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Rheumatoid arthritis (RA) is a chronic autoimmunity illness, mainly featured with synovitis of the joint. The specificity of ferroptosis is disparate in different diseases, and the mechanism of ferroptosis in RA has some uncertainty yet. Therefore, the mechanism of ferroptosis was deeply observed in RA patients and animal models. In this paper, plasma of RA patients, the tumor necrosis factor-alpha-induced human synovial fibroblasts, and an animal model of arthritis induced by collagen were applied to initially inquire about the therapeutic effect of ferroptosis. For the RA patients, ELISA detected protein expression of glutathione (GSH), GPX4, Nrf2, Keap-1, and ferritin. In cell experiments, erastin or fer-1 regulated the invasion of human synovial fibroblast cells, mitochondrial membrane potential, reactive oxygen species (ROS) expression, marker protein, and so on. For the animal experiments, 32 Sprague–Dawley male rats were randomly separated into four groups with a collagen-induced RA model for 14 days and administered with erastin or fer-1 for 35 days. The expressions of GSH, GPX4, Nrf2, and Keap-1 were lower, and the ferritin was higher in RA patients, and the expressions of these proteins varied significantly after disease remission. In addition, ferroptosis inactivation also reduced the proliferation and migration ability, mitochondrial membrane potential, and ROS in cells. We discovered unexpectedly that activation of ferroptosis meaningfully forbore the foot swelling in animals with CIA, reduced arthritis scores, destruction of bone, and articular synovitis, and also decreased the high expression of inflammatory factors in plasma. There is a nonlinear relationship between human disease manifestations and animal model pathology. Ferroptosis regulating in RA for humans or animals may produce different effects. [ABSTRACT FROM AUTHOR]

Purpose: C‐reactive protein (CRP) functions as a nonspecific marker in various inflammatory disorders, particularly in evaluating the efficacy of pharmacological treatments in patients with ulcerative colitis. The existing body of evidence does not offer adequate support for the direct implication of CRP in modulating the advancement of ulcerative colitis. Methods: Our study employed a rigorous mouse model. An ulcerative colitis mouse model was established by subjecting CRP‐deficient mice to dextran sulfate sodium (DSS) treatment. The phenotype of the mice, which encompassed parameters such as body weight, colon length, and spleen weight, was meticulously evaluated. Additionally, various physiological and biochemical indicators were assessed, including colon histopathology, expression levels of inflammatory factors, and staining of the intestinal mucus layer. Results: The absence of CRP did not significantly affect the phenotype, physiological characteristics, and biochemical indices in a mouse model of ulcerative colitis compared to mice with wild‐type CRP. Additionally, eliminating intestinal bacteria flora interference through antibiotic treatment revealed that mice lacking CRP did not demonstrate any notable variations in the ulcerative colitis model. Meanwhile, the survival rate of mice lacking CRP did not exhibit a statistically significant difference compared to wild‐type mice. Conclusion: The results of our study suggest that CRP may not directly mediate ulcerative colitis. Instead, it is more likely to be a bystander that is present alongside with elevated inflammatory factors. Further investigation is warranted to determine the precise role of CRP in humans, given the significant limitations associated with the use of mouse models. [ABSTRACT FROM AUTHOR]

Ricinodendron heudelotii is a plant of the Euphorbiaceae family, used in traditional medicine to treat numerous diseases, including high blood pressure. The aim of this study is to evaluate the antioxidant and vasorelaxant effects of the aqueous extract of the stem bark of R. heudelotii. The pharmacological studies were carried out using the aqueous extract obtained by infusion. The antioxidant capacity of R. heudelotii was assessed by in vitro tests with DPPH (2,2‐diphenyl‐1‐picryl‐hydrazyl), ABTS (2,2 ′‐azino‐bis (3‐ethylbenz‐thiazoline‐6‐sulfonic acid), iron‐reducing capacity (FRAP), and inhibition of nitric oxide (NO) release. In vitro studies, the aortic rings obtained from adult Wistar albino rats of both sexes were used to determine the vasorelaxant effects of the extract of R. heudelotii on the NO and prostacyclin (PGI2) pathways as well as its involvement on various potassium channels were determined on intact or naked fragments of rat aorta precontracted with phenylephrine (10-6 M) or KCl (60 mM). The aqueous extract of R. heudelotii exhibited a remarkable DPPH (EC50: 1.68 μg/mL) and ABTS (EC50: 106.30 μg/mL) and nitric oxide (53.71% inhibition at 1000 μg/mL) radical scavenging activities as well as reducing power (absorbance of 1.56 at 1000 μg/mL). The nitric oxide inhibitor, NG‐nitro‐L‐arginine methyl ester (L‐NAME), and prostacyclin inhibitor, indomethacin, significantly attenuated the vasodilatory effect of R. heudelotii. Tetraethylammonium could not inhibit the vasodilatory effect of the extract, unlike glibenclamide and barium chloride. Ricinodendron heudelotii extract possesses antioxidant properties and vasorelaxing effect linked to endothelium‐related factors, and this relaxation was partially mediated mainly through the inhibition of Kir and KATP channels. [ABSTRACT FROM AUTHOR]

