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1.
Clin Infect Dis ; 2022 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-35037056

RESUMO

BACKGROUND: Acute respiratory infections (ARI) are the most common infectious diseases globally. Community surveillance may provide a more comprehensive picture of disease burden than medically-attended illness alone. METHODS: In this longitudinal study conducted from 2012-2017 in the Washington Heights/Inwood area of New York City, we enrolled 405 households with 1,915 individuals. Households were sent research text messages twice weekly inquiring about ARI symptoms. Research staff confirmed symptoms by follow-up call. If ≥2 criteria for ARI were met (fever/feverish, cough, congestion, pharyngitis, myalgias), staff obtained a mid-turbinate nasal swab in participants' homes. Swabs were tested using the FilmArray RT-PCR respiratory panel. RESULTS: Among participants, 43.9% were children, and 12.8% had a chronic respiratory condition. During the five years, 114,724 text messages were sent; the average response rate was 78.8% +/- 6.8%. Swabs were collected for 91.4% (2756/3016) of confirmed ARI; 58.7% had a pathogen detected. Rhino/enteroviruses (51.9%), human coronaviruses (13.9%) and influenza (13.2%) were most commonly detected. The overall incidence was 0.62 ARI/person-year, highest (1.73) in <2 year-olds and lowest (0.46) in 18-49 year-olds. Approximately one-fourth of those with ARI sought healthcare; percents differed by pathogen, demographic factors, and presence of a chronic respiratory condition. CONCLUSIONS: Text messaging is a novel method for community-based surveillance that could be used both seasonally as well as during outbreaks, epidemics and pandemics. The importance of community surveillance to accurately estimate disease burden is underscored by the findings of low rates of care-seeking that varied by demographic factors and pathogens.

2.
Cell Death Dis ; 13(1): 29, 2022 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-35013107

RESUMO

Methylglyoxal (MGO) is an active metabolite of glucose and plays a prominent role in the pathogenesis of diabetic vascular complications, including endothelial cell apoptosis induced by oxidative stress. Metformin (MET), a widely prescribed antidiabetic agent, appears to reduce excessive reactive oxygen species (ROS) generation and limit cell apoptosis. However, the molecular mechanisms underlying this process are still not fully elucidated. We reported here that MET prevents MGO-induced apoptosis by suppressing oxidative stress in vitro and in vivo. Protein expression and protein phosphorylation were investigated using western blotting, ELISA, and immunohistochemical staining, respectively. Cell viability and apoptosis were assessed by the MTT assay, TUNEL staining, and Annexin V-FITC and propidium iodide double staining. ROS generation and mitochondrial membrane potential (MMP) were measured with fluorescent probes. Our results revealed that MET prevented MGO-induced HUVEC apoptosis, inhibited apoptosis-associated biochemical changes such as loss of MMP, the elevation of the Bax/Bcl-2 ratio, and activation of cleaved caspase-3, and attenuated MGO-induced mitochondrial morphological alterations in a dose-dependent manner. MET pretreatment also significantly suppressed MGO-stimulated ROS production, increased signaling through the ROS-mediated PI3K/Akt and Nrf2/HO-1 pathways, and markedly elevated the levels of its downstream antioxidants. Finally, similar results were obtained in vivo, and we demonstrated that MET prevented MGO-induced oxidative damage, apoptosis, and inflammation. As expected, MET reversed MGO-induced downregulation of Nrf2 and p-Akt. In addition, a PI3K inhibitor (LY-294002) and a Nrf2 inhibitor (ML385) observably attenuated the protective effects of MET on MGO-induced apoptosis and ROS generation by inhibiting the Nrf2/HO-1 pathways, while a ROS scavenger (NAC) and a permeability transition pores inhibitor (CsA) completely reversed these effects. Collectively, these findings broaden our understanding of the mechanism by which MET regulates apoptosis induced by MGO under oxidative stress conditions, with important implications regarding the potential application of MET for the treatment of diabetic vascular complications.

