Matrix Metalloproteins Research Articles

The Application of Mesenchymal Stem Cells in Different Cardiovascular Disorders: Ways of Administration, and the Effectors.

The heart is an organ with a low ability to renew and repair itself. MSCs have cell surface markers such as CD45-, CD34-, CD31-, CD4+, CD11a+, CD11b+, CD15+, CD18+, CD25+, CD49d+, CD50+, CD105+, CD73+, CD90+, CD9+, CD10+, CD106+, CD109+, CD127+, CD120a+, CD120b+, CD124+, CD126+, CD140a+, CD140b+, adherent properties and the ability to differentiate into cells such as adipocytes, osteoblasts and chondrocytes. Autogenic, allogeneic, normal, pretreated and genetically modified MSCs and secretomes are used in preclinical and clinical studies. MSCs and their secretomes (the total released molecules) generally have cardioprotective effects. Studies on cardiovascular diseases using MSCs and their secretomes include myocardial infraction/ischemia, fibrosis, hypertrophy, dilated cardiomyopathy and atherosclerosis. Stem cells or their secretomes used for this purpose are administered to the heart via intracoronary (Antegrade intracoronary and retrograde coronary venous injection), intramyocardial (Transendocardial and epicardial injection) and intravenous routes. The protective effects of MSCs and their secretomes on the heart are generally attributed to their differentiation into cardiomyocytes and endothelial cells, their immunomodulatory properties, paracrine effects, increasing blood vessel density, cardiac remodeling, and ejection fraction and decreasing apoptosis, the size of the wound, end-diastolic volume, end-systolic volume, ventricular myo-mass, fibrosis, matrix metalloproteins, and oxidative stress. The present review aims to assist researchers and physicians in selecting the appropriate cell type, secretomes, and technique to increase the chance of success in designing therapeutic strategies against cardiovascular diseases.

Comparative analysis of testicular fusion in Spodoptera litura (cutworm) and Bombyx mori (silkworm): Histological and transcriptomic insights

Spodoptera litura commonly known as the cutworm, is among the most destructive lepidopteran pests affecting over 120 plants species. The powerful destructive nature of this lepidopteran is attributable to its high reproductive capacity. The testicular fusion that occurs during metamorphosis from larvae to pupa in S.litura positively influences the reproductive success of the offspring. In contrast, Bombyx mori, the silkworm, retains separate testes throughout its life and does not undergo this fusion process. Microscopic examination reveals that during testicular fusion in S.litura, the peritoneal sheath becomes thinner and more translucent, whereas in B.mori, the analogous region thickens. The outer basement membrane in S.litura exhibits fractures, discontinuity, and uneven thickness accompanied by a significant presence of cellular secretions, large cell size, increased vesicles, liquid droplets, and a proliferation of rough endoplasmic reticulum and mitochondria. In contrast, the testicular peritoneal sheath of B.mori at comparable developmental stage exhibits minimal change. Comparative transcriptomic analysis of the testicular peritoneal sheath reveals a substantial difference in gene expression between the two species. The disparity in differential expressed genes (DEGs) is linked to an enrichment of numerous transcription factors, intracellular signaling pathways involving Ca2+ and GTPase, as well as intracellular protein transport and signaling pathways. Meanwhile, structural proteins including actin, chitin-binding proteins, membrane protein fractions, cell adhesion, extracellular matrix proteins are predominantly identified. Moreover, the study highlights the enrichment of endopeptidases, serine proteases, proteolytic enzymes and matrix metalloproteins, which may play a role in the degradation of the outer membrane. Five transcription factors-Slforkhead, Slproline, Slcyclic, Slsilk, and SlD-ETS were identified, and their expression pattern were confirmed by qRT-PCR. they are candidates for participating in the regulation of testicular fusion. Our findings underscore significant morphological and trancriptomic variation in the testicular peritoneal sheath of S.litura compared to the silkworm, with substantial changes at the transcriptomic level coinciding with testicular fusion. The research provides valuable clues for understanding the complex mechanisms underlying this unique phenomenon in insects.

