Synergistic Activity of Rhamnolipid Biosurfactant and Nanoparticles Synthesized Using Fungal Origin Chitosan Against Phytopathogens

Phytopathogens pose severe implications in the quantity and quality of food production by instigating several diseases. Biocontrol strategies comprising the application of biomaterials have offered endless opportunities for sustainable agriculture. We explored multifarious potentials of rhamnolipid-BS (RH-BS: commercial), fungal chitosan (FCH), and FCH-derived nanoparticles (FCHNPs). The high-quality FCH was extracted from Cunninghamella echinulata NCIM 691 followed by the synthesis of FCHNPs. Both, FCH and FCHNPs were characterized by UV-visible spectroscopy, DLS, zeta potential, FTIR, SEM, and Nanoparticle Tracking Analysis (NTA). The commercial chitosan (CH) and synthesized chitosan nanoparticles (CHNPs) were used along with test compounds (FCH and FCHNPs). SEM analysis revealed the spherical shape of the nanomaterials (CHNPs and FCHNPs). NTA provided high-resolution visual validation of particle size distribution for CHNPs (256.33 ± 18.80 nm) and FCHNPs (144.33 ± 10.20 nm). The antibacterial and antifungal assays conducted for RH-BS, FCH, and FCHNPs were supportive to propose their efficacies against phytopathogens. The lower MIC of RH-BS (256 μg/ml) was observed than that of FCH and FCHNPs (>1,024 μg/ml) against Xanthomonas campestris NCIM 5028, whereas a combination study of RH-BS with FCHNPs showed a reduction in MIC up to 128 and 4 μg/ml, respectively, indicating their synergistic activity. The other combination of RH-BS with FCH resulted in an additive effect reducing MIC up to 128 and 256 μg/ml, respectively. Microdilution plate assay conducted for three test compounds demonstrated inhibition of fungi, FI: Fusarium moniliforme ITCC 191, FII: Fusarium moniliforme ITCC 4432, and FIII: Fusarium graminearum ITCC 5334 (at 0.015% and 0.020% concentration). Furthermore, potency of test compounds performed through the in vitro model (poisoned food technique) displayed dose-dependent (0.005%, 0.010%, 0.015%, and 0.020% w/v) antifungal activity. Moreover, RH-BS and FCHNPs inhibited spore germination (61–90%) of the same fungi. Our efforts toward utilizing the combination of RH-BS with FCHNPs are significant to develop eco-friendly, low cytotoxic formulations in future

Rapid Antibody-Based COVID-19 Mass Surveillance: Relevance, Challenges, and Prospects in a Pandemic and Post-Pandemic World.

The aggressive outbreak of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) as COVID-19 (coronavirus disease-2019) pandemic demands rapid and simplified testing tools for its effective management. Increased mass testing and surveillance are crucial for controlling the disease spread, obtaining better pandemic statistics, and developing realistic epidemiological models. Despite the advantages of nucleic acid- and antigen-based tests such as accuracy, specificity, and non-invasive approaches of sample collection, they can only detect active infections. Antibodies (immunoglobulins) are produced by the host immune system within a few days after infection and persist in the blood for at least several weeks after infection resolution. Antibody-based tests have provided a substitute and effective method of ultra-rapid detection for multiple contagious disease outbreaks in the past, including viral diseases such as SARS (severe acute respiratory syndrome) and MERS (Middle East respiratory syndrome). Thus, although not highly suitable for early diagnosis, antibody-based methods can be utilized to detect past infections hidden in the population, including asymptomatic ones. In an active community spread scenario of a disease that can provide a bigger window for mass detections and a practical approach for continuous surveillance. These factors encouraged researchers to investigate means of improving antibody-based rapid tests and employ them as reliable, reproducible, sensitive, specific, and economic tools for COVID-19 mass testing and surveillance. The development and integration of such immunoglobulin-based tests can transform the pandemic diagnosis by moving the same out of the clinics and laboratories into community testing sites and homes. This review discusses the principle, technology, and strategies being used in antibody-based testing at present. It also underlines the immense prospect of immunoglobulin-based testing and the efficacy of repeated planned deployment in pandemic management and post-pandemic sustainable screenings globally

