Association of interleukin-6 with sarcopenia and its components in older adults: a systematic review and meta-analysis of cross-sectional studies.

BACKGROUND: Observational studies have documented increased serum IL-6 levels in elderly individuals afflicted with sarcopenia. Nevertheless, the relationship between serum IL-6 concentrations and sarcopenia prevalence in the aging population is yet to be defined. METHODS: We executed a systematic review and meta-analysis of cross-sectional studies that scrutinized serum IL-6 levels in older adults with and without sarcopenia. Relevant studies were sourced from PubMed, Scopus, Embase, Cochrane Library, and Web of Science from inception until 10 September 2023. The standard mean differences (SMDs) in serum IL-6 levels between studies were synthesized using a random-effects model. To examine the influence of demographic and clinical factors on these outcomes, we performed subgroup analyses and meta-regression, focusing on variables such as sex, age, and body mass index (BMI). We also assessed the relationship between serum IL-6 levels and the defining components of sarcopenia: muscle mass, muscle strength, and physical performance. We used Fisher's Z transformation to standardize the interpretation of effect sizes from these relationships. The transformed values were then converted to summary correlation coefficients (r) for a clear and unified summary of the results. RESULTS: We included twenty-one cross-sectional studies involving 3,902 participants. Meta-analysis revealed significantly elevated serum IL-6 levels in older adults with sarcopenia compared with those without sarcopenia (SMD = 0.31; 95% CI 0.18, 0.44). The difference was highly pronounced in the subgroups of male and those with female percentage below 50% or a mean BMI below 24 kg/m2. Serum IL-6 levels were inversely correlated with muscle mass (summary r = -0.18; 95% CI -0.30, -0.06), but not with handgrip strength (summary r = -0.10; 95%CI: -0.25, 0.05) or gait speed (summary r = -0.09; 95%CI: -0.24, 0.07). CONCLUSIONS: This meta-analysis establishes a link between increased serum IL-6 levels and sarcopenia in the elderly, particularly in relation to decreased muscle mass.

Several studies have demonstrated elevated serum IL-6 levels in elderly individuals with sarcopenia, while the relationship between serum IL-6 levels and sarcopenia remains unclear.This is a systematic review and meta-analysis of 21 cross-sectional studies for the relationship between serum IL-6 levels and sarcopenia.Elevated serum IL-6 levels appear to be associated with sarcopenia in older adults, especially in relation to reduced muscle mass.

Prediction of osteoporosis and osteopenia by routine computed tomography of the lumbar spine in different regions of interest.

BACKGROUND: We aimed to investigate the utility of Hounsfield units (HU) obtained from different regions of interest in opportunistic lumbar computed tomography (CT) to predict osteoporosis coupling with data of dual-energy X-ray absorptiometry (DXA). METHODS: A total of 100 patients who attended a university hospital in Shanghai, China, and had undergone CT and DXA tests of the lumbar spine within 3 months were included in this retrospective review. Images were reviewed on axial sections, and regions of interest (ROI) markers were placed on the round, oval, anterior, left, and right of the L1-L4 vertebra to measure the HU. The mean values of CT HU were then compared to the bone mineral density (BMD) measured by DXA. Receiver operator characteristic curves were generated to determine the threshold for diagnosis and its sensitivity and specificity values. RESULTS: The differences in CT HU of different ROI based on DXA definitions of osteoporosis, osteopenia, and normal individuals were statistically significant (p < 0.01). The HU values of the different ROI correlated well with the BMD values (Spearman coefficient all > 0.75, p < 0.01). The threshold for diagnosing osteoporosis varies from 87 to 111 HU in different ROIs, and the threshold for excluding osteoporosis or osteopenia is 99-125 HU. CONCLUSION: This is the first study on osteoporosis diagnosis of different ROI with routine CT lumbar scans. There is a strong correlation between CT HU of different ROI in the lumbar spine and BMD, and HU measurements can be used to predict osteoporosis.