Studies of Erk1/2 with Respect to Tumor Aggressiveness in B16f10 Murine Melanoma Cells

Melanoma is a very aggressive form of skin cancer and have the potential to spread from a small sized primary tumor and metastasizes to different locations like lungs, bones, lymph nodes, liver and even brain. Extracellular signal regulated kinase (ERK) molecule present in MAPK pathway plays a major role in different carcinogenic processes like cell migration, cell invasiveness by altering the extracellular matrix (ECM). Cell invasiveness is facilitated by matrix metalloproteins (MMPs) by means of degradation of gelatinase enzyme regulated by a family of receptor proteins called integrins. ECM ligand fibronectin causes increased secretion of MMPs, specially MMP2 and MMP9 facilitating invasiveness and metastasis in cancer cells. This study aims to find the modulatory role of ERK 1/ 2 with respect to tumor aggressiveness on both MMP2 and MMP9 on melanoma metastasis and invasion. ERK pathway was downregulated through administration of inhibitors and ERK 1/ 2 siRNA gene silencing the effect on MMP2 and MMP9 was studied. The studies were done in B16F10 melanoma cell line and mice model. Significant changes were found in levels of MMP2 and MMP9 after downregulating the ERK pathway and can therefore a correlation between ERK and MMP activities was concluded. Elucidating these molecular phenomena in melanoma, this result can help in developing and improving targeted cancer therapies with multiple options in drug discovery.

Objective Monitoring of Cardiovascular Biomarkers using Artificial Intelligence (AI)

Different CVDs (CVD) are the leading wreak of mortality and disability worldwide. The pathology of CVD is complex; multiple biological pathways have been involved. Biomarkers act as a measure of usual or pathogenic biological processes. They play a significant part in the definition, prognostication, and decision-making with respect to the treatment of cardiovascular events. Inthis article, we had summarized key biomarkers which are essential to predict CVDs. We had studied prevalence, pattern of expression of biomarkers (salivary, inflammatory, oxidative stress, chemokines, antioxidants, genetic, etc.), its measurable impact, benefits of early detection and its scope. A considerable number of deaths due to cardiovascular diseases (CVDs) can be attributed to tobacco smoking and it rises the precarious of deathfrom coronary heart disease and cerebrovascular diseases. Cytokines which is categorized into pro inflammatory and anti-inflammatory take part in as biomarkers in CHD, MI, HF. Troponin, growth differentiation factor-15(GDF-15), C-reactive protein, fibrinogen, uric acid diagnose MI and CAD. Matrix Metalloproteins, Cell Adhesion Molecules, Myeloperoxidase, Oxidative stress biomarkers, Incendiary biomarkers are useful to predict the risk of UA, MI, and HF. Increased Endothelin-1, Natriuretic peptides, copeptin, ST-2, Galectin-3, mid-regional-pro-adrenomedullin, catecholamines are used to prognosticate Heart failure. Modern technologies like Artificial Intelligence (AI), Biosensor and high-speed data communication made it possible to collect the high-resolution data in real time. The high-resolution data can be analyzed with advance Machine Learning (ML) algorithms, it will not only help to discover the disease patterns but also an real-time and objective monitoring of bio-signals can help to discover the unknown patterns linked with CVD.

Platelet protects angiotensin II-driven abdominal aortic aneurysm formation through inhibition of inflammation.

Inflammation is the primary cause of abdominal aortic aneurysm (AAA) formation and development. It has been reported that platelets protect against septic shock by inhibiting inflammation. However, it is unclear whether platelets protect AAA progress via suppressing inflammation. A mouse model of AAA was established by a daily administration of angiotensin II (Ang II, 1000ng/kg/min) for 28-day. The AAA mice received 1×109 platelets transfusion in normal saline every 3rd day for 1month. Hematoxylin and eosin, Masson's trichrome, and elastic van Gieson staining techniques were used to analyze the morphology of the abdominal aorta. Immunohistochemistry was used to detect any infiltration of inflammatory cells, inflammatory factors, and matrix metalloproteins (MMPs) in the aortic tissue. Western blot and enzyme-linked immunosorbent assay (ELISA) were used to examine the inflammatory factor proteins levels in the aortic wall and peripheral blood, respectively. Platelets infusion significantly suppressed the Ang II-driven elevation of aortic diameter, AAA formation (52.38% decrease, P<0.05), aortic expansion, elastic lamina destruction, and inflammatory response. In addition, MMP-2 and MMP-9 production were also reduced by platelets transfusion. For the first time, our study reported the beneficial effect of platelet transfusion in suppressing the Ang II-driven AAA progress in mice through the inhibition of inflammation.

