White mulberry Morus alba and jackfruit Artocarpus heterophyllus are two of seven chosen Vietnamese folk plants which showed the highest tyrosinase inhibition activity. Besides, both of them showed antioxidant and ant...White mulberry Morus alba and jackfruit Artocarpus heterophyllus are two of seven chosen Vietnamese folk plants which showed the highest tyrosinase inhibition activity. Besides, both of them showed antioxidant and antibacterial activities. Especially, the Sulforhodamine B (SRB) assay test result of the root core extract of M. alba figured out its non-toxicity on foreskin fibroblasts.展开更多
Melanocytes that form stratum basale of skin epidermis express tyrosinase enzyme, which catalyzes initial two rate-limiting steps in the biotransformation of tyrosine into dark pigment called melanin. Even today, Tyro...Melanocytes that form stratum basale of skin epidermis express tyrosinase enzyme, which catalyzes initial two rate-limiting steps in the biotransformation of tyrosine into dark pigment called melanin. Even today, Tyrosinase inhibitors are among the promising candidates in cosmetic industry for skin-lightening formulations. Overexpression of tyrosinase causes excess melanin biosynthesis and deposition resulting in dark skin color. Moreover, localized overexpression of tyrosinase cause variety of hyperpigmentation disorders like melanoma, melasma, chloasma, dark patches, liver patches, etc. There has been a renewed interest in the natural products as main ingredients in the formulation of safe products for skin-whitening and treatment options for hyperpigmentation disorders. In the present communication, the results of our investigations on tyrosinase inhibition, modulation of intracellular tyrosinase and melanin levels in cultured B16F10 melanoma cells by Bacopa monnieri (L.) methanol extract (BME) are presented and discussed as safe option for skin lightening and to treat hyperpigmentation disorders. BME showed 11%, 29%, 54% and 80% inhibition of mushroom tyrosinase activity at an initial 100, 200, 400 and 600 μg of extract. Treatment of α-melanocyte stimulating hormone (α-MSH) stimulated cultured murine melanoma B16F10 cells with 100 μg/ml of the extract showed a decrease in the levels of cellular melanin and cellular tyrosinase content by 22% and 46% respectively. The cytotoxicity studies by MTT assay revealed that the LC50 of the BME is ≥1000 μg/ml in cultured mouse melanoma B16F10 and HEK293 cells.展开更多
Epimedin B(EB)is one of the main flavonoid ingredients present in Epimedium brevicornum Maxim.,a traditional herb widely used in China.Our previous study showed that EB was a stronger inducer of melanogenesis and an a...Epimedin B(EB)is one of the main flavonoid ingredients present in Epimedium brevicornum Maxim.,a traditional herb widely used in China.Our previous study showed that EB was a stronger inducer of melanogenesis and an activator of tyrosinase(TYR).However,the role of EB in melanogenesis and the mechanism underlying the regulation remain unclear.Herein,as an extension to our previous investigation,we provide comprehensive evidence of EB-induced pigmentation in vivo and in vitro and elucidate the melanogenesis mechanism by assessing its effects on the TYR family of proteins(TYRs)in terms of expression,activity,and stability.The results showed that EB increased TYRs expression through microphthalmia-associated transcription factor-mediated p-Akt(referred to as protein kinase B(PKB))/glycogen synthase kinase 3β(GSK3β)/β-catenin,p-p70 S6 kinase cascades,and protein 38(p38)/mitogen-activated protein(MAP)kinase(MAPK)and extracellular regulated protein kinases(ERK)/MAPK pathways,after which EB increased the number of melanosomes and promoted their maturation for melanogenesis in melanoma cells and human primary melanocytes/skin tissues.Furthermore,EB exerted repigmentation by stimulating TYR activity in hydroquinone-and N-phenylthiourea-induced TYR inhibitive models,including melanoma cells,zebrafish,and mice.Finally,EB ameliorated monobenzone-induced depigmentation in vitro and in vivo through the enhancement of TYRs stability by inhibiting TYR misfolding,TYR-related protein 1 formation,and retention in the endoplasmic reticulum and then by downregulating the ubiquitination and proteolysis processes.These data conclude that EB can target TYRs and alter their expression,activity,and stability,thus stimulating their pigmentation function,which might provide a novel rational strategy for hypopigmentation treatment in the pharmaceutical and cosmetic industries.展开更多
Dysregulation of G9a,a histone-lysine N-methyltransferase,has been observed in Alzheimer’s disease and has been correlated with increased levels of chronic inflammation and oxidative stress.Likewise,microRNAs are inv...Dysregulation of G9a,a histone-lysine N-methyltransferase,has been observed in Alzheimer’s disease and has been correlated with increased levels of chronic inflammation and oxidative stress.Likewise,microRNAs are involved in many biological processes and diseases playing a key role in pathogenesis,especially in multifactorial diseases such as Alzheimer’s disease.Therefore,our aim has been to provide partial insights into the interconnection between G9a,microRNAs,oxidative stress,and neuroinflammation.To better understand the biology of G9a,we compared the global microRNA expression between senescence-accelerated mouse-prone 8(SAMP8)control mice and SAMP8 treated with G9a inhibitor UNC0642.We found a downregulation of miR-128 after a G9a inhibition treatment,which interestingly binds to the 3′untranslated region(3′-UTR)of peroxisome-proliferator activator receptor γ(PPARG)mRNA.Accordingly,Pparg gene expression levels were higher in the SAMP8 group treated with G9a inhibitor than in the SAMP8 control group.We also observed modulation of oxidative stress responses might be mainly driven Pparg after G9a inhibitor.To confirm these antioxidant effects,we treated primary neuron cell cultures with hydrogen peroxide as an oxidative insult.In this setting,treatment with G9a inhibitor increases both cell survival and antioxidant enzymes.Moreover,up-regulation of PPARγby G9a inhibitor could also increase the expression of genes involved in DNA damage responses and apoptosis.In addition,we also described that the PPARγ/AMPK axis partially explains the regulation of autophagy markers expression.Finally,PPARγ/GADD45αpotentially contributes to enhancing synaptic plasticity and neurogenesis after G9a inhibition.Altogether,we propose that pharmacological inhibition of G9a leads to a neuroprotective effect that could be due,at least in part,by the modulation of PPARγ-dependent pathways by miR-128.展开更多
