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21 ± 0.53 and -0.1 ± 0.17, respectively, and for the motion sickness questionnaire -2.34 ± 1.54 and -0.91 ± 1.41, respectively. Examination of a possible connection between initial symptom severity and adaptation rate failed to reveal a significant relationship.CONCLUSIONS We recommend the use of oral scopolamine to accelerate habituation and find it a relatively safe short-term treatment for airsickness. Our results support the notion that scopolamine accelerates the natural adaptation process.Doron O, Samuel O, Karfunkel-Doron D, Tal D. Scopolamine treatment and adaptation to airsickness. Aerosp Med Hum Perform. 2020; 91(4)313-317.KSL-W peptide has demonstrated antibacterial and antifungal activity and inhibitory effects against oral biofilm. This study aimed to check out the effect of chlorhexidine (CLX) or KSL-W peptide-loaded poloxamer 407-based microemulsions for buccal delivery on Fusobacterium nucleatum (F. nucleatum) biofilm. The formulation (F) containing 10% copolymer poloxamer 407 dispersion (1%), 40% oleic acid and 50% PPG-5-CETETH-20 was characterized by polarized light microscopy (PLM), small-angle X-ray scattering (SAXS), rheology, bioadhesive and syringeability; and in the treatment of a biofilm produced by F. nucleatum. The darkfield images obtained by PLM and the SAXS curves with an extended peak indicated that the system was characteristic of microemulsions. In a continuous analysis, microemulsions exhibited Newtonian behavior. In frequency, the oscillatory analysis profile presented predominantly viscous behavior. Bioadhesive force detected in the analysis of F (7.4 ± 1.81 mN˙ s) and syringeability (17.83± 5.97 N · mm) being adequate values for buccal administration. After 4 h, KSL-W-loaded F shown over 20% higher effectiveness than chlorhexidine-loaded microemulsions. In conclusion, the KSL-W-loaded microemulsions showed a considerable reduction in F. nucleatum biofilm formation and presented promising structural properties for buccal drug delivery.Resveratrol (RES) is a natural non-flavonoid polyphenol with cardioprotective activities, antioxidant, antiplatelet, and antiinflammatory. However, its low aqueous solubility, chemical stability, and oral bioavailability, as well as a short circulation half-life greatly limit its clinical applications. To overcome these limitations of RES, we synthesized a methoxy poly(ethylene glycol)-b-oligomerization(D, L-Leucine) (mPEG-b-O(D, L-Leu)) nanoparticle (NP) as the carrier of RES and evaluated the myocardial-protective effectiveness of this RES/NP complex in rat myocardial ischemia-reperfusion injury models. We gauged the characterization of the NP through proton nuclear magnetic resonance spectroscopy, gel permeation chromatography, transmission electron microscope, and Fourier transform infrared spectroscopy and then loaded RES on the nanocarrier by hydrophobic interactions under physiological pH to extend the release time of RES and prolong its circulation half-life. Subsequently, we used rat cardiomyocytes (H9C2 cells) and rat MI/RI model to investigate the relationship between drug composition and myocardial preservation properties. It was found that RES was encapsulated quickly and efficiently, and displayed an effectual loading-capacity and in vitro sustained-release. Anti-MI/RI effect of the RES/NP complex was found satisfactory in rat models in vivo using free RES as the control. This study suggested that NP may prove to be a potent nanocarrier to augment the pharmacotherapy of RES against MI/RI.Titanium dioxide nanoparticles (TiO₂ NPs) are largely manufactured and extensively applied for the treatment of environmental pollution. Studies have proved that exposure to TiO₂ NPs leads to toxicity of the reproductive system. However, very few studies have highlighted the involvement of nuclear factor erythroid-2 related factor 2 (Nrf2) under TiO₂ NPinduced spermatogenic apoptosis. Our findings suggested that TiO₂ NPs could cross the blood-testis barrier and were aggregated or deposed in spermatogenic cells, which resulted in spermatogenic apoptosis. Furthermore, exposure to TiO₂ NPs caused an overproduction of reactive oxygen species and the peroxidation of lipids, proteins, and DNA. Such exposure also caused significant decreases in the activities of SOD, GSH-PX, GST, and GSH content in the testis. Importantly, exposure to TiO₂ NPs resulted in an up-regulation of Keap1 expression and a down-regulation of Nrf2 and its target gene products, NQO1, HO-1, GCLC, PKC, and PI3K. The present study implies that TiO₂ NPs could lead to spermatogenic apoptosis, and Nrf2 is the initial factor that responded to such reproductive toxicity by regulating the expression of antioxidative proteins.MXene (Ti₃C₂Tx), as