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1.
Sci Rep ; 14(1): 18345, 2024 08 07.
Article in English | MEDLINE | ID: mdl-39112598

ABSTRACT

Pressure ulcers (PU) are caused by persistent long-term pressure, which compromises the integrity of the epidermis, dermis, and subcutaneous adipose tissue layer by layer, making it difficult to heal. Platelet products such as platelet lysate (PL) can promote tissue regeneration by secreting numerous growth factors based on clinical studies on skin wound healing. However, the components of PL are difficult to retain in wounds. Gelatin methacrylate (GelMA) is a photopolymerizable hydrogel that has lately emerged as a promising material for tissue engineering and regenerative medicine. The PL liquid was extracted, flow cytometrically detected for CD41a markers, and evenly dispersed in the GelMA hydrogel to produce a surplus growth factor hydrogel system (PL@GM). The microstructure of the hydrogel system was observed under a scanning electron microscope, and its sustained release efficiency and biological safety were tested in vitro. Cell viability and migration of human dermal fibroblasts, and tube formation assays of human umbilical vein endothelial cells were applied to evaluate the ability of PL to promote wound healing and regeneration in vitro. Real-time polymerase chain reaction (PCR) and western blot analyses were performed to elucidate the skin regeneration mechanism of PL. We verified PL's therapeutic effectiveness and histological analysis on the PU model. PL promoted cell viability, migration, wound healing and angiogenesis in vitro. Real-time PCR and western blot indicated PL suppressed inflammation and promoted collagen I synthesis by activating STAT3. PL@GM hydrogel system demonstrated optimal biocompatibility and favorable effects on essential cells for wound healing. PL@GM also significantly stimulated PU healing, skin regeneration, and the formation of subcutaneous collagen and blood vessels. PL@GM could accelerate PU healing by promoting fibroblasts to migrate and secrete collagen and endothelial cells to vascularize. PL@GM promises to be an effective and convenient treatment modality for PU, like chronic wound treatment.


Subject(s)
Angiogenesis , Blood Platelets , Gelatin , Methacrylates , Pressure Ulcer , Skin , Wound Healing , Animals , Humans , Mice , Angiogenesis/drug effects , Blood Platelets/metabolism , Cell Movement/drug effects , Cell Survival/drug effects , Fibroblasts/metabolism , Fibroblasts/drug effects , Gelatin/chemistry , Gelatin/pharmacology , Human Umbilical Vein Endothelial Cells , Hydrogels/chemistry , Methacrylates/chemistry , Methacrylates/pharmacology , Neovascularization, Physiologic/drug effects , Pressure Ulcer/therapy , Regeneration/drug effects , Skin/blood supply , Skin/drug effects , Skin/metabolism , Skin/pathology , STAT3 Transcription Factor/metabolism , Wound Healing/drug effects
2.
Org Lett ; 26(32): 6866-6871, 2024 Aug 16.
Article in English | MEDLINE | ID: mdl-39093330

ABSTRACT

We developed a protocol for the synthesis of highly functionalized 5,6-dihydro-imidazo[1,2-c][1,2,3]triazole derivatives 4-5 (DHITs) from 1-diazonaphthalen-2(1H)-one derivatives with heterocyclic ketene aminals (HKAs). This strategy involved cycloaddition and skeletal rearrangement entailing the heating of a mixture of substrates 1 with HKAs 2-3 and THF without any catalyst. As a result, a series of DHITs 4-5 were produced by cleaving one bond (1 C═N bond) and forming three bonds (1 N-N and 2 C-N bonds) in a single step. This protocol achieved the dual functionalization of diazo building blocks involving both the aromatic nitrogen alkylation reaction to form an ArC-N bond without any metal catalyst and the intermolecular cycloaddition of the N═N bond. These strategies can be used to synthesize functionalized DHITs for combinatorial and parallel syntheses via one-pot reactions without any catalyst.

