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1.
Nature ; 626(8001): 1042-1048, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38418917

RESUMO

The loss of the tail is among the most notable anatomical changes to have occurred along the evolutionary lineage leading to humans and to the 'anthropomorphous apes'1-3, with a proposed role in contributing to human bipedalism4-6. Yet, the genetic mechanism that facilitated tail-loss evolution in hominoids remains unknown. Here we present evidence that an individual insertion of an Alu element in the genome of the hominoid ancestor may have contributed to tail-loss evolution. We demonstrate that this Alu element-inserted into an intron of the TBXT gene7-9-pairs with a neighbouring ancestral Alu element encoded in the reverse genomic orientation and leads to a hominoid-specific alternative splicing event. To study the effect of this splicing event, we generated multiple mouse models that express both full-length and exon-skipped isoforms of Tbxt, mimicking the expression pattern of its hominoid orthologue TBXT. Mice expressing both Tbxt isoforms exhibit a complete absence of the tail or a shortened tail depending on the relative abundance of Tbxt isoforms expressed at the embryonic tail bud. These results support the notion that the exon-skipped transcript is sufficient to induce a tail-loss phenotype. Moreover, mice expressing the exon-skipped Tbxt isoform develop neural tube defects, a condition that affects approximately 1 in 1,000 neonates in humans10. Thus, tail-loss evolution may have been associated with an adaptive cost of the potential for neural tube defects, which continue to affect human health today.


Assuntos
Processamento Alternativo , Evolução Molecular , Hominidae , Proteínas com Domínio T , Cauda , Animais , Humanos , Camundongos , Processamento Alternativo/genética , Elementos Alu/genética , Modelos Animais de Doenças , Genoma/genética , Hominidae/anatomia & histologia , Hominidae/genética , Íntrons/genética , Defeitos do Tubo Neural/genética , Defeitos do Tubo Neural/metabolismo , Fenótipo , Isoformas de Proteínas/deficiência , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Proteínas com Domínio T/deficiência , Proteínas com Domínio T/genética , Proteínas com Domínio T/metabolismo , Cauda/anatomia & histologia , Cauda/embriologia , Éxons/genética
2.
Biochem Biophys Res Commun ; 707: 149782, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38493745

RESUMO

Polycystic ovary syndrome (PCOS) is a common reproductive endocrine disorder in women of reproductive age, which often leads to female infertility. Chronic inflammation is a significant factor in the development of PCOS. Our study aimed to explore the impact of mesencephalic astrocyte-derived neurotrophic factor (MANF), a scientifically validated anti-inflammatory factor, on 99 diagnosed PCOS patients. We also investigated its effects on PCOS mice induced with dehydroepiandrosterone (DHEA) and KGN cells induced with dihydrotestosterone (DHT). Our findings revealed a decrease in serum MANF levels in PCOS patients, which were negatively associated with serum tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) levels. The administration of recombinant human MANF (rhMANF) in PCOS mice demonstrated a decrease in pro-inflammatory cytokines and monocytes/macrophages in both peripheral blood and ovarian tissues. Furthermore, the inclusion of rhMANF notably ameliorated DHEA-induced ovarian dysfunction and fibrosis by negatively regulating the toll-like receptor 4 (TLR4)-nuclear factor kappa B (NF-κB)-NLR family, pyrin domain containing protein 3 (NLRP3) pathway. Additionally, in vitro experiments showed that the up-regulation of MANF offset DHT-induced inhibition of viability and apoptosis in KGN cells. Collectively, this study highlights the anti-inflammatory properties of MANF in PCOS and suggests its potential as a therapeutic approach for the management of PCOS.


Assuntos
Síndrome do Ovário Policístico , Feminino , Humanos , Camundongos , Animais , Síndrome do Ovário Policístico/tratamento farmacológico , Síndrome do Ovário Policístico/complicações , NF-kappa B/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Receptor 4 Toll-Like , Astrócitos/metabolismo , Anti-Inflamatórios/uso terapêutico , Fatores de Crescimento Neural , Desidroepiandrosterona/farmacologia , Desidroepiandrosterona/uso terapêutico
3.
Cell Commun Signal ; 22(1): 335, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38890746

