A synonymous mutation of rs1137070 cause the mice Maoa gene transcription and translation to decrease.

The Monoamine Oxidase-A (MAOA) EcoRV polymorphism (rs1137070) is a unique synonymous mutation (c.1409 T > C) within the MAOA gene, which plays a crucial role in Maoa gene expression and function. This study aimed to explore the relationship between the mouse Maoa rs1137070 genotype and differences in MAOA gene expression. Mice carrying the CC genotype of rs1137070 exhibited a significantly lower Maoa expression level, with an odds ratio of 2.44 compared to the T carriers. Moreover, the wild-type TT genotype of MAOA demonstrated elevated mRNA expression and a longer half-life. We also delved into the significant expression and structural disparities among genotypes. Furthermore, it was evident that different aspartic acid synonymous codons within Maoa influenced both MAOA expression and enzyme activity, highlighting the association between rs1137070 and MAOA. To substantiate these findings, a dual-luciferase reporter assay confirmed that GAC was more efficient than GAT binding. Conversely, the synonymous mutation altered Maoa gene expression in individual mice. An RNA pull-down assay suggested that this alteration could impact the interaction with RNA-binding proteins. In summary, our results illustrate that synonymous mutations can indeed regulate the downregulation of gene expression, leading to changes in MAOA function and their potential association with neurological-related diseases.

Network pharmacology provides new insights into the mechanism of traditional Chinese medicine and natural products used to treat pulmonary hypertension.

BACKGROUND: Pulmonary hypertension (PH) is a rare cardiovascular disease with high morbidity and mortality rates. It is characterized by increased pulmonary arterial pressure. Current research into relevant therapeutic drugs and targets for PH, however, is insufficient still. Traditional Chinese medicine (TCM) and natural products have a long history as therapeutics for PH. Network pharmacology is an approach that integrates drug-target interactions and signaling pathways based on biomarkers information obtained from drug and disease databases. The concept of network pharmacology shows many similarities with the TCM philosophy. Network pharmacology help elucidate the mechanisms of TCM in PH. This review presents representative applications of network pharmacology in the study of the mechanisms of TCM and natural products for the treatment of PH. METHODS: In this review, we used ("pulmonary hypertension" OR "pulmonary arterial hypertension" OR "chronic thromboembolic pulmonary hypertension") AND ("network pharmacology" OR "systematic pharmacology") as keywords to search for reports from PubMed, Web of Science, and Google Scholar databases from ten years ago. The studies were screened and those chosen are summarized here. The TCM and natural products inPH and their corresponding targets and signaling pathways are described. Additionally, we discuss the application of network pharmacology in the study of TCM in PH to provide insights for future application strategies. RESULTS: Network pharmacology have shown that AKT-related pathways, HIF-1 signaling pathway, MAPK signaling pathway, TGF-ß-Smad pathway, cell cycle-related pathways and inflammation-related pathways are the main signaling pathways enriched in the PH targets of TCM. Reservatrol, curcumol, genistin, formononetin, wogonin, luteolin, baicalein, berberine, triptolide and tanshinone llA are active ingredients specific for PH treatment. A number of databases and tools specific for the treatment of PH are used in network pharmacology and natural product research. CONCLUSION: Through the reasonable combination of molecular docking, omics technology and bioinformatics technology, the mechanism of multi-targets can be explained more comprehensively. Analyzing the complex mechanism of TCM from the clinical perspective may be a potential development trend of network pharmacology. Combination of predicted targets and traditional pharmacology improves efficiency of drug development.

Nicotine-induced transcriptional changes and mitochondrial dysfunction in the ventral tegmental area revealed by single-nucleus transcriptomics.

