Cell type-specific activation of p38 MAPK in the brain regions of hypoxic preconditioned mice

Activation of p38 mitogen-activated protein kinase (p38 MAPK) has been implicated as a mechanism of ischemia/hypoxia-induced cerebral injury. The current study was designed to explore the involvement of p38 MAPK in the development of cerebral hypoxic preconditioning (HPC) by observing the changes in dual phosphorylation (p-p38 MAPK) at threonine180 and tyrosine182 sites, protein expression, and cellular distribution of p-p38 MAPK in the brain of HPC mice. We found that the p-p38 MAPK levels, not protein expression, increased significantly (p < 0.05) in the regions of frontal cortex, hippocampus, and hypothalamus of mice in response to repetitive hypoxic exposure (H1–H6, n = 6 for each group) when compared to values of the control normoxic group (H0, n = 6) using Western blot analysis. Similar results were also confirmed by an immunostaining study of the p-p38 MAPK location in the frontal cortex, hippocampus, and hypothalamus of mice from HPC groups. To further define the cell type of p-p38 MAPK positive cells, we used a double-labeled immunofluorescent staining method to co-localize p-p38 MAPK with neurofilaments heavy chain (NF-H, neuron-specific marker), S100 (astrocyte-specific marker), and CD11b (microglia-specific maker), respectively. We found that the increased p-p38 MAPK occurred in microglia of cortex and hippocampus, as well as in neurons of hypothalamus of HPC mice. These results suggest that the cell type-specific activation of p38 MAPK in the specific brain regions might contribute to the development of cerebral HPC mechanism in mice.     

Effect of sevoflurane and halothane anesthesia on cognitive function and immune function in young rats

In the current study, we scrutinized the effect of sevoflurane and halothane on cognitive and immune function in young rats. The rats were divided into following groups: sevoflurane, halothane and sevoflurane + halothane groups, respectively. The rats were regularly treated with the pre-determined treatment. We also scrutinized the serum proinflammatory cytokines including IL-10, IL-4 and IL-2; brain level IL-1β; hippocampal neuronal apoptosis concentration were estimated. The water maze test was performed in rats for the estimation of cognitive ability. During the water maze test, on the 1st day the sevoflurane group showed the latency; sevoflurane and sevoflurane + halothane group demonstrated the declined latency gradually as compared to the control group rats after the 3 days. The latency of the control, halothane, sevoflurane + halothane group rats showed the reduced latency and also showed the reduced crossing circle times. The hippocampal neuron apoptosis was significantly increased in halothane and sevoflurane + halothane group as compared to control group rats, respectively. Control group rats demonstrated the increased neuron apoptosis. The proinflammatory cytokines including IL-10 and IL-4 was significantly higher in sevoflurane, halothane and sevoflurane + halothane group rats after anesthesia and the whole brain IL-1β was significantly decrease in the sevoflurane, halothane and sevoflurane + halothane as compared to control group. Sevoflurane can inhibit the anesthesia effect of halothane on the immune and cognitive function of rats.     

Effects of benfotiamine and coenzyme Q10 on kidney damage induced gentamicin

Objective

Gentamicin (GM) is an effective antibiotic against severe infection but has limitations related to nephrotoxicity. In this study, we investigated whether benfotiamine (BFT) and coenzyme Q10 (CoQ10), could ameliorate the nephrotoxic effect of GM in rats.

Combination of intensity modulated radiotherapy followed treatment with p38 MAPK activation inhibitor inhibits the proliferation of MCF-7 breast cancer cells

The present study was aimed to investigate the effect of intensity modulated radiotherapy (IMRT) followed by treatment with inhibitor for p38 MAPK, SB203580 on the rate of proliferation in drug resistant MCF-7 breast cancer cells. Interestingly, the results from immuno histochemistry and western blot assays revealed higher level of distribution of activated p38 MAPK in the drug resistant breast cancer tissues compared to the primary tissues. Treatment of the drug resistant MCF-7 cells with SB203580 led to a significant decrease in the phosphorylation of p38 MAPK. Exposure to IMRT caused a significant decrease in the rate of proliferation in drug resistant MCF-7breast cancer cells (P < 0.05). MCF-7 cells were subjected to IMRT for 45 min followed by treatment with SB203580 for 12 h. The results from MTT assay revealed inhibition in the rate of proliferation of MCF-7 cells more efficiently compared to the IMRT or SB203580 when used separately (P < 0.02). The effect of IMRT and SB203580 on inhibition of MCF-7 cell proliferation showed synergistic relation. Since MAPK signaling pathway plays an important role in the development of drug resistance, therefore, inhibition of p38 MAPK activation by the combination of IMRT followed by treatment with inhibitor for p38 MAPK can be a promising strategy for breast cancer treatment. Thus combination of IMRT exposure and treatment with SB203580 can be used for the inhibition of drug resistant breast cancer.     

