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1.
Int Med Case Rep J ; 17: 359-365, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38651079

RESUMO

Immune checkpoint inhibitors (ICI) have become a new hope for many patients with advanced cancer by blocking tumor immune escape. Bladder cancer is a common malignant tumor of the urinary tract epithelium that often relapses and metastasizes after surgery, chemotherapy, and radiotherapy. Immunotherapy has dramatically improved patient survival rates and clinical benefits as a new, potentially effective therapy. However, avoidance of various immune-related adverse events (irAEs) remains an implausible idea. ICI-induced myocarditis is different from viral myocarditis, and mortality is still high with the current treatment. We report the case of an 82-year-old female patient with ICI-induced fulminant myocarditis and myasthenia gravis. Although she actively accepted the current mainstream treatment for immune-related myocarditis and myasthenia, she died of heart and respiratory failure. Analyzing and reporting the patient's disease development process and the changes in related indicators may help peers gain a deeper understanding of immune-related adverse events and reduce the mortality of immune-related myocarditis.

2.
Front Pharmacol ; 14: 1297124, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38089048

RESUMO

Ischemia-reperfusion (I/R) injury refers to a new injury caused by reperfusion after the restoration of ischemic tissue or organ blood supply. Salvianic acid A (danshensu) is a primary active ingredient extracted from Salvia miltiorrhiza. It has a protective function against I/R injury in the cardiovascular system, brain, liver, kidney, gastrointestinal tract, and other organs. This article reviews evidence of the protective effects of Salvianic acid A and its potential mechanisms of action in organ I/R injury protection. The aim of this review is to investigate the role of Salvianic acid A in the treatment of I/R injury, providing a reference resource that could facilitate subsequent studies.

3.
Eur J Nucl Med Mol Imaging ; 50(12): 3538-3557, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37460750

RESUMO

BACKGROUND: Positron emission tomography (PET) scanning is an important diagnostic imaging technique used in disease diagnosis, therapy planning, treatment monitoring, and medical research. The standardized uptake value (SUV) obtained at a single time frame has been widely employed in clinical practice. Well beyond this simple static measure, more detailed metabolic information can be recovered from dynamic PET scans, followed by the recovery of arterial input function and application of appropriate tracer kinetic models. Many efforts have been devoted to the development of quantitative techniques over the last couple of decades. CHALLENGES: The advent of new-generation total-body PET scanners characterized by ultra-high sensitivity and long axial field of view, i.e., uEXPLORER (United Imaging Healthcare), PennPET Explorer (University of Pennsylvania), and Biograph Vision Quadra (Siemens Healthineers), further stimulates valuable inspiration to derive kinetics for multiple organs simultaneously. But some emerging issues also need to be addressed, e.g., the large-scale data size and organ-specific physiology. The direct implementation of classical methods for total-body PET imaging without proper validation may lead to less accurate results. CONCLUSIONS: In this contribution, the published dynamic total-body PET datasets are outlined, and several challenges/opportunities for quantitation of such types of studies are presented. An overview of the basic equation, calculation of input function (based on blood sampling, image, population or mathematical model), and kinetic analysis encompassing parametric (compartmental model, graphical plot and spectral analysis) and non-parametric (B-spline and piece-wise basis elements) approaches is provided. The discussion mainly focuses on the feasibilities, recent developments, and future perspectives of these methodologies for a diverse-tissue environment.


Assuntos
Algoritmos , Tomografia por Emissão de Pósitrons , Humanos , Cinética , Tomografia por Emissão de Pósitrons/métodos
4.
Biosens Bioelectron ; 231: 115285, 2023 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-37058958

RESUMO

As a full-fidelity simulation of human cells, tissues, organs, and even systems at the microscopic scale, Organ-on-a-Chip (OOC) has significant ethical advantages and development potential compared to animal experiments. The need for the design of new drug high-throughput screening platforms and the mechanistic study of human tissues/organs under pathological conditions, the evolving advances in 3D cell biology and engineering, etc., have promoted the updating of technologies in this field, such as the iteration of chip materials and 3D printing, which in turn facilitate the connection of complex multi-organs-on-chips for simulation and the further development of technology-composite new drug high-throughput screening platforms. As the most critical part of organ-on-a-chip design and practical application, verifying the success of organ model modeling, i.e., evaluating various biochemical and physical parameters in OOC devices, is crucial. Therefore, this paper provides a logical and comprehensive review and discussion of the advances in organ-on-a-chip detection and evaluation technologies from a broad perspective, covering the directions of tissue engineering scaffolds, microenvironment, single/multi-organ function, and stimulus-based evaluation, and provides a more comprehensive review of the progress in the significant organ-on-a-chip research areas in the physiological state.