Public transport equity in Shenyang: Using structural equation modelling

In China, with the rapid development of urbanisation, the contradiction between supply and demand has become increasingly severe, particularly in large and medium-sized cities. Improving public transport equity can help to reduce the social exclusion of lower-income and socially vulnerable groups in relation to the urban transport system, and guarantee that public transport systems are given priority in terms of development. Using the concept of transport-related social equity, this study aims to explore the effects of public transport equity in relation to the quality of public transport, public participation, and public transport-related policy using Shenyang as a case study. Data are analysed using Structural Equation Model (SEM). Our findings show that the three latent variables of accessibility, affordability, and social impacts can be seen as representing the main characteristics of public transport equity; while improvements in public transport quality, public participation, and public transport-related polices play a significant role in reducing public transport inequity. Moreover, the findings indicate that public participation has direct, significant, positive influences on public transport quality and public transport-related policies. In terms of policy implications, we suggest that policies designed to improve public transport service quality, extend public transport fare concessions, and promote public participation in the public transport policy decision-making process should be given priority in the next round of urban comprehensive planning in order to reduce public transport-related social inequity in Shenyang and China more generally

Chitosan nanoparticles for the oral delivery of tenofovir disoproxil fumarate: formulation optimization, characterization and <i>ex vivo</i> and <i>in vivo</i> evaluation for uptake mechanism in rats

<p><b>Objective:</b> Design chitosan based nanoparticles for tenofovir disoproxil fumarate (TDF) with the purpose of enhancing its oral absorption.</p> <p><b>Significance:</b> TDF is a prodrug that has limited intestinal absorption because of its susceptibility to gut wall esterases. Hence, design of chitosan based polymeric novel nanocarrier systems can protect TDF from getting metabolized and also enhance the oral absorption.</p> <p><b>Methods:</b> The nanoparticles were prepared using the ionic gelation technique. The factors impacting the particle size and entrapment efficiency of the nanoparticles were evaluated using design of experiments approach. The optimized nanoparticles were characterized and evaluated for their ability to protect TDF from esterase metabolism. The nanoparticles were then studied for the involvement of active transport in their uptake during the oral absorption process. Further, <i>in vivo</i> pharmacokinetic studies were carried out for the designed nanoparticles.</p> <p><b>Results:</b> The application of design of experiments in the optimization process was useful to determine the critical parameters and evaluate their interaction effects. The optimized nanoparticles had a particle size of 156 ± 5 nm with an entrapment efficiency of 48.2 ± 1%. The nanoparticles were well characterized and provided metabolic protection for TDF in the presence of intestinal esterases. The nanoparticles were able to increase the AUC of tenofovir by 380%. The active uptake mechanisms mainly involving clathrin-mediated uptake played a key role in increasing the oral absorption of tenofovir.</p> <p><b>Conclusions:</b> These results show the ability of the designed chitosan based nanoparticles in enhancing the oral absorption of TDF along the oral route by utilizing the active endocytic uptake pathways.</p

LSD1 Inhibition Attenuates Tumor Growth by Disrupting PLK1 Mitotic Pathway

Lysine-specific demethylase 1 (LSD1) is a histone modifier that is highly overexpressed in lung adenocarcinoma, which results in aggressive tumor biology. Tumor cell proliferation and migration analysis after LSD1 inhibition in the lung adenocarcinoma cell line PC9, using the LSD1 inhibitor HCI-2509 and siRNA, demonstrated that LSD1 activity was essential for proliferation and migration capacities of tumor cells. Moreover, reduced proliferation rates after LSD1 inhibition were shown to be associated with a cell-cycle arrest of the tumor cells in the G2-M-phase. Expression profiling followed by functional classification and pathway analysis indicated prominent repression of the polo-like kinase 1 (PLK1) pathway upon LSD1 inhibition. In contrast, transient overexpression of exogenous PLK1 plasmid rescued the LSD1 inhibition-mediated downregulation of PLK1 pathway genes. Mechanistically, LSD1 directly regulates expression of PLK1 by binding to its promoter region that subsequently affects expression of its downstream target genes. Notably, using lung adenocarcinoma TCGA datasets a significant correlation between LSD1 and PLK1 along with its downstream targets was observed. Furthermore, the LSD1/ PLK1 linkage was confirmed by IHC analysis in a clinical lung adenocarcinoma cohort (n 1/4 43). Conclusively, this is the first study showing a direct transcriptional link between LSD1 and PLK1. Implications: These findings point to a role of LSD1 in regulating PLK1 and thus efficient G2-M-transitionmediating proliferation of tumor cells and suggest targeting the LSD1/ PLK1 axis as a novel therapeutic approach for lung adenocarcinoma treatment