Photoprotective effects of sphingomyelin-containing milk phospholipids in ultraviolet B–irradiated hairless mice by suppressing nuclear factor-κB expression

Ceramide-containing phospholipids improve skin hydration and barrier function and are ideal for use in skin care products. In this study, we evaluated the photoprotective effect of milk phospholipids on the skin condition of UVB-irradiated hairless mice. Skin parameters were assessed following oral administration of milk phospholipids. The UVB irradiation induced photoaging in mice. The animals were divided into 5 groups: a control group (oral administration of saline with no UBV irradiation), UVB group (oral administration of saline with UVB irradiation), and 3 UVB irradiation groups receiving the milk phospholipids at 3 different concentrations of oral administration, 50 mg/kg (ML group), 100 mg/kg (MM group), and 150 mg/kg (MH group), for 8 wk. An increase in skin hydration and transepidermal water loss were improved in the 150 mg/kg of milk phospholipid-administered group. Hematoxylin and eosin staining revealed a decrease in epidermal thickness in the milk phospholipid-administered groups (50, 100, and 150 mg/kg of body weight). In particular, the 100 and 150 mg/kg groups showed significant changes in the area, length, and depth of the wrinkles compared with the UVB group. Moreover, the gene expression of matrix metalloproteins was attenuated, and that of proinflammatory cytokines, especially tumor necrosis factor-α, was significantly reduced in the milk phospholipid-administered groups than in the UVB group. The reduced ceramide and increased sphingosine-1-phosphate levels in the skin tissue due to UVB exposure were restored to levels similar to those of the control group following milk phospholipid administration. These results were confirmed to be due to the downregulation of protein expression of nuclear factor kappa-B (NF-κB) and phosphorylated IκB-α (inhibitor of κB α). Collectively, oral administration of milk phospholipids improves skin health through a synergistic effect on photoprotective activity.

Comparison between Cervical Ureaplasma spp. Colonization and the Intensity of Inflammatory Mediators in the Amniotic Fluid Retrieved during Cesarean Delivery in Preterm Birth

We investigated whether cervical Ureaplasma spp. colonization affects the intensity of inflammatory mediators in amniotic fluid retrieved during cesarean delivery in singleton preterm birth. One hundred fifty-three cases in singleton preterm birth with 24–34 weeks’ gestation were enrolled. The intensities of seven inflammatory mediators (interleukin (IL)-1β, IL-6, IL-8, IL-10, tumor necrosis factor-α, and matrix metalloproteins (MMP)-8, MMP-9) of amniotic fluid were measured. We tested cervical swab specimens using real-time polymerase chain reaction assays to detect Ureaplasma spp. colonization. Histologic chorioamnionitis (HCA) was diagnosed when acute inflammation was observed in any of the placental tissues. Mean gestational age at delivery and birth weight were 30.9 ± 2.4 weeks and 1567 ± 524 g, respectively. Cervical Ureaplasma spp. colonization was detected 78 cases. The incidence of HCA was 32.3% (43/133). Although the intensities of all inflammatory mediators were significantly different according to presence or absence of HCA, there were no significant differences according to cervical Ureaplasma spp. colonization. In all 43 cases with HCA and 90 cases without HCA, there were no significant differences between cervical Ureaplasma spp. colonization and the intensity of inflammatory mediators. Cervical Ureaplasma spp. colonization did not affect the intensity of inflammatory mediators in the amniotic fluid retrieved during cesarean delivery.

In vitro and in silico studies on the biochemistry and anti-cancer activity of phytochemicals from Plumbago zeylanica

Plumbago zeylanica is an effective medicinal plant and a potent herb for various diseases. The leaves of P. zeylanica were subjected to crude extraction using Ethyl acetate. Chromatographic analysis of the crude extracts of P. zeylanica were studied in thin layer chromatography on a silica gel matrix. Further the extracts were purified in column chromatography and the fractions were eluted in Ethyl acetate, Chloroform solvent system. The molecules eluted in the fractions were checked in UV-spectroscopy and further characterised by GC-MS analysis. Phenol, 2,4, bis (1,1-dimethyl ethyl)-(7311) highlighted from the chromatographic studies was studied for in silico anticancer effect on matrix metalloproteins, whose dysfunction cause oral squamous cell carcinoma.

