Hypertrophic scar(HS)is an undesirable skin abnormality following deep burns or operations.Although intralesional multi-injection with the suspension of triamcinolone acetonide(TA)and 5-fluorouracil(5-Fu)has exhibited...Hypertrophic scar(HS)is an undesirable skin abnormality following deep burns or operations.Although intralesional multi-injection with the suspension of triamcinolone acetonide(TA)and 5-fluorouracil(5-Fu)has exhibited great promise to HS treatment in clinical,the difference of metabolic behavior between TA and 5-Fu remarkably compromised the treatment efficacy.Besides,the traditional injection with great pain is highly dependent on the skill of the experts,which results in poor compliance.Herein,a bilayer dissolving microneedle(BMN)containing TA and 5-Fu(TA-5-Fu-BMN)with biphasic release profile was designed for HS therapy.Equipped with several micro-scale needle tips,the BMN could be self-pressed into the HS with uniform drug distribution and less pain.Both in vitro permeation and in vivo HS retention tests revealed that TA and 5-Fu could coexist in the scar tissue for a sufficient time period due to the well-designed biphasic release property.Subsequently,the rabbit ear HS model was established to assess therapeutic efficacy.The histological analysis showed that TA-5-Fu-BMN could significantly reduce abnormal fibroblast proliferation and collagen fiber deposition.It was also found that the value of scar elevation index was ameliorated to a basal level,together with the downregulation of mRNA and protein expression of Collagen I(Col I)and transforming growth factor-β1(TGF-β1)after application of TA-5-Fu-BMN.In conclusion,the BMN with biphasic release profiles could serve as a potential strategy for HS treatment providing both convenient administrations as well as controlled drug release behavior.展开更多
Liposome could form a long-term drug reservoir in the skin for sustained drug release,which is beneficial to improving efficacy and alleviating adverse effects.Thus,it has become a better option for anti-alopecia drug...Liposome could form a long-term drug reservoir in the skin for sustained drug release,which is beneficial to improving efficacy and alleviating adverse effects.Thus,it has become a better option for anti-alopecia drugs delivery.However,cholesterol used as the fluidity buffer in conventional liposomes is a precursor for testosterone biosynthesis,which could convert to dihydrotestosterone,resulting in hair follicle damage and potentiating hair loss.To overcome the limitations,in this study we prepared a cholesterol-free liposome(PPD-Lip)using protopanaxadiol(PPD)instead of cholesterol to avoid the biosynthesis of testosterone which is adverse to alopecia therapy.PPD-Lip also worked as an active ingredient to facilitate hair growth by promoting dermal papilla cells proliferation and migration,upregulating mRNA levels of hair growth-related positive regulators,and accelerating angiogenesis in vitro.Meanwhile,it promoted hair regrowth in telogen and androgenetic alopecia mice models in vivo.In addition,our study showed that as the liposomal vehicle,PPD-Lip loaded with dutasteride exerted a stronger efficacy in the treatment of androgenetic alopecia and such a strategy could extend to other anti-alopecia agents.To the best of our knowledge,being easy for clinical transformation,the PPD-based liposomal delivery system provides a promising and multifunctional alternative platform for the delivery of alopecia treatment agents.展开更多
This study systematically investigated the effects of a low-intensity magnetic field on the influence of keratinase activity, peptide yield, and structural and functional properties of peptides produced during solid-s...This study systematically investigated the effects of a low-intensity magnetic field on the influence of keratinase activity, peptide yield, and structural and functional properties of peptides produced during solid-state fermentation (SSF) of mixed organic substrates (chicken feather powder and okara) using a mutant strain of Bacillus licheniformis. Initially, the magnetic field-assisted SSF (MSSF) conditions were optimized, which provided the optimized conditions as the number of treatments 3 at every 24 h (24, 48, and 72 h) with 4 h holding time at 120 Gs of magnetic intensity (mI). Under the optimum conditions, keratinase activity and peptide production increased by 10.31% and 13.77%, respectively. Further, in order to evaluate the influence of magnetic field treatment on the peptides, MSSF experiments were done under different mI conditions (40, 80, 120, and 160 Gs), followed by the evaluation of the structural changes of the extracted peptides. The structural analysis revealed that mI had a significant impact on the keratin surface. In contrast, secondary structure analysis confirmed the unfolding of the peptide with decreased α-keratin and increased β-keratin, thereby boosting the bioactive properties of the peptides. The highest hydroxyl free radical (.OH), 1,1-diphenyl-2-picrylhydrazyl (DPPH) scavenging and Fe2+ chelating rates (56.55, 71.36, and 50.72%, respectively) were found at 120 Gs, which were insignificant with the results at 160 Gs. Therefore, MSSF has a positive effect on the proteolysis mechanism, which can increase bioactive peptide production from keratin.展开更多
Saline-alkaline soils are found worldwide, affecting over 1 billion hectares of arable lands especially in arid and semiarid regions. Alkaline soils are characterized by the high pH and low nutrient availability as we...Saline-alkaline soils are found worldwide, affecting over 1 billion hectares of arable lands especially in arid and semiarid regions. Alkaline soils are characterized by the high pH and low nutrient availability as well as high concentrations of bicarbonate and carbonate, being highly detrimental to crop production. According to the UN Food and Agriculture Organization ( FAO and ITPS, 2015 ), approximately 60% of saline soils are concurrently affected by alkalization, posing a serious threat to food security. In recent decades, the breeding objectives for staple crops were mainly focused on yield, quality, and resistance to diseases, leaving alkaline tolerance largely overlooked. Now more than ever, we need to understand the mechanisms of plant alkaline tolerance to develop new crop varieties better adapted to alkaline soil conditions.展开更多
基金supported by the National Natural Science Foundation of China[grant No.81803466]the Research and Development Plan for Key Areas in Guangdong Province[grant No.2019B020204002]the National Science and Technology Major Program[grant No.2017zx09101001].
