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Abstract Inflammatory bowel disease (IBD) is a chronic disorder characterized by recurrent gastrointestinal inflammation, lacking a precise aetiology and definitive cure. The gut microbiome is vital in preventing and treating IBD due to its various physiological functions. In the interplay between the gut microbiome and human health, extracellular vesicles secreted by gut bacteria (BEVs) are key mediators. Herein, we explore the role of Roseburia intestinalis (R)‐derived EVs (R‐EVs) as potent anti‐inflammatory mediators in treating dextran sulfate sodium‐induced colitis. R was selected as an optimal BEV producer for IBD treatment through ANCOM analysis. R‐EVs with a 76 nm diameter were isolated from R using a tangential flow filtration system. Orally administered R‐EVs effectively accumulated in inflamed colonic tissues and increased the abundance of Bifidobacterium on microbial changes, inhibiting colonic inflammation and prompting intestinal recovery. Due to the presence of Ile‐Pro‐Ile in the vesicular structure, R‐EVs reduced the DPP4 activity in inflamed colonic tissue and increased the active GLP‐1, thereby downregulating the NFκB and STAT3 via the PI3K pathway. Our results shed light on the impact of BEVs on intestinal recovery and gut microbiome alteration in treating IBD.

Plant-derived vesicles (PDVs) are membranous structures that originate from plant cells and are responsible for multiple physiological and pathological functions. In the last decade, PDVs have gained much attention for their involvement in different biological processes, including intercellular communication and defense response, and recent scientific evidence has opened a new avenue for their applications in cancer treatment. Nevertheless, much remains unknown about these vesicles, and current research remains inconsistent. This review aims to provide a comprehensive introduction to PDVs, from their biological characteristics to purification methods, and to summarize the status of their potential development for cancer therapy.

Over thousands of years, natural bioactive compounds derived from plants (bioactive phytocompounds, BPCs) have been used worldwide to address human health issues. Today, they are a significant resource for drug discovery in the development of modern medicines. Although many BPCs have promising biological activities, most of them cannot be effectively utilized in drugs for therapeutic applications because of their inherent limitations of low solubility, structural instability, short half-life, poor bioavailability, and non-specific distribution to organs. Researchers have utilized emerging nanoformulation (NF) technologies to overcome these limitations as they have demonstrated great potential to improve the solubility, stability, and pharmacokinetic and pharmacodynamic characteristics of BPCs. This review exemplifies NF strategies for resolving the issues associated with BPCs and summarizes recent advances in their preclinical and clinical applications for imaging and therapy. This review also highlights how innovative NF technologies play a leading role in next-generation BPC-based drug development for extended therapeutic applications. Finally, this review discusses the opportunities to take BPCs with meaningful clinical impact from bench to bedside and extend the patent life of BPC-based medicines with new formulations or application to new adjacent diseases beyond the primary drug indications.

Centella asiatica is a herbaceous plant containing medicinal and cosmetic properties: anti-bacterial, anti-aging, memory enhancing and wound healing. The lack of information impedes the development of suitable growth conditions for C. asiatica in the hydroponic system. Maintaining proper electrical conductivity (EC) of a nutrient solution is considered crucial for plant growth and the accumulation of bioactive compounds in a plant grown in hydroponics. This study aimed to investigate an optimal EC that enhances the growth of C. asiatica and its centellosides content. Seedlings were grown in commercial nutrient solution and treated with four different strengths of EC (0.6, 1.2, 1.8 and 2.4 indicated T1, T2, T3 and T4, respectively) under controlled environment conditions. Our results demonstrate that the number of leaves, leaf area, number of runners, shoot fresh weight and shoot dry weight were significantly increased in T2 among the treatments. However, these growth parameters were lowest in T4. Furthermore, the content of asiaticoside, madecassoside, asiatic acid and madecassic acid was the highest in plants that were treated with T2. The expression of centelloside biosynthesis-related genes is also affected by the strength of the nutrient solution. A positive correlation was observed between the number of leaves, leaf area and centellosides content. This study provides valuable background on optimal EC content in the nutrient solution in a hydroponic system with enhanced centellosides content to leverage the C. asiatica production.

