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1.
Mar Drugs ; 22(2)2024 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-38393030

RESUMO

Sargassaceae, the most abundant family in Fucales, was recently formed through the merging of the two former families Sargassaceae and Cystoseiraceae. It is widely distributed in the world's oceans, notably in tropical coastal regions, with the exception of the coasts of Antarctica and South America. Numerous bioactivities have been discovered through investigations of the chemical diversity of the Sargassaceae family. The secondary metabolites with unique structures found in this family have been classified as terpenoids, phlorotannins, and steroids, among others. These compounds have exhibited potent pharmacological activities. This review describes the new discovered compounds from Sargassaceae species and their associated bioactivities, citing 136 references covering from March 1975 to August 2023.


Assuntos
Phaeophyceae , Humanos , Oceanos e Mares , Regiões Antárticas
2.
Artigo em Inglês | MEDLINE | ID: mdl-38401094

RESUMO

Objective: This study aims to evaluate the efficacy of interventional treatment in patients with hypoperfusion cerebral infarction in the territory of the lenticulostriate arteries caused by middle cerebral artery (MCA) stenosis. Methods: A prospective, single-center, non-blinded research design was employed to assess the efficacy of interventional treatment for hypoperfusion cerebral infarction in the territory of the lenticulostriate arteries caused by MCA stenosis. Clinical and surgical data were collected from patients with MCA atherosclerotic disease who underwent interventional therapy at our hospital between January 2020 and December 2022. The intervention group consisted of 8 patients meeting the criteria for hypoperfusion cerebral infarction caused by MCA stenosis, while the control group comprised 8 patients with hypoperfusion cerebral infarction caused by middle cerebral artery stenosis who received conventional treatment. Clinical and imaging characteristics, perioperative complications, and follow-up outcomes were compared between the two groups. Results: Pre-intervention cerebral perfusion imaging revealed significantly prolonged rMTT and rTTP, decreased rCBF, and altered rCBV within the territory of the lenticulostriate arteries in all 8 patients. Follow-up imaging showed restoration of blood flow and comparable perfusion to the healthy contralateral side. A case demonstrating successful restoration of vessel patency, good recovery, and absence of complications was presented. Both groups had favorable outcomes during follow-up, with no cases of stroke, transient ischemic attack (TIA), or death in the perioperative period. There were no significant differences in relative perfusion parameters, NIHSS scores, and mRS scores between the two groups. Conclusion: Interventional treatment demonstrates good efficacy and low risk of complications in treating cortical watershed cerebral infarction caused by middle cerebral artery stenosis. It is an effective and safe alternative to conventional treatment.

3.
Ecotoxicol Environ Saf ; 259: 115023, 2023 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-37201425

RESUMO

In highly intensive greenhouse vegetable production, soil acidification was caused by excessive fertilization, increasing cadmium (Cd) concentrations in the vegetables, which bears environmental hazards and is a negative influence on vegetables and humans. Transglutaminases (TGases), a central mediator for certain physiological effects of polyamines (PAs) in the plant kingdom, play important roles in plant development and stress response. Despite increased research on the crucial role of TGase in protecting against environmental stresses, relatively little is known about the mechanisms of Cd tolerance. In this study, we found, TGase activity and transcript level, which was upregulated by Cd, and TGase-induced Cd tolerance related to endogenous bound PAs increase and formation of nitric oxide (NO). Plant growth of tgase mutants was hypersensitive to Cd, chemical complementation by putrescine, sodium nitroprusside (SNP, nitric oxide donor) or gain of function TGase experiments restore Cd tolerance. α-diflouromethylornithine (DFMO, a selective ODC inhibitor) and 2-4-carboxyphenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (cPTIO, NO scavenger), were respectively found declined drastically endogenous bound PA and NO content in TGase overexpression plants. Likewise, we reported that TGase interacted with polyamine uptake protein 3 (Put3), and the silencing of Put3 largely reduced TGase-induced Cd tolerance and bound PAs formation. This salvage strategy depends on TGase-regulated synthesis of bound PAs and NO that is able to positively increase the concentration of thiol and phytochelatins, elevate Cd in the cell wall, as well as induce the levels of expression Cd uptake and transport genes. Collectively, these findings indicate that TGase-mediated enhanced levels of bound PA and NO acts as a vital mechanism to protect the plant from Cd-caused toxicity.