Transcriptome analysis reveals upregulation of immune response pathways at the invasive tumour front of metastatic seminoma germ cell tumours

Background Testicular germ cell tumours (TGCTs) have a high metastasis rate. However, the mechanisms related to their invasion, progression and metastasis are unclear. Therefore, we investigated gene expression changes that might be linked to metastasis in seminomatous testicular germ cell tumour (STGCT) patients. Methods Defined areas [invasive tumour front (TF) and tumour centre (TC)] of non-metastatic (with surveillance and recurrence-free follow-up >2 years) and metastatic STGCTs were collected separately using laser capture microdissection. The expression of 760 genes related to tumour progression and metastasis was analysed using nCounter technology and validated with quantitative real-time PCR and enzyme-linked immunosorbent assay. Results Distinct gene expression patterns were observed in metastatic and non-metastatic seminomas with respect to both the TF and TC. Comprehensive pathway analysis showed enrichment of genes related to tumour functions such as inflammation, angiogenesis and metabolism at the TF compared to the TC. Remarkably, prominent inflammatory and cancer-related pathways, such as interleukin-6 (IL-6) signalling, integrin signalling and nuclear factor-kappa B signalling, were significantly upregulated in the TF of metastatic vs non-metastatic tumours. Conclusions IL-6 signalling was the most significantly upregulated pathway in metastatic vs non-metastatic tumours and therefore could constitute a therapeutic target for future personalised therapy. In addition, this is the first study showing intra- and inter-tumour heterogeneity in STGCT

Preclinical studies reveal that LSD1 inhibition results in tumor growth arrest in lung adenocarcinoma independently of driver mutations

Lung adenocarcinoma (LUAD) is the most prevalent subtype of non-small cell lung cancer. Despite the development of novel targeted and immune therapies, the 5-year survival rate is still only 21%, indicating the need for more efficient treatment regimens. Lysine-specific demethylase 1 (LSD1) is an epigenetic eraser that modifies histone 3 methylation status, and is highly overexpressed in LUAD. Using representative human cell culture systems and two autochthonous transgenic mouse models, we investigated inhibition of LSD1 as a novel therapeutic option for treating LUAD. The reversible LSD1 inhibitor HCI-2509 significantly reduced cell growth with an IC50 of 0.3-5 mu min vitro, which was linked to an enhancement of histone 3 lysine methylation. Most importantly, growth arrest, as well as inhibition of the invasion capacities, was independent of the underlying driver mutations. Subsequent expression profiling revealed that the cell cycle and replication machinery were prominently affected after LSD1 inhibition. In addition, our data provide evidence that LSD1 blockade significantly interferes with EGFR downstream signaling. Finally, our in vitro results were confirmed by preclinical therapeutic approaches, including the use of two autochthonous transgenic LUAD mouse models driven by either EGFR or KRAS mutations. Importantly, LSD1 inhibition resulted in significantly lower tumor formation and a strong reduction in tumor progression, which were independent of the underlying mutational background of the mouse models. Hence, our findings provide substantial evidence indicating that tumor growth of LUAD can be markedly decreased by HCI-2509 treatment, suggesting its use as a single agent maintenance therapy or combined therapeutical application in novel concerted drug approaches

Author Correction: LSD1 modulates the non-canonical integrin β3 signaling pathway in non-small cell lung carcinoma cells

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