Objective:To investigate the effect of TSH inhibition therapy in the postoperative management of patients with differentiated thyroid cancer.Methods:Seventy patients diagnosed with differentiated thyroid cancer were s...Objective:To investigate the effect of TSH inhibition therapy in the postoperative management of patients with differentiated thyroid cancer.Methods:Seventy patients diagnosed with differentiated thyroid cancer were selected for the study.TSH inhibition therapy was administered to the research group,while thyroxine replacement therapy was provided to the control group during the postoperative management phase.This allowed for a comparative analysis between the two groups.Results:In comparison with the control group,the research group exhibited significant decreases in serum TSH,T3,and T4 levels after treatment,while FT4 and FT3 levels significantly increased(P<0.05).Additionally,significant decreases in Tg,VEGF,TSGF,CD44V6,and sIL-2R levels were observed in the research group after treatment(P<0.05).No significant differences were found in pre-treatment thyroid function between the two groups(P>0.05).Conclusion:The application of TSH inhibition therapy in the postoperative management of patients with differentiated thyroid cancer demonstrates promising outcomes.展开更多
Tyrosinase is an important enzyme in controlling the formation of melanin in melanosome,and plays a key role in the pigmentation of hair and skin.The abnormal expression or activation of tyrosinase is associated with ...Tyrosinase is an important enzyme in controlling the formation of melanin in melanosome,and plays a key role in the pigmentation of hair and skin.The abnormal expression or activation of tyrosinase is associated with several diseases such as albinism,vitiligo,melanoma and Parkinson disease.Excessive deposition of melanin could cause diseases such as freckles and brown spots in the human body,and it is also closely related to browning of fruits and vegetables and insect molting.Detecting and inhibiting the activity of tyrosinase is of extraordinary value in the progress of diagnosis and treatment of these diseases.Therefore,many selective optical detection probes and small molecular inhibitors have been developed,and have made significant contributions to the basic and clinical research on these diseases.In this paper,the detection and inhibition of tyrosinase and their application in whitening products are reviewed,with special emphasis on development of fluorescent probes and inhibitors.Hopefully,this review will help design more efficient and sensitive tyrosinase probes and inhibitors,as well as shed light on novel treatment of diseases such as melanoma.展开更多
Dawson-type phosphotungstic polyoxometalate α/β-K6P2W18O62·10H2O(P2W18) was synthesized and its inhibitory effect on the mushroom tyrosinase was investigated. It could inhibit diphenolase activity of mushroom t...Dawson-type phosphotungstic polyoxometalate α/β-K6P2W18O62·10H2O(P2W18) was synthesized and its inhibitory effect on the mushroom tyrosinase was investigated. It could inhibit diphenolase activity of mushroom tyrosinase as an irreversible inhibitor. When the concentration of the enzyme reached 0.0176 mg/mL, the concentration of P2W18 leading to 50% activity lost(IC50) was 0.05 mmol/L for monophenolase and 0.64 mmol/L for diphenolase. In addition, the antimicrobial activity of P2W18 was evaluated by zone of inhibition test. The results show that P2W18 possesses effective antimicrobial ability against Escherichia coli, Bacillus subtilis, yeast, especially Escherichia coli and yeast.展开更多
Fibroblast activation protein(Fap)is a serine protease that degrades denatured type I collagen,α2-antiplasmin and FGF21.Fap is highly expressed in bone marrow stromal cells and functions as an osteogenic suppressor a...Fibroblast activation protein(Fap)is a serine protease that degrades denatured type I collagen,α2-antiplasmin and FGF21.Fap is highly expressed in bone marrow stromal cells and functions as an osteogenic suppressor and can be inhibited by the bone growth factor Osteolectin(Oln).Fap is also expressed in synovial fibroblasts and positively correlated with the severity of rheumatoid arthritis(RA).However,whether Fap plays a critical role in osteoarthritis(OA)remains poorly understood.Here,we found that Fap is significantly elevated in osteoarthritic synovium,while the genetic deletion or pharmacological inhibition of Fap significantly ameliorated posttraumatic OA in mice.Mechanistically,we found that Fap degrades denatured type II collagen(Col II)and Mmp13-cleaved native Col II.Intra-articular injection of r Fap significantly accelerated Col II degradation and OA progression.In contrast,Oln is expressed in the superficial layer of articular cartilage and is significantly downregulated in OA.Genetic deletion of Oln significantly exacerbated OA progression,which was partially rescued by Fap deletion or inhibition.Intra-articular injection of r Oln significantly ameliorated OA progression.Taken together,these findings identify Fap as a critical pathogenic factor in OA that could be targeted by both synthetic and endogenous inhibitors to ameliorate articular cartilage degradation.展开更多
The additive manufacturing(AM)of Ni-based superalloys has attracted extensive interest from both academia and industry due to its unique capabilities to fabricate complex and high-performance components for use in hig...The additive manufacturing(AM)of Ni-based superalloys has attracted extensive interest from both academia and industry due to its unique capabilities to fabricate complex and high-performance components for use in high-end industrial systems.However,the intense temperature gradient induced by the rapid heating and cooling processes of AM can generate high levels of residual stress and metastable chemical and structural states,inevitably leading to severe metallurgical defects in Ni-based superalloys.Cracks are the greatest threat to these materials’integrity as they can rapidly propagate and thereby cause sudden and non-predictable failure.Consequently,there is a need for a deeper understanding of residual stress and cracking mechanisms in additively manufactured Ni-based superalloys and ways to potentially prevent cracking,as this knowledge will enable the wider application of these unique materials.To this end,this paper comprehensively reviews the residual stress and the various mechanisms of crack formation in Ni-based superalloys during AM.In addition,several common methods for inhibiting crack formation are presented to assist the research community to develop methods for the fabrication of crack-free additively manufactured components.展开更多
