of significant morbidity and mortality throughout the world. This virus leads to lung disease, while causing acute myocardial injury and chronic damage to the cardiovascular system. As a consequence of the damage to the lung parenchyma and altered pulmonary circulation, pulmonary hypertension (PH) can develop, with its respective consequence. The pathophysiology of this type of PH is complex and multifactorial, considering potential factors for alterations in pulmonary circulation. In recent studies, the evidenced prevalence of PH in patients with CoViD-19 is around 12%, but its evolution is not yet clear. The CoViD-19 pandemic has had a significant impact on all aspects of PH, from diagnosis and management to observing an increased risk of death in patients with pulmonary arterial hypertension (PAH). In a survey of 77 comprehensive PAH healthcare centers, the incidence of CoViD-19 infection was 2.1 cases per 1,000 PAH patients, similar to the incidence of CoViD-19 infection in the general population. Although this pandemic has altered the standard of routine medical care and acute management, particularly in those patients with PAH, the risks associated with CoViD-19 are significant, presenting new challenges in the care of patients with PH. Since PAH patients have been shown to have worse outcomes in the setting of this pandemic, it is essential to work proactively to decrease the risk of CoViD-19 infection, while continuing to provide a high level of medical care. The impact of CoViD-19 on the provision of health care and on society in general required that new protocols be established for the treatment of PAH to reduce the risk of exposure or transmission of CoViD-19. Similarly, there has been a decline in stable patient testing. Currently, the way we provide healthcare is evidenced by an increase in telemedicine visits, less exposure to healthcare settings for patients and healthcare professionals, aiding our continued need to provide services to patients. patients within the CoViD-19 environment and adapting to a different way of interacting, broadening our understanding of the best way to care for our patients

A doença coronavírus 2019 (CoViD-19) causa síndrome respiratória aguda grave coronavírus 2 (SARS-CoV-2), sendo particularmente prejudicial para pacientes com doença cardiovascular subjacente e causando uma importante morbidade e mortalidade em todo o mundo. Este vírus leva à doença pulmonar, enquanto causa lesão aguda do miocárdio e dano crônico ao sistema cardiovascular. Como consequência do dano ao parênquima pulmonar e da circulação pulmonar alterada, pode ocorrer hipertensão pulmonar (HP), com suas respectivas consequências. A fisiopatologia desse tipo de HP é complexa e multifatorial, considerando fatores potenciais para alterações da circulação pulmonar. Em estudos recentes, a prevalência de HP evidenciada em pacientes com CoViD-19 gira em torno de 12%, mas sua evolução ainda não está clara. A pandemia CoViD-19 teve um impacto significativo em todos os aspectos da HP, desde o diagnóstico e tratamento até a observação de um risco aumentado de morte em pacientes com hipertensão arterial pulmonar (HAP). Em uma pesquisa com 77 centros de saúde com HAP abrangentes, a incidência de infecção por CoViD-19 foi de 2,1 casos por 1.000 pacientes com HAP, semelhante à incidência de infecção por CoViD-19 na população em geral. Embora essa pandemia tenha alterado o padrão de cuidados médicos de rotina e tratamento agudo, particularmente em pacientes com HAP, os riscos associados ao CoViD-19 são significativos, apresentando novos desafios no cuidado de pacientes com HP. Como os pacientes com HAP demonstraram ter resultados piores no cenário dessa pandemia, é essencial trabalhar proativamente para diminuir o risco de infecção por CoViD-19, enquanto continua a fornecer um alto nível de cuidados médicos. O impacto do CoViD-19 na prestação de cuidados de saúde e na sociedade em geral exigiu o estabelecimento de novos protocolos para o tratamento da HAP para reduzir o risco de exposição ou transmissão do CoViD-19. Da mesma forma, houve um declínio nos testes de pacientes estáveis. Atualmente, a forma como prestamos serviços de saúde é evidenciada por um aumento nas visitas de telemedicina, menos exposição aos ambientes de saúde para pacientes e profissionais de saúde, auxiliando nossa necessidade contínua de fornecer serviços aos pacientes. Pacientes dentro do ambiente CoViD-19 e adaptando-se de uma maneira diferente de interagir, ampliando nosso entendimento sobre a melhor forma de cuidar de nossos pacientes.

