Low back pain(LBP),as a leading cause of disability,is a common musculoskeletal disorder that results in major social and economic burdens.Recent research has identified inflammation and related signaling pathways as ...Low back pain(LBP),as a leading cause of disability,is a common musculoskeletal disorder that results in major social and economic burdens.Recent research has identified inflammation and related signaling pathways as important factors in the onset and progression of disc degeneration,a significant contributor to LBP.Inflammatory mediators also play an indispensable role in discogenic LBP.The suppression of LBP is a primary goal of clinical practice but has not received enough attention in disc research studies.Here,an overview of the advances in inflammation-related pain in disc degeneration is provided,with a discussion on the role of inflammation in IVD degeneration and pain induction.Puncture models,mechanical models,and spontaneous models as the main animal models to study painful disc degeneration are discussed,and the underlying signaling pathways are summarized.Furthermore,potential drug candidates,either under laboratory investigation or undergoing clinical trials,to suppress discogenic LBP by eliminating inflammation are explored.We hope to attract more research interest to address inflammation and pain in IDD and contribute to promoting more translational research.展开更多
Conventional neuroimaging techniques cannot truly reflect the change of regional cerebral blood flow in patients with carpal tunnel syndrome.Pseudo-continuous arterial spinning labeling(pCASL)as an efficient non-invas...Conventional neuroimaging techniques cannot truly reflect the change of regional cerebral blood flow in patients with carpal tunnel syndrome.Pseudo-continuous arterial spinning labeling(pCASL)as an efficient non-invasive neuroimaging technique can be applied to directly quantify the neuronal activities of individual brain regions that show the persistent symptoms owing to its better spatial resolution and increased signal-to-noise ratio.Therefore,this prospective observational study was conducted in 27 eligible female carpal tunnel syndrome,aged 57.7±6.51 years.Psychometric tests,nerve conduction studies and pCASL neuroimaging assessment were performed.The results showed that the relevant activated brain regions in the cortical,subcrotical,and cerebral regions were correlated with numbness,pain,functionality,median nerve status and motor amplitude of median nerve(K=21–2849,r=–0.77–0.76,P<0.05).There was a tendency of pain processing which shifted from the nociceptive circuitry to the emotional and cognitive one during the process of chronic pain caused by carpal tunnel syndrome.It suggests the necessity of addressing the ignored cognitive or emotional state when managing patients with carpal tunnel syndrome.Approval for this study was obtained from the Institutional Review Board of The University of Hong Kong/Hospital Authority Hong Kong West,China(HKU/HA HKW IRB,approval No.UW17-129)on April 11,2017.This study was registered in Clinical Trial Registry of The University of Hong Kong,China(registration number:HKUCTR-2220)on April 24,2017.展开更多
Introduction:Magnesium(Mg)has a prophylactic potential against the onset of hyperlipidemia.Similar to statin,Mg is recommended as lipid-lowering medication for hypercholesterolemia and concomitantly exhibits an associ...Introduction:Magnesium(Mg)has a prophylactic potential against the onset of hyperlipidemia.Similar to statin,Mg is recommended as lipid-lowering medication for hypercholesterolemia and concomitantly exhibits an association with increased bone mass.The combination of statin with Mg ions(Mg^(2+))may be able to alleviate the high-fat diet(HFD)-induced bone loss and reduce the side-effects of statin.This study aimed to explore the feasibility of combined Mg^(2+)with simvastatin(SIM)for treating HFD-induced bone loss in mice and the involving mechanisms.Materials and methods:C57BL/6 male mice were fed with a HFD or a normal-fat diet(NFD).Mice were intraperitoneally injected SIM and/or orally received water with additional Mg^(2+)until sacrificed.Enzyme-linked immunosorbent assay was performed to measure cytokines and cholesterol in serum and liver lysates.Bone mineral density(BMD)and microarchitecture were assessed by micro-computed tomography(μCT)in different groups.The adipogenesis in palmitate pre-treated HepG2 cells was performed under various treatments.Results:μCT analysis showed that the trabecular bone mass was significantly lower in the HFD-fed group than that in NFD-fed group since week 8.The cortical thickness in HFD-fed group had a significant decrease at week 24,as compared with NFD-fed group.The combination of Mg^(2+)and SIM significantly attenuated the trabecular bone loss in HFD-fed mice via arresting the osteoclast formation and bone resorption.Besides,such combination also reduced the hepatocytic synthesis of cholesterol and inhibited matrix metallopeptidase 13(Mmp13)mRNA expression in pre-osteoclasts.Conclusions:The combination of Mg^(2+)and SIM shows a synergistic effect on attenuating the HFD-induced bone loss.Our current formulation may be a cost-effective alternative treatment to be indicated for obesity-related bone loss.展开更多
