Long-chain acyl-coenzyme A (CoA) synthase 4 (ACSL4) is an enzyme that esterifies CoA into specific polyunsaturated fatty acids, such as arachidonic acid and adrenic acid. Based on accumulated ...evidence, the ACSL4-catalyzed biosynthesis of arachidonoyl-CoA contributes to the execution of ferroptosis by triggering phospholipid peroxidation. Ferroptosis is a type of programmed cell death caused by iron-dependent peroxidation of lipids; ACSL4 and glutathione peroxidase 4 positively and negatively regulate ferroptosis, respectively. In addition, ACSL4 is an essential regulator of fatty acid (FA) metabolism. ACSL4 remodels the phospholipid composition of cell membranes, regulates steroidogenesis, and balances eicosanoid biosynthesis. In addition, ACSL4-mediated metabolic reprogramming and antitumor immunity have attracted much attention in cancer biology. Because it facilitates the cross-talk between ferroptosis and FA metabolism, ACSL4 is also a research hotspot in metabolic diseases and ischemia/reperfusion injuries. In this review, we focus on the structure, biological function, and unique role of ASCL4 in various human diseases. Finally, we propose that ACSL4 might be a potential therapeutic target.
Cancer is the second leading cause of death globally. Millions of persons die due to cancer each year. In the last two decades, the anticancer effects of natural flavonoids have become a hot topic in ...many laboratories. Meanwhile, flavonoids, of which over 8000 molecules are known to date, are potential candidates for the discovery of anticancer drugs. The current review summarizes the major flavonoid classes of anticancer efficacy and discusses the potential anti-cancer mechanisms through inflammation and oxidative stress action, which were based on database and clinical studies within the past years. The results showed that flavonoids could regulate the inflammatory response and oxidative stress of tumor through some anti-inflammatory mechanisms such as NF-κB, so as to realize the anti-tumor effect.
The damage to the endocrine pancreas among patients with diseases of the exocrine pancreas (DP) leads to reduced glycemic deterioration, ultimately resulting in diabetes of the exocrine pancreas ...(DEP). The present research aims to investigate the mechanism responsible for glycemic deterioration in DP patients, and to identify useful biomarkers, with the ultimate goal of enhancing clinical practice awareness. Gene expression profiles of patients with DP in this study were acquired from the Gene Expression Omnibus database. The original study defines DP patients to belong in one of three categories: non-diabetic (ND), impaired glucose tolerance (IGT) and DEP, which correspond to normoglycemia, early and late glycemic deterioration, respectively. After ensuring quality control, the discovery cohort included 8 ND, 20 IGT, and 12 DEP, while the validation cohort included 27 ND, 15 IGT, and 20 DEP. Gene set enrichment analysis (GSEA) employed differentially expressed genes (DEGs), while immunocyte infiltration was determined using single sample gene set enrichment analysis (ssGSEA). Additionally, correlation analysis was conducted to establish the link between clinical characteristics and immunocyte infiltration. The least absolute shrinkage and selection operator regression and random forest combined to identify biomarkers indicating glycemic deterioration in DP patients. These biomarkers were further validated through independent cohorts and animal experiments. With glycemic deterioration, biological processes in the pancreatic islets such as nutrient metabolism and complex immune responses are disrupted in DP patients. The expression of ACOT4, B2M, and ACKR2 was upregulated, whereas the expression of CACNA1F was downregulated. Immunocyte infiltration in the islet microenvironment showed a significant positive correlation with the age, body mass index (BMI), HbA1c and glycemia at the 2-h of patients. It was a crucial factor in glycemic deterioration. Additionally, B2M demonstrated a significant positive correlation with immunocyte infiltration and clinical features. Quantitative real-time PCR (qRT-PCR) and western blotting confirmed the upregulation in B2M. Immunofluorescent staining suggested the alteration of B2M was mainly in the alpha cells and beta cells. Overall, the study showed that gradually increased immunocyte infiltration was a significant contributor to glycemic deterioration in patients with DP, and it also highlighted B2M as a biomarker.
