Sham-operated Control Group Research Articles

Adipose-derived stem cell and their extracellular vesicles ameliorates immune function, and cardiac markers in experimental model of cardiorenal syndrome type III: TNF-α, IFN-γ and IL-10 cytokine production and their correlation with genotype

Cardio-renal syndrome (CRS) denotes the convergence of heart-kidney interactions across several mechanisms. The current study is conducted to evaluate the anti-inflammatory role of adipose tissue-derived stem cells (ASCs) versus adipose stem cell-derived extracellular vesicles (ADSCs-EVs) in experimental model of cardiorenal syndrome type III. The study was conducted on 50 male rats that were equally divided to: group I (control group); Group II (experimental cardiorenal syndrome group) which induced by right renal artery ligation (ICRSIII); Group III (Sham-operated control group) which underwent surgical incision without renal artery ligation; Group IV (ICRSIII which received ADSCs-extracellular vesicles (ADSCs-EVs); Group V (ICRSIII which received adipose tissue stem cells (ASCs). Assessment of pro-inflammatory cytokines; IL-10, IL-1α, IL-6, IL-1 β, IFN-γ, NF-α and their mRNA gene expression quantitation, (NGAL), and brain natriuretic peptide (BNP) as markers of cardiac dysfunction, as well as histopathological examination of renal tissue was examined by H& E, Masson trichrome and periodic acid-Schiff stains (PAS). The ICRS group exhibited significant acute tubular injury with tubular dilation, loss of brush borders, epithelial flattening, and occasional sloughed cells in lumen. Use of either ADSCs-EVs or ASCs significantly ameliorated the histological findings of tubular injury. Proinflammatory cytokines, BNP and NGAL were significantly elevated in ICRSIII group as compared to all other studied groups. Administration of ADSCs-EVs or ASCs led to significant decrease in all proinflammatory cytokines as well as BNP and NGAL levels with no significant difference between them. In conclusion, ADSCs-EXs and ASCs exhibited significant repairing effects in experimental-induced cardiorenal syndrome type III as evidenced by amelioration of histological findings of tubular injury, anti-inflammatory effects, and the significant decrease in markers of cardiac dysfunction. ADSC-EVs reprogramed injured cardiac cells by activating regenerative processes.

Effect of oligonol, a lychee-derived polyphenol, on skeletal muscle in ovariectomized rats by regulating body composition, protein turnover, and mitochondrial quality signaling.

Oligonol is a low‐molecular‐weight polyphenol product derived from lychee (Litchi chinensis Sonn.) fruits. This study was focused on the effects of oligonol on the skeletal muscle of ovariectomized rats. We randomly divided female Sprague–Dawley rats into three groups: a sham surgery control group (Sham), an ovariectomy (OVX) group, and an OVX group treated with oligonol (OVX + Oligonol). Oligonol was intraperitoneally administrated at 30 mg/kg daily for 6 weeks. Oligonol treatment after OVX decreased body weight and fat mass, regulated lipid metabolism in skeletal muscle, without loss of lean mass and bone. Bone turnover was not affected by oligonol. In protein synthesis and degradation, oligonol increased the levels of the mammalian target of rapamycin and its downstream targets, eukaryotic initiation factor 4E‐binding protein 1 and 70‐kDa ribosomal protein S6 kinase, and it stimulated the expression of ubiquitin‐proteasome pathway proteins, the forkhead box transcription factors of the class O and the muscle ring‐finger protein‐1. Moreover, oligonol treatment enhanced mitochondrial biogenesis and dynamics. Thus, our results indicated that oligonol treatment had beneficial effects on the skeletal muscle in an estrogen‐deficiency rat model.

Urethral injection of dedifferentiated fat cells ameliorates sphincter damage and voiding dysfunction in a rat model of persistence stress urinary incontinence