Nicotine is widely recognized as the primary contributor to tobacco dependence. Previous studies have indicated that molecular and behavioral responses to nicotine are primarily mediated by ventral tegmental area (VTA) neurons, and accumulating evidence suggests that glia play prominent roles in nicotine addiction. However, VTA neurons and glia have yet to be characterized at the transcriptional level during the progression of nicotine self-administration. Here, a male mouse model of nicotine self-administration was established and the timing of three critical phases (pre-addiction, addicting, and post-addiction phase) was characterized. Single-nucleus RNA sequencing (snRNA-seq) in the VTA at each phase was performed to comprehensively classify specific cell subtypes. Adaptive changes occurred during the addicting and post-addiction phases, with the addicting phase displaying highly dynamic neuroplasticity that profoundly impacted the transcription in each cell subtype. Furthermore, significant transcriptional changes in energy metabolism-related genes were observed, accompanied by notable structural alterations in neuronal mitochondria during the progression of nicotine self-administration. The results provide insights into mechanisms underlying the progression of nicotine addiction, serving as important resource for identifying potential molecular targets for nicotine cessation.

Effectiveness of silver and iodine dressings on wound healing: a systematic review and meta-analysis.

OBJECTIVE: To evaluate the effects of silver and iodine dressings on healing time, healing rate, exudate amount, pain and anti-infective efficacy. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Databases including PubMed, Cochrane Library, Embase, Web of Science and CINAHL were surveyed up to May 2024. ELIGIBILITY CRITERIA: Randomised controlled trials comparing silver and iodine dressings on wound healing in humans. DATA EXTRACTION AND SYNTHESIS: Evidence certainty was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation approach. Data extraction was done independently by two reviewers, with the risk of bias assessed using the Cochrane tool. Narrative synthesis was performed to evaluate the effects of silver and iodine dressings on healing time, healing rate, pain, exudate amount and anti-infective efficacy. Meta-analysis using Review Manager V.5.4 calculated standardised mean differences for healing time and relative risks for rate to quantify the impacts of the treatments. RESULTS: 17 studies (18 articles) were included. The meta-analysis indicated that silver dressings significantly reduced healing time compared with iodine dressings (SMD=-0.95, 95% CI -1.62 to -0.28, I2=92%, p=0.005, moderate-quality evidence), with no significant difference in enhancing healing rate (RR=1.29, 95% CI 0.90 to 1.85, I2=91%, p=0.16, low-quality evidence). Based on low-quality evidence, for exudate amount (3/17), 66.7% (2/3) of the studies favoured silver dressings over iodine in reducing exudate volume. For pain (7/17), 57.1% (4/7) of the studies reported no significant difference between silver and iodine dressings, while 42.9% (3/7) studies indicated superior pain relief with silver dressings. For anti-infective efficacy (11/13), 54.5% (6/11) of the studies showed equivalence between silver and iodine dressings, while 36.4% (4/11) suggested greater antibacterial efficacy for silver. CONCLUSION: Silver dressings, demonstrating a comparable healing rate to iodine dressings, significantly reduce healing time, suggesting their potential as a superior adjunct in wound care. PROSPERO REGISTRATION NUMBER: CRD42020199602.

Differentiation of cultured hair follicle neural crest stem cells into functional melanocytes.

Many autologous melanocytes are required for surgical treatment of depigmentation diseases such as vitiligo. However, primary cultured melanocytes have a limited number of in vitro passages. The production of functional epidermal melanocytes from stem cells provides an unprecedented source of cell therapy for vitiligo. This study explores the clinical application of melanocytes induced by hair follicle neural crest stem cells (HFNCSCs). This study established an in vitro differentiation model of HFNCSCs into melanocytes. Results demonstrate that most differentiated melanocytes expressed the proteins C-KIT, MITF, S-100B, TYRP1, TYRP2, and tyrosinase. The HFNCSC-derived melanocytes were successfully transplanted onto the dorsal skin of mice and survived in the local tissues, expressing marker protein of melanocytes. In conclusion, HFNCSCs in mice can be induced to differentiate into melanocytes under specific conditions. These induced melanocytes exhibit the potential to facilitate repigmentation in the lesion areas of vitiligo-affected mice, suggesting a promising avenue for therapeutic intervention.

A Sweet Synthesis of MXenes.