Neurotrophic factors stimulate the activation of hepatic stellate cells in liver fibrosis.

BACKGROUND AND AIMS: Patients with liver fibrosis who have pain in the liver region may have changed nerve factors. The expression of neurokines and hepatic nerves in liver fibrosis, however, was little understood. In order to better understand how liver fibrosis develops, we plan to look into the hepatic nerve and neurokine changes and how they relate to hepatic stellate cells (HSCs). METHODS: The expression of neurokines in liver samples from 55 chronic hepatitis B patients and the carbon tetrachloride (CCl4) animal model were studied. The co-staining of Nissl and α-SMA allowed us to investigate the neurons and their interaction with α-SMA in fibrotic livers, as well as the expression of the glial cell marker glial fibrillary acidic protein (GFAP) and its relationship with α-SMA, a marker of HSCs. SH-SY5Y cells were treated with a fibrotic serum to imitate the hepatic microenvironment on neuronal cells. We also used brain-derived neurotrophic factor (BDNF) to stimulate mouse primary HSCs and LX2. RESULTS: The levels of mRNA for neurokines such as BDNF, GFAP, and growth-associated protein (GAP43) are significantly increased in both human and animal liver fibrosis. As liver fibrosis advances, we found that Nissl bodies and α-SMA may co-localize, suggesting a connection between hepatic nerves and HSCs. Human fibrotic serum may increase neurkines, notably BDNF, in SH-SY5Y cells. We also found that BDNF increased pro-inflammatory cytokines and fibrogenic markers in hHSCs. CONCLUSIONS: Patients with hepatic fibrosis had significantly higher levels of BDNF, GFAP, GAP43, and nerve fibers. HSC and nerve fibers interact, and nerves also create neurogenic substances that promote liver fibrosis and HSC activation.

Serum Glial Cell Line-Derived Neurotrophic Factor (sGDNF) Is a Novel Biomarker in Predicting Cirrhosis in Patients with Chronic Hepatitis B.

Objectives: We assessed the potential of glial cell line-derived neurotrophic factor (GDNF) as a useful biomarker to predict cirrhosis in chronic hepatitis B (CHB) patients. Methods: A total of 735 patients from two medical centers (385 CHB patients and 350 healthy controls) were included to determine the association of serum and tissue GDNF levels with biopsy-proven cirrhosis. The diagnostic accuracy of serum GDNF (sGDNF) was estimated and compared with other indices of cirrhosis. Results: We showed significantly higher levels of sGDNF in CHB patients with fibrosis (28.4 pg/ml vs. 11.6 pg/ml in patients without) and patients with cirrhosis (33.8 pg/ml vs. 23.5 pg/ml in patients without). The areas under receiver operating curve (AUROCs) of sGDNF were 0.83 (95% confidence interval (CI): 0.80-0.87) for predicting liver fibrosis and 0.84 (95% CI: 0.79-0.89) for cirrhosis. Findings from the serum protein level and hepatic mRNA expression were consistent. Using the best cutoff to predict cirrhosis, we categorized the patients into sGDNF-high and sGDNF-low groups. The sGDNF-high group had significantly larger Masson's trichrome and reticulin staining-positive area, higher Scheuer score, and METAVIR fibrosis stage (all p < 0.001) but not steatosis. On multivariable regression, sGDNF was independently associated with cirrhosis with an odds ratio of 6.98 (95% CI: 1.10-17.94). Finally, we demonstrated that sGDNF outperformed AST to platelet ratio index, FIB-4, fibroscore, forn index, and fibrometer in differentiating F4 vs. F3. Conclusion: Using serum, tissue mRNA, and biopsy data, our study revealed a significant potential of sGDNF as a novel noninvasive biomarker for cirrhosis in CHB patients.

Effects of Artemisia annua L. Essential Oil on Osteoclast Differentiation and Function Induced by RANKL.

