Sarcopenia in hepatocellular carcinoma: Current knowledge and future directions

World Journal of Gastroenterology, Journal Year: 2022, Volume and Issue: 28(4), P. 432 - 448

Published: Jan. 19, 2022

Liver cancer is the second most occurring worldwide and one of leading causes cancer-related deaths. Hepatocellular carcinoma (HCC) common (80%-90%) type among malignant liver cancers. Sarcopenia occurs very early in HCC can predict provide an opportunity to improve muscle health before engaging treatment options such as loco-regional, systemic, transplant management. Multiple prognostic stating systems have been developed HCC, Barcelona Clinic Cancer, Child-Pugh score Albumin-Bilirubin grade. However, evaluation patients' performance status a major limitation these scoring systems. In this review, we aim summarize current knowledge recent advances about role sarcopenia cirrhosis general, while focusing specifically on HCC. Additionally, predicting clinical outcomes prognostication patients undergoing loco-regional therapies, resection, transplantation systematic therapy has discussed. A literature review was performed using databases PubMed/MEDLINE, EMBASE, Cochrane, Web Science, CINAHL April 1, 2021, identify published reports independently HCC-related mortality especially treatments surgical systemic therapies. Basic research focused evaluating balance anabolic catabolic pathways responsible for health. Early studies shown promising results methods which potentially increase prognosis patients. As it Further, measurement obviate confounding caused by abdominal ascites The use add existing better prognosticate

Language: Английский

---

Regulation of bone homeostasis: signaling pathways and therapeutic targets

MedComm, Journal Year: 2024, Volume and Issue: 5(8)

Published: July 24, 2024

As a highly dynamic tissue, bone is continuously rebuilt throughout life. Both formation by osteoblasts and resorption osteoclasts constitute reconstruction homeostasis. The equilibrium of homeostasis governed many complicated signaling pathways that weave together to form an intricate network. These coordinate the meticulous processes resorption, ensuring structural integrity vitality skeletal system. Dysregulation homeostatic regulatory network contributes development progression diseases. Significantly, imbalanced further disrupts triggers cascade reaction exacerbates disease engenders deleterious cycle. Here, we summarize influence on homeostasis, elucidating interplay crosstalk among them. Additionally, review mechanisms underpinning imbalances across diverse landscapes, highlighting current prospective therapeutic targets clinical drugs. We hope this will contribute holistic understanding molecular sustaining which are promising research shed light targeted

Language: Английский

---

Liver‐Secreted Extracellular Vesicles Promote Cirrhosis‐Associated Skeletal Muscle Injury Through mtDNA‐cGAS/STING Axis

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 13, 2025

Abstract Skeletal muscle atrophy (sarcopenia) is a serious complication of liver cirrhosis, and chronic inflammation plays pivotal role in its pathologenesis. However, the detailed mechanism through which injured tissues mediate skeletal inflammatory injury remains elusive. Here, it reported that hepatocytes might secrete mtDNA‐enriched extracellular vesicles (EVs) to trigger by activating cGAS‐STING pathway. Briefly, secreted increased amounts EVs into circulation, are then engulfed primarily macrophages subsequently induce signaling its‐mediated response muscles. In contrast, suppression hepatic EV secretion or STING significantly alleviated cirrhosis‐induced vivo. Circulating from cirrhotic patients showed higher levels mtDNA, EV‐mtDNA positively correlated with severity injury. hepatocytes, mitochondrial damage promoted release cytosolic mtDNA subsequent EVs. This study reveals hepatocyte‐derived via mtDNA‒STING axis, while targeted blockade represents potential therapeutic approach for preventing cirrhosis‐associated atrophy.

Language: Английский

---

Mendelian randomization studies of risk and protective factors for osteoporosis: a systematic review and meta-analysis

Frontiers in Endocrinology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 16, 2025

Mendelian randomization is believed to attenuate the biases inherent in observational studies, yet a meta-analysis of studies osteoporosis has not been conducted thus far. This study aims evaluate connection between potential causal factors and risk by synthesizing evidence from studies. The databases PubMed, Web Science, Embase were systematically searched for investigating influencing up May 2024. Meta-analyses assess associations various pathogenic using Randomization quality was evaluated according Strengthening Reporting Observational Studies Epidemiology via (STROBE-MR) guidelines. A total 706 potentially relevant articles screened, resulting inclusion 53 systematic review, which 30 eligible meta-analysis. combined findings these revealed that rheumatoid arthritis, inflammatory bowel disease, sex hormone binding globulin, depression, non-alcoholic fatty liver primary biliary cholangitis asthma are associated with increased osteoporosis, while basal metabolic rate gut microbiota (NB1n) serves as protective factor. However, association obesity, type 2 diabetes mellitus, metformin, ulcerative colitis, leisure sedentary behaviors, systemic lupus erythematosus, serum iron found be nonsignificant. In summary, our indicates significant relationships osteoporosis's onset progression have established cholangitis, rate, (NB1n), asthma. https://www.crd.york.ac.uk/prospero/, identifier PROSPERO CRD42024540504.