3.
Front Pharmacol ; 15: 1388540, 2024.
Article in English | MEDLINE | ID: mdl-39108744

ABSTRACT

Background: Atherosclerosis (AS) is a chronic arterial pathology and a leading cause of vascular disease-related mortality. Fatty streaks in the arterial wall develop into atherosclerosis and characteristic plaques. Clinical interventions typically involve lipid-lowering medications and drugs for stabilizing vulnerable plaques, but no direct therapeutic agent specifically targets atherosclerosis. Garlic, also locally known as DASUAN, is recognized as a widely sold herbal dietary supplement esteemed for its cardiovascular benefits. However, the specific mechanisms of garlic's anti-atherosclerotic effects remain unclear. Aims: This study aims to elucidate the pharmacological mechanisms through which garlic ameliorates atherosclerosis. Methods: The study identified the major active components and targets of garlic by screening the TCMSP, TCM-ID, and, ETCM databases. Atherosclerosis-associated targets were obtained from the DisGeNET, GeneCards, and DiGSeE databases, and garlic intervention targets were determined through intersection. Utilizing the intersected genes, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted using R software. A garlic component-disease target network was constructed using Cytoscape. RNA-seq datasets from the GEO database were utilized to identify differentially expressed genes (DEGs) associated with atherosclerosis. The target genes were intersected with DEGs and the FerrDb (ferroptosis database). Molecular docking predicted the binding interactions between active components and the core targets. In vitro and in vivo experiments validated the identified core targets. Results: The integration of garlic drug targets with atherosclerotic disease targets identified 230 target genes. Intersection with RNA-seq DEGs revealed 15 upregulated genes, including 8 target genes related to ferroptosis. Molecular docking indicated favorable affinities between garlic active components [Sobrol A, (+)-L-Alliin, Benzaldoxime, Allicin] and target genes (DPP4, ALOX5, GPX4). Experimental validation showed that GARLIC reduces the expression of ferroptosis-related genes in AS, suggesting its therapeutic potential through the regulation of ferroptosis. Conclusion: Garlic ameliorates atherosclerosis by targeting intra-plaque ferroptosis and reducing lipid peroxidation. These findings provide novel insights into the pharmacological mechanisms underlying the efficacy of garlic in treating AS.

4.
Front Microbiol ; 15: 1396699, 2024.
Article in English | MEDLINE | ID: mdl-38957618

ABSTRACT

Background: Previous research has hinted at a crucial link between gut microbiota and arterial embolism and thrombosis, yet the causal relationship remains enigmatic. To gain a deeper understanding, we aimed to comprehensively explore the causal relationship and elucidate the impact of the gut microbiota on the risk through a two-sample Mendelian randomization (MR) study. Methods: Genetic instrumental variables for gut microbiota were identified from a genome-wide association study (GWAS) of 18,340 participants. Summary statistics for IBS were drawn from a GWAS including 1,076 cases and 381,997 controls. We used the inverse-variance weighted (IVW) method as the primary analysis. To test the robustness of our results, we further performed the weighted median method, MR-Egger regression, and MR pleiotropy residual sum and outlier test. Results: We identified three bacterial traits that were associated with the risk of arterial embolism and thrombosis: odds ratio (OR): 1.58, 95% confidence interval (CI): 1.08-2.31, p = 0.017 for genus Catenibacterium; OR: 0.64, 95% CI: 0.42-0.96, p = 0.031 for genus Dialister; and OR: 2.08, 95% CI: 1.25-3.47, p = 0.005 for genus Odoribacter. The results of sensitivity analyses for these bacterial traits were consistent (P<0.05). Conclusion: Our systematic analyses provided evidence to support a potential causal relationship between several gut microbiota taxa and the risk of arterial embolism and thrombosis. More studies are required to show how the gut microbiota affects the development of arterial embolism and thrombosis.

