Schwann cell transplantation is considered one of the most promising cell-based therapy to repair injured spinal cord due to its unique growth-promoting and myelin-forming properties.A the Food and Drug Administration...Schwann cell transplantation is considered one of the most promising cell-based therapy to repair injured spinal cord due to its unique growth-promoting and myelin-forming properties.A the Food and Drug Administration-approved Phase I clinical trial has been conducted to evaluate the safety of transplanted human autologous Schwann cells to treat patients with spinal cord injury.A major challenge for Schwann cell transplantation is that grafted Schwann cells are confined within the lesion cavity,and they do not migrate into the host environment due to the inhibitory barrier formed by injury-induced glial scar,thus limiting axonal reentry into the host spinal cord.Here we introduce a combinatorial strategy by suppressing the inhibitory extracellular environment with injection of lentivirus-mediated transfection of chondroitinase ABC gene at the rostral and caudal borders of the lesion site and simultaneously leveraging the repair capacity of transplanted Schwann cells in adult rats following a mid-thoracic contusive spinal cord injury.We report that when the glial scar was degraded by chondroitinase ABC at the rostral and caudal lesion borders,Schwann cells migrated for considerable distances in both rostral and caudal directions.Such Schwann cell migration led to enhanced axonal regrowth,including the serotonergic and dopaminergic axons originating from supraspinal regions,and promoted recovery of locomotor and urinary bladder functions.Importantly,the Schwann cell survival and axonal regrowth persisted up to 6 months after the injury,even when treatment was delayed for 3 months to mimic chronic spinal cord injury.These findings collectively show promising evidence for a combinatorial strategy with chondroitinase ABC and Schwann cells in promoting remodeling and recovery of function following spinal cord injury.展开更多
The selective aerobic oxidation of benzyl alcohol to benzaldehyde has attracted considerable attention because benzaldehyde is a high value-added product. The rate of this typical gas–liquid reaction is significantly...The selective aerobic oxidation of benzyl alcohol to benzaldehyde has attracted considerable attention because benzaldehyde is a high value-added product. The rate of this typical gas–liquid reaction is significantly affected by mass transfer. In this study, CoTPP-mediated(CoTPP: cobalt(II) mesotetraphenylporphyrin) selective benzyl alcohol oxidation with oxygen was conducted in a membrane microchannel(MMC) reactor and a bubble column(BC) reactor, respectively. We observed that 83% benzyl alcohol was converted within 6.5 min in the MMC reactor, but only less than 10% benzyl alcohol was converted in the BC reactor. Hydrodynamic characteristics and gas–liquid mass transfer performances were compared for the MMC and BC reactors. The MMC reactor was assumed to be a plug flow reactor,and the dimensionless variance was 0.29. Compared to the BC reactor, the gas–liquid mass transfer was intensified significantly in MMC reactor. It could be ascribed to the high gas holdup(2.9 times higher than that of BC reactor), liquid film mass transfer coefficient(8.2 times higher than that of BC reactor), and mass transfer coefficient per unit interfacial area(3.8 times higher than that of BC reactor). Moreover,the Hatta number for the MMC reactor reached up to 0.61, which was about 15 times higher than that of the BC reactor. The computational fluid dynamics calculations for mass fractions in both liquid and gas phases were consistent with the experimental data.展开更多
Background:Based on the theory of“five Zang-organs corresponding to the seasons”in traditional Chinese medicine(TCM),physiological functions including emotions vary with the seasons.We aimed to investigate the seaso...Background:Based on the theory of“five Zang-organs corresponding to the seasons”in traditional Chinese medicine(TCM),physiological functions including emotions vary with the seasons.We aimed to investigate the seasonal photoperiod effects of melatonin(MT)released from the pineal gland on the MT receptor(MTR)-Gs/Gi-cyclic adenosine monophosphate(cAMP)-protein kinase A(PKA)-cAMP response element-binding protein(CREB)signaling pathway in the hippocampus.Methods:Rats were divided into three groups:control,operation(surgery with pineal gland removal),and pseudo-operation groups(same surgery as operation group but without removing pineal gland),and fed at specific time across the four seasons.The levels of MTR,adenylate cyclase(AC),cAMP,PKA,and CREB