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1.
Diabetologia ; 67(7): 1235-1244, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38634887

RESUMO

AIMS/HYPOTHESIS: This study compares the efficacy and safety of a tubeless, on-body automated insulin delivery (AID) system with that of a tubeless, on-body sensor-augmented pump (SAP). METHODS: This multicentre, parallel-group, RCT was conducted at 13 tertiary medical centres in South Korea. Adults aged 19-69 years with type 1 diabetes who had HbA1c levels of <85.8 mmol/mol (<10.0%) were eligible. The participants were assigned at a 1:1 ratio to receive a tubeless, on-body AID system (intervention group) or a tubeless, on-body SAP (control group) for 12 weeks. Stratified block randomisation was conducted by an independent statistician. Blinding was not possible due to the nature of the intervention. The primary outcome was the percentage of time in range (TIR), blood glucose between 3.9 and 10.0 mmol/l, as measured by continuous glucose monitoring. ANCOVAs were conducted with baseline values and study centres as covariates. RESULTS: A total of 104 participants underwent randomisation, with 53 in the intervention group and 51 in the control group. The mean (±SD) age of the participants was 40±11 years. The mean (±SD) TIR increased from 62.1±17.1% at baseline to 71.5±10.7% over the 12 week trial period in the intervention group and from 64.7±17.0% to 66.9±15.0% in the control group (difference between the adjusted means: 6.5% [95% CI 3.6%, 9.4%], p<0.001). Time below range, time above range, CV and mean glucose levels were also significantly better in the intervention group compared with the control group. HbA1c decreased from 50.9±9.9 mmol/mol (6.8±0.9%) at baseline to 45.9±7.4 mmol/mol (6.4±0.7%) after 12 weeks in the intervention group and from 48.7±9.1 mmol/mol (6.6±0.8%) to 45.7±7.5 mmol/mol (6.3±0.7%) in the control group (difference between the adjusted means: -0.7 mmol/mol [95% CI -2.0, 0.8 mmol/mol] (-0.1% [95% CI -0.2%, 0.1%]), p=0.366). No diabetic ketoacidosis or severe hypoglycaemia events occurred in either group. CONCLUSIONS/INTERPRETATION: The use of a tubeless, on-body AID system was safe and associated with superior glycaemic profiles, including TIR, time below range, time above range and CV, than the use of a tubeless, on-body SAP. TRIAL REGISTRATION: Clinical Research Information Service (CRIS) KCT0008398 FUNDING: The study was funded by a grant from the Korea Medical Device Development Fund supported by the Ministry of Science and ICT; the Ministry of Trade, Industry and Energy; the Ministry of Health and Welfare; and the Ministry of Food and Drug Safety (grant number: RS-2020-KD000056).


Assuntos
Glicemia , Diabetes Mellitus Tipo 1 , Hipoglicemiantes , Sistemas de Infusão de Insulina , Insulina , Humanos , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 1/sangue , Masculino , Pessoa de Meia-Idade , Adulto , Feminino , Insulina/administração & dosagem , Insulina/uso terapêutico , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Glicemia/análise , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/uso terapêutico , Idoso , Hemoglobinas Glicadas/metabolismo , Hemoglobinas Glicadas/análise , República da Coreia , Automonitorização da Glicemia/métodos , Adulto Jovem
2.
Medicine (Baltimore) ; 103(11): e37536, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38489707

