The Oxidative Inactivation of Tissue Inhibitor of Metalloproteinase-1 (TIMP-1) by Hypochlorous Acid (HOCl) is Suppressed by Anti-Rheumatic Drugs

Tissue inhibitors of metalloproteinases (TIMPs) prevent uncontrolled connective tissue destruction by limiting the activity of matrix metalloproteinases (MMPs). That TIMPs should be susceptible to oxidative inactivation is suggested by their complex tertiary structure which is dependent upon 6 disulphide bonds. We examined the oxidative inactivation of human recombinant TIMP-1 (hr TIMP-1) by HOCl and the inhibition of this process by anti-rheumatic agents.

TIMP-1 was exposed to HOCl in the presence of a variety of disease modifying anti-rheumatic drugs. TIMP-1 activity was measured by its ability to inhibit BC1 collagenase activity as measured by a fluorimetric assay using the synthetic pEptide substrate (DNP-Pro-Leu-Ala-Leu-Trp-Ala-Arg), best cleaved by MMP-1.

The neutrophil derived oxidant HOCl, but not the derived oxidant N-chlorotaurine, can inactivate TIMP-1 at concentrations achieved at sites of inflammation. Anti-rheumatic drugs have the ability to protect hrTIMP-1 from inactivation by HOCl. For D-penicil-lamine, this effect occurs at plasma levels achieved with patients taking the drug but for other anti-rheumatic drugs tested this occurs at relatively high concentrations that are unlikely to be achieved in vivo, except possibly in a microenvironment. These results are in keeping with the concept that biologically derived oxidants can potentiate tissue damage by inactivating key but susceptible protein inhibitors such as TIMP-1 which form the major local defence against MMP induced tissue breakdown.     

An electrochemical biosensor for prostate cancer biomarker detection using graphene oxide–gold nanostructures

In this paper, a most sensitive electrochemical biosensor for detection of prostate‐specific antigen (PSA) was designed. To reach the goal, a sandwich type electrode composed of reduced graphene oxide/ gold nanoparticles (GO/AuNPs), Anti‐Total PSA monoclonal antibody, and anti‐Free PSA antibody was assembled. The functionalized materials were thoroughly characterized by atomic force microscope spectroscopy, transmission electron microscopy, and X‐ray diffraction techniques. The electrochemical properties of each of the modification step were evaluated by cyclic voltammetry and electrochemical impedance spectroscopy. The results presented that the proposed biosensor possesses high sensitivity toward total and free PSA. Furthermore, the fabricated biosensor revealed an excellent selectivity for PSA in comparison to the other tumor markers such as BHCG, Alb, CEA, CA125, and CA19‐9. The limit of detection for the proposed electrochemical biosensor was estimated to be around 0.2 and 0.07 ng/mL for total and free PSA antigen, respectively.     

Sensitive Hemoglobin Concentration Sensor Based on Graphene-Plasmonic Nano-structures

Plasmonics - In this paper, half-cylindrical-shaped rods are arranged in a row in order to form hemoglobin concentration sensors. The proposed structures can effectively detect hemoglobin...     

Predominant Leptospiral Serogroups Circulating among Humans,Livestock and Wildlife in Katavi-Rukwa Ecosystem,Tanzania

BackgroundLeptospirosis is a worldwide zoonotic disease and a serious, under-reported public health problem, particularly in rural areas of Tanzania. In the Katavi-Rukwa ecosystem, humans, livestock and wildlife live in close proximity, which exposes them to the risk of a number of zoonotic infectious diseases, including leptospirosis.ConclusionsThe results of this study demonstrate that leptospiral antibodies are widely prevalent in humans, livestock and wildlife from the Katavi-Rukwa ecosystem. The disease poses a serious economic and public health threat in the study area. This epidemiological study provides information on circulating serogroups, which will be essential in designing intervention measures to reduce the risk of disease transmission.     

LED light mediates phenolic accumulation and enhances antioxidant activity in Melissa officinalis L. under drought stress condition

The popularity of lemon balm in conventional medicine is suggested by the existence of two groups of compounds, namely essential oil and phenylpropanoids pathway derivatives. One of the promising approaches to improve tolerance to drought stress induced oxidative damage in seedlings grown in greenhouses and plant growth chambers is replacing the traditional and high-cost light technologies by recently developed light emitting diodes (LED). In this experiment, we analyzed the role of various LED lights including red (R), blue (B), red (70%) + blue (30%) (RB), and white (W) as well as normal greenhouse light (as control) to stimulate defense mechanisms against drought stress in two genotypes of Melissa officinalis L. The present study demonstrates that pre-treatment with LEDs with high-intensity output for 4 weeks alleviated harmful effects of drought stress in the two genotypes. Under drought stress, RB LED pre-treated plantlets of the two genotypes exhibited the highest relative growth index of shoot and root and total phenolic and anthocyanin content compared to those irradiated with other LEDs and greenhouse lights. The highest amount of malondialdehyde level was detected in R LED exposed plants. In response to drought, LED-exposed plants especially RB light-irradiated plants of the two genotypes maintained significantly higher antioxidant and phenylalanine ammonia-lyase (PAL) enzyme activities and higher expression level of the PAL1 and 4CL-1 genes compared to those irradiated with greenhouse light. We concluded that RB LED light provides a better growth condition and resistance to drought stress for the two genotypes of lemon balm by the highest antioxidant activity and the least amount of damage to the cell membranes. Our data suggest that LED light pre-treatments as moderate stress activate antioxidant systems, enhance the scavenging of ROS and induce drought stress tolerance in the two genotypes of lemon balm plants.

