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1.
J Cell Mol Med ; 2021 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-34609056

RESUMO

Thymoquinone (TQ) has been reported as an anti-tumour drug widely studied in various tumours, and its mechanism and effect of which has become a focus of current research. However, previous studies from our laboratory and other groups found that TQ showed weak anti-tumour effects in many cancer cell lines and animal models. Therefore, it is necessary to modify and optimize the structure of TQ to obtain new chemical entities with high efficiency and low toxicity as candidates for development of new drugs in treating cancer. Therefore, we designed and synthesized several TQ derivatives. Systematic analysis, including in vitro and in vivo, was conducted on a panel of triple-negative breast cancer (TNBC) cells and mouse model to demonstrate whether TQFL12, a new TQ derivative, is more efficient than TQ. We found that the anti-proliferative effect of TQFL12 against TNBC cells is significantly stronger than TQ. We also demonstrated TQFL12 affects different aspects in breast cancer development including cell proliferation, migration, invasion and apoptosis. Moreover, TQFL12 inhibited tumour growth and metastasis in cancer cell-derived xenograft mouse model, with less toxicity compared with TQ. Finally, mechanism research indicated that TQFL12 increased AMPK/ACC activity by stabilizing AMPKα, while molecular docking supported the direct interaction between TQFL12 and AMPKα. Taken together, our findings suggest that TQFL12, as a novel chemical entity, possesses a better inhibitory effect on TNBC cells and less toxicity in both in vitro and in vivo studies. As such, TQFL12 could serve as a potential therapeutic agent for breast cancer.

2.
Hua Xi Kou Qiang Yi Xue Za Zhi ; 39(5): 540-546, 2021 Oct 01.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-34636201

RESUMO

OBJECTIVES: This study aims to explore the effect of acidic culture conditions on the proliferation, apoptosis, and migration ability of human tongue squamous cell carcinoma SCC15 and CAL27 cells and its potential molecular mechanism. METHODS: After acidic culture for different periods, methyl thiazolyl tetrazolium (MTT) method was adop-ted to detect the cell proliferation of SCC15 and CAL27. Flow cytometry was employed to detect the apoptosis level of SCC15 and CAL27 cells. The migration ability of SCC15 and CAL27 after acidic culture was detected by scratch hea-ling test. Real-time fluorescence quantitative polymerase chain reaction (FQ-PCR) was used to detect the mRNA expression of cyclooxygenase 2 (COX-2) and survivin in SCC15 and CAL27 cells after acidic culture. RESULTS: After culture for 24 h under acidic microenvironment, SCC15 and CAL27 cells grew rapidly and reached the stationary phase after adjustment for 3 days. The apoptosis levels of SCC15 and CAL27 cells decreased after acidic culture, but the most significant reduction occurred after 6 h of acidic culture. The scratch healing rates of SCC15 and CAL27 cells increased after acidic culture. The results of FQ-PCR showed that the mRNA expression levels of COX-2 and survivin in SCC15 and CAL27 cells increased after acidic culture. CONCLUSIONS: Extracellular acidic microenvironment can inhibit the apoptosis of tongue squamous carcinoma cells, promote their migration, and induce more adaptable and malignant tongue squamous carcinoma cells. The mechanism may be related to COX-2 and survivin and their signal pathways.


Assuntos
Carcinoma de Células Escamosas , Neoplasias Bucais , Neoplasias da Língua , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Humanos , Língua , Microambiente Tumoral
3.
Mol Genet Genomic Med ; : e1822, 2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34668645