Assuntos
Óxido Nítrico , Solanum lycopersicum , Cádmio/toxicidade , Cádmio/metabolismo , Parede Celular/metabolismo , Óxido Nítrico/metabolismo , Fitoquelatinas , Plantas/metabolismo , Poliaminas/farmacologia , Solanum lycopersicum/genética
4.
Int J Mol Sci ; 24(5)2023 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-36902274

RESUMO

Daylily (Hemerocallis citrina Baroni) is an edible plant widely distributed worldwide, especially in Asia. It has traditionally been considered a potential anti-constipation vegetable. This study aimed to investigate the anti-constipation effects of daylily from the perspective of gastro-intestinal transit, defecation parameters, short-chain organic acids, gut microbiome, transcriptomes and network pharmacology. The results show that dried daylily (DHC) intake accelerated the defecation frequency of mice, while it did not significantly alter the levels of short-chain organic acids in the cecum. The 16S rRNA sequencing showed that DHC elevated the abundance of Akkermansia, Bifidobacterium and Flavonifractor, while it reduced the level of pathogens (such as Helicobacter and Vibrio). Furthermore, a transcriptomics analysis revealed 736 differentially expressed genes (DEGs) after DHC treatment, which are mainly enriched in the olfactory transduction pathway. The integration of transcriptomes and network pharmacology revealed seven overlapping targets (Alb, Drd2, Igf2, Pon1, Tshr, Mc2r and Nalcn). A qPCR analysis further showed that DHC reduced the expression of Alb, Pon1 and Cnr1 in the colon of constipated mice. Our findings provide a novel insight into the anti-constipation effects of DHC.


Assuntos
Constipação Intestinal , Hemerocallis , Laxantes , Animais , Camundongos , Constipação Intestinal/terapia , Microbioma Gastrointestinal , Hemerocallis/química , Farmacologia em Rede , RNA Ribossômico 16S , Laxantes/química , Laxantes/farmacologia , Laxantes/uso terapêutico , Ceco/efeitos dos fármacos
5.
Toxicol Appl Pharmacol ; 434: 115820, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34896432

RESUMO

Arsenic is a well-known environmental pollutant due to its toxicity, which can do harm to animals and human. Curcumin is a polyphenolic compound derived from turmeric, commonly accepted to have antioxidant properties. However, whether curcumin can ameliorate the damage caused by arsenic trioxide (ATO) in duck skeletal muscle remains largely unknown. Therefore, the present study aims to investigate the potential molecular mechanism of curcumin against ATO-induced skeletal muscle injury. The results showed that treating with curcumin could attenuate body weight loss induced by ATO and reduced arsenic content accumulation in the skeletal muscle of duck. Curcumin was also able to alleviated the oxidative stress triggered by ATO, which was manifested by the increase of T-AOC and SOD, and MDA decrease. Moreover, we observed that curcumin could ease mitochondrial damage and vacuolate degeneration of nucleus. Our further investigation found that ATO disrupted normal mitochondrial fission/fusion (Drp1, OPA1, Mfn1/2) and restrained mitochondrial biogenesis (PGC-1α, Nrf1/2, TFAM), while curcumin could promote mitochondrial fusion and activated PGC-1α pathway. Furthermore, curcumin was found that it could not only reduce the mRNA and protein levels of mitophagy (PINK1, Parkin, LC3, p62) and pro-apoptotic genes (p53, Bax, Caspase-3, Cytc), but also increased the levels of anti-apoptotic genes (Bcl-2). In conclusion, curcumin was able to alleviate ATO-induced skeletal muscle damage by improving mitophagy and preserving mitochondrial function, which can serve as a novel strategy to take precautions against ATO toxicity.


Assuntos
Arsênio/toxicidade , Curcumina/uso terapêutico , Mitocôndrias/efeitos dos fármacos , Doenças Musculares/induzido quimicamente , Proteínas Quinases/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Animais , Anti-Inflamatórios não Esteroides/uso terapêutico , Biologia Computacional , Patos , Poluentes Ambientais/uso terapêutico , Regulação da Expressão Gênica/efeitos dos fármacos , Mitocôndrias/metabolismo , Mitofagia/efeitos dos fármacos , Músculo Esquelético/efeitos dos fármacos , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Proteínas Quinases/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ubiquitina-Proteína Ligases/genética
6.
Mar Drugs ; 20(2)2022 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-35200643

