Biological Moieties Research Articles

Ti-based MOFs with acetic acid pendings as an efficient catalyst in the preparation of new spiropyrans with biological moieties

The strategy of designing heterogeneous porous catalysts by a post-modification method is a smart strategy to increase the catalytic power of desired catalysts. Accordingly, in this report, metal-organic frameworks based on titanium with acetic acid pending were designed and synthesized via post-modification method. The structure of the target catalyst has been investigated using different techniques such as FT-IR, XRD, SEM, EDX, Mapping, and N2 adsorption/desorption (BET/the BJH) the correctness of its formation has been proven. The catalytic application of Ti-based MOFs functionalized with acetic acid was evaluated in the preparation of new spiropyrans, and the obtained results show that the catalytic performance is improved by this modification. The strategy of designing heterogeneous porous catalysts through post-modification methods presents a sophisticated approach to enhancing the catalytic efficacy of desired catalysts. In this context, our study focuses on the synthesis and characterization of metal-organic frameworks (MOFs) based on titanium, functionalized with acetic acid pendants, using a post-modification method. Various characterization techniques, including Fourier-transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), mapping, and N2 adsorption/desorption (BET/BJH), were employed to investigate the structure and composition of the synthesized catalyst. These techniques collectively confirmed the successful formation and structural integrity of the target catalyst. The structure of the synthesized products was confirmed by melting point, 1H-NMR and 13C-NMR and FT-IR techniques. Examining the general process of catalyst synthesis and its catalytic application shows that the mentioned modification is very useful for catalytic purposes. The presented catalyst was used in synthesis of a wide range of biologically active spiropyrans with good yields. The simultaneous presence of several biologically active cores in the synthesized products will highlight the biological properties of these compounds. The present study offers a promising insight into the rational design, synthesis, and application of task-specific porous catalysts, particularly in the context of synthesizing biologically active candidate molecules.

Biofabrication of Centella asiatica mediated metal (Silver and Iron) nanoparticles and their enhanced antimicrobial, anticancer activity in retinoblastoma Y79 cancer cells

In recent years, metallic nanoparticles have played a significant role in nanotechnology and bio fabrication, being considered an alternative to antibiotics due to their feasibility for use in both bacterial detection and infection prevention. Moreover, recent studies have demonstrated the green process of developing nanoparticles with anticancer activity against many human cancer cell lines. In the current investigation, the biogenic synthesis of silver and iron nanoparticles using the aqueous leaf extract of Centella asiatica was performed. The leaf extracts underwent characterization for antioxidant activity, TLC analysis, phytochemical analysis, and GC-MS analysis of Centella asiatica. The leaf extracts revealed the antioxidant potential of the phytoconstituents, namely phenolic and flavonoid contents, responsible for the anticancer activity. The synthesized silver and iron nanoparticles were analysed using various techniques, including UV-Vis absorption spectroscopy, X-ray diffraction, Fourier transform infrared spectroscopy, scanning electron microscopy with energy-dispersive spectroscopy, and transmission electron microscopy. Confirmation of silver and iron nanoparticle formation was achieved through UV-Vis absorption spectra, showing absorption peaks at 362 nm and 342 nm, respectively. Fourier transform infrared spectroscopy analysis confirmed the biological moieties involved in synthesis and stability. X-ray diffraction (XRD) analysis verified the crystallinity of the nanomaterials, while scanning electron microscopy depicted spherical shapes for silver nanoparticles and similarly round shapes for iron nanoparticles. EDS analysis revealed 87.12 % silver and 40.12 % iron content in the respective nanoparticles. TEM imaging displayed predominantly spherical silver nanoparticles, sized at 50 nm. The antimicrobial efficacy of the biosynthesized silver and iron nanoparticles was evaluated using the well diffusion method, along with the determination of the minimum inhibitory concentration. Results indicated moderate effectiveness of silver nanoparticles against Escherichia coli (7±0.036) and Aspergillus niger (5±0.034) compared to iron nanoparticles. The minimum inhibitory concentrations against Staphylococcus aureus were 46.51–86.74 % for silver nanoparticles and 42.79–77.44 % for iron nanoparticles. The anticancer effect was evaluated using human retinoblastoma (Y79) cell lines. The cytotoxicity study using the MTT assay revealed that Centella asiatica-mediated silver nanoparticles exhibited significant cytotoxicity to human retinoblastoma cells, with a low IC50 value of 49.56 μg/ml. Based on the results, it is feasible to infer that biofabricated nanoparticles could potentially serve as antibacterial and antifungal compounds. Furthermore, the synthesized silver nanoparticles, followed by iron nanoparticles, showed high effectiveness against human retinoblastoma cancer cells, indicating potential for future drug discovery to inhibit retinoblastoma cancer for biomedical applications.