RESUMO

BACKGROUND: To summarize the relationship between different MMUT gene mutations and the response to vitamin B12 in MMA. METHODS: This was a retrospective study of patients diagnosed with mut-type MMA. All patients with mut-type MMA were tested for responsiveness to vitamin B12. RESULTS: There were 81, 27, and 158 patients in the completely responsive, partially responsive, and nonresponsive groups, respectively, and the proportions of symptom occurrence were 30/81 (37.0%), 21/27 (77.8%), and 131/158 (82.9%), respectively (p < .001). The median levels of posttreatment propionyl carnitine (C3), C3/acetyl carnitine (C2) ratio in the blood, and methylmalonic acid in the urine were all lower than pretreatment, and the median level of C3/C2 ratio in the completely responsive group was within the normal range. In 266 patients, 144 different mutations in the MMUT gene were identified. Patients with the mutations of c.1663G>A, c.2080C>T, c.1880A>G, c.1208G>A, etc. were completely responsive and with the mutations of c.1741C>T, c.1630_1631GG>TA, c.599T>C, etc. were partially responsive. The proportions of healthy/developmental delay outcomes in the three groups were 63.0%/23.5%, 33.3%/40.7%, and 13.3%/60.1%, respectively (p < .001). CONCLUSION: Different mutations in the MMUT gene are associated with the effect of vitamin B12 treatment.

4.
Chem Asian J ; 2021 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-34618408

RESUMO

Polyallenes, as a typical type of reactive polymers, are of great significance and have aroused widespread interest because they contain double bonds that can be post-modified into other functionalities to afford varieties of functional materials. This Minireview firstly highlights the recent advances in the preparation of polyallenes, including preparation of helical polyallenes through directly polymerization of chiral allene monomers or helix-sense-selective polymerization (HSSP) of achiral allene monomers, synthesis of 1,2-regulated polyallenes and 2,3-regulated polyallenes via selective polymerization of allene monomers, polymerization of allene monomers catalyzed by Ni(II)-terminated poly(3-hexylthiophene) (P3HT), and so on. Then, latest progress on the self-assembly and stimuli-responses of polyallene-based diblock, ABA and ABC triblock copolymers is summarized. We hope this Minireview will inspire more interest in developing polyallenes and encourage further advances in functional materials.

5.
Nat Commun ; 12(1): 5532, 2021 09 20.
Artigo em Inglês | MEDLINE | ID: mdl-34545089

RESUMO

Isopropenyl ethers are critical intermediates for accessing medicinally valuable ketal-based prodrugs and biomaterials, but traditional approaches for the synthesis of isopropenyl ethers suffer from poor functional group compatibility and harsh reaction conditions. Here, we develop an organocatalytic transisopropenylation approach to solve these challenges, enabling the synthesis of isopropenyl ethers from various hydroxyl-group-containing small-molecule drugs, polymers, and functional building blocks. The method provides a straightforward and versatile synthesis of isopropenyl ethers, features excellent tolerance of diverse functional groups, applies to a wide range of substrates, and allows scalable synthesis. The development of this organocatalytic transisopropenylation approach enables access to modular preparation of various acid-sensitive ketal-linked prodrugs and functionalized ketalated biomaterials. We expect our syntheses and transformations of isopropenyl ethers will find utility in several diverse fields, including medicinal chemistry, drug delivery, and biomaterials.


Assuntos
Álcoois/química , Materiais Biocompatíveis/química , Prenilação , Pró-Fármacos/química , Células 3T3 , Acetona/química , Álcoois/síntese química , Animais , Catálise , Feminino , Células HCT116 , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus
6.
J Agric Food Chem ; 69(32): 9451-9460, 2021 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-34372660

