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1.
Front Immunol ; 12: 652687, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33868291

RESUMO

T cells undergo metabolic reprogramming and multiple biological processes to satisfy their energetic and biosynthetic demands throughout their lifespan. Several of these metabolic pathways result in the generation of reactive oxygen species (ROS). The imbalance between ROS generation and scavenging could result in severe damage to the cells and potential cell death, ultimately leading to T cell-related diseases. Interestingly, ROS play an essential role in T cell immunity. Here, we introduce the important connectivity between T cell lifespan and the metabolic reprogramming among distinct T cell subsets. We also discuss the generation and sources of ROS production within T cell immunity as well as highlight recent research concerning the effects of ROS on T cell activities.

2.
Sci Rep ; 11(1): 9018, 2021 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-33907245

RESUMO

Histone/protein deacetylases (HDAC) 1 and 2 are typically viewed as structurally and functionally similar enzymes present within various co-regulatory complexes. We tested differential effects of these isoforms in renal ischemia reperfusion injury (IRI) using inducible knockout mice and found no significant change in ischemic tolerance with HDAC1 deletion, but mitigation of ischemic injury with HDAC2 deletion. Restriction of HDAC2 deletion to the kidney via transplantation or PAX8-controlled proximal renal tubule-specific Cre resulted in renal IRI protection. Pharmacologic inhibition of HDAC2 increased histone acetylation in the kidney but did not extend renal protection. Protein analysis demonstrated increased HDAC1-associated CoREST protein in HDAC2-/- versus WT cells, suggesting that in the absence of HDAC2, increased CoREST complex occupancy of HDAC1 can stabilize this complex. In vivo administration of a CoREST inhibitor exacerbated renal injury in WT mice and eliminated the benefit of HDAC2 deletion. Gene expression analysis of endothelin showed decreased endothelin levels in HDAC2 deletion. These data demonstrate that contrasting effects of HDAC1 and 2 on CoREST complex stability within renal tubules can affect outcomes of renal IRI and implicate endothelin as a potential downstream mediator.

3.
Mol Med ; 27(1): 39, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33858325

RESUMO

OBJECTIVES: Targeted inhibition of inflammatory response can reduce diabetic cerebral ischemia-reperfusion (I/R) injure. Pyroptosis is characterized by caspase-1 dependence and the release of a large number of pro-inflammatory factors. LncRNA-Fendrr is associated with a variety of diseases, but Fendrr has not been studied in diabetic cerebral I/R. NLR-family CARD-containing protein 4 (NLRC4) regulate the pyroptosis of microglia cells. This study was designed to investigate whether Fendrr is involved in the effects of diabetic cerebral I/R injury. METHODS: The diabetic brain I/R model in mice was constructed. Mouse microglia cell line BV-2 cells were exposed to high glucose followed by hypoxia/reoxygenation (H/R). Fendrr and some pyroptosis-associated proteins were detected by qRT-PCR, western blot or ELISA. HE staining was used to detect pathological changes. Microglia pyroptosis was detected by TUNEL staining. RNA pull-down and RNA Immunoprecipitation were used to detect binding of Fendrr to HERC2 (E3 ubiquitin ligase), and CO-IP detected binding of HERC2 to NLRC4. The ubiquitination of NLRC4 was detected by ubiquitination experiments. RESULTS: Fendrr was significantly increased in the diabetic cerebral I/R model, and NLRC4 inflammatory complex and pyroptosis mediated inflammatory factors were increased. NLRC4 and inflammatory cytokines associated with pyroptosis were decreased in the high glucose-treated hypoxia/reoxygenation (H/R)-induced microglia after Fendrr knockdown. Fendrr bound to HERC2 protein, and HERC2 bound to NLRC4. Meanwhile, Fendrr could inhibit the ubiquitination of NLRC4, HERC2 promoted the ubiquitination of NLRC4 protein. Moreover, the effect of Fendrr overexpression in the diabetic cerebral I/R model of microglia can be reversed by HERC2 overexpression. CONCLUSION: Fendrr can protect against the ubiquitination and degradation of NLRC4 protein through E3 ubiquitin ligase HERC2, thereby accelerating the pyroptosis of microglia.

