Mitigatory Effects Research Articles

Assessment on vulnerability of road networks considering the dynamic impact of urban waterlogging and the mitigation effect of LID measures

The urban waterlogging stemming from the rainstorm exerts a considerable adverse influence on road networks. Accurately evaluating the vulnerability of road networks during waterlogging is a crucial measure to alleviate flood risk and damage. Nevertheless, previous research merely considered the maximum inundation depth of waterlogging, but neglecting the dynamic variation of waterlogging. In this study, we firstly develop a coupled hydrodynamic model (IFMS-Urban + SWMM) and integrated it with a road traffic model to analyze the impact of waterlogging on road networks; then, a time factor is involved to assess the dynamic variation of flood vulnerability by using a novel index road vulnerability recovery index (RVRI); finally, the mitigatory effect of low impact development infrastructure/practices (LIDs) on the vulnerability of transportation roads under waterlogging was investigated. The results show that, both the coupled hydrodynamic model and road traffic model were verified for logical soundness and show strong adaptability. The urban waterlogging becomes increasingly severe with the increase of return period of rainstorms and leads to a corresponding rise in the vulnerability of the road network. The evaluation system of road network vulnerability becomes more comprehensive and reasonable with the consideration of the time factor. The well-arranged LIDs can effectively reduce the vulnerability of road network. This study serves as a valuable reference for dynamically assessing the vulnerability of road networks to urban waterlogging, offering guidance for urban waterlogging prevention, road traffic management, and road operation and maintenance in urbanized areas.

Dihydromyricetin protects sevoflurane-induced mitochondrial dysfunction in HT22 hippocampal cells.

Sevoflurane (Sev) is a commonly used inhalation anaesthetic that has been shown to cause hippocampus dysfunction through multiple underlying molecular processes, including mitochondrial malfunction, oxidative stress and inflammation. Dihydromyricetin (DHM) is a 2,3-dihydroflavonoid with various biological properties, such as anti-inflammation and anti-oxidative stress. The purpose of this study was to investigate the effect of DHM on Sev-induced neuronal dysfunction. HT22 cells were incubated with 10, 20 and 30 μM of DHM for 24 h, and then stimulated with 4% Sev for 6 h. The effects and mechanism of DHM on inflammation, oxidative stress and mitochondrial dysfunction were explored in Sev-induced HT22 cells by Cell Counting Kit-8, flow cytometry, enzyme-linked immunosorbent assay, reverse transcription-quantitative polymerase chain reaction, colorimetric detections, detection of the level of reactive oxygen species (ROS), mitochondrial ROS and mitochondrial membrane potential (MMP), immunofluorescence and western blotting. Our results showed that DHM increased Sev-induced cell viability of HT22 cells. Pretreatment with DHM attenuated apoptosis, inflammation, oxidative stress and mitochondrial dysfunction in Sev-elicited HT22 cells by remedying the abnormality of the indicators involved in these progresses, including apoptosis rate, the cleaved-caspase 3 expression, as well as the level of tumour necrosis factor α, interleukin (IL)-1β, IL-6, malondialdehyde, superoxide dismutase, catalase, ROS, mitochondrial ROS and MMP. Mechanically, pretreatment with DHM restored the Sev-induced the expression of SIRT1/FOXO3a pathway in HT22 cells. Blocking of SIRT1 counteracted the mitigatory effect of DHM on apoptosis, inflammation, oxidative stress and mitochondrial dysfunction in Sev-elicited HT22 cells. Collectively, pretreatment with DHM improved inflammation, oxidative stress and mitochondrial dysfunction via SIRT1/FOXO3a pathway in Sev-induced HT22 cells.