RESUMO

Lead (Pb) is a common toxic heavy metal pollutant in the environment that seriously endangers the health of animals. The liver is a key target organ affected by Pb toxicity. Plant extracts allicin and quercetin have a strong antioxidant capacity that can promote the excretion of heavy metals by improving the body's antioxidant defense and chelating heavy metal ions. To explore the preventive and therapeutic effects of allicin and quercetin on Pb poisoning in chickens, 96 chickens were randomly divided into eight groups: control, Pb, allicin, quercetin, allicin + quercetin, Pb + allicin, Pb + quercetin, and Pb + allicin + quercetin groups. The chickens were given feed containing the above treatments for 90 days. The results indicated that Pb can affect the growth and development of the liver, damage the circulatory system, destroy the structure of mitochondria and nuclei in liver cells, cause an imbalance in the oxidation system, inhibit PI3K protein, and activate the mitochondrial apoptotic pathway. Allicin and quercetin, alone or in combination, can improve the antioxidant capacity of the liver and alleviate liver tissue damage caused by Pb. In summary, allicin and quercetin could alleviate oxidative damage and apoptosis in the Pb-poisoned chicken liver through the PI3K signaling pathway, with stronger effects achieved by their combination.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Quercetina , Animais , Galinhas , Dissulfetos , Chumbo/toxicidade , Estresse Oxidativo , Fosfatidilinositol 3-Quinases/genética , Transdução de Sinais , Ácidos Sulfínicos
7.
Ecotoxicol Environ Saf ; 224: 112620, 2021 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-34392152

RESUMO

Cadmium (Cd) has been described as a potential inflammatory inducer, while increasing evidence shows that inappropriate inflammation is a contributing factor to kidney injury. Hence, research on Cd-triggered inflammatory response is of great significance for elucidating the mechanism of Cd-induced nephrotoxicity. Bromodomain-containing 4 (BRD4) is an important epigenetic regulator involved in the development of many inflammatory diseases, but its regulatory roles in Cd-triggered inflammatory response remain to be clarified. Here, we found that treatment with Cd in Sprague-Dawley rats (2 mg/kg bw, i.p., 5 consecutive days) and in rat kidney cell line (NRK-52E, 0-10 µM, 12 h) induced the transcription of inflammatory cytokines, which could be reduced by JQ1 (BRD4 inhibitor, 25 mg/kg bw, i.p., 3 consecutive days in vivo; 0.5 µM, 12 h in vitro) or BRD4 small interfering RNA (siRNA, in vitro), suggesting that BRD4 participates in Cd-triggered inflammatory response. Next, our study clarified the roles of BRD4 in Cd-triggered inflammatory response. The inhibition of BRD4 decreased Cd-promoted NF-κB nuclear translocation and activation in vivo and in vitro. Cd increased the acetylation level of RelA K310 and enhanced BRD4 binding to acetylated NF-κB RelA in vivo and in vitro, which were abrogated by inhibiting BRD4. In summary, our study suggests that BRD4 is involved in Cd-triggered transcription of inflammatory cytokines by mediating the activation of NF-κB signaling pathway and increasing itself binding to acetylated NF-κB RelA in rat kidney, therefore, BRD4 could be a potential therapeutic target for Cd-induced renal diseases.

8.
Biomolecules ; 11(7)2021 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-34356602

RESUMO

Cadmium (Cd) is a potential pathogenic factor in the nervous system associated with various neurodegenerative disorders. Puerarin (Pur) is an isoflavone purified from the Chinese medical herb, kudzu root, and exhibits antioxidant and antiapoptotic properties in the brain. In this study, the detailed mechanisms underlying the neuroprotective potential of Pur against Cd-induced neuronal injury was evaluated for the first time in vivo in a rat model and in vitro using primary rat cerebral cortical neurons. The results of the in vivo experiments showed that Pur ameliorated Cd-induced neuronal injury, reduced Cd levels in the cerebral cortices, and stimulated Cd excretion in Cd-treated rats. We also observed that the administration of Pur rescued Cd-induced oxidative stress, and attenuated Cd-induced apoptosis by concomitantly suppressing both the Fas/FasL and mitochondrial pathways in the cerebral cortical neurons of rats both in vivo and in vitro. Our results demonstrate that Pur exerted its neuroprotective effects by stimulating Cd excretion, ameliorating Cd-induced oxidative stress and apoptosis in rat cerebral cortical neurons.


