Maternal dietary copper deficiency induces cardiomyopathy and liver injury in mice by activating autophagy.

Maternal nutritional deficiencies during pregnancy result in birth defects and elevate the risk of cardiovascular diseases and metabolic diseases. Accumulating evidence suggests that deficiency of copper, a fundamental trace element involved in several pivotal physiological processes, promotes the onset of multiple diseases, notably heart and liver diseases. Yet, exploration into the effects of maternal copper deficiency (CuD) on offspring is still limited. In this study, we hypothesized that maternal CuD induced cardiomyopathy and liver injury in offspring through the activation of autophagy. We established a maternal CuD mouse model by feeding pregnant C57BL/6 mice with a CuD diet until the end of the experiment. Echocardiography, histological analysis, western blotting, and quantitative polymerase chain reaction were performed on offspring at postnatal day 14. We found that maternal CuD caused growth retardation and early postnatal death in the offspring. Furthermore, our results revealed that CuD induced cardiac systolic dysfunction, cardiac hypertrophy, hepatic steatosis, and liver injury. Moreover, higher expression of LC3 and lower expression of p62 were observed in the heart tissues and liver tissues of CuD mice compared with the control group, indicating that CuD induced autophagy activation. In conclusion, maternal CuD caused severely deleterious effects on the heart and liver of the offspring via activating autophagy.

Fructose aggravates copper-deficiency-induced cardiac remodeling by inhibiting SERCA2a.

OBJECTIVES: Accumulating evidence demonstrates that copper deficiency (CuD) is a risk factor for cardiovascular diseases, besides, fructose has been strongly linked to the development of cardiovascular diseases. However, how CuD or fructose causes cardiovascular diseases is not clearly delineated. The present study aims to investigate the mechanism of CuD or fructose on cardiac remodeling. METHODS: We established a model of CuD- or fructose-induced cardiac hypertrophy in 3-week-old male Sprague-Dawley (SD) rats by CuD diet supplemented with or without 30% fructose for 4 weeks. In vitro study was performed by treating cardiomyocytes with tetrathiomolydbate (TM) and fructose. Echocardiography, histology analysis, immunofluorescence, western blotting, and qPCR were performed. KEY FINDINGS: Our findings revealed that CuD caused noticeable cardiac hypertrophy either in the presence or absence of fructose supplement. Fructose exacerbated CuD-induced cardiac remodeling and intramyocardial lipid accumulation. Furthermore, we presented that the inhibition of autophagic flux caused by Ca2+ disturbance is the key mechanism by which CuD- or fructose-induced cardiac remodeling. The reduced expression of sarcoplasmic/endoplasmic reticulum Ca2+ ATPase 2a (SERCA2a) in cardiomyocytes accounts for the elevated cytoplasmic Ca2+ concentration. CONCLUSIONS: Collectively, our study suggested that fructose aggravated CuD-induced cardiac remodeling through the blockade of autophagic flux via SERCA2a decreasing-induced Ca2+ imbalance.

Fructose aggravates copper-deficiency-induced non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD), is the most common cause of chronic liver disease, affecting 24% of the global population. Accumulating evidence demonstrates that copper deficiency (CuD) is implicated in the development of NAFLD, besides, high fructose consumption by promoting inflammation contributes to NAFLD. However, how CuD and/or fructose (Fru) causes NAFLD is not clearly delineated. The present study aims to investigate the role of CuD and/or fructose supplement on hepatic steatosis and hepatic injury. We established a CuD rat model by feeding weaning male Sprague-Dawley rats for 4 weeks with CuD diet. Fructose was supplemented in drinking water. We found the promoting role of CuD or Fructose (Fru) in the progress of NAFLD, which was aggravated by combination of the two. Furthermore, we presented the alteration of hepatic lipid profiles (including content, composition, and saturation), especially ceramide (Cer), cardiolipin (CL), phosphatidylcholine (PC) and phosphatidylethanolamine (PE) was closely associated with CuD and/or Fru fed induced-NAFLD in rat models. In conclusion, insufficient copper intake or excessive fructose supplement resulted in adverse effects on the hepatic lipid profile, and fructose supplement causes a further hepatic injury in CuD-induced NAFLD, which illuminated a better understanding of NAFLD.

A Systematic Review and Meta-Analysis of the Facet Joint Orientation and Its Effect on the Lumbar.