3.
BMC Genomics ; 22(1): 884, 2021 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-34872498

RESUMO

BACKGROUND: Bovine viral diarrhea virus (BVDV) is a major pathogen that causes bovine viral diarrhea/mucosal disease (BVD-MD), which has become a global infectious disease due to its wide spread and the lack of effective treatment. The process of BVDV infection is complex. Once infected, host immune cells are activated and modulated. As a major immune cell, peripheral blood lymphocyte cells (PBLCs) are the primary target of BVDV. In order to further understand the mechanism of BVDV- host interaction, the expression profiles of host lymphocytes mRNAs associated with BVDV infection were investigated by transcriptomic sequencing analysis. RESULTS: The transcriptomic sequencing analysis was performed on bovine PBLCs infected with CP BVDV-2 GS2018 after 12 h of infection. Gene expression profiling demonstrated that 1052 genes were differentially expressed in GS2018 infected PBLCs compared with the control group. Of these genes, 485 genes were up-regulated and 567 were down-regulated. The 19 differential expressed genes (DEGs) were selected for validation using quantitative real-time PCR and the results were consistent with the results of RNA-Seq. Gene ontology enrichment and KEGG pathway analysis showed that 1052 DEGs were significantly enriched in 16 pathways, including cytokine-cytokine receptor interaction, IL17, PI3K-Akt, MAPK and TNF signaling pathway. PPI network analysis showed that IL17A, IFN-γ and TNF-α interacted with various proteins and may play crucial roles in BVDV-2 infection. Of note, we confirmed that GS2018 induced Th17 cell differentiation in PBLCs and persistently increased the expression levels of IL17A. In turn, the replication of GS2018 was inhibited by IL17A. CONCLUSION: In this study, the transcription changes of DEGs related to host immune responses in bovine PBLCs were caused by CP BVDV-2 infection. In particular, the effector molecules IL17A of Th17 cells were significantly up-regulated, which inhibited viral replication. These results will contribute to exploration and further understanding of the host immune response mechanism and interaction between host and BVDV-2.

4.
Front Immunol ; 12: 767813, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34858424

RESUMO

Viral infections seriously affect the health of organisms including humans. Now, more and more researchers believe that microRNAs (miRNAs), one of the members of the non-coding RNA family, play significant roles in cell biological function, disease occurrence, and immunotherapy. However, the roles of miRNAs in virus infection (entry and replication) and cellular immune response remain poorly understood, especially in low vertebrate fish. In this study, based on the established virus-cell infection model, Singapore grouper iridovirus (SGIV)-infected cells were used to explore the roles of miR-124 of Epinephelus coioides, an economically mariculture fish in southern China and Southeast Asia, in viral infection and host immune responses. The expression level of E. coioides miR-124 was significantly upregulated after SGIV infection; miR-124 cannot significantly affect the entry of SGIV, but the upregulated miR-124 could significantly promote the SGIV-induced cytopathic effects (CPEs), the viral titer, and the expressions of viral genes. The target genes of miR-124 were JNK3/p38α mitogen-activated protein kinase (MAPK). Overexpression of miR-124 could dramatically inhibit the activation of NF-κB/activating protein-1 (AP-1), the transcription of proinflammatory factors, caspase-9/3, and the cell apoptosis. And opposite results happen when the expression of miR-124 was inhibited. The results suggest that E. coioides miR-124 could promote viral replication and negatively regulate host immune response by targeting JNK3/p38α MAPK, which furthers our understanding of virus and host immune interactions.

