Endophyte mediated biocontrol mechanisms of phytopathogens in agriculture.

The global human population is growing and demand for food is increasing. Global agriculture faces numerous challenges, including excessive application of synthetic pesticides, emergence of herbicide-and pesticide-resistant pathogenic microbes, and more frequent natural disasters associated with global warming. Searches for valuable endophytes have increased, with the aim of making agriculture more sustainable and environmentally friendly. Endophytic microbes are known to have a variety of beneficial effects on plants. They can effectively transfer nutrients from the soil into plants, promote plant growth and development, increase disease resistance, increase stress tolerance, prevent herbivore feeding, reduce the virulence of pathogens, and inhibit the growth of rival plant species. Endophytic microbes can considerably minimize the need for agrochemicals, such as fertilizers, fungicides, bactericides, insecticides, and herbicides in the cultivation of crop plants. This review summarizes current knowledge on the roles of endophytes focusing on their mechanisms of disease control against phytopathogens through the secretion of antimicrobial substances and volatile organic compounds, and the induction of systemic resistance in plants. Additionally, the beneficial roles of these endophytes and their metabolites in the control of postharvest diseases in plants have been summarized.

Biologically inspired nanoformulations for the control of bacterial canker pathogens Clavibacter michiganensis subsp. michiganensis and subsp. capsici.

Clavibacter michiganensis subsp. michiganensis (Cmm) and C. michiganensis subsp. capsici (Cmc) are phytopathogenic bacteria that cause bacterial canker disease in tomatoes and peppers, respectively. Bacterial canker disease poses serious challenges to solanaceous crops, causing significant yield losses and economic costs. Effective management necessitates the development of sustainable control strategies employing nanobiotechnology. In this study, the antibacterial effects of four Aspergillus sojae-mediated nanoformulations, including cobalt oxide nanoparticles (Co3O4 NPs), zinc oxide nanoparticles (ZnO NPs), cobalt ferrite nanoparticles (CoFe2O4 NPs), and CoFe2O4/functionalized multi-walled carbon nanotube (fMWCNT) bionanocomposite, were evaluated against Cmm and Cmc. The diameters of the zone of inhibition of A. sojae-mediated Co3O4 NPs, ZnO NPs, CoFe2O4 NPs, and CoFe2O4/fMWCNT bionanocomposite against Cmm and Cmc were 23.60mm, 22.09mm, 27.65mm, 22.51mm, and 19.33mm, 17.66mm, 21.64mm, 18.77mm, respectively. The broth microdilution assay was conducted to determine the minimal inhibitory and bactericidal concentrations. The MICs of Co3O4 NPs, ZnO NPs, CoFe2O4 NPs, and CoFe2O4/fMWCNT bionanocomposite against Cmm were 2.50mg/mL, 1.25mg/mL, 2.50mg/mL, and 2.50mg/mL, respectively. While, their respective MBCs against Cmm were 5.00mg/mL, 2.50mg/mL, 5.00mg/mL, and 5.00mg/mL. The respective MICs of Co3O4 NPs, ZnO NPs, CoFe2O4 NPs, and CoFe2O4/fMWCNT bionanocomposite against Cmc were 2.50mg/mL, 1.25mg/mL, 5.00mg/mL, and 5.00mg/mL. While, their respective MBCs against Cmc were 5.00mg/mL, 2.50mg/mL, 10.00mg/mL, and 10.00mg/mL. The morphological and ultrastructural changes of Cmm and Cmc cells were observed using field-emission scanning and transmission electron microscopy before and after treatment with sub-minimal inhibitory concentrations of the nanoformulations. Nanoformulation-treated bacterial cells became deformed and disrupted, displaying pits, deep cavities, and groove-like structures. The cell membrane detached from the bacterial cell wall, electron-dense particles accumulated in the cytoplasm, cellular components disintegrated, and the cells were lysed. Direct physical interactions between the prepared nanoformulations with Cmm and Cmc cells might be the major mechanism for their antibacterial potency. Further research is required for the in vivo application of the mycosynthesized nanoformulations as countermeasures to combat bacterial phytopathogens.

