Rivista e Edizione

Volume 72 (2022): Edizione 4 (December 2022)

Volume 72 (2022): Edizione 3 (September 2022)

Volume 72 (2022): Edizione 2 (June 2022)

Volume 72 (2022): Edizione 1 (March 2022)

Volume 71 (2021): Edizione 4 (December 2021)

Volume 71 (2021): Edizione 3 (September 2021)

Volume 71 (2021): Edizione 2 (June 2021)

Volume 71 (2021): Edizione 1 (March 2021)

Volume 70 (2020): Edizione 4 (December 2020)

Volume 70 (2020): Edizione 3 (September 2020)

Volume 70 (2020): Edizione 2 (June 2020)

Volume 70 (2020): Edizione 1 (March 2020)

Volume 69 (2019): Edizione 4 (December 2019)

Volume 69 (2019): Edizione 3 (September 2019)

Volume 69 (2019): Edizione 2 (June 2019)

Volume 69 (2019): Edizione 1 (March 2019)

Volume 68 (2018): Edizione 4 (December 2018)

Volume 68 (2018): Edizione 3 (September 2018)

Volume 68 (2018): Edizione 2 (June 2018)

Volume 68 (2018): Edizione 1 (March 2018)

Volume 67 (2017): Edizione 4 (December 2017)

Volume 67 (2017): Edizione 3 (September 2017)

Volume 67 (2017): Edizione 2 (June 2017)

Volume 67 (2017): Edizione 1 (March 2017)

Volume 66 (2016): Edizione 4 (December 2016)

Volume 66 (2016): Edizione 3 (September 2016)

Volume 66 (2016): Edizione 2 (June 2016)

Volume 66 (2016): Edizione 1 (March 2016)

Volume 65 (2015): Edizione 4 (December 2015)

Volume 65 (2015): Edizione 3 (September 2015)

Volume 65 (2015): Edizione 2 (June 2015)

Volume 65 (2015): Edizione 1 (March 2015)

Volume 64 (2014): Edizione 4 (December 2014)

Volume 64 (2014): Edizione 3 (September 2014)

Volume 64 (2014): Edizione 2 (June 2014)

Volume 64 (2014): Edizione 1 (March 2014)

Volume 63 (2013): Edizione 4 (December 2013)

Volume 63 (2013): Edizione 3 (September 2013)

Volume 63 (2013): Edizione 2 (June 2013)

Volume 63 (2013): Edizione 1 (March 2013)

Volume 62 (2012): Edizione 4 (December 2012)

Volume 62 (2012): Edizione 3 (September 2012)

Volume 62 (2012): Edizione 2 (June 2012)

Volume 62 (2012): Edizione 1 (March 2012)

Volume 61 (2011): Edizione 4 (December 2011)

Volume 61 (2011): Edizione 3 (September 2011)

Volume 61 (2011): Edizione 2 (June 2011)

Volume 61 (2011): Edizione 1 (March 2011)

Volume 60 (2010): Edizione 4 (December 2010)

Volume 60 (2010): Edizione 3 (September 2010)

Volume 60 (2010): Edizione 2 (June 2010)

Volume 60 (2010): Edizione 1 (March 2010)

Volume 59 (2009): Edizione 4 (December 2009)

Volume 59 (2009): Edizione 3 (September 2009)

Volume 59 (2009): Edizione 2 (June 2009)

Volume 59 (2009): Edizione 1 (March 2009)

Volume 58 (2008): Edizione 4 (December 2008)

Volume 58 (2008): Edizione 3 (September 2008)

Volume 58 (2008): Edizione 2 (June 2008)

Volume 58 (2008): Edizione 1 (March 2008)

Volume 57 (2007): Edizione 4 (December 2007)

Volume 57 (2007): Edizione 3 (September 2007)

Volume 57 (2007): Edizione 2 (June 2007)

Volume 57 (2007): Edizione 1 (March 2007)

Dettagli della rivista
Formato
Rivista
eISSN
1846-9558
Pubblicato per la prima volta
28 Feb 2007
Periodo di pubblicazione
4 volte all'anno
Lingue
Inglese

Cerca

Volume 72 (2022): Edizione 1 (March 2022)

Dettagli della rivista
Formato
Rivista
eISSN
1846-9558
Pubblicato per la prima volta
28 Feb 2007
Periodo di pubblicazione
4 volte all'anno
Lingue
Inglese

