Rac3, but not Rac1, promotes ox-LDL induced endothelial dysfunction by downregulating autophagy.

The endothelial dysfunction induced by oxidized low-density lipoprotein (ox-LDL) plays an important role in the pathogenesis of atherosclerosis, which can lead to oxidative stress and inflammation. The role of autophagy in the process of atherosclerosis has drawn increasing attention. The human umbilical vein endothelial cells (HUVECs), whose Ras-related C3 botulinum toxin substrate 1 (Rac1) and Rac3 was knockdown, were used to detect whether the possible molecular mechanisms of Rac1 and Rac3 for anti-inflammatory in endothelial cells was effected by downregulation of autophagy. The HUVECs were incubated with ox-LDL. The inflammatory factors and autophagy proteins were evaluated to ascertain and compare the effect of Rac1 and Rac3 on autophagy. Then, 3-methyladenine (3-MA) as an inhibiter of autophagy was used to detect whether the effect of Rac1 and Rac3 was related to autophagy. ox-LDL-induced cell dysfunction in HUVECs was determined by testing the formation of foam cells, the expression of nuclear factor (NF)-κB and nucleotide-binding oligomerization domain (NOD)-like receptor protein 3 and NF-κB p65 and other inflammatory factors, the release of reactive oxygen species by oxidative stress and the dysfunction of the cytomembrane. And ApoE-/- mice on a high-fat diet were used as an animal model to detect the effect of Rac1 and Rac3 in vivo. The results showed that when Rac1 and Rac3 were decreased in HUVECs, the cell dysfunction caused by ox-LDL was inhibited. If 3-MA was used to inhibit autophagy in Rac1 and Rac3 knockdown cells, the injury induced by ox-LDL on the cells was recovered. These results indicated that the effect of Rac1 and Rac3 was combined with ox-LDL, which was related to inhibition of autophagy. The effect of Rac3 was more significant than that of Rac1.

Twelve Chinese herbal preparations for the treatment of depression or depressive symptoms in cancer patients: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Patients with cancer are vulnerable to depression or other depressive conditions. The aim of this paper was to evaluate the efficacy and safety of Chinese herbal medicine (CHM) for the treatment of depression or depressive symptoms in cancer patients. METHODS: CENTRAL, MEDLINE, EMBASE, PsycINFO, CNKI, VIP, SinoMed, and online clinical trial registry websites were searched for relevant RCTs until May 2017. The methodological quality of each included study was assessed with the "risk of bias" tool. Review Manager 5.3.5 was used to analyze the data. RESULTS: We identified 18 RCTs that included data from 1441 participants. Twelve different types of Chinese herbal preparations were investigated by these studies, and they showed a better therapeutic effect in most comparisons when measured in terms of depression rating scale scores, with SMDs (95% CI) of - 2.30 (- 3.54, - 1.05) (CHM versus no treatment), - 0.61 (- 1.03, - 0.18) (CHM versus antidepressants), and - 0.55 (- 1.07, - 0.02) (CHM plus psychological treatments versus psychological treatments), or when measured in terms of treatment response rate, with RRs (95% CI) of 1.65 (1.19, 2.29) (CHM versus no treatment), 1.15 (1.03, 1.28) (CHM versus psychological treatments), 1.32 (1.07, 1.63) (CHM plus antidepressants versus antidepressants), and 1.70 (1.02, 2.85) (CHM plus psychological treatments versus psychological treatments). Compared with antidepressants, these CHMs showed borderline superiority for improving the response rate, with an RR (95% CI) of 1.08 (0.93, 1.26). Subgroup analysis based on psychiatric diagnosis (depression versus depressive symptoms) did not modify the direction of these estimates and neither could it explain the high level of heterogeneity. Patients in the CHM group experienced fewer adverse events of cardiac toxicity (P = 0.02), functional gastrointestinal disorders (P = 0.008), sleep disturbances (P = 0.02), blurred vision (P = 0.02) and fatigue (P = 0.03) than the patients in the no treatment group or the antidepressants group. CONCLUSIONS: According to the investigation of the twelve herbal preparations, the CHM intervention appears to alleviate depressive symptoms in cancer patients, either alone or combined with antidepressants or psychological treatments. However, a high risk of bias and high heterogeneity made the mean estimates uncertain. Well-designed trials with comprehensive and transparent reporting are warranted in the future.

Elucidating the Relationship between Neutrophil-Lymphocyte Ratio and Plaque Composition in Patients with Drug-Eluting Stent Restenosis by Virtual Histology-Intravascular Ultrasound.

