Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 264
Filtrar
1.
Neuropharmacology ; 204: 108895, 2021 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-34813859

RESUMO

Social memory is the ability to discriminate familiar conspecific from the unknown ones. Prefrontal neurons are essentially required for social memory, but the mechanism associated with this regulation remains unknown. It is also unclear to what extent the neuronal representations of social memory formation and retrieval events overlap in the prefrontal cortex (PFC) and which event drives social memory strength. Here we asked these questions by using a repeated social training paradigm for social recognition in FosTRAP mice. We found that after 4 days' repeated social training, female mice developed stable social memory. Specifically, repeated social training activated more cells that were labeled with tdTomato during memory retrieval compared with the first day of memory encoding. Besides, combining TRAP with c-Fos immunostaining, we found about 30% of the FosTRAPed cells were reactivated during retrieval. Moreover, the number of retrieval-induced but not first-day encoding-induced tdTomato neurons correlates with the social recognition ratio in the prelimbic but not other subregions. The activated cells during the retrieval session also showed increased NMDA receptor-mediated synaptic transmission compared with that in non-labeled pyramidal neurons. Blocking NMDA receptors by MK-801 impaired social memory but not sociability. Therefore, our results reveal that repetitive training elevates mPFC involvement in social memory retrieval via enhancing NMDA receptor-mediated synaptic transmission, thus rendering stable social memory.

2.
J Periodontal Res ; 2021 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-34748647

RESUMO

BACKGROUND AND OBJECTIVE: Clinical studies have shown that metabolic syndrome (MetS) exacerbates periodontitis. However, the underlying mechanisms remain largely unknown. Since our animal study has shown that high-fat diet-induced MetS exacerbates lipopolysaccharide (LPS)-stimulated periodontitis in mouse model and our in vitro study showed that acid sphingomyelinase (aSMase) plays a key role in the amplification of LPS-triggered pro-inflammatory response by palmitic acid (PA) in macrophages, we tested our hypothesis that inhibitor of aSMase attenuates MetS-exacerbated periodontitis in animal model. Furthermore, to explore the potential underlying mechanisms, we tested our hypothesis that aSMase inhibitor downregulates pro-inflammatory and pro-osteoclastogenic gene expression in macrophages in vitro. MATERIAL AND METHODS: We induced MetS and periodontitis in C57BL/6 mice by feeding high-fat diet (HFD) and periodontal injection of A. actinomycetemcomitans LPS, respectively, and treated mice with imipramine, a well-established inhibitor of aSMase. Micro-computed tomography (micro-CT), tartrate-resistant acid phosphatase staining, histological and pathological evaluations as well as cell cultures were performed to evaluate alveolar bone loss, osteoclast formation, periodontal inflammation and pro-inflammatory gene expression. RESULTS: Analysis of metabolic parameter showed that while HFD induced MetS by increasing bodyweight, insulin resistance, cholesterol and free fatty acids, imipramine reduced free fatty acids but had no significant effects on other metabolic parameters. MicroCT showed that either MetS or periodontitis significantly reduced bone volume fraction (BVF) of maxilla and the combination of MetS and periodontitis further reduced BVF. However, imipramine increased BVF in mice with both MetS and periodontitis to a level similar to that in mice with periodontitis alone, suggesting that imipramine abolished the synergy between MetS and periodontitis on alveolar bone loss. Consistently, results showed that imipramine inhibited osteoclast formation and periodontal inflammation in mice with both MetS and periodontitis. To elucidate the mechanisms by which imipramine attenuates MetS-exacerbated periodontitis, we showed that imipramine inhibited the upregulation of pro-inflammatory cytokines and transcription factor c-FOS as well as ceramide production by LPS plus PA in macrophages. CONCLUSION: This study has shown that imipramine as an inhibitor of aSMase abolishes the synergy between MetS and periodontitis on alveolar bone loss in animal model and inhibits pro-inflammatory and pro-osteoclastogenic gene expression in macrophages in vitro. This study provides the first evidence that aSMase is a potential therapeutic target for MetS-exacerbated periodontitis.

3.
Small ; 17(45): e2103463, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34761524

RESUMO

Cancer immunotherapy based on natural killer (NK) cells is demonstrated to be a promising strategy. However, NK cells are deficient in ligands that target specific tumors, resulting in limited antitumor efficacy. Here, a glycoengineering approach to imitate the chimeric antigen receptor strategy and decorate NK cells with nanobodies to promote NK-based immunotherapy in solid tumors is proposed. Nanobody 7D12, which specifically recognizes the human epidermal growth factor receptor (EGFR) that is overexpressed on many solid tumors, is coupled to the chemically synthesized DBCO-PEG4 -GGG-NH2 by sortase A-mediated ligation to generate DBCO-7D12. The NK92MI cells bearing azide groups are then equipped with DBCO-7D12 via bioorthogonal click chemistry. The resultant 7D12-NK92MI cells exhibit high specificity and affinity for EGFR-overexpressing tumor cells in vitro and in vivo by the 7D12-EGFR interaction, causing increased cytokine secretion to more effectively kill EGFR-positive tumor cells, but not EGFR-negative cancer cells. Importantly, the 7D12-NK92MI cells also show a wide anticancer spectrum and extensive tumor penetration. Furthermore, mouse experiments reveal that 7D12-NK92MI treatment achieves excellent therapeutic efficacy and outstanding safety. The authors' works provide a cell modification strategy using specific protein ligands without genetic manipulation and present a potential novel method for cancer-targeted immunotherapy by NK cells.

4.
Front Cell Dev Biol ; 9: 734818, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34692691

RESUMO

Pancreatic cancer is a common malignant tumor with high mortality, and novel therapeutic options have focused on ameliorating its poor prognosis. TEOA, a traditional Chinese herbal medicine, exhibits anti-inflammatory and anti-cancer activities. Our recent study has shown that TEOA inhibits proliferation and induces DNA damage in diffuse large B-cell lymphoma cells by activating the ROS-mediated p38 MAPK pathway. However, its effects on pancreatic cancer cells remain unknown. In the present study, we evaluated the effects of TEOA on the proliferation, migration of pancreatic cancer cells and explored the possible underlying mechanism of action. We found that TEOA significantly inhibited the proliferation and migration of pancreatic cancer cells in a time- and dose-dependent manner. Mechanistically, TEOA significantly induced mitochondrial dysfunction in PANC1 and SW1990 cells, as evidenced by the collapse of the mitochondrial membrane potential, exhausted ATP level, and excessive accumulation of intracellular ROS. Notably, our further experiments showed that TEOA induced autophagic cell death in pancreatic ductal adenocarcinoma cells by inactivating the ROS-dependent mTOR/p70S6k signaling pathway. More importantly, both pharmacological or genetic blocking of the autophagic flux signal could partly restore the cytotoxicity of TEOA, whereas activation of autophagy by rapamycin or EBSS induced starvation facilitated the cytotoxicity of TEOA. Concomitantly, N-acetylcysteine, a ROS scavenger, abolished the inhibition of the mTOR signaling pathway, thus preventing autophagy and restoring cell viability. Taken together, our results reveal that TEOA can lead to ROS-dependent autophagic cell death of pancreatic cancer cells by inducing mitochondrial dysfunction, which might be a promising therapeutic agent for pancreatic cancer.

5.
Clin Lab ; 67(10)2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34655195

RESUMO

BACKGROUND: Currently, there are few studies on the correlation between platelet counts (PLT), plateletcrit (PCT), and platelet-to-lymphocyte ratio (PLR) in small cell lung carcinoma (SCLC) with and without pleural effusion. This study is to investigate their likely correlation and to evaluate the potential diagnostic or prognostic applications of these platelet parameters. METHODS: A total of 218 each of patients with primary SCLC and healthy controls were included. Hematological indicators and other clinically relevant information were collected. Comparisons of the differences between groups were applied to the independent samples t-test or the chi-squared test. ROC curve analysis was used to access the diagnostic performance of PLT, PCT, and PLR. RESULTS: Compared with healthy controls, PLT, PCT, and PLR in SCLC were significantly higher. On the other hand, mean platelet volume, lymphocytes, and hemoglobin were significantly lower. The levels of PLT, PCT, and PLR were related to malignant pleural effusion, while not related to lymph node or distant metastasis. The incidence of pleural effusion in patients with SCLC was positively correlated with the levels of PLT, PCT, and PLR. ROC curve analysis showed that PLT, PCT, and PLR were valuable markers for SCLC, and the combination of the three has higher diagnostic efficacy. CONCLUSIONS: Platelet parameters were significantly different between SCLC and controls. PLT, PCT, and PLR could be used to assess the presence of pleural effusion.


Assuntos
Neoplasias Pulmonares , Derrame Pleural , Carcinoma de Pequenas Células do Pulmão , Plaquetas , Humanos , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/diagnóstico , Linfócitos , Volume Plaquetário Médio , Contagem de Plaquetas , Derrame Pleural/diagnóstico , Estudos Retrospectivos , Carcinoma de Pequenas Células do Pulmão/complicações , Carcinoma de Pequenas Células do Pulmão/diagnóstico
6.
Environ Res ; : 112266, 2021 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-34688642

RESUMO

An environmentally friendly wood adhesive developed from waterborne polyurethane (WPU) grafted gelatin (G) was investigated in this research. First, the G was extracted from chromium shavings waste, and then mixed with a prepolymer emulsion of WPU to synthesis the graft copolymer (WPUG) via a solvent-free emulsion copolymerization. The synthesized copolymer was characterized using the mechanical properties test, TGA, FT-IR, and other analysis technology. The results indicated that the WPUG had a good overall performance. Specifically, the contact angle reached 111.5°, the tensile strength reached 32.91 MPa, the temperature of the maximum weight loss was greater than 350 °C. The WPUG adhesive had excellent bonding power and mechanical properties; the dry bonding strength reached 4.21 MPa when the ratio between free amino groups of the G and isocyanate-groups of the WPU (the R value) was 1.5. This preparation of the graft copolymer not only satisfies the need of environment-friendly wood adhesives, but it also effectively improves the recyclability of chromium shavings waste.

7.
J Hazard Mater ; 416: 125942, 2021 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-34492869

RESUMO

A novel Ralstonia Bcul-1 strain was isolated from soil samples that was closest to Ralstonia pickettii. Broad-spectrum resistance was identified to a group of heavy metal ions and tolerance to concentrations of Cd2+ up to 400 mg L-1. Low concentrations of heavy metal ions did not have distinctive impact on heavy metal resistance genes and appeared to induce greater expression. Under exposure to Cd2+, cell wall components were significantly enhanced, and some proteins were also simultaneously expressed allowing the bacteria to adapt to the high Cd2+ living environment. The maximum removal rate of Cd2+ by the Ralstonia Bcul-1 strain was 78.97% in the culture medium supplemented with 100 mg L-1 Cd2+. Ralstonia Bcul-1 was able to survive and grow in a low nutrient and cadmium contaminated (0.42 mg kg-1) vegetable soil, and the cadmium removal rate was up to 65.76% in 9th growth. Ralstonia Bcul-1 mixed with biochar could maintain sustainable growth of this strain in the soil up to 75 d and the adsorption efficiency of cadmium increased by 16.23-40.80% as compared to biochar application alone. Results from this work suggests that Ralstonia Bcul-1 is an ideal candidate for bioremediation of nutrient deficient heavy metal contaminated soil.


Assuntos
Metais Pesados , Poluentes do Solo , Biodegradação Ambiental , Cádmio/toxicidade , Metais Pesados/toxicidade , Ralstonia , Solo , Poluentes do Solo/análise , Poluentes do Solo/toxicidade
8.
J Fungi (Basel) ; 7(9)2021 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-34575769

RESUMO

Leccinum is one of the most important groups of boletes. Most species in this genus are ectomycorrhizal symbionts of various plants, and some of them are well-known edible mushrooms, making it an exceptionally important group ecologically and economically. The scientific problems related to this genus include that the identification of species in this genus from China need to be verified, especially those referring to European or North American species, and knowledge of the phylogeny and diversity of the species from China is limited. In this study, we conducted multi-locus (nrLSU, tef1-α, rpb2) and single-locus (ITS) phylogenetic investigations and morphological observisions of Leccinum from China, Europe and North America. Nine Leccinum species from China, including three new species, namely L. album, L.parascabrum and L.pseudoborneense, were revealed and described. Leccinum album is morphologically characterized by the white basidioma, the white hymenophore staining indistinct greenish blue when injured, and the white context not changing color in pileus but staining distinct greenish blue in the base of the stipe when injured. Leccinumparascabrum is characterized by the initially reddish brown to chestnut-brown and then pale brownish to brown pileus, the white to pallid and then light brown hymenophore lacking color change when injured, and the white context lacking color change in pileus but staining greenish blue in the base of the stipe when injured. Leccinumpseudoborneense is characterized by the pale brown to dark brown pileus, the initially white and then brown hymenophore lacking color change when injured, and the white context in pileus and stipe lacking color change in pileus but staining blue in stipe when bruised. Color photos of fresh basidiomata, line drawings of microscopic features and detailed descriptions of the new species are presented.

9.
Cell Death Dis ; 12(9): 839, 2021 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-34497268

RESUMO

Ferroptosis, a new form of programmed cell death, not only promotes the pathological process of various human diseases, but also regulates cancer progression. Current perspectives on the underlying mechanisms remain largely unknown. Herein, we report a member of the NEET protein family, CISD3, exerts a regulatory role in cancer progression and ferroptosis both in vivo and in vitro. Pan-cancer analysis from TCGA reveals that expression of CISD3 is generally elevated in various human cancers which are consequently associated with a higher hazard ratio and poorer overall survival. Moreover, knockdown of CISD3 significantly accelerates lipid peroxidation and accentuates free iron accumulation triggered by Xc- inhibition or cystine-deprivation, thus causing ferroptotic cell death. Conversely, ectopic expression of the shRNA-resistant form of CISD3 (CISD3res) efficiently ameliorates the ferroptotic cell death. Mechanistically, CISD3 depletion presents a metabolic reprogramming toward glutaminolysis, which is required for the fuel of mitochondrial oxidative phosphorylation. Both the inhibitors of glutaminolysis and the ETC process were capable of blocking the lipid peroxidation and ferroptotic cell death in the shCISD3 cells. Besides, genetic and pharmacological activation of mitophagy can rescue the CISD3 knockdown-induced ferroptosis by eliminating the damaged mitochondria. Noteworthily, GPX4 acts downstream of CISD3 mediated ferroptosis, which fails to reverse the homeostasis of mitochondria. Collectively, the present work provides novel insights into the regulatory role of CISD3 in ferroptotic cell death and presents a potential target for advanced antitumor activity through ferroptosis.