HD-tDCS mitigates the executive vigilance decrement only under high cognitive demands

Maintaining vigilance is essential for many everyday tasks, but over time, our ability to sustain it inevitably decreases, potentially entailing severe consequences. High-definition transcranial direct current stimulation (HD-tDCS) has proven to be useful for studying and improving vigilance. This study explores if/how cognitive load affects the mitigatory effects of HD-tDCS on the vigilance decrement. Participants (N = 120) completed a modified ANTI-Vea task (single or dual load) while receiving either sham or anodal HD-tDCS over the right posterior parietal cortex (rPPC). This data was compared with data from prior studies (N = 120), where participants completed the standard ANTI-Vea task (triple load task), combined with the same HD-tDCS protocol. Against our hypotheses, both the single and dual load conditions showed a significant executive vigilance (EV) decrement, which was not affected by the application of rPPC HD-tDCS. On the contrary, the most cognitively demanding task (triple task) showed the greatest EV decrement; importantly, it was also with the triple task that a significant mitigatory effect of the HD-tDCS intervention was observed. The present study contributes to a more nuanced understanding of the specific effects of HD-tDCS on the vigilance decrement considering cognitive demands. This can ultimately contribute to reconciling heterogeneous effects observed in past research and fine-tuning its future clinical application.

Potential therapeutic benefit of spinal cord stimulation in restless legs syndrome: scoping review and mechanistic considerations.

Restless legs syndrome (RLS) is a prevalent sensorimotor disorder that can dramatically impair sleep quality, daytime function, and quality of life. Although many patients benefit from standard pharmacological therapy, some patients suffer from insufficient treatment response or medication intolerance. Novel treatment approaches are therefore necessary. Given the overlap between RLS and pain syndromes in both pathophysiological mechanisms and certain treatment options, we aimed to perform a scoping review of the available evidence on spinal cord stimulation (SCS) for RLS and discuss potential mechanistic implications. We identified a total of 16 cases of patients with RLS who underwent SCS, all from case reports or case series. The published evidence is insufficient to assess SCS efficacy in patients with RLS, but SCS remains a promising investigational therapy in RLS on the basis of its potential mitigatory effects in the central hyperexcitability of the sensorimotor cortex through neuromodulation of spinal, subcortical, and cortical areas. A call for further research in this field is presented, with suggestions for future directions and trial designs.

Does spatial functional division in urban agglomerations reduce negative externalities in large cities? Evidence from urban agglomerations in China

The spatial unit of urban agglomerations is extremely important for reducing negative externalities in large cities. Although there is a large body of literature on reducing negative externalities within a single city, few studies have focused on the important role of urban agglomerations. To offer a new method for reducing negative externalities in large cities and fill in this gap in the literature, our paper examines the effect of spatial functional division in urban agglomerations on negative externalities in large cities by applying the concept of spatial functional division to data on 19 urban agglomerations and data on negative externalities from 35 large cities in China. We first show that spatial functional division in urban agglomerations can significantly reduce negative externalities. The robustness of the results was confirmed using the instrumental variable approach, alternative indicators, and other robustness checks. Furthermore, we identified the productivity improvement mechanisms in large cities that generate the observed mitigatory effects of spatial functional division in urban agglomerations on negative externalities in large cities. The heterogeneous analyzes indicate that spatial functional division in urban agglomerations has a stronger mitigatory effect on negative externalities in large cities in the context of higher inter-city connectivity, greater polycentricity, and official approval regarding urban agglomerations’ regional planning. Our findings emphasize the importance of urban agglomerations for reducing negative externalities in large cities, particularly in China, where urban agglomerations have been rapidly developing and spatial functional division in urban agglomerations has been continuously improving.

Cryptotanshinone-Doped Photothermal Synergistic MXene@PDA Nanosheets with Antibacterial and Anti-Inflammatory Properties for Wound Healing.