Assuntos
Técnicas Biossensoriais , Sistemas Microfisiológicos , Animais , Humanos , Organoides , Engenharia Tecidual , Microfluídica , Dispositivos Lab-On-A-Chip
5.
Acta Pharm Sin B ; 13(2): 460-477, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36873163

RESUMO

Medication during pregnancy is widespread, but there are few reports on its fetal safety. Recent studies suggest that medication during pregnancy can affect fetal morphological and functional development through multiple pathways, multiple organs, and multiple targets. Its mechanisms involve direct ways such as oxidative stress, epigenetic modification, and metabolic activation, and it may also be indirectly caused by placental dysfunction. Further studies have found that medication during pregnancy may also indirectly lead to multi-organ developmental programming, functional homeostasis changes, and susceptibility to related diseases in offspring by inducing fetal intrauterine exposure to too high or too low levels of maternal-derived glucocorticoids. The organ developmental toxicity and programming alterations caused by medication during pregnancy may also have gender differences and multi-generational genetic effects mediated by abnormal epigenetic modification. Combined with the latest research results of our laboratory, this paper reviews the latest research progress on the developmental toxicity and functional programming alterations of multiple organs in offspring induced by medication during pregnancy, which can provide a theoretical and experimental basis for rational medication during pregnancy and effective prevention and treatment of drug-related multiple fetal-originated diseases.

6.
EBioMedicine ; 90: 104518, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36933413

RESUMO

BACKGROUND: Neurological damage caused by coronavirus disease 2019 (COVID-19) has attracted increasing attention. Recently, through autopsies of patients with COVID-19, the direct identification of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in their central nervous system (CNS) has been reported, indicating that SARS-CoV-2 might directly attack the CNS. The need to prevent COVID-19-induced severe injuries and potential sequelae is urgent, requiring the elucidation of large-scale molecular mechanisms in vivo. METHODS: In this study, we performed liquid chromatography-mass spectrometry-based proteomic and phosphoproteomic analyses of the cortex, hippocampus, thalamus, lungs, and kidneys of SARS-CoV-2-infected K18-hACE2 female mice. We then performed comprehensive bioinformatic analyses, including differential analyses, functional enrichment, and kinase prediction, to identify key molecules involved in COVID-19. FINDINGS: We found that the cortex had higher viral loads than did the lungs, and the kidneys did not have SARS-COV-2. After SARS-CoV-2 infection, RIG-I-associated virus recognition, antigen processing and presentation, and complement and coagulation cascades were activated to different degrees in all five organs, especially the lungs. The infected cortex exhibited disorders of multiple organelles and biological processes, including dysregulated spliceosome, ribosome, peroxisome, proteasome, endosome, and mitochondrial oxidative respiratory chain. The hippocampus and thalamus had fewer disorders than did the cortex; however, hyperphosphorylation of Mapt/Tau, which may contribute to neurodegenerative diseases, such as Alzheimer's disease, was found in all three brain regions. Moreover, SARS-CoV-2-induced elevation of human angiotensin-converting enzyme 2 (hACE2) was observed in the lungs and kidneys, but not in the three brain regions. Although the virus was not detected, the kidneys expressed high levels of hACE2 and exhibited obvious functional dysregulation after infection. This indicates that SARS-CoV-2 can cause tissue infections or damage via complicated routes. Thus, the treatment of COVID-19 requires a multipronged approach. INTERPRETATION: This study provides observations and in vivo datasets for COVID-19-associated proteomic and phosphoproteomic alterations in multiple organs, especially cerebral tissues, of K18-hACE2 mice. In mature drug databases, the differentially expressed proteins and predicted kinases in this study can be used as baits to identify candidate therapeutic drugs for COVID-19. This study can serve as a solid resource for the scientific community. The data in this manuscript will serve as a starting point for future research on COVID-19-associated encephalopathy. FUNDING: This study was supported by grants from the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, the National Natural Science Foundation of China, and the Natural Science Foundation of Beijing.


