RESULTS:
1 - 20 of 136 for "'IL-6'"
Targeting the IL-6 Pathway in Multiple Myeloma and its Implications in Cancer-Associated Gene Hypermethylation
Aberrant methylation of tumor suppressor genes (TSG) is an important epigenetic event in cancer including multiple myeloma (MM). Interleukin-6 (IL-6) which plays a significant role in the pathogenesis of MM also regulates DNA methylation. However attempts to bring IL-6 blockade to the clinic have had limited success. We hypothesize that IL-6 regulation of hypermethylation may be an important pathway leading to rational chemotherapeutic/anti-IL-6 combinations. We first studied the correlation of IL-6 expression and dependence in MM cell lines: U266B1 RPMI8226 and KAS6/1. We confirmed that KAS6/1 is IL-6-dependent whereas U266B1 and RPMI8226 cells are IL-6-independent and that blocking IL-6 inhibited the growth of U266B1 (36% inhibition; p<0.05) and KAS6/1 (68% inhibition; p<0.01) but not the RPMI8226 cells. Using RT-PCR we showed that U266B1 cells express IL-6 but RPMI8226 and KAS6/1 cells do not. This IL-6 expression pattern correlates with the anti-IL-6 inhibition findings. To correlate IL-6 sensitivity with hypermethylation of TSG we investigated promoter methylation of CDH1 and DcR1. We found that the promoter of DcR1 and CDH1 is methylated in U266B1 cells and un-methylated in RPMI8226 cells. Furthermore the DcR1 promoter was un-methylated in KAS6/1 cells. These data support our hypothesis that an IL-6-dependent pathway may regulate hypermethylation of TSG in MM. Newer chemotherapeutic agents that affect methylation are being studied in combination with IL-6 blockade.
Dehydroepiandrosterone Modulates Survival and Immune Functions During Sepsis Depending on the Way of Drug Administration
Background: Administration of dehydroepiandrosterone (DHEA) has been demonstrated to improve survival and cellular immune functions during systemic inflammation. Although there is evidence that the route of drug application may profoundly affect the DHEA-induced effects the impact of this parameter remains to be established. Materials and Methods: Male NMRI mice were subjected to sham-operation (laparotomy) or sepsis (cecal ligation and puncture). Animals received saline or DHEA (20 mg/kg/day) given either subcutaneously intravenously or intraperitoneally. Termination of animals was performed 48 hrs after induction of sepsis in order to monitor splenocyte proliferation (3H-thymidine incorporation assay) splenocyte apoptosis (Annexin V binding capacity) and cytokine release (IL-1β and IL-6 ELISA). Results: Subcutaneous DHEA administration improved the survival rate of septic mice 48 hrs after induction of CLP (75% vs. 47%). This effect was paralleled by a restoration of splenocyte proliferation a decreased cellular apoptosis rate of splenocytes and an attenuation of pro-inflammatory cytokine release. In contrast no significant effects on the survival rate or cellular immune functions were observed following intravenous or intraperitoneal DHEA administration. Conclusions: Subcutaneous administration of DHEA induced an increased survival rate and improved cellular immune functions in septic mice. In contrast no comparable effects were noticed following intravenous or intraperitoneal administration of DHEA.
Origanum vulgare L.: In vitro Assessment of Cytotoxicity, Molecular Docking Studies, Antioxidant and Anti-inflammatory Activity in LPS Stimulated RAW 264.7 Cells
Background: Inflammation involves a dynamic network that is highly regulated by signals that initiate the inflammation process as well as signals that downregulate it. However an imbalance between the two leads to tissue damage. Throughout the world inflammatory disease becomes common in the aging society. The drugs which are used clinically have serious side effects. Natural products or compounds derived from natural products show diversity in structure and play an important role in drug discovery and development. Objective: Oreganum Vulgare is used in traditional medicine for various ailments including respiratory and rheumatic disorders severe cold suppression of tumors. The current study aims to evaluate the anti-inflammatory potential by evaluating various in vitro parameters. Methods: Inflammation-induced in macrophages via LPS is the most accepted model for evaluating the antiinflammatory activity of various plant extracts and lead compounds. Results: The extracts (OVEE OVEAF) as well as the isolated compound(OVRA)of Oreganum Vulgare inhibit the pro-inflammatory cytokines (IL-6 and TNF-α) and NO without affecting cell viability. Conclusion: Our study established that the leaf extracts of Oreganum vulgare L. exhibit anti-inflammatory activity and thus confirm its importance in traditional medicine.
