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1.
Angew Chem Int Ed Engl ; : e202402509, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38588046

RESUMO

Membranes are important in the pharmaceutical industry for the separation of antibiotics and salts. However, its widespread adoption has been hindered by limited control of the membrane microstructure (pore architecture and free-volume elements), separation threshold, scalability, and operational stability. In this study, 4,4',4'',4'''-methanetetrayltetrakis(benzene-1,2-diamine) (MTLB) as prepared as a molecular building block for fabricating thin-film composite membranes (TFCMs) via interfacial polymerization. The relatively large molecular size and rigid molecular structure of MTLB, along with its non-coplanar and distorted conformation, produced thin and defect-free selective layers (~27 nm) with ideal microporosities for antibiotic desalination. These structural advantages yielded an unprecedented high performance with a water permeance of 45.2 L m-2 h-1 bar-1 and efficient antibiotic desalination (NaCl/adriamycin selectivity of 422). We demonstrated the feasibility of the industrial scaling of the membrane into a spiral-wound module (with an effective area of 2.0 m2). This module exhibited long-term stability and performance that surpassed those of state-of-the-art membranes used for antibiotic desalination. This study provides a scientific reference for the development of high-performance TFCMs for water purification and desalination in the pharmaceutical industry.

2.
Sci Total Environ ; 918: 170543, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38309369

RESUMO

Polychlorinated biphenyls (PCBs) are a class of endocrine-disrupting chemicals (EDCs) widely present in the environment. PCBs have been of concern due to their anti/estrogen-like effects, which make them more toxic to the female reproductive system. However, there is still a lack of systematic reviews on the reproductive toxicity of PCBs in females, so the adverse effects and mechanisms of PCBs on the female reproductive system were summarized in this paper. Our findings showed that PCBs are positively associated with lower pregnancy rate, hormone disruption, miscarriage and various reproductive diseases in women. In animal experiments, PCBs can damage the structure and function of the ovaries, uterus and oviducts. Also, PCBs could produce epigenetic effects and be transferred to the offspring through the maternal placenta, causing development retardation, malformation and death of embryos, and damage to organs of multiple generations. Furthermore, the mechanisms of PCBs-induced female reproductive toxicity mainly include receptor-mediated hormone disorders, oxidative stress, apoptosis, autophagy, and epigenetic modifications. Finally, we also present some directions for future research on the reproductive toxicity of PCBs. This detailed information provided a valuable reference for fully understanding the reproductive toxicity of PCBs.


Assuntos
Poluentes Ambientais , Bifenilos Policlorados , Gravidez , Animais , Feminino , Humanos , Bifenilos Policlorados/toxicidade , Bifenilos Policlorados/análise , Revisões Sistemáticas como Assunto , Reprodução , Estrogênios , Ovário , Poluentes Ambientais/análise
3.
Adv Mater ; 36(19): e2311013, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38341656

RESUMO

Stimulus-responsive membranes demonstrate promising applications in switchable oil/water emulsion separations. However, they are unsuitable for the treatment of double emulsions like oil-in-water-in-oil (O/W/O) and water-in-oil-in-water (W/O/W) emulsions. For efficient separation of these complicated emulsions, fine control over the wettability, response time, and aperture structure of the membrane is required. Herein, dual-coated fibers consisting of primary photothermal-responsive and secondary CO2-responsive coatings are prepared by two steps. Automated weaving of these fibers produces membranes with photothermal- and CO2-responsive characteristics and narrow pore size distributions. These membranes exhibit fast switching wettability between superhydrophilicity (under CO2 stimulation) and high hydrophobicity (under near-infrared stimulation), achieving on-demand separation of various O/W/O and W/O/W emulsions with separation efficiencies exceeding 99.6%. Two-dimensional low-field nuclear magnetic resonance and correlated spectra technique are used to clarify the underlying mechanism of switchable double emulsion separation. The approach can effectively address the challenges associated with the use of stimulus-responsive membranes for double emulsion separation and facilitate the industrial application of these membranes.

