BACKGROUND: Osteoarthritis (OA), a degenerative joint disorder, is a major reason of disability in adults. Accumulating evidences have proved that bone marrow mesenchymal stem cells (BMSCs)-carried exosomes play a significant therapeutic effect on OA. However, the precise regulatory network remains unknown. METHODS: OA and normal cartilage samples were acquired from patients, and chondrocytes were exposed to IL-1b to conduct a cellular OA model. Exosomes prepared from BMSCs were identified using nanoparticle tracking analysis (NTA) and transmission electron microscopy (TEM). Cell viability was determined with CCK-8 assay. Inflammatory injury was assessed by LDH and inflammatory factors (TNF-a and IL-6) using corresponding ELISA kits, respectively. Ferroptosis was evaluated by GSH, MDA and iron levels using corresponding kits, and ROS level with DCFH-DA. The expressions of genes/proteins were determined with RT-qPCR/western bolt. RNA immunoprecipitation and luciferase activity assay were conducted for testing the interactions of small nucleolar RNA host gene 7 (SNHG7)/ferroptosis suppressor protein 1 (FSP1) and miR-485-5p. RESULTS: The expressions of SNHG7 and FSP1 were both reduced in IL-1b-induced chondrocytes and OA cartilage tissues, and there was a positive correlation between them in clinical level. Moreover, SNHG7 was enriched in BMSCsderived exosomes (BMSCs-Exos) and could be internalized by chondrocytes. Functional analysis illustrated that BMSCsExos administration repressed inflammatory injury, oxidative stress and ferroptosis in IL-1b-induced chondrocytes, while these changes were reinforced when SNHG7 was overexpressed in BMSCs-Exos. Notably, FSP1 silencing in chondrocytes abolished the beneficial effects mediated by exosomal SNHG7. CONCLUSIONS Exosomal SNHG7 released from BMSCs inhibited inflammation and ferroptosis in IL-1b-induced chondrocytes through miR-485-5p/FSP1 axis. This work suggested that BMSCs-derived exosomal SNHG7 would be a prospective target for OA treatment.

BACKGROUND: Osteoarthritis (OA), a degenerative joint disorder, is a major reason of disability in adults. Accumulating evidences have proved that bone marrow mesenchymal stem cells (BMSCs)-carried exosomes play a significant therapeutic effect on OA. However, the precise regulatory network remains unknown. METHODS: OA and normal cartilage samples were acquired from patients, and chondrocytes were exposed to IL-1b to conduct a cellular OA model. Exosomes prepared from BMSCs were identified using nanoparticle tracking analysis (NTA) and transmission electron microscopy (TEM). Cell viability was determined with CCK-8 assay. Inflammatory injury was assessed by LDH and inflammatory factors (TNF-a and IL-6) using corresponding ELISA kits, respectively. Ferroptosis was evaluated by GSH, MDA and iron levels using corresponding kits, and ROS level with DCFH-DA. The expressions of genes/proteins were determined with RT-qPCR/western bolt. RNA immunoprecipitation and luciferase activity assay were conducted for testing the interactions of small nucleolar RNA host gene 7 (SNHG7)/ferroptosis suppressor protein 1 (FSP1) and miR-485-5p. RESULTS: The expressions of SNHG7 and FSP1 were both reduced in IL-1b-induced chondrocytes and OA cartilage tissues, and there was a positive correlation between them in clinical level. Moreover, SNHG7 was enriched in BMSCsderived exosomes (BMSCs-Exos) and could be internalized by chondrocytes. Functional analysis illustrated that BMSCsExos administration repressed inflammatory injury, oxidative stress and ferroptosis in IL-1b-induced chondrocytes, while these changes were reinforced when SNHG7 was overexpressed in BMSCs-Exos. Notably, FSP1 silencing in chondrocytes abolished the beneficial effects mediated by exosomal SNHG7. CONCLUSIONS Exosomal SNHG7 released from BMSCs inhibited inflammation and ferroptosis in IL-1b-induced chondrocytes through miR-485-5p/FSP1 axis. This work suggested that BMSCs-derived exosomal SNHG7 would be a prospective target for OA treatment.