Croton Oil-induced Hemorrhoidal Rats: Evaluation of Anti-inflammatory Mediated Anti-hemorrhoidal Activity of Tridax procumbens Whole Plant
Background: Hemorrhoids are anorectal disorders characterized by dilation of rectal blood vessels inflammation and prolapse of the anal tissue. The disease affects both men and women equally. In consequence the increasing prevalence of the disease needs potential agents with efficiency and low cost to support the treatment. Objective: The treatment of hemorrhoids in modern medicine is still found to be in its infancy as there is no precise treatment for the specific disease. Tridax procumbens Linn (T. procumbens) belongs to the family Asteraceae. From the literature the plant was found to have a traditional use for the treatment of hemorrhoids. Hence the present research was focused on evaluating the antiinflammatory mediated anti-hemorrhoidal potential of ethanolic whole plant extract of T. procumbens (EWETP) in croton oil-induced hemorrhoidal rats. Methods: An in vitro study was conducted to evaluate the percentage inhibition of protein (egg albumin) denaturation by Tridax procumbens. This study determined the initial protective role of plant extracts against inflammatory proteins. An in vivo anti-inflammatory-mediated anti-hemorrhoidal study was carried out on T. procumbens in various groups of croton oil-induced hemorrhoidal rats. Wistar albino rats were selected for the present research and hemorrhoids were induced in experimental animals using a croton oil preparation containing 6% croton oil deionised water pyridine and diethyl ether. Pilex ointment was taken as a reference drug in this study. Inflammation seems to be a major pathway for the progression of hemorrhoids. Hence in the present research Evans blue (EB) extravasation technique was applied to quantify inflammatory proteins. On the last day of the study blood samples were drawn from experimental animals to analyse serum and blood for TNF- α IL-6 and the percentage of neutrophils count. Recto anal coefficient was calculated to measure croton oil-induced rectal inflammation in animals. Histopathological studies were carried out separately on a second set of animals to identify the protective role of T.procumbens on rectal tissue cell histology. Molecular docking studies were carried out to rule out the possible interaction of plant phytoconstituents with the COX-2 enzyme. Results: Results showed that intra rectal application of croton oil preparation in albino rats developed hemorrhoids by elevating serum TNF-α and IL-6 in positive control group animals compared to normal group rats. Treatment of albino rats with T. procumbens at doses of 200 mg/kg and 400 mg/kg in groups IV and V has shown a significant reduction in serum TNF-α and IL-6. Furthermore in the study T. procumbens exhibited a significant dose-dependent reduction of EB dye extravasation in study animals. The study observations also revealed the inhibitory effect of plant extract on the blood percentage of neutrophils count and recto anal coefficient compared to the positive control group rats. Histopathological studies conducted on rectoanal tissues showed the presence of minimal rectal tissue changes in plant extract-treated group animals compared to positive control group rats. Molecular docking studies explored the possible interaction of phenolic compounds of plant extract with the COX enzyme. Conclusion: It was concluded that Tridax procumbens had a protective role against inflammatory mediators in hemorrhoids. In hemorrhoidal rats ethanolic leaf extract was found to reduce the plasma percentage of neutrophils and other inflammatory cytokines TNF-α and IL-6. It could be used as a therapeutic anti-inflammatory mediated anti-hemorrhoidal agent.
Soybean Peptide QRPR Activates Autophagy and Attenuates the Inflammatory Response in the RAW264.7 Cell Model
Background: There are few studies on the autophagy and inflammatory effects of soy peptides on the inflammatory cell model. Further insight into the underlying relationship of soybean peptides and autophagy needs to be addressed. Therefore it is worthwhile investigating the possible mechanisms of soybean peptides especially autophagy and the inflammatory effects. Objective: In this study we used a RAW264.7 cell inflammation model to study the inhibitory effect and mechanism of soybean peptide QRPR on inflammation. Methods: We used LPS-induced inflammation model in RAW264.7 cells to study the inhibitory effect and mechanism of soybean peptide QRPR on inflammation. First Cell viability was determined by cell activity assay. Subsequently the concentrations of the inflammatory cytokines IL-6 and TNF-α were measured by ELISA. IL-6 TNF-α Beclin1 LC3 P62 PIK3 AKT p-AKT pmTOR and mTOR protein expression were detected by western-blot. PIK3 AKT and mTOR gene expression level were quantified by quantitative real-time PCR. Double-membrane structures of autophagosomes and autolysosomes were observed by transmission electron microscopy. The PI3K/AKT/mTOR signaling pathway in LPS-induced RAW264.7 cells was speculated when the autophagy was activated. Results: The results showed that QRPR activates autophagy in the inflammatory cell model and that the inhibitory effect of QRPR on inflammation is reduced after autophagy was inhibited. Western- blot and real-time PCR results indicated that QRPR activates autophagy in LPS-induced RAW264.7 cells by modulating the PI3K/AKT/mTOR signaling pathway and it shows a significant time dependence. Conclusion: This study indicated that the soybean peptide QRPR activates autophagy and attenuates the inflammatory response in the LPS-induced RAW264.7 cell model.