RESUMO

OBJECTIVE: Kappa opioid receptor (KOR) signaling is involved in joint development and inflammation in Osteoarthritis (OA), while the biochemical mechanism remains unclarified. This study aims to investigate downstream molecular events of KOR activation, to provide novel perspectives in OA pathology. METHODS: U50,488H, a selective KOR agonist, was intra-articularly injected in mice upon destabilization of the medial meniscus (DMM) as OA models, with PBS injection as control. The behavioral and histological evaluation was assessed by hot plate test and red solid green staining, respectively. Alterations in mRNA and protein expression were assessed by RNA-seq, RT-qPCR, immunohistochemistry and western blotting (WB) in chondrocytes treated with TNF-α or TNF-α + U50,488H. Proteins interacted with KOR were explored using proximity labeling followed by mass spectrometry and then testified by co-immunoprecipitation (Co-IP) assay and immunofluorescence (IF). RESULTS: OA-induced pain was reduced and cartilage degeneration was alleviated upon KOR activation in DMM mice. In chondrocytes, activation of KOR reversed the upregulation of MMPs, IL-6, IL-1ß and phosphorylated(p-) STAT3, stimulated by TNF-α, while the expression of NF-κB, MAPKs and AKT signaling weren't reversed. RNA-seq and IF results presented that KOR activation evidently reduced STAT3 nuclear translocation in chondrocytes upon TNF-α stimuli. The reduction may be resulted from the binding of KOR and STAT3 in the plasma membrane, revealed by proximity labeling and Co-IP results. CONCLUSIONS: KOR activation protects cartilage from OA, and this protective effect is mainly exerted via sequestering STAT3 on the plasma membrane, resulting in inactivation of STAT3-dependent immune responses which otherwise contributes to OA.


Assuntos
Membrana Celular , Condrócitos , Osteoartrite , Receptores Opioides kappa , Fator de Transcrição STAT3 , Animais , Masculino , Camundongos , (trans)-Isômero de 3,4-dicloro-N-metil-N-(2-(1-pirrolidinil)-ciclo-hexil)-benzenoacetamida/farmacologia , Membrana Celular/metabolismo , Membrana Celular/efeitos dos fármacos , Condrócitos/metabolismo , Condrócitos/patologia , Condrócitos/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Osteoartrite/patologia , Osteoartrite/metabolismo , Receptores Opioides kappa/metabolismo , Receptores Opioides kappa/genética , Transdução de Sinais/efeitos dos fármacos , Fator de Transcrição STAT3/metabolismo
4.
Mol Biol Rep ; 51(1): 518, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38622261

RESUMO

BACKGROUND: Cold atmospheric plasma (CAP) has been widely used in biomedical research, especially in vitro cancer therapy. Cutaneous squamous cell carcinoma (CSCC) is a malignant tumor originating from epidermal keratinocytes. However, the mechanism of CAP therapy on CSCC remains unclear. METHODS AND RESULTS: The animal models of CSCC induced by 7,12-dimethylbenz(a) anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA) were constructed. For the CAP treatment group, after each TPA application, CAP was administered for 3 min twice weekly after drying. HE staining were used to detect the pathological status of tumor tissue in each group. The levels of PCNA, Bcl-2, Bax, MMP2 and MMP9 were evaluated by western blot and qPCR. TUNEL staining were used to detect apoptosis in tumor tissues. In vivo, serum samples were used for ELISA of total ROS. MTT assay was used to detect the viability of A431 cells. Western blot and qPCR were used to detect the levels of PCNA, Bcl-2, Bax, MMP2 and MMP9 in A431 cells. A431 cell proliferation was examined by colony formation assay. The proportions of apoptosis of A431 cells were detected by flow cytometry. Transwell assessed the ability of A431 cells migration and proliferation. We found that CAP could induce skin cancer cells apoptosis and inhibit the progress of skin cancer. Through experiments in vitro, reactive oxygen species (ROS) generated by N-acetylcysteine (NAC) and CAP inhibited the proliferation and migration of A431 skin cancer cells while promoting apoptosis. CONCLUSIONS: These evidences suggest the protective effect of CAP in CSCC, and CAP has the potential clinical application of CSCC.


