Diabetic peripheral neuropathy is a common complication of diabetes mellitus.Elucidating the pathophysiological metabolic mechanism impels the generation of ideal therapies.However,existing limited treatments for diab...Diabetic peripheral neuropathy is a common complication of diabetes mellitus.Elucidating the pathophysiological metabolic mechanism impels the generation of ideal therapies.However,existing limited treatments for diabetic peripheral neuropathy expose the urgent need for cell metabolism research.Given the lack of comprehensive understanding of energy metabolism changes and related signaling pathways in diabetic peripheral neuropathy,it is essential to explore energy changes and metabolic changes in diabetic peripheral neuropathy to develop suitable treatment methods.This review summarizes the pathophysiological mechanism of diabetic peripheral neuropathy from the perspective of cellular metabolism and the specific interventions for different metabolic pathways to develop effective treatment methods.Various metabolic mechanisms(e.g.,polyol,hexosamine,protein kinase C pathway)are associated with diabetic peripheral neuropathy,and researchers are looking for more effective treatments through these pathways.展开更多
A rat model of extra-vertebral foramen cervical nerve entrapment was established according to the following parameters： stimulation intensity 20 V; frequency 50 Hz; pulse width 200 μs; duration 333 ms/s for a total ...A rat model of extra-vertebral foramen cervical nerve entrapment was established according to the following parameters： stimulation intensity 20 V; frequency 50 Hz; pulse width 200 μs; duration 333 ms/s for a total of 8 hours. After the electrical stimulation, rats exhibited mild muscle fiber atrophy, mild inflammatory exudates, connective tissue local fibrosis and chondrocyte metaplasia. Mean muscle fiber cross-sectional area was reduced. The nerve myelin sheath continuity was partially demyelinated. The microstructure of nerve cells was disrupted and these symptoms worsened with prolongation of the stimulation. The shoulder, neck and upper extremity muscles on the tested side demonstrated positive sharp waves and fibrillations. The severity increased with continuation of the stimulation. High amplitude and polyphasic motor unit potentials gradually appeared. Similar findings were seen in the contralateral side, but at a less severe level.展开更多
OBJECTIVE： To sum up the treatment of brachial plexus root avulsion and the progress in functional reconstruction and rehabilitation following brachial plexus root avulsion. DATA SOURCES： A search of Medline was per...OBJECTIVE： To sum up the treatment of brachial plexus root avulsion and the progress in functional reconstruction and rehabilitation following brachial plexus root avulsion. DATA SOURCES： A search of Medline was performed to select functional reconstruction and rehabilitation following brachial plexus injury-related English articles published between January 1990 and July 2006, with key words of ＂brachial plexus injury, reconstruction and rehabilitation＂. Meanwhile, a computer-based search of CBM was carried out to select the similar Chinese articles published between January 1998 and July 2006, with key words of ＂brachial plexus injury, reconstruction and rehabilitation＂. STUDY SELECTION： The materials were checked primarily, and the literatures of functional reconstruction and rehabilitation of brachial plexus injury were selected and the full texts were retrieved. Inclusive criteria： ①Functional reconstruction following brachial plexus injury. ②Rehabilitation method of brachial plexus injury. Exclusive criteria： Reviews, repetitive study, and Meta analytical papers. DATA EXTRACTION： Forty-six literatures about functional reconstruction following brachial plexus injury were collected, and 36 of them met the inclusive criteria. DATA SYNTHESIS： Brachial plexus injury causes the complete or incomplete palsy of muscle of upper extremity. The treatment of brachial plexus is to displace not very important nerves to the distal end of very important nerve, called nerve transfer, which is an important method to treat brachial plexus injury. Postoperative rehabilitations consist of sensory training and motor functional training. It is very important to keep the initiativeness of exercise. Besides recovering peripheral nerve continuity by operation, combined treatment and accelerating neural regeneration, active motors of cerebral cortex is also the important factor to reconstruct peripheral nerve function. CONCLUSION： Consciously and actively strengthening functional exercise after operation is helpful to form cerebral plasticity and produce voluntary movements, can re-educate re-dominated muscle, obviously improves postoperative therapeutic effect and promote functional reconstruction.展开更多
