RES Treatment Research Articles

Britannilactone 1-O-acetate induced ubiquitination of NLRP3 inflammasome through TRIM31 as a protective mechanism against reflux esophagitis-induced esophageal injury

BackgroundReflux esophagitis (RE) is a disease in which inflammation of the esophageal mucosa owing to the reflux of gastric contents into the esophagus results in cytokine damage. Britannilactone 1-O-acetate (Brt) has anti-inflammatory effects, significantly inhibiting the activation of the NLRP3 inflammasome, leading to a decrease in inflammatory factors including IL-1 β, IL-6, and TNF-α. However, the mechanism underlying its protective effect against RE-induced esophageal injury remains unclear. In the present study, we investigated the protective mechanism of TRIM31 against NLRP3 ubiquitination-induced RE both in vivo and in vitro.MethodsA model of RE was established in vivo in rats by the method of “4.2 mm pyloric clamp + 2/3 fundoplication”. In vitro, the mod was constructed by using HET-1A (esophageal epithelial cells) and exposing the cells to acid, bile salts, and acidic bile salts. The 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay was used to screen the concentration of administered drugs, and the viability of HET-1A cells in each group. HE staining was used to assess the degree of pathological damage in esophageal tissues. Toluidine blue staining was used to detect whether the protective function of the esophageal epithelial barrier was damaged and restored. The enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of IL-1 β, IL-6, and TNF-α factors in serum. Immunohistochemistry (IHC) was used to detect the expression level of NLRP3 in esophageal tissues. The molecular docking and Co-immunoprecipitation assay (Co-IP assay) were used to detect the TRIM31 interacts with NLRP3. Western blotting detected the Claudin-4, Claudin-5, The G-protein-coupled receptor calcium-sensitive receptor (CaSR), NLRP3, TRIM31, ASC, C-Caspase1, and Caspase1 protein expression levels.ResultsBrt could alleviate RE inflammatory responses by modulating serum levels of IL-1 β, IL-6, and TNF-α. It also activated the expression of NLRP3, ASC, Caspase 1, and C-Caspase-1 in HET-1A cells. Brt also attenuated TRIM31/NLRP3-induced pathological injury in rats with RE through a molecular mechanism consistent with the in vitro results.ConclusionsBrt promotes the ubiquitination of NLRP3 through TRIM31 and attenuates esophageal epithelial damage induced by RE caused by acidic bile salt exposure. This study provides valuable insights into the mechanism of action of Brt in the treatment of RE and highlights its promising application in the prevention of NLRP3 inflammatory vesicle-associated inflammatory pathological injury.Graphical

Roxarsone reduces earthworm-mediated nutrient cycling by suppressing aggregate formation and enzymic activity in soil with manure application

The application of manure and earthworms are frequently used in fertilization practices to improve C, N, and P cycling in soil, which may be adversely affected by roxarsone (ROX), as an organoarsenical pollutant. To effectively address this issue, in this work, the interactive impacts of ROX and earthworm Eisenia foetida on the aggregate formation, input of organic carbon (OC), and changes in the available N and P following 56-day cultivation were systematically investigated. Compared to the control, earthworms increased the mean weight diameter (MWD) of the soil aggregates from 0.6 to 1.1 mm. Thereby, they activated soil enzymes including catalase (CAT), sucrase (SC), urease (UE), and neutral phosphatase (NP), with the soil's pH decreased to 7.1. Consequently, the values of OC, soluble nitrite (NO3-N), and Olsen-P content were respectively increased by 0.78-, 1.69-, and 0.87- folds in the E treatment (14.3 vs. 25.5 g/kg, 12.8 vs. 33.3 mg/kg, and 7.8 vs. 14.6 mg/kg). Although the changes in the R treatment were slight, ROX reduced the earthworm-mediated improvements of soil fertility during the application of the RE treatment compared to the E treatment, i.e., the values of MWD, OC, NO3-N, and Olsen-P were reduced to 0.9 mm, 20.4 g/kg, 25.4 mg/kg, and 11.6 mg/kg, respectively. From the well-fitted structural equation models, it was demonstrated that earthworms enhanced the aggregate formation and nutrient cycling of OC, NO3-N, and Olsen-P, which were inhibited by ROX. Overall, these adverse effects can be offset by earthworm addition, which can play the dual role of monitor and driver for the soil properties. Our work provides insightful strategies for ROX-bearing manure management.