Assuntos
COVID-19 , Camundongos , Humanos , Feminino , Animais , SARS-CoV-2 , Enzima de Conversão de Angiotensina 2 , Proteômica , Camundongos Transgênicos , Pulmão , Hipocampo , Rim , Tálamo , Modelos Animais de Doenças
7.
Acta Pharmaceutica Sinica B ; (6): 460-477, 2023.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wpr-971711

RESUMO

Medication during pregnancy is widespread, but there are few reports on its fetal safety. Recent studies suggest that medication during pregnancy can affect fetal morphological and functional development through multiple pathways, multiple organs, and multiple targets. Its mechanisms involve direct ways such as oxidative stress, epigenetic modification, and metabolic activation, and it may also be indirectly caused by placental dysfunction. Further studies have found that medication during pregnancy may also indirectly lead to multi-organ developmental programming, functional homeostasis changes, and susceptibility to related diseases in offspring by inducing fetal intrauterine exposure to too high or too low levels of maternal-derived glucocorticoids. The organ developmental toxicity and programming alterations caused by medication during pregnancy may also have gender differences and multi-generational genetic effects mediated by abnormal epigenetic modification. Combined with the latest research results of our laboratory, this paper reviews the latest research progress on the developmental toxicity and functional programming alterations of multiple organs in offspring induced by medication during pregnancy, which can provide a theoretical and experimental basis for rational medication during pregnancy and effective prevention and treatment of drug-related multiple fetal-originated diseases.

8.
Front Physiol ; 13: 1018971, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36479346

RESUMO

Ischemia/reperfusion (I/R) injury is a common clinical problem after coronary angioplasty, cardiopulmonary resuscitation, and organ transplantation, which can lead to cell damage and death. Mitsugumin 53 (MG53), also known as Trim72, is a conservative member of the TRIM family and is highly expressed in mouse skeletal and cardiac muscle, with minimal amounts in humans. MG53 has been proven to be involved in repairing cell membrane damage. It has a protective effect on I/R injury in multiple oxygen-dependent organs, such as the heart, brain, lung, kidney, and liver. Recombinant human MG53 also plays a unique role in I/R, sepsis, and other aspects, which is expected to provide new ideas for related treatment. This article briefly reviews the pathophysiology of I/R injury and how MG53 mitigates multi-organ I/R injury.

9.
Zool Res ; 43(6): 1041-1062, 2022 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-36349357

RESUMO

Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes diverse clinical manifestations and tissue injuries in multiple organs. However, cellular and molecular understanding of SARS-CoV-2 infection-associated pathology and immune defense features in different organs remains incomplete. Here, we profiled approximately 77 000 single-nucleus transcriptomes of the lung, liver, kidney, and cerebral cortex in rhesus macaques ( Macaca mulatta) infected with SARS-CoV-2 and healthy controls. Integrated analysis of the multi-organ dataset suggested that the liver harbored the strongest global transcriptional alterations. We observed prominent impairment in lung epithelial cells, especially in AT2 and ciliated cells, and evident signs of fibrosis in fibroblasts. These lung injury characteristics are similar to those reported in patients with coronavirus disease 2019 (COVID-19). Furthermore, we found suppressed MHC class I/II molecular activity in the lung, inflammatory response in the liver, and activation of the kynurenine pathway, which induced the development of an immunosuppressive microenvironment. Analysis of the kidney dataset highlighted tropism of tubule cells to SARS-CoV-2, and we found membranous nephropathy (an autoimmune disease) caused by podocyte dysregulation. In addition, we identified the pathological states of astrocytes and oligodendrocytes in the cerebral cortex, providing molecular insights into COVID-19-related neurological implications. Overall, our multi-organ single-nucleus transcriptomic survey of SARS-CoV-2-infected rhesus macaques broadens our understanding of disease features and antiviral immune defects caused by SARS-CoV-2 infection, which may facilitate the development of therapeutic interventions for COVID-19.