a novel 2D material, has produced a great interest due to its promising properties in biomedical applications, nevertheless, there is a lack of studies dedicated to investigate the possible toxic effect of MXene in embryos. Herein, we aim to scrutinize the potential toxicity of MXene nanosheets on the early stage of the embryo as well as angiogenesis. Avian embryos at 3 and 5 days of incubation were used as an experimental model in this investigation. Our findings reveal that MXene may produce adverse effect on the early stage of embryogenesis as ∼46% of MXene-exposed embryos died during 1-5 days after exposure. We also found that MXene at tested concentration inhibits angiogenesis of the chorioallantoic membrane of the embryo after 5 days of incubation. https://www.selleckchem.com/products/cd532.html More significantly, RT-PCR analysis of seven genes, which are key regulators of cell proliferation, survival, cell death and angiogenesis, revealed that these genes were deregulated in brain, heart and liver tissues from MXene-treated embryos in comparison with their matched controls. Our study clearly suggests that MXene at studied concentration might induce a toxic effect on the early stage of embryogenesis; nevertheless, more investigations are necessary to understand the effect at low concentrations and elucidate its mechanism at the early stage of normal development.Pancreatic ductal adenocarcinoma (PDAC) is radioresistant. Due to their strong X-ray absorption capacity, gold nanoparticles (AuNPs) have been used as radiosensitizers for cancer therapeutics. Herein, we describe a novel conjugate complex consisting of a peptide for targeting plectin-1 (PTP) specifically expressed on the PDAC cell membrane and AuNPs, termed AuNP-PTP, to be used for PDAC radiotherapy in vitro and in vivo. Previous studies revealed that compared with unmodified AuNPs, AuNP-PTP along with relevant low-energy X-ray irradiation of 6 MV at a dose of 2 Gy (RF) increased the targeting efficiency and induced apoptosis in treated PANC-1 cells and tumours. Importantly, extensive histopathological examination did not reveal evidence of acute or chronic injury in mice due to AuNPs or AuNP-PTP for up to six weeks despite the presence of X-ray exposure. The delicate AuNP-PTP hybrid provides a novel strategy to enhance radiotherapy efficiency in PDAC treatment.
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21 ± 0.53 and -0.1 ± 0.17, respectively, and for the motion sickness questionnaire -2.34 ± 1.54 and -0.91 ± 1.41, respectively. Examination of a possible connection between initial symptom severity and adaptation rate failed to reveal a significant relationship.CONCLUSIONS We recommend the use of oral scopolamine to accelerate habituation and find it a relatively safe short-term treatment for airsickness. Our results support the notion that scopolamine accelerates the natural adaptation process.Doron O, Samuel O, Karfunkel-Doron D, Tal D. Scopolamine treatment and adaptation to airsickness. Aerosp Med Hum Perform. 2020; 91(4)313-317.KSL-W peptide has demonstrated antibacterial and antifungal activity and inhibitory effects against oral biofilm. This study aimed to check out the effect of chlorhexidine (CLX) or KSL-W peptide-loaded poloxamer 407-based microemulsions for buccal delivery on Fusobacterium nucleatum (F. nucleatum) biofilm. The formulation (F) containing 10% copolymer poloxamer 407 dispersion (1%), 40% oleic acid and 50% PPG-5-CETETH-20 was characterized by polarized light microscopy (PLM), small-angle X-ray scattering (SAXS), rheology, bioadhesive and syringeability; and in the treatment of a biofilm produced by F. nucleatum. The darkfield images obtained by PLM and the SAXS curves with an extended peak indicated that the system was characteristic of microemulsions. In a continuous analysis, microemulsions exhibited Newtonian behavior. In frequency, the oscillatory analysis profile presented predominantly viscous behavior. Bioadhesive force detected in the analysis of F (7.4 ± 1.81 mN˙ s) and syringeability (17.83± 5.97 N · mm) being adequate values for buccal administration. After 4 h, KSL-W-loaded F shown over 20% higher effectiveness than chlorhexidine-loaded microemulsions. In conclusion, the KSL-W-loaded microemulsions showed a considerable reduction in F. nucleatum biofilm formation and presented promising structural properties for buccal drug delivery.Resveratrol (RES) is a natural non-flavonoid polyphenol with cardioprotective activities, antioxidant, antiplatelet, and antiinflammatory. However, its low aqueous solubility, chemical stability, and oral bioavailability, as well as a short circulation half-life greatly limit its clinical applications. To overcome these limitations of RES, we synthesized a methoxy