Two-dimensional transition metal carbides/nitrides (MXenes) have shown great promise in various applications. However, mass production of MXenes suffers from the excessive use of toxic fluorine-containing reagents. Herein, a new method was validated for synthesizing MXenes from five MAX ceramics. The method features a minimized (stoichiometric) dosage of F-containing reagent (NaBF4) and polyols (glycerol, erythritol, and xylitol) as the reaction solvent. Due to the sweetness of polyols and the low environmental impact, we refer to this method as a "sweet" synthesis of MXenes. An in-depth molecular dynamics simulation study, combined with experimental kinetic parameters, further revealed that the diffusion of F- in the confined interplanar space is rate-determining for the etching reaction. The expansion of interlayer spacing by polyols effectively reduces the diffusion activation energy of F- and accelerates the etching reaction.

The association of genetic polymorphisms within the dopaminergic system with nicotine dependence: A narrative review.

Nicotine, the main compound in cigarettes, leads to smoking addiction. Nicotine acts on the limbic dopamine reward loop in the midbrain by binding to nicotinic acetylcholine receptors, promoting the release of dopamine, and resulting in a rewarding effect or satisfaction. This satisfaction is essential for continued and compulsive tobacco use, and therefore dopamine plays a crucial role in nicotine dependence. Numerous studies have identified genetic polymorphisms of dopaminergic pathways which may influence susceptibility to nicotine addiction. Dopamine levels are greatly influenced by synthesis, storage, release, degradation, and reuptake-related genes, including genes encoding tyrosine hydroxylase, dopamine decarboxylase, dopamine transporter, dopamine receptor, dopamine 3-hydroxylase, catechol-O-methyltransferase, and monoamine oxidase. In this paper, we review research progress on the effects of polymorphisms in the above genes on downstream smoking behavior and nicotine dependence, to offer a theoretical basis for the elucidation of the genetic mechanism underlying nicotine dependence and future personalized treatment for smoking cessation.

Delivery of Lutein by Using Modified Burdock Polysaccharide Aggregates: Preparation, Characterization, and In Vitro Release Properties.

Novel self-assembled aggregates of stearic acid (SA)-modified burdock polysaccharide (BP) for loading lutein were constructed, and the release and absorption properties of lutein in the aggregates in simulated gastrointestinal fluid were investigated. Three different degrees of substitution (DS) of SA-BPs were used to embed lutein, resulting in the encapsulation efficiency exceeding 90%. The aggregates were uniformly spherical, with a particle size range of 227-341 nm. XRD analysis revealed that lutein was present in a non-crystalline state within the aggregates. FT-IR and FS analysis demonstrated that lutein was located in the hydrophobic domains of SA-BP. The highest bioavailability of lutein in these aggregates reached 4.36 times that in the unmodified samples. These aggregates were able to remain stable in gastric juice and enhance the release rate of lutein in intestinal fluid. The transport of lutein-loaded SA-BP aggregates in Caco-2 cells competed with P-glycoprotein inhibitors, mainly promoting the transmembrane absorption of lutein through caveolae (or lipid raft)-related and clathrin-dependent endocytosis pathways. The above results suggest that SA-BP aggregates have the potential to be promising carriers for the efficient delivery of hydrophobic lutein.

A Planar-Structured Dinuclear Cobalt(II) Complex with Indirect Synergy for Photocatalytic CO2-to-CO Conversion.

Dinuclear metal synergistic catalysis (DMSC) has been proved an effective approach to enhance catalytic efficiency in photocatalytic CO2 reduction reaction, while it remains challenge to design dinuclear metal complexes that can show DMSC effect. The main reason is that the influence of the microenvironment around dinuclear metal centres on catalytic activity has not been well recognized and revealed. Herein, we report a dinuclear cobalt complex featuring a planar structure, which displays outstanding catalytic efficiency for photochemical CO2-to-CO conversion. The turnover number (TON) and turnover frequency (TOF) values reach as high as 14457 and 0.40 s-1 respectively, 8.6 times higher than those of the corresponding mononuclear cobalt complex. Control experiments and theoretical calculations revealed that the enhanced catalytic efficiency of the dinuclear cobalt complex is due to the indirect DMSC effect between two CoII ions, energetically feasible one step two-electron transfer process by Co2 I,I intermediate to afford Co2 II,II(CO2 2-) intermediate and fast mass transfer closely related with the planar structure.

