Temporomandibular joint osteoarthritis (TMJ-OA) is a common disease often accompanied by pain, seriously affecting physical and mental health of patients. Abnormal innervation at the osteochondral junction has been considered as a predominant origin of arthralgia, while the specific mechanism mediating pain remains unclear. To investigate the underlying mechanism of TMJ-OA pain, an abnormal joint loading model was used to induce TMJ-OA pain. We found that during the development of TMJ-OA, the increased innervation of sympathetic nerve of subchondral bone precedes that of sensory nerves. Furthermore, these two types of nerves are spatially closely associated. Additionally, it was discovered that activation of sympathetic neural signals promotes osteoarthritic pain in mice, whereas blocking these signals effectively alleviates pain. In vitro experiments also confirmed that norepinephrine released by sympathetic neurons promotes the activation and axonal growth of sensory neurons. Moreover, we also discovered that through releasing norepinephrine, regional sympathetic nerves of subchondral bone were found to regulate growth and activation of local sensory nerves synergistically with other pain regulators. This study identified the role of regional sympathetic nerves in mediating pain in TMJ-OA. It sheds light on a new mechanism of abnormal innervation at the osteochondral junction and the regional crosstalk between peripheral nerves, providing a potential target for treating TMJ-OA pain.
Animals ; Osteoarthritis/physiopathology* ; Mice ; Sympathetic Nervous System/physiopathology* ; Temporomandibular Joint Disorders/physiopathology* ; Arthralgia ; Sensory Receptor Cells ; Disease Models, Animal ; Norepinephrine ; Male ; Temporomandibular Joint/physiopathology* ; Pain Measurement

Objective To investigate the therapeutic effects of the newly developed phosphodiesterase 5 inhibitor,CPD1,on pathological myocardial hypertrophy induced by abdominal aortic constriction(AAC)in rats,and its impact on activation of the autophagy signaling pathway in myocardial tissue.Methods Male Sprague Dawley rats weighing 180～200 g were divided randomly into five groups:Control,Sham,model(AAC),CPD1 treatment(AAC-CPD1,5 mg/kg),and sildenafil treatment(AAC-Sif,20 mg/kg)groups.Rats in all groups except the Control group underwent blunt dissection of the abdominal aorta at the branch point of the left renal artery.Rats in the AAC and treatment groups also underwent constriction and ligation surgery,while rats in the Sham group underwent dissection without ligation.After 3 days of modeling,rats in the treatment groups received either CPD1 or sildenafil via gavage,while rats in the Control,Sham,and AAC groups received an equal volume of physiological saline by gavage,once daily for 8 weeks.Small-animal ultra-high-resolution echocardiography and left ventricular catheterization were employed to assess left heart function and the heart mass index,and expression levels of the hypertrophy indicator,atrial natriuretic peptide(ANP),the key autophagy pathway factor,p62,and LC3A/B in rat left heart tissue were evaluated by Western blot and reverse transcription-polymerase chain reaction.Results Abdominal aortic stenosis affected left heart function in rats,characterized by an increased cardiac mass index and significant enlargement of myocardial cell cross-sectional area.ANP expression levels in left heart tissue were significantly elevated(P＜0.05),while autophagy signaling activity was reduced,with notable accumulation of LC3Ⅰprotein and reduced conversion to LC3Ⅱ.Expression levels of p62 protein were significantly increased.CPD1 and sildenafil significantly improved left ventricular function in AAC rats,reduced cardiac hypertrophy,inhibited expression levels of ANP and p62 proteins(P＜0.05),activated autophagy signaling,and promoted the conversion of LC3Ⅰ to LC3Ⅱ.Notably,low-dose CPD1 treatment was equivalent to high-dose sildenafil.Conclusions CPD1 promotes the activation of the autophagy signaling pathway in left heart tissue,inhibits the expression of p62 and ANP,reduces the cross-sectional area of myocardial cells,and improves pathological myocardial hypertrophy and left heart function impairment caused by AAC.CPD1 also has the advantage of a lower effective dose compared with sildenafil,offering a new treatment option for pathological myocardial hypertrophy.