Resveratrol downregulates acute pulmonary thromboembolism-induced pulmonary artery hypertension via p38 mitogen-activated protein kinase and monocyte chemoattractant protein-1 signaling in rats

AimsIn the present study, we explored the hypothesis that initiation of PH involves the upregulation of monocyte chemoattractant protein-1 (MCP-1) in acute PTE. We evaluated the effects of resveratrol and the role of p38 mitogen-activated protein kinase (MAPK) in this process.Main methodsA rat model of acute PTE was established by infusion of an autologous blood clot into the pulmonary artery through a polyethylene catheter. Rats were randomly divided into 1, 4, and 8 hour time groups. Resveratrol, C1142 (a rodent chimeric mAb that neutralizes rat MCP-1) or SB203580 (a p38MAPK specific inhibitor) was administered to the animals beginning 1 h prior to the start of the acute PTE protocol. At each time point, the mean pulmonary artery pressure (mPAP), mRNA and protein expressions of MCP-1 were measured. The phosphorylation of p38 MAPK (p-pMAPK) was also detected.Key findingsAcute PTE elicited significant increases in mean pulmonary artery pressure (mPAP), and up-regulated the expression of monocyte chemoattractant protein-1 (MCP-1) and phosphorylation of p38 mitogen-activated protein kinase (p-p38 MAPK). Administration of C1142 markedly reduced mPAP. Furthermore, pre-treatment of rats with resveratrol significantly reduced mPAP and down-regulated the expression of MCP-1, which was associated with robustly suppressed acute PTE-induced p-p38MAPK expression.SignificanceThese findings suggested that MCP-1 was involved in the formation of acute PTE-induced PH, and resveratrol down-regulated the expression of MCP-1 by inhibiting acute PTE-induced p-p38MAPK activation, which contributed to the decrease in PH.     

Potential role of cyanidin 3-glucoside (C3G) in diabetic cardiomyopathy in diabetic rats: An in vivo approach

The present study aimed to evaluate the importance of cyanidin 3-glucoside (C3G) of diabetic cardiomyopathy in diabetic rats. The rats were induced with diabetic using streptozotocin and total triglyceride (TG) and total cholesterol (TC) were determined. The range of myocardial enzymes such as aspartate aminotransferase (AST), creatine kinase (CK) and lactate dehydrogenase (LD) were also estimated, further, the Immuno histochemical analysis and western blot investigation were determined for the actual activity of C3G. Results indicated that the marker enzymes such as CK, LD and AST were significantly (P < 0.05) increased in STZ administered rats (DM group), while the levels of these elevated marker enzymes of cardiac injury significantly (P < 0.05) declined in the DM + C3G group, as compared to the diabetic group of rats. Additionally, a decrease in the level of TNF-alpha and interleukin-6, was noticed in the C3G treated group as compared to diabetic group. Finally, blotting analysis clearly confirmed that theC3G treatment resulted to higher level response of Bcl-2 and lower level response of caspase-3 and BAX. In conclusion, C3G a natural antioxidant may prevent cardiovascular complications by ameliorating oxidative damage, inflammation, metabolic dysfunctions and apoptosis pathways in type 2 diabetes.     