In this study, we investigated the effect of biphasic microcurrent electrical stimulation (b‐MES) on the epidermal healing process using a rat model of skin abrasion. We analyzed the expression levels of growth factors [fibroblast growth factor 2 (FGF2) and epidermal growth factor (EGF)] and keratin subtypes (K10) in both the b‐MES and control groups at different time points after wounding. The b‐MES group showed a significantly accelerated healing process of the epithelial tissue, resulting in more consistent healing as compared to the control group. A molecular biological analysis showed that the FGF2 mRNA expression level on Day 2 after wounding was significantly higher in the b‐MES group, whereas the EGF mRNA expression level on Days 1, 2, and 4 after wounding was significantly lower in the b‐MES group. Additionally, the K10 mRNA expression level on Days 1 and 2 after wounding was significantly higher in the b‐MES group. Our study findings suggest that b‐MES facilitates wound healing by regulating the growth factors. However, the precise mechanisms underlying these effects remain to be fully elucidated. Further research is needed to fully understand the therapeutic potential of b‐MES and its applications in clinical setting. Clinically, m‐MES requires shunting due to residual electrical charge at the application site. However, b‐MES alternates polarity, leaving no charge at the site of application. Therefore, b‐MES also has the advantage of being safer and allowing treatment for longer periods of time. [ABSTRACT FROM AUTHOR]

Background. Diarrhea is the common gastrointestinal disorder accounting for 2.5 billion episodes and 1.5 million deaths annually. Limitations and inaccessibility of currently available medications are the main problem associated with treatment of diarrhea. Hence, medicinal plants are usually preferred to manage diarrhea because they may contain constituents with high activity and fewer side effects. Even though the dose, safety, and efficacy of Colocasia esculenta (L.) Schott are not substantiated scientifically, several societies use it for the treatment of diarrhea. Objective. This study was targeted at exploring the in vivo antidiarrheal activities of 80% methanol extract and solvent fractions of peels of Colocasia esculenta (L.) Schott in Swiss albino mice. Methods. The plant was collected and extracted with 80% methanol, followed by fractionation with distilled water, chloroform, and diethyl ether. Castor oil‐induced diarrhea, enteropooling, and motility tests were used to evaluate antidiarrheal activity. The test groups received graded doses of 100 mg/kg, 200 mg/kg, and 400 mg/kg. Negative controls received 10 ml/kg of 2% Tween 80 while positive controls received loperamide (3 mg/kg) or atropine (5 mg/kg). Results. The crude and solvent fractions of the plant extract have induced significant effects in reduction of the number and weight of wet stools at all tested doses. However, delay in onset of diarrhea was observed only at 400 mg/kg (P < 0.001) for both crude extract and solvent fractions. In antienteropooling test, 80% methanol extract and solvent fractions have significantly reduced the weight and volume of intestinal contents, especially at 200 mg/kg and 400 mg/kg. Regarding the antimotility test, the crude extract reduced motility at all tested doses, whereas the solvent fractions reduced intestinal motility mainly at 400 mg/kg (P < 0.001). Conclusion. The study has revealed that the 80% methanol extract and solvent fractions of the plant possess antidiarrheal activities supporting the traditional antidiarrheal claims of the plant. [ABSTRACT FROM AUTHOR]