Language: Английский

---

Relationship between prevalence and risk of osteoporosis or osteoporotic fracture with non-alcoholic fatty liver disease: A systematic review and meta-analysis

Osteoporosis International, Journal Year: 2022, Volume and Issue: 33(11), P. 2275 - 2286

Published: June 28, 2022

Language: Английский

---

Osteosarcopenia in NAFLD/MAFLD: An Underappreciated Clinical Problem in Chronic Liver Disease

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(8), P. 7517 - 7517

Published: April 19, 2023

Chronic liver disease (CLD), including non-alcoholic fatty (NAFLD) and its advanced form, steatohepatitis (NASH), affects a significant portion of the population worldwide. NAFLD is characterised by fat accumulation in liver, while NASH associated with inflammation damage. Osteosarcopenia, which combines muscle bone mass loss, an emerging clinical problem chronic that often underappreciated. The reductions share several common pathophysiological pathways; insulin resistance systemic are most crucial predisposing factors related to presence gravity worsening outcome disease. This article explores relationship between osteosarcopenia NAFLD/MAFLD, focusing on diagnosis, prevention treatment this condition patients CLD.

Language: Английский

---

Causal association of NAFLD with osteoporosis, fracture and falling risk: a bidirectional Mendelian randomization study

Frontiers in Endocrinology, Journal Year: 2023, Volume and Issue: 14

Published: Aug. 9, 2023

The causal association between non-alcoholic fatty liver disease (NAFLD) and osteoporosis remains controversial in previous epidemiological studies. We employed a bidirectional two-sample Mendelian analysis to explore the relationship NAFLD osteoporosis.The instrumental variables (IVs) were obtained from large Genome-wide study (GWAS) meta-analysis dataset of European descent. Two-sample randomization (MR) analyses used estimate effect on osteoporosis, fracture, fall. Reverse was conducted NAFLD. inverse-variance weighted (IVW) method primary this analysis. MR-Egger determine horizontal pleiotropic. heterogeneity IVs detected by IVW analyses.Five SNPs (rs2980854, rs429358, rs1040196, rs738409, rs5764430) chosen as for In forward MR analysis, IVW-random indicated (OR= 1.0021, 95% CI: 1.0006-1.0037, P= 0.007) but not fracture 1.0016, 0.998-1.0053, 0.389) fall 0.9912, 0.9412-1.0440, 0.740). Furthermore, reverse did support 1.0002, 0.9997-1.0007, 0.231). No pleiotropic all analyses.The results indicate osteoporosis. patients have higher risk falling risk. addition, our do

Language: Английский

---

Two-sample Mendelian randomization analysis evaluates causal associations between inflammatory bowel disease and osteoporosis

Frontiers in Public Health, Journal Year: 2023, Volume and Issue: 11

Published: May 26, 2023

Over the past few years, multiple observational studies have speculated a potential association between inflammatory bowel disease (IBD), which includes ulcerative colitis (UC) and Crohn's (CD), osteoporosis. However, no consensus has been reached regarding their interdependence pathogenesis. Herein, we sought to further explore causal associations them. We validated IBD reduced bone mineral density in humans based on genome-wide (GWAS) data. To investigate relationship osteoporosis, performed two-sample Mendelian randomization study using training validation sets. Genetic variation data for IBD, CD, UC, osteoporosis were derived from published individuals of European ancestry. After series robust quality control steps, included eligible instrumental variables (SNPs) significantly associated with exposure (IBD/CD/UC). adopted five algorithms, including MR Egger, Weighted median, Inverse variance weighted, Simple mode, infer In addition, evaluated robustness analysis by heterogeneity test, pleiotropy leave-one-out sensitivity multivariate randomization. Genetically predicted CD was positively risk, ORs 1.060 (95% CIs 1.016, 1.106; p = 0.007) 1.044 1.002, 1.088; 0.039) sets, respectively. did not reveal significant UC (p > 0.05). Furthermore, found that overall prediction, 1.050 0.999, 1.103; 0.055) 1.063 1.019, 1.109; 0.005) demonstrated complementing framework genetic variants predispose autoimmune disease.

Language: Английский

---

AI-based opportunistic quantitative image analysis of lung cancer screening CTs to reduce disparities in osteoporosis screening

Bone, Journal Year: 2024, Volume and Issue: 186, P. 117176 - 117176

Published: June 25, 2024

Language: Английский

---

Mendelian‐randomization study revealed causal relationship between nonalcoholic fatty liver disease and osteoporosis/fractures

Journal of Gastroenterology and Hepatology, Journal Year: 2024, Volume and Issue: 39(5), P. 847 - 857

Published: Jan. 19, 2024

Abstract Background Patients with nonalcoholic fatty liver disease (NAFLD) are reported to have a higher risk of osteoporosis/fractures; however, the causal relationship remains unclear. Methods Publicly available genome‐wide association studies (GWASs) were used for Mendelian randomization (MR) analysis. GWASs NAFLD and fractures obtained from FinnGen Consortium. bone mineral density (BMD) derived meta‐analysis. obesity, diabetes, function, serum lipid‐related metrics clarify whether accompanying symptoms contributed fractures. Moreover, two additional applied. Results A was not observed between BMD using However, femoral neck‐BMD (FN‐BMD), suggestive fibrosis FN‐BMD, osteoporosis identified in replication GWASs. Genetically proxied body mass index (BMI), high‐density lipoprotein (HDL), hip circumference increased likelihood lower limb The waist‐to‐hip ratio decreased, whereas glycated hemoglobin (HbA1C) homeostasis model assessment β‐cell function (HOMA‐B) forearm Low‐density (LDL) reduced, HbA1C incidence Alkaline phosphatase (ALP) raised foot after multivariate MR analysis (adjusted BMI), all relationships became insignificant. Conclusions caused reduced BMD, genetically predicted HDL, LDL, HbA1C, HOMA‐B, ALP, circumference, causally BMI may mediate relationships. Larger required verify this finding.

Language: Английский

---