Plague Formation Research Articles

A study on the possible neurotoxic effects of CUMYL-4CN-BINACA in Sprague Dawley rats

Substances such as Δ9-tetrahydrocannabinol (THC) and cannabidiol cross the blood–brain barrier. Detecting the damage of these substances in the brain provides important data in drug abuse studies. The aim of the study is to define the neurotoxicity of a novel synthetic cannabinoid (CUMYL-4CN-BINACA) in the Sprague-Dawley rats. Histopathological, immunohistochemical, behavioral, and biochemical examinations were performed to determine the acute and subacute toxicity of the cannabinoid. Three cannabinoid doses were administered for 2 days in the acute exposure groups and 14 days in the subacute exposure groups. Observations were made for 14 days and various changes such as mortality, injury, and illness were recorded daily. No mortality was determined. Serious pathological changes such as neurodegeneration, focal plague formation, vacuolation, edema, congestion, and fibrosis were observed in the cerebral cortex and hippocampus of the brain in a dose-dependent manner. Brain tissue caspase-3 activity showed that the cannabinoid triggered apoptosis in the rat brain. The detected cellular oxidative stress (higher lipid peroxidation and lower antioxidant enzyme activity) also supported neurotoxicity. Significant behavioral abnormalities were also observed in the acute groups, while no behavioral changes were detected in the subacute groups. This study showed for the first time that CUMYL-4CN-BINACA adversely affects the rat brain. It can be estimated that the abuse of the cannabinoid may harm human health in the same way.

Severe COVID-19-A Review of Suggested Mechanisms Based on the Role of Extracellular Matrix Stiffness.

The severity of COVID-19 commonly depends on age-related tissue stiffness. The aim was to review publications that explain the effect of microenvironmental extracellular matrix stiffness on cellular processes. Platelets and endothelial cells are mechanosensitive. Increased tissue stiffness can trigger cytokine storm with the upregulated expression of pro-inflammatory cytokines, such as tumor necrosis factor alpha and interleukin IL-6, and tissue integrity disruption, leading to enhanced virus entry and disease severity. Increased tissue stiffness in critically ill COVID-19 patients triggers platelet activation and initiates plague formation and thrombosis development. Cholesterol content in cell membrane increases with aging and further enhances tissue stiffness. Membrane cholesterol depletion decreases virus entry to host cells. Membrane cholesterol lowering drugs, such as statins or novel chitosan derivatives, have to be further developed for application in COVID-19 treatment. Statins are also known to decrease arterial stiffness mitigating cardiovascular diseases. Sulfated chitosan derivatives can be further developed for potential use in future as anticoagulants in prevention of severe COVID-19. Anti-TNF-α therapies as well as destiffening therapies have been suggested to combat severe COVID-19. The inhibition of the nuclear factor kappa-light-chain-enhancer of activated B cells pathway must be considered as a therapeutic target in the treatment of severe COVID-19 patients. The activation of mechanosensitive platelets by higher matrix stiffness increases their adhesion and the risk of thrombus formation, thus enhancing the severity of COVID-19.

The trans DNA cleavage activity of Cas12a provides no detectable immunity against plasmid or phage.

Cas12a is a type V-A CRISPR-Cas RNA-guided endonuclease. It cleaves dsDNA at specific site, and then is activated for nonspecific ssDNA cleavage in trans in vitro. The immune function of the trans activity is still unknown. To address this question, we constructed a Cas12a targeting system in Escherichia coli, where Cas12a cleaved a high-copy target plasmid to unleash the trans ssDNA cleavage activity. Then, we analyzed the effect of the Cas12a targeting on a non-target plasmid and a ssDNA phage. The results show that Cas12a efficiently eliminates target plasmid but exerts no impact on the maintenance of the non-target plasmid or plague formation efficiency of the phage. In addition, a two-spacer CRISPR array, which facilitates target plasmid depletion, still has no detectable effect on the non-target plasmid or phage either. Together, the data suggest that the trans ssDNA cleavage of Cas12a does not contribute to immunity in vivo.