Resveratrol activates MAPK/ERK pathway to regulate oestrogen metabolism in type I endometrial cancer

ObjectiveEndometrial cancer (EC) is an oestrogen-dependent tumour, the occurrence of which is closely related to an imbalance of oestrogen homeostasis. Our previous studies explored the effects of Resveratrol(Res) on oestrogen metabolism. However, systematic research on the exact mechanism of action of Res is still lacking. Based on network pharmacology, molecular docking and animal experiments, the effects and molecular mechanisms of Res on endometrial cancer were investigated.MethodsThe target of Res was obtained from the high-throughput experiment and reference-guided database of TCM (HERB) and the Encyclopedia of Traditional Chinese Medicine (ETCM) databases, and the target of endometrial cancer was obtained by using the Genecards database. Venny map was used to obtain the intersection target of Res in the treatment of endometrial cancer, and the protein interaction network of the intersection target was constructed by importing the data into the STRING database. Then, the drug–disease–target interaction network was constructed based on Cytoscape 3.9.1 software. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed for intersection targets using the OmicShare cloud platform. Res and core targets were analysed by molecular docking. EC model mice induced by MNNG were randomly divided into the control group, Res group, MNNG group, MNNG + Res group, and MNNG + Res + MAPK/ERKi group. The protein levels of ERK and p-ERK in the mouse uterus were detected by Western blot. The levels of E1, E2, E3, 16-epiE3, 17-epiE3, 2-MeOE1, 4-MeOE1, 2-MeOE2, 4-MeOE2, 3-MeOE1, 2-OHE1, 4-OHE1, 2-OHE2, 4-OHE2, and 16α-OHE1 in the serum and endometrial tissue of mice were measured by LC‒MS/MS.ResultsA total of 174 intersection targets of Res anti-endometrial cancer were obtained. The signalling pathways analysed by KEGG enrichment included the AGE-RAGE signalling pathway in diabetic complications, the PI3K-Akt signalling pathway and the MAPK signalling pathway. The top 10 core targets were MAPK3, JUN, TP53, CASP3, TNF, IL1B, AKT1, FOS, VEGFA and INS. Molecular docking showed that in addition to TNF, other targets had good affinity for Res, and the binding activity with MAPK3 was stable. Western blot results showed that Res increased the phosphorylation level of ERK and that MAPK/ERKi decreased ERK activation. In the LC-MS/MS analysis, the levels of 2-MeOE1, 2-MeOE2 and 4-MeOE1 in serum and uterine tissue showed a significantly decreasing trend in the MNNG group, while that of 4-OHE2 was increased (P < 0.05). The concentrations of 4-MeOE1 in serum and 2-MeOE1 and 2-MeOE2 in the endometrial tissue of mice were significantly increased after Res treatment, and those of 4-OHE2 in the serum and uterus of mice were significantly decreased (P < 0.05). Meanwhile, in the MAPK/ERKi intervention group, the effect of Res on the reversal of oestrogen homeostasis imbalance was obviously weakened.ConclusionRes has multiple targets and multiple approaches in the treatment of endometrial cancer. In this study, it was found that Res regulates oestrogen metabolism by activating the MAPK/ERK pathway. This finding provides a new perspective for subsequent research on the treatment of endometrial cancer.

Resveratrol Ameliorates Retinal Ischemia-Reperfusion Injury by Modulating the NLRP3 Inflammasome and Keap1/Nrf2/HO-1 Signaling Pathway.

Glaucoma, as an ischemia-reperfusion (I/R) injury disease, leading irreversible blindness through the loss of retinal ganglion cells (RGCs), mediated by various pathways. Resveratrol (Res) is a polyphenolic compound that exerts protective effects against I/R injury in many tissues. This article aimed to expound the underlying mechanisms through which Res protects RGCs and reduces visual dysfunction in vivo. An experimental glaucoma model was created using 6-8-week wild-type male C57BL/6J mice. Res was injected intraperitoneally for 5 days. The mice were then grouped according to the number of days after surgery and whether Res treatment was administered. We applied the Brn3a-labeled immunofluorescence staining and flash electroretinography (ERG) to assess the survival of RGCs and visual function. The expression of components of the NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome, the interleukin-1-beta (IL-1β), and vital indicators of kelch-like ECH-associated protein 1 (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2)/heme-oxygenase 1 (HO-1) pathway at the protein and RNA levels were detected respectively. The survival of RGCs was reduced after surgery compared to controls, whereas Res application rescued RGCs and improved visual dysfunction. In conclusion, our results discovered that Res administration showed neuroprotective effects through inhibition of the NLRP3 inflammasome pathway and activation of Keap1/Nrf2/HO-1 pathway. Thus, we further elucidated the potential of Res in glaucoma therapy.

Resveratrol ameliorates ulcerative colitis by upregulating Nrf2/HO‑1 pathway activity: Integrating animal experiments and network pharmacology.