Assuntos
Carcinoma de Células Escamosas , Gases em Plasma , Neoplasias Cutâneas , Animais , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/patologia , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/patologia , Espécies Reativas de Oxigênio/farmacologia , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 9 da Matriz/genética , Gases em Plasma/farmacologia , Antígeno Nuclear de Célula em Proliferação/genética , Proteína X Associada a bcl-2 , Apoptose , Linhagem Celular Tumoral , Proliferação de Células
5.
Mol Biol Rep ; 51(1): 654, 2024 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-38735002

RESUMO

BACKGROUND: Cervical cancer is a common gynecologic malignant tumor, but the critical factors affecting cervical cancer progression are still not well demonstrated. Mesencephalic astrocyte-derived neurotrophic factor (MANF) has been widely recognized as an anti-inflammatory factor to regulate macrophage polarization. In this study, the effect and mechanism of MANF on cervical cancer were preliminarily explored. METHODS AND RESULTS: Kaplan-Meier curve was used to show the overall survival time of the involved cervical cancer patients with high and low MANF expression in cervical cancer tissues. MANF was highly expressed in peritumoral tissues of cervical carcinoma by using immunohistochemistry and western blot. MANF mRNA level was detected by using qRT-PCR. Dual-labeled immunofluorescence showed MANF was mainly expressed in macrophages of cervical peritumoral tissues. Moreover, MANF-silenced macrophages promoted HeLa and SiHa cells survival, migration, invasion and EMT via NF-κB signaling activation. The results of tumor formation in nude mice indicated MANF-silenced macrophages promoted cervical tumor formation in vivo. CONCLUSION: Our study reveals an inhibitory role of MANF in cervical cancer progression, indicating MANF as a new and valuable therapeutic target for cervical cancer treatment.


Assuntos
Progressão da Doença , Macrófagos , Camundongos Nus , Fatores de Crescimento Neural , Neoplasias do Colo do Útero , Humanos , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/metabolismo , Feminino , Fatores de Crescimento Neural/metabolismo , Fatores de Crescimento Neural/genética , Animais , Macrófagos/metabolismo , Camundongos , Movimento Celular/genética , NF-kappa B/metabolismo , Linhagem Celular Tumoral , Transdução de Sinais , Fenótipo , Células HeLa , Regulação Neoplásica da Expressão Gênica , Transição Epitelial-Mesenquimal/genética , Proliferação de Células , Pessoa de Meia-Idade
6.
Cell Mol Biol (Noisy-le-grand) ; 70(4): 100-106, 2024 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-38678620

RESUMO

Nervonic acid (NA) is a primary long-chain fatty acid and has been confirmed to have neuroprotective effects in neurologic diseases. Oxidative stress and neuronal damage are the main causes of Parkinson's disease (PD). This study mainly explored whether NA is involved in regulating oxidative stress and apoptosis in MPTP-induced mouse model and MPP-induced cell model. Through behavior tests, we proved that MPTP-induced motor dysfunction in mice was recovered by NA treatment. NA can reduce MPTP-induced neuronal damage, manifested by elevated levels of TH and dopamine, as well as decreased levels of α-syn. In the in vitro model, we observed from CCK8 assay and flow cytometry that the induction of MPP markedly suppressed cell activity and enhanced cell apoptosis, but these functions were all reversed by NA. Furthermore, NA administration reversed the increase in ROS production and MDA levels induced by MPTP or MPP, as well as the decrease in SOD levels, suggesting the antioxidant properties of NA in PD. Meanwhile, we confirmed that NA can regulate oxidative stress and neuronal damage by activating the MEK/ERK pathway. Overall, we concluded that NA could alleviate MPTP-induced PD via MEK/ERK pathway.


Assuntos
Sistema de Sinalização das MAP Quinases , Camundongos Endogâmicos C57BL , Estresse Oxidativo , Animais , Masculino , Camundongos , 1-Metil-4-Fenil-1,2,3,6-Tetra-Hidropiridina , Apoptose/efeitos dos fármacos , Modelos Animais de Doenças , Dopamina/metabolismo , Neurônios Dopaminérgicos/efeitos dos fármacos , Neurônios Dopaminérgicos/metabolismo , Neurônios Dopaminérgicos/patologia , Ácidos Graxos Monoinsaturados/farmacologia , Ácidos Graxos Monoinsaturados/uso terapêutico , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/patologia , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Estresse Oxidativo/efeitos dos fármacos , Doença de Parkinson/metabolismo , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson Secundária/induzido quimicamente , Doença de Parkinson Secundária/tratamento farmacológico , Espécies Reativas de Oxigênio/metabolismo
7.
Mar Drugs ; 22(5)2024 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-38786621