(1) Background: In-stent Restenosis (ISR) is a major factor influencing the prognosis and revascularization of target lesions. The plaque composition is unclear; therefore, it is critical to investigate ISR composition to identify clinical intervention markers. (2) Methods: This study was conducted on 36 patients with drug-eluting stent restenosis. The patients were classified into a Low Neutrophil-Lymphocyte Ratio (L-NLR) and High Neutrophil-Lymphocyte Ratio (H-NLR) according to the median NLR level of 36 patients. Discrepancies in the current information such as baseline data, biochemical examination, cardiac ultrasound data, etc., were examined to identify the underlying risk factors, and a multifactorial linear regression analysis of plaque properties was conducted. (3) Results: NLR = 2.64 was utilized to classify 18 patients into the L-NLR group and 18 patients into the H-NLR group. There were statistically significant differences in age, a pre-percutaneous coronary intervention (PCI) SYNTAX II score, a C-reactive protein (CRP), interleukin (IL)-6, plaque loading, a fibro-lipid tissue area, calcified nubs, and virtual histology-thin fibrous cap atherosclerotic (VH-TCFA). The significant impacts of variations in age, neutrophil-lymphocyte ratio (NLR) levels, and IL-6 levels on the plaque stress and percentage of the fibro-lipid tissue in virtual histology-intravascular ultrasound (VH-IVUS) were identified through multifactorial linear regression. (4) Conclusions: The high NLR group demonstrated increased myocardial injury severity, consistent with higher SYNTAX II scores, a higher plaque burden, and higher proportions of vulnerable components. NLR proved to be a risk factor for both the plaque load and the proportion of the fibro-lipid tissue in ISR.

Rapid adsorptive removal of emerging and legacy per- and polyfluoroalkyl substances (PFASs) from water using zinc chloride-modified litchi seed-derived biochar.

The present study successfully synthesized a novel biochar adsorbent (M-L-BC) using litchi seed modified with zinc chloride for PFASs removal in water. M-L-BC greatly enhanced removal of all examined PFASs (>95 %) as compared to the pristine biochar (<40 %). The maximum adsorption capacity was observed for PFOS, reaching 29.6 mg/g. Adsorption kinetics of PFASs followed the pseudo-second-order model (PSO), suggesting the predominance of chemical adsorption. Moreover, characterization and density functional theory (DFT) calculations jointly revealed involvement of surface complexation, electrostatic interactions, hydrogen bonding, and hydrophobic interactions in PFAS adsorption. Robust PFAS removal was demonstrated for M-L-BC across a wide range of pH (3-9), and coexisting ions had limited impact on adsorption of PFASs except PFBA. Furthermore, M-L-BC showed excellent performance in real water samples and retained reusability after five cycles of regeneration. Overall, M-L-BC represents a promising and high-quality adsorbent for efficient and sustainable removal of PFASs from water.

Characteristics of the Vasa Gene in Silurus asotus and Its Expression Response to Letrozole Treatment.

The identification and expression of germ cells are important for studying sex-related mechanisms in fish. The vasa gene, encoding an ATP-dependent RNA helicase, is recognized as a molecular marker of germ cells and plays a crucial role in germ cell development. Silurus asotus, an important freshwater economic fish species in China, shows significant sex dimorphism with the female growing faster than the male. However, the molecular mechanisms underlying these sex differences especially involving in the vasa gene in this fish remain poorly understood. In this work, the vasa gene sequence of S. asotus (named as Savasa) was obtained through RT-PCR and rapid amplification of cDNA end (RACE), and its expression in embryos and tissues was analyzed using qRT-PCR and an in situ hybridization method. Letrozole (LT) treatment on the larvae fish was also conducted to investigate its influence on the gene. The results revealed that the open reading frame (ORF) of Savasa was 1989 bp, encoding 662 amino acids. The SaVasa protein contains 10 conserved domains unique to the DEAD-box protein family, showing the highest sequence identity of 95.92% with that of Silurus meridionalis. In embryos, Savasa is highly expressed from the two-cell stage to the blastula stage in early embryos, with a gradually decreasing trend from the gastrula stage to the heart-beating stage. Furthermore, Savasa was initially detected at the end of the cleavage furrow during the two-cell stage, later condensing into four symmetrical cell clusters with embryonic development. At the gastrula stage, Savasa-positive cells increased and began to migrate towards the dorsal side of the embryo. In tissues, Savasa is predominantly expressed in the ovaries, with almost no or lower expression in other detected tissues. Moreover, Savasa was expressed in phase I-V oocytes in the ovaries, as well as in spermatogonia and spermatocytes in the testis, implying a specific expression pattern of germ cells. In addition, LT significantly upregulated the expression of Savasa in a concentration-dependent manner during the key gonadal differentiation period of the fish. Notably, at 120 dph after LT treatment, Savasa expression was the lowest in the testis and ovary of the high concentration group. Collectively, findings from gene structure, protein sequence, phylogenetic analysis, RNA expression patterns, and response to LT suggest that Savasa is maternally inherited with conserved features, serving as a potential marker gene for germ cells in S.asotus, and might participate in LT-induced early embryonic development and gonadal development processes of the fish. This would provide a basis for further research on the application of germ cell markers and the molecular mechanisms of sex differences in S. asotus.

