Resveratrol, a phytochemical commonly found in the skin of grapes and berries, was tested for its biofilm inhibitory activity against Vibrio cholerae. Biofilm inhibition was assessed using crystal ...violet assay. MTT assay was performed to check the viability of the treated bacterial cells and the biofilm architecture was analysed using confocal laser scanning microscopy. The possible target of the compound was determined by docking analysis. Results showed that subinhibitory concentrations of the compound could significantly inhibit biofilm formation in V. cholerae in a concentration-dependent manner. AphB was found to be the putative target of resveratrol using docking analysis. The results generated in this study proved that resveratrol is a potent biofilm inhibitor of V. cholerae and can be used as a novel therapeutic agent against cholera. To our knowledge, this is the first report of resveratrol showing antibiofilm activity against V. cholerae.
Aim
Category A classified Bacillus anthracis is highly fatal pathogen that causes anthrax and creates challenges for global security and public health. In this study, development of a safe and ideal ...next‐generation subunit anthrax vaccine has been evaluated in mouse model.
Method and Results
Protective antigen (PA) and BA3338, a surface layer homology (SLH) domain possessing protein were cloned, expressed in heterologous system and purified by IMAC. Recombinant PA and BA3338 with alum were administered in mouse alone or in combination. The humoral and cell‐mediated immune response was measured by ELISA and vaccinated animals were challenged with B. anthracis spores via intraperitoneal route. The circulating IgG antibody titre of anti‐PA and anti‐BA3338 was found significantly high in the first and second booster sera. A significant enhanced level of IL‐4, IFN‐γ and IL‐12 was observed in antigens stimulated supernatant of splenocytes of PA + BA3338 vaccinated animals. A combination of PA and BA3338 provided 80% protection against 20 LD50 lethal dose of B. anthracis spores.
Conclusion
Both antigens induced admirable humoral and cellular immune response as well as protective efficacy against B. anthracis spores.
Significance and Impact of the Study
This study has been evaluated for the first time using BA3338 as a vaccine candidate alone or in combination with well‐known anthrax vaccine candidate PA. The findings of this study demonstrated that BA3338 could be a co‐vaccine candidate for development of dual subunit vaccine against anthrax.
Colorectal cancer (CRC) is a complex disease with genetic and epigenetic alterations in many key oncogenes and tumor suppressor genes. The active principle of a gum resin from Boswellia serrata, ...3-acetyl-11-keto-β-boswellic acid (AKBA), has recently gained attention as a chemopreventive compound due to its ability to target key oncogenic proteins such as 5-lipoxygenase and nuclear factor-kappaB. AKBA has been shown to inhibit the growth of CRC cells; however, the precise molecular mechanisms underlying its anticancer activities in CRC remain unclear. We hypothesized that boswellic acids may achieve their chemopreventive effects by modulating specific microRNA (miRNA) pathways. We found that AKBA significantly up-regulated expression of the let-7 and miR-200 families in various CRC cell lines. Both let-7 and miR-200 are putative tumor-suppressive miRNAs. AKBA modulated the expression of several downstream targets of the let-7 and miR-200 families, such as CDK6, vimentin and E-cadherin. These data were further strengthened by miRNA knockdown studies, which revealed that inhibition of let-7i facilitated enhanced cancer cell proliferation, migration and invasion. In addition, AKBA also induced similar modulation of the let-7 and miR-200 downstream genes in CRC tumors orthotopically implanted in nude mice. These results indicate that AKBA-induced antitumor effects in CRC occur, at least partly through the up-regulation of specific miRNA pathways. Our data provide novel evidence that anticancer effects of boswellic acids are due in part to their ability to regulate cellular epigenetic machinery and further highlight the promise for this phytochemical in the preventative and therapeutic applications of CRC.
INTRODUCTION: With the onset of frailty, there is often a rapid, progressive, and self-perpetuating downward spiral towards death. Frailty has enormous impact on acute hospital care and has been ...shown to be a more effective predictor of mortality than conventional clinical measures. METHODS: Hospitalized older patients admitted in medical wards at a teaching public hospital were studied to determine the prevalence of frailty; its association with anemia, congestive heart failure, clinically active tuberculosis and cognitive impairment; as well as its impact upon short-term outcome. RESULTS: A total of 250 older hospitalized patients were included, and their frailty status was assessed using Fried’s criteria. Of these, 83 (33.2%) patients were frail, with frailty found to be significantly associated with increasing age. A lower mean level of haemoglobin (p, 0.002), higher chance of congestive heart failure (p, <0.001), lower mean MMSE score (p, <0.001), was found in frail older patients. Frail subjects had a higher median hospital stay. There were total of 5 deaths, all among the frail group. CONCLUSION: Our study showed that almost a third of hospitalized older patients are frail, and have anemia, higher frequency of CHF, cognitive impairment, longer hospital stay and higher mortality.