5.
Anal Chim Acta ; 1317: 342884, 2024 Aug 15.
Article in English | MEDLINE | ID: mdl-39030017

ABSTRACT

BACKGROUND: A proportion of Haematococcus pluvialis under the light stress can effectively conduct astaxanthin biosynthesis, leading to the increase in cell size. Although the size is a critical indicator for identifying the astaxanthin-rich H. pluvialis cells, the cut-off size to be separated varies from sample to sample. RESULTS: Here, we report an ultrastretchable, straight elasto-inertial microchannel with tunable separation threshold to continuously separate the light-induced H. pluvialis cells by size. The symmetrical sheath flows confine the particles to the channel sidewalls, and large particles can cross the interface of viscoelastic fluids to the equilibrium position at the channel centerline. By stretching the microfluidic chip, the medium-sized particles can gradually migrate to the channel centerline in the narrower and longer channel, bringing the tunable separation threshold. Results show that the separation performance of the ultrastretchable microfluidic device is affected by total flow rate, flow rate ratio of sheath to sample, polyethylene oxide (PEO) solution configuration. Lastly, size-tunable separation of light-induced H. pluvialis cells is demonstrated. SIGNIFICANCE: To the best of our knowledge, this is the first report on cell migration in co-flow configurations in the ultra-stretchable microfluidics. Separation of H. pluvialis is not only a relevant end application in harvesting the astaxanthin-rich species, but the separated populations of highly productive microalgal cells will open a venue for cellular directed evolution.


Subject(s)
Lab-On-A-Chip Devices , Light , Chlorophyceae/chemistry , Xanthophylls/chemistry , Xanthophylls/isolation & purification , Microfluidic Analytical Techniques/instrumentation , Particle Size
6.
Cardiovasc Toxicol ; 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-39008240

ABSTRACT

This study aimed to evaluate the correlation of plasma deoxycholic acid (DCA) levels with clinical and hemodynamic parameters in acute pulmonary embolism (APE) patients. Total 149 APE adult patients were prospectively recruited. Plasma DCA levels were measured using rapid resolution liquid chromatography-quadrupole time-of-flight mass spectrometry. Baseline clinical and hemodynamic parameters were evaluated according to plasma DCA levels. The plasma DCA levels were significantly lower in APE patients than in those without APE (P < 0.001). APE patients with adverse events had lower plasma DCA levels (P < 0.001). Low DCA group patients presented more adverse cardiac function, higher NT-proBNP levels (P = 0.010), and higher WHO functional class levels (P = 0.023). Low DCA group also presented with an adverse hemodynamic status, with higher pulmonary vascular resistance levels (P = 0.027) and lower cardiac index levels (P = 0.024). Both cardiac function and hemodynamic parameters correlated well with plasma DCA levels. Kaplan-Meier survival analysis demonstrated that APE patients with lower plasma DCA levels had a significantly higher event rate (P = 0.009). In the univariate and multivariate Cox regression analyses, the plasma DCA level was an independent predictor of clinical worsening events after adjusting for age, sex, WHO functional class, NT-proBNP level, pulmonary vascular resistance, and cardiac index (HR 0.370, 95% CI 0.161, 0.852; P = 0.019). Low plasma DCA levels predicted adverse cardiac function and hemodynamic collapse. A low DCA level was correlated with a higher clinical worsening event rate and could be an independent predictor of clinical outcomes in multivariate analysis.

7.
Polymers (Basel) ; 16(11)2024 May 31.
Article in English | MEDLINE | ID: mdl-38891507

ABSTRACT

The most prevalent type of hemodialysis membrane is polysulfone (PSf). However, due to inadequate biocompatibility, it significantly compromises the safety of dialysis for patients. In this study, we modify the surface of the PSf membrane with 2,4-dihydroxybenzophenone (DBPh) groups to serve as anchoring sites during UV irradiation. Subsequently, a tailored sulfonated dihydroxy propyl chitosan (SDHPCS) is grafted onto the modified PSf membrane to compensate for the deficiencies in hydrophilic additives. The modified PSf membrane exhibits outstanding hydrophilicity and stability, as demonstrated by its characterization and evaluation. This paper focuses on investigating the interaction between platelet membrane formation, protein adsorption, and anticoagulant activity. The results show that the modified PSf membrane exhibits remarkable enhancement in surface hydrophilicity, leading to a significant reduction in protein and platelet adsorption as well as adhesion.