RESUMO

Methicillin-resistant Staphylococcus aureus (MRSA) is highly concerning as a principal infection pathogen. The investigation of higher effective natural anti-MRSA agents from marine Streptomyces parvulus has led to the isolation of actinomycin D, that showed potential anti-MRSA activity with MIC and MBC values of 1 and 8 µg/mL, respectively. Proteomics-metabolomics analysis further demonstrated a total of 261 differential proteins and 144 differential metabolites induced by actinomycin D in MRSA, and the co-mapped correlation network of omics, indicated that actinomycin D induced the metabolism pathway of producing the antibiotic sensitivity in MRSA. Furthermore, the mRNA expression levels of the genes acnA, ebpS, clfA, icd, and gpmA related to the key differential proteins were down-regulated measured by qRT-PCR. Molecular docking predicted that actinomycin D was bound to the targets of the two key differential proteins AcnA and Icd by hydrogen bonds and interacted with multiple amino acid residues of the proteins. Thus, these findings will provide a basic understanding to further investigation of actinomycin D as a potential anti-MRSA agent.


Assuntos
Antibacterianos/farmacologia , Dactinomicina/farmacologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Streptomyces/metabolismo , Antibacterianos/isolamento & purificação , Proteínas de Bactérias/metabolismo , Dactinomicina/isolamento & purificação , Metabolômica , Testes de Sensibilidade Microbiana , Simulação de Acoplamento Molecular , Proteômica
7.
Mar Drugs ; 20(5)2022 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-35621983

RESUMO

Marine fungi represent an important and sustainable resource, from which the search for novel biological substances for application in the pharmacy or food industry offers great potential. In our research, novel polysaccharide (AUM-1) was obtained from marine Aureobasidium melanogenum SCAU-266 were obtained and the molecular weight of AUM-1 was determined to be 8000 Da with 97.30% of glucose, 1.9% of mannose, and 0.08% galactose, owing to a potential backbone of α-D-Glcp-(1→2)-α-D-Manp-(1→4)-α-D-Glcp-(1→6)-(SO3-)-4-α-D-Glcp-(1→6)-1-ß-D-Glcp-1→2)-α-D-Glcp-(1→6)-ß-D-Glcp-1→6)-α-D-Glcp-1→4)-α-D-Glcp-6→1)-[α-D-Glcp-4]26→1)-α-D-Glcp and two side chains that consisted of α-D-Glcp-1 and α-D-Glcp-(1→6)-α-D-Glcp residues. The immunomodulatory effect of AUM-1 was identified. Then, the potential molecular mechanism by which AUM-1 may be connected to ferroptosis was indicated by metabonomics, and the expression of COX2, SLC7A11, GPX4, ACSL4, FTH1, and ROS were further verified. Thus, we first speculated that AUM-1 has a potential effect on the ferroptosis-related immunomodulatory property in RAW 264.7 cells by adjusting the expression of GPX4, regulated glutathione (oxidative), directly causing lipid peroxidation owing to the higher ROS level through the glutamate metabolism and TCA cycle. Thus, the ferroptosis related immunomodulatory effect of AUM-1 was obtained.


Assuntos
Ferroptose , Aureobasidium , Configuração de Carboidratos , Sequência de Carboidratos , Fungos , Polissacarídeos/farmacologia , Espécies Reativas de Oxigênio
8.
Ecotoxicol Environ Saf ; 246: 114177, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36244176

RESUMO

Oxidative stress in plants caused by UV-B stress has always been a great challenge to the yield of agricultural products. Carbon dots (CDs) with enzyme-like activity have been developed, and inhibiting oxidative stress in animals has been achieved, but little is known about abiotic stress resistance in plants, especially UV-B stress. In this study, CDs were synthesized from Scutellaria baicalensis via a hydrothermal method. The ability of CDs to scavenge reactive oxygen species (ROS) in vivo and in vitro and to enhance antioxidant resistance in vivo was evaluated. The results show that CDs promoted the nutrient assimilation ability of lettuce seedlings and protected the plants from UV-B stress by increasing the activities of superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), glutathione reductase (GR), and ascorbate peroxidase (APX). Moreover, the antioxidant metabolism of plants can be activated by CDs and the expression levels of aquaporin (AQP) genes PIP1 and PIP2 are also up-regulated. These results facilitate the design and fabrication of CDs to meet the challenge of abiotic stress in food production.