Nanomedicine for Combination Urologic Cancer Immunotherapy.

Urologic cancers, particularly kidney, bladder, and prostate cancer, have a growing incidence and account for about a million annual deaths worldwide. Treatments, including surgery, chemotherapy, radiotherapy, hormone therapy, and immunotherapy are the main therapeutic options in urologic cancers. Immunotherapy is now a clinical reality with marked success in solid tumors. Immunological checkpoint blockade, non-specific activation of the immune system, adoptive cell therapy, and tumor vaccine are the main modalities of immunotherapy. Immunotherapy has long been used to treat urologic cancers; however, dose-limiting toxicities and low response rates remain major challenges in the clinic. Herein, nanomaterial-based platforms are utilized as the "savior". The combination of nanotechnology with immunotherapy can achieve precision medicine, enhance efficacy, and reduce toxicities. In this review, we highlight the principles of cancer immunotherapy in urology. Meanwhile, we summarize the nano-immune technology and platforms currently used for urologic cancer treatment. The ultimate goal is to help in the rational design of strategies for nanomedicine-based immunotherapy in urologic cancer.

The effect of probiotics on the serum lipid levels in non-obese healthy adults with hyperlipidemia: A systematic review and meta-analysis of randomized controlled trials.

INTRODUCTION: Introduction: probiotics might have a potential effect to manage serum lipid levels as nutraceuticals. Objective: this systematic review was conducted to explore whether probiotics have an efficient result in non-obese healthy adults with hyperlipidemia. Methods: PubMed, Embase, the Cochrane Central Register of Controlled Trials, and Web of Science were searched for randomized controlled trials (from their commencement to January 2021). This meta-analysis was performed by Review Manager 5.3 and STATA 15.1. Changes in serum lipid levels after the intervention were used to evaluate the effect of the probiotics, which were expressed as the weighted mean difference (WMD) with a 95 % confidence interval (CI). Results: a total of 16 studies, which could be regarded as 21 independent trials with 1429 participants, were included in this meta-analysis following our inclusion criteria. It could be observed that probiotics could significantly lower total cholesterol (TC) (WMD: -0.34 mmol/L, 95 % CI: -0.45 to -0.23 mmol/L; p < 0.001, I2 = 73.9 %) and low-density lipoprotein cholesterol (LDL-C) (WMD: -0.26 mmol/L, 95 % CI: -0.36 to -0.17 mmol/L; p < 0.001, I2 = 79.0 %) levels in non-obese healthy adults with hyperlipidemia, while no significant effect between the probiotic intervention and control groups was observed on high-density lipoprotein cholesterol (HDL-C) (WMD: 0.00 mmol/L, 95 % CI: -0.02 to 0.02 mmol/L; p = 0.001, I2 = 56.6 %) and triglyceride (TG) (WMD: -0.08 mmol/L, 95 % CI: -0.18 to 0.01 mmol/L; p = 0.003, I2 = 52.4 %) levels. Conclusion: this systematic review showed that probiotics may provide a promising way to reduce serum lipid levels in non-obese healthy adults with hyperlipidemia, but their specific effect still needs more clinical experiments to be proven.

