Day For 4weeks Research Articles

Reproductive toxicity investigation of silica nanoparticles in male pubertal mice.

Silica nanoparticles (SiNPs), one of the most produced nanoparticles (NPs) in the world, are used in all aspects of life. The increased application of SiNPs, especially in medicine, has raised considerable concern regarding their toxicological impact. Previous studies have shown that SiNPs can pass through the reproductive barrier and cause reproductive organ dysfunction by destroying Sertoli cells, Leydig cells, and germ cells. However, little is known about the mechanism of SiNPs-induced reproductive toxicity. In the present study, 5-week-old male mice were intraperitoneally administered SiNPs per day for 1week at a dose of 0.2mg per mouse. The results showed that SiNPs could cause damage to the structure of the testis and the epididymis and change the reproductive organ coefficients, leading to decreases of 56.1% and 55.3% in the rates of sperm concentration and motility and an increase of 168.8% in the rate of sperm abnormality. Moreover, the serum testosterone level obviously decreased from 18.77 to 5.23µg/ml after exposure, and the transcription statuses of some key genes involved in the synthesis and transport of testosterone in the testis were also affected. Additional experiments showed that SiNPs exposure during puberty induced oxidative stress and an inflammatory response, as shown by the changed activity of superoxide dismutase (SOD), increased contents of malondialdehyde (MDA), and excess expression of proinflammatory factors, including TNF-α and IL-1β. Furthermore, the administration of SiNPs caused DNA damage and cell apoptosis, which were presented by the increased apoptotic cells in the sections of testis and epididymis and activation of the TNF-α/TNFR I-mediated pro-apoptotic pathway. In conclusion, these results indicate that SiNPs exposure during puberty significantly damaged the structure and function of the testis and epididymis by inducing oxidative stress and cell apoptosis. This study provides novel insight into SiNPs-induced reproductive toxicity during puberty, which warrants a more careful assessment of SiNPs before their application in juvenile supplies.

Beneficial effects of transdermal administration of tamoxifen on capsular contracture after breast implantation in murine models.

Capsular contracture is the most common complication with smooth-type silicone implants. We investigated the preventive effect of an active metabolite of tamoxifen, 4-hydroxytamoxifen (4-OH TAM), on capsular contracture. A silicone sheet was implanted into the back of 28 female ICR mice. Mixtures of gel with 0.2% 4-OH TAM and 0.1% 4-OH TAM were administered transdermally once a day for 4weeks. Saline was administered to the control. After killing the mice, capsular thickness was measured in H&E-stained specimens. Estrogen receptor (ER), α-smooth muscle actin (α-SMA), and transforming growth factor-β (TGF-β) expressions were immunohistochemically investigated in the capsules. The capsule was thinner in the 0.2% 4-OH TAM gel group than in the control group (control, 0.1% 4-OH TAM gel, 0.2% 4-OH TAM gel: 52.8 ± 3.4µm, 54.2 ± 6.8µm, 46.4 ± 3.3µm, respectively). ER was found in most fibroblasts of all samples. α-SMA expression in the capsule was significantly lower in the 4-OH TAM gel groups than in the control group (control = 70.0 ± 3.4%, 0.1% 4-OH TAM = 57.0 ± 3.4%, 0.2% 4-OH TAM = 49.4 ± 4.9%). TGF-β expression was significantly reduced by the 4-OH TAM gel injections dose-dependently (control = 67.3 ± 2.2%, 0.1% 4-OH TAM = 52.4 ± 3.1%, 0.2% 4-OH TAM = 45.1 ± 2.4%). The transdermal administration of 0.1% and 0.2% 4-OH TAM gels inhibited capsule development. The inhibition of TGF-β expression is a mechanism by which 4-OH TAM suppresses fibroblast growth, preventing capsular formation.

Effects of repetitive transcranial magnetic stimulation combined with cognitive training on resting-state brain activity in Alzheimer's disease.

