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This study tested the hypothesis that combined therapy with human umbilical cord‐derived mesenchymal stem cells (HUCDMSCs) and hyperbaric oxygen (HBO) was superior to either one on preserving neurological function and reducing brain haemorrhagic volume (BHV) in rat after acute intracerebral haemorrhage (ICH) induced by intracranial injection of collagenase. Adult male SD rats (n = 30) were equally divided into group 1 (sham‐operated control), group 2 (ICH), group 3 (ICH +HUCDMSCs/1.2 × 106 cells/intravenous injection at 3h and days 1 and 2 after ICH), group 4 (ICH +HBO/at 3 hours and days 1 and 2 after ICH) and group 5 (ICH +HUCDMSCs‐HBO), and killed by day 28 after ICH. By day 1, the neurological function was significantly impaired in groups 2‐5 than in group 1 (P

This study tested the hypothesis that melatonin (Mel) therapy preserved the brain architectural and functional integrity against ischaemic stroke (IS) dependently through suppressing the inflammatory/oxidative stress downstream signalling pathways. Adult male B6 (n = 6 per each B6 group) and TLR4 knockout (ie TLR4-/- ) (n = 6 per each TLR4-/- group) mice were categorized into sham control (SCB6 ), SCTLR4-/- , ISB6 , ISTLR4-/- , ISB6 + Mel (i.p. daily administration) and ISTLR4-/- + Mel (i.p. daily administration). By day 28 after IS, the protein expressions of inflammatory (HMBG1/TLR2/TLR4/MAL/MyD88/RAM TRIF/TRAF6/IKK-α/p-NF-κB/nuclear-NF-κB/nuclear-IRF-3&7/IL-1β/IL-6/TNF-α/IFN-γ) and oxidative stress (NOX-1/NOX-2/ASK1/p-MKK4&7/p-JNK/p-c-JUN) downstream pathways as well as mitochondrial-damaged markers (cytosolic cytochrome C/cyclophilin D/SRP1/autophagy) were highest in group ISB6 , lowest in groups SCB6 and SCTLR4-/- , lower in group ISTLR4-/- + Mel than in groups ISTLR4-/- and ISB6 + Mel and lower in group ISB6 + Mel than in group ISTLR4-/- (all P

As microplastics (MPs) dispersed into the environment, people might be exposed to MPs. Most pollutants either pass through or concentrate in the kidney. Therefore, nephrotoxicity tests are needed to verify the toxic potential of MPs. Here we used human embryonic kidney 293 (HEK293) cells to determine the association between nephrotoxicity and round-shape polystyrene MPs (PSMPs) (3.54 ± 0.39 μm) under realistic environmental exposure concentrations. Results revealed that PSMPs can adhere to the cell membrane and get entirely engulfed by HEK293 cells. PSMPs can induce cytotoxicity by oxidative stress via inhibition of the antioxidant heme oxygenase-1. Depolarization of the mitochondrial membrane potential and formation of autophagosomes confirmed that apoptosis and autophagy can be simultaneously induced by PSMPs. The inflammatory factor was only activated (33 cytokines) by noncytotoxic concentration of PSMPs (3 ng/mL); however, the cytotoxic concentration (300 ng/mL) of PSMPs induced autophagy, which might further reduce NLRP3 expression, thus contributing to dampening inflammation (35 cytokines) in HEK293 cells. PSMPs (300 ng/mL) can impair kidney barrier integrity and increase the probability of developing acute kidney injury through the depletion of the zonula occludens-2 proteins and α1-antitrypsin. Altogether, our results demonstrated that environmental exposure to PSMPs may lead to an increased risk of renal disease.