A 90-day subchronic exposure to heated tobacco product aerosol caused differences in intestinal inflammation and microbiome dysregulation in rats.

INTRODUCTION: Smoking is one of the most important predisposing factors of intestinal inflammatory diseases. Heated tobacco product (HTP) is a novel tobacco category that is claimed to deliver reduced chemicals to human those reported in combustible cigarette smoke (CS). However, the effect of HTP on intestine is still unknown. METHODS: In the framework of Organization for Economic Co-operation and Development guidelines 413 guidelines, Sprague-Dawley rats were exposed to HTP aerosol and CS for 13 weeks. The atmosphere was characterized and oxidative stress and inflammation of intestine were investigated after exposure. Furthermore, the faeces we performed with 16S sequencing and metabolomics analysis. RESULTS: HTP aerosol and CS led to obvious intestinal damage evidenced by increased intestinal pro-inflammatory cytokines and oxidative stress in male and female rats After HTP and CS exposure, the abundance that obviously changed were Lactobacillus and Turiciacter in male rats and Lactobacillus and Prevotella in female rats. HTP mainly induced the metabolism of amino acids and fatty acyls such as short-chain fatty acids and tryptophan, while CS involved into the main metabolism of bile acids, especially indole and derivatives. Although different metabolic pathways in the gut mediated by HTP and CS, both to inflammation and oxidative stress were ultimately induced. CONCLUSIONS: HTP aerosol and CS induced intestinal damage mediated by different gut microbiota and metabolites, while both lead to inflammation and oxidative stress. IMPLICATIONS: The concentration of various harmful components in heated tobacco product aerosol is reported lower than that of traditional cigarette smoke, however, its health risk impact on consumers remains to be studied. Our research findings indicate that heated tobacco product and cigarette smoke inhalation induced intestinal damage through different metabolic pathways mediated by gut microbiome, indicating the health risk of heated tobacco product in intestine.

Susceptibility evaluation and PK/PD integration of tulathromycin against Actinobacillus pleuropneumoniae during the mutant selection window.

Introduction: Actinobacillus pleuropneumoniae (APP) is a serious pathogen that affects the development of livestock breeding. Due to excessive use of antimicrobial drugs, many multidrug-resistant bacteria have emerged and spread, which have threatened the livestock industry. Therefore, we established a peristaltic pump infection model (PPIM) to evaluate the susceptibility change and pharmacokinetic/pharmacodynamic (PK/PD) integration of tulathromycin against APP during the mutant selection window (MSW) for preventing the emergence of mutant-resistant bacteria. Methods: The 99% minimum inhibitory concentration (MIC99) and mutant prevention concentration (MPC) of tulathromycin against APP were measured using the agar-plate method. After the model of dynamic infection had been established based on tulathromycin data in lungs, different dosages were administered to make the drug concentrations located in different parts of the MSW. The population and sensitivity of APP were monitored. Tulathromycin concentrations were measured by high-performance liquid chromatography-tandem mass spectrometry. Finally, a sigmoid Emax model was used to analyze the relationships between PK/PD parameters and antibacterial effects. Results and discussion: The values of MIC, MIC99, and MPC of tulathromycin against APP were 2, 1.4, and 44.8 µg/mL, respectively. The PPIM was stable. An elimination effect without regrowth was observed at 5.6 to 44.8 µg/mL (-4.48 to -7.05 Log10 CFU/mL, respectively). The MIC of APP increased 32-fold at 8 MIC99. AUC168 h/MIC99 had the best fit with the antibacterial effect (R 2 = 0.9867). The AUC168 h/MIC99 required to achieve bacteriostatic, bactericidal, and clearance effects were 1.80, 87.42, and 198 h, respectively. Our results could provide guidance for the clinical application of tulathromycin to treat APP infection and avoid the generation of drug-resistant bacteria.

Advancements in bioscavenger mediated detoxification of organophosphorus poisoning.

