Search Results (25)

Fast-dissolving tablets (FDTs) have arisen as a novel way to tackle issues encountered by patients with dysphagia, including youngsters, older people, and those with neurodegenerative or developmental disabilities. This review emphasises the crucial function of natural polymers as super disintegrants in improving fast-disintegrating tablet formulation. Natural polymers, such as chitosan, guar gum, xanthan gum, and fenugreek seed mucilage, are biocompatible, biodegradable, and offer better affordability than synthetics. Natural polymers can quickly break down and disintegrate oral tablets. They also help accelerate drug release bioavailability and patient compliance. This article discusses the benefits of natural polymers, such as environmentally sustainable processing, cost effectiveness, and patient engagement, as well as challenges and limitations. The comprehensive comparison between natural polymers and synthetic polymers emphasises the benefits of natural substances to overcome challenges in the production and promotion of sustainable pharmaceutical practices. Spray drying, freezing, and nanotechnology are advancements in FDT production technology. Apart from its ownership, like Zydis and Durasolv, the combination of these techniques aids in the creation of a medicine system that may be adjusted. They prioritize patients and are also effective. Prospective studies should focus on the expansion of natural polymer procurement and distillation processes to improve the use of FDT. Full article

Background: MicroRNAs (miRNAs) play crucial roles in regulating tissue-specific gene expression and plant development. This study explores the identification and functional characterization of miRNAs in Plukenetia volubilis (sacha inchi), an economically and nutritionally significant crop native to the Amazon basin, across three organs: root, stem, and leaf. Methods: Small RNA libraries were sequenced on the Illumina Novaseq 6000 platform, yielding high-quality reads that facilitated the discovery of known and novel miRNAs using miRDeep-P. Results: A total of 277 miRNAs were identified, comprising 71 conserved and 206 novel miRNAs, across root, stem, and leaf tissues. In addition, differential expression analysis using DESeq2 identified distinct miRNAs exhibiting tissue-specific regulation. Notably, novel miRNAs like novel_1, novel_88, and novel_189 showed significant roles in processes such as auxin signaling, lignin biosynthesis, and stress response. Functional enrichment analysis of miRNA target genes revealed pathways related to hormonal regulation, structural reinforcement, and environmental adaptation, highlighting tissue-specific functions. The Principal Component Analysis and PERMANOVA confirmed clear segregation of miRNA expression profiles among tissues, underlining organ-specific regulation. Differential expression patterns emphasized unique regulatory roles in each organ: roots prioritized stress response and nutrient uptake, leaves focused on photosynthesis and UV protection, and stems contributed to structural integrity and nutrient transport, suggesting evolutionary adaptations in P. volubilis. Conclusions: This study identified novel miRNA-mediated networks that regulate developmental and adaptive processes in P. volubilis, underscoring its molecular adaptations for resilience and productivity. By characterizing both conserved and novel miRNAs, the findings lay a foundation for genetic improvement and molecular breeding strategies aimed at enhancing agronomic traits, stress tolerance, and the production of bioactive compounds. Full article

Gas hydrate formation in pipelines transporting multiphase fluids from petroleum reservoirs can lead to the formation of blockages, representing a significant flow assurance challenge. Key issues caused by hydrates include substantial increases in the viscosity of mixed liquid phases and the deposition of hydrates on the pipeline wall. This study compares two existing transient multiphase flow simulators, OLGA and LedaFlow, in terms of their estimation of hydrate formation effects on multiphase flow. Here, we compared in detail the hydrate kinetic models, parameters used, and initial condition setup approaches that influence hydrate formation and affect multiphase flow properties. Based on the comparison between the simulation results, it was found that using both simulators with default setups may not lead to comparable results under certain conditions. Adjusting input parameters, such as the stoichiometric coefficient and hydrate formation enthalpy, is necessary in order to obtain equivalent results. Hydrate modules in both simulators have also been applied to a field case. With appropriate setup, OLGA and LedaFlow produce comparable results during steady-state simulations, which align with field observations. This work provides guidelines for setting up OLGA and LedaFlow simulation models to obtain equivalent results. Full article