Nanobiosensors: Concepts and Emerging Clinical Applications.

Biosensors have been one of the most fascinating topics for scientists for a long time. This is because biological moieties are multifaceted and are unswervingly related to the presence of a healthy atmosphere. The biosensor approach has also endured profound changes in recent years. Biosensors have been emphasized for various applications, including food quality estimation, surveillance systems, and health and metabolic abnormality diagnostics. The advances in nanotechnology have led to a considerable potential to enhance biosensors' sensitivity, robustness, and anti-interference capabilities. Several new nanomaterials (such as nanoparticles, nanotubes, nanorods, and nanowires) have been fabricated due to the evolution of nanotechnology, and their unique features are gradually being identified, allowing for much faster detection and reproducibility. Biosensor performance has also been enhanced substantially as a result of their use. Because of their capacity to detect a wide range of compounds at deficient concentrations, nanobiosensors have sparked much interest. This article discusses biosensors based on various nanomaterials, their evolution, accompanying features, and their applications in multiple fields.

Mycofabrication of bimetal oxide nanoparticles (CuO/TiO2) using the endophytic fungus Trichoderma virens: Material properties and microbiocidal effects against bacterial pathogens

Bimetallic oxide nanoparticles (NPs) have gained the interest of researchers owing to the synergistic mechanism of action by the elements present. Mycosynthesis of nanostructures is a promising, facile, and an environmentally friendly approach. In the present study, CuO/TiO2 NPs were produced using the cell-free filtrate of the endophytic fungus Trichoderma virens. The reaction of the fungal filtrate with the two metal salts, CuSO4.5H2O and TiO2, resulted in the mycosynthesis of the CuO/TiO2 NPs. The prepared bimetal oxide NPs were characterized using XRD, FTIR spectroscopy, EDX, DLS, zeta potential analysis, XPS, Raman scattering, FESEM, and HRTEM. The mycosynthesized CuO/TiO2 NPs exhibited diffraction peaks characteristic of the monoclinic CuO and tetragonal rutile TiO2 crystal planes. Homogeneity and stability were observed as a result of the biological moieties present in the fungal filtrate, which capped the CuO/TiO2 NPs. The prepared CuO/TiO2 NPs were distributed as flake/plate-like and quasi-spherical/nanorod CuO and TiO2 NPs, respectively. A broad-spectrum antibacterial effect was recorded, with zones of inhibition as follows: foodborne pathogens Escherichia coli (14.34 mm), Salmonella enterica serovar Typhimurium (11.32 mm), and Staphylococcus aureus (9.63 mm); and phytopathogenic bacteria involving Clavibacter michiganensis subsp. michiganensis (Cmm, 12.16 mm), C. michiganensis subsp. capsici (Cmc, 11.26 mm), wild type and streptomycin-resistant Pectobacterium carotovorum subsp. carotovorum (Pcc, 11.06 and 12.37 mm, respectively), and wild type and streptomycin-resistant Xanthomonas citri pv citri (Xcc, 12.48 and 12.69 mm, respectively). The minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) of the CuO/TiO2 NPs were determined using the broth microdilution assay. NP-treated bacterial cells at sub-MICs had rough surfaces with membrane defects and exhibited shrinkage, reduction of cell edges, cracks, and fractures on their surfaces. This study provides insights into the potential of the mycosynthesized CuO/TiO2 NPs as alternative nano-antimicrobial agents, which could be employed for future biomedical, agricultural, and pharmaceutical applications.

Development of Human-Derived Photocrosslinkable Gelatin Hydrogels for Tissue Engineering.

