Ausgaben

Zeitschriften und Ausgaben

Volumen 72 (2022): Heft 3 (September 2022)

Volumen 72 (2022): Heft 2 (June 2022)

Volumen 72 (2022): Heft 1 (March 2022)

Volumen 71 (2021): Heft 4 (December 2021)

Volumen 71 (2021): Heft 3 (September 2021)

Volumen 71 (2021): Heft 2 (June 2021)

Volumen 71 (2021): Heft 1 (March 2021)

Volumen 70 (2020): Heft 4 (December 2020)

Volumen 70 (2020): Heft 3 (September 2020)

Volumen 70 (2020): Heft 2 (June 2020)

Volumen 70 (2020): Heft 1 (March 2020)

Volumen 69 (2019): Heft 4 (December 2019)

Volumen 69 (2019): Heft 3 (September 2019)

Volumen 69 (2019): Heft 2 (June 2019)

Volumen 69 (2019): Heft 1 (March 2019)

Volumen 68 (2018): Heft 4 (December 2018)

Volumen 68 (2018): Heft 3 (September 2018)

Volumen 68 (2018): Heft 2 (June 2018)

Volumen 68 (2018): Heft 1 (March 2018)

Volumen 67 (2017): Heft 4 (December 2017)

Volumen 67 (2017): Heft 3 (September 2017)

Volumen 67 (2017): Heft 2 (June 2017)

Volumen 67 (2017): Heft 1 (March 2017)

Volumen 66 (2016): Heft 4 (December 2016)

Volumen 66 (2016): Heft 3 (September 2016)

Volumen 66 (2016): Heft 2 (June 2016)

Volumen 66 (2016): Heft 1 (March 2016)

Volumen 65 (2015): Heft 4 (December 2015)

Volumen 65 (2015): Heft 3 (September 2015)

Volumen 65 (2015): Heft 2 (June 2015)

Volumen 65 (2015): Heft 1 (March 2015)

Volumen 64 (2014): Heft 4 (December 2014)

Volumen 64 (2014): Heft 3 (September 2014)

Volumen 64 (2014): Heft 2 (June 2014)

Volumen 64 (2014): Heft 1 (March 2014)

Volumen 63 (2013): Heft 4 (December 2013)

Volumen 63 (2013): Heft 3 (September 2013)

Volumen 63 (2013): Heft 2 (June 2013)

Volumen 63 (2013): Heft 1 (March 2013)

Volumen 62 (2012): Heft 4 (December 2012)

Volumen 62 (2012): Heft 3 (September 2012)

Volumen 62 (2012): Heft 2 (June 2012)

Volumen 62 (2012): Heft 1 (March 2012)

Volumen 61 (2011): Heft 4 (December 2011)

Volumen 61 (2011): Heft 3 (September 2011)

Volumen 61 (2011): Heft 2 (June 2011)

Volumen 61 (2011): Heft 1 (March 2011)

Volumen 60 (2010): Heft 4 (December 2010)

Volumen 60 (2010): Heft 3 (September 2010)

Volumen 60 (2010): Heft 2 (June 2010)

Volumen 60 (2010): Heft 1 (March 2010)

Volumen 59 (2009): Heft 4 (December 2009)

Volumen 59 (2009): Heft 3 (September 2009)

Volumen 59 (2009): Heft 2 (June 2009)

Volumen 59 (2009): Heft 1 (March 2009)

Volumen 58 (2008): Heft 4 (December 2008)

Volumen 58 (2008): Heft 3 (September 2008)

Volumen 58 (2008): Heft 2 (June 2008)

Volumen 58 (2008): Heft 1 (March 2008)

Volumen 57 (2007): Heft 4 (December 2007)

Volumen 57 (2007): Heft 3 (September 2007)

Volumen 57 (2007): Heft 2 (June 2007)

Volumen 57 (2007): Heft 1 (March 2007)

Zeitschriftendaten
Format
Zeitschrift
eISSN
1846-9558
Erstveröffentlichung
28 Feb 2007
Erscheinungsweise
4 Hefte pro Jahr
Sprachen
Englisch

Suche

Volumen 72 (2022): Heft 3 (September 2022)

Zeitschriftendaten
Format
Zeitschrift
eISSN
1846-9558
Erstveröffentlichung
28 Feb 2007
Erscheinungsweise
4 Hefte pro Jahr
Sprachen
Englisch

Suche

10 Artikel
access type Uneingeschränkter Zugang

AXL inhibitors selected by molecular docking: Option for reducing SARS-CoV-2 entry into cells