Phenotypic screenings are usually combined with deconvolution techniques to characterize the mechanism of action for the retrieved hits. These studies can be supported by various computational analyses, although docking simulations are rarely employed. The present study aims to assess if multiple docking calculations can prove successful in target prediction. In detail, the docking simulations submitted to the MEDIATE initiative are utilized to predict the viral targets involved in the hits retrieved by a recently published cytopathic screening. Multiple docking results are combined by the EFO approach to develop target-specific consensus models. The combination of multiple docking simulations enhances the performances of the developed consensus models (average increases in EF1% value of 40% and 25% when combining three and two docking runs, respectively). These models are able to propose reliable targets for about half of the retrieved hits (31 out of 59). Thus, the study emphasizes that docking simulations might be effective in target identification and provide a convincing validation for the collaborative strategies that inspire the MEDIATE initiative. Disappointingly, cross-target and cross-program correlations suggest that common scoring functions are not specific enough for the simulated target. Full article

Recent studies have demonstrated the association of APP and Aβ with cancer, suggesting that BACE1 may play an important role in carcinogenesis. In the present study, we assessed BACE1’s usefulness as a therapeutic target in prostate cancer (PCa). BACE1 expression was observed in human PCa tissue samples, patient-derived xenografts (PDX), human PCa xenograft tissue in nude mice, and transgenic adenocarcinoma of the mouse prostate (TRAMP) tissues by immunohistochemistry (IHC) analysis. Additionally, the downstream product of BACE1 activity, i.e., Aβ1-42 expression, was also observed in these PCa tissues by IHC as well as by PET imaging in TRAMP mice. Furthermore, BACE1 gene expression and activity was confirmed in several established PCa cell lines (LNCaP, C4-2B-enzalutamide sensitive [S], C4-2B-enzalutamide resistant [R], 22Rv1-S, 22Rv1-R, PC3, DU145, and TRAMP-C1) by real-time PCR and fluorometric assay, respectively. Treatment with a pharmacological inhibitor of BACE1 (MK-8931) strongly reduced the proliferation of PCa cells in in vitro and in vivo models, analyzed by multiple assays (MTT, clonogenic, and trypan blue exclusion assays and IHC). Cell cycle analyses revealed an increase in the sub-G1 population and a significant modulation in other cell cycle stages (G1/S/G2/M) following MK-8931 treatment. Most importantly, in vivo administration of MK-8931 intraperitoneal (30 mg/kg) strongly inhibited TRAMP-C1 allograft growth in immunocompetent C57BL/6 mice (approximately 81% decrease, p = 0.019). Furthermore, analysis of tumor tissue using the prostate cancer-specific pathway array revealed the alteration of several genes involved in PCa growth and progression including Forkhead O1 (FOXO1). All together, these findings suggest BACE1 as a novel therapeutic target in advanced PCa. Full article

Zinc (Zn²⁺) is an essential element that can promote proper organ function, cell growth, and immune response; it can also, however, be present in too great a quantity. Zinc toxicity caused by overexposure may result in both minor and major physiological effects, with chronic exposure at low levels and acute exposure at high levels being harmful or even toxic. This investigation examines the effects of acute exposure to relatively high concentrations of Zn²⁺ on sensory nerve function and nerve conduction. A proprioceptive nerve in marine crab (Callinectes sapidus) limbs was used as a model to assess the effects of Zn²⁺ on stretch-activated channels (SACs) and evoked nerve conduction. Exposure to Zn²⁺ slowed nerve condition rapidly; however, several minutes were required before the SACs in sensory endings were affected. A depression in conduction speed and an increase followed by a decrease in amplitude were observed for the evoked compound action potential, while the frequency of nerve activity upon joint movement and stretching of the chordotonal organ significantly decreased. These altered responses could be partially reversed via extensive flushing with fresh saline to remove the zinc. This indicates that subtle, long-term exposure to Zn²⁺ may alter an organism’s SAC function for channels related to proprioception and nerve conduction. Full article

Animals are exposed to lithium (Li⁺) in the natural environment as well as by contact with industrial sources and therapeutic treatments. Low levels of exposure over time and high volumes of acute levels can be harmful and even toxic. The following study examines the effect of high-volume acute levels of Li⁺ on sensory nerve function and nerve conduction. A proprioceptive nerve in the limbs of a marine crab (Callinectes sapidus) was used as a model to address the effects on stretch-activated channels (SACs) and evoked nerve conduction. The substitution of Li⁺ for Na⁺ in the bathing saline slowed nerve conduction rapidly; however, several minutes were required before the SACs in sensory endings were affected. The evoked compound action potential slowed in conduction and slightly decreased in amplitude, while the frequency of nerve activity with joint movement and chordotonal organ stretching significantly decreased. Both altered responses could be partially restored with the return of a Na⁺-containing saline. Long-term exposure to Li⁺ may alter the function of SACs in organisms related to proprioception and nerve conduction, but it remains to be investigated. Full article

Culicoides sonorensis midges vector multiple livestock arboviruses, resulting in significant economic losses worldwide. Due to the tight association between virus transmission, blood feeding, and egg development, understanding midge physiology is paramount to limiting pathogen transmission. Previous studies have demonstrated the importance of small non-coding RNAs (ncRNAs), specifically microRNAs (miRNAs), in multiple aspects of vector physiology. These small ncRNAs regulate gene expression at the post-transcriptional level and display differential expression during pathogen infection. Due to the lack of annotated miRNAs in the biting midge and associated expression profiles, we used small RNA-Seq and miRDeep2 analyses to determine the Culicoides miRNAs in whole females and midgut tissues in response to blood feeding. Our analyses revealed 76 miRNAs within C. sonorensis composed of 73 orthologous and three candidate novel miRNAs, as well as conserved miRNA clusters. miRNA conservation suggests an interesting evolutionary relationship between miRNA expression and hematophagy in the infraorder Culicomorpha. We also identified multiple blood meal-regulated and tissue-enriched miRNAs. Lastly, we further identified miRNAs with expression patterns potentially associated with virus infection by probing publicly available datasets. Together, our data provide a foundation for future ncRNA work to untangle the dynamics of gene regulation associated with midge physiology. Full article

Root tubers of Asphodelus bento-rainhae subsp. bento-rainhae (AbR), a vulnerable endemic species, and Asphodelus macrocarpus subsp. macrocarpus (AmR) have traditionally been used in Portugal to treat inflammatory and infectious skin disorders. The present study aims to evaluate the in vitro antimicrobial activity of crude 70% and 96% hydroethanolic extracts of both medicinal plants, specifically against multidrug-resistant skin-related pathogens, to identify the involved marker secondary metabolites and also to assess the pre-clinical toxicity of these medicinal plant extracts. Bioguided fractionation of the 70% hydroethanolic extracts of both species using solvents of increasing polarity, namely diethyl ether (DEE: AbR-1, AmR-1), ethyl acetate (AbR-2, AmR-2) and aqueous (AbR-3, AmR-3) fractions, enabled the identification of the DEE fractions as the most active against all the tested Gram-positive microorganisms (MIC: 16 to 1000 µg/mL). Furthermore, phytochemical analyses using TLC and LC-UV/DAD-ESI/MS techniques revealed the presence of anthracene derivatives as the main constituents of DEE fractions, and five known compounds, namely 7′-(chrysophanol-4-yl)-chrysophanol-10’-C-beta-D-xylopyranosyl-anthrone (p), 10,7′-bichrysophanol (q), chrysophanol (r), 10-(chrysophanol-7′-yl)-10-hydroxychrysophanol-9-anthrone (s) and asphodelin (t), were identified as the main marker compounds. All these compounds showed high antimicrobial activity, particularly against Staphylococcus epidermidis (MIC: 3.2 to 100 µg/mL). Importantly, no cytotoxicity against HepG2 and HaCaT cells (up to 125 µg/mL) for crude extracts of both species and genotoxicity (up to 5000 µg/mL, with and without metabolic activation) for AbR 96% hydroethanolic extract was detected using the MTT and Ames tests, respectively. Overall, the obtained results contribute to the concrete validation of the use of these medicinal plants as potential sources of antimicrobial agents in the treatment of skin diseases. Full article