Antipyretic and Anti-inflammatory Effects of Sanchen Pediatric Antipyretic Paste
Objective: This study aimed to investigate the antipyretic and anti-inflammatory effects and mechanisms of Sanchen Pediatric antipyretic Paste (SPAP). Methods: Rats were randomly divided into 7 groups: negative control group positive control group positive treatment group SPAP high-dose medium-dose and low-dose groups and blank substrate group. Except normal control group rats in other groups were subcutaneously injected with 10% dry yeast suspension (10 mL/kg) on the back to establish a fever model and the normal group was given the same volume of saline. At the 4 h and 7 h after modeling each treatment group was subjected to corresponding SPAP intervention. Anal temperature was measured every one hour after modeling for 10 consecutive times. The average temperature-rise curve maximum temperature and body temperature response index (TRI) were calculated to evaluate the efficacy of SPAP. After the last temperature measurement abdominal aortic blood was collected and serum was separated from blood. The levels of IL-6 TNF-α and CRP in serum were determined by enzyme-linked immunosorbent assay. Results: The body temperature of the positive control group was significantly increased (p < 0.01) 4 hours after model establishment and that of the SPAP groups significantly decreased (p < 0.01) after 5 hours of the model establishment. The levels of Serum IL-6 TNF-α and CRP were significantly decreased (p < 0.01) in a dose-dependent manner. Conclusion: SPAP has an obvious antipyretic effect on fever caused by dry yeast in rats. One of its antipyretic mechanisms may be associated with inhibiting inflammatory reactions by reducing the production or accelerating the degradation of endogenous thermogenic cytokines such as IL-6 TNF- α and CRP.
Inflammatory Cytokines Pathways as Potential Therapeutic Targets for Gastric Cancer
Gastric cancer is the fourth most common cancer and the second most common cause of cancer deaths worldwide. The 90% of gastric cancers are adenocarcinomas and two main types can be distinguished: diffuse and intestinal. The process preceding the diffuse-type carcinomas is not well known whereas the precursor stages of the intestinal-type are histologically well identified. The colonization of the gastric mucosa by Helicobacter pylori and the associated inflammatory response induced by the presence of inflammatory cytokines have been postulated as initiators of the neoplastic transformation. TNF-α IL-1β IL-6 and IFN-γ cytokines have been detected in H. pylori-infected stomachs and can activate specific transcription factors that would regulate the expression of genes implicated in the transformation of the gastric mucosa. In vivo mouse models of gastric cancer have been recently developed to analyse the implication of the inflammatory cytokines in the regulation of specific genes involved in the gastric neoplastic transformation. The signalling pathways activated by proinflammatory cytokines represent new valid approaches for antitumor therapies and the specific transcription factors activated are potential targets for inhibition. STAT3 and NF-kappaB that are hyperactivated in many human tumors are implicated in the transcription of genes that promote oncogenesis and metastasis by the participation in cell proliferation apoptosis migration angiogenesis and immune evasion processes. Different approaches such as peptidomimetics and small molecule inhibitors have been synthesised. Their potential antitumoral effects are being analysed in different tumor models and some data from pre-clinical assays are available. The association between inflammation and gastric cancer development makes this human tumor type a potential target for the use of these therapeutic approaches.
