Mitochondrial dysfunction leads to osteoarthritis (OA) and disc degeneration. Hypoxia inducible factor-1α (HIF-1α) mediated mitophagy has a protective role in several diseases. However, the ...underlying mechanism of HIF-1α mediated mitophagy in OA remains largely unknown. This current study was performed to determine the effect of HIF-1α mediated mitophagy on OA. Therefore, X-ray and tissue staining including HE staining, safranin O-fast green (S-O) and Alcian Blue were used to assess imageology and histomorphology differences of mouse knee joint. Transcriptional analysis was used to find the possible targets in osteoarthritis. Western blot analysis, RT-qPCR and immunofluorescence staining were used to detect the changes in gene and protein levels in the vitro experiment. The expression of HIF-1α was increased in human and mouse OA cartilage. HIF-1α knockdown by siRNA further impair the hypoxia-induced mitochondrial dysfunction; In contrast, HIF-1α mediated protective role was reinforced by prolylhydroxylase (PHD) inhibitor dimethyloxalylglycine (DMOG). In addition, HIF-1α stabilization could alleviate apoptosis and senescence via mitophagy in chondrocytes under hypoxia condition, which could also ameliorate surgery-induced cartilage degradation in mice OA model. In conclusion, HIF-1α mediated mitophagy could alleviate OA, which may serve as a promising strategy for OA treatment.
The pathophysiology of spinal cord injury (SCI) involves primary injury and secondary injury. Secondary injury is a major target for SCI therapy, whereas microglia play an important role in secondary ...injury. The immunoresponsive gene 1 (Irg-1) has been recorded as one of the most significantly upregulated genes in SCI tissues in gene chip data; however, its role in SCI remains unclear. This study aims to illustrate the role of Irg-1 as well as its regulated metabolite itaconate in SCI. It was demonstrated that the expression of Irg-1 was increased in spinal cord tissues in mice as well as in microglia stimulated by lipopolysaccharides (LPS). It was also shown that overexpression of Irg-1 may suppress LPS-induced inflammation in microglia, while these protective effects were attenuated by Nrf2 silencing. In vivo, overexpression of Irg-1 was shown to suppress neuroinflammation and improve motor function recovery. Furthermore, treatment of microglia with itaconate demonstrated similar inflammation suppressive effects as Irg-1 overexpression in vitro and improved motor function recovery in vivo. In conclusion, the current study shows that Irg-1 and itaconate are involved in the recovery process of SCI, either Irg-1 overexpression or itaconate treatment may provide a promising strategy for the treatment of SCI.
Evident adolescent idiopathic scoliosis (AIS) incurs high treatment costs, low quality of life, and many complications. Early screening of AIS is essential to avoid progressing to an evident stage. ...However, there is no valid serum biomarker for AIS for early screening. Antibody-based array is a large-scale study of proteins, which is expected to reveal a serum protein signature as biomarker for AIS. There are two segments of the research, including biomarkers screening and validation. In the biomarkers screening group, a total of 16 volunteers participated in this study, and we carried out differentially expressed proteins screening via protein array assay between No-AIS group and the AIS group, through which GeneSet enrichment analysis was performed. In the validation group with a total of 62 volunteers, the differentially expressed proteins from screening group were verified by Enzyme-Linked immunosorbent assay (ELISA), and then multiple regression analysis. In our study, there were twenty-nine differentially expressed proteins in AIS, through Protein array assay and GeneSet enrichment analysis in the biomarkers screening group. Then the expression of FAP, CD23 and B2M decreased as the degree of AIS increased via ELISA in validation group (FAP, p < 0.0001; CD23, p = 0.0002; B2M, p < 0.0001). Further, the results of multiple regression analysis showed that FAP, CD23 are linked to Cobb angle, whereas B2M were excluded because of multicollinearity. Altogether, we found that serum protein FAP and CD23 are intimately related to AIS, suggesting FAP and CD23 are expected to serve as the serum biomarkers, which significantly facilitate frequent longitudinal monitoring as to keep track of disease progression and tailor treatment accordingly.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Oxidative stress-induced mitochondrial dysfunction is implicated in the pathogenesis of intervertebral disc degeneration (IVDD). Sirtuin 3 (SIRT3), a sirtuin family protein located in mitochondria, ...is essential for mitochondrial homeostasis; however, the role of SIRT3 in the process of IVDD has remained elusive. Here, we explored the expression of SIRT3 in IVDD in vivo and in vitro; we also explored the role of SIRT3 in senescence, apoptosis, and mitochondrial homeostasis under oxidative stress. We subsequently activated SIRT3 using honokiol to evaluate its therapeutic potential for IVDD. We assessed SIRT3 expression in degenerative nucleus pulposus (NP) tissues and oxidative stress-induced nucleus pulposus cells (NPCs). SIRT3 was knocked down by lentivirus and activated by honokiol to determine its role in oxidative stress-induced NPCs. The mechanism by which honokiol affected SIRT3 regulation was investigated in vitro, and the therapeutic potential of honokiol was assessed in vitro and in vivo. We found that the expression of SIRT3 decreased with IVDD, and SIRT3 knockdown reduced the tolerance of NPCs to oxidative stress. Honokiol (10 μM) improved the viability of NPCs under oxidative stress and promoted their properties of anti-oxidation, mitochondrial dynamics and mitophagy in a SIRT3-dependent manner. Furthermore, honokiol activated SIRT3 through the AMPK-PGC-1α signaling pathway. Moreover, honokiol treatment ameliorated IVDD in rats. Our study indicated that SIRT3 is involved in IVDD and showed the potential of the SIRT3 agonist honokiol for the treatment of IVDD.