4.
Arch Toxicol ; 98(3): 663-687, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38252150

RESUMO

Microcystin-LR (MC-LR) is a toxin produced by cyanobacteria, which is widely distributed in eutrophic water bodies and has multi-organ toxicity. Previous cytotoxicity studies have mostly elucidated the effects of MC-LR on intracellular-related factors, proteins, and DNA at the molecular level. However, there have been few studies on the adverse effects of MC-LR on cell ultrastructure and function. Therefore, research on the cytotoxicity of MC-LR in recent years was collected and summarized. It was found that MC-LR can induce a series of cytotoxic effects, including decreased cell viability, induced autophagy, apoptosis and necrosis, altered cell cycle, altered cell morphology, abnormal cell migration and invasion as well as leading to genetic damage. The above cytotoxic effects were related to the damage of various ultrastructure and functions such as cell membranes and mitochondria. Furthermore, MC-LR can disrupt cell ultrastructure and function by inducing oxidative stress and inhibiting protein phosphatase activity. In addition, the combined toxic effects of MC-LR and other environmental pollutants were investigated. This review explored the toxic targets of MC-LR at the subcellular level, which will provide new ideas for the prevention and treatment of multi-organ toxicity caused by MC-LR.


Assuntos
Toxinas Marinhas , Microcistinas , Microcistinas/toxicidade , Apoptose , Estresse Oxidativo
5.
Angew Chem Int Ed Engl ; 63(4): e202316315, 2024 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-38030580

RESUMO

Covalent organic framework (COF) membranes featuring uniform topological structures and devisable functions, show huge potential in water purification and molecular separation. Nevertheless, the inability of uniform COF membranes to be produced on an industrial scale and their nonenvironmentally friendly fabrication method are the bottleneck preventing their industrial applications. Herein, we report a new green and industrially adaptable scraping-assisted interfacial polymerization (SAIP) technique to fabricate scalable and uniform TpPa COF membranes. The process used non-toxic and low-volatility ionic liquids (ILs) as organic phase instead of conventional organic solvents for interfacial synthesis of TpPa COF layer on a support membrane, which can simultaneously achieve the purposes of (i) improving the greenness of membrane-forming process and (ii) fabricating a robust membrane that can function beyond the conventional membranes. This approach yields a large-area, continuous COF membrane (19×25 cm2 ) with a thickness of 78 nm within a brief period of 2 minutes. The resulting membrane exhibited an unprecedented combination of high permeance (48.09 L m-2 h-1 bar-1 ) and antibiotic desalination efficiency (e.g., NaCl/adriamycin separation factor of 41.8), which is superior to the commercial benchmarking membranes.

6.
Small ; : e2306956, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-38100256

RESUMO

Porous frameworks that display dynamic responsiveness are of interest in the fields of smart materials, information technology, etc. In this work, a novel copper-based dynamic metal-organic framework [Cu3 TTBPE6 (H2 O)2 ] (H4 TTBPE = 1,1,2,2-tetrakis(4″-(1H-tetrazol-5-yl)-[1,1″-biphenyl]-4-yl)ethane), denoted as HNU-1, is reported which exhibits modulable photoelectromagnetic properties. Due to the synergetic effect of flexible tetraarylethylene-backboned ligands and diverse copper-tetrazole coordination chemistries, a complex 3D tunneling network is established in this MOF by the layer-by-layer staggered assembly of triplicate monolayers, showing a porosity of 59%. These features further make it possible to achieve dynamic transitions, in which the aggregate-state MOF can be transferred to different structural states by changing the chemical environment or upon heating while displaying sensitive responsiveness in terms of light absorption, photoluminescence, and magnetic properties.

7.
J Am Chem Soc ; 145(44): 24328-24337, 2023 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-37878504

RESUMO

We report herein an organic charge transfer cocrystal complex, consisting of a stable radical TPVr and an electron acceptor TCNQF4, as a rare sort of all-organic-based magnetic bistable materials with a thermally activated magnetic hysteresis loop over the temperature range from 170 to 260 K. Detailed X-ray crystallographic studies and theoretical calculations revealed that while a π-associated radical anion dimer was formed upon an integer charge transfer process from TPVr to the TCNQF4 molecules within the cocrystal lattice, the resulting TCNQF4·- π-dimers were found to exhibit varied intradimer π-stacking distances and singly occupied molecular orbital overlaps at different temperatures, thus yielding two different singlet states with distinct singlet-triplet gaps above and below the loop, which eventually contributed to the thermally excited molecular magnetic bistability.