Humans are threatened by bacteria and other microorganisms, resulting in countless pathogen-related infections and illnesses. Accumulation of reactive oxygen species (ROS) in infected wounds activates strong inflammatory responses. The overuse of antibiotics has led to increasing bacterial resistance. Therefore, effective ROS scavenging and bactericidal capacity are essential and the advanced development of collaborative therapeutic techniques to combat bacterial infections is needed. Here, this work developes an MXene@polydopamine-cryptotanshinone (MXene@PDA-CPT) antibacterial nanosystem with excellent reactive oxygen and nitrogen species scavenging ability, which effectively inactivates drug-resistant bacteria and biofilms, thereby promoting wound healing. In this system, the adhesion of polydopamine nanoparticles to MXene produced a photothermal synergistic effect and free radical scavenging activity, presenting a promising antibacterial and anti-inflammatory strategy. This nanosystem causes fatal damage to bacterial membranes. The loading of cryptotanshinone further expanded the advantages of the system, causing a stronger bacterial killing effect and inflammation mitigatory effect with desired biosafety and biocompatibility. In addition, combining nanomaterials and active ingredients of traditional Chinese medicine, this work provides a new rationale for the future development of wound dressings, which contributes to eliminating bacterial resistance, delaying disease deterioration, and alleviating the pain of patients.

Alleviation Syndrome of High-Cholesterol-Diet-Induced Hypercholesterolemia in Mice by Intervention with Lactiplantibacillus plantarum WLPL21 via Regulation of Cholesterol Metabolism and Transportation as Well as Gut Microbiota.

Probiotics are prospective for the prevention and treatment of cardiovascular diseases. Until now, systematic studies on the amelioration of hypercholesterolemia have been rare in terms of (cholesterol metabolism and transportation, reshaping of gut microbiota, as well as yielding SCFAs) intervention with lactic acid bacteria (LAB). In this study, strains of Lactiplantibacillus plantarum, WLPL21, WLPL72, and ZDY04, from fermented food and two combinations (Enterococcus faecium WEFA23 with L. plantarum WLPL21 and WLPL72) were compared for their effect on hypercholesterolemia. Comprehensively, with regard to the above aspects, L. plantarum WLPL21 showed the best mitigatory effect among all groups, which was revealed by decreasing total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels, upregulated cholesterol metabolism (Cyp27a1, Cyp7b1, Cyp7a1, and Cyp8b1) levels in the liver, cholesterol transportation (Abca1, Abcg5, and Abcg8) in the ileum or liver, and downregulated Npc1l1. Moreover, it reshaped the constitution of gut microbiota; specifically, the ratio of Firmicutes to Bacteroidetes (F/B) was downregulated; the relative abundance of Allobaculum, Blautia, and Lactobacillus was upregulated by 7.48-14.82-fold; and that of Lachnoclostridium and Desulfovibrio was then downregulated by 69.95% and 60.66%, respectively. In conclusion, L. plantarum WLPL21 improved cholesterol metabolism and transportation, as well as the abundance of gut microbiota, for alleviating high-cholesterol-diet-induced hypercholesterolemia.

Umbelliferone loaded PEGylated liposomes: preparation, characterization and its mitigatory effects on Dalton's ascites lymphoma development.

Umbelliferone (UB) is a phenylpropanoid-based pharmacologically active agent with promising anti-tumor activities. However, complete elucidation of its therapeutic efficacy remains challenging due to low solubility and bioavailability. The present study aimed to develop a liposomal delivery system for UB to enhance its therapeutic efficacy against Dalton's ascites lymphoma tumor model. Umbelliferone-encapsulated nanoliposomes (nLUB) were prepared using the thin-film hydration method and performed a series of characterizations to confirm successful development. The nLUB showed a particle size of 116 ± 3.2nm with a negative surface charge and encapsulation efficiency of 78%. In vitro study results showed that nLUB treatment significantly enhanced cellular uptake and apoptosis induction in lymphoma cells compared to free UB. nLUB treatment significantly stabilized body weight, reduced tumor growth, and improved the serum biochemical and hematological parameters of experimental animals, thereby improving their overall survivability compared to an free UB. Our result indicates that nanoencapsulation enhanced the therapeutic potential of UB, which may find its way to clinical application in the near future.