Hydrogels are often used as biomimetic matrices for tissue regeneration. The source of the hydrogel is of utmost importance, as it affects the physicochemical characteristics and must be carefully selected to stimulate specific cell behaviors. Naturally derived polymeric biomaterials have inherent biological moieties, such as cell binding and protease cleavage sites, and thus can provide a suitable microenvironment for cells. Human-derived matrices can mitigate potential risks associated with the immune response and disease transmission from animal-derived biomaterials. In this article, we developed glycidyl methacrylate-modified human-derived gelatin (hGelGMA) hydrogels for use in tissue engineering applications. By adjusting the glycidyl methacrylate concentration in the reaction mixture, we synthesized hGelGMA with low, medium, and high degrees of modification referred to as hGelGMA-L, hGelGMA-M, and hGelGMA-H, respectively. The amount of polymeric networks in the hydrogels was increased proportionally with the degree of modification. This change has resulted in a decreasing trend in pore size, porosity, and consequent swelling ratio. Similarly, increasing the polymer concentration also exhibited slower enzymatic degradation. On the other hand, increasing the polymer concentration led to an improvement in mechanical properties, where the compressive moduli of hGelGMA-L, hGelGMA-M, and hGelGMA-H hydrogels have changed at 2.9 ± 1.0, 13.7 ± 0.9, and 26.4 ± 2.5 kPa, respectively. The cytocompatibility of hGelGMA was assessed by 3D encapsulation of human-derived cells, including human dermal fibroblasts (HDFs) and human mesenchymal stem cells (hMSCs), in vitro. Regardless of the degree of glycidyl methacrylate modification, the hGelGMA hydrogels preserved the viability of encapsulated cells and supported their growth and proliferation. HDF cells showed a higher metabolic activity in hGelGMA-H, while MSCs exhibited an increased metabolic activity when they were encapsulated in hGelGMA-M or hGelGMA-H. These results showed that photocrosslinkable human-derived gelatin-based hydrogels can be synthesized and their physical properties can be distinctly fine-tuned to different extents as a function of their degrees of modification depending on the needs of the target tissue. Due to its promising physical and biological properties, it is anticipated that hGelGMA can be utilized in a wide spectrum of tissue engineering applications.

Stimuli-Responsive Protein Hydrogels: Their Design, Properties, and Biomedical Applications.

Protein-based hydrogels are considered ideal biomaterials due to their high biocompatibility, diverse structure, and their improved bioactivity and biodegradability. However, it remains challenging to mimic the native extracellular matrices that can dynamically respond to environmental stimuli. The combination of stimuli-responsive functionalities with engineered protein hydrogels has facilitated the development of new smart hydrogels with tunable biomechanics and biological properties that are triggered by cyto-compatible stimuli. This review summarizes the recent advancements of responsive hydrogels prepared from engineered proteins and integrated with physical, chemical or biological responsive moieties. We underscore the design principles and fabrication approaches of responsive protein hydrogels, and their biomedical applications in disease treatment, drug delivery, and tissue engineering are briefly discussed. Finally, the current challenges and future perspectives in this field are highlighted.

Nanobio Interface Between Proteins and 2D Nanomaterials.

Two-dimensional (2D) nanomaterials have significantly contributed to recent advances in material sciences and nanotechnology, owing to their layered structure. Despite their potential as multifunctional theranostic agents, the biomedical translation of these materials is limited due to a lack of knowledge and control over their interaction with complex biological systems. In a biological microenvironment, the high surface energy of nanomaterials leads to diverse interactions with biological moieties such as proteins, which play a crucial role in unique physiological processes. These interactions can alter the size, surface charge, shape, and interfacial composition of the nanomaterial, ultimately affecting its biological activity and identity. This review critically discusses the possible interactions between proteins and 2D nanomaterials, along with a wide spectrum of analytical techniques that can be used to study and characterize such interplay. A better understanding of these interactions would help circumvent potential risks and provide guidance toward the safer design of 2D nanomaterials as a platform technology for various biomedical applications.

Biomarkers as Biomedical Bioindicators: Approaches and Techniques for the Detection, Analysis, and Validation of Novel Biomarkers of Diseases.

A biomarker is any measurable biological moiety that can be assessed and measured as a potential index of either normal or abnormal pathophysiology or pharmacological responses to some treatment regimen. Every tissue in the body has a distinct biomolecular make-up, which is known as its biomarkers, which possess particular features, viz., the levels or activities (the ability of a gene or protein to carry out a particular body function) of a gene, protein, or other biomolecules. A biomarker refers to some feature that can be objectively quantified by various biochemical samples and evaluates the exposure of an organism to normal or pathological procedures or their response to some drug interventions. An in-depth and comprehensive realization of the significance of these biomarkers becomes quite important for the efficient diagnosis of diseases and for providing the appropriate directions in case of multiple drug choices being presently available, which can benefit any patient. Presently, advancements in omics technologies have opened up new possibilities to obtain novel biomarkers of different types, employing genomic strategies, epigenetics, metabolomics, transcriptomics, lipid-based analysis, protein studies, etc. Particular biomarkers for specific diseases, their prognostic capabilities, and responses to therapeutic paradigms have been applied for screening of various normal healthy, as well as diseased, tissue or serum samples, and act as appreciable tools in pharmacology and therapeutics, etc. In this review, we have summarized various biomarker types, their classification, and monitoring and detection methods and strategies. Various analytical techniques and approaches of biomarkers have also been described along with various clinically applicable biomarker sensing techniques which have been developed in the recent past. A section has also been dedicated to the latest trends in the formulation and designing of nanotechnology-based biomarker sensing and detection developments in this field.