Overexpression of SOCS2 Inhibits EMT and M2 Macrophage Polarization in Cervical Cancer via IL-6/JAK2/STAT3 Pathway
Objective: SOCS2 is a member of the suppressor of cytokine signaling (SOCS) protein family associated with the occurrence and development of multiple cancers. This study revealed the expression and molecular mechanisms of SOCS2 in cervical cancer. Methods: In this study RT-qPCR Western Blot and immunohistochemistry were used to detect the expression level of SOCS2 in cervical cancer tissues and tumor cells. We overexpressed SOCS2 in SiHa cells via lentivirus. In-vitro experiments were used to investigate the changes in cervical cancer cell proliferation migration and invasion ability before and after SOCS2 overexpression. Western Blot was used to detect the expression of IL-6/JAK2/STAT3 pathway and EMTrelated proteins. M0 macrophages were co-cultured with the tumor-conditioned medium. The effect of SOCS2 on macrophage polarization was examined by RT-qPCR. Results: SOCS2 expression level was significantly downregulated in cervical cancer tissues. SOCS2 was negatively correlated with CD163+M2 macrophages. Overexpression of SOCS2 inhibited the proliferation migration and invasion of cervical cancer cells. The expressions of Twist- 2 N-cadherin and Vimentin were decreased while the expression of E-cadherin was increased. Moreover the expression of IL-6 p-JAK2 and p-STAT3 were decreased. After the addition of RhIL-6 the expression of E-cadherin protein in the LV-SOCS2 group was reversed. CM in the LV-SOCS2 group inhibited the polarization of M2 macrophages. Conclusion: SOCS2 acts as a novel biological target and suppressor of cervical cancer through IL- 6/JAK2/STAT3 pathway.
Evaluation Of Anti-inflammatory Mediated Anti-hemorrhoidal Activity of Lawsonia inermis on Croton Oil Induced Hemorrhoidal Rats
Background: Hemorrhoids are a common recto-anal disorder commonly known as piles or tissue clumps in the rectum. In normal individuals they were known as anal cushions. In the anus they are composed of rectal blood vessels muscles and elastic fibres. When bulged it can cause bleeding constipation itching severe pain and bleeding in the anus. Inflammation of the anal cushion remains major pathogenesis for the development of hemorrhoids. Inflammatory mediators like neutrophils TNF-α and IL-6 seem to play a major role in the development of disease. Objective: This study aims to carry out the ethanolic leaf extract of Lawsonia inermis (L. inermis) and evaluate its anti-hemorrhoidal activity both in vitro and in vivo. Furthermore Molecular Docking was performed on the crystal structure of COX-2 with the selective compound 23d-(R) (PDB ID: 3NTG) protein. Methods: The current study is to estimate an anti-inflammatory mediated anti-hemorrhoidal activity of ethanolic leaf extract of L. inermis at different doses of 200 mg/kg/ir and 400 mg/kg/ir in croton oil-induced hemorrhoidal rats. Pilex ointment is taken as a reference standard in the present study. Evan's blue extravasation technique were applied in the study to quantify the proinflammatory protein. Results: From the study results a dose-dependent effect was found for ethanolic leaf extract of Lawsonia inermis at 200 mg/kg and 400 mg/kg causing a significant reduction of serum Proinflammatory mediators TNF-α IL-6 and plasma neutrophils in croton oil-induced hemorrhoidal rats. Conclusion: Studies represented that the plant extract can significantly inhibit protein denaturation of egg albumin in in vitro and found to reduce croton oil induced inflammatory mediators in hemorhhoidal rats.
Pro-Inflammatory Cytokines and their Actions on the Metabolic Disturbances Associated with Cancer: Implications in Cachexia
The main aim of the present review is to summarize and evaluate the different molecular mechanisms and catabolic mediators (mainly cytokines) involved in cancer cachexia since they may represent targets for future promising clinical investigations.
Biologics and the Cardiovascular System: A Double-Edged Sword
Patients with chronic inflammatory diseases such as rheumatoid arthritis have a higher risk of cardiovascular diseases and related mortality compared to the general population. This risk is first due to classical cardiovascular risk factors but also due to systemic inflammation which is independently involved causing accelerated atherosclerosis myocardial infarction cerebrovascular disease and heart failure (HF). Pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha) interleukin (IL)-1 and IL-6 could be major actors on this pathophysiology. Biologics are effective specific treatments in the management of inflammatory rheumatic and systemic diseases. In this review beneficial and deleterious effects on the heart and vessels of the biologics used in the management of inflammatory arthritis and vasculitides will be discussed focusing on TNF-alpha IL-6 and IL-1 blockades and anti-CD20. Noninflammatory cardiac conditions such as heart failure myocardial infarction and cardiovascular conditions such as atherosclerosis as well as inflammatory diseases including vasculitides will be discussed.