Air nanobubbles(A-NBs)were used to inhibit the brass corrosion in circulating cooling water for the first time in the study.The results of mass loss method and electrochemical method showed that A-NBs had the obvious ...Air nanobubbles(A-NBs)were used to inhibit the brass corrosion in circulating cooling water for the first time in the study.The results of mass loss method and electrochemical method showed that A-NBs had the obvious corrosion inhibition effect.The inhibition rate reached 52%at 35℃.The impedance and surface characterization results of corrosion samples indicated that the corrosion inhibition mechanisms of A-NBs mainly included adsorption of corrosion ions,promoting the formation of the passivation film on metal surface and the formation of the bubble layer and scale film on metal surface.A-NBs are potential excellent corrosion inhibitors.展开更多
Drilling technologies based on oil-based drillingfluids and strong inhibitory saltwaterfluids are affected by draw-backs such as downhole accidents where sticking and wellbore instabilities occur.Existing polyamine dril...Drilling technologies based on oil-based drillingfluids and strong inhibitory saltwaterfluids are affected by draw-backs such as downhole accidents where sticking and wellbore instabilities occur.Existing polyamine drillingfluids also exhibit problems such as easy decomposition and poor inhibition performances.In order to mitigate these issues,additives can be used,such as polyamine inhibitors and the synthesis of nanometerfiltrate reducers.Tests conducted in the frame of this study with a polyamine drillingfluid and such additives show that thisfluid has the same inhibitory,plugging,lubricating,and wellbore-stability performances as oil-based drillingfluids.However,it has long-term anti-wear performances even better than those of oil-based drillingfluids.The out-comes of a series of comparisons with other sample cases(other wells)are reported and the advantages related to the proposedfluid discussed in detail.展开更多
By analyzing the corrosion of phosphate completion fluid on the P110 steel at 170 °C, the high-temperature corrosion mechanism of phosphate completion fluid was revealed, and a corrosion inhibition method by memb...By analyzing the corrosion of phosphate completion fluid on the P110 steel at 170 °C, the high-temperature corrosion mechanism of phosphate completion fluid was revealed, and a corrosion inhibition method by membrane transformation was proposed and an efficient membrane-forming agent was selected. Scanning electron microscope (SEM) images, X-ray energy spectrum and X-ray diffraction results were used to characterize the microscopic morphology, elemental composition and phase composition of the precipitation membrane on the surface of the test piece. The effect and mechanism of corrosion inhibition by membrane transformation were clarified. The phosphate completion fluid eroded the test piece by high-temperature water vapor and its hydrolyzed products to form a membrane of iron phosphate corrosion product. By changing the corrosion reaction path, the Zn2+ membrane-forming agent could generate KZnPO4 precipitation membrane with high temperature resistance, uniform thickness and tight crystal packing on the surface of the test piece, which could inhibit the corrosion of the test piece, with efficiency up to 69.63%. The Cu2+ membrane-forming agent electrochemically reacted with Fe to precipitate trace elemental Cu on the surface of the test piece, thus forming a protective membrane, which could inhibit metal corrosion, with efficiency up to 96.64%, but the wear resistance was poor. After combining 0.05% Cu2+ and 0.25% Zn2+, a composite protective membrane of KZnPO4 crystal and elemental Cu was formed on the surface of the test piece. The corrosion inhibition efficiency reached 93.03%, which ensured the high corrosion inhibition efficiency and generated a precipitation membrane resistant to temperature and wear.展开更多
The objective of this study is the phytochemical analysis and the determination of the antibacterial activity of aqueous and hydro-ethanolic extracts obtained from the leaves and bark of the trunk of Albizia zygia, ag...The objective of this study is the phytochemical analysis and the determination of the antibacterial activity of aqueous and hydro-ethanolic extracts obtained from the leaves and bark of the trunk of Albizia zygia, against Escherichia coli and Salmonella typhi bacteria in aquatic microcosms. Phytochemical screening was performed as described by Pareck. The results obtained show that the hydro-ethanolic and aqueous extracts of Albizia zygia trunk bark recorded higher extraction yields (26.71% and 33.2% respectively) compared to the aqueous and hydro-ethanolic extracts of leaves of the same plant. Secondary metabolites with antibacterial activities such as anthraquinones, anthocyanins, flavonoids, polyphenols, tannins and saponins were found in both types of extracts. Flavonoids and anthocyanins were relatively more abundant than the other chemical constituents. The highest cellular inhibition rate of Escherichia coli was 99.88%, obtained after 9 hours of exposure in the hydro-ethanolic extract solution of trunk bark at the concentration 1.5 g/L. The Salmonella typhi rate was 99.95% after 9 hours of exposure of bacterial cells to the hydro-ethanol extract of the bark of the trunk at the concentration 1.5 g/L. This rate increased proportionally with the bacterial-extract contact time. The temperature of the medium did not significantly influence bacterial inhibition (P > 0.05). The obtained results justify the use of the plant Albizia zygia in the reduction of the flow of bacterio-pollutants contained in water intended for consumption.展开更多