Cerca

10 Articoli
Accesso libero

Evaluation of COVID-19 protease and HIV inhibitors interactions

Pubblicato online: 30 Aug 2021
Pagine: 1 - 8

Astratto

Abstract

The epidemic of the novel coronavirus disease (COVID-19) that started in 2019 has evoked an urgent demand for finding new potential therapeutic agents. In this study, we performed a molecular docking of anti-HIV drugs to refine HIV protease inhibitors and nucleotide analogues to target COVID-19. The evaluation was based on docking scores calculated by AutoDock Vina and top binding poses were analyzed. Our results suggested that lopinavir, darunavir, atazanavir, remdesivir, and tipranavir have the best binding affinity for the 3-chymotrypsin-like protease of COVID-19. The comparison of the binding sites of three drugs, namely, darunavir, atazanavir and remdesivir, showed an overlap region of the protein pocket. Our study showed a strong affinity between lopinavir, darunavir, atazanavir, tipranavir and COVID-19 protease. However, their efficacy should be confirmed by in vitro studies since there are concerns related to interference with their active sites.

Parole chiave

  • COVID-19
  • SARS-CoV-2
  • docking study
  • anti-HIV drugs
  • protease inhibitors
Accesso libero

Update on glasdegib in acute myeloid leukemia – broadening horizons of Hedgehog pathway inhibitors

Pubblicato online: 30 Aug 2021
Pagine: 9 - 34

Astratto

Abstract

Numerous new emerging therapies, including oral targeted chemotherapies, have recently entered the therapeutic arsenal against acute myeloid leukemia (AML). The significant shift toward the use of these novel therapeutics, administered either alone or in combination with intensive or low-intensity chemotherapy, changes the prospects for the control of this disease, especially for elderly patients. Glasdegib, an oral Hedgehog pathway inhibitor, showed satisfactory response rates associated with moderate toxicity and less early mortality than standard induction regimens in this population. It was approved in November 2018 by the FDA and in June 2020 by the EMA for use in combination with low-dose cytarabine as a treatment of newly-diagnosed AML in patients aged ≥ 75 and/or unfit for intensive induction chemotherapy. The current paper proposes an extensive, up-to-date review of the preclinical and clinical development of glasdegib. Elements of its routine clinical use and the landscape of ongoing clinical trials are also stated.

Parole chiave

  • glasdegib
  • PF-04449913
  • PF-913
  • acute myeloid leukemia
  • Hedgehog pathway
  • smoothened
Accesso libero

Application of neurotoxin- and pesticide-induced animal models of Parkinson’s disease in the evaluation of new drug delivery systems

Pubblicato online: 30 Aug 2021
Pagine: 35 - 58

Astratto

Abstract

Parkinson’s disease (PD) is the second most prevalent neuro-degenerative disease after Alzheimer´s disease. It is characterized by motor symptoms such as akinesia, bradykinesia, tremor, rigidity, and postural abnormalities, due to the loss of nigral dopaminergic neurons and a decrease in the dopa-mine contents of the caudate-putamen structures. To this date, there is no cure for the disease and available treatments are aimed at controlling the symptoms. Therefore, there is an unmet need for new treatments for PD. In the past decades, animal models of PD have been proven to be valuable tools in elucidating the nature of the pathogenic processes involved in the disease, and in designing new pharmacological approaches. Here, we review the use of neurotoxin-induced and pesticide-induced animal models of PD, specifically those induced by rotenone, paraquat, maneb, MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) and 6-OHDA (6-hydroxydopamine), and their application in the development of new drug delivery systems for PD.

Parole chiave

  • Parkinson’s disease
  • rotenone
  • paraquat
  • maneb
  • MPTP
  • 6-OHDA
  • animal model
  • controlled drug delivery
Accesso libero

Molecular networking-assisted flavonoid profile of Gypsophila glomerata extract in relation to its protective effects on carbon tetrachloride-induced hepatorenal damage in rats

Pubblicato online: 30 Aug 2021
Pagine: 59 - 77

Astratto

Abstract

The aim of the study was to provide an in-depth characterization of the methanol-aqueous extract from the aerial parts of Gypsophila glomerata Pall. Ex Adams (Caryophyllaceae) (EGG) and to assess its protective potential on carbon tetrachloride (CCl4)-induced liver and kidney damage in male Wistar rats. Twenty-two flavonoid C-, O- and C,O--glycosides in EGG were annotated by mass spectrometry--based molecular networking; nine of them are reported in this species for the first time. Fourteen-day oral administration of EGG at a dose 200 mg kg−1 bm prevented significantly CCl4-induced liver injury, discerned by an amelioration of the markers of oxidative stress (GSH and MDA) and transaminase activity. EGG decreased the serum level of urea and creatinine as well. The observed improvement of biochemical parameters was supported by histopathological observations. The protective hepatorenal effects of EGG, rich in 2“-О-pentosyl-6-С-hexosyl-apigenin/luteolin/ methylluteolin and their acetyl- and methoxycinnamoyl-derivatives, were comparable with the effects of the positive control silymarin.