Repetitive transcranial magnetic stimulation (rTMS) is a promising tool to modulate brain plasticity, but the neural basis has been little addressed. The purpose was to investigate the effects of rTMS on resting-state brain activity in patients with Alzheimer's disease (AD). Seventeen patients with mild or moderate AD were enrolled and randomly divided into one of the two intervention groups: (1) real rTMS combined with cognitive training (real group, n = 9); (2) sham rTMS with cognitive training (sham group, n = 8). 10Hz rTMS was used to stimulate the left dorsolateral prefrontal cortex and then the left lateral temporal lobe for 20min each day for 4weeks. Each patient underwent neuropsychological assessment and resting-state functional magnetic resonance imaging (rsfMRI) before and after treatment. The fractional amplitude of low frequency fluctuation (fALFF) of rsfMRI data in real group were: (1) compared to sham; (2) correlated with rTMS-induced cognitive alterations. Significantly increased fALFF in right cerebellum/declive, left lingual/cuneus and left cingulate gyrus, as well as decreased fALFF in left middle frontal gyrus were found after 10Hz rTMS, but not after sham stimulation. Using these suprathreshold regions, we found that rTMS increased functional connectivity between the right cerebellum/declive and left precentral/postcentral gyrus. The fALFF increase in left lingual/cuneus and right cerebellum/declive was associated with significant improvement in cognitive function. rTMS combined with cognitive training induced increased low frequency fluctuation neural oscillations and functional connectivity in brain regions subserving cognition, suggesting a possible neuronal mechanism of the beneficial effects of rTMS.

Anti-tuberculosis drugs used in a directly observed treatment short course (DOTS) schedule alter endocrine patterns and reduce the ovarian reserve and oocyte quality in the mouse.

Tuberculosis is one of the major infectious diseases, with people of reproductive age group having a high risk of infection. The present study was designed to understand the consequences of anti-tuberculosis drugs (ATDs) used in DOTS (directly observed treatment short course) schedule on ovarian function. Adult female Swiss albino mice were orally administered with combinations of ATDs used in the DOTS schedule every day for 4weeks. At 2weeks after the cessation of ATDs administration, the endocrine changes and ovarian function were assessed in mice. Administration of ATDs to mice resulted in a prolonged estrous cycle, reduced ovarian follicle reserve, alteration in FSH, LH, and progesterone level, and decreased the number of ovulated oocytes. Further, the degree of fragmentation, degeneration, abnormal distribution of cytoplasmic organelles, abnormal spindle organisation, and chromosomal misalignment were higher in oocytes that were ovulated following superovulation. Blastocysts derived from ATDs treated mice had significantly lower total cell numbers and greater DNA damage. A marginal increase in the number of resorbed fetuses was observed in all the ATDs treated groups except in the multidrug resistance treatment group. Male progeny of ATDs treated mice had decreased sperm count and lower progressive motility, while female progeny exhibited a non-significant reduction in the number of oocytes ovulated. Theresults of this study suggest that ATDs can have significant adverse effects on the ovarian reserve, cytoplasmic organisation of oocytes, and can potentially cause transgenerational changes. The findings of the present study indicate ovarian toxicity of ATDs and warrant further research in the direction of identifying alternate drugs with minimal toxicity, and strategies to mitigate the ovarian toxicity induced by these drugs.

A new therapeutic effect of fenofibrate in Duchenne muscular dystrophy: The promotion of myostatin degradation.

Duchenne muscular dystrophy (DMD) is a degenerative muscle disease with no effective drug treatment. This study investigated the positive effects of fenofibrate on dystrophic muscles. Myostatin expression in serum and muscle tissue from patients with Duchenne muscular dystrophy and mdx mice were tested. Primary myoblasts isolated from mdx mice were challenged with an inflammatory stimulus and treated with fenofibrate. In animal experiments, 6-week-old male mdx mice were treated with fenofibrate (100 mg kg-1 ) administered orally once per day for 6weeks. Effects of fenofibrate were evaluated by tests of muscle function plus histology and biochemical analyses of serum. Expression of myostatin, MuRF1, and atrogin-1 in skeletal muscle was evaluated by western blotting and real-time PCR. Total and oxidative myosin heavy chain (MHC) were assessed via immunofluorescence. Expression of myostatin protein was increased in dystrophic muscle of patients with Duchenne muscular dystrophy and mdx mice. Fenofibrate enhanced myofibre differentiation by down-regulating the expression of myostatin protein but not mRNA in primary myoblasts of mdx mice. Fenofibrate significantly improved muscle function while ameliorating muscle damage in mdx mice. These benefits were accompanied by an anti-inflammatory effect. Fenofibrate treatment returned myofibre function by inhibiting the expressions of myostatin, MuRF1, and atrogin-1 protein in the gastrocnemius muscle and diaphragm, while leaving the mRNA level of myostatin unaffected. Fenofibrate substantially slows muscle dystrophy by promoting the degradation of myostatin protein, which may indicate a new therapeutic focus for patients with Duchenne muscular dystrophy.

