Anti-arthritic potential of marine macroalgae Turbinaria ornata in Complete Freund’s Adjuvant induced rats

T. ornata a macroalgae rich in bioactive molecules possess various biological activities. Herein, the aim of the study is to evaluate the aqueous extract and the sulphated polysaccharide isolated from T. ornata for its anti-arthritic potential in Complete Freund’s Adjuvant (CFA) induced arthritis in rats. Anti-arthritic potential of aqueous T. ornata (ATO) and T. ornata sulphated polysaccharide (TSP) was evidenced by the significant reduction in paw volume and arthritic score. Inflammatory and antioxidant markers were found to be restored in the drug treated groups which was found to be in line with dexamethasone a standard anti-inflammatory drug. The histopathological and radiological examination adds on the support to the above findings confirming the anti-arthritic potential of ATO and TSP. It is interesting to note that the sulphated polysaccharide inhibits inflammation and bone damage at very low dose itself. Hence, TSP could be considered as a better candidate in the management of chronic inflammatory diseases like rheumatoid arthritis.     

Insight into the photophysics of strong dual emission (blue & green) producing graphene quantum dot clusters and their application towards selective and sensitive detection of trace level Fe3+ and Cr6+ ions

Graphene-nanostructured systems, such as graphene quantum dots (GQDs), are well known for their interesting light-emitting characteristics and are being applied to a variety of luminescence-based applications. The emission properties of GQDs are complex. Therefore, understanding the science of the photophysics of coupled quantum systems (like quantum clusters) is still challenging. In this regard, we have successfully prepared two different types of GQD clusters, and explored their photophysical properties in detail. By co-relating the structure and photophysics, it was possible to understand the emission behavior of the cluster in detail. This gave new insight into understanding the clustering effect on the emission behaviour. The results clearly indicated that although GQDs are well connected, the local discontinuity in the structure prohibits the dynamics of photoexcited charge carriers going from one domain to another. Therefore, an excitation-sensitive dual emission was possible. Emission yield values of about 18% each were recorded at the blue and green emission wavelengths at a particular excitation energy. This meant that the choice of emission color was decided by the excitation energy. Through systematic analysis, it was found that both intrinsic and extrinsic effects contributed to the blue emission, whereas only the intrinsic effect contributed to the green emission. These excitation-sensitive dual emissive GQD clusters were then used to sense Fe³⁺ and Cr⁶⁺ ions in the nanomolar range. While the Cr⁶⁺ ions were able to quench both blue and green emissions, the Fe³⁺ ions quenched blue emission only. The insensitivity of the Fe³⁺ ions in the quenching of the green emission was also understood through quantum chemical calculations.

Schematic representation for the origin of blue and green emissions, and the resultant PL emission spectra from the GQD interconnected cluster-type sample.     

Simple and Rapid Method To Determine Antimycobacterial Potency of Compounds by Using Autoluminescent Mycobacterium tuberculosis

A major obstacle in the process of discovery of drugs against Mycobacterium tuberculosis is its extremely slow growth rate and long generation time (∼20 to 24 h). Consequently, determination of MICs and minimum bactericidal concentrations (MBCs) of potential drug candidates using current methods requires 7 days (resazurin-based MIC assay [REMA]) and 1 month (CFU enumeration), respectively. We employed a synthetic luciferase operon optimized for expression in high-GC-content bacteria and adapted it for use in mycobacteria. Using luminescence-based readouts, we were able to determine the MICs and bactericidal activities of approved tuberculosis (TB) drugs, which correlated well with currently used methods. Although luminescence-based readouts have been used previously to determine the MICs and bactericidal activities of approved TB drugs, in this study we adapted this assay to carry out a pilot screen using a library of 1,114 compounds belonging to diverse chemical scaffolds. We found that MICs derived from a 3-day luminescence assay matched well with REMA-based MIC values. To determine the bactericidal potencies of compounds, a 1:10 dilution of the cultures from the MIC plate was carried out on day 7, and the bactericidal concentrations determined based on time to positivity in 2 weeks were found to be comparable with MBC values determined by the conventional CFU approach. Thus, the luminescent mycobacterium-based approach not only is very simple and inexpensive but also allowed us to generate the information in half the time required by conventional methods.     

Detection of rickettsioses and Q fever in Sri Lanka

Current serological evidence suggests the presence of scrub typhus and spotted fever group (SFG) rickettsiosis in Sri Lanka. Our objective was to identify rickettsial agents/Q fever as aetiological causes for patients who were presumed having rickettsioses by the presence of an eschar or a rash. Sera from patients with unknown origin fever from Matara were tested by immunofluorescence for SFG rickettsial antigens, typhus group rickettsiae, Orientia tsutsugamushi, and Coxiella burnetii antigens. Thirteen (7.3%) of the patients presented with a rash, 11 (6.1%) had an inoculation eschar, and 16 patients recalled a tick or flea bite. We found that 25 (14%) patients had scrub typhus, 6 (3%) SFG rickettsioses, 3 (1.6%) acute Q fever, 3 (1.6%) murine typhus, and 3 (1.6%) were infected by Rickettsia felis. In addition to already described scrub and murine typhus, we found that R. felis and C. burnetii infections should be considered in Sri Lanka.     