Assuntos
Antioxidantes , Lactuca , Lactuca/metabolismo , Antioxidantes/metabolismo , Scutellaria baicalensis/metabolismo , Carbono/metabolismo , Catalase/metabolismo , Ascorbato Peroxidases/metabolismo , Superóxido Dismutase/metabolismo , Estresse Oxidativo , Espécies Reativas de Oxigênio/metabolismo
9.
Int J Mol Sci ; 23(11)2022 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-35682691

RESUMO

Flowering Chinese cabbage (Brassica campestris L. ssp. chinensis var. utilis Tsen et Lee) is one of the most popular vegetables in China. However, the loss of the functional ingredients in postharvest flowering Chinese cabbage during storage is still serious, owing to the unclear causes of the metabolic shifts. Herein, benzoic acid, chlorine dioxide, and 1-methylcyclopropene (1-MCP) could maintain the quality of postharvest flowering Chinese cabbage, and 1-MCP showed the best effect. Furthermore, transcript-metabolite profiling of the treatments revealed a transcript-metabolite correlation network of the flavonoid biosynthesis pathways with a range of 3 to 3662 differentially expressed genes (DEGs) and a range of 23 to 37 differentially accumulated metabolites (DAMs). Surprisingly, 1-MCP had the best effect on shelf life among the treatments, although chlorine dioxide could stimulate the expression of four critical differential genes (Bra007142, Bra008792, Bra009358, and Bra027457) involved in delaying flavonoid degradation (hesperetin, chalcone, rutin, baicalein). As a result, our findings will help to improve our understanding of the regulation of flavonoid production in relation to the quality of postharvest flowering Chinese cabbage during storage.


Assuntos
Brassica , Flavonoides , Ácido Benzoico , Brassica/genética , Compostos Clorados , Ciclopropanos , Flavonoides/metabolismo , Flavonoides/farmacologia , Regulação da Expressão Gênica de Plantas , Óxidos
10.
Molecules ; 27(14)2022 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-35889255

RESUMO

Dietary phytochemicals play an important role in the prevention and treatment of colon cancer. It is reported that group B of soyasaponin, derived from dietary pulses, has anti-colonic effects on some colon cancer cell lines. However, it is uncertain which specific soybean saponins play a role. In our study, as one of the group B soyasaponin, the anti-colon cancer activity of soyasaponins I (SsI) was screened, and we found that it had the inhibitory effect of proliferation on colon cancer cell lines HCT116 (IC50 = 161.4 µM) and LoVo (IC50 = 180.5 µM), but no effect on HT29 between 0-200 µM. Then, nine potential targets of SsI on colon cancer were obtained by network pharmacology analysis. A total of 45 differential metabolites were identified by metabolomics analysis, and the KEGG pathway was mainly enriched in the pathways related to the absorption and metabolism of amino acids. Finally, molecular docking analysis predicted that SsI might dock with the protein of DNMT1, ERK1. The results indicated that the effect of SsI on HCT116 might be exerted by influencing amino acid metabolism and the estrogen signaling pathway. This study may provide the possibility for the application of SsI against colon cancer.


Assuntos
Neoplasias do Colo , Ácido Oleanólico , Saponinas , Neoplasias do Colo/tratamento farmacológico , Humanos , Simulação de Acoplamento Molecular , Ácido Oleanólico/análogos & derivados , Ácido Oleanólico/farmacologia , Compostos Fitoquímicos/farmacologia , Saponinas/farmacologia
11.
J Sci Food Agric ; 102(7): 2855-2863, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-34741307

RESUMO

BACKGROUND: Pea sprouts are considered a healthy food. Sucrose is a key nutritional factor affecting taste and flavor. Meanwhile, selenium (Se) is an essential micronutrient that plays multiple roles in wide variety of physiological processes and improves crop quality and nutritional value. Nonetheless, the effects of the combination of sucrose and Se treatment on growth, quality, and sugar metabolism of pea sprouts have not been explored. RESULTS: The results revealed that sucrose at 10 mg L-1 obviously increased fresh weight, vitamin C, soluble protein, soluble sugar, fructose, glucose, and sucrose contents. Se treatments also improved nutritional quality, but higher Se (2.5 mg L-1 ) significantly inhibited the growth of seedlings. Interestingly, the combined application of sucrose (10 mg L-1 ) and Se (1.25 mg L-1 ) could effectively promote vitamin C, sucrose, and fructose contents, especially the Se content, compared with Se application alone. Additionally, there were significant differences in the regulation of sugar metabolism between Se alone and combined application of sucrose and Se. Acid invertase and neutral invertase play a pivotal role in the accumulation of soluble sugar under Se treatments alone, and acid invertase might be the key enzyme to limit sugar accumulation under combined application of sucrose and Se. CONCLUSION: The moderate combined application of sucrose (10 mg L-1 ) and Se (1.25 mg L-1 ) more effectively regulated sugar metabolism and improved nutritional quality than Se application alone did. © 2021 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.