BACKGROUND: Osteoarthritis (OA), a degenerative joint disorder, is a major reason of disability in adults. Accumulating evidences have proved that bone marrow mesenchymal stem cells (BMSCs)-carried exosomes play a significant therapeutic effect on OA. However, the precise regulatory network remains unknown. METHODS: OA and normal cartilage samples were acquired from patients, and chondrocytes were exposed to IL-1b to conduct a cellular OA model. Exosomes prepared from BMSCs were identified using nanoparticle tracking analysis (NTA) and transmission electron microscopy (TEM). Cell viability was determined with CCK-8 assay. Inflammatory injury was assessed by LDH and inflammatory factors (TNF-a and IL-6) using corresponding ELISA kits, respectively. Ferroptosis was evaluated by GSH, MDA and iron levels using corresponding kits, and ROS level with DCFH-DA. The expressions of genes/proteins were determined with RT-qPCR/western bolt. RNA immunoprecipitation and luciferase activity assay were conducted for testing the interactions of small nucleolar RNA host gene 7 (SNHG7)/ferroptosis suppressor protein 1 (FSP1) and miR-485-5p. RESULTS: The expressions of SNHG7 and FSP1 were both reduced in IL-1b-induced chondrocytes and OA cartilage tissues, and there was a positive correlation between them in clinical level. Moreover, SNHG7 was enriched in BMSCsderived exosomes (BMSCs-Exos) and could be internalized by chondrocytes. Functional analysis illustrated that BMSCsExos administration repressed inflammatory injury, oxidative stress and ferroptosis in IL-1b-induced chondrocytes, while these changes were reinforced when SNHG7 was overexpressed in BMSCs-Exos. Notably, FSP1 silencing in chondrocytes abolished the beneficial effects mediated by exosomal SNHG7. CONCLUSIONS Exosomal SNHG7 released from BMSCs inhibited inflammation and ferroptosis in IL-1b-induced chondrocytes through miR-485-5p/FSP1 axis. This work suggested that BMSCs-derived exosomal SNHG7 would be a prospective target for OA treatment.

BACKGROUND: Osteoarthritis (OA), a degenerative joint disorder, is a major reason of disability in adults. Accumulating evidences have proved that bone marrow mesenchymal stem cells (BMSCs)-carried exosomes play a significant therapeutic effect on OA. However, the precise regulatory network remains unknown. METHODS: OA and normal cartilage samples were acquired from patients, and chondrocytes were exposed to IL-1b to conduct a cellular OA model. Exosomes prepared from BMSCs were identified using nanoparticle tracking analysis (NTA) and transmission electron microscopy (TEM). Cell viability was determined with CCK-8 assay. Inflammatory injury was assessed by LDH and inflammatory factors (TNF-a and IL-6) using corresponding ELISA kits, respectively. Ferroptosis was evaluated by GSH, MDA and iron levels using corresponding kits, and ROS level with DCFH-DA. The expressions of genes/proteins were determined with RT-qPCR/western bolt. RNA immunoprecipitation and luciferase activity assay were conducted for testing the interactions of small nucleolar RNA host gene 7 (SNHG7)/ferroptosis suppressor protein 1 (FSP1) and miR-485-5p. RESULTS: The expressions of SNHG7 and FSP1 were both reduced in IL-1b-induced chondrocytes and OA cartilage tissues, and there was a positive correlation between them in clinical level. Moreover, SNHG7 was enriched in BMSCsderived exosomes (BMSCs-Exos) and could be internalized by chondrocytes. Functional analysis illustrated that BMSCsExos administration repressed inflammatory injury, oxidative stress and ferroptosis in IL-1b-induced chondrocytes, while these changes were reinforced when SNHG7 was overexpressed in BMSCs-Exos. Notably, FSP1 silencing in chondrocytes abolished the beneficial effects mediated by exosomal SNHG7. CONCLUSIONS Exosomal SNHG7 released from BMSCs inhibited inflammation and ferroptosis in IL-1b-induced chondrocytes through miR-485-5p/FSP1 axis. This work suggested that BMSCs-derived exosomal SNHG7 would be a prospective target for OA treatment.