RESUMO

This study aimed to investigate the association between the intensity of statin therapy and the development of cardiovascular disease (CVD) and diabetes in individuals without prior diabetes who were being treated for dyslipidemia with statins for the primary prevention of CVD, using the National Health Insurance Service-Health Screening database. The database is a longitudinal cohort study of Korean men and women 40 years of age or older who underwent comprehensive biannual screening health examinations by Korean National Health Insurance Service from January 1, 2002, to December 31, 2015. We included patients in the health screening checkup cohort who underwent health checkups in 2009 and 2010.The primary outcome was the occurrence of a first major cardiovascular or cerebrovascular event, new-onset diabetes. A total of 20,322 participants without prior diabetes at baseline from 2009 to 2015 were followed up for a mean duration of 81.2 ±â€…6.6 months. The mean age of all participants at baseline was 59.2 ±â€…8.4 years and 43.0% of them were male. Their index low lipoprotein cholesterol level was 130.4 ±â€…mg/dL, the mean duration of taking statins was 337.4 ±â€…52.3 days, and 93.9% of them had been taking moderate-intensity statins. At that time, a total of 641 diabetes cases occurred, 41 from using low-intensity statins, 588 from moderate-intensity statins, and 11 from high-intensity statins. The results indicated no significant differences in the incidence of death, CVD death, or CVD among those in the strong statin group compared with the reference groups. While statin treatment for the primary prevention of CVD in patients with dyslipidemia showed a subtle difference in the incidence of diabetes, there was no difference in the occurrence of CVD or CVD death according to statin intensity.


Assuntos
Doenças Cardiovasculares , Diabetes Mellitus , Dislipidemias , Inibidores de Hidroximetilglutaril-CoA Redutases , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Estudos Longitudinais , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/prevenção & controle , Doenças Cardiovasculares/etiologia , Dislipidemias/complicações , Dislipidemias/tratamento farmacológico , Dislipidemias/epidemiologia , Prevenção Primária/métodos , Diabetes Mellitus/epidemiologia , República da Coreia/epidemiologia
3.
RSC Adv ; 14(11): 7720-7727, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38449823

RESUMO

Chemical warfare agents (CWAs) pose a persistent threat to human safety, and bis(2-chloroethyl) sulfide, or sulfur mustard (SM) is one of the most dangerous substances and is able to cause serious harm. Detecting SM gas is vital, but current methods have high-temperature requirements and limited selectivity, mainly because of the lack of CWA receptor development, and this makes them challenging to use. To address this issue, we present a trisaryl phosphoric triamide-based resin receptor that preferentially interacts with a SM simulant 2-chloroethyl ethyl sulfide (2-CEES) through dipole interactions. The receptor was synthesized through a facile process using an amine and a triethyl phosphate and the properties of its coating were enhanced using epoxy chemistry. The receptor's superior triamide structure was evaluated using a quartz crystal microbalance and reactivity was confirmed by observing the variations in reactivity according to the number of phosphoramides. The receptor showed better reactivity to 2-CEES vapor than to the known poly(epichlorohydrin) and showed selectivity to other volatile organic compounds. Moreover, its durability was evident even 30 days post-coating. The applicability of this receptor extends to array sensors, sound acoustic wave sensors, and chemo-resistive and chemo-capacitive sensors, and it promises advances in chemical warfare agent detection.

4.
APL Bioeng ; 8(1): 010902, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38420624

RESUMO

Organoids significantly advanced our comprehension of organ development, function, and disease modeling. This Perspective underscores the potential of heart-kidney-connected organoids in understanding the intricate relationship between these vital organs, notably the cardiorenal syndrome, where dysfunction in one organ can negatively impact the other. Conventional models fall short in replicating this complexity, necessitating an integrated approach. By co-culturing heart and kidney organoids, combined with microfluidic and 3D bioprinting technologies, a more accurate representation of in vivo conditions can be achieved. Such interconnected systems could revolutionize our grasp of multi-organ diseases, drive drug discovery by evaluating therapeutic agents on both organs simultaneously, and reduce the need for animal models. In essence, heart-kidney-connected organoids present a promising avenue to delve deeper into the pathophysiology underlying cardiorenal disorders, bridging existing knowledge gaps, and advancing biomedical research.