Parole chiave

  • CCl
  • molecular network
  • hepatorenal toxicity
  • flavonoids
Accesso libero

Design, synthesis and molecular modeling study of substituted indoline-2-ones and spiro[indole-heterocycles] with potential activity against Gram-positive bacteria

Pubblicato online: 30 Aug 2021
Pagine: 79 - 95

Astratto

Abstract

Longstanding and firsthand infectious diseases are challenging community health threats. A new series of isatin derivatives bearing β-hydroxy ketone, chalcone, or spiro-heterocycle moiety, was synthesized in a good yield. Chemical structures of the synthesized compounds were elucidated using spectroscopic techniques and elemental analysis. Antibacterial activities of the compounds were then evaluated in vitro and by in silico modeling. The compounds were more active against Gram-positive bacteria, Staphylococcus aureus (MIC = 0.026–0.226 mmol L−1) and Bacillus subtilis (MIC = 0.348–1.723 mmol L–1) than against Gram-negative bacteria (MIC = 0.817–7.393 mmol L–1). Only 3-hydroxy-3-(2-(2,5-dimethylthiophen-3-yl)-2-oxoethyl)indolin-2-one (1b) was found as active as imipenem against S. aureus (MIC = 0.026 mmol L–1). In silico docking of the compounds in the binding sites of a homology modeled structure of S. aureus histidine kinase-Walk allowed us to shed light on the binding mode of these novel inhibitors. The highest antibacterial activity of 1b is consistent with its highest docking score values against S. aureus histidine kinase.

Parole chiave

  • 2-indolinone
  • spiro[indole-heterocyles]
  • antimicrobial
  • docking study
Accesso libero

UPLC-HRESI-MS and GC-MS analysis of the leaves of Nicotiana glauca

Pubblicato online: 30 Aug 2021
Pagine: 97 - 108

Astratto

Abstract

The alkaloid-rich fraction obtained by fractionation of the crude methanolic extract of the leaves of wild tobacco tree Nicotiana glauca Graham (Solanaceae) was analyzed using UPLC-MS and GC-MS. Anabasine, a piperidine alkaloid, was identified as the major constituent with approximately 60 % (m/m) of the alkaloid-rich fraction. In addition to anabasine, six secondary metabolites were identified using high-resolution UPLC-MS. Anabasine was quantified in the leaves to be 1 mg g−1 dry plant material. The GC-MS analysis revealed five compounds with anabasine as the major component, while nicotine was not detected. Moreover, GC-MS was used for the analysis of the volatile oil that was obtained by hydro-distillation from the leaves of N. glauca. The volatile plant oil was found to be rich in oxygenated sesquiterpenes (e.g., β-bisabolol) and carboxylic acids and esters (e.g., ethyl linoleate and hexadecanoic acid), whereas anabasine was not detected.

Parole chiave

  • tobacco tree
  • UPLC-HRESIMS
  • GC-MS
  • anabasine
  • nicotine
  • volatile oil
  • methanolic extract
Accesso libero

Knockdown of Annexin A1 induces apoptosis, causing G2/M arrest and facilitating phagocytosis activity in human leukemia cell lines

Pubblicato online: 30 Aug 2021
Pagine: 109 - 122

Astratto

Abstract

Annexin A1 (ANXA1) is an endogenous protein involved in the control of proliferation, cell cycle, phagocytosis, and apoptosis in several types of cancer. To investigate the effects of ANXA1 knockdown in leukemia cells, transfection with specific ANXA1 siRNA was performed. Cell cycle and apoptosis were analyzed using flow cytometry and a mechanism involving caspases and Bcl-2 was quantified using Western blotting. Phagocytosis activity was evaluated using hematoxylin & eosin staining. The ANXA1 expression was significantly downregulated after the knockdown and apoptosis was induced in tested cells. The expression of caspase-9 and -3 increased in U937 and Jurkat cells respectively. Bcl-2 expression was downregulated in K562 and Jurkat cells while upregulated in U937. The number of leukemic cells arrested at the G2/M phase and the phagocytosis index were significantly increased in transfected cells. This suggests that ANXA1 knockdown might be a potential approach in the therapeutic strategy for leukemia.