Bacteriocin-Nanoconjugates (Bac10307-AgNPs) Biosynthesized from Lactobacillus acidophilus-Derived Bacteriocins Exhibit Enhanced and Promising Biological Activities.

The proteinaceous compounds produced by lactic acid bacteria are called bacteriocins and have a wide variety of bioactive properties. However, bacteriocin's commercial availability is limited due to short stability periods and low yields. Therefore, the objective of this study was to synthesize bacteriocin-derived silver nanoparticles (Bac10307-AgNPs) extracted from Lactobacillus acidophilus (L. acidophilus), which may have the potential to increase the bioactivity of bacteriocins and overcome the hurdles. It was found that extracted and purified Bac10307 had a broad range of stability for both temperature (20-100 °C) and pH (3-12). Further, based on Sodium dodecyl-sulfate polyacrylamide gel electrophoresis (SDS-PAGE) analysis, its molecular weight was estimated to be 4.2 kDa. The synthesized Bac10307-AgNPs showed a peak of surface plasmon resonance at 430 nm λmax. Fourier transform infrared (FTIR) confirmed the presence of biological moieties, and transmission electron microscopy (TEM) coupled with Energy dispersive X-Ray (EDX) confirmed that AgNPs were spherical and irregularly shaped, with a size range of 9-20 nm. As a result, the Bac10307-AgNPs displayed very strong antibacterial activity with MIC values as low as 8 μg/mL for Staphylococcus aureus (S. aureus) and Pseudomonas aeruginosa (P. aeruginosa), when compared to Bac10307 alone. In addition, Bac10307-AgNPs demonstrated promising in vitro antioxidant activity against 2,2-diphenyl-1-picrylhydrazyl (DPPH) (IC50 = 116.04 μg/mL) and in vitro cytotoxicity against human liver cancer cells (HepG2) (IC50 = 135.63 μg/mL), more than Bac10307 alone (IC50 = 139.82 μg/mL against DPPH and 158.20 μg/mL against HepG2). Furthermore, a protein-protein molecular docking simulation study of bacteriocins with target proteins of different biological functions was also carried out in order to ascertain the interactions between bacteriocins and target proteins.

Pulmonary hazard identifications of Graphene family nanomaterials: Adverse outcome pathways framework based on toxicity mechanisms.

Graphene-family nanomaterials (GFNs) are revolutionary new nanomaterials that have attracted significant attention in the field of nanomaterials, but the ensuing problems lie in the potential threats to public health and the ecosystem caused by these nanomaterials. From the perspective of GFN-related health risk assessments, this study reviews the current status of GFN-induced pathological lung events with a focus on the damage caused to different biological moieties (molecular, cellular, tissue, and organ) and the mechanistic relationships between different toxic endpoints. These multiple sites of damage were matched with existing adverse outcome pathways (AOPs) in an online knowledge base to obtain available molecular initiation events (MIEs), key events (KEs), and adverse outcomes (AOs). Among them, the MIEs were discussed in combination with the structure-activity relationship due to the correlation between toxicity and physical and chemical properties of GFNs. Based on the collection of information regarding MIEs, Kes, and AOs in addition to upstream and downstream causal extrapolation, the AOP framework for GFN-induced pulmonary toxicity was developed, highlighting the possible mechanisms of GFN-induced lung damage. This review intended to combine AOP with classic toxicological methods with a view to rapidly and accurately establishing a nanotoxicology infrastructure so as to contribute to public health risk assessment strategies through iteration from and animal models up to the population level.

Engineering a Novel Self-Assembled Multi-siRNA Nanocaged Architecture with Controlled Enzyme-Mediated siRNA Release.

