Relationship between oxidative stress and nuclear factor-erythroid-2-related factor 2 signaling in diabetic cardiomyopathy (Review).

Diabetic cardiomyopathy (DCM) is the leading cause of death worldwide, and oxidative stress was discovered to serve an important role in the pathophysiology of the condition. An imbalance between free radicals and antioxidant defenses is known to be associated with cellular dysfunction, leading to the development of various types of cardiac disease. Nuclear factor-erythroid-2-related factor 2 (NRF2) is a transcription factor that controls the basal and inducible expression levels of various antioxidant genes and other cytoprotective phase II detoxifying enzymes, which are ubiquitously expressed in the cardiac system. Kelch-like ECH-associated protein 1 (Keap1) serves as the main intracellular regulator of NRF2. Emerging evidence has revealed that NRF2 is a critical regulator of cardiac homeostasis via the suppression of oxidative stress. The activation of NRF2 was discovered to enhance specific endogenous antioxidant defense factors, one of which is antioxidant response element (ARE), which was subsequently illustrated to detoxify and counteract oxidative stress-associated DCM. The NRF2 signaling pathway is closely associated with the development of various types of cardiac disease, including ischemic heart disease, heart failure, myocardial infarction, atrial fibrillation and myocarditis. Therefore, it is hypothesized that drugs targeting this pathway may be developed to inhibit the activation of NRF2 signaling, thereby preventing the occurrence of DCM and effectively treating the disease.

Curcumin protects cardiomyopathy damage through inhibiting the production of reactive oxygen species in type 2 diabetic mice.

Type 2 diabetes mellitus (DM)-induced cardiomyopathy is a multifactorial and complex disease involving oxidative stress, lipids, and fibrosis. It is based on metabolic disorders and microvascular disease and causes extensive focal necrosis of the heart muscle. Curcumin (CUR) is a natural polyphenol isolated from turmeric rhizomes and plays an important role in the antioxidant, anti-apoptotic and anti-inflammatory effects of diabetes. Therefore, we established a mouse model of diabetic cardiomyopathy (DCM) in type 2 diabetic db/db mice in our study. We divided the experiment into three groups: the control group, DM group and DM + CUR group.We performed cardiac dissection on mice treated in different conditions and conducted special pathological staining on isolated cardiac tissue. We were surprised to find that a high glucose environment can promote cardiomyocyte apoptosis by TUNEL assay. In addition, after detecting dihydroethiidine (DHE), hematoxylin-eosin (H&E) and Oil Red O staining, we unexpectedly found that CUR can inhibit the production of reactive oxygen species (ROS), reduce myocardial apoptosis, and myocardial lipid accumulation. CUR upregulated the expression of Bcl-2, and downstream the expression of Bax and Caspase-3 proteins by immunohistochemical determination and western blotting. Therefore, these results suggest that CUR has a certain protective effect on diabetic cardiomyopathy by inhibiting the production of ROS.

Alveolar adenoma with poor imaging: a case report.

Alveolar adenoma is an isolated, well-defined peripheral lung tumor that originates from type II alveolar cells. The tumor consists of a network of simple, low-cubic, epithelium-coated lacunae with varying amounts of fine and inconspicuous-to-thick spindle cells that sometimes contain mucus sample matrix. Few cases of alveolar adenoma have been reported. These tumors are usually detected by imaging examinations where the alveolar adenoma typically presents as a peripheral, solitary cystic nodule in the lung. The presentation may mimic that of other types of lung tumors, consequently leading to difficulties in the differential diagnosis of this condition. Thus, accurate diagnosis of alveolar adenoma is based on a combination of pathological sections and immunohistochemistry. This study describes an alveolar adenoma in a 59-year-old female patient. Chest X-ray imaging and chest computed tomography identified malignant lesions in the right upper lobe. The patient subsequently underwent a thoracoscopic right upper lobectomy. The diagnosis of alveolar adenoma was confirmed after pathological examination of the excised postoperative tissue. The disease course was stable, and there was no recurrence of pulmonary lesions during 3 years of postoperative patient follow-up. Herein, we report the case of a patient with benign alveolar adenoma with poor imaging and pathological results.

Effects of adiponectin on osteoclastogenesis from mouse bone marrow-derived monocytes.