Articular cartilage(AC) injuries often lead to cartilage degeneration and may ultimately result in osteoarthritis(OA) due to the limited self-repair ability. To date, numerous intra-articular delivery systems carrying...Articular cartilage(AC) injuries often lead to cartilage degeneration and may ultimately result in osteoarthritis(OA) due to the limited self-repair ability. To date, numerous intra-articular delivery systems carrying various therapeutic agents have been developed to improve therapeutic localization and retention, optimize controlled drug release profiles and target different pathological processes. Due to the complex and multifactorial characteristics of cartilage injury pathology and heterogeneity of the cartilage structure deposited within a dense matrix, delivery systems loaded with a single therapeutic agent are hindered from reaching multiple targets in a spatiotemporal matched manner and thus fail to mimic the natural processes of biosynthesis, compromising the goal of full cartilage regeneration. Emerging evidence highlights the importance of sequential delivery strategies targeting multiple pathological processes. In this review, we first summarize the current status and progress achieved in single-drug delivery strategies for the treatment of AC diseases. Subsequently, we focus mainly on advances in multiple drug delivery applications, including sequential release formulations targeting various pathological processes, synergistic targeting of the same pathological process, the spatial distribution in multiple tissues, and heterogeneous regeneration. We hope that this review will inspire the rational design of intraarticular drug delivery systems(DDSs) in the future.展开更多
Magnesium metal and its alloys are being developed as effective orthopedic implants;however,the mechanisms underlying the actions of magnesium on bones remain unclear.Cystic fibrosis,the most common genetic disease in...Magnesium metal and its alloys are being developed as effective orthopedic implants;however,the mechanisms underlying the actions of magnesium on bones remain unclear.Cystic fibrosis,the most common genetic disease in Caucasians caused by the mutation of CFTR,has shown bone disorder as a key clinical manifestation,which currently lacks effective therapeutic options.Here we report that implantation of magnesium-containing implant stimulates bone formation and improves bone fracture healing in CFTR-mutant mice.Wnt/β-catenin signaling in the bone is enhanced by the magnesium implant,and inhibition of Wnt/β-catenin by iCRT14 blocks the magnesium implant to improve fracture healing in CFTR-mutant mice.We further demonstrate that magnesium ion enters osteocytes,increases intracellular cAMP level and activates ATF4,a key transcription factor known to regulate Wnt/β-catenin signaling.In vivo knockdown of ATF4 abolishes the magnesium implant-activated β-catenin in bones and reverses the improved-fracture healing in CFTR-mutant mice.In addition,oral supplementation of magnesium activates ATF4 and β-catenin as well as enhances bone volume and density in CFTR-mutant mice.Together,these results show that magnesium implantation or supplementation may serve as a potential anabolic therapy for cystic fibrosis-related bone disease.Activation of ATF4-dependent Wnt/β-catenin signaling in osteocytes is identified as a previously undefined mechanism underlying the beneficial effect of magnesium on bone formation.展开更多
基金the National Natural Science Foundation of China(81772386,81702191,81572175,81371984,and 81071511)the Guangdong-Hong Kong Joint Innovation Project of Guangdong Province(2017A050506019)the Natural Science Foundation of Guangdong Province,China(2020A1515011031).
文摘Low back pain(LBP),as a leading cause of disability,is a common musculoskeletal disorder that results in major social and economic burdens.Recent research has identified inflammation and related signaling pathways as important factors in the onset and progression of disc degeneration,a significant contributor to LBP.Inflammatory mediators also play an indispensable role in discogenic LBP.The suppression of LBP is a primary goal of clinical practice but has not received enough attention in disc research studies.Here,an overview of the advances in inflammation-related pain in disc degeneration is provided,with a discussion on the role of inflammation in IVD degeneration and pain induction.Puncture models,mechanical models,and spontaneous models as the main animal models to study painful disc degeneration are discussed,and the underlying signaling pathways are summarized.Furthermore,potential drug candidates,either under laboratory investigation or undergoing clinical trials,to suppress discogenic LBP by eliminating inflammation are explored.We hope to attract more research interest to address inflammation and pain in IDD and contribute to promoting more translational research.
文摘Conventional neuroimaging techniques cannot truly reflect the change of regional cerebral blood flow in patients with carpal tunnel syndrome.Pseudo-continuous arterial spinning labeling(pCASL)as an efficient non-invasive neuroimaging technique can be applied to directly quantify the neuronal activities of individual brain regions that show the persistent symptoms owing to its better spatial resolution and increased signal-to-noise ratio.Therefore,this prospective observational study was conducted in 27 eligible female carpal tunnel syndrome,aged 57.7±6.51 years.Psychometric tests,nerve conduction studies and pCASL neuroimaging assessment were performed.The results showed that the relevant activated brain regions in the cortical,subcrotical,and cerebral regions were correlated with numbness,pain,functionality,median nerve status and motor amplitude of median nerve(K=21–2849,r=–0.77–0.76,P<0.05).There was a tendency of pain processing which shifted from the nociceptive circuitry to the emotional and cognitive one during the process of chronic pain caused by carpal tunnel syndrome.It suggests the necessity of addressing the ignored cognitive or emotional state when managing patients with carpal tunnel syndrome.Approval for this study was obtained from the Institutional Review Board of The University of Hong Kong/Hospital Authority Hong Kong West,China(HKU/HA HKW IRB,approval No.UW17-129)on April 11,2017.This study was registered in Clinical Trial Registry of The University of Hong Kong,China(registration number:HKUCTR-2220)on April 24,2017.