The Role of Flavonoids in Inhibiting IL-6 and Inflammatory Arthritis
Rheumatoid arthritis (RA) is a chronic autoimmune disease that primarily affects the synovial joints. RA has well-known clinical manifestations and can cause progressive disability and premature death along with socioeconomic burdens. Interleukin-6 (IL-6) has been implicated in the pathology of RA where it can stimulate pannus formation osteoclastogenesis and oxidative stress. Flavonoids are plant metabolites with beneficial pharmacological effects including anti-inflammatory antioxidant antidiabetic anticancer etc. Flavonoids are polyphenolic compounds found in a variety of plants vegetables and fruits. Many flavonoids have demonstrated anti-arthritic activity mediated mainly through the suppression of pro-inflammatory cytokines. This review thoroughly discusses the accumulated data on the role of flavonoids on IL-6 in RA.
Modulation of Proinflammatory Bacteria- and Lipid-Coupled Intracellular Signaling Pathways in a Transwell Triple Co-Culture Model by Commensal Bifidobacterium Animalis R101-8
Background and Aims: Following a fat-rich diet alterations in gut microbiota contribute to enhanced gut permeability metabolic endotoxemia and low grade inflammation–associated metabolic disorders. To better understand whether commensal bifidobacteria influence the expression of key metaflammation-related biomarkers (chemerin MCP-1 PEDF) and modulate the pro-inflammatory bacteria- and lipid–coupled intracellular signaling pathways we aimed at i) investigating the influence of the establishment of microbial signaling molecules-based cell-cell contacts on the involved intercellular communication between enterocytes immune cells and adipocytes and ii) assessing their inflammatory mediators’ expression profiles within an inflamed adipose tissue model. Material and Methods: Bifidobacterium animalis R101-8 and Escherichia coli TG1 respectively were added to the apical side of a triple co-culture model consisting of intestinal epithelial HT-29/B6 cell line human monocyte-derived macrophage cells and adipose-derived stem cell line in the absence or presence of LPS or palmitic acid. mRNA expression levels of key lipid metabolism genes HILPDA MCP-1/CCL2 RARRES2 SCD SFRP2 and TLR4 were determined using TaqMan qRT-PCR. Protein expression levels of cytokines (IL-1β IL-6 and TNF-α) key metaflammation-related biomarkers including adipokines (chemerin and PEDF) chemokine (MCP- 1) as well as cellular triglycerides were assessed by cell-based ELISA while those of p-ERK p-JNK p-p38 NF-ΚB p-IΚBα pc-Fos pc-Jun and TLR4 were assessed by Western blotting. Results: B. animalis R101-8 inhibited LPS- and palmitic acid-induced protein expression of inflammatory cytokines IL-1β IL-6 TNF-α concomitant with decreases in chemerin MCP-1 PEDF and cellular triglycerides and blocked NF-kB and AP-1 activation pathway through inhibition of p- IΚBα pc-Jun and pc-Fos phosphorylation. B. animalis R101-8 downregulated mRNA and protein levels of HILPDA MCP-1/CCL2 RARRES2 SCD and SFRP2 and TLR4 following exposure to LPS and palmitic acid. Conclusion: B. animalis R101-8 improves biomarkers of metaflammation through at least two molecular/signaling mechanisms triggered by pro-inflammatory bacteria/lipids. First B. animalis R101-8 modulates the coupled intracellular signaling pathways via metabolizing saturated fatty acids and reducing available bioactive palmitic acid. Second it inhibits NF-kB’s and AP-1’s transcriptional activities resulting in the reduction of pro-inflammatory markers. Thus the molecular basis may be formed by which commensal bifidobacteria improve intrinsic cellular tolerance against excess pro-inflammatory lipids and participate in homeostatic regulation of metabolic processes in vivo.