RESUMO

Alginate oligosaccharides (AOS), products of alginate degradation by endotype alginate lyases, possess favorable biological activities and have broad applications. Although many have been reported, alginate lyases with homogeneous AOS products and secretory production by an engineered host are scarce. Herein, the alginate lyase AlyC7 from Vibrio sp. C42 was characterized as a trisaccharide-producing lyase exhibiting high activity and broad substrate specificity. With PelB as the signal peptide and 500 mM glycine as the additive, the extracellular production of AlyC7 in Escherichia coli reached 1122.8 U/mL after 27 h cultivation in Luria-Bertani medium. The yield of trisaccharides from sodium alginate degradation by the produced AlyC7 reached 758.6 mg/g, with a purity of 85.1%. The prepared AOS at 20 µg/mL increased the root length of lettuce, tomato, wheat, and maize by 27.5%, 25.7%, 9.7%, and 11.1%, respectively. This study establishes a robust foundation for the industrial and agricultural applications of AlyC7.


Assuntos
Escherichia coli , Polissacarídeo-Liases , Trissacarídeos , Vibrio , Polissacarídeo-Liases/metabolismo , Trissacarídeos/biossíntese , Vibrio/enzimologia , Especificidade por Substrato , Alginatos , Zea mays , Oligossacarídeos
8.
Entropy (Basel) ; 26(2)2024 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-38392414

RESUMO

Public transportation infrastructure is a typical, complex, coupled network that is usually composed of connected bus lines and subway networks. This study proposes an entropy-based node importance identification method for this type of coupled network that is helpful for the integrated planning of urban public transport and traffic flows, as well as enhancing network information dissemination and maintaining network resilience. The proposed method develops a systematic entropy-based metric based on five centrality metrics, namely the degree centrality (DC), betweenness centrality (BC), closeness centrality (CC), eigenvector centrality (EC), and clustering coefficient (CCO). It then identifies the most important nodes in the coupled networks by considering the information entropy of the nodes and their neighboring ones. To evaluate the performance of the proposed method, a bus-subway coupled network in Chengdu, containing 10,652 nodes and 15,476 edges, is employed as a case study. Four network resilience assessment metrics, namely the maximum connectivity coefficient (MCC), network efficiency (NE), susceptibility (S), and natural connectivity (NC), were used to conduct group experiments. The experimental results demonstrate the following: (1) the multi-functional fitting analysis improves the analytical accuracy by 30% as compared to fitting with power law functions only; (2) for both CC and CCO, the improved metric's performance in important node identification is greatly improved, and it demonstrates good network resilience.

9.
Angew Chem Int Ed Engl ; : e202407975, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38818660

RESUMO

The bonding effects between 3d transition-metal single sites and supports originate from crystal field stabilization energy (CFSE). The 3d transition-metal atoms of the spontaneous geometrical distortions, that is the Jahn-Teller effect, can alter CFSE, thereby leading to the Irving-Williams series. However, engineering single-atom sites (SASs) using the Irving-Williams series as an ideal guideline has not been reported to date. Herein, alkynyl-linked covalent phenanthroline frameworks (CPFs) with phenanthroline units are developed to anchor the desired 3d single metal ions from d5 to d10 (Mn2+, Fe3+, Co2+, Ni2+, Cu2+, and Zn2+). The Irving-Williams series was employed to accurately predict the bonding effects between 3d transition-metal atoms and phenanthroline units. To verify this, theoretical calculations and experimental results reveal that Cu-SASs/CPFs exhibits higher stability and faster charge-transfer efficiency, far surpassing other metal-SASs/CPFs. As expected, Cu-SASs/CPFs demonstrates a high photoreduction of CO2-to-CO activity (~30.3 µmol·g-1·h-1) and an exceptional photooxidation of CH3CHO-to-CH3COOH activity (~24.7 µmol·g-1·h-1). Interestingly, the generated *O2- is derived from the process of CO2 reduction, thereby triggering a CH3CHO oxidation reaction. This work provides a novel design concept for designing SASs by the Irving-Williams to regulate the catalytic performances.