The mitigation of the executive vigilance decrement via HD-tDCS over the right posterior parietal cortex and its association with neural oscillations.

Vigilance-maintaining a prolonged state of preparation to detect and respond to specific yet unpredictable environmental changes-usually decreases across prolonged tasks, causing potentially severe real-life consequences, which could be mitigated through transcranial direct current stimulation (tDCS). The present study aimed at replicating previous mitigatory effects observed with anodal high-definition tDCS (HD-tDCS) over the right posterior parietal cortex (rPPC) while extending the analyses on electrophysiological measures associated with vigilance. In sum, 60 participants completed the ANTI-Vea task while receiving anodal (1.5mA, n = 30) or sham (0mA, n = 30) HD-tDCS over the rPPC for ~ 28min. EEG recordings were completed before and after stimulation. Anodal HD-tDCS specifically mitigated executive vigilance (EV) and reduced the alpha power increment across time-on-task while increasing the gamma power increment. To further account for the observed behavioral and physiological outcomes, a new index of Alphaparietal/Gammafrontal is proposed. Interestingly, the increment of this Alphaparietal/Gammafrontal Index with time-on-task is associated with a steeper EV decrement in the sham group, which was mitigated by anodal HD-tDCS. We highlight the relevance of replicating mitigatory effects of tDCS and the need to integrate conventional and novel physiological measures to account for how anodal HD-tDCS can be used to modulate cognitive performance.

The Mitigatory Effect of Shen-Qi Compound on the Diabetic Thoracic Aortic Complications through Inhibiting the Inflammatory Microenvironment by miR-223-3p/RBP-J/IRF8 Axis.

Background Disruption of the vascular immunological inflammatory microenvironment is linked to metabolic memory impairment. Even though it has been proven that the Shen-Qi compound (SQC) can efficiently halt metabolic memory and preserve vascular endothelial cells, extensive studies need to be done to investigate if it can also change the vascular immune-inflammatory microenvironment by regulating the immune system. This will help figure out the role of stopping metabolic memory. Methods After 4 weeks on a high-fat diet (HFD), GK rats were used to create a model for diabetic thoracic aortic problems. The effect and mechanisms of SQC on diabetic thoracic aortic complications were assessed by hematoxylin-eosin (H&E) staining, enzyme-linked immunosorbent assay (ELISA), biochemical analysis, terminal deoxynucleotidyl transferase deoxyuridine triphosphate (dUTP) nick end labeling (TUNEL), reverse transcription, real-time polymerase chain reaction (RT-qPCR), immunofluorescence (IF), western blot, and luciferase reporter assays. Results SQC treatment ameliorates the HFD-induced pathological symptoms as well as the HFD-induced increased concentrations of fasting blood glucose (FBG), fasting insulin (FINS), total cholesterol (TC), triglycerides (TGs), and low-density lipoprotein cholesterol (LDL-C) and decreased concentrations of high-density lipoprotein cholesterol (HDL-C). Besides, SQC counteracted the HFD-induced average fluorescence intensity of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1), as well as the concentrations of endothelin-1 (ET-1) and monocyte chemoattractant protein-1 (MCP-1), while rescuing the HFD-induced concentrations of nitric oxide (NO) and nitric oxide synthetase (NOS). Also, SQC decreases apoptosis and oxidative stress in rats with diabetic thoracic aortic complications. In addition, SQC facilitated the polarization of macrophages, stimulated the activation of dendritic cells, and regulated the inflammatory milieu in rats with diabetic thoracic aortic complications. Furthermore, SQC also modulated the miR-223-3p/RBP-J/IRF8 axis in the macrophages of rats with diabetic thoracic aortic complications. Conclusion SQC ameliorated diabetic thoracic aortic complications through the regulation of apoptosis, oxidative stress, and inflammatory microenvironment mediating by the miR-223-3p/RBP-J/IRF8 axis.

Alleviation of Ammonium Toxicity in Salvia splendens 'Vista Red' with Silicon Supplementation.