Parole chiave

  • Annexin A1
  • siRNA transfection
  • apoptosis
  • cell cycle
  • phagocytosis
  • leukemia
Accesso libero

Neuroprotective effects of arbutin against oxygen and glucose deprivation-induced oxidative stress and neuroinflammation in rat cortical neurons

Pubblicato online: 30 Aug 2021
Pagine: 123 - 134

Astratto

Abstract

In this study, the neuroprotective potential of arbutin (100 µmol L−1) pre-treatment and post-treatment against oxygen/ glucose deprivation (OGD) and reoxygenation (R) induced ischemic injury in cultured rat cortical neurons was explored. The OGD (60 min) and reoxygenation (24 h) treatment significantly (p < 0.001) compromised the antioxidant defence in cultured neurons. Subsequently, an increase (p < 0.001) in lipid peroxidation and inflammatory cytokines (tumour necrosis factor-α and nuclear factor kappa-B) declined neuron survival. In pre- and post-condition experiments, treatment with arbutin enhanced both survival (p < 0.01) and integrity (p < 0.05) of cultured neurons. Results showed that arbutin protects (p < 0.05) against peroxidative changes, inflammation, and enhanced the antioxidant activity (e.g., glutathione, superoxide dismutase and catalase) in cultured neurons subjected to OGD/R. It can be inferred that arbutin could protect against ischemic injuries and stroke. The anti-ischemic activity of arbutin can arrest post-stroke damage to the brain.

Parole chiave

  • arbutin
  • cerebral ischemia
  • inflammation
  • oxidative stress
Accesso libero

Optimizing glycerosome formulations via an orthogonal experimental design to enhance transdermal triptolide delivery

Pubblicato online: 30 Aug 2021
Pagine: 135 - 146

Astratto

Abstract

Triptolide exerts strong anti-inflammatory and immunomodulatory effects; however, its oral administration might be associated with side effects. Transdermal administration can improve the safety of triptolide. In this study, glycerosomes were prepared as the transdermal vehicle to enhance the transdermal delivery of triptolide. With entrapment efficiency and drug loading as dependent variables, the glycerosome formulation was optimized using an orthogonal experimental design. Phospholipid-to-cholesterol and phospholipid-to-triptolide mass ratios of 30:1 and 5:1, respectively and a glycerol concentration of 20 % (V/V) were used in the optimization. The glycerosomes prepared with the optimized formulation showed good stability, with an average particle size of 153.10 ± 2.69 nm, a zeta potential of –45.73 ± 0.60 mV and an entrapment greater than 75 %. Glycerosomes significantly increased the transdermal delivery of triptolide compared to conventional liposomes. As efficient carriers for the transdermal delivery of drugs, glycerosomes can potentially be used as an alternative to oral triptolide administration.

Parole chiave

  • nanocarriers
  • liposomes
  • glycerosomes
  • transdermal
  • rheumatoid arthritis
Accesso libero

Initiation of insulin therapy in patients with type 2 diabetes: An observational study

Pubblicato online: 30 Aug 2021
Pagine: 147 - 157

Astratto

Abstract

The aim of the study was to assess the initiation of insulin therapy in patients with type 2 diabetes using health claims data on prescription medicines. The study evaluated time to insulin initiation and prescribing patterns of other anti-diabetic medicines before and after insulin initiation. Five years after starting non-insulin antidiabetic therapy, 6.4 % of patients were prescribed insulin, which is substantially lower compared to other similar studies. Among all patients who initiated insulin therapy in 2013, 30 % did not continue any other antidiabetic therapy. However, this proportion was lowered to 20 % in 2018. Before insulin initiation in 2018, metformin was prescribed in only 67 % of patients and sulfonylureas in 78 % of patients. Moreover, metformin and sulfonylureas were discontinued after insulin initiation in 26 and 37 % of patients, resp. More attention should be paid to the continuation of oral anti-diabetics, particularly metformin, after insulin initiation.