5.
Photodiagnosis Photodyn Ther ; 37: 102695, 2021 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-34923157

RESUMO

BACKGROUND: Recently, the number of nontuberculous mycobacterium (NTM) infections caused by iatrogenic procedures, especially rapid NTM skin infections, has been increasing. Due to the nonspecific clinical manifestations and nonstandard treatment guidelines, these infections are often misdiagnosed and challenging to treat. METHODS: In this study, eight patients had NTM skin infections caused by iatrogenic procedures, and were diagnosed by bacterial culture and flight mass spectrometry tests. They were treated with 5-aminolevulinic acid-photodynamic therapy (ALA-PDT) combined with antibiotic therapy. RESULTS: All eight patients enrolled in the study were cured with 100% efficacy after receiving combination therapy with ALA-PDT and antibiotics for 3-6 months. All patients experienced redness and pain during treatment but no other discomfort and were satisfified with the results of their treatments. CONCLUSION: Local ALA-PDT combined with antibiotics is a safe and effective method of treating NTM skin infections.

6.
Food Sci Nutr ; 9(11): 6262-6273, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34760256

RESUMO

Doxorubicin (DOX) is an anthracycline antibiotic used in the clinical treatment of cancer, but its use is limited due to its cardiotoxic effects. Therefore, it is necessary to explore natural compounds that are effective in protecting against the cardiotoxicity caused by DOX. Neutral Morchella conica polysaccharides-2 (NMCP-2) is a natural polysaccharide with antioxidant activity that was isolated and purified from Morchella conica in our laboratory's previous study. This study aimed to investigate the possible protective effect of NMCP-2 on DOX-induced cardiotoxicity and the potential underlying mechanisms. The model of DOX-induced H9C2 cells and the model of DOX-induced mice were used in this study. In in vitro studies of H9C2 myocardial cells, NMCP-2 effectively increased the activity of H9C2 cells, reducing the levels of lactate dehydrogenase (LDH). In the mouse model of DOX-induced chronic cardiotoxicity, NMCP-2 significantly reduced the cardiac index, reduced the release of serum cardiac enzymes, and improved the pathology of murine myocardial tissues, thereby alleviating DOX-induced cardiotoxicity. Further mechanism studies showed that pretreatment with NMCP-2 counteracted the oxidative stress induced by DOX, as indicated by increasing superoxide dismutase (SOD), catalase (CAT), glutathione (GSH) activities, and malondialdehyde (MDA) production decreased. In addition, we observed NMCP-2 inhibited the activation of the mitochondrial apoptosis pathway and regulated the disordered expression of Bcl-2 and Bax in the myocardial tissues of DOX-treated mice. These findings indicated that NMCP-2, a natural bioactive compound, could potentially be used as a food supplement to reduce the cardiotoxicity caused by DOX.

7.
Front Cell Infect Microbiol ; 11: 707402, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34804988

RESUMO

The continuous development of urbanization has dramatically changed people's living environment and lifestyle, accompanied by the increased prevalence of chronic diseases. However, there is little research on the effect of urbanization on gut microbiome in residents. Here we investigated the relation between living environment and gut microbiota in a homogenous population along an urban-rural gradient in Ningxia China. According to the degree of urbanization, the population is divided into four groups: mountainous rural (MR) represents non-urbanized areas, mountainous urban (MU) and plain rural (PR) represent preliminary urbanization, and plain urban (PU) is a representative of complete urbanization. Studies have found that with the deepening of urbanization, the prevalence of chronic diseases, such as diabetes, dyslipidemia, fatty liver, gallstones, and renal cysts, have gradually increased. The intestinal richness and diversity of the microbial community were significantly reduced in the PR and the PU groups compared with the MR and the MU groups. Based on linear discriminant analysis selection, the significantly enriched genera Faecalibacterium, Prevotella, and Pseudobutyrivibrio in the MR group gradually decreased in the MU, the PR, and the PU groups. Effect size results revealed that both residence and diet had an effect on intestinal microbiota. Our results suggested that the disparate patterns of gut microbiota composition were revealed at different levels of urbanization, providing an opportunity to understand the pathogenesis of chronic diseases and the contribution of the "rural microbiome" in potential protection against the occurrence of chronic diseases.