NATURAL PRODUCT-BASED AMYLOID PROTEIN INHIBITORS

Neurodegenerative disorders like Alzheimer’s are associated by plague formation of protein aggregates called amyloid proteins. Many natural-based products such as flavonoids, phenolic acids, iso-flavones, and polyunsaturated fatty acids play major role in therapeutic ability to degrade, slow down, and recondition the amyloid protein (amyloid protein inhibitors). These compounds extracted from plants have shown consequential potential in in vitro studies as well as in vivo studies. For requisite for brain nutritive growth, omega 3 fatty acids are important, whereas ß-carotene plays indispensable role in cognitive impairment and oxidative stress in the brain. It is described that omega 3 fatty acids are extracted from the source (flaxseed) by oil press method and ß-carotene is synthesized by physiochemical process from carrot. The main objective of this particular research topic is to provide more effectiveness in detaining the growth of amyloid protein inhibitors in brain. It is observed that the product with omega 3 and ß-carotene slow down the protein aggregation more efficiently than omega 3 capsules alone and intra-cerebroventricular injected streptozotocin. This can be determined by in silico activity of acetylcholinesterase. The analyses show extensive reciprocity between inhibitors and amyloid proteins. The administration of omega 3 with ß-carotene depreciates the amyloid protein aggregates more efficiently. Hence, it is suggested that the product can be used as treatment for neurodegenerative diseases like Alzheimer’s.

Current Status of Bovine Ocular Squamous Cell Carcinoma

Bovine ocular squamous cell carcinoma (BOSCC) is one of the important malignant neoplasms of cattle arising from squamous epithelium. The tumour was recorded at the age of three to eight years, and it affects most countries of the world. The possible etiologies include ultraviolet radiation, exposure to sunlight, nutrition, lack of pigmentation, bovine papilloma virus, increased altitude, decreased latitude, and hereditary and outdoor farming systems. Breeds of Hereford, Holstein, Jersey, Holstein cross and Jersey cross cattle are mostly affected, Common sites of the lower eyelid, third eyelid, limbus corneoscleral junction and cornea conjunctival junction were reported. Grossly the tumour is having plague, keratoma, papilloma and carcinoma formation. Cytological and histopathological appearance of BOSCC categorized as poorly differentiated squamous cell carcinoma, moderately squamous cell carcinoma and well differentiated squamous cell carcinoma. Immunohistochemistry using cytokeratin, MNF116, involucrin, P53, ki67 are the useful markers of BOSCC. Surgical extirpation is the choice of management of BOSCC and continued exposure to sunlight to be avoided to control this BOSCC.

Nitric Oxide Inhibition Assay and the Respective Target Identification of an Aptamer Designed to Control Atherosclerosis.

Aptamers are emerging newer therapeutics and diagnostics whichcan be designed to bind any kind of target proteins. Vascular endothelial damage by the excess amount of nitric oxide production in systemic circulation leads to the secretion of inflammatory chemoattractants and cell adhesions are the prime pro-atherogenic events in the formation of plagues at atrial intimal layers due to oxidation - sensitive mechanisms. Nitric oxide inhibition assay is one of the valuable qualitative anti-atherosclerosis matrices. In this research, Nitric oxide inhibition efficiency of an ssDNA aptamer on cell lines was studied, and the respective targets of that aptamer were identified by network analysis. The aptamer used here was originally designed for Selectin P Ligand Protein to control the atherogenic process. 20 nM of aptamer solution in LipofectamineTM 2000 sshowshighest level 70.5% inhibition of nitric oxide liberation on 24 hours cultured medium of lipopolysaccharide stimulated murine macrophage RAW 264.7 cell lines. Protein interaction network analysis of the nitric oxide synthesis pathway interactors and the molecular docking analysis with network resulted in proteins such as AKT serine/threonine kinase 1, calmodulin, estrogen receptor 1, and nitric oxide synthase-3, which confirmed that the G - quadruplex Model of 18-mer sequence effectively bound to the active sites of estrogen receptor 1, and nitric oxide synthase-3. The aptamer designed for atherosclerotic target has also exertedsignificant nitric oxide inhibition to control the atherogenic events through the proteins such as, AKT1, NOS3 and ESR1.