Assuntos
Apoptose/efeitos dos fármacos , Cádmio , Córtex Cerebral , Isoflavonas/farmacologia , Neurônios/metabolismo , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Animais , Cádmio/farmacocinética , Cádmio/toxicidade , Córtex Cerebral/lesões , Córtex Cerebral/metabolismo , Masculino , Ratos , Ratos Sprague-Dawley
9.
Mikrochim Acta ; 188(8): 243, 2021 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-34231032

RESUMO

The design and development of a 3D hierarchical CdS/NiO heterojunction and its application in a self-powered cathodic photoelectrochemical (PEC) bioanalysis is introduced. Specifically, NiO nanoflakes (NFs) were in situ formed on carbon fibers via a facile liquid-phase deposition method followed by an annealing step and subsequent integration with CdS quantum dots (QDs). The glucose oxidase (GOx) was then coated on the photocathode to allow the determination of glucose. Under 5 W 410 nm LED light and at a working voltage of 0.0 V (vs. Ag/AgCl), this method can assay glucose concentrations down to 1.77×10-9 M. The linear range was 5×10-7 M to 1×10-3 M, and the relative standard deviation (RSD) was below 5%. The photocathodic biosensor achieved target detection with high sensitivity and selectivity. This work is expected to stimulate more passion in the development of innovative hierarchical heterostructures for advanced self-powered photocathodic bioanalysis. Design of 3D hierarchical CdS/NiO heterojunction and its application in a self-powered cathodic photoelectrochemical (PEC) bioanalysis.

10.
Cell Biol Toxicol ; 2021 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-34308505

RESUMO

Mitochondrial-associated endoplasmic reticulum (ER) membranes (MAMs) play a key role in several physiological functions, including calcium ion (Ca2+) transfer and autophagy; however, the molecular mechanism controlling this interaction in cadmium (Cd)-induced neurotoxicity is unknown. This study shows that Cd induces alterations in MAMs and mitochondrial Ca2+ levels in PC12 cells and primary neurons. Ablation or silencing of mitofusin 2 (Mfn2) in PC12 cells or primary neurons blocks the colocalization of ER and mitochondria while reducing the efficiency of mitochondrial Ca2+ uptake. Moreover, Mfn2 defects reduce interactions or colocalization between GRP75 and VDAC1. Interestingly, the enhancement of autophagic protein levels, colocalization of LC3 and Lamp2, and GFP-LC3 puncta induced by Cd decreased in Mfn2-/- or Grp75-/- PC12 cells and Mfn2- or Grp75-silenced primary neurons. Notably, the specific Ca2+ uniporter inhibitor RuR blocked both mitochondrial Ca2+ uptake and autophagy induced by Cd. Finally, this study proves that the mechanism by which IP3R-Grp75-VDAC1 tethers in MAMs is associated with the regulation of autophagy by Mfn2 and involves their role in mediating mitochondrial Ca2+ uptake from ER stores. These results give new evidence into the organelle metabolic process by demonstrating that Ca2+ transport between ER-mitochondria is important in autophagosome formation in Cd-induced neurodegeneration.

11.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 33(6): 676-679, 2021 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-34296685

RESUMO

OBJECTIVE: To investigate the diagnostic value of neutrophil CD64 index in sepsis patients in intensive care unit (ICU). METHODS: A prospective case-control study was conducted, the patients admitted to ICU of Jiangbei People's Hospital Affiliated to Nantong University from December 2016 to June 2020 were enrolled. According to the criteria of Sepsis 3, 107 patients diagnosed with sepsis were classified as the sepsis group, 112 patients without infection were classified as control group. Peripheral venous blood samples were collected within 24 hours after ICU admission, neutrophil CD64 index, C-reactive protein (CRP), procalcitonin (PCT), white blood cell count (WBC) were detected. Receiver operating characteristic curve (ROC curve) was used to evaluate the diagnostic value of neutrophil CD64 index, CRP, PCT and WBC for sepsis. RESULTS: The neutrophil CD64 index, CRP and PCT in sepsis group were significantly higher than those in control group [neutrophil CD64 index: 9.03±5.59 vs. 3.18±1.50, CRP (mg/L): 146.9±68.3 vs. 46.5±35.8, PCT (ng/L): 31.82±14.71 vs. 1.87±1.42, all P < 0.05]. ROC curve analysis showed that neutrophil CD64 index, CRP and PCT had certain diagnostic value for sepsis, the area under ROC curve (AUC) were 0.924, 0.915 and 0.879, respectively, the 95% confidence intervals (95%CI) were 0.871-0.978, 0.855-0.975, 0.807-0.951, respectively, P values were 0.016, 0.017 and 0.026, respectively. Among the three indicators, the diagnostic value of neutrophil CD64 index was much higher. When the optimal cut-off value was 4.32, the sensitivity and specificity were 83.6% and 88.7%, respectively, which were higher than the sensitivity (75.1%, 76.3%) and specificity (87.2%, 82.5%) of CRP and PCT. CONCLUSIONS: Neutrophil CD64 index is a valuable biomarker for the diagnosis of sepsis in ICU.


Assuntos
Neutrófilos , Sepse , Proteína C-Reativa/análise , Calcitonina , Estudos de Casos e Controles , Humanos , Unidades de Terapia Intensiva , Prognóstico , Estudos Prospectivos , Curva ROC , Sepse/diagnóstico
12.
Environ Pollut ; 284: 117514, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34261220

RESUMO

Based on the fact that mycotoxins and the food-borne bacteria coexist in the natural environment and pose a significant health hazard to humans and animals, it is important to investigate the immunosuppressive mechanism of ZEA (zearalenone), DON (deoxynivalenol), and their combination in bacterial infections. In this study, we established a mouse model of mycotoxin low-dose exposure combined with Listeria monocytogenes infection and investigated the effects of ZEA, DON and their combination on Th1-mediated anti-intracellular bacterial infection based on CD4+ T cell activation and differentiation using both in vitro and in vivo analyses. The present study showed that both ZEA and DON aggravated Listeria monocytogenes infection in mice and affected the activation of CD4+ T cells and Th1 differentiation, including the effects on costimulatory molecules CD28 and CD152 and on cross-linking of IL-12 and IL-12R, by inhibiting T cell receptor (TCR) signaling. When compared with ZEA, DON was found to have a greater impact on many related indicators. Surprisingly, the combined effects of ZEA and DON did not appear to enhance toxicity compared to treatment with the individual mycotoxins. Our findings more clearly revealed that exposure to low-dose ZEA and DON caused immunosuppression in the body by mechanisms including inhibition of CD4+ T cells activation and reduction of Th1 cell differentiation, thus exacerbating infection of animals by Listeria monocytogenes.


Assuntos
Listeria monocytogenes , Zearalenona , Animais , Linfócitos T CD4-Positivos , Diferenciação Celular , Imunidade Celular , Camundongos , Linfócitos T , Tricotecenos
13.
Acta Trop ; 222: 106048, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34273315

RESUMO

Praziquantel (PZQ), the only choice of chemotherapy for schistosomiasis recommended by World Health Organization (WHO), has been widely used over 40 years. The long-term, and rapid expansion of, PZQ use for disease control across a large populations continues to raise concern regarding the potential for emergence and establishment of drug resistance. Recent research has also proposed that the long survival and low sensitivity of unpaired worms, derived from either incomplete treatment cure rates or single-sex schistosome infections within final hosts, could exacerbate the risk of PZQ resistance (PZQ-R) emerging. With the aim of assessing whether PZQ efficacy amongst S. japonicum may have changed over time in China, we performed a unique systematic review and meta-analyses on datasets which evaluated the efficacy of PZQ via laboratory assays of field S. japonicum isolates on experimental mice over time. Relevant published literatures from four electronic bibliographic databases and lists of article references were searched. Two indexes, d, a measure used in meta-analyses for worm burden difference between two groups, and r, a traditional measure for worm reduction percentage after treatment but without considering sample size were calculated for each study. A total of 25 papers including 127 experimental studies with eligible data on 2230 mice were retrieved. The pooled d (D) was 3.91 (3.56-4.25) and pooled r (R) was 54.52% (52.55%-56.52%). D significantly increased over time, whereas R non-significantly decreased; both estimates were significantly associated with the total drug dose. Such findings suggested no evidence of PZQ-R emergence S. japonicum to date. However, we consider the potential role of parasite origins, PZQ dosage, and single versus mixed gender infections of the results published to date, and the avenues now needed for further research.


Assuntos
Anti-Helmínticos , Praziquantel , Esquistossomose Japônica , Animais , Anti-Helmínticos/uso terapêutico , Resistência a Medicamentos , Camundongos , Praziquantel/uso terapêutico , Schistosoma japonicum , Esquistossomose Japônica/tratamento farmacológico
14.
Metallomics ; 13(7)2021 07 12.
Artigo em Inglês | MEDLINE | ID: mdl-34185081

RESUMO

Cadmium (Cd) is a toxic metal and an environmental pollutant and can cause neurotoxicity by inducing apoptosis. Fas (CD95/Apo-1) is a cell-surface receptor that triggers apoptosis upon ligand binding, mediated through the mitochondrial apoptotic pathway. However, the role and regulatory mechanism of Fas in Cd-induced neuronal apoptosis remain understudied. Here, we demonstrate that activation of caspase-8 and the c-Jun N-terminal kinase (JNK) pathway are mechanisms underlying Cd-induced Fas-mediated activation of the mitochondrial apoptotic pathway in rat cerebral cortical neurons. In vitro, Cd induced apoptosis in primary cortical neurons by activating caspase-8, JNK, and the mitochondrial apoptotic pathway. Fas knockdown enhanced cell viability in the presence of Cd and inhibited apoptosis by blocking Cd-activated Fas, caspase-8, and JNK. Fas knockdown also inhibited the decrease of mitochondrial membrane potential, cleavage of caspase-9/3 and poly (ADP-ribose) polymerase 1, and impaired nuclear translocation of apoptosis-inducing factor and endonuclease G. In vivo, Fas knockdown alleviated Cd-induced neuronal injury and inhibited apoptosis, activation of caspase-8, JNK, and mitochondrial apoptotic pathways in rat cerebral cortical neurons. In summary, our results demonstrate that Cd-activated Fas relays apoptotic signals from the cell surface to the mitochondria via caspase-8 and JNK activation in rat cerebral cortical neurons, leading to aggravation of the neuronal injury.

15.
Nat Prod Res ; : 1-6, 2021 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-34180326

RESUMO

A new triarylindanone, namely selagindanone A (1), and a new isobenzofuranone (2), 3,4-bis(4-hydroxyphenyl)isobenzofuran-1(3H)-one, were isolated from Selaginella tamariscina. Their structures were elucidated by comprehensive spectroscopic and mass spectrometric analyses, including 1 D-, 2 D-NMR and HR-ESI-MS. Compound 1 possesses a unique structural feature of triaryl-substituted in the skeleton of 1-indanone. In addition, compound 2 showed weak cytotoxicity against human hepatocellular carcinoma SMMC-7721 and HepG2 cell lines.

16.
Ecotoxicol Environ Saf ; 220: 112367, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34052758

RESUMO

Zearalenone, which is ubiquitous in grains and animal feed, is a mycotoxin that can cause serious damage to animals and humans. Sertoli cells (SCs) can be used to study ZEA male reproductive toxicity in vitro. SCs provide energy for germ cells, where AMPK regulates intracellular energy. In order to explore the regulatory effect of AMPK on ZEA-induced lactate decline, we activated AMPK by AICAR and then inhibited AMPK by Compound C with ZEA-treated SCs for 24 h to detect intracellular lactate production-related indicators. Cell viability in the presence of 20 µmol/L ZEA and either 50 µmol/L AICAR or 5 µmol/L Compound C, respectively, did not damage SCs, and could effectively either activate or inhibit AMPK. Inhibition of AMPK promoted the production of pyruvate and lactate via increased expression of the glycolysis-related genes Pgam1 and the lactate production-related proteins GLUT1, LDHA, and MCT4. Activating AMPK inhibited the production of lactate and pyruvate by suppressing the expression of glycolysis-related genes HK1, Pgam1, and Gpi1 and that of lactate production-related proteins LDHA and MCT4. Zearalenone destroys the energy balance in SCs, activates P-AMPK, which inhibit the production of lactate and pyruvate in SCs. This also leads to the decrease of energy supply of SCs to spermatogenic cells, damages to reproductive system.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Estrogênios não Esteroides/toxicidade , Ácido Láctico/metabolismo , Células de Sertoli/efeitos dos fármacos , Zearalenona/toxicidade , Animais , Metabolismo Energético/efeitos dos fármacos , Glicólise/efeitos dos fármacos , Glicólise/genética , Masculino , Ácido Pirúvico/metabolismo , Ratos , Células de Sertoli/metabolismo
17.
J Am Chem Soc ; 143(17): 6401-6406, 2021 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-33904721

RESUMO

Chiral propargylsilanes and chiral allenylsilanes have emerged as versatile building blocks for organic synthesis. However, efficient methods for preparing these organosilicon compounds are lacking. We herein report a highly enantioselective method for synthesis of chiral propargylsilanes and chiral allenylsilanes from readily available alkynyl sulfonylhydrazones. Specifically, chiral spiro phosphate dirhodium complexes were used to catalyze asymmetric insertion of alkynyl carbenes into the Si-H bonds of silanes to afford a variety of chiral propargylsilanes with excellent enantioselectivity. Subsequently, a platinum catalyst was used for stereospecific isomerization of the chiral propargylsilanes to the corresponding chiral allenylsilanes.

18.
Trop Anim Health Prod ; 53(2): 259, 2021 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-33852074

RESUMO

The aim of this study was to identify differentially expressed long non-coding RNAs (lncRNAs) molecules and predict their target genes related to muscle development and lipid metabolism in longissimus dorsi (LD) muscles of Bama Xiang pigs under constant heat stress. Ten male Bama Xiang pigs with an average initial body weight of 14 kg were randomly divided into control group (22°C) and heat stress (35 °C) group. The experiment lasted for 28 days. All the pigs were slaughtered at the end of the experiment, and LD muscles were collected for muscle quality analysis and transcriptome sequencing. Heat stress reduced meat quality of Bama Xiang pigs. lncRNAs in LD were identified systematically by deep RNA sequencing between the two groups. The results showed that 365 lncRNAs from the LD were identified, including 128 intergenic lncRNAs, 82 intronic lncRNAs, and 155 anti-sense lncRNAs. The differences lie in transcript of length, number of exons and wider size distribution, and expression level per KB fragment in three subtypes of lncRNAs. The three types of transposable elements coverage, including Line/L1, SINE/tRNA, and LTR/ERVL-MaLR, are the highest in mRNA and the three subtypes of lncRNAs in pigs. lncRNAs and mRNAs were different in comparison of features. The results predicted the target genes of the significant differentially expressed lncRNAs related to muscle development and lipid metabolism. This is the first study to expand the knowledge about muscle-related lncRNAs biology in Bama Xiang pigs under heat stress and will contribute to the development of alleviating the adverse effects of heat stress on pork quality targeting lncRNAs.