BACKGROUND: Osteoarthritis (OA), a degenerative joint disorder, is a major reason of disability in adults. Accumulating evidences have proved that bone marrow mesenchymal stem cells (BMSCs)-carried exosomes play a significant therapeutic effect on OA. However, the precise regulatory network remains unknown. METHODS: OA and normal cartilage samples were acquired from patients, and chondrocytes were exposed to IL-1b to conduct a cellular OA model. Exosomes prepared from BMSCs were identified using nanoparticle tracking analysis (NTA) and transmission electron microscopy (TEM). Cell viability was determined with CCK-8 assay. Inflammatory injury was assessed by LDH and inflammatory factors (TNF-a and IL-6) using corresponding ELISA kits, respectively. Ferroptosis was evaluated by GSH, MDA and iron levels using corresponding kits, and ROS level with DCFH-DA. The expressions of genes/proteins were determined with RT-qPCR/western bolt. RNA immunoprecipitation and luciferase activity assay were conducted for testing the interactions of small nucleolar RNA host gene 7 (SNHG7)/ferroptosis suppressor protein 1 (FSP1) and miR-485-5p. RESULTS: The expressions of SNHG7 and FSP1 were both reduced in IL-1b-induced chondrocytes and OA cartilage tissues, and there was a positive correlation between them in clinical level. Moreover, SNHG7 was enriched in BMSCsderived exosomes (BMSCs-Exos) and could be internalized by chondrocytes. Functional analysis illustrated that BMSCsExos administration repressed inflammatory injury, oxidative stress and ferroptosis in IL-1b-induced chondrocytes, while these changes were reinforced when SNHG7 was overexpressed in BMSCs-Exos. Notably, FSP1 silencing in chondrocytes abolished the beneficial effects mediated by exosomal SNHG7. CONCLUSIONS Exosomal SNHG7 released from BMSCs inhibited inflammation and ferroptosis in IL-1b-induced chondrocytes through miR-485-5p/FSP1 axis. This work suggested that BMSCs-derived exosomal SNHG7 would be a prospective target for OA treatment.

Accumulating evidence has confirmed the links between transfer RNA (tRNA) modifications and tumor progression. The present study is the first to explore the role of tRNA methyltransferase 5 (TRMT5), which catalyzes the m1G37 modification of mitochondrial tRNAs in hepatocellular carcinoma (HCC) progression. Here, based on bioinformatics and clinical analyses, we identified that TRMT5 expression was upregulated in HCC, which correlated with poor prognosis. Silencing TRMT5 attenuated HCC proliferation and metastasis both in vivo and in vitro, which may be partially explained by declined extracellular acidification rate (ECAR) and oxygen consumption rate (OCR). Mechanistically, we discovered that knockdown of TRMT5 inactivated the hypoxia-inducible factor-1 (HIF-1) signaling pathway by preventing HIF-1α stability through the enhancement of cellular oxygen content. Moreover, our data indicated that inhibition of TRMT5 sensitized HCC to doxorubicin by adjusting HIF-‍1α. In conclusion, our study revealed that targeting TRMT5 could inhibit HCC progression and increase the susceptibility of tumor cells to chemotherapy drugs. Thus, TRMT5 might be a carcinogenesis candidate gene that could serve as a potential target for HCC therapy.
Humans ; Carcinoma, Hepatocellular/pathology* ; Cell Hypoxia ; Cell Line, Tumor ; Gene Expression Regulation, Neoplastic ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism* ; Liver Neoplasms/pathology* ; Signal Transduction/genetics* ; tRNA Methyltransferases/metabolism*

Purpose To investigate the clinicopathological characteristics,diagnosis,and differential diagnosis of invasive mucinous adenocarcinoma(IMA)and mixed invasive mucinous and non-mucinous adenocarcinoma(mIMA).Methods The clinical data were collected in 36 patients with primary IMA and 17 patients with mIMA,and the expression of TTF-1,CK7,CK20,SATB2,CDX2,EGFR,HNF4a,etc.was detected by immunohistochemical EnVision two-step method.The Sanger se-quencing and the FISH were used for KRAS mutation and NRG1 gene rearrangement detection.The clinicopathological character-istics were analyzed with review of relevant literature.Results There were 9 cases(25.0％)and 3(8.3％)cases of papillary and micropapillary structures in IMA,while 13 cases(76.5％)(P＜0.001)and 9 cases(52.9％)(P=0.001)were present in mIMA.There were 5 cases(13.9％)of high nuclear grade of IMA and 10 cases(58.8％)of high nuclear grade of mIMA(P=0.002).TTF-1 had a positive rate of 37.5％in IMA,but 60.0％and 80.0％in the mucinous adenocarcinoma and non-mucinous adenocarcinoma components of mIMA(P=0.021),respectively.The positive rates of CK7,CK20,and CDX2 in IMA were 90.6％,21.9％,and 9.4％,and the positive rates in mucinous adenocarcinoma and non-mucinous adenocarcinoma components of mIMA were 100％,20％,20％and 100％,6.7％,6.7％,respectively and no SATB2 expression was found in all cases.There was no significant difference in the expres-sion of total EGFR and two EGFR mutation-specific antibodies(L858R,DEL19)between IMA and mIMA.There were 3 cases of mucinous adenocarcinoma with L858R positive in mIMA,and 2 of them were negative for non-mueinous adenocarcinoma.In another case,the non-mueinous adenocarcinoma component of mIMA expressed DEL19,but the mucinous adenocarcinoma component was not expressed.The positive rate of HNF4a in IMA was 72.0％(18/25),and those of HNF4a in mucinous adenocarcinoma and non-mucinous adenocarcinoma in mIMA were 41.7％(5/12)and 33.3％(4/12),respectively(P=0.048).KRAS gene sequencing was carried out in 19 cases of IMA,among which 9 cases(47.4％)had mutations,G12D and G12V were most commonly detected,and 4 cases of mIMA were sequenced,but none of them showed KRAS mutations.FISH detection showed that 2 cases(7.1％)IMAs had NRG1 translocation rearrangement.Conclusion Pulmonary mIMA is more aggressive than IMA.For example,mIMA has significantly more papillary structure,micropapillary structure,and high nu-clear grade cases than IMA.The differences in immunohisto-chemical expression and KRAS mutation between the two are sta-tistically significant.

Objective:To investigate the clinical significance of vertebral body partition in the unipedicular percutaneous vertebroplasty (PVP) for osteoporotic vertebral fractures.Methods:From July 2019 to October 2021, 89 patients with osteoporotic vertebral fracture were treated by unipedicular PVP at Department of Spinal Surgery, Zhengzhou Orthopaedic Hospital. They were 37 males and 52 females, with a mean age of (70.5±4.8) years (from 60 to 80 years). According to the vertebral body partition, the patients were divided into group a (32 cases), group b (20 cases), group c (21 cases), group d (11 cases), group e (0 case) and group f (5 cases). The therapeutic effects were evaluated by comparing the improvement rates of visual analogue scale (VAS) and Oswestry disability index (ODI) between preoperation and postoperative 1-day among all partition groups. The imaging efficacy was evaluated by comparing the proportions of bone cement diffusion area in the posteroanterior and lateral DR films and the leakage of bone cement among all partition groups.Results:The improvement rates of VAS score between preoperation and postoperation: group a [77.8 (75.0, 82.5) %] > group b [71.4 (71.4, 71.4) %] > group c [66.7 (66.7, 66.7) %] > group d [60.0 (60.0, 62.5) %] > group f [57.1 (50.0, 57.1)%], showing a statistically significant difference between any 2 groups ( P<0.001). The improvement rates of ODI score: group a (58.0%±4.2%) > group b (47.5%±2.5%) > group c (42.9%±2.9%) > group d (39.6%±3.2%) > group f (34.2%±8.4%), showing a statistically significant difference between any 2 groups ( P<0.001). The proportions of bone cement diffusion area: group a (76.9%±3.5%) > group b (71.3%±3.1%) > group c (66.1%±3.6%) > group d (60.2%±2.6%) > group f (54.0%±4.2%), showing a statistically significant difference between any 2 groups ( P<0.001). Bone cement leakage occurred in 7 cases, including 3 ones of anterior vertebral leakage (1 case in group a and 2 cases in group b), and 4 ones of leakage into the paravertebral venous plexus (2 cases in group c and 2 cases in group d). There was no intraspinal leakage, or symptoms of nerve compression or lesion. Conclusion:In the unipedicular PVP for osteoporotic vertebral fractures, our vertebral body partition can guide puncturing for bone cement injection because it indicates the optimal and the risky partitions.