10.
Redox Biol ; 46: 102122, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34482117

RESUMO

Hepatocellular carcinoma (HCC) is one of the paramount causes of cancer-related death worldwide. Despite recent advances have been made in clinical treatments of HCC, the general prognosis of patients remains poor. Therefore, it is imperative to develop a less toxic and more effective therapeutic strategy. Currently, series of cellular, molecular, and pharmacological experimental approaches were utilized to address the unrecognized characteristics of disulfiram (DSF), pursuing the goal of repurposing DSF for cancer therapy. We found that DSF/Cu selectively exerted an efficient cytotoxic effect on HCC cell lines, and potently inhibited migration, invasion, and angiogenesis of HCC cells. Importantly, we confirmed that DSF/Cu could intensively impair mitochondrial homeostasis, increase free iron pool, enhance lipid peroxidation, and eventually result in ferroptotic cell death. Of note, a compensatory elevation of NRF2 accompanies the process of ferroptosis, and contributes to the resistance to DSF/Cu. Mechanically, we found that DSF/Cu dramatically activated the phosphorylation of p62, which facilitates competitive binding of Keap1, thus prolonging the half-life of NRF2. Notably, inhibition of NRF2 expression via RNA interference or pharmacological inhibitors significantly facilitated the accumulation of lipid peroxidation, and rendered HCC cells more sensitive to DSF/Cu induced ferroptosis. Conversely, fostering NRF2 expression was capable of ameliorating the cell death activated by DSF/Cu. Additionally, DSF/Cu could strengthen the cytotoxicity of sorafenib, and arrest tumor growth both in vitro and in vivo, by simultaneously inhibiting the signal pathway of NRF2 and MAPK kinase. In summary, these results provide experimental evidence that inhibition of the compensatory NRF2 elevation strengthens HCC cells more vulnerable to DSF/Cu induced ferroptosis, which facilitates the synergistic cytotoxicity of DSF/Cu and sorafenib.


Assuntos
Carcinoma Hepatocelular , Ferroptose , Neoplasias Hepáticas , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Linhagem Celular Tumoral , Cobre , Dissulfiram/farmacologia , Humanos , Proteína 1 Associada a ECH Semelhante a Kelch/genética , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Fator 2 Relacionado a NF-E2/genética
11.
Front Endocrinol (Lausanne) ; 12: 665145, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34512542

RESUMO

The aquaporin 2 (AQP2) plays a critical role in water reabsorption to maintain water homeostasis. AQP2 mutation leads to nephrogenic diabetes insipidus (NDI), characterized by polyuria, polydipsia, and hypernatremia. We previously reported that a novel AQP2 mutation (G215S) caused NDI in a boy. In this study, we aimed to elucidate the cell biological consequences of this mutation on AQP2 function and clarify the molecular pathogenic mechanism for NDI in this patient. First, we analyzed AQP2 expression in Madin-Darby canine kidney (MDCK) cells by AQP2-G215S or AQP2-WT plasmid transfection and found significantly decreased AQP2-G215S expression in cytoplasmic membrane compared with AQP2-WT, independent of forskolin treatment. Further, we found co-localization of endoplasmic reticulum (ER) marker (Calnexin) with AQP2-G215S rather than AQP2-WT in MDCK cells by immunocytochemistry. The functional analysis showed that MDCK cells transfected with AQP2-G215S displayed reduced water permeability compared with AQP2-WT. Visualization of AQP2 structure implied that AQP2-G215S mutation might interrupt the folding of the sixth transmembrane α-helix and/or the packing of α-helices, resulting in the misfolding of monomer and further impaired formation of tetramer. Taken together, these findings suggested that AQP2-G215S was misfolded and retained in the ER and could not be translocated to the apical membrane to function as a water channel, which revealed the molecular pathogenic mechanism of AQP2-G215S mutation and explained for the phenotype of NDI in this patient.

12.
MycoKeys ; 81: 165-183, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34349607

RESUMO

Gyroporus species with cyanescent oxidation reactions were investigated, based on morphology and phylogenetic analysis of DNA sequences from the nuclear ribosomal large subunit (nrLSU), the nuclear ribosomal internal transcribed spacer (ITS) and the mitochondrial adenosine triphosphate ATP synthase subunit 6 (atp6). Three species, including two new species, namely G. alpinus and G. flavocyanescens and one previously-described species, namely G. brunneofloccosus, are revealed from China. Collections formerly reported from China as "G. cyanescens" are either G. alpinus or G. flavocyanescens. The new species are documented and illustrated in detail, while the concept of G. brunneofloccosus is refined with additional recently-collected materials. Additionally, the cyanescent species G. pseudomicrosporus, previously described from China, is shown to be a member of the genus Gyrodon, based on re-examination of the type specimen. A key to the cyanescent Gyroporus species from China is provided.

