Urinary tract infections and risk of preterm birth: a systematic review and meta-analysis.

This systematic review and meta-analysis assessed the association between urinary tract infections (UTIs) during pregnancy and the risk of preterm birth (PTB). We searched multiple databases for relevant observational studies, categorizing them as UTI-based (comparing PTB incidence in women with and without UTIs) or PTB-based (comparing UTI prevalence in women with and without PTB). Using a random-effects model in Stata software version 17.0, we estimated pooled and adjusted odds ratios (ORs) with 95% confidence intervals (CIs), and performed subgroup, sensitivity, and cumulative analyses to explore heterogeneity. In total, 30 studies comprising 32 datasets were included, involving a total of 249,810 cases and 2,626,985 healthy controls. The meta-analysis revealed a significant positive association between UTIs during pregnancy and PTB occurrence (OR, 1.92; 95% CI, 1.62-2.27). A sub-group analysis based on studies, the participants showed significant association in both PTB-based (OR, 2.01; 95% CI, 1.58-2.56) and UTI-based studies (OR, 1.79; 95% CI, 1.42-2.26). However, Egger's test indicated the presence of publication bias (p=0.020), and substantial heterogeneity was observed across the included studies (I2=96.6; p< 0.001). These findings emphasize the critical importance of early detection and effective management of UTIs in pregnant women to reduce the risk of PTB and its associated adverse outcomes. While the results highlight a robust link between UTIs during pregnancy and PTB risk, the potential influence of publication bias and substantial heterogeneity should be considered to interpret these findings. Further research is needed to better understand the underlying mechanisms and to develop targeted interventions for high-risk pregnant women.

Oenothein B from Eugenia uniflora leaves exerts pro-angiogenic effects by increasing VEGF and TNF-α levels.

Oenothein B (OeB), a dimeric ellagitannin with a macrocyclic structure, is reported to have beneficial effects, including antioxidant, antitumor, antiviral, and antimutagenic effects, on human health. Despite the remarkable properties of OeB, its role in neovascularization process has not yet been evaluated. Thus, this study aimed to evaluate the angiogenic activity of OeB using a chorioallantoic membrane (CAM) assay at different concentrations (6.25, 12.5, and 25 µg/µL), employing digital imaging and histological analysis. Furthermore, to elucidate the mechanisms by which OeB influences angiogenesis, we assessed the levels of vascular endothelial growth factor (VEGF) and tumor necrosis factor-alpha (TNF-α) in CAM using immunohistochemical analysis. All concentrations of OeB significantly increased (p < 0.05) the percentage of vascularization as well as the levels of all the angiogenesis-associated parameters evaluated, indicating the pronounced pro-angiogenic activity of OeB. Our results showed that inflammation was one of the most relevant phenomena observed in CAM histology along with angiogenesis. In addition, a significant increase in VEGF and TNF-α levels was observed in all the CAMs compared to the negative control (p < 0.05). We suggest that OeB may induce the presence of inflammatory cells in CAM, leading to increased VEGF and TNF-α levels that result in the induction of angiogenesis. Therefore, OeB presents a favorable profile that could be further explored for the development of drugs for pro-angiogenic and tissue repair therapies.

Evaluation of infliximab-induced genotoxicity and possible action on BCL-2 and P53 genes.

Although the last pandemic created an urgency for development of vaccines, there was a continuous and concerted effort to search for therapeutic medications among existing drugs with different indications. One of the medications of interest that underwent this change was infliximab (IFM). This drug is used as an anti-inflammatory, predominantly in patients with Crohn 's disease, colitis ulcerative, and rheumatoid arthritis. In addition to these patients, individuals infected with Coronavirus Disease (COVID-19) were administered this chimeric monoclonal antibody (IMF) to act as an immunomodulator for patients in the absence of comprehensive research. Consequently, the present study aimed to examine the genotoxic effects attributed to IFM treatment employing different assays in vivo using mouse Mus musculus. Therefore, IFM was found to induce genotoxic effects as evidenced by the comet assay but did not demonstrate genotoxic potential utilizing mouse bone marrow MN test. The results of evaluating the expression of the P53 and BCL-2 genes using RT-qPCR showed stimulation of expression of these genes at 24 hr followed by a decline at 48 hr. Although the comet assay provided positive results, it is noteworthy that based upon negative findings in the micronucleus test, the data did not demonstrate significant changes in the genetic material that might affect the therapeutic use of IFM. The stimulation of expression of P53 and BCL-2 genes at 24 hr followed by a decline at 48 hr suggest a transient, if any, effect on genetic material. However, there is still a need for more research to more comprehensively understand the genotoxic profile of this medication.