Soil and Mineral Nutrients in Plant Health: A Prospective Study of Iron and Phosphorus in the Growth and Development of Plants.

Plants being sessile are exposed to different environmental challenges and consequent stresses associated with them. With the prerequisite of minerals for growth and development, they coordinate their mobilization from the soil through their roots. Phosphorus (P) and iron (Fe) are macro- and micronutrient; P serves as an important component of biological macromolecules, besides driving major cellular processes, including photosynthesis and respiration, and Fe performs the function as a cofactor for enzymes of vital metabolic pathways. These minerals help in maintaining plant vigor via alterations in the pH, nutrient content, release of exudates at the root surface, changing dynamics of root microbial population, and modulation of the activity of redox enzymes. Despite this, their low solubility and relative immobilization in soil make them inaccessible for utilization by plants. Moreover, plants have evolved distinct mechanisms to cope with these stresses and coregulate the levels of minerals (Fe, P, etc.) toward the maintenance of homeostasis. The present study aims at examining the uptake mechanisms of Fe and P, and their translocation, storage, and role in executing different cellular processes in plants. It also summarizes the toxicological aspects of these minerals in terms of their effects on germination, nutrient uptake, plant-water relationship, and overall yield. Considered as an important and indispensable component of sustainable agriculture, a separate section covers the current knowledge on the cross-talk between Fe and P and integrates complete and balanced information of their effect on plant hormone levels.

Muscle relaxant and antipyretic effects of pentacyclic triterpenes isolated from the roots of Diospyros lotus L.

The present article describes the muscle relaxant and antipyretic effects of pentacyclic triterpenes, oleanolic acid (OA), ursolic acid (UA) and betulinic acid (BA) isolated from roots of Diospyros lotus in animal models. The muscle relaxant effects of isolated pentacyclic triterpenes were determined by chimney and inclined plane tests. In the chimney test, pretreatment of pentacyclic triterpenes evoked significant dose dependent influence on muscle coordination. When administered intraperitoneally (i.p.) to mice at 10 mg/kg for 90 min, OA, UA, and BA exhibited muscle relaxant effects of 66.72 %, 60.21 %, and 50.77 %, respectively. Similarly, OA, UA, and BA (at 10 mg/kg) illustrated 65.74 %, 59.84 % and 51.40 % muscle relaxant effects in the inclined plane test. In the antipyretic test, significant amelioration was caused by pretreatment of all compounds in dose dependent manner. OA, UA, and BA (at 5 mg/kg) showed 39.32 %, 34.32 % and 29.99 % anti-hyperthermic effects, respectively 4 h post-treatment, while at 10 mg/kg, OA, UA, and BA exhibited 71.59 %, 60.99 % and 52.44 % impact, respectively. The muscle relaxant effect of benzodiazepines is well known for enhancement of GABA receptors. There may exist a similar mechanism for muscle relaxant effect of pentacyclic triterpenes. The in-silico predicted binding pattern of all the compounds reflects good affinity of compounds with GABAA receptor and COX-2. These results indicate that the muscle relaxant and antipyretic activities of these molecules can be further improved by structural optimization.

Characterization of Plant-Derived Natural Inhibitors of Dipeptidyl Peptidase-4 as Potential Antidiabetic Agents: A Computational Study.