Mutations at specific hotspots in non-coding regions of ADGRG6, PLEKHS1, WDR74, TBC1D12 and LEPROTL1 frequently occur in bladder cancer (BC). These mutations could function as biomarkers for the ...non-invasive detection of BC but this remains largely unexplored. Massively-parallel sequencing of non-coding hotspots was applied to 884 urine cell pellet DNAs: 591 from haematuria clinic patients (165 BCs, 426 non-BCs) and 293 from non-muscle invasive BC surveillance patients (29 with recurrence). Urine samples from 142 non-BC haematuria clinic patients were used to optimise variant calling. Non-coding mutations are readily detectable in the urine of BC patients and undetectable, or present at much lower frequencies, in the absence of BC. The mutations can be used to detect incident BC with 66% sensitivity (95% CI 58-75) at 92% specificity (95% CI 88-95) and recurrent disease with 55% sensitivity (95% CI 36-74) at 85% specificity (95% CI 80-89%) using a 2% variant allele frequency threshold. In the NMIBC surveillance setting, the detection of non-coding mutations in urine in the absence of clinically detectable disease was associated with an increased relative risk of future recurrence (RR = 4.62 (95% CI 3.75-5.48)). As urinary biomarkers, non-coding hotspot mutations behave similarly to driver mutations in BC-associated genes and could be included in biomarker panels for BC detection.
•The influence of sliding coatings in mitigating against granular impact is investigated.•Including angularity of the particle shapes is critical in capturing measurements.•Momentum transfer ...reductions for rigid targets are observed with sliding coatings.•Loss of performance in employing sliding coatings on deformable targets.
The use of sliding coating layers on structures is investigated as an approach to manipulate the transfer of momentum during the impact of granular matter with rigid and deformable structures. We first report an experimental investigation of the momentum transfer into rigid stationary targets with fixed and sliding coating layer impacted by high velocity granular slugs. Friction between the impacting granular particles and the target surface enhances the momentum transfer during the interaction with the target. By introducing a sliding coating layer with a lubricated target surface-coating interface, the momentum transfer is reduced: the coating slides on the target surface dragged along by friction between the coating and the particles but, the low friction between the coating and the target reduces the transfer of frictional forces into the target. Coupled discrete element and Lagrangian finite element simulations with rod-shaped granular particles are shown to capture the measurements with high fidelity. This numerical approach is then used to investigate the use of sliding coatings on deformable edge-clamped plates. Introduction of a coating layer while keeping the total mass of the plate constant, reduces the thickness of the plates and this in turn reduces their bending strength. The consequence is that momentum transfer reductions are lost as a result of the reduced bending strength and the minimum plate deflection is attained when no coating layer is present. We thus conclude that sliding coating layers can result in momentum transfer reductions when used on relatively rigid targets but result in a degradation of impact resistance performance when used on highly deformable structures.
In this study, an ELISA was developed for simultaneous detection of antibodies against both the important toxins of B. anthracis i.e. protective antigen (PA) and lethal factor (LF). A chimera of PA ...and LF was made by fusion and cloned and expressed in E. coli. The purified recombinant protein was used in plate ELISA for serodiagnosis of anthrax. The chimera could detect antibodies against both the toxins of Bacillus anthracis. The human serum samples (n = 98) collected from anthrax endemic and non-endemic areas were tested employing ELISA. The ELISA gave sensitivity of 100% (95% Confidence Interval CI, 92.13 to 100) and specificity of 97.78% (95% Confidence Interval CI, 88.23 to 99.94) with a J index of 0.97. The efficiency of ELISA was found to be 98.9% with the positive predictive value (PPV) and negative predictive value (NPV) of 97.8% and 100%, respectively. The chimera of PA and LF could be a better diagnostic antigen for serodiagnosis as the assay detects antibodies against both the toxins in early as well delayed infection cases of anthrax. Therefore, it can be a very useful tool for the surveillance as well as for confirmation of cutaneous anthrax cases.
MicroRNAs (miRNAs) are short non-coding RNAs that interfere with translation of specific target mRNAs and thereby regulate diverse biological processes. Recent studies have suggested that miRNAs ...might have a role in osteoblast differentiation and bone formation. Here, we show that miR-542-3p, a well-characterized tumor suppressor whose downregulation is tightly associated with tumor progression via C-src-related oncogenic pathways, inhibits osteoblast proliferation and differentiation. miRNA array profiling in Medicarpin (a pterocarpan with proven bone-forming effects) induced mice calvarial osteoblast cells and further validation by quantitative real-time PCR revealed that miR-542-3p was downregulated during osteoblast differentiation. Over-expression of miR-542-3p inhibited osteoblast differentiation, whereas inhibition of miR-542-3p function by anti-miR-542-3p promoted expression of osteoblast-specific genes, alkaline phosphatase activity and matrix mineralization. Target prediction analysis tools and experimental validation by luciferase 3' UTR reporter assay identified BMP-7 (bone morphogenetic protein 7) as a direct target of miR-542-3p. It was seen that over-expression of miR-542-3p leads to repression of BMP-7 and inhibition of BMP-7/PI3K- survivin signaling. This strongly suggests that miR-542-3p suppresses osteogenic differentiation and promotes osteoblast apoptosis by repressing BMP-7 and its downstream signaling. Furthermore, silencing of miR-542-3p led to increased bone formation, bone strength and improved trabecular microarchitecture in sham and ovariectomized (Ovx) mice. Although miR-542-3p is known to be a tumor repressor, we have identified second complementary function of miR-542-3p where it inhibits BMP-7-mediated osteogenesis. Our findings suggest that pharmacological inhibition of miR-542-3p by anti-miR-542-3p could represent a therapeutic strategy for enhancing bone formation in vivo.
PDF