Oxidative Stress Triggers Defective Autophagy in Endothelial Cells: Role in Atherothrombosis Development

Atherothrombosis, a multifactorial and multistep artery disorder, represents one of the main causes of morbidity and mortality worldwide. The development and progression of atherothrombosis is closely associated with age, gender and a complex relationship between unhealthy lifestyle habits and several genetic risk factors. The imbalance between oxidative stress and antioxidant defenses is the main biological event leading to the development of a pro-oxidant phenotype, triggering cellular and molecular mechanisms associated with the atherothrombotic process. The pathogenesis of atherosclerosis and its late thrombotic complications involve multiple cellular events such as inflammation, endothelial dysfunction, proliferation of vascular smooth muscle cells (SMCs), extracellular matrix (ECM) alterations, and platelet activation, contributing to chronic pathological remodeling of the vascular wall, atheromatous plague formation, vascular stenosis, and eventually, thrombus growth and propagation. Emerging studies suggest that clotting activation and endothelial cell (EC) dysfunction play key roles in the pathogenesis of atherothrombosis. Furthermore, a growing body of evidence indicates that defective autophagy is closely linked to the overproduction of reactive oxygen species (ROS) which, in turn, are involved in the development and progression of atherosclerotic disease. This topic represents a large field of study aimed at identifying new potential therapeutic targets. In this review, we focus on the major role played by the autophagic pathway induced by oxidative stress in the modulation of EC dysfunction as a background to understand its potential role in the development of atherothrombosis.

Deciphering the Molecular Role of Non-coding RNA in Malignant Cardiac Disease

Non-coding RNA (NcRNA) is a functional RNA which contributes to the gene regulation at both transcriptional and post-transcriptional level. NcRNA lack in the encoding of proteins, but this does not counteract the generic functioning of the cells. It is a group of RNA with versatile functioning. They are classified into small nuclear RNA, tRNA, rRNA, and microRNA. The cumulative functioning of ncRNA includes slicing as well as the management of chromosomes. The long ncRNA plays a vital role in malignant cardiovascular disease such as atherosclerosis, myocardial infarction, and injury. They act by different pathways and undergo different mechanisms that include binding to CBX, activating mesoderm posterior-1, modulating MKX25, and targeting bone morphogenetic proteins. They have an intricate role in cardiovascular disorders as some of the long ncRNAs contribute to the inhibition of plague formation in the heart, thus reducing the risk for atherosclerosis and thus retarding the development of heart failure. Whereby microRNA acts as a prognostic biomarker in the early detection of heart injury. MicroRNA has even been identified for the inhibition of angiogenesis, and Piwi-interacting RNA is important in genetic diversity. Thus, ncRNA is one of the factors in the leading cause of malignant cardiac disorder and is responsible for cardiac remodelling andheart failure.

Microglia prevent beta-amyloid plaque formation in the early stage of an Alzheimer\u2019s disease mouse model with suppression of glymphatic clearance

BackgroundSoluble beta-amyloid (Aβ) can be cleared from the brain through various mechanisms including enzymatic degradation, glial cell phagocytosis, transport across the blood-brain barrier, and glymphatic clearance. However, the relative contribution of each clearance system and their compensatory effects in delaying the pathological process of Alzheimer’s disease (AD) are currently unknown.MethodsFluorescent trace, immunofluorescence, and Western blot analyses were performed to compare glymphatic clearance ability and Aβ accumulation among 3-month-old APP695/PS1-dE9 transgenic (APP/PS1) mice, wild-type mice, aquaporin 4 knock out (AQP4−/−) mice, and AQP4−/−/APP/PS1 mice. The consequence of selectively eliminating microglial cells, or downregulating apolipoprotein E (apoE) expression, on Aβ burden, was also investigated in the frontal cortex of AQP4−/−/APP/PS1 mice and APP/PS1 mice.ResultsAQP4 deletion in APP/PS1 mice significantly exaggerated glymphatic clearance dysfunction, and intraneuronal accumulation of Aβ and apoE, although it did not lead to Aβ plaque deposition. Notably, microglia, but not astrocytes, increased activation and phagocytosis of Aβ in the cerebral cortex of AQP4−/−/APP/PS1 mice, compared with APP/PS1 mice. Selectively eliminating microglia in the frontal cortex via local injection of clodronate liposomes resulted in deposition of Aβ plaques in AQP4−/−/APP/PS1 mice, but not APP/PS1 mice. Moreover, knockdown of apoE reduced intraneuronal Aβ levels in both APP/PS1 mice and AQP4−/−/APP/PS1 mice, indicating an inhibitory effect of apoE on Aβ clearance.ConclusionThe above results suggest that the glymphatic system mediated Aβ and apoE clearance and microglia mediated Aβ degradation synergistically prevent Aβ plague formation in the early stages of the AD mouse model. Protecting one or both of them might be beneficial to delaying the onset of AD.