Objective:To investigate the effects and possible mechanisms of the combination of DMDD(2-dodecyl-6-methoxycyclohexa-2-5-diene-1-4-dione),a traditional Chinese medicine monomer,and sorafenib on the malignant biologica...Objective:To investigate the effects and possible mechanisms of the combination of DMDD(2-dodecyl-6-methoxycyclohexa-2-5-diene-1-4-dione),a traditional Chinese medicine monomer,and sorafenib on the malignant biological behavior of human hepatocellular carcinoma Huh7 cells.Methods:The experiment was divided into four groups:Huh7 cells control group,DMDD group,sorafenib group and DMDD and sorafenib combination group.The CCK-8 assay was used to measure the viability of Huh7 cells,and the Kim's formula was used to determine the synergistic effect.The plate cloning experiment was conducted to test colony formation ability of Huh7 cells.The scratch and Transwell experiments were performed to evaluate the migration ability and the invasion ability of Huh7 cells.The cell cycle of Huh7 cells was detected by flow cytometry.RT-qPCR and Western blot were used to measure the mRNA transcription level and protein expression level of PHGDH in the serine synthesis pathway.Results:The plate cloning experiment,scratch experiment,and Transwell migration experiment showed that the combined application of DMDD and Sorafenib significantly enhanced the inhibitory effect on the proliferation,migration,and invasion ability of Huh7 cells compared to the control group,DMDD group,and Sorafenib group(P<0.05).According to the Kim's formula,the combination of DMDD(final concentrations of 2,4,8μmol/L)and Sorafenib(final concentrations of 1,2,4μmol/L)had a synergistic inhibitory effect on the proliferation of Huh7 cells(Q>1.15).6,10μmol/L DMDD combined with 3,5μmol/L Sorafenib showed additive effect.The cell cycle of Huh7 cells was detected by flow cytometry,and the results showed that after 48 hours of drug intervention,the proportion of G2/M phase cells in the control group,DMDD group,Sorafenib group,and combination group were(10.63±0.32)%,(35.77±1.22)%,(30.03±2.22)%,and(38.97±0.60)%,respectively.Compared with the control group,the proportion of G2/M phase cells in the three groups significantly increased(P<0.0001).Compared with the Sorafenib group,the proportion of G2/M phase cells in the combination group significantly increased(P<0.0001).RT-qPCR and Western blot results showed that the combined application of DMDD and Sorafenib significantly inhibited the mRNA transcription level and protein expression level of PHGDH(P<0.05).Conclusion:The combined application of DMDD and Sorafenib has a synergistic effect that can enhance the inhibitory effect on the proliferation,invasion,and migration ability of Huh7 cells.The mechanism of this effect is related to the synergistic inhibition of the gene transcription and protein expression of PHGDH in the serine synthesis pathway.展开更多
Nonalcoholic fatty liver disease continues to be one of the major health challenges facing the world,with estimates of non-alcoholic steatohepatitis(NASH)prevalence in over 25 percent of the world’s population.NASH r...Nonalcoholic fatty liver disease continues to be one of the major health challenges facing the world,with estimates of non-alcoholic steatohepatitis(NASH)prevalence in over 25 percent of the world’s population.NASH represents a spectrum of disease that may lead to hepatic fibrosis and eventual cirrhosis,with the risk of cirrhosis decompensation,and hepatocellular carcinoma.New therapies are desperately needed for NASH,especially for later stages of fibrosis and cirrhosis.Galectin-3 inhibition is being explored as a new liver antifibrotic therapy.This concise review will outline the state of the art of this new therapeutic target.展开更多
Wet dust removal systems used to control dust in the polishing or grinding process of Mg alloy products are frequently associated with potential hydrogen explosion caused by magnesium-water reaction.For purpose of avo...Wet dust removal systems used to control dust in the polishing or grinding process of Mg alloy products are frequently associated with potential hydrogen explosion caused by magnesium-water reaction.For purpose of avoiding hydrogen explosion risks,we try to use a combination of chitosan(CS)and sodium phosphate(SP)to inhibit the hydrogen evolution reaction between magnesium alloy waste dust and water.The hydrogen evolution curves and chemical kinetics modeling for ten different mixing ratios demonstrate that 0.4wt%CS+0.1wt%SP yields the best inhibition efficiency with hydrogen generation rate of almost zero.SEM and EDS analyses indicate that this composite inhibitor can create a uniform,smooth,tight protective film over the surface of the alloy dust particles.FTIR and XRD analysis of the chemical composition of the surface film show that this protective film contains CS and SP chemically adsorbed on the surface of ZK60 but no detectable Mg(OH)_(2),suggesting that magnesium-water reaction was totally blocked.Our new method offers a thorough solution to hydrogen explosion by inhibiting the hydrogen generation of magnesium alloy waste dust in a wet dust removal system.展开更多
With the help of model experiments, we are able to offer a detailed proposal for the inhibition of DNA duplication and no inhibition of RNA viral infectivity. As a backbone, we introduced methyl phosphotriester (MPTE)...With the help of model experiments, we are able to offer a detailed proposal for the inhibition of DNA duplication and no inhibition of RNA viral infectivity. As a backbone, we introduced methyl phosphotriester (MPTE). Duplex formation according to the traditional Watson and Crick base-pairing: [(MPTE)<sub>n−1</sub> DNA] * DNA and [(MPTE)<sub>n−1</sub> DNA] * RNA, where n = number of DNA and RNA bases. However, in the latter case, inhibition is obtained by reduction of the number of MPTE linkages, as is confirmed with model experiments and under biological conditions with micro (mi)RNA substrates. The latter results have recently been published. One or more single MPTEs are disseminated over different places of DNA without neighbour MPTEs (Prof. Wen-Yih Chen and his group, Taiwan).展开更多
文摘White mulberry Morus alba and jackfruit Artocarpus heterophyllus are two of seven chosen Vietnamese folk plants which showed the highest tyrosinase inhibition activity. Besides, both of them showed antioxidant and antibacterial activities. Especially, the Sulforhodamine B (SRB) assay test result of the root core extract of M. alba figured out its non-toxicity on foreskin fibroblasts.
