A comprehensive review on Moringa oleifera nanoparticles: importance of polyphenols in nanoparticle synthesis, nanoparticle efficacy and their applications.

Moringa oleifera is one of the popular functional foods that has been tremendously exploited for synthesis of a vast majority of metal nanoparticles (NPs). The diverse secondary metabolites present in this plant turn it into a green tool for synthesis of different NPs with various biological activities. In this review, we discussed different types of NPs including silver, gold, titanium oxide, iron oxide, and zinc oxide NPs produced from the extract of different parts of M. oleifera. Different parts of M. oleifera take a role as the reducing, stabilizing, capping agent, and depending on the source of extract, the color of solution changes within NP synthesis. We highlighted the role of polyphenols in the synthesis of NPs among major constituents of M. oleifera extract. The different synthesis methods that could lead to the formation of various sizes and shapes of NPs and play crucial role in biomedical application were critically discussed. We further debated the mechanism of interaction of NPs with various sizes and shapes with the cells, and further their clearance from the body. The application of NPs made from M. oleifera extract as anticancer, antimicrobial, wound healing, and water treatment agent were also discussed. Small NPs show better antimicrobial activity, while they can be easily cleared from the body through the kidney. In contrast, large NPs are taken by the mono nuclear phagocyte system (MPS) cells. In case of shape, the NPs with spherical shape penetrate into the bacteria, and show stronger antibacterial activity compared to the NPs with other shapes. Finally, this review aims to correlate the key characteristics of NPs made from M. oleifera extract, such as size and shape, to their interactions with the cells for designing and engineering them for bio-applications and especially for therapeutic purposes.

A comprehensive and systemic review of ginseng-based nanomaterials: Synthesis, targeted delivery, and biomedical applications.

Among 17 Panax species identified across the world, Panax ginseng (Korean ginseng), Panax quinquefolius (American ginseng), and Panax notoginseng (Chinese ginseng) are highly recognized for the presence of bioactive compound, ginsenosides and their pharmacological effects. P. ginseng is widely used for synthesis of different types of nanoparticles compared to P. quinquefolius and P. notoginseng. The use of nano-ginseng could increase the oral bioavailability, membrane permeability, and thus provide effective delivery of ginsenosides to the target sites through transport system. In this review, we explore the synthesis of ginseng nanoparticles using plant extracts from various organs, microbes, and polymers, as well as their biomedical applications. Furthermore, we highlight transporters involved in transport of ginsenoside nanoparticles to the target sites. Size, zeta potential, temperature, and pH are also discussed as the critical parameters affecting the quality of ginseng nanoparticles synthesis.

Advancing sustainable agriculture: a critical review of smart and eco-friendly nanomaterial applications.

Undoubtedly, nanoparticles are one of the ideal choices for achieving challenges related to bio sensing, drug delivery, and biotechnological tools. After gaining success in biomedical research, scientists are exploring various types of nanoparticles for achieving sustainable agriculture. The active nanoparticles can be used as a direct source of micronutrients or as a delivery platform for delivering the bioactive agrochemicals to improve crop growth, crop yield, and crop quality. Till date, several reports have been published showing applications of nanotechnology in agriculture. For instance, several methods have been employed for application of nanoparticles; especially metal nanoparticles to improve agriculture. The physicochemical properties of nanoparticles such as core metal used to synthesize the nanoparticles, their size, shape, surface chemistry, and surface coatings affect crops, soil health, and crop-associated ecosystem. Therefore, selecting nanoparticles with appropriate physicochemical properties and applying them to agriculture via suitable method stands as smart option to achieve sustainable agriculture and improved plant performance. In presented review, we have compared various methods of nanoparticle application in plants and critically interpreted the significant differences to find out relatively safe and specific method for sustainable agricultural practice. Further, we have critically analyzed and discussed the different physicochemical properties of nanoparticles that have direct influence on plants in terms of nano safety and nanotoxicity. From literature review, we would like to point out that the implementation of smaller sized metal nanoparticles in low concentration via seed priming and foliar spray methods could be safer method for minimizing nanotoxicity, and for exhibiting better plant performance during stress and non-stressed conditions. Moreover, using nanomaterials for delivery of bioactive agrochemicals could pose as a smart alternative for conventional chemical fertilizers for achieving the safer and cleaner technology in sustainable agriculture. While reviewing all the available literature, we came across some serious drawbacks such as the lack of proper regulatory bodies to control the usage of nanomaterials and poor knowledge of the long-term impact on the ecosystem which need to be addressed in near future for comprehensive knowledge of applicability of green nanotechnology in agriculture.