Recently,Joshua C.Chen,Gauri Bhave,and Jacob T.Robinson from Rice University reported a magnetoelectric nonlinear metamaterial(MNM)for neural signal transmission and nerve function restoration.1 Nonlinear charge trans...Recently,Joshua C.Chen,Gauri Bhave,and Jacob T.Robinson from Rice University reported a magnetoelectric nonlinear metamaterial(MNM)for neural signal transmission and nerve function restoration.1 Nonlinear charge transport between the semiconductor layers enabled this magnetoelectric(ME)metamaterial to have a nonlinear ME coupling coefficient,which allowed for self-rectification(Figure 1).展开更多
Osteoarthritis(OA)is the most common disabling joint disease with no effective disease modifying drugs.Extracellular vesicles released by several types of mesenchymal stem cells could promote cartilage repair and amel...Osteoarthritis(OA)is the most common disabling joint disease with no effective disease modifying drugs.Extracellular vesicles released by several types of mesenchymal stem cells could promote cartilage repair and ameliorate OA pathology in animal models,representing a novel therapeutic strategy.In this study,we demonstrated that extracellular vesicles derived from human umbilical cord mesenchymal stem cells(hUC-EVs)could maintain chondrocyte homeostasis and alleviate OA,and further revealed a novel molecular mechanism of this therapeutic effect.miR-223,which could directly bind with the 3′UTR of NLRP3 mRNA,was found to be a key miRNA for hUC-EVs to exert beneficial effects on inflammation inhibiting and cartilage protecting.For enhancing the effect on mitigating osteoarthritis,exogenous miR-223 was loaded into hUC-EVs by electroporation,and a collagen II-targeting peptide(WYRGRL)was modified onto the surface of hUC-EVs by genetic engineering to achieve a more targeted and efficient RNA delivery to the cartilage.The dual-engineered EVs showed a maximal effect on inhibiting the NLRP3 inflammasome activation and chondrocyte pyroptosis,and offered excellent results for the treatment of OA.This study provides a novel theoretical basis and a promising therapeutic strategy for the application of engineered extracellular vesicles in OA treatment.展开更多
Osteoarthritis(OA)is a prevalent chronic inflammatory disease in joints.Current interventions confront systemic toxicity and insufficient bioavailability.The unbalanced microenvironment of OA joints mainly fosters ove...Osteoarthritis(OA)is a prevalent chronic inflammatory disease in joints.Current interventions confront systemic toxicity and insufficient bioavailability.The unbalanced microenvironment of OA joints mainly fosters over-expressed reactive oxygen species(ROS),extracellular matrix disintegration,and apoptosis of chondrocytes.In this study,a kind of ROS-scavenging,biodegradable and drug-free nanoparticles(PP NPs)were constructed by the crosslinking of poly(propylene fumarate)(PPF)and ROS-scavenging poly(thioketal)(PTK).The high content of PTK and high crosslinking density of PPF and PTK innovatively endowed the NPs with slow degradation and prolonged ROS-elimination ability.The NPs were further surface-modified with chondroitin sulfate(CS),one of the dietary supplements for osteoarthritis.The intrinsic properties of resultant PP-CS NPs were excavated in vitro and in vivo.The PP-CS NPs could desirably consume 1,10-diphenyl-2-picrylhydrazyl(DPPH)radicals without toxicity to RAW264.7 cells in vitro.With an average diameter of~300 nm,the PP-CS NPs could be intra-articular administrated in OA rats and showed prolonged joint retention time,allowing only one injection per month.Moreover,the PP-CS NPs possessed a prolonged ROS depletion and M2 macrophage induction effect,down-regulated inflammatory cytokines,and reduced glycosaminoglycans loss.Consequently,the PP-CS NPs protected articular surface erosion,inhibited uneven cartilage matrix,and attenuated OA progression.展开更多
The slow regenerating rate and misdirected axonal growth are primary concerns that disturb the curative outcome of peripheral nerve repair.Biophysical intervention through nerve scaffolds can provide efficient,tunable...The slow regenerating rate and misdirected axonal growth are primary concerns that disturb the curative outcome of peripheral nerve repair.Biophysical intervention through nerve scaffolds can provide efficient,tunable and sustainable guidance for nerve regrowth.Herein,we fabricate the reduced graphene oxide(rGO)/polycaprolactone(PCL)scaffold characterized with anisotropic microfibers and oriented nanogrooves by electrospinning technique.Adipose-derived stem cells(ADSCs)are seeded on the scaffolds in vitro and the viability,neural differentiation efficiency and neurotrophic potential are investigated.RGO/PCL conduits reprogram the phenotype of seeded cells and efficiently repair 15 mm sciatic nerve defect in rats.In summary,biophysical cues on nerve scaffolds are key determinants to stem cell phenotype,and ADSC-seeded rGO/PCL oriented scaffolds are promising,controllable and sustainable approaches to enable peripheral nerve regeneration.展开更多