Ulcerative colitis (UC) is a chronic idiopathic inflammatory condition affecting the rectum and colon. Inflammation and compromisation of the intestinal mucosal barrier are key in UC pathogenesis. Resveratrol (Res) is a naturally occurring polyphenol that exhibits anti‑inflammatory and antioxidant properties. Nuclear factor erythroid‑2‑related factor 2/heme oxygenase 1 (Nrf2/HO‑1) pathway regulates occurrence and development of numerous types of diseases through anti‑inflammatory and antioxidant activity. However, it is not clear whether Nrf2/HO‑1 pathway is involved in the treatment of Res in UC. Therefore, the present study aimed to investigate whether Res modulates the Nrf2/HO‑1 signaling pathway to attenuate UC in mice. Dextran sulfate sodium (DSS) was used to induce experimental UC in male C57BL/6J mice. Disease activity index (DAI) and hematoxylin eosin (H&E) staning was used to assessed the magnitude of colonic lesions in UC mice. ELISA) was utilized to quantify inflammatory cytokines (IL‑6, IL‑1β, TNF‑α and IL‑10) in serum and colon tissues. Immunohistochemistry and Western blot were used to evaluate the expression levels of tight junction (TJ) proteins [zonula occludens (ZO)‑1 and Occludin] in colon tissues. Pharmacokinetic (PK) parameters of Res were derived from TCMSP database. Networkpharmacology was employed to identify the biological function and pharmacological mechanism of Res in the process of relieving UC, and the key target was screened. The binding ability of Res and key target was verified by molecular docking. Finally, the effectiveness of key target was substantiated by Western blot. Res decreased DAI, ameliorated histopathological changes such as crypt loss, disappeatance of the mucosal epithelium, and inflammatory infiltration in mice. Additionally, Res decreased expression of pro‑inflammatory cytokines IL‑6, IL‑1β and TNF‑α and increased anti‑inflammatory factor IL‑10 expression. Res also restored the decreased protein expression of ZO‑1 and occludin after DSS treatment, increasing the integrity of the intestinal mucosal barrier. The PK properties of Res suggested that Res possesses the therapeutic potential for oral administration. Network pharmacology revealed that Res alleviated UC through anti‑inflammatory and antioxidant pathways, and confirmed that Nrf2 has a high binding affinity with Res and is a key target of Res against UC. Western blotting demonstrated that Res treatment increased the protein levels of Nrf2 and HO‑1. In conclusion, Res treatment activated the Nrf2/HO‑1 pathway to decrease clinical symptoms, inflammatory responses, and intestinal mucosal barrier damage in experimental UC mice.

Biotransformation of roxarsone by earthworms and subsequent risk of soil arsenic release: The role of gut bacteria

The organoarsenical feed additive roxarsone (ROX) is a ubiquitous threat due to the unpredictable levels of arsenic (As) released by soil bacteria. The earthworms representing soil fauna communities provide hotspots for As biotransformation genes (ABGs). Nonetheless, the role of gut bacteria in this regard is unclear. In this study, the changes in As speciation, bacterial ABGs, and communities were analyzed in a ROX-contaminated soil (50 mg/kg As in ROX form) containing the earthworm Eisenia feotida. (RE vs. R treatment). After 56 d, earthworms reduced the levels of both ROX and total As by 59 % and 17 %, respectively. The available As content was 10 % lower in the RE than in R treatment. Under ROX stress, the total ABG abundance was upregulated in both earthworm gut and soil, with synergistic effects observed following RE treatment. Besides, the enrichment of arsM and arsB genes in earthworm gut suggested that gut bacteria may facilitate As removal by enhancing As methylation and transport function in soil. However, the bacteria carrying ABGs were not associated with the ABG abundance in earthworm gut indicating the unique strategies of earthworm gut bacteria compared with soil bacteria due to different microenvironments. Based on a well-fit structural equation model (P = 0.120), we concluded that gut bacteria indirectly contribute to ROX transformation and As detoxification by modifying soil ABGs. The positive findings of earthworm-induced ROX transformation shed light on the role of As biomonitoring and bioremediation in organoarsenical-contaminated environments.

Dietary resveratrol improves immunity and antioxidant defense in ewes by regulating the rumen microbiome and metabolome across different reproductive stages.