10.
Neuroimage ; 271: 120041, 2023 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-36933626

RESUMO

Brain lesion segmentation provides a valuable tool for clinical diagnosis and research, and convolutional neural networks (CNNs) have achieved unprecedented success in the segmentation task. Data augmentation is a widely used strategy to improve the training of CNNs. In particular, data augmentation approaches that mix pairs of annotated training images have been developed. These methods are easy to implement and have achieved promising results in various image processing tasks. However, existing data augmentation approaches based on image mixing are not designed for brain lesions and may not perform well for brain lesion segmentation. Thus, the design of this type of simple data augmentation method for brain lesion segmentation is still an open problem. In this work, we propose a simple yet effective data augmentation approach, dubbed as CarveMix, for CNN-based brain lesion segmentation. Like other mixing-based methods, CarveMix stochastically combines two existing annotated images (annotated for brain lesions only) to obtain new labeled samples. To make our method more suitable for brain lesion segmentation, CarveMix is lesion-aware, where the image combination is performed with a focus on the lesions and preserves the lesion information. Specifically, from one annotated image we carve a region of interest (ROI) according to the lesion location and geometry with a variable ROI size. The carved ROI then replaces the corresponding voxels in a second annotated image to synthesize new labeled images for network training, and additional harmonization steps are applied for heterogeneous data where the two annotated images can originate from different sources. Besides, we further propose to model the mass effect that is unique to whole brain tumor segmentation during image mixing. To evaluate the proposed method, experiments were performed on multiple publicly available or private datasets, and the results show that our method improves the accuracy of brain lesion segmentation. The code of the proposed method is available at https://github.com/ZhangxinruBIT/CarveMix.git.


Assuntos
Neoplasias Encefálicas , Imageamento por Ressonância Magnética , Humanos , Imageamento por Ressonância Magnética/métodos , Processamento de Imagem Assistida por Computador/métodos , Redes Neurais de Computação , Encéfalo
11.
Microb Cell Fact ; 22(1): 179, 2023 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-37689719

RESUMO

BACKGROUND: Alginate oligosaccharides (AOs) are the degradation products of alginate, a natural polysaccharide abundant in brown algae. AOs generated by enzymatic hydrolysis have diverse bioactivities and show broad application potentials. AOs production via enzymolysis is now generally with sodium alginate as the raw material, which is chemically extracted from brown algae. In contrast, AOs production by direct degradation of brown algae is more advantageous on account of its cost reduction and is more eco-friendly. However, there have been only a few attempts reported in AOs production from direct degradation of brown algae. RESULTS: In this study, an efficient Laminaria japonica-decomposing strain Pseudoalteromonas agarivorans A3 was screened. Based on the secretome and mass spectrum analyses, strain A3 showed the potential as a cell factory for AOs production by secreting alginate lyases to directly degrade L. japonica. By using the L. japonica roots, which are normally discarded in the food industry, as the raw material for both fermentation and enzymatic hydrolysis, AOs were produced by the fermentation broth supernatant of strain A3 after optimization of the alginate lyase production and hydrolysis parameters. The generated AOs mainly ranged from dimers to tetramers, among which trimers and tetramers were predominant. The degradation efficiency of the roots reached 54.58%, the AOs production was 33.11%, and the AOs purity was 85.03%. CONCLUSION: An efficient, cost-effective and green process for AOs production directly from the underutilized L. japonica roots by using strain A3 was set up, which differed from the reported processes in terms of the substrate and strain used for fermentation and the AOs composition. This study provides a promising platform for scalable production of AOs, which may have application potentials in industry and agriculture.


Assuntos
Alginatos , Laminaria , Análise Custo-Benefício , Oligossacarídeos
12.
Mol Biol Rep ; 50(4): 3085-3097, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36689049

RESUMO

BACKGROUND: Low temperature plasma (LTP) exerts a protective effect in inflammation via enhancing MANF expression. Hyperactivation and dysfunction of theca cells induced by inflammatory agents is accompanied by polycystic ovary syndrome (PCOS), which is a common reproductive and endocrine disorder. However, the effect of LTP on theca cells is still unknown. METHODS AND RESULTS: Theca cells were stimulated with IL-1ß or TNF-α for 12 h, then treated with LTP for 100 s. After 8 h, medium supernatant and theca cells were collected. Production of androgen from theca cells were detected by ELISA. The PCNA and Annexin V levels in theca cells were detected by using immunofluorescent staining. The levels of PCNA, BCL-2 and BAX were evaluated by western blot and qPCR. MTT assay was used to detect the viability of theca cells. The proportions of apoptosis of theca cells were detected by Flow cytometry. The mRNA levels of androgenic genes were detected by qPCR. The MANF levels in medium supernatant and cell lysate were detected by using ELISA, western and qPCR. BIP and CHOP expressions were detected by using western blot and qPCR. We found that LTP irradiation decreased inflammatory agents-induced upregulation of androgen and androgenic genes in theca cells. And LTP irradiation relieves IL-1ß or TNF-α-induced pathological proliferation and apoptosis in theca cells. In terms of mechanism, LTP irradiation increased MANF level in theca cells to inhibit BIP and CHOP expression. CONCLUSION: These evidences suggest the protective effect of LTP on theca cells in inflammatory microenvironment, and LTP has the potential clinical application of PCOS.


