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1.
Ann Palliat Med ; 10(8): 9304-9308, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34488417

RESUMO

Hypercalcemia is a clinical emergency which can cause hypercalcemic crisis and even endanger patients' lives. The increase of serum calcium concentration is caused by the redistribution of calcium in bone and the inhibition of parathyroid secretion, which is known as non-parathyroid hypercalcemia. In this report, we presented a rare case of non-parathyroid hypercalcemia during lactation in order to optimize the diagnosis and treatment of this condition. A 27-year-old female patient was admitted to Wuxi People's Hospital on July 11, 2019 due to "fatigue, anorexia, and pain in both knees for half a month". The patient had fatigue and discomfort, accompanied by pain in both knees without obvious inducement. At the same time, the patient had decreased food intake. In the past 3 days, the symptoms worsened, accompanied by limb numbness. The serum calcium level was increased and the parathyroid hormone (PTH) level was decreased. The patient was diagnosed with hypercalcemia, and was treated with calcitonin and lactation termination. The knee pain disappeared and serum calcium returned to normal during a 2-week follow-up. To conclude, the correlation between hypercalcemia and lactation needs to be considered for non-parathyroid hypercalcemia during lactation. After excluding other possible causes, lactation termination therapy may be an effective therapeutic strategy for non-parathyroid hypercalcemia caused by excessive lactation.


Assuntos
Hipercalcemia , Adulto , Cálcio , Feminino , Humanos , Hipercalcemia/etiologia , Lactação , Dor , Hormônio Paratireóideo
2.
J Craniofac Surg ; 2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34519710

RESUMO

ABSTRACT: Fat fixation is a key step in filling tear trough depression with inferior eyelid orbital septum fat. The ideal position for inferior eyelid fat fixation is to cross the tear trough ligament causing tear trough depression and the orbicularis retaining ligament, with the distal end fixed at the farthest end of the dissected lacuna deep down the inferior orbicularis oculi muscle. Traditional suturing is difficult in the deep narrow lacunae, but a buried guide needle can be used to suture and fix the fat in the deepest lacuna. In this study, 264 patients who underwent tear trough filling using a buried guide needle to fix the released inferior eyelid orbital septum fat from 2017 to 2020 were followed up. The preoperative and postoperative imaging findings were compared to evaluate the effectiveness of the operation and postoperative complications. The inferior eyelid bulging, loose skin, and tear trough depression significantly improved than that before the operation. None of the patients had any severe complications, such as inferior eyelid ectropion, lagophthalmos, scar hyperplasia, and diplopia, in the long term (6 months) postoperatively. Five patients showed mild eyelid-eyeball separation and recovered in 1 month. Four patients had diplopia, and 3 patients had chemosis; all recovered in 7 days. The tear trough depression was not corrected completely in 2 patients. The operation showed satisfactory results in the improvement of tear trough depression in addition to alleviation of inferior eyelid bulging and loose inferior eyelid skin that is caused by the traditional inferior eyelid pouch removal.

3.
Addict Behav ; 124: 107096, 2021 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-34469784

RESUMO

Research has demonstrated that posttraumatic stress disorder (PTSD) is associated with internet-related problematic behaviors. However, studies have not explored the linkage between PTSD symptoms and internet gaming disorder (IGD) symptoms. The current study aimed to investigate the relationship between posttraumatic stress symptoms (PTSS) and IGD symptoms via network analysis. We conducted a cross-sectional study with 341 Chinese young adults directly exposed to a typhoon and examined the network structure of PTSS and IGD symptoms, along with bridge symptoms, to elucidate how they co-occur. Results indicated that 'avoiding external reminders' and 'anhedonia' were identified as the most central symptoms in the PTSD network, whereas 'preoccupation,' 'gaming despite harms', and 'loss of control' ranked highest on centrality in the IGD network. Two bridge symptoms emerged within the combined PTSD and IGD network model: 'concentration difficulties' and 'conflict due to gaming' from among the PTSS and IGD symptoms, respectively. These findings reveal novel associations between PTSS and IGD symptoms and provide an empirically-based hypothesis for how these two disorders may co-occur among individuals exposed to natural disasters.