Objective To determine the radiation dose of sensitive organs under different protective methods in lung CT scanning environment, and to explore the best protective scheme of corresponding organs. Methods Annealed thermoluminescence dose elements were placed in the stomach, liver, colon, and thyroid gland of a simulated human body model. The dose effect experiment of protective methods included non-protective group, half lead apron group, and full lead apron group. The dose effect experiment of protective thickness included 0.50 mmpb full lead apron group and 0.35 mmpb full lead apron group. The same exposure conditions of lung CT scan were used in the above experiments. Results Compared with the non-protective group, the exposure dose of the stomach, liver, colon, and thyroid gland increased significantly in the half lead apron group (P < 0.05), and the exposure dose of the thyroid gland and colon decreased significantly in the full lead apron group (P < 0.05). There were no significant differences in the exposure dose of the liver, stomach, and colon in the simulated human body model between the 0.35 mmpb full lead apron group and the 0.50 mmpb full lead apron group. Conclusion For lung CT scan, the protective measure of lead apron may not reduce the exposure dose of subjects. The protective thickness of lead apron does not necessarily have a substantial influence on the exposure dose of human body.

Objective:To study the variation in activity in patient′s body with differentiated thyroid cancer (DTC) treated with 131I and external dose level, analyze the relationship between the both, and estimate the correction factor for the dose equivalent rate for the patients with residual activity of 400 MBq. Methods:A total of 43 DTC patients who received 131I therapy for the first time after total thyroidectomy were studied. The dose was 1 850-3 700 MBq and average dose was (2 405±777) MBq. The measurements of residual activity in patient′s body and of dose equivalent rate at 0.3, 1 and 3 m in front of the patients were performed at 2, 6, 20, 22, 24, 27, 30, 44, 46, 48, 54, 68 and 72 h after administration of 131I. Results:The residual activity in patient′s body after 131I therapy varied with time as a function of A= A0 (1.033 16e -0.062 4t+ 0.017 17). It can be estimated that the effective half-life of DTC patients treated with thyroid remnant 131I ablation therapy is 12.19 h. It needs only 26.4-38.9 h to reduce the internal activity to the 400 MBq. The functions of variation with time of normalized dose equivalent rate at 0.3, 1, and 3 m away from patients were: H· 0.3=127.220 7e -0.054 8t+ 3.765 71; H· 1=30.225 8e -0.064 4t+ 0.824 67; and H· 3=4.161 9e -0.061 5t+ 0.167 97, respectively. There was a positive correlation between residual activity and dose equivalent rate at 1 m ( r=0.982, P<0.05), and the function is H· 1=0.025 A+ 1.245. When residual activities in DTC patient′s body were 1 000, 700 and 400 MBq, the corresponding dose equivalent rates at 1 m from patients were 26.2, 18.7 and 11.2 μSv/h, respectively. The correction factors for dose equivalent rate at 0.3, 1 and 3 m from patients with 400 MBq were 0.25, 0.49 and 0.70, respectively. Conclusions:DTC patients with administration of 131I activity below 3 700 MBq need only to be hospitalized for two days to reach the discharge standards. When the residual activity in DTC patient′s body drops to 400 MBq, the dose equivalent rate at 1 m is far less than 25 μSv/h. Simply using the point source formula to estimate the dose equivalent rate around the patient will result in overestimation. Therefore, the correction factor used in the estimation of radiation doses to patients by using the formula needs to be further studied so as to make the model-based estimated result more consistent with the actual situation.