As one of the cancers that seriously threatens women's health, ovarian cancer has a high morbidity and mortality rate. Surgery and chemotherapy are the basic treatment strategies for ovarian cancer, ...and chemotherapy resistance is a significant factor in affecting the prognosis, survival cycle, and recurrence of ovarian cancer. This article aims to analyze articles about ovarian cancer and drug resistance via bibliometric software, offering new ideas and directions for researchers in this field.
Both Citespace and Vosviewer are bibliometric software on the Java platform. Articles were collected on ovarian cancer and drug resistance in the Web of Science Core Collection database from 2013 to 2022. The countries, institutions, journals, authors, keywords, and references were analyzed, and the development status of this field was indicated from multiple perspectives.
Studies on ovarian cancer and drug resistance generally showed an increasing trend from 2013 to 2022. The People's Republic of China and Chinese institutions contributed more to this field.
published the most articles, and the journal with the most citations was
. Li Li was the author with the most publications, and Siegel RL was the author with the most citations. Through burst detection, it can be found that the research hotspots in this field mainly focused on the in-depth exploration of the drug resistance mechanism of ovarian cancer and the progress of PARP inhibitors and bevacizumab in the treatment of ovarian cancer.
Many studies on the mechanism of drug resistance in ovarian cancer have been discovered; however, the deeper mechanism remains to be explored. Compared with traditional chemotherapy drugs, PARP inhibitors and bevacizumab have shown better efficacy, but PARP inhibitors have initially shown drug resistance. The future direction of this field should be to overcome the resistance of existing drugs and actively develop new ones.
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•The effects of astaxanthin on gout were observed in a randomized controlled trial.•Astaxanthin has a lowering effect on the index of gout arthritis.•Astaxanthin combined with western ...medicine may be an alternative method for gout.•Contributing a rationale for astaxanthin as a dietary supplement to assist in gout.
Gout is a form of arthritis caused by hyperuricemia that can significantly affect a patient's quality of life. Here, we investigated the therapeutic effects of astaxanthin, a carotenoid with strong anti-inflammatory and antioxidant properties, on gout. The results of animal experiments showed that in terms of animal serological indicators, astaxanthin has the same effect as colchicine in treating gouty arthritis. The outcomes of clinical trials showed that the astaxanthin at 8 mg/d combined with celecoxib at 100 mg/d worked better than celecoxib at 200 mg/d according to ESR and UA, and according to CRP, the effect was comparable. The molecular mechanisms underlying the therapeutic effects of astaxanthin included inhibition of COX-2 and anti-inflammation and anti-oxidation. Collectively, astaxanthin ameliorated gout in rats’ model of gouty arthritis and clinical trials suggesting that it has potential as a dietary supplement to assist in the treatment of gouty arthritis.
Artificial molecular photoswitches that can be reversibly controlled into different configurations by external light stimulation have broad application prospects in various fields, such as materials ...and chemical biology. Among them, the pyrrole hemithioindigo (PHT) photoswitch has a geometric structure similar to that of the fluorescent protein chromophore. What happens when the chromophore is replaced by PHT, and does it achieve similar functions to the original one? To answer these questions, we carried out ONIOM(QM/MM) and classical molecular dynamics studies on the photoisomerization mechanism and spectroscopic properties of PHT in the fluorescent protein. The results showed that in the protein environment, the fate of excited PHT is governed by the competition between fluorescence emission and hula-twist isomerization. Due to the strong steric hindrance effects caused by the interlacing residues in the protein that restrict the PHT conformation transformation, the cis-to-trans isomerization process of PHT needs to overcome a barrier of at least 4.9 kcal/mol; thus, fluorescence emission is more dominant in competition. It is also found that the intermolecular interaction between LYS67 and the carbonyl oxygen of PHT has a significant effect on the fluorescence emission. These results revealed the photochemical reaction mechanism of a light-driven molecular switch in the fluorescent protein and provided further theoretical support for the field of chemical biology.
Objective
The objective of our study was to integrate the efficacy results of post-nephrectomy adjuvant therapies in renal cell carcinoma (RCC) patients with risk of recurrence, and attempt to ...determine the optimal intervention choice.
Methods
We performed standard meta-analysis procedures in compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The PubMed, Embase, and Cochrane Library databases were searched from inception to 22 September 2022. Randomized controlled trials reporting overall survival (OS) or disease-free survival (DFS) of adjuvant therapies, including immune checkpoint inhibitors (ICIs) and targeted therapies, in adult post-nephrectomy RCC patients were eligible for inclusion.