Background. This work focused on investigating the role of programmed death ligand 2 (PD‐L2) in the progression of breast cancer by utilizing breast cancer specimens and cells. Materials and Methods. The serum levels of soluble PD‐L2 (sPD‐L2) in breast cancer patients and healthy individuals were analyzed by means of the enzyme‐linked immunosorbent assay, and the PD‐L2 levels within 416 resected breast cancer specimens were assessed through immunohistochemistry. Concurrently, in vitro cell experiments and in vivo animal experiments were carried out to analyze the relationship between PD‐L2 and the invasion and migration of breast cancer. Results. The concentration of sPD‐L2 in breast cancer patients significantly increased compared to that in the control groups. Additionally, breast cancer patients with high concentrations of sPD‐L2 had higher Ki67 values (≥30%) and tumor grades. PD‐L2 was expressed in 79.09% of the cancer samples, which exhibited a positive correlation with the progesterone receptor (PR) and the human epidermal growth factor receptor 2 (HER2). Furthermore, we discovered that knockdown of PD‐L2 inhibited the migratory and invasive abilities of both MCF‐7 and MDA‐MB231 cells. Conclusion. Our findings demonstrated that knockdown of PD‐L2 suppressed tumor growth, providing novel insights into important biological functions. [ABSTRACT FROM AUTHOR]

Background and Aims: Acute liver injury (ALI) often follows biliary acute pancreatitis (BAP), but the exact cause and effective treatment are unknown. The aim of this study was to investigate the role of the gut microflora–bile acids–liver axis in BAP‐ALI in mice and to assess the potential therapeutic effects of Yinchenhao decoction (YCHD), a traditional Chinese herbal medicine formula, on BAP‐ALI. Methods: Male C57BL/6 mice were allocated into three groups: negative control (NC), BAP model, and YCHD treatment groups. The severity of BAP‐ALI, intrahepatic bile acid levels, and the gut microbiota were assessed 24 h after BAP‐ALI induction in mice. Results: Our findings demonstrated that treatment with YCHD significantly ameliorated the severity of BAP‐ALI, as evidenced by the mitigation of hepatic histopathological changes and a reduction in liver serum enzyme levels. Moreover, YCHD alleviated intrahepatic cholestasis and modified the composition of bile acids, as indicated by a notable increase in conjugated bile acids. Additionally, 16S rDNA sequencing analysis of the gut microbiome revealed distinct alterations in the richness and composition of the microbiome in BAP‐ALI mice compared to those in control mice. YCHD treatment effectively improved the intestinal flora disorders induced by BAP‐ALI. Spearman's correlation analysis revealed a significant association between the distinct compositional characteristics of the intestinal microbiota and the intrahepatic bile acid concentration. Conclusions: These findings imply a potential link between gut microbiota dysbiosis and intrahepatic cholestasis in BAP‐ALI mice and suggest that YCHD treatment may confer protection against BAP‐ALI via the gut microflora–bile acids–liver axis. [ABSTRACT FROM AUTHOR]

Background. Ouabain, a Na+, K+‐ATPase inhibitor, is elevated in hypertensive patients. Evidence suggests ouabain contributes to hypertension mainly through activation of the sympathetic nervous system (SNS). Renal nerves play a vital role in the regulation of SNS activity, so we hypothesize that renal denervation may attenuate the development of ouabain‐induced hypertension. Methods and Results. Forty Sprague‐Dawley rats were divided into following groups (n = 10 each): control group (sham surgery plus intraperitoneal saline injection), RDN group (renal denervation (RDN) plus intraperitoneal saline injection), ouabain group (sham surgery plus intraperitoneal ouabain injection), and ouabain + RDN group (RDN plus intraperitoneal ouabain injection). After eight weeks, compared with the control group, rats in the ouabain group exhibited elevated blood pressure (P < 0.05), increased plasma epinephrine, norepinephrine, angiotensin II, and aldosterone levels (P < 0.05). These indexes could be significantly ameliorated by RDN. RDN also reduced the thickening of aortic tunica media and downregulated the expression of proliferating cell nuclear antigen (PCNA) in the thoracic aorta induced by ouabain. Masson staining and echocardiography showed that myocardial fibrosis and increased left ventricular mass in the ouabain group could be attenuated by RDN. Conclusions. The present study reveals that renal nerves play an important role in the development of ouabain‐induced hypertension. RDN could inhibit the pressor effect and the myocardial remodeling induced by ouabain potentially via inhibiting catecholamine release and vascular smooth muscle cell proliferation. Clinical studies are needed to explore whether RDN may exhibit better antihypertensive effects on hypertensive patients with high plasma ouabain levels as compared to those with normal plasma ouabain levels. [ABSTRACT FROM AUTHOR]