This study tested the hypothesis that combined adipose-derived mesenchymal stem cell (ADMSC) and low-energy extracorporeal shock wave (ECSW) therapy could protect brain from brain death (BD)-induced injury. Adult male Sprague Dawley rats were categorized into group 1 (sham control), group 2 (BD), group 3 (BD + ECSW [0.15 mJ/mm2/300 impulses] applied to the skull surface 3 hours after BD induction), group 4 (BD + ADMSC [1.2 × 106 cell] by intravenous injection 3 hours after BD induction) and group 5 (BD + ECSW + ADMSC). By 6 hours after BD induction, circulating/spleen levels of immune cells (CD3/CD4+, CD8/CD4+, Treg+) and circulating levels of inflammatory cells (MPO/Ly6G/CD11a/b) and soluble mediators (TNF-α/IL-6) were lowest in group 1 and significantly progressively reduced from groups 2 to 5 (all p < 0.0001). Brain protein expressions of inflammatory (TNF-α/NF-κB/MMP-9/IL-1β), apoptotic (caspase-3/PARP/mitochondrial-BAX), oxidative stress/DNA-damage (NOX-1/NOX-2/oxidized protein/γ-H2AX) biomarkers exhibited an identical pattern, whereas anti-oxidant (SIRT1/SIRT3) and mitochondrial-integrity (mitochondrial-cytochrome-C) biomarkers exhibited an opposite pattern to inflammatory biomarkers among the 5 groups (all p < 0.0001). The cellular expressions of inflammatory/brain-edema (F4/80/CD14+/GFAP/AQP4) biomarkers exhibited an identical pattern to inflammation among the 5 groups (all p < 0.0001). In conclusion, ECSW-ADMSC therapy is superior to either alone for attenuating brain from BD-induced damage.

We investigated the effects of nickel oxide nanoparticles (NiONPs) on the pulmonary inflammopathology. NiONPs were intratracheally installed into mice, and lung injury and inflammation were evaluated between 1 and 28 days. NiONPs caused significant increases in LDH, total protein, and IL-6 and a decrease in IL-10 in the BALF and increases in 8-OHdG and caspase-3 in lung tissues at 24 h. Airway inflammation was present in a dose-dependent manner from the upper to lower airways at 24 h of exposure as analyzed by SPECT. Lung parenchyma inflammation and small airway inflammation were observed by CT after NiONP exposure. 8-OHdG in lung tissues had increased with formation of fibrosis at 28 days. Focal adhesion was the most important pathways identified at 24 h as determined by protemics, whereas glutathione metabolism was the most important identified at 28 days. Our results demonstrated the pulmonary inflammopathology caused by NiONPs based on image-to-biochemical approaches.

This study tested the hypothesis that both allogenic adipose-derived mesenchymal stem cells (ADMSCs) and human inducible pluripotent stem cell-derived MSCs (iPS-MSCs) offered a comparable effect for protecting the lung against ischemia-reperfusion (IR) injury in rodent through downregulating the inflammatory, oxidative stress, and autophagic signaling pathways. Adult male Sprague–Dawley rats ( n = 32) were categorized into group 1 (sham-operated control), group 2 (IRI), group 3 [IRI + ADMSCs (1.0 × 106cells)/tail-vein administration at 0.5/18/36 h after IR], and group 4 [IRI + iPS-MSCs (1.0 × 106cells)/tail-vein administration at 0.5/18/36 h after IR], and lungs were harvested at 72 h after IR procedure. In vitro study demonstrated that protein expressions of three signaling pathways in inflammation (TLR4/MyD88/TAK1/IKK/I-κB/NF-κB/Cox-2/TNF-α/IL-1ß), mitochondrial damage/cell apoptosis (cytochrome C/cyclophilin D/DRP1/ASK1/APAF-1/mitochondrial-Bax/caspase3/8/9), and autophagy/cell death (ULK1/beclin-1/Atg5,7,12, ratio of LCB3-II/LC3B-I, p-AKT/m-TOR) were significantly higher in lung epithelial cells + 6h hypoxia as compared with the control, and those were significantly reversed by iPS-MSC treatment (all P < 0.001). Flow cytometric analysis revealed that percentages of the inflammatory cells in bronchioalveolar lavage fluid and circulation, and immune cells in circulation/spleen as well as circulatory early and late apoptotic cells were highest in group 2, lowest in group 1, and significantly higher in group 3 than in group 4 (all P < 0.0001). Microscopy showed the lung injury score and numbers of inflammatory cells and Western blot analysis showed the signaling pathways of inflammation, mitochondrial damage/cell apoptosis, autophagy, and oxidative stress exhibited an identical pattern of flow cytometric results among the four groups (all P < 0.0001). Both xenogeneic and allogenic MSCs protected the lung against IRI via suppressing the inflammatory, oxidative stress, and autophagic signaling.

