BACKGROUND:The inflammatory response of microglia is closely related to neuronal survival,regeneration,and functional recovery after spinal cord injury.Peroxiredoxin 1 is not only involved in the regulation of oxidative stress,but also has an important effect on cell proliferation,apoptosis,and inflammatory response.OBJECTIVE:To investigate the role and mechanism of peroxiredoxin 1 in the inflammatory response of microglia following spinal cord injury.METHODS:(1)Twelve female C57BL/6 mice were randomly divided into sham-operated(n=6)and spinal cord injury(n=6)groups.The sham-operated group was not modeled and acute spinal cord injury models were constructed in the spinal cord injury group using the modified Allen's method.Spinal cord tissue at the injured site was taken at 7 days after modeling and transcriptome sequencing was performed to identify differentially expressed genes.The expression of peroxiredoxin 1 in spinal cord tissues was verified using western blot and RT-qPCR.(2)Mouse microglia BV2 were divided into two groups:the control group was stimulated with lipopolysaccharide for 6 hours,and in the knockout group,lipopolysaccharide stimulation was applied for 6 hours at 24 hours after peroxiredoxin 1 was knocked down in the cells.RT-qPCR was performed to detect mRNA expression of peroxiredoxin 1,inflammatory factors(interleukin 1β,interleukin 6,inducible nitric oxide synthase,tumor necrosis factor α,C-C motif chemokine ligand 2,and C-X-C motif chemokine ligand 2),and western blot was performed to detect the expression of peroxiredoxin 1,inducible nitric oxide synthase,and reactive oxygen/mitogen-activated protein kinase signaling pathway proteins.Mouse microglia BV2 were treated in two groups:the control group was stimulated by hydrogen peroxide for 4 hours,and the knockout group was stimulated by hydrogen peroxide for 4 hours at 24 hours after knockdown of peroxiredoxin 1.The level of reactive oxygen species was detected by 2,7-dichlorodihydrofluorescein diacetate probe.RESULTS AND CONCLUSION:(1)Results from transcriptome sequencing,western blot and RT-qPCR confirmed that peroxiredoxin 1 expression levels in mouse spinal cord tissues were significantly higher in the spinal cord injury group than the sham-operated group(P＜0.05).(2)Peroxiredoxin 1 knockdown in microglial cells led to decreased expression of peroxiredoxin 1 mRNA and protein(P＜0.05),increased mRNA expression of interleukin 1β,interleukin 6,inducible nitric oxide synthase,tumor necrosis factor α,C-C motif chemokine ligand 2,and C-X-C motif chemokine ligand 2(P＜0.05),increased protein expression of inducible nitric oxide synthase,P-P38,P-JNK and P-ERK proteins(P＜0.05),and increased level of reactive oxygen species(P＜0.05).To conclude,peroxiredoxin 1 regulates microglial inflammation by targeting the reactive oxygen species/mitogen-activated protein kinase signaling pathway.