Comparison of Vertebral Artery Ultrasound, Magnetic Resonance Angiography and Digital Subtraction Angiography in the Diagnosis of Vertebral Artery Stenosis in Patients with Posterior Circulation Ischemia

SUMMARY: The aim of this study was to compare the clinical value of vertebral artery ultrasound (VAU), Magnetic Resonance Angiography (MRA) and Digital Subtraction Angiography (DSA) on vertebral artery stenosis in patients with posterior circulation ischemia. Seventy-three patients with posterior circulation ischemia underwent vertebral artery ultrasound and magnetic resonance angiography as well as digital subtraction angiography, and the diagnosis of vertebral artery stenosis (VAS) and the degree of stenosis (normal, mild stenosis, moderate stenosis, severe stenosis, and occlusion) were recorded and compared between digital subtraction angiogram and vertebral artery ultrasound and magnetic resonance angiography. The vertebral artery stenosis rates on digital subtraction angiography and vertebral artery ultrasound were 87.30 % (55/63) and 49.20 % (31/63), respectively, and the difference was statistically significant. The rates of vertebral artery stenosis on digital subtraction angiography and, magnetic resonance angiography was 90.38 % (47/52) and 88.46 % (46/ 52), respectively, and the differences was not statistically significant. The sensitivity, accuracy, negative predictive value, and positive predictive value of vertebral artery ultrasound in diagnosing vertebral artery stenosis were 51.35 %, 54.76 %, 18.18 %, and 95.00 %, respectively, lower than those of magnetic resonance angiography, which were 91.89 %, 90.48 %, 57.14 %, and 97.14 %, respectively. Of the noninvasive imaging techniques, vertebral artery ultrasound does not accurately characterize vertebral artery stenosis and its degree of stenosis. Magnetic resonance angiography effectively screens for vertebral artery stenosis and its degree of stenosis, and can be used as a reliable tool for vertebral artery stenosis in posterior circulation cerebral infarction, and can be used in conjunction with digital subtraction angiogram in order to improve diagnostic convenience and accuracy.

El objetivo de este estudio fue comparar el valor clínico de la ecografía de la arteria vertebral (VAU), la angiografía por resonancia magnética (ARM) y la angiografía por sustracción digital (DSA) en la estenosis de la arteria vertebral en pacientes con isquemia de la circulación posterior. A 73 pacientes con isquemia de la circulación posterior se les realizó una ecografía de la arteria vertebral y una angiografía por resonancia magnética, así como una angiografía por sustracción digital, y se les diagnosticó estenosis de la arteria vertebral (EVA) y el grado de estenosis (normal, estenosis leve, estenosis moderada, estenosis grave, y oclusión) se registraron y compararon la angiografía por sustracción digital y la ecografía de la arteria vertebral y la angiografía por resonancia magnética. Las tasas de estenosis de la arteria vertebral en la angiografía por sustracción digital y la ecografía de la arteria vertebral fueron del 87,30 % (55/63) y del 49,20 % (31/63), respectivamente, y la diferencia fue estadísticamente significativa. Las tasas de estenosis de la arteria vertebral en la angiografía por sustracción digital y la angiografía por resonancia magnética fueron del 90,38 % (47/52) y del 88,46 % (46/52), respectivamente, y las diferencias no fueron estadísticamente significativas. La sensibilidad, precisión, valor predictivo negativo y valor predictivo positivo de la ecografía de la arteria vertebral en el diagnóstico de estenosis de la arteria vertebral fueron 51,35 %, 54,76 %, 18,18 % y 95,00 %, respectivamente, inferiores a los de la angiografía por resonancia magnética, que fueron 91,89 %, 90,48 %, 57,14 % y 97,14 %, respectivamente. De las técnicas de imagen no invasivas, la ecografía de la arteria vertebral no caracteriza con precisión la estenosis de la arteria vertebral y su grado de estenosis. La angiografía por resonancia magnética detecta eficazmente la estenosis de la arteria vertebral y su grado de estenosis, y puede usarse como una herramienta confiable para la estenosis de la arteria vertebral en el infarto cerebral de circulación posterior, y puede ser utilizada junto con la angiografía por sustracción digital para mejorar el diagnóstico y la exactitud.

Dioclea violacea lectin inhibits tumorigenesis and tumor angiogenesis in vivo.