in the hippocampus were analyzed using ELISA.The concentrations of Gs and Gi were analyzed using Western blot.The expression of CREB mRNA was detected by PCR.Results:For intragroup comparisons,compared with spring,the levels of Gs/Gi in the control group were higher in summer,autumn,and winter(P=.009 in summer;P<.001 in autumn and winter);the levels of MTR,cAMP,PKA,and CREB in the control group were significantly higher in autumn and winter than in spring(all P<.001).The levels of MTR,cAMP,PKA,and CREB in each season were significantly lower in the operation group than in the control group(all P<.05).Significant differences were noted in Gs/Gi levels between the operation group and control group in spring,autumn,and winter(all P<.05).Conclusion:Our findings suggest that MTR-Gs/Gi-cAMP-PKA-CREB signaling pathway is involved in the seasonal photoperiod effects of the pineal gland on the hippocampus and may underpin seasonal changes in emotions.It can support the prevention and treatment of the seasonal onset of mental disorders,and enrich the theory of“five Zang-organs corresponding to the seasons”.展开更多
Inflammatory bowel disease(IBD)represents a chronic inflammatory condition profoundly impacting the gastrointestinal tract.Its prevalence has markedly risen in both developed and developing nations over recent decades...Inflammatory bowel disease(IBD)represents a chronic inflammatory condition profoundly impacting the gastrointestinal tract.Its prevalence has markedly risen in both developed and developing nations over recent decades.Despite the absence of definitive etiological elucidation,therapeutic strategies predominantly revolve around pharmacological interventions aimed at symptom mitigation.Alginate(AG)is a polysaccharide of marine origin that has garnered significant attention due to its inherent biocompatibility,pH sensitivity,and cross-linking.Its exploration within drug delivery systems for IBD treatment stems from its natural sourcing,non-cytotoxic nature,and economic viability.Notably,AG demonstrates facile interpolymeric cross-linking,facilitating the formation of a cohesive network conducive to sustained drug release kinetics.AG-based carrier systems for sustained drug release,and targeted drug delivery have been widely studied.This article reviews the pathogenesis of IBD and the current drugs,AG-based drug delivery systems and their properties in alleviating IBD.The prospect of further development of AG in the field of biopharmaceutical and drug delivery is prospected.展开更多
基金supported in part by NIH R01 NS100531,R01 NS103481NIH R21NS130241(to LD)+3 种基金Merit Review Award I01 BX002356,I01 BX003705 from the U.S.Department of Veterans AffairsIndiana Spinal Cord and Brain Injury Research Foundation(No.19919)Mari Hulman George Endowment Funds(to XMX)Indiana Spinal Cord&Brain Injury Research Fund from ISDH(to NKL and LD)。
文摘Schwann cell transplantation is considered one of the most promising cell-based therapy to repair injured spinal cord due to its unique growth-promoting and myelin-forming properties.A the Food and Drug Administration-approved Phase I clinical trial has been conducted to evaluate the safety of transplanted human autologous Schwann cells to treat patients with spinal cord injury.A major challenge for Schwann cell transplantation is that grafted Schwann cells are confined within the lesion cavity,and they do not migrate into the host environment due to the inhibitory barrier formed by injury-induced glial scar,thus limiting axonal reentry into the host spinal cord.Here we introduce a combinatorial strategy by suppressing the inhibitory extracellular environment with injection of lentivirus-mediated transfection of chondroitinase ABC gene at the rostral and caudal borders of the lesion site and simultaneously leveraging the repair capacity of transplanted Schwann cells in adult rats following a mid-thoracic contusive spinal cord injury.We report that when the glial scar was degraded by chondroitinase ABC at the rostral and caudal lesion borders,Schwann cells migrated for considerable distances in both rostral and caudal directions.Such Schwann cell migration led to enhanced axonal regrowth,including the serotonergic and dopaminergic axons originating from supraspinal regions,and promoted recovery of locomotor and urinary bladder functions.Importantly,the Schwann cell survival and axonal regrowth persisted up to 6 months after the injury,even when treatment was delayed for 3 months to mimic chronic spinal cord injury.These findings collectively show promising evidence for a combinatorial strategy with chondroitinase ABC and Schwann cells in promoting remodeling and recovery of function following spinal cord injury.