文摘Melanocytes that form stratum basale of skin epidermis express tyrosinase enzyme, which catalyzes initial two rate-limiting steps in the biotransformation of tyrosine into dark pigment called melanin. Even today, Tyrosinase inhibitors are among the promising candidates in cosmetic industry for skin-lightening formulations. Overexpression of tyrosinase causes excess melanin biosynthesis and deposition resulting in dark skin color. Moreover, localized overexpression of tyrosinase cause variety of hyperpigmentation disorders like melanoma, melasma, chloasma, dark patches, liver patches, etc. There has been a renewed interest in the natural products as main ingredients in the formulation of safe products for skin-whitening and treatment options for hyperpigmentation disorders. In the present communication, the results of our investigations on tyrosinase inhibition, modulation of intracellular tyrosinase and melanin levels in cultured B16F10 melanoma cells by Bacopa monnieri (L.) methanol extract (BME) are presented and discussed as safe option for skin lightening and to treat hyperpigmentation disorders. BME showed 11%, 29%, 54% and 80% inhibition of mushroom tyrosinase activity at an initial 100, 200, 400 and 600 μg of extract. Treatment of α-melanocyte stimulating hormone (α-MSH) stimulated cultured murine melanoma B16F10 cells with 100 μg/ml of the extract showed a decrease in the levels of cellular melanin and cellular tyrosinase content by 22% and 46% respectively. The cytotoxicity studies by MTT assay revealed that the LC50 of the BME is ≥1000 μg/ml in cultured mouse melanoma B16F10 and HEK293 cells.
基金supported by the Open Project of National Major Science and Technology Infrastructure of Translational Medicine,China(Grant No.:TMSK-2021−404)the SIMM-SHUTCM Joint Innovation Research Program,China(2022)+1 种基金the Youth Innovation Research Foundation,China(Grant No.:A1-U21-205-01010109)the National Natural Science Foundation of China(Grant No.:81972932).
文摘Epimedin B(EB)is one of the main flavonoid ingredients present in Epimedium brevicornum Maxim.,a traditional herb widely used in China.Our previous study showed that EB was a stronger inducer of melanogenesis and an activator of tyrosinase(TYR).However,the role of EB in melanogenesis and the mechanism underlying the regulation remain unclear.Herein,as an extension to our previous investigation,we provide comprehensive evidence of EB-induced pigmentation in vivo and in vitro and elucidate the melanogenesis mechanism by assessing its effects on the TYR family of proteins(TYRs)in terms of expression,activity,and stability.The results showed that EB increased TYRs expression through microphthalmia-associated transcription factor-mediated p-Akt(referred to as protein kinase B(PKB))/glycogen synthase kinase 3β(GSK3β)/β-catenin,p-p70 S6 kinase cascades,and protein 38(p38)/mitogen-activated protein(MAP)kinase(MAPK)and extracellular regulated protein kinases(ERK)/MAPK pathways,after which EB increased the number of melanosomes and promoted their maturation for melanogenesis in melanoma cells and human primary melanocytes/skin tissues.Furthermore,EB exerted repigmentation by stimulating TYR activity in hydroquinone-and N-phenylthiourea-induced TYR inhibitive models,including melanoma cells,zebrafish,and mice.Finally,EB ameliorated monobenzone-induced depigmentation in vitro and in vivo through the enhancement of TYRs stability by inhibiting TYR misfolding,TYR-related protein 1 formation,and retention in the endoplasmic reticulum and then by downregulating the ubiquitination and proteolysis processes.These data conclude that EB can target TYRs and alter their expression,activity,and stability,thus stimulating their pigmentation function,which might provide a novel rational strategy for hypopigmentation treatment in the pharmaceutical and cosmetic industries.
基金supported by the Ministerio de Economía,Industria y Competitividad(Agencia Estatal de Investigación,AEI,to CGF and MP)Fondo Europeo de Desarrollo Regional(MINECO-FEDER)(PID2022-139016OA-I00,PDC2022-133441-I00,to CGF and MP),Generalitat de Catalunya(2021 SGR 00357+3 种基金to CGF and MP)co-financed by Secretaria d’Universitats i Recerca del Departament d’Empresai Coneixement de la Generalitat de Catalunya 2021(Llavor 00086,to CGF)the recipient of an Alzheimer’s Association Research Fellowship(AARF-21-848511)the Agència de Gestiód’Ajuts Universitaris i de Recerca(AGAUR)for her FI-SDUR fellowship(2021FISDU 00182).
文摘Dysregulation of G9a,a histone-lysine N-methyltransferase,has been observed in Alzheimer’s disease and has been correlated with increased levels of chronic inflammation and oxidative stress.Likewise,microRNAs are involved in many biological processes and diseases playing a key role in pathogenesis,especially in multifactorial diseases such as Alzheimer’s disease.Therefore,our aim has been to provide partial insights into the interconnection between G9a,microRNAs,oxidative stress,and neuroinflammation.To better understand the biology of G9a,we compared the global microRNA expression between senescence-accelerated mouse-prone 8(SAMP8)control mice and SAMP8 treated with G9a inhibitor UNC0642.We found a downregulation of miR-128 after a G9a inhibition treatment,which interestingly binds to the 3′untranslated region(3′-UTR)of peroxisome-proliferator activator receptor γ(PPARG)mRNA.Accordingly,Pparg gene expression levels were higher in the SAMP8 group treated with G9a inhibitor than in the SAMP8 control group.We also observed modulation of oxidative stress responses might be mainly driven Pparg after G9a inhibitor.To confirm these antioxidant effects,we treated primary neuron cell cultures with hydrogen peroxide as an oxidative insult.In this setting,treatment with G9a inhibitor increases both cell survival and antioxidant enzymes.Moreover,up-regulation of PPARγby G9a inhibitor could also increase the expression of genes involved in DNA damage responses and apoptosis.In addition,we also described that the PPARγ/AMPK axis partially explains the regulation of autophagy markers expression.Finally,PPARγ/GADD45αpotentially contributes to enhancing synaptic plasticity and neurogenesis after G9a inhibition.Altogether,we propose that pharmacological inhibition of G9a leads to a neuroprotective effect that could be due,at least in part,by the modulation of PPARγ-dependent pathways by miR-128.