Diabetes, characterized by elevated blood sugar levels, poses significant health and economic risks, correlating with complications like cardiovascular disease, kidney failure, and blindness. Dipeptidyl peptidase-4 (DPP-4), also referred to as T-cell activation antigen CD26 (EC 3.4.14.5.), plays a crucial role in glucose metabolism and immune function. Inhibiting DPP-4 was anticipated as a potential new therapy for diabetes. Therefore, identification of plant-based natural inhibitors of DPP-4 would help in eradicating diabetes worldwide. Here, for the identification of the potential natural inhibitors of DPP-4, we developed a phytochemicals library consisting of over 6000 phytochemicals detected in 81 medicinal plants that exhibited anti-diabetic potency. The library has been docked against the target proteins, where isorhamnetin, Benzyl 5-Amino-5-deoxy-2,3-O-isopropyl-alpha-D-mannofuranoside (DTXSID90724586), and 5-Oxo-7-[4-(trifluoromethyl) phenyl]-4H,6H,7H-[1,2]thiazolo[4,5-b]pyridine 3-carboxylic acid (CHEMBL3446108) showed binding affinities of -8.5, -8.3, and -8.3 kcal/mol, respectively. These compounds exhibiting strong interactions with DPP-4 active sites (Glu205, Glu206, Tyr547, Trp629, Ser630, Tyr662, His740) were identified. ADME/T and bioactivity predictions affirmed their pharmacological safety. Density functional theory calculations assessed stability and reactivity, while molecular dynamics simulations demonstrated persistent stability. Analyzing parameters like RMSD, RG, RMSF, SASA, H-bonds, MM-PBSA, and FEL confirmed stable protein-ligand compound formation. Principal component analysis provided structural variation insights. Our findings suggest that those compounds might be possible candidates for developing novel inhibitors targeting DPP-4 for treating diabetes.

Nanocomposites against Pseudomonas aeruginosa biofilms: Recent advances, challenges, and future prospects.

Pseudomonas aeruginosa is an opportunistic bacterial pathogen that causes life-threatening and persistent infections in immunocompromised patients. It is the culprit behind a variety of hospital-acquired infections owing to its multiple tolerance mechanisms against antibiotics and disinfectants. Biofilms are sessile microbial aggregates that are formed as a result of the cooperation and competition between microbial cells encased in a self-produced matrix comprised of extracellular polymeric constituents that trigger surface adhesion and microbial aggregation. Bacteria in biofilms exhibit unique features that are quite different from planktonic bacteria, such as high resistance to antibacterial agents and host immunity. Biofilms of P. aeruginosa are difficult to eradicate due to intrinsic, acquired, and adaptive resistance mechanisms. Consequently, innovative approaches to combat biofilms are the focus of the current research. Nanocomposites, composed of two or more different types of nanoparticles, have diverse therapeutic applications owing to their unique physicochemical properties. They are emerging multifunctional nanoformulations that combine the desired features of the different elements to obtain the highest functionality. This review assesses the recent advances of nanocomposites, including metal-, metal oxide-, polymer-, carbon-, hydrogel/cryogel-, and metal organic framework-based nanocomposites for the eradication of P. aeruginosa biofilms. The characteristics and virulence mechanisms of P. aeruginosa biofilms, as well as their devastating impact and economic burden are discussed. Future research addressing the potential use of nanocomposites as innovative anti-biofilm agents is emphasized. Utilization of nanocomposites safely and effectively should be further strengthened to confirm the safety aspects of their application.

The Interplay between Heat Shock Proteins and Cancer Pathogenesis: A Novel Strategy for Cancer Therapeutics.

Heat shock proteins (HSPs) are developmentally conserved families of protein found in both prokaryotic and eukaryotic organisms. HSPs are engaged in a diverse range of physiological processes, including molecular chaperone activity to assist the initial protein folding or promote the unfolding and refolding of misfolded intermediates to acquire the normal or native conformation and its translocation and prevent protein aggregation as well as in immunity, apoptosis, and autophagy. These molecular chaperonins are classified into various families according to their molecular size or weight, encompassing small HSPs (e.g., HSP10 and HSP27), HSP40, HSP60, HSP70, HSP90, and the category of large HSPs that include HSP100 and ClpB proteins. The overexpression of HSPs is induced to counteract cell stress at elevated levels in a variety of solid tumors, including anticancer chemotherapy, and is closely related to a worse prognosis and therapeutic resistance to cancer cells. HSPs are also involved in anti-apoptotic properties and are associated with processes of cancer progression and development, such as metastasis, invasion, and cell proliferation. This review outlines the previously mentioned HSPs and their significant involvement in diverse mechanisms of tumor advancement and metastasis, as well as their contribution to identifying potential targets for therapeutic interventions.