Assuntos
COVID-19 , Animais , COVID-19/genética , COVID-19/veterinária , Macaca mulatta , SARS-CoV-2 , Transcriptoma , Carga Viral/veterinária
10.
Indian J Dermatol ; 67(3): 314, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36386064

RESUMO

A 30-year-old woman presented with an acute-onset high-grade fever (103°F), multiple episodes of throbbing abdominal pain in the right quadrant, and pustular red lesions on the left leg. The radiological findings were suggestive of autoimmune cholangitis and pancreatitis. The skin lesions recurred on different portions of the body, and histopathological findings showed lobular and septal lymphohistiocytic infiltrate without vasculitis. The epidermis had focal ulcerations, and the dermis showed the presence of subcutaneous fat and an infiltrate of lymphocytes, histiocytes, and neutrophils (described as lobular and septal panniculitis without vasculitis). Based on the clinical and histopathological features, a diagnosis of migratory panniculitis was made. The patient was managed with analgesics, antibiotics, and a long course of steroids; the patient responded well to these medications. To the best of our knowledge, this is one of the first case reports of migratory panniculitis associated with IgG4-related disease. Patients with migratory panniculitis should be investigated for the presence of IgG4-related autoimmune disease. However, steroids remain the drug of choice when these conditions occur together.

11.
Med Phys ; 49(8): 5244-5257, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35598077

RESUMO

BACKGROUND: Fast and accurate multiorgans segmentation from computed tomography (CT) scans is essential for radiation treatment planning. Self-attention(SA)-based deep learning methodologies provide higher accuracies than standard methods but require memory and computationally intensive calculations, which restricts their use to relatively shallow networks. PURPOSE: Our goal was to develop and test a new computationally fast and memory-efficient bidirectional SA method called nested block self-attention (NBSA), which is applicable to shallow and deep multiorgan segmentation networks. METHODS: A new multiorgan segmentation method combining a deep multiple resolution residual network with computationally efficient SA called nested block SA (MRRN-NBSA) was developed and evaluated to segment 18 different organs from head and neck (HN) and abdomen organs. MRRN-NBSA combines features from multiple image resolutions and feature levels with SA to extract organ-specific contextual features. Computational efficiency is achieved by using memory blocks of fixed spatial extent for SA calculation combined with bidirectional attention flow. Separate models were trained for HN (n = 238) and abdomen (n = 30) and tested on set aside open-source grand challenge data sets for HN (n = 10) using a public domain database of computational anatomy and blinded testing on 20 cases from Beyond the Cranial Vault data set with overall accuracy provided by the grand challenge website for abdominal organs. Robustness to two-rater segmentations was also evaluated for HN cases using the open-source data set. Statistical comparison of MRRN-NBSA against Unet, convolutional network-based SA using criss-cross attention (CCA), dual SA, and transformer-based (UNETR) methods was done by measuring the differences in the average Dice similarity coefficient (DSC) accuracy for all HN organs using the Kruskall-Wallis test, followed by individual method comparisons using paired, two-sided Wilcoxon-signed rank tests at 95% confidence level with Bonferroni correction used for multiple comparisons. RESULTS: MRRN-NBSA produced an average high DSC of 0.88 for HN and 0.86 for the abdomen that exceeded current methods. MRRN-NBSA was more accurate than the computationally most efficient CCA (average DSC of 0.845 for HN, 0.727 for abdomen). Kruskal-Wallis test showed significant difference between evaluated methods (p=0.00025). Pair-wise comparisons showed significant differences between MRRN-NBSA than Unet (p=0.0003), CCA (p=0.030), dual (p=0.038), and UNETR methods (p=0.012) after Bonferroni correction. MRRN-NBSA produced less variable segmentations for submandibular glands (0.82 ± 0.06) compared to two raters (0.75 ± 0.31). CONCLUSIONS: MRRN-NBSA produced more accurate multiorgan segmentations than current methods on two different public data sets. Testing on larger institutional cohorts is required to establish feasibility for clinical use.


Assuntos
Processamento de Imagem Assistida por Computador , Tomografia Computadorizada por Raios X , Abdome , Atenção , Cabeça , Processamento de Imagem Assistida por Computador/métodos , Tomografia Computadorizada por Raios X/métodos
12.
Semin Immunopathol ; 44(3): 363-374, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35238952

RESUMO

Atherosclerosis is a chronic inflammatory disease of the vascular system that is characterized by the deposition of modified lipoproteins, accumulation of immune cells, and formation of fibrous tissue within the vessel wall. The disease occurs in vessels throughout the body and affects the functions of almost all organs including the lymphoid system, bone marrow, heart, brain, pancreas, adipose tissue, liver, kidneys, and gastrointestinal tract. Atherosclerosis and associated factors influence these tissues via the modulation of local vascular functions, induction of cholesterol-associated pathologies, and regulation of local immune responses. In this review, we discuss how atherosclerosis interferers with functions of different organs via several common pathways and how the disturbance of immunity in atherosclerosis can result in disease-provoking dysfunctions in multiple tissues. Our growing appreciation of the implication of atherosclerosis and associated microenvironmental conditions in the multi-organ pathology promises to influence our understanding of CVD-associated disease pathologies and to provide new therapeutic opportunities.


Assuntos
Aterosclerose , Tecido Adiposo , Aterosclerose/etiologia , Trato Gastrointestinal , Humanos , Rim , Fígado
13.
Tob Induc Dis ; 20: 02, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35087358

RESUMO

INTRODUCTION: It is commonly considered that COPD or at least emphysema represents accelerated lung aging induced in part by oxidative damage from cigarette smoke components. However, the issue if there are any aging signs in other organs in patients with COPD or emphysema remains unclear. The aim of this study is to explore whether there is multiple organ aging in the animal model of emphysema induced by cigarette smoke extract (CSE), and to ascertain the possible mechanisms, if any. METHODS: The animal model of emphysema was induced by CSE. Histomorphological changes in lung, heart, liver, kidney and spleen tissues were measured after staining with hematoxylin and eosin (H&E). The concentrations of stem cell factor (SCF), CyclinD1 and superoxide dismutase (SOD) in serum were determined by ELISA kit. The expressions of p16 (INK4a), Sca-1, eNOS proteins and mRNA in lung, heart, liver, kidney and spleen tissues were detected by Western blotting and quantitative reverse transcriptase polymerase chain reaction (qRT-PCR), respectively. Decitabine (Dec) was applied to examine whether it could alter the changes caused by CSE. RESULTS: The histomorphology of lung tissue was significantly changed, while other organs exhibited normal structure and histomorphology. The concentrations of SCF, CyclinD1 and SOD in serum were lower in the CSE group than in the control group. The expression levels of p16(INK4a) protein and mRNA in lung, heart, liver, kidney and spleen tissues were higher in the CSE group than in the control group, while the expression levels of Sca-1 and eNOS proteins and mRNA were lower in the CSE group than in the control group, in the tissues described above. Dec could partly alleviate the damages caused by CSE and the degree of alleviation resulted by Dec varied from organ to organ. CONCLUSIONS: In addition to the aging of the lung tissue in the emphysema animal model induced by CSE, the tissues of the heart, liver, kidney and spleen were also in the progress of aging, but the sensibility and affinity of lung to CSE were higher than those of the other organs. Multiple organ aging may also exist in the animal model of emphysema induced by CSE. DEC can partly alleviate the multiple organ aging caused by CSE.

14.
Transpl Int ; 34(12): 2570-2577, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34668605

RESUMO

Women with absolute uterine factor infertility cannot get pregnant. The current experience in uterine transplantation is limited and the use of a deceased donor uterus in this area is incipient after some initial unsuccessful attempts. The birth of healthy babies through this modality in four different centers has given a new impetus to the use of this transplantation technique. We aimed to develop a technique for uterus procurement and preparation for transplantation from a brain dead donor. Fifteen uteri were retrieved from multi-organ donor patients, 10 of these were used in bench surgeries with the proposed technique. All procedures were performed after obtaining family's consent. This study allowed the clinical use of two of the 15 organs that were procured for transplantation. One of these organs resulted in the first live birth worldwide using a uterus transplanted from a deceased donor, a landmark in reproductive medicine. Another outcome was the optimization of the surgical technique involving less manipulation of the uterine vascular pedicles. The success of this novel technique suggests that the proposed model can be replicated and optimized further to facilitate the transplantation of uterus from deceased donors.