     

Suitability evaluation of some specific crops in Souma area (Iran), using Cervatana and Almagra models

In the present study Cervatana and Almagra models from decision support system, MicroLEIS DSS, were applied to segregation of arable land surfaces from the marginal ones and suitability evaluation of wheat (Triticum aestivum), maize (Zea mays) and alfalfa (Medicago sativa) in Souma area with approximately 4100 ha extension in West Azarbaijan. Obtained results from both models are presented and discussed in this research work. Soil morphological and analytical data were collected from 35 soil profiles, representative of the study area and stored in SDBm plus database. The control or vertical section of soil for applying and running the models for annual selected crops, was calculated by soil layer generator 0.0–50 cm in depth, or between the surface and the limit of useful depth when the latter is between 0.0 and 50 cm. According to results, 80.49% of the total area was good capable for agricultural uses and 19.51% must be reforested and not dedicated to agriculture. The lands with good capability for agricultural uses is classified as highly suitable area (S2) for wheat, maize and alfalfa, but results in 822 ha for maize and in 126 ha for alfalfa refers to an excellent suitable (S1) and moderately suitable (S3) classes respectively. The most important limitation factors are soil texture and carbonate alone or together and maize — wheat — alfalfa can be selected as the best crop rotation. A simple map subsystem (ArcView GIS) was used for basic data and models result demonstration on a map.     

Fabrication of 14 different RNA nanoparticles for specific tumor targeting without accumulation in normal organs

Due to structural flexibility, RNase sensitivity, and serum instability, RNA nanoparticles with concrete shapes for in vivo application remain challenging to construct. Here we report the construction of 14 RNA nanoparticles with solid shapes for targeting cancers specifically. These RNA nanoparticles were resistant to RNase degradation, stable in serum for >36 h, and stable in vivo after systemic injection. By applying RNA nanotechnology and exemplifying with these 14 RNA nanoparticles, we have established the technology and developed “toolkits” utilizing a variety of principles to construct RNA architectures with diverse shapes and angles. The structure elements of phi29 motor pRNA were utilized for fabrication of dimers, twins, trimers, triplets, tetramers, quadruplets, pentamers, hexamers, heptamers, and other higher-order oligomers, as well as branched diverse architectures via hand-in-hand, foot-to-foot, and arm-on-arm interactions. These novel RNA nanostructures harbor resourceful functionalities for numerous applications in nanotechnology and medicine. It was found that all incorporated functional modules, such as siRNA, ribozymes, aptamers, and other functionalities, folded correctly and functioned independently within the nanoparticles. The incorporation of all functionalities was achieved prior, but not subsequent, to the assembly of the RNA nanoparticles, thus ensuring the production of homogeneous therapeutic nanoparticles. More importantly, upon systemic injection, these RNA nanoparticles targeted cancer exclusively in vivo without accumulation in normal organs and tissues. These findings open a new territory for cancer targeting and treatment. The versatility and diversity in structure and function derived from one biological RNA molecule implies immense potential concealed within the RNA nanotechnology field.     

Pitfalls in screening streptococci for retrieving superior streptokinase (SK) genes: no activity correlation for streptococcal culture supernatant and recombinant SK

Streptokinase (SK), the heterogeneous protein family secreted by some groups of β-hemolytic streptococci (βHS), is a plasminogen activator and well-known drug for thrombolytic therapy. Differences in plasminogen activation property of streptococcal culture supernatants (SCS) have been traditionally used to identify superior producer strains and SK genes (skc) for recombinant SK (rSK) production. However, the role of SK heterogeneity and whether SK activities in SCS correlate with that of their corresponding rSK is a matter of debate. To address these concerns, SCS of nine group C streptococci (GCS) screened among 252 βHS clinical isolates were compared for plasminogen activation using S-2251 chromogenic assay. The GCS (Streptococcus equisimilis) showing the highest (GCS-S87) and lowest (GCS-S131) activities were selected for PCR-based isolation of skc, cloning and rSK production in Escherichia coli. The 6×His-tagged rSK proteins were purified by NI–NTA chromatography, analyzed by SDS-PAGE and Western blotting and their activities were determined. While SCS of GCS-S87 and GCS-S131 showed different plasminogen activations (95 and 35 %, respectively) compared to that of the reference strain (GCS-9542), but interestingly rSK of all three strains showed close specific activities (1.33, 1.70, and 1.55 × 10⁴ IU mg^?1). Accordingly, SKS87 and SKS131 had more than 90 % sequence identity at the amino acids level compared to SK9542. Therefore, SK heterogeneity by itself may not contribute to the differences in plasminogen activation properties of SCS and evaluation of this activity in SCS might not be a proper assay for screening superior skc.