Dual Roles of Canagliflozin on Cholangiocarcinoma Cell Growth and Enhanced Growth Suppression in Combination with FK866

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(3), P. 978 - 978

Published: Jan. 24, 2025

Cholangiocarcinoma-associated mortality has been increasing over the past decade. The sodium-glucose cotransporter 2 inhibitor, canagliflozin, demonstrated anti-tumor effects against several types of cancers; however, studies examining its potential impact on cholangiocarcinoma are lacking. This study investigated canagliflozin and nicotinamide adenine dinucleotide (NAD)+ salvage pathway activation sirtuin 1 tumor growth. We evaluated cell proliferation gene expression in lines analyzed proliferation, apoptosis, migration. Canagliflozin treatment decreased viability cells a concentration-dependent manner but increased at low concentrations lines. At high concentrations, arrested cycle checkpoint G0/G1 phase. In contrast, it proportion S also reduced migratory ability manner. upregulated phosphoribosyltransferase (NAMPT), NAD+, activated NAD+ pathway. growth-inhibitory effect was enhanced when combined with an NAMPT inhibitor. inhibits growth migration is However, further investigation required because growth-promoting through

Language: Английский

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Revisiting the association between sodium-glucose cotransporter-2 inhibitors and the risk of neoplasm in patients with type 2 diabetes: new insights from an updated systematic review and meta-analysis of randomized controlled trials

Expert Review of Clinical Pharmacology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 31, 2025

To evaluate the association between sodium-glucose cotransporter-2 inhibitors (SGLT-2i) and risk of neoplasm in patients with Type 2 diabetes (T2D). Literature retrieval was conducted using databases from inception to June 2024. Randomized controlled trials (RCTs) comparing SGLT-2i placebo or other treatments T2D, reports events were included. Results computed as ratio (RR) 95% confidence intervals (CI). A total 53 RCTs 126,232 participants No significant differences found for overall (RR = 1.08, CI: 0.99 1.19, I2 23%) treatment compared non-users. However, decreased pulmonary 0.83, 0.69 0.99, 0.0%) observed users non-users, while increased prostate 1.21, 1.00 1.47, 0.0%). Compared use not associated neoplasm. neoplasms less frequent users, an www.crd.york.ac.uk/prospero identifier is CRD42021273681.

Language: Английский

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Clinical Variables that Predict Liver-related Events in Steatotic Liver Disease Diagnosed by a Liver Biopsy

Internal Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Objective Identifying patients at high risk of steatotic liver disease (SLD) is crucial. The fibrosis stage the most reliable marker liver-related mortality. However, noninvasive stratification methods remain controversial. Therefore, we analyzed events in who underwent a biopsy for metabolic dysfunction-associated (MASLD) or cryptogenic SLD our hospital. Methods We retrospectively reviewed clinical course to identify occurrence events. Patients This study included 146 diagnosed with through biopsy. Results Liver-related occurred 20 and were more frequent those advanced than without fibrosis. steatosis exhibit reduced progression. obesity and/or diabetes complications had lower better prognosis others. non-invasive fibrosis-4 (FIB-4) index non-alcoholic fatty (NAFLD) prognosis-related "NAFLD outcomes score (NOS)" effectively differentiated Standard laboratory data analyses revealed that total bilirubin low albumin levels factors. A multivariate analysis significant factors other NOS absence complications, FIB-4 index, level independent Conclusion score, are lean phenotypes non-diabetic should also be assessed using markers determine their risks potential outcomes.

Language: Английский

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Pathogenic Mechanisms of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)-Associated Hepatocellular Carcinoma

Cells, Journal Year: 2025, Volume and Issue: 14(6), P. 428 - 428

Published: March 13, 2025

Hepatocellular carcinoma (HCC) is the sixth most common cancer and third leading cause of deaths worldwide. The etiology HCC has now dramatically changed from viral hepatitis to metabolic dysfunction-associated steatotic liver disease (MASLD). main pathogenesis MASLD-related hepatic lipid accumulation hepatocytes, which causes chronic inflammation subsequent progression fibrosis. Chronic generates oxidative stress DNA damage in contribute genomic instability, resulting development HCC. Several molecular pathways are also linked MASLD. In particular, MAPK PI3K-Akt-mTOR upregulated MASLD, promoting survival proliferation cells. addition, MASLD been reported enhance patients with infection. Although there no approved medication for besides resmetirom USA, some preventive strategies onset Sodium-glucose cotransporter-2 (SGLT2) inhibitor, a class medications, exert anti-tumor effects on by regulating reprogramming. Moreover, CD34-positive cell transplantation improves fibrosis intrahepatic angiogenesis supplying various growth factors. Furthermore, exercise through an increase energy consumption as well changes chemokines myokines. this review, we summarize recent progress made pathogenic mechanisms MASLD-associated introduced new therapeutic preventing based

Language: Английский

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Evaluating the Effectiveness of Pegbelfermin in MASH‐Associated Hepatic Fibrosis A Meta‐Analysis and Systematic Review of Randomized Controlled Trials

JGH Open, Journal Year: 2025, Volume and Issue: 9(3)