Computational studies of Vitexin isolated from Vitex negundo against Rheumatoid Arthritis targets

One of the chronic inflammatory autoimmune diseases that need attention to be treated is Rheumatoid arthritis. Especially RA encounters more female cases manifests progressive destruction of bone and cartilage. Expression of more inflammatory cytokines and Matrix Metallo-Proteins at the synovial tissue destruct collagen structure and worsen the condition. Generally anti-inflammatory drugs and immune-modulatory agents are used to deduce the progression of disease. Such chemical entities have proven many side effects and expensive. This study provides a glimpse of structural based drug designing using bioactive pharmakon from a folk chloric herb. Vitex negundo is a traditionally available plant that has been reported to possess pharmaco-beneficiary bioactive flavonoids especially, vitexin. Virtual screening involves docking of vitexin with three different targets that is responsible for triggering collagenase enzyme was achieved using Autodock. Binding energy of vitexin and TNF α receptor1(TNFR1) was found to be slightly higher when compared to docking results of TNF α converting enzyme (TACE) and Human Inhibitory Kinase β (hIKβ) proteins. The molecular interactions were visualized using BIOVIA discovery studio visualizer. This study may evident that vitexin has enhanced pharmacological benefits that need to be ensured through in vitro and in vivo assays.

Computational and In Vitro Investigation of (-)-Epicatechin and Proanthocyanidin B2 as Inhibitors of Human Matrix Metalloproteinase 1.

Matrix metalloproteinases 1 (MMP-1) energetically triggers the enzymatic proteolysis of extracellular matrix collagenase (ECM), resulting in progressive skin aging. Natural flavonoids are well known for their antioxidant properties and have been evaluated for inhibition of matrix metalloproteins in human. Recently, (-)-epicatechin and proanthocyanidin B2 were reported as essential flavanols from various natural reservoirs as potential anti-inflammatory and free radical scavengers. However, their molecular interactions and inhibitory potential against MMP-1 are not yet well studied. In this study, sequential absorption, distribution, metabolism, and excretion (ADME) profiling, quantum mechanics calculations, and molecular docking simulations by extra precision Glide protocol predicted the drug-likeness of (-)-epicatechin (−7.862 kcal/mol) and proanthocyanidin B2 (−8.145 kcal/mol) with the least reactivity and substantial binding affinity in the catalytic pocket of human MMP-1 by comparison to reference bioactive compound epigallocatechin gallate (−6.488 kcal/mol). These flavanols in docked complexes with MMP-1 were further studied by 500 ns molecular dynamics simulations that revealed substantial stability and intermolecular interactions, viz. hydrogen and ionic interactions, with essential residues, i.e., His218, Glu219, His222, and His228, in the active pocket of MMP-1. In addition, binding free energy calculations using the Molecular Mechanics Generalized Born Surface Area (MM/GBSA) method suggested the significant role of Coulomb interactions and van der Waals forces in the stability of respective docked MMP-1-flavonol complexes by comparison to MMP-1-epigallocatechin gallate; these observations were further supported by MMP-1 inhibition assay using zymography. Altogether with computational and MMP-1–zymography results, our findings support (-)-epicatechin as a comparatively strong inhibitor of human MMP-1 with considerable drug-likeness against proanthocyanidin B2 in reference to epigallocatechin gallate.

Cyclosporine A induces kidney dysfunction by the alteration of molecular mediators involved in slit diaphragm regulation and matrix metalloproteins: the mitigating effect of curcumin

ABSTRACT Background This research aimed at investigating the cyclosporine A intake impact with/without curcumin on podocyte protein gene expressions and matrix metalloproteins (MMPs) changes in rat kidney. Methods Thirty-two Wistar male rats were assigned to the control, sham, cyclosporine A, and cyclosporine A with curcumin groups. Results A significant increase was observed in CD2AP, ACTN4, podocin and also MMP9 and 2, cystatin C levels in the cyclosporine A group following treatment for four weeks, whereas a decrease was found in nephrin gene expression than the control group. In addition, a significant reduction was observed in the cyclosporine A group in glomerular filtration rate (GFR), urine creatinine, and increased plasma creatinine levels than the control group. Using curcumin plus cyclosporine A ameliorated gene expression alterations and increased the reduced amount of GFR, urine urea, and creatinine while reducing the increased plasma cystatine C, urea, and creatinine levels compared with the cyclosporine A group. Conclusion Accordingly, cyclosporine A-induced kidney abnormalities are possibly associated with changes in podocyte intra- and extra-cellular protein gene expression that influence the quality of filtrated fluid via altering the foot process shape and slit diaphragm size. Finally, such impacts are reduced via curcumin as an antioxidant and anti-inflammatory compound.