Ammonium (NH4+) toxicity seriously hampers the yield and quality of salvia plants because most varieties or sub-species are highly sensitive to NH4+. Silicon (Si) is an alternative that is used to minimize these disturbances and maintain better growth under NH4+ toxicity. Nevertheless, the mitigatory effects of Si on NH4+-stressed salvia are unknown. Therefore, this study was carried out to determine how Si assists to alleviate the NH4+ toxicity degree in salvia. To this end, salvia plants were cultivated in a controlled environment supplied with a constant N (nitrogen) level (13 meq·L−1) in the form of three NH4+:NO3− ratios (0:100, 50:50, 100:0), each with (1.0 meq·L−1) or without Si. Physiological disorders and typical NH4+ toxicity symptoms, as well as interrupted photosynthesis, were observed in the 100% NH4+-treated plants. Furthermore, cation uptake inhibition and oxidative damage were also imposed by the 100% NH4+ supply. In contrast, in the presence of Si, the NH4+ toxicity degree was attenuated and plant growth was ensured. Accordingly, the NH4+ toxicity appearance ratio decreased significantly. Furthermore, Si-treated plants showed an ameliorated photosynthetic ability, elevated internal K and Ca levels, and enhanced antioxidative capacity, as reflected by improved major antioxidant enzyme activities, as well as diminished accumulation of ROS (reactive oxygen species) and MDA (malondialdehyde). Our findings enlightened the agronomic importance of additional Si to nutrient solutions, especially pertaining to bedding plants at risk of NH4+ toxicity.

Genome-Wide Characterization of the Aquaporin Gene Family in Radish and Functional Analysis of RsPIP2-6 Involved in Salt Stress.

Aquaporins (AQPs) constitute a highly diverse family of channel proteins that transport water and neutral solutes. AQPs play crucial roles in plant development and stress responses. However, the characterization and biological functions of RsAQPs in radish (Raphanus sativus L.) remain elusive. In this study, 61 non-redundant members of AQP-encoding genes were identified from the radish genome database and located on nine chromosomes. Radish AQPs (RsAQPs) were divided into four subfamilies, including 21 plasma membrane intrinsic proteins (PIPs), 19 tonoplast intrinsic proteins (TIPs), 16 NOD-like intrinsic proteins (NIPs), and 5 small basic intrinsic proteins (SIPs), through phylogenetic analysis. All RsAQPs contained highly conserved motifs (motifs 1 and 4) and transmembrane regions, indicating the potential transmembrane transport function of RsAQPs. Tissue- and stage-specific expression patterns of AQP gene analysis based on RNA-seq data revealed that the expression levels of PIPs were generally higher than TIPs, NIPs, and SIPs in radish. In addition, quantitative real-time polymerase chain reaction (qRT-PCR) revealed that seven selected RsPIPs, according to our previous transcriptome data (e.g., RsPIP1-3, 1-6, 2-1, 2-6, 2-10, 2-13, and 2-14), exhibited significant upregulation in roots of salt-tolerant radish genotype. In particular, the transcriptional levels of RsPIP2-6 dramatically increased after 6 h of 150 mM NaCl treatment during the taproot thickening stage. Additionally, overexpression of RsPIP2-6 could enhance salt tolerance by Agrobacterium rhizogenes-mediated transgenic radish hairy roots, which exhibited the mitigatory effects of plant growth reduction, leaf relative water content (RWC) reduction and alleviation of O2– in cells, as shown by nitro blue tetrazolium (NBT) staining, under salt stress. These findings are helpful for deeply dissecting the biological function of RsAQPs on the salt stress response, facilitating practical application and genetic improvement of abiotic stress resistance in radish.

An update on healthspan and lifespan enhancing attributes of tea amidst the emerging understanding of aging biology

A cellular senescence-centric understanding of biological aging and age-related chronic diseases is rapidly emerging. As a result, strategies aimed at mitigating the deleterious aspects of cellular senescence are increasingly becoming desirable. Tea is a globally admired and nutrient-rich beverage that not only refreshes the senses but is also implicated in several health beneficial effects including the extension of organismal healthspan and lifespan. The present review discusses the emerging anti-cellular senescence attributes of tea consumption and provides a perspective that the anti-aging aspects of tea should be studied in the purview of cellular senescence. Current understanding of the integrative effects of the immune system and gut microbiome on cellular senescence have also been discussed with the rationale of mitigatory effects of tea. Future research directions and recommendations have been provided which may ultimately help augment tea-oriented successful and healthy aging approaches. • A cellular senescence-centric theory of aging is rapidly emerging. • Tea polyphenols can affect the development and removal of senescent cells. • Tea polyphenols can suppress DNA damage, mitigate SASP and maintain telomere length. • Immunostimulating attributes of tea consumption during aging are also known. • Tea phenols act as second-generation prebiotics and modulate gut dysbiosis during aging.

Black-White Racial Context and U.S. American Youths’ Moral Judgments of and Responses to Social Exclusion Bullying

Bullied adolescents experience myriad poor outcomes, yet certain responses can have significant mitigatory effects. However, research has yet to examine how the racial context of these interactions affects adolescents’ evaluations of and beliefs about responding to social-exclusionary bullying (SEB). The sample comprised 219 ninth-grade Black (N = 84; females = 46) and White (N = 135; females = 81) students (Mage = 14.84, SD = 0.68; Nfemales= 92) recruited from 5 schools in a large, racially diverse, middle-class Mid-Atlantic metropolitan area of the United States. Participants judged the wrongfulness of 4 scenarios of same- and cross-race SEB and selected how the victims should respond to the victimization. Responses were coded as aggressive, assertive, adult assistance-seeking, or avoidant. Gender, scenario, and response strategy main and interaction effects emerged. The Black-excluder and White-victim scenario was rated least wrong. Assertive responses were selected more often in scenarios with White-excluders; avoidant responses were selected more often in scenarios with Black-excluders. Results suggest that racial context relates significantly to adolescents’ evaluations of and responses to SEB scenarios.

Phloretin mitigates oxidative injury, inflammation, and fibrogenic responses via restoration of autophagic flux in in vitro and preclinical models of NAFLD

Nonalcoholic fatty liver disease (NAFLD) with growing incidences is a major health concern worldwide. Alteration in cellular redox homeostasis and autophagy plays a critical role in the progression of NAFLD to more severe outcomes. The lack of safe and effective therapy for the disease necessitates the exploration of new therapeutic compounds. Therefore, in the present study, we investigated the potential of phloretin to maintain redox equilibrium and prevent disease progression via modulation of autophagy in NAFLD. Free fatty acid exposed Huh7 cells were used to evaluate the efficacy of phloretin in vitro. Further, phloretin was administered orally to western diet induced NAFLD in C57BL/6J mice at different doses. The chronic exposure to fatty acids and the western diet triggered lipid accumulation in the Huh7 cells and western diet-fed mice liver, respectively. In addition, mitochondrial dysfunction, oxidative stress, inflammation and decreased hepatic autophagy were observed in disease condition. Phloretin encouraged autophagy mediated hepatic lipid clearance and restored mitochondrial membrane potential and redox homeostasis. It also reduced histological injury by reducing hepatic lipogenesis and facilitating fatty acid oxidation. Moreover, findings of the study also revealed the mitigatory effect of phloretin on inflammatory and fibrogenic markers. Altogether, the study suggested that phloretin effectively attenuates NAFLD progression via upregulating autophagy-mediated lipid breakdown and inhibits oxidative damage, hepatic inflammation and fibrosis.