Facet tropism is recognized as the difference in the positioning of the facet joints in association with each other in the sagittal plane. This guides to an imbalanced biomechanical force over the facet joints and the intervertebral disc during rotation and other physiological activities. A systematic review and meta-analysis of Web of Science, EMBASE, PubMed, Cochrane Library, SCOPUS, and CINHAL from 2004 to 2021 to recognize the related research studies was performed. The data for meta-analysis were obtained from multiple studies to get the combined effect of the facet tropism on the lumbar disc herniation (LDH) and the degenerative lumbar spondylolisthesis (LDS). 117 articles were incorporated in the systematic review, where 41 studies were selected for meta-analysis, out of which 7 studies were found eligible as per the inclusion criteria. When degenerative lumbar spondylolisthesis was compared with the normal group, 95% CI was observed at 1.94 (1.59, 2.28). There was a comparison of disc herniation with the normal group in L4/L5, with a 95% CI of 0.60 (0.05, 1.14). The L5/S1 disc herniation was compared with the normal group and was found to be 0.21 (-0.48, 0.90). Therefore, it was observed that facet tropism is related to lumbar disc herniation and degenerative lumbar spondylolisthesis. Our meta-analysis demonstrated a unique link between the facet tropism and the lumbar disk degeneration along with degenerative lumbar spondylolisthesis.

A Systematic Review and Meta-Analysis on Comparative Kinematics in the Lumbopelvic Region in the Patients Suffering from Spinal Pain.

Background: Lumbopelvic kinematics has been observed to include different parameters and directly relate to the movement of the hip spine. In the current scenario, more than 65 million people have been suffering from spinal pain, and 18% of adults experience chronic spinal pain. Methods: This systematic review and meta-analysis selected 9 studies for analysis via electronic databases like EMBASE, MEDLINE, Web of Science, Scopus, CINAHL, and Cochrane (CENTRAL). After collecting the data, the dataset has been systematically analyzed through statistical methodologies using RevMan and Stata. Results: Out of 116 studies initially scrutinized, nine were finally selected for the meta-analysis. When range of motion was studied via meta-analysis, it was noted that a considerable reduced movement was noted in the lumbar region of the spine when people were suffering from lower back pain in comparison to control group people. Hence, reduced lumbar range of motion, no difference in the angle of lordosis, and no significant difference in extension and rotation in people with lower back pain were found. However, variability was noted in people suffering from lower back pain for flexion and lateral flexion. A significant heterogeneity was found between the studies which lacked some details and standardization of the criteria which were used for defining patients with lower back pain or without them (control group). Results show that spinal pain is the main reason behind the limitation of lumbar range of motion. It is clear from the data set of mean and standard deviation, and this is clear to establish the relationship between the causes of pelvic and spinal pain. In flexion-based ROM, the mean difference was found to be -9.77 (95% CI: -21.86, 2.32). Similarly, for lateral flexion, the mean difference was found to be -5.58 (with 95% CI: -10.38, -0.79). Conclusion: It can be concluded that spinal disease is too influential for people; thereby, it affects day-to-day life activities by creating painful and restricted movements. It is concluded that people suffering from lower back pain have reduced proprioception and range of movement in the lumbar region when compared to control groups with no lower back pain, which mainly focus on flexion and lateral flexion.

Serum levels of irisin in postmenopausal women with osteoporotic hip fractures.

OBJECTIVE: The purpose of this study was to evaluate the role of circulating serum levels of irisin in predicting hip fracture occurrence in a cohort of Chinese postmenopausal women. METHODS: This was a cross-section and case-control study. Four hundred and thirty postmenopausal women aged 50-90 years were included (215 with hip fractures and 215 age-matched cases without fracture). Clinical features, bone mineral density (BMD) and serum biomarkers levels including irisin were measured at baseline. Cox proportional hazards regression analysis was used to assess the correlation between irisin and fracture risk. RESULTS: The mean age of those participants was 68.7 (S.D. 11.7) and 53.0% were order than 65. The irisin serum levels were positively related to total body BMD and total hip BMD. Women with hip fractures showed lower mean serum levels of irisin compared normal control women (457.6 ± 172.6 ng/ml vs. 602.2 ng/ml; P < 0.001). The irisin levels in third and fourth quartiles were associated with the risk of hip fracture (the lowest quartile of irisin levels as the reference), and risk of fracture reduced by 67% (hazard ratio [HR] = 0.33; 95 %CI: 0.18-0.54; P < 0.001) and 84% (HR = 0.16; 95 %CI: 0.09-0.29; P < 0.001). The irisin levels in third and fourth quartiles were also associated with the risk of osteoporosis, and risk of fracture reduced by 55% (HR = 0.45; 95 %CI: 0.21-0.63; P = 0.003) and 73% (HR = 0.27; 95 %CI: 0.15-0.47; P < 0.001). CONCLUSION: Decreased serum levels of circulating irisin are associated with high risk of osteoporosis-related hip fractures and osteoporosis.