COVID-19 y metabolismo: una mirada más allá del sistema respiratorio y de la enfermedad trombótica / COVID-19 and metabolism: a look beyond the respiratory system and thrombotic disease

Resumen La COVID-19 es una enfermedad infecciosa causada por el coronavirus del síndrome respiratorio agudo severo 2 (SARS-CoV-2) que tiene importantes manifestaciones sobre el sistema cardiovascular y respiratorio. Esta enfermedad, descrita en los primeros días de diciembre de 2019 en la ciudad de Wuhan, capital de la provincia de Hubei, en China, tuvo una rápida expansión mundial y fue declarada por la Organización Mundial de la Salud como pandemia el 11 de marzo de 2020. Tiene diferentes presentaciones clínicas, como neumonía, hipoxemia, falla renal, falla multisistémica, compromiso endotelial que lleva a lesiones trombóticas venosas y arteriales, y problemas cardiacos como insuficiencia cardiaca, miocarditis, arritmias e infarto de miocardio de los tipos 1 y 2. La mayoría de las personas presentan una enfermedad leve o no complicada (80%), y otras (20%) pueden desarrollar un cuadro grave con neumonía, síndrome de dificultad respiratoria, choque cardiogénico, trombosis y tormenta de citocinas (el 15% se manejan con oxigenoterapia y el 5% ameritan tratamiento en la unidad de cuidados intensivos). La mortalidad está relacionada con la edad y con la comorbilidad (hipertensión arterial, diabetes mellitus, enfermedades respiratorias, enfermedades cardiacas en general, enfermedades renales y obesidad). El objetivo de esta revisión narrativa es describir las alteraciones metabólicas y la relación de la diabetes mellitus, la obesidad, el síndrome metabólico y la dislipidemia con la morbilidad y la mortalidad vinculadas a la COVID-19.

Abstract COVID-19 is an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and that has important manifestations on the cardiovascular system and respiratory. This disease described in the first days of December 2019 in the city of Wuhan, capital of the province of Hubei, China, with a rapid global expansion and declared by the World Health Organization as a pandemic on March 11, 2020, has different clinical presentations such as pneumonia, hypoxemia, kidney failure, multisystem failure, endothelial involvement leading to venous and arterial thrombotic lesions, and heart problems such as heart failure, myocarditis, arrhythmias, and type 1 and 2 myocardial infarction. Most people have a mild or uncomplicated disease (80%), and others (20%) may develop a severe case with pneumonia, respiratory distress syndrome, cardiogenic shock, thrombosis, and cytokine storm (15% are managed with oxygen therapy and 5% merit treatment in the intensive care unit). Mortality is related to age and comorbidity (high blood pressure, diabetes mellitus, respiratory diseases, heart diseases in general, kidney diseases, and obesity). The objective of this narrative review is to describe the metabolic alterations and the relationship between diabetes mellitus, obesity, metabolic syndrome, and dyslipidemia with the morbidity and mortality associated with COVID-19 infection.

Papel de los tejidos orales durante la infección por SARS-CoV-2 / Role of oral tissues in SARS-CoV-2 infection