Mitigation of Salinity Stress Effects on Broad Bean Productivity Using Calcium Phosphate Nanoparticles Application

Water salinity is one of the major abiotic stresses, and the use of saline water for the agricultural sector will incur greater demand in the coming decades. Recently, nanoparticles (NPs) have been used for developing numerous plant fertilizers as a smart and powerful form of material with dual action that can alleviate the adverse effects of salinity and provide the plant with more efficient nutrient forms. This study evaluated the influence of calcium phosphate NPs (CaP-NPs) as a soil fertilizer application on the production and bioactive compounds of broad bean plants under salinity stress. Results showed that salinity had deleterious effects on plant yield with 55.9% reduction compared to control. On the other hand, CaP-NPs dramatically improved plant yield by 30% compared to conventional fertilizer under salinity stress. This improvement could be attributed to significantly higher enhancement in total soluble sugars, antioxidant enzymes, proline content, and total phenolics recorded use of nano-fertilizer compared to conventional use under salt stress. Additionally, nano-fertilizer reflected better mitigatory effects on plant growth parameters, photosynthetic pigments, and oxidative stress indicators (MDA and H2O2). Therefore, our results support the replacement of traditional fertilizers comprising Ca2+ or P with CaP-nano-fertilizers for higher plant productivity and sustainability under salt stress.

Dietary synbiotic ameliorates constipation through the modulation of gut microbiota and its metabolic function

The purpose of this study is to investigate the mitigatory effect of a novel synbiotic (SBT) on constipation from the perspective of gut microbiome and metabolome. Here, intake of SBT effectively attenuated diphenoxylate-induced constipation, recuperated colonic epithelial integrity and increased serum levels of gastrointestinal excitatory neurotransmitters (P substance, vasoactive intestinal peptide, motilin, gastrin and serotonin). 16S rRNA sequencing showed that SBT intake rehabilitated the composition and functionality of gut microbiota. Relative abundances of short-chain fatty acids (SCFAs)-producing bacteria including Lactobacillus, Faecalibaculum and Bifidobacterium were elevated by administration of SBT. The gas chromatography-mass spectrometry analysis confirmed that fecal concentrations of propionate and butyrate were significantly increased in the rats intervened with SBT. In addition, SBT ingestion reduced the relative levels of opportunistic pathogens, such as Oscillibacter, Parasutterella and Parabacteroides. Microbial functional prediction showed that the relative abundances of lipopolysaccharide (LPS) biosynthesis and arachidonic acid metabolism were downregulated with SBT administration, which were in accordance with the serum metabolomics results. Furthermore, serum levels of LPS, tumour necrosis factor alpha and interleukin 6 were significantly decreased, indicating that SBT supplementation suppressed inflammatory responses. Therefore, this study demonstrated that consumption of SBT ameliorated constipation possibly by regulating gut microbiota, promoting the SCFAs production and inhibiting inflammatory responses in rats. Our study also indicated that SBT may provide a novel alternative strategy for the treatment of constipation clinically in future.

Network Pharmacological Analysis and Experimental Validation of the Mechanisms of Action of Si-Ni-San Against Liver Fibrosis.