8.
World J Emerg Med ; 15(3): 206-213, 2024.
Article in English | MEDLINE | ID: mdl-38855370

ABSTRACT

BACKGROUND: This study aims to explore whether Xuebijing (XBJ) can improve intestinal microcirculation dysfunction in sepsis and its mechanism. METHODS: A rat model of sepsis was established by cecal ligation and puncture (CLP). A total of 30 male SD rats were divided into four groups: sham group, CLP group, XBJ + axitinib group, and XBJ group. XBJ was intraperitoneally injected 2 h before CLP. Hemodynamic data (blood pressure and heart rate) were recorded. The intestinal microcirculation data of the rats were analyzed via microcirculation imaging. Enzyme-linked immunosorbent assay (ELISA) kits were used to detect the serum levels of interleukin-6 (IL-6), C-reactive protein (CRP), and tumor necrosis factor-α (TNF-α) in the rats. Histological analysis and transmission electron microscopy were used to analyze the injury of small intestinal microvascular endothelial cells and small intestinal mucosa in rats. The expression of vascular endothelial growth factor A (VEGF-A), phosphoinositide 3-kinase (PI3K), phosphorylated PI3K (p-PI3K), protein kinase B (Akt), and phosphorylated Akt (p-Akt) in the small intestine was analyzed via Western blotting. RESULTS: XBJ improved intestinal microcirculation dysfunction in septic rats, alleviated the injury of small intestinal microvascular endothelial cells and small intestinal mucosa, and reduced the systemic inflammatory response. Moreover, XBJ upregulated the expression of VEGF-A, p-PI3K/total PI3K, and p-Akt/total Akt in the rat small intestine. CONCLUSION: XBJ may improve intestinal microcirculation dysfunction in septic rats possibly through the VEGF-A/PI3K/Akt signaling pathway.

9.
Polymers (Basel) ; 16(12)2024 Jun 10.
Article in English | MEDLINE | ID: mdl-38931987

ABSTRACT

This study that modified polysulfone membranes with different end-group chemical functionalities were prepared using chemical synthesis methods and experimentally characterized. The molecular dynamics (MD) method were used to discuss the adsorption mechanism of proteins on functionalized modified polysulfone membrane materials from a molecular perspective, revealing the interactions between different functionalized membrane surfaces and protein adsorption. Theoretical analysis combined with basic experiments and MD simulations were used to explore the orientation and spatial conformational changes of protein adsorption at the molecular level. The results show that BSA exhibits different variability and adsorption characteristics on membranes with different functional group modifications. On hydrophobic membrane surfaces, BSA shows the least stable configuration stability, making it prone to nonspecific structural changes. In addition, surface charge effects lead to electrostatic repulsion for BSA and reduce the protein adsorption sites. These MD simulation results are consistent with experimental findings, providing new design ideas and support for modifying blood-compatible membrane materials.

10.
Org Lett ; 26(23): 4980-4985, 2024 Jun 14.
Article in English | MEDLINE | ID: mdl-38832696

ABSTRACT

An unprecedented selective chromone annulation reaction controlled by solvent for the divergent synthesis of two types of 2,3-disubstituted chromone skeletons has been developed. A variety of 2-chromonyl-3-hydrazono-chromones and 2-alkoxy-3-hydrazono-chromones were constructed efficiently from readily available o-hydroxyphenylenaminones (o-HPEs) and aryldiazonium salts at room temperature. This strategy is highly chemoselective and features mild reaction conditions, broad substrate scope, broad functional group tolerance, easy gram-scale preparation, and simple filtration to obtain the pure products without tedious column chromatography.

12.
Anal Chem ; 96(26): 10620-10629, 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38888085

ABSTRACT

Flexible surface-enhanced Raman scattering (SERS) substrates adaptable to strains enable effective sampling from irregular surfaces, but the preparation of highly stable and sensitive flexible SERS substrates is still challenging. This paper reports a method to fabricate a high-performance strain-adaptable SERS substrate by self-assembly of Au nanoparticles (AuNPs) on polydimethylsiloxane (PDMS) nanowrinkles. Nanowrinkles are created on prestrained PDMS slabs by plasma-induced oxidation followed by the release of the prestrain, and self-assembled AuNPs are transferred onto the nanowrinkles to construct the high-performance SERS substrate. The results show that the nanowrinkled structure can improve the surface roughness and enhance the SERS signals by ∼4 times compared to that of the SERS substrate prepared on flat PDMS substrates. The proposed SERS substrate also shows good adaptability to dynamic bending up to ∼|0.4| 1/cm with excellent testing reproducibility. Phenolic pollutants, including aniline and catechol, were quantitatively tested by the SERS substrate. The self-assembled flexible SERS substrate proposed here provides a powerful tool for chemical analysis in the fields of environmental monitoring and food safety inspection.