Limosilactobacillus fermentum Strains with Claimed Probiotic Properties Exert Anti-oxidant and Anti-inflammatory Properties and Prevent Cardiometabolic Disorder in Female Rats Fed a High-Fat Diet.

This study assessed the effects of a mixed formulation containing Limosilactobacillus (L.) fermentum 139, L. fermentum 263, and L. fermentum 296 on cardiometabolic parameters, inflammatory markers, short-chain fatty acid (SCFA) fecal contents, and oxidative stress in colon, liver, heart, and kidney tissues of female rats fed a high-fat diet (HFD). Female Wistar rats were allocated into control diet (CTL, n = 6), HFD (n = 6), and HFD receiving L. fermentum formulation (HFD-LF, n = 6). L. fermentum formulation (1 × 109CFU/mL of each strain) was administered two twice a day for 4weeks. Administration of L. fermentum increased acetate and succinate fecal contents and reduced hyperlipidemia and hyperglycemia in rats fed a HFD (p < 0.05). Administration of L. fermentum decreased low-grade inflammation and improved antioxidant capacity along the gut, liver, heart, and kidney tissues in female rats fed a HFD (p < 0.05). Administration of L. fermentum prevented dyslipidemia, inflammation, and oxidative stress in colon, liver, heart, and kidney in female rats fed a HFD.

The Efficacy of High- or Low-Frequency Transcranial Magnetic Stimulation in Alzheimer's Disease Patients with Behavioral and Psychological Symptoms of Dementia.

Alzheimer's disease (AD) is usually accompanied by different degrees of behavioral and psychological symptoms of dementia (BPSD). Transcranial magnetic stimulation (TMS) has been applied for the treatment of AD as a painless and noninvasive therapy. However, the efficacy of repetitive TMS (rTMS) with different frequencies in AD with BPSD remains unknown. A total of 32 AD patients with psychobehavioral symptoms were selected as the study subjects. Among them, 16 patients were included in the high-frequency TMS group with an average disease duration of 6.22 ± 2.55years. The low-frequency TMS group was gender and age matched with a disease course of 7.02 ± 3.33-year average duration. The high-frequency TMS group received TMS treatment twice per day for 4weeks under 80% MT stimulation intensity, 10-Hz frequency for 0.5h each time, and the low-frequency TMS group received TMS treatment of 2-Hz frequency for 0.5h each time. Neuropsychological status was assessed by the Behavioral Pathology in Alzheimer's Disease Rating Scale (BEHAVE-AD) score. The behavioral ability was assessed by the Abilities of Daily Living (ADL) scale; cognitive function was evaluated by Mini-Mental State Examination (MMSE). The levels of β amyloid 40 and 42 (Aβ40 and Aβ42) in plasma were detected using a double-antibody sandwich enzyme-linked immunosorbent assay. All patients underwent brain magnetic resonance imaging (MRI) before and after the experiment. After 2weeks of treatment, the BEHAVE-AD and ADL scores of the patients in the high-frequency group were significantly lower than those before the treatment, and they continued to decrease after 4weeks of treatment. The BEHAVE-AD and ADL scores of the low-frequency TMS group were also significantly lower than before treatment. The comparison between groups at different time points showed that the BEHAVE-AD and ADL scores of the patients in the high-frequency group were significantly lower than those of the patients in the low-frequency TMS group. The MMSE of high-frequency TMS-treated patients increased from 14.22 ± 3.55 before treatment to 14.67 ± 2.22 at 2week's treatment and 17.33 ± 3.11 at 4week's treatment (p < 0.01) in contrast to 14.19 ± 3.47, 14.28 ± 3.41, and 14.49 ± 2.79, respectively, found in the low-frequency TMS group. At week 4, the high-frequency TMS-treated group's plasma Aβ40 did not change compared to that before treatment. No effects on plasma Aβ42 were observed between the high- vs. low-frequency TMS groups. The incidence of adverse reactions during treatment was comparable between groups. These results indicate that high-frequency TMS has the advantages of fast results, good efficacy, and high safety for the treatment of psychobehavioral abnormalities in AD patients. In addition, our study suggests that high-frequency TMS intervention can further improve the cognitive function of AD patients.