INTRODUCCIÓN: Introducción: los probióticos podrían tener efecto para controlar los niveles de lípidos séricos como nutracéuticos. Objetivo: esta revisión sistemática se realizó para explorar si los probióticos tienen un resultado eficiente en adultos sanos no obesos con hiperlipidemia. Métodos: se realizaron búsquedas de ensayos controlados aleatorios en PubMed, Embase, el Registro Cochrane Central de Ensayos Controlados y Web of Science (desde su inicio hasta enero de 2021). Este metanálisis fue realizado mediante Review Manager 5.3 y STATA 15.1. Los cambios de los niveles de lípidos séricos después de la intervención se utilizaron para evaluar el efecto de los probióticos, que se expresaron como la diferencia de medias ponderada (DMP) con un intervalo de confianza (IC) del 95 %. Resultados: en este metaanálisis se incluyeron un total de 16 estudios, que podrían considerarse 21 ensayos independientes con 1429 participantes, siguiendo nuestros criterios de inclusión. Se pudo observar que los probióticos podían reducir significativamente el colesterol total (CT) (DMP: -0,34 mmol/L, IC del 95 %: -0,45 a -0,23 mmol/L; p < 0,001, I2 = 73,9 %) y el colesterol de lipoproteínas de baja densidad (C-LDL) (DMP: -0,26 mmol/L, IC del 95 %: -0,36 a -0,17 mmol/L; p < 0,001, I2 = 79,0 %) en los adultos sanos no obesos con hiperlipidemia, mientras que no hubo efectos significativos entre los grupos de intervención y de control en el colesterol de lipoproteínas de alta densidad (HDL-C) (DMP: 0,00 mmol/L, IC del 95 %: -0,02 a 0,02 mmol/L; p = 0,001, I2 = 56,6 %) y los triglicéridos (TG) (DMP: -0,08 mmol/L, IC del 95 %: -0,18 a 0,01 mmol/L; p = 0,003, I2 = 52,4 %). Conclusión: esta revisión sistemática manifestó que los probióticos podrían suponer una forma prometedora de reducir los niveles de lípidos séricos en los adultos sanos no obesos con hiperlipidemia, pero se necesitan más experimentos clínicos para demostrar su efecto específico.

Microenvironment immune response induced by tumor ferroptosis-the application of nanomedicine.

Ferroptosis is a non-apoptotic regulatory form of cell death that has sparked significant interest and research in cancer treatment and certain small chemical inducers have been used in the clinic. These inducers's weak water solubility, poor targeting, rapid metabolism; and other undesirable characteristics; however, for therapeutic approaches that combine immunotherapy and ferroptosis, challenges such as medication delivery, the complexity of the tumor microenvironment, and immunosuppression remain. The targeted, low toxicity, and efficient distribution benefits of nanotechnology have considerably enhanced the therapeutic efficacy of combining immunotherapy with ferroptosis. This paper describes the distinct mechanism of ferroptosis in tumor therapy and immunotherapy, as well as the application and benefits of nanotechnology in the combination of tumor immunotherapy and ferroptosis. Systematic review registration: http://clinicaltrials.gov/, NCT00941070.

Drug-Coated Balloon vs. Stent for de novo Non-small Coronary Artery Disease: A Systematic Review and Meta-Analysis.

Introduction: Drug-coated balloon (DCB) has been an attractive option in de novo vessels. A systematic review and meta-analysis were conducted to evaluate the efficacy and safety of DCB vs. stent for treating de novo lesions in non-small vessels. Methods: Studies in PubMed, Embase, the Cochrane Central Register of Controlled Trials, and Web of Science were searched (from their commencement to March 2021). This meta-analysis was performed by Review Manager 5.3. Results: A total of 3 random controlled trials (RCTs) with 255 patients and 2 observational studies (OS) with 265 patients were included in this meta-analysis following our inclusion criteria. It could be observed that DCB presented no significant difference in cardiac death (CD) (RR 0.33, 95% CI [0.01, 8.29], p = 0.50 in OS), myocardial infarction (MI) (RR 0.49, 95% CI [0.09, 2.50], p = 0.39 in RCT), target lesion revascularization (TLR) (RR 0.64, 95% CI [0.19, 2.18], p = 0.47 in RCT) (RR 1.72, 95% CI [0.56, 5.26], p = 0.34 in OS), and late lumen loss (LLL) (SMD -0.48, 95% CI [-1.32, 0.36], p = 0.26 in RCT) for de novo non-small coronary artery disease (CAD) compared with stents, whereas minimal lumen diameter (MLD) including MLD1 (SMD -0.67, 95% CI [-0.92 -0.42], p < 0.00001 in RCT) and MLD2 (SMD -0.36, 95% CI [-0.61 -0.11], p = 0.004 in RCT) was smaller in DCB group. Conclusion: This systematic review showed that DCB might provide a promising way on de novo non-small coronary artery disease compared with stents. However, more RCTs are still needed to further prove the benefits of the DCB strategy. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/#recordDetails.

PI3K regulates the activation of NLRP3 inflammasome in atherosclerosis through part-dependent AKT signaling pathway.