Graphene and its derivatives are fascinating materials for their extraordinary electrochemical and mechanical properties.In recent decades,many researchers explored their applications in tissue engineering and regener...Graphene and its derivatives are fascinating materials for their extraordinary electrochemical and mechanical properties.In recent decades,many researchers explored their applications in tissue engineering and regenerative medicine.Reduced graphene oxide(rGO)possesses remarkable structural and functional resemblance to graphene,although some residual oxygen-containing groups and defects exist in the structure.Such structure holds great potential since the remnantoxygenated groups can further be functionalized or modified.Moreover,oxygen-containing groups can improve the dispersion of rGO in organic or aqueous media.Therefore,it is preferable to utilize rGO in the production of composite materials.The rGO composite scaffolds provide favorable extracellular microenvironment and affect the cellular behavior of cultured cells in the peripheral nerve regeneration.On the one hand,rGO impacts on Schwann cells and neurons which are major components of peripheral nerves.On the other hand,rGO-incorporated composite scaffolds promote the neurogenic differentiation of several stem cells,including embryonic stem cells,mesenchymal stem cells,adipose-derived stem cells and neural stem cells.This review will briefly introduce the production and major properties of rGO,and its potential in modulating the cellular behaviors of specific stem cells.Finally,we present its emerging roles in the production of composite scaffolds for nerve tissue engineering.展开更多
基金supported by the Projects of the National Key R&D Program of China,Nos.2021YFC2400803(to YO),2021YFC2400801(to YQ)the National Natural Science Foundation of China,Nos.82002290(to YQ),82072452(to YO),82272475(to YO)+5 种基金the Young Elite Scientist Sponsorship Program by Cast,No.YESS20200153(to YQ)the Sino-German Mobility Programme,No.M-0699(to YQ)the Excellent Youth Cultivation Program of Shanghai Sixth People’s Hospital,No.ynyq202201(to YQ)the Shanghai Sailing Program,No.20YF1436000(to YQ)the Medical Engineering Co-Project of University of Shanghai for Science and Technology,10-22-310-520(to YO)a grant from Shanghai Municipal Health Commission,No.202040399(to YO).
文摘Diabetic peripheral neuropathy is a common complication of diabetes mellitus.Elucidating the pathophysiological metabolic mechanism impels the generation of ideal therapies.However,existing limited treatments for diabetic peripheral neuropathy expose the urgent need for cell metabolism research.Given the lack of comprehensive understanding of energy metabolism changes and related signaling pathways in diabetic peripheral neuropathy,it is essential to explore energy changes and metabolic changes in diabetic peripheral neuropathy to develop suitable treatment methods.This review summarizes the pathophysiological mechanism of diabetic peripheral neuropathy from the perspective of cellular metabolism and the specific interventions for different metabolic pathways to develop effective treatment methods.Various metabolic mechanisms(e.g.,polyol,hexosamine,protein kinase C pathway)are associated with diabetic peripheral neuropathy,and researchers are looking for more effective treatments through these pathways.
基金the National Natural Science Foundation of China,No. 81171707the Major State Basic Research Program of China,No.2012CB933600+2 种基金Shanghai Pujiang Program,No.11PJD016China Postdoctoral Science Foundation,No. 20090460629Fund for Key Disciplines of Shanghai Municipal Education Commission,No.J50206
文摘A rat model of extra-vertebral foramen cervical nerve entrapment was established according to the following parameters： stimulation intensity 20 V; frequency 50 Hz; pulse width 200 μs; duration 333 ms/s for a total of 8 hours. After the electrical stimulation, rats exhibited mild muscle fiber atrophy, mild inflammatory exudates, connective tissue local fibrosis and chondrocyte metaplasia. Mean muscle fiber cross-sectional area was reduced. The nerve myelin sheath continuity was partially demyelinated. The microstructure of nerve cells was disrupted and these symptoms worsened with prolongation of the stimulation. The shoulder, neck and upper extremity muscles on the tested side demonstrated positive sharp waves and fibrillations. The severity increased with continuation of the stimulation. High amplitude and polyphasic motor unit potentials gradually appeared. Similar findings were seen in the contralateral side, but at a less severe level.