The aim of the present study was to investigate the effects of adiponectin on bone marrow-derived monocytes (BMMs) in the process of osteoclastogenesis. Primary BMMs derived from the mouse bone marrow were cultured, which were then treated with different concentrations of adiponectin and macrophage colony stimulating factor (M-CSF). Cell viability was determined by measuring the absorbance after 24 h with Cell Counting Kit-8 reagent. BMM cells treated with adiponectin and receptor activator of nuclear factor-κB ligand (RANKL) were induced and differentiated to mature osteoclasts for 1 week, and then stained with tartrate-resistant acid phosphatase (TRAP). The number of osteoclasts was evaluated under light microscopy. The expression of adiponectin in BMMs at the gene and protein levels was further assessed with reverse transcription-quantitative polymerase chain reaction and western blotting, respectively. The cellular proliferation experiment demonstrated that the optical density value decreased gradually with an increase of adiponectin concentration, with statistically significant differences detected among groups. In addition, the number of osteoclasts in the adiponectin-treated group was significantly reduced compared with that in the control group. Adiponectin expression was confirmed in BMMs at both the protein and mRNA levels. In conclusion, the present data demonstrated that adiponectin has a significant inhibitory effect on the osteoclast differentiation and proliferation of BMMs, suggesting a novel strategy for preventing osteoporosis.

Adiponectin inhibits osteoclastogenesis by suppressing NF-κB and p38 signaling pathways.

Adiponectin (APN) has been shown to play a key role in regulating bone mineral density (BMD). Nevertheless, the effects of APN on receptor activator of NF-κB ligand (RANKL)-induced osteoclast formation and mechanism of regulation are not entirely clear. The study, therefore, aimed to evaluate the effect of APN on osteoclastogenesis. Our results showed that APN inhibits osteoclastogenesis and resorption function in vitro by suppressing nuclear factor-κB (NF-κB) and p38 signaling pathways, which is essential for osteoclast formation. Moreover, APN blocked the formation of F-actin rings and attenuated osteoclast-mediated bone resorptive function. Therefore, we concluded that APN may provide a potential treatment for osteoclast-related diseases, such as osteoporosis.

Recurrent multiple neurofibromatosis type 1 of the right lower limb.

Neurofibromatosis type 1 is an autosomal dominant inherited disease, which is characterized by the presence of multiple neurofibromas. We encountered a case in which a sporadic dispersed neurofibroma recurred locally on numerous occasions extending over 16 years. The patient developed multiple masses with a focus of neurofibroma on the right lower limb, which were excised. The patient was initially diagnosed with inflammatory changes via computed tomography and magnetic resonance imaging; however, subsequently, pathological and immunohistochemical examinations revealed an intraneural neurofibroma. The patient underwent a comprehensive and complete local resection several times. After a continuous postoperative follow-up strategy, the patient recovered well. This report describes a case of primary manifestations of multiple and recurrent neurofibromas. We aim to emphasize the possibility of a unique, recurrent, non-healing neurofibroma and review the diagnostic techniques utilized to reach a definitive diagnosis. Early and complete surgical resection is an effective method to treat and prevent this type of neurofibroma.

Expression of adiponectin in the subchondral bone of lumbar facet joints with different degrees of degeneration.

BACKGROUND: Osteoarthritis research has been most commonly performed in the setting of the articular cartilage of the knee. To the best of our knowledge, no studies have evaluated the role of adiponectin in osteoarthritis of the lumbar facet joint (FJOA). Therefore, in this study, we explored whether adiponectin was expressed in the lumbar facet joints and evaluated the role of adiponectin in FJOA. METHODS: We enrolled patients who underwent lumbar computed tomography (CT) and magnetic resonance imaging (MRI) at the Orthopedic Department of the First Affiliated Hospital of Nanchang from May 2015 to June 2016. Lumbar facet joints were obtained from 135 patients at the time of lumbar fusion surgery and divided into three groups according to the Weishaupt grade. Cytokine levels in the subchondral bones were evaluated by enzyme-linked immunosorbent assays (ELISAs), and adiponectin levels were determined by immunohistochemistry, western blotting, and quantitative polymerase chain reaction (qPCR). RESULTS: By ELISA, adiponectin levels were examined in the subchondral bone for lumbar facet joint, and adiponectin was found to be negatively correlated with BMI in 52 patients (p < 0.001, r = -0.861). By immunohistochemistry analysis, adiponectin was found to be expressed in the subchondral bone of the lumbar facet, whereas the cartilage area was negative for adiponectin expression. Immunostaining intensity and area was related to the degeneration of the lumbar facet joint, and, in our research, considerably decreased staining intensity and area were observed in more severely degenerated lumbar facet joints. Furthermore, the expression of adiponectin was also reduced in degenerated lumbar facet joints, and the level of decline corresponded to degeneration detected by western blotting and qPCR analysis (n = 27, p < 0.0001). CONCLUSIONS: Adiponectin expression was observed in the subchondral bone of the lumbar facet joint and decreased as the degree of degeneration increased. Thus, the results of this study provide new insights into the relationship between adiponectin and osteoarthritis.