BACKGROUND:The inflammatory response of microglia is closely related to neuronal survival,regeneration,and functional recovery after spinal cord injury.Peroxiredoxin 1 is not only involved in the regulation of oxidative stress,but also has an important effect on cell proliferation,apoptosis,and inflammatory response.OBJECTIVE:To investigate the role and mechanism of peroxiredoxin 1 in the inflammatory response of microglia following spinal cord injury.METHODS:(1)Twelve female C57BL/6 mice were randomly divided into sham-operated(n=6)and spinal cord injury(n=6)groups.The sham-operated group was not modeled and acute spinal cord injury models were constructed in the spinal cord injury group using the modified Allen's method.Spinal cord tissue at the injured site was taken at 7 days after modeling and transcriptome sequencing was performed to identify differentially expressed genes.The expression of peroxiredoxin 1 in spinal cord tissues was verified using western blot and RT-qPCR.(2)Mouse microglia BV2 were divided into two groups:the control group was stimulated with lipopolysaccharide for 6 hours,and in the knockout group,lipopolysaccharide stimulation was applied for 6 hours at 24 hours after peroxiredoxin 1 was knocked down in the cells.RT-qPCR was performed to detect mRNA expression of peroxiredoxin 1,inflammatory factors(interleukin 1β,interleukin 6,inducible nitric oxide synthase,tumor necrosis factor α,C-C motif chemokine ligand 2,and C-X-C motif chemokine ligand 2),and western blot was performed to detect the expression of peroxiredoxin 1,inducible nitric oxide synthase,and reactive oxygen/mitogen-activated protein kinase signaling pathway proteins.Mouse microglia BV2 were treated in two groups:the control group was stimulated by hydrogen peroxide for 4 hours,and the knockout group was stimulated by hydrogen peroxide for 4 hours at 24 hours after knockdown of peroxiredoxin 1.The level of reactive oxygen species was detected by 2,7-dichlorodihydrofluorescein diacetate probe.RESULTS AND CONCLUSION:(1)Results from transcriptome sequencing,western blot and RT-qPCR confirmed that peroxiredoxin 1 expression levels in mouse spinal cord tissues were significantly higher in the spinal cord injury group than the sham-operated group(P＜0.05).(2)Peroxiredoxin 1 knockdown in microglial cells led to decreased expression of peroxiredoxin 1 mRNA and protein(P＜0.05),increased mRNA expression of interleukin 1β,interleukin 6,inducible nitric oxide synthase,tumor necrosis factor α,C-C motif chemokine ligand 2,and C-X-C motif chemokine ligand 2(P＜0.05),increased protein expression of inducible nitric oxide synthase,P-P38,P-JNK and P-ERK proteins(P＜0.05),and increased level of reactive oxygen species(P＜0.05).To conclude,peroxiredoxin 1 regulates microglial inflammation by targeting the reactive oxygen species/mitogen-activated protein kinase signaling pathway.

Osteoporosis is a common bone disease， whose incidence is still on the rise， posing great challenges to patients and society. This review mainly studies the pathogenesis of osteoporosis from the aspects of oxidative stress， inflammatory response， and glucolipotoxicity-induced injury and clarifies the efficacy and mechanism of some active ingredients of traditional Chinese medicine against osteoporosis through the integration of in vitro and in vivo experiments. The experimental results suggest that some active ingredients can improve bone resorption markers and maintain bone homeostasis by modulating inflammation， oxidative stress， etc. These active ingredients regulate osteoporosis through the receptor activator of nuclear transcription factor-κB （NF-κB） ligand （RANKL） pathway， osteoprotegerin （OPG） pathway， Wnt/β-catenin pathway， NF-κB pathway， mitogen-activated protein kinase （MAPK） pathway， adenosine monophosphate （AMP）-activated protein kinase （AMPK）/mammalian target of rapamycin （mTOR） pathway， and oxidative stress pathway. This review provides ideas for the progress of the prevention and treatment of osteoporosis with the active ingredients of traditional Chinese medicine， aiming to provide new potential lead compounds and reference for the development of innovative drugs and clinical therapy for the treatment of osteoporosis.