Online veröffentlicht: 13 Apr 2022
Seitenbereich: 329 - 343

Zusammenfassung

Abstract

The COVID-19 pandemic is ongoing and the benefit from vaccines is still insufficient since COVID-19 continues to be dia g-nosed in vaccinated individuals. It is, therefore, necessary to propose specific pharmacological treatments against COVID-19. A new therapeutic target on the human cellular membrane is AXL (anexelekto), proposed as an independent pathway by which interaction with the S protein of SARS-CoV-2 allows the virus to enter the cell, without the participation of ACE2. AXL serves as another gate through which SARS-CoV-2 can enter cells. Therefore, any stage of COVID-19 could be ameliorated by hindering the interaction between AXL and SARS-CoV-2. This study proposes ten compounds (1–10), selected by mole-cu lar docking and using a library of nearly 500,000 compounds, to develop a new drug that will decrease the interaction of AXL with the S protein of SARS-CoV-2. These compounds have a specific potential site of interaction with AXL, between Glu59, His61, Glu70 and Ser74 amino acids. This site is necessary for the interaction of AXL with the S protein. With this, we propose to develop a new adjuvant treatment against COVID-19.

Schlüsselwörter

  • COVID-19
  • SARS-CoV-2
  • AXL ligand
  • molecular docking
  • NTD-S1
  • S protein
access type Uneingeschränkter Zugang

The effectiveness of dexamethasone as a combination therapy for COVID-19

Online veröffentlicht: 13 Apr 2022
Seitenbereich: 345 - 358

Zusammenfassung

Abstract

Coronavirus disease 2019 (COVID-19) was reported as a global pandemic in March 2020 after invading many countries and leaving behind tens of thousands of infected patients in a brief time span. Approval of a few vaccines has been obtained and their efficacy of varying degrees established. Still, there is no effective pharmaceutical agent for the treatment of COVID-19 though several drugs are undergoing clinical trials. Recent studies have shown that dexamethasone, a corticosteroid, can reduce the rate of COVID-19-related mortality in the intensive care unit by 35 % for patients who are on mechanical ventilation. Although variable efficacy of other combination therapies has been reported for treating COVID-19 associated with acute respiratory distress syndrome (ARDS), dexamethasone is an extensively used drug in many treatment regimens against COVID-19. The current review aims to explore the role of dexamethasone as an efficient combination treatment for COVID-19.

Schlüsselwörter

  • dexamethasone
  • glucocorticosteroids
  • acute respiratory distress syndrome
  • Coronavirus disease 2019
  • combination therapy
  • SARS-CoV-2
  • immunosuppressive
access type Uneingeschränkter Zugang

Potential anti-ageing effects of probiotic-derived conditioned media on human skin cells

Online veröffentlicht: 13 Apr 2022
Seitenbereich: 359 - 374

Zusammenfassung

Abstract

In this study, the protective functions of bacteria-free conditioned media from Bifidobacterium and Lactobacillus species against ultraviolet radiation-induced skin ageing and associated cellular damage were investigated. The effects of ultraviolet radiation-induced reactive oxygen species production were suppressed by all conditioned media; particularly, the loss of cell viability and downregulation of collagen gene expression were significantly reversed by the conditioned media from B. longum and B. lactis. Further exa mination of potential anti-pigmentation effects revealed that the B. lactis-derived conditioned media significantly inhibited tyrosinase activity and alpha-melanocyte-stimulating hormone-induced melanin production in human epidermal melanocytes. Further, the conditioned media suppressed the phosphorylation of extracellular signal- related kinase, which functions as an upstream regulator of melanogenesis. Therefore, B. lactis-derived conditioned media can potentially protect against cellular damage involved in skin-ageing processes.

Schlüsselwörter

  • anti-ageing
  • skin cells
  • probiotics
  • conditioned media
  • protection
  • anti-pigmentation
access type Uneingeschränkter Zugang

Polyphenol content and antioxidant activity of phytoestrogen containing food and dietary supplements: DPPH free radical scavenging activity by HPLC

Online veröffentlicht: 13 Apr 2022
Seitenbereich: 375 - 388

Zusammenfassung

Abstract

Soy, red clover, chaste tree, hop and flax have all been found to contain a wide range of phytoestrogenic compounds, and a large number of dietary supplements contain their extracts as principal ingredients. This study is aimed to evaluate the total polyphenolic content and antioxidant activity of phytoestrogen-containing food and formulated dietary supplements. The HPLC-DPPH method was applied for DPPH free radical scavenging activity testing of various phytoestrogen-containing samples. Polyphenol content and antioxidant activity in dietary supplements were higher than in functional food samples; multiple-botanical-source preparations showed higher polyphenol content and antioxidant activity than the mono-botanical counterparts. Furthermore, the correlation between polyphenol content and anti-oxidant activity was strongly statistically significant, so it might be concluded that antioxidant activity is proportional to the content of these secondary metabolites. The most striking batch-to-batch deviations were represented by one chaste berry-based product (RSD 41.3 %) and one red clover derived product (RSD 57.9 %). The results of this study contribute to a better understanding of the phenolic profile and antioxidant properties of phytoestrogen containing food and dietary supplements.