Objective(s). Given the increasing rate of methicillin‐resistant Staphylococcus aureus (MRSA) resistance to antibiotics, the use of plant‐based antimicrobials to treat the infection has been considered. This study is aimed at evaluating the effect of Myrtus communis leaf extract ointment and silver nanoparticles on the healing of burn wounds caused by MRSA in rats. Materials and Methods. In a research experiment, 48 male Wistar rats were anesthetized and second‐degree burns were induced on their backs. The rats' wounds were then uniformly inoculated with MRSA. Various treatments were applied to the burn wounds daily, including Myrtus ointment, silver nanoparticles, silver nanoparticles‐Myrtus ointment, silver sulfadiazine‐Myrtus ointment, silver sulfadiazine 1%, mupirocin ointment, and a positive control. The study measured the antimicrobial effects, wound area, percentage of wound healing, antioxidant capacities, malondialdehyde, and nitric oxide concentrations in the serum of the rats. Data analysis was performed using GraphPad software, with one‐way ANOVA and Tukey's tests used to determine the statistical significance of the results. Results. Rats treated with Myrtus ointment, silver nanoparticles‐Myrtus ointment, and mupirocin had reduced bacterial growth compared to the positive control group, nanoparticle ointment, and silver sulfadiazine (P < 0.05). The wound area of the Myrtus ointment group decreased significantly on the seventh and fourteenth days, as well as the level of MDA and nitric oxide, compared to the other groups. In Myrtus and silver sulfadiazine‐Myrtus ointment increased the thickness of the epidermis and dermis compared to the other groups. Conclusion. Based on the anti‐inflammatory, antimicrobial, and wound healing properties of Myrtus, with further studies, an ointment of this plant may be used as a main or complementary treatment for burn wound infections caused by MRSA. [ABSTRACT FROM AUTHOR]

Heart‐Protecting Musk Pill (HMP) is a Traditional Chinese Medicine (TCM) that has been used for the prevention and treatment of coronary heart disease in clinic. The current study investigated the effect of HMP on the concentrations of interleukin‐6 (IL‐6) and tumor necrosis factor‐alpha (TNF‐α) and observed the relationship between level changes of inflammatory cytokines and ventricular remodeling in rats with acute myocardial infarction (AMI). Animal models of AMI were made by coronary artery ligation in Sprague‐Dawley (SD) rats. AMI rats showed increased levels of IL‐6 and TNF‐α. Treatment with HMP decreases IL‐6 and TNF‐α concentrations in rats with AMI. Histopathological and transmission electron microscopic findings were also essentially in agreement with biochemical findings. The results of our study revealed that inflammatory cytokines IL‐6 and TNF‐α induce cardiac remodeling in rats after AMI; HMP improves cardiac function and ameliorates ventricular remodeling by downregulating the expression of IL‐6 and TNF‐α and further suppressing the ultrastructural changes of myocardial cells. [ABSTRACT FROM AUTHOR]

Introduction. To investigate the effects of acupuncture on endogenous metabolites in the liver of type 2 diabetes mellitus (T2DM) with nonalcoholic fatty liver disease (NAFLD) mice-based metabolomics. Methods. Proton nuclear magnetic resonance (1H-NMR) metabolomics combined with multivariate statistical analysis and univariate analysis were used to analyze the changes of endogenous metabolites in the liver of mice in each group and to provide new clinical ideas for acupuncture in the treatment of glycolipid metabolism disorders caused by T2DM and NAFLD. Results. After 4 weeks of continuous treatment, fasting blood glucose (FBG), insulin (INS), total cholesterol (TC), and triglyceride (TG) decreased significantly in mice in the acupuncture treatment group (ATG), and the content of liver glycogen increased significantly. Based on 1H-NMR metabolomic analysis, a total of 47 metabolites were identified in the liver of T2DM with NAFLD mice, of which eight metabolites: UDP-N-acetylglucosamine, adenosine, glutamate, isoleucine, ATP, 3-hydroxybutyric acid, NADP+, and leucine were significantly altered by acupuncture treatment. Through the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, it is found that acupuncture has an intervention effect on five metabolic pathways, mainly involving amino acid metabolism, energy metabolism, and oxidative stress. Conclusion. Our study shows that acupuncture can regulate the liver metabolism mode of T2DM in NAFLD mice. It can reduce blood glucose and lipid accumulation in the liver, and these findings provide a new idea and theoretical basis for acupuncture in the treatment of diseases related to glucose and lipid metabolism. [ABSTRACT FROM AUTHOR]