文摘Objective:To investigate the effect of TSH inhibition therapy in the postoperative management of patients with differentiated thyroid cancer.Methods:Seventy patients diagnosed with differentiated thyroid cancer were selected for the study.TSH inhibition therapy was administered to the research group,while thyroxine replacement therapy was provided to the control group during the postoperative management phase.This allowed for a comparative analysis between the two groups.Results:In comparison with the control group,the research group exhibited significant decreases in serum TSH,T3,and T4 levels after treatment,while FT4 and FT3 levels significantly increased(P<0.05).Additionally,significant decreases in Tg,VEGF,TSGF,CD44V6,and sIL-2R levels were observed in the research group after treatment(P<0.05).No significant differences were found in pre-treatment thyroid function between the two groups(P>0.05).Conclusion:The application of TSH inhibition therapy in the postoperative management of patients with differentiated thyroid cancer demonstrates promising outcomes.
基金This work was financially supported by the National Natural Science Foundation of China(81672508,21675085)Jiangsu Provincial Foundation for Distinguished Young Scholars(BK20170041,BK20170042)+5 种基金the Joint Research Funds of Department of Science&Technology of Shaanxi Province and Northwestern Polytechnical University(2020GXLH-Z-008,2020GXLH-Z-023)the Natural Science Basic Research Programof Shaanxi(Program No.2019JM-016)Key Research and Development Program of Shaanxi(2020ZDLGY13-04)Open Research Fund of Anhui Key Laboratory of Tobacco Chemistry(20181140)China-Sweden Joint Mobility Project(51811530018)Fundamental Research Funds for the Central Universities.
文摘Tyrosinase is an important enzyme in controlling the formation of melanin in melanosome,and plays a key role in the pigmentation of hair and skin.The abnormal expression or activation of tyrosinase is associated with several diseases such as albinism,vitiligo,melanoma and Parkinson disease.Excessive deposition of melanin could cause diseases such as freckles and brown spots in the human body,and it is also closely related to browning of fruits and vegetables and insect molting.Detecting and inhibiting the activity of tyrosinase is of extraordinary value in the progress of diagnosis and treatment of these diseases.Therefore,many selective optical detection probes and small molecular inhibitors have been developed,and have made significant contributions to the basic and clinical research on these diseases.In this paper,the detection and inhibition of tyrosinase and their application in whitening products are reviewed,with special emphasis on development of fluorescent probes and inhibitors.Hopefully,this review will help design more efficient and sensitive tyrosinase probes and inhibitors,as well as shed light on novel treatment of diseases such as melanoma.
基金Supported by the National Natural Science Foundation of China(No.20871054)the Science and Technology Foundation of Fujian Province, China(No.JK2011027, 2012J01045)
文摘Dawson-type phosphotungstic polyoxometalate α/β-K6P2W18O62·10H2O(P2W18) was synthesized and its inhibitory effect on the mushroom tyrosinase was investigated. It could inhibit diphenolase activity of mushroom tyrosinase as an irreversible inhibitor. When the concentration of the enzyme reached 0.0176 mg/mL, the concentration of P2W18 leading to 50% activity lost(IC50) was 0.05 mmol/L for monophenolase and 0.64 mmol/L for diphenolase. In addition, the antimicrobial activity of P2W18 was evaluated by zone of inhibition test. The results show that P2W18 possesses effective antimicrobial ability against Escherichia coli, Bacillus subtilis, yeast, especially Escherichia coli and yeast.
基金National Key R&D Program of China(2022YFA1103200,2017YFA0106400,2021YFA1100900)Ministry of Science and Technology of China(2020YFC2002804)+3 种基金National Natural Science Foundation of China(91749124,81772389,82070108)Major Program of Development Fund for Shanghai Zhangjiang National Innovation Demonstration Zone(ZJ2018-ZD-004)Fundamental Research Funds for the Central Universities(22120190149 and kx0200020173386)Peak Disciplines(Type IV)of Institutions of Higher Learning in Shanghai。
文摘Fibroblast activation protein(Fap)is a serine protease that degrades denatured type I collagen,α2-antiplasmin and FGF21.Fap is highly expressed in bone marrow stromal cells and functions as an osteogenic suppressor and can be inhibited by the bone growth factor Osteolectin(Oln).Fap is also expressed in synovial fibroblasts and positively correlated with the severity of rheumatoid arthritis(RA).However,whether Fap plays a critical role in osteoarthritis(OA)remains poorly understood.Here,we found that Fap is significantly elevated in osteoarthritic synovium,while the genetic deletion or pharmacological inhibition of Fap significantly ameliorated posttraumatic OA in mice.Mechanistically,we found that Fap degrades denatured type II collagen(Col II)and Mmp13-cleaved native Col II.Intra-articular injection of r Fap significantly accelerated Col II degradation and OA progression.In contrast,Oln is expressed in the superficial layer of articular cartilage and is significantly downregulated in OA.Genetic deletion of Oln significantly exacerbated OA progression,which was partially rescued by Fap deletion or inhibition.Intra-articular injection of r Oln significantly ameliorated OA progression.Taken together,these findings identify Fap as a critical pathogenic factor in OA that could be targeted by both synthetic and endogenous inhibitors to ameliorate articular cartilage degradation.