BACKGROUND:Cervical disc herniation can cause pain in the neck and shoulder area,as well as radiating pain in the upper limbs.The incidence rate is increasing year by year and tends to affect younger individuals.Fully understanding the biomechanical characteristics of the cervical spine in adolescents is of great significance for preventing and delaying the onset of cervical disc herniation in this age group. OBJECTIVE:To reconstruct cervical spine models for both healthy adolescents and adolescent patients with cervical disc herniation utilizing finite element analysis techniques,to analyze the motion range of the C1-T1 cervical vertebrae as well as the biomechanical characteristics of the annulus fibrosus,nucleus pulposus,endplates,and the cartilage of the small joints. METHODS:A normal adolescent's cervical spine and an adolescent patient with cervical disc herniation were selected in this study.The continuous scan cervical spine CT raw image data were imported into Mimics 21.0 in DICOM format.The C1-T1 vertebrae were reconstructed separately.Subsequently,the established models were imported into the 3-Matic software for disc reconstruction.The perfected models were then imported into Hypermesh software for meshing of the vertebrae,nucleus pulposus,annulus fibrosus,and ligaments,creating valid geometric models.After assigning material properties,the final models were imported into ABAQUS software to observe the joint motion range of the C1-C7 cervical vertebrae segments under different conditions,and to analyze the biomechanical characteristics of the annulus fibrosus,nucleus pulposus,endplates,and small joint cartilage of each cervical spine segment. RESULTS AND CONCLUSION:(1)In six different conditions,the joint motion range of the C1 vertebra in the cervical spine models of both normal adolescent and adolescent patient with cervical disc herniation was higher than that of the other vertebrae.Additionally,the joint motion range of each cervical spine segment in normal adolescent was greater than that in adolescent patient with cervical disc herniation.(2)In the cervical spine model of normal adolescent,the maximum stress values in the annulus fibrosus and nucleus pulposus were found on the left side during C2-3 flexion conditions(0.43 MPa and 0.17 MPa,respectively).In the cervical spine model of adolescent patient with cervical disc herniation,the maximum stress values were found on the left side during C7-T1 flexion conditions(0.54 MPa and 0.18 MPa,respectively).(3)In the cervical spine model of normal adolescent,the maximum stress value on the endplate was found on the left side of the upper endplate of C3 during flexion conditions(1.46 MPa).In the model of adolescent patient with cervical disc herniation,the maximum stress value on the endplate was found on the left side of the lower endplate of C7 during flexion conditions(1.32 MPa).(4)In the cervical spine model of normal adolescent,the maximum stress value in the small joint cartilage was found in the C2-3 left rotation conditions(0.98 MPa).In adolescent patient with cervical disc herniation,the stress in the small joint cartilage significantly increased under different conditions,especially in C1-2,with the maximum stress found during left flexion(3.50 MPa).(5)It is concluded that compared to normal adolescent,adolescent patient with cervical disc herniation exhibits altered cervical curvature and a decrease in overall joint motion range in the cervical spine.In adolescent with cervical disc herniation,there is a significant increase in stress on the annulus fibrosus,nucleus pulposus,and endplates in the C7-T1 segment.The stress on the left articular cartilage of the C1-2 is notable.Abnormal cervical curvature may be the primary factor causing these stress changes.

Prostate cancer is the second most common cancer in men, accounting for 14.1% of new cancer cases in 2020. The aggressiveness of prostate cancer is highly variable, depending on its grade and stage at the time of diagnosis. Despite recent advances in prostate cancer treatment, some patients still experience recurrence or even progression after undergoing radical treatment. Accurate initial staging and monitoring for recurrence determine patient management, which in turn affect patient prognosis and survival. Classical imaging has limitations in the diagnosis and treatment of prostate cancer, but the use of novel molecular probes has improved the detection rate, specificity, and accuracy of prostate cancer detection. Molecular probe-based imaging modalities allow the visualization and quantitative measurement of biological processes at the molecular and cellular levels in living systems. An increased understanding of tumor biology of prostate cancer and the discovery of new tumor biomarkers have allowed the exploration of additional molecular probe targets. The development of novel ligands and advances in nano-based delivery technologies have accelerated the research and development of molecular probes. Here, we summarize the use of molecular probes in positron emission tomography (PET), single-photon emission computed tomography (SPECT), magnetic resonance imaging (MRI), optical imaging, and ultrasound imaging, and provide a brief overview of important target molecules in prostate cancer.
Humans ; Male ; Prostatic Neoplasms/diagnosis* ; Molecular Probes ; Molecular Imaging/methods* ; Magnetic Resonance Imaging ; Positron-Emission Tomography ; Tomography, Emission-Computed, Single-Photon ; Ultrasonography ; Optical Imaging ; Biomarkers, Tumor ; Precision Medicine/methods*

BACKGROUND:Osteoporosis is defined as a chronic metabolic bone disease,and a large amount of evidence has shown that gut microbiota is involved in osteoporosis.However,the causal relationship between gut microbiota and osteoporosis is yet unclear.OBJECTIVE:To evaluate the potential causal relationship between gut microbiota and osteoporosis using the two-sample Mendelian randomization.METHODS:Pooled statistics from the MiBioGen Consortium's Genome-Wide Association Analysis(GWAS)of gut microbiota and GWAS data from the UK Biometric Sample database for osteoporosis were used.Inverse variance weighting(IVW),MR-Egger regression,weighted median,weighted model and simple model were used to study the causal relationship between gut microbiota and osteoporosis.Sensitivity analysis was used to test whether the results of Mendelian randomization are reliable.RESULTS AND CONCLUSION:The inverse variance weighted method showed that there was a causal relationship between gut microbiota and osteoporosis.Among them,the R7 genus of Christensenaceae(MR Egger:β=-0.007;IVW:β=-0.004,P=0.028),Coprococus 3(MR Egger:β=-0.008;IVW:β=-0.003,P=0.046)and Trichospirillum(MR Egger:β=-0.009;IVW:β=-0.004,P=0.003)may be protective factors for osteoporosis,while Hotella(MR Egger:β=0.006;IVW:β=0.002,P=0.033)and Eubacterium oxyoxide(MR Egger:β=0.001;IVW:β=0.003,P=0.046)may be potential risk factors for osteoporosis.Eubacterium oxyoxide and Hotella can increase the risk of osteoporosis,while R7 of Christensenaceae,Coprococcus 3 and Spirillum can reduce the risk of osteoporosis.Whether this conclusion also applies to non-European populations will need to be verified in the future by large clinical trials in different groups.