Schlüsselwörter

  • functional food
  • dietary supplements
  • phytoestrogens
  • polyphenol content
  • antioxidant activity
  • HPLC
access type Uneingeschränkter Zugang

Design and development of novel 1,2,3-triazole chalcone derivatives as potential anti-osteosarcoma agents via inhibition of PI3K/Akt/mTOR signalling pathway

Online veröffentlicht: 13 Apr 2022
Seitenbereich: 389 - 402

Zusammenfassung

Abstract

Osteosarcoma (OS) is an uncommon tumour that mainly affects bone in children and adolescents. The current treatment options of OS are of limited significance due to their immense side effects. In the present manuscript, we have developed a novel series of 1,2,3-triazole chalcone derivatives as potential agents against OS. The compounds were synthesized and evaluated for their PI3K and mTOR inhibitory activity using luminescent kinase assay, and Lance ultra assay, resp. The entire set of compounds showed significant to moderate inhibition of both kinases in the nanomolar range. The three most active compounds: 4e (N-(4-(3-(1-(4-bromophenyl)-1H-1,2,3-triazol-4-yl)acryloyl)phenyl)-4-nitrobenzamide), 4f (N-(4-(3-(1-(4-bromophenyl)-1H-1,2,3-triazol-4-yl)acryloyl)phenyl)-4-chlorobenzamide) and 4g (4-bromo-N-(4-(3-(1-(4-bromophenyl)-1H-1,2,3-triazol-4-yl)acryloyl)phenyl)benzamide), were evaluated for anticancer activity against human OS cancer cell line (MG-63), liver cancer cell line (HepG2), lung cancer cell line (A549) and cervical cancer (HeLa), using MTT assay. Among the tested series, compound 4e showed a better inhibitory profile than gedatolisib against PI3K and was approximately comparable to that of gedatolisib against mTOR. The most significant inhibitory activity was observed for compound 4e against all cell lines (MG-63, HepG2, A549 and HeLa), still somewhat lower to comparable to that of gedatolisib, but with the highest potency against MG-63 cells. Compound 4e was further tested for anti-cancer activity against other OS cells and showed to be equipo-tent to gedatolisib against U2OS and Saos-2 cells. Moreover, it was also found non-toxic to normal cells (BEAS-2B and MCF 10A). The effect of compound 4e was further determined on apoptosis of Saos-2 cells by Annexin-PI assay, where it significantly amplified the percentage of apoptotic cells. Novel 1,2,3-triazole chalcone derivatives are potential agents against OS.

Schlüsselwörter

  • 1,2,3-triazole-chalcone hybrids
  • osteosarcoma
  • kinase inhibition
access type Uneingeschränkter Zugang

Dasatinib enhances curcumin-induced cytotoxicity, apoptosis and protective autophagy in human schwannoma cells HEI-193: The role of Akt/mTOR/p70S6K signalling pathway

Online veröffentlicht: 13 Apr 2022
Seitenbereich: 403 - 414

Zusammenfassung

Abstract

The present study was carried out in human schwannoma cells (HEI-193) to determine the combined anti-cancer effect of curcumin and dasatinib. Cells were treated with curcumin only, dasatinib only, or the combination of curcumin and dasatinib for 24 hours. Cellular toxicity, cell proliferation, and cell death were determined by LDH, MTT, and trypan blue dye assays, respectively. ELISA based kit was used to determine apoptotic cell death. Western blotting was used to determine the expression of apoptotic and autophagy-associated protein markers. Similarly, expression levels of Akt/mTOR/p70S6K signalling pathway-related proteins were studied using Western blotting. Cell death and apoptosis were significantly higher in HEI-193 cells treated with curcumin and dasatinib combination compared to individual controls. The combination of curcumin and dasatinib significantly enhances autophagy markers compared to individual controls. Furthermore, the combination of curcumin and dasatinib significantly activates Akt/mTOR/p70S6K signalling pathway compared to individual controls. In conclusion, our results suggest that the combination of curcumin and dasatinib significantly enhances cytotoxicity, apoptosis, and protective autophagy in HEI-193 cells through Akt/mTOR/p70S6K signalling pathway.