PurposeDedifferentiated fat (DFAT) cells are mature adipocyte-derived multipotent cells that can be applicable to cell-based therapy for stress urinary incontinence (SUI). This study developed a persistence SUI model that allows long-term evaluation using a combination of vaginal distention (VD) and bilateral ovariectomy (OVX) in rats. Then, the therapeutic effects of DFAT cell transplantation in the persistence SUI model was examined.MethodsIn total, 48 Sprague–Dawley rats were divided into four groups and underwent VD (VD group), bilateral OVX (OVX group), VD and bilateral OVX (VD + OVX group), or sham operation (Control group). At 2, 4, and 6 weeks after injury, leak point pressure (LPP) and histological changes of the urethral sphincter were evaluated. Next, 14 rats undergoing VD and bilateral OVX were divided into two groups and administered urethral injection of DFAT cells (DFAT group) or fibroblasts (Fibroblast group). At 6 weeks after the injection, LPP and histology of the urethral sphincter were evaluated.ResultsThe VD + OVX group retained a decrease in LPP with sphincter muscle atrophy at least until 6 weeks after injury. The LPP and urethral sphincter muscle atrophy in the DFAT group recovered better than those in the fibroblast group.ConclusionsThe persistence SUI model was created by a combination of VD and bilateral OVX in rats. Urethral injection of DFAT cells inhibited sphincter muscle atrophy and improved LPP in the persistence SUI model. These findings suggest that the DFAT cells may be an attractive cell source for cell-based therapy to treat SUI.

The neuroprotection of electro-acupuncture via the PGC-1α/TFAM pathway in transient focal cerebral ischemia rats

ATP depletion is one of the pathological bases in cerebral ischemia. Electro-acupuncture (EA) is widely used in clinical practice for ischemia. However, the mechanism of EA remains unclear. The purpose of this study was to investigate whether EA could activate the AMPK/PGC-1α/TFAM signaling pathway and, consequently, increase the preservation of ATP in rats with ischemia. In this study, 48 rats were randomly divided into four groups as a sham-operation control group (sham group), a middle cerebral artery occlusion group (MCAO group), an EA group, and an EA group blocked by the AMPK inhibitor compound C (EA + CC group) (N = 12/group). The rats of the EA group and EA + CC group received the EA treatment for 7 days. The rats that belonged in the two remaining groups were only grasped in the same condition. Then, their brain tissues were collected for further detection. When compared with other groups, EA significantly reduced neurological deficits score and increased motor function. The cerebral infarction volume was significantly reduced in the EA group according to TTC staining. With western blot, we found that EA improved the ratio of p-AMPKα/AMPKα (P < 0.05), however, there is no difference between the MCAO group and sham group (P > 0.05). In addition, EA also increased the expression of PGC-1α and TFAM (all P < 0.05). By Elisa, we observed that EA increased the preservation of ATP (P < 0.05) and mitochondrial respiratory enzymes, including Complex I (P < 0.05), Complex IV (P < 0.05), but not Complex III (P > 0.05). In summary, we conclude that EA may protect against ischemic damage in MCAO rats, improve the preservation of ATP and mitochondrial respiratory enzymes. This effect may be positively regulated by the activation of the PGC-1α/TFAM signaling pathway.

Imaging of Heart Type Fatty Acid Binding Protein Under Acute Reperfusion Ischemia Using Radio-labeled Antibody in Rat Heart Model.

Purpose: Heart-type fatty acid binding protein (H-FABP) is primary transporter of free fatty acid and plays an important role in myocardial metabolism, which is characterized by high specificity and rapid appearance under ischemic condition. The objective of this study was to clarify the usefulness of imaging study of targeting H-FABP appearance using radio-labeled antibody, and correlation with myocardial fatty acid metabolism and perfusion in acute reperfusion ischemia. Method: Wistar rats were allotted to sham-operated control group (sham; n=4), ischemia non-reperfused group (IG; n=5), and ischemia-reperfusion group (RG; n=5). Ligation of left coronary artery (LCA) was performed for IG and RG. 20 min of ischemia was followed by 60min of reperfusion for RG. 125I labeled anti H-FABP antibody (anti H-FABP), BMIPP and 99mTc-sestamibi (MIBI) was injected intravenously. Multi-tracer digital autoradiogram was performed using µ-imager®. The ratio of radioactivity in LCA related (culprit) area to the inferior (remote) area (target uptake ratio=TUR) was generated. Results: In sham group, no visually detectable accumulation was observed for the anti H-FABP image, and TURMIBI and TURBMIPP were equivalent to 1. In IG, TURMIBI and TURBMIPP were remarkably low (0.12±0.01, 0.24±0.07). In RG, TURMIBI was significantly lower (0.20±0.03, p<0.05 vs. other groups). However, TURBMIPP was significantly higher (2.78±1.28, p<0.05) compared to the sham and IG, whereas anti H-FABP showed markedly higher ratio in the reperfused area compared to the sham and IG (3.43±0.73 vs. 0.31±0.13 and 1.09±0.07 for IG and sham; p<0.05, and <0.01, respectively). Conclusion: Anti H-FABP accumulated specifically in reperfused area under acute ischemia, and it accorded to the area where fatty acid metabolism was activated. This study has shown the future potential for clinical application in vivo imaging of acute coronary syndrome.