Assuntos
Selênio , Sacarose , Ácido Ascórbico , Metabolismo dos Carboidratos , Carboidratos , Frutose/metabolismo , Pisum sativum/metabolismo , Selênio/metabolismo , Sacarose/metabolismo , Açúcares , beta-Frutofuranosidase/metabolismo
12.
Ecotoxicol Environ Saf ; 228: 112965, 2021 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-34775344

RESUMO

Arsenic trioxide (ATO) has confirmed as a global pollutant, the toxic effect of which was not fully understood and lack effective therapies to against its associated toxicities. Curcumin (Cur) is a beneficial natural pigment for its antioxidant and anti-inflammatory properties. The purpose of this paper was to illustrate the antagonism of Cur against ATO-induced neurotoxicity. A total of 40 ducks were divided randomly into 4 groups and conducted via bite and sup for 28 days: control group (Control); 2 mg/kg ATO group (Low ATO); 4 mg/kg ATO group (Middle ATO); 8 mg/kg ATO group (High ATO); 400 mg/kg Cur group + 8 mg/kg ATO (Cur+ATO). The results showed that ATO exposure can hinder the duck growth and arsenic element accumulation rate increased in a dose-dependent manner. We observed neuronal shrinkage and vacuolize of HE staining in the ATO-treated group. In addition, SOD activity and T-AOC level reduced while MDA content increased in the ATO-exposed group. ATO exposure can decrease the expression of anti-oxidation related mRNA and proteins (Nrf2, SOD-1, GPX-1, CAT, Trx and HO-1) and anti-inflammatory makers (IL-4, IL-10), increased the expression of Keap1, NF-κB and pro-inflammatory makers (TNF-α, IL-1ß, IL-18, IL-2, IL-6, INOS and COX-2). ATO treated might cause blood-brain barrier (BBB) damage through degradation of the tight junction proteins (TJs) occludin and ZO-1. Importantly, the experimental results also showed that Cur can alleviate oxidative stress, inflammatory response and BBB injury caused by ATO exposure through Nrf2 and NF-κB signaling pathway. The results suggested Cur exerted as a food additive and provided novel potential benefits of ATO toxicology in inflammation of the brain.

13.
Ecotoxicol Environ Saf ; 219: 112350, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34022626

RESUMO

Arsenic trioxide (ATO) has been known as common environmental pollution, and is deemed to a threat to global public health. Curcumin (Cur) is a phytoconstituent, which has been demonstrated to have antioxidant effects. In the current experiment, we investigated the efficacy of Cur against ATO-induced kidney injury and explored the potential molecular mechanisms that have not yet been fully elucidated in ducks. The results showed that treatment with Cur attenuated ATO-induced body weight loss, reduced the content of ATO in the kidney, and improved ATO-induced kidney pathological damage. Cur also remarkably alleviated the ascent of ATO-induced MDA level and activated the Nrf2 pathway. Using the TEM, we found Cur relieved mitochondrial swelling, autolysosomes generating and nuclear damage. Simultaneously, Cur was found that it not only significantly reduced autophagy-related mRNA and protein levels (mTOR, LC3-Ⅰ, LC3-Ⅱ, Atg-5, Beclin1, Pink1 and Parkin) and but also decreased apoptosis-related mRNA and protein expression levels (cleaved caspase-3, Cytc, p53 and Bax). Furthermore, through nontargeted metabolomics analysis, we observed that lipid metabolism balance was disordered by ATO exposure, while Cur administration alleviated the disturbance of lipid metabolism. These results showed ATO could induce autophagy and apoptosis by overproducing ROS in the kidney of ducks, and Cur might relieve excessive autophagy, apoptosis and disturbance of lipid metabolism by regulating oxidative stress. Collectively, our findings explicate the potential therapeutic value of Cur as a new strategy to a variety of disorders caused by ATO exposure.