4.
Bioorg Chem ; 116: 105323, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34482170

RESUMO

Diabetic retinopathy (DR) remains high incidence and accounts for severe impact on vision in diabetics, but its mechanism is still poorly understood. Abnormal migration and proliferation of endothelial cells (ECs) drive neovascular retinopathies, which has an important role in promoting the occurrence and development of DR. In this study, we designed and synthesized a series of PEDF-derived peptides as angiogenesis inhibitors. Especially, compound G24 significantly inhibited the cell proliferation in VEGF-activated human umbilical vein endothelial cells (HUVECs) with IC50 values of 2.88 ± 0.19 µM. Further biological evaluation demonstrated that compound G24 exhibited strong inducing-effects on cell apoptosis and internalization of 67LR, and advanced inhibitory potency in cell migration and angiogenesis formed by HUVECs in vitro. In summary, the optimal compound G24 as a novel angiogenesis inhibitor showed the potentiality in the further research for the treatment for DR.

6.
Biomaterials ; 277: 121115, 2021 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-34488118

RESUMO

Conductive polymers with high near-infrared absorbance, have attracted considerable attention in the design of intelligent nanomedicines for cancer therapy, especially chemo-photothermal therapy. However, the unknown long-term biosafety of conductive polymers in vivo due to non-degradability hinders their clinic application. Herein, a H2O2-triggered degradable conductive polymer, polyacrylic acid (PAA) stabilized poly(pyrrole-3-COOH) (PAA@PPyCOOH), is fabricated to form nanoparticles with doxorubicin (DOX) for safe and precise chemo-phototherapy. The PAA@PPyCOOH was found to be an ideal photothermal nano-agent with good dispersity, excellent biocompatibility and high photothermal conversion efficiency (56%). After further loading of doxorubicin (DOX), PAA@PPyCOOH@DOX demonstrates outstanding photothermal performance, as well as pH/H2O2 dual-responsive release of DOX in tumors with an acidic and overexpressed H2O2 microenvironment, resulting in superior chemo-photothermal therapeutic effects. The degradation mechanism of PAA@PPyCOOH is proposed to be the ring-opening reaction between the pyrrole-3-COOH unit and H2O2. More importantly, the nanoparticles can be specifically degraded by excess H2O2 in tumor, and the degradation products were confirmed to be excreted via urine and feces. In vivo therapeutic evaluation of chemo-photothermal therapy reveals tumor growth of 4T1 breast cancer model is drastically inhibited and no apparent side-effect is detected, thus indicating substantial potential in clinic application.

7.
Int J Nanomedicine ; 16: 6017-6034, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34511903

RESUMO

Background: The broader application of adoptive cell therapy (ACT) in cancer immunotherapies (particularly for solid tumors) has always been limited by the immunosuppressive tumor microenvironment (TME) and the insufficient targetability of effector T cells, resulting in unsatisfied therapeutic outcome. Here, we designed a new strategy by using aptamer-based immunoliposomes to modify PD-1-silencing T cells, which were activated by dendritic cell (DC)/tumor fusion cells (FCs) to improve the antitumor potency of cytotoxic T lymphocytes (CTLs/CD8+ T cells). Methods: PD-1 gene was knocked out from CD8+ T cells using CRISPR/Cas9 system to liberate T cell activity from immunosuppression. The PD-1- T cells were stimulated with DC/tumor FCs, followed by further functional modification of tumor-specific nanoliposomes (hEnd-Apt/CD3-Lipo) to generate FC/PD-1- CTLs. The activation and proliferation and specificity of the modified FC/PD-1- CTLs were measured. The antitumor activity of these CTLs against HepG2-tumors was evaluated in xenograft NOD/SCID mice, and the antitumor mechanism was investigated based on tissue immunohistochemistry and serum ELISA. Results: Our results indicated that the modification of hEnd-Apt/CD3-Lipo nanocomposites on the FC/PD-1- CTLs had a more substantial synergetic effect in inhibiting tumor growth and prolonging animal survival, rather than other control liposomes. Furthermore, the hEnd-Apt/CD3-Lipo-modified FC/PD-1- CTLs showed a stronger antitumor outcome in the tumor-bearing mouse model, through the mechanisms of suppressing tumor cell proliferation, promoting tumor apoptosis, reducing angiogenesis but increasing the infiltration of the FC/PD-1- CTLs in the tumor tissue, as well as upregulating the systemic levels of IFN-γ, IL-2, TNF-α and IL-6 cytokines, by comparison of the control settings. Conclusion: In sum, our investigation suggests an enhancement of antitumor effect by the surface modification of endoglin-targeting nanoliposomes upon DC/tumor FC-activated PD-1- CTLs, therefore, provides a new tumoral endoglin-targeted approach as a promising strategy to reduce immunosuppression of tumor microenvironment and improve the immunotherapeutic outcome of anticancer ACT.

8.
Anal Chem ; 2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34519497

RESUMO

Autophagy plays a critical role in many vitally important physiological and pathological processes, such as the removal of damaged and aged organelles and redundant proteins. Although autophagy is mainly a protective process for cells, it can also cause cell death. In this study, we employed in situ and ex situ surface-enhanced Raman scattering (SERS) spectroscopies to obtain chemical information of lysosomes of HepG2 cells. Results reveal that the SERS profiles of the isolated lysosomes are different from the in situ spectra, indicating that lysosomes lie in different microenvironments in these two cases. We further investigated the molecular changes of isolated lysosomes according to the autophagy induced by starvation via ex situ SERS. During autophagy, the conformation of proteins and the structures of lipids have been affected, and autophagy-related molecular evidence is given for the first time in the living lysosomes. We expect that this study will provide a reference for understanding the cell autophagy mechanism.

10.
FASEB J ; 35(10): e21885, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34478585

RESUMO

In a recently published phase III clinical trial, gemcitabine (GEM) plus cisplatin (DDP) induction chemotherapy significantly improved recurrence-free survival and overall survival and became the standard of care among patients with locoregionally advanced NPC. However, the molecular mechanisms of GEM synergized with DPP in NPC cells remain elucidated. These findings prompt us to explore the effect of the combination between GEM and DDP in NPC cell lines through proliferative phenotype, immunofluorescence, flow cytometry, and western blotting assays. In vitro studies reveal that GEM or DPP treated alone induces cell cycle arrest, promotes cell apoptosis, forces DNA damage response, and GEM synergism with DDP significantly increases the above effects in NPC cells. In vivo studies indicate that GEM or DPP treated alone significantly inhibits the tumor growth and prolongs the survival time of mice injected with SUNE1 cells compared to the control group. Moreover, the mice treated with GEM combined with DDP have smaller tumors and survive longer than those in GEM or DPP treated alone group. In addition, P-gp may be the key molecule that regulates the synergistic effect of gemcitabine and cisplatin. GEM synergizes with DPP to inhibit NPC cell proliferation and tumor growth by inducing cell cycle arrest, cell apoptosis, and DNA damage response, which reveals the mechanisms of combined GEM and DDP induction chemotherapy in improving locoregionally advanced NPC.

11.
Curr Med Sci ; 2021 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-34476663

RESUMO

OBJECTIVE: Generic drugs provide an opportunity for savings in drug expenditure since they are available at a lower cost and do not affect patients' health. A better understanding of pharmacists' knowledge, attitudes, and perception can promote the quality use of generic drugs. The objective of this study was to investigate the knowledge, attitudes, and perception of pharmacists from tertiary hospitals in China regarding generic drugs. METHODS: A cross-sectional survey using a postal questionnaire was conducted, which was sent to 200 hospital pharmacists randomly selected from tertiary hospitals in Hubei Province. A total of 125 questionnaires out of 200 were received. Of the respondents, 80 were female and 45 were male. RESULTS: The majority of respondents (87.2%) could clearly distinguish between original and generic drugs. Pharmacists agreed that generic drugs were less effective (52.8%) and produced more side effects (52%). Fortynine respondents thought that generic drug products were not adequately tested. Approximately 78% and 60% of the pharmacists indicated that generic substitution was not feasible for drugs with narrow therapeutic windows and drugs for critical diseases, respectively. Most of them supported the recommendation of generic drugs based on professional judgment. CONCLUSION: Our study showed that a considerable portion of Chinese hospital pharmacists hold negative perceptions of generic drugs. Interventions to improve pharmacists' knowledge of generic drugs are needed.

12.
Zhen Ci Yan Jiu ; 46(8): 684-9, 2021 Aug 25.
Artigo em Chinês | MEDLINE | ID: mdl-34472754

RESUMO

OBJECTIVE: To observe the effect of transcutaneous electric acupoints stimulation (TEAS) on vascular endothelial function and inflammatory factors after percutaneous coronary intervention (PCI) in patients. METHODS: A total of 94 patients with coronary heart disease and undergoing PCI were randomized into a TEAS group and a sham-TEAS group, 47 cases in each one. In the TEAS group, TEAS started at unilateral Neiguan (PC6) and Ximen (PC4) 30 min before PCI till the end of PCI. In the sham-TEAS group, the procedure and persistent time were same as the TEAS group, but no electric stimulation was performed. Before treatment and at 8 h and 24 h after PCI, the levels of serum endothelin-1 (ET-1), von Willebrand factor (vWF), nitric oxide (NO), blood flow dependent diastolic function (FMD), interleukin-6 (IL-6), inteleukin-10 (IL-10), matrix metalloproteinase-9 (MMP-9) and high-sensitivity C-reactive protein (hs-CRP) were detected in the patients successively. RESULTS: Compared with the levels before PCI, the levels of ET-1 and vWF were all increased at 8 h and 24 h after PCI in the two groups (P<0.05) and the levels in the TEAS group were remarkably lower than those in the sham-TEAS group (P<0.05). Compared with the levels before PCI, the levels of NO and FMD at 8 h and 24 h after PCI were all reduced in the two groups (P<0.05) and the levels in the TEAS group were higher obviously than those in the sham-TEAS group (P<0.05). Compared with the levels before PCI, the levels of hs-CRP, MMP-9, IL-6 and IL-10 were all increased at 8 h and 24 h after PCI in the two groups (P<0.05); Compared with the sham-TEAS group, the levels of hs-CRP, MMP-9 and IL-6 were reduced and the level of IL-10 was increased at 8 h and 24 h after PCI in the TEAS group (P<0.05). CONCLUSION: TEAS effectively improves the vascular endothelial function and reduces serum inflammatory factors after PCI.


Assuntos
Doença das Coronárias , Intervenção Coronária Percutânea , Estimulação Elétrica Nervosa Transcutânea , Pontos de Acupuntura , Proteína C-Reativa , Doença das Coronárias/terapia , Humanos , Intervenção Coronária Percutânea/efeitos adversos
13.
Artigo em Inglês | MEDLINE | ID: mdl-34480736

RESUMO

INTRODUCTION: At present, some studies have reported that nasal rosacea may be an independent disease, but phenotypic characteristics and risk factors for nasal rosacea remain unknown. This study aimed to clarify the clinical features and explore the risk factors for nasal rosacea. METHODS: A hospital-based retrospective study was conducted, including 1615 rosacea patients and 1501 healthy individuals. The patients were divided into three groups based on the involved areas of the lesions (non-nasal, intermediate and nasal rosacea group). Their demographic data and clinical features were obtained from patients' medical records, and risk factors of nasal rosacea were analyzed. RESULTS: There were 927 (57.4%), 647 (40.1%) and 41 (2.5%) cases in the non-nasal, intermediate and nasal rosacea groups, respectively. Of 41 patients with nasal rosacea, all (100.0%) had fixed erythema and 17 cases (41.5%) had phymatous changes. Compared with control group, male gender (adjusted odds ratio [aOR] = 2.39, 95% confidence interval [CI] = 1.14, 4.99), obesity (aOR = 3.19, 95% CI 1.86, 11.79) and alcohol use (aOR = 1.58, 95% CI 1.22, 5.40) were risk factors for nasal rosacea, but these three factors were not risk factors for non-nasal rosacea and intermediate rosacea groups. Among patients with nasal lesions (compared with patients without nasal phymatous changes), family history of rosacea was a risk factor (aOR = 2.12, 95% CI 1.01, 4.46) for nasal phymatous changes and Fitzpatrick IV skin type was a protective factor (aOR = 0.49, 95% CI 0.28, 0.86). CONCLUSION: Nasal rosacea has relatively specific clinical features and independent risk factors, suggesting that it may be a special type of rosacea.

14.
Blood Purif ; : 1-4, 2021 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-34500449

RESUMO

Anemia is a common complication of chronic kidney disease (CKD). Recombinant human erythropoietin (rHu-EPO) is used extensively in patients with CKD. However, anti-erythropoietin (anti-EPO) antibody has been reported during rHu-EPO treatment, which causes pure red cell aplasia (PRCA). We presented a case of 75-year-old man, who underwent hemodialysis for 2 years. He developed PRCA during rHu-EPO treatment. The rHu-EPO was immediately discontinued, and the patient was given roxadustat treatment. After 6 months of roxadustat treatment, the anti-EPO antibody was disappeared, and hemoglobin recovered normal range. The results suggest that roxadustat can be used to treat patients with anti-EPO antibody-mediated PRCA without immunosuppressive therapy.

15.
Drug Des Devel Ther ; 15: 3425-3441, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34385814

RESUMO

Objective: Chaihu Shugan San (CSS) is a common antidepressant prescription in traditional Chinese medicines. However, its active ingredients and mechanisms are unknown. The aim of this study was to explore the potential active ingredients and pharmacological mechanisms of CSS for the treatment of major depressive disorder (MDD). Methods: Active compounds in CSS were screened using the Traditional Chinese Medicine Systems Pharmacology database. Compound-related targets were retrieved using the SwissTargetPrediction database. MDD-related targets were determined using DisGeNET, Therapeutic Target Database and DrugBank databases. The common targets of active compounds in CSS and MDD were retained to construct a compound-MDD target network. Then, functional enrichment analysis and protein-protein interaction analysis were performed to identify hub targets and explore the underlying molecular mechanisms. Finally, hub-targeted genes and pathways were validated by Western blotting and immunofluorescence using chronic unpredictable mild stress (CUMS) mice with or without CSS treatment. The affinities between the active compounds in CSS and hub-targeted genes were evaluated by molecular docking. Results: Network pharmacology analysis revealed 24 potential targets for treatment of MDD by CSS. Functional enrichment analysis showed that PI3K/AKT signaling pathway was likely to be evidently affected by CSS in the treatment of MDD. In vivo experiments showed that CSS could improve depressive-like behaviors and promote neurogenesis in CUMS mice. Furthermore, CSS could increase phosphorylated (p) PI3K/PI3K and pAKT/AKT levels and decrease the pGSK3ß/GSK3ß level in the hippocampus of CUMS mice. The active compounds mainly included quercetin and luteolin, which showed good docking scores targeting the PI3K protein. Conclusion: This network pharmacological and experimental study highlights that the PI3K/AKT pathway is the potential mechanism by which CSS is involved in MDD treatment. Quercetin, luteolin, and kaempferol are probable active compounds in CSS, and these results might provide valuable guidance for further studies of MDD treatment.

16.
Nucleic Acids Res ; 2021 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-34428297

RESUMO

RapA is a bacterial RNA polymerase (RNAP)-associated Swi2/Snf2 ATPase that stimulates RNAP recycling. The ATPase activity of RapA is autoinhibited by its N-terminal domain (NTD) but activated with RNAP bound. Here, we report a 3.4-Å cryo-EM structure of Escherichia coli RapA-RNAP elongation complex, in which the ATPase active site of RapA is structurally remodeled. In this process, the NTD of RapA is wedged open by RNAP ß' zinc-binding domain (ZBD). In addition, RNAP ß flap tip helix (FTH) forms extensive hydrophobic interactions with RapA ATPase core domains. Functional assay demonstrates that removing the ZBD or FTH of RNAP significantly impairs its ability to activate the ATPase activity of RapA. Our results provide the structural basis of RapA ATPase activation by RNAP, through the active site remodeling driven by the ZBD-buttressed large-scale opening of NTD and the direct interactions between FTH and ATPase core domains.

17.
BMC Cardiovasc Disord ; 21(1): 392, 2021 08 12.
Artigo em Inglês | MEDLINE | ID: mdl-34384373

RESUMO

BACKGROUND: To investigate the clinical features of patients with Stanford type A acute aortic dissection (AAD) and analyze the risk factors affecting postoperative in-hospital mortality rate. METHODS: The demographic and clinical data were retrospectively collected and analyzed from 118 AAD patients admitted to the Affiliated Hospital of Hangzhou Normal University from June 2016 to April 2019. All patients underwent surgical treatment and were grouped into death and survival groups. The risk factors affecting postoperative in-hospital death were analyzed using multivariate logistic regression analysis. RESULTS: The male to female ratio in the patients was 3.8:1 and the mean age was 50.11 ± 9.91 years. The patient's main comorbidities were hypertension (70.33%) and coronary heart disease (10.17%). The main symptoms included chest pain and back pain (72.89%). The highest incidence of complications was pericardial effusion (48.31%), followed by pleural effusion (22.88%). The mean systolic blood pressure, white blood cell count and D-dimer in the patients were over the ranges of normal people. The incidences of cardiac and renal insufficiency were 18.64% and 16.95% respectively, and the postoperative in-hospital mortality rate was 12.71%. Univariable analysis showed that age, renal insufficiency, cardiac insufficiency, D-dimer level, cardiopulmonary bypass time, operation time, blood transfusion volume and postoperative hemostasis were significant factors leading to the death (P < 0.05). Multivariate logistic regression analysis showed that age > 65, renal insufficiency, cardiopulmonary bypass time ≥ 250 min and postoperative hemostasis were independent risk factors for the death (P < 0.05). CONCLUSIONS: AAD patients frequently have underlying diseases with pain as the main symptom. Age > 65 years, renal insufficiency, cardiopulmonary bypass time ≥ 250 min and postoperative hemostasis are significantly risk factors for postoperative mortality.

18.
Emerg Microbes Infect ; 10(1): 1683-1690, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34348599

RESUMO

At the end of 2019, A new type of beta-CoV, SARS-CoV-2 emerged and triggered the COVID-19 pandemic, which spread overwhelmingly around the world in less than a year. However, the origin and direct ancestral viruses of SARS-CoV-2 remain unknown. RaTG13, a novel coronavirus found in bats in China's Yunnan Province, is the closest relative virus of the SARS-CoV-2 identified so far. In this study, a new SARS-CoV-2 related virus, provisionally named PrC31, was discovered in Yunnan province by retrospectively analyse bat next generation sequencing (NGS) data of intestinal samples collected in 2018. PrC31 shared 90.7% and 92.0% nucleotide identities to the genomes of SARS-CoV-2 and the bat SARSr-CoV ZC45, respectively. Sequence alignment of PrC31 showed that several genomic regions, especially orf1a and orf8 had the highest homology with those corresponding genomic regions of SARS-CoV-2 than any other related viruses. Phylogenetic analysis indicated that PrC31 shared a common ancestor with SARS-CoV-2 in evolutionary history. The differences between the PrC31 and SARS-CoV-2 genomes were mainly manifested in the spike genes. The amino acid homology between the receptor binding domains of PrC31 and SARS-CoV-2 was only 64.2%. Importantly, recombination analysis revealed that PrC31 underwent multiple complex recombination events (including three recombination breakpoints) involving the SARS-CoV and SARS-CoV-2 sub-lineages, indicating that PrC31 evolved from yet-to-be-identified intermediate recombination strains. Combined with previous studies, it is revealed that the beta-CoVs may possess a more complex recombination mechanism than we thought.