13.
J Cell Mol Med ; 28(11): e18370, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38818568

ABSTRACT

The Finkel-Biskis-Jinkins Osteosarcoma (c-Fos; encoded by FOS) plays an important role in several cardiovascular diseases, including atherosclerosis and stroke. However, the relationship between FOS and venous thromboembolism (VTE) remains unknown. We identified differentially expressed genes in Gene Expression Omnibus dataset, GSE48000, comprising VTE patients and healthy individuals, and analysed them using CIBERSORT and weighted co-expression network analysis (WGCNA). FOS and CD46 expressions were significantly downregulated (FOS p = 2.26E-05, CD64 p = 8.83E-05) and strongly linked to neutrophil activity in VTE. We used GSE19151 and performed PCR to confirm that FOS and CD46 had diagnostic potential for VTE; however, only FOS showed differential expression by PCR and ELISA in whole blood samples. Moreover, we found that hsa-miR-144 which regulates FOS expression was significantly upregulated in VTE. Furthermore, FOS expression was significantly downregulated in neutrophils of VTE patients (p = 0.03). RNA sequencing performed on whole blood samples of VTE patients showed that FOS exerted its effects in VTE via the leptin-mediated adipokine signalling pathway. Our results suggest that FOS and related genes or proteins can outperform traditional clinical markers and may be used as diagnostic biomarkers for VTE.


Subject(s)
Computational Biology , MicroRNAs , Neutrophils , Proto-Oncogene Proteins c-fos , Venous Thromboembolism , Humans , MicroRNAs/genetics , MicroRNAs/blood , MicroRNAs/metabolism , Neutrophils/metabolism , Venous Thromboembolism/genetics , Venous Thromboembolism/metabolism , Venous Thromboembolism/blood , Computational Biology/methods , Proto-Oncogene Proteins c-fos/genetics , Proto-Oncogene Proteins c-fos/metabolism , Gene Expression Regulation , Male , Gene Expression Profiling , Gene Regulatory Networks , Female , Biomarkers/blood , Biomarkers/metabolism
14.
BMC Med ; 22(1): 172, 2024 Apr 23.
Article in English | MEDLINE | ID: mdl-38650037

ABSTRACT

BACKGROUND: Lenvatinib is widely used in treatment of unresectable hepatocellular carcinoma (uHCC), but the benefit of its combination with immunotherapy needs to be verified. This study evaluated the efficacy and safety of tislelizumab plus lenvatinib in systemic treatment-naïve patients with uHCC. METHODS: In this multicenter, single-arm, phase 2 study, systemic treatment-naïve patients with uHCC received tislelizumab 200 mg every three weeks plus lenvatinib (bodyweight ≥ 60 kg: 12 mg; < 60 kg: 8 mg; once daily). Dose-limiting toxicities (DLTs) were evaluated in safety run-in phase to determine whether to enter the expansion phase. The primary endpoint was objective response rate (ORR) assessed by independent review committee (IRC) per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1). Based on Simon's two-stage design, > 6 responders were needed in stage 1 (n = 30) to continue the study, and ≥ 18 responders were needed by the end of stage 2 (n = 60) to demonstrate statistical superiority to a historical control of lenvatinib monotherapy. RESULTS: Sixty-four patients were enrolled. No DLTs were reported. The study achieved statistical superiority (p = 0.0003) with 23 responders assessed by IRC per RECIST v1.1 in the first 60 patients of the efficacy evaluable analysis set (n = 62). After a median follow-up of 15.7 months, confirmed ORR and disease control rate were 38.7% (24/62, 95% confidence interval [CI], 26.6-51.9) and 90.3% (56/62, 95% CI, 80.1-96.4), respectively. Median progression-free survival was 8.2 months (95% CI, 6.8-not evaluable). Overall survival rate at 12 months was 88.6% (95% CI, 77.7-94.4). Grade ≥ 3 treatment-related adverse events occurred in 18 (28.1%) patients. CONCLUSIONS: Tislelizumab plus lenvatinib demonstrated promising antitumor activity with favourable tolerability as first-line therapy for patients with uHCC. TRIAL REGISTRATION: ClinicalTrials.gov (NCT04401800).