Primary cardiac angiosarcoma (PCAS) is a rare type of tumour. Furthermore, descriptions of the demographic features and prognostic factors of PCAS patients have been poorly reported.
A population ...cohort study was conducted using retrospectively extracted data from the SEER (Surveillance, Epidemiology and End Results) database for patients with histological diagnoses of PCAS; the extracted information included demographic, treatment and outcome data.
A total of 168 cases of PCAS from 1973 to 2013 were included. The mean age at diagnosis was 44.4 ± 15.5 years. PCAS was more prevalent in men than in women. The majority of PCAS patients were white (67.3%), while the incidence of PCAS in black individuals was relatively infrequent (19.0%). In addition, 87 cases were classified as distant stage, 44 as regional stage, and 33 as localized stage. The median disease-specific survival (DSS) was 7.22 months, and the 1-, 2- and 5-year DSS rate for PCAS patients was 34.7%, 14.3% and 10.2%, respectively. Further multivariate analyses showed that an age at (greater than or equal to) 45 years (HR 2.165), no radiotherapy (HR 1.629), tumour size > 5 cm (HR 3.182), and the summary stage was associated with worse PCAS-related survival. Cancer-directed surgery and radiotherapy significantly improved the DSS for patients with PCAS (P < 0.05). The C-index of the nomograms was 0.706 (95% CI 0.654-0.758), and the calibration curves showed good agreement between the nomogram prediction and actual observation.
PCAS is a rare cancer that is prone to have poor prognoses. To understand PCAS more thoroughly, more cases with adequate information are needed.
Human papillomavirus (HPV) is associated with an increased risk of cervical cancer. Using a vaccine to prevent HPV infections could be a cost-effective strategy to decrease the incidence of cervical ...cancer. Learning about the characteristics of CIN patients with HPV infection in Wenzhou is a key step in guiding the use of HPV vaccines and screening for cervical cancer.
We undertook a retrospective analysis including 2612 women who were treated in the Department of Gynecology and Obstetrics from Jan 2016 to Nov 2017. All of the patients were examined by HPV testing and histology.
The prevalence of HR-HPV among women with cervical intraepithelial lesions aged 65-69 years (38.8%) was significantly higher than that of the other age groups. The percentage of patients diagnosed with HPV-positive HSIL progressively increased with age to a maximum of 18.0% in the group of 40 to 44 years of age. HPV 16, 52, and 58 were the three most dominant genotypes among these women, and single infections (950, 73.3%) were more common than multiple infections (346, 26.7%). Compared to cervicitis, the odds ratios (ORs) for LSIL associated with HPV 33, 52, 16 and HPV 58 infection were 5.98, 3.91, 3.65, 3.65, and 3.188, respectively; for HSIL associated with HPV 16, 33, 58 and HPV 31 were 9.30, 7.68, 5.97, and 4.21, respectively. In LSIL, the frequencies of HR-HPV 52,16,58,18 were 19.3,18.2,10.9, and 7.8%, respectively.
Our study provides important data about the HPV genotype distribution and its correlation with cervical intraepithelial lesions in the Wenzhou population.
•Survival time of lung cancer with BM observed was very lower than other foundings.•The only two homogeneous factors were male gender and metastasis to the liver.•A number of heterogeneous risk ...factors have been found like age.
To analyse the homogeneous and heterogeneous risk factors for occurrence and prognosis in lung cancer patients diagnosed with bone metastasis (BM) by using the Surveillance, Epidemiology, and End Results (SEER) database.
The medical records of lung cancer patients with or without bone metastasis were identified in the SEER database between 2010 and 2015. A multivariate logistic regression analysis was performed to identify risk factors, and a multivariate Cox regression was used to determine the prognostic effects of every variable on survival.
In total, 34,585 eligible patients from the SEER database were included in the analysis. Male gender and metastasis to the liver were factors that were both positively associated with a risk for the development and prognosis of bone metastasis in patients with lung cancer. Younger age, poor tumour differentiation grade, higher N stage (N3), adenocarcinoma and metastasis to the brain were all positively correlated with a risk of occurrence of BM, but these factors were not correlated with an unfavourable prognosis. Age, race, marital status, tumour size and pathologic type were independent risk factors for the prognosis of bone metastasis.