文摘OBJECTIVE： To sum up the treatment of brachial plexus root avulsion and the progress in functional reconstruction and rehabilitation following brachial plexus root avulsion. DATA SOURCES： A search of Medline was performed to select functional reconstruction and rehabilitation following brachial plexus injury-related English articles published between January 1990 and July 2006, with key words of ＂brachial plexus injury, reconstruction and rehabilitation＂. Meanwhile, a computer-based search of CBM was carried out to select the similar Chinese articles published between January 1998 and July 2006, with key words of ＂brachial plexus injury, reconstruction and rehabilitation＂. STUDY SELECTION： The materials were checked primarily, and the literatures of functional reconstruction and rehabilitation of brachial plexus injury were selected and the full texts were retrieved. Inclusive criteria： ①Functional reconstruction following brachial plexus injury. ②Rehabilitation method of brachial plexus injury. Exclusive criteria： Reviews, repetitive study, and Meta analytical papers. DATA EXTRACTION： Forty-six literatures about functional reconstruction following brachial plexus injury were collected, and 36 of them met the inclusive criteria. DATA SYNTHESIS： Brachial plexus injury causes the complete or incomplete palsy of muscle of upper extremity. The treatment of brachial plexus is to displace not very important nerves to the distal end of very important nerve, called nerve transfer, which is an important method to treat brachial plexus injury. Postoperative rehabilitations consist of sensory training and motor functional training. It is very important to keep the initiativeness of exercise. Besides recovering peripheral nerve continuity by operation, combined treatment and accelerating neural regeneration, active motors of cerebral cortex is also the important factor to reconstruct peripheral nerve function. CONCLUSION： Consciously and actively strengthening functional exercise after operation is helpful to form cerebral plasticity and produce voluntary movements, can re-educate re-dominated muscle, obviously improves postoperative therapeutic effect and promote functional reconstruction.
文摘Recently,Joshua C.Chen,Gauri Bhave,and Jacob T.Robinson from Rice University reported a magnetoelectric nonlinear metamaterial(MNM)for neural signal transmission and nerve function restoration.1 Nonlinear charge transport between the semiconductor layers enabled this magnetoelectric(ME)metamaterial to have a nonlinear ME coupling coefficient,which allowed for self-rectification(Figure 1).
基金the Key Project of National Natural Science Foundation of China(81830076)the National Natural Science Foundation of China(82272568)+1 种基金the Shanghai Engineering Technology Research Center and Professional Technology Service Platform project of 2020“Science and Technology Innovation Action Plan”of Shanghai(20DZ2254100)the Biomedical Technology Support Special Project of Shanghai 2021“Science and Technology Innovation Action Plan”(21S31902300).
文摘Osteoarthritis(OA)is the most common disabling joint disease with no effective disease modifying drugs.Extracellular vesicles released by several types of mesenchymal stem cells could promote cartilage repair and ameliorate OA pathology in animal models,representing a novel therapeutic strategy.In this study,we demonstrated that extracellular vesicles derived from human umbilical cord mesenchymal stem cells(hUC-EVs)could maintain chondrocyte homeostasis and alleviate OA,and further revealed a novel molecular mechanism of this therapeutic effect.miR-223,which could directly bind with the 3′UTR of NLRP3 mRNA,was found to be a key miRNA for hUC-EVs to exert beneficial effects on inflammation inhibiting and cartilage protecting.For enhancing the effect on mitigating osteoarthritis,exogenous miR-223 was loaded into hUC-EVs by electroporation,and a collagen II-targeting peptide(WYRGRL)was modified onto the surface of hUC-EVs by genetic engineering to achieve a more targeted and efficient RNA delivery to the cartilage.The dual-engineered EVs showed a maximal effect on inhibiting the NLRP3 inflammasome activation and chondrocyte pyroptosis,and offered excellent results for the treatment of OA.This study provides a novel theoretical basis and a promising therapeutic strategy for the application of engineered extracellular vesicles in OA treatment.
基金supported by the Key research and development program of Zhejiang Province(No.2021C03113)the Natural Science Foundation of Zhejiang Province(No.LD21E030001).