The Single Nucleotide Polymorphisms of Chromosome 9p21 and CD147 Were Relevant with the Carotid Plaque Risk in Acute Cerebral Infarction Patients Among Chinese Han Population.

This study focused on the relevance between the carotid plaque formation and the single nucleotide polymorphisms of chromosome 9p21 and CD147 in acute non-cardiogenic cerebral infarction. A total of 937 eligible patients were enrolled and categorized into carotid plaque group or non-carotid plaque group. The baseline data was analyzed, and the SNPs of chromosome 9p21 and CD147 were detected. After analyzing the results of clinic data and SNPs, we found that age, total cholesterol, low density lipoprotein, systolic blood pressure, fasting serum glucose, and NIHSS score are associated with plaque formation. Meanwhile, rs10757274, rs4977574, and rs4919862 existed statistical differences between two groups. We also analyzed linkage disequilibrium, haplotype, and inheritance models of these three SNPs, and drew the ROC curve to assess diagnostic efficiency. The results showed that mutations of SNP rs10757274 and rs4977574 in chromosome 9p21 together with SNP rs4919862 located in gene CD147 were highly relevant with the carotid plague formation in acute cerebral ischemia patients. Compared with single SNP genotype mutation, combined allele mutations on rs10757274 or rs4977574 in chromosome 9p21 with rs4919862 in CD147 resulted in much higher risks of patients, which might be associated with acute cerebral infarction happening.

Peptides Hydrolysate Derived from Collagen of Snakehead Murrel (Channa striata) Skin Demonstrate Anti-cholesterol and Anti-oxidant activities

Anti-cholesterol and anti-oxidant play a crucial role to combat cardiovascular disease (CVD), due to formation of arterial plagues from oxidation of cholesterol. In the past decades, bioactive peptides demonstrating anti-cholesterol and anti-oxidant activities have emerged as the alternative drugs. In this study, acid soluble collagen was extracted from the skin of snakehead murrel and employed to induce secretion of collagenase by Bacillus licheniformis F11.4. The collagenases secreted were in turn used to produce peptides hydrolysate and were grouped in two distinct collagenase fractions, designated as fraction D and F. Peptides hydrolysate produced by the fraction D was found to demonstrate HMG-CoA inhibitor activity comparable to pravastatin and limited anti-oxidant activity. Meanwhile, peptides hydrolysate generated using the fraction F demonstrated anti-oxidant activity comparable to BHT (2mM), vitamin C (2mM), and vitamin E (2mM), but limited HMG-CoA activity. Combination of the fraction D and F resulted in substantial HMG-CoA inhibition and anti-oxidant activities.

Development of a plaque assay based on Avicel-crystal violet staining for detection of Middle East respiratory syndrome coronavirus infection and neutralizing antibody

Objective To establish a plaque assay for detection of Middle East respiratory syndrome coronavirus (MERS-CoV) infection. Methods Vero and Huh7.5 cells were infected with MERS-CoV (EMC/2012) strains for different days (two or three days) and covered with different overlays (agarose or Avicel). The optimal host cells, time of infection and overlay were screened out by analyzing plague formation to establish the plaque assay for detection of MERS-CoV infection. Neutralizing antibodies against MERS-CoV were detected by the established assay. Results Clear plaques were observed on Vero cells infected with MERS-CoV at 3 days post-infection (p.i.), while only tip-size plaques were observed at 2 days p. i.. Clearer and bigger sizes of plaques were observed under the overlay of Avicel than those under the agarose. The Avicel-based plaque assay was suitable for detecting neutralizing antibodies against MERS-CoV. Conclusion We develop a modified plaque assay for detecting MERS-CoV based on Avicel-crystal violet staining. It is easier to operate the modified plaque assay in biological safety level 3 (BSL-3) laboratories. This study paves a way for quantification of MERS-CoV and detection of neutralizing antibodies against MERS-CoV. Key words: Middle East respiratory syndrome coronavirus (MERS-CoV); Biological safety level 3 (BSL-3) laboratory; Plaque assay; Vero cell; Avicel; Neutralization test

Carotid plague formation is associated with ankle-brachial index in elderly people.

This study aimed at examining whether ankle-brachial index (ABI) and brachial-ankle pulse wave velocity (baPWV) were independently associated with carotid Intima-media thickness (CIMT) or carotid artery plaque (CAP) in elderly people. A cross-sectional analysis was performed in 155 individuals aged over 75years who underwent the measurements of ABI and baPWV. Low ABI was defined as ABI ≤ 1.0. High baPWV was defined as baPWV > 2000cm/s. The CIMT and CAP were measured with a B-mode tomographic ultrasound system. Neither ABI nor baPWV was associated with CIMT in this elderly population. The group with low ABI (≤ 1.0) was significantly associated with a higher prevalence of carotid plaque (P = 0.001), while the relationship between baPWV and prevalence of carotid plaque was not found. Linear regression analysis showed that the value of ABI was significantly associated with the thickness of carotid plaque. Even in the full adjusted model, each 0.01unit ABI decreasing still increased 0.1663mm of carotid plaque thickness (P = 0.004). Logistic Regression Analysis demonstrated that ABI lower than 1.0 had predictive value in the formation of carotid plaque with top quartile thickness (OR 2.834, 95% CI 1.131-7.099, P = 0.026). Furthermore, individuals with low ABI (≤ 1.0) were more likely to form hypoechoic carotid plaques according to ultrasonography. Low ABI but not high baPWV was associated with the formation of carotid plaque. Furthermore, ABI was significantly associated with the thickness and morphology of carotid plaque in elderly people.

Relation of neutrophil-to-lymphocyte, platelet-to-lymphocyte ratio and CRP level with coronary artery disease severity in patients undergoing coronary angiography

Background: coronary artery disease (CAD) is the leading cause of morbidity and mortality throughout the world. It has a complex pathophysiology, and inflammation seems to play an important role in CAD. Previous studies have shown that higher levels of inflammatory markers are associated with the severity of CAD and worse cardiovascular outcome. Although endothelial damage has been known as the triggering factor for the formation of atherosclerotic plagues, inflammatory process is responsible in the initiation and progression of the atherosclerosis. The neutrophil-to-lymphocyte ratio (NLR) and platelet- to-lymphocyte ratio (PLR) have recently been investigated as new predictors for worse cardiovascular outcome. Previous studies have shown that NLR is associated with morbidity and mortality in many cardiovascular diseases such as hypertension, heart failure, infective endocarditis, and acute coronary syndromes (ACS). Aims: The aim of this study was to explore the relation of NLR , PLR and CRP level with severity of coronary artery disease (CAD) using the Syntax score (Sxscore). Patients and Methods: This study was conducted to investigate the relationship between the severity of coronary artery disease and inflammatory markers (lymphocyte ratio, lymphocyte platelet, CRP) by sytax score in patients undergoing elective coronary angiography, the active number of 100 patients with a chronic stable was taken Coronary angiography, different markers for coronary assessment, renal function tests, INR, ECG and Echocardiography. A complete clinical evaluation was performed for each of our patients Results: Coronary lesions were evaluated by the result of camel synthesis and there was a strong relationship between NLR, PLR, CRP level, and coronary heart disease r. 526 p 0.001, r 0.317 p 0.001, r 0.699 p 0.001 However, when we divided the patient for a result Syntax The results show some difference in determining who are drafting the sentence above 21, we found a negative relationship between NLR, PLR and syntax points, while the CRP level was positively correlated at the level of the structure below 31 a significant negative correlation was found with the construct conclusion above 31. Conclusion: Our study concluded that the severity of coronary artery disease is associated with NLR, PLR, CRP levels to some extent in the patient with angina for chronic stable chest.

Relation of neutrophil-to-lymphocyte, platelet-to-lymphocyte ratio and CRP level with coronary artery disease severity in patients undergoing coronary angiography