Lactate dehydrogenase and caspase activity in nasopharyngeal secretions are predictors of bronchiolitis severity

Background

Bronchiolitis is the leading cause of hospitalization in infants. Biomarkers of disease severity might help in clinical management.

Objective

To determine the clinical predictiveness of NW-LDH, NW-caspase 3/7, and NW-LDH/NW-caspase 3/7 ratio in bronchiolitis.

Methods

Previously healthy children less than 24 months of age with bronchiolitis were recruited from the Texas Children''s emergency room and intensive care unit from October 2010 to April 2011. Demographic, clinical information, and NW samples were obtained at enrollment. NW samples were analyzed for respiratory viruses, caspase 3/7, and LDH.

Results

A viral pathogen was detected in 91·6% of 131 children, with the most common being respiratory syncytial virus and human rhinovirus. A single infection was found in 61·8% of subjects and co-infection in 29·8%. Children admitted to ICU had significantly higher NW-LDH than children sent home from the ER or admitted to the general floor (P = 0·02). Children infected with RSV had the highest NW-LDH concentration (P = 0·03) compared with other viral infections. NW-LDH and NW-caspase were significantly correlated (r = 0·77, P < 0·0001). The univariate models showed NW-LDH and NW-LDH/NW- caspase 3/7 ratio were directly associated with hospitalization. Mutivariate regression analyses suggested a complex interaction between the biomarkers, demographics, and disposition.

Conclusions

NW-LDH, NW-caspase 3/7 and NW-LDH/NW-caspase 3/7 ratio and their interactions with demographic factors are predictive of bronchiolitis severity and can help distinguish children requiring ICU-level care from those admitted to the general floor, or discharged home from the emergency center.     

Microbial flora in gut of Culex quinquefasciatus breeding in cess pits.

The number and types of microorganisms in the gut of Culex quinquefasciatus larvae varied considerably from one site of collection to another. Larval gut, in general, contained enormous number of bacteria, a few fungi and negligible number of actinomycetes which belonged to 15 bacterial, 6 fungal and 4 actinomycete genera, respectively. Bacillus sp., Staphylococcus sp. and Pseudomonas sp. among bacteria, Aspergillus among fungi and Streptomyces sp. among actinomycetes were frequently encountered. Escherichia, Proteus, Aspergillus and Streptomyces were the most abundant genera. Isolates of Bacillus, Pseudomonas, Shigella and Staphylococcus caused 100% mortality during the early instar of larval development. None of the fungal isolates effected 100% mortality while Nocardiopsis sp. among actinomycetes gave 100% mortality. One of the Escherichia isolate suppressed the adult emergence completely while 27 others, belonging to most of the genera found, suppressed significantly. Isolates of Aspergillus, Alternaria and Streptomyces inhibited the emergence of adults completely.     

Selective Inhibition of PTP1B by Vitalboside A from Syzygium cumini Enhances Insulin Sensitivity and Attenuates Lipid Accumulation Via Partial Agonism to PPARγ: In Vitro and In Silico Investigation

Although antidiabetic drugs show good insulin‐sensitizing property for T2DM, they also exhibit undesirable side‐effects. Partial peroxisome proliferator‐activated receptor γ agonism with protein tyrosine phosphatase 1B inhibition is considered as an alternative therapeutic approach toward the development of a safe insulin sensitizer. Bioactivity‐based fractionation and purification of Syzygium cumini seeds led to the isolation and identification of bifunctional Vitalboside A, which showed antidiabetic and anti‐adipogenic activities, as measured by glucose uptake in L6 and 3T3‐L1 adipocytes and Nile red assay. A non‐competitive allosteric inhibition of protein tyrosine phosphatase 1B by Vitalboside A was observed, which was confirmed by docking studies. Inhibitor studies with wortmannin and genistein showed an IRTK‐ and PI3K‐dependent glucose uptake. A PI3K/AKT‐dependent activation of GLUT4 translocation and an inactivation of GSK3β were observed, confirming its insulin‐sensitizing potential. Vitalboside A exhibited partial transactivation of peroxisome proliferator‐activated receptor γ with an increase in adiponectin secretion, which was confirmed using docking analysis. Vitalboside A is a bifunctional molecule derived from edible plant showing inhibition of PTP1B and partial agonism to peroxisome proliferator‐activated receptor γ which could be a promising therapeutic agent in the management of obesity and diabetes.