8.
BMJ Open ; 13(7): e070958, 2023 07 24.
Artigo em Inglês | MEDLINE | ID: mdl-37487683

RESUMO

INTRODUCTION: Guided tissue regeneration (GTR) combined with bone grafting for periodontal regenerative surgery has ideal clinical results for intrabony defect. However, some sites of intrabony defects often suffer from insufficient keratinised gingival width, which affects the efficacy and long-term prognosis of periodontal tissue regeneration. Free gingival graft (FGG) is an effective surgical procedure to widen the keratinised gingiva, but there are few clinical studies on FGG prior to GTR combination with bone grafting to improve clinical outcomes. METHODS: This study is an open-label randomised controlled trial. 68 patients with periodontitis with at least one intrabony defect depth with ≥3 mm are recruited and randomly grouped. In the test group, FGG is performed first, followed by GTR and bone grafting 3 months later; while in the control group, only periodontal tissue regenerative procedures are performed. After completion of all procedures, the patients will be recalled at 3 months, 6 months and 12 months and the relevant clinical and radiographic examinations will be carried out and statistical analysis of the data will also be performed. The present research has received approval from the Ethics Committee of Shanghai Stomatological Hospital (No.2022-007) on 4 August 2022. DISCUSSION: Exploring the effectiveness of the two-stage approach of FGG prior to periodontal tissue regenerative surgery for the treatment of keratinised gingival width deficient intrabony defects can provide a high-level evidence-based basis for the formulation of relevant treatment strategies in clinical practice. ETHICS AND DISSEMINATION: The present research has received approval from the Ethics Committee of Shanghai Stomatological Hospital (No.2022-007) on 4 August 2022. The patients will be incorporated into this trial only after their written informed consent has been obtained. The study will be performed according to the 2013 revision of the Helsinki Declaration of 1975. Personal information of all subjects will be stored in the Department of Periodontology of Shanghai Stomatological Hospital. Data of the present research will be registered with the Clinical Trials Registry Platform. Additionally, we will disseminate the results through scientific journals. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ID: ChiCTR 2200063180. Registered on 1 September 2022.


Assuntos
Gengiva , Procedimentos Cirúrgicos Bucais , Periodontite , Humanos , Povo Asiático , China , Assistência Odontológica , Gengiva/transplante , Procedimentos Cirúrgicos Bucais/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa , Retalhos de Tecido Biológico , Periodontite/cirurgia
9.
Environ Sci Pollut Res Int ; 30(35): 83113-83137, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37347330

RESUMO

Endocrine disrupting chemicals (EDCs) are increasingly concerned substance endangering human health and environment. However, there is no unified standard for identifying chemicals as EDCs, which is also controversial internationally. In this review, the procedures for EDC identification in different organizations/countries were described. Importantly, three aspects to be considered in identifying chemical substances as EDCs were summarized, which were mechanistic data, animal experiments, and epidemiological information. The relationships between them were also discussed. To elaborate more clearly on these three aspects of evidence, scientific data on some chemicals including bisphenol A, 1,2-dibromo-4-(1,2 dibromoethyl) cyclohexane and perchlorate were collected and evaluated. Altogether, the above three chemicals were assessed for interfering with hormones and elaborated their health hazards from macroscopic to microscopic. This review is helpful for standardizing the identification procedure of EDCs.


Assuntos
Disruptores Endócrinos , Poluentes Ambientais , Animais , Humanos , Hormônios
10.
Angew Chem Int Ed Engl ; 62(27): e202305011, 2023 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-37158763

RESUMO

[3]Radialene has a peculiar topology and cross-conjugation system, representing a unique molecular scaffold in organic materials. Herein, we report a special class of stereoisomeric α-cyano triaryl[3]radialenes (CTRs) that show concentration-caused quenching in solution but emit red-shifted and enhanced luminescence in the crystalline state. Clustering of multiple cyano groups and their through-space interactions with the [3]radialene ring significantly extend π-electron communication meanwhile rigidifying the propeller conformation multivalently, thus playing a key role behind the state-dependent luminescence. These radialenes with a substantial electron affinity undergo a reversible electron transfer transition to anionic radicals with good stability, showing switching of photoabsorption, photoluminescence and electron spin resonance (ESR) signal. We also established proof-of-concept applications of CTRs for multimodal information encryption and chemical sensing.