Assuntos
RNA Longo não Codificante , Animais , Resposta ao Choque Térmico , Masculino , Desenvolvimento Muscular , Músculo Esquelético , Análise de Sequência de RNA/veterinária , Suínos/genética
19.
Neurotox Res ; 39(4): 1103-1115, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33689146

RESUMO

Although many studies have reported toxic effects of cadmium (Cd) and lead (Pb) in the central nervous system, few studies have investigated the combined toxicity of Cd and Pb. The mechanisms by which these combined heavy metals induce toxicity, as well as effective means to exert neuroprotection from these agents, remain poorly understood. To investigate the protective effects of alpha-lipoic acid (α-LA) on Cd- and/or Pb-induced cortical damage in rats, 48 Sprague-Dawley rats were exposed to drinking water containing 50 mg/L of Cd and/or 300 mg/L of Pb for 12 weeks, in the presence or absence of α-LA co-treatment (50 mg/kg) via gavage. We observed that exposure to Cd and/or Pb decreased the brain weight/body weight ratio and increased Cd and/or Pb contents as well as ultrastructural damage to the cerebral cortex. Cd and/or Pb also induced endoplasmic-reticulum (ER) stress and activated Fas (CD95/APO-1)/Fas ligand (FasL) and mitochondrial apoptotic pathways. Furthermore, co-treatment of Cd and Pb further exacerbated part of these phenotypes than treatment of Cd or Pb alone. However, simultaneous supplementation with α-LA attenuated Cd and/or Pb-induced neurotoxicity by increasing the brain weight/body weight ratio, reducing Cd and/or Pb contents, ameliorating both nuclear/mitochondrial damage and ER stress, and attenuating activation of Fas/FasL and mitochondrial apoptotic pathways. Collectively, our results indicate that the accumulation of Cd and/or Pb causes cortical damage and that α-LA exerts protection against Cd- and/or Pb-induced neurotoxicity. These findings highlight that α-LA may be exploited for the treatment and prevention of Cd- and/or Pb-induced neurotoxicity.

20.
Ecotoxicol Environ Saf ; 214: 112058, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33714136

RESUMO

Nuclear factor erythroid 2-related factor 2 (Nrf2) is a nuclear transcription factor of great concern which is widely involved in physiological and pathological processes of the organism, but the role and regulatory mechanism of Nrf2 in kidney exposed to cadmium (Cd) remain largely unknown. Here we demonstrated that Cd exposure induced injury in primary rat proximal tubular (rPT) cells and NRK-52E cell line, which was accompanied by autophagic flux blockade and subsequent accumulation of p62. Cd-activated nucleus translocation of Nrf2 depended on p62, which promoted antioxidant genes transcription, but it failed to against Cd-induced cell injury and ultimately succumbed to Cd toxicity. CDDO Methyl Ester (CDDO-ME) or ML385 treatment aggravated or alleviated rPT cells injury induced by Cd respectively, indicating that Nrf2 nucleus translocation played a negative role during Cd-induced rPT cells injury. Phosphorylation of 5' AMP-activated protein kinase (AMPK) decreased together with enhanced Nrf2 nucleus translocation in rPT cells exposed to Cd. Dephosphorylation of AMPK induced by Cd were facilitated or restored by CDDO-ME or ML385 treatment, which confirmed AMPK is a downstream factor of Nrf2. Simultaneously, CDDO-ME further enhanced Phosphorylation of mTOR and AKT which increased during Cd exposure. While, Cd-induced phosphorylation of mTOR and AKT were reversed by ML385 treatment. These results illustrated that Cd mediated Nrf2 nucleus translocation depends on p62 accumulation which results from autophagic flux inhibition. The enhanced nucleus translocation of Nrf2 suppresses phosphorylation of AMPK to inactivate AKT/mTOR signaling, and results in rPT cells injury finally.


Assuntos
Cádmio/toxicidade , Poluentes Ambientais/toxicidade , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Antioxidantes/metabolismo , Autofagia/efeitos dos fármacos , Núcleo Celular/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Túbulos Renais Proximais/citologia , Túbulos Renais Proximais/metabolismo , Túbulos Renais Proximais/patologia , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo
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