Published: March 1, 2025

ABSTRACT Introduction Metabolic dysfunction‐associated steatohepatitis (MASH), an advanced form of fatty liver disease, is characterized by inflammation and fibrosis, with emerging interest in fibroblast growth factor (FGF)‐21 analogs, particularly pegbelfermin (PGBF). This study evaluates the efficacy safety PGBF treating MASH‐associated hepatic fibrosis. Methods meta‐analysis followed Cochrane guidelines PRISMA standards. A comprehensive search databases up to January 2023 focused on randomized controlled trials (RCTs) comparing placebo for MASH. Meta‐analyses were performed RevMan 5.4 using a random‐effects model. Results Data from 452 participants across three RCTs analyzed. Significant improvements adiponectin concentration observed both 10 mg [MD = 18.23, 95% CI (6.35, 30.11), p 0.003] 20 18.09, (5.88, 30.31), 0.004] groups compared placebo. reductions PRO‐C3 noted −25.50, (−43.95, −7.05), 0.007] −19.54, (−33.33, −5.76), 0.005] groups. improvement MASH was seen group [RR 2.84, (1.18, 6.78), 0.02] but not group. No significant stiffness, Modified Ishak scores, collagen proportionate area, ALT AST levels, or treatment‐emergent adverse events (TEAEs) either dosage Conclusions Pegbelfermin, promising therapy has demonstrated effectiveness at mg, significantly improving biomarkers including PRO‐C3, while maintaining generally safe profile.

Language: Английский

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Expanding the Use of SGLT2 Inhibitors in T2D Patients Across Clinical Settings

Cells, Journal Year: 2025, Volume and Issue: 14(9), P. 668 - 668

Published: May 2, 2025

Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are currently recommended in patients with type 2 diabetes (T2D) to reduce serum glucose levels. Moreover, robust evidence has clearly demonstrated their beneficial cardiovascular and renal effects, making this class of drugs pivotal for the treatment T2D, especially when complicated by diabetic kidney disease or heart failure. However, several other comorbidities frequently encountered T2D beyond these long-term complications, internal medicine setting. For some comorbidities, such as MAFLD cognitive impairment, association is increasingly recognized, hypothesis a common pathophysiologic background, whereas, others, coincident epidemiology linked ageing populations, including that subjects, may be advocated. In effort personalizing treatment, on potential effects SGLT2i different clinical conditions accumulating. The purpose narrative review update current literature settings glycaemic control, elucidate molecular mechanisms which they exert effects.

Language: Английский

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Sodium-Glucose Cotransporter-2 Inhibitors in Liver Cirrhosis: A Systematic Review of Their Role in Ascites Management, Slowing Disease Progression, and Safety

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(10), P. 4781 - 4781

Published: May 16, 2025

Sodium-glucose cotransporter-2 inhibitors (SGLT2Is) are widely used for type 2 diabetes mellitus (T2DM), conferring cardiovascular and renal benefits with evidence supporting their role in metabolic-associated steatotic liver disease (MASLD), the fastest rising etiology cirrhosis. Our study collects synthesizes all available data on SGLT2I use cirrhosis to summarize potential risks. We systematically reviewed literature adults cirrhosis, focusing 6 outcome domains, including ascites reduction, progression, hemodynamics, acute kidney injury (AKI), electrolyte abnormalities, infection risk. identified 16 studies: compensated (n = 5), decompensated 3), refractory 8). All studies of 11) reported reduction. Most (7 9) indicated SGLT2Is slowed progression by reducing clinical decompensation 4) or improving laboratory markers 3). A minority revealed safety concerns 9 showing hemodynamic instability out 10 5 Current strongly supports management suggests slowing across severities. Longer-term prospective trials patients non-refractory real-world essential clarify potentially expand management.

Language: Английский

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Sodium–Glucose Cotransporter 2 Inhibitor Use and Risk of Liver-Related Events in Patients With Type 2 Diabetes: A Meta-analysis of Observational Cohort Studies

Diabetes Care, Journal Year: 2025, Volume and Issue: 48(6), P. 1042 - 1052

Published: May 20, 2025

BACKGROUND There is uncertainty regarding effect of sodium–glucose cotransporter 2 (SGLT2) inhibitors on the risk major adverse liver-related outcomes (MALOs). PURPOSE We performed a meta-analysis observational cohort studies to quantify magnitude association between SGLT2 inhibitor use and developing MALOs for people with type diabetes mellitus (T2DM). DATA SOURCES systematically reviewed three large electronic databases from inception January 2025. STUDY SELECTION included active-comparator, new-user comparison versus other glucose-lowering medications in patients T2DM. EXTRACTION The primary outcome was incidence rate defined as composite hepatic decompensation events, hepatocellular carcinoma, liver transplantation, or deaths. Secondary each above individual events. Meta-analysis random-effects models. SYNTHESIS identified eight aggregate data 626,104 T2DM (397,806 new users 228,298 agents). During median 2.7 years, associated significantly lower (random-effects hazard ratio 0.83, 95% CI 0.72–0.95; I2 = 83.1%) deaths (0.64, 0.50–0.82; 0%). significant reduction observed comparisons dipeptidyl peptidase 4 inhibitors, metformin, pioglitazone but not glucagon-like peptide 1 receptor agonists. Sensitivity analyses did modify these results. A funnel plot show publication bias. LIMITATIONS Observational design high level heterogeneity are main limitations. CONCLUSIONS

Language: Английский

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