Assuntos
Androgênios , Síndrome do Ovário Policístico , Feminino , Humanos , Androgênios/metabolismo , Células Tecais/metabolismo , Antígeno Nuclear de Célula em Proliferação/metabolismo , Temperatura , Fator de Necrose Tumoral alfa/metabolismo , Síndrome do Ovário Policístico/metabolismo , Microambiente Tumoral , Fatores de Crescimento Neural/metabolismo
13.
Mol Biol Rep ; 50(3): 2025-2031, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36538172

RESUMO

BACKGROUND: Low temperature plasma (LTP) is a developing field in recent years to play important roles of sterilization, material modification and wound healing. Breast cancer is a common gynecological malignant tumor. Recent studies have shown that LTP is a promising selective anti-cancer treatment. The effect of LTP on breast cancer is still unclear. In this study, We treated breast cancer cell lines with low temperature plasma for different periods of time and analyzed the relevant differences. METHODS AND RESULTS: SK-BR-3 cell nutrient solution was firstly treated by ACP for 0, 10, 20, 40, 80 and 120 s, which was next used to cultivateSK-BR-3cells for overnight.we found that LTP was able to suppress cell vitality, proliferation, invasion and migration of SK-BR-3 cells. Also, SK-BR-3 apoptosis was induced by LTP in a time-dependent manner. CONCLUSION: These evidences suggest the negative effect of LTP on malignant development of SK-BR-3 cells, and LTP has the potential clinical application for breast cancer treatment.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/metabolismo , Proliferação de Células , Temperatura , Linhagem Celular Tumoral , Células MCF-7 , Apoptose
14.
Dig Dis Sci ; 68(11): 4196-4211, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37707747

RESUMO

BACKGROUND: Ischemia-reperfusion injury (IRI) is an important cause of graft dysfunction post-liver transplantation, where donor liver with severe steatosis is more sensitive to IRI. Liver IRI involves ferroptosis and can be alleviated by heme oxygenase-1-modified bone marrow mesenchymal stem cells (HO-1/BMMSCs). AIMS: To explore the role and mechanism of HO-1/BMMSCs in severe steatotic liver IRI. METHODS: A severe steatotic liver IRI rat model and a hypoxia/reoxygenation (H/R) of severe steatosis hepatocyte model were established. Liver and hepatocyte damage was evaluated via liver histopathology and cell activity. Ferroptosis was evaluated through ferroptosis indexes. Nuclear factor erythroid 2-related factor 2 (Nrf2) was knocked down in severe steatotic hepatocytes. The role of Nrf2 and AMPK in HO-1/BMMSC inhibition of ferroptosis was examined using the AMP-activated protein kinase (AMPK) pathway inhibitor Compound C. RESULTS: The HO-1/BMMSCs alleviated severe steatotic liver IRI and ferroptosis. HO-1/BMMSCs promoted ferritin heavy chain 1(FTH1), Nrf2, and phosphorylated (p)-AMPK expression in the H/R severe steatotic hepatocytes. Nrf2 knockdown decreased FTH1 expression levels but did not significantly affect p-AMPK expression levels. The protective effect of HO-1/BMMSCs against H/R injury in severe steatotic hepatocytes and the inhibitory effect on ferroptosis were reduced. Compound C decreased p-AMPK, Nrf2, and FTH1 expression levels, weakened the HO-1/BMMSC protective effect against severe steatotic liver IRI and H/R-injured severe steatotic hepatocytes, and reduced the inhibition of ferroptosis. CONCLUSIONS: Ferroptosis was involved in HO-1/BMMSC reduction of severe steatotic liver IRI. HO-1/BMMSCs protected against severe steatotic liver IRI by inhibiting ferroptosis through the AMPK-Nrf2-FTH1 pathway. HO-1/BMMSCs activate AMPK, which activates Nrf2, promotes its nuclear transcription, then promotes the expression of its downstream protein FTH1, thereby inhibiting ferroptosis and attenuating severe steatotic liver IRI in rats. Glu: glutamic acid; Cys: cystine; GSH: glutathione; GPX4: glutathione peroxidase 4; HO-1/BMMSCs: HO-1-modified BMMSCs; Fer-1: ferrostatin-1; DFO: deferoxamine; FTH1: ferritin heavy chain1; p-AMPK: phosphorylated AMP-activated protein kinase; Nrf2: nuclear factor erythroid 2-related factor 2; IRI: ischemia-reperfusion injury; MCD: methionine-choline deficiency.