Background: Organophosphorus compounds, widely used in agriculture and industry, pose a serious threat to human health due to their acute neurotoxicity. Although traditional interventions for organophosphate poisoning are effective, they often come with significant side effects. Objective: This paper aims to evaluate the potential of enzymes within biological organisms as organophosphorus bioclearing agents. It analyses the technical challenges in current enzyme research, such as substrate specificity, stereoselectivity, and immunogenicity, while exploring recent advancements in the field. Methods: A comprehensive review of literature related to detoxifying enzymes or proteins was conducted. Existing studies on organophosphorus bioclearing agents were summarised, elucidating the biological detoxification mechanisms, with a particular focus on advancements in protein engineering and novel delivery methods. Results: Current bioclearing agents can be categorised into stoichiometric and catalytic bioclearing agents, both of which have shown some success in preventing organophosphate poisoning. Technological advancements have significantly improved various properties of bioclearing agents, yet challenges remain, particularly in substrate specificity, stereoselectivity, and immunogenicity. Future research will focus on expanding the substrate spectrum, enhancing catalytic efficiency, prolonging in vivo half-life, and developing convenient administration methods. Conclusion: With the progression of clinical trials, bioclearing agents are expected to become widely used as a new generation of therapeutic organophosphate detoxifiers.

Evaluation the kill rate and mutant selection window of danofloxacin against Actinobacillus pleuropneumoniae in a peristaltic pump model.

BACKGROUND: Actinobacillus pleuropneumoniae is a serious pathogen in pigs. The abundant application of antibiotics has resulted in the gradual emergence of drugresistant bacteria, which has seriously affected treatment of disease. To aid measures to prevent the emergence and spread of drug-resistant bacteria, herein, the kill rate and mutant selection window (MSW) of danofloxacin (DAN) against A. pleuropneumoniae were evaluated. METHODS: For the kill rate study, the minimum inhibitory concentration (MIC) was tested using the micro dilution broth method and time-killing curves of DAN against A. pleuropneumoniae grown in tryptic soy broth (TSB) at a series drug concentrations (from 0 to 64 MIC) were constructed. The relationships between the kill rate and drug concentrations were analyzed using a Sigmoid Emax model during different time periods. For the MSW study, the MIC99 (the lowest concentration that inhibited the growth of the bacteria by ≥ 99%) and mutant prevention concentration (MPC) of DAN against A. pleuropneumoniae were measured using the agar plate method. Then, a peristaltic pump infection model was established to simulate the dynamic changes of DAN concentrations in pig lungs. The changes in number and sensitivity of A. pleuropneumoniae were measured. The relationships between pharmacokinetic/pharmacodynamic parameters and the antibacterial effect were analyzed using the Sigmoid Emax model. RESULTS: In kill rate study, the MIC of DAN against A. pleuropneumoniae was 0.016 µg/mL. According to the kill rate, DAN exhibited concentration-dependent antibacterial activity against A. pleuropneumoniae. A bactericidal effect was observed when the DAN concentration reached 4-8 MIC. The kill rate increased constantly with the increase in DAN concentration, with a maximum value of 3.23 Log10 colony forming units (CFU)/mL/h during the 0-1 h period. When the drug concentration was in the middle part of the MSW, drugresistant bacteria might be induced. Therefore, the dosage should be avoided to produce a mean value of AUC24h/MIC99 (between 31.29 and 62.59 h. The values of AUC24h/MIC99 to achieve bacteriostatic, bactericidal, and eradication effects were 9.46, 25.14, and > 62.59 h, respectively. CONCLUSION: These kill rate and MSW results will provide valuable guidance for the use of DAN to treat A. pleuropneumoniae infections.

Mechanistic investigation of wogonin in delaying the progression of endothelial mesenchymal transition by targeting the TGF-ß1 pathway in pulmonary hypertension.