Objective: This study aimed to assess the main components of Artemisia annua L. essential oil (AEO) and determine their effect on the proliferation and differentiation of RAW264.7 cells induced by receptor activator for nuclear factor-ligand (RANKL) in vitro. Then, we tried to explain part of the function of its possible mechanisms. Materials and Methods: Essential oil was extracted from Artemisia annua L. Osteoclasts were induced in vitro by RANKL in mouse RAW264.7 cells. The experimental group was treated with different concentrations of AEO, while the control group was not treated with AEO. CCK8 was used to detect osteoclast proliferation. The osteoclasts were stained with TRAP. Western blot was used to detect protein in the MAPK pathway and the NF-κB pathway after treatment with different concentrations of AEO. RT-PCR was used to determine the expression of osteoclast-related mRNA in cells. Results: The GC-MS analysis was used to obtain the main components of AEO, including camphor, borneol, camphor, borneol, terpinen-4-ol, p-cymene, eucalyptol, deoxyartemisinin, and artemisia ketone. The CCK8 results showed that the AEO volume ratio of 1 : 4000, 1 : 5000, and 1 : 6000 did not affect the proliferation of RAW264.7 cells. However, TRAP staining showed that AEO decreased osteoclast formation. Western blot results showed that the expression of protein TRAF6, p-p38, p-ERK, p-p65, and NFATc1 decreased in the MAPK pathway and the NF-κB pathway affected by AEO. Furthermore, RT-PCR results showed that the expression of osteoclast resorption-related mRNAs (MMP-9, DC-STAMP, TRAP, and CTSK) and osteoclast differentiation-related mRNAs (OSCAR, NFATc1, c-Src, and c-Fos) also decreased in the experimental group. Conclusions: AEO inhibits osteoclast differentiation in vitro, probably by reducing TRAF6 activation, acting on the MAPK pathway and NF-κB pathway, and inhibiting the expression of osteoclast-related genes.

Glial cell line-derived neurotrophic factor contributes to alcoholic-induced liver injury by regulating the NF-κB pathway.

BACKGROUND: Alcoholic liver disease (ALD) is associated with high morbidity and mortality worldwide. The pathogenesis of ALD is not completely understood. Although accumulating evidence suggests an important role of glial cell line-derived neurotrophic factor (GDNF) in several diseases, there are no data concerning its role in ALD. This study compared patients with ALD with control subjects and used a mouse model and a cell culture model to investigate the function of GDNF in ALD and its mechanism of action in hepatocyte injury. METHODS: Serum levels of GDNF were measured in 25 patients with ALD and 25 healthy control subjects. A 4-week Lieber-DeCarli ethanol (EtOH) liquid diet combined with the Gao-Binge model was used in the mouse study. Mouse primary hepatocytes and Huh-7 cells were used for cell experiments. The parameters of liver injury, inflammatory cytokines, and lipid metabolism were measured. RESULTS: Patients with alcoholic hepatitis had higher serum GDNF than control subjects. Expression of GDNF mRNA and protein was markedly increased in mice in the chronic-plus-binge ALD mouse model. The level of GDNF mRNA was upregulated in primary hepatic stellate cells isolated from ethanol-fed mouse liver. Ethanol induced GDNF expression in LX2 cells. The levels of inflammatory cytokines (tumor necrosis factor α, interleukin 1ß, and monocyte chemotactic protein 1) were significantly increased after GDNF stimulation in primary hepatocytes and Huh-7 cells. After GDNF stimulation, levels of both p-AKT and p-NF-κB were significantly increased in primary hepatocytes and Huh-7 cells. The NF-κB activity induced by GDNF was significantly decreased by an NF-κB inhibitor, which limited hepatocyte injury and inflammation. CONCLUSIONS: The concentration of GDNF is increased in the circulation of ALD patients. GDNF promotes alcohol-induced liver injury and inflammation via the activation of NF-κB, which mediates hepatocyte injury and inflammatory cytokine expression. Based on these findings, GDNF is a potential therapeutic target for preventing or ameliorating liver injury in ALD.