15.
BMC Vet Res ; 19(1): 129, 2023 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-37608311

RESUMO

BACKGROUND: Porcine circovirus 4 (PCV4), a newly emerging virus that was first discovered in 2019, may pose a potential threat to the pig industry. Droplet digital PCR (ddPCR) is an absolute quantitative method that has high sensitivity and accuracy. In this study, we developed a novel ddPCR assay to detect PCV4. Furthermore, we evaluated the detection limit, sensitivity, specificity and reproducibility of the ddPCR and TaqMan real-time quantitative PCR (qPCR) and tested 160 clinical samples to compare the detection rate of the two methods. RESULTS: The detection limit for ddPCR was 0.54 copies/µL, 10.6 times greater sensitivity than qPCR. Both ddPCR and qPCR assays exhibited good linearity and repeatability, and the established ddPCR method was highly specific for PCV4. The results of clinical sample testing showed that the positivity rate of ddPCR (5.6%) was higher than that of qPCR (4.4%). CONCLUSIONS: This study successfully developed a sensitive, specific and repeatable ddPCR assay for PCV4 detection, which can be widely used in clinical diagnosis of PCV4 infections.


Assuntos
Circovirus , Animais , Suínos , Circovirus/genética , Reprodutibilidade dos Testes , Reação em Cadeia da Polimerase em Tempo Real/veterinária , Bioensaio/veterinária
16.
Bull Environ Contam Toxicol ; 111(3): 43, 2023 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-37715810

RESUMO

Three modified biochar (Cunninghamia lanceolata) with iron and manganese elementals (FMBCs) were successfully prepared and used to remove hexavalent chromium (Cr(VI)) from aqueous solutions. The biochar before and after decoration were characterized by advanced instruments. The adsorption capacities of modified biochar in different Cr(VI) (20 mg·L- 1, 1 mg·L- 1) solutions were 4868.28 mg·kg- 1 and 300 mg·kg- 1. The Cr(VI) removal was highest at pH 2. The possible adsorption was considered to be ion exchange adsorption, chemisorption, and electrostatic attraction. Meanwhile, interfering ions are conducive to increasing the adsorption content. FMBCs prepared at different temperatures showed different characteristics, single-use and cycle-use performance, and high and low concentration removal superiority. The result indicated that FMBCs had a promising potential as an adsorbent to remove toxic and harmful Cr(VI) from aqueous solutions.


Assuntos
Ferro , Manganês , Adsorção
17.
Org Biomol Chem ; 20(46): 9127-9131, 2022 11 30.
Artigo em Inglês | MEDLINE | ID: mdl-36377719

RESUMO

An Fe-catalyzed unprotected hydroxylamine mediated Heck-type coupling between sulfinic acids and alkenes for the regioselective synthesis of (E)-vinyl sulfones has been developed. Mechanism studies indicated for the first time that a radical process may be involved and that hydroxylamines play multiple roles, including those of a mild oxidant and an in situ base. It was found for the first time that this transformation not only realizes C-S bond construction promoted by unprotected hydroxylamines, but also provides a practical and complementary method for the preparation of structurally important (E)-vinyl sulfones.