Dioclea violacea seed mannose-binding lectin (DvL) has attracted considerable attention because of its interesting biological activities, including antitumor, antioxidant, and anti-inflammatory activities. This study evaluated the cytotoxic effect of DvL on tumor and normal cells using the mitochondrial activity reduction (MTT) assay, the carcinogenic and anti-carcinogenic activity by the epithelial tumor test (ETT) in Drosophila melanogaster, and the anti-angiogenic effect by the chick embryo chorioallantoic membrane (CAM) assay. Data demonstrated that DvL promoted strong selective cytotoxicity against tumor cell lines, especially A549 and S180 cells, whereas normal cell lines were weakly affected. Furthermore, DvL did not promote carcinogenesis in D. melanogaster at any concentration tested, but modulated DXR-induced carcinogenesis at the highest concentrations tested. In the CAM and immunohistochemical assays, DvL inhibited sarcoma 180-induced angiogenesis and promoted the reduction of VEGF and TGF-ß levels at all concentrations tested. Therefore, our results demonstrated that DvL is a potent anticancer, anti-angiogenic, and selective cytotoxic agent for tumor cells, suggesting its potential application as a prototype molecule for the development of new drugs with chemoprotective and/or antitumor effects.

Tellimagrandin-I and camptothin a exhibit chemopreventive effects in Salmonella enterica serovar Typhimurium strains and human lymphocytes.

Tellimagrandin-I (TL) and camptothin A (CA) are ellagitannins widely found in diverse plant species. Numerous studies demonstrated their significant biological activities, which include antitumor, antioxidant, and hepatoprotective properties. Despite this protective profile, the effects of TL and CA on DNA have not been comprehensively investigated. Thus, the aim of this study was to determine the mutagenic and antimutagenic effects attributed to TL and CA exposure on Salmonella enterica serovar Typhimurium strains using the Ames test. In addition, the cytotoxic and genotoxic effects were examined on human lymphocytes, employing both trypan blue exclusion and CometChip assay. The antigenotoxic effect was determined following TL and CA exposure in the presence of co-treatment with doxorubicin (DXR). Our results from the Ames test indicated that TL or CA did not display marked mutagenic activity. However, TL or CA demonstrated an ability to protect DNA against the damaging effects of the mutagens 4-nitroquinoline-1-oxide and sodium azide, thereby exhibiting antimutagenic properties. In relation to human lymphocytes, TL or CA did not induce significant cytotoxic or genotoxic actions on these cells. Further, these ellagitannins exhibited an ability to protect DNA from damage induced by DOX during co-treatment, indicating their potential beneficial usefulness as antigenotoxic agents. In conclusion, the protective effects of TL or CA against mutagens, coupled with their absence of genotoxic and cytotoxic effects on human lymphocytes, emphasize their potential therapeutic value in chemopreventive strategies.

Urinary tract infections and risk of preterm birth: a systematic review and meta-analysis

ABSTRACT This systematic review and meta-analysis assessed the association between urinary tract infections (UTIs) during pregnancy and the risk of preterm birth (PTB). We searched multiple databases for relevant observational studies, categorizing them as UTI-based (comparing PTB incidence in women with and without UTIs) or PTB-based (comparing UTI prevalence in women with and without PTB). Using a random-effects model in Stata software version 17.0, we estimated pooled and adjusted odds ratios (ORs) with 95% confidence intervals (CIs), and performed subgroup, sensitivity, and cumulative analyses to explore heterogeneity. In total, 30 studies comprising 32 datasets were included, involving a total of 249,810 cases and 2,626,985 healthy controls. The meta-analysis revealed a significant positive association between UTIs during pregnancy and PTB occurrence (OR, 1.92; 95% CI, 1.62-2.27). A sub-group analysis based on studies, the participants showed significant association in both PTB-based (OR, 2.01; 95% CI, 1.58-2.56) and UTI-based studies (OR, 1.79; 95% CI, 1.42-2.26). However, Egger's test indicated the presence of publication bias (p=0.020), and substantial heterogeneity was observed across the included studies (I2=96.6; p< 0.001). These findings emphasize the critical importance of early detection and effective management of UTIs in pregnant women to reduce the risk of PTB and its associated adverse outcomes. While the results highlight a robust link between UTIs during pregnancy and PTB risk, the potential influence of publication bias and substantial heterogeneity should be considered to interpret these findings. Further research is needed to better understand the underlying mechanisms and to develop targeted interventions for high-risk pregnant women.