Acacia catechu seed extract provokes cytotoxicity via apoptosis by intrinsic pathway in HepG2 cells.

Acacia catechu Willd (Fabaceae) is a thorny tree widely distributed in India and commonly used as traditional Ayurvedic medicine for various ailments. The current study evaluates the cytotoxic potentials of A. catechu ethanolic seed extract (ACSE) in HepG2 cells, a human hepatocellular carcinoma cell line. The HepG2 cells were treated with 0.1, 0.3, 1, 3, 10, 30, 100, 300 and 1000 µg/ml of ACSE and the cytotoxic effect was evaluated by MTT and lactate dehydrogenase (LDH) leakage assays. The IC50 of ACSE was found at 77.04 µg/ml and therefore, further studies were carried out with the concentrations of 35 and 70 µg/ml. The intracellular reactive oxygen species (ROS) generation and apoptosis-related morphological changes were evaluated. Gene expressions of Bax, Bcl-2, cytochrome C (Cyt-c), caspases-9 and 3 were analyzed by qPCR. The ACSE treatments caused LDH leakage was associated with an increased ROS generation. The increased ROS generation was associated with the downregulation of intracellular antioxidant enzyme superoxide dismutase and reduced glutathione content. AO/EB and PI staining also confirmed chromatin condensation and apoptosis. The flow cytometric analysis showed an accumulation of HepG2 cells at sub G0/G1 (apoptotic) phase upon ACSE treatments. The ACSE induced cytotoxicity and oxidative stress were related to increased apoptotic marker gene expressions such as Bax, Cyt-c, caspase-9 and 3, and decreased anti-apoptotic marker Bcl-2. The current finding suggests that ACSE has apoptosis-inducing potential via the mitochondrial pathway in HepG2 cells.

Sphingomonas horti sp. nov., a novel bacterial species isolated from soil of a tomato garden.

A novel bacterial strain, designated MAH-20T, was isolated from a soil sample of a tomato garden. Cells of strain MAH-20T were Gram-stain negative, aerobic, motile, and rod-shaped. The colonies were light brown colored, smooth, spherical, and 0.2-0.7 mm in diameter when grown on Luria-Bertani agar for 2 days. Strain MAH-20T grows at 15-40 °C (optimum growth temperature 30-32 °C), at pH 5.0-10.0 (optimum growth pH 7.0) and at 0-2.0% NaCl. The strain showed positive activity for both oxidase and catalase tests. Cells were able to hydrolyze starch, DNA, urea, gelatin, L-arginine, and Tween 20. According to the 16S rRNA gene sequence similarity, the strain MAH-20T was identified as a new member of the genus Sphingomonas and had the close sequence similarity with Sphingomonas changbaiensis V2M44T (98.9%) and Sphingomonas tabacisoli X1-8T (98.1%). The genomic ANI value between strain MAH-20T and S. changbaiensis NBRC 104936T was 84.4%. The novel strain MAH-20T has a draft genome size of 3,350,026 bp (25 contigs), annotated with 3210 protein-coding genes, 46 tRNA, and 3 rRNA genes. The genomic DNA G + C content of isolate was 67.3 mol%, the predominant quinone was ubiquinone 10 and the major fatty acids were C16:0, C17:1 ω6c and summed feature 8 (comprising C18:1 ω7c and/or C18:1 ω6c). On the basis of DNA-DNA hybridization results, phenotypic, genotypic, and chemotaxonomic data, the isolated strain MAH-20T represents a novel species, for which the name Sphingomonas horti sp. nov. is proposed, with MAH-20T as the type strain (= KACC 19746T = CGMCC1.13658T).

Paenibacillus roseus sp. nov., a ginsenoside-transforming bacterium isolated from forest soil.