Assuntos
Hidroxilaminas , Ferro , Hidroxilaminas/química , Ferro/química , Catálise , Sulfonas/química
18.
Environ Sci Technol ; 56(7): 4162-4172, 2022 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-35324172

RESUMO

Photosynthetic carbon fixation is fundamental for plant growth and is a key process driving the global carbon cycle. This study explored the mechanism of disturbed carbon fixation in Oryza sativa L. by organic pollutants 2,3,4,5-tetrachlorobiphenyl (CB 61), 4'-hydroxy-2,3,4,5-tetrachlorobiphenyl (4'-OH-CB 61), 2,2',4,4'-tetrabromo diphenyl ether (BDE 47), tricyclazole (TRI), and pyrene. The biomass of rice exposed to 4'-OH-CB 61, TRI, and BDE 47 was on average 80.63% of that of the control (p < 0.05), and the inhibition of net photosynthetic rate was 59.15% by 4'-OH-CB 61. Proteomics confirmed that 4'-OH-CB 61 significantly downregulated the enzymes in the photosynthetic carbon fixation pathway, which was attributed to the decrease in ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco), the rate-limiting enzyme in the Calvin cycle. In detail, decreased Rubisco activity (6.96-33.44%) and downregulated OsRBCS2-5 encoding small Rubisco subunits (-6.80 < log2FC < -2.13) by 4'-OH-CB 61, TRI, and BDE 47 were in line with biomass yield reduction. Molecular docking and dynamic simulation suggested that the three pollutants potentially competed with CO2 for binding to the active sites in Rubisco, leading to reduced CO2 capture efficiency. These results revealed the molecular mechanism of organic pollution-induced rice yield reduction, contributing to improving the understanding of crop growth and carbon sequestration capacity of organics-contaminated soils globally.


Assuntos
Poluentes Ambientais , Oryza , Biomassa , Ciclo do Carbono , Dióxido de Carbono/metabolismo , Poluentes Ambientais/metabolismo , Simulação de Acoplamento Molecular , Oryza/metabolismo , Fotossíntese/fisiologia
19.
Environ Sci Technol ; 55(8): 4889-4898, 2021 04 20.
Artigo em Inglês | MEDLINE | ID: mdl-33750107

RESUMO

Crops can initiate various defense responses to environmental stresses. The process is often accompanied by extensive transcriptional and metabolic changes to reallocate metabolites. However, it remains unclear how organic pollutants activate the defense systems to reallocate metabolites in crops. The current study demonstrates that three defense systems, including the cytochrome P450s (CYP450s), glutathione S-transferases (GSTs), and phenylpropanoid biosynthesis, were sequentially activated after Oryza sativa was exposed to 2,3,4,5-tetrachlorobipheny l (PCB 61) and its derivatives 4'-hydroxy-2,3,4,5-tetrachlorobiphenyl (OH-PCB 61) and 4'-methoxy-2,3,4,5-tetrachlorobiphenyl (MeO-PCB 61), respectively. Genes encoding CYP76Ms and CYP72As were significantly upregulated after 0.5 h of exposure, followed by the GST-coding gene GSTU48, suggesting that the biotransformation and detoxification of PCB 61, OH-PCB 61, and MeO-PCB 61 occurred. Subsequently, CCR1 and CCR10 involved in phenylpropanoid biosynthesis were activated after 12 h, potentially reducing the oxidative stress induced by PCB 61 and its derivatives. Furthermore, ß-d-glucan exohydrolase involved in both phenylpropanoid biosynthesis and starch and sucrose metabolism was significantly downregulated by 7.04-fold in the OH-PCB 61-treated group, potentially contributing to the inhibition of sugar hydrolysis. These findings provide insights into increasing rice adaptability to organic pollutants by reinforcing the enzyme-mediated defense systems, characterizing a novel and critical strategy that enables augmented crop outputs and quality in environments stressed by organic contaminants.


Assuntos
Poluentes Ambientais , Oryza , Bifenilos Policlorados , Biotransformação , Hidroxilação
20.
Appl Opt ; 60(23): 6829-6836, 2021 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-34613162

RESUMO

To solve the serious loss problem for central energy of the Cassegrain antenna, this paper designs a beam-shaping system, named E-A system, to convert the elliptical divergent beam with astigmatism from a laser diode into an annular collimation beam. This E-A system, comprised only of lenses with quadratic surfaces, can simultaneously realize four functions, i.e., aberration correction, beam circularization, beam collimation, and dark hollow beam generation. By adjusting the parameters, the E-A system can be used to shape elliptical astigmatic beams with different parameters. Further, the E-A system can maintain good performance at wavelengths from 500 to 1647 nm. After considering various practical factors, the transmission efficiency of the entire transmitting system can be increased to 93.91% at a wavelength of 1550 nm.

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