Results
Seven studies involving 7548 participants were included in our analyses. In contrast with placebo, DFS benefit with ICIs was only observed in female RCC patients and RCC patients with high programmed death-ligand 1 (PD-L1) expression (≥ 1%), sarcomatoid features, and M0 intermediate–high risk. Network meta-analyses demonstrated that pembrolizumab exhibited both DFS and OS benefit compared with placebo, sunitinib, sorafenib, and girentuximab, and only DFS benefit compared with atezolizumab and nivolumab plus ipilimumab.
Conclusions
Our results suggest that post-nephrectomy RCC patients with sarcomatoid differentiation and high PD-L1 expression were more responsive to ICIs. Furthermore, pembrolizumab monotherapy exhibited superior DFS and OS results over other adjuvant therapies.
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•The PAN-H1.6Mn1.6O4 composite nanofiber membranes were prepared by electrospinning.•Nanofiber membrane has higher Li+ adsorption capacity than that of dense membrane.•Nanofiber ...membrane shows high selectivity and Qe for Li+ in salt-lake brine.•Li+ can be enriched by dynamic adsorption via the column packed with membrane.
In this paper, polyacrylonitrile (PAN) as the binder and Li1.6Mn1.6O4 as the powder were used to prepare the composite nanofiber flat-sheet membrane-type adsorbent (ESNM-H) via the electrospinning method. The influence factor on membrane adsorption capacity for Li+ were investigated, such as the concentration of PAN, precursor content, and membrane thickness. When the content of PAN and Li1.6Mn1.6O4 were 10 wt% and 18 wt%, respectively, the equilibrium adsorption capacity for Li+ on ESNM-H with the thickness of 164 ± 4 μm was 1328 mg/m2, and the actual adsorption capacity of powder H1.6Mn1.6O4 incorporated in the nanofiber membrane remained 92% of the unsupported powder. In the artificial salt-lake brine, the adsorption selectivity of ESNM-H for Li+ was higher to other interfering ions (Na+, Ca2+, K+ and Mg2+). After eight cycles, the adsorption capacity of ESNM-H decreased by 8%. The ESNM-H exhibited the better long-term stability. The ESNM-H packed column was enriched with Li+ from 100 mg/L to 726 mg/L after ten consecutive dynamic adsorption–desorption cycles. The overall results show that the composite nanofiber flat-sheet membrane-type adsorbent fabricated via the electrospinning method has potential applications and recyclability in adsorbing Li+ from salt-lake brine.
•Efficacy and safety assessment of mineralocorticoid receptor antagonists on CKD.
The objective of our study is to evaluate the efficacy and safety of mineralocorticoid receptor antagonists (MRAs) ...and determine the optimal MRA treatment regimen in patients with chronic kidney disease (CKD).
We searched PubMed, Embase, Web of Science, and the Cochrane Library from their inception to June 20, 2022. The composite kidney outcome, cardiovascular events, urinary albumin to creatinine ratio (UACR), estimated glomerular filtration rate (EGFR), serum potassium, systolic blood pressure (SBP), diastolic blood pressure (DBP), creatine and creatine clearance were included for analysis. We conducted pairwise meta-analyses and Bayesian network meta-analyses (NMA) and calculated the surface under the cumulative ranking curve (SUCRA).
We included 26 studies with 15,531 participants. By pairwise meta-analyses, we found that MRA treatment could significantly reduce UACR in CKD patients with or without diabetes. Notably, compared to placebo, Finerenone was associated with a lower risk of composite kidney outcome and cardiovascular events. Data from NMA demonstrated an overt UACR reduction without increasing serum potassium by Apararenone, Esaxerenone, and Finerenone in CKD patients. Spironolactone decreased SBP and DBP but elevated CKD patients' serum potassium.
Compared to placebo, Apararenone, Esaxerenone, and Finerenone might ameliorate albuminuria in CKD patients without causing elevated serum potassium levels. Remarkably, Finerenone conferred a cardiovascular benefit, and Spironolactone lowered blood pressure in CKD patients.
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