A novel, pink-pigmented, Gram-stain-positive, aerobic, motile, rod-shaped and ginsenoside-converting bacterium, designated strain MAHUQ-46T, was isolated from soil of a forest. Strain MAHUQ-46T grew in the pH range 6.0-9.0 (optimum, 7.5), at temperatures between 10 and 37 °C (optimum, 30 °C) and at 0-3% (w/v) NaCl (optimum, 0.5%). 16S rRNA gene sequence analysis showed that strain MAHUQ-46T was closely related to Paenibacillus pinihumi S23T (97.3% similarity), followed by Paenibacillus elymi KUDC6143T (96.7%). The draft genome of strain MAHUQ-46T had a total length of 5,367,904 base pairs. A total of 4,857 genes were identified, in which 4,629 were protein-coding genes and 137 were RNA genes. The genome annotation of MAHUQ-46T showed 172 carbohydrate genes, some of them may be responsible for the biosynthesis of ginsenoside Rd from major ginsenoside Rb1. The DNA G + C content was 48.4 mol% and the major quinone was MK-7. Main fatty acids of strain MAHUQ-46T were C15: 0 anteiso, C16: 0 and C17: 0 anteiso. The polar lipids comprised phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol, phosphatidyl-N-methylethanolamine, two unidentified aminophospholipids and five unidentified phospholipids. Diagnostic diamino acid of peptidoglycan was meso-diaminopimelic acid. The novel strain MAHUQ-46T was able to rapidly synthesize ginsenoside Rd from major ginsenoside Rb1. The synthesized ginsenoside was confirmed by TLC and HPLC analysis. According to the phenotypic, genetic and chemotaxonomic evidence, strain MAHUQ-46T was clearly distinguishable from validly published species of genus Paenibacillus and should, therefore, be categorized as a novel species for which the name Paenibacillus roseus sp. nov. is proposed. The type strain is MAHUQ-46T (= KACC 21242T = CGMCC 1.17353T).

Pinibacter aurantiacus gen. nov., sp. nov., isolated from rhizospheric soil of a pine tree.

A Gram-stain-negative, aerobic and rod-shaped novel bacterial strain, designated MAH-26T, was isolated from rhizospheric soil of a pine tree. The colonies were orange coloured, smooth, spherical and 0.7-1.8 mm in diameter when grown on Reasoner's 2A (R2A) agar for 2 days. Strain MAH-26T was able to grow at 10-40 °C, at pH 6.0-9.0 and with 0-1.0 % NaCl. Cell growth occurred on nutrient agar, R2A agar, tryptone soya agar and Luria-Bertani agar. The strain gave positive results in oxidase and catalase tests. Strain MAH-26T was closely related to Flavihumibacter sediminis CJ663T and Parasegetibacter terrae SGM2-10T with a low 16S rRNA gene sequence similarity (92.8 and 92.9 %, respectively) and phylogenetic analysis indicated that the strain formed a distinct phylogenetic lineage from the members of the closely related genera of the family Chitinophagaceae. Strain MAH-26T has a draft genome size of 6 857 405 bp, annotated with 5173 protein-coding genes, 50 tRNA and two rRNA genes. The genomic DNA G+C content was 41.5 mol%. The predominant isoprenoid quinone was menaquinone 7. The major fatty acids were identified as iso-C15:0, iso-C15:1 G and iso-C17:0 3OH. On the basis of phylogenetic inference and phenotypic, chemotaxonomic and molecular properties, strain MAH-26T represents a novel species of a novel genus of the family Chitinophagaceae, for which the name Pinibacter aurantiacus gen. nov., sp. nov. is proposed. The type strain of Pinibacter aurantiacus is MAH-26T (=KACC 19749T=CGMCC 1.13701T).

Synergistic effect of anethole and doxorubicin alleviates cell proliferation, cell cycle arrest, and ER stress and promotes ROS-mediated apoptosis in triple-negative breast cancer cells.

The heterogeneity and poor prognosis of triple-negative breast cancer (TNBC) have limited the treatment options and made clinical management challenging. This has nurtured a major effort to discover druggable molecular targets. Currently, chemotherapy is the primary treatment strategy for this disease. Doxorubicin is the most frequently used chemotherapeutic drug for TNBC and due to the fact that chemotherapeutic drugs have a lot of side effects, we evaluated the synergistic effect of the phytocompound anethole and doxorubicin. The cytotoxic effect of anethole in combination with doxorubicin on MDA-MB-231 cells was evaluated by various parameters, including apoptosis, cell cycle analysis, DNA damage, and cell proliferation. Furthermore, mitochondrial membranepotential (MMP), endoplasmic reticulum (ER) stress, and reactive oxygen species (ROS) levels were also evaluated in the cells treated with/without anethole and doxorubicin. Expression of the apoptotic proteins was evaluated by Western blot analysis. Initial evaluation of cytotoxicity of anethole on MDA-MB-231 cells demonstrated preferential suppression of cell proliferation and when treated along with doxorubicin it showed enhanced cytotoxicity with a synergistic effect. Cell cycle analysis revealed arrest at different stages of the cell cycle, such as sub G0-G1, G0-G1, S, and G2M in various treatment groups and apoptotic cell death was subsequently evident with propidium iodide (PI) staining. The synergistic action of anethole and doxorubicin effectively induced mitochondrial membrane potential loss, which, in turn, led to a burst of ROS production, which eventually produced unfolded protein response by damaging the ER. Synergistic anticancer effect was observed on exposure of MDA-MB-231 cells to anethole and doxorubicin in inducing cell death.