Advancements in biosurfactant production using agro-industrial waste for industrial and environmental applications.

The adverse effects of waste generation on the environment and public health have raised global concerns. The utilization of waste as a raw material to develop products with enhanced value has opened up novel prospects for promoting environmental sustainability. Biosurfactants obtained from agro-industrial waste are noteworthy due to their sustainability and environmental friendliness. Microorganisms have been employed to generate biosurfactants as secondary metabolites by making use of waste streams. The utilization of garbage as a substrate significantly reduces the expenses associated with the process. Furthermore, apart from reducing waste and offering alternatives to artificial surfactants, they are extensively employed in bioremediation, food processing, agriculture, and various other industrial pursuits. Bioremediation of heavy metals and other metallic pollutants mitigated through the use of bacteria that produce biosurfactants which has been the more recent research area with the aim of improving its quality and environmental safety. Moreover, the production of biosurfactants utilizing agricultural waste as a raw material aligns with the principles of waste minimization, environmental sustainability, and the circular economy. This review primarily focuses on the production process and various types of biosurfactants obtained from waste biomass and feedstocks. The subsequent discourse entails the production of biosurfactants derived from various waste streams, specifically agro-industrial waste.

Friedelin: Structure, Biosynthesis, Extraction, and Its Potential Health Impact.

Pharmaceutical companies are investigating more source matrices for natural bioactive chemicals. Friedelin (friedelan-3-one) is a pentacyclic triterpene isolated from various plant species from different families as well as mosses and lichen. The fundamental compounds of these friedelane triterpenoids are abundantly found in cork tissues and leaf materials of diverse plant genera such as Celastraceae, Asteraceae, Fabaceae, and Myrtaceae. They possess many pharmacological effects, including anti-inflammatory, antioxidant, anticancer, and antimicrobial activities. Friedelin also has an anti-insect effect and the ability to alter the soil microbial ecology, making it vital to agriculture. Ultrasound, microwave, supercritical fluid, ionic liquid, and acid hydrolysis extract friedelin with reduced environmental impact. Recently, the high demand for friedelin has led to the development of CRISPR/Cas9 technology and gene overexpression plasmids to produce friedelin using genetically engineered yeast. Friedelin with low cytotoxicity to normal cells can be the best phytochemical for the drug of choice. The review summarizes the structural interpretation, biosynthesis, physicochemical properties, quantification, and various forms of pharmacological significance.

Abiotic Stress in Rice: Visiting the Physiological Response and Its Tolerance Mechanisms.

Rice (Oryza sativa L.) is one of the most significant staple foods worldwide. Carbohydrates, proteins, vitamins, and minerals are just a few of the many nutrients found in domesticated rice. Ensuring high and constant rice production is vital to facilitating human food supplies, as over three billion people around the globe rely on rice as their primary source of dietary intake. However, the world's rice production and grain quality have drastically declined in recent years due to the challenges posed by global climate change and abiotic stress-related aspects, especially drought, heat, cold, salt, submergence, and heavy metal toxicity. Rice's reduced photosynthetic efficiency results from insufficient stomatal conductance and natural damage to thylakoids and chloroplasts brought on by abiotic stressor-induced chlorosis and leaf wilting. Abiotic stress in rice farming can also cause complications with redox homeostasis, membrane peroxidation, lower seed germination, a drop in fresh and dry weight, necrosis, and tissue damage. Frequent stomatal movements, leaf rolling, generation of reactive oxygen radicals (RORs), antioxidant enzymes, induction of stress-responsive enzymes and protein-repair mechanisms, production of osmolytes, development of ion transporters, detoxifications, etc., are recorded as potent morphological, biochemical and physiological responses of rice plants under adverse abiotic stress. To develop cultivars that can withstand multiple abiotic challenges, it is necessary to understand the molecular and physiological mechanisms that contribute to the deterioration of rice quality under multiple abiotic stresses. The present review highlights the strategic defense mechanisms rice plants adopt to combat abiotic stressors that substantially affect the fundamental morphological, biochemical, and physiological mechanisms.