Parole chiave

  • diabetes mellitus
  • insulin
  • metformin
  • sulfonylurea
10 Articoli
Accesso libero

Evaluation of COVID-19 protease and HIV inhibitors interactions

Pubblicato online: 30 Aug 2021
Pagine: 1 - 8

Astratto

Abstract

The epidemic of the novel coronavirus disease (COVID-19) that started in 2019 has evoked an urgent demand for finding new potential therapeutic agents. In this study, we performed a molecular docking of anti-HIV drugs to refine HIV protease inhibitors and nucleotide analogues to target COVID-19. The evaluation was based on docking scores calculated by AutoDock Vina and top binding poses were analyzed. Our results suggested that lopinavir, darunavir, atazanavir, remdesivir, and tipranavir have the best binding affinity for the 3-chymotrypsin-like protease of COVID-19. The comparison of the binding sites of three drugs, namely, darunavir, atazanavir and remdesivir, showed an overlap region of the protein pocket. Our study showed a strong affinity between lopinavir, darunavir, atazanavir, tipranavir and COVID-19 protease. However, their efficacy should be confirmed by in vitro studies since there are concerns related to interference with their active sites.

Parole chiave

  • COVID-19
  • SARS-CoV-2
  • docking study
  • anti-HIV drugs
  • protease inhibitors
Accesso libero

Update on glasdegib in acute myeloid leukemia – broadening horizons of Hedgehog pathway inhibitors

Pubblicato online: 30 Aug 2021
Pagine: 9 - 34

Astratto

Abstract

Numerous new emerging therapies, including oral targeted chemotherapies, have recently entered the therapeutic arsenal against acute myeloid leukemia (AML). The significant shift toward the use of these novel therapeutics, administered either alone or in combination with intensive or low-intensity chemotherapy, changes the prospects for the control of this disease, especially for elderly patients. Glasdegib, an oral Hedgehog pathway inhibitor, showed satisfactory response rates associated with moderate toxicity and less early mortality than standard induction regimens in this population. It was approved in November 2018 by the FDA and in June 2020 by the EMA for use in combination with low-dose cytarabine as a treatment of newly-diagnosed AML in patients aged ≥ 75 and/or unfit for intensive induction chemotherapy. The current paper proposes an extensive, up-to-date review of the preclinical and clinical development of glasdegib. Elements of its routine clinical use and the landscape of ongoing clinical trials are also stated.

Parole chiave

  • glasdegib
  • PF-04449913
  • PF-913
  • acute myeloid leukemia
  • Hedgehog pathway
  • smoothened
Accesso libero

Application of neurotoxin- and pesticide-induced animal models of Parkinson’s disease in the evaluation of new drug delivery systems

Pubblicato online: 30 Aug 2021
Pagine: 35 - 58

Astratto

Abstract

Parkinson’s disease (PD) is the second most prevalent neuro-degenerative disease after Alzheimer´s disease. It is characterized by motor symptoms such as akinesia, bradykinesia, tremor, rigidity, and postural abnormalities, due to the loss of nigral dopaminergic neurons and a decrease in the dopa-mine contents of the caudate-putamen structures. To this date, there is no cure for the disease and available treatments are aimed at controlling the symptoms. Therefore, there is an unmet need for new treatments for PD. In the past decades, animal models of PD have been proven to be valuable tools in elucidating the nature of the pathogenic processes involved in the disease, and in designing new pharmacological approaches. Here, we review the use of neurotoxin-induced and pesticide-induced animal models of PD, specifically those induced by rotenone, paraquat, maneb, MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) and 6-OHDA (6-hydroxydopamine), and their application in the development of new drug delivery systems for PD.

Parole chiave

  • Parkinson’s disease
  • rotenone
  • paraquat
  • maneb
  • MPTP
  • 6-OHDA
  • animal model
  • controlled drug delivery
Accesso libero

Molecular networking-assisted flavonoid profile of Gypsophila glomerata extract in relation to its protective effects on carbon tetrachloride-induced hepatorenal damage in rats

Pubblicato online: 30 Aug 2021
Pagine: 59 - 77

Astratto

Abstract

The aim of the study was to provide an in-depth characterization of the methanol-aqueous extract from the aerial parts of Gypsophila glomerata Pall. Ex Adams (Caryophyllaceae) (EGG) and to assess its protective potential on carbon tetrachloride (CCl4)-induced liver and kidney damage in male Wistar rats. Twenty-two flavonoid C-, O- and C,O--glycosides in EGG were annotated by mass spectrometry--based molecular networking; nine of them are reported in this species for the first time. Fourteen-day oral administration of EGG at a dose 200 mg kg−1 bm prevented significantly CCl4-induced liver injury, discerned by an amelioration of the markers of oxidative stress (GSH and MDA) and transaminase activity. EGG decreased the serum level of urea and creatinine as well. The observed improvement of biochemical parameters was supported by histopathological observations. The protective hepatorenal effects of EGG, rich in 2“-О-pentosyl-6-С-hexosyl-apigenin/luteolin/ methylluteolin and their acetyl- and methoxycinnamoyl-derivatives, were comparable with the effects of the positive control silymarin.

Parole chiave

  • CCl
  • molecular network
  • hepatorenal toxicity
  • flavonoids
Accesso libero

Design, synthesis and molecular modeling study of substituted indoline-2-ones and spiro[indole-heterocycles] with potential activity against Gram-positive bacteria

Pubblicato online: 30 Aug 2021
Pagine: 79 - 95

Astratto

Abstract

Longstanding and firsthand infectious diseases are challenging community health threats. A new series of isatin derivatives bearing β-hydroxy ketone, chalcone, or spiro-heterocycle moiety, was synthesized in a good yield. Chemical structures of the synthesized compounds were elucidated using spectroscopic techniques and elemental analysis. Antibacterial activities of the compounds were then evaluated in vitro and by in silico modeling. The compounds were more active against Gram-positive bacteria, Staphylococcus aureus (MIC = 0.026–0.226 mmol L−1) and Bacillus subtilis (MIC = 0.348–1.723 mmol L–1) than against Gram-negative bacteria (MIC = 0.817–7.393 mmol L–1). Only 3-hydroxy-3-(2-(2,5-dimethylthiophen-3-yl)-2-oxoethyl)indolin-2-one (1b) was found as active as imipenem against S. aureus (MIC = 0.026 mmol L–1). In silico docking of the compounds in the binding sites of a homology modeled structure of S. aureus histidine kinase-Walk allowed us to shed light on the binding mode of these novel inhibitors. The highest antibacterial activity of 1b is consistent with its highest docking score values against S. aureus histidine kinase.

Parole chiave

  • 2-indolinone
  • spiro[indole-heterocyles]
  • antimicrobial
  • docking study
Accesso libero

UPLC-HRESI-MS and GC-MS analysis of the leaves of Nicotiana glauca

Pubblicato online: 30 Aug 2021
Pagine: 97 - 108

Astratto

Abstract

The alkaloid-rich fraction obtained by fractionation of the crude methanolic extract of the leaves of wild tobacco tree Nicotiana glauca Graham (Solanaceae) was analyzed using UPLC-MS and GC-MS. Anabasine, a piperidine alkaloid, was identified as the major constituent with approximately 60 % (m/m) of the alkaloid-rich fraction. In addition to anabasine, six secondary metabolites were identified using high-resolution UPLC-MS. Anabasine was quantified in the leaves to be 1 mg g−1 dry plant material. The GC-MS analysis revealed five compounds with anabasine as the major component, while nicotine was not detected. Moreover, GC-MS was used for the analysis of the volatile oil that was obtained by hydro-distillation from the leaves of N. glauca. The volatile plant oil was found to be rich in oxygenated sesquiterpenes (e.g., β-bisabolol) and carboxylic acids and esters (e.g., ethyl linoleate and hexadecanoic acid), whereas anabasine was not detected.

Parole chiave

  • tobacco tree
  • UPLC-HRESIMS
  • GC-MS
  • anabasine
  • nicotine
  • volatile oil
  • methanolic extract
Accesso libero

Knockdown of Annexin A1 induces apoptosis, causing G2/M arrest and facilitating phagocytosis activity in human leukemia cell lines

Pubblicato online: 30 Aug 2021
Pagine: 109 - 122

Astratto

Abstract

Annexin A1 (ANXA1) is an endogenous protein involved in the control of proliferation, cell cycle, phagocytosis, and apoptosis in several types of cancer. To investigate the effects of ANXA1 knockdown in leukemia cells, transfection with specific ANXA1 siRNA was performed. Cell cycle and apoptosis were analyzed using flow cytometry and a mechanism involving caspases and Bcl-2 was quantified using Western blotting. Phagocytosis activity was evaluated using hematoxylin & eosin staining. The ANXA1 expression was significantly downregulated after the knockdown and apoptosis was induced in tested cells. The expression of caspase-9 and -3 increased in U937 and Jurkat cells respectively. Bcl-2 expression was downregulated in K562 and Jurkat cells while upregulated in U937. The number of leukemic cells arrested at the G2/M phase and the phagocytosis index were significantly increased in transfected cells. This suggests that ANXA1 knockdown might be a potential approach in the therapeutic strategy for leukemia.