Pulmonary hypertension (PH) is characterized by pulmonary vascular remodeling, which endothelial-to-mesenchymal transition (EndMT) being its main progressive phase. Wogonin, a flavonoid extracted from the root of Scutellaria baicalensis Georgi, hinders the abnormal proliferation of cells and has been employed in the treatment of several cardiopulmonary diseases. This study was designed to investigate how wogonin affected EndMT during PH. Monocrotaline (MCT) was used to induce PH in rats. Binding capacity of TGF-ß1 receptor to wogonin detected by molecular docking and molecular dynamics. EndMT model was established in pulmonary microvascular endothelial cells (PMVECs) by transforming growth factor beta-1 (TGF-ß1). The result demonstrated that wogonin (20 mg/kg/day) attenuated right ventricular systolic pressure (RVSP), right ventricular hypertrophy and pulmonary vascular thickness in PH rats. EndMT in the pulmonary vascular was inhibited after wogonin treatment as evidenced by the restored expression of CD31 and decreased expression of α-SMA. Wogonin has strong affinity for both TGFBRI and TGFBRII, and has a better binding stability for TGFBRI. In TGF-ß1-treated PMVECs, wogonin (0.3, 1, and 3 µM) exhibited significant inhibitory effects on this transformation process via down-regulating the expression of p-Smad2 and Snail, while up-regulating the expression of p-Smad1/5. Additionally, results of Western blot and fluorescence shown that the expression of α-SMA were decrease with increasing level of CD31 in PMVECs. In conclusion, our research showed that wogonin suppressed EndMT via the TGF-ß1/Smad pathway which may lead to its alleviated effect on PH. Wogonin may be a promising drug against PH.

Dual Regulation of Nicotine on NLRP3 Inflammasome in Macrophages with the Involvement of Lysosomal Destabilization, ROS and α7nAChR.

Nicotine, the primary alkaloid in tobacco products, has been shown to have immunoregulatory function in at least 20 diseases. The biological mechanism of action of nicotine immunoregulation is complex, resulting in an improvement of some disease states and exacerbation of others. Given the central role of the NLRP3 inflammasome in macrophages among multiple inflammatory diseases, this study examined how nicotine alters NLRP3 inflammasome activation in macrophages. NLRP3 inflammasome activation was examined mechanistically in the context of different nicotine dosages. We show NLRP3 inflammasome activation, apoptosis-associated speck-like protein (ASC) expression, caspase-1 activity and subsequent IL-1ß secretion were positively correlated with nicotine in a dose-dependent relationship, and destabilization of lysosomes and ROS production were also involved. At high concentrations of nicotine surpassing 0.25 mM, NLRP3 inflammasome activity declined, along with increased expression of the anti-inflammatory Alpha7 nicotinic acetylcholine receptor (α7nAChR) and the inhibition of TLR4/NF-κB signaling. Consequently, high doses of nicotine also reduced ASC expression, caspase-1 activity and IL-1ß secretion in macrophages. Collectively, these results suggest a dual regulatory function of nicotine on NLRP3 inflammasome activation in macrophages, that is involved with the pro-inflammatory effects of lysosomal destabilization and ROS production. We also show nicotine mediates anti-inflammatory effects by activating α7nAChR at high doses.

Unveiling the role of proton concentration in dinuclear metal complexes for boosting photocatalytic CO2 reduction.

The reaction kinetics of photocatalytic CO2 reduction is highly dependent on the transfer rate of electrons and protons to the CO2 molecules adsorbed on catalytic centers. Studies on uncovering the proton effect in catalysts on photocatalytic activity of CO2 reduction are significant but rarely reported. In this paper, we, from the molecular level, revealed that the photocatalytic activity of CO2 reduction is closely related to the proton availability in catalysts. Specifically, four dinuclear Co(II) complexes based on Robson-type ligands with different number of carboxylic groups (-nCOOH; n = 0, 2, 4, 6) were designed and synthesized. All these complexes show photocatalytic activity for CO2 reduction to CO in a water-containing system upon visible-light illumination. Interestingly, the CO yields increase positively with the increase of the carboxylic-group number in dinuclear Co(II) complexes. The one containing -6COOH shows the best photocatalytic activity for CO2 reduction to CO, with the TON value reaching as high as 10,294. The value is 1.8, 3.4, and 7.8 times higher than those containing -4COOH, -2COOH, and -0COOH, respectively. The high TON value also makes the dinuclear Co(II) complex with -6COOH outstanding among reported homogeneous molecular catalysts for photocatalytic CO2 reduction. Control experiments and density functional theory calculation indicated that more carboxylic groups in the catalyst endow the catalyst with more proton relays, thus accelerating the proton transfer and boosting the photocatalytic CO2 reduction. This study, at a molecular level, elucidates that more carboxylic groups in catalysts are beneficial for boosting the reaction kinetics of photocatalytic CO2 reduction.

Identification of active compounds in Vernonia anthelmintica (L.) willd by targeted metabolome MRM and kaempferol promotes HaCaT cell proliferation and reduces oxidative stress.

Introduction: Vernonia anthelmintica (L.) Willd. is a traditional treatment for vitiligo in Xinjiang. However, its therapeutic mechanism remains unclear owing to its complex composition and limited research on its chemical profile. Methods: We employed a targeted metabolome approach, combining selective reaction monitoring/multiple response monitoring (SRM/MRM) with high-performance liquid chromatography and MRM mass spectrometry to quantitatively analyze the flavonoid constituents of Vernonia anthelmintica. We also used network pharmacology and molecular docking to identify potential vitiligo-linked compounds and targets of V. anthelmintica seeds. Additionally, we assessed HaCaT cell proliferation by AAPH-induced, alongside changes in SOD activity and MDA content, following treatment with V. anthelmintica components. Finally, flow cytometry was used to detect apoptosis and ROS levels. Results and Discussion: We identified 36 flavonoid compounds in V. anthelmintica seeds, with 14 compounds exhibiting druggability. AKT1, VEGFA, ESR1, PTGS2, and IL2 have been identified as key therapeutic target genes, with PI3K/AKT signaling being an important pathway. Notably, kaempferol, one of the identified compounds, exhibited high expression in network pharmacology analysis. Kaempferol exhibited a strong binding affinity to important targets. Further, kaempferol enhanced HaCaT cell viability, inhibited apoptosis, reduced MDA levels, suppressed ROS activity, and upregulated SOD activity, increase the expression of cellular antioxidant genes, including HO-1, GCLC, GCLM, Nrf2, NQO1 and Keap1, providing significant protection against oxidative stress damage in vitro. Here, we present the first comprehensive study integrating SRM/MRM approaches and network analysis to identify active flavonoid compounds within V. anthelmintica (L.) Willd. Moreover, we revealed that its active ingredient, kaempferol, offers protection against AAPH-induced damage in keratinocytes, highlighting its potential as a clinical resource.

Efficacy of radiofrequency ablation combined with sorafenib for treating liver cancer complicated with portal hypertension and prognostic factors.

BACKGROUND: Patients with liver cancer complicated by portal hypertension present complex challenges in treatment. AIM: To evaluate the efficacy of radiofrequency ablation in combination with sorafenib for improving liver function and its impact on the prognosis of patients with this condition. METHODS: Data from 100 patients with liver cancer complicated with portal hypertension from May 2014 to March 2019 were analyzed and divided into a study group (n = 50) and a control group (n = 50) according to the treatment regimen. The research group received radiofrequency ablation (RFA) in combination with sorafenib, and the control group only received RFA. The short-term efficacy of both the research and control groups was observed. Liver function and portal hypertension were compared before and after treatment. Alpha-fetoprotein (AFP), glypican-3 (GPC-3), and AFP-L3 levels were compared between the two groups prior to and after treatment. The occurrence of adverse reactions in both groups was observed. The 3-year survival rate was compared between the two groups. Basic data were compared between the survival and non-surviving groups. To identify the independent risk factors for poor prognosis in patients with liver cancer complicated by portal hypertension, multivariate logistic regression analysis was employed. RESULTS: When comparing the two groups, the research group's total effective rate (82.00%) was significantly greater than that of the control group (56.00%; P < 0.05). Following treatment, alanine aminotransferase and aspartate aminotransferase levels increased, and portal vein pressure decreased in both groups. The degree of improvement for every index was substantially greater in the research group than in the control group (P < 0.05). Following treatment, the AFP, GPC-3, and AFP-L3 levels in both groups decreased, with the research group having significantly lower levels than the control group (P < 0.05). The incidence of diarrhea, rash, nausea and vomiting, and fatigue in the research group was significantly greater than that in the control group (P < 0.05). The 1-, 2-, and 3-year survival rates of the research group (94.00%, 84.00%, and 72.00%, respectively) were significantly greater than those of the control group (80.00%, 64.00%, and 40.00%, respectively; P < 0.05). Significant differences were observed between the survival group and the non-surviving group in terms of Child-Pugh grade, history of hepatitis, number of tumors, tumor size, use of sorafenib, stage of liver cancer, histological differentiation, history of splenectomy and other basic data (P < 0.05). Logistic regression analysis demonstrated that high Child-Pugh grade, tumor size (6-10 cm), history of hepatitis, no use of sorafenib, liver cancer stage IIIC, and previous splenectomy were independent risk factors for poor prognosis in patients with liver cancer complicated with portal hypertension (P < 0.05). CONCLUSION: Patients suffering from liver cancer complicated by portal hypertension benefit from the combination of RFA and sorafenib therapy because it effectively restores liver function and increases survival rates. The prognosis of patients suffering from liver cancer complicated by portal hypertension is strongly associated with factors such as high Child-Pugh grade, tumor size (6-10 cm), history of hepatitis, lack of sorafenib use, liver cancer at stage IIIC, and prior splenectomy.