4.
Viruses ; 13(5)2021 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-33923025

RESUMO

The viral antigen (Ag)-specific CD8+ cytotoxic T lymphocytes (CTLs) derived from pluripotent stem cells (PSCs), i.e., PSC-CTLs, have the ability to suppress the human immunodeficiency virus (HIV) infection. After adoptive transfer, PSC-CTLs can infiltrate into the local tissues to suppress HIV replication. Nevertheless, the mechanisms by which the viral Ag-specific PSC-CTLs elicit the antiviral response remain to be fully elucidated. In this study, we generated the functional HIV-1 Gag epitope SL9-specific CTLs from the induced PSC (iPSCs), i.e., iPSC-CTLs, and investigated the suppression of SL9-specific iPSC-CTLs on viral replication and the protection of CD4+ T cells. A chimeric HIV-1, i.e., EcoHIV, was used to produce HIV replication in mice. We show that adoptive transfer of SL9-specific iPSC-CTLs greatly suppressed EcoHIV replication in the peritoneal macrophages and spleen in the animal model. Furthermore, we demonstrate that the adoptive transfer significantly reduced expression of PD-1 on CD4+ T cells in the spleen and generated persistent anti-HIV memory T cells. These results indicate that stem cell-derived viral Ag-specific CTLs can robustly accumulate in the local tissues to suppress HIV replication and prevent CD4+ T cell exhaustion through reduction of PD-1 expression.

5.
Neuropharmacology ; 187: 108492, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33582153

RESUMO

In this work, modulation by orexin-A of the release of glutamate and GABA from bipolar and amacrine cells respectively was studied by examining the effects of the neuropeptide on miniature excitatory postsynaptic currents (mEPSCs) and miniature inhibitory postsynaptic currents (mIPSCs) of rat retinal ganglion cells (GCs). Using RNAscope in situ hybridization in combination with immunohistochemistry, we showed positive signals for orexin receptor-1 (OX1R) mRNA in the bipolar cell terminals and those for orexin receptor-2 (OX2R) mRNA in the amacrine cell terminals. With whole-cell patch-clamp recordings in rat retinal slices, we demonstrated that application of orexin-A reduced the interevent interval of mEPSCs of GCs through OX1R. However, it increased the interevent interval of mIPSCs, mediated by GABAA receptors, through OX2R. Furthermore, orexin-A-induced reduction of mEPSC interevent interval was abolished by the application of PI-PLC inhibitors or PKC inhibitors. In contrast, orexin-A-induced increase of GABAergic mIPSC interevent interval was mimicked by 8-Br-cAMP or an adenylyl cyclase activator, but was eliminated by PKA antagonists. Finally, application of nimodipine, an L-type Ca2+ channel blocker, increased both mEPSC and mIPSC interevent interval, and co-application of orexin-A no longer changed the mEPSCs and mIPSCs. We conclude that orexin-A increases presynaptic glutamate release onto GCs by activating L-type Ca2+ channels in bipolar cells, a process that is mediated by an OX1R/PI-PLC/PKC signaling pathway. However, orexin-A decreases presynaptic GABA release onto GCs by inhibiting L-type Ca2+ channels in amacrine cells, a process that is mediated by an OX2R/cAMP-PKA signaling pathway.