Purification of Matrixins from Marine Cephalopod.

Matrixins play a major role in tissue regeneration and also in various patho-physiological processes. Discovery of matrix metallo proteins (MMPs) and their detailed structural and functional analysis would lead to the development of numerous potent synthetic inhibitors of matrixins to treat certain diseases. In the present investigation, a marine cephalopod- Octopus sp. collected from Cochin, in the south western Indian Ocean was used as animal model for purification of matrixins. The measurements, count, indices and other morphometric characters were noted down before assessing the presence of matrixins in the crude extract of Octopus samples. Purification of matrixins was carried out employing gel filtration chromatography and the purified matrixins was confirmed by gelatin zymogram. The purity of the protein was checked by both native and SDS-PAGE. The studies have provided clear indications of production of MMPs or matrixins with gelatinolytic activity in Octopus sp.

Engineering Stimuli-Activatable Boolean Logic Prodrug Nanoparticles for Combination Cancer Immunotherapy.

Prodrug nanoparticles that codeliver the immune modulators to the tumor site are highly recommendable for cancer immunotherapy yet remain challenging. However, effective stimuli-responsive strategies that exploit the endogenous hallmarks of the tumor have paved the way for cancer immunotherapy. For the first time, the development of the Boolean logic prodrug nanoparticles (BLPNs) for tumor-targeted codelivery of immune modulators (e.g., immune activator and immune inhibitor) and combination immunotherapy is reported herein. A library of stimuli-activatable BLPNs is fabricated yielding YES/AND logic outputs by adjusting the input combinations, including extracellular matrix metalloproteins 2/9 (MMP-2/9), intracellular acidity (pH = 5.0-6.0), and reduction (glutathione) in the tumor microenvironment. Tunable and selective control over BLPNs dissociation and prodrug activation is achieved by specifying the connectivity of orthogonal stimuli-labile spacers while exploiting the endogenous signals at the tumor sites. The tumor-specific distribution of the BLPNs and stimuli-activation of the immune modulators for highly efficient cancer immunotherapy are further demonstrated. The results reported in this study may open a new avenue for tumor-specific delivery of immune therapeutics and precise cancer immunotherapy.

Design and synthesis of coumarin–imidazole hybrid and phenyl-imidazoloacrylates as potent antimicrobial and antiinflammatory agents

An improved one pot, multi-component synthesis of tri- and tetrasubstituted coumarin–imidazole hybrid has been synthesized at C4 position in good to excellent yield. The reaction was performed under various catalysts and optimization condition results obtained are satisfactory. Wherein, trisubstituted coumarin–imidazole hybrid compounds were converted into phenyl-imidazole acrylates. Further, all the newly synthesized compounds were screened for their antimicrobial activity against Gram-positive Bacillus flexus and Gram-negative Pseudomonas spp. bacterial strains and two strains of fungi studies having Scopulariopsis spp. and Aspergillus terreus organisms. Similarly, antiinflammatory activity of all the compounds was screened against MMP-2 and MMP-9. Both antimicrobial and antiinflammatory results are excellent, among all compounds, sodium acrylate compounds are quite promising against microbial strains and matrix metalloproteins (MMPs). All the isolated compounds were characterized by IR, NMR, and mass spectral analysis.

Copper-induced reduction in myocardial fibrosis is associated with increased matrix metalloproteins in a rat model of cardiac hypertrophy.

Trientine (TETA), a copper (Cu) chelator, is capable of replenishing Cu in the heart, and Cu repletion reduces cardiac fibrosis in a rodent model of cardiac hypertrophy. This study was undertaken to explore possible mechanisms by which Cu repletion diminishes cardiac fibrosis. Adult male Sprague-Dawley rats were subjected to ascending aortic constriction to induce cardiac hypertrophy. Four months after the operation, cardiac hypertrophy along with fibrosis was fully developed. TETA treatment was then followed at a dose of 21.9 mg kg-1, twice a day, administered orally for six weeks. At the end of the treatment, the hearts were harvested and all of the tissue samples were subjected to qRT-PCR, western blot, Sirius red staining, hydroxyproline assay, and immunostaining analyses. TETA treatment significantly increased the content of Cu in the hypertrophied myocardium, decreased type III collagen deposition and reduced cardiac fibrosis. On the other hand, this treatment did not alter the increase in fibroblasts induced by pressure overload, but significantly increased matrix metalloproteinase-2 (MMP-2), which is the enzyme mainly responsible for degradation of collagens in the heart. In addition, the mRNA and protein levels of tissue inhibitors of matrix metalloproteinase-1 and -2 (TIMP-1 and TIMP-2) were both remarkably increased in the hypertrophic myocardium, and normalized after TETA treatment. The data thus demonstrated that the reduction in cardiac fibrosis by TETA-induced Cu repletion is associated at least in part with an enhanced MMP-2 activity, leading to collagen degradation.