Assuntos
Trióxido de Arsênio/toxicidade , Curcumina/farmacologia , Substâncias Protetoras/farmacologia , Animais , Antioxidantes/metabolismo , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Patos/metabolismo , Dislipidemias/metabolismo , Rim/efeitos dos fármacos , Nefropatias/induzido quimicamente , Estresse Oxidativo/efeitos dos fármacos , Serina-Treonina Quinases TOR
14.
Ecotoxicol Environ Saf ; 220: 112394, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34091186

RESUMO

Arsenic (As) and antimony (Sb) are known as an environmental contaminant with cardiotoxicity properties. The endoplasmic reticulum (ER) is the largest calcium reservoir in the cell, and its calcium homeostasis disorder plays a vital role in endoplasmic reticulum stress (ERS) and apoptosis. The objective of this study was to investigate whether As and Sb induced apoptosis via endoplasmic reticulum stress (ERS) linked to calcium homeostasis disturbance. In this study, thirty-two adult mice were gavage-fed daily with As2O3 (4 mg/kg), SbCl3 (15 mg/kg) and co-treat with SbCl3 (15 mg/kg) and As2O3 (4 mg/kg) daily for 60 days. It was observed that As or/and Sb caused histopathological lesions and ER expansion of the heart. Meanwhile, the gene expression of ER Ca2+ release channels (RyR2 and IP3R) and calmodulin-dependent protein kinase II (CaMKII) increased while the levels of mRNA and protein of ER Ca2+ uptake channel (SERCA2) downregulated significantly compared to the controls. Then, As or/and Sb induced ERS and triggered the ER apoptotic pathway by activating unfolded protein response (UPR)-associated genes ((PERK, ATF6, IRE1, XBP1, JNK, GRP78), and apoptosis-related genes (Caspase12, Caspase3, p53, CHOP). Above indicators in As + Sb group became more severe than that of As group and Sb group. Overall, our results proved that the cardiotoxicity caused by As or/and Sb might be concerning disturbing calcium homeostasis, which induced apoptosis through the ERS pathway.


Assuntos
Antimônio/toxicidade , Arsênio/toxicidade , Cálcio/metabolismo , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Retículo Endoplasmático/efeitos dos fármacos , Coração/efeitos dos fármacos , Animais , Antimônio/metabolismo , Apoptose , Arsênio/metabolismo , Canais de Cálcio/metabolismo , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Cardiotoxicidade/metabolismo , Cardiotoxinas , Caspase 3/metabolismo , Morte Celular , Regulação para Baixo , Retículo Endoplasmático/metabolismo , Chaperona BiP do Retículo Endoplasmático , Poluentes Ambientais/toxicidade , Homeostase/efeitos dos fármacos , Masculino , Metais Pesados/toxicidade , Camundongos , Miocárdio/metabolismo , Miocárdio/patologia , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/metabolismo , Resposta a Proteínas não Dobradas
15.
Int J Mol Sci ; 22(22)2021 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-34830114

RESUMO

Staphylococcus aureus (S. aureus) is a common pathogen that causes various serious diseases, including chronic infections. Discovering new antibacterial agents is an important aspect of the pharmaceutical field because of the lack of effective antibacterial drugs. In our research, we found that one anti-S. aureus substance is actinomycin D, originating from Streptomyces parvulus (S. parvulus); then, we further focused on the anti-S. aureus ability and the omics profile of S. aureus in response to actinomycin D. The results revealed that actinomycin D had a significant inhibitory activity on S. aureus with a minimum inhibitory concentration (MIC) of 2 µg/mL and a minimum bactericidal concentration (MBC) of 64 µg/mL. Bacterial reactive oxygen species (ROS) increased 3.5-fold upon treatment with actinomycin D, as was measured with the oxidation-sensitive fluorescent probe DCFH-DA, and H2O2 increased 3.5 times with treatment by actinomycin D. Proteomics and metabolomics, respectively, identified differentially expressed proteins in control and treatment groups, and the co-mapped correlation network of proteomics and metabolomics annotated five major pathways that were potentially related to disrupting the energy metabolism and oxidative stress of S. aureus. All findings contributed to providing new insight into the mechanisms of the anti-S. aureus effects of actinomycin D originating from S. parvulus.


Assuntos
Antibacterianos/farmacologia , Dactinomicina/farmacologia , Metabolômica , Proteômica , Espécies Reativas de Oxigênio/metabolismo , Staphylococcus aureus/metabolismo , Streptomyces/química , Antibacterianos/química , Dactinomicina/química
16.
Cancer Cell Int ; 20(1): 561, 2020 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-33292235

RESUMO

BACKGROUND: EGFR tyrosine kinase inhibitors (TKIs) have been developed for the treatment of EGFR mutated NSCLC. Parthenolide, a natural product of parthenolide, which belongs to the sesquiterpene lactone family and has a variety of biological and therapeutic activities, including anti-cancer effects. However, its effect on non-small cell lung cancer is little known. METHODS: The CCK8 assay and colony formation assays were used to assess cell viability. Flow cytometry was used to measure the cell apoptosis. In silico molecular docking was used to evaluate the binding of parthenolide to EGFR. Network pharmacology analysis was was used to evaluate the key gene of parthenolide target NSCLC. Western blotting was used to evaluate the key proteins involved apoptosis and EGFR signalling. The effect of parthenolide treatment in vivo was determined by using a xenograft mouse model. RESULTS: In this study, parthenolide could induce apoptosis and growth inhibition in the EGFR mutated lung cancer cells. Parthenolide also reduces the phosphorylation of EGFR as well as its downstream signaling pathways MAPK/ERK and PI3K/Akt. Molecular docking analysis of EGFR binding site with parthenolide show that the anti-cancer effect of parthenolide against NSCLC is mediated by a strong binding to EGFR. Network pharmacology analysis show parthenolide suppresses NSCLC via inhibition of EGFR expression. In addition, parthenolide inhibits the growth of H1975 xenografts in nude mice, which is associated with the inhibition of the EGFR signaling pathway. CONCLUSIONS: Taken together, these results demonstrate effective inhibition of parthenolide in NSCLC cell growth by targeting EGFR through downregulation of ERK and AKT expression, which could be promisingly used for patients carrying the EGFR mutation.

17.
Ecotoxicol Environ Saf ; 190: 110158, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31918257

RESUMO

Copper (Cu) is an essential trace element for most organisms. However, excessive Cu can be highly toxic. The purpose of this study was to elucidate the mechanism underlying Cu toxicity in the kidneys of rats after treatment with CuCl2 (15 [control], 30, 60, or 120 mg/kg in the diet) for 180 days. Histological and ultrastructural changes, antioxidant enzyme activity, and the mRNA and protein levels of apoptosis and autophagy-related genes were measured. The results showed that Cu exposure led to significant accumulation of copper in kidneys and disorganized kidney morphology. The activities of total anti-oxidation capacity (T-AOC) and superoxide dismutase (SOD) in the kidneys decreased significantly, while the malondialdehyde (MDA) content increased. Furthermore, excessive Cu markedly upregulated the expression of autophagy and apoptosis-related genes (LC3A, LC3B, ATG-5, Beclin-1, Caspase3, CytC, P53, Bax), but downregulated the expression of P62, mTOR and BCL-2. Moreover, the LC3B/LC3A, ATG-5, Beclin-1, P53, Caspase3 proteins were up-regulated while P62 was down-regulated in the kidney tissues of the treatment groups. Overall, these findings provide strong evidence that excess Cu can trigger autophagy and apoptosis via the mitochondrial pathway by inducing oxidative stress in rat kidneys.


Assuntos
Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Cobre/toxicidade , Rim/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Animais , Antioxidantes/metabolismo , Proteínas Reguladoras de Apoptose/genética , Proteínas Reguladoras de Apoptose/metabolismo , Rim/metabolismo , Rim/patologia , Malondialdeído/metabolismo , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Ratos , Superóxido Dismutase/metabolismo
18.
Arch Microbiol ; 201(6): 757-767, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30840101

RESUMO

Bacteria in corals have been studied in detail in the past decades. However, the biodiversity and bioactivity of fungi in corals are still poorly understood. This study investigated the biodiversity and antifouling activity of fungi in soft corals Cladiella krempfi and Sarcophyton tortuosum from the South China Sea. A high diverse and abundant fungal community was found in the two soft corals. Furthermore, five isolates shared 83-95% similarity with their closest relatives, indicating that they might be novel species in genera Phaeoshaeria and Mucor. In addition, approximately 50% of the representative isolates exhibited distinct antifouling activity. In particular, isolates Fungal sp. SCAU132 and Fungal sp. SCAU133 displayed very strong antifouling activity against Bugula neritina, suggesting they can provide a potential resource for further investigation on isolation of novel antifouling metabolites. To our knowledge, this study is the first report to investigate the biodiversity and antifouling activity of fungi in C. krempfi and S. tortuosum.