11.
PLoS Pathog ; 19(4): e1011346, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-37083862

RESUMO

Oomycetes are a group of filamentous microorganisms that include some of the biggest threats to food security and natural ecosystems. However, much of the molecular basis of the pathogenesis and the development in these organisms remains to be learned, largely due to shortage of efficient genetic manipulation methods. In this study, we developed modified transformation methods for two important oomycete species, Phytophthora infestans and Plasmopara viticola, that bring destructive damage in agricultural production. As part of the study, we established an improved Agrobacterium-mediated transformation (AMT) method by prokaryotic expression in Agrobacterium tumefaciens of AtVIP1 (VirE2-interacting protein 1), an Arabidopsis bZIP gene required for AMT but absent in oomycetes genomes. Using the new method, we achieved an increment in transformation efficiency in two P. infestans strains. We further obtained a positive GFP transformant of P. viticola using the modified AMT method. By combining this method with the CRISPR/Cas12a genome editing system, we successfully performed targeted mutagenesis and generated loss-of-function mutations in two P. infestans genes. We edited a MADS-box transcription factor-encoding gene and found that a homozygous mutation in MADS-box results in poor sporulation and significantly reduced virulence. Meanwhile, a single-copy avirulence effector-encoding gene Avr8 in P. infestans was targeted and the edited transformants were virulent on potato carrying the cognate resistance gene R8, suggesting that loss of Avr8 led to successful evasion of the host immune response by the pathogen. In summary, this study reports on a modified genetic transformation and genome editing system, providing a potential tool for accelerating molecular genetic studies not only in oomycetes, but also other microorganisms.


Assuntos
Ecossistema , Phytophthora infestans , Phytophthora infestans/genética , Agrobacterium tumefaciens/genética , Virulência/genética , Mutação
12.
Toxicology ; 490: 153507, 2023 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-37030550

RESUMO

Eutrophication of water bodies can lead to cyanobacterial blooms, with the resultant release of microcystins (MCs), posing a threat to the ecosystem and human health. MCs are environmental toxins with male reproductive toxicity. However, there is a dearth of reviews focusing on sperm or spermatogenesis. In this paper, studies on sperm toxicity caused by MCs in recent 20 years were collected and summarized, aiming at revealing the toxic effects and potential mechanisms of MCs on sperm. Based on the previous findings, MCs can decline sperm quality and count, and cause malformation in vertebrates and invertebrates. The reason might be that MCs cause indirect damage to sperm through impairing the structure and function of the testis. The mechanisms of MCs-induced sperm toxicity mainly result from alterations in genetic material, abnormalities in the structure and function of sperm. The epigenetic modifications such as miRNA and piRNA were also involved in MC-LR-induced sperm damage. In conclusion, MCs exposure is harmful to sperm, but its direct effects and mechanisms on sperm are still not known, which remains a significant research direction. Our review will provide a basis for the protection of male reproductive health damage caused by microcystins.


Assuntos
Ecossistema , Microcistinas , Animais , Masculino , Humanos , Microcistinas/toxicidade , Sêmen , Testículo , Espermatozoides
13.
Environ Toxicol ; 38(6): 1239-1250, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36880395

RESUMO

Microcystins (MCs) is a class of cyclic heptapeptide compounds with biological activity. There is no effective treatment for liver injury caused by MCs. Hawthorn is a medicinal and edible plant traditional Chinese medicine with hypolipidemic, reducing inflammation and oxidative stress in the liver. This study discussed the protective effect of hawthorn fruit extract (HFE) on liver damage caused by MC-LR and the underlying molecular mechanism. After MC-LR exposure, pathological changes were observed and hepatic activity of ALT, AST and ALP were increased obviously, but they were remarkably restored with HFE administration. In addition, MC-LR could significantly reduce SOD activity and increase MDA content. Importantly, MC-LR treatment resulted in mitochondrial membrane potential decreased, and Cytochrome C release, eventually leading to cell apoptosis rate increase. HFE pretreatment could significantly alleviate the above abnormal phenomena. To examine the mechanism of protection, the expression of critical molecules in the mitochondrial apoptosis pathway was examined. The levels of Bcl-2 was inhibited, and the levels of Bax, Caspase-9, Cleaved Caspase-9, and Cleaved caspase-3 were upregulated after MC-LR treatment. HFE reduced MC-LR-induced apoptosis via reversing the expression of key proteins and genes in the mitochondrial apoptotic pathway. Hence, HFE could alleviate MC-LR induced hepatotoxicity by reducing oxidative stress and apoptosis.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Crataegus , Caspase 9 , Frutas , Estresse Oxidativo , Apoptose , Microcistinas/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle
14.
Ecotoxicol Environ Saf ; 256: 114845, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37001189