13.
Bioorg Chem ; 115: 105256, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34426153

RESUMO

Asperphenamate is a natural product that has attracted considerable interest from researchers worldwide. In the last decade, aiming to increase the biological activity and improve druggability, modifications of the A-ring moiety in asperphenamate have been performed. Our laboratory has also recently reported functional derivatizations of the A ring and studied its effect on the inhibition of cysteine cathepsin L. However, the functional significance of the B-ring fragment toward cathepsin L has not been evaluated thus far. In this paper, forty-four derivatives of the B-ring substituted with different N-phenylsulfonyl groups were designed and synthesized. Among them, the paratrifluromethyl analog B-2a and the 2, 4-difluoro-5-chloro derivative B-11b showed more potent inhibitory activity against cathepsin L than the control compound, ABR, which displayed the strongest inhibitory effect on cathepsin L and S among all reported asperphenamate derivatives. In particular, compound B-2a showed more pronounced selectivity against cathepsin L than the other derivatives. Molecular docking revealed that the N-phenylsulfonylamide moiety was vital for the interactions between B-2a and cathepsin L. Moreover, B-2a displayed no toxicity against normal cells. Therefore, compound B-2a was selected for further studies. Wound-healing assays, Transwell chamber assays and breast cancer lung metastasis mouse models demonstrated that B-2a exhibited antimetastatic ability in vitro and in vivo.

14.
Inorg Chem ; 60(15): 11140-11146, 2021 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-34242014

RESUMO

The nodal-line semimetals have recently gained attention as a promising material due to their exotic electronic structure and properties. Here, we investigated the structural evolution and physical properties of nodal-line semimetal ZrSiSe under pressure via experiments and theoretical calculations. An isostructural electronic transition is observed at ∼6 GPa. Upon further compression, the original tetragonal phase starts to transform into an orthorhombic phase at ∼13 GPa and the two phases coexist until the maximal experimental pressure. By analysis of the electronic band structure, we suggest that the significant changes in the Fermi surface contribute to the occurrence of the isostructural electronic transition. The results provide a new insight into the structure and properties of ZrSiSe.

15.
Anal Methods ; 13(27): 3012-3016, 2021 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-34212163

RESUMO

By combining a Hill-type pH probe and a pH-insensitive naphthalimide fluorophore, we synthesized a FRET-based ratiometric pH probe (PHHF), exhibiting a reduced pH transition width, representing a unique approach for development of sensitive probes for detection of biorelevant pH changes.


Assuntos
Corantes Fluorescentes , Naftalimidas , Células HeLa , Humanos , Concentração de Íons de Hidrogênio
16.
Cell Death Dis ; 12(7): 705, 2021 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-34262021

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) is an extremely lethal cancer with limited treatment options. Cisplatin (DDP) is used as a mainstay of chemotherapeutic agents in combination with other drugs or radiotherapy for PDAC therapy. However, DDP exhibits severe side-effects that can lead to discontinuation of therapy, and the acquired drug resistance of tumor cells presents serious clinical obstacles. Therefore, it is imperative to develop a more effective and less toxic therapeutic strategy. We and others have previously discovered that dihydroartemisinin (DHA) represents a safe and promising therapeutic agent to preferentially induce cancer cell ferroptosis. In the present study, we find that DHA could intensively strengthen the cytotoxicity of DDP and significantly reduce its effective concentrations both in vitro and in vivo. Combination of DHA and DDP synergistically inhibits the proliferation and induces DNA damage of PDAC cells. Mechanically, the combinative treatment impairs mitochondrial homeostasis, characterized by destroyed mitochondrial morphology, decreased respiratory capacity, reduced ATP production, and accumulated mitochondria-derived ROS. Further studies show that ferroptosis contributes to the cytotoxic effects in PDAC cells under the challenge of DHA and DDP, together with catastrophic accumulation of free iron and unrestricted lipid peroxidation. Moreover, pharmacologic depleting of the free iron reservoir or reconstituted expression of FTH contributes to the tolerance of DHA/DDP-induced ferroptosis, while iron addition accelerates the ferroptotic cell death. In summary, these results provide experimental evidence that DHA acts synergistically with DDP and renders PDAC cells vulnerable to ferroptosis, which may act as a promising therapeutic strategy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Artemisininas/farmacologia , Carcinoma Ductal Pancreático/tratamento farmacológico , Cisplatino/farmacologia , Ferroptose/efeitos dos fármacos , Ferro/metabolismo , Neoplasias Pancreáticas/tratamento farmacológico , Trifosfato de Adenosina/metabolismo , Animais , Carcinoma Ductal Pancreático/metabolismo , Carcinoma Ductal Pancreático/patologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Dano ao DNA , Resistencia a Medicamentos Antineoplásicos , Sinergismo Farmacológico , Humanos , Camundongos Endogâmicos BALB C , Camundongos Nus , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Invasividade Neoplásica , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia , Espécies Reativas de Oxigênio/metabolismo , Carga Tumoral/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
17.
Artigo em Inglês | MEDLINE | ID: mdl-34281138

RESUMO

Engaging in regular exercise results in a range of physiological adaptations offering benefits for exercise capacity and health, independent of age, gender or the presence of chronic diseases. Accumulating evidence shows that lack of time is a major impediment to exercise, causing physical inactivity worldwide. This issue has resulted in momentum for interval training models known to elicit higher enjoyment and induce adaptations similar to or greater than moderate-intensity continuous training, despite a lower total exercise volume. Although there is no universal definition, high-intensity interval exercise is characterized by repeated short bursts of intense activity, performed with a "near maximal" or "all-out" effort corresponding to ≥90% of maximal oxygen uptake or >75% of maximal power, with periods of rest or low-intensity exercise. Research has indicated that high-intensity interval training induces numerous physiological adaptations that improve exercise capacity (maximal oxygen uptake, aerobic endurance, anaerobic capacity etc.) and metabolic health in both clinical and healthy (athletes, active and inactive individuals without any apparent disease or disorder) populations. In this paper, a brief history of high-intensity interval training is presented, based on the novel findings of some selected studies on exercise capacity and health, starting from the early 1920s to date. Further, an overview of the mechanisms underlying the physiological adaptations in response to high-intensity interval training is provided.


Assuntos
Treinamento Intervalado de Alta Intensidade , Adaptação Fisiológica , Atletas , Exercício Físico , Tolerância ao Exercício , Humanos , Consumo de Oxigênio , Resistência Física
18.
J Clin Lab Anal ; 35(9): e23903, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34273195

RESUMO

BACKGROUND: This study aimed to explore the association of mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) with acute ischemic stroke (AIS) risk and also to explore its association with T helper type 1 (Th1) cells, Th17 cells, disease severity, and prognosis in AIS patients. METHODS: One hundred twenty first-episode AIS patients and 120 non-AIS patients with high-stroke-risk factors (as controls) were recruited. Besides, in the cluster of differentiation 4-positive (CD4+ ) T cells, the MALT1 gene expression was detected by reverse transcription quantitative polymerase chain reaction; meanwhile, Th1 and Th17 were detected by flow cytometry. Moreover, serum interferon (IFN)-γ and interleukin (IL)-17 were determined by enzyme-linked immunosorbent assay. RESULTS: MALT1 expression was increased in AIS patients compared with controls and also it could differentiate AIS patients from controls, with an area under curve of 0.905 (95% confidence interval: 0.869-0.941). In AIS patients, MALT1 positively correlated with Th1 cells, Th17 cells, IFN-γ, and IL-17. Besides, MALT1 positively correlated with the National Institutes of Health Stroke Scale score. Furthermore, the Kaplan-Meier curve and univariate Cox's regression analyses showed no correlation of MALT1 high expression with recurrence-free survival (RFS) in AIS patients, although after adjustment using multivariant Cox's regression, high MALT1 expression independently correlated with worse RFS in AIS patients. CONCLUSION: MALT1 expression is increased and positively correlates with disease severity, Th1 cells, and Th17 cells, whose high expression severs as an independent risk factor for worse RFS in AIS patients.