Schlüsselwörter

  • human schwannoma cells
  • curcumin
  • dasatinib
  • cell apoptosis
  • autophagy
access type Uneingeschränkter Zugang

Bivalirudin exerts antiviral activity against respiratory syncytial virus-induced lung infections in neonatal mice

Online veröffentlicht: 13 Apr 2022
Seitenbereich: 415 - 425

Zusammenfassung

Abstract

Respiratory syncytial virus (RSV) is the most common cause of small airways inflammation in the lungs (bronchiolitis) in neonates and immunocompromised adults. The deregulation of cellular and plasma components leads to increased morbidity and mortality. The activation of the clotting cascade plays a key role in the progression of disease severity during viral infection. The current investigation studied the effect of bivalirudin (BR) on the progression and cellular effects of RSV-induced infection in the neonatal mice model. Mice (5–7 days old) were inoculated intranasally with RSV with or without BR administration (2 mg kg−1 day−1, i.v.) for 2 weeks. Tissue histopathology, inflammatory signalling genes such as TLR, and cytokines were analyzed. The results showed pneumocytes exhibiting nuclear pyknosis, cellular infiltration in lung tissue and increased lung titers in RSV-infected mice compared to the control. Furthermore, RSV-infected mice demonstrated altered clotting parameters such as D-dimer, soluble thrombomodulin, and increased inflammatory cytokines IL-5, 6, IFN-γ, IL-13, and CXCL1. Additionally, the mRNA expression analysis displayed increased levels of IL-33, TLR3, and TLR7 genes in RSV-infected lung tissue. Further, to delineate the role of micro RNAs, the qRT-PCR analysis was done, and the results displayed an increase in miR-136, miR-30b, and let-7i. At the same time, the down-regulated expression of miR-221 in RSV-infected mice compared to the control. BR treatment reduced the cellular infiltration with reduced inflammatory cytokines and normalized clotting indices. Thus, the study shows that RSV infection induces specific changes in lung tissue and the clotting related signalling mechanism. Additionally, BR treatment significantly reduces bronchiolitis and prevents the severity of the infections suggesting that BR can possibly be used to reduce the viral-mediated infections in neonates.

Schlüsselwörter

  • respiratory syncytial virus
  • neonates
  • mice
  • bivalirudin
  • inflammatory cytokines
access type Uneingeschränkter Zugang

Fingolimod exerts in vitro anticancer activity against hepatocellular carcinoma cell lines via YAP/TAZ suppression

Online veröffentlicht: 13 Apr 2022
Seitenbereich: 427 - 436

Zusammenfassung

Abstract

Hepatocellular carcinoma (HCC) remains a notably global health challenge with high mortality rates and poor prognosis. The deregulation of the Hippo signalling pathway, especially the overexpression and activation of downstream effector Yes-associated protein (YAP), has been demonstrated to result in the rapid malignant evolution of HCC. In this context, multiple efforts have been dedicated to targeting YAP for HCC therapy, but effective YAP inhibitors are still lacking. In this study, through a YAP-TEAD (8×GTIIC) luciferase reporter assay, we identified fingolimod, an immunomodulatory drug approved for the treatment of multiple sclerosis, as a novel YAP inhibitor. Fingolimod suppressed the proliferation of HCC cell lines by downregulating the protein levels as well as the trans-activating function of YAP. Overall, our current study not only identifies fingolimod as a novel YAP-targeting in hibitor, but also indicates that this clinically-approved drug could be utilized as a potential and feasible therapeutic drug for HCC.

Schlüsselwörter

  • fingolimod
  • hepatocellular carcinoma
  • hippo signalling
  • YAP/TAZ
access type Uneingeschränkter Zugang

Metabolomics reveal the mechanism for anti-renal fibrosis effects of an n-butanol extract from Amygdalus mongolica