Bone marrow mesenchymal stem cell therapy regulates gut microbiota to improve post-stroke neurological function recovery in rats

BACKGROUNDAs a cellular mode of therapy, bone marrow mesenchymal stem cells (BMSCs) are used to treat stroke. However, their mechanisms in stroke treatment have not been established. Recent evidence suggests that regulation of dysregulated gut flora after stroke affects stroke outcomes.AIMTo investigate the effects of BMSCs on gut microbiota after ischemic stroke.METHODSA total of 30 Sprague-Dawley rats were randomly divided into three groups, including sham operation control group, transient middle cerebral artery occlusion (MCAO) group, and MCAO with BMSC treatment group. The modified Neurological Severity Score (mNSS), beam walking test, and Morris water maze test were used to evaluate neurological function recovery after BMSC transplantation. Nissl staining was performed to elucidate on the pathology of nerve cells in the hippocampus. Feces from each group of rats were collected and analyzed by 16s rDNA sequencing.RESULTSBMSC transplantation significantly reduced mNSS (P < 0.01). Rats performed better in the beam walking test in the BMSC group than in the MCAO group (P < 0.01). The Morris water maze test revealed that the BMSC treatment group exhibited a significant improvement in learning and memory. Nissl staining for neuronal damage assessment after stroke showed that in the BMSC group, cells were orderly arranged with significantly reduced necrosis. Moreover, BMSCs regulated microbial structure composition. In rats treated with BMSCs, the abundance of potential short-chain fatty acid producing bacteria and Lactobacillus was increased.CONCLUSIONBMSC transplantation is a potential therapeutic option for ischemic stroke, and it promotes neurological functions by regulating gut microbiota dysbiosis.

Evaluation of the protective effects of gossypin for ischemia/reperfusion injury in ovary tissue.

Ovarian ischemia-reperfusion (I/R) injury is a serious gynecological condition that affects women of reproductive age and reduces ovarian reserve. Management of I/R injury with detorsion causes reperfusion damage, in which oxidative stress plays a central role. This study aimed to investigate whether the gossypin (GOS) with antioxidant properties, a flavonoid, has beneficial effects on the biochemical, molecular, and histopathological aspects of ovarian I/R injury. Thirty-three female Balb/c mice were randomly divided into five groups as follows: Healthy (Sham-operated control group), I/R (IR group), I/R + GOS 5 (I/R with GOS 5mg/kg), I/R + GOS 10 (I/R with GOS 10mg/kg), and I/R + GOS 20 (I/R with GOS 20 mg/kg). This was followed by 3h of ischemia and subsequent reperfusion for 3h after detorsion was exposed. GOS was injected 2h before reperfusion. IL-1β, IL-6, TNF-α, NF-κB, and CASP-3 mRNA expressions, SOD (superoxide dismutase) activity, GSH (glutathione), and MDA (malondialdehyde) levels, and histopathological changes were evaluated in ovarian tissue. Histological examination indicated that treatment of ovarian I/R injury with GOS led to the improvement of ovarian tissue, which was accompanied by an increase in SOD activity and GSH level and a decrease in MDA level, NF-κB, TNF-α, IL-1β, and IL-6 expressions. GOS was also corrected by reducing the elevated expression of CASP-3 as apoptosis-change marker. These findings indicate that the treatment of GOS may be useful as a conservative approach to reverse I/R injury via amelioration of oxidative stress parameters and histopathological scores, attenuation of inflammation, and the suppression of apoptosis.