Assuntos
Antozoários/microbiologia , Biodiversidade , Fungos/fisiologia , Animais , Antozoários/classificação , Incrustação Biológica , Briozoários/fisiologia , China , Fungos/classificação , Fungos/genética , Fungos/isolamento & purificação , Oceanos e Mares , Filogenia
19.
Int J Med Sci ; 16(8): 1078-1088, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31523169

RESUMO

Yunnan Baiyao (YB) as a kind of famous Chinese herbal medicine, possessed hemostatic, invigorating the circulation of blood, and anti-inflammatory effects. Identifying strategies to protect patients at risk for hospital-acquired pressure ulcers (HAPU) is essential. Herein, our results showed that YB treatment can effectively reduce the acne wound area and improve efficacy in a comparative study of 60 cases HAPU patients with S. aureus positive of acne wound pathogens. Furthermore, YB inhibited HIa expression and suppressed accessory gene regulator (agr) system controlled by regulatory RNA II and RNA III molecule using pALC1740, pALC1742 and pALC1743 S. aureus strain linked to gfpuvr reporter gene. Moreover, YB downregulated cao mRNA expression and inhibited coagulase activity by RT-PCR, slide and tube coagulase test. Additionally, YB downregulated seb, sec, sed, and tsst-1 mRNA expression to suppress enterotoxin and tsst-1 secretion and adhesion function related genes sarA, icaA, and cidA mRNA expression. Taken together, the data suggest that YB may reduce HAPU via suppressing virulence gene expression and biofilm formation of S. aureus.


Assuntos
Antibacterianos/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Úlcera por Pressão/tratamento farmacológico , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus/efeitos dos fármacos , Idoso , Animais , Proteínas de Bactérias/genética , Toxinas Bacterianas/genética , Biofilmes/efeitos dos fármacos , Feminino , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Proteínas Hemolisinas/genética , Humanos , Doença Iatrogênica , Masculino , Pessoa de Meia-Idade , Úlcera por Pressão/microbiologia , Coelhos , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/genética , Staphylococcus aureus/patogenicidade , Transativadores/genética , Resultado do Tratamento , Virulência/genética
20.
Int J Mol Sci ; 20(14)2019 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-31337149

RESUMO

Penicillium italicum is the principal pathogen causing blue mold of citrus. Searching for novel antifungal agents is an important aspect of the post-harvest citrus industry because of the lack of higher effective and low toxic antifungal agents. Herein, the effects of 2-methoxy-1,4-naphthoquinone (MNQ) on P. italicum and its mechanism were carried out by a series of methods. MNQ had a significant anti-P. italicum effect with an MIC value of 5.0 µg/mL. The label-free protein profiling under different MNQ conditions identified a total of 3037 proteins in the control group and the treatment group. Among them, there were 129 differentially expressed proteins (DEPs, up-regulated > 2.0-fold or down-regulated < 0.5-fold, p < 0.05), 19 up-regulated proteins, 26 down-regulated proteins, and 67 proteins that were specific for the treatment group and another 17 proteins that were specific for the control group. Of these, 83 proteins were sub-categorized into 23 hierarchically-structured GO classifications. Most of the identified DEPs were involved in molecular function (47%), meanwhile 27% DEPs were involved in the cellular component and 26% DEPs were involved in the biological process. Twenty-eight proteins identified for differential metabolic pathways by KEGG were sub-categorized into 60 classifications. Functional characterization by GO and KEGG enrichment results suggests that the DEPs are mainly related to energy generation (mitochondrial carrier protein, glycoside hydrolase, acyl-CoA dehydrogenase, and ribulose-phosphate 3-epimerase), NADPH supply (enolase, pyruvate carboxylase), oxidative stress (catalase, glutathione synthetase), and pentose phosphate pathway (ribulose-phosphate 3-epimerase and xylulose 5-phosphate). Three of the down-regulated proteins selected randomly the nitro-reductase family protein, mono-oxygenase, and cytochrome P450 were verified using parallel reaction monitoring. These findings illustrated that MNQ may inhibit P. italicum by disrupting the metabolic processes, especially in energy metabolism and stimulus response that are both critical for the growth of the fungus. In conclusion, based on the molecular mechanisms, MNQ can be developed as a potential anti-fungi agent against P. italicum.


Assuntos
Proteínas Fúngicas/metabolismo , Naftoquinonas/farmacologia , Penicillium/efeitos dos fármacos , Penicillium/metabolismo , Proteoma , Proteômica , Biologia Computacional/métodos , Proteínas Fúngicas/genética , Ontologia Genética , Anotação de Sequência Molecular , Naftoquinonas/química , Penicillium/genética , Proteômica/métodos
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