Analysis of Auxin-Encoding Gene Family in Vigna radiata and It's Cross-Species Expression Modulating Waterlogging Tolerance in Wild Vigna umbellata.

Mungbean is known to be susceptible to waterlogging (WL) stress. Some of the wild species have the potential to tolerate this through various physiological and molecular mechanisms. Auxin Response Factor (ARF) and Auxin/Indole Acetic Acid (AUX/IAA), an early responsive gene family, has multiple functions in growth, development, and stress tolerance. Here, we report the first comprehensive analysis of the ARF and AUX/IAA gene family in mungbean. A total of 26 ARF and 19 AUX/IAA genes were identified from the mungbean genome. The ARF and AUX/IAA candidates were clearly grouped into two major clades. Further, the subgrouping within the major clades indicated the presence of significant diversity. The gene structure, motif analysis, and protein characterization provided the clue for further fundamental research. Out of the10 selected candidate genes, VrARF-5, VrARF-11, VrARF-25, and VrAUX/IAA-9 were found to significantly multiple-fold gene expression in the hypocotyl region of WL-tolerant wild relatives (PRR 2008-2) provides new insight into a role in the induction of lateral root formation under WL stress. The analysis provides an insight into the structural diversity of ARF and AUX/IAA genes in mungbean. These results increase our understanding of ARF and AUX/IAA genes and therefore offer robust information for functional investigations, which can be taken up in the future and will form a foundation for improving tolerance against waterlogging stress.

Crossroad between the Heat Shock Protein and Inflammation Pathway in Acquiring Drug Resistance: A Possible Target for Future Cancer Therapeutics.

The development of multidrug resistance (MDR) against chemotherapeutic agents has become a major impediment in cancer therapy. Understanding the underlying mechanism behind MDR can guide future treatment for cancer with better therapeutic outcomes. Recent studies evidenced that crossroads interaction between the heat shock proteins (HSP) and inflammatory responses under the tumor microenvironment plays a pivotal role in modulating drug responsiveness and drug resistance through a complex cytological process. This review aims to investigate the interrelationship between inflammation and HSP in acquiring multiple drug resistance and investigate strategies to overcome the drug resistance to improve the efficacy of cancer treatment. HSP plays a dual regulatory effect as an immunosuppressive and immunostimulatory agent, involving the simultaneous blockade of multiple signaling pathways in acquiring MDR. For example, HSP27 shows biological effects on monocytes by causing IL10 and TNFα secretion and blocking monocyte differentiation to normal dendritic cells and tumor-associated macrophages to promote cancer progression and chemoresistance. Thus, the HSP function and immune-checkpoint release modalities provide a therapeutic target for a therapeutically beneficial approach for enhancing anti-tumor immune responses. The interconnection between inflammation and HSP, along with the tumor microenvironment in acquiring drug resistance, has become crucial for rationalizing the effect of HSP immunomodulatory activity with immune checkpoint blockade. This relationship can overcome drug resistance and assist in the development of novel combinatorial cancer immunotherapy in fighting cancer with decreasing mortality rates.

Current and future directions of USP7 interactome in cancer study.