6.
Arch Environ Contam Toxicol ; 80(2): 402-413, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33534037

RESUMO

In this study, we assessed the effects of 11-day exposure of sulfadiazine (SD), sulfamethazine (SM2), norfloxacin (NOR), and enrofloxacin (ENR) on the growth, chlorophyll a (Chl. a) content, phycobiliproteins (PBPs) content, and alkaline phosphatase (ALP) activity of Chrysosporum ovalisporum, examined the removal rate of these antibiotics by C. ovalisporum, and performed acute toxicology test with Daphnia magna to determine the effect of interaction between antibiotics and cyanobacteria on aquatic animals. The results showed that the stress of SD and SM2 increased extracellular ALP activity and weakly inhibited the algal growth and the contents of Chl. a and PBPs compared with that noted in the control. ENR and NOR treatment groups exerted significant inhibition on algal growth as well as Chl. a and PBPs contents and ALP activity, although the cyanobacterium could degrade these two antibiotics more than SD and SM2. The results also revealed that the interaction between antibiotics and cyanobacteria could inhibit D. magna feeding.


Assuntos
Antibacterianos/metabolismo , Cianobactérias/metabolismo , Poluentes Químicos da Água/metabolismo , Animais , Clorofila A , Daphnia/efeitos dos fármacos , Água
7.
BMC Mol Cell Biol ; 22(1): 8, 2021 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-33485325

RESUMO

BACKGROUND: Warts, hypogammaglobulinemia, recurrent bacterial infections and myelokathexis (WHIM) syndrome is a primary immunodeficiency disease (PID) usually caused by autosomal dominant mutations in the chemokine receptor CXCR4 gene. To date, a total of nine different mutations including eight truncation mutations and one missense mutation (E343K, CXCR4E343K) distributed in the C-terminus of CXCR4 have been identified in humans. Studies have clarified that the loss of phosphorylation sites in the C-terminus of truncated CXCR4 impairs the desensitization process, enhances the activation of G-protein, prolongs downstream signaling pathways and introduces over immune responses, thereby causing WHIM syndrome. So far, there is only one reported case of WHIM syndrome with a missense mutation, CXCR4E343K, which has a full length of C-terminus with entire phosphorylation sites, no change in all potential phosphorylation sites. The mechanism of the missense mutation (CXCR4E343K) causing WHIM syndrome is unknown. This study aimed to characterize the effect of mutation at the 343 site of CXCR4 causing the replacement of arginine/E with glutamic acid/K on the receptor signal transduction, and elucidate the mechanism underling CXCR4E343K causing WHIM in the reported family. RESULTS: We completed a series of mutagenesis to generate different mutations at the 343 site of CXCR4 tail, and established a series of HeLa cell lines stably expressing CXCR4WT or CXCR4E343D (glutamic acid/E replaced with aspartic acid/D) or CXCR4E343K (glutamic acid/E replaced with lysine/K) or CXCR4E343R (glutamic acid/E replaced with arginine/R) or CXCR4E343A (glutamic acid/E replaced with alanine/A) and then systematically analyzed functions of the CXCR4 mutants above. Results showed that the cells overexpressing of CXCR4E343D had no functional changes with comparison that of wild type CXCR4. However, the cells overexpressing of CXCR4E343K or CXCR4E343R or CXCR4E343A had enhanced cell migration, prolonged the phosphorylation of ERK1/2, p38, JNK1/2/3, aggravated activation of PI3K/AKT/NF-κB signal pathway, introduced higher expression of TNFa and IL6, suggesting over immune response occurred in CXCR4 mutants with charge change at the 343 site of receptor tail, as a result, causing WHIM syndrome. Biochemical analysis of those mutations at the 343 site of CXCR4 above shows that CXCR4 mutants with no matter positive or neutral charge have aberrant signal pathways downstream of activated mutated CXCR4, only CXVR4 with negative charge residues at the site shows normal signal pathway post activation with stromal-derived factor (SDF1, also known as CXCL12). CONCLUSION: Taken together, our results demonstrated that the negative charge at the 343 site of CXCR4 plays an essential role in regulating the down-stream signal transduction of CXCR4 for physiological events, and residue charge changes, no matter positive or neutral introduce aberrant activities and functions of CXCR4, thus consequently lead to WHIM syndrome.