Background This study tested the optimal time point for left intra-carotid arterial (LICA) administration of circulatory-derived autologous endothelial progenitor cells (EPCs) for improving the outcome in rat after acute ischemic stroke (IS). Methods and results Adult male SD rats (n = 70) were equally categorized into group 1 (sham-operated control), group 2 (IS), group 3 (IS+EPCs/1.2 × 106 cells/by LICA administration 3 h after IS), group 4 (IS+EPCs/LICA administration post-day-3 IS), group 5 (IS+EPCs/LICA administration post-day-7 IS), group 6 (IS+EPCs/LICA administration post-day-14 IS), and group 7 (IS+EPCs/LICA administration post-day-28 IS). The brain infarct volume (BIV) (at day 60/MRI) was lowest in group 1, highest in group 2, and significantly progressively increased from groups 3 to 7, whereas among the IS animals, the neurological function was significantly preserved in groups 3 to 6 than in groups 2 and 7 post-day-60 IS (all P P P P Conclusion Early EPC administration provided better benefits on improving functional/image/molecular-cellular outcomes after acute IS in rat.

This study tested the hypothesis that combined hyperbaric oxygen (HBO) and melatonin (Mel) was superior to either one for protecting the brain functional and parenchymal integrity from acute ischemic stroke (IS) injury. Adult-male Sprague-Dawley rats were divided into groups 1 (sham-operated control), 2 (IS), 3 (IS + HBO), 4 (IS + Mel), and 5 (IS + HBO-Mel). By day 28 after IS, the brain infarct area (BIA) was lowest in group 1, highest in group 2, significantly higher in groups 3 and 4 than in group 5, but not different between groups 3 and 4. The neurological function at day 7, 14, and 28 exhibited an opposite pattern to BIA among the 5 groups. The protein expressions of inflammatory (IL-1β/IL-6/iNOS/TNF-α/p-NF-κB), apoptotic (cleaved-caspase3/cleaved-PARP/mitochondrial Bax), mitochondrial/DNA-damaged (cytochrome-C/γ-H2AX), oxidative stress (NOX-1/NOX-2), and autophagy (i.e. ratio of CL3B-II/CL3B-I) biomarkers displayed an identical pattern of BIA among 5 groups. Cellular expressions of inflammation (F4/80+/GFAP+) and DNA-damaged biomarker (γ-H2AX+) exhibited an identical pattern, whereas the integrities of myelin sheath/neuron (MPB+/NeuN+), endothelial cell (CD31+/vWF+), and number of small vessels exhibited an opposite pattern of BIA among the 5 groups. Combined HBO-Mel therapy offered an additional benefit in protecting the brain against IS injury.

We tested the hypothesis that melatonin prevents brain death (BD) tissue extract (BDEX)-induced cardiac damage by suppressing inflammatory damage-associated molecular pattern (DAMP) signaling in rats. Six hours after BD induction, levels of a DAMP component (HMGB1) and inflammatory markers (TLR-2, TLR-4, MYD88, IκB, NF-κB, IL-1β, IFN-γ, TNF-α and IL-6) were higher in brain tissue from BD animals than controls. Levels of HMGB1 and inflammatory markers were higher in BDEX-treated H9C2 cardiac myoblasts than in cells treated with healthy brain tissue extract. These increases were attenuated by melatonin but re-induced with luzindole (all P < 0.001). Additional male rats (n = 30) were divided into groups 1 (negative control), 2 (healthy brain tissue extract implanted in the left ventricular myocardium [LVM]), 3 (BDEX-LVM), 4 (BDEX-LVM + melatonin), and 5 (BDEX-LVM + melatonin + luzindole). Collagen deposition/fibrosis and LVM levels of MTR2, HMGB1, inflammatory markers, oxidative stress, apoptosis, mitochondrial damage and DNA damage were highest in group 3, lowest in groups 1 and 2, and higher in group 5 than in group 4. Heart function and LVM levels of MTR1 and anti-inflammatory, mitochondrial-integrity and anti-oxidative markers exhibited a pattern opposite that of the inflammatory markers in the five groups (all P < 0.0001). These results indicate melatonin inhibits BDEX-induced cardiac damage by suppressing the DAMP inflammatory axis.

Inhaled zinc oxide nanoparticles (ZnONPs) have high deposition rates in the alveolar region of the lungs; however, the adverse health effects of ZnONPs on the respiratory system are unclear. Herein, pathobiological responses of the respiratory system of mice that received intratracheal administration of ZnONPs were investigated by a combination of molecular and imaging (SPECT and CT) approaches. Also, normal BEAS-2B and adenocarcinoma A549 cells were used to confirm the results in mice. First, female BALB/c mice were administrated a series of doses of 20-nm ZnONPs and were compared to the phosphate-buffered saline control for 24-h and 28-day follow-up observations. Field emission-scanning electron microscopy and an energy-dispersive X-ray microanalysis were first used to characterize ZnONPs. After 24h, instilled ZnONPs had caused significant increases in lactic dehydrogenase (LDH) in bronchoalveolar lavage fluid (BALF) and 8-hydroxy-2'-deoxyguanosine (8-OHdG), caspase-3, and the p63 tumor marker in lung tissues (p

We investigated the cardioprotective effect of melatonin (Mel) and exendin-4 (Ex4) treatment in a rat model of cardiorenal syndrome (CRS). Male-adult SD rats (n=48) were randomly and equally divided into sham-control (SC), dilated cardiomyopathy (DCM) (doxorubicin 7 mg/kg i.p. every five days/ 4 doses), CRS (defined as DCM + CKD) only, CRS-Mel (20 mg/kg/day), CRS-Ex4 (10 μg/kg/day) and CRS-Mel-Ex4. In-vitro results showed protein expressions of oxidative-stress (NOX-1/NOX-2/oxidized protein), DNA/mitochondrial-damaged (γ-H2AX/cytosolic cytochrome-C) and apoptotic (cleaved caspase-3/PARP) biomarkers, and senescence (β-galactosidase cells) were upregulated, whereas mitochondrial ATP level was decreased in doxorubicin/ p-Cresol-treated H9C2 cells that were revised by Mel and Ex4 treatments (all p

Intermittent hypoxia is a characteristic pathological change in obstructive sleep apnoea (OSA) that can initiate oxidative stress reaction and pro-inflammatory cytokine release. The purpose of this study was to assess the effect and protective mechanism of Astragaloside IV (AS-IV) in intermittent hypoxia-induced human lung epithelial Beas-2B cells. Human lung epithelial Beas-2B cells were exposed to intermittent hypoxia or normoxia in the absence or presence of AS-IV. MTT assay was performed to determine the cell viability. The levels of reactive oxygen species (ROS), lactate dehydrogenase (LDH), malonaldehyde (MDA), and superoxide dismutase (SOD) were measured to evaluate oxidative stress. The levels of cytokines interleukin (IL)-8, IL-1β, and IL-6 were evaluated by enzyme-linked immunosorbent assay and real-time PCR. The expression of Toll-like receptor 4 (TLR4), mitogen-activated protein kinase (MAPK), and nuclear transcription factor-kappa B (NF-κB) signalling pathways was analysed by western blot. The results showed that AS-IV significantly reduced the levels of ROS, LDH, MDA, IL-8, IL-1β, and IL-6, and increased the level of SOD in intermittent hypoxia-induced Beas-2B cells. It also suppressed the phosphorylation of MAPKs, including P38, c-Jun N-terminal kinase and extracellular signal-regulated kinase, and inhibited the activation of the NF-κB signalling pathway by reducing the phosphorylation of IκBα and p65. AS-IV attenuates inflammation and oxidative stress by inhibiting TLR4-mediated MAPK/NF-κB signalling pathways in intermittent hypoxia-induced Beas-2B cells.

Objective: Endothelial cells (ECs) are important metabolic and endocrinal organs which play a significant role in regulating vascular function. Vascular ECs, located between the blood and vascular tissues, can not only complete the metabolism of blood and interstitial fluid but also synthesize and secrete a variety of biologically active substances to maintain vascular tension and keep a normal flow of blood and long-term patency. Therefore, this article presents a systematic review of common injuries and healing mechanisms for the vascular endothelium. Data Sources: An extensive search in the PubMed database was undertaken, focusing on research published after 2003 with keywords including endothelium, vascular, wounds and injuries, and wound healing. Study Selection: Several types of articles, including original studies and literature reviews, were identified and reviewed to summarize common injury and repair processes of the endothelial lining. Results: Endothelial injury is closely related to the development of multiple cardiovascular and cerebrovascular diseases. However, the mechanism of vascular endothelial injury is not fully understood. Numerous studies have shown that the mechanisms of EC injury mainly involve inflammatory reactions, physical stimulation, chemical poisons, concurrency of related diseases, and molecular changes. Endothelial progenitor cells play an important role during the process of endothelial repair after such injuries. What’s more, a variety of restorative cells, changes in cytokines and molecules, chemical drugs, certain RNAs, regulation of blood pressure, and physical fitness training protect the endothelial lining by reducing the inducing factors, inhibiting inflammation and oxidative stress reactions, and delaying endothelial caducity. Conclusions: ECs are always in the process of being damaged. Several therapeutic targets and drugs were seeked to protect the endothelium and promote repair. Key words: Endothelium; Vascular; Wound Healing; Wounds and Injuries

We evaluated the ability of extracorporeal shock wave (ECSW)-assisted melatonin (Mel) therapy to offer an additional benefit for alleviating the neuropathic pain (NP) in rats. Left sciatic nerve was subjected to chronic constriction injury (CCI) to induce NP. Animals (n = 30) were randomized into group 1 (sham-operated control), group 2 (CCI only), group 3 (CCI + ECSW), group 4 (CCI + Mel) and group 5 (CCI + ECSW + Mel). By days 15, 22 and 29 after CCI, the thermal paw withdrawal latency (TPWL) and mechanical paw withdrawal threshold (MPWT) were highest in group 1, lowest in group 2, significantly higher in group 5 than in groups 3 and 4, but they showed no difference between the later two groups (all p

This study tested the hypothesis that shock wave therapy (SW) enhances mitochondrial uptake into the lung epithelial and parenchymal cells to attenuate lung injury from acute respiratory distress syndrome (ARDS). ARDS was induced in rats through continuous inhalation of 100% oxygen for 48 h, while SW entailed application 0.15 mJ/mm2for 200 impulses at 6 Hz per left/right lung field. In vitro and ex vivo studies showed that SW enhances mitochondrial uptake into lung epithelial and parenchyma cells (allp<0.001). Flow cytometry demonstrated that albumin levels and numbers of inflammatory cells (Ly6G+/CD14+/CD68+/CD11b/c+) in bronchoalveolar lavage fluid were the highest in untreated ARDS, were progressively reduced across SW, Mito, and SW + Mito (allp<0.0001), and were the lowest in sham controls. The same profile was also seen for fibrosis/collagen deposition, levels of biomarkers of oxidative stress (NOX-1/NOX-2/oxidized protein), inflammation (MMP-9/TNF-α/NF-κB/IL-1β/ICAM-1), apoptosis (cleaved caspase 3/PARP), fibrosis (Smad3/TGF-β), mitochondrial damage (cytosolic cytochrome c) (allp<0.0001), and DNA damage (γ-H2AX+), and numbers of parenchymal inflammatory cells (CD11+/CD14+/CD40L+/F4/80+) (p<0.0001). These results suggest that SW-assisted Mito therapy effectively protects the lung parenchyma from ARDS-induced injury.

Acute renal injury is a common severe clinical syndrome, occurring in many clinical situations. It is necessary to explore effective drugs to treat it. Eupafolin is a flavonoid compound, derived from Phyla nodiflora, which has been previously reported to possess a variety of pharmacological activities, including anti-inflammatory and antioxidant effects. However, it is known little about how it works in acute renal injury. Also, eupafolin is characterized by skin penetration and poor water solubility, limiting its clinical applications. Thus, we synthesized an eupafolin nanoparticle delivery system. We found that eupafolin nanoparticle could address the physicochemical defects of raw eupafolin and increase water solubility without any toxicity to normal renal cells via reducing particle size. Eupafolin nanoparticle attenuated LPS-induced acute renal injury in mice through inhibiting oxidative stress and inflammation accompanied with up-regulated SOD activity and down-regulated pro-inflammatory cytokines. Additionally, inactivation of NF-κB and MAPKs of p38, ERK1/2 and JNK signaling pathways was a main molecular mechanism by which eupafolin nanoparticle improved renal injury. Together, eupafolin nanoparticle exhibits effective anti-oxidant and anti-inflammatory activities, which could be used as a potential drug to ameliorate acute renal injury clinically.

Despite promising environmental applications for nano zerovalent iron (nZVI), concerns remain about the potential accumulation and toxic effects of nZVI particles. Here, we use an alveolar-capillary co-culture model to investigate a possible link between low-level epithelial exposure to nZVI and pulmonary and cardiovascular toxicity. While nZVI was unable to pass through the epithelial barrier into the endothelium, nZVI exposure did cause oxidative and inflammatory responses in both epithelial and endothelial cells. Therefore, toxic effects induced by nZVI are not restricted to epithelial cells but can be transferred into the endothelium. Communication between A549 and EA.hy926 cells is responsible for amplification of nZVI-induced toxic responses. Decreases in transepithelial electrical resistance and zonula occludens proteins after epithelial exposure to nZVI impaired epithelial barrier integrity. Increases in oxidized α1-antitrypsin and oxidized low-density lipoprotein in the co-culture model suggest that nZVI exposure increases the risk of chronic obstructive pulmonary disease and atherosclerosis. Therefore, inhalation of nZVI has the potential to induce cardiovascular disease through oxidative and inflammatory mediators produced from the damaged lung epithelium in chronic lung diseases.

This study tested the hypothesis that rosuvastatin reduces thrombus burden through inhibiting inflammation and suppressing reactive oxygen species (ROS) generation in an inferior vena cava stenosis (IVCST)-induced deep vein thrombosis (DVT) rat model. 12-week-old male Sprague-Dawley rats (n = 24) were equally divided into sham control (group 1: laparotomy only), IVCST (group 2: IVC stenosis), and IVCST + rosuvastatin (20 mg/kg/day, orally after induction of IVC stenosis) (group 3). IVC diameter was measured by days 0 and 14 and the right hindlimb thickness was measured by day 0, 7, and 14 prior to scarifying the animals. The results showed significantly increased IVC diameter and hindlimb thickness in group 2 than in groups 1 and 3, and significantly increased in group 3 than in group 1 by day 14 after the procedure (all p < 0.001). Additionally, WBC count and prevalence of helper T cells, cytotoxic T cells, regulatory T cells, and early and late apoptotic mononuclear cells (MNCs) in circulation were significantly higher in group 2 than in group 1, and were significantly suppressed in group 3 after treatment (all p < 0.001). Furthermore, inflammation at cellular (CD68+ cells) and protein (MMP-9, TNF-α) levels, oxidative stress (oxidized protein) and reactive oxygen species (NOX-1, NOX-2) in IVC also showed similar changes as those of immune cells in circulation among the three groups (all p < 0.01). Rosuvastatin treatment significantly reduced IVC thrombus burden through inhibiting inflammatory response and oxidative stress in a rodent model of DVT.

This study tested whether combined therapy with melatonin and apoptotic adipose-derived mesenchymal stem cells (A-ADMSCs) offered additional benefit in ameliorating sepsis-induced acute kidney injury. Adult male Sprague-Dawley rats (n = 65) were randomized equally into five groups: Sham controls (SC), sepsis induced by cecal-ligation and puncture (CLP), CLP-melatonin, CLP-A-ADMSC, and CLP-melatonin-A-ADMSC. Circulating TNF-α level at post-CLP 6 hr was highest in CLP and lowest in SC groups, higher in CLP-melatonin than in CLP-A-ADMSC and CLP-melatonin-A-ADMSC groups (all P < 0.001). Immune reactivity as reflected in the number of splenic helper-, cytoxic-, and regulatory-T cells at post-CLP 72 hr exhibited the same pattern as that of circulating TNF-α among all groups (P < 0.001). The histological scoring of kidney injury and the number of F4/80+ and CD14+ cells in kidney were highest in CLP and lowest in SC groups, higher in CLP-melatonin than in CLP-A-ADMSC and CLP-melatonin-A-ADMSC groups, and higher in CLP-A-ADMSC than in CLP-melatonin-A-ADMSC groups (all P < 0.001). Changes in protein expressions of inflammatory (RANTES, TNF-1α, NF-κB, MMP-9, MIP-1, IL-1β), apoptotic (cleaved caspase 3 and PARP, mitochondrial Bax), fibrotic (Smad3, TGF-β) markers, reactive-oxygen-species (NOX-1, NOX-2), and oxidative stress displayed a pattern identical to that of kidney injury score among the five groups (all P < 0.001). Expressions of antioxidants (GR+, GPx+, HO-1, NQO-1+) were lowest in SC group and highest in CLP-melatonin-A-ADMSC group, lower in CLP than in CLP-melatonin and CLP-A-ADMSC groups, and lower in CLP-melatonin- than in CLP-A-ADMSC-tretaed animals (all P < 0.001). In conclusion, combined treatment with melatonin and A-ADMSC was superior to A-ADMSC alone in protecting the kidneys from sepsis-induced injury.

Background and aim Procedural failure and untoward clinical outcomes after surgery remain problematic in critical limb ischemia (CLI) patients. This study tested a clopidogrel-cilostazol combination treatment compared with either treatment alone in attenuating CLI and improving CLI-region blood flow in rats. Methods Male Sprague–Dawley rats (n = 40) were equally divided into five groups: control, CLI induction only, CL I + cilostazol (12.0 mg/day/kg), CLI + clopidogrel (8.0 mg/kg/day) and CLI + combined cilostazol-clopidogrel. After treatment for 21 days, Laser Doppler imaging was performed. Results On day 21, the untreated CLI group had the lowest ratio of ischemic/normal blood flow (p Conclusion Combined cilostazol-clopidogrel therapy is superior to either agent alone in improving ischemia in rodent CLI.