Pedunculagin and tellimagrandin-I stimulate inflammation and angiogenesis and upregulate vascular endothelial growth factor and tumor necrosis factor-alpha in vivo.

Pedunculagin (PD) and tellimagrandin-I (TL), isolated from Myrciaria cauliflora seeds and Eucaliptus microcorys leaves, respectively, have attracted great attention owing to their relevant biological activities, such as antitumor, antioxidant, and hepatoprotective activities. This study investigated the angiogenic potential of PD and TL using a chick embryo chorioallantoic membrane (CAM) assay. Using the CAM assay, our results showed that both PD and TL promoted a significant increase in the number and caliber of blood vessels, the thickness of the CAM, and the presence of fibroblasts and inflammatory cells. Moreover, an increase of tumor necrosis factor-α and vascular endothelial growth factor was observed in the CAM treated with PD and TL, indicating the induction of angiogenic factors. Thus, the remarkable profile of PD and TL in inducing angiogenesis opens up new perspectives for their potential utilization in different therapeutic approaches involving neovascularization.

Mexican Americans agree to participate in longitudinal clinical research more than non-Hispanic whites.

BACKGROUND: The National Institutes of Health has advocated for improved minority participation in clinical research, including clinical trials and observational epidemiologic studies since 1993. An understanding of Mexican Americans (MAs) participation in clinical research is important for tailoring recruitment strategies and enrollment techniques for MAs. However, contemporary data on MA participation in observational clinical stroke studies are rare. We examined differences between Mexican Americans (MAs) and non-Hispanic whites (NHWs) participation in a population-based stroke study. METHODS: We included 3,594 first ever stroke patients (57.7% MAs, 48.7% women, median [IQR] age 68 [58-79]) from the Brain Attack Surveillance in Corpus Christi Project, 2009-2020 in Texas, USA, who were approached and invited to participate in a structured baseline interview. We defined participation as completing a baseline interview by patient or proxy. We used log-binomial models adjusting for prespecified potential confounders to estimate prevalence ratios (PR) of participation comparing MAs with NHWs. We tested interactions of ethnicity with age or sex to examine potential effect modification in the ethnic differences in participation. We also included an interaction between year and ethnicity to examine ethnic-specific temporal trends in participation. RESULTS: Baseline participation was 77.0% in MAs and 64.2% in NHWs (Prevalence Ratio [PR] 1.20; 95% CI, 1.14-1.25). The ethnic difference remained after multivariable adjustment (1.17; 1.12-1.23), with no evidence of significant effect modification by age or sex (Pinteraction by age = 0.68, Pinteraction by sex = 0.83). Participation increased over time for both ethnic groups (Ptrend < 0.0001), but the differences in participation between MAs and NHWs remained significantly different throughout the 11-year time period. CONCLUSION: MAs were persistently more likely to participate in a population-based stroke study in a predominantly MA community despite limited outreach efforts towards MAs during study enrollment. This finding holds hope for future research studies to be inclusive of the MA population.

Chemopreventive effect and induction of DNA repair by oenothein B ellagitannin isolated from leaves of Eugenia uniflora in Swiss Webster treated mice.

Oenothein B (OeB) is a dimeric ellagitannin with potent antioxidative, antitumor, immunomodulatory, and anti-inflammatory properties. Despite the promising activities of OeB, studies examining the genotoxic or protective effects of this ellagitannin on DNA are scarce. Therefore, to further comprehensively elucidate the chemopreventive profile of OeB, the aim of this study was to evaluate the mutagenic and antimutagenic actions of OeB using Salmonella typhimurium strains with the Ames test. The micronucleus (MN) test and comet assay were used to assess the anticytotoxic and antigenotoxic effects of OeB on mouse bone marrow cells following differing treatments (pre-, co-, and post-treatment) in response to cyclophosphamide (CPA)-induced DNA damage. In addition, histopathological analyses were performed to assess liver and kidney tissues of Swiss Webster treated mice. Our results did not detect mutagenic or antimutagenic activity attributed to OeB at any concentration in the Ames test. Regarding the MN test, data showed that this ellagitannin exerted antigenotoxic and anticytotoxic effects against CPA-induced DNA damage under all treatment conditions. However, no anticytotoxic action was observed in MN test after pre-treatment with the highest doses of OeB. In addition, OeB demonstrated antigenotoxic effects in the comet assay for all treatments. Histopathological analyses indicated that OeB attenuated the toxic effects of CPA in mouse liver and kidneys. These findings suggest that OeB exerted a chemoprotective effect following pre- and co-treatments and a DNA repair action in post-treatment experiments. Our findings indicate that OeB protects DNA against CPA-induced damaging agents and induces post-damage DNA repair.