8.
Cell Rep ; 33(11): 108500, 2020 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-33326785

RESUMO

Immune cell function is influenced by metabolic conditions. Low-glucose, high-lactate environments, such as the placenta, gastrointestinal tract, and the tumor microenvironment, are immunosuppressive, especially for glycolysis-dependent effector T cells. We report that nicotinamide adenine dinucleotide (NAD+), which is reduced to NADH by lactate dehydrogenase in lactate-rich conditions, is a key point of metabolic control in T cells. Reduced NADH is not available for NAD+-dependent enzymatic reactions involving glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and 3-phosphoglycerate dehydrogenase (PGDH). We show that increased lactate leads to a block at GAPDH and PGDH, leading to the depletion of post-GAPDH glycolytic intermediates, as well as the 3-phosphoglycerate derivative serine that is known to be important for T cell proliferation. Supplementing serine rescues the ability of T cells to proliferate in the presence of lactate-induced reductive stress. Directly targeting the redox state may be a useful approach for developing novel immunotherapies in cancer and therapeutic immunosuppression.

9.
Immunol Cell Biol ; 2020 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-33141986

RESUMO

Over the past decade, autophagy has emerged as a critical regulatory mechanism of the immune system through critically controlling various aspects of T cell biology and determining the fate of different T cell subsets. Autophagy maintains T cell development and survival by regulating the degradation of organelles and apoptotic proteins. The autophagic process also impacts the formation of memory T cells. Alteration of autophagy in T cells may lead to a variety of pathological conditions such as inflammation, autoimmune diseases and cancer. In this review, we discuss how autophagy impacts T cell differentiation, survival and memory, and its implication in immunotherapy for various diseases.

10.
IEEE Trans Cybern ; PP2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-33055052

RESUMO

Using semitensor products (STPs) of matrices, sampled-data state-feedback control (SDSFC) with the Lebesgue sampling region Sτ is first considered to stabilize a Boolean control network (BCN) to a fixed point, under which a necessary and sufficient condition for stabilization is obtained when the considered BCN with the Lebesgue sampling region is converted to a switching system. Meanwhile, the corresponding asynchronous SDSFC gains are designed from a sequence of reachable sets. Then, an algorithm is shown to obtain the minimal number of controlling times and all states globally stabilize to the desired state with the fastest convergence rate under the minimal number of controlling times. Besides, the results have been extended to p Lebesgue sampling regions Sτi, i=1,2,..., p. And some results are presented for this situation, including the necessary and sufficient conditions stabilization under the p Lebesgue sampling regions, the asynchronous SDSFC gains, and the algorithm to obtain the optimal states sampling regions. Examples are listed to show the effectiveness of our results, and the biological example indicates that the SDSFC with Lebesgue sampling is also suitable for stochastic BCNs.

11.
Heart Surg Forum ; 23(5): E621-E626, 2020 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-32990579

RESUMO

BACKGROUND: Coronary artery disease (CAD) is the most common cause of heart failure (HF), and impaired ejection fraction (EF<50%) is a crucial precursor to HF. Coronary artery bypass grafting (CABG) is an effective surgical solution to CAD-related HF. In light of the high risk of cardiac surgery, appropriate scores for groups of patients are of great importance. We aimed to establish a novel score to predict in-hospital mortality for impaired EF patients undergoing CABG. METHODS: Clinical information of 1,976 consecutive CABG patients with EF<50% was collected from January 2012 to December 2017. A novel system was developed using the logistic regression model to predict in-hospital mortality among patients with EF<50% who were to undergo CABG. The scoring system was named PGLANCE, which is short for seven identified risk factors, including previous cardiac surgery, gender, load of surgery, aortic surgery, NYHA stage, creatinine, and EF. AUC statistic was used to test discrimination of the model, and the calibration of this model was assessed by the Hosmer-lemeshow (HL) statistic. We also evaluated the applicability of PGLANCE to predict in-hospital mortality by comparing the 95% CI of expected mortality to the observed one. Results were compared with the European Risk System in Cardiac Operations (EuroSCORE), EuroSCORE II, and Sino System for Coronary Operative Risk Evaluation (SinoSCORE). RESULTS: By comparing with EuroSCORE, EuroSCORE II and SinoSCORE, PGLANCE was well calibrated (HL P = 0.311) and demonstrated powerful discrimination (AUC=0.846) in prediction of in-hospital mortality among impaired EF CABG patients. Furthermore, the 95% CI of mortality estimated by PGLANCE was closest to the observed value. CONCLUSION: PGLANCE is better with predicting in-hospital mortality than EuroSCORE, EuroSCORE II, and SinoSCORE for Chinese impaired EF CABG patients.