Online veröffentlicht: 13 Apr 2022
Seitenbereich: 437 - 448

Zusammenfassung

Abstract

To reveal the mechanism of anti-renal fibrosis effects of an n-butanol extract from Amygdalus mongolica, renal fibrosis was induced with unilateral ureteral obstruction (UUO) and then treated with an n-butanol extract (BUT) from Amygdalus mongolica (Rosaceae). Sixty male Sprague-Dawley rats were randomly divided into the sham-operated, renal fibrosis (RF) model, benazepril hydrochloride-treated model (1.5 mg kg−1) and BUT-treated (1.75, 1.5 and 1.25 g kg−1) groups and the respective drugs were administered intragastrically for 21 days. Related biochemical indices in rat serum were determined and histopathological morphology observed. Serum metabolomics was assessed with HPLC-Q-TOF-MS. The BUT reduced levels of blood urea nitrogen, serum creatinine and albumin and lowered the content of malondialdehyde and hydroxyproline in tissues. The activity of superoxide dismutase in tissues was increased and an improvement in the severity of RF was observed. Sixteen possible biomarkers were identified by metabolomic analysis and six key metabolic pathways, including the TCA cycle and tyrosine metabolism, were analyzed. After treatment with the extract, 8, 12 and 9 possible biomarkers could be detected in the high-, medium- and low-dose groups, respectively. Key biomarkers of RF, identified using metabolomics, were most affected by the medium dose. A. mongolica BUT extract displays a protective effect on RF in rats and should be investigated as a candidate drug for the treatment of the disease.

Schlüsselwörter

  • renal fibrosis
  • protective effect
  • metabolomics
  • mechanism
access type Uneingeschränkter Zugang

Evaluation and molecular modelling of bis-Schiff base derivatives as potential leads for management of diabetes mellitus

Online veröffentlicht: 13 Apr 2022
Seitenbereich: 449 - 458

Zusammenfassung

Abstract

Developing a medication to cure and manage diabetes mellitus complications is of interest in medicinal chemistry. Toward this end, six bis-biphenyl-salicylaldehyde Schiff base derivatives have been evaluated for their α-glucosidase inhibition, antiglycation and anti-inflammation potentials. Four compounds (compounds 25) showed an excellent α-glucosidase inhibitory effect superior to that produced by acarbose. Additionally, the docking study revealed that these compounds are anchored within the binding pocket of α-glucosidase via hydrogen bonding, π-stacking and hydrophobic interactions, comparable to a high number of hydrogen bonding involved in anchoring acarbose. Interestingly, all tested compounds showed varying degrees of antiglycation activity with superior activity for two of them (compound 1 and compound 6) compared to the standard rutin. Moreover, the results indicated an outstanding anti-inflammatory activity for two compounds (compounds 1 and 6) compared to ibuprofen.

Schlüsselwörter

  • bis-Schiff bases
  • diabetes mellitus
  • glycation
  • postprandial hyperglycemia
  • α-glucosidase
  • docking study
10 Artikel
access type Uneingeschränkter Zugang

AXL inhibitors selected by molecular docking: Option for reducing SARS-CoV-2 entry into cells

Online veröffentlicht: 13 Apr 2022
Seitenbereich: 329 - 343

Zusammenfassung

Abstract

The COVID-19 pandemic is ongoing and the benefit from vaccines is still insufficient since COVID-19 continues to be dia g-nosed in vaccinated individuals. It is, therefore, necessary to propose specific pharmacological treatments against COVID-19. A new therapeutic target on the human cellular membrane is AXL (anexelekto), proposed as an independent pathway by which interaction with the S protein of SARS-CoV-2 allows the virus to enter the cell, without the participation of ACE2. AXL serves as another gate through which SARS-CoV-2 can enter cells. Therefore, any stage of COVID-19 could be ameliorated by hindering the interaction between AXL and SARS-CoV-2. This study proposes ten compounds (1–10), selected by mole-cu lar docking and using a library of nearly 500,000 compounds, to develop a new drug that will decrease the interaction of AXL with the S protein of SARS-CoV-2. These compounds have a specific potential site of interaction with AXL, between Glu59, His61, Glu70 and Ser74 amino acids. This site is necessary for the interaction of AXL with the S protein. With this, we propose to develop a new adjuvant treatment against COVID-19.

Schlüsselwörter

  • COVID-19
  • SARS-CoV-2
  • AXL ligand
  • molecular docking
  • NTD-S1
  • S protein
access type Uneingeschränkter Zugang

The effectiveness of dexamethasone as a combination therapy for COVID-19

Online veröffentlicht: 13 Apr 2022
Seitenbereich: 345 - 358

Zusammenfassung

Abstract

Coronavirus disease 2019 (COVID-19) was reported as a global pandemic in March 2020 after invading many countries and leaving behind tens of thousands of infected patients in a brief time span. Approval of a few vaccines has been obtained and their efficacy of varying degrees established. Still, there is no effective pharmaceutical agent for the treatment of COVID-19 though several drugs are undergoing clinical trials. Recent studies have shown that dexamethasone, a corticosteroid, can reduce the rate of COVID-19-related mortality in the intensive care unit by 35 % for patients who are on mechanical ventilation. Although variable efficacy of other combination therapies has been reported for treating COVID-19 associated with acute respiratory distress syndrome (ARDS), dexamethasone is an extensively used drug in many treatment regimens against COVID-19. The current review aims to explore the role of dexamethasone as an efficient combination treatment for COVID-19.