The ubiquitin-proteasome system (UPS) is an essential protein quality controller for regulating protein homeostasis and autophagy. Ubiquitination is a protein modification process that involves the binding of one or more ubiquitins to substrates through a series of enzymatic processes. These include ubiquitin-activating enzymes (E1), ubiquitin-conjugating enzymes (E2), and ubiquitin ligases (E3). Conversely, deubiquitination is a reverse process that removes ubiquitin from substrates via deubiquitinating enzymes (DUBs). Dysregulation of ubiquitination-related enzymes can lead to various human diseases, including cancer, through the modulation of protein ubiquitination. The most structurally and functionally studied DUB is the ubiquitin-specific protease 7 (USP7). Both the TRAF and UBL domains of USP7 are known to bind to the [P/A/E]-X-X-S or K-X-X-X-K motif of substrates. USP7 has been shown to be involved in cancer pathogenesis by binding with numerous substrates. Recently, a novel substrate of USP7 was discovered through a systemic analysis of its binding motif. This review summarizes the currently discovered substrates and cellular functions of USP7 in cancer and suggests putative substrates of USP7 through a comprehensive systemic analysis.

Synergistic effect of YOD1 and USP21 on the Hippo signaling pathway.

BACKGROUND: Deubiquitinating enzymes (DUBs) comprise a family of proteases responsible for cleaving the peptide or isopeptide bond between ubiquitin and its substrate proteins. Ubiquitin is essential for regulating diverse cellular functions by attaching to target proteins. The Hippo signaling pathway plays a crucial role in controlling tissue size, cell proliferation, and apoptosis. In a previous study, we discovered that YOD1 regulates the Hippo signaling pathway by deubiquitinating the neural precursor cell expressed developmentally down-regulated protein 4 (NEDD4), an E3 ligase of large tumor suppressor kinase 1 (LATS1). Here, our aim was to investigate potential substrates of YOD1 implicated in the Hippo signaling pathway. METHODS: We employed various bioinformatics tools (BioGRID, STRING, and Cytoscape) to identify novel potential substrates of YOD1. Furthermore, we used western blotting, co-immunoprecipitation (co-IP), glutathione S-transferase (GST) pull-down, immunocytochemistry (ICC) assays to investigate cellular interactions. To evaluate cell proliferation, we performed cell counting kit-8 (CCK-8), wound healing, colony forming, and flow cytometry assays using A549, HEK293T, and HeLa cells. Additionally, we assessed the expression levels of YAP and p-YAP in A549, HEK293T, and HeLa cells through western blotting. RESULTS: Our investigations revealed that YOD1 interacts with ubiquitin-specific proteases 21 (USP21), a DUB involved in the Hippo signaling pathway, and deubiquitinates the microtubule-affinity regulating kinase (MARK). Intriguingly, YOD1 and USP21 mutually deubiquitinate each other; while YOD1 regulates the protein stability of USP21, USP21 does not exert a regulatory effect on YOD1. Moreover, we observed the synergistic effect of YOD1 and USP21 on cell proliferation through the modulation of the Hippo signaling pathway. CONCLUSIONS: Our study revealed multiple cellular interactions between YOD1 and USP21. Moreover, our findings suggest that the combined activities of YOD1 and USP21 synergistically influence cell proliferation in A549 cells by regulating the Hippo signaling pathway.

New Insights into the Latest Advancement in α-Amylase Inhibitors of Plant Origin with Anti-Diabetic Effects.

The rising predominance of type 2 diabetes, combined with the poor medical effects seen with commercially available anti-diabetic medications, has motivated the development of innovative treatment approaches for regulating postprandial glucose levels. Natural carbohydrate digestion enzyme inhibitors might be a viable option for blocking dietary carbohydrate absorption with fewer side effects than manufactured medicines. Alpha-amylase is a metalloenzyme that facilitates digestion by breaking down polysaccharides into smaller molecules such as maltose and maltotriose. It also contributes to elevated blood glucose levels and postprandial hyperglycemia. As a result, scientists are being urged to target α-amylase and create inhibitors that can slow down the release of glucose from carbohydrate chains and prolong its absorption, thereby resulting in lower postprandial plasma glucose levels. Natural α-amylase inhibitors derived from plants have gained popularity as safe and cost-effective alternatives. The bioactive components responsible for the inhibitory actions of various plant extracts have been identified through phytochemical research, paving the way for further development and application. The majority of the findings, however, are based on in vitro investigations. Only a few animal experiments and very few human investigations have confirmed these findings. Despite some promising results, additional investigation is needed to develop feasible anti-diabetic drugs based on plant-derived pancreatic α-amylase inhibitors. This review summarizes the most recent findings from research on plant-derived pancreatic α-amylase inhibitors, including plant extracts and plant-derived bioactive compounds. Furthermore, it offers insights into the structural aspects of the crucial therapeutic target, α-amylases, in addition to their interactions with inhibitors.