Cathepsin B Is Not an Intrinsic Factor Related to Asparaginase Resistance of the Acute Lymphoblastic Leukemia REH Cell Line.

L-Asparaginase (ASNase) is a biopharmaceutical used as an essential drug in the treatment of acute lymphoblastic leukemia (ALL). Yet, some cases of ALL are naturally resistant to ASNase treatment, which results in poor prognosis. The REH ALL cell line, used as a model for studying the most common subtype of ALL, is considered resistant to treatment with ASNase. Cathepsin B (CTSB) is one of the proteases involved in the regulation of in vivo ASNase serum half-life and it has also been associated with the progression and resistance to treatment of several solid tumors. Previous works have shown that, in vitro, ASNase is degraded when incubated with REH cell lysate, which is prevented by a specific CTSB inhibitor, suggesting a function of this protease in the ASNase resistance of REH cells. In this work, we utilized a combination of CRISPR/Cas9 gene targeting and enzymatic measurements to investigate the relevance of CTSB on ASNase treatment resistance in the ALL model cell line. We found that deletion of CTSB in REH ALL cells did not confer ASNase treatment sensitivity, thus suggesting that intrinsic expression of CTSB is not a mechanism that drives the resistant nature of these ALL cells to enzymes used as the first-line treatment against leukemia.

Effect of doramectin on programmed cell death pathway in glioma cells.

PURPOSE: Doramectin (DRM) is a kind of avermectin drugs, and it has been shown that DRM has anti-cancer effects. However, the molecular mechanism of DRM in programmed cell death (PCD) aspects is still unclear. The objective of this study was to confirm whether DRM induced PCD in glioma cells. METHODS: In this experiment, the MTT assay and Ki-67 assay were used to detect in vitro cell viability and in vivo tumor proliferation. Then, the effect of DRM on PCD was analyzed by transcriptome comparison. Next, Endogenous apoptosis was detected by transmission electron microscopy (TEM), the DNA gel electrophoresis, JC-1 assay, western blotting and qRT-PCR. Meanwhile, necroptosis was detected by TEM, Hoechst 33342, FITC and PI staining assay, western blotting. RESULTS: We found DRM induced apoptosis through Bcl-2/Bax/Caspase-3 pathway. And, DRM induced ROS overproduction, then ROS caused necroptosis through RIPK1/RIPK3/MLKL pathway, Mitochondria acted as a bridge between the two pathways. CONCLUSION: Our research provided new insight with the function of anti-cancer of DRM. These results demonstrated DRM may be used as potential therapeutic agents inducing apoptosis and necroptosis for cancer therapy.

Impact of Coronary Artery Disease on The Outcomes of Catheter Ablation in Patients with Atrial Fibrillation.

INTRODUCTION: The objective of this study is to investigate the possible impact of coronary artery disease (CAD) on clinical outcomes of catheter ablation in patients with atrial fibrillation (AF). METHODS: Patients with AF who underwent coronary computed tomography and catheter ablation were enrolled. The presence of stenotic severity and plaque, characteristics of coronary arteries, clinical data, and adverse outcomes of catheter ablation were analysed. RESULTS: A total of 243 patients were enrolled, 100 (41%) patients with CAD. The CHA2DS2-VASc (congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, stroke or transient ischemic attack, vascular disease, age 65-74 years, and sex category) score of AF patients with CAD was significantly (P<0.001) higher than of those without CAD. Presence of stenotic artery and plaques increased significantly with increase of CHA2DS2-VASc score (P<0.05). There was no significant (P=0.342) difference in AF recurrence between patients with and without CAD (30% versus 24%). Age, AF type, duration of AF, heart failure, CHA2DS2-VASc score, left ventricular ejection fraction, and left atrial diameter were significantly (P<0.05) correlated with AF recurrence in univariant analysis. Multivariable analysis revealed that duration of AF (hazard ratio [HR] 1.769), heart failure (HR 1.821), and left atrial diameter (HR 1.487, P=0.022) remained significant independent predictors of AF recurrence. Patients with AF and concomitant CAD were significantly (P=0.030) associated with a worse outcome. CONCLUSION: CAD concomitant with AF may be associated with a worse clinical outcome even though CAD does not significantly affect the risk of AF recurrence after ablation therapy.

miRNA-576-5p promotes endometrial cancer cell growth and metastasis by targeting ZBTB4.

PURPOSE: MicroRNAs (miRNAs) have already been shown to have a strong correlation with the invasion and metastasis capacity of tumor cells. The present research examined the function of miRNA-576-5p (miR-576-5p) in the development of endometrial cancer (EC). METHODS: miR-576-5p and ZBTB4 expression in EC and benign endometrial tissues was measured using quantitative real-time PCR (qRT-PCR) and western blot. To evaluate the proliferation ability of tumor cells in vitro, 2,5-diphenyl-2H-tetrazolium bromide (MTT) and colony formation assays were carried out. The effect of miR-576-5p on the proliferation ability of EC cells in vivo was measured by the tumor formation in nude mice. The migration and invasion ability of tumor cells was determined using the transwell assay. To confirm the association between expressions of miR-576-5p and zinc finger and BTB domain containing four (ZBTB4), western blot, qRT-PCR, and luciferase assay were carried out. RESULTS: miR-576-5p expression increased significantly in EC samples than in benign endometrial tissues. The level of miR-576-5p was significantly higher in the polymerase ε (POLE) ultramutated subgroup compared to the other three subgroups. High levels of miR-576-5p expression were linked to a shorter progression-free interval time in the copy number high subgroup. Furthermore, upregulated miR-576-5p facilitated EC cell invasion and migration in vitro and promoted the proliferation of EC tumor cell lines both in vitro and in vivo. Moreover, this study showed that the expression of ZBTB4 decreased in patients with EC, and the dual-luciferase reporter assay confirmed that miR-576-5p binds directly to the 3'-UTR of ZBTB4 and inhibits the expression of ZBTB4. An increase in miR-576-5p expression leads to a decrease in the mRNA and protein expression level of ZBTB4. The effects of miR-576-5p can be reversed by overexpression of ZBTB4. CONCLUSION: miR-576-5p promoted proliferation and metastasis capacity of EC cells by inhibiting ZBTB4 expression. We hypothesized that miR-576-5p could be a prospective therapeutic target for EC.

Impact of Coronary Artery Disease on The Outcomes of Catheter Ablation in Patients with Atrial Fibrillation

ABSTRACT Introduction: The objective of this study is to investigate the possible impact of coronary artery disease (CAD) on clinical outcomes of catheter ablation in patients with atrial fibrillation (AF). Methods: Patients with AF who underwent coronary computed tomography and catheter ablation were enrolled. The presence of stenotic severity and plaque, characteristics of coronary arteries, clinical data, and adverse outcomes of catheter ablation were analysed. Results: A total of 243 patients were enrolled, 100 (41%) patients with CAD. The CHA2DS2-VASc (congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, stroke or transient ischemic attack, vascular disease, age 65-74 years, and sex category) score of AF patients with CAD was significantly (P<0.001) higher than of those without CAD. Presence of stenotic artery and plaques increased significantly with increase of CHA2DS2-VASc score (P<0.05). There was no significant (P=0.342) difference in AF recurrence between patients with and without CAD (30% versus 24%). Age, AF type, duration of AF, heart failure, CHA2DS2-VASc score, left ventricular ejection fraction, and left atrial diameter were significantly (P<0.05) correlated with AF recurrence in univariant analysis. Multivariable analysis revealed that duration of AF (hazard ratio [HR] 1.769), heart failure (HR 1.821), and left atrial diameter (HR 1.487, P=0.022) remained significant independent predictors of AF recurrence. Patients with AF and concomitant CAD were significantly (P=0.030) associated with a worse outcome. Conclusion: CAD concomitant with AF may be associated with a worse clinical outcome even though CAD does not significantly affect the risk of AF recurrence after ablation therapy.

Oroxin A ameliorates the oleic acid-induced A549 cell injury through the suppression of pyroptosis and degradation of alveolar surfactant.

The destruction of the pulmonary epithelial barrier in acute respiratory distress syndrome is caused by the damage of the alveolar epithelial cells. Oroxin A is an effective flavonoid component derived from the medicinal plant Oroxylum indicum (L.) Kurz. In this study, the oleic acid (OA)-induced A549 cell injury model was established in vitro to explore the protective mechanism of Oroxin A. The experiment was divided into the following groups: control, OA and OA + Oroxin A group. The OA-induced A549 cell injury was dose (time)-dependent and was detected by the CCK-8 assay. The protein and mRNA expression levels associated with pyroptosis are detected by Western blotting and RT-qPCR. After Oroxin A treatment, the levels of IL-1ß, IL-18 and LDH released were significantly lower than the OA group. In terms of pyroptosis, Oroxin A can inhibit the expression of pyroptosis-related protein and mRNA. Significantly, the surfactant protein C (SPC) level in the OA + Oroxin A group was significantly higher than that in the OA group. The treatment with Oroxin A alleviates the OA-induced injury in the A549 cells, and its mechanism may be related to the inhibition of A549 cells pyroptosis and prevention of the degradation of the SPC.