Background: Si-Ni-San (SNS), a commonly used traditional Chinese medicine (TCM) formula, has potency against liver diseases, such as hepatitis and non-alcoholic fatty liver disease (NAFLD). However, the therapeutic efficacy and pharmacological mechanisms of action of SNS against liver fibrosis remain largely unclear. Methods: A carbon tetrachloride (CCl4)-induced liver fibrosis mouse model was adopted for the first time to investigate the beneficial effects of SNS on liver fibrosis. The potential mechanisms of action of SNS were explored using the network pharmacology-based strategy and validated with the aid of diverse assays. Results: SNS treatment reduced collagen and ECM deposition, downregulated fibrosis-related factor (hyaluronic acid and laminin) contents in serum, maintained the morphological structure of liver tissue, and improved liver function in the liver fibrosis model. Based on network pharmacology results, apoptosis, inflammation and angiogenesis, together with the associated pathways (including VEGF, TNF, caspase, PPAR-γ and NF-κB), were identified as the mechanisms underlying the effects of SNS on liver fibrosis. Further in vivo experiments validated the significant mitigatory effects of SNS on inflammatory infiltration and pro-inflammatory cytokine contents (IFNγ, IL-1β and TGF-β1) in liver tissues of mice with liver fibrosis. SNS suppressed pathologic neovascularization as well as levels of VEGFR1, VEGF and VEGFR2 in liver tissues. SNS treatment additionally inhibited hepatic parenchyma cell apoptosis in liver tissues of mice with liver fibrosis and regulated apoptin expression while protecting L02 cells against apoptosis induced by TNF-α and Act D in vitro. Activation of hepatic stellate cells was suppressed and the balance between MMP13 and TIMP1 maintained in vitro by SNS. These activities may be associated with SNS-induced NF-κB suppression and PPAR-γ activation. Conclusion: SNS effectively impedes liver fibrosis progression through alleviating inflammation, ECM accumulation, aberrant angiogenesis and apoptosis of hepatic parenchymal cells along with inhibiting activation of hepatic stellate cells through effects on multiple targets and may thus serve as a novel therapeutic regimen for this condition.

Vitamin C and E Supplementation Can Mitigate NaF Mediated Hematological and Hepatic Disorders in Adult Wistar Rats

The study aimed to investigate the effect of combined vitamin E and C, on hematological and hepatic systems of adult male Wistar rats with fluoride toxicity. Eighteen rats were randomly divided into three groups such as control, treated (given NaF, 20 mg/kg bw/rat/day), and supplemented (NaF and vitamin E-200 mg/kg bw + C- 400 mg/kg bw). Altered hematological parameters like erythrocyte count, leukocyte count and hemoglobin concentration were seen in NaF groups. Estimation of osmotic fragility of erythrocyte showed a marked increase fragile erythrocytes in fluoride-treated groups compared to control and supplemented groups. Total thiol concentration was also decreased due fluoride fluoride-induced oxidative stress and it was protected in supplementary groups. The oxidative imbalance induced by NaF in liver was evaluated by estimating the activity of antioxidant enzyme superoxide dismutase and catalase and with estimation of lipid peroxidation and protein oxidation product malondialdehyde and protein carbonyl. All enzymatic and non-enzymatic markers of oxidative imbalance were significantly altered (increased/decreased) due to fluoride toxicity, which was again observed to be protected in the supplemented group. The histopathological analysis of the liver also proved the mitigatory effect of the combined vitamin E+C on fluorideinduced hepatic insult.

Mitigation of silver nanoparticle toxicity by humic acids in gills of Piaractus mesopotamicus fish.

Silver nanoparticles (AgNPs) are one of the most produced nanoproducts due to their unique biocide properties. The natural organic matter has an important impact on nanoparticle's dispersion as it may alter their fate and transport, as well as their bioavailability and toxicity. Therefore, this study aimed to evaluate the mitigatory effect of humic acids (HAs) on AgNP toxicity. For this purpose, we carried out an ex vivo exposure of gill of Piaractus mesopotamicus fish to 100 μg L-1 of AgNPs or AgNO3, alone and in combination with 10 mg L-1 of HAs. In parallel, a complete AgNP characterization in the media, including the presence of HAs, was provided, and the Ag+ release was measured. We analyzed Ag bioaccumulation, antioxidant enzymes activities, lipid peroxidation, antioxidant capacity against peroxyl radicals, and reduced glutathione levels in fish tissue. Our results indicated the Ag+ release from AgNPs decreased 28% when the HAs were present in the media. The Ag accumulation in gill tissue exposed to AgNPs alone was higher than the AgNO3 exposure, and sixfold higher than the treatment with the HA addition. Moreover, after both Ag forms, the catalase enzyme augmented its activity. However, those responses were mitigated when the HAs were present in the media. Then, our results suggested the mitigation by HAs under the exposure to both Ag forms, providing valuable information about the fate and behavior of this emergent pollutant.