The morbidity of bone metastasis in lung cancer patients is dismal, with a rate of 25.9%. The findings of this study estimate the homogeneous and heterogeneous risk factors for the occurrence and prognosis of bone metastasis in lung cancer patients, which may provide clinical guidelines for physicians.
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Objective
Neck imbalance negatively affects body aesthetics of adolescent idiopathic scoliosis (AIS) patients. The evaluation of neck imbalance is currently limited to radiographic parameters, but ...lacks visual indicators. Therefore, the purpose of this study was to establish indexes of neck imbalance based on body image and to investigate whether these indexes can truly reflect neck imbalance in AIS patients.
Methods
We performed a cross‐sectional study at a single institution between June 2017 and September 2020 and there were 115 subjects involved in this research. All patients were diagnosed with adolescent idiopathic scoliosis, Lenke type I/II. Radiographic parameters measured included cervical axis tilt (CAT), T1 tilt, first rib angle (FRA), clavicle angle (CA), radiographic shoulder height (RSH), proximal thoracic curve (PTC), apical vertebra translation of proximal thoracic (AVT of PT), main thoracic curve (MTC), apical vertebra translation of main thoracic (AVT of MT) and coronal balance (CB/C7PL‐CSVL). Neck imbalance indexes were obtained and measured following a standardized manner. Intra‐class correlation coefficient (ICC) analysis was performed for neck imbalance indexes to determine their intra‐observer and inter‐observer reliability, and correlation tests were performed for neck imbalance indexes with the radiographic parameters mentioned above.
Results
Strong intraobserver and interobserver reliability were observed in neck imbalance index (NII) 1 (0.91 and 0.88), neck imbalance index 2 (0.85 and 0.81) and NII 3 (0.82 and 0.80), P < 0.05. Significant correlation was found in cervical axis tilt (R = 0.81 for NII 1, R = 0.77 for NII 2 and R = 0.78 for NII 3), T1 tilt (R = 0.43 for NII 1, R = 0.52 for NII 2 and R = 0.48 for NII 3), first rib angle (R = 0.41 for NII 1, R = 0.48 for NII 2 and R = 0.43 for NII 3), proximal thoracic curve (R = 0.36 for NII 2) and apical vertebra translation of proximal thoracic (R = −0.37 for NII 2 and R = −0.35 for NII 3) with neck imbalance indexes. Neck imbalance index 1 showed the highest correlation with cervical axis tilt (R = 0.81, P < 0.01).
Conclusions
Neck imbalance indexes established in our study were in good correlation with cervical axis tilt (CAT), At the meantime, they showed significant correlations with T1 tilt and first rib angle (FRA). Our study provides a practical method for measurement of neck imbalance regarding realistic perspective and makes up for the lack of photographic indexes about neck imbalance.
To help with the assessment of adolescent idiopathic scoliosis (AIS) patients' visual neck imbalance, we designed a set of new indexes based on body image of AIS patients.
Spinal cord injury (SCI) is a destructive and complex disorder of the central nervous system (CNS) for which there is no clinical treatment. Blood-spinal cord barrier (BSCB) rupture is a critical ...event in SCI that aggravates nerve injury. Therefore, maintaining the integrity of the BSCB may be a potential method to treat SCI. Here, we showed that patchouli alcohol (PA) exerts protective effects against SCI. We discovered that PA significantly prevented hyperpermeability of the BSCB by reducing the loss of tight junctions (TJs) and endothelial cells. PA also suppressed endoplasmic reticulum stress and apoptosis
in vitro
. Furthermore, in a rat model of SCI, PA effectively improved neurological deficits. Overall, these results prove that PA exerts neuroprotective effects by maintaining BSCB integrity and thus be a promising candidate for SCI treatment.
Purpose
To determine the incidence of and risk factors for residual back pain in osteoporotic vertebral compression fracture (OVCF) patients after percutaneous kyphoplasty (PKP) treatment, we ...performed a retrospective analysis of prospective data.
Methods
Patients who underwent bilateral PKP and met this study’s inclusion criteria were retrospectively reviewed. Back pain intensity was assessed using a visual analogue scale (VAS) after surgery. Residual back pain was defined as the presence of postoperative moderate-severe pain (average VAS score ≥ 4), and the variables included patient characteristics, baseline symptoms, radiological parameters and surgical factors. Univariate and multivariate logistic regression analyses were performed to identify risk factors.
Results
A total of 809 patients were included, and residual back pain was identified in 63 (7.8%) patients. Of these patients, 52 patients had complete data for further analysis. Multivariate logistic regression analysis showed that risk factors for back pain included the presence of an intravertebral vacuum cleft (OR 2.93,
P
= 0.032), posterior fascia oedema (OR 4.11,
P
= 0.014), facet joint violations (OR 12.19,
P
< 0.001) and a separated cement distribution (OR 2.23,
P
= 0.043).
Conclusion
The incidence of postoperative residual back pain was 7.8% among 809 OVCF patients following PKP. The presence of an intravertebral vacuum cleft, posterior fascia oedema, facet joint violations and a separated cement distribution were identified as independent risk factors for residual back pain.
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