Parole chiave

  • Annexin A1
  • siRNA transfection
  • apoptosis
  • cell cycle
  • phagocytosis
  • leukemia
Accesso libero

Neuroprotective effects of arbutin against oxygen and glucose deprivation-induced oxidative stress and neuroinflammation in rat cortical neurons

Pubblicato online: 30 Aug 2021
Pagine: 123 - 134

Astratto

Abstract

In this study, the neuroprotective potential of arbutin (100 µmol L−1) pre-treatment and post-treatment against oxygen/ glucose deprivation (OGD) and reoxygenation (R) induced ischemic injury in cultured rat cortical neurons was explored. The OGD (60 min) and reoxygenation (24 h) treatment significantly (p < 0.001) compromised the antioxidant defence in cultured neurons. Subsequently, an increase (p < 0.001) in lipid peroxidation and inflammatory cytokines (tumour necrosis factor-α and nuclear factor kappa-B) declined neuron survival. In pre- and post-condition experiments, treatment with arbutin enhanced both survival (p < 0.01) and integrity (p < 0.05) of cultured neurons. Results showed that arbutin protects (p < 0.05) against peroxidative changes, inflammation, and enhanced the antioxidant activity (e.g., glutathione, superoxide dismutase and catalase) in cultured neurons subjected to OGD/R. It can be inferred that arbutin could protect against ischemic injuries and stroke. The anti-ischemic activity of arbutin can arrest post-stroke damage to the brain.

Parole chiave

  • arbutin
  • cerebral ischemia
  • inflammation
  • oxidative stress
Accesso libero

Optimizing glycerosome formulations via an orthogonal experimental design to enhance transdermal triptolide delivery

Pubblicato online: 30 Aug 2021
Pagine: 135 - 146

Astratto

Abstract

Triptolide exerts strong anti-inflammatory and immunomodulatory effects; however, its oral administration might be associated with side effects. Transdermal administration can improve the safety of triptolide. In this study, glycerosomes were prepared as the transdermal vehicle to enhance the transdermal delivery of triptolide. With entrapment efficiency and drug loading as dependent variables, the glycerosome formulation was optimized using an orthogonal experimental design. Phospholipid-to-cholesterol and phospholipid-to-triptolide mass ratios of 30:1 and 5:1, respectively and a glycerol concentration of 20 % (V/V) were used in the optimization. The glycerosomes prepared with the optimized formulation showed good stability, with an average particle size of 153.10 ± 2.69 nm, a zeta potential of –45.73 ± 0.60 mV and an entrapment greater than 75 %. Glycerosomes significantly increased the transdermal delivery of triptolide compared to conventional liposomes. As efficient carriers for the transdermal delivery of drugs, glycerosomes can potentially be used as an alternative to oral triptolide administration.

Parole chiave

  • nanocarriers
  • liposomes
  • glycerosomes
  • transdermal
  • rheumatoid arthritis
Accesso libero

Initiation of insulin therapy in patients with type 2 diabetes: An observational study

Pubblicato online: 30 Aug 2021
Pagine: 147 - 157

Astratto

Abstract

The aim of the study was to assess the initiation of insulin therapy in patients with type 2 diabetes using health claims data on prescription medicines. The study evaluated time to insulin initiation and prescribing patterns of other anti-diabetic medicines before and after insulin initiation. Five years after starting non-insulin antidiabetic therapy, 6.4 % of patients were prescribed insulin, which is substantially lower compared to other similar studies. Among all patients who initiated insulin therapy in 2013, 30 % did not continue any other antidiabetic therapy. However, this proportion was lowered to 20 % in 2018. Before insulin initiation in 2018, metformin was prescribed in only 67 % of patients and sulfonylureas in 78 % of patients. Moreover, metformin and sulfonylureas were discontinued after insulin initiation in 26 and 37 % of patients, resp. More attention should be paid to the continuation of oral anti-diabetics, particularly metformin, after insulin initiation.

Parole chiave

  • diabetes mellitus
  • insulin
  • metformin
  • sulfonylurea

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