基金supported by Theme-based Research Scheme from RGC-Hong Kong(No.T13-402/17N)partially supported by Health and Medical Research Fund(17180671)National Natural Science Foundation of China(81802152).
文摘Introduction:Magnesium(Mg)has a prophylactic potential against the onset of hyperlipidemia.Similar to statin,Mg is recommended as lipid-lowering medication for hypercholesterolemia and concomitantly exhibits an association with increased bone mass.The combination of statin with Mg ions(Mg^(2+))may be able to alleviate the high-fat diet(HFD)-induced bone loss and reduce the side-effects of statin.This study aimed to explore the feasibility of combined Mg^(2+)with simvastatin(SIM)for treating HFD-induced bone loss in mice and the involving mechanisms.Materials and methods:C57BL/6 male mice were fed with a HFD or a normal-fat diet(NFD).Mice were intraperitoneally injected SIM and/or orally received water with additional Mg^(2+)until sacrificed.Enzyme-linked immunosorbent assay was performed to measure cytokines and cholesterol in serum and liver lysates.Bone mineral density(BMD)and microarchitecture were assessed by micro-computed tomography(μCT)in different groups.The adipogenesis in palmitate pre-treated HepG2 cells was performed under various treatments.Results:μCT analysis showed that the trabecular bone mass was significantly lower in the HFD-fed group than that in NFD-fed group since week 8.The cortical thickness in HFD-fed group had a significant decrease at week 24,as compared with NFD-fed group.The combination of Mg^(2+)and SIM significantly attenuated the trabecular bone loss in HFD-fed mice via arresting the osteoclast formation and bone resorption.Besides,such combination also reduced the hepatocytic synthesis of cholesterol and inhibited matrix metallopeptidase 13(Mmp13)mRNA expression in pre-osteoclasts.Conclusions:The combination of Mg^(2+)and SIM shows a synergistic effect on attenuating the HFD-induced bone loss.Our current formulation may be a cost-effective alternative treatment to be indicated for obesity-related bone loss.
基金supported by the National Key R&D Program of China (2019YFA0110600, China)Medical Research and Development Projects (BLB20J001, China)。
文摘Articular cartilage(AC) injuries often lead to cartilage degeneration and may ultimately result in osteoarthritis(OA) due to the limited self-repair ability. To date, numerous intra-articular delivery systems carrying various therapeutic agents have been developed to improve therapeutic localization and retention, optimize controlled drug release profiles and target different pathological processes. Due to the complex and multifactorial characteristics of cartilage injury pathology and heterogeneity of the cartilage structure deposited within a dense matrix, delivery systems loaded with a single therapeutic agent are hindered from reaching multiple targets in a spatiotemporal matched manner and thus fail to mimic the natural processes of biosynthesis, compromising the goal of full cartilage regeneration. Emerging evidence highlights the importance of sequential delivery strategies targeting multiple pathological processes. In this review, we first summarize the current status and progress achieved in single-drug delivery strategies for the treatment of AC diseases. Subsequently, we focus mainly on advances in multiple drug delivery applications, including sequential release formulations targeting various pathological processes, synergistic targeting of the same pathological process, the spatial distribution in multiple tissues, and heterogeneous regeneration. We hope that this review will inspire the rational design of intraarticular drug delivery systems(DDSs) in the future.
基金supported in part by Theme-based Research Scheme of Hong Kong(No.T13-402/17 N)Health and Medical Research Fund of Hong Kong(15161441 and 18190481)+3 种基金Early Career Scheme of Hong Kong(No.24104517)Start-up fund at the Hong Kong Polytechnic UniversityNational Natural Science Foundation of China(81802152)Natural Science Foundation of Guangdong Province(2019A1515012224 and 2021A1515011204).
文摘Magnesium metal and its alloys are being developed as effective orthopedic implants;however,the mechanisms underlying the actions of magnesium on bones remain unclear.Cystic fibrosis,the most common genetic disease in Caucasians caused by the mutation of CFTR,has shown bone disorder as a key clinical manifestation,which currently lacks effective therapeutic options.Here we report that implantation of magnesium-containing implant stimulates bone formation and improves bone fracture healing in CFTR-mutant mice.Wnt/β-catenin signaling in the bone is enhanced by the magnesium implant,and inhibition of Wnt/β-catenin by iCRT14 blocks the magnesium implant to improve fracture healing in CFTR-mutant mice.We further demonstrate that magnesium ion enters osteocytes,increases intracellular cAMP level and activates ATF4,a key transcription factor known to regulate Wnt/β-catenin signaling.In vivo knockdown of ATF4 abolishes the magnesium implant-activated β-catenin in bones and reverses the improved-fracture healing in CFTR-mutant mice.In addition,oral supplementation of magnesium activates ATF4 and β-catenin as well as enhances bone volume and density in CFTR-mutant mice.Together,these results show that magnesium implantation or supplementation may serve as a potential anabolic therapy for cystic fibrosis-related bone disease.Activation of ATF4-dependent Wnt/β-catenin signaling in osteocytes is identified as a previously undefined mechanism underlying the beneficial effect of magnesium on bone formation.