poly(ethylene glycol)-b-oligomerization(D, L-Leucine) (mPEG-b-O(D, L-Leu)) nanoparticle (NP) as the carrier of RES and evaluated the myocardial-protective effectiveness of this RES/NP complex in rat myocardial ischemia-reperfusion injury models. We gauged the characterization of the NP through proton nuclear magnetic resonance spectroscopy, gel permeation chromatography, transmission electron microscope, and Fourier transform infrared spectroscopy and then loaded RES on the nanocarrier by hydrophobic interactions under physiological pH to extend the release time of RES and prolong its circulation half-life. Subsequently, we used rat cardiomyocytes (H9C2 cells) and rat MI/RI model to investigate the relationship between drug composition and myocardial preservation properties. It was found that RES was encapsulated quickly and efficiently, and displayed an effectual loading-capacity and in vitro sustained-release. Anti-MI/RI effect of the RES/NP complex was found satisfactory in rat models in vivo using free RES as the control. This study suggested that NP may prove to be a potent nanocarrier to augment the pharmacotherapy of RES against MI/RI.Titanium dioxide nanoparticles (TiO₂ NPs) are largely manufactured and extensively applied for the treatment of environmental pollution. Studies have proved that exposure to TiO₂ NPs leads to toxicity of the reproductive system. However, very few studies have highlighted the involvement of nuclear factor erythroid-2 related factor 2 (Nrf2) under TiO₂ NPinduced spermatogenic apoptosis. Our findings suggested that TiO₂ NPs could cross the blood-testis barrier and were aggregated or deposed in spermatogenic cells, which resulted in spermatogenic apoptosis. Furthermore, exposure to TiO₂ NPs caused an overproduction of reactive oxygen species and the peroxidation of lipids, proteins, and DNA. Such exposure also caused significant decreases in the activities of SOD, GSH-PX, GST, and GSH content in the testis. Importantly, exposure to TiO₂ NPs resulted in an up-regulation of Keap1 expression and a down-regulation of Nrf2 and its target gene products, NQO1, HO-1, GCLC, PKC, and PI3K. The present study implies that TiO₂ NPs could lead to spermatogenic apoptosis, and Nrf2 is the initial factor that responded to such reproductive toxicity by regulating the expression of antioxidative proteins.MXene (Ti₃C₂Tx), as a novel 2D material, has produced a great interest due to its promising properties in biomedical applications, nevertheless, there is a lack of studies dedicated to investigate the possible toxic effect of MXene in embryos. Herein, we aim to scrutinize the potential toxicity of MXene nanosheets on the early stage of the embryo as well as angiogenesis. Avian embryos at 3 and 5 days of incubation were used as an experimental model in this investigation. Our findings reveal that MXene may produce adverse effect on the early stage of embryogenesis as ∼46% of MXene-exposed embryos died during 1-5 days after exposure. We also found that MXene at tested concentration inhibits angiogenesis of the chorioallantoic membrane of the embryo after 5 days of incubation. https://www.selleckchem.com/products/cd532.html More significantly, RT-PCR analysis of seven genes, which are key regulators of cell proliferation, survival, cell death and angiogenesis, revealed that these genes were deregulated in brain, heart and liver tissues from MXene-treated embryos in comparison with their matched controls. Our study clearly suggests that MXene at studied concentration might induce a toxic effect on the early stage of embryogenesis; nevertheless, more investigations are necessary to understand the effect at low concentrations and elucidate its mechanism at the early stage of normal development.Pancreatic ductal adenocarcinoma (PDAC) is radioresistant. Due to their strong X-ray absorption capacity, gold nanoparticles (AuNPs) have been used as radiosensitizers for cancer therapeutics. Herein, we describe a novel conjugate complex consisting of a peptide for targeting plectin-1 (PTP) specifically expressed on the PDAC cell membrane and AuNPs, termed AuNP-PTP, to be used for PDAC radiotherapy in vitro and in vivo. Previous studies revealed that compared with unmodified AuNPs, AuNP-PTP along with relevant low-energy X-ray irradiation of 6 MV at a dose of 2 Gy (RF) increased the targeting efficiency and induced apoptosis in treated PANC-1 cells and tumours. Importantly, extensive histopathological examination did not reveal evidence of acute or chronic injury in mice due to AuNPs or AuNP-PTP for up to six weeks despite the presence of X-ray exposure. The delicate AuNP-PTP hybrid provides a novel strategy to enhance radiotherapy efficiency in PDAC treatment.
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