Deficiency of HtrA4 in BeWo cells downregulates angiogenesis through IL-6/JAK/STAT3 signaling.

In a previous study, we investigated the effects of high-temperature requirement factor A4 (HtrA4) deficiency on trophoblasts using the BeWo KO cell line. However, the effects of this deficiency on angiogenesis remain unclear. To explore the role of HtrA4 in angiogenesis, HUVECs were co-cultured with wild-type BeWo cells (BeWo WT), BeWo KO, and HtrA4-rescued BeWo KO (BeWo KO-HtrA4 rescue) cells. Dil staining and dextran analysis revealed that HUVECs co-cultured with BeWo KO formed tubes, but they were often disjointed compared to those co-cultured with BeWo WT, BeWo KO-HtrA4 rescue, and HUVECs controls. RT-PCR, ELISA, and western blot analysis were performed to assess angiogenesis-related factors at the mRNA and protein levels. HtrA4 deficiency inhibited IL-6 expression in trophoblasts, and the reduced secretion of IL-6 decreases VEGFA expression in HUVECs by modulating the JAK2/STAT3 signaling pathway to prevent tube formation. Moreover, rescuing HtrA4 expression restored the HUVEC tube formation ability. Interestingly, IL-6 expression was lower in supernatants with only cultured HUVECs than in co-cultured HUVECs with BeWo WT cells, but the HUVEC tube formation ability was similar. These findings suggest that the promoting angiogenesis-related signaling pathway differs between only HUVECs and co-cultured HUVECs, and that the deficiency of HtrA4 weakens the activation of the IL-6/JAK/STAT3/VEGFA signaling pathway, reducing the ability of tube formation in HUVECs. HtrA4 deficiency in trophoblasts hinders angiogenesis and may contribute to placental dysfunction.

Detection of Antagonistic Compounds Synthesized by Bacillus velezensis against Xanthomonas citri subsp. citri by Metabolome and RNA Sequencing.

Biological control of plant diseases has gained attraction for controlling various bacterial diseases at a field trial stage. An isolated endophytic bacterium, Bacillus velezensis 25 (Bv-25), from Citrus species had strong antagonistic activity against Xanthomonas citri subsp. citri (Xcc), which causes citrus canker disease. When Bv-25 was incubated in Landy broth or yeast nutrient broth (YNB), the ethyl acetate extract of Landy broth exhibited higher levels of antagonistic activity against Xcc compared to that of YNB. Therefore, the antimicrobial compounds in the two ethyl acetate extracts were detected by high performance liquid chromatography-mass spectrometry. This comparison revealed an increase in production of several antimicrobial compounds, including difficidin, surfactin, fengycin, and Iturin-A or bacillomycin-D by incubation in Landy broth. RNA sequencing for the Bv-25 grown in Landy broth were performed, and the differential expressions were detected for the genes encoding the enzymes for the synthesis of antimicrobial compounds, such as bacilysin, plipastatin or fengycin, surfactin, and mycosubtilin. Combination of metabolomics analysis and RNA sequencing strongly suggests that several antagonistic compounds, especially bacilysin produced by B. velezensis, exhibit an antagonistic effect against Xcc.

Cellular Functions of High-Temperature Requirement Factor A4 in Placenta.