BACKGROUND:Osteoporosis is defined as a chronic metabolic bone disease,and a large amount of evidence has shown that gut microbiota is involved in osteoporosis.However,the causal relationship between gut microbiota and osteoporosis is yet unclear.OBJECTIVE:To evaluate the potential causal relationship between gut microbiota and osteoporosis using the two-sample Mendelian randomization.METHODS:Pooled statistics from the MiBioGen Consortium's Genome-Wide Association Analysis(GWAS)of gut microbiota and GWAS data from the UK Biometric Sample database for osteoporosis were used.Inverse variance weighting(IVW),MR-Egger regression,weighted median,weighted model and simple model were used to study the causal relationship between gut microbiota and osteoporosis.Sensitivity analysis was used to test whether the results of Mendelian randomization are reliable.RESULTS AND CONCLUSION:The inverse variance weighted method showed that there was a causal relationship between gut microbiota and osteoporosis.Among them,the R7 genus of Christensenaceae(MR Egger:β=-0.007;IVW:β=-0.004,P=0.028),Coprococus 3(MR Egger:β=-0.008;IVW:β=-0.003,P=0.046)and Trichospirillum(MR Egger:β=-0.009;IVW:β=-0.004,P=0.003)may be protective factors for osteoporosis,while Hotella(MR Egger:β=0.006;IVW:β=0.002,P=0.033)and Eubacterium oxyoxide(MR Egger:β=0.001;IVW:β=0.003,P=0.046)may be potential risk factors for osteoporosis.Eubacterium oxyoxide and Hotella can increase the risk of osteoporosis,while R7 of Christensenaceae,Coprococcus 3 and Spirillum can reduce the risk of osteoporosis.Whether this conclusion also applies to non-European populations will need to be verified in the future by large clinical trials in different groups.

Objective To investigate the proportions of myeloid-derived suppressor cells(MDSCs)and their subsets,including poly-morphonuclear MDSCs(PMN-MDSCs),early-stage MDSCs(e-MDSCs),monocytic MDSCs(M-MDSCs),and lectin-like oxidized low-density lipoprotein receptor-1(LOX-1)positive PMN-MDSCs,in the peripheral blood of ovarian cancer(OC)patients and ana-lyze their correlations with clinicopathological parameters of the patients.Methods The proportions of MDSCs and their subsets in the peripheral blood of 38 OC patients(OC group)and 46 healthy individuals(healthy control group)were detected by flow cytometry.The levels of serum IL-10 and TGF-β were detected using ELISA.The OC group was further divided into LOX-1 high and low expres-sion subgroups based on the median proportion of LOX-1+PMN-MDSCs in MDSCs.Results The proportions of MDSCs,PMN-MDSCs,and LOX-1+PMN-MDSCs in the peripheral blood mononuclear cells(PBMCs)of the OC group were significantly higher than those in the healthy control group(U=492,P＜0.001;t=8.741,P＜0.000 1;U=223,P＜0.000 1).The proportions of M-MDSCs and e-MDSCs in the OC group were significantly lower than those in the healthy control group(t=4.366,P＜0.000 1;t=6.927,P＜0.000 1).The proportion of LOX-1+PMN-MDSCs in the lymph node metastasis group of OC patients was significantly higher than that in the non-metastasis group(t=2.249,P＜0.05).The levels of serum IL-10 and TGF-β in the OC group were significantly higher than those in the healthy control group(P＜0.05).In addition,the level of serum TGF-β in the LOX-1 high expression group was significantly higher than that in the LOX-1 low expression group(t=2.302,P＜0.05).Conclusion The proportion of LOX-1+PMN-MDSCs in the peripheral blood of OC patients is significantly increased and closely related to lymph node metastasis.