Treatment with a p38 MAPK inhibitor attenuates cisplatin nephrotoxicity starting after the beginning of renal damage

AimsCisplatin (CP) promotes increased production of reactive oxygen species, which can activate p38 mitogen activated protein kinases (p38 MAPKs) leading to apoptosis and increased expression of proinflammatory mediators that intensify the cytotoxic effects of CP. We investigated the effect of the treatment with SB203580, a p38 MAPKs inhibitor, on oxidative stress, on the oxidation-associated signal, p38 MAPK and on apoptosis in CP-injected rats, starting after the beginning of the renal damage.Main methodsRats (n = 21) were injected with CP (5 mg/kg, i.p.) and 3 and 4 days after some of them (n = 8) were treated with SB203580 (0.5 mg/kg, i.p.). Controls (n = 6) received saline (i.p.). Two or five days after saline or CP injections, plasma creatinine, urinary volume, sodium and potassium fractional excretions, blood urea nitrogen and urinary lipid peroxidation were measured. The kidneys were removed for histological, apoptosis, immunohistochemical and Western blot studies.Key findingsCP caused abnormalities in kidney functions and structure associated with raised urinary peroxidation levels and higher number of apoptotic cells in the outer medulla. The immunostaining studies showed increased numbers of macrophages/monocytes and p-p38 MAPKs positive cells in the renal outer medulla. The increase of p-p38 MAPKs expression was confirmed by Western blot analysis. All of these alterations were attenuated by treatment with SB203580.SignificanceThese data suggest that the beneficial effect of SB203580 on CP-induced renal damage might be related, in part, to the blockade of p38 MAPK activation with reduction of the inflammatory process, oxidative stress and apoptotic cell death.     

The role of macrophages in the development of biliary injury in a lipopolysaccharide-aggravated hepatic ischaemia-reperfusion model

Introduction

Endotoxins, in the form of lipopolysaccharides (LPS), are potent inducers of biliary injury. However the mechanism by which injury develops remains unclear. We hypothesized that hepatic macrophages are pivotal in the development of endotoxin-induced biliary injury and that no injury would occur in their absence.

Dexamethasone-induced cardioprotection: A role for the phosphatase MKP-1?

AimsPrevious studies suggested that p38 MAPK activation during sustained myocardial ischaemia and reperfusion was harmful. We hypothesize that attenuation of p38MAPK activity via dephosphorylation by the dual-specificity phosphatase MKP-1 should be protective against ischaemia/reperfusion injury. Since the glucocorticoid, dexamethasone, induces the expression of MKP-1, the aim of this study was to determine whether upregulation of this phosphatase by dexamethasone protects the heart against ischaemia/reperfusion injury.Main methodsMale Wistar rats were treated with dexamethasone (3 mg/kg/day ip) for 10 days, before removal of the hearts for Western blot (ip Dex ? P) or perfusion in the working mode (ip Dex + P). Hearts were subjected to 20 min global or 35 min regional ischaemia (36.5 °C) and 30 or 120 min reperfusion. In a separate series, dexamethasone (1 µM) was added to the perfusate for 10 min (Pre + Dex) before or after (Rep + Dex) ischaemia.Key findingsDexamethasone, administered intraperitoneally or added directly to the perfusate, significantly improved post-ischaemic functional recovery and reduced infarct size compared to untreated controls (p < 0.05). These were associated with enhanced up-regulation of MKP-1 protein expression (arbitrary units (mean ± SD): Untreated: 1; ip Dex ? P: 2.59 ± 0.22; ip Dex + P: 1.51 ± 0.22; Pre + Dex: 4.11 ± 0.73, Rep + 15′Dex: 1.51 ± 0.14; untreated vs. all groups, p < 0.05) and attenuation of p38 MAPK activation (p < 0.05) in all dexamethasone-treated groups, except for Rep + 10′Dex. ERK and PKB/Akt activation were unchanged.SignificanceDexamethasone-induced cardioprotection was associated with upregulation of the phosphatase MKP-1 and inactivation of pro-apoptotic p38 MAPK.     