The aim of this study was to investigate the effect of shade screens on the physiological activity, growth parameters and fruit characteristics of the paprika (Capsicum annuum L.) plant. Plants were grown in a protected greenhouse and treated under two different shade screens, S1 (single screen) and S2 (double screens; 10% low light intensity compared to S1), during summer at a particular time of the day. The results revealed that the plant height was significantly enlarged by the S2 treatment. However, the number of leaves, leaf fresh weight and leaf dry weight were significantly decreased under S2-treated plants compared to those grown in the S1 treatment. The stem diameter and shoot fresh weight were not significantly different between the treatments. The sap flow and normalized difference vegetation index (NDVI) were higher in S1-treated plants than in those grown in the S2 treatment. The chlorophyll fluorescence fluctuated in both treatments. The fruit fresh weight, number of fruits, fruit pericarp thickness, fruit firmness, fruit volume, sugar content and acidity were significantly higher in S1-treated plants than in S2. Hunter values a and b were significantly higher in S2-treated plants. Moreover, the fruit length and width were not significantly different between the two treatments. The sugar content and acidity of paprika showed a positive correlation. These results suggest that, compared to a double screen for shade in the greenhouse, a single screen is suitable for the growth of paprika plants and enhanced their fruit production.

Plant growth in a controlled environment system is highly dependent on the availability of light. The light-emitting diode (LED) is capable of providing the needed quality and quantity of light for the plant. The purpose of this study was to determine the effect of white LED light intensity on the growth of in vitro propagated apple (M-9) seedlings in a controlled environment system. Seedlings were grown for 30 days under five different white LED light intensities: 100–500 (L1), 250–500 (L2), 500–500 (L3), 250–250 (L4), and 100–100 (L5). Our findings indicate that seedlings treated with L3 grew substantially taller than seedlings treated with L1, L2, or L5. The number of leaves, stem diameter, shoot fresh weight, root fresh weight, and shoot dry weight of L3 treated seedlings were considerably greater than those growing in other treatments. Furthermore, root length, root dry weight, chlorophyll content, and photosynthesis rate were considerably increased in the L3 treatment group compared to the L5 treatment group. However, there was no significant difference in the stomatal conductance or transpiration rate of apple seedlings between the light treatments. Moreover, a positive correlation was seen between stomatal conductance and transpiration rate. These results suggest that light intensity PPFD 500-500 were favorable for the initial growth of in vitro propagated apple seedlings.

Two new pyrrolosesquiterpenes, glaciapyrroles D (1) and E (2) were discovered along with the previously reported glaciapyrrole A (3) from Streptomyces sp. GGS53 strain isolated from deep-sea sediment. This study elucidated the planar structures of 1 and 2 using nuclear magnetic resonance (NMR), mass spectrometry (MS), ultraviolet (UV), and infrared (IR) spectroscopic data. The absolute configurations of the glaciapyrroles were determined by Mosher’s method, circular dichroism spectroscopy, and X-ray crystallography. Under 366 nm UV irradiation, the glaciapyrroles were systematically converted to the corresponding photoglaciapyrroles (4–6) via photoisomerization, resulting in the diversification of the glaciapyrrole family compounds. The transformation of the glaciapyrrole Z to E isomers occurred in a 1:1 ratio, based on virtual validation of the photoisomerization of these olefinic compounds by 1H-NMR spectroscopy and liquid chromatography/mass spectrometry (LC/MS) analysis. Finally, when encapsulated in poly(lactic-co-glycolic acid) nanoparticles, glaciapyrrole E and photoglaciapyrrole E displayed significant inhibitory activity against influenza A virus. This is the first report of antiviral effects from glaciapyrrole family compounds, whose biological functions have only been subjected to limited studies so far.

The production of horticultural crops in the outdoor environment facing various environmental factors, such as cyclones, droughts, heavy rain, and hailstorms, significantly affects the papaya production in the sub-tropical regions, especially in Bangladesh. Protected cultivation of horticultural crops is a common practice in developed countries. However, it is rarely observed in the developing countries, particularly for papaya production. Therefore, this study was carried out to find a protective approach to papaya cultivation to mitigate the environmental factors to obtain a quality yield. This production system consists of three treatments, including net house, poly shed house, UV poly shed house, and open field conditions (control). The results revealed that plants grown in the net house had significantly higher leaf number (30), fruit number (68), and fruit yield (56.28 kg/plant) than the control grown plant. Papaya cultured in the net house also showed significantly higher accumulation of chlorophyll, ascorbic acid, total phenol, reducing sugar, and β-carotene than those grown in other environments. In terms of peel color, papaya grown in the net house had the highest a* value (redness), whereas that grown in the open field had the lowest. Thus, the study demonstrated that papaya can be cultivated successfully in a net house with increased yield and phytochemical content. The findings provide a fundamental production strategy for quality papaya production in Bangladesh.

The biological carbon pump in the southwestern East Sea (Japan Sea, EJS hereafter) was investigated based on examination of sinking particulate matter samples intercepted by bottom-tethered sediment traps deployed on a mooring at three depths (500, 1000, and 2000 m) between 2011 and 2017. The total particle flux increased as the sampling depth increased, while particulate organic carbon (POC) flux was greatest at 500 m. The lithogenic material content was high at all depths, and accounted for an average of ∼42% of the particulate matter. The total particle flux at all sampling depths consistently shifted toward much higher values in 2014–2016. During this period, the POC flux at 500 m increased by 32% while net primary production (NPP) increased only slightly. Consequently, the POC flux/NPP ratio increased significantly, indicating greater biological pump efficiency than in earlier years of the study. The flux of lithogenic material derived primarily from sediment resuspension was much greater at 500 m in 2014−2016 compared with previous years, implying its potential role as a ballast mineral in enhancing particle export and transfer to the deep sea interior. The radiocarbon isotope ratio of POC was higher, and the excess Mn content values were lower at 500 m in 2014–2016, suggesting that the resuspended sediment at 500 m likely originated from a shallow region during this period, and differed in provenance from the lithogenic material intercepted at 2000 m. The period of enhanced particle flux coincided with the 2015/16 El Niño and a mesoscale warm (anticyclonic) eddy that persisted for 2 years in the study region. The East Korean Warm Current and the eddy may have facilitated the transport of resuspended particles entrained in the Korea Strait and/or the western shelf and upper slope of the basin to the study site.

Substrate composition and container size are considered crucial for apple rootstock grown in a plug seedling system. This study investigated the effect of substrate material’s proportion and different container volumes on the growth of apple rootstock (M-9) plants propagated by tissue culture. In substrate composition, three different ratios of peat moss (PM): vermiculite (VL): perlite (PL) at 1:1:1 (S1), 1:2:3 (S2), 3:1:2 (S3) were used. For container size, plants were grown in 1000 mL (C1), 500 mL (C2), and 300 mL (C3) containers filled by 1:1:1 mixture of PM, VL and PL. In both cases, plants were treated eleven weeks in a green house. Our results demonstrate that the plant height, number of leaves, leaf area, shoot fresh weight and root fresh weight of apple rootstock were significantly higher in substrate composition S3 compared with S1 composition. However, chlorophyll content (SPAD) and photosynthesis rate were unaffected by variation of substrate composition. Furthermore, rootstock grown in C1 container showed plant height, number of leaves, leaf area, number of nodes, root length, shoot and root’s fresh and dry weight were significantly higher than those grown in C2 and C3 volume containers. The chlorophyll content and transpiration rate were not significantly affected by the different container volumes. These results suggest that the substrate ratio 3:1:2 of PM:VL:PL and container size 1000 mL were more favorable than other treatments for initial growth and development of the tissue culture propagated apple rootstock plants.

This study aimed to examine the total viable bacteria (TVBC); total coliform (TCC); fecal coliform (TFC); pathogenic Pseudomonas spp., Staphylococcus aureus, and total fungi (TF); and the effect of different low-cost disinfectants (sterile water, salt water, blanched, and vinegar) in decontamination of 12 types of fruit and 10 types of vegetables. In fruit samples, the lowest TVBC was enumerated at 3.18 ± 0.27 log CFU/g in Indian gooseberry and the highest at 6.47 ± 0.68 log CFU/g in guava. Staphylococci (2.04 ± 0.53–5.10 ± 0.02 log CFU/g), Pseudomonas (1.88 ± 0.03–5.38 ± 0.08 log CFU/g), and total fungi (2.60 ± 0.18–7.50 ± 0.15 log CFU/g) were found in all fruit samples; however, no Salmonella was detected in fruit samples. Similarly, the lowest TVBC recorded 5.67± 0.49 log CFU/g in cucumber and the highest 7.37 ± 0.06 log CFU/g in yard long bean. The Staphylococci (3.48 ± 0.13–4.81 ± 0.16 log CFU/g), Pseudomonas (3.57± 0.21– 4.75 ± 0.23 log CFU/g), TCC (1.85 ± 1.11–56.50 ± 37.14 MPN/g), TFC (1.76 ± 0.87– 3.78 ± 3.76 MPN/g), and TF (3.79 ± 0.18–4.40 ± 0.38 log CFU/g) were recorded in all vegetables samples, but no Salmonella was detected in yard long bean, pointed gourd, carrot, tomato, cucumber, or brinjal. However, vinegar showed the highest microbial load reduction of selected fruit and vegetables among the different treatments. With vinegar treatment, the highest reduction of TVBC (1.61-log) and TF (2.54-log) was observed for fruits, and TVBC (2.31-log) and TF (2.41-log) for vegetables. All the disinfectant treatments resulted in significant (p < 0.01) bacterial load reduction compared to control for the studied fruits and vegetable samples.

Abstract DNA methylation is a prominent epigenetic modification in plants and animals regulated by similar mechanisms but the process of DNA demethylation is profoundly different. Unlike vertebrates that require a series of enzymatic conversions of 5-methylcytosine (5mC) into other bases for DNA demethylation, plants utilize the DEMETER (DME) family of 5mC DNA glycosylases to catalyze a direct removal of 5mC from DNA. Here we introduced Arabidopsis DME into human HEK-293T cells to allow direct 5mC excision, and observed that direct DNA demethylation activity was successfully implemented by DME expression. In addition, DME induced diverse cellular responses such as cell proliferation inhibition, cell cycle dysregulation and S phase arrest. Microarray and methylome analyses revealed that DME upregulated a number of genes including cell cycle components, heat shock proteins, and notably, various interferon-stimulated genes. Moreover, DME-mediated DNA demethylation activated endogenous repeat elements, which are likely to form dsRNAs as viral mimics and eventually trigger interferon cascades to establish the antiviral state. This work demonstrates that plant DNA demethylase catalyzes DNA demethylation with a bypass of initial base conversion steps, and the interferon signaling plays a pivotal role to alleviate genotoxic stresses associated with DME-induced DNA demethylation in mammalian cells.

Botrytis cinerea is a necrotrophic pathogen causing a major problem in the export and post-harvest of strawberries. Inappropriate use of fungicides leads to resistance among fungal pathogens. Therefore, it is necessary to evaluate the sensitivity of B. cinerea to various classes of fungicide and to determine the effectiveness of different concentrations of commonly used fungicides. We thus evaluated the effectiveness of six classes of fungicide in inhibiting the growth and development of this pathogen, namely, fludioxonil, iprodione, pyrimethanil, tebuconazole, fenpyrazamine, and boscalid. Fludioxonil was the most effective (EC₅₀ < 0.1 μg/ml), and pyrimethanil was the least effective (EC₅₀ = 50 μg/ml), at inhibiting the mycelial growth of B. cinerea. Fenpyrazamine and pyrimethanil showed relatively low effectiveness in inhibiting the germination and conidial production of B. cinerea. Our results are useful for the management of B. cinerea and as a basis for monitoring the sensitivity of B. cinerea strains to fungicides.

Photothermal therapy (PTT) has attracted extensive research attention as a noninvasive and selective treatment strategy for numerous cancers. PTT functions via photothermal effects induced by converting light energy into heat on near-infrared laser irradiation. Despite the great advances in PTT for cancer treatment, the photothermal therapeutics using laser devise only or non-specific small molecule PTT agents has been limited because of its low photothermal conversion efficiency, concerns about the biosafety of the photothermal agents, their low tumor accumulation, and a heat resistance of specific types of cancer. Using nanomaterials as PTT agents themselves, or for delivery of PTT agents, offers improved therapeutic outcomes with fewer side effects through enhanced photothermal conversion efficiency, accumulation of the PTT agent in the tumor tissue, and, by extension, through combination with other therapies. Herein, we review PTT’s current clinical progress and present the future outlooks for clinical applications. To better understand clinical PTT applications, we describe nanomaterial-mediated photothermal effects and their mechanism of action in the tumor microenvironment. This review also summarizes recent studies of PTT alone or in combination with other therapies. Overall, innovative and strategically designed PTT platforms are promising next-generation noninvasive cancer treatments to move closer toward clinical applications.

Irrational applications of insecticides on vegetable crops are very common in Bangladesh, resulting in harmful consequences for the environment and human health. Therefore, a study was conducted to evaluate the efficacy of biological and botanical insecticides on okra shoot and fruit borer grown in open fields. Four insecticides were used in this study, namely Bacillus thuringiensis (Bt), Spinosad 45 SC, Abamectin 1.8 EC, and Azadirachtin 1% EC an untreated control. The experiment used a randomized complete block design (RCBD) with three replications. The results showed that the rate of shoot infestation was the lowest in the Spinosad-treated plot (3.80%), and the highest was in the control (20.67%). The lowest fruit infestation (3.56%) was recorded in the treated plot of Spinosad. The rate of reduction of fruit infestation over control was 80.69, 60.14, 56.45, and 55.58% in the plots treated with Spinosad, Bt, Azadirachtin, and Abamectin, respectively. Consequently, the Spinosad-treated plot attained the highest yield (8.65 t ha−1), which was followed by the plots treated with Azadirachtin (6.74 t ha−1), Bt (6.28 t ha−1), and Abamectin (6.12 t ha−1). The highest net return and benefit–cost ratio (BCR) were 542.36 US$ and 2.64, obtained respectively from the Spinosad-treated plot. The second highest BCR (1.70) was obtained from the Azadiratin-treated plot, and the lowest BCR (1.18) was recorded in the Abamectin-treated plot. Therefore, the studied insect management practices could be incorporated to attain higher yields and economic benefits for growing okra in Bangladesh.

Seed priming is a technique that can potentially facilitate rapid and consistent germination and subsequent plant growth. The present study investigates the effect of different seed priming treatments and processing times on germination and growth efficiency for the effective cultivation of Yard-long bean. Thirteen different primings were used to determine the stimulatory effect on the germination and yield performance of the Yard-long bean. The priming treatments included control (without priming); hydro priming for 12, 18, 24, and 30 h; halo priming (1% CaCl2) for 12, 18, 24, and 30 h; and halo priming (2% KNO3) for 12, 18, 24, and 30 h. Studies showing the highest level of germination (86.66%), germination index (35.69), seedling vigor index (1833.80), number of branches (7.20), and pod yields per plant (1836.00 g) were recorded from halo priming with 1% CaCl2 at 12 h treatment. Halo priming with 1% CaCl2 at 12 h is thus considered to be a compatible priming technique for the germination of seeds and a higher yield of Yard-long bean.

Chicken is a major food source for humans, hence it is important to understand the mechanisms involved in nutrient absorption in chicken. In the gastrointestinal tract (GIT), the microbiota plays a central role in enhancing nutrient absorption and strengthening the immune system, thereby affecting both growth and health of chicken. There is little information on the diversity and functions of chicken GIT microbiota, its impact on the host, and the interactions between the microbiota and host. Here, we review the recent metagenomic strategies to analyze the chicken GIT microbiota composition and its functions related to improving metabolism and health. We summarize methodology of metagenomics in order to obtain bacterial taxonomy and functional inferences of the GIT microbiota and suggest a set of indicator genes for monitoring and manipulating the microbiota to promote host health in future.

In this extensive review, we elucidate the importance of proteases and their role in drug development in various diseases with an emphasis on cancer. First, key proteases are introduced along with their function in disease progression. Next, we link these proteases as targets for the development of prodrugs and provide clinical examples of protease-activatable prodrugs. Finally, we provide significant design considerations needed for the development of the next generation protease-targeted and protease-activatable prodrugs.

The p104 protein inhibits cellular proliferation when overexpressed in NIH3T3 cells and has been shown to associate with p85α, Grb2, and PLCγ1. In order to isolate other proteins that interact with p104, yeast two-hybrid screening was performed. Rac1 was identified as a binding partner of p104 and the interaction between p104 and Rac1 was confirmed by immunoprecipitation. Using a glutathione S-transferase (GST) pull-down assay with various p104 fragments, the 814–848 amino acid residue at the carboxyl-terminal region of p104 was identified as the key component to interact with Rac1. The CrkII which is involved in the Rac1-mediated cellular response was also found to interact with p104 protein. NIH3T3 cells which overexpressed p104 showed a decrease of Rac1 activity. However, neither the proline-rich domain mutant, which is unable to interact with CrkII, nor the carboxy-terminal deletion mutant could attenuate Rac1 activity. During the differentiation of myoblasts, the amount of p104 protein as well as transcript level was increased. The overexpression of p104 enhanced myotube differentiation, whereas siRNA of p104 reversed this process. In this process, more Rac1 and CrkII were bound to increased p104. Based on these results, we conclude that p104 is involved in muscle cell differentiation by modulating the Rac1 activity.

Purpose BVAC-B is an autologous B cell- and monocyte-based immunotherapeutic vaccine that contains cells transfected with a recombinant human epidermal growth factor receptor 2 (HER2) gene and loaded with the natural killer T cell ligand alpha-galactosylceramide. Here, we report the first BVAC-B study in patients with HER2-positive advanced gastric cancer. Materials and Methods Patients with advanced gastric cancer refractory to standard treatment with HER2+ immunohistochemistry ≥ 1 were eligible for treatment. Patients were administered low (2.5×107 cells/dose), medium (5.0×107 cells/dose), or high dose (1.0×108 cells/dose) of BVAC-B intravenously four times every 4 weeks. Primary endpoints included safety and maximum tolerated BVAC-B dose. Secondary endpoints included preliminary clinical efficacy and BVAC-B-induced immune responses. Results Eight patients were treated with BVAC-B at low (n=1), medium (n=1), and high doses (n=6). No dose-limiting toxicity was observed, while treatment-related adverse events (TRAEs) were observed in patients treated with medium and high doses. The most common TRAEs were grade 1 (n=2) and grade 2 (n=2) fever. Out of the six patients treated with high-dose BVAC-B, three had stable disease with no response. Interferon gamma, tumor necrosis factor-α, and interleukin-6 increased after BVAC-B treatment in all patients with medium and high dose, and HER2-specific antibody was detected in some patients. Conclusion BVAC-B monotherapy had a safe toxicity profile with limited clinical activity; however, it activated immune cells in heavily pretreated patients with HER2-positive gastric cancer. Earlier treatment with BVAC-B and combination therapy is warranted for evaluation of clinical efficacy. [ABSTRACT FROM AUTHOR]