Pharmacophore Generation, Quantitative Structure-Activity Relationship (QSAR), and Molecular Dynamic Simulation of Newly Substituted N-(6- Chloro-3-cyano-4-phenyl-4H-chromen-2-yl)-2-(4-chloro-phenoxy)-acetamide for Anticancer Activity
Objective: The main objective of the study was to develop the Quantitative Structure- Activity Relationship (QSAR) and pharmacophore model by using data obtained from HT-29 cells to develop potent lead molecule for the scientific community. Materials and Methods: Common pharmacophore model atom-based 3D-QSAR and molecular dynamic (MD) simulation were carried out via computational techniques by using 4H-chromene derivatives. Results: The reliable common pharmacophoric hypothesis DHH13 was generated and 3.95 survival value was also found. Furthermore the statistically significant 3D-QSAR model was developed where r2=0.52 was found by using the Partial least squares (PLS) regression method. Phase predicted activity and Log GI50 demonstrated an important atomic position in the structure of ligands to ascertain anti colon cancer activity. Also MD simulation was carried out between top rank leads targeting IL-6 that provided better binding conformational and complex stability into the active pocket site of the target throughout the MD simulation. Conclusion: The outcome of this design shows that the pharmacophore model and 3D-QSAR might be helpful for researchers in the field of medicinal chemistry to design and develop potential anti colon cancer compounds.
Anti-Interleukin-6 Receptor Antibody Treatment in Inflammatory Autoimmune Diseases
Tocilizumab (namely MRA) a humanized anti-interleukin (IL)-6 receptor monoclonal antibody is under development by Roche for the treatment of inflammatory autoimmune diseases such as rheumatoid arthritis (RA) systemic onset juvenile idiopathic arthritis (JIA) adult-onset Still's disease Castleman's disease and Crohn's disease. Tocilizumab has a long plasma half-life so it can be administered intravenously biweekly or monthly. Phase I and II clinical trials showed that tocilizumab (2 4 5 8 or 10 mg/kg) reduced disease activity significantly in a dose-dependent manner. Tocilizumab not only improved signs and symptoms but also normalized inflammatory markers such as Creactive protein erythrocyte sedimentation rate (ESR) fibrinogen and serum amyloid A and reversed joint damage of RA. The efficacy of tocilizumab in the treatment of RA was at least as good as methotrexate. Tocilizumab was generally safe and well tolerated. Some adverse events such as significant rises in total cholesterol and triglyceride levels liver function disorders decreases in white blood cell counts diarrhoea and infection were observed. In summary preliminary clinical results suggest that tocilizumab is effective and generally well tolerated in the treatment of IL-6-related inflammatory autoimmune diseases. Like other anti-cytokine immunotherapies caution and close monitoring for the adverse events especially infection are necessary in subsequent clinical trials.
Systemic Inflammation, Infection, ApoE Alleles, and Alzheimer Disease: A Position Paper
Alzheimer disease (AD) includes inflammatory processes in the senile plaques and surrounding glia with increased expression of acute phase proteins such as C-reactive protein (CRP) and IL-6. Increased IL-6 expression during normal brain aging suggests a link of age-related inflammation to the onset of AD during aging. Blood levels of CRP and IL-6 are also associated with higher risk of Alzheimer disease and cognitive decline during aging. Some infections are known to induce inflammation and amyloid deposits. For example HIV induces the deposition of the same beta-amyloid as in Alzheimer disease. The ApoE4 allele may increase HIV-associated dementia in addition to its well-known effect on accelerating the onset age of AD. Many other adverse effects of apoE4 are recognized which suggested the hypothesis that apoE4 persists in human populations because of balancing selection (Charlesworth-Martin hypothesis). The apoE4 allele was acquired during human evolution and may have conferred initial advantages in pathogen resistance. As evidence for this hypothesis apoE4 carriers have less severe liver damage during hepatitis C infections. As human lifespan lengthened and cognitive and cardiovascular health became more important the apoE3 allele spread while the E4 allele was maintained in all populations by balancing selection.