6.
Cell Death Dis ; 14(12): 812, 2023 12 09.
Artigo em Inglês | MEDLINE | ID: mdl-38071243

RESUMO

Mesenchymal stem cells (MSCs) have great therapeutic advantages due to their immunosuppressive properties. The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor whose signaling plays an important role in the immune system. AHR may be involved in the regulation of MSC-associated immunomodulatory functions. However, the mechanisms by which AHR controls the immunosuppressive functions of MSCs are not well understood. Here, we report that Ahr-deficient MSCs show decreased therapeutic efficacy against graft-versus-host disease (GVHD) compared to wild-type (WT)-MSCs. This was probably due to decreased iNOS protein expression, which is a key regulatory enzyme in MSC immunomodulation. The expression of eukaryotic elongation factor 2 kinase (eEF2K), which inhibits the elongation stage of protein synthesis, is significantly increased in the Ahr-deficient MSCs. Inhibition of eEF2K restored iNOS protein expression. AHR is known to act as an E3 ligase together with CUL4B. We observed constitutive binding of AHR to eEF2K. Consequently, ubiquitination and degradation of eEF2K were inhibited in Ahr-deficient MSCs and by the AHR antagonist CH223191 in WT-MSCs. In summary, AHR regulates the immunomodulatory functions of MSCs through ubiquitination of eEF2K, thereby controlling iNOS protein synthesis and its product, nitric oxide levels.


Assuntos
Células-Tronco Mesenquimais , Receptores de Hidrocarboneto Arílico , Receptores de Hidrocarboneto Arílico/genética , Receptores de Hidrocarboneto Arílico/metabolismo , Quinase do Fator 2 de Elongação/genética , Quinase do Fator 2 de Elongação/metabolismo , Ubiquitinação , Células-Tronco Mesenquimais/metabolismo , Imunomodulação
7.
Front Vet Sci ; 10: 1298736, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38105775

RESUMO

A 13-year-old neutered male Korean short-hair cat presented with anorexia, lethargy, and a severely distended abdomen, suggestive of ascites. Abdominocentesis yielded serosanguineous fluid. A subsequent diagnostic workup, including blood tests, ascitic fluid analysis, imaging studies [radiography, ultrasound, and computed tomography (CT)], and histopathological examination, was performed to identify the underlying cause. Imaging studies revealed characteristics of encapsulating peritoneal sclerosis (EPS) such as peritoneal thickening, fat stranding, and calcification. During laparotomy, fibrous membranes encapsulating the abdominal organs and ascites were observed, and multiple calcified regions were detected on the abdominal wall. Histopathological analysis confirmed the diagnosis of poorly differentiated invasive malignant neoplasms, which were further classified as carcinomatosis based on positive cytokeratin and negative vimentin immunohistochemistry results. To our knowledge, this is the first report of sclerosing peritoneal carcinomatosis with osseous metaplasia in a cat.

8.
J Transl Med ; 21(1): 806, 2023 11 12.
Artigo em Inglês | MEDLINE | ID: mdl-37951886

RESUMO

BACKGROUND: Cardiovascular disease (CVD) is a major complication in type 1 diabetes mellitus (T1D) patients. Previous studies have suggested that statins may be helpful for prevention of CVD in T1D, but there are limited data on the role of statins in T1D. We investigated the relationship between statin treatment and cardiovascular risk in T1D patients using a population-based cohort. METHODS: We conducted a retrospective cohort study using the Korean nationwide health insurance database from January 2007 to December 2017. This study included 11,009 T1D patients aged ≥ 20 years without a prior history of CVD. The primary outcome was a composite development of stroke or myocardial infarction. Statin use during follow-up was treated as a time-varying variable. We performed a multivariable time-dependent Cox regression analysis adjusting for sex, age, type of insurance, hypertension, renal disease, and use of antiplatelets and renin-angiotensin-aldosterone system inhibitors. RESULTS: During the mean follow-up of 9.9 ± 3.7 years of follow-up, 931 T1D patients (8.5%) suffered primary outcome. Statin treatment was associated with a reduced risk of the primary outcome (adjusted hazard ratio, 0.76; 95% confidence interval 0.66-0.88; p < 0.001). Statin use led to decreased risks of ischemic stroke and myocardial infarction, but was not related to hemorrhagic stroke. We also found that the risk of cardiovascular events decreased as the cumulative exposure duration of statins increased. CONCLUSIONS: Statin use was associated with a lower risk of cardiovascular events in T1D patients. Further prospective studies are needed to confirm the potential role of statins in prevention of CVD in patients with T1D.