基金This work was supported by Shenzhen-Hong Kong Science and Technology Innovation Cooperation Zone Shenzhen Park Project:HZQB-KCZYB-2020030the National Natural Science Foundation of China(No.91860131and No.52074157)+2 种基金Guangdong Provincial Department of Science and Technology,Key-Area Research and Development Program of Guangdong Province(No.2020B090923002)the National Key Research and Development Program of China(No.2017YFB0702901)the Shenzhen Science and Technology Innovation Commission(No.JCYJ20170817111811303,No.KQTD20170328154443162and No.ZDSYS201703031748354).
文摘The additive manufacturing(AM)of Ni-based superalloys has attracted extensive interest from both academia and industry due to its unique capabilities to fabricate complex and high-performance components for use in high-end industrial systems.However,the intense temperature gradient induced by the rapid heating and cooling processes of AM can generate high levels of residual stress and metastable chemical and structural states,inevitably leading to severe metallurgical defects in Ni-based superalloys.Cracks are the greatest threat to these materials’integrity as they can rapidly propagate and thereby cause sudden and non-predictable failure.Consequently,there is a need for a deeper understanding of residual stress and cracking mechanisms in additively manufactured Ni-based superalloys and ways to potentially prevent cracking,as this knowledge will enable the wider application of these unique materials.To this end,this paper comprehensively reviews the residual stress and the various mechanisms of crack formation in Ni-based superalloys during AM.In addition,several common methods for inhibiting crack formation are presented to assist the research community to develop methods for the fabrication of crack-free additively manufactured components.
基金supported by National Natural Science Foundation of China(52170074).
文摘Air nanobubbles(A-NBs)were used to inhibit the brass corrosion in circulating cooling water for the first time in the study.The results of mass loss method and electrochemical method showed that A-NBs had the obvious corrosion inhibition effect.The inhibition rate reached 52%at 35℃.The impedance and surface characterization results of corrosion samples indicated that the corrosion inhibition mechanisms of A-NBs mainly included adsorption of corrosion ions,promoting the formation of the passivation film on metal surface and the formation of the bubble layer and scale film on metal surface.A-NBs are potential excellent corrosion inhibitors.
文摘Drilling technologies based on oil-based drillingfluids and strong inhibitory saltwaterfluids are affected by draw-backs such as downhole accidents where sticking and wellbore instabilities occur.Existing polyamine drillingfluids also exhibit problems such as easy decomposition and poor inhibition performances.In order to mitigate these issues,additives can be used,such as polyamine inhibitors and the synthesis of nanometerfiltrate reducers.Tests conducted in the frame of this study with a polyamine drillingfluid and such additives show that thisfluid has the same inhibitory,plugging,lubricating,and wellbore-stability performances as oil-based drillingfluids.However,it has long-term anti-wear performances even better than those of oil-based drillingfluids.The out-comes of a series of comparisons with other sample cases(other wells)are reported and the advantages related to the proposedfluid discussed in detail.
基金Supported by the National Natural Science Foundation of China(5215000105)Huo Yingdong Education Foundation(171043).
文摘By analyzing the corrosion of phosphate completion fluid on the P110 steel at 170 °C, the high-temperature corrosion mechanism of phosphate completion fluid was revealed, and a corrosion inhibition method by membrane transformation was proposed and an efficient membrane-forming agent was selected. Scanning electron microscope (SEM) images, X-ray energy spectrum and X-ray diffraction results were used to characterize the microscopic morphology, elemental composition and phase composition of the precipitation membrane on the surface of the test piece. The effect and mechanism of corrosion inhibition by membrane transformation were clarified. The phosphate completion fluid eroded the test piece by high-temperature water vapor and its hydrolyzed products to form a membrane of iron phosphate corrosion product. By changing the corrosion reaction path, the Zn2+ membrane-forming agent could generate KZnPO4 precipitation membrane with high temperature resistance, uniform thickness and tight crystal packing on the surface of the test piece, which could inhibit the corrosion of the test piece, with efficiency up to 69.63%. The Cu2+ membrane-forming agent electrochemically reacted with Fe to precipitate trace elemental Cu on the surface of the test piece, thus forming a protective membrane, which could inhibit metal corrosion, with efficiency up to 96.64%, but the wear resistance was poor. After combining 0.05% Cu2+ and 0.25% Zn2+, a composite protective membrane of KZnPO4 crystal and elemental Cu was formed on the surface of the test piece. The corrosion inhibition efficiency reached 93.03%, which ensured the high corrosion inhibition efficiency and generated a precipitation membrane resistant to temperature and wear.
文摘The objective of this study is the phytochemical analysis and the determination of the antibacterial activity of aqueous and hydro-ethanolic extracts obtained from the leaves and bark of the trunk of Albizia zygia, against Escherichia coli and Salmonella typhi bacteria in aquatic microcosms. Phytochemical screening was performed as described by Pareck. The results obtained show that the hydro-ethanolic and aqueous extracts of Albizia zygia trunk bark recorded higher extraction yields (26.71% and 33.2% respectively) compared to the aqueous and hydro-ethanolic extracts of leaves of the same plant. Secondary metabolites with antibacterial activities such as anthraquinones, anthocyanins, flavonoids, polyphenols, tannins and saponins were found in both types of extracts. Flavonoids and anthocyanins were relatively more abundant than the other chemical constituents. The highest cellular inhibition rate of Escherichia coli was 99.88%, obtained after 9 hours of exposure in the hydro-ethanolic extract solution of trunk bark at the concentration 1.5 g/L. The Salmonella typhi rate was 99.95% after 9 hours of exposure of bacterial cells to the hydro-ethanol extract of the bark of the trunk at the concentration 1.5 g/L. This rate increased proportionally with the bacterial-extract contact time. The temperature of the medium did not significantly influence bacterial inhibition (P > 0.05). The obtained results justify the use of the plant Albizia zygia in the reduction of the flow of bacterio-pollutants contained in water intended for consumption.
基金This study was supported by National Natural Foundation Project of China(81860504)。
文摘Objective:To investigate the effects and possible mechanisms of the combination of DMDD(2-dodecyl-6-methoxycyclohexa-2-5-diene-1-4-dione),a traditional Chinese medicine monomer,and sorafenib on the malignant biological behavior of human hepatocellular carcinoma Huh7 cells.Methods:The experiment was divided into four groups:Huh7 cells control group,DMDD group,sorafenib group and DMDD and sorafenib combination group.The CCK-8 assay was used to measure the viability of Huh7 cells,and the Kim's formula was used to determine the synergistic effect.The plate cloning experiment was conducted to test colony formation ability of Huh7 cells.The scratch and Transwell experiments were performed to evaluate the migration ability and the invasion ability of Huh7 cells.The cell cycle of Huh7 cells was detected by flow cytometry.RT-qPCR and Western blot were used to measure the mRNA transcription level and protein expression level of PHGDH in the serine synthesis pathway.Results:The plate cloning experiment,scratch experiment,and Transwell migration experiment showed that the combined application of DMDD and Sorafenib significantly enhanced the inhibitory effect on the proliferation,migration,and invasion ability of Huh7 cells compared to the control group,DMDD group,and Sorafenib group(P<0.05).According to the Kim's formula,the combination of DMDD(final concentrations of 2,4,8μmol/L)and Sorafenib(final concentrations of 1,2,4μmol/L)had a synergistic inhibitory effect on the proliferation of Huh7 cells(Q>1.15).6,10μmol/L DMDD combined with 3,5μmol/L Sorafenib showed additive effect.The cell cycle of Huh7 cells was detected by flow cytometry,and the results showed that after 48 hours of drug intervention,the proportion of G2/M phase cells in the control group,DMDD group,Sorafenib group,and combination group were(10.63±0.32)%,(35.77±1.22)%,(30.03±2.22)%,and(38.97±0.60)%,respectively.Compared with the control group,the proportion of G2/M phase cells in the three groups significantly increased(P<0.0001).Compared with the Sorafenib group,the proportion of G2/M phase cells in the combination group significantly increased(P<0.0001).RT-qPCR and Western blot results showed that the combined application of DMDD and Sorafenib significantly inhibited the mRNA transcription level and protein expression level of PHGDH(P<0.05).Conclusion:The combined application of DMDD and Sorafenib has a synergistic effect that can enhance the inhibitory effect on the proliferation,invasion,and migration ability of Huh7 cells.The mechanism of this effect is related to the synergistic inhibition of the gene transcription and protein expression of PHGDH in the serine synthesis pathway.
基金The author acknowledges Dr.Pol Boudes for reviewing this manuscript and Dr.Zachary Goodman for providing the galectin-3 antibody histological images.
文摘Nonalcoholic fatty liver disease continues to be one of the major health challenges facing the world,with estimates of non-alcoholic steatohepatitis(NASH)prevalence in over 25 percent of the world’s population.NASH represents a spectrum of disease that may lead to hepatic fibrosis and eventual cirrhosis,with the risk of cirrhosis decompensation,and hepatocellular carcinoma.New therapies are desperately needed for NASH,especially for later stages of fibrosis and cirrhosis.Galectin-3 inhibition is being explored as a new liver antifibrotic therapy.This concise review will outline the state of the art of this new therapeutic target.
基金This work was supported by the National Natural Science Foundation of China(52074066).
文摘Wet dust removal systems used to control dust in the polishing or grinding process of Mg alloy products are frequently associated with potential hydrogen explosion caused by magnesium-water reaction.For purpose of avoiding hydrogen explosion risks,we try to use a combination of chitosan(CS)and sodium phosphate(SP)to inhibit the hydrogen evolution reaction between magnesium alloy waste dust and water.The hydrogen evolution curves and chemical kinetics modeling for ten different mixing ratios demonstrate that 0.4wt%CS+0.1wt%SP yields the best inhibition efficiency with hydrogen generation rate of almost zero.SEM and EDS analyses indicate that this composite inhibitor can create a uniform,smooth,tight protective film over the surface of the alloy dust particles.FTIR and XRD analysis of the chemical composition of the surface film show that this protective film contains CS and SP chemically adsorbed on the surface of ZK60 but no detectable Mg(OH)_(2),suggesting that magnesium-water reaction was totally blocked.Our new method offers a thorough solution to hydrogen explosion by inhibiting the hydrogen generation of magnesium alloy waste dust in a wet dust removal system.
文摘With the help of model experiments, we are able to offer a detailed proposal for the inhibition of DNA duplication and no inhibition of RNA viral infectivity. As a backbone, we introduced methyl phosphotriester (MPTE). Duplex formation according to the traditional Watson and Crick base-pairing: [(MPTE)<sub>n−1</sub> DNA] * DNA and [(MPTE)<sub>n−1</sub> DNA] * RNA, where n = number of DNA and RNA bases. However, in the latter case, inhibition is obtained by reduction of the number of MPTE linkages, as is confirmed with model experiments and under biological conditions with micro (mi)RNA substrates. The latter results have recently been published. One or more single MPTEs are disseminated over different places of DNA without neighbour MPTEs (Prof. Wen-Yih Chen and his group, Taiwan).