Assuntos
Microbioma Gastrointestinal , China/epidemiologia , Doença Crônica , Humanos , Prevalência , Urbanização
8.
Int J Bioprint ; 7(4): 397, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34805591

RESUMO

The hydrogel formed by polyethylene glycol-aliphatic polyester block copolymers is an ideal bioink and biomaterial ink for three-dimensional (3D) bioprinting because of its unique temperature sensitivity, mild gelation process, good biocompatibility, and biodegradability. However, the gel forming mechanism based only on hydrophilic-hydrophobic interaction renders the stability and mechanical strength of the formed hydrogels insufficient, and cannot meet the requirements of extrusion 3D printing. In this study, cellulose nanocrystals (CNC), which is a kind of rigid, hydrophilic, and biocompatible nanomaterial, were introduced to enhance the hydrogels so as to meet the requirements of extrusion 3D printing. First, a series of poly(ε-caprolactone/lactide)-b-poly(ethylene glycol)-b-poly(ε-caprolactone/lactide) (PCLA-PEG-PCLA) triblock copolymers with different molecular weights were prepared. The thermodynamic and rheological properties of CNC-enhanced hydrogels were investigated. The results showed that the addition of CNC significantly improved the thermal stability and mechanical properties of the hydrogels, and within a certain range, the enhancement effect was directly proportional to the concentration of CNC. More importantly, the PCLA-PEG-PCLA hydrogels enhanced by CNC could be extruded and printed through temperature regulation. The printed objects had high resolution and fidelity with effectively maintained structure. Moreover, the hydrogels have good biocompatibility with a high cell viability. Therefore, this is a simple and effective strategy. The addition of the hydrophilic rigid nanoparticles such as CNC improves the mechanical properties of the soft hydrogels which made it able to meet the requirements of 3D bioprinting.

9.
Front Psychiatry ; 12: 725197, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34616319

RESUMO

Objective: There are few studies about the relationship between social capital (SC) and depression among type 2 diabetes mellitus (T2DM) patients, and the mechanism explaining how SC leads to decreased depression is unclear. The current study aims to explore the relationship between SC and depressive symptoms among the T2DM patients in northwest China, with a particular focus on the mediating role of sleep quality. Methods: A cross-sectional study of 1,761 T2DM patients from Ningxia Province was conducted. The Center for Epidemiological Survey Depression Scale (CES-D) and self-report sleep quality questionnaire coupled with the SC scales were administered during the face-to-face survey. The Bootstrap methods PROCESS program is employed to test the mediation model. Results: The prevalence of depressive symptoms among T2DM patients was 24.8%. After controlling for covariates, the SC (r = -0.23, p < 0.001) was negatively correlated with CES-D score; the sleep quality was also negatively correlated with CES-D score (r = -0.31, p < 0.001); and the SC was positively correlated with sleep quality (r = 0.10, p < 0.001). Logistic regression analysis showed that SC was inversely related to the risk of depressive symptoms. Meanwhile, sleep quality was negatively associated with depressive symptoms. Sleep quality has mediated the relationship between SC and depressive symptoms among T2DM patients (explaining 12.6% of the total variance). Conclusions: We elucidated how SC interacted with depressive symptoms through the mediation pathway of sleep quality using a representative sample of the Chinese diabetes patients. The findings indicate that the improvement of SC and sleep quality may help in maintaining mental health among T2DM patients. Hence, clinicians can suggest that patients communicate more with others to improve the SC and, in turn, maintain their health.