The RNA interference (RNAi) chemical and structural design space has evolved since its original definitions. Although this has led to the development of RNAi molecules that are starting to address the issues of silencing efficiency and delivery to target organs and cells, there is an on-going interest to improve upon their properties to attain wider therapeutic applicability. Taking advantage of the flexibility given by DNA and RNA structural and chemical properties, we here investigated unconventional RNAi encoding structures, designated by caged-siRNA structures (CsiRNAs), to explore novel features that could translate into advantageous properties for cellular delivery and intracellular activity. Using the principles of controlled nucleic acid self-assembly, branched DNA-RNA hybrid intermediates were formed, ultimately leading to the assembly of a "closed" structure encompassing multiple RNAi units. The RNAi active regions are further triggered by an encoded RNAse H-mediated release mechanism, while the overall structure possesses easily addressable anchors for hybridization-based functionalization with active biological moieties. We confirmed the production of correct structures and demonstrated that the encoded RNAi sequences maintain gene silencing activity even within this novel unconventional nanoarchitecture, aided by the intracellularly triggered RNAse H release mechanism. With this design, functionalization is easily achieved with no negative effects on the silencing activity, warranting further development of these novel molecular structures as a multi-RNAi platform for therapeutic delivery.

Advances in design of polymer brush functionalized inorganic nanomaterials and their applications in biomedical arena.

Grafting of polymer brush (assembly of polymer chains tethered to the substrate by one end) is emerging as one of the most viable approach to alter the surface of inorganic nanomaterials. Inorganic nanomaterials despite their intrinsic functional superiority, their applications remain restricted due to their incompatibility with organic or biological moieties vis-à-vis agglomeration issues. To overcome such a shortcoming, polymer brush modified surfaces of inorganic nanomaterials have lately proved to be of immense potential. For example, polymer brush-modified inorganic nanomaterials can act as efficient substrates/platforms in biomedical applications, ranging from drug-delivery to protein-array due to their integrated advantages such as amphiphilicity, stimuli responsiveness, enhanced biocompatibility, and so on. In this review, the current state of the art related to polymer brush-modified inorganic nanomaterials focusing, not only, on their synthetic strategies and applications in biomedical field but also the architectural influence of polymer brushes on the responsiveness properties of modified nanomaterials have comprehensively been discussed and its associated future perspective is also presented. This article is categorized under: Diagnostic Tools > In Vivo Nanodiagnostics and Imaging Therapeutic Approaches and Drug Discovery > Emerging Technologies Nanotechnology Approaches to Biology > Nanoscale Systems in Biology.

An update on dual targeting strategy for cancer treatment.

The key issue in the treatment of solid tumors is the lack of efficient strategies for the targeted delivery and accumulation of therapeutic cargoes in the tumor microenvironment (TME). Targeting approaches are designed for more efficient delivery of therapeutic agents to cancer cells while minimizing drug toxicity to normal cells and off-targeting effects, while maximizing the eradication of cancer cells. The highly complicated interrelationship between the physicochemical properties of nanoparticles, and the physiological and pathological barriers that are required to cross, dictates the need for the success of targeting strategies. Dual targeting is an approach that uses both purely biological strategies and physicochemical responsive smart delivery strategies to increase the accumulation of nanoparticles within the TME and improve targeting efficiency towards cancer cells. In both approaches, either one single ligand is used for targeting a single receptor on different cells, or two different ligands for targeting two different receptors on the same or different cells. Smart delivery strategies are able to respond to triggers that are typical of specific disease sites, such as pH, certain specific enzymes, or redox conditions. These strategies are expected to lead to more precise targeting and better accumulation of nano-therapeutics. This review describes the classification and principles of dual targeting approaches and critically reviews the efficiency of dual targeting strategies, and the rationale behind the choice of ligands. We focus on new approaches for smart drug delivery in which synthetic and/or biological moieties are attached to nanoparticles by TME-specific responsive linkers and advanced camouflaged nanoparticles.

Bicyclostreptins are radical SAM enzyme-modified peptides with unique cyclization motifs.

Microbial natural products comprise diverse architectures that are generated by equally diverse biosynthetic strategies. In peptide natural products, amino acid sidechains are frequently used as sites of modification to generate macrocyclic motifs. Backbone amide groups, among the most stable of biological moieties, are rarely used for this purpose. Here we report the discovery and biosynthesis of bicyclostreptins-peptide natural products from Streptococcus spp. with an unprecedented structural motif consisting of a macrocyclic β-ether and a heterocyclic sp3-sp3 linkage between a backbone amide nitrogen and an adjacent α-carbon. Both reactions are installed, in that order, by two radical S-adenosylmethionine (RaS) metalloenzymes. Bicyclostreptins are produced at nM concentrations and are potent growth regulation agents in Streptococcus thermophilus. Our results add a distinct and unusual chemotype to the growing family of ribosomal peptide natural products, expand the already impressive catalytic scope of RaS enzymes, and provide avenues for further biological studies in human-associated streptococci.