Assuntos
Quirópteros/virologia , Recombinação Genética , SARS-CoV-2/genética , SARS-CoV-2/isolamento & purificação , Sequência de Aminoácidos , Animais , China , Genoma Viral , Filogenia , SARS-CoV-2/classificação , Alinhamento de Sequência , Proteínas Virais/genética
19.
Nat Immunol ; 22(9): 1140-1151, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34426691

RESUMO

Tissue-resident memory T (TRM) cells are non-recirculating cells that exist throughout the body. Although TRM cells in various organs rely on common transcriptional networks to establish tissue residency, location-specific factors adapt these cells to their tissue of lodgment. Here we analyze TRM cell heterogeneity between organs and find that the different environments in which these cells differentiate dictate TRM cell function, durability and malleability. We find that unequal responsiveness to TGFß is a major driver of this diversity. Notably, dampened TGFß signaling results in CD103- TRM cells with increased proliferative potential, enhanced function and reduced longevity compared with their TGFß-responsive CD103+ TRM counterparts. Furthermore, whereas CD103- TRM cells readily modified their phenotype upon relocation, CD103+ TRM cells were comparatively resistant to transdifferentiation. Thus, despite common requirements for TRM cell development, tissue adaptation of these cells confers discrete functional properties such that TRM cells exist along a spectrum of differentiation potential that is governed by their local tissue microenvironment.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Diferenciação Celular/imunologia , Plasticidade Celular/imunologia , Microambiente Celular/imunologia , Memória Imunológica/imunologia , Animais , Antígenos CD/imunologia , Linfócitos T CD8-Positivos/citologia , Feminino , Cadeias alfa de Integrinas/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Transdução de Sinais/imunologia , Fator de Crescimento Transformador beta1/metabolismo
20.
Environ Pollut ; 290: 118027, 2021 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-34428706

RESUMO

With the fast growth of the production and application of engineered nanomaterials (ENMs), nanoparticles (NPs) that escape into the environment have drawn increasing attention due to their ecotoxicological impacts. Motile microalgae are a type of primary producer in most ecosystems; however, the impacts of NPs on the motility of microalgae have not been studied yet. So the toxic impacts of three common metal oxide NPs (nTiO2, nZnO, and nFe2O3) on swimming speed and locomotion mode of a marine microalgae, Platymonas subcordiformis, were investigated in this study. Our results demonstrated that both the velocity and linearity (LIN) of swimming were significantly decreased after the exposure of P. subcordiformis to the tested NPs. In addition, the obtained data indicate that NPs may suppress the motility of P. subcordiformis by constraining the energy available for swimming, as indicated by the significantly lower amounts of intracellular ATP and photosynthetic pigments and the lower activities of enzymes catalyzing glycolysis. Incubation of P. subcordiformis with the tested NPs generally resulted in the overproduction of reactive oxygen species (ROS), aggravation of lipid peroxidation, and induction of antioxidant enzyme activities, suggesting that imposing oxidative stress, which may impair the structural basis for swimming (i.e. the membrane of flagella), could be another reason for the observed motility suppression. Moreover, NP exposure led to significant reductions in the cell viability of P. subcordiformis, which may be due to the disruption of the energy supply (i.e., photosynthesis) and ROS-induced cellular damage. Our results indicate that waterborne NPs may pose a great threat to motile microalgae and subsequently to the health and stability of the marine ecosystem.

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