Assuntos
Doenças Cardiovasculares , Diabetes Mellitus Tipo 1 , Inibidores de Hidroximetilglutaril-CoA Redutases , Infarto do Miocárdio , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/tratamento farmacológico , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/induzido quimicamente , Estudos de Coortes , Estudos Retrospectivos , Fatores de Risco , Fatores de Risco de Doenças Cardíacas
9.
Tissue Eng Part A ; 29(21-22): 594-603, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37847176

RESUMO

Immune-related applications of mesenchymal stromal cells (MSCs) in cell therapy seek to exploit immunomodulatory paracrine signaling pathways to reduce inflammation. A key MSC therapeutic challenge is reducing patient outcome variabilities attributed to insufficient engraftment/retention of injected heterogenous MSCs. To address this, we propose directly transplantable human single-cell-derived clonal bone marrow MSC (hcBMSC) sheets. Cell sheet technology is a scaffold-free tissue engineering strategy enabling scalable production of highly engraftable cell constructs retaining endogenous cell-cell and cell-matrix interactions, important to cell function. cBMSCs, as unique MSC subset populations, facilitate rational selection of therapeutically relevant MSC clones from donors. Here, we combine human cBMSCs with cell sheet technology, demonstrating cell sheet fabrication as a method to significantly upregulate expression of immunomodulatory molecules interleukin (IL)-10, indoleamine 2,3-dioxygenase (IDO-1), and prostaglandin E synthase 2 (PTGES2) across GMP-grade hcBMSC lines and whole human bone marrow-derived MSCs compared to respective conventional cell suspensions. When treated with carbenoxolone, a gap junction inhibitor, cell sheets downregulate IL-10 and IDO-1 expression, implicating functional roles for intercellular sheet interactions. Beyond producing directly transferable multicellular hcBMSC constructs, cell sheet technology amplifies hcBMSC expression of immunomodulatory factors important to therapeutic action. In addition, this work demonstrates the importance of cell-cell interactions as a tissue engineering design criterion to enhance consistent MSC functions.


Assuntos
Células-Tronco Mesenquimais , Humanos , Células-Tronco Mesenquimais/metabolismo , Imunomodulação , Células da Medula Óssea , Engenharia Tecidual , Comunicação Parácrina
10.
Int J Biol Macromol ; 253(Pt 5): 127069, 2023 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-37751819

RESUMO

We propose a general green method coupled with a solid-state vibration ball milling strategy for the synthesis of various metal nanoparticles (MNPs), employing a polymeric carbohydrate dextran (Dx) as a reducing and stabilizing molecule. The synthesis of size-controlled Dx-based MNPs (Dx@MNPs), featuring comparatively narrow size distributions, was achieved by controlling the mass ratio of the reactants, reaction time, frequency of the vibration ball mill, and molecular weight of Dx. Notably, this process was conducted at ambient temperatures, without the aid of solvents and accelerating agents, such as NaOH, and conventional reductants as well as stabilizers. Thermal properties of the resulting Dx@MNPs nanocomposites were extensively investigated, highlighting the influence of metal precursors and reaction conditions. Furthermore, the catalytic activity of synthesized nanocomposites was evaluated through the reduction reaction of 4-nitrophenol, exhibiting great catalytic performance. In addition, we demonstrated the excellent biocompatibility of the as-prepared Dx@MNPs toward human embryonic kidney (HEK-293) cells, revealing their potential for anticancer activities. This novel green method for synthesizing biocompatible MNPs with Dx expands the horizons of carbohydrate-based materials as well as MNP nanocomposites for large-scale synthesis and controlled size distribution for various industrial and biomedical applications.