Objective To investigate the proportions of myeloid-derived suppressor cells(MDSCs)and their subsets,including poly-morphonuclear MDSCs(PMN-MDSCs),early-stage MDSCs(e-MDSCs),monocytic MDSCs(M-MDSCs),and lectin-like oxidized low-density lipoprotein receptor-1(LOX-1)positive PMN-MDSCs,in the peripheral blood of ovarian cancer(OC)patients and ana-lyze their correlations with clinicopathological parameters of the patients.Methods The proportions of MDSCs and their subsets in the peripheral blood of 38 OC patients(OC group)and 46 healthy individuals(healthy control group)were detected by flow cytometry.The levels of serum IL-10 and TGF-β were detected using ELISA.The OC group was further divided into LOX-1 high and low expres-sion subgroups based on the median proportion of LOX-1+PMN-MDSCs in MDSCs.Results The proportions of MDSCs,PMN-MDSCs,and LOX-1+PMN-MDSCs in the peripheral blood mononuclear cells(PBMCs)of the OC group were significantly higher than those in the healthy control group(U=492,P＜0.001;t=8.741,P＜0.000 1;U=223,P＜0.000 1).The proportions of M-MDSCs and e-MDSCs in the OC group were significantly lower than those in the healthy control group(t=4.366,P＜0.000 1;t=6.927,P＜0.000 1).The proportion of LOX-1+PMN-MDSCs in the lymph node metastasis group of OC patients was significantly higher than that in the non-metastasis group(t=2.249,P＜0.05).The levels of serum IL-10 and TGF-β in the OC group were significantly higher than those in the healthy control group(P＜0.05).In addition,the level of serum TGF-β in the LOX-1 high expression group was significantly higher than that in the LOX-1 low expression group(t=2.302,P＜0.05).Conclusion The proportion of LOX-1+PMN-MDSCs in the peripheral blood of OC patients is significantly increased and closely related to lymph node metastasis.

BACKGROUND:The study of the physical properties of scaffolds has always been a hot topic in the field of tissue engineering research.However,for vascular stimulating scaffolds,in addition to meeting the basic performance of the scaffold,other methods are also needed to promote the regeneration of blood vessels within the scaffold,in order to achieve the ultimate goal of repairing bone tissue. OBJECTIVE:A visualization analysis was carried out on the literature published in and outside China on scaffold stimulation for bone tissue engineering,to explore the research hotspots and research status in this field,and to provide a reference for subsequent studies. METHODS:Using the CNKI database and Web of Science core database as retrieval databases,the relevant literature on vascular scaffolds for bone tissue engineering was retrieved.The literature that did not conform to the research object was removed.The obtained data were imported into CiteSpace 6.1.R2 software.Visualization analysis was performed on authors,national institutions,and keywords in the research field. RESULTS AND CONCLUSION:(1)China,the United States,and Germany were the top three countries with the most articles on scaffold stimulation for bone tissue engineering.(2)The top 3 institutions in the CNKI database were Southern Medical University,Huazhong University of Science and Technology,and Donghua University.In the core database of Web of Science,Shanghai Jiao Tong University,Sichuan University and Chinese Academy of Sciences ranked the top 3 in terms of the number of institutional publications.(3)The top 3 keywords in the CNKI database were"tissue engineering,vascularization,angiogenesis".The top 3 keywords in the Web of Science core database were"mesenchymal stem cell,scaffold,vascularization".(4)Through the analysis of co-citation and highly cited references,the main concerns were as follows:vascularization strategies:scaffold design,angiogenic factor delivery,in vitro co-culture,and in vivo pre-vascularization.Technology:3D printing,electrospinning,vascular transplantation,vascular fusion.Mechanisms:immune regulation and macrophages,drug/growth factor delivery,the relationship between endothelial cells and osteoblasts,the paracrine relationship between bone cells and endothelial cells,signaling molecular pathways,angiogenesis,and anti-angiogenesis molecules.(5)The researches concerning vascular stimulating scaffolds in bone tissue engineering in and outside China attach great importance to the application of stem cells and 3D printing technology.Current research focuses on biological 3D printing technology,scaffold modification methods,and the development and application of intelligent biomaterials based on bone repair mechanisms.