Comparison between carotid ultrasound and digital subtraction angiography in the diagnosis of carotid artery stenosis in patients with cerebral infarction / Comparación entre la ecografía carotídea y la angiografía por sustracción digital en el diagnostic de estenosis de la arteria carótida en pacientes con infarto cerebral

SUMMARY: This study aimed to compare the clinical value of carotid ultrasound and digital subtraction angiography (DSA) for carotid artery stenosis in patients with cerebral infarction. Sixty patients with cerebral infarction underwent carotid ultrasound and DSA. Carotid artery stenosis, degree of stenosis (mild, moderate, severe, and occlusion), and carotid artery plaques were recorded and compared. Carotid stenosis rate was 96.67 % (58/60) and 91.67 % (55/60) on DSA and carotid ultrasound, respectively, and the difference was not statistically significant. Mild, moderate, and severe carotid artery stenosis and occlusion were diagnosed in 35, 28, 20, and 17 arteries, respectively, with DSA, and in 39, 25, 10, and 9 arteries, respectively, with carotid ultrasound. There was a statistically significant difference in the degree of carotid stenosis between the two methods (p<0.05). The kappa value of carotid plaques detected by carotid ultrasound and DSA was 0.776, indicating good consistency. Both carotid ultrasound and DSA are effective for screening carotid artery stenosis and carotid atherosclerotic plaques. While carotid ultrasound is faster and more convenient, DSA can more accurately detect the degree of stenosis and presence of occlusion. Thus, our recommendation is a combination of carotid ultrasound and DSA in clinical settings to improve the convenience and accuracy of diagnosis.

Este estudio tuvo como objetivo comparar el valor clínico de la ecografía carotídea y la angiografía por sustracción digital (DSA) para la estenosis de la arteria carótida en pacientes con infarto cerebral. Sesenta pacientes con infarto cerebral fueron sometidos a ecografía carotídea y DSA. Se registraron y compararon la estenosis de la arteria carótida, el grado de estenosis (leve, moderada, grave y oclusión) y las placas de la arteria carótida. La tasa de estenosis carotídea fue del 96,67 % (58/60) y del 91,67 % (55/60) en DSA y ecografía carotídea, respectivamente, y la diferencia no fue estadísticamente significativa. Se diagnosticaron estenosis y oclusión de la arteria carótida leve, moderada y grave en 35, 28, 20 y 17 arterias, respectivamente, con DSA, y en 39, 25, 10 y 9 arterias, respectivamente, con ecografía carotídea. Hubo una diferencia estadísticamente significativa en el grado de estenosis carotídea entre los dos métodos (p<0,05). El valor kappa de las placas carotídeas detectadas por ecografía carotídea y DSA fue de 0,776, lo que indica una buena consistencia. Tanto la ecografía carotídea como la DSA son eficaces para detectar la estenosis de la arteria carótida y las placas ateroscleróticas carotídeas. Si bien la ecografía carotídea es más rápida y conveniente, la DSA puede detectar con mayor precisión el grado de estenosis y la presencia de oclusión. Por lo tanto, nuestra recomendación es una combinación de ecografía carotídea y DSA en entornos clínicos para mejorar la conveniencia y precisión del diagnóstico.

Protective effects and DNA repair induction of a coumarin-chalcone hybrid against genotoxicity induced by mutagens.