Assuntos
Dextranos , Nanopartículas Metálicas , Humanos , Solventes , Células HEK293
11.
Nat Commun ; 14(1): 5085, 2023 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-37607969

RESUMO

Soliton molecules, bound states of two solitons, can be important for the informatics using solitons and the quest for exotic particles in a wide range of physical systems from unconventional superconductors to nuclear matter and Higgs field, but have been observed only in temporal dimension for classical wave optical systems. Here, we identify a topological soliton molecule formed spatially in an electronic system, a quasi 1D charge density wave of indium atomic wires. This system is composed of two coupled Peierls chains, which are endowed with a Z4 topology and three distinct, right-chiral, left-chiral, and non-chiral, solitons. Our scanning tunneling microscopy measurements identify a bound state of right- and left-chiral solitons with distinct in-gap states and net zero phase shift. Our density functional theory calculations reveal the attractive interaction of these solitons and the hybridization of their electronic states. This result initiates the study of the interaction between solitons in electronic systems, which can provide novel manybody electronic states and extra data-handling capacity beyond the given soliton topology.

12.
J Clin Med ; 12(9)2023 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-37176601

RESUMO

BACKGROUND: Although the clinical outcomes of diabetes have improved, diabetes remains the principal cause of end-stage renal disease. The aim of the study is to investigate whether mortality trends in individuals with type 2 diabetes and kidney transplantation (KT) have changed. METHODS: This study analyzed data from the National Health Insurance Service claims database linked to death records from the National Statistical Information Service in Korea. Information from a total of 2521 deaths of KT recipients was collected from 2006 to 2018. RESULTS: The age at death of KT recipients increased from 57.4 years in 2006 to 65.2 years in 2018, with a mean change of +0.65 years/year (p < 0.001). The overall age at death increased by 0.55 and 0.66 years/year in the type 2 diabetes and non-diabetes populations, respectively. The age at death was significantly higher in the type 2 diabetes group, and was maintained during the study period. The proportion of death due to malignancy and cerebrovascular and heart disease was maintained, that due to type 2 diabetes decreased and that due to pneumonia increased. Neither diabetes nor hypertension determined the age at death, and the age at KT was the most prominent factor affecting age at death in KT recipients. CONCLUSIONS: The age at death in KT recipients increased over the 12 years between 2006 and 2018, with similar trends in the type 2 diabetes and non-diabetes groups. The age at KT was higher in patients with type 2 diabetes, and was the main contributor to the age at death in KT recipients.

13.
J Hazard Mater ; 455: 131588, 2023 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-37172388

RESUMO

Real-time monitoring and quantification of exhaust pollutants is crucial but is troublesome because of extremely harsh thermochemical conditions, and in this regard mixed-potential sensing technology can be a realistic solution. In this study, BiVO4 nanoparticles are decorated onto the preformed porous sensing electrode (SE) backbone by homogeneous infiltration process to improve the sensing performance in mixed-potential sensor. The influence of nanoparticle decoration on phase composition, microstructure and sensing performance are analyzed by physical and electrochemical techniques. Corresponding results indicate that the microstructure tailoring enhances the sensor performance, by extending the triple phase boundary (TPB) and surface area of SE itself. The sensitivity (-119.47 mV/decade) and response time (20 s) of i-BVO SE-based sensor at 600 â„ƒ are 20 % higher and 8 s faster than bare BiVO4 SE-based sensor (99.24 mV/decade and 28 s). Additionally, the i-BVOǀYSZǀPt cell exhibits good selectivity and cross-sensitivity toward NH3 without any dependency on oxygen partial pressure (pO2). The fabricated sensor is also found stable towards cyclic and long-term operations. Electrochemical Impendence Spectroscopy (EIS) and DC polarization studies were performed to confirm the mixed-potential behavior. Conclusively, the superior sensing performance of i-BVO SE compared to various oxide based SEs highlights its suitability for mixed-potential NH3 sensing.