BACKGROUND:Early treatment methods for colorectal cancer include endoscopy and surgical resection,but there are many postoperative complications.Chemotherapy is the most common treatment for late-stage colorectal cancer,but chemotherapy can cause gastrointestinal dysfunction,bone marrow suppression,liver and kidney function damage,and other adverse reactions.As a result,most patients are not proactive and do not cooperate with treatment.OBJECTIVE:To review the mechanism of action,latest treatment progress,and current problems of mesenchymal stem cells in the treatment of colorectal cancer,and provide a basis for future clinical application.METHODS:PubMed,CNKI,and WanFang databases were searched for relevant literature using the keywords of"mesenchymal stem cells,colorectal cancer,cancer stem cell,tumor microenvironment"in Chinese and English,respectively.Finally,119 articles were included for analysis.RESULTS AND CONCLUSION:(1)Mesenchymal stem cells have both promoting and inhibiting effects on colorectal cancer.(2)The tumor homing characteristics of mesenchymal stem cells enable them to migrate accurately to the tumor site and release drugs,which increases the safety and effectiveness of the treatment of colorectal cancer.(3)Exosomes derived from mesenchymal stem cells can serve as good carriers and shows a good application prospect in the targeted therapy of colorectal cancer.(4)Using viral vectors,non-viral vectors,or other transfection tools,drugs with mature anti-tumor effects can be loaded into mesenchymal stem cells for the treatment of colorectal cancer.(5)The combined use of mesenchymal stem cells and chemotherapy drugs can improve the efficacy of chemotherapy drugs and reduce the adverse reactions of chemotherapy drugs.(6)The mechanism by which mesenchymal stem cells promote the development of colorectal cancer is mainly related to the expression status of signal transduction and chemotactic factors in colorectal cancer cells and the transformation of mesenchymal stem cells into cancer-related fibroblasts.(7)Mesenchymal stem cells may have the characteristics of driving cancer stem cells,promoting tumor initiation and increasing tumor invasion.(8)There are still some unavoidable problems in the treatment of colorectal cancer with mesenchymal stem cells:lack of standardized treatment plans and efficacy evaluation,high treatment costs,preservation and transportation of mesenchymal stem cells,and the proportion of combined use of mesenchymal stem cells and chemotherapy drugs.

Objective To investigate the therapeutic effects of the newly developed phosphodiesterase 5 inhibitor,CPD1,on pathological myocardial hypertrophy induced by abdominal aortic constriction(AAC)in rats,and its impact on activation of the autophagy signaling pathway in myocardial tissue.Methods Male Sprague Dawley rats weighing 180～200 g were divided randomly into five groups:Control,Sham,model(AAC),CPD1 treatment(AAC-CPD1,5 mg/kg),and sildenafil treatment(AAC-Sif,20 mg/kg)groups.Rats in all groups except the Control group underwent blunt dissection of the abdominal aorta at the branch point of the left renal artery.Rats in the AAC and treatment groups also underwent constriction and ligation surgery,while rats in the Sham group underwent dissection without ligation.After 3 days of modeling,rats in the treatment groups received either CPD1 or sildenafil via gavage,while rats in the Control,Sham,and AAC groups received an equal volume of physiological saline by gavage,once daily for 8 weeks.Small-animal ultra-high-resolution echocardiography and left ventricular catheterization were employed to assess left heart function and the heart mass index,and expression levels of the hypertrophy indicator,atrial natriuretic peptide(ANP),the key autophagy pathway factor,p62,and LC3A/B in rat left heart tissue were evaluated by Western blot and reverse transcription-polymerase chain reaction.Results Abdominal aortic stenosis affected left heart function in rats,characterized by an increased cardiac mass index and significant enlargement of myocardial cell cross-sectional area.ANP expression levels in left heart tissue were significantly elevated(P＜0.05),while autophagy signaling activity was reduced,with notable accumulation of LC3Ⅰprotein and reduced conversion to LC3Ⅱ.Expression levels of p62 protein were significantly increased.CPD1 and sildenafil significantly improved left ventricular function in AAC rats,reduced cardiac hypertrophy,inhibited expression levels of ANP and p62 proteins(P＜0.05),activated autophagy signaling,and promoted the conversion of LC3Ⅰ to LC3Ⅱ.Notably,low-dose CPD1 treatment was equivalent to high-dose sildenafil.Conclusions CPD1 promotes the activation of the autophagy signaling pathway in left heart tissue,inhibits the expression of p62 and ANP,reduces the cross-sectional area of myocardial cells,and improves pathological myocardial hypertrophy and left heart function impairment caused by AAC.CPD1 also has the advantage of a lower effective dose compared with sildenafil,offering a new treatment option for pathological myocardial hypertrophy.

BACKGROUND:Early treatment methods for colorectal cancer include endoscopy and surgical resection,but there are many postoperative complications.Chemotherapy is the most common treatment for late-stage colorectal cancer,but chemotherapy can cause gastrointestinal dysfunction,bone marrow suppression,liver and kidney function damage,and other adverse reactions.As a result,most patients are not proactive and do not cooperate with treatment.OBJECTIVE:To review the mechanism of action,latest treatment progress,and current problems of mesenchymal stem cells in the treatment of colorectal cancer,and provide a basis for future clinical application.METHODS:PubMed,CNKI,and WanFang databases were searched for relevant literature using the keywords of"mesenchymal stem cells,colorectal cancer,cancer stem cell,tumor microenvironment"in Chinese and English,respectively.Finally,119 articles were included for analysis.RESULTS AND CONCLUSION:(1)Mesenchymal stem cells have both promoting and inhibiting effects on colorectal cancer.(2)The tumor homing characteristics of mesenchymal stem cells enable them to migrate accurately to the tumor site and release drugs,which increases the safety and effectiveness of the treatment of colorectal cancer.(3)Exosomes derived from mesenchymal stem cells can serve as good carriers and shows a good application prospect in the targeted therapy of colorectal cancer.(4)Using viral vectors,non-viral vectors,or other transfection tools,drugs with mature anti-tumor effects can be loaded into mesenchymal stem cells for the treatment of colorectal cancer.(5)The combined use of mesenchymal stem cells and chemotherapy drugs can improve the efficacy of chemotherapy drugs and reduce the adverse reactions of chemotherapy drugs.(6)The mechanism by which mesenchymal stem cells promote the development of colorectal cancer is mainly related to the expression status of signal transduction and chemotactic factors in colorectal cancer cells and the transformation of mesenchymal stem cells into cancer-related fibroblasts.(7)Mesenchymal stem cells may have the characteristics of driving cancer stem cells,promoting tumor initiation and increasing tumor invasion.(8)There are still some unavoidable problems in the treatment of colorectal cancer with mesenchymal stem cells:lack of standardized treatment plans and efficacy evaluation,high treatment costs,preservation and transportation of mesenchymal stem cells,and the proportion of combined use of mesenchymal stem cells and chemotherapy drugs.