Schlüsselwörter

  • dexamethasone
  • glucocorticosteroids
  • acute respiratory distress syndrome
  • Coronavirus disease 2019
  • combination therapy
  • SARS-CoV-2
  • immunosuppressive
access type Uneingeschränkter Zugang

Potential anti-ageing effects of probiotic-derived conditioned media on human skin cells

Online veröffentlicht: 13 Apr 2022
Seitenbereich: 359 - 374

Zusammenfassung

Abstract

In this study, the protective functions of bacteria-free conditioned media from Bifidobacterium and Lactobacillus species against ultraviolet radiation-induced skin ageing and associated cellular damage were investigated. The effects of ultraviolet radiation-induced reactive oxygen species production were suppressed by all conditioned media; particularly, the loss of cell viability and downregulation of collagen gene expression were significantly reversed by the conditioned media from B. longum and B. lactis. Further exa mination of potential anti-pigmentation effects revealed that the B. lactis-derived conditioned media significantly inhibited tyrosinase activity and alpha-melanocyte-stimulating hormone-induced melanin production in human epidermal melanocytes. Further, the conditioned media suppressed the phosphorylation of extracellular signal- related kinase, which functions as an upstream regulator of melanogenesis. Therefore, B. lactis-derived conditioned media can potentially protect against cellular damage involved in skin-ageing processes.

Schlüsselwörter

  • anti-ageing
  • skin cells
  • probiotics
  • conditioned media
  • protection
  • anti-pigmentation
access type Uneingeschränkter Zugang

Polyphenol content and antioxidant activity of phytoestrogen containing food and dietary supplements: DPPH free radical scavenging activity by HPLC

Online veröffentlicht: 13 Apr 2022
Seitenbereich: 375 - 388

Zusammenfassung

Abstract

Soy, red clover, chaste tree, hop and flax have all been found to contain a wide range of phytoestrogenic compounds, and a large number of dietary supplements contain their extracts as principal ingredients. This study is aimed to evaluate the total polyphenolic content and antioxidant activity of phytoestrogen-containing food and formulated dietary supplements. The HPLC-DPPH method was applied for DPPH free radical scavenging activity testing of various phytoestrogen-containing samples. Polyphenol content and antioxidant activity in dietary supplements were higher than in functional food samples; multiple-botanical-source preparations showed higher polyphenol content and antioxidant activity than the mono-botanical counterparts. Furthermore, the correlation between polyphenol content and anti-oxidant activity was strongly statistically significant, so it might be concluded that antioxidant activity is proportional to the content of these secondary metabolites. The most striking batch-to-batch deviations were represented by one chaste berry-based product (RSD 41.3 %) and one red clover derived product (RSD 57.9 %). The results of this study contribute to a better understanding of the phenolic profile and antioxidant properties of phytoestrogen containing food and dietary supplements.

Schlüsselwörter

  • functional food
  • dietary supplements
  • phytoestrogens
  • polyphenol content
  • antioxidant activity
  • HPLC
access type Uneingeschränkter Zugang

Design and development of novel 1,2,3-triazole chalcone derivatives as potential anti-osteosarcoma agents via inhibition of PI3K/Akt/mTOR signalling pathway

Online veröffentlicht: 13 Apr 2022
Seitenbereich: 389 - 402

Zusammenfassung

Abstract

Osteosarcoma (OS) is an uncommon tumour that mainly affects bone in children and adolescents. The current treatment options of OS are of limited significance due to their immense side effects. In the present manuscript, we have developed a novel series of 1,2,3-triazole chalcone derivatives as potential agents against OS. The compounds were synthesized and evaluated for their PI3K and mTOR inhibitory activity using luminescent kinase assay, and Lance ultra assay, resp. The entire set of compounds showed significant to moderate inhibition of both kinases in the nanomolar range. The three most active compounds: 4e (N-(4-(3-(1-(4-bromophenyl)-1H-1,2,3-triazol-4-yl)acryloyl)phenyl)-4-nitrobenzamide), 4f (N-(4-(3-(1-(4-bromophenyl)-1H-1,2,3-triazol-4-yl)acryloyl)phenyl)-4-chlorobenzamide) and 4g (4-bromo-N-(4-(3-(1-(4-bromophenyl)-1H-1,2,3-triazol-4-yl)acryloyl)phenyl)benzamide), were evaluated for anticancer activity against human OS cancer cell line (MG-63), liver cancer cell line (HepG2), lung cancer cell line (A549) and cervical cancer (HeLa), using MTT assay. Among the tested series, compound 4e showed a better inhibitory profile than gedatolisib against PI3K and was approximately comparable to that of gedatolisib against mTOR. The most significant inhibitory activity was observed for compound 4e against all cell lines (MG-63, HepG2, A549 and HeLa), still somewhat lower to comparable to that of gedatolisib, but with the highest potency against MG-63 cells. Compound 4e was further tested for anti-cancer activity against other OS cells and showed to be equipo-tent to gedatolisib against U2OS and Saos-2 cells. Moreover, it was also found non-toxic to normal cells (BEAS-2B and MCF 10A). The effect of compound 4e was further determined on apoptosis of Saos-2 cells by Annexin-PI assay, where it significantly amplified the percentage of apoptotic cells. Novel 1,2,3-triazole chalcone derivatives are potential agents against OS.