14.
Sci Rep ; 13(1): 4421, 2023 03 17.
Artigo em Inglês | MEDLINE | ID: mdl-36932137

RESUMO

Allogeneic "off-the-shelf" mesenchymal stem/stromal cell (MSC) therapy requires scalable, quality-controlled cell manufacturing and distribution systems to provide clinical-grade products using cryogenic cell banking. However, previous studies report impaired cell function associated with administering freeze-thawed MSCs as single cell suspensions, potentially compromising reliable therapeutic efficacy. Using long-term culture-adapted clinical-grade clonal human bone marrow MSCs (cBMSCs) in this study, we engineered cBMSC sheets in 24 h to provide rapid preparation. We then sought to determine the influence of cBMSC freeze-thawing on both in vitro production of pro-regenerative factors and in vivo ability to reduce renal fibrosis in a rat model compared to freshly harvested cBMSCs. Sheets from freeze-thawed cBMSCs sheets exhibited comparable in vitro protein production and gene expression of pro-regenerative factors [e.g., hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF), and interleukin 10 (IL-10)] to freshly harvested cBMSC sheets. Additionally, freeze-thawed cBMSC sheets successfully suppressed renal fibrosis in vivo in an established rat ischemia-reperfusion injury model. Despite previous studies reporting that freeze-thawed MSCs exhibit impaired cell functions compared to fresh MSC single cell suspensions, cell sheets engineered from freeze-thawed cBMSCs do not exhibit impaired cell functions, supporting critical steps toward future clinical translation of cBMSC-based kidney disease treatment.


Assuntos
Nefropatias , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Humanos , Ratos , Animais , Fator A de Crescimento do Endotélio Vascular/metabolismo , Medula Óssea , Fibrose , Nefropatias/terapia , Nefropatias/metabolismo
15.
Cancers (Basel) ; 15(3)2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36765892

RESUMO

Microbes play different roles in metabolism, local or systemic inflammation, and immunity, and the human microbiome in tumor microenvironment (TME) is important for modulating the response to immunotherapy in cancer patients. Renal cell carcinoma (RCC) is an immunogenic tumor, and immunotherapy is the backbone of its treatment. Correlations between the microbiome and responsiveness to immune checkpoint inhibitors have been reported. This review summarizes the recent therapeutic strategies for RCC and the effects of TME on the systemic therapy of RCC. The current understanding and advances in microbiome research and the relationship between the microbiome and the response to immunotherapy for RCC are also discussed. Improving our understanding of the role of the microbiome in RCC treatment will facilitate the development of microbiome targeting therapies to modify the tumor microbiome and improve treatment outcomes.

16.
Tissue Eng Part C Methods ; 29(2): 54-62, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36719774

RESUMO

Chronic kidney disease (CKD) is the irreversible loss of nephron function, leading to a build-up of toxins, prolonged inflammation, and ultimately fibrosis. Currently, no effective therapies exist to treat CKD due to its complex pathophysiology. Mesenchymal stem/stromal cell (MSC) transplantation is a promising strategy to treat kidney diseases, and multiple clinical trials are currently ongoing. We previously demonstrated that rat bone marrow-derived MSC (BMSC) sheets transplanted onto surgically decapsulated kidney exert therapeutic effects that suppressed renal fibrosis progression based on enhanced vascularization. However, there are clinical concerns about kidney decapsulation such as impaired glomerular filtration rate and Na+ ion and H2O excretion, leading to kidney dysfunction. Therefore, for transitioning from basic research to translational research using cell sheet therapy for kidney disease, it is essential to develop a new cell sheet transplantation strategy without kidney decapsulation. Significantly, we employed cell sheets engineered from clinical-grade human clonal BMSC (cBMSC) and transplanted these onto intact renal capsule to evaluate their therapeutic ability in the rat ischemia-reperfusion injury (IRI) model. Histological analysis 1-day postsurgery showed that cBMSC sheets engrafted well onto intact renal capsule. Interestingly, some grafted cBMSCs migrated into the renal parenchyma. At 1-3 days postsurgery (acute stage), grafted cBMSC sheets prevented tubular epithelial cell injury. At 28 days postsurgery (chronic phase), we observed that grafted cBMSC sheets suppressed renal fibrosis in the rat IRI model. Taken together, engineered cBMSC sheet transplantation onto intact renal capsule suppresses tubular epithelial cell injury and renal fibrosis, supporting further development as a possible clinically relevant strategy. Impact statement Chronic kidney disease (CKD) produces irreversible loss of nephron function, leading to toxemia, prolonged inflammation, and ultimately kidney fibrosis. Currently, no therapies exist to effectively treat CKD due to its complex pathophysiology. Mesenchymal stem/stromal cells (MSCs) are widely known to secret therapeutic paracrine factors, which is expected to provide a new effective therapy for unmet medical needs. However, unsatisfied MSC quality and administration methods to patients limit their therapeutic effects. In this study, we engineered clonal bone marrow-derived MSC sheets and established clinically relevant cell sheet transplantation strategy to treat renal fibrosis, which would improve MSC treatment for kidney disease.