12.
IEEE Trans Cybern ; PP2020 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-32886617

RESUMO

In this article, pinning control has been applied to stabilize a kind of stochastic network with finite states called probabilistic logical networks (PLNs). First, the solvability of pinning controllers, including the selection of pinning nodes and the corresponding control design, is addressed to guarantee the stabilization of PLNs. Then, based on the complete matrices set, one necessary and sufficient condition is obtained for PLNs to be stabilized by exact p nodes. In addition, an algorithm is presented for obtaining the minimal number of pinning nodes and how exact they are. As an application, our algorithm is used to calculate the minimal number of pinning nodes for the stabilization of logical networks (LNs). Examples are given to illustrate the process of choosing pinning nodes and show the efficiency of the obtained results.

13.
J Environ Sci (China) ; 97: 141-148, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32933729

RESUMO

Sulfonamides (SAs) are common antimicrobial drugs, which are frequently detected in surface water systems, and are difficult to degrade, posing a potential threat to the aquatic environment. However, little is known about the potential adverse effects of SAs on non-target organisms (e.g., microalgae) in the aquatic ecosystem. In this study, the effect of SAs (sulfadiazine (SD), sulfamerazine (SM1), and sulfamethazine (SM2) at 1, 5, 20, and 50 mg/L concentrations, respectively) on the freshwater microalga Dictyosphaerium sp. was investigated, with respect to changes of biomass and chlorophyll a content and induction of extracellular polymer substances (EPS), including protein and polysaccharide contents. At the same time, the residue of SAs was determined. The results showed that Dictyosphaerium sp. was tolerant to the three SAs, and the chlorophyll a content in Dictyosphaerium sp. significantly decreased on day 7, followed by a "compensation phenomena". The increase in protein and polysaccharide contents played a defensive role in Dictyosphaerium sp. against antibiotic stress, and there was a strong positive correlation between polysaccharide contents and antibiotic concentrations. Dictyosphaerium sp. exhibited 35%-45%, 30%-42%, and 26%-51% removal of SD, SM1, and SM2, respectively. This study is helpful to understand the changes of EPS in the defense process of microalgae under the action of antibiotics, and provides a new insight for the ecological removal of antibiotic pollution in natural surface water system.


Assuntos
Microalgas , Sulfonamidas , Clorofila A , Ecossistema , Água Doce
14.
J Clin Invest ; 130(12): 6242-6260, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32790649

RESUMO

The transcription factor MEF2D is important in the regulation of differentiation and adaptive responses in many cell types. We found that among T cells, MEF2D gained new functions in Foxp3+ T regulatory (Treg) cells due to its interactions with the transcription factor Foxp3 and its release from canonical partners, like histone/protein deacetylases. Though not necessary for the generation and maintenance of Tregs, MEF2D was required for the expression of IL-10, CTLA4, and Icos, and for the acquisition of an effector Treg phenotype. At these loci, MEF2D acted both synergistically and additively to Foxp3, and downstream of Blimp1. Mice with the conditional deletion in Tregs of the gene encoding MEF2D were unable to maintain long-term allograft survival despite costimulation blockade, had enhanced antitumor immunity in syngeneic models, but displayed only minor evidence of autoimmunity when maintained under normal conditions. The role played by MEF2D in sustaining effector Foxp3+ Treg functions without abrogating their basal actions suggests its suitability for drug discovery efforts in cancer therapy.