Resveratrol (Res), a natural plant antitoxin polyphenol, is widely used in animal husbandry due to its antioxidant and anti-inflammatory properties, and current research has focused on humans, sows, and female mice. This study aimed to analyze the effects of dietary Res supplementation in ewes on antioxidant activity, immune responses, hormone levels, rumen microbiota and metabolites across various reproductive stages (estrus, pregnancy, and lactation). Twenty-four healthy ewe lambs (Hu sheep, 2 months old) with a similar body weight (BW) (mean: 21.79 ± 2.09 kg) were selected and randomly divided into two groups: the control group (Con) and the Res group (Res). The Res group received 10 mg/kg Res (based on BW) in addition to their basal diet. Res increased the levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E2) in ewes at sexual maturity (p < 0.05). Additionally, Res supplementation induced significant increases in serum glutathione peroxidase (GSH-Px), IgG, FSH, and LH levels during estrus (p < 0.05); serum IgA, IgG and IgM during pregnancy and lactation (p < 0.05); and serum LH, glucose, GSH-Px, and catalase (CAT) levels during lactation (p < 0.05). Meanwhile, serum interleukin 1β (IL-1β) (p =0.005) and cholesterol levels (p = 0.041) during the lactation stage decreased following Res supplementation. Notably, colostrum IgA, IgG, and fat concentrations were significantly higher in the Res group than in the Con group (p < 0.05). Moreover, Res altered the rumen microbiota in ewes. Specifically, the relative abundance of Prevotella (p < 0.05) during pregnancy and Rikenellaceae_RC9_gut_group (p < 0.001) during lactation were significantly increased in ewes under Res treatment. The abundance of Rikenellaceae_RC9_gut_group was positively correlated with the levels of Ig A, Ig M, E2, FSH, LH, GSH-PX, and CAT. Additionally, Res altered the activity of metabolic pathways such as progesterone-mediated oocyte maturation, the estrogen signaling pathway, ovarian steroidogenesis, and the AMPK signaling pathway, and the levels of AICAR and 2-hydroxyestradiol metabolites, both during pregnancy and lactation. There findings show that Res can improve health, antioxidant status, and immune activity throughout the reproductive cycle in ewes by regulating rumen microorganisms and metabolites.

The Important Role of Hemispherotomy for Rasmussen Encephalitis: Clinical and Functional Outcomes

BackgroundRasmussen encephalitis (RE) is characterized by pharmacoresistant epilepsy and progressive neurological deficits concurrent with unilateral hemispheric atrophy. Evidence of an inflammatory autoimmune process has been extensively described in the literature; however, the precise etiology of RE is still unknown. Despite data supporting a beneficial effect of early immunosuppressive and immunomodulatory interventions, surgical disconnection of the affected hemisphere is considered the treatment of choice for these patients. The aim of this study was to report a series of children and adolescents who underwent hemispheric surgery (HS) for the treatment of RE, analyzing their clinical, electrographic, and neuroimaging features pre-operatively, as well as their postoperative status, including seizure and functional outcomes. MethodsAll patients with RE who underwent HS in the Epilepsy Surgery Center (CIREP) of the University Hospital of Ribeirão Preto Medical School, between 1995 and 2020 were retrospectively reviewed. Preoperative and postoperative analyses included gender; age at epilepsy onset; seizure semiology; seizure frequency; interictal and ictal electroencephalographic (EEG) findings; age at surgery; duration of epilepsy; surgical complications; duration of follow-up; histopathological findings; and postoperative seizure, cognitive, and functional outcomes. ResultsForty-four patients were evaluated. Mean age at seizure onset and epilepsy duration was 6 years and 2.5 years, respectively. Mean age at surgery was 9 years, with an average follow-up ranging from 3 months to 23 years. All patients presented with severe epilepsy and distinct neurological abnormalities on MRI. Before HS, different degrees of abnormal intellectual performance as well as hemiparesis were seen in 86% and 90%, respectively. Histopathology examination confirmed this diagnosis in 95% patients. At the last follow-up, 68% of patients were seizure free, and 70% were classified as Engel Class I or II. Postoperatively, the cognitive status remained unchanged in 64% of patients. Likewise, the gross motor function remained unchanged in 54% of patients and 74% had functional hand ability after HS. ConclusionsConsidering the progressive damage course of RE, hemispheric surgery should be offered to pediatric patients. It has manageable risks and results in good seizure outcome, and the preoperative functional status of these children is often preserved (even when the left hemisphere is involved), thus improving their quality of life.

Multidisciplinary management in the treatment of intrahepatic cholangiocarcinoma.

Multidisciplinary management in the treatment of intrahepatic cholangiocarcinoma.

Resveratrol Improves Paclitaxel-Induced Cognitive Impairment in Mice by Activating SIRT1/PGC-1α Pathway to Regulate Neuronal State and Microglia Cell Polarization.

This study aimed to investigate the effect of resveratrol (Res) on paclitaxel (PTX)-induced cognitive impairment and elucidate the underlying molecular mechanisms. Morris Water Maze (MWM) test was used to evaluate the mice's spatial learning and memory abilities. Western blotting was applied to detect protein expression of receptor-interacting protein (RIP3), mixed lineage kinase domain-like protein (MLKL), silencing information regulator 2 related enzyme 1 (SIRT1), peroxisome proliferator activated receptor coactivator-1 (PGC-1α), NADPH oxidase 2 (NOX2), NOX4, postsynaptic density zone 95 (PSD95), arginase-1 (Arg-1) and inducible nitric oxide synthase (iNOS). Immunofluorescence of RIP3, MLKL, Arg-1, Iba-1 and iNOS was conducted to observe the apoptosis of hippocampal cells and the polarization of microglia. qRT-PCR was performed to detect BDNF mRNA expressions. DHE staining was used to assess the level of oxidative stress response. Golgi-Cox staining and dendritic spine counting were applied to visualize synaptic structural plasticity. Postsynaptic density was performed by transmission electron microscope. ELISA was used to detect the contents of tumour necrosis factor alpha (TNF-α), IL-1β, IL-4, and IL-10. PTX-induced cognitive impairment model was constructed after the application of PTX, represented as longer latency to platform and less platform crossing times over the whole period in PTX group. After Res treatment, the above indicators were reversed, indicating that cognitive function was improved. Moreover, Res reduced neuronal apoptosis and oxidative stress through SIRT1/PGC-1α pathway in mice, manifesting as down-regulated expression of RIP3, MLKL, NOX2 and NOX4. Meanwhile, Res increased the density of dendritic spines and the expression of PSD95 and BDNF, thereby ameliorating the PTX induced synaptic damage. Besides, M2 microglia was in the majority, eliciting the expression of anti-inflammatory cytokines IL-4 and IL-10 after Res treatment in PTX+Res group, while immunofluorescence images results demonstrated an decrease in the proportion of M2 microglia a following SIRT1 inhibitor EX-527. Res improves PTX-induced cognitive impairment in mice by activating SIRT1/PGC-1α pathways to regulate neuronal state and microglia cell polarization.

Voxel-S-Value based 3D treatment planning methods for Y-90 microspheres radioembolization based on Tc-99m-macroaggregated albumin SPECT/CT

Partition model (PM) for Y-90 microsphere radioembolization is limited in providing 3D dosimetrics. Voxel-S-Values (VSV) method has good agreement with Monte Carlo (MC) simulations for 3D absorbed dose conversion. We propose a new VSV method and compare its performance along with PM, MC and other VSV methods for Y-90 RE treatment planning based on Tc-99m MAA SPECT/CT. Twenty Tc-99m-MAA SPECT/CT patient data are retrospectively analyzed. Seven VSV methods are implemented: (1) local energy deposition; (2) liver kernel; (3) liver kernel and lung kernel; (4) liver kernel with density correction (LiKD); (5) liver kernel with center voxel scaling (LiCK); (6) liver kernel and lung kernel with density correction (LiLuKD); (7) proposed liver kernel with center voxel scaling and lung kernel with density correction (LiCKLuKD). Mean absorbed dose and maximum injected activity (MIA) obtained by PM and VSV are evaluated against MC results, and 3D dosimetrics generated by VSV are compared with MC. LiKD, LiCK, LiLuKD and LiCKLuKD have the smallest deviation in normal liver and tumors. LiLuKD and LiCKLuKD have the best performance in lungs. MIAs are similar by all methods. LiCKLuKD could provide MIA consistent with PM, and precise 3D dosimetrics for Y-90 RE treatment planning.

Long-term outcomes of robot-assisted and laparoscopic operations for cardiofundal and subtotal hiatal hernias

Aim. To compare the long-term outcomes and qualitive of life (QOL) of robot-assisted fundoplication (RAF) and laparoscopic fundoplication (LF) in patients with cardiofundal and subtotal hiatal hernias (HH). Materials and methods. The study included 62 patients with HH, who underwent antireflux surgery in the clinic of Faculty Surgery No. 1 of Sechenov University in the period from January 2015 to February 2021. The main group included 32 patients who underwent robot-assisted fundoplication (RAF) according to A. F. Chernousov, the comparison group included 30 patients who underwent laparoscopic fundoplication (LF). Complaints of the patient, X-ray, endoscopic studies, PH-impedance-metry in the long-term period were evaluated. To assess the quality of life, the questionnaires SF 36 (The Short Form-36) and GERD-HRQL (Health-Related Quality of Life in Patients with Gastroesophageal Reflex Disease) were used. Results. Periodic heartburn in the long-term period was noted by 2 (6%) patients of the RAF group and 4 (13%) in the LF group. Endoscopic signs of mild esophagitis were detected in 1 (3%) patient from each group. X-ray in 9 (28%) patients of the RAF group and 11 (37%) patients of the LF group showed migration of the esophageal-gastric junction above the diaphragm level with complete preservation of the antireflux function of the fundoplication cuff. The QOL indicators of the SF 36 questionnaire did not differ in both groups and were comparable to the population of “conditionally healthy” people. The indicators of the GERD-HRQL questionnaire were better in the RAF group, but the differences had no statistical significance (RAF - 2.53 ± 5.1 points versus LF - 5.23 ± 9.4 points, p-value = 0.321). Conclusion. RAF and LF in the modification of A. F. Chernousov are equally effective in the treatment of RE and GPOD in the long-term period and provide good indicators of quality of life that do not differ statistically from each other.

Radial Extracorporeal Shock Wave Therapy Combined with Resveratrol Derivative Alleviates Chronic Nonbacterial Prostatitis in Rats.

Resveratrol (Res) is a non-flavonoid polyphenol compound with biological pleiotropic properties, but low bioavailability limits its application value. Here, we synthesized a new Res derivative ((E)-5-(dimethylamino)-2-(4-methoxystyryl)phenol), and attempted to determine the function of Res derivative combined with radial extracorporeal shock wave therapy (rESWT) in chronic nonbacterial prostatitis (CNP). CNP model rats were constructed by subcutaneous administration of prostatein suspension (15mg/ml), followed by rESWT treatment alone or in associated with Res or Res derivatives. In this study, inflammatory cell infiltration and tissue fibrosis in the prostate tissues of CNP rats were significantly deteriorated, which was effectively abolished by rESWT treatment alone or in combination with Res or Res derivative. The expression of interleukin 1β (IL-1β), tumor necrosis factor-α (TNF-α), nerve growth factor (NGF), and nuclear factor kappa-B (NF-κB) were increased, while silent information regulator 1 (SIRT1) expression was suppressed in the prostate tissues of CNP rats, which were then rescued by rESWT treatment alone or in associated with Res or Res derivative. Importantly, compared with Res derivative treatment alone or rESWT combined with Res treatment, combination treatment with rESWT and Res derivative was more effective in alleviating inflammation and fibrosis, in reducing IL-1β, TNF-α, NGF, and SIRT1 expression, and in facilitating SIRT1 expression. Overall, rESWT combined with Res derivative treatment improved CNP in rat by reducing inflammation and fibrosis, which attributed to regulate the expression of SIRT1 and NF-κB. Thus, this work provides a theoretical basis for rESWT combined with Res derivative in the clinical treatment of CNP.

Resveratrol alleviates bleomycin-induced pulmonary fibrosis by inhibiting epithelial-mesenchymal transition and down-regulating TLR4/NF-κB and TGF-β1/smad3 signalling pathways in rats

BackgroundPulmonary fibrosis (PF) is a difficult clinical condition with no effective treatment and a high mortality rate. Patients usually die of respiratory failure. In the present, we hypothesized that resveratrol (Res) could suppress bleomycin (BLM)-induced PF in rats and examined the detailed mechanism. MethodsThe successfully established BLM-induced PF rat models and normal healthy rats were randomly assigned into the control, model, Res-low, Res-medium, and Res-high groups. The extent of PF in rats was determined by Masson and H&E staining. ELISA was used to detect changes in the inflammatory factors IL-1β, IL-6, TNF-α, SOD, and GSH-PX in lung tissue. Microscopic lung fibrosis scoring was done using the Ashcroft scale. Western blotting and RT-qPCR assays were used to analyze the effects of Res on the epithelial-mesenchymal transition (EMT). ResultsThe administration of Res ameliorated the BLM-induced PF in vivo. Res could inhibit pro-inflammatory factors and regulates oxidative stress levels. It also revealed that Res downregulated Vimentin and upregulated E-cadherin expression. Res inhibited fibrosis and inflammatory responses in rat lung tissue. The activation of the TLR4/NF-κB and TGF-β1/smad3 signaling pathways were inhibited following Res treatment. ConclusionThe present study suggested that Res may protect against BLM-induced PF by inhibiting the EMT and down-regulating the TLR4/NF-κB and TGF-β1/smad3 signaling pathways.

The Neuroprotective Role of Purslane in a chronic model of Depression Induced By reserpine in mice: Prevention of Behavioral, Mitochondrial and Neuro Dysfunction.

Portulaca oleracea is a universal species with a broad range of biological activities, including antioxidant and neuroprotective actions. The present study aimed to estimate the neuroprotective effect of purslane ethanolic extract (PEE) and aqueous extract (PAE) on depression model induced by reserpine. Methods: Seventy five male mice were divided into 5 groups (15 mice of each). 1st group control (C), 2nd group treated with reserpine 0.1 mg/kg (Res) as a single dose at the day 15th of the beginning of experiment, 3rd group treated with Escitalopram 1mg/kg for 15 days plus 0.1 mg/kg Res at a latest day of the treatment. 4th group treated with PEE 2 mg/kg for 15 days plus 0.1 mg/kg Res at a latest day of the treatment. 5th group treated with PAE 5 g/kg for 15 days plus 0.1 mg/kg Res at a latest day of the treatment. Forced swimming test (FST) was performed 1 hour later after Res treatment. Results: Revealed data showed that the Res treated group induced significant (P&gt;0.05) decrease in FST, decrease of brain monoamines [norepinephrine (NE), dopamine (DA) and serotonin (5HT)], brain cell energy [adenosine triphosphate (ATP)] increase metabolic energy [adenosine diphosphate (ADP) and adenosine monophosphate (AMP)]. On the other hand other treatment groups showed significant amelioration in comparing with Res group and almost recovery in comparing with control group. Conclusion: Obtained data concluded that PEE more potent than PAE, ameliorate depression induced by reserpine and act as a neuroprotective, neuromodulator and stimulate monoamines secretion.

Mesoporous Silica Nanoparticles Loaded with Resveratrol Are Used for Targeted Breast Cancer Therapy.

Objective The characteristics of poor pharmacokinetics, stability, and low solubility seriously limited the clinical application of resveratrol (Res) in breast cancer. Thus, this study intends to develop a delivery system for Res which could be better used in breast cancer therapy. Methods Resveratrol-modified mesoporous silica nanoparticles (MSN-Res) were chemically constructed. Their shape and encapsulation were detected by transmission electron microscope, Fourier transforms infrared spectrometer, and UV spectroscopy, respectively. MGF-7 tumor-bearing mice were established by subcutaneous injection, and the pathological changes were detected by hematoxylin-eosin staining. CCK-8 and Ki-67 immunohistochemical staining were used for proliferation evaluation in vitro and in vivo. Flow cytometry, TUNEL, wound healing, and transwell assay detected cell apoptosis, invasion, and migration. Results MSN-Res was successfully prepared with high biosafety. MSN-Res inhibited MGF-7 cell proliferation, invasion, and migration and promoted apoptosis in vitro. Furthermore, MSN-Res showed better performance compared Res in breast cancer mouse models. In addition, we found that MSN-Res inhibited tumor growth via inhibiting the NF-κB signaling pathway. Conclusion MSN-Res inhibited breast cancer progression with better efficacy compared with Res treatment alone by inhibiting the NF-κB signaling pathway, suggesting that MSN-Res is a more effective adjuvant treatment method for breast cancer. Thus, our findings may provide a new and safer means of using phytochemicals in combinatorial therapy of breast cancer.

Research progress on the mechanism of radiation enteritis.

Radiation enteritis (Re) is one of the most common complications of radiation therapy for abdominal tumors. The efficacy of cancer treatment by radiation is often limited by the side effects of Re. Re can be acute or chronic. Treatment of acute Re is essentially symptomatic. However, chronic Re usually requires surgical procedures. The underlying mechanisms of Re are complex and have not yet been elucidated. The purpose of this review is to provide an overview of the pathogenesis of Re. We reviewed the role of intestinal epithelial cells, intestinal stem cells (ISCs), vascular endothelial cells (ECs), intestinal microflora, and other mediators of Re, noting that a better understanding of the pathogenesis of Re may lead to better treatment modalities.

Resveratrol alleviates pyraclostrobin-induced lipid peroxidation, oxidative stress, and DNA damage in rats.

Pyraclostrobin (Pyra) is a fungicide in the strobilurin class and has proven to be very toxic to organisms primarily aquatic species. Resveratrol (Res) is a phytoalexin that exhibits multiple bioactivities as anti-oxidative, anti-inflammatory, cardiovascular protective, and anti-aging and is found in plant species such as mulberry, peanut, and grape. This study aimed to determine the protective effect of Res against Pyra-induced lipid peroxidation, oxidative stress, and DNA damage in rats. For this purpose, a total of 48 male rats divided into 6 groups - 8 in each group - were exposed to 30 mg/kg Pyra by oral gavage once a day for 30 days and to three different concentrations of Res (5, 10, and 20 mg/kg) together with Pyra. Pyra administration increased liver enzyme parameters and malondialdehyde (MDA) levels whereas decreased glutathione (GSH) levels and activities of superoxide dismutase (SOD) and catalase (CAT). Also, Pyra treatment increased pro-apoptotic (Bax), apoptotic (Caspase-3, Caspase-8, and Caspase-9), pro-inflammatory (NFκB), cancer (CYP2E1), and cell regulatory (p53) gene expressions and decreased anti-apoptotic (Bcl-2) gene expression in the liver. Furthermore, DNA damage in blood and histopathological changes in the liver and kidney were observed with Pyra administration. In contrast, Res administrations in a dose-dependent manner improved Pyra-induced lipid peroxidation, oxidative and DNA damages, expression levels of these genes in the liver, and histopathological changes in the liver and kidney. Consequently, the treatment of Res, known for its anti-oxidant and protective properties, exhibited a protective effect on Pyra-induced lipid peroxidation, oxidant/anti-oxidant status, gene expressions, and DNA damage in rats.

Protective effect of resveratrol against cadmium-induced toxicity on ovine oocyte in vitro maturation and fertilization

BackgroundHeavy metal cadmium (Cd) is a widespread environmental contaminant with a potential toxicity that might negatively affect female reproduction and fertility. It has been reported that Cd exposure impaired the quality of oocytes and led to a defective maturation and fertilization, through oxidative stress induction. Resveratrol (Res) is a natural polyphenol with strong antioxidant properties that exhibited protective role in preventing oocyte redox homeostasis disruption and quality decline. Here, we explored whether the addition of Res to in vitro maturation (IVM) medium might act as a protection against Cd-induced toxicity on ovine oocyte maturation and fertilization. Firstly, we evaluated the effect of supplementing IVM medium with two different Res concentrations (1 and 2 μmol/L) on nuclear maturation and fertilization of oocytes matured under CdCl2 (2 μmol/L) exposure. Therefore, the concentration of 1 μmol/L Res was selected to analyse the effects of this compound on intracellular ROS levels, mitochondrial (mt) distribution and activity, chromatin configuration, cytoskeleton morphology, cortical granules (CGs) distribution and mRNA expression of genes associated with cellular response to oxidative stress (i.e. SIRT1, SOD 1, GPX1, GSR, CAT) in Cd-exposed in vitro matured oocytes.ResultsWe found that 1 μmol/L Res restored the reduced oocyte meiotic competence induced by Cd exposure as well as, Res sustained oocyte ability to be normally fertilized and decreased polyspermic fertilization at both tested concentrations. Moreover, we demonstrated that 1 μmol/L Res mitigated Cd-induced alterations of oocyte cytoplasmic maturation by reducing reactive oxygen species (ROS) accumulation, preventing mt dysfunction, maintaining the correct meiotic spindle and cortical F-actin assembly and the normal cortical granule distribution as well as up-regulating SIRT1, SOD1 and GPX1 genes.ConclusionsTaken together, our findings highlighted the beneficial influence exerted by Res in preventing Cd-induced disturbance of nuclear and cytoplasmic maturation and subsequent fertilization in ovine oocytes. Res treatment may help to establish defence strategies counteracting Cd-induced toxicity on the female gamete.

Resveratrol Modulates Bone Mineral Density and Bone Mineral Content in A Rat Model of Male Hypogonadism.

To determine whether resveratrol (Res) can correct osteoporosis induced in a rat model of male hypogonadism. Thirty-two rats were randomly divided into 4 groups, 8 in each group; 1) a control sham group: underwent a similar surgical procedure for induction of orchiectomy (ORCD) without ligation of any arteries or veins or removal of the testis and epididymis; 2) a control + Res-treated group (Con+Res): underwent sham surgery similar to the control, but was then treated with Res, as described below; 3) an ORCD-induced group: bilateral ORCD surgery as described above, and 4) a ORCD+Res-treated group: bilateral ORCD surgery followed by Res treatment. Res treatment began 4 weeks after ORCD and continued for 12 weeks. After 12 weeks, bone mineral density (BMD) and bone mineral content (BMC) were measured in the tibia and femur of each rat's right hind leg. Blood levels of bone turnover indicators such as deoxypyridinoline (Dpd), N-telopeptide of type I collagen (NTX I), alkaline phosphatase (ALP), and osteocalcin (OC), as well as receptor activator of nuclear factor kappa B (RANK) and osteoprotegerin (OPG) were assessed. ORCD significantly decreased BMD (P<0.01) and significantly increased bone resorption, manifested by increased RANK. In addition, it inhibited serum levels of OPG and OC. Res treatment after ORCD effectively increased serum levels of bone formation markers such as OPG and OC, compared with testisectomized rats (P<0.05). Res could ameliorate bone loss induced by male hypogonadism, possible via restoration of the normal balance between RANK and OPG.