PI3K is a downstream target of multiple cell-surface receptors, which acts as a crucial modulator of both cell polarization and survival. PI3K/AKT signaling pathway is commonly involved in cancer, atherosclerosis, and other diseases. However, its role in cardiovascular diseases, especially in atherosclerosis, remains to be further investigated. To determine the effect of PI3K/AKT signaling pathway on cellular inflammatory response and oxidative stress, PI3K inhibitor (GDC0941) and AKT inhibitor (MK2206) were used. First, THP-1 cells were incubated with ox-LDL (100 µg/ml) to establish an in vitro atherosclerosis model. The inflammatory factors and foam cell formation were then evaluated to ascertain and compare the effects of PI3K and AKT inhibition. ApoE-/- mice fed a high-fat diet were used to assess the roles of PI3K and AKT in aortic plaque formation. Our results showed that the inhibition of PI3K or AKT could suppress the activation of NLRP3, decreased the expression levels of p-p65/p65 and reduced the production of mitochondrial reaction oxygen species (mitoROS) in THP-1 cells. Inhibition of PI3K or AKT could also reduced atherosclerosis lesion and plaque area, and decreased the levels of NLRP3 and IL-1ß in ApoE-/- mice. The effect of PI3K inhibition was more significant than AKT. Therefore, PI3K inhibition can retard the progress of atherosclerosis. Besides, there may be other AKT-independent pathways that regulate the formation of atherosclerosis.

Efficacy of probiotics on stress in healthy volunteers: A systematic review and meta-analysis based on randomized controlled trials.

BACKGROUND: Probiotics seems to play a beneficial role in stressed populations; thus, a systematic review and meta-analysis to assess the effects of probiotics on stress in healthy subjects were conducted. METHODS: Randomized controlled trials on the effects of probiotics on stress in healthy subjects were retrieved from five databases. The effects of probiotics on subjective stress level, stress-related subthreshold anxiety/depression level, cortisol level, and adverse reactions were analyzed. Separate subgroup analyses were conducted on single-strain probiotics versus multi-strain probiotics, and short-term administration versus long-term administration. RESULTS: Seven studies were included, involving a total of 1,146 subjects. All the studies were rated as low or moderate risk of bias. Our research found that probiotic administration can generally reduce the subjective stress level of healthy volunteers and may improve their stress-related subthreshold anxiety/depression level, but no significant effect was observed in the subgroup analysis. The effect of probiotics on cortisol level was not significant. Adverse reactions were reported in only one of seven studies, but left undescribed. CONCLUSION: Current evidence suggests that probiotics can reduce subjective stress level in healthy volunteers and may alleviate stress-related subthreshold anxiety/depression level, without significant effect on cortisol level, and there is not enough support to draw conclusions about adverse effects; thus, more reliable evidence from clinical trials is needed.

Does marital status correlate with the female breast cancer risk? A systematic review and meta-analysis of observational studies.

OBJECTIVE: To investigate that whether an association between marital status and the female breast cancer risk exists. METHODS: The MEDLINE, EMBASE and PsycINFO databases were searched from their inception to July 2019. The Newcastle-Ottawa Scale was used to rate the methodological quality of included studies. Study data were pooled using random-effects meta-analyses to compare the breast cancer risk between unmarried, widowed, divorced or lifelong single women and married women. This study is registered with PROSPERO (number CRD42018112368). RESULTS: Forty-nine publications were included in the meta-analysis. Compared with married women, unmarried and lifelong single women had an elevated risk of breast cancer, and the pooled ORs of case-control studies were 1.20 (95% CI: 1.07 to 1.35) and 1.24 (95% CI: 1.05 to 1.45), respectively. In the subgroup analyses under these two comparisons, hospital-based estimates and multivariate-adjusted estimates demonstrated a strong association, while population-based estimates and age-adjusted estimates produced nonsignificant results. The pooled OR of cohort studies examining the effect of being a lifelong single woman was 1.10 (95% CI: 1.04 to 1.16). Heterogeneity was moderate to substantial across case-control studies (I2: 46% to 82%), which may be partially explained by differences in geographic regions, publication years and control types. Possible publication bias was indicated by the funnel plot and Egger's test (P = 0.03). CONCLUSIONS: Marital status may correlate with the risk of developing female breast cancer. However, suboptimal selection of controls, insufficient exploration of confounding effects, inadequate ascertainment of marital status, and possible publication bias may have limited the quality of the available evidence. Overall, conclusions that marital status is an independent risk factor for breast cancer could not be drawn, and further prospective rigorous cohort studies are warranted.