La actual pandemia de COVID-19 provocada por el virus SARS-CoV-2 es un problema de salud que afecta a la población globalmente. Su desarrollo puede ser asintomático o exhibir manifestaciones clínicas moderadas o severas dependiendo en gran medida de la respuesta inmune de quien la padece. Esta enfermedad afecta principalmente a los pulmones a través del desarrollo del síndrome respiratorio agudo severo (SRAS), tanto como por la «tormenta de citocinas¼, una respuesta inflamatoria exacerbada que podría provocar una falla multisistémica y, en casos severos, la muerte. Se conoce que la enzima convertidora de angiotensina 2 (ECA-2), presente en diversos tejidos del cuerpo, actúa como receptor funcional del virus SARS-CoV-2 facilitando la entrada de éste a las células. Se ha demostrado la presencia de dicho receptor en varios tejidos orales, por lo que se puede considerar a la cavidad bucal como una vía latente de infección por dicho coronavirus, ya que su mecanismo de transmisión es a través de la inhalación de partículas virales, ya sea por vía nasal u oral. Así mismo, la presencia de carga vírica en la saliva y algunos de los síntomas de la COVID-19, por ejemplo la ageusia, pueden indicar la presencia de contagio viral en etapas tempranas. La presente revisión muestra evidencia que sugiere que diversos tejidos en la cavidad oral podrían ser considerados sitios potenciales de contagio por el SARS-CoV-2, teniendo un papel importante en el mecanismo de transmisión y en el desarrollo de coinfecciones (AU)

The COVID-19 pandemic caused by the SARS-CoV-2 virus is currently a global healthcare problem. The onset of this disease can exhibit several clinical manifestations ranging from mild to severe symptoms, depending on the individual's immune response. COVID-19 primarily affects the lungs by developing the Severe Acute Respiratory Syndrome (SARS) and the «cytokine storm¼, an exacerbated inflammatory reaction that can lead to multiorgan failure and consequently death. The angiotensin-converting enzyme 2 (ACE-2), present in several tissues in the human body, is known to act as the functional receptor of the SARS-CoV-2 germ facilitating its entrance into the cells. Such receptor is also present in diverse oral cavity tissues, indicating a latent route of infection due to its influence in the transmission mechanism by inhalation, either oral or nasal, of virus particles. Also, viral load in saliva and taste disorder symptoms like ageusia could indicate a viral infection in its early stages. This article presents evidence suggesting that several tissues in the oral cavity can be considered potential sites of SARS-CoV-2 infection, thus playing an essential role in the transmission mechanism and development of co-infections (AU)

Papel do imunometabolismo, receptores Toll-Like e ECA 2 na COVID-19 / Role of immunometabolism, Toll-Like receptors, and ACE-2 in COVID-19

No combate à infecção pelo coronavírus 2 da síndrome respiratória aguda grave (SARS-CoV-2), o organismo se utiliza de mecanismos da imunidade inata, dentre eles os receptores Toll- Like (TLR), responsáveis pela sinalização da inflamação através da liberação de mediadores químicos e recrutamento de células imunitárias. Na patologia causada pela doença do SARS-CoV-2 2019 (COVID-19), ganha especial importância o TLR-4, visto que a sua estimulação exacerbada vem sendo relacionada ao estado hiperinflamatório em fases avançadas da COVID-19. Outro receptor que desempenha um papel primordial na infecção pelo SARS-CoV-2, servindo como porta de entrada para o vírus e progressão da doença, é a enzima conversora de angiotensina 2 (ECA 2), cuja ligação com a proteína S viral causa desregulação de vários sistemas fundamentais para a homeostase, como o sistema renina-angiotensina-aldosterona. Pacientes com doenças cardiometabólicas como obesidade, diabetes, aterosclerose e hipertensão vêm sendo classificados como alto risco para desenvolver as formas graves da COVID-19, visto que o estado inflamatório, já existente nessas doenças, pode ser agravado pelo desequilíbrio metabólico causado pelo SARS-CoV-2. A elucidação desses e de outros mecanismos relacionados à fisiopatologia da COVID-19 é imprescindível para uma melhora na estratificação de risco, nas escolhas terapêuticas e no prognóstico desses pacientes. Desta forma, nesta revisão objetivamos discutir as relações entre TLR-4, ECA 2, doenças cardiometabólicas, infecção pelo SARS-CoV-2 e gravidade da COVID-19.