Fingolimod protects against cerebral ischemia reperfusion injury in rats by reducing inflammatory cytokines and inhibiting the activation of p38 MAPK and NF-κB signaling pathways

Fingolimod (FTY720) is a sphingosine 1-phosphate (S1P) receptor agonist. Here, to understand biological activity of FTY720 pretreatment and post-treatment on cerebral ischemia reperfusion injury (CIRI), rat transient middle cerebral artery occlusion/reperfusion (tMCAO/R) model was generated. Neurological deficit scoring was assessed after tMCAO/R. Four groups were established including sham-operated control group, operated group, and two FTY720-treated groups. Neuron damage was observed by Nissl staining. Gene expression was measured using qPCR and western blot analysis. Tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β) and interleukin 6 (IL-6) levels were evaluated by enzyme-linked immunosorbent assay (ELISA). We uncovered that neurological score in two FTY720-treated groups was significantly lower than that in the operated group. FTY720 pretreatment or posttreatment groups had a significantly increased number of Nissl bodies in cerebral cortex as compared with the operated group, indicating that FTY720 administration reduced neuronal damage. Besides, FTY720 posttreatment improved memory impairment induced by tMCAO/R. In addition, IL-1β, IL-6, and TNF-α levels in the cerebral cortex and hippocampus of two FTY720-treated groups were significantly decreased in comparison to the operated group, showing that FTY720 could reduce the release of inflammatory cytokines in brain tissue. Furthermore, phosphorylation of p38MAPK and NF-κB pathway-related molecules in ischemic brain tissues of FTY720 group were markedly down-regulated compared to the operated group. Together, FTY720 pretreatment or posttreatment improved the neurological deficit of middle cerebral ischemia/reperfusion rat model and reduced neuronal damage by decreasing the levels of inflammatory cytokines and attenuating the phosphorylation levels of p38MAPK and NF-κB pathway-associated molecules. FTY720 exhibits neuroprotective effects against ischemic reperfusion injury in rats.

Therapeutic Effect of Combining Anisodamine With Neostigmine on Local Scar Formation Following Roux-en-Y Choledochojejunostomy in a Novel Rat Model.

Background: The present study aimed to explore the potential effect of combining anisodamine with neostigmine on local scar formation following Roux-en-Y choledochojejunostomy (RCJS) in a novel rat model. Methods: The biliary obstruction model of Sprague Dawley (SD) rats was established in advance, and 54 rats were divided into nine groups randomly (sham operation group, anisodamine group, neostigmine group, combination group, and control group). Anisodamine (25 mg/kg) and neostigmine (50 μg/kg) were injected to the abdominal cavity separately or simultaneously for 1 week since the first day after surgery according to their allocated intervention, while the same amount of saline (0.5 ml) was injected intraperitoneally in the control group. Indexes including body weight, the diameter of the common bile duct, liver function, inflammatory indexes, and the condition of scar formation in different groups at certain time were evaluated in our study. Results: Recovery of liver function (ALT, AST, TB, DB, and GGT) and systematic inflammation indexes (CRP, TNF-α, and IL-1β) in the combination group was prior to that in the control group (p < 0.05), while no statistical difference in the serum level of IL-10 was observed among groups. Rats in the combination group represented a wider anastomotic diameter and lower expression of α-SMA and TGF-β1 at anastomotic stoma compared to the control group (p < 0.05). Histopathological staining showed slighter proliferation of collagen and smooth muscle fibers in rats’ bile duct wall and less local scar formation at anastomotic stoma compared to the control group. Conclusion: The combination of anisodamine and neostigmine can alleviate local and systemic inflammatory response, promote the recovery of liver function, and reduce scar formation in rats after the RCJS procedure.

Neuropeptide W Attenuates Oxidative Multi-Organ Injury in Rats Induced with Intra-Abdominal Sepsis.

Sepsis leads to systemic hypotension, disturbed perfusion, inflammation, and tissue toxicity in vital organs. Neuropeptide W (NPW) has modulatory effects in the control of blood pressure and inflammatory processes, implicating a potential beneficial effect against sepsis-induced oxidative damage. Under anesthesia, male Sprague Dawley rats underwent cecal ligation and puncture. Immediately after surgery, either saline or TNF-alpha inhibitor (etanercept; 1 mg/kg) antibiotic (ceftriaxon; 10 mg/kg) combination or NPW (0.1, 1, or 3 μg/kg) was given subcutaneously, and injections were repeated on the 12thand 24thh. The sham-operated control group was treated with saline at the same time points. All rats were euthanized on the 25thh of surgery. Sepsis resulted in oxidative damage of the brain, heart, lung, liver, and kidney. Elevations in blood urea nitrogen and alkaline phosphatase, showing renal and hepatic dysfunction, were not evident when septic rats were treated with NPW. NPW reduced serum levels of C-reactive protein, corticosterone, and interleukin-6, while histopathologically verified tissue damage in all the studied tissues was ameliorated. NPW treatment suppressed lipid peroxidation in the heart, lung, and brain, and the depleted antioxidant GSH levels of the brain and heart were replenished by NPW. Moreover, sepsis-related neutrophil recruitment to the liver and lung was also suppressed by NPW. Although the survival rate of the rats was not significantly prolonged by NPW, most of these improvements in systemic and local inflammatory events were comparable with those reached by the etanercept and antibiotic combination, suggesting the therapeutic impact of NPW during the acute period of sepsis.