Zataria multiflora would attenuate the hepatotoxicity of long-term albendazole treatment in mice with cystic echinococcosis

Hepatic injury is the major limitation of long-term albendazole administration in patients with cystic echinococcosis (CE), which could give rise to cessation of treatment. The objective of the present study was to evaluate the protective effects of Zataria multiflora aromatic water (AW) against the hepatic injury induced by long-term albendazole treatment in mice with CE. Fifty healthy BALB/c female mice were infected intraperitoneally by injection of 1500 protoscoleces per animal. Five months after infection, the infected animals were divided into five treatment groups including Z. multiflora (40 ml/l in drinking water for 90 days), albendazole (200 mg/kg/day for 90 days), Z. multiflora + albendazole 200 (40 ml/l Z. multiflora and 200 mg/kg/day albendazole for 90 days), Z. multiflora + albendazole100 (40 ml/l Z. multiflora and 100 mg/kg/day albendazole for 90 days), and untreated (control) group. At the end of the treatment period, anesthesia was performed and blood samples were collected directly from the heart prior to euthanasia. Liver variables and oxidative stress markers were measured in the blood serum samples. A decrease in serum liver enzyme activity in the both Z. multiflora + albendazole groups was observed when compared to control, Z. multiflora and albendazole groups; however, the results for Z. multiflora + albendazole 100 were significant (p < 0.007) and superior compared to those for Z. multiflora + albendazole 200. No significant differences for oxidative stress markers were observed between the different groups. The results of the present study revealed that a combined therapy with Z. multiflora AW and albendazole is effective against hepatic injury induced by CE and/or long term albendazole administration in mice with cystic echinococcosis.     

The roles of aerobic exercise training and suppression IL-6 gene expression by RNA interference in the development of insulin resistance

ObjectiveTo demonstrate the hypothesis that aerobic exercise training inhibits the development of insulin resistance through IL-6 and probe into the possible molecular mechanism about it.MethodsRats were raised with high-fat diets for 8 weeks to develop insulin resistance, and glucose infusion rates (GIRs) were determined by hyperinsulinemic–euglycemic clamping to confirm the development of insulin resistance. Aerobic exercise training (the speed and duration time in the first week were respectively 16 m/min and 50 min, and speed increased 1 m/min and duration time increased 5 min every week following it) and/or IL-6shRNA plasmid injection (rats received IL-6shRNA injection via the tail vein every two weeks) were adopted during the development of insulin resistance. The serum IL-6, leptin, adiponectin, fasting blood glucose, fasting serum insulin, GIR, IL-6 gene expression levels, p-p38 in various tissues and p-STAT3/t-STAT3 ratio in the liver were measured.ResultsRats fed with high-fat diets for 8 weeks were developed insulin resistance and the IL-6mRNA levels of IL-6shRNA injection groups in various tissues were significantly lower than those of control group (P < 0.05), respectively. The development of insulin resistance in exercise rats significantly decreased, however, compared with that, the GIR of exercise rats injected by IL-6shRNA was lower (P < 0.05). The IL-6mRNA levels were highest in the fat tissue and lowest in the skeletal muscles in all the rats. The serum adiponectin levels decreased (P < 0.05) following the development of insulin resistance, and it increased (P < 0.05) when the rats were intervened by aerobic exercise training for 8 weeks at the same time. However, there were not significant differences when serum leptin concentrations were compared (P > 0.05). The p-p38 significantly increased in the rats fed with high-fat diets, however, p-p38 of the exercise high-fat diets rats in the liver and fat tissues significantly decreased than that (P < 0.05). The changes of p-p38 in exercise rats injected by IL-6shRNA were irregular. The activation of STAT3 in the liver significantly increased (P < 0.05) following the development of insulin resistance, and it decreased (P < 0.05) when the rats were intervened by aerobic exercise training for 8 weeks at the same time, and the gene silencing of IL-6 did not have effects on the activation of STAT3 in the liver (P > 0.05).ConclusionsIn conclusion, aerobic exercise training prevented the development of insulin resistance through IL-6 to a certain degree. The gene expression and secretion of IL-6 could inhibit the development of insulin resistance. The mechanism of the effects were possibly related with elevating the levels of serum adiponectin, and/or inhibiting the activation of STAT3 in the liver and p38MAPK in the skeletal muscles, liver and fat tissues.     

Protective role of CoQ10 or L-carnitine on the integrity of the myocardium in doxorubicin induced toxicity

Doxorubicin (DOX) is a chemotherapeutic agent used for treatment of different cancers and its clinical usage is hindered by the oxidative injury-related cardiotoxicity. This work aims to declare if the harmful effects of DOX on heart can be alleviated with the use of Coenzyme Q10 (CoQ10) or L-carnitine. The study was performed on seventy two female Wistar albino rats divided into six groups, 12 animals each: Control group; DOX group (10 mg/kg); CoQ10 group (200 mg/kg); L-carnitine group (100 mg/kg); DOX + CoQ10 group; DOX + L-carnitine group. CoQ10 and L-carnitine treatment orally started 5 days before a single dose of 10 mg/kg DOX that injected intraperitoneally (IP) then the treatment continued for 10 days. At the end of the study, serum biochemical parameters of cardiac damage, oxidative stress indices, and histopathological changes were investigated. CoQ10 or L-carnitine showed a noticeable effects in improving cardiac functions evidenced reducing serum enzymes as serum interleukin-1 beta (IL-1 β), tumor necrosis factor alpha (TNF-α), leptin, lactate dehydrogenase (LDH), Cardiotrophin-1, Troponin-I and Troponin-T. Also, alleviate oxidative stress, decrease of cardiac Malondialdehyde (MDA), Nitric oxide (NO) and restoring cardiac reduced glutathione levels to normal levels. Both corrected the cardiac alterations histologically and ultrastructurally. With a visible improvements in α-SMA, vimentin and eNOS immunohistochemical markers. CoQ10 or L-carnitine supplementation improves the functional and structural integrity of the myocardium.     

Expression of IL-32 modulates NF-κB and p38 MAP kinase pathways in human esophageal cancer

BackgroundEsophageal cancer is the seventh leading cause of cancer death in males in USA, and there is a strong link has been demonstrated between inflammation and esophageal cancer, interleukin (IL)-32 is a recently described pro-inflammatory cytokine characterized by the induction of nuclear factor NF-κB activation, the p38MAPK also plays an important role in key cellular processes related to inflammation and cancer. We investigated whether the IL-32 expression may be involved in esophageal carcinogenesis through modulates the activity of NF-κB and p-p38 MAPK.MethodMalignant esophageal tissue and blood samples were obtained from 65 operated untreated patients, normal samples was obtained from 35 patients operated for other reasons as control. IL-32 expression visualized by immunohistochemistry, Real time RT–PCR for IL-32 mRNA expression, NF-κB phosphorylation and phosphorylated p38mapk were analyzed by immunoblotting, ELISA for further detection IL-32 and cytokines (TNF-α, IL-1β, IL-6 and IL-8) concentration in the patient’s sera.ResultsIL-32 expression was increased in immunohistochemical staining for malignant esophageal tissue and it’s correlated with the relative expression level of IL-32 mRNA P = 0.007, the P-NF-κB level elevated in tumor tissue compared with control and no difference in the total NF-κB level P = 0.003 while the IL-32 up-regulated the P-pNF-κB in the esophageal tumor P = 0.005. There is increase in p-p38MAPK activation underlying IL-32 expression in tumor P = 0.004, but no change in total p38 MAPK in malignant esophagus. The plasma level of IL-32 expression was increased in malignant esophageal patients P = 0.01, with increased in the levels of the cytokines TNF-α, IL-6, and IL-1β P<0.05.ConclusionsUnderstanding the pathway of IL-32 expression to stimulate the secretion cytokines via the activation of NF-κB and up-regulation of p-p38MAPK may or may not prove to be a therapeutic target, or a biomarker, and future studies will finally answer this hypothesis generated.     

Promising role of ferulic acid,atorvastatin and their combination in ameliorating high fat diet-induced stress in mice

AimsThe present study evaluated a comparative and combined hepatoprotective effect of atorvastatin (AS) and ferulic acid (F) against high fat diet (HFD) induced oxidative stress in terms of hyperlipidemia, anti-oxidative status, lipid peroxidation and inflammation.Main methodsMale Swiss albino mice were given a diet containing high fat (H) (23.9% wt/wt), supplemented with AS (10 mg/kg) or F (100 mg/kg) and both (10 and 100 mg/kg) for 8 weeks. The control mice (C) were fed with normal diet.Key findingsThe H mice exhibited increased body weight; hyperlipidemia; serum level of tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6); hepatic lipid profile; lipid accumulation; reactive oxygen species (ROS) of hepatocytes, lipid peroxidation and liver antioxidant capacity was decreased. Immunofluorescent and Western blot assay revealed activation of nuclear factor kappa B (NF-κB) signaling pathway. The addition of F or AS and both in the diet significantly counteracted HFD induced body weight gain; hyperlipidemia; TNF-α, IL-6; hepatic lipid profile; fatty infiltration; NF-κB signaling pathway; ROS; lipid peroxidation and moreover elevated levels of hepatic antioxidant enzymes activity were observed.SignificanceSimultaneous treatment with AS, F and their combination protected against HFD induced weight gain and oxidative stress. The protection may be attributed to the hypolipidemic and free radical scavenging activity of AS or F and their combination. This study illustrates that AS and F have relatively similar hypolipidemic, antioxidative, anti-inflammatory actions and the AS + F combination along with HFD has shown outstanding effects as compared to other treated groups.     

AMD3100 treatment attenuates pulmonary angiogenesis by reducing the c-kit (+) cells and its pro-angiogenic activity in CBDL rat lungs

Recent studies have shown that pulmonary angiogenesis is an important pathological process in the development of hepatopulmonary syndrome (HPS), and growing evidence has indicated that Stromal cell-derived factor 1/C-X-C chemokine receptor type 4 (SDF-1/CXCR4) axis is involved in pulmonary vascular disease by mediating the accumulation of c-kit + cells. This study aimed to test the effect of AMD3100, an antagonist of CXCR4, in HPS pulmonary angiogenesis. Common bile duct ligation (CBDL) rats were used as experimental HPS model and were treated with AMD3100 (1.25 mg/kg/day, i.p.) or 0.9% saline for 3 weeks. The sham rats underwent common bile duct exposure without ligation. The c-kit + cells accounts and its angiogenic-related functions, prosurvival signals, pulmonary angiogenesis and arterial oxygenation were analysed in these groups. Our results showed that pulmonary SDF-1/CXCR4, Akt, Erk and VEGF/VEGFR2 were significantly activated in CBDL rats, and the numbers of circulating and pulmonary c-kit + cells were increased in CBDL rats compared with control rats. Additionally, the angiogenic-related functions of c-kit + cells and pulmonary microvessel counts were also elevated in CBDL rats. CXCR4 inhibition reduced pulmonary c-kit + cells and microvessel counts and improved arterial oxygenation within 3 weeks in CBDL rats. The pulmonary prosurvival signals and pro-angiogenic activity of c-kit + cells were also down-regulated in AMD3100-treated rats. In conclusion, AMD3100 treatment attenuated pulmonary angiogenesis in CBDL rats and prevented the development of HPS via reductions in pulmonary c-kit + cells and inhibition of the prosurvival signals. Our study provides new insights in HPS treatment.     

Biological control of invasive apple snails by two species of carp: Effects on non-target species matter

Molluscivorous fish, especially carp, have been adopted as bio-control agents of the invasive apple snail Pomacea canaliculata, but previous studies have focused on their effectiveness, with little attention paid to their undesirable effects on non-target plants and animals. We conducted an 8-week mesocosm study to compare the effectiveness of two indigenous fish, common carp (Cyprinus carpio) and black carp (Mylopharyngodon piceus), in removing P. canaliculata, and their potential side effects on macrophytes and non-target mollusks in a freshwater wetland. Three species of macrophytes and a community of mollusks in the wetland sediment were enclosed in 1 × 1 × 1 m enclosures either with apple snails (AS), with apple snails and common carp (AS + CC), with apple snails and black carp (AS + BC), or without apple snails and fish. Both species of carp were effective predators of P. canaliculata, removing most of the individuals in the enclosures except a few that were too big to fit into their mouth. By reducing apple snail population, black carp reduced grazing of apple snail on macrophytes. In contrast, although common carp controlled apple snail population, it did not reduce overall loss in plant biomass as the fish might also fed on macrophytes. Both species of carp preyed on non-target mollusks. Application of bio-control agents in invasive species management needs to consider their effects on both the pest and non-target plants and animals. Adoption of common and/or black carp to control apple snail populations thus depends on the weight given to their effectiveness and subtle different effects on non-target organisms by wetland management authority.     

Comparative analysis of conventional and biological treatment in healing of bone disease

The healing of Bone tissue consists of a complex process. Hence, we designed our study to evaluate chondrial diseases, which are as they have a very low healing capacity. Seventy two elderly osteoarthritis (OA) and 54-paediatric juvenile idiopathic arthritis (JIA) patients were included. The group was divided as 24 OA patients and 18 JIA patients in each group. Group I received Hyualuronic acid and glucocorticoides. Group II received platelet rich plasma and fibrin glue. Group III received PRP, fibrin glue, and MSC. 40 control patients received only PRP treatment. Out of 72 OA patients 35 (48.6%) male and 37 (51.4%) female with mean age of 48 ± 6.5 years. 64 (88.9%) Patients had pain and swelling. 52 (72.2%) lacked flexibility. 42 (58.3%) had hypertrophy. 28 (38.9%) had less cartilage thickness. 34 (47.2%) were in grade 3, grade 2 has 28 (38.9%) and grade 1 has 10 (13.9%) patients respectively. Among 54 JIA patients 28 (51.9%) male and 26 (48.1%) female patients with mean, age 4.6 ± 3.8 years. 39 (72.2%) had pain and swelling. 32 (59.3%) lacked flexibility. 29 (53.7%) children’s had functional disability. Group I patients showed 30% improvement with no statistical significance (P < 0.21). Group II showed 45% improvement with statistical significance (P < 0.01). In Group III 80%, improvement was observed with statistical significance (P < 0.001). In 40 control patients, 60% improvement was observed. In conclusion, use of these MSC, PRP, and PPP are safe and less cost effective for treating OA and JIA.     

Crocetin treatment inhibits proliferation of colon cancer cells through down-regulation of genes involved in the inflammation

Background

The current study was designed to investigate the effect of crocetin on the proliferation inhibition of colon cancer cells and the underlying mechanism.

Oviposition of Aedes aegypti Linnaeus, 1762 and Aedes albopictus Skuse, 1894 (Diptera: Culicidae) under laboratory and field conditions using ovitraps associated to different control agents,Manaus, Amazonas,Brazil

The aim of this study was to analyze the effectiveness of different control agents of Aedes aegypti and Aedes albopictus associated with ovitraps under laboratory and field conditions. Five treatments were used: grass infusion + Bacillus thuringiensis israelensis (gI + Bti), grass infusion + Saccharopolyspora spinosa (gI + Ss), grass infusion + Pyriproxyfen (gI + P), distilled water + Toxorhynchites haemorrhoidalis (dW + Th), and grass infusion (gI) (control). The highest mean number of eggs of both species were obtained with grass infusion in the laboratory. Among control agents, the lowest mean of A. aegypti eggs occurred with gI + Ss and the lowest mean of A. albopictus eggs occurred with dW + Th. There was no difference between treatments in A. aegypti (P = 0.4320) and A. albopictus (P = 0.7179). In the field, the highest mean number of eggs for both species were obtained with gI + Ss, and the lowest values were obtained with gI + P (P = 0.0124). The treatments can be applied to both the surveillance and the control, but ovitraps with biological larvicide Bti were more effective and safer considering the number of eggs laid and selectivity of pathogens for mosquitoes.     

Cooperative binding promotes demand-driven recruitment of AnxA8 to cholesterol-containing membranes

The functionality of cellular membranes is critically determined by their lipid composition. Within the endolysosomal system, cholesterol is mainly found in more peripheral compartments. In contrast, cholesterol levels are low in late endosomes/lysosomes (LEL), and the occurrence of enlarged pools of this lipid is commonly linked to endolysosomal dysfunction. Here, we show that Annexin A8 (AnxA8), a member of the annexin family of Ca^2 +-dependent membrane-binding proteins, participates in the endosomal regulation of cholesterol homeostasis. Depletion of AnxA8 caused accumulation of cholesterol in LEL, and pharmacological inhibition of the LEL cholesterol export recruited AnxA8 to the cholesterol-laden LEL. Biophysical analysis revealed that cholesterol enhanced the Ca^2 +-dependent affinity of AnxA8 to lipid bilayers, and induced positive cooperativity of membrane binding. Our findings identify AnxA8 as a regulator of LEL cholesterol balance and point to altered membrane binding cooperativity induced by aberrant lipid composition in the target membrane as a means to control the demand-driven recruitment of this cytosolic regulatory protein.