Ramlibacter pinisoli sp. nov., a novel bacterial species isolated from pine garden soil.

A Gram-stain-negative, aerobic, non-motile and rod- or coccoid-shaped novel bacterial strain, designated MAH-25T, was isolated from soil sampled in a pine garden. The colonies were observed to be light pink-coloured, smooth, spherical and 1-2 mm in diameter when grown on nutrient agar for 2 days. Strain MAH-25T was found to be able to grow at 15-35 °C, at pH 5.0-8.0 and at 0-2.0 % NaCl. Cell growth occurred on Reasoner's 2A agar and nutrient agar. The strain was found to be positive in both oxidase and catalase tests. According to 16S rRNA gene sequence comparisons, the isolate was identified as a member of the genus Ramlibacter and closely related to Ramlibacter solisilvae 5-10T (98.0 % similarity), Ramlibacter henchirensis TMB834T (97.7 %), Ramlibacter tataouinensis TTB310T (97.6 %) and Ramlibacter rhizophilus YS3.2.7T (97.3 %). The average nucleotide identity and digital DNA-DNA hybridization values between strain MAH-25T and the four closely related type strains were in the range of 78.8-81.3 % and 22.3-24.1 %, respectively. The novel strain MAH-25T has a draft genome size of 5 505 957 bp (11 contigs), annotated with 5210 protein-coding genes, 46 tRNA and three rRNA genes. The genomic DNA G+C content was determined to be 70.3 mol%. The predominant isoprenoid quinone was ubiquinone 8 (Q-8). The major fatty acids were identified as C16 : 0, summed feature 3 (C16 : 1 ω7c and/or C16 : 1 ω6c) and summed feature 8 (C18 : 1 ω7c and/or C18 : 1 ω6c). The main polar lipids were phosphatidylethanolamine, phosphatidylglycerol and diphosphatidylglycerol. On the basis of DNA-DNA hybridization, genotypic analysis, chemotaxonomic and physiological data, strain MAH-25T represents a novel species within the genus Ramlibacter, for which the name Ramlibacter pinisoli sp. nov. is proposed, with MAH-25T (=KACC 19839T=CGMCC1.13660T) as the type strain.

Evaluation of the sub-acute toxicity of Acacia catechu Willd seed extract in a Wistar albino rat model.

Acacia catechu (A. catechu) or Khair (Hindi) is used in several herbal preparations in the Ayurvedic system of medicine in India. Traditionally, this drug is beneficial against several gastrointestinal and stomach related ailments, and leprosy. The present investigation was carried out to evaluate the sub-acute oral toxicity of the ethanolic extract of A. catechu seeds in Wistar albino rats. Results obtained from the quantitative chemical analysis of A. catechu seed extract were compared with commercially available standards. A. catechu seed extract was administered orally at the doses of 250, 500 and 1000 mg/kg b.w. daily for 28 days. General behavior, bodyweight and mortality were examined during the entire study period. At the end of 28 days, hematological and biochemical parameters along with the relative organ weights were determined. It was observed that the extract did not induce death or any significant changes in the body weight, relative weight of vital organs and in hematological parameters for up to a dose of 1000 mg/kg. The oral administration of the plant extract did not produce any significant changes in the levels of glucose. In addition, there were no significant changes in the activity of both hepatotoxic and nephrotoxic marker enzymes in the serum. Oral administration of A. catechu also did not produce any significant changes in the levels of oxidative markers. Furthermore, the findings from the biochemical studies were, well corroborated with the histological findings.

Ecofriendly Synthesis of Silver Nanoparticles by Terrabacter humi sp. nov. and Their Antibacterial Application against Antibiotic-Resistant Pathogens.

It is essential to develop and discover alternative eco-friendly antibacterial agents due to the emergence of multi-drug-resistant microorganisms. In this study, we isolated and characterized a novel bacterium named Terrabacter humi MAHUQ-38T, utilized for the eco-friendly synthesis of silver nanoparticles (AgNPs) and the synthesized AgNPs were used to control multi-drug-resistant microorganisms. The novel strain was Gram stain positive, strictly aerobic, milky white colored, rod shaped and non-motile. The optimal growth temperature, pH and NaCl concentration were 30 °C, 6.5 and 0%, respectively. Based on 16S rRNA gene sequence, strain MAHUQ-38T belongs to the genus Terrabacter and is most closely related to several Terrabacter type strains (98.2%-98.8%). Terrabacter humi MAHUQ-38T had a genome of 5,156,829 bp long (19 contigs) with 4555 protein-coding genes, 48 tRNA and 5 rRNA genes. The culture supernatant of strain MAHUQ-38T was used for the eco-friendly and facile synthesis of AgNPs. The transmission electron microscopy (TEM) image showed the spherical shape of AgNPs with a size of 6 to 24 nm, and the Fourier transform infrared (FTIR) analysis revealed the functional groups responsible for the synthesis of AgNPs. The synthesized AgNPs exhibited strong anti-bacterial activity against multi-drug-resistant pathogens, Escherichia coli and Pseudomonas aeruginosa. Minimal inhibitory/bactericidal concentrations against E. coli and P. aeruginosa were 6.25/50 and 12.5/50 µg/mL, respectively. The AgNPs altered the cell morphology and damaged the cell membrane of pathogens. This study encourages the use of Terrabacter humi for the ecofriendly synthesis of AgNPs to control multi-drug-resistant microorganisms.

Comprehensive Genome Analysis on the Novel Species Sphingomonas panacis DCY99T Reveals Insights into Iron Tolerance of Ginseng.

Plant growth-promoting rhizobacteria play vital roles not only in plant growth, but also in reducing biotic/abiotic stress. Sphingomonas panacis DCY99T is isolated from soil and root of Panax ginseng with rusty root disease, characterized by raised reddish-brown root and this is seriously affects ginseng cultivation. To investigate the relationship between 159 sequenced Sphingomonas strains, pan-genome analysis was carried out, which suggested genomic diversity of the Sphingomonas genus. Comparative analysis of S. panacis DCY99T with Sphingomonas sp. LK11 revealed plant growth-promoting potential of S. panacis DCY99T through indole acetic acid production, phosphate solubilizing, and antifungal abilities. Detailed genomic analysis has shown that S. panacis DCY99T contain various heavy metals resistance genes in its genome and the plasmid. Functional analysis with Sphingomonas paucimobilis EPA505 predicted that S. panacis DCY99T possess genes for degradation of polyaromatic hydrocarbon and phenolic compounds in rusty-ginseng root. Interestingly, when primed ginseng with S. panacis DCY99T during high concentration of iron exposure, iron stress of ginseng was suppressed. In order to detect S. panacis DCY99T in soil, biomarker was designed using spt gene. This study brings new insights into the role of S. panacis DCY99T as a microbial inoculant to protect ginseng plants against rusty root disease.

Sphingobium tyrosinilyticum sp. nov., a tyrosine hydrolyzing bacterium isolated from Korean radish garden.

A yellow-pigmented novel bacterial strain, MAH-12T, was isolated from a soil sample of Korean radish garden and was characterized using a polyphasic approach. Cells were Gram-staining negative, non-motile and rod-shaped. The strain was aerobic, catalase positive, optimum growth temperature and pH were 28-30 °C and 6.0, respectively. The novel strain is able to hydrolyze L-tyrosine, starch, esculin and 4-nitrophenyl-ß-D-galactopyranoside. On the basis of 16S rRNA gene sequence analysis, strain MAH-12T belongs to the genus Sphingobium and is most closely related to several Sphingobium type strains (97.2-97.8%). In DNA-DNA hybridization tests, the DNA relatedness between strain MAH-12T and its closest phylogenetic neighbors was below 45.0%. The DNA G + C content was 64.0 mol% and the predominant respiratory quinone was ubiquinone-10. The major cellular fatty acids were summed feature 8 (C18:1 ω7c and/or C18:1 ω6c) and C16:0. The DNA-DNA hybridization results and results of the genotypic analysis in combination with chemotaxonomic and physiological data demonstrated that strain MAH-12T represented a novel species within the genus Sphingobium, for which the name Sphingobium tyrosinilyticum is proposed. The type strain is MAH-12T (= KACC 19297T = CGMCC 1.16225T). The NCBI GenBank accession number for the 16S rRNA gene sequence of strain MAH-12T is KY964278 and the digital protologue database taxon number of strain MAH-12T is TA00463.

Coprisin/Compound K Conjugated Gold Nanoparticles Induced Cell Death through Apoptosis and Ferroptosis Pathway in Adenocarcinoma Gastric Cells.

Ferroptosis and apoptosis are programmed cell death pathways with distinct characteristics. Sometimes, cancer cells are aided by the induction of a different pathway, such as ferroptosis, when they develop chemoresistance and avoid apoptosis. Identifying the nanomedicine that targets dual pathways is considered as one of the best strategies for diverse cancer types. In our previous work, we synthesized gold nanoparticles (GNP) utilizing Gluconacetobacter liquefaciens in conjunction with compound K (CK) and coprisin (CopA3), yielding GNP-CK-CopA3. Here, we assessed the inhibitory effect of GNP-CK-CopA3 on AGS cells and the induction of apoptosis using Hoechst and PI, Annexin V-FITC/PI, and qRT-PCR. Subsequently, we conducted downstream proteomic analysis and molecular dynamic stimulation to identify the underlying molecular mechanisms. Our investigation of cultured AGS cells treated with varying concentrations of GNP-CK-CopA3 demonstrated the anticancer properties of these nanoparticles. Penetration of GNP-CK-CopA3 into AGS cells was visualized using an enhanced dark field microscope. Apoptosis induction was initially confirmed by treating AGS cells with GNP-CK-CopA3, as evidenced by staining with dyes such as Hoechst and PI. Additionally, mitochondrial disruption and cellular localization induced by GNP-CK-CopA3 were validated through Mito-tracker staining and transmission electron microscopy images. Annexin V-FITC/PI staining was used to distinguish early and late-stage apoptosis or necrosis based on fluorescence patterns. The gene expression of apoptotic markers indicated the initiation of cellular apoptosis. Further, proteomic analysis suggested that the treatment of GNP-CK-CopA3 to AGS cells led to the suppression of 439 proteins and the stimulation of 832 proteins. Among these, ferroptosis emerged as a significant interconnected pathway where glutathione peroxidase 4 (GPX4) and glutathione synthetase (GSS) were significant interacting proteins. Molecular docking and dynamic simulation studies confirmed the binding affinity and stability between CopA3 and CK with GSS and GPX4 proteins, suggesting the role of GNP-CK-CopA3 in ferroptosis induction. Overall, our study showed GNP-CK-CopA3 could play a dual role by inducing apoptosis and ferroptosis to induce AGS cell death.

Lysine-Rich Polypeptide Modulates Forkhead Box O3 and Phosphoinositide 3-Kinase-Protein Kinase B Pathway To Induce Apoptosis in Breast Cancer.

The PI3K/AKT/FOXO3 pathway is one of the most frequently involved signaling pathways in cancer, including breast cancer. Therefore, we synthesized a novel lysine-rich polypeptide (Lys-PP) using de novo assembly method and evaluated its anticancer effect. We characterized the structural and physicochemical properties of Lys-PP using various techniques. Later, we used integrated approaches such as in silico, in vitro, and in vivo analysis to confirm the anticancer and therapeutic effect of Lys-PP. First, RNA sequencing suggests Lys-PP disrupted the central carbon metabolic pathway through the modulation of prolactin signaling. Additionally, docking analysis also confirmed the significant association of PI3K/AKT and FOXO3 pathway to induce an apoptotic effect on cancer. Second, Lys-PP exhibited a significant cytotoxicity effect against MDA-MB-231 but no cytotoxic effects on RAW 264.7 and HEK-293, respectively. The cytotoxic effect of Lys-PP-induced apoptosis by an increase in FOXO3a protein expression and a decrease in PI3K/AKT pathway was confirmed by quantitative real-time polymerase chain reaction, immunoblotting, and fluorescent microscopy. Later, immunohistochemistry and hematoxylin and eosin staining on MDA-MD-231 showed increased FOXO3a expression and cell death in the xenograft mice model. Further, liver function, metabolic health, or lipid profile upon Lys-PP showed the absence of significant modulation in the biomarkers except for kidney-related biomarkers. Overall, our comprehensive study provides the first evidence of Lys-PP antibreast cancer action, which could serve as a potential treatment in an alternative or complementary medicine practice.

Integrative transcriptome analysis of triple negative breast cancer profiles for identification of druggable targets.

As triple negative breast cancer (TNBC) lacks a specific target, exploration of abnormally expressed genes during the progression of TNBC is important for a better understanding of tumorigenesis and to find a specific target. We intended to figure out genes associated with TNBC, which can provide unique insights into gene dysregulation in TNBC while also pointing to new possible therapeutic targets for TNBC. A meta-analysis of multiple TNBC mRNA profiles was performed to identify consistently differentially expressed genes (CDGs). The pathways involved in modulating these genes were analyzed by MsigDB, and the interaction map was constructed. These CDGs were evaluated for their expression in cell lines, and drugs that could modulate the expression of CDGs were obtained using the connectivity map. CDGs were docked with doxorubicin and anethole, which is a phytocompound. The expression of selected CDGs was analyzed in MDA-MB-231 cells after treatment with doxorubicin and anethole. We found 45 CDGs, out of which 36 were upregulated and 9 were downregulated. MDA-MB-231 cell line was found to have high expression of CDGs, and drug that could modulate the expression of CDGs was doxorubicin. Docking results revealed that anethole and doxorubicin had good interaction with the CDGs especially with the genes AURKA, CDC6, DEPDC1, KIF23, KPNA2, MELK, CTNNB1, FLI1 and E2F1. Gene expression studies of the selected CDGs showed that the synergistic effect of anethole and doxorubicin effectively downregulated the expression. The CDGs identified from multiple cohorts have clinical significance and may be effectively exploited in the targeted therapy for TNBC.Communicated by Ramaswamy H. Sarma.

Bacterial mediated green synthesis of silver nanoparticles and their antibacterial and antifungal activities against drug-resistant pathogens.

In the healthcare sector, the production of bioactive silver nanoparticles (AgNPs) with antimicrobial properties is of great importance. In this study, a novel bacterial strain, Paenibacillus sp. MAHUQ-63, was identified as a potential candidate for facile and rapid biosynthesis of AgNPs. The synthesized AgNPs were used to control the growth of human pathogens, Salmonella Enteritidis and Candida albicans. The bacterial culture supernatant was used to synthesize the nanoparticles (NPs). Field emission transmission electron microscope examination showed spherical-shaped NPs with 15-55 nm in size. Fourier transform-infrared analysis identified various functional groups. The synthesized AgNPs demonstrated remarkable activity against S. Enteritidis and C. albicans. The zones of inhibition for 100 µl (0.5 mg ml-1) of AgNPs against S. Enteritidis and C. albicans were 18.0 ± 1.0 and 19.5 ± 1.3 mm, respectively. The minimum inhibitory concentrations were 25.0 and 12.5 µg ml-1 against S. Enteritidis and C. albicans, respectively. Additionally, the minimum bactericidal concentrations were 25.0 µg ml-1 against both pathogenic microbes. The field emission scanning electron microscopy analysis showed that the treatment of AgNPs caused morphological and structural damage to both S. Enteritidis and C. albicans. Therefore, these AgNPs can be used as a new and effective antimicrobial agent.

Bioactive ZnO Nanoparticles: Biosynthesis, Characterization and Potential Antimicrobial Applications.

In recent years, biosynthesized zinc oxide nanoparticles (ZnONPs) have gained tremendous attention because of their safe and non-toxic nature and distinctive biomedical applications. A diverse range of microbes (bacteria, fungi and yeast) and various parts (leaf, root, fruit, flower, peel, stem, etc.) of plants have been exploited for the facile, rapid, cost-effective and non-toxic synthesis of ZnONPs. Plant extracts, microbial biomass or culture supernatant contain various biomolecules including enzymes, amino acids, proteins, vitamins, alkaloids, flavonoids, etc., which serve as reducing, capping and stabilizing agents during the biosynthesis of ZnONPs. The biosynthesized ZnONPs are generally characterized using UV-VIS spectroscopy, TEM, SEM, EDX, XRD, FTIR, etc. Antibiotic resistance is a serious problem for global public health. Due to mutation, shifting environmental circumstances and excessive drug use, the number of multidrug-resistant pathogenic microbes is continuously rising. To solve this issue, novel, safe and effective antimicrobial agents are needed urgently. Biosynthesized ZnONPs could be novel and effective antimicrobial agents because of their safe and non-toxic nature and powerful antimicrobial characteristics. It is proven that biosynthesized ZnONPs have strong antimicrobial activity against various pathogenic microorganisms including multidrug-resistant bacteria. The possible antimicrobial mechanisms of ZnONPs are the generation of reactive oxygen species, physical interactions, disruption of the cell walls and cell membranes, damage to DNA, enzyme inactivation, protein denaturation, ribosomal destabilization and mitochondrial dysfunction. In this review, the biosynthesis of ZnONPs using microbes and plants and their characterization have been reviewed comprehensively. Also, the antimicrobial applications and mechanisms of biosynthesized ZnONPs against various pathogenic microorganisms have been highlighted.

Toxicological and molecular adverse effect of Illicium verum fruit constituents toward Bradysia procera.

BACKGROUND: Bradysia procera, a ginseng stem fungus gnat, is one of the most serious insect pests of Korean ginseng (Panax ginseng), causing significant damage to plant growth. The goal of this study was to determine the toxicity and mechanism of action of phenylpropanoids (trans-anethole and estragole) isolated from the methanol extract and hydrodistillate of Illicium verum fruit against third-instar larvae and eggs of Bradysia procera. RESULTS: The filter-paper mortality bioassay revealed that estragole [median lethal concentration (LC50 ) = 4.68 g/cm2 ] has a significant fumigant effect, followed by trans-anethole (LC50 = 43.92 g/cm2 ). However, estragole had the lowest toxic effect when compared to commercially available insecticides. After 7 days, estragole and trans-anethole at 75 g/cm2 inhibited egg hatchability up to 97% and 93%, respectively. At 0.09 g/cm2 , insecticides had an inhibitory effect on egg-hatching ability ranging from 88% to 94%. Furthermore, in both closed and open containers, these active constituents were able to consistently induce vapor-phased toxicity. Both estragole and trans-anethole have the ability to inhibit acetylcholinesterase (AChE), which is involved in neurotransmitter function. However, the active constituent estragole from I. verum fruit acted as a potent AChE inhibitor and had a slightly lower effect on cyclic adenosine monophosphate (AMP) than octopamine alone. CONCLUSION: This finding suggests that estragole may influence Bradysia procera neurotransmitter function via both the AChE and octopaminergic receptors. More research is needed to demonstrate the potential applications of I. verum fruit-derived products as potential larvicides and ovicides for Bradysia procera population control. © 2022 Society of Chemical Industry.

Green Synthesis and Potential Antibacterial Applications of Bioactive Silver Nanoparticles: A Review.

Green synthesis of silver nanoparticles (AgNPs) using biological resources is the most facile, economical, rapid, and environmentally friendly method that mitigates the drawbacks of chemical and physical methods. Various biological resources such as plants and their different parts, bacteria, fungi, algae, etc. could be utilized for the green synthesis of bioactive AgNPs. In recent years, several green approaches for non-toxic, rapid, and facile synthesis of AgNPs using biological resources have been reported. Plant extract contains various biomolecules, including flavonoids, terpenoids, alkaloids, phenolic compounds, and vitamins that act as reducing and capping agents during the biosynthesis process. Similarly, microorganisms produce different primary and secondary metabolites that play a crucial role as reducing and capping agents during synthesis. Biosynthesized AgNPs have gained significant attention from the researchers because of their potential applications in different fields of biomedical science. The widest application of AgNPs is their bactericidal activity. Due to the emergence of multidrug-resistant microorganisms, researchers are exploring the therapeutic abilities of AgNPs as potential antibacterial agents. Already, various reports have suggested that biosynthesized AgNPs have exhibited significant antibacterial action against numerous human pathogens. Because of their small size and large surface area, AgNPs have the ability to easily penetrate bacterial cell walls, damage cell membranes, produce reactive oxygen species, and interfere with DNA replication as well as protein synthesis, and result in cell death. This paper provides an overview of the green, facile, and rapid synthesis of AgNPs using biological resources and antibacterial use of biosynthesized AgNPs, highlighting their antibacterial mechanisms.