The neuroprotective effect and RNA-sequence analysis of postconditioning on the ischemic stroke with diabetes mellitus tree shrew model.

IntroductionPatients with comorbidity of ischemic stroke (IS) and diabetes mellitus (DM) show poor neurological functional recovery, and ischemic postconditioning (IPOC) should be considered a powerful neuroprotective method for IS. However, whether it should be introduced for patients with IS and DM remains controversial. This study established a DM with IS (DMIS) tree shrew model, which was intervened by IPOC to assess its neuroprotective effects and also to analyze the relevant mechanism by RNA‐sequence and bioinformatics analysis.MethodsFifty‐four tree shrews were randomly divided into a sham operation control group, a DMIS group, and an IPOC group (DMIS model), with 18 tree shrews per group. Triphenyl tetrazolium chloride (TTC), hematoxylin‐eosin (HE) staining, transmission electron microscopy (TEM), and RNA‐sequence analysis were performed to assess the IPOC effect.ResultsIPOC reduced infarct size and reduced nerve cell injury in IS tree shrews with DM. RNA‐seq analysis showed that IPOC significantly increased the expression of the homeobox protein SIX3, while downregulating the expression of HLA class II histocompatibility antigens DQ beta 1 chain, CAS1 domain‐containing protein 1, and cytokine receptor‐like factor 2. The most downregulated signaling pathways include the NF‐κB signaling pathway, TNF signaling pathway, and Fc gamma R‐mediated phagocytosis.ConclusionsIPOCs have a neuroprotective effect in a DMIS animal model that reduces infarct size and nerve cell injury. This mechanism might be related to reducing inflammation and stress responses that decreases the activity of TNF and NF‐κB signaling pathways.

Investigation of the effect of melatonin administration on inflammatory mediators; MMP-2, TGF-β and VEGF levels in rats with sepsis.

Sepsis causes life-threatening tissue and organ dysfunctions caused by endogenous mediators in response to infection. Melatonin is a powerful endogenous anti-inflammatory agent and effective in reducing cellular damage. This study aimed to evaluate the changes in serum and liver tissue levels of VEGF, TGF-β and MMP-2 in melatonin-treated septic rats. Twenty-one Wistar-albino male rats were included in this study. Rats were randomly divided into three groups. Group 1 is sham-operated control (C) group, Group 2 is caecal ligation and puncture (CLP) group and Group 3 is melatonin-treated (10mg/kg) (M-CLP) group. Serum and tissue samples were analysed. All procedures were carried out according to the ethical rules specified in Helsinki Declaration. Sera MMP-2 levels were found higher than tissue MMP-2 levels in C and CLP (respectively, P=.048, P=.01). In CLP and M-CLP, serum TGF-β levels were higher than tissue TGF-β levels(respectively, P=.05, P=.01). Serum VEGF levels in CLP were found to be significantly higher than both C and M-CLP(P<.01). MMP-2 levels may have increased because of the prevention of oxidative damage in sepsis, and this may increase the anti-inflammatory effect. Melatonin treatment may have a therapeutic effect against sepsis since it prevents the increase in serum VEGF level. A powerful endogenous antioxidant, may be a promising therapeutic agent on the mortality and morbidity of the disease, because of its lowering effect on serum VEGF, which is a poor prognostic factor in sepsis.

Proangiogenic functions of osteopontin-derived synthetic peptide RSKSKKFRR in endothelial cells and postischemic brain.

The aim of this study was to investigate the potential therapeutic effects of a newly discovered osteopontin-derived synthetic peptide "RSKKFRR" in a rat model of ischemic stroke. A total of 24 male SD rats were randomly divided into three groups. The model of ischemic stroke was made up of the middle cerebral artery occlusion (MACO). The rats were divided into sham operation group (Sham), control group (MACO + PBS) and treatment group (MACO + OPNpt9), eight rats in each group. In the control group and the treatment group, PBS or OPNpt9 was injected into the nasal cavity after MACO once a day, and the area of new blood vessels and the recovery of nerve function were observed 14 days later. Whether the proliferation, migration and tube formation of HUVECs were promoted by OPNpt9 was tested. The expression levels of related proangiogenic factors were also detected. OPNpt9 was found to contribute to cerebral microvascular remodeling and neurological improvement in ischemic rats while promoting endothelial cell migration, proliferation and tube formation in vitro. These effects were mediated by activation of the p-ERK/MMP-9/VEGF pathway. In conclusion, OPNpt9 promotes angiogenesis and neurological recovery after ischemic stroke.

PD62-11 THERAPEUTIC EFFECT OF LIPOSOMAL DELIVERY OF HYDROGEN SULFIDE AND XENON ON ERECTILE FUNCTION AFTER CAVERNOUS NERVE INJURY

You have accessJournal of UrologySexual Function/Dysfunction: Basic Research & Pathophysiology (PD62)1 Sep 2021PD62-11 THERAPEUTIC EFFECT OF LIPOSOMAL DELIVERY OF HYDROGEN SULFIDE AND XENON ON ERECTILE FUNCTION AFTER CAVERNOUS NERVE INJURY Baibing Yang, Dustin Luse, Song Gao, Shaolin Huang, Yong-jian Geng, and Run Wang Baibing YangBaibing Yang More articles by this author , Dustin LuseDustin Luse More articles by this author , Song GaoSong Gao More articles by this author , Shaolin HuangShaolin Huang More articles by this author , Yong-jian GengYong-jian Geng More articles by this author , and Run WangRun Wang More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002099.11AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Erectile dysfunction (ED) is a neurovascular disorder mediated by dysfunction of the nitric oxide/cyclic guanosine monophosphate (NO/cGMP) pathway, and poor relaxation of corpus cavernosum smooth muscle. The two gaseous molecules, hydrogen sulfide (H2S) and xenon (Xe), have been shown to exert neurovascular protective effects in the setting of ischemic and traumatic injuries. Administration of H2S and Xe has been shown to reduce infarct sizes and improve function in animal models of cerebral ischemia–reperfusion injury. The current study tested the hypothesis that to a similar extent, H2S and Xe both can preserve erectile function after cavernous nerve injury. METHODS: A model of cavernous nerve injury ED was employed using bilateral cavernous nerve crush (BCNC) on adult male Sprague Dawley rats. The experimental and control groups were BCNC + saline, BCNC + H2S, BCNC + Xe treatment and a sham surgery control group. H2S treatment was used as positive control, which has been reported to improve erectile function through smooth muscle relaxation. H2S and Xe were packed in echogenic liposomes (ELIPs, liposome diameter ranged from 800 nm to several microns) respectively and injected through the rat tail vein (5mg ELIPs). Gas was released from ELIPs under ultrasound exposure at the root of penis. Intracavernosal pressure (ICP) and mean arterial pressure (MAP) were examined after ultrasound exposure and recorded for all groups. RESULTS: Rats injured by BCNC showed erectile dysfunction evidence by reduced ICP/MAP. Treatment with H2S and Xe blocked the BCNC adverse impact on erectile function by 1.83- and 1.75-fold increases respectively when compared with BCNC group. CONCLUSIONS: Liposomal delivery of H2S and Xe demonstrates potential as a novel therapy for ED after cavernous nerve injury. Source of Funding: None © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e1076-e1076 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Baibing Yang More articles by this author Dustin Luse More articles by this author Song Gao More articles by this author Shaolin Huang More articles by this author Yong-jian Geng More articles by this author Run Wang More articles by this author Expand All Advertisement Loading ...

Expression and related mechanisms of miR-330-3p and S100B in an animal model of cartilage injury.

ObjectiveTo investigate the roles of and relationship between microRNA (miR)-330-3p and S100 calcium-binding protein B (S100B) in an animal model of cartilage injury.MethodsThis study included 30 New Zealand male rabbits randomly divided into three groups: an intervention group, a model group and a sham surgery control group. Modelling was performed in the intervention and model groups, but in the sham surgery group, only the skin was cut. After modelling, the intervention and model groups were injected with the miR-330-3p overexpression vector GV268-miR-330-3p or the control GV268-N-ODN vector, respectively, twice a week for 7 weeks.ResultsLevels of interleukin-1β and tumour necrosis factor-α in the synovial fluid were significantly higher in the model group than in the intervention and control groups. The level of miR-330-3p in the cartilage tissue was significantly higher in the control group than in the model group but it was significantly lower compared with the intervention group. Levels of S100B, fibroblast growth factor receptor 1 and fibroblast growth factor-2 in the cartilage tissue of rabbits in the model group were significantly higher compared with the control and intervention groups.ConclusionThese findings demonstrate that the upregulation of miR-330-3p can inhibit the expression of S100B.