Patients with severe periodontal disease often involve multidisciplinary therapy.This paper reports a case of adult patients with severe periodontitis who was treated by orthodontics,restoration,and periodontics.The space between upper central incisors was closed,aesthetics and periodontal conditions were significantly improved.

Patients with severe periodontal disease often involve multidisciplinary therapy.This paper reports a case of adult patients with severe periodontitis who was treated by orthodontics,restoration,and periodontics.The space between upper central incisors was closed,aesthetics and periodontal conditions were significantly improved.

BACKGROUND:Currently,the treatment methods for colorectal cancer include surgical resection and chemotherapy.However,the subsequent quality of life of patients cannot be improved due to the multiple surgical complications and drug resistance in the later stage of chemotherapy.OBJECTIVE:To review the mechanism of action,latest progress and existing problems of exosomes derived from mesenchymal stem cells in the treatment of colorectal cancer.METHODS:PubMed,CNKI and WanFang databases were searched for relevant literature using the search terms of"mesenchymal stem cells exosomes,colorectal cancer,chemotherapy,treatment"in Chinese and English,respectively.Finally,96 articles were included for analysis.RESULTS AND CONCLUSION:(1)Mesenchymal stem cell-derived exosomes play different roles in the treatment of colorectal cancer mainly through the microRNAs and long-chain non-coding RNAs carried by themselves to mediate different signaling pathways.(2)Mesenchymal stem cell-derived exosomes are highly stable and biocompatible,which makes them excellent carriers of therapeutic drugs.(3)Mesenchymal stem cell-derived exosomes have different effects on resistance to different types of chemotherapeutic agents.

BACKGROUND:Currently,the treatment methods for colorectal cancer include surgical resection and chemotherapy.However,the subsequent quality of life of patients cannot be improved due to the multiple surgical complications and drug resistance in the later stage of chemotherapy.OBJECTIVE:To review the mechanism of action,latest progress and existing problems of exosomes derived from mesenchymal stem cells in the treatment of colorectal cancer.METHODS:PubMed,CNKI and WanFang databases were searched for relevant literature using the search terms of"mesenchymal stem cells exosomes,colorectal cancer,chemotherapy,treatment"in Chinese and English,respectively.Finally,96 articles were included for analysis.RESULTS AND CONCLUSION:(1)Mesenchymal stem cell-derived exosomes play different roles in the treatment of colorectal cancer mainly through the microRNAs and long-chain non-coding RNAs carried by themselves to mediate different signaling pathways.(2)Mesenchymal stem cell-derived exosomes are highly stable and biocompatible,which makes them excellent carriers of therapeutic drugs.(3)Mesenchymal stem cell-derived exosomes have different effects on resistance to different types of chemotherapeutic agents.

Objective To explore the effect of cannabinoid receptor 2(CB2)on orthodontic tooth movement(OTM)rate and periodontal tissue reconstruction of pressure area in mice.Methods Thirty CB2-/-male mice and thirty littermate control WT male mice were individually accepted the orthodontic appliance at their age of 6 weeks.The mice were respectively scarified at 3 days,7 days,14 days and 21 days after the operation.Then the tooth movement distance was examined through the stereomicroscope.Hematoxylin-eosin staining was performed to explore the biological responses of periodontium at the distal mesial root pressure area.Anti-tartrate acid phospha-tase staining was performed to calculate the number and distribution of osteoclasts at the distal mesial root pressure area,and MMP-9 was evaluated by immunohistochemistry to examine the number of MMP-9(+)monocytes and multinucleated cells in the same district as the TRAP staining.Results Compared with those WT mice at 3,7,14 and 21 days,OTM distance showed a gradual increased tendency according with experimental time over 21 days.The widths of periodontal ligament on the pressure side were markedly greater in CB2-/-mice than WT mice at 7,14 and 21 days(P＜0.000 1).The numbers of TRAP positive osteoclasts were significantly greater in CB2-/-mice than those in WT mice at 14 days of OTM(P＜0.001).MMP-9 immunohistochemical staining showed that the number of MMP-9(+)monocytes and multinucleated cells was more in CB2-/-mice than that in WT mice at 14 days of OTM(P＜0.05).Conclusion The absence of CB2 accelerates orthodontic tooth movement under or-thodontic force.The absence of CB2 reinforces bone resorption in orthodontic tooth movement compressive area dur-ing orthodontic tooth movement.