Background. Premature infants are exposed to numerous stressors in neonatal intensive care unit (NICU) during a crucial period for brain development; this period exerts long-term influences on cognitive and behavioral development. Aims. To evaluate the effect of NICU-related stress on neonatal rat pups and explore the effect of Chinese medicine treatment (CMT). Methods. Sixty male rat pups were randomly assigned to three groups: the control group, the NICU group (NICU-related stress), and the CMT group (NICU-related stress plus CMT). All stressors and interventions were administered from 0 to 7 days after birth. Body weight, serum corticosterone levels, and behavior in the open field (OF) test, elevated plus maze (EPM) test, sucrose preference test, and Morris water maze (MWM) test were recorded, and blood samples were collected at five different time points (T0, T1, T2, T3, and T4). Results. The body weights of rats in the CMT and control groups were heavier than those in the NICU group in both early life and adulthood (P < 0.05). Serum corticosterone levels significantly differed with time (except T0 vs. T1 and T3 vs. T4) but did not significantly differ among the three groups (F = 0.441 , P = 0.894). Regardless of age, spatial memory and anxiety-like and depression-like behavior did not differ among the three groups. Conclusion. NICU-related stress exerted a long-term effect on rat growth and development but did not affect spatial memory, anxiety-like behavior, depression-like behavior, or serum corticosterone levels. CMT alleviated the impact of NICU-related stress on rats and promoted the growth and development of neonatal rats. [ABSTRACT FROM AUTHOR]

Objective. This study was to construct a ceRNA (lncRNA-miRNA-mRNA) regulatory network for prostate cancer (PCa) and to explore the prognostic correlation, key biological functions, and pathways of core RNAs. Methods. Three subgene expression matrices (miRNA, lncRNA, and mRNA expression matrix) were taken from the TCGA database and used in this investigation. Differential expression analysis and differential expression miRNAs were carried out. Next, the ceRNA (lncRNA-miRNA-mRNA) regulatory complex was used to visualize our data and show how they interacted. Ultimately, the primary molecular roles and biological pathways of PCa were identified using enrichment analysis by the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO). An effect of AC016773.1 on prostate cancer cell proliferation was investigated by knocking out AC016773.1 in an animal model. The interrelationship between AC016773.1 and hsa-mir-25 was validated using RNA immunoprecipitation technology. Results. The lncRNA, miRNA, and mRNA expression matrices obtained from the TCGA database contain 16901, 1881, and 19962 transcripts, respectively. Through differential expression analysis, we obtained 2010 de lncRNA comparative information, 75 lncRNA and miRNA interaction pairs, and 31 targeted de mRNAs. Through the differential expression analysis of RNA nodes in the ceRNA regulatory network, we found that compared with the NP group, in the PCa group, there were 14 lncRNAs upregulated and 25 lncRNAs downregulated, 1 miRNA upregulated and 3 miRNA downregulated, and 10 mRNA upregulated and 21 mRNA downregulated. In KEGG enrichment analysis, the pathways identified by targeted DE-mRNAs were mainly related to calcium signaling pathway, EGFR tyrosine kinase inhibitor resistance, melanoma, PI3K−Akt signaling pathway, and proteoglycans in cancer. In animal models, it was found that knocking down AC016773.1 significantly reduced tumor volume and weight, indicating that AC016773.1 may promote the proliferation of PCa cells. The use of RNA immunoprecipitation technology indicates a direct binding between AC016773.1 and hsa-mir-25. Conclusion. We elucidated the network regulatory relationship of lncRNA-miRNA-mRNA in PCa and further explored the key molecular functions, biological pathways, and prognostic value of targeted DE-mRNAs. [ABSTRACT FROM AUTHOR]