Assuntos
Infertilidade Feminina , Morte Encefálica , Seleção do Doador , Feminino , Humanos , Gravidez , Doadores de Tecidos , Útero
15.
R I Med J (2013) ; 104(8): 11-14, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34582507

RESUMO

Coronavirus disease 2019 (COVID-19) may cause a hypercoagulability state and thrombotic complications. Multiorgan infarctions in young patients are very rare. Here we report a 35-year-old male patient with COVID-19 complicated by multiorgan infarctions. The patient had a past medical history of uncontrolled insulin-dependent diabetes mellitus and was admitted to the intensive care unit with progressive hypoxia in the setting of SARS-CoV-2 infection. The patient received prophylactic anticoagulant during the entire hospital course. During the hospitalization, the patient developed hypoxic respiratory arrest, diffuse anoxic brain injury and brain herniation. Postmortem examination demonstrated multiple infarctions and thromboses involving the heart, bilateral lungs, kidneys, and spleen. In conclusion, multiple organ infarctions may occur in young patients with COVID-19 despite prophylactic anticoagulation therapy.


Assuntos
COVID-19 , Adulto , Autopsia , Humanos , Infarto , Pulmão , Masculino , SARS-CoV-2 , Adulto Jovem
16.
Biomed Pharmacother ; 138: 111465, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34311522

RESUMO

Acidic mammalian chitinase (CHIA) belongs to the 18-glycosidase family and is expressed in epithelial cells and certain immune cells (such as neutrophils and macrophages) in various organs. Under physiological conditions, as a hydrolase, CHIA can degrade chitin-containing pathogens, participate in Type 2 helper T (Th2)-mediated inflammation, and enhance innate and adaptive immunity to pathogen invasion. Under pathological conditions, such as rhinitis, ocular conjunctivitis, asthma, chronic atrophic gastritis, type 2 diabetes, and pulmonary interstitial fibrosis, CHIA expression is significantly changed. In addition, studies have shown that CHIA has an anti-apoptotic effect, promotes epithelial cell proliferation and maintains organ integrity, and these effects are not related to chitinase degradation. CHIA can also be used as a biomolecular marker in diseases such as chronic atrophic gastritis, dry eye, and acute kidney damage caused by sepsis. Analysis of the authoritative TCGA database shows that CHIA expression in gastric adenocarcinoma, liver cancer, renal clear cell carcinoma and other tumors is significantly downregulated compared with that in normal tissues, but the specific mechanism is unclear. This review is based on all surveys conducted to date and summarizes the expression patterns and functional diversity of CHIA in various organs. Understanding the physiological and pathophysiological relevance of CHIA in multiple organs opens new possibilities for disease treatment.


Assuntos
Encéfalo/enzimologia , Quitinases/metabolismo , Sistema Digestório/enzimologia , Olho/enzimologia , Rim/enzimologia , Sistema Respiratório/enzimologia , Animais , Encéfalo/fisiopatologia , Diabetes Mellitus Tipo 2/enzimologia , Diabetes Mellitus Tipo 2/fisiopatologia , Sistema Digestório/fisiopatologia , Olho/fisiopatologia , Humanos , Rim/fisiopatologia , Sistema Respiratório/fisiopatologia , Transdução de Sinais
17.
Annu Rev Anal Chem (Palo Alto Calif) ; 14(1): 155-183, 2021 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-33974806

RESUMO

Adverse effects of environmental toxicants to human health have traditionally been assayed using in vitro assays. Organ-on-chip (OOC) is a new platform that can bridge the gaps between in vitro assays (or 3D cell culture) and animal tests. Microenvironments, physical and biochemical stimuli, and adequate sensing and biosensing systems can be integrated into OOC devices to better recapitulate the in vivo tissue and organ behavior and metabolism. While OOCs have extensively been studied for drug toxicity screening, their implementation in environmental toxicology assays is minimal and has limitations. In this review, recent attempts of environmental toxicology assays using OOCs, including multiple-organs-on-chip, are summarized and compared with OOC-based drug toxicity screening. Requirements for further improvements are identified and potential solutions are suggested.