文摘Hypertrophic scar(HS)is an undesirable skin abnormality following deep burns or operations.Although intralesional multi-injection with the suspension of triamcinolone acetonide(TA)and 5-fluorouracil(5-Fu)has exhibited great promise to HS treatment in clinical,the difference of metabolic behavior between TA and 5-Fu remarkably compromised the treatment efficacy.Besides,the traditional injection with great pain is highly dependent on the skill of the experts,which results in poor compliance.Herein,a bilayer dissolving microneedle(BMN)containing TA and 5-Fu(TA-5-Fu-BMN)with biphasic release profile was designed for HS therapy.Equipped with several micro-scale needle tips,the BMN could be self-pressed into the HS with uniform drug distribution and less pain.Both in vitro permeation and in vivo HS retention tests revealed that TA and 5-Fu could coexist in the scar tissue for a sufficient time period due to the well-designed biphasic release property.Subsequently,the rabbit ear HS model was established to assess therapeutic efficacy.The histological analysis showed that TA-5-Fu-BMN could significantly reduce abnormal fibroblast proliferation and collagen fiber deposition.It was also found that the value of scar elevation index was ameliorated to a basal level,together with the downregulation of mRNA and protein expression of Collagen I(Col I)and transforming growth factor-β1(TGF-β1)after application of TA-5-Fu-BMN.In conclusion,the BMN with biphasic release profiles could serve as a potential strategy for HS treatment providing both convenient administrations as well as controlled drug release behavior.
基金supported by the National Natural Science Foundation of China(Nos.81973264,82104080,and 81773659)Guangdong Basic and Applied Basic Research Foundation(Nos.2020A1515010593,2019A1515011954,and 2021A1515012621)Guangdong Provincial Key Laboratory of Construction Foundation(No.2019B030301005).
文摘Liposome could form a long-term drug reservoir in the skin for sustained drug release,which is beneficial to improving efficacy and alleviating adverse effects.Thus,it has become a better option for anti-alopecia drugs delivery.However,cholesterol used as the fluidity buffer in conventional liposomes is a precursor for testosterone biosynthesis,which could convert to dihydrotestosterone,resulting in hair follicle damage and potentiating hair loss.To overcome the limitations,in this study we prepared a cholesterol-free liposome(PPD-Lip)using protopanaxadiol(PPD)instead of cholesterol to avoid the biosynthesis of testosterone which is adverse to alopecia therapy.PPD-Lip also worked as an active ingredient to facilitate hair growth by promoting dermal papilla cells proliferation and migration,upregulating mRNA levels of hair growth-related positive regulators,and accelerating angiogenesis in vitro.Meanwhile,it promoted hair regrowth in telogen and androgenetic alopecia mice models in vivo.In addition,our study showed that as the liposomal vehicle,PPD-Lip loaded with dutasteride exerted a stronger efficacy in the treatment of androgenetic alopecia and such a strategy could extend to other anti-alopecia agents.To the best of our knowledge,being easy for clinical transformation,the PPD-based liposomal delivery system provides a promising and multifunctional alternative platform for the delivery of alopecia treatment agents.
基金the National Natural Science Foundation of China(Grant No.:31601516)for the financial support.
文摘This study systematically investigated the effects of a low-intensity magnetic field on the influence of keratinase activity, peptide yield, and structural and functional properties of peptides produced during solid-state fermentation (SSF) of mixed organic substrates (chicken feather powder and okara) using a mutant strain of Bacillus licheniformis. Initially, the magnetic field-assisted SSF (MSSF) conditions were optimized, which provided the optimized conditions as the number of treatments 3 at every 24 h (24, 48, and 72 h) with 4 h holding time at 120 Gs of magnetic intensity (mI). Under the optimum conditions, keratinase activity and peptide production increased by 10.31% and 13.77%, respectively. Further, in order to evaluate the influence of magnetic field treatment on the peptides, MSSF experiments were done under different mI conditions (40, 80, 120, and 160 Gs), followed by the evaluation of the structural changes of the extracted peptides. The structural analysis revealed that mI had a significant impact on the keratin surface. In contrast, secondary structure analysis confirmed the unfolding of the peptide with decreased α-keratin and increased β-keratin, thereby boosting the bioactive properties of the peptides. The highest hydroxyl free radical (.OH), 1,1-diphenyl-2-picrylhydrazyl (DPPH) scavenging and Fe2+ chelating rates (56.55, 71.36, and 50.72%, respectively) were found at 120 Gs, which were insignificant with the results at 160 Gs. Therefore, MSSF has a positive effect on the proteolysis mechanism, which can increase bioactive peptide production from keratin.
文摘Saline-alkaline soils are found worldwide, affecting over 1 billion hectares of arable lands especially in arid and semiarid regions. Alkaline soils are characterized by the high pH and low nutrient availability as well as high concentrations of bicarbonate and carbonate, being highly detrimental to crop production. According to the UN Food and Agriculture Organization ( FAO and ITPS, 2015 ), approximately 60% of saline soils are concurrently affected by alkalization, posing a serious threat to food security. In recent decades, the breeding objectives for staple crops were mainly focused on yield, quality, and resistance to diseases, leaving alkaline tolerance largely overlooked. Now more than ever, we need to understand the mechanisms of plant alkaline tolerance to develop new crop varieties better adapted to alkaline soil conditions.