Cardiovascular diseases (CVDs) have been the major cause of mortality all around the globe. Lespedeza cuneata abbreviated as L. cuneata with the authority name of Dumont de Courset (G. Don) is a perennial flowering plant commonly grown in Asian countries such as Korea, Japan, China, and Taiwan. We aimed to investigate the L. cuneata extract's antiplatelet and antithrombotic properties as GC-MS analysis indicated that the extract contained short-chain fatty acids, which have been reported to possess beneficial cardiovascular effects. L. cuneata was extracted using water, 50% EtOH, 70% EtOH, and 100% EtOH. For in vitro antiplatelet analysis, washed platelets were prepared and incubated with L. cuneata with 200 μg/mL of 50% EtOH in the presence of 1 mM of CaCl2 for 1 minute followed by agonist (collagen 2.5 μg/mL or ADP 10 μM or thrombin 0.1 U/mL) stimulation for 5 minutes over light transmission aggregometer. Scanning electron microscopy was performed to assess platelet shape change. ATP release and intracellular calcium mobilization were quantified to assess the granular content. Fibrinogen-binding assay and clot retraction assay assessed integrin αIIbβ3-mediated inside-out and outside-in signaling. Protein phosphorylation expression was investigated by western blot analysis. Finally, the in vivo antithrombotic efficacy was investigated by oral dosage of L. cuneata 200 and 400 mg/kg and aspirin 100 mg/kg for 7 days, and tail bleeding and FeCl3-induced murine thrombus model were performed. In vitro platelet aggregation and platelet shape change were dose-dependently suppressed by L. cuneata. Calcium mobilization, dense granules secretion, integrin αIIbβ3-mediated inside-out and outside-in signaling, and protein phosphorylation of MAPK and PI3K/Akt pathways were significantly inhibited. In vivo assays revealed that L. cuneata prevents side effects of synthetic drugs via nonsignificantly increasing bleeding time and improving coronary artery blood flow and animal survival. Our results demonstrate that L. cuneata exhibited potent antiplatelet and antithrombotic effects and can be considered a potential herbal medicine with cardioprotective effects. [ABSTRACT FROM AUTHOR]

Inflammatory and antimicrobial diseases constitute a major burden for society, and fighting them is a WHO strategic priority. Most of the treatments available to fight inflammatory diseases are anti-inflammatory drugs, such as corticosteroids or immunomodulators that lack cellular specificity and lead to numerous side effects. In addition to suppressing undesired inflammation and reducing disease progression, these drugs lessen the immune system protective functions. Furthermore, treating infectious diseases is more and more challenging due to the rise of microbial resistance to antimicrobial drugs. Thus, controlling the inflammatory process locally without compromising the ability to combat infections is an essential feature in the treatment of inflammatory diseases. We isolated three forms (DRS-DA2N, DRS-DA2NE, and DRS-DA2NEQ) of the same peptide, DRS-DA2, which belongs to the dermaseptin family, from the Mexican tree frog Pachymedusa dacnicolor. Interestingly, DRS-DA2N and DRS-DA2NEQ exhibit a dual activity by inducing the death of leukocytes as well as that of Gram-negative and Gram-positive bacteria, including multiresistant strains, without affecting other cells such as epithelial cells or erythrocytes. We showed that the death of both immune cells and bacteria is induced rapidly by DRS-DA2 and that the membrane is permeabilized, leading to the loss of membrane integrity. We also validated the capacity of DRS-DA2 to regulate the pool of inflammatory cells in vivo in a mouse model of noninfectious peritonitis. After the induction of peritonitis, a local injection of DRS-DA2N could decrease the number of inflammatory cells locally in the peritoneal cavity without inducing a systemic effect, as no changes in the number of inflammatory cells could be detected in blood or in the bone marrow. Collectively, these data suggest that this peptide could be a promising tool in the treatment of inflammatory diseases, such as inflammatory skin diseases, as it could reduce the number of inflammatory cells locally without suppressing the ability to combat infections. [ABSTRACT FROM AUTHOR]