15.
Water Res ; 185: 116220, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32736282

RESUMO

To improve the efficiency of antibiotic degradation, the photosynergistic performance of bismuth vanadate (BiVO4) with a microalga, Dictyosphaerium sp., was demonstrated under visible-light irradiation for the first time. Sulfamethazine (SM2) was selected as a representative sulfanilamide antibiotic, and the photocatalytic degradation mechanism of SM2 was evaluated in media via the BiVO4-algae system. The hydrothermally synthesized sample was characterized using X-ray powder diffraction, X-ray photoelectron spectroscopy, ultraviolet-visible diffuse reflectance spectroscopy, transmission electron microscopy, Brunauer-Emmett-Teller surface area, and Fourier transform infrared spectroscopy techniques. The results demonstrated that the prepared photocatalyst corresponded to phase-pure monoclinic scheelite BiVO4. The synthesized BiVO4 showed superior photocatalytic properties under irradiation with visible light, and more than 80% of photocatalytic degradation efficiency was obtained by the BiVO4-algae system. Based on quenching experiments, the photocatalytic degradation of SM2 in the BiVO4-algae system was primarily accomplished via the generation of triplet state dissolved organic matter, and hydroxyl radicals played a small role in the degradation process. The direct oxidation of holes made no contribution to the degradation. Metabolomics data showed that a total of 91 metabolites were significantly changed between the two comparison groups (algae-SM2 group vs algae group; algae-BiVO4-SM2 group vs algae-BiVO4 group). The glycometabolism pathways were increased and the tricarboxylic acid cycle was activated when BiVO4 was present. The study provides a distinctive approach to remove antibiotics using visible light in the aqueous environment.


Assuntos
Microalgas , Bismuto , Catálise , Luz , Fotólise , Sulfametazina
16.
Int J Clin Pharmacol Ther ; 58(10): 531-538, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32716292

RESUMO

OBJECTIVE: The aim of this study was to analyze the pharmacokinetics/pharmacodynamics (PK/PD) of higher-dose tigecycline (100 mg q12h) in severely infected intensive care unit (ICU) patients receiving continuous renal replacement therapy (CRRT). MATERIALS AND METHODS: In this prospective single-center observational study, severely infected patients receiving intravenous tigecycline were enrolled. They were divided into a CRRT group (7 cases) and a non-CRRT group (9 cases). The blood samples and CRRT ultrafiltrate were collected. The drug concentration in each sample was determined by a HPLC-UV method. The pharmacokinetic parameters were simulated and calculated with DAS 2.0. The PK/PD parameters were evaluated according to published data. The registration number of this study is NCT02931526 in ClinicalTrials.gov. RESULTS: In the non-CRRT group, Cmax, Cmin, and AUC0-24 were 1.00 ± 0.66 µg×mL-1, 0.20 ± 0.12 µg×mL-1, and 22.12 ± 14.46 µg×h×mL-1, respectively. The clinical efficiency was 55.6%, and the bacterial clearance rate was 77.8%. In the CRRT group, Cmax, Cmin, and AUC0-24 were 0.96 ± 0.31 µg×mL-1, 0.22 ± 0.12 µg×mL-1, and 19.90 ± 8.14 µg×h×mL-1, respectively. The clinical efficiency was 28.6%, and the bacterial clearance rate was 28.6%. The individual differences of tigecycline plasma concentrations in our study were widely variable, and the differences of the two groups' PK/PD parameters had no statistical significance (p < 0.05). CONCLUSION: CRRT may have had little influence in tigecycline metabolism in our study, and therapeutic drug monitoring needs to be introduced for critically ill patients because of various pharmacokinetic parameters.


Assuntos
Terapia de Substituição Renal Contínua , Antibacterianos , Estado Terminal , Humanos , Estudos Prospectivos , Tigeciclina
17.
Huan Jing Ke Xue ; 41(6): 2688-2697, 2020 Jun 08.
Artigo em Chinês | MEDLINE | ID: mdl-32608784

RESUMO

Enrofloxacin (ENR), a fluoroquinolones antibiotic, is widely used in the medical and aquaculture fields. Its residues in surface waters in China are high. However, few studies have evaluated both its toxicity to phytoplankton and the degradation or removal by microalgae. In this study, the growth, photosynthetic activity, and exopolysaccharides (EPS) of freshwater micro-green algae Dictyosphaerium sp. and the dynamics of ENR concentrations (0, 5, 25, 50, and 100 mg·L-1) were studied through an exposure experiment for 12 days. Results showed that the biomass and photosynthetic pigment content of Dictyosphaerium sp. increased with increasing exposure time in each treatment; however, it showed a significant inhibitory effect on the growth and pigment accumulation of Dictyosphaerium sp. compared with the control group (P<0.01). The LC50 of ENR to Dictyosphaerium sp. was (241.29±7.33) mg·L-1 after 96-h exposure, indicating that Dictyosphaerium sp. could adapt to the stress conditions of high concentration ENR. Meanwhile, when the concentration of enrofloxacin was<5 mg·L-1, it was found to promote the maximum photosynthetic rate (Fv/Fm) of Dictyosphaerium sp. On the contrary, when the concentration of enrofloxacin was>5 mg·L-1, photosynthetic inhibition was observed (P<0.01). The actual photosynthetic rate (Yield) and the maximum electron transfer rate (ETRmax) showed a trend of initially decreasing and then increasing in 12 days. It can gradually adapt to the stress conditions and recover certain photosynthetic activity after 6 days' exposure. In addition, ENR can also stimulate the EPS (RPS and CPS) release. At the end of the experiment, the removal rates of ENR in the four control groups (no algae addition groups) (5, 25, 50, and 100 mg·L-1ENR) were 7.27%, 5.56%, 5.30%, and 4.88%, respectively, while the removal rates of the treatment groups were 3.21, 3.01, 2.69, and 2.83 times of the no algae groups, indicating that Dictyosphaerium sp. had a significant promoting effect on the removal of ENR (P<0.01). Overall, our results can provide new insights for the understanding of the ecological toxicity of fluoroquinolone antibiotics to primary producers in the aquatic system and also provide new ideas for the ecological removal of antibiotic residues in water bodies and the biological resource utilization of freshwater microalgae.


Assuntos
Clorófitas , Poluentes Químicos da Água/análise , China , Enrofloxacina , Fluoroquinolonas/análise , Água Doce
18.
Neurosci Lett ; 731: 135109, 2020 07 13.
Artigo em Inglês | MEDLINE | ID: mdl-32492476

RESUMO

Our earlier studies have shown that the axon growth inhibitory molecule Nogo affects axon routing at the optic chiasm likely through a differential regulation of Nogo receptor on the optic axons. Using isoform specific antibodies, we further showed that Nogo-A was predominantly expressed by retinal ganglion cells and their axons, while Nogo-B was highly localized on the radial glia at the midline of the chiasm, suggesting a role of Nogo-B in regulating turning of uncrossed axons. To further investigate the roles of Nogo-A in axon divergence, we analyzed the routing of axons in the chiasm of Nogo-A knockout mice during the growth of axons across the midline. At E13 to E16, there was no significant difference in the contralateral projection (P = 0.6943 for E13; P = 0.9867 for E14; P = 0.4121 for E15 and P = 0.3402 for E16). The results also showed the absence of Nogo-A did not cause any obvious change to the ipsilateral projection at the optic chiasm, both for the early generated uncrossed axons at E13 and E14 and the late cohorts at E15-E16, when compared with the wild-type mice (P = 0.4788 for E13; P = 0.188 for E14; P = 0.3152 for E15 and P = 0.432 for E16). These findings support that Nogo-A is not the major isoform to guide the axon divergence in the mouse optic chiasm.