10.
Cell Death Discov ; 7(1): 305, 2021 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-34686659

RESUMO

ABATRACT: Obesity is known to be associated with adipose tissue inflammation and insulin resistance. Importantly, in obesity, the accumulation of proinflammatory macrophages in adipose tissue correlates with insulin resistance. We hypothesized that the receptor for advanced glycation end products (RAGE) and associated ligands are involved in adipose tissue insulin resistance, and that the activation of the AGE-RAGE axis plays an important role in obesity-associated inflammation. C57BL/6J mice (WT) and RAGE deficient (RAGE-/-) mice were fed a high fat diet (HFD) and subjected to glucose and insulin tolerance tests. Epdidymal adipose tissue (eAT) was collected and adipose stromal vascular cells isolated using flow cytometry. Visceral adipose tissue macrophage polarization was assessed by quantitative real time PCR. Immunoblotting was performed to evaluate the insulin signaling in adipose tissues. In additional studies, cell trafficking was assessed by injecting labeled blood monocytes into recipient mice. RAGE-/- mice displayed improved insulin sensitivity and glucose tolerance, accompanied by decreased body weight and eAT mass. Exogenous methylglyoxal (MGO) impaired insulin-stimulated AKT signaling in adipose tissues from WT mice fed a normal chow diet, but not in RAGE-/- mice. In contrast, in obese mice, treatment with MGO did not reduce insulin-induced phosphorylation of AKT in WT-HFD mice. Moreover, insulin-induced AKT phosphorylation was found to be impaired in adipose tissue from RAGE-/--HFD mice. RAGE-/- mice displayed improved inflammatory profiles and evidence for increased adipose tissue browning. This observation is consistent with the finding of reduced plasma levels of FFA, glycerol, IL-6, and leptin in RAGE-/- mice compared to WT mice. Collectively the data demonstrate that RAGE-mediated adipose tissue inflammation and insulin-signaling are potentially important mechanisms that contribute to the development of obesity-associated insulin resistance.

11.
Genes (Basel) ; 12(10)2021 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-34680985

RESUMO

Cysticercus pisiformis (C. pisiformis), the larval form of Taenia pisiformis, parasitize mainly the liver, omentum and mesentery of rabbits and cause huge economic losses in the rabbit breeding industry. MicroRNA (miRNA), a short non-coding RNA, is widely and stably distributed in the plasma and serum. Numerous data demonstrates that, after parasitic infection, miRNAs become the key regulatory factor for controlling host biological processes. However, the roles of serum miRNAs in C. pisiformis-infected rabbits have not been elucidated. In this study, we compared miRNA expression profiles between the C. pisiformis-infected and healthy rabbit serum using RNA-seq. A total of 192 miRNAs were differentially expressed (fold change ≥ 2 and p < 0.05), including 79 up- and 113 downregulated miRNAs. These data were verified by qRT-PCR (real time quantitative polymerase chain reaction) analysis. Additionally, GO analysis showed that the target genes of these dysregulated miRNAs were most enriched in cellular, single-organism and metabolic processes. KEGG pathway analysis showed that these miRNAs target genes were involved in PI3K-Akt, viral carcinogenesis and B cell receptor signaling pathways. Interestingly, after aligning clean reads to the T. pisiformis genome, four (miR-124-3p_3, miR-124-3p_4, miR-124a and novel-miR1) T. pisiformis-derived miRNAs were found. Of these, novel-miR1was upregulated in different periods after C. pisiformis infection, which was verified qRT-PCR, and pre- novel-miR-1 was amplified from the cysticerci by RT-PCR, implying novel-miR-1 was derived from C. pisiformis and has great potential for the diagnosis of Cysticercosis pisiformis infection. This is the first investigation of miRNA expression profile and function in the serum of rabbits infected by C. pisiformis, providing fundamental data for developing diagnostic targets for Cysticercosis pisiformis.

12.
ACS Appl Mater Interfaces ; 13(37): 44184-44194, 2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34499482

RESUMO

Photoelectrochemical (PEC) water splitting over TiO2 photoanodes is a promising strategy for hydrogen production due to its eco-friendly, energy-saving, and low-cost nature. However, the intrinsic drawbacks of TiO2, i.e., the too wide band gap and rapid exciton recombination, significantly limit further enhancement of its performance. Herein, we report a TiO2 nanotube array (TNA), which is implanted by Cu ions and decorated by polymeric carbon nitride (PCN) nanosheets, as a photoanode for the high-efficiency PEC water splitting. In such designed material, Cu-ion implantation can effectively tailor the electronic structure of TiO2, thus narrowing the band gap and enhancing the electronic conductivity. Meanwhile, the PCN decoration induces TiO2/PCN heterojunctions, enhancing the visible light absorption and accelerating the exciton separation. Upon this synergistic effect, the modified TNA photoanode shows significantly improved PEC capability. Its photocurrent density, solar-to-hydrogen efficiency, and applied bias photon-to-current efficiency achieve 1.89 mA cm-2 at 1.23 VRHE (V vs reversible hydrogen electrode), 2.31%, and 1.20% at 0.46 VRHE, respectively. Importantly, this modified TNA supported on a meshlike Ti substrate can be readily integrated with a perovskite solar cell to realize unassisted PEC water splitting.

13.
J Nerv Ment Dis ; 209(10): 753-758, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34582402

RESUMO

ABSTRACT: Although most studies have shown the psychological strains associated with increased risk of suicidal behaviors, how psychological strains are linked to suicidal behaviors is still unclear. The current study examines the possible mediation effect of psychological distress and hopelessness on the relationship between psychological strains and suicidal behaviors among Chinese medical college students. A cross-sectional survey was conducted from November 2017 to March 2018 involving 5703 medical college students, and the 12-month prevalence of suicidal behaviors was 12.89%. Psychological strains significantly associated with suicidal behaviors, and psychological distress and hopelessness partially explained this relationship. A positive psychological intervention program is needed to buffer the psychological strains, which is a crucial predictor for suicidal behaviors among Chinese medical college students.

14.
Front Microbiol ; 12: 682921, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34394029

RESUMO

Gene silencing induced by hairpin RNA or virus infection expression is one of the major tools in genetics studies in plants. However, when dealing with essential genes, virus-induced gene silencing (VIGS) and transgenic expression of hairpin RNA could lead to plant death, while transient expression of hairpin RNA in leaves is often less competent in downregulating target gene mRNA levels. Here, we developed a transient double-stranded RNA (dsRNA) expression system assisted by a modified viral RNA-dependent RNA polymerase (RdRp) in plant leaves. We show that this system is more effective in inducing gene silencing than the intron-spliced hairpin RNA expression. Furthermore, by using this system, we tested the role of the early secretory pathway during infection of Soybean mosaic potyvirus (SMV). We found that key components of the coat protein complex II vesicles are required for the multiplication of SMV. Overall, this dsRNA-based gene silencing system is effective in downregulating plant gene expression and can be used to identify host genes involved in plant-virus interactions.

15.
J Cell Mol Med ; 25(15): 7462-7471, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34240802

RESUMO

Mitsugumin 53 (MG53), which is expressed predominantly in striated muscle, has been demonstrated to be a myokine/cardiokine secreted from striated muscle under specific conditions. The important roles of MG53 in non-striated muscle tissues have also been examined in multiple disease models. However, no previous study has implicated MG53 in the control of endothelial cell function. In order to explore the effects of MG53 on endothelial cells, human umbilical vein endothelial cells (HUVECs) were stimulated with recombinant human MG53 (rhMG53). Then, rhMG53 uptake, focal adhesion kinase (FAK)/Src/Akt/ERK1/2 signalling pathway activation, cell migration and tube formation were determined in vitro. The efficacy of rhMG53 in regulating angiogenesis was also detected in postnatal mouse retinas. The results demonstrated that rhMG53 directly entered into endothelial cells in a cholesterol-dependent manner. The uptake of rhMG53 directly bound to FAK in endothelial cells, which resulted in a significant decrease in FAK phosphorylation at Y397. Accompanied by the dephosphorylation of FAK, rhMG53 uncoupled FAK-Src interaction and reduced the phosphorylation of Src at Y416. Consequently, the activation of FAK/Src downstream signalling pathways, such as Akt and ERK1/2, was also significantly inhibited by rhMG53. Furthermore, rhMG53 remarkably decreased HUVEC migration and tube formation in vitro and postnatal mouse retinal angiogenesis in vivo. Taken together, these data indicate that rhMG53 inhibits angiogenesis through regulating FAK/Src/Akt/ERK1/2 signalling pathways. This may provide a novel molecular mechanism for the impaired angiogenesis in ischaemic diseases.