Background: coronary artery disease (CAD) is the leading cause of morbidity and mortality throughout the world. It has a complex pathophysiology, and inflammation seems to play an important role in CAD. Previous studies have shown that higher levels of inflammatory markers are associated with the severity of CAD and worse cardiovascular outcome. Although endothelial damage has been known as the triggering factor for the formation of atherosclerotic plagues, inflammatory process is responsible in the initiation and progression of the atherosclerosis. The neutrophil-to-lymphocyte ratio (NLR) and platelet- to-lymphocyte ratio (PLR) have recently been investigated as new predictors for worse cardiovascular outcome. Previous studies have shown that NLR is associated with morbidity and mortality in many cardiovascular diseases such as hypertension, heart failure, infective endocarditis, and acute coronary syndromes (ACS). Aims: The aim of this study was to explore the relation of NLR , PLR and CRP level with severity of coronary artery disease (CAD) using the Syntax score (Sxscore). Patients and Methods: This study was conducted to investigate the relationship between the severity of coronary artery disease and inflammatory markers (lymphocyte ratio, lymphocyte platelet, CRP) by sytax score in patients undergoing elective coronary angiography, the active number of 100 patients with a chronic stable was taken Coronary angiography, different markers for coronary assessment, renal function tests, INR, ECG and Echocardiography. A complete clinical evaluation was performed for each of our patients Results: Coronary lesions were evaluated by the result of camel synthesis and there was a strong relationship between NLR, PLR, CRP level, and coronary heart disease r. 526 p 0.001, r 0.317 p 0.001, r 0.699 p 0.001 However, when we divided the patient for a result Syntax The results show some difference in determining who are drafting the sentence above 21, we found a negative relationship between NLR, PLR and syntax points, while the CRP level was positively correlated at the level of the structure below 31 a significant negative correlation was found with the construct conclusion above 31. Conclusion: Our study concluded that the severity of coronary artery disease is associated with NLR, PLR, CRP levels to some extent in the patient with angina for chronic stable chest.

Harmine, a small molecule derived from natural sources, inhibits enterovirus 71 replication by targeting NF-κB pathway

Enterovirus 71 (EV71) infection of young children can cause neurological manifestations, which is mainly responsible for the fatality. Although a vaccine is recently available for preventing enterovirus 71 infection, its efficacy remains to be seen. Therefore, there is a pressing need for anti-viral agents for the treatment of EV71 infection. By screening a natural compound library for inhibitory activity of EV71 replication, we identified a small molecule, harmine, that inhibited EV71 replication by targeting NF-κB signaling pathway. Harmine is a β-carboline alkaloid found in the medicinal plant Peganum harmala, which is used as a folk antitumor medicine in China and other parts of the Asia. The estimated EC50 value for harmine to block EV71 infection was 20 μM, while the CC50 was estimated at 500 μM in vitro. Harmine inhibited replication of EV71, as evidenced by its ability to diminish plague formation induced by EV71 and to reduce the level of viral RNA and protein. Mechanistic studies indicated that harmine suppressed EV71 replication through inhibition of NF-κB signaling pathway. Harmine treatment also reduced EV71-induced reactive oxygen species (ROS) formation, which was associated with a decline in EV71-associated NF-κB activation. In addition, the harmine treatment could protect AG129 mice against EV71 replication in vivo. These findings suggest that harmine may present as a candidate antiviral drug for the treatment of EV71 infection.

Microbiological and Histopathological studies on cholesterol reducing effect of lactobacillus acidophilus

A total of 50 albino rats were used to carry out an in vivo study on the cholesterol lowering impact of isolated L. acidophilus isolated from diatery supplements. Blood serum of the experimental rats as well as their liver, heart and aorta tissues were analyzed and examined .The attained results revealed a great decrease in serum cholesterol due to the use of live or dead bacterial cells. The histopathological results collected from examination of liver revealed that in live lactobacillus treated group display significant amelioration compare to non treated group, while no significant improvement detected in dead lactobacillus treated group. The corresponding results of the heart in showed that some pathological lesions seen in cardiac tissue in high cholesterol feeding group, still observed. This is besides atrophy of many cardiomyocytes and apoptosis. Signe of improvement was noticed in dead lactobacillus treated hypercholesterolemic group, where the severity and incidence of the pathological lesions observed in hypercholesterolemia animals was significantly reduced. Concerning the aorta, the attained results demonstrated that in live lactobacillus treated group, early plague formation was observed in few areas, however fibrin covered wide area of the endothelial layer. Significant amelioration in aorta tissues of dead lactobacillus treated hypercholesterolemia group was detected.

EXPLORATION OF BACTRIOPHAGE VIRULENT TO XANTHOMONAS CAMPESTRIS PV CAMPETRIS TOWARD DEVELOPMENT AS BIOCONTROL AGENT FOR CABBAGE BLACK ROT DISEASE

<p>Black rot disease which is caused by Xanthomonas campestris pv campetris is animportant disease on cabbage and so far could not be controlled satisfactory yet.Recently, people getting conscious the negative effect of applicating synthetic pesticidesand the importance of using biocontrol agents fo controlling pests because they arerelatively save and environmentally friendly. Bacteriophage is viruse that infectsbacteria. The use of phages for disease control is a fast expanding area of plantprotection with great potential to replace the chemical control and now prevalent.Phages can be used effectively as part of integrated disease management strategies.The relative ease of preparing phage treatments and low cost of production of theseagents make them good candidates for widespread use in developing countries as well.So far, in Indonesia bacteriophage exploration for development as biocontrol agents hasnot been conducted yet. On the other hand, Indonesia is one of view countries having alot of biodiversity resourches in the world. So it can be predicted that it is a lot ofbacteriophages strains naturally, which could be developed for biocontrol agents ofblack rot disease in cabbage. This research was aimed to isolate some bacteriophagevirulent to Xanthomonas campestris pv campetris from field. X. campestris pv campetris has been isolated from diseased cabbage in Blumbang, Tawangmangu.Biological characterization assay of 10 diseased cabbage leaf samples showed that allsample were indicated innfected by X. campestris pv campetris. Whereas plaque assayof 10 samples taken from fields showed indication of plague formation. This researchstill be continued to explore more samples form Tawangmangu, and also from othercabbage field in Central Java.</p>

Aβ Metabolism and the Role of APOE in Alzheimer’s Disease

Disturbance of the production and clearance of Aβ in the brain is the main cause of memory and cognition decline and contributes strongly to the development of AD. In human, APOE gene has three isoforms, ε2, ε3 and ε4, with APOE ε4 as the most risk gene among them. In the development of AD pathophysiology, ApoE4 is positively associated with Aβ plague formation, but the mechanisms are not clear. In this review, we proposed a hypothesis that the effect of ApoE4 on Aβ possibly involves three processes: 1) ApoE4 can directly interact with Aβ and interferes Aβ clearance. 2) ApoE4 can compete with Aβ for the same receptor, that hinds the cellular uptake pathways of Aβ. 3) ApoE4 also modulates other Aβ degrading proteases like IDE to downregulate Aβ degradation, but the mechanisms needs to be further investigated. These findings suggest that the effect of ApoE in AD pathogenesis is complicated and modulation of ApoE is an attractive strategy for AD therapy.

Chronic administration of methamphetamine promotes atherosclerosis formation in ApoE−/− knockout mice fed normal diet

ObjectiveChronic methamphetamine (METH) abuse could induce neurotoxicity due to reactive oxygen species generation and sympathetic activation. Both factors are associated with atherosclerosis, so we tested the hypothesis that chronic METH administration might also promote atherosclerosis formation in Apo E−/− knockout mice fed normal diet. Methods and ResultsMale ApoE−/− mice (6 weeks-old) were treated with saline (NS) or METH [4 mg/kg/day (M4) or 8 mg/kg/day (M8) through intraperitoneal injection] for 24 weeks. Atherosclerotic lesion area on oil red O stained en face aorta was dose-dependently increased in M4 and M8 groups compared to NS group. Percentage of atherosclerotic lesion area was significantly higher in M8 group compared to NS and M4 groups. Plasma CRP was increased and inflammatory cytokine (ICAM-1, VCAM-1, TNF-α, and INF-γ) expression on aortic root was upregulated in METH groups compared to NS group. Neuropeptide Y (NPY) protein and mRNA expressions in aortic root and myocardial tissue were determined by Western blot and real time PCR, which were significantly upregulated in M4 and M8 groups. Moreover, mRNA expressions of NPY1R, NPY2R and NPY5R in aortic and myocardial tissue were also significantly upregulated in M4 and M8 groups. Raw264.7 cells were treated with NPY, NPY receptor antagonists, METH (10 μM or 100 μM) with or without lipopolysaccharide (LPS), and the expressions of TNF-α, CRP, MCP-1 and reactive oxygen species (ROS) production were significantly increased in METH and LPS + METH groups compared to control and LPS groups. Co-treatment with NPY1R antagonist decreased the expressions of TNF-α, CRP and MCP-1 in NPY and METH treated cells. ConclusionsChronic METH administration can promote inflammation and atherosclerotic plague formation in ApoE−/− mice fed normal chow. NPY might be involved in the pathogenesis of METH-induced atherogenic effects through NPY Y1 receptor pathway.