Assuntos
Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Insuficiência Renal Crônica , Humanos , Ratos , Animais , Rim , Insuficiência Renal Crônica/patologia , Insuficiência Renal Crônica/prevenção & controle , Inflamação/patologia , Fibrose
19.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1008868

RESUMO

This study aims to explore the influence of Polygonati Rhizoma on the pyroptosis in the rat model of diabetic macroangiopathy via the NOD-like receptor thermal protein domain associated protein 3(NLRP3)/cysteinyl aspartate specific proteinase-1(caspase-1)/gasdermin D(GSDMD) pathway. The rat model of diabetes was established by intraperitoneal injection of streptozotocin(STZ) combined with a high-fat, high-sugar diet. The blood glucose meter, fully automated biochemical analyzer, hematoxylin-eosin(HE) staining, enzyme-linked immunosorbent assay, immunofluorescence, immunohistochemistry, and Western blot were employed to measure blood glucose levels, lipid levels, vascular thickness, inflammatory cytokine levels, and expression levels of pyroptosis-related proteins. The mechanism of pharmacological interventions against the injury in the context of diabetes was thus explored. The results demonstrated the successful establishment of the model of diabetes. Compared with the control group, the model group showed elevated levels of fasting blood glucose, total cholesterol(TC), triglycerides(TG) and low-density lipoprotein cholesterol(LDL-c), lowered level of high-density lipoprotein cholesterol(HDL-c), thickened vascular intima, and elevated serum and aorta levels of tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β) and interleukin-18(IL-18). Moreover, the model group showed increased NLRP3 inflammasomes and up-regulated levels of caspase-1 and GSDMD in aortic vascular cells. Polygonati Rhizoma intervention reduced blood glucose and lipid levels, inhibited vascular thickening, lowered the levels of TNF-α, IL-1β, IL-18 in the serum and aorta, attenuated NLRP3 inflammasome expression, and down-regulated the expression levels of caspase-1 and GSDMD, compared with the model group. In summary, Polygonati Rhizoma can slow down the progression of diabetic macroangiopathy by inhibiting pyroptosis and alleviating local vascular inflammation.


Assuntos
Animais , Ratos , Caspase 1/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Interleucina-18 , Glicemia , Piroptose , Fator de Necrose Tumoral alfa , Complicações do Diabetes , Doenças Vasculares , Inflamassomos , Colesterol , Lipídeos , Diabetes Mellitus
20.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1009836

RESUMO

The three-day-old female infant was admitted to the hospital due to respiratory distress after birth. She was born premature at 36+2 weeks gestational age. Prenatal ultrasound suggested abnormal development of the fetal liver vessels, and she had dyspnea that required respiratory support after birth. Chest X-ray indicated an enlarged cardiac silhouette, and cardiac ultrasound revealed enlargement of the right atrium and right ventricle. Diagnosis of hepatic hemangioma with arteriovenous fistula was confirmed through liver ultrasound and abdominal enhanced CT. At 19 days old, she underwent ligation of the hepatic artery under general anesthesia, which led to an improvement in cardiac function and she was subsequently discharged. Genetic testing revealed a mutation in the ACVRL1 gene, which was inherited from the mother. The article primarily introduces a case of neonatal heart failure caused by hepatic hemangioma with arteriovenous fistula, and multi-disciplinary diagnosis and treatment of this disease.


Assuntos
Feminino , Humanos , Recém-Nascido , Gravidez , Receptores de Activinas Tipo II , Fístula Arteriovenosa/complicações , Dispneia , Insuficiência Cardíaca/etiologia , Hemangioma/complicações , Fígado
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