In the fight against the infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the body uses mechanisms from the innate immune system, such as Toll-Like receptors (TLR), responsible for inflammation signaling through release of chemical mediators and recruitment of immune cells. In the disease caused by SARS-CoV-2 (COVID-19), TLR-4 assumes special importance because its exacerbated stimulation has been related to a hyperinflammatory state in advanced stages of COVID-19. Another receptor that plays a major role in SARS-CoV-2 infection, serving as a gateway to the virus and impacting disease progression, is angiotensin-converting enzyme 2 (ACE-2), whose binding to the viral S protein causes dysregulation of several key systems for homeostasis, such as the renin-angiotensin-aldosterone system. The elucidation of these and other mechanisms related to the pathophysiology of COVID-19 is essential for an improvement in risk stratification, therapeutic choices, and prognosis for these patients. Thus, we aimed to discuss in this review the relationships between TLR-4, ACE-2, cardiometabolic diseases, SARS-CoV-2 infection, and severity of COVID-19.

Megacolon tóxico en paciente con COVID-19 / Toxic megacolon in a patient with Covid-19

Introducción: La pandemia derivada de la enfermedad por el nuevo coronavirus 2019 (COVID-19) se ha convertido en una emergencia de salud pública mundial, debido a que puede desarrollar complicaciones que amenazan la vida. Si bien se sabe que el SARS-CoV-2 causa enfermedad pulmonar sustancial, se han observado muchas manifestaciones extrapulmonares, incluyendo el compromiso del sistema gastrointestinal. El megacolon tóxico es una complicación rara pero, potencialmente, mortal que se asocia más con la enfermedad inflamatoria intestinal. Sin embargo, cualquier afección que conduzca a la inflamación del colon puede conducir a una dilatación tóxica. Objetivo: Se presenta el caso de un paciente con un síndrome de dificultad respiratoria aguda secundario a una infección por SARS-COV-2. De manera concomitante presentó un cuadro de dilatación no obstructiva del colon, asociado con toxicidad sistémica. Caso clínico: El desarrollo de megacolon tóxico en un paciente con SARS-COV-2 puede estar justificado debido a que el virus infecta las células huésped a través del receptor de la enzima convertidora de angiotensina 2. Se cumplieron los criterios diagnósticos para megacolon tóxico. Conclusiones: Esta también se encuentra altamente expresada en las células epiteliales intestinales, por lo tanto, se debe considerar su diagnóstico oportuno para una intervención temprana, en aras de reducir la tasa de mortalidad tanto como sea posible(AU)

Introduction: The pandemic derived from the 2019 novel coronavirus disease (COVID-19) has become a global public health emergency, due to the fact that it can develop life-threatening complications. Although SARS-CoV-2 is known to cause substantial lung disease, many extra-pulmonary manifestations have been observed, including involvement of the gastrointestinal system. Toxic mega colon is a rare but life-threatening complication most associated with inflammatory bowel disease. However, any condition that leads to inflammation of the colon can lead to toxic dilation. Objective: To report the case of a patient with ARDS secondary to a SARS-COV-2 infection. Concomitantly, she had non-obstructive dilation of the colon, associated with systemic toxicity. Clinical case report: The development of toxic mega colon in a patient with SARS-COV-2 may be justified because the virus infects host cells through the angiotensin-converting enzyme 2 receptor. The diagnostic criteria for toxic megacolon were met. Conclusions: It is also highly expressed in intestinal epithelial cells, therefore, its timely diagnosis should be considered for early intervention, in order to reduce the mortality rate as much as possible(AU)

Proteína de la espícula del virus SARS-CoV-2 y su relación con la enzima convertidora de angiotensina-2 / Proteína de pico do vírus SARS-CoV-2 e sua relação com a enzima conversora de angiotensina-2 / Spike protein of the SARS-CoV-2 virus and its relationship with the angiotensin-converting enzyme-2

Introducción: La COVID-19 causada por el virus del SARS-CoV-2 es una pandemia que ha cobrado la vida de millones de personas y sobrecargado los servicios sanitarios de todo el mundo. Objetivo: Describir la relación entre la proteína de la espícula (proteína S, proteína espicular o spike) del SARS-CoV-2 y enzima convertidora de angiotensina 2 como desencadenante primario de la infección por la COVID-19. Método: Se realizó una búsqueda bibliográfica en Google Académico, SciELO y PubMed, con los descriptores iniciales COVID-19 y SARS-CoV-2. El periodo de publicación seleccionado fue entre los años 2019-2021, sin restricciones en cuanto al tipo de artículo. Los trabajos debieron estar disponibles en español e inglés a texto completo. Resultados: La proteína de la espícula del SARS-CoV-2, que desempeña un papel clave en el reconocimiento del receptor y en el proceso de fusión de la membrana celular, está compuesta por dos subunidades, S1 y S2. La subunidad S1 contiene un dominio de unión al receptor RBD (por sus siglas en inglés, receptor-binding domain) que se une al receptor del huésped, la enzima convertidora de angiotensina 2, mientras que la subunidad S2 interviene en la fusión de la membrana viral y celular. La ubicuidad tisular de la enzima convertidora de angiotensina 2 explica las múltiples manifestaciones clínicas de la enfermedad. Conclusiones: El conocimiento de la relación entre el SARS-CoV-2 y su receptor enzima convertidora de angiotensina 2 permite no solo conocer la fisiopatología de la COVID-19, sino el diseño de fármacos antivirales y vacunas que contribuyen a la prevención y tratamiento de esta enfermedad viral.

Introduction: COVID-19 caused by the SARS-CoV-2 virus is a pandemic that has claimed the lives of millions of people and overloaded health services around the world. Objective: To describe the relationship between the spike protein (S) of SARS-CoV-2 and the angiotensin-converting enzyme 2 as the primary trigger of COVID-19 infection. Method: A bibliographic search was carried out in Google Scholar, SciELO and PubMed, with the initial descriptors COVID-19 and SARS-CoV-2. The publication period selected was between the years 2019 to 2021, without restrictions regarding the type of article. The papers had to be available in full text in Spanish and English. Results: The spike protein of SARS-CoV-2, which plays a key role in receptor recognition and in the cell membrane fusion process, is composed of two subunits, S1 and S2. The S1 subunit contains a receptor-binding domain (RBD) that binds to the host's receptor, angiotensin-converting enzyme 2, while the S2 subunit is involved in the viral and cellular membrane fusion. The tissue ubiquity of angiotensin converting enzyme 2 explains the multiple clinical manifestations of the disease. Conclusions: The knowledge of the relationship between SARS-CoV-2 and its receptor the angiotensin-converting enzyme 2, allows not only to know the pathophysiology of COVID-19, but also the design of antiviral drugs and vaccines that contribute to the prevention and treatment of this viral disease.

Introdução: COVID-19 causada pelo vírus SARS-CoV-2 é uma pandemia que ceifou a vida de milhões de pessoas e sobrecarregou os serviços de saúde em todo o mundo. Objetivo: Descrever a relação entre a proteína spike (S) do SARS-CoV-2 e a enzima conversora de angiotensina 2 como o principal fator desencadeante da infecção por COVID-19. Método: Foi realizada uma busca bibliográfica no Google Scholar, SciELO e PubMed, com os descritores iniciais COVID-19 e SARS-CoV-2. O período de publicação selecionado foi entre os anos de 2019 a 2021, sem restrições quanto ao tipo de artigo. Os artigos deveriam estar disponíveis na íntegra em espanhol e inglês. Resultados: A proteína spike do SARS-CoV-2, que desempenha um papel fundamental no reconhecimento do receptor e no processo de fusão da membrana celular, é composta por duas subunidades, S1 e S2. A subunidade S1 contém um domínio de ligação ao receptor (RBD) que se liga ao receptor do hospedeiro, a enzima conversora de angiotensina 2, enquanto a subunidade S2 está envolvida na fusão da membrana viral e celular. A onipresença tecidual da enzima conversora da angiotensina 2 explica as múltiplas manifestações clínicas da doença. Conclusões: O conhecimento da relação entre o SARS-CoV-2 e seu receptor, a enzima conversora de angiotensina 2, permite não só conhecer a fisiopatologia da COVID-19, mas também o desenho de antivirais e vacinas que contribuam para a prevenção e tratamento desta doença viral.

Preparation and tumor-specific molecular imaging of a novel PET probe targeting angiotensin converting enzyme 2 / 中华核医学与分子影像杂志

Objective:To prepare a novel molecular imaging probe targeting angiotensin converting enzyme (ACE) 2 by using 68Ga labeled with 1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid (DOTA)-DX600, then the probe was evaluated in cervical cancer model by microPET/CT imaging. Methods:68Ga labeled DOTA-DX600 at 95 ℃, and the quality control, stability in vitro and lipid-water partition coefficient (log P) were tested. Tumor-bearing mouse models were constructed using stably transfected ACE2 highly expressed cervical cancer cells (Hela). The distribution and uptake of 68Ga-DOTA-DX600 in normal KM mice and tumor-bearing mice were determined by microPET/CT imaging, and the maximum standardized uptake value (SUV max) of the main organs and tumors were obtained by semi-quantitative analysis of the region of interest (ROI). Results:The preparation time of 68Ga-DOTA-DX600 was about 20 min, the specific activity of the probe was (18.74±3.72)×10 6 GBq/mol, the labeling rate was 82.3%, and the radiochemical purity was about 99% after purification. After placement in saline or 5% human serum albumin (HSA) solution at room temperature for 2 h, the radiochemical purity of the probe was more than 96%. The lipid-water partition coefficient (log P) was -2.44 ±0.04 ( n=3), which indicated as a good hydrophilicity. In normal KM mice, 68Ga-DOTA-DX600 metabolized faster in the blood and mainly distributed in the kidneys. The probe showed good tumor targeting ability in the tumor-bearing mice and the SUV max of the tumor were 0.25±0.01 and 0.21±0.01 at 30 min and 60 min after injection, respectively, and the tumor uptake was inhibited by DX600. Conclusion:68Ga-DOTA-DX600 can be obtained conveniently and fast and shows a good targeting ability to tumors, which provide potential application value for researches on targeting ACE2.

Nanomedicine for acute respiratory distress syndrome: The latest application, targeting strategy, and rational design

Acute respiratory distress syndrome (ARDS) is characterized by the severe inflammation and destruction of the lung air-blood barrier, leading to irreversible and substantial respiratory function damage. Patients with coronavirus disease 2019 (COVID-19) have been encountered with a high risk of ARDS, underscoring the urgency for exploiting effective therapy. However, proper medications for ARDS are still lacking due to poor pharmacokinetics, non-specific side effects, inability to surmount pulmonary barrier, and inadequate management of heterogeneity. The increased lung permeability in the pathological environment of ARDS may contribute to nanoparticle-mediated passive targeting delivery. Nanomedicine has demonstrated unique advantages in solving the dilemma of ARDS drug therapy, which can address the shortcomings and limitations of traditional anti-inflammatory or antioxidant drug treatment. Through passive, active, or physicochemical targeting, nanocarriers can interact with lung epithelium/endothelium and inflammatory cells to reverse abnormal changes and restore homeostasis of the pulmonary environment, thereby showing good therapeutic activity and reduced toxicity. This article reviews the latest applications of nanomedicine in pre-clinical ARDS therapy, highlights the strategies for targeted treatment of lung inflammation, presents the innovative drug delivery systems, and provides inspiration for strengthening the therapeutic effect of nanomedicine-based treatment.