Schlüsselwörter

  • 1,2,3-triazole-chalcone hybrids
  • osteosarcoma
  • kinase inhibition
access type Uneingeschränkter Zugang

Dasatinib enhances curcumin-induced cytotoxicity, apoptosis and protective autophagy in human schwannoma cells HEI-193: The role of Akt/mTOR/p70S6K signalling pathway

Online veröffentlicht: 13 Apr 2022
Seitenbereich: 403 - 414

Zusammenfassung

Abstract

The present study was carried out in human schwannoma cells (HEI-193) to determine the combined anti-cancer effect of curcumin and dasatinib. Cells were treated with curcumin only, dasatinib only, or the combination of curcumin and dasatinib for 24 hours. Cellular toxicity, cell proliferation, and cell death were determined by LDH, MTT, and trypan blue dye assays, respectively. ELISA based kit was used to determine apoptotic cell death. Western blotting was used to determine the expression of apoptotic and autophagy-associated protein markers. Similarly, expression levels of Akt/mTOR/p70S6K signalling pathway-related proteins were studied using Western blotting. Cell death and apoptosis were significantly higher in HEI-193 cells treated with curcumin and dasatinib combination compared to individual controls. The combination of curcumin and dasatinib significantly enhances autophagy markers compared to individual controls. Furthermore, the combination of curcumin and dasatinib significantly activates Akt/mTOR/p70S6K signalling pathway compared to individual controls. In conclusion, our results suggest that the combination of curcumin and dasatinib significantly enhances cytotoxicity, apoptosis, and protective autophagy in HEI-193 cells through Akt/mTOR/p70S6K signalling pathway.

Schlüsselwörter

  • human schwannoma cells
  • curcumin
  • dasatinib
  • cell apoptosis
  • autophagy
access type Uneingeschränkter Zugang

Bivalirudin exerts antiviral activity against respiratory syncytial virus-induced lung infections in neonatal mice

Online veröffentlicht: 13 Apr 2022
Seitenbereich: 415 - 425

Zusammenfassung

Abstract

Respiratory syncytial virus (RSV) is the most common cause of small airways inflammation in the lungs (bronchiolitis) in neonates and immunocompromised adults. The deregulation of cellular and plasma components leads to increased morbidity and mortality. The activation of the clotting cascade plays a key role in the progression of disease severity during viral infection. The current investigation studied the effect of bivalirudin (BR) on the progression and cellular effects of RSV-induced infection in the neonatal mice model. Mice (5–7 days old) were inoculated intranasally with RSV with or without BR administration (2 mg kg−1 day−1, i.v.) for 2 weeks. Tissue histopathology, inflammatory signalling genes such as TLR, and cytokines were analyzed. The results showed pneumocytes exhibiting nuclear pyknosis, cellular infiltration in lung tissue and increased lung titers in RSV-infected mice compared to the control. Furthermore, RSV-infected mice demonstrated altered clotting parameters such as D-dimer, soluble thrombomodulin, and increased inflammatory cytokines IL-5, 6, IFN-γ, IL-13, and CXCL1. Additionally, the mRNA expression analysis displayed increased levels of IL-33, TLR3, and TLR7 genes in RSV-infected lung tissue. Further, to delineate the role of micro RNAs, the qRT-PCR analysis was done, and the results displayed an increase in miR-136, miR-30b, and let-7i. At the same time, the down-regulated expression of miR-221 in RSV-infected mice compared to the control. BR treatment reduced the cellular infiltration with reduced inflammatory cytokines and normalized clotting indices. Thus, the study shows that RSV infection induces specific changes in lung tissue and the clotting related signalling mechanism. Additionally, BR treatment significantly reduces bronchiolitis and prevents the severity of the infections suggesting that BR can possibly be used to reduce the viral-mediated infections in neonates.