RESUMO

As a common pollutant in the water environment, microcystin leucine arginine (MC-LR) can enter semen and damage the sperm in animals. However, the mechanism by which MC-LR damages human sperm is unclear. Therefore, human sperm samples were obtained from the Henan Provincial Sperm Bank and exposed to different concentrations (0, 1, 10, and 100 µg/L) of MC-LR for 1, 2, 4, and 6 h, to invegest the effects and potential mechanism of MC-LR on sperm. The results showed that MC-LR mainly accumulated in the neck and flagellum of human sperm. Compared to the control group, the sperm capacitation rate and motility were significantly decreased in the 100 µg/L group. After exposure of 100 µg/L of MC-LR, the central microtubule and microtubule doublet of sperm flagellum were blurred, asymmetrical, or even lost. Furthermore, the expression levels of flagellin DNAH17, SPEF2, SPAG16, SPAG6, and CFAP44 in human sperm were reduced. Also, the phosphorylation levels of CaMKKß and AMPK can be inhibited by MC-LR. These findings revealed that MC-LR can induce functional and structural damage in human sperm, and the Ca2+/CaMKKß/AMPK pathway may be involved in this process. This study will provide a basis for prevention and treatment of male fertility declines caused by MC-LR.


Assuntos
Proteínas Quinases Ativadas por AMP , Arginina , Animais , Humanos , Masculino , Arginina/farmacologia , Quinase da Proteína Quinase Dependente de Cálcio-Calmodulina , Leucina , Microcistinas/farmacologia , Fosforilação , Sêmen , Espermatozoides , Sinalização do Cálcio
15.
Angew Chem Int Ed Engl ; 62(22): e202301719, 2023 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-36988141

RESUMO

Dynamic materials undergoing adaptive solid-state transitions are attractive for soft mechanics and information technology. Here, we report a novel porous framework system based on macrocyclic trimers assembled from open-shell tetraarylethylene building blocks with aryldicyanomethyl radicals as coupling linkers. Under mechanical, thermal, or chemical stimuli, the framework showed adaptability by activating conformational dynamics and radical-based transformations, thus displaying macroscopic responsiveness in terms of light absorption, luminescence, and magnetism. We studied the dynamic processes by variable-temperature nuclear magnetic resonance (VT-NMR), variable-temperature electron spin resonance (VT-ESR), and superconducting quantum interference device (SQUID) measurement and further established a proof-of-concept application for multi-modal information encryption. The strategy may open avenues for rational design of solid-state photoelectromagnetic dynamic materials by merging dynamic covalent coupling chemistry and functional aggregation principles.

16.
Adv Healthc Mater ; 12(20): e2202827, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-36977522

RESUMO

Cardiovascular disease remains the leading cause of mortality worldwide. The inability of cardiac tissue to regenerate after an infarction results in scar tissue formation, leading to cardiac dysfunction. Therefore, cardiac repair has always been a popular research topic. Recent advances in tissue engineering and regenerative medicine offer promising solutions combining stem cells and biomaterials to construct tissue substitutes that could have functions similar to healthy cardiac tissue. Among these biomaterials, plant-derived biomaterials show great promise in supporting cell growth due to their inherent biocompatibility, biodegradability, and mechanical stability. More importantly, plant-derived materials have reduced immunogenic properties compared to popular animal-derived materials (e.g., collagen and gelatin). In addition, they also offer improved wettability compared to synthetic materials. To date, limited literature is available to systemically summarize the progression of plant-derived biomaterials in cardiac tissue repair. Herein, this paper highlights the most common plant-derived biomaterials from both land and marine plants. The beneficial properties of these materials for tissue repair are further discussed. More importantly, the applications of plant-derived biomaterials in cardiac tissue engineering, including tissue-engineered scaffolds, bioink in 3D biofabrication, delivery vehicles, and bioactive molecules, are also summarized using the latest preclinical and clinical examples.


Assuntos
Materiais Biocompatíveis , Alicerces Teciduais , Animais , Materiais Biocompatíveis/farmacologia , Engenharia Tecidual/métodos , Medicina Regenerativa/métodos , Colágeno
17.
Toxicol Ind Health ; 39(4): 188-203, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36772983

RESUMO

The occurrence of thyroid dysfunction is affected by environmental factors, and BPA is a ubiquitous environmental pollutant with the potential to cause thyroid dysfunction. However, the limited epidemiological evidence shows an inconsistent association between BPA exposure and thyroid dysfunction. Therefore, the literature on the impact of BPA on thyroid was sorted and analyzed to study the relationship between BPA and adult thyroid function. The studies published on or before 23rd May 2022 from PubMed, Web of Science, and Scopus were collected analyzing the association between BPA exposure and the levels of thyroid hormones. The methodological quality of each study was assessed, the sensitivity analysis and subgroup analysis based on study population and gender were also performed, and publication bias was evaluated. A total of 2969 literature studies were retrieved. Based on inclusion and exclusion criteria, eleven studies were included. Our results showed that BPA concentration was negatively correlated with FT4 and TSH in males. Pooled correlation coefficients between BPA and FT4/TSH were -0.027 (95%CI = -0.030∼-0.024) and -0.058 (95%CI = -0.111∼-0.004). BPA concentration was positively correlated with FT4 in females, and the pooled correlation coefficient was 0.006 (95%CI = 0.003-0.008). The effects of BPA on thyroid hormone levels were significantly different between males and females. BPA may significantly decrease the levels of FT4 and TSH in males but increase the levels of FT4 in females. Considering the high heterogeneity among studies and the limited investigations into subgroups, the relationship between BPA exposure and thyroid dysfunction needs to be further investigated.


Assuntos
Glândula Tireoide , Hormônios Tireóideos , Masculino , Feminino , Humanos , Adulto , Fenóis/toxicidade , Tireotropina , Tiroxina
18.
Ecotoxicol Environ Saf ; 252: 114592, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36731181

RESUMO

Microcystin-LR (MC-LR), one of aquatic environmental contaminants with reproductive toxicity produced by cyanobacterial blooms, but its toxic effects and mechanisms on the ovary are not fully understood. Here, proteomic techniques and molecular biology experiments were performed to study the potential mechanism of MC-LR-caused ovarian toxicity. Results showed that protein expression profile of ovarian granulosa cells (KK-1) was changed by 17 µg/mL MC-LR exposure. Comparing with the control group, 118 upregulated proteins as well as 97 downregulated proteins were identified in MC-LR group. Function of differentially expressed proteins was found to be enriched in pathways related to adherent junction, such as cadherin binding, cell-cell junction, cell adhesion and focal adherens. Furthermore, in vitro experiments, MC-LR significantly downregulated the expression levels of proteins associated with adherent junction (ß-catenin, N-cadherin, and α-catenin) as well as caused cytoskeletal disruption in KK-1 cells (P < 0.05), indicating that the adherent junction was damaged. Results of in vivo experiments have shown that after 14 days of acute MC-LR exposure (40 µg/kg), damaged adherent junction and an increased number of atretic follicles were observed in mouse ovaries. Moreover, MC-LR activated JNK, an upstream regulator of adherent junction proteins, in KK-1 cells and mouse ovarian tissues. In contrast, JNK inhibition alleviated MC-LR-induced adherent junction damage in vivo and in vitro, as well as the number of atretic follicles. Taken together, findings from the present study indicated that JNK is involved in MC-LR-induced granulosa cell adherent junction damage, which accelerated follicular atresia. Our study clarified a novel mechanism of MC-LR-caused ovarian toxicity, providing a theoretical foundation for protecting female reproductive health from environmental pollutants.


Assuntos
Atresia Folicular , Proteômica , Animais , Feminino , Camundongos , Células da Granulosa , Microcistinas/toxicidade , MAP Quinase Quinase 4/metabolismo
19.
Environ Toxicol ; 38(2): 343-358, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36288207

RESUMO

Environmental cyanotoxin exposure may be a trigger of testicular cancer. Activation of PI3K/AKT/mTOR signaling pathway is the critical molecular event in testicular carcinogenesis. As a widespread cyanotoxin, microcystin-leucine arginine (MC-LR) is known to induce cell malignant transformation and tumorigenesis. However, the effects of MC-LR on the regulatory mechanism of PI3K/AKT/mTOR pathway in seminoma, the most common testicular tumor, are unknown. In this study, mouse spermatogonia cell line (GC-1) and nude mice were used to investigate the effects and mechanisms of MC-LR on the malignant transformation of spermatogonia by nude mouse tumorigenesis assay, cell migration invasion assay, western blot, and cell cycle assay, and so forth. The results showed that, after continuous exposure to environmentally relevant concentrations of MC-LR (20 nM) for 35 generations, the proliferation, migration, and invasion abilities of GC-1 cells were increased by 120%, 340%, and 370%, respectively. In nude mice, MC-LR-treated GC-1 cells formed tumors with significantly greater volume (0.998 ± 0.768 cm3 ) and weight (0.637 ± 0.406 g) than the control group (0.067 ± 0.039 cm3 ; 0.094 ± 0.087 g) (P < .05). Furthermore, PI3K inhibitor Wortmannin inhibited the PI3K/AKT/mTOR pathway and its downstream proteins (c-MYC, CDK4, CCND1, and MMP14) activated by MC-LR. Blocking PI3K alleviated MC-LR-induced cell cycle disorder and malignant proliferation, migration and invasive of GC-1 cells. Altogether, our findings suggest that MC-LR can induce malignant transformation of mouse spermatogonia, and the PI3K/AKT/mTOR pathway-mediated cell cycle dysregulation may be an important target for malignant proliferation. This study provides clues to further reveal the etiology and pathogenesis of seminoma.


Assuntos
Ciclo Celular , Seminoma , Espermatogônias , Neoplasias Testiculares , Animais , Masculino , Camundongos , Arginina/farmacologia , Arginina/metabolismo , Carcinogênese/metabolismo , Divisão Celular , Proliferação de Células , Leucina , Camundongos Nus , Microcistinas/toxicidade , Microcistinas/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Seminoma/induzido quimicamente , Seminoma/metabolismo , Seminoma/patologia , Espermatogônias/metabolismo , Espermatogônias/patologia , Neoplasias Testiculares/induzido quimicamente , Neoplasias Testiculares/metabolismo , Neoplasias Testiculares/patologia , Serina-Treonina Quinases TOR/metabolismo , Transdução de Sinais
20.
Medicina (Kaunas) ; 58(9)2022 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-36143857

RESUMO

Adequate alveolar bone volume is a prerequisite condition for successful orthodontic tooth movement and posttreatment stability. Mandibular anterior teeth are more likely to exhibit dehiscence and fenestration in adult patients, which make orthodontic treatment in adults challenging, especially when the amount of retraction of the anterior teeth is large. Herein, we report the treatment of augmented corticotomy only on the lingual side in the mandibular anterior region to increase the volume of soft and hard tissue assisting orthodontics in a Class I bialveolar protrusive malocclusion and propose management strategies of mandibular incisor retractions. A 22-year-old female with a chief complaint of protrusive mouth presented to the Department of Orthodontics for orthodontic treatment, diagnosed with Class I bialveolar protrusive. The orthodontic treatment plan involved the extraction of four premolars and extensive retraction of the anterior teeth using microimplant anchorage. In consideration of the fenestration and dehiscence in the mandibular anterior alveolar bone and the pattern of tooth movement, augmented corticotomy was performed on the lingual side combined with bone grafting. Clinical and radiographic evaluation after treatment revealed significant improvements in the facial profile and in periodontal phenotype. Augmented corticotomy assisting orthodontic treatment could be a promising treatment strategy for adult patients with alveolar protrusion to maintain periodontal health.


Assuntos
Má Oclusão , Ortodontia , Cefalometria , Feminino , Humanos , Incisivo , Mandíbula/cirurgia , Técnicas de Movimentação Dentária
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