Design and Synthesis of Benzene Homologues Tethered with 1,2,4-Triazole and 1,3,4-Thiadiazole Motifs Revealing Dual MCF-7/HepG2 Cytotoxic Activity with Prominent Selectivity via Histone Demethylase LSD1 Inhibitory Effect.

In this study, an efficient multistep synthesis of novel aromatic tricyclic hybrids incorporating different biological active moieties, such as 1,3,4-thiadiazole and 1,2,4-triazole, was reported. These target scaffolds are characterized by having terminal lipophilic or hydrophilic parts, and their structures are confirmed by different spectroscopic methods. Further, the cytotoxic activities of the newly synthesized compounds were evaluated using in vitro MTT cytotoxicity screening assay against three different cell lines, including HepG-2, MCF-7, and HCT-116, compared with the reference drug Taxol. The results showed variable performance against cancer cell lines, exhibiting MCF-7 and HepG-2 selectivities by active analogs. Among these derivatives, 1,2,4-triazoles 11 and 13 and 1,3,4-thiadiazole 18 were found to be the most potent compounds against MCF-7 and HepG-2 cancer cells. Moreover, structure–activity relationship (SAR) studies led to the identification of some potent LSD1 inhibitors. The tested compounds showed good LSD1 inhibitory activities, with an IC50 range of 0.04–1.5 μM. Compounds 27, 23, and 22 were found to be the most active analogs with IC50 values of 0.046, 0.065, and 0.074 μM, respectively. In addition, they exhibited prominent selectivity against a MAO target with apparent cancer cell apoptosis, resulting in DNA fragmentation. This research provides some new aromatic-centered 1,2,4-triazole-3-thione and 1,3,4-thiadiazole analogs as highly effective anticancer agents with good LSD1 target selectivity.

Newly synthesized lanthanides complexes of ferrocene-based Schiff base with high biological activities and improved molecular docking data

Amino acids are the fundamental building blocks of proteins and are involved in all major biological activities. Schiff bases being active biological moieties and possessing diverse pharmacological activities. Herein, the previously synthesized Schiff base ligand (HL) underwent metal complex formation, to get their La(III), Er(III) and Yb(III) metal complexes. These metal complexes were characterized using different spectroscopic tools as elemental analysis, FT-IR, mass, UV-Vis spectra, thermal analysis (TG) and scanning electron microscope (SEM). According to the elemental analysis data, the complexes were found to have octahedral geometry with the formula [M(L)(H2O)2Cl]Cl.nH2O (M = La(III), n = 2; Er(III), n = 4 and Yb(III), n = 1). The ligand binds to the metal ions with mononegative tridentate mode through the carboxylic oxygen, imidazole nitrogen and azomethine nitrogen as deduced from the IR spectra. The complexes decomposed within two or three steps from room temperature to 1000 °C as elucidated from TG. Also, biological and anticancer activities were tested and promising activities. Molecular docking was studied on two different proteins, the receptor of breast cancer mutant oxidoreductase (3HB5) and the receptor of colon cancer isomerase (2HQ6). The results recommended that Yb(III) complex can be used as breast and colon cancer drugs.

A Designer Nanoparticle Platform for Controlled Intracellular Delivery of Bioactive Macromolecules: Inhibition of Ubiquitin-Specific Protease 7 in Breast Cancer Cells.

Biological therapeutics represent an increasing and critical component of newly approved drugs; however, the inability to deliver biologics intracellularly in a controlled manner remains a major limitation. We have developed a semi-synthetic, tunable phage-like particle (PLP) platform derived from bacteriophage λ. The shell surface can be decorated with small-molecule, biological and synthetic moieties, alone or in combination and in defined ratios. Here, we demonstrate that the platform can be used to deliver biological macromolecules intracellularly and in a controlled manner. Ubiquitin-specific protease 7 (USP7) is a deubiquitinating enzyme that has been widely recognized as an ideal target for the treatment of a variety of cancers. Recently, UbV.7.2, a novel biologic derived from the ubiquitin scaffold, was developed for inhibition of USP7, but issues remain in achieving efficient and controlled intracellular delivery of the biologic. We have shown that decoