Pub Date : 2020-10-08DOI: 10.2174/2212796814999201008130819
S. Makar, Abhrajyoti Ghosh, Divya., S. Shivhare, Ajay Kumar, S. Singh
Despite advances in the development of cytotoxic and targeted therapies, pancreatic adenocarcinoma (PAC) remains a significant cause of cancer mortality worldwide. It is also difficult to detect it at an early stage due to a number of factors. Most of the patients are present with locally advanced or metastatic disease, which precludes curative resection. In the absence of effective screening methods, considerable efforts have been made to identify better systemic treatments during the past decade. This review describes the recent advances in molecular mechanisms involved in pancreatic cancer initiation, progression, and metastasis. Additionally, the importance of deregulated cellular signaling pathways and various cellular proteins as potential targets for developing novel therapeutic strategies against incurable forms of pancreatic cancer is reported. The emphasis is on the critical functions associated with growth factors and their receptors viz. c-MET/HGF, CTHRC1, TGF-β, JAK-STAT, cyclooxygenase pathway, WNT, CCK, MAPK-RAS-RAF, PI3K-AKT, Notch, src, IGF-1R, CDK2NA and chromatin regulation for the sustained growth, survival, and metastasis of pancreatic cancer cells. It also includes various therapeutic strategies viz. immunotherapy, surgical therapy, radiation therapy and chemotherapy.
{"title":"Molecular Processes Involved in Pancreatic Cancer and Therapeutics","authors":"S. Makar, Abhrajyoti Ghosh, Divya., S. Shivhare, Ajay Kumar, S. Singh","doi":"10.2174/2212796814999201008130819","DOIUrl":"https://doi.org/10.2174/2212796814999201008130819","url":null,"abstract":"\u0000\u0000Despite advances in the development of cytotoxic and targeted therapies, pancreatic\u0000adenocarcinoma (PAC) remains a significant cause of cancer mortality worldwide. It is\u0000also difficult to detect it at an early stage due to a number of factors. Most of the patients are\u0000present with locally advanced or metastatic disease, which precludes curative resection. In\u0000the absence of effective screening methods, considerable efforts have been made to identify\u0000better systemic treatments during the past decade. This review describes the recent advances\u0000in molecular mechanisms involved in pancreatic cancer initiation, progression, and metastasis.\u0000Additionally, the importance of deregulated cellular signaling pathways and various cellular\u0000proteins as potential targets for developing novel therapeutic strategies against incurable\u0000forms of pancreatic cancer is reported. The emphasis is on the critical functions associated\u0000with growth factors and their receptors viz. c-MET/HGF, CTHRC1, TGF-β, JAK-STAT, cyclooxygenase\u0000pathway, WNT, CCK, MAPK-RAS-RAF, PI3K-AKT, Notch, src, IGF-1R,\u0000CDK2NA and chromatin regulation for the sustained growth, survival, and metastasis of\u0000pancreatic cancer cells. It also includes various therapeutic strategies viz. immunotherapy,\u0000surgical therapy, radiation therapy and chemotherapy.\u0000","PeriodicalId":10784,"journal":{"name":"Current Chemical Biology","volume":"2 3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83115674","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-10-05DOI: 10.2174/2212796814999201005195509
Kiel D. Neumann, J. Blecha, Chih-Kai Chao, Tony L. Huynh, K. Zinn, H. VanBrocklin, C. Thompson, J. Gerdes
To investigate dynamic live tissue organophosphorus nerve agent uptake and distribution fates resulting in acetylcholinesterase inhibition, we recently reported the first-in-class fluorine-18 [18F] radiolabeled Positron Emission Tomography (PET) imaging tracer known as [18F]O-(2-fluoroethyl)-O-(p-nitrophenyl)methylphosphonate. This tracer has been initially studied in live rats with PET imaging. We sought to evaluate the PET tracer in vivo using a new dose formulation of saline, ethanol and L-ascorbic acid, and compare the influence of this formulation on in vivo tracer performance to previous data collected using a CH3CN:PBS formulation. A high molar activity [18F]tracer radiosynthesis was used. Doses were formulated as saline, ethanol (≤ 1%) and L-ascorbic acid (0.1%), pH 4.0-4.5. Stability was evaluated to 6 h. Dose injection (i.v.) into male rats was followed by either ex vivo biodistribution profiling at 5, 30, 90 min, or dynamic 90 min PET imaging. Rat biodistribution and PET imaging data were compared. An optimized radiosynthesis (8 ± 2 % RCY) resulted in stable doses for 6 h (>99%). Arterial blood included a tracer and a single metabolite. The ex vivo biodistribution and live tissue PET imaging data revealed rapid radioactivity uptake and distributed tissue levels: heart and lung, highest; liver, moderate; and brain, lowest. Imaging and biodistribution data were highly correlated with expected radioactivity tissue uptake and distribution in target organs. Lower brain radioactivity levels by PET imaging were found for the new formulation (saline, 1% L-ascorbic acid, < 1% ethanol) as compared to the established CH3CN:PBS formulation. Overall, we found that the i.v. dose formulation changed the in vivo profile of an organophosphorus PET tracer that is considered an important finding for future organophosphorus PET tracer studies.
为了研究动态活组织有机磷神经毒剂的摄取和分布情况，导致乙酰胆碱酯酶抑制，我们最近报道了一类首创的氟-18 [18F]放射性标记正电子发射断层扫描(PET)成像示踪剂[18F]O-(2-氟乙基)-O-(对硝基苯)甲基膦酸盐。这种示踪剂已经在活体大鼠中进行了PET成像的初步研究。我们试图用生理盐水、乙醇和l -抗坏血酸组成的新剂量配方来评估PET示踪剂的体内性能，并将该配方对活体示踪剂性能的影响与之前使用CH3CN:PBS配方收集的数据进行比较。采用高摩尔活度[18F]示踪剂放射性合成。剂量配制为生理盐水、乙醇(≤1%)和l -抗坏血酸(0.1%)，pH 4.0-4.5。稳定性评价至6h。将剂量注射到雄性大鼠后，分别在5、30、90分钟或动态90分钟PET成像时进行离体生物分布分析。比较大鼠生物分布和PET成像数据。优化的放射合成(8±2% RCY)可使剂量稳定6小时(>99%)。动脉血含有一种示踪剂和一种代谢物。离体分布和活体组织PET成像数据显示放射性快速吸收和分布组织水平:心脏和肺，最高;肝脏,温和;大脑，最低。成像和生物分布数据与预期的放射性组织摄取和靶器官的分布高度相关。与已建立的CH3CN:PBS配方相比，通过PETimaging发现新配方(生理盐水，1% l -抗坏血酸，< 1%乙醇)的脑放射性水平较低。总的来说，我们发现静脉注射剂量配方改变了有机磷PET示踪剂的体内特征，这被认为是未来有机磷PET示踪剂研究的重要发现。
{"title":"Dose Formulation, Biodistribution and PET Imaging Studies of a First-in-Class Fluorine-18 Organophosphorus Cholinesterase Inhibitor Tracer in Rat","authors":"Kiel D. Neumann, J. Blecha, Chih-Kai Chao, Tony L. Huynh, K. Zinn, H. VanBrocklin, C. Thompson, J. Gerdes","doi":"10.2174/2212796814999201005195509","DOIUrl":"https://doi.org/10.2174/2212796814999201005195509","url":null,"abstract":"\u0000\u0000To investigate dynamic live tissue organophosphorus nerve agent\u0000uptake and distribution fates resulting in acetylcholinesterase inhibition, we recently reported\u0000the first-in-class fluorine-18 [18F] radiolabeled Positron Emission Tomography (PET) imaging\u0000tracer known as [18F]O-(2-fluoroethyl)-O-(p-nitrophenyl)methylphosphonate. This tracer\u0000has been initially studied in live rats with PET imaging.\u0000\u0000\u0000\u0000We sought to evaluate the PET tracer in vivo using a new dose formulation of saline,\u0000ethanol and L-ascorbic acid, and compare the influence of this formulation on in vivo\u0000tracer performance to previous data collected using a CH3CN:PBS formulation.\u0000\u0000\u0000\u0000A high molar activity [18F]tracer radiosynthesis was used. Doses were formulated\u0000as saline, ethanol (≤ 1%) and L-ascorbic acid (0.1%), pH 4.0-4.5. Stability was evaluated to 6\u0000h. Dose injection (i.v.) into male rats was followed by either ex vivo biodistribution profiling\u0000at 5, 30, 90 min, or dynamic 90 min PET imaging. Rat biodistribution and PET imaging data\u0000were compared.\u0000\u0000\u0000\u0000An optimized radiosynthesis (8 ± 2 % RCY) resulted in stable\u0000doses for 6 h (>99%). Arterial blood included a tracer and a single metabolite. The ex vivo\u0000biodistribution and live tissue PET imaging data revealed rapid radioactivity uptake and distributed\u0000tissue levels: heart and lung, highest; liver, moderate; and brain, lowest.\u0000\u0000\u0000\u0000Imaging and biodistribution data were highly correlated with expected radioactivity\u0000tissue uptake and distribution in target organs. Lower brain radioactivity levels by PET\u0000imaging were found for the new formulation (saline, 1% L-ascorbic acid, < 1% ethanol) as\u0000compared to the established CH3CN:PBS formulation. Overall, we found that the i.v. dose\u0000formulation changed the in vivo profile of an organophosphorus PET tracer that is considered\u0000an important finding for future organophosphorus PET tracer studies.\u0000","PeriodicalId":10784,"journal":{"name":"Current Chemical Biology","volume":"23 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85360239","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-09-30DOI: 10.2174/2212796814999200930120925
Hasnain Hussain, Wei-jie Yan, Z. Ngaini, N. Julaihi, Rina Tommy, S. Bhawani
Sago palm is an important agricultural starch-producing crop in Malaysia. The trunk of sago palm is responsible for the the starch to reach maturity for harvesting after ten years. However, there are sago palms that fail to develop thier trunk after 17 years of being planted. This is known as a stressed “non-trunking” sago palm, which reduces the economic value of the palms. The study was initiated to compare the differences in metabolite expression between trunking and non-trunking sago palms and secondly to determine the potential metabolite- makers that are related to differential phenotypes of sago palms. Metabolites were extracted using various solvents and analysed using NMR spectroscopy and GC-MS spectrometry. Data obtained were subjected to principal component analysis. The study determined differential metabolites expression in the leaf extracts of normal trunking sago palm compared to the non-trunking palms. Metabolite groups differently expressed between trunking and non-trunking sago palm are oils and waxes, haloalkanes, sulfite esters, phosphonates, phosphoric acid, thiophene ester, terpenes and tocopherols. GC-MS analysis of Jones & Kinghorn extraction method determined two sets of metabolite markers, explaining the differences in metabolites expression of trunking and nontrunking sago palms in ethyl acetate and methanol extract of 89.55% comprising sulfurous ester compounds and 87.04% comprising sulfurous ester, sulfurous acid and cyclohexylmethyl hexyl ester, respectively. Two sets of metabolite markers were expressed in the trunking and nontrunking sago palms. These metabolites can potentially be used as markers for identifying normal and stressed plants.
{"title":"Differential Metabolites Markers from Trunking and Stressed Non-Trunking Sago Palm (Metroxylon sagu Rottb.)","authors":"Hasnain Hussain, Wei-jie Yan, Z. Ngaini, N. Julaihi, Rina Tommy, S. Bhawani","doi":"10.2174/2212796814999200930120925","DOIUrl":"https://doi.org/10.2174/2212796814999200930120925","url":null,"abstract":"\u0000\u0000Sago palm is an important agricultural starch-producing crop in Malaysia.\u0000The trunk of sago palm is responsible for the the starch to reach maturity for harvesting\u0000after ten years. However, there are sago palms that fail to develop thier trunk after 17\u0000years of being planted. This is known as a stressed “non-trunking” sago palm, which reduces\u0000the economic value of the palms.\u0000\u0000\u0000\u0000The study was initiated to compare the differences in metabolite expression between\u0000trunking and non-trunking sago palms and secondly to determine the potential metabolite-\u0000makers that are related to differential phenotypes of sago palms.\u0000\u0000\u0000\u0000Metabolites were extracted using various solvents and analysed using NMR spectroscopy\u0000and GC-MS spectrometry. Data obtained were subjected to principal component\u0000analysis.\u0000\u0000\u0000\u0000The study determined differential metabolites expression in the leaf extracts of\u0000normal trunking sago palm compared to the non-trunking palms. Metabolite groups differently\u0000expressed between trunking and non-trunking sago palm are oils and waxes, haloalkanes,\u0000sulfite esters, phosphonates, phosphoric acid, thiophene ester, terpenes and tocopherols.\u0000GC-MS analysis of Jones & Kinghorn extraction method determined two sets of metabolite\u0000markers, explaining the differences in metabolites expression of trunking and nontrunking\u0000sago palms in ethyl acetate and methanol extract of 89.55% comprising sulfurous\u0000ester compounds and 87.04% comprising sulfurous ester, sulfurous acid and cyclohexylmethyl\u0000hexyl ester, respectively.\u0000\u0000\u0000\u0000Two sets of metabolite markers were expressed in the trunking and nontrunking\u0000sago palms. These metabolites can potentially be used as markers for identifying\u0000normal and stressed plants.\u0000","PeriodicalId":10784,"journal":{"name":"Current Chemical Biology","volume":"31 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72889478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-09-25DOI: 10.2174/2212796814999200925162943
Amirhosein Maali, M. Sarfi, M. Mirzakhani, G. Goodarzi, Mahmoud Maniati, S. Tehrani, D. Qujeq
Tumor cell growth and survival are the outcomes of communication between tumor cells and tumor microenvironment (TME). In other words, tumor cell growth and survival are greatly affected by the interaction between adjacent cells and tumor cells. In this paper, we review the recent advances in studies of TME, including metabolic interplays between tumor cells and their non-malignant neighbors (peaceful interaction and autophagy), trades of signaling pathways (approach to most important ones; cytokine pathway, NF-kB pathway, intra-tumoral hypoxia, oxidative stress, and nitric oxide-depended pathways), miRNAs (as the regulatory molecules which are present in TME), and Tumor-associated Exosomes (TAEs). Characterization of TME bio-molecules, nutrient changes, and cellular and molecular interactions help to clarify the progression of cancer and find novel targets for the treatment of cancer.
{"title":"Peaceful Existence of Tumor Cells with Their Non-malignant Neighbors: The Trade of Tumor Cells with Tumor Microenvironment","authors":"Amirhosein Maali, M. Sarfi, M. Mirzakhani, G. Goodarzi, Mahmoud Maniati, S. Tehrani, D. Qujeq","doi":"10.2174/2212796814999200925162943","DOIUrl":"https://doi.org/10.2174/2212796814999200925162943","url":null,"abstract":"\u0000\u0000Tumor cell growth and survival are the outcomes of communication between tumor\u0000cells and tumor microenvironment (TME). In other words, tumor cell growth and survival\u0000are greatly affected by the interaction between adjacent cells and tumor cells. In this\u0000paper, we review the recent advances in studies of TME, including metabolic interplays between\u0000tumor cells and their non-malignant neighbors (peaceful interaction and autophagy),\u0000trades of signaling pathways (approach to most important ones; cytokine pathway, NF-kB\u0000pathway, intra-tumoral hypoxia, oxidative stress, and nitric oxide-depended pathways),\u0000miRNAs (as the regulatory molecules which are present in TME), and Tumor-associated\u0000Exosomes (TAEs). Characterization of TME bio-molecules, nutrient changes, and cellular\u0000and molecular interactions help to clarify the progression of cancer and find novel targets for\u0000the treatment of cancer.\u0000","PeriodicalId":10784,"journal":{"name":"Current Chemical Biology","volume":"77 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88880852","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-09-07DOI: 10.2174/2212796814999200907162105
H. Hemmami, B. B. Seghir, A. Rebiai, A. Khelef, Zeghoud Soumeia
The genus Capsicum contains various sweet and hot pepper varieties, including Capsicum annum L. The various species in this genus are used as herbs, vegetables, or medicines, and recent studies have shown that they are a rich source of bioactive compounds as well. In this study, our objective was to evaluate the antioxidant activity as well as the content of phenols (TPC), the content of flavonoids (TFC) and total condensed tannins (TCT) of ethanolic extracts of the fresh and dried sweet pepper Capsicum annuum L. The antioxidant activities of the extracts were examined using different biochemical assays, namely diphenylpicrylhydrazyl (DPPH), total antioxidant capacity (TAC) and ferric reducing power (FRAP). The total phenolic contents (TPC) were determined spectrophotometrically according to the Folin-Ciocalteu colorimetric method. Total flavonoid content was measured by the aluminum chloride colorimetric assay. High-performance liquid chromatography (HPLC) has been used to identify the phenolic compounds in ethanolic extracts. The obtained results showed the presence of considerable amounts of total phenolic (757.3±3.5 mgGAE/100g), flavonoid (482.66±1.5 mgQE/100g) and Condensed Tannins (15.97±0.5 mg GAE/100g) content in dry red pepper extract. The use of HPLC has allowed the identification of Gallic Acid, Ascorbic Acid, Chlorogenic Acid, Caffeic Acid, Quercetin, Vanillin, and Rutin in pepper ethanolic extracts. Green and yellow dry peppers contain significant amounts of gallic acid exceeding (134.0 μg /mg). The fresh yellow and red peppers also contained significant amounts of Quercetin exceeding (109.3 μg/mg), the dry red pepper has the strongest antioxidant activity. In conclusion, these findings can be regarded as very promising and justify further study, including the identification of antioxidant components in pepper extracts. Our work constitutes a first step in the study of fresh and dry sweet pepper as a promising source of natural antioxidants.
{"title":"Comparative Study on Polyphenols Content and Antioxid ant Activity of Three Sweet Peppers Varieties (Capsicum annuum L.)","authors":"H. Hemmami, B. B. Seghir, A. Rebiai, A. Khelef, Zeghoud Soumeia","doi":"10.2174/2212796814999200907162105","DOIUrl":"https://doi.org/10.2174/2212796814999200907162105","url":null,"abstract":"\u0000\u0000The genus Capsicum contains various sweet and hot pepper varieties,\u0000including Capsicum annum L. The various species in this genus are used as herbs, vegetables,\u0000or medicines, and recent studies have shown that they are a rich source of bioactive\u0000compounds as well.\u0000\u0000\u0000\u0000In this study, our objective was to evaluate the antioxidant activity as well as the\u0000content of phenols (TPC), the content of flavonoids (TFC) and total condensed tannins\u0000(TCT) of ethanolic extracts of the fresh and dried sweet pepper Capsicum annuum L.\u0000\u0000\u0000\u0000The antioxidant activities of the extracts were examined using different biochemical\u0000assays, namely diphenylpicrylhydrazyl (DPPH), total antioxidant capacity (TAC) and ferric\u0000reducing power (FRAP). The total phenolic contents (TPC) were determined spectrophotometrically\u0000according to the Folin-Ciocalteu colorimetric method. Total flavonoid content\u0000was measured by the aluminum chloride colorimetric assay. High-performance liquid chromatography\u0000(HPLC) has been used to identify the phenolic compounds in ethanolic extracts.\u0000\u0000\u0000\u0000The obtained results showed the presence of considerable amounts of total phenolic\u0000(757.3±3.5 mgGAE/100g), flavonoid (482.66±1.5 mgQE/100g) and Condensed Tannins\u0000(15.97±0.5 mg GAE/100g) content in dry red pepper extract. The use of HPLC has allowed\u0000the identification of Gallic Acid, Ascorbic Acid, Chlorogenic Acid, Caffeic Acid, Quercetin,\u0000Vanillin, and Rutin in pepper ethanolic extracts. Green and yellow dry peppers contain significant\u0000amounts of gallic acid exceeding (134.0 μg /mg). The fresh yellow and red peppers\u0000also contained significant amounts of Quercetin exceeding (109.3 μg/mg), the dry red pepper\u0000has the strongest antioxidant activity.\u0000\u0000\u0000\u0000In conclusion, these findings can be regarded as very promising and justify further\u0000study, including the identification of antioxidant components in pepper extracts. Our\u0000work constitutes a first step in the study of fresh and dry sweet pepper as a promising source\u0000of natural antioxidants.\u0000","PeriodicalId":10784,"journal":{"name":"Current Chemical Biology","volume":"15 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73497154","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-09-07DOI: 10.2174/2212796814999200907162619
I. Zhigacheva, V. Binyukov, E. Mil, N. Krikunova, I. Generozova, M. Rasulov
The binding of free iron ions in the composition of nitrosyl complexes is probably one of the mechanisms of the antioxidant action of nitric oxide. The study of the protective properties of nitric oxide is often carried out using exogenous NO donors. In our work, we used nitric oxide donor - sodium μ2-dithiosulfate-tetranitosyldiferrate tetrahydrate (TNIC-thio). The aim of our work was to investigate the possibility of using TNIC-thio to increase the resistance of plants to stress factors. Since the implementation of anti-stress programs requires a lot of energy expenditure, we studied the functional state of the mitochondria of pea seedlings under conditions of water deficiency and treatment with TNIC-thio. The functional state of the mitochondria was studied as per the level of lipid peroxidation by the spectrofluorimetry, by a fatty acid composition of mitochondrial membranes with the chromatography technique and by the morphology of mitochondria with the atomic force microscopy. Water deficiency has caused changes in the Fatty Acid (FA) composition, which manifested themselves in increasing the content of saturated FAs and decreasing the content of unsaturated FAs containing 18 and 20 carbon atoms. Treatment of pea seeds with 10–8 M TNIC-thio under these conditions led to the prevention of LPO, prevention of changes in the FA composition of mitochondrial membranes and reduction in the number of swollen organelles. It can be assumed that the protective effect of TNIC-thio is due to the preservation of the functional state of the mitochondria.
{"title":"Iron-Sulfur-Nitrosyl Complex Increases the Resistance of Pea Seedling to Water Deficiency","authors":"I. Zhigacheva, V. Binyukov, E. Mil, N. Krikunova, I. Generozova, M. Rasulov","doi":"10.2174/2212796814999200907162619","DOIUrl":"https://doi.org/10.2174/2212796814999200907162619","url":null,"abstract":"\u0000\u0000The binding of free iron ions in the composition of nitrosyl complexes\u0000is probably one of the mechanisms of the antioxidant action of nitric oxide. The study\u0000of the protective properties of nitric oxide is often carried out using exogenous NO donors.\u0000In our work, we used nitric oxide donor - sodium μ2-dithiosulfate-tetranitosyldiferrate tetrahydrate\u0000(TNIC-thio).\u0000\u0000\u0000\u0000The aim of our work was to investigate the possibility of using TNIC-thio to increase\u0000the resistance of plants to stress factors. Since the implementation of anti-stress programs\u0000requires a lot of energy expenditure, we studied the functional state of the mitochondria\u0000of pea seedlings under conditions of water deficiency and treatment with TNIC-thio.\u0000\u0000\u0000\u0000The functional state of the mitochondria was studied as per the\u0000level of lipid peroxidation by the spectrofluorimetry, by a fatty acid composition of mitochondrial\u0000membranes with the chromatography technique and by the morphology of mitochondria\u0000with the atomic force microscopy.\u0000\u0000\u0000\u0000Water deficiency has caused changes in the Fatty Acid (FA) composition, which\u0000manifested themselves in increasing the content of saturated FAs and decreasing the content\u0000of unsaturated FAs containing 18 and 20 carbon atoms. Treatment of pea seeds with 10–8 M\u0000TNIC-thio under these conditions led to the prevention of LPO, prevention of changes in the\u0000FA composition of mitochondrial membranes and reduction in the number of swollen organelles.\u0000\u0000\u0000\u0000 It can be assumed that the protective effect of TNIC-thio is due to the preservation\u0000of the functional state of the mitochondria.\u0000","PeriodicalId":10784,"journal":{"name":"Current Chemical Biology","volume":"37 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78240646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-08-31DOI: 10.2174/2212796814999200818095036
B. Mengiste, Tizazu Zenebe, Kassahun Dires, E. Lulekal, Awol Mekonnen, Nigus Zegeye, Y. Shiferaw
The Eucalyptus globulus extractions have been used by the traditional healers to treat diseases in the study area. Our previous study revealed that the essential oil has antimicrobial and antifungal activity. This study determined phytochemical analysis, skin irritation, acute and subacute toxicity of Eucalyptus globulus essential oil in mice and rats. The phytochemicals were analyzed using GC-MS mass spectrometry. The acute toxicity study was determined at three dose levels of 1500 mg/kg, 1750mg/kg, and 2000 mg/kg. The essential oil limit test at a dose of 1000 mg/kg was administered to mice for 28 consecutive days for sub-acute toxicity study. The mice mortality, behavioral change, injury and other signs of illness were recorded once daily. Biochemical parameters were evaluated. Liver and kidney were analyzed for histopathological analyses. The 5% ointment formulation was applied to the rat skin to determine skin irritation effects. The Eucalyptus globulus essential oil showed no effect on the mice at a dose of 1500mg/kg and below, but caused signs of toxicity and death at a dose of 1750mg/kg and above compared to the controls (p<0.05). The LD50 value was 1650 mg/kg. There was no significant difference (p > 0.05) in the body weights, gross abnormalities of the organs and biochemical parameters compared to the control at 1000 mg/kg subacute toxicity study. No histopathological changes were detected in the organs tested. The 5% ointment formulation did not show any abnormal skin reaction. In the present study, the Eucalyptus globulus essential oil was comparable with other studies in terms of both chemical composition and its effects on sub-acute and topical application. This toxicity study demonstrated that Eucalyptus globulus essential oil is nontoxic at a relatively lower concentration.
{"title":"Safety Evaluation of Eucalyptus globulus Essential Oils through Acute and Sub-acute Toxicity and Skin Irritation in Mice and Rats","authors":"B. Mengiste, Tizazu Zenebe, Kassahun Dires, E. Lulekal, Awol Mekonnen, Nigus Zegeye, Y. Shiferaw","doi":"10.2174/2212796814999200818095036","DOIUrl":"https://doi.org/10.2174/2212796814999200818095036","url":null,"abstract":"\u0000\u0000The Eucalyptus globulus extractions have been used by the traditional\u0000healers to treat diseases in the study area. Our previous study revealed that the essential\u0000oil has antimicrobial and antifungal activity. This study determined phytochemical analysis,\u0000skin irritation, acute and subacute toxicity of Eucalyptus globulus essential oil in mice\u0000and rats.\u0000\u0000\u0000\u0000The phytochemicals were analyzed using GC-MS mass spectrometry. The acute\u0000toxicity study was determined at three dose levels of 1500 mg/kg, 1750mg/kg, and 2000\u0000mg/kg. The essential oil limit test at a dose of 1000 mg/kg was administered to mice for 28\u0000consecutive days for sub-acute toxicity study. The mice mortality, behavioral change, injury\u0000and other signs of illness were recorded once daily. Biochemical parameters were evaluated.\u0000Liver and kidney were analyzed for histopathological analyses. The 5% ointment formulation\u0000was applied to the rat skin to determine skin irritation effects.\u0000\u0000\u0000\u0000The Eucalyptus globulus essential oil showed no effect on the mice at a dose of\u00001500mg/kg and below, but caused signs of toxicity and death at a dose of 1750mg/kg and\u0000above compared to the controls (p<0.05). The LD50 value was 1650 mg/kg. There was no\u0000significant difference (p > 0.05) in the body weights, gross abnormalities of the organs and\u0000biochemical parameters compared to the control at 1000 mg/kg subacute toxicity study. No\u0000histopathological changes were detected in the organs tested. The 5% ointment formulation\u0000did not show any abnormal skin reaction.\u0000\u0000\u0000\u0000In the present study, the Eucalyptus globulus essential oil was comparable with\u0000other studies in terms of both chemical composition and its effects on sub-acute and topical\u0000application.\u0000\u0000\u0000\u0000This toxicity study demonstrated that Eucalyptus globulus essential oil is nontoxic\u0000at a relatively lower concentration.\u0000","PeriodicalId":10784,"journal":{"name":"Current Chemical Biology","volume":"12 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83422832","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-08-18DOI: 10.2174/2212796814999200818103157
P. Borah, V. S. Mattaparthi
Aggregation of misfolded proteins under stress conditions in the cell might lead to several neurodegenerative disorders. Amyloid-beta (Aβ1-42) peptide, the causative agent of Alzheimer’s disease, has the propensity to fold into β-sheets under stress, forming aggregated amyloid plaques. This is influenced by factors such as pH, temperature, metal ions, mutation of residues, and ionic strength of the solution. There are several studies that have highlighted the importance of ionic strength in affecting the folding and aggregation propensity of Aβ1-42 peptide. To understand the effect of ionic strength of the solution on the aggregation propensity of Aβ1-42 peptide, using computational approaches. In this study, Molecular Dynamics (MD) simulations were performed on Aβ1-42 peptide monomer placed in (i) 0 M, (ii) 0.15 M, and (iii) 0.30 M concentration of NaCl solution. To prepare the input files for the MD simulations, we have used the Amberff99SB force field. The conformational dynamics of Aβ1-42 peptide monomer in different ionic strengths of the solutions were illustrated from the analysis of the corresponding MD trajectory using the CPPtraj tool. From the MD trajectory analysis, we observe that with an increase in the ionic strength of the solution, Aβ1-42 peptide monomer shows a lesser tendency to undergo aggregation. From RMSD and SASA analysis, we noticed that Aβ1-42 peptide monomer undergoes a rapid change in conformation with an increase in the ionic strength of the solution. In addition, from the radius of gyration (Rg) analysis, we observed Aβ1-42 peptide monomer to be more compact at moderate ionic strength of the solution. Aβ1-42 peptide was also found to hold its helical secondary structure at moderate and higher ionic strengths of the solution. The diffusion coefficient of Aβ1-42 peptide monomer was also found to vary with the ionic strength of the solution. We observed a relatively higher diffusion coefficient value for Aβ1-42 peptide at moderate ionic strength of the solution. Our findings from this computational study highlight the marked effect of ionic strength of the solution on the conformational dynamics and aggregation propensity of Aβ1-42 peptide monomer.
{"title":"Effect of Ionic Strength on the Aggregation Propensity of Aβ1-42 Peptide: An In-silico Study","authors":"P. Borah, V. S. Mattaparthi","doi":"10.2174/2212796814999200818103157","DOIUrl":"https://doi.org/10.2174/2212796814999200818103157","url":null,"abstract":"\u0000\u0000Aggregation of misfolded proteins under stress conditions in the cell\u0000might lead to several neurodegenerative disorders. Amyloid-beta (Aβ1-42) peptide, the causative\u0000agent of Alzheimer’s disease, has the propensity to fold into β-sheets under stress, forming\u0000aggregated amyloid plaques. This is influenced by factors such as pH, temperature, metal\u0000ions, mutation of residues, and ionic strength of the solution. There are several studies that\u0000have highlighted the importance of ionic strength in affecting the folding and aggregation\u0000propensity of Aβ1-42 peptide.\u0000\u0000\u0000\u0000To understand the effect of ionic strength of the solution on the aggregation propensity\u0000of Aβ1-42 peptide, using computational approaches.\u0000\u0000\u0000\u0000 In this study, Molecular Dynamics (MD) simulations were performed\u0000on Aβ1-42 peptide monomer placed in (i) 0 M, (ii) 0.15 M, and (iii) 0.30 M concentration\u0000of NaCl solution. To prepare the input files for the MD simulations, we have used the\u0000Amberff99SB force field. The conformational dynamics of Aβ1-42 peptide monomer in different\u0000ionic strengths of the solutions were illustrated from the analysis of the corresponding\u0000MD trajectory using the CPPtraj tool.\u0000\u0000\u0000\u0000From the MD trajectory analysis, we observe that with an increase in the ionic\u0000strength of the solution, Aβ1-42 peptide monomer shows a lesser tendency to undergo aggregation.\u0000From RMSD and SASA analysis, we noticed that Aβ1-42 peptide monomer undergoes\u0000a rapid change in conformation with an increase in the ionic strength of the solution. In addition,\u0000from the radius of gyration (Rg) analysis, we observed Aβ1-42 peptide monomer to be\u0000more compact at moderate ionic strength of the solution. Aβ1-42 peptide was also found to\u0000hold its helical secondary structure at moderate and higher ionic strengths of the solution.\u0000The diffusion coefficient of Aβ1-42 peptide monomer was also found to vary with the ionic\u0000strength of the solution. We observed a relatively higher diffusion coefficient value for Aβ1-42\u0000peptide at moderate ionic strength of the solution.\u0000\u0000\u0000\u0000Our findings from this computational study highlight the marked effect of ionic\u0000strength of the solution on the conformational dynamics and aggregation propensity of Aβ1-42\u0000peptide monomer.\u0000","PeriodicalId":10784,"journal":{"name":"Current Chemical Biology","volume":"231 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74473598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-08-18DOI: 10.2174/2212796814666200818111849
M. Emam, A. T. Keshta, Y. Mohamed, Y. Attia
Wound healing is a complex process necessary for repairing damaged tissues and preventing infection. Selenium nanoparticles (Se NPs) were known due to their antioxidant and antimicrobial effects, also niacin has angiogenesis and antioxidant effects that are important in wound healing. The present study was conducted to investigate the effect of Se NPs and niacin in reducing and accelerating the wound healing time in mice. A simple wet chemical method has been modified to synthesize Se NPs in order to investigate their effect and niacin on reducing the wound healing in 80 adult female albino mice (250 mm2 full thickness open excision wound) that were divided into eight groups (10 mice/each). After 30-days, the mice were sacrificed, blood and tissue samples were taken for analysis. The results showed that the percentage of wound area had been significantly reduced in Se NPs and niacin treated groups compared to the positive control. The level of Vascular Endothelial cell Growth Factor and Collagenase I in Se NPs and niacin groups significantly exceed those of other groups while Nitric Oxide (NO) was significantly decreased in treated groups. Liver and kidney functions showed the lower toxicity effect of Se NPs and niacin. Skin tissue showed the wound healing effect of Se NPs and niacin by regenerating skin layer compared to the positive group. Se NPs and niacin play an important role in accelerating and reducing the time of wound healing while they were antagonistic to each other.
{"title":"Insight on Ameliorative Role of Selenium Nanoparticles and Niacin in Wound Healing on Adult Female Albino Mice","authors":"M. Emam, A. T. Keshta, Y. Mohamed, Y. Attia","doi":"10.2174/2212796814666200818111849","DOIUrl":"https://doi.org/10.2174/2212796814666200818111849","url":null,"abstract":"\u0000\u0000 Wound healing is a complex process necessary for repairing damaged\u0000tissues and preventing infection. Selenium nanoparticles (Se NPs) were known due to\u0000their antioxidant and antimicrobial effects, also niacin has angiogenesis and antioxidant effects\u0000that are important in wound healing.\u0000\u0000\u0000\u0000The present study was conducted to investigate the effect of Se NPs and niacin in\u0000reducing and accelerating the wound healing time in mice.\u0000\u0000\u0000\u0000A simple wet chemical method has been modified to synthesize Se NPs in order to\u0000investigate their effect and niacin on reducing the wound healing in 80 adult female albino\u0000mice (250 mm2 full thickness open excision wound) that were divided into eight groups (10\u0000mice/each). After 30-days, the mice were sacrificed, blood and tissue samples were taken for\u0000analysis.\u0000\u0000\u0000\u0000The results showed that the percentage of wound area had been significantly reduced\u0000in Se NPs and niacin treated groups compared to the positive control. The level of\u0000Vascular Endothelial cell Growth Factor and Collagenase I in Se NPs and niacin groups significantly\u0000exceed those of other groups while Nitric Oxide (NO) was significantly decreased\u0000in treated groups. Liver and kidney functions showed the lower toxicity effect of Se NPs and\u0000niacin. Skin tissue showed the wound healing effect of Se NPs and niacin by regenerating\u0000skin layer compared to the positive group.\u0000\u0000\u0000\u0000Se NPs and niacin play an important role in accelerating and reducing the time\u0000of wound healing while they were antagonistic to each other.\u0000","PeriodicalId":10784,"journal":{"name":"Current Chemical Biology","volume":"97 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76194781","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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