文摘Osteoarthritis(OA)is a prevalent chronic inflammatory disease in joints.Current interventions confront systemic toxicity and insufficient bioavailability.The unbalanced microenvironment of OA joints mainly fosters over-expressed reactive oxygen species(ROS),extracellular matrix disintegration,and apoptosis of chondrocytes.In this study,a kind of ROS-scavenging,biodegradable and drug-free nanoparticles(PP NPs)were constructed by the crosslinking of poly(propylene fumarate)(PPF)and ROS-scavenging poly(thioketal)(PTK).The high content of PTK and high crosslinking density of PPF and PTK innovatively endowed the NPs with slow degradation and prolonged ROS-elimination ability.The NPs were further surface-modified with chondroitin sulfate(CS),one of the dietary supplements for osteoarthritis.The intrinsic properties of resultant PP-CS NPs were excavated in vitro and in vivo.The PP-CS NPs could desirably consume 1,10-diphenyl-2-picrylhydrazyl(DPPH)radicals without toxicity to RAW264.7 cells in vitro.With an average diameter of~300 nm,the PP-CS NPs could be intra-articular administrated in OA rats and showed prolonged joint retention time,allowing only one injection per month.Moreover,the PP-CS NPs possessed a prolonged ROS depletion and M2 macrophage induction effect,down-regulated inflammatory cytokines,and reduced glycosaminoglycans loss.Consequently,the PP-CS NPs protected articular surface erosion,inhibited uneven cartilage matrix,and attenuated OA progression.
基金support of the following funding:Shanghai Sailing Program(No.20YF1436000)National Natural Science Foundation of China(Grant No.82002290)+2 种基金National Natural Science Foundation of China(Grant No.82072452)National Natural Science Foundation of China(Grant No.81830076)Young Elite Scientist Sponsorship Program by Cast(No.YESS20200153).
文摘The slow regenerating rate and misdirected axonal growth are primary concerns that disturb the curative outcome of peripheral nerve repair.Biophysical intervention through nerve scaffolds can provide efficient,tunable and sustainable guidance for nerve regrowth.Herein,we fabricate the reduced graphene oxide(rGO)/polycaprolactone(PCL)scaffold characterized with anisotropic microfibers and oriented nanogrooves by electrospinning technique.Adipose-derived stem cells(ADSCs)are seeded on the scaffolds in vitro and the viability,neural differentiation efficiency and neurotrophic potential are investigated.RGO/PCL conduits reprogram the phenotype of seeded cells and efficiently repair 15 mm sciatic nerve defect in rats.In summary,biophysical cues on nerve scaffolds are key determinants to stem cell phenotype,and ADSC-seeded rGO/PCL oriented scaffolds are promising,controllable and sustainable approaches to enable peripheral nerve regeneration.
基金The study was sponsored by the Shanghai Sailing Program(No.20YF1436000)Projects of National Natural Science Foundation of China(Grant Nos 82002290 and 81830076)+2 种基金Municipal Hospital Newly-developing Cutting-edge Technologies Joint Research Program of Shanghai Shenkang Hospital Development Center(No.SHDC12018130)Special Fund for Research on People’s Livelihood(Medical Treatment and Public Health)of Shanghai Pudong Science,Technology and Economic Commission Scientific and Technological Development Fund(No.PKJ2018-Y52)Shanghai Pudong Health Commission Special Program for Clinical Research in the Health Industry(No.PW2018E-01)。
文摘Graphene and its derivatives are fascinating materials for their extraordinary electrochemical and mechanical properties.In recent decades,many researchers explored their applications in tissue engineering and regenerative medicine.Reduced graphene oxide(rGO)possesses remarkable structural and functional resemblance to graphene,although some residual oxygen-containing groups and defects exist in the structure.Such structure holds great potential since the remnantoxygenated groups can further be functionalized or modified.Moreover,oxygen-containing groups can improve the dispersion of rGO in organic or aqueous media.Therefore,it is preferable to utilize rGO in the production of composite materials.The rGO composite scaffolds provide favorable extracellular microenvironment and affect the cellular behavior of cultured cells in the peripheral nerve regeneration.On the one hand,rGO impacts on Schwann cells and neurons which are major components of peripheral nerves.On the other hand,rGO-incorporated composite scaffolds promote the neurogenic differentiation of several stem cells,including embryonic stem cells,mesenchymal stem cells,adipose-derived stem cells and neural stem cells.This review will briefly introduce the production and major properties of rGO,and its potential in modulating the cellular behaviors of specific stem cells.Finally,we present its emerging roles in the production of composite scaffolds for nerve tissue engineering.