An extensive review of literature: considering bone reaction to different agents in orthodontically induced root and alveolar resorption

Objective: Orthodontically induced root resorption is a common problem in day to day practice. If such root resorption could be prevented, it would be an important contribution toward reducing risk factors in orthodontic treatment. The aim of the review is to focus on different agents which can be therapeutically useful in orthodontic tooth movement. Methods and Materials: The article reviews various agents inhibiting as well as promoting root and alveolar bone resorption to orthodontic tooth movement based on advanced PubMed Central (PMC), Cochrane database, Wiley online search of the English language literature from the year 1951 to present in order to help us select the most suitable among them fulfilling the desired criteria of being safe, having less adverse effects, minimal contraindications, rare cross reactions, economically viable, having a scope to be used for successful prognosis and possibly not requiring any special considerations to interpret the results. Results: Forty-nine articles were included in the review, but their interpretation was hindered by the variability in experimental design, magnitude of force applied during tooth movement, and medication regimens. Corticosteroid hormones, parathyroid hormone, and thyroxin have all been shown to increase tooth movement. Bisphosphonates had a strong inhibitory effect. Conclusion: By this review, we conclude that low laser therapy and arginylglycylaspartic acid (RGD) peptide emerges as the clear winner and can result in better prognosis in orthodontic treatment. These techniques are new and cannot replace the conventional agents as a whole. Keywords: Root resorption; Integrins; Matrix metalloproteins; Echistatin; Low laser therapy; Doxycycline

Inhibition of matrix metalloproteins 9 attenuated Candida albicans induced inflammation in mouse cornea.

Since the severe corneal ulceration of mouse cornea is known to occur with inflammation. As one of imperative matrix metalloproteinase, the potential roles of matrix metalloproteins 9 (MMP9) in corneal ulceration and keratitis are still unveiled caused by fungal invasion. In this study, Candida albicans (CA) inoculated wild-type KM mice cornea was used as a model pathogen in corneal inflammation. CA invasion significantly stimulated the expression of collagen IV and MMP9 detected by RT-PCR, Real-time PCR and Immunofluorescent staining in mouse cornea as soon as 6 hours post infection, and relatively decreased at 1 day post infection. For examining the role of MMP9 in fungal keratitis, the mice corneas were subconjunctivally injected MMP9 antibody or recombinant MMP9 protein 6 hours prior to CA inoculation, using rabbit IgG as control. Subconjunctival injection of recombinant MMP9 protein prior to CA inoculation enhanced, whereas MMP9 antibody attenuated corneal ulceration and inflammation, examining basement membrane, fungal load, myeloperoxidase (MPO) and proinflammatory cytokines including Macrophage inflammatory protein 2 (MIP2), Interleukin-1β (IL-1β) and Tumor necrosis factor-α (TNF-α). Inhibition of MMP9 could potentially attenuate Candida albicans induced inflammation in mouse cornea.

Cross-talk between ciliary epithelium and trabecular meshwork cells in-vitro: a new insight into glaucoma.