BAO-Ag-NPs as Promising Suppressor of ET-1/ICAM-1/VCAM-1 Signaling Pathway in ISO-induced AMI in Rats
Objectives: Acute myocardial infarction (AMI) is the most prevalent cause of myocardial fibrosis and the leading cause of mortality from cardiovascular disease. The goal of this work was to synthesize Balanites aegyptiaca oil-silver nanoparticles (BAO-Ag-NPs) and evaluate their cardioprotective effect against ISO-induced myocardial infarction in rats as well as their mechanism. Materials and Methods: BAO was isolated and the unsaturated fatty acids were estimated. BAO-Ag-NPs was prepared LD50 was calculated to evaluate its cardioprotective activity against ISO (85 mg/kg)-induced AMI. Different doses of BAO-Ag-NPs (1/50 LD50; 46.6 mg/kg.b.w and 1/20 LD50; 116.5 mg) were received to the rats. Results: The total fatty acids and unsaturated fatty acids generated by BAO were 909.63 and 653.47 mg/100 g oil respectively. Oleic acid methyl ester 9-octadecenoic acid methyl ester and 9 12-Octadecadienoic acid methyl ester were the predominant ingredients with concentrations of 107.6 243.42 and 256.77 mg/100 g oil respectively. According to TEM and DLS examinations BAO-Ag-NPs have a size of 38.20 ± 2.5 nm and a negative zeta potential of -19.82 ± 0.30 mV respectively. The LD50 of synthesized BAO-Ag-NPs is 2330 mg. On the other hand BAOAg- NPs reduce myocardial necrosis by lowering increased BNP cTnI CK-MB TC TG MDA MMP2 TGF-β1 PGE2 and IL-6 levels. Furthermore BAO-Ag-NPs inhibit the expression of ET-1 ICAM-1 and VCAM-1 genes as well as enhance HDL-C CAT and GSH levels when compared to the ISO-treated group of rats. Histopathological findings suggested that BAO-Ag- NPs enhance cardiac function by increasing posterior wall thickness in heart tissues. Conclusion: BAO-Ag-NPs protect against AMI in vivo by regulating inflammation excessive autophagy and oxidative stress as well as lowering apoptosis via suppression of the ET-1 ICAM-1 and VCAM-1 signaling pathways.
Effect of Estradiol on Chondrocytes in the Active Stage of Collagenase- Induced Osteoarthritis
Aim: The aim of the present study is to examine the effect of estradiol on chondrocyte inflammatory potential and apoptosis in a mouse model of osteoarthritis (OA). Background: OA is a degenerative joint disease related to articular cartilage disintegration together with substantial changes in the subchondral bone. Estradiol (ED) is considered to be an important player in maintaining bone homeostasis. Increasing evidence support the association between the severity of cartilage erosion and chondrocyte death. Objective: It is of great importance to elucidate the role of chondrocytes in the development of OA in relation to estrogen levels. Methods: The present work was conducted on a model of collagenase-induced osteoarthritis (CIOA) in ICR (CD-2) mice. The cytokine and MMP-3 concentrations were assayed by ELISA and apoptosis of chondrocytes was determined by flow cytometry. Results: ED decreased the number of cultured TGF-β1 positive chondrocytes reduced the percentage of double-positive CD220+/TNF-α+ chondrocytes. ED reduced the rate of apoptosis and MMP- 13 production of stimulated arthritic chondrocytes and inhibited the release of inflammatory IL-6 and IL-8 cytokines in vitro. Conclusion: Our results show that ED affects chondrocyte functions as a part of its anti-arthritic mechanism of action and it might be a perspective drug for healing OA.
Molecular Mechanisms of Liver Cancer
Liver cancer hepatocellular carcinoma (HCC) in particular is one of the most deadly cancers worldwide and the incidence of HCC is increasing rapidly in the United States and other developed countries. Epidemiological studies have identified major risk factors for HCC including infection with hepatitis B and C virus (HBV and HCV) exposure to certain chemicals high intake of alcohol as well as metabolic diseases such as obesity and diabetes that are rapidly rising in the US. Although the etiologies for liver carcinogenesis are relatively well defined the exact mechanism and pathways leading to cancer development are still unclear. Chronic liver injury followed by inflammation and irregular liver regeneration has been suggested as an important step in hepatocarcinogenesis. Therefore the identification of key factors that protect the liver from injury and inflammation could provide valuable insight into the development of HCC. In this review we will summarize the recent findings in HCC studies mainly focusing on the new molecular link among inflammation liver repair and HCC.
Liver Cancer Stem Cells as an Important Target in Liver Cancer Therapies
Hepatic cancer is one of most common cause of cancer-related death. Hepato-epithelial cancers are believed to originate from the malignant transformation of liver-resident stem/progenitor cells. Liver cancer stem cells have been characterized recently and the phenotype of liver cancer stem cells has been defined as CD133+ CD44+ cancer cells. Recently it has been also demonstrated about the relevance of targeting liver cancer stem cells due to cancer stem cells are related to cancer metastasis. These advances no doubt to bring the new strategy in liver cancer treatment and control in this disease. This review describes the current status and progress about cancer stem cell research in liver and discuss of the implications of these studies in new liver cancer treatment strategies.