Background. Catheter ablation failure poses a clinical challenge for epicardial or intramural ventricular arrhythmia (VA); however, guidewire ablation within the coronary venous system (CVS) may be effective and safe for targeting VAs. Methods. The ex vivo phase included four steps. In step 1, the steam pop incidence rates during guidewire ablation at power settings of 5, 10, 15, 20, and 25 W were analyzed using 10 mm- and 20 mm-tip guidewires. In step 2, guidewire ablation was performed for application durations of 10, 20, 30, 40, 50, 60, and 90 s, and the lesion size was measured. In step 3, the effects of saline infusion (0, 1, 2, 3, and 4 mL/min) on lesion dimensions and steam pop formation were examined. In step 4, an orthogonal array was constructed to obtain the optimal guidewire ablation parameters. In the in vivo phase, guidewire ablation within the CVS was performed in three dogs, and the lesion features in 10 days after ablation were observed. Results. In step 1, the steam pop incidence rates at 5, 10, 15, 20, and 25 W were 0%, 0%, 12.5%, 62.5%, and 100% using the 10 mm-tip guidewires and 0%, 0%, 0%, 25%, and 75% using the 20 mm-tip guidewires, respectively. In step 2, we found that the lesion areas increased with an increase in the ablation duration (the maximum lesion diameters at 30, 60, and 90 s were 4.9 ± 0.4, 7.0 ± 0.8, and 9.2 ± 0.7 mm in the 10 mm group and 3.2 ± 0.5, 4.5 ± 0.4, and 5.3 ± 0.7 mm in the 20 mm-tip group, respectively). In step 3, we observed that saline infusion was negatively correlated with ablation lesions but had a lower risk of steam pop. The optimal parameters for the 20 mm-tip guidewire ablation were 15 W, 50 s, and 2 mL/min or 20 W, 70 s, and 2 mL/min. In the in vivo phase, effective ablation lesions with maximum and minimum diameters of 3.2 ± 0.3 and 2.8 ± 0.5 mm, respectively, were created by the guidewires during the 10-day observation period after ablation. Conclusion. This novel radiofrequency guidewire ablation technique can feasibly create effective lesions within the CVS, which may improve the efficacy of catheter ablation for challenging epicardial or intramural VA. [ABSTRACT FROM AUTHOR]

Background. Traditional herbal medicine practitioners in the Ashanti region of Ghana use the fruit peels of Citrus limon (L.) Osbeck (C. limon) in preventive and curative treatment of many cancers including liver cancer. This ethnobotanical claim remains to be verified scientifically. Aim of the Study. This study investigated prophylactic hepatoprotective and anti-HCC effects of C. limon peel extract (LPE) in CCl4/olive oil-induced HCC-like rats. Materials and Methods. After preparation of LPE, it was subjected to phytochemical screening using standard phytochemical methods. A total of 30 healthy adult male Sprague-Dawley rats (weighing 150-200 g) were randomly assigned into six groups of 5 rats each. Rats in the control group received olive oil (5 mL/kg ip) twice weekly for 16 weeks. Rats in the model group received CCl4/olive oil (2 mL/kg, ip) twice weekly for 16 weeks. Rats in capecitabine (10 mg/kg po) and LPE (50, 100, and 200 mg/kg po) groups received CCl4/olive oil (2 mL/kg, i.p) in the morning and their respective treatments in the afternoon twice a week for 16 weeks. Rats in all groups had free access to food and water ad libitum. Body weight and survival rates were monitored. Rats were sacrificed under deep anesthesia, blood was collected, and liver and other organs were isolated. Aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), gamma-glutamyltransferase (GGT), prothrombin time, bilirubin, C-reactive protein (CRP), alpha- (α-) fetoprotein (AFP), and liver histology were assessed. Results. Alkaloids, tannins, flavonoids, terpenoids, and saponins were detected in LPE. Model rats demonstrated increased serum levels of AFP, CRP, ALP, GGT, ALT, and AST, prothrombin time, total bilirubin, direct bilirubin, blood lymphocyte, and monocyte counts, but decreased serum albumin and total protein compared to control rats. Unlike the control, model rats demonstrated fat accumulation in periportal and centrilobular hepatocytes and neoplastic transformation. Semiquantitation of periodic acid Schiff- (PAS-) stained liver sections showed decreased glycogen storage in hepatocytes of model rats compared to control rats. Compared to the model, LPE treatment protected against CCl4-induced hepatocarcinogenesis, which was evidenced by decreased AFP, CRP, liver enzymes, total and direct bilirubin, prothrombin time, and blood lymphocyte and monocyte counts; attenuation of fat accumulation; and increased glycogen storage, albumin, and total protein. Conclusion. LPE abates CCl4-induced hepatocarcinogenesis by attenuating liver inflammation and improving metabolic, biosynthetic, and detoxification functions of the liver. The prophylactic hepatoprotective and anti-hepatocarcinogenic effects of LPE are attributable to its phytochemical composition raising hopes of finding potential anticancer bioactive compounds from C. limon fruit peels. [ABSTRACT FROM AUTHOR]