MicroRNA-126 from stem cell extracellular vesicles encapsulated in a tri-layer hydrogel scaffold promotes bladder angiogenesis by activating CXCR4/SDF-1α pathway

Restricted by insufficient waterproofness and stretching resistance, hydrogel alone is seldomly applied in bladder wall regeneration. A tri-layer hydrogel scaffold comprising bladder acellular matrix graft-alginate di-aldehyde-gelatin hydrogel-silk mesh (BAMG-HS) was designed to encapsulate human adipose stem cells (ASCs)-derived extracellular vesicles (EVs), aiming to facilitate bladder regeneration. The proangiogenic composite biomaterial was evaluated in a rat model of bladder augmentation, where rats were randomly allocated to BAMG-HS-EVs (n = 6 sampled at 2, 4, and 12 weeks, respectively), BAMG-HS (n = 6, 12 weeks) and sham operation control groups (n = 6, 12 weeks). The tri-layer hydrogel scaffold has excellent mechanical and biodegradable properties, promotes angiogenesis and facilitates bladder morphological regenerations of urothelium, smooth muscle and neural fibers, and functional restoration without unmitigated fibrosis or dysregulated inflammation. Human ASCs-EVs activate bladder CXCR4/SDF-1α pathway, and enhance human umbilical vein endothelial cells (HUVEC) proliferation, invasiveness and tube-like structure formation. After internalization by HUVEC, they up-regulate microRNA-126 and inhibit RGS16 to activate CXCR4/SDF-1α pathway, thus enhancing VEGF secretion via ERK1/2 phosphorylation.

The myosin activator omecamtiv mecarbil improves wall stress in a rat model of chronic aortic regurgitation.

In patients with chronic aortic regurgitation (AR), excessive preload and afterload increase left ventricle wall stress, leading to left ventricular systolic dysfunction. Thus, the objective of the present study was to evaluate the effects of the myosin activator omecamtiv mecarbil (OM) on left ventricle wall stress in an experimental rat model of severe chronic AR. Forty adult male Wistar rats were randomized into two experimental groups: induction of AR (acute phase) by retrograde puncture (n = 34) or a sham intervention (n = 6). Rats that survived the acute phase (n = 18) were randomized into an OM group (n = 8) or a placebo group (n = 10). Equal volumes of OM (1.2 mg/kg/h) or placebo (0.9% NaCl) were continuously infused into the femoral vein over 30 min. OM significantly decreased end‐systolic and end‐diastolic and maximum wall stress in this experimental rat model of chronic severe AR (p < 0.001) and increased systolic performance assessed by fractional shortening and left ventricle end‐systolic diameter; both p < 0.05). These effects were correlated with decreased indices of global cardiac function (cardiac output and stroke volume; p < 0.05) but were not inferior to baseline pump indices. Infusion with placebo did not affect global cardiac function but decreased end‐systolic wall stress (p < 0.05) and increased systolic performance (all p < 0.001). In the sham‐operated (control) group, OM decreased diastolic wall stress (p < 0.05). Based on these results, OM had a favorable effect on left ventricle wall stress in an experimental rat model of severe chronic AR.

Transcutaneous electrical acupoint stimulation before surgery reduces chronic pain after mastectomy: A randomized clinical trial