The Effectiveness of Cognitive Behavioral Therapy-Based Intervention on Improving Sleep-Related Outcomes for People with Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background: Sleep-related outcomes in people with diabetes are poor, which is closely linked to reducing the development of diabetes. Cognitive behavioral therapy (CBT) based intervention presents innovative solutions that can help improve sleep-related outcomes. Aim: This synthesis aims to assess the effectiveness of CBT-based intervention compared to controls in Randomized Controlled Trials (RCTs) for sleep-related outcomes among people with diabetes. Methods: Eight electronic databases were systematically searched: PubMed, EMBASE, Cochrane library, Web of Science, PsycINFO, CINAHL, China National Knowledge Infrastructure (CNKI), and Wan Fang database. We examined CBT-based intervention's effectiveness on sleep-related outcomes in people with diabetes in RCTs identified in these databases from their inception to 1st November 2023, and updated on 15 January 2024. The risk of bias was assessed using the Cochrane Risk of Bias tool by two reviewers. The meta-analysis of included studies was conducted by RevMan 5.3 software. Results: Seven studies in total (n = 2633 participants) were included in this systematic review based on our inclusion criteria. The systematic review found CBT-based intervention significantly improved sleep quality (Pittsburgh Sleep Quality Index, PSQI scores) at immediate post-intervention [95% CI=(-1.31 to -0.32), p = 0.001], six months [95% CI=(-0.75 to -0.22), p = 0.0003], and 12 months [95% CI=(-0.72 to -0.24), <0.0001], compared to control groups. Furthermore, our findings demonstrated that six sessions [95% CI= (-0.38 to -0.13), p < 0.0001] or more than six sessions [95% CI=(-1.76 to -0.02), p = 0.05] of CBT-based intervention could improve sleep quality compared to controls (I2=0%). Interestingly, CBT-based intervention improves total sleep time at post-intervention in people with diabetes compared to the control group [95% CI= (-0.57 to -0.12), p = 0.003]. However, there was no significant that CBT-based intervention is beneficial to time to fall asleep [95% CI (-1.89 to 0.43), p = 0.22] and sleep efficiency [95% CI (-1.27 to 0.27), p = 0.20] after intervention, compared to control group. Conclusion: CBT-based intervention appears to have a beneficial effect on improving sleep quality and total sleep time among people with diabetes. CBT-based intervention could be considered a strategy among healthcare providers to enhance sleep quality and total sleep time for people with diabetes. More RCTs with rigorous designs and long-term follow-up are warranted to provide conclusive evidence of the CBT-based intervention on sleep-related outcomes and to explore the mechanisms by which the CBT-based interventions improve sleep-related outcomes.