19.
Sci Rep ; 10(1): 9292, 2020 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-32518311

RESUMO

Vascularized composite allotransplantation (VCA) allows tissue replacement after devastating loss but is currently limited in application and may be more widely performed if maintenance immunosuppression was not essential for graft acceptance. We tested whether peri-transplant costimulation blockade could prolong VCA survival and required donor bone-marrow cells, given that bone-marrow might promote graft immunogenicity or graft-versus-host disease. Peritransplant CD154 mAb/rapamycin (RPM) induced long-term orthotopic hindlimb VCA survival (BALB/c->C57BL/6), as did CTLA4Ig/RPM. Surprisingly, success of either protocol required a bone-marrow-associated, radiation-sensitive cell population, since long-bone removal or pre-transplant donor irradiation prevented long-term engraftment. Rejection also occurred if Rag1-/- donors were used, or if donors were treated with a CXCR4 inhibitor to mobilize donor BM cells pre-transplant. Donor bone-marrow contained a large population of Foxp3+ T-regulatory (Treg) cells, and donor Foxp3+ Treg depletion, by diphtheria toxin administration to DEREG donor mice whose Foxp3+ Treg cells expressed diphtheria toxin receptor, restored rejection with either protocol. Rejection also occurred if CXCR4 was deleted from donor Tregs pre-transplant. Hence, long-term VCA survival is possible across a full MHC disparity using peritransplant costimulation blockade-based approaches, but unexpectedly, the efficacy of costimulation blockade requires the presence of a radiation-sensitive, CXCR4+ Foxp3+ Treg population resident within donor BM.

20.
Transpl Immunol ; 61: 101308, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32535143

RESUMO

BACKGROUND: Vascularized composite allotransplantation (VCA) is a novel and life-enhancing procedure to restore a patient's function and/or appearance. Current immunosuppression in VCA recipients is based on calcineurin inhibitor (CNI) therapy that can lead to severe complications, such that inducing immune tolerance is a major goal of VCA research. In contrast to CNI, rapamycin (RPM) is thought to be beneficial to the development of immune tolerance by suppressing T-effector cells (Teffs) and expanding T-regulatory (Treg) cells. However, we found high dose RPM monotherapy prolonged VCA survival by only a few days, leading us to explore the mechanisms responsible. METHODS: A mouse orthotopic forelimb transplantation model (BALB/c- > C57BL/6) was established using WT mice, as well as C57BL/6 recipients with conditional deletion of T-bet within their Treg cells. Events in untreated VCA recipients or those receiving RPM or FK506 therapy were analyzed by flow-cytometry, histopathology and real-time qPCR. RESULTS: Therapy with RPM (2 mg/kg/d, p < .005) or FK506 (2 mg/kg/d, p < .005) each prolonged VCA survival. In contrast to FK506, RPM increased the ratio of splenic Treg to Teff cells (p < .05) by suppressing Teff and expanding Treg cells. While the proportion of activated splenic CD4 + Foxp3- T cells expressing IFN-γ were similar in control and RPM-treated groups, RPM decreased the proportions ICOS+ and CD8+ IFN-γ + splenic T cells. However, RPM also downregulated CXCR3+ expression by Tregs, and forelimb allografts had reduced infiltration by CXCR3+ Treg cells. In addition, allograft recipients whose Tregs lacked T-bet underwent accelerated rejection compared to WT mice despite RPM therapy. CONCLUSIONS: We demonstrate that while RPM increased the ratio of Treg to Teff cells and suppressed CD8+ T cell allo-activation, it failed to prevent CD4 Teff cell activation and impaired CXCR3-dependent Treg graft homing, thereby limiting the efficacy of RPM in VCA recipients.

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