Study objectiveDespite multiple interventions, the incidence of chronic pain after mastectomy could be as high as 50% after surgery. This study aimed to determine the efficacy of transcutaneous electrical acupoint stimulation (TEAS) before anesthesia induction in reducing chronic pain and to compare the effect of combined acupoint TEAS with that of single acupoint TEAS. DesignA multicenter randomized clinical trial. SettingThe study was conducted at six medical centers in China from May 2016 to April 2018. Final follow-up was on October 26, 2018. ParticipantsEligible patients were women scheduled for radical mastectomy under general anesthesia. InterventionsPatients were randomly and equally grouped into sham control (n = 188), single acupoint (PC6, n = 198), or combined acupoints (PC6 and CV17, n = 190) TEAS groups using a centralized computer-generated randomization system. TEAS was applied for 30 min before anesthesia induction. The sham-operated control group received electrode attachment but without stimulation. Anesthesiologists, surgeons, and outcome assessors were blinded to the interventions. MeasuresThe primary endpoint was the incidence of chronic pain 6 months after surgery. Incidences were compared among the groups using the unadjusted χ2 test. ResultsOf the 576 randomized patients, 568 completed the trial. In the intention-to-treat analysis, post-mastectomy pain at 6 months was reported in 42 of 190 patients (22.1%) in the combined acupoints group, 65 of 188 patients (34.6%) in the sham-operated group (P = 0.007; relative risk [RR], 95% confidence interval [CI]: 0.68, 0.52–0.89), and 72 of 198 patients (36.4%) in the single acupoint group (P = 0.002; RR, 95% CI: 0.72, 0.55–0.93). Remifentanil consumption during surgery and postoperative nausea and vomiting at 24 h after surgery were lower in the combined acupoint group than that in the sham-operated group. ConclusionTEAS at combined acupoints before surgery was associated with reduced chronic pain 6 months after surgery.Trial registration:Clinicaltrials.gov identifier: NCT02741726. Registered on April 13, 2016.

Protective effect of rhaponticin on ovariectomy-induced osteoporosis in rats.

Rhaponticin is a constituent isolated from numerous medicinal herbs. It has been reported earlier that rhaponticin possesses numerous biological effects like antiallergic, antidiabetic, hepatoprotective, and antithrombosis. The goal of this exploration was to scrutinize the therapeutic potential of rhaponticin on ovariectomy (OVX)-triggered osteoporosis in rats. Female Sprague Dawley rats were arbitrarily allocated to a sham-operated control group I, group II, which underwent OVX, and groups III and IV that underwent OVX were administered with rhaponticin (10and 20 mg/kg). Rhaponticin was supplemented orally after 4 weeks of OVX and continued for about 16 weeks. Our findings exhibit that rhaponticin prevented the BMD diminution of femurs, induced by OVX, and protected the worsening of trabecular microarchitecture that are assisted through a noteworthy decline in skeletal remodeling as noticed through the diminished status of bone markers in a dose-dependent manner (10 and 20 mg/kg). OVX rats treated with rhaponticin efficiently enhanced body weight, lipid profiles, uterine index, bone turnover markers, inflammatory markers, and augmented the incidence of calcium in the OVX rats. Rhaponticin was established to restrain the functions of acid phosphatase, estradiol, and bone gla protein in OVX rats. Also, rhaponticin displayed some beneficial effects on histomorphometric and histopathological examination. It was observed that tabular area and thickness were reinstated in sham control and rhaponticin-treated OVXrats. We recognized that rhaponticin did not induce a damaging outcome on the skeletal organization of OVX rats. Moreover, we denote that rhaponticin can be an exceptional agent for the treatment and deal with associated bone diseases.

Identification of key candidate genes in local dorsal root ganglion inflammation by integrated bioinformatics analysis.

The purpose of the present study was to identify potential markers of local dorsal root ganglion (DRG) inflammation to aid diagnosis, treatment and prognosis evaluation of DRG pain. A localized inflammation of the DRG (LID) rat model was used to study the contribution of inflammation to pain. The dataset GSE38859 was obtained from the Gene Expression Omnibus database. Pre-treatment standardization of gene expression data for each experiment was performed using the R/Bioconductor Limma package. Differentially expressed genes (DEGs) were identified between a LID model and a sham surgery control group. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses of DEGs and gene set enrichment analysis (GSEA) were carried out using the ‘clusterProfiler’ package in R. Using the Search Tool for Retrieval of Interacting Genes, a protein-protein interaction network was constructed and visualized. Candidate genes with the highest potential validity were validated using reverse transcription-quantitative PCR and western blotting. In total, 66 DEGs were enriched in GO terms related to inflammation and the immune response processes. KEGG analysis revealed 14 associated signaling pathway terms. Protein-protein interaction network analysis revealed 9 node genes, 3 of which were among the top 10 DEGs. Matrix metallopeptidase 9, chemokine CXCL9, and complement component 3 were identified as key regulators of DRG inflammatory pain progression.