Coumarins and chalcones are compounds widely found in plants or obtained by synthetic methods which possess several biological properties including antioxidant, anti-inflammatory, and antitumor effects. A series of coumarin-chalcone hybrids were synthesized to improve their biological actions and reduce potential adverse effects. Considering the applications of these molecules, a coumarin-chalcone hybrid [7-methoxy-3-(E)-3-(3,4,5-trimethoxyphenyl) acryloyl-2 H-chromen-2-one] (4-MET) was synthesized and the genotoxic, cytotoxic, and protective effects assessed against damage induced by different mutagens. First, in silico tools were used to predict biological activity of 4-MET which indicated a chemopreventive potential. Subsequently, the genotoxic/antigenotoxic activities of 4-MET were determined both in vitro (Ames test) and in vivo (micronucleus (MN) test and comet assay). In addition, molecular docking simulations were performed between 4-MET and glutathione reductase, an important cellular detoxifying enzyme. Our results indicated that 4-MET was not mutagenic in the Ames test; however, when co-treated with sodium azide or 4-nitroquinoline 1-oxide (4-NQO), 4-MET significantly reduced the harmful actions of these mutagens. Except for a cytotoxic effect after 120 hr treatment, 4-MET alone did not produce cytotoxicity or genotoxicity in the MN test and comet assay. Nonetheless, all treatments of 4-MET with cyclophosphamide (CPA) showed a chemoprotective effect against DNA damage induced by CPA. Further, molecular docking analysis indicated a strong interaction between 4-MET and the catalytic site of glutathione reductase. These effects may be related to (1) damage prevention, (2) interaction with detoxifying enzymes, and (3) DNA-repair induction. Therefore, data demonstrated that 4-MET presents a favorable profile to be used in chemopreventive therapies.

Toxic Potential of Cerrado Plants on Different Organisms.

Cerrado has many compounds that have been used as biopesticides, herbicides, medicines, and others due to their highly toxic potential. Thus, this review aims to present information about the toxicity of Cerrado plants. For this purpose, a review was performed using PubMed, Science Direct, and Web Of Science databases. After applying exclusion criteria, 187 articles published in the last 20 years were selected and analyzed. Detailed information about the extract preparation, part of the plant used, dose/concentration tested, model system, and employed assay was provided for different toxic activities described in the literature, namely cytotoxic, genotoxic, mutagenic, antibacterial, antifungal, antiviral, insecticidal, antiparasitic, and molluscicidal activities. In addition, the steps to execute research on plant toxicity and the more common methods employed were discussed. This review synthesized and organized the available research on the toxic effects of Cerrado plants, which could contribute to the future design of new environmentally safe products.

Phytochemical Composition and Protective Effect of Vernonanthura polyanthes Leaf against In Vivo Doxorubicin-Mediated Toxicity.

Vernonanthura polyanthes (Spreng.) A.J. Vega & Dematt. (syn.: Vernonia polyanthes Less) is popularly known as "assa-peixe" and its leaves are used in folk medicine mainly to treat respiratory diseases. In this study, we evaluated the cytogenotoxic and anticytogenotoxic potential of the V. polyanthes leaf aqueous extract (VpLAE) and its n-butanol fraction (n-BF) in the presence or absence of doxorubicin (DXR) (pre-, co-, and post-treatments) on a murine model for 24 h or 120 h. The micronucleus test (MN) and the comet assay were used to assess the cytogenotoxic and anticytogenotoxic potential of VpLAE and n-BF (250, 500, and 1000 mg/kg) administered via gavage to Swiss Webster mice. The chemical profiles of VpLAE and n-BF were assessed by liquid chromatography coupled to mass spectrometry, and their metabolites were putatively identified. Lastly, the possible biological activities related to the (anti) cytogenotoxicity of the compounds were predicted using the PASS online webserver. The in vivo results showed that different doses of VpLAE and n-BF did not present cytotoxic activity; however, the MN test revealed a slight mutagenic activity for the 24 h treatments. Moderate genotoxic effects were demonstrated for all treatments in the comet assay. Regarding anticytotoxicity and antimutagenicity, VpLAE and n-BF presented a high cytoprotective potential against DXR toxic effects. In the co-treatment, VpLAE reduced the DXR genotoxicity by ~27%, and n-BF did not demonstrate antigenotoxic potential. In contrast, an antigenotoxic effect was observed for both VpLAE and n-BF in the pre- and post-treatments, reducing DXR genotoxicity by ~41% and ~47%, respectively. Chemical analysis of VpLAE and n-BF showed the presence of eight phenolic compounds, including seven chlorogenic acids and a flavonoid. The PASS online tool predicted antimutagenic, anticancer, antineoplastic, chemoprotective, antioxidant, and radical scavenging activities for all constituents identified in VpLAE and n-BF. V. polyanthes leaves presented a protective effect against DXR cytogenotoxicity. In general, VpLAE and n-BF showed a greater antigenotoxic potential in the pre- and post-treatments. The metabolites putatively identified in VpLAE and n-BF exhibited antioxidant and chemoprotective potential according to computational prediction analysis. Altogether, our results highlight the potential application of V. polyanthes to protect against toxic manifestations induced by DXR.