PurposeIt is assumed that the non-pigmented ciliary epithelium plays a role in regulating intraocular pressure via its neuroendocrine activities. To test this hypothesis, we investigated the effect on a human trabecular meshwork (TM) cell line (NTM) of co-culture with a human non-pigmented ciliary epithelium cell line (ODM-2).MethodsThe cellular cross-talk between ODM-2 and NTM cells was studied in a co-culture system in which the two cell types were co-cultured for 5 to 60min or 2, 4 and 8h and then removed from the co-culture and analyzed. Analyses of the ERK and p38 mitogen-activated protein kinase (MAPK) pathways and of the activity of TM phosphatases and matrix metalloproteins (MMPs) were performed. Acid and alkaline phosphatase activity was determined by the DiFMUP (6, 8-difluoro-4-methylumbelliferyl phosphate) assay. MMP levels were determined by gelatin zymography.ResultsExposure of NTM cells to ODM-2 cells led to the activation of the MAPK signal transduction pathways in NTM cells within 5min of co-culture. Phosphorylation of ERK1/ERK2 and p38 peaked at 10 and 15min and then decreased over time. Interaction between ODM-2 and NTM cells promoted the expression of MMP-9 in the NTM cells after 4h of co-culture.ConclusionsOur findings provide support for the hypothesis that crosstalk does indeed take place between ODM-2 and NTM cells. Future studies should be designed to determine the relationship between the MMP system, MAPK kinases and phosphatases. Manipulation of these signaling molecules and the related NTM signal transduction pathways may provide targets for developing improved treatments for glaucoma.

Antiproliferative and apoptotic-inducing potential of ellagic acid against 1,2-dimethyl hydrazine-induced colon tumorigenesis in Wistar rats

Colon cancer remains one of the major worldwide causes of cancer-related morbidity and mortality in Western countries and is increasingly common in Asia. Ellagic acid (EA), a major component of polyphenol possesses attractive remedial features. The aim of this study is to divulge the potential effect of EA during 1,2-dimethyl hydrazine (DMH)-induced colon cancer in male Wistar albino rats. The rats were segregated into four groups: group I, control rats; group II, rats received EA (60mg/kg b.wt./day, orally); rats in group III, induced with DMH (20mg/kg b.wt.) subcutaneously for 15weeks; DMH-induced group IV rats were initiated with EA treatment. Colon of the rats treated with DMH exhibited higher glycoconjugates and proliferation index such as elevated expressions of argyrophilic nucleolar organizing regions (AgNORs), proliferating cell nuclear antigen (PCNA), cyclin D1, matrix metalloproteins (MMP-2 and -9), and mast cells. DMH induction also increased phase I-metabolizing enzymes with simultaneous decrease in the phase II detoxifying enzymes. In contrast, dietary administration of EA significantly (p<0.05) down regulated the proliferation index and restored back the levels of biotransformation enzymes. The carcinogenic insult also altered the expression of pro-apoptotic protein p53, whereas dietary EA administration significantly (p<0.01) up regulates p53 expression to further induce apoptotic pathway. Ultrastructural changes in colon were also in accord with the above aberrations. Overall findings suggested that the suppression of colon cancer by EA in vivo involves inhibition of cell proliferation, activation of apoptosis, and efficient detoxification.

Relation between some environmental pollutants and recurrent spontaneous abortion

Reproductive health is exquisitely sensitive to characteristics of an individual’s environment including physical, biological, behavioral, cultural and socioeconomic factors. This study was launched to elucidate the effect of the exposure to chemical pollutants as aromatic amines viz. (benzidine, mono-acetyl benzidine, diacetyl benzidine, α,β-naphthylamine) as well as the biological pollutants e.g., human cytomegalovirus (HCMV) as risk factors for recurrent spontaneous abortion (RSA) through determination of MDA as a marker of oxidative stress and determination of some antioxidant markers. The results of the current study revealed that the aborter mothers were being exposed to environmental pollutants as aromatic amines which were manifested by the presence of benzidine, mono-acetyl-benzidine, di-acetyl-benzidine, α,β-naphthylamine in most of their urine samples, where the level of aromatic amines were more 13.6, 10, 15, and 4-folds than the control group, respectively. Also, the data suggest that in early pregnancy failure there is an increase in markers of oxidative stress and a probable decrease in maternal antioxidant defenses (22nmol/ml and 17mg/l, 550U/l, respectively). Generation of ROS in large quantities, in the first trimester placenta which has limited antioxidant defenses may cause DNA damage, oxidation of protein and lipid resulting in extensive cell death. Also, it was demonstrated that high elevation of HCMV inhibits cytotrophoblasts proliferation, migration invasion and matrix metalloproteins (MMP) expression. Obviously, placental toxicological responses are partly due to pharmaco/toxico dynamic responses to the chemicals. Conclusively, the aforementioned findings emphasis that, the exposures to environmental chemical and/or biological risk factors are implicated in the pathogenesis of recurrent spontaneous abortion.