Schlüsselwörter

  • respiratory syncytial virus
  • neonates
  • mice
  • bivalirudin
  • inflammatory cytokines
access type Uneingeschränkter Zugang

Fingolimod exerts in vitro anticancer activity against hepatocellular carcinoma cell lines via YAP/TAZ suppression

Online veröffentlicht: 13 Apr 2022
Seitenbereich: 427 - 436

Zusammenfassung

Abstract

Hepatocellular carcinoma (HCC) remains a notably global health challenge with high mortality rates and poor prognosis. The deregulation of the Hippo signalling pathway, especially the overexpression and activation of downstream effector Yes-associated protein (YAP), has been demonstrated to result in the rapid malignant evolution of HCC. In this context, multiple efforts have been dedicated to targeting YAP for HCC therapy, but effective YAP inhibitors are still lacking. In this study, through a YAP-TEAD (8×GTIIC) luciferase reporter assay, we identified fingolimod, an immunomodulatory drug approved for the treatment of multiple sclerosis, as a novel YAP inhibitor. Fingolimod suppressed the proliferation of HCC cell lines by downregulating the protein levels as well as the trans-activating function of YAP. Overall, our current study not only identifies fingolimod as a novel YAP-targeting in hibitor, but also indicates that this clinically-approved drug could be utilized as a potential and feasible therapeutic drug for HCC.

Schlüsselwörter

  • fingolimod
  • hepatocellular carcinoma
  • hippo signalling
  • YAP/TAZ
access type Uneingeschränkter Zugang

Metabolomics reveal the mechanism for anti-renal fibrosis effects of an n-butanol extract from Amygdalus mongolica

Online veröffentlicht: 13 Apr 2022
Seitenbereich: 437 - 448

Zusammenfassung

Abstract

To reveal the mechanism of anti-renal fibrosis effects of an n-butanol extract from Amygdalus mongolica, renal fibrosis was induced with unilateral ureteral obstruction (UUO) and then treated with an n-butanol extract (BUT) from Amygdalus mongolica (Rosaceae). Sixty male Sprague-Dawley rats were randomly divided into the sham-operated, renal fibrosis (RF) model, benazepril hydrochloride-treated model (1.5 mg kg−1) and BUT-treated (1.75, 1.5 and 1.25 g kg−1) groups and the respective drugs were administered intragastrically for 21 days. Related biochemical indices in rat serum were determined and histopathological morphology observed. Serum metabolomics was assessed with HPLC-Q-TOF-MS. The BUT reduced levels of blood urea nitrogen, serum creatinine and albumin and lowered the content of malondialdehyde and hydroxyproline in tissues. The activity of superoxide dismutase in tissues was increased and an improvement in the severity of RF was observed. Sixteen possible biomarkers were identified by metabolomic analysis and six key metabolic pathways, including the TCA cycle and tyrosine metabolism, were analyzed. After treatment with the extract, 8, 12 and 9 possible biomarkers could be detected in the high-, medium- and low-dose groups, respectively. Key biomarkers of RF, identified using metabolomics, were most affected by the medium dose. A. mongolica BUT extract displays a protective effect on RF in rats and should be investigated as a candidate drug for the treatment of the disease.

Schlüsselwörter

  • renal fibrosis
  • protective effect
  • metabolomics
  • mechanism
access type Uneingeschränkter Zugang

Evaluation and molecular modelling of bis-Schiff base derivatives as potential leads for management of diabetes mellitus

Online veröffentlicht: 13 Apr 2022
Seitenbereich: 449 - 458

Zusammenfassung

Abstract

Developing a medication to cure and manage diabetes mellitus complications is of interest in medicinal chemistry. Toward this end, six bis-biphenyl-salicylaldehyde Schiff base derivatives have been evaluated for their α-glucosidase inhibition, antiglycation and anti-inflammation potentials. Four compounds (compounds 25) showed an excellent α-glucosidase inhibitory effect superior to that produced by acarbose. Additionally, the docking study revealed that these compounds are anchored within the binding pocket of α-glucosidase via hydrogen bonding, π-stacking and hydrophobic interactions, comparable to a high number of hydrogen bonding involved in anchoring acarbose. Interestingly, all tested compounds showed varying degrees of antiglycation activity with superior activity for two of them (compound 1 and compound 6) compared to the standard rutin. Moreover, the results indicated an outstanding anti-inflammatory activity for two compounds (compounds 1 and 6) compared to ibuprofen.

Schlüsselwörter

  • bis-Schiff bases
  • diabetes mellitus
  • glycation
  • postprandial hyperglycemia
  • α-glucosidase
  • docking study

Planen Sie Ihre Fernkonferenz mit Scienceendo