19.
J Int Med Res ; 49(6): 3000605211021733, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34167353

RESUMO

BACKGROUND: Mycoplasma pneumoniae (MP) pneumonia in children can be challenging to treat, and the impact of MP blood infection is unclear. The present study aims to determine the prevalence and clinical characteristics of MP septicemia among pediatric patients. METHODS: Children hospitalized at our center for MP pneumonia between October 2017 and June 2018 were included. Healthy controls visiting our outpatient clinic for regular physical examinations were also enrolled. MP was detected by real-time polymerase chain reaction (qPCR) analysis of plasma and peripheral blood mononuclear cell (PBMC) samples. RESULTS: Sixty-one children with MP pneumonia and 30 healthy children were included. Among children with MP infection, 31 (50.8%) were positive for MP by qPCR (19 in plasma samples, 8 in PBMC samples, and 4 in both). All healthy controls were negative for MP by qPCR. CONCLUSIONS: The prevalence of MP septicemia in children with MP pneumonia is moderate. However, detection of MP in blood samples may have limited clinical value for guiding treatment.


Assuntos
Pneumonia por Mycoplasma , Sepse , Criança , Humanos , Leucócitos Mononucleares , Mycoplasma pneumoniae/genética , Pneumonia por Mycoplasma/complicações , Pneumonia por Mycoplasma/diagnóstico , Pneumonia por Mycoplasma/epidemiologia , Prevalência , Sepse/diagnóstico , Sepse/epidemiologia
20.
Front Pediatr ; 9: 674310, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34095034

RESUMO

Backgroud: Postinfectious bronchiolitis obliterans (PIBO) is a rare respiratory disease. In recent years, the disease has been recognized and diagnosed increasingly in children. Pulmonary function is important for diagnosis, identifying the severity of the PIBO and monitoring progression. But there have been only a few studies that followed the evolution of PIBO on the basis of pulmonary function tests (PFTs). Objective: The study targeted the evolution of pulmonary function and bronchodilator response in a case series of Chinese children with PIBO. Methods: Twelve children between the ages of 6-99 months with PIBO were studied retrospectively from 2009 to 2019. Forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), the FEV1/FVC ratio, and maximal midexpiratory flow velocity 25-75% (MMEF25-75%) were collected at each PFT, and bronchodilator responses were evaluated. Spirometric parameters were monitored over time, and generalized linear mixed models were used to analyze longitudinal panel data. Results: The median baseline PFT values for FVC, FEV1, the FEV1/FVC ratio, and MMEF25-75% were 41.6, 39.75, 90.7, and 22.2%, respectively. At the initial PFTs, 10 (83.3%) patients demonstrated a significant bronchodilator response. FVC and FEV1 increased by 8.212%/year and 5.007%/year, respectively, and the FEV1/FVC ratio decreased by an average of 3.537%/year. MMEF25-75% showed improvement at an average rate of 1.583% every year. Overall, FEV1 and MMEF25-75% showed different degrees of improvement after the use of inhaled bronchodilators at each PFT session for 10 patients, and FEV1 measures demonstrated significant (>12%) ß2-bronchodilation in 56% of PFT sessions. Conclusions: Pediatric patients with PIBO showed an obstructive defect in pulmonary function. The FVC, FEV1, and MMEF25-75% improved as they grew older, while the FEV1/FVC ratio decreased. This may be due to the development of lung parenchyma more than airway growth. Airway obstruction in some patients improved with the use of ß2 agonists.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...