MicroRNA transcriptomes from fresh tumors and the adjacent normal tissues were profiled in 10 Korean patients diagnosed with lung adenocarcinoma using a next-generation sequencing (NGS) technique called miRNA-seq. The sequencing quality was assessed using FastQC, and low-quality or adapter-contaminated portions of the reads were removed using Trim Galore. Quality-assured reads were analyzed using miRDeep2 and Bowtie. The abundance of known miRNAs was estimated using the reads per million (RPM) normalization method. Subsequently, using DESeq2 and Wx, we identified differentially expressed miRNAs and potential miRNA biomarkers for lung adenocarcinoma tissues compared to adjacent normal tissues, respectively. We defined reliable miRNA biomarkers for lung adenocarcinoma as those detected by both methods. The miRNA-seq data are available in the Gene Expression Omnibus (GEO) database under accession number GSE196633, and all processed data can be accessed via the Mendeley data website. Full article

Following the concept of RNA dependence and exploiting its application in the R-DeeP screening approach, we have identified RNA-dependent proteins in A549 lung adenocarcinoma cells. RNA-dependent proteins are defined as proteins whose interactome depends on RNA and thus entails RNA-binding proteins (RBPs) as well as proteins in ribonucleoprotein complexes (RNPs) without direct RNA interaction. With this proteome-wide technique based on sucrose density gradient ultracentrifugation and fractionation followed by quantitative mass spectrometry and bioinformatic analysis, we have identified 1189 RNA-dependent proteins including 170 proteins which had never been linked to RNA before. R-DeeP provides quantitative information on the fraction of a protein being RNA-dependent as well as it allows the reconstruction of protein complexes based on co-segregation. The RNA dependence of three newly identified RNA-dependent proteins, DOCK5, ELMO2, also known as CED12A, and ABRAXAS1, also known as CCDC98, was validated using western blot analysis, and the direct RNA interaction was verified by iCLIP2 for the migration-related protein DOCK5 and the mitosis-related protein ABRAXAS1. The R-DeeP 2.0 database provides proteome-wide and cell line-specific information from A549 and HeLa S3 cells on proteins and their RNA dependence to contribute to understanding the functional role of RNA and RNA-binding proteins in cancer cells. Full article

Person re-identification has become an essential application within computer vision due to its ability to match the same person over non-overlapping cameras. However, it is a challenging task because of the broad view of cameras with a large number of pedestrians appearing with various poses. As a result, various approaches of supervised model learning have been utilized to locate and identify a person based on the given input. Nevertheless, several of these approaches perform worse than expected in retrieving the right person in real-time over multiple CCTVs/camera views. This is due to inaccurate segmentation of the person, leading to incorrect classification. This paper proposes an efficient and real-time person re-identification system, named ReID-DeePNet system. It is based on fusing the matching scores generated by two different deep learning models, convolutional neural network and deep belief network, to extract discriminative feature representations from the pedestrian image. Initially, a segmentation procedure was developed based on merging the advantages of the Mask R-CNN and GrabCut algorithm to tackle the adverse effects caused by background clutter. Afterward, the two different deep learning models extracted discriminative feature representations from the pedestrian segmented image, and their matching scores were fused to make the final decision. Several extensive experiments were conducted, using three large-scale and challenging person re-identification datasets: Market-1501, CUHK03, and P-DESTRE. The ReID-DeePNet system achieved new state-of-the-art Rank-1 and mAP values on these three challenging ReID datasets. Full article

MicroRNAs (miRNAs) are a class of small non-coding RNAs involved in many biological processes, including the immune pathways that control bacterial, parasitic, and viral infections. Pathogens probably modify host miRNAs to facilitate successful infection, so they might be useful targets for vaccination strategies. There are few data on differentially expressed miRNAs in the black-legged tick Ixodes scapularis after infection with Borrelia burgdorferi, the causative agent of Lyme disease in the United States. Small RNA sequencing and qRT-PCR analysis were used to identify and validate differentially expressed I. scapularis salivary miRNAs. Small RNA-seq yielded 133,465,828 (≥18 nucleotides) and 163,852,135 (≥18 nucleotides) small RNA reads from Borrelia-infected and uninfected salivary glands for downstream analysis using the miRDeep2 algorithm. As such, 254 miRNAs were identified across all datasets, 25 of which were high confidence and 51 low confidence known miRNAs. Further, 23 miRNAs were differentially expressed in uninfected and infected salivary glands: 11 were upregulated and 12 were downregulated upon pathogen infection. Gene ontology and network analysis of target genes of differentially expressed miRNAs predicted roles in metabolic, cellular, development, cellular component biogenesis, and biological regulation processes. Several Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, including sphingolipid metabolism; valine, leucine and isoleucine degradation; lipid transport and metabolism; exosome biogenesis and secretion; and phosphate-containing compound metabolic processes, were predicted as targets of differentially expressed miRNAs. A qRT-PCR assay was utilized to validate the differential expression of miRNAs. This study provides new insights into the miRNAs expressed in I. scapularis salivary glands and paves the way for their functional manipulation to prevent or treat B. burgdorferi infection. Full article

Cocaine use disorder has been reported to cause transgenerational effects. However, due to the lack of standardized biomarkers, the effects of cocaine use during pregnancy on postnatal development and long-term neurobiological and behavioral outcomes have not been investigated thoroughly. Therefore, in this study, we examined extracellular vesicles (EVs) in adult (~12 years old) female and male rhesus monkeys prenatally exposed to cocaine (n = 11) and controls (n = 9). EVs were isolated from the cerebrospinal fluid (CSF) and characterized for the surface expression of specific tetraspanins, concentration (particles/mL), size distribution, and cargo proteins by mass spectrometry (MS). Transmission electron microscopy following immunogold labeling for tetraspanins (CD63, CD9, and CD81) confirmed the successful isolation of EVs. Nanoparticle tracking analyses showed that the majority of the particles were <200 nm in size, suggesting an enrichment for small EVs (sEV). Interestingly, the prenatally cocaine-exposed group showed ~54% less EV concentration in CSF compared to the control group. For each group, MS analyses identified a number of proteins loaded in CSF-EVs, many of which are commonly listed in the ExoCarta database. Ingenuity pathway analysis (IPA) demonstrated the association of cargo EV proteins with canonical pathways, diseases and disorders, upstream regulators, and top enriched network. Lastly, significantly altered proteins between groups were similarly characterized by IPA, suggesting that prenatal cocaine exposure could be potentially associated with long-term neuroinflammation and risk for neurodegenerative diseases. Overall, these results indicate that CSF-EVs could potentially serve as biomarkers to assess the transgenerational adverse effects due to prenatal cocaine exposure. Full article

Hypoxia and hypoxia-related biomarkers are the major determinants of prostate cancer (PCa) aggressiveness. Therefore, a better understanding of molecular players involved in PCa cell survival under hypoxia could offer novel therapeutic targets. We previously reported a central role of mitochondrial protein carnitine palmitoyltransferase (CPT1A) in PCa progression, but its role in regulating PCa survival under hypoxia remains unknown. Here, we employed PCa cells (22Rv1 and MDA-PCa-2b) with knockdown or overexpression of CPT1A and assessed their survival under hypoxia, both in cell culture and in vivo models. The results showed that CPT1A knockdown in PCa cells significantly reduced their viability, clonogenicity, and sphere formation under hypoxia, while its overexpression increased their proliferation, clonogenicity, and sphere formation. In nude mice, 22Rv1 xenografts with CPT1A knockdown grew significantly slower compared to vector control cells (~59% reduction in tumor volume at day 29). On the contrary, CPT1A-overexpressing 22Rv1 xenografts showed higher tumor growth compared to vector control cells (~58% higher tumor volume at day 40). Pathological analyses revealed lesser necrotic areas in CPT1A knockdown tumors and higher necrotic areas in CPT1A overexpressing tumors. Immunofluorescence analysis of tumors showed that CPT1A knockdown strongly compromised the hypoxic areas (pimonidazole+), while CPT1A overexpression resulted in more hypoxia areas with strong expression of proliferation biomarkers (Ki67 and cyclin D1). Finally, IHC analysis of tumors revealed a significant decrease in VEGF or VEGF-D expression but without significant changes in biomarkers associated with microvessel density. These results suggest that CPT1A regulates PCa survival in hypoxic conditions and might contribute to their aggressiveness. Full article