Assuntos
Ecotoxicologia , Dispositivos Lab-On-A-Chip , Animais , Bioensaio , Humanos , Análise de Sequência com Séries de Oligonucleotídeos
18.
Virulence ; 12(1): 918-936, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-33757410

RESUMO

The coronavirus disease 19 (COVID-19) caused by the novel coronavirus known as SARS-CoV-2 has caused a global public health crisis. As of 7 January 2021, 87,640,402 confirmed cases and 1,891,692 mortalities have been reported worldwide. Studies focusing on the epidemiological and clinical characteristics of COVID-19 patients have suggested a dysregulated immune response characterized by lymphopenia and cytokine storm in these patients. The exaggerated immune response induced by the cytokine storm causes septic shock, acute respiratory distress syndrome (ARDS), and/or multiple organs failure, which increases the fatality rate of patients with SARS-CoV-2 infection. Herein, we review the recent research progress on epidemiology, clinical features, and system pathology in COVID-19. Moreover, we summarized the recent therapeutic strategies, which are either approved, under clinical trial, and/or under investigation by the local or global health authorities. We assume that treatments should focus on the use of antiviral drugs in combination with immunomodulators as well as treatment of the underlying comorbidities.


Assuntos
COVID-19/imunologia , COVID-19/patologia , SARS-CoV-2/patogenicidade , Imunidade Adaptativa , Antivirais/uso terapêutico , COVID-19/virologia , Síndrome da Liberação de Citocina/tratamento farmacológico , Síndrome da Liberação de Citocina/imunologia , Síndrome da Liberação de Citocina/patologia , Síndrome da Liberação de Citocina/virologia , Humanos , Imunidade Inata , Fatores Imunológicos/uso terapêutico , Linfopenia/tratamento farmacológico , Linfopenia/imunologia , Linfopenia/patologia , Linfopenia/virologia , SARS-CoV-2/imunologia , Carga Viral , Tratamento Farmacológico da COVID-19
19.
Talanta ; 226: 122097, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33676654

RESUMO

Standard two/three dimensional (2D/3D)-cell culture platforms have facilitated the understanding of the communications between various cell types and their microenvironments. However, they are still limited in recapitulating the complex functionalities in vivo, such as tissue formation, tissue-tissue interface, and mechanical/biochemical microenvironments of tissues and organs. Intestine-on-a-chip platforms offer a new way to mimic intestinal behaviors and functionalities by constructing in vitro intestinal models in microfluidic devices. This review summarizes the advances and limitations of the state-of-the-art 2D/3D-cell culture platforms, animal models, intestine chips, and the combined multi-organ chips related with intestines. Their applications to studying intestinal functions, drug testing, and disease modeling are introduced. Different intestinal cell sources are compared in terms of gene expression abilities and the recapitulated intestinal morphologies. Among these cells, cells isolated form human intestinal tissues and derived from pluripotent stem cells appear to be more suitable for in vitro reconstruction of intestinal organs. Key challenges of current intestine-on-a-chip platforms and future directions are also discussed.


Assuntos
Técnicas de Cultura de Células , Dispositivos Lab-On-A-Chip , Animais , Humanos , Intestinos
20.
Infect Disord Drug Targets ; 21(4): 514-526, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32888278

RESUMO

The pandemic spread of COVID 19 caused by the novel Coronavirus (SARS-CoV- 2) produced a tremendous effect on the life of humanity across the globe. The epidemiological studies revealed the drastic spectrum of SARS-CoV 2 infection ranging from mere flu-like symptoms to severe respiratory suppression within a short period. Initially, cases have been confined in the emerging point, Wuhan, China. But, within a few months, it has spread all over 212 countries around the globe and presently has become a severe threat to human life. Even though it is a severe acute respiratory syndrome virus, recent reports came with multiple organ effects of SARS-CoV 2, suggesting the virulence potential of this novel virus to sweep the planet in the absence of a proper vaccine or therapy. In this review, we discuss the multi-organ pathophysiology of COVID-19 infection, together with the treatment methods adopted and innovative diagnostic methods used.


Assuntos
COVID-19 , Humanos , Pandemias , SARS-CoV-2
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