16.
Stem Cell Res Ther ; 12(1): 408, 2021 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-34266493

RESUMO

BACKGROUND: Accumulating evidence suggests that enhanced adipose tissue macrophages (ATMs) are associated with metabolic disorders in obesity and type 2 diabetes. However, therapeutic persistence and reduced homing stem cell function following cell delivery remains a critical hurdle for the clinical translation of stem cells in current approaches. METHODS: We demonstrate that the effect of a combined application of photoactivation and adipose-derived stem cells (ASCs) using transplantation into visceral epididymal adipose tissue (EAT) in obesity. Cultured ASCs were derived from subcutaneous white adipose tissue isolated from mice fed a normal diet (ND). RESULTS: In diet-induced obesity, implantation of light-treated ASCs improved glucose tolerance and ameliorated systemic insulin resistance. Intriguingly, compared with non-light-treated ASCs, light-treated ASCs reduced monocyte infiltration and the levels of ATMs in EAT. Moreover, implantation of light-treated ASCs exerts more anti-inflammatory effects by suppressing M1 polarization and enhancing macrophage M2 polarization in EAT. Mass spectrometry revealed that light-treated human obese ASCs conditioned medium retained a more complete secretome with significant downregulation of pro-inflammatory cytokines and chemokines. CONCLUSIONS: These data suggest that the combined application of photoactivation and ASCs using transplantation into dysfunctional adipose tissue contribute to selective suppression of inflammatory responses and protection from insulin resistance in obesity and type 2 diabetes.


Assuntos
Diabetes Mellitus Tipo 2 , Resistência à Insulina , Tecido Adiposo , Animais , Diabetes Mellitus Tipo 2/terapia , Glucose , Inflamação , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Obesos , Células-Tronco
17.
Int J Bioprint ; 7(3): 389, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34286155

RESUMO

The thermo-sensitive hydrogel formed by triblock copolymers of polyethylene glycols and aliphatic polyesters serves as a promising candidate for bioink due to its excellent biodegradability and biocompatibility. However, the thermo-crosslinking alone cannot achieve a robust hydrogel to support the 3D printed constructs without collapse. Herein, a photo-crosslinkable group was introduced into the triblock copolymers to achieve a dual-sensitive hydrogel. A triblock copolymer poly(lactide-co-glycolide)-polyethylene glycol-poly(lactide-co-glycolide) decorated with acrylate group in the chain end was prepared. The obtained aqueous solutions of the copolymers could transform into hydrogels with excellent shear thinning properties and rapid elastic recovery properties spontaneously on the increase of temperature. The resulted thermogels also allowed for photo-crosslinking by exposure to ultraviolet radiation, with storage modulus dramatically increased to stable the printed constructs. Through a two-step crosslinking strategy, complicated tissue-like constructs with high shape fidelity can be printed using the dual-sensitive inks. Moreover, the mechanical strength, swelling ratio, and printability of the hydrogels can be tuned by varying the substitution rate of the acrylate group without compromising the inks' extrudability. We expect that the dual-sensitive hydrogels may be used as bioinks to print large constructs for applications in tissue engineering.