Repeated Multiple Neurofibromatosis Type 1 in the Right Lower Limb: A Case Report.

Neurofibromatosis type 1 (NF1) is an autosomal-dominant genetic disease characterized by the presence of multiple neurofibromas. We encountered a unique case of NF1 that manifested as a recurrent soft tissue neurofibroma in the right lower limb that developed over a period of 16 years. The patient presented with a painless mass that was initially diagnosed as inflammatory changes via computed tomography and magnetic resonance imaging. However, the condition was subsequently diagnosed as an intraneural neurofibroma via pathological and immunohistochemical examination, which showed a focal to patchy lymphocytic chronic inflammatory infiltrate and several non-encapsulated masses with clear boundaries that were easily distinguishable from the adjacent neurofibroma. The mass relapsed three times over 3 years since it was discovered, for which the patient underwent comprehensive and complete local resection several times. Postoperative continuous follow-up confirmed that the patient recovered well. Early and complete surgical resection is an effective method for treating and preventing recurrent neurofibromas. However, because of the importance of pathologic examination in the diagnosis of such cases, this uncommon entity might be underreported in patients with NF1.

Quantitative evaluation of lumbar intervertebral disc degeneration by axial T2* mapping.

To quantitatively evaluate the clinical value and demonstrate the potential benefits of biochemical axial T2* mapping-based grading of early stages of degenerative disc disease (DDD) using 3.0-T magnetic resonance imaging (MRI) in a clinical setting.Fifty patients with low back pain and 20 healthy volunteers (control) underwent standard MRI protocols including axial T2* mapping. All the intervertebral discs (IVDs) were classified morphologically. Lumbar IVDs were graded using Pfirrmann score (I to IV). The T2* values of the anterior annulus fibrosus (AF), posterior AF, and nucleus pulposus (NP) of each lumbar IVD were measured. The differences between groups were analyzed regarding specific T2* pattern at different regions of interest.The T2* values of the NP and posterior AF in the patient group were significantly lower than those in the control group (P < .01). The T2* value of the anterior AF was not significantly different between the patients and the controls (P > .05). The mean T2*values of the lumbar IVD in the patient group were significantly lower, especially the posterior AF, followed by the NP, and finally, the anterior AF. In the anterior AF, comparison of grade I with grade III and grade I with grade IV showed statistically significant differences (P = .07 and P = .08, respectively). Similarly, in the NP, comparison of grade I with grade III, grade I with grade IV, grade II with grade III, and grade II with grade IV showed statistically significant differences (P < .001). In the posterior AF, comparison of grade II with grade IV showed a statistically significant difference (P = .032). T2 values decreased linearly with increasing degeneration based on the Pfirrmann scoring system (ρ < -0.5, P < .001).Changes in the T2* value can signify early degenerative IVD diseases. Hence, T2* mapping can be used as a diagnostic tool for quantitative assessment of IVD degeneration.

[Correlation study between sagittal lumbar facet joint and degenerative lumbar spondylolisthesis].

Objective: To study the relationship between sagittal facet joint and degenerative lumber spondylolisthesis (DLS) by observing the changes of the lumbar facet joint angle. Methods: Fifty-seven patients with DLS who met the inclusion criteria between January 2013 and February 2016 were collected (DLS group). There were 26 males and 31 females, with the mean age of 54.0 years (range, 34-84 years). Forty patients without DLS at same stage were collected as control group. There were 23 males and 17 females with the mean age of 55.6 years (range, 29-82 years). There was no significant difference in gender and age between 2 groups ( P>0.05). The lumbar facet joint angles were measured and compared by MRI scanning images in 2 groups. In DLS group, X-ray films were used to evaluated the degree of the lumbar spondylolisthesis on the basis of the Meyerding standard, and compared the facet joint angles between patients of different DLS degree. Results: Facet joint angles in the DLS group [(34.18± 4.81)°] were significantly smaller than those in control group [(45.87±1.09)°] ( t=15.073, P=0.000). In DLS group, the patients were rated as degree Ⅰ in 24 cases, degree Ⅱ in 19 cases, degree Ⅲ in 14 cases. As the degree of DLS increased, the lumbar joint angle decreased gradually, and showing significantly differences between patients of different DLS degree ( P<0.05). Conclusion: Sagittal lumbar facet joint may be one of the main risk factors of DLS.