Subject(s)
Antibodies, Monoclonal, Humanized , Carcinoma, Hepatocellular , Liver Neoplasms , Phenylurea Compounds , Quinolines , Humans , Carcinoma, Hepatocellular/drug therapy , Quinolines/therapeutic use , Quinolines/adverse effects , Quinolines/administration & dosage , Male , Liver Neoplasms/drug therapy , Phenylurea Compounds/therapeutic use , Phenylurea Compounds/adverse effects , Phenylurea Compounds/administration & dosage , Female , Middle Aged , Aged , Antibodies, Monoclonal, Humanized/therapeutic use , Antibodies, Monoclonal, Humanized/adverse effects , Antibodies, Monoclonal, Humanized/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Treatment Outcome , Adult
15.
Org Lett ; 26(18): 3810-3815, 2024 May 10.
Article in English | MEDLINE | ID: mdl-38678579

ABSTRACT

A visible-light-driven photocatalytic protocol is established for the diastereoselective synthesis of pyrrolo[3,2,1-jk]carbazoles via a radical-triggered multicomponent bicyclization reaction starting from readily available indole-tethered 1,6-enynes and α-benzyl-α-bromomalonates under mild conditions. This photocatalytic approach exhibits a wide substrate compatibility and excellent tolerability toward various functional groups and boasts the benefit of efficient ring formation and chemical bond creation.

16.
Org Lett ; 26(18): 3828-3833, 2024 May 10.
Article in English | MEDLINE | ID: mdl-38684050

ABSTRACT

The photocatalyzed radical-triggered thio/selenosulfonylation-bicyclization of indole-tethered 1,6-enynes has been established for the first time, enabling the synthesis of various previously unreported thio/selenosulfonylated benzo[c]pyrrolo[1,2,3-lm]carbazoles with moderate to good yields under mild conditions. The reaction pathway was proposed, consisting of energy transfer, homolytic cleavage, radical addition, 5-exo-dig, radical coupling, and a Mallory reaction cascade. This approach exhibits a wide substrate compatibility and excellent tolerability toward various functional groups and is characterized by its remarkable efficiency in both bond formation and annulation.

17.
J Nanobiotechnology ; 22(1): 187, 2024 Apr 17.
Article in English | MEDLINE | ID: mdl-38632623

ABSTRACT

Pathological conditions linked to shear stress have been identified in hematological diseases, cardiovascular diseases, and cancer. These conditions often exhibit significantly elevated shear stress levels, surpassing 1000 dyn/cm2 in severely stenotic arteries. Heightened shear stress can induce mechanical harm to endothelial cells, potentially leading to bleeding and fatal consequences. However, current technology still grapples with limitations, including inadequate flexibility in simulating bodily shear stress environments, limited range of shear stress generation, and spatial and temporal adaptability. Consequently, a comprehensive understanding of the mechanisms underlying the impact of shear stress on physiological and pathological conditions, like thrombosis, remains inadequate. To address these limitations, this study presents a microfluidic-based shear stress generation chip as a proposed solution. The chip achieves a substantial 929-fold variation in shear stress solely by adjusting the degree of constriction in branch channels after PDMS fabrication. Experiments demonstrated that a rapid increase in shear stress up to 1000 dyn/cm2 significantly detached 88.2% cells from the substrate. Long-term exposure (24 h) to shear stress levels below 8.3 dyn/cm2 did not significantly impact cell growth. Furthermore, cells exposed to shear stress levels equal to or greater than 8.3 dyn/cm2 exhibited significant alterations in aspect ratio and orientation, following a normal distribution. This microfluidic chip provides a reliable tool for investigating cellular responses to the wide-ranging shear stress existing in both physiological and pathological flow conditions.