基金financially supported by the National Key Research and Development Program of China (2020YFA0210900)the National Natural Science Foundation of China (21938001 and 21878344)+1 种基金Guangdong Provincial Key Research and Development Programme (2019B110206002)the Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program (2017BT01C102)。
文摘The selective aerobic oxidation of benzyl alcohol to benzaldehyde has attracted considerable attention because benzaldehyde is a high value-added product. The rate of this typical gas–liquid reaction is significantly affected by mass transfer. In this study, CoTPP-mediated(CoTPP: cobalt(II) mesotetraphenylporphyrin) selective benzyl alcohol oxidation with oxygen was conducted in a membrane microchannel(MMC) reactor and a bubble column(BC) reactor, respectively. We observed that 83% benzyl alcohol was converted within 6.5 min in the MMC reactor, but only less than 10% benzyl alcohol was converted in the BC reactor. Hydrodynamic characteristics and gas–liquid mass transfer performances were compared for the MMC and BC reactors. The MMC reactor was assumed to be a plug flow reactor,and the dimensionless variance was 0.29. Compared to the BC reactor, the gas–liquid mass transfer was intensified significantly in MMC reactor. It could be ascribed to the high gas holdup(2.9 times higher than that of BC reactor), liquid film mass transfer coefficient(8.2 times higher than that of BC reactor), and mass transfer coefficient per unit interfacial area(3.8 times higher than that of BC reactor). Moreover,the Hatta number for the MMC reactor reached up to 0.61, which was about 15 times higher than that of the BC reactor. The computational fluid dynamics calculations for mass fractions in both liquid and gas phases were consistent with the experimental data.
基金This study was supported by the National Natural Science Foundation of China(81774162).
文摘Background:Based on the theory of“five Zang-organs corresponding to the seasons”in traditional Chinese medicine(TCM),physiological functions including emotions vary with the seasons.We aimed to investigate the seasonal photoperiod effects of melatonin(MT)released from the pineal gland on the MT receptor(MTR)-Gs/Gi-cyclic adenosine monophosphate(cAMP)-protein kinase A(PKA)-cAMP response element-binding protein(CREB)signaling pathway in the hippocampus.Methods:Rats were divided into three groups:control,operation(surgery with pineal gland removal),and pseudo-operation groups(same surgery as operation group but without removing pineal gland),and fed at specific time across the four seasons.The levels of MTR,adenylate cyclase(AC),cAMP,PKA,and CREB in the hippocampus were analyzed using ELISA.The concentrations of Gs and Gi were analyzed using Western blot.The expression of CREB mRNA was detected by PCR.Results:For intragroup comparisons,compared with spring,the levels of Gs/Gi in the control group were higher in summer,autumn,and winter(P=.009 in summer;P<.001 in autumn and winter);the levels of MTR,cAMP,PKA,and CREB in the control group were significantly higher in autumn and winter than in spring(all P<.001).The levels of MTR,cAMP,PKA,and CREB in each season were significantly lower in the operation group than in the control group(all P<.05).Significant differences were noted in Gs/Gi levels between the operation group and control group in spring,autumn,and winter(all P<.05).Conclusion:Our findings suggest that MTR-Gs/Gi-cAMP-PKA-CREB signaling pathway is involved in the seasonal photoperiod effects of the pineal gland on the hippocampus and may underpin seasonal changes in emotions.It can support the prevention and treatment of the seasonal onset of mental disorders,and enrich the theory of“five Zang-organs corresponding to the seasons”.
基金supported by the China Postdoctoral Science Foundation(Grant No.2021MD703801)Youth Talent Cultivation Fund Project of Dalian Medical University(Grant No.508021)Open Foundation of the State Key Laboratory of Marine Food Processing&Safety Control(Grant No.SKL2023M03).
文摘Inflammatory bowel disease(IBD)represents a chronic inflammatory condition profoundly impacting the gastrointestinal tract.Its prevalence has markedly risen in both developed and developing nations over recent decades.Despite the absence of definitive etiological elucidation,therapeutic strategies predominantly revolve around pharmacological interventions aimed at symptom mitigation.Alginate(AG)is a polysaccharide of marine origin that has garnered significant attention due to its inherent biocompatibility,pH sensitivity,and cross-linking.Its exploration within drug delivery systems for IBD treatment stems from its natural sourcing,non-cytotoxic nature,and economic viability.Notably,AG demonstrates facile interpolymeric cross-linking,facilitating the formation of a cohesive network conducive to sustained drug release kinetics.AG-based carrier systems for sustained drug release,and targeted drug delivery have been widely studied.This article reviews the pathogenesis of IBD and the current drugs,AG-based drug delivery systems and their properties in alleviating IBD.The prospect of further development of AG in the field of biopharmaceutical and drug delivery is prospected.