18.
Microorganisms ; 9(7)2021 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-34209741

RESUMO

Cysticercus pisiformis, the larval stage of Taenia pisiformis, causes serious illness in rabbits that severely impacts the rabbit breeding industry. An inhibitive Th2 immune response can be induced by let-7-enriched exosomes derived from T. pisiformis cysticercus. However, the underlying molecular mechanisms are not completely understood. Here, we report that exosomal miR-let-7-5p released by T. pisiformis cysticercus played a critical role in the activation of M2 macrophages. We found that overexpression of let-7-5p in M1 macrophages decreased M1 phenotype expression while promoting polarization to the M2 phenotype, which is consistent with experimental data in exosome-treated macrophages alone. In contrast, knockdown of let-7-5p in exosome-like vesicles promoted M1 polarization and decreased M2 phenotype expression. Furthermore, down-regulation of transcription factor CCAAT/enhancer-binding protein (C/EBP)-δ resulted in the decrease of M1 phenotype markers and increase of M2 phenotype markers. These results suggested that let-7 enriched in exosome-like vesicles from T. pisiformis metacestodes can induce M2 macrophage polarization via targeting C/EBP δ, which may be involved in macrophage polarization induced by T. pisiformis metacestodes. The finding helps to expand our knowledge of the molecular mechanism of immunosuppression and Th2 immune response induced by metacestodes.

19.
Mol Plant ; 14(11): 1881-1900, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34303025

RESUMO

Soybean mosaic virus (SMV) causes severe yield losses and seed quality reduction in soybean (Glycine max) production worldwide. Rsc4 from cultivar Dabaima is a dominant genetic locus for SMV resistance, and its mapping interval contains three nucleotide-binding domain leucine-rich repeat-containing (NLR) candidates (Rsc4-1, Rsc4-2, and Rsc4-3). The NLR-type resistant proteins were considered as important intracellular pathogen sensors in the previous studies. In this study, based on transient expression assay in Nicotiana benthamiana leaves, we found that the longest transcript of Rsc4-3 is sufficient to confer resistance to SMV, and CRISPR/Cas9-mediated editing of Rsc4-3 in resistant cultivar Dabaima compromised the resistance. Interestingly, Rsc4-3 encodes a cell-wall-localized NLR-type resistant protein. We found that the internal polypeptide region responsible for apoplastic targeting of Rsc4-3 and the putative palmitoylation sites on the N terminus are essential for the resistance. Furthermore, we showed that viral-encoded cylindrical inclusion (CI) protein partially localizes to the cell wall and can interact with Rsc4-3. Virus-driven or transient expression of CI protein of avirulent SMV strains is enough to induce resistance response in the presence of Rsc4-3, suggesting that CI is the avirulent gene for Rsc4-3-mediated resistance. Taken together, our work identified a unique NLR that recognizes plant virus in the apoplast, and provided a simple and effective method for identifying resistant genes against SMV infection.

20.
Microorganisms ; 9(5)2021 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-34062985

RESUMO

Taenia asiatica is a zoonotic parasite found in the human intestine and pig liver that evolved various strategies to survive the host's defenses. Exosomes are membranous vesicles released by cells and are an important vehicle in parasite-host interactions. However, no literature exists on the specific infection mechanisms of T. asiatica against the host defense response, and further research is required to understand the parasite-host interaction. In this study, we investigated the host's differentially expressed genes (DEGs) while stimulating them with exosomes derived from the T. asiatica adult worm (Tas-exo) on LoVo by RNA-seq analysis. Our results identified 348 genes as being significantly differentially expressed for the Tas-exo group when comparing with that of the NC group. Some of these genes are related to modulation of cell proliferation and cell autophagy. Surprisingly, autophagy and cell proliferation have crucial roles in the defense against parasites; accordingly, we detected cell proliferation and autophagy in LoVo cells by CCK8, immunofluorescence, and Western blotting, demonstrating that Tas-exo could inhibit LoVo cell proliferation and autophagy via AMPK pathway. When P62 and p-mTOR/mTOR expression were significantly increased, BeclinI and pAMPK/AMPK were significantly decreased. These results expand our understanding of parasite-host interactions mediated by exosomes.

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