Subject(s)
Microfluidics , Thrombosis , Humans , Endothelial Cells , Cell Line , Thrombosis/pathology , Stress, Mechanical
18.
Clin Mol Hepatol ; 30(3): 468-486, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38637957

ABSTRACT

BACKGROUND/AIMS: Chronic hepatitis C (CHC) patients who failed antiviral therapy are at increased risk for hepatocellular carcinoma (HCC). This study assessed the potential role of metformin and statins, medications for diabetes mellitus (DM) and hyperlipidemia (HLP), in reducing HCC risk among these patients. METHODS: We included CHC patients from the T-COACH study who failed antiviral therapy. We tracked the onset of HCC 1.5 years post-therapy by linking to Taiwan's cancer registry data from 2003 to 2019. We accounted for death and liver transplantation as competing risks and employed Gray's cumulative incidence and Cox subdistribution hazards models to analyze HCC development. RESULTS: Out of 2,779 patients, 480 (17.3%) developed HCC post-therapy. DM patients not using metformin had a 51% increased risk of HCC compared to non-DM patients, while HLP patients on statins had a 50% reduced risk compared to those without HLP. The 5-year HCC incidence was significantly higher for metformin non-users (16.5%) versus non-DM patients (11.3%; adjusted sub-distribution hazard ratio [aSHR]=1.51; P=0.007) and metformin users (3.1%; aSHR=1.59; P=0.022). Statin use in HLP patients correlated with a lower HCC risk (3.8%) compared to non-HLP patients (12.5%; aSHR=0.50; P<0.001). Notably, the increased HCC risk associated with non-use of metformin was primarily seen in non-cirrhotic patients, whereas statins decreased HCC risk in both cirrhotic and non-cirrhotic patients. CONCLUSION: Metformin and statins may have a chemopreventive effect against HCC in CHC patients who failed antiviral therapy. These results support the need for personalized preventive strategies in managing HCC risk.


Subject(s)
Antiviral Agents , Carcinoma, Hepatocellular , Hepatitis C, Chronic , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Liver Neoplasms , Metformin , Humans , Carcinoma, Hepatocellular/prevention & control , Carcinoma, Hepatocellular/etiology , Carcinoma, Hepatocellular/epidemiology , Hepatitis C, Chronic/complications , Hepatitis C, Chronic/drug therapy , Male , Liver Neoplasms/prevention & control , Liver Neoplasms/epidemiology , Liver Neoplasms/etiology , Metformin/therapeutic use , Female , Middle Aged , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Antiviral Agents/therapeutic use , Taiwan/epidemiology , Incidence , Aged , Adult , Risk Factors , Proportional Hazards Models , Diabetes Mellitus
19.
Open Med (Wars) ; 19(1): 20240926, 2024.
Article in English | MEDLINE | ID: mdl-38584830

ABSTRACT

Ex vivo liver resection combined with autologous liver transplantation offers the opportunity to treat otherwise unresectable hepatobiliary malignancies and has been applied in clinic. The implementation of enhanced recovery after surgery (ERAS) program improves the outcome of surgical procedures. This is a retrospective single-center study including 11 cases of patients with liver cancer that underwent autologous liver transplantation and received ERAS: cholangiocarcinoma of the hilar region (n = 5), intrahepatic cholangiocarcinoma (n = 3), gallbladder cancer (n = 1), liver metastasis from colorectal cancer (n = 1), and liver metastasis from gastrointestinal mesenchymal tumor (n = 1). There were no deaths within 30 days and major complications occurred in two patients, and four patients were readmitted upon the first month after the surgery. Median hospital stay was 20 days (range 13-44) and median open diet was Day 4 (range 2-9) after surgery and median early post-operative activity was Day 5 (range 2-9) after surgery. In conclusion, autologous liver transplantation is feasible in the treatment of otherwise unresectable hepatobiliary malignancies, and our study showed favorable results with autologous liver transplantation in ERAS modality. ERAS modality provides a good option for some patients whose tumors cannot be resected in situ and offers a chance for rapid recovery.

20.
Chem Rec ; 24(4): e202300327, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38438715

ABSTRACT

Potassium-ion battery is rich in resources and cheap in price, in the era of lithium-ion battery commercialization, potassium-ion battery is the most likely to replace it. Based on the classification and summary of electrode materials for potassium-ion batteries, this paper focuses on the introduction of manganese-based oxide KxMnO2. The layered KxMnO2 has a large layer spacing and can be embedded with large size potassium-ions. This paper focuses on the preparation and doping of manganese-based cathode materials for potassium-ion batteries, summarizes the main challenges of KxMnO2-based cathode materials in the current stage of research and further looks into its future development direction.

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