The expression of High-temperature requirement factor A4 (HtrA4) mRNA is significantly lower in the chorionic villi of patients with recurrent pregnancy loss (RPL) than in the control group. We conducted an investigation into the cellular functions of HtrA4 using the CRISPR/Cas9 system and shRNA-HtrA4 to create knockout BeWo cells and HtrA4 knockdown JEG3 cells. Our results indicated that the knockout BeWo cells exhibited reduced capacity for invasion and fusion, but increased levels of proliferation and migration, with a significantly shortened cell cycle compared to wild-type cells. Wild-type BeWo cells highly expressed cell invasion- and fusion-related factors, while knockout BeWo cells highly expressed migration-, proliferation-, and cell cycle-related factors. The shRNA-HtrA4 JEG3 cells showed a decreased capacity for invasion, but an increased capacity for migration, accompanied by a decrease in the expression of cell invasion-related factors and an increase in migration-related factors. Moreover, our ELISA results revealed that the serum HtrA4 level was lower in patients with RPL than in the controls. These findings suggest that HtrA4 depletion may be associated with placental dysfunction.

Current Status and De Novo Synthesis of Anti-Tumor Alkaloids in Nicotiana.

Alkaloids are the most diversified nitrogen-containing secondary metabolites, having antioxidant and antimicrobial properties, and are extensively used in pharmaceuticals to treat different types of cancer. Nicotiana serves as a reservoir of anti-cancer alkaloids and is also used as a model plant for the de novo synthesis of various anti-cancer molecules through genetic engineering. Up to 4% of the total dry weight of Nicotiana was found to be composed of alkaloids, where nicotine, nornicotine, anatabine, and anabasine are reported as the dominant alkaloids. Additionally, among the alkaloids present in Nicotiana, ß-carboline (Harmane and Norharmane) and Kynurenines are found to show anti-tumor effects, especially in the cases of colon and breast cancers. Creating new or shunting of existing biosynthesis pathways in different species of Nicotiana resulted in de novo or increased synthesis of different anti-tumor molecules or their derivatives or precursors including Taxadiane (~22.5 µg/g), Artemisinin (~120 µg/g), Parthenolide (~2.05 ng/g), Costunolide (~60 ng/g), Etoposide (~1 mg/g), Crocin (~400 µg/g), Catharanthine (~60 ng/g), Tabersonine (~10 ng/g), Strictosidine (~0.23 mg/g), etc. Enriching the precursor pool, especially Dimethylallyl Diphosphate (DMAPP), down-regulating other bi-product pathways, compartmentalization or metabolic shunting, or organelle-specific reconstitution of the precursor pool, might trigger the enhanced accumulation of the targeted anti-cancer alkaloid in Nicotiana.

A pilot randomized clinical trial of biomedical link with mental health in art therapy intervention programs for alcohol use disorder: Changes in NK cells, addiction biomarkers, electroencephalography, and MMPI-2 profiles.

OBJECTIVE: Alcohol intake is a major risk factor for various diseases. Elucidating alcohol use disorder (AUD) is important in preventing diseases and promoting health. We aimed to investigate the effect of art therapy on emotional (Minnesota Multiphasic Personality Inventory-2 [MMPI-2]) and physical (natural killer [NK] cell count, expression of stress-associated proteins [SAP], and electroencephalography) changes in patients with AUD. METHODS: Participants were randomly divided into two groups (n = 35), with the experimental group undergoing art therapy involving weekly 60-min group therapy sessions for 10 weeks. Statistical analysis was performed using Ranked ANCOVA and Wilcoxon's signed rank test. Western blotting was performed to analyze serum SAP levels. RESULTS: We observed an association between psychological mechanisms and stress proteins. There was an increased number of NK cells in the experimental group after the program. Moreover, compared with the control group, the experimental group showed significant changes in SAP expression. Further, the experimental group showed a positive change in the MMPI-2 profile, as well as a decrease in depression, anxiety, impulsivity, and alcohol dependence. CONCLUSIONS: Continuous psychological support could be applied as a stress-control program for preventing stress recurrence and post-discharge relapse. Our findings strengthen the link between biomedical science and mental health in rehabilitation treatment for AUD.