Mitochonic acid-5 ameliorates chlorhexidine gluconate-induced peritoneal fibrosis in mice.

Peritoneal fibrosis is a serious complication of long-term peritoneal dialysis, attributable to inflammation and mitochondrial dysfunction. Mitochonic acid-5 (MA-5), an indole-3-acetic acid derivative, improves mitochondrial dysfunction and has therapeutic potential against various diseases including kidney diseases. However, whether MA-5 is effective against peritoneal fibrosis remains unclear. Therefore, we investigated the effect of MA-5 using a peritoneal fibrosis mouse model. Peritoneal fibrosis was induced in C57BL/6 mice via intraperitoneal injection of chlorhexidine gluconate (CG) every other day for 3weeks. MA-5 was administered daily by oral gavage. The mice were divided into control, MA-5, CG, and CG + MA-5 groups. Following treatment, immunohistochemical analyses were performed. Fibrotic thickening of the parietal peritoneum induced by CG was substantially attenuated by MA-5. The number of α-smooth muscle actin-positive myofibroblasts, transforming growth factor β-positive cells, F4/80-positive macrophages, monocyte chemotactic protein 1-positive cells, and 4-hydroxy-2-nonenal-positive cells was considerably decreased. In addition, reduced ATP5a1-positive and uncoupling protein 2-positive cells in the CG group were notably increased by MA-5. MA-5 may ameliorate peritoneal fibrosis by suppressing macrophage infiltration and oxidative stress, thus restoring mitochondrial function. Overall, MA-5 has therapeutic potential against peritoneal fibrosis.

New insight on the role of liraglutide in alleviating dexamethasone-induced pancreatic cytotoxicity via improving redox status, autophagy flux, and PI3K/Akt/Nrf2 signaling.

Chronic glucocorticoids therapy is commonly complicated by steroid diabetes, although the underlying mechanisms are still elusive. Liraglutide, a glucagon-like peptide-1, was initially found to induce glycemic control and recently it was found to have many pleotropic effects; however, its role in pancreas remains unknown. The present study aims to estimate the protective role of liraglutide on dexamethasone-induced pancreatic cytotoxicity and hyperglycemia, highlighting the possible underlying biochemical, molecular, and cellular mechanisms. Twenty-eight male Wistar rats were involved in this study and were randomly divided into four groups. Group III and IV were treated with 1mg/kg dexamethasone daily for 10days. Group II and IV were treated with liraglutide in a dose of 0.8mg/kg per day for 2weeks. Pancreatic caspase-9, nuclear factor erythroid 2-related factor 2 (Nrf2), phospho-protein kinase-B (pAkt), and sequestrome 1 (p62) levels were assessed by immunoassay. Moreover, phosphoinositide 3-kinase (PI3K) expression by real-time PCR, microtubule-associated protein light chain 3 (LC3B) expression by immunohistochemistry, glycemic status, β-cell function by homoeostasis model assessment (HOMA) β index, and pancreatic redox status were assessed. Liraglutide improved blood glucose level, β-cell function, pancreatic caspase-9 level, redox status, and autophagy. Additionally, it increased pancreatic PI3K, pAkt, and Nrf2 levels. Moreover, preservation of pancreatic histological and the ultrastructural morphological features of β- and α-cells were observed. In conclusion, liraglutide protected against dexamethasone-induced pancreatic injury and hyperglycemia and decelerated the progression towards steroid diabetes via activating PI3K/Akt/Nrf2 signaling and autophagy flux pathways.

Synergistic Effect of Omega-3 and Probiotic Supplementation on Preventing Ligature-Induced Periodontitis.

Omega-3 and probiotics were shown to improve periodontal health by modulating the host immune response. Recently, the combination of omega-3 and probiotics has been shown to have a potential synergistic effect on host modulation. The aim of this study was to evaluate the prophylactic role of an omega-3 and probiotic combination on alveolar bone loss (ABL) via inflammatory response in an experimental periodontitis model. Forty-three rats were divided into 5 groups as control (C, n = 8), periodontitis (P, n = 8), omega-3 + periodontitis (O, n = 8), probiotic + periodontitis (Pro, n = 10), and omega-3 + probiotic + periodontitis (OPro, n = 9). Additionally to a standardized diet, omega-3 and/or probiotics were supplemented with oral gavage to the O, Pro, and OPro groups for 44days. Periodontitis was induced by ligature to the P, O, Pro, and OPro groups on the 30th day for 2weeks. ABL levels were measured histopathologically, and serum interleukin (IL) 1β, IL6, and IL10 levels were analysed by enzyme-linked immunosorbent assay. ABL increased in all periodontitis groups (P, O, Pro, and OPro), compared to C group. Compared to P group, all oral gavage groups (O, Pro, and OPro) revealed decreased ABL, which was lowest in OPro group. IL1β and IL6 decreased and IL10 increased in OPro group, compared to P group. In conclusion, prophylactic administration of omega-3 and probiotic combination reduced ABL and improved serum IL1β, IL6, and IL10 levels more than their single use.

Secukinumab and metformin ameliorate dermal fibrosis by decreasing tissue interleukin-17 levels in bleomycin-induced dermal fibrosis.

Although the pathogenesis of systemic sclerosis is not exactly known, it is thought that immune activation has prominent roles in pathogenesis. Secukinumab is a monoclonal antibody against interleukin (IL)-17A. Metformin, a widely used antidiabetic medication, has anti-proliferative, immunomodulating and anti-fibrotic activities. The purpose of our study is to determine the therapeutic efficacy of secukinumab and metformin on bleomycin (BLM) induced dermal fibrosis. Fifty Balb/c female mice were divided into 5 groups: (group 1 control, 2 sham, 3 secukinumab, 4 metformin and 5 secukinumab+metformin). The mice in the control group received 100μL phosphate-buffered saline (PBS), while the mice in other groups received 100μL (100μg) BLM in PBS subcutaneously (sc) every day for 4weeks. In addition, mice in groups 3 and 5 received secukinumab at a dose of 10mg/kg/wk sc, and mice in the groups 4 and 5 received oral metformin 50mg/kg/d for 28days. All groups of mice were sacrificed at the end of the 4th week and tissue samples were taken for analysis. In addition to histopathological analysis, skin tissue messenger RNA (mRNA) expressions of IL-17 and collagen 3A were measured by real-time polymerase chain reaction. Repeated BLM injections had caused dermal fibrosis. In addition, the mRNA expressions of IL-17 and collagen 3A were increased in the BLM group. Secukinumab and metformin ameliorated dermal fibrosis. They decreased dermal thickness and tissue IL-17A and collagen 3A mRNA levels. Secukinumab and metformin exhibit anti-fibrotic effects in the BLM-induced dermal fibrosis.

Improved Endothelium-Dependent Relaxation of Thoracic Aorta in Niclosamide-Treated Diabetic Rats.

Diabetes-induced endothelial dysfunction is critical for the development of diabetic cardiovascular complications. The aim of this study was to investigate the effect of niclosamide (Nic) on vascular endothelial dysfunction in streptozotocin (STZ)-induced diabetic rats. Male Sprague-Dawley rats were injected with a single intraperitoneal injection of STZ (75mg/kg) to induce type 1 diabetes, and Nic (10mg/kg) was intraperitoneally administered per day for 4weeks. Endothelial function was evaluated as carbachol (CCh, an endothelium-dependent vasodilator)-evoked relaxation in the experiments performed on isolated thoracic aortas. The changes in the protein expressions of phosphorylated eNOS at serine 1177 (p-eNOSSer1177) and phosphorylated VASP at serine 239 (p-VASPSer239) of the rat aortas were analyzed by western blotting to determine whether NO/cGMP signaling is involved in the mechanism of Nic. STZ-injected rats had higher fasting blood glucose and less body weight compared to control rats (p < 0.05). Nic treatment did not affect blood glucose levels or body weights of the rats. CCh-induced endothelium-dependent relaxation of the aortic rings was significantly decreased in diabetic rats compared to control (Emax = 66.79 ± 7.41% and 90.28 ± 5.55%, respectively; p < 0.05). CCh-induced relaxation response was greater in Nic-treated diabetic rats compared to diabetic rats (Emax = 91.56 ± 1.20% and 66.79 ± 7.41%, respectively; p < 0.05). Phosphorylation of eNOS and VASP in aortic tissues was significantly reduced in diabetic rats, which were markedly increased by Nic treatment (p < 0.05). We demonstrated that Nic improved endothelial dysfunction possibly through the activation of NO/cGMP signaling without affecting hyperglycemia in diabetic rats. Our results suggesting that Nic has potential of repurposing for diabetic cardiovascular complications.

Transcriptome analysis reveals lung-specific miRNAs associated with impaired mucociliary clearance induced by cigarette smoke in an in vitro human airway tissue model.

Exposure to cigarette smoke (CS) is strongly associated with impaired mucociliary clearance (MCC), which has been implicated in the pathogenesis of CS-induced respiratory diseases, such as chronic obstructive pulmonary diseases (COPD). In this study, we aimed to identify microRNAs (miRNAs) that are associated with impaired MCC caused by CS in an in vitro human air-liquid-interface (ALI) airway tissue model. ALI cultures were exposed to CS (diluted with 0.5 L/min, 1.0 L/min, and 4.0 L/min of clean air) from smoking five 3R4F University of Kentucky reference cigarettes under the International Organization for Standardization (ISO) machine smoking regimen, every other day for 1week (a total of 3days, 40min/day). Transcriptome analyses of ALI cultures exposed to the high concentration of CS identified 5090 differentially expressed genes and 551 differentially expressed miRNAs after the third exposure. Genes involved in ciliary function and ciliogenesis were significantly perturbed by repeated CS exposures, leading to changes in cilia beating frequency and ciliary protein expression. In particular, a time-dependent decrease in the expression of miR-449a, a conserved miRNA highly enriched in ciliated airway epithelia and implicated in motile ciliogenesis, was observed in CS-exposed cultures. Similar alterations in miR-449a have been reported in smokers with COPD. Network analysis further indicates that downregulation of miR-449a by CS may derepress cell-cycle proteins, which, in turn, interferes with ciliogenesis. Investigating the effects of CS on transcriptome profile in human ALI cultures may provide not only mechanistic insights, but potential early biomarkers for CS exposure and harm.

Zinc is a strong stimulant of metallothionein synthesis in the ischaemic testis tissue.

This study was performed to determine the effect of zinc supplementation effects on metallothionein levels in testis ischaemia-reperfusion of rats. The experimental groups were designed as Control, Sham, Ischaemia-Reperfusion (I/R) and I/R+Zinc supplemented. Zinc supplemented as 5mg/kg day for 3weeks. Testis tissues were analysed for metallothionein by immunohistochemical staining procedures. Group comparison showed that the zinc-supplemented ischaemia-reperfusion group had a significantly higher level of cells strongly stained with metallothionein than all other groups. A general evaluation of the results suggests that zinc supplementation is a strong stimulant of metallothionein synthesis in the ischaemic testis tissue.

Cottonseed Oil Alleviates Ischemic Stroke-Induced Oxidative Stress Injury Via Activating the Nrf2 Signaling Pathway.

Oxidative stress is believed to be one of the primary causes in ischemic stroke injury, and the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway is the most important endogenous antioxidative stress damage pathway. Cottonseed oil (CSO), which is used mostly as a solvent for lipid-soluble drugs, has been shown to exert antioxidative effects against peripheral tissue injury. However, the effects and mechanisms of CSO on ischemic stroke-induced oxidative stress injury and the Nrf2 signaling pathway remain largely unknown. In this study, we investigated the potential of CSO in regulating oxidative stress injury induced by middle cerebral artery occlusion and reperfusion (MCAO-R), or oxygen and glucose deprivation and reperfusion (OGD-R). We found that 1.3mL/kg CSO treatment of male rats with a subcutaneous injection once every other day for 3weeks significantly improved neurological deficit; reduced infarction volume; alleviated neuronal injuries; reduced the content of ROS and MDA; increased the activity of SOD, GSH, and GSH-PX; and markedly increased the expression of Nrf2. Furthermore, treatment with 10-9μL/mL CSO to a neuron cell line (HT-22) for 24h significantly increased cell viability and decreased cell apoptosis after OGD-R injury; significantly reduced the levels of ROS and MDA; increased the activity of SOD, GSH, and GSH-PX; and induced an increase in Nrf2 nuclear translocation. Based on our findings, we conclude that CSO treatment alleviates ischemic stroke injury-induced oxidative stress via activating the Nrf2 signaling pathway, highlighting the potential that CSO has as a therapeutic for ischemic strokes.

Ischemic Conditioning Ameliorated Hypertension and Vascular Remodeling of Spontaneously Hypertensive Rat via Inflammatory Regulation.

Vascular remodeling is an initial step in the development of hypertension. Limb remote ischemic conditioning (LRIC) is a physiological treatment that induces endogenous protective effect during acute ischemic injury. However, the impact of long-term LRIC on hypertension, a chronic disease, is unknown. In this study, we aimed to investigate the LRIC effect on blood pressure and vascular remodeling in spontaneously hypertensive rat (SHR) model and patients with prehypertension and early-stage hypertension. LRIC of rats was performed once a day for 6-weeks. Blood pressure, vascular remodeling (cross-sectional area, extracellular deposition, and smooth muscle cell area), inflammation (inflammatory factors, and inflammatory cells) were compared among normotensive Wistar-Kyoto rats (WKY), WKY RIC group, SHR control group, and SHR RIC. Long-term LRCI treatment (twice a day for 4-weeks) was performed on patients with prehypertension or early-stage hypertension. Blood pressure and pulse wave velocity (PWV) were analyzed before and after LRIC treatment. LRIC treatment decreased blood pressure in SHR (n = 9-10). LRIC ameliorated vascular remodeling by decreasing cross-sectional area, suppressing deposition of the extracellular matrix, and hypertrophy of smooth muscle cell in conduit artery and small resistance artery (n = 7). LRIC decreased proinflammatory factors while increasing the anti-inflammatory factors in the circulation (n = 5). LRIC decreased circulating monocyte and natural killer T-cell levels (n = 5). Furthermore, LRIC treatment decreased blood pressure and improved vascular stiffness in patients (n = 20). In conclusion, long term LRIC could decrease blood pressure and ameliorate vascular remodeling via inflammation regulation. LRIC could be a preventive treatment for people with blood pressure elevation or prehypertension.

Hepatoprotective effect of ethanolic extract of Origanum vulgare against doxycycline toxicity.

The current study evaluates the ameliorative action of Origanumvulgareethanolic extract against the hepatotoxic effects of experimental doxycycline overdose in rats. Forty male Sprague-Dawley rats (160–200 gm) were divided into four groups: the control group, administered distilled water (10 ml/kg b.w.); group (2) administered doxycycline (39.2 ml/kg b.w.) in distilled water; group (3) administered O. Vulgare ethanolic extract (20 mg/kg b.w.) +doxycycline (39.2 ml/kg b.w.) in distilled water and group (4) administered O. Vulgare ethanolic extract (60 mg/kg b.w.) + doxycycline (39.2 ml/kg b.w.) in distilled water. All rats were administrated once per day for 4weeks. Doxycycline administrated rats showed alteration in histological structure in the liver as vacuolization, necrosis, inflammation, and sinusoidal dilatations. Also increased Kupffer cells population and congestion and dilatation of central vain with fibrin thrombi filling their lumen were shown.Ultra structurally destructed cell membrane of hepatocyte, Pyknotic and karyolitic nuclei, losses in some cytoplasmic organelles, swollen mitochondria, fragmentation of rER and discarded lysosomes were observed. All of those improved by the ethanolic extract of Origanum vulgare.

Associations between affect, craving, and smoking in Korean smokers: An ecological momentary assessment study

Cigarette smoking remains the largest cause of preventable death in the United States and worldwide. In South Korea and other Asian countries, a large proportion of males smoke, increasing the need to examine cigarette smoking in these populations. Research suggests that the association between positive affect and negative affect, and between affect and craving, may differ across cultures, and that it is useful to examine these associations using Ecological Momentary Assessment (EMA). South Korean smokers (N = 20, Mean Age = 21.15, 25% female) completed baseline questionnaires and downloaded an EMA app which prompted 4 random assessments (RAs) each day for 1-week. At each assessment, participants responded to items assessing momentary negative affect (NA) and positive affect (PA), craving, and number of cigarettes smoked since the previous EMA assessment. Linear mixed models (LMMs) were used to analyze EMA data (544 assessments), separating out between- and within- subject associations. There was a significant positive association between positive affect and negative affect at the between-subjects level. Both positive affect and negative affect were significantly positively associated with craving at between-subjects and within-subject levels. Craving was associated with subsequent smoking behavior at the within-subjects level. Overall, results suggest that associations between positive affect and negative affect may be different in South Korean smokers than in Western smokers, and that there are robust associations between both negative and positive affect and craving.

Management of chronic hand and foot eczema. An Australia/New Zealand Clinical narrative.

Chronic hand/foot eczemas are common, but treatment is often challenging, with widespread dissatisfaction over current available options. Detailed history is important, particularly with regard to potential exposure to irritants and allergens. Patch testing should be regarded as a standard investigation. Individual treatment outcomes and targets, including systemic therapy, should be discussed early with patients, restoring function being the primary goal, with clearing the skin a secondary outcome. Each new treatment, where appropriate, should be considered additive or overlapping to any previous therapy. Management extends beyond mere pharmacological or physical treatment, and requires an encompassing approach including removal or avoidance of causative factors, behavioural changes and social support. To date, there is little evidence to guide sequences or combinations of therapies. Moderately symptomatic patients (e.g. DLQI≥10) should be started on a potent/super-potent topical corticosteroid applied once or twice per day for 4weeks, with tapering to twice weekly application. If response is inadequate, consider phototherapy, and then a 12-week trial of a retinoid (alitretinoin or acitretin). Second line systemic treatments include methotrexate, ciclosporin and azathioprine. For patients presenting with severe symptomatic disease (DLQI≥15), consider predniso(lo)ne 0.5-1.0mg/kg/day (or ciclosporin 3 - 5mg/kg/day) for 4-6weeks with tapering, and then treating as for moderate disease as above. In non-responders, botulinum toxin and/or iontophoresis, if associated with hyperhidrosis, may sometimes help. Some patients only respond to long-term systemic corticosteroids. The data on sequencing of newer agents, such as dupilumab or JAK inhibitors, are immature.

Ginseng attenuates fipronil-induced hepatorenal toxicity via its antioxidant, anti-apoptotic, and anti-inflammatory activities in rats.

Fipronil (FPN) is a relatively new and broad spectrum insecticide that induces toxic effects to animals and humans through induction of oxidative stress. Ginseng is a medicinal plant that has antioxidant, anti-inflammatory, and anti-apoptotic activities. Thus, the current study was conducted to evaluate the anti-toxic potential of ginseng aqueous extract (GAE) against FPN-induced hepatorenal toxicity in rats. Thirty-two male Wistar albino rats were randomly allocated into four equal groups. Rats of the control group received distilled water. The second group was administrated with GAE at a dose of 200mg/kg b.w. orally day by day for 6weeks. The third group was intoxicated with FPN at a dose of 4.85mg/kg b.w. orally day by day for 6weeks. The fourth group was administrated with GAE 2h before FPN intoxication. Intoxication of rats with FPN significantly elevated the activities of serum alanine aminotransferase and aspartate aminotransferase and serum levels of urea and creatinine, as well as increased malondialdehyde level and protein expressions of caspase-3 and cyclooxygenase-2 in hepatic and renal tissues. However, it significantly decreased hepatic and renal GSH content and catalase activity. In addition, it induced histopathological alterations in hepatic and renal tissue architectures. Conversely, concomitant oral administration of GAE ameliorated the FPN-induced biochemical, pathological, and histochemical alterations in both hepatic and renal tissues. This study indicated that ginseng attenuates FPN-induced hepatorenal toxicity, possibly via its antioxidant, anti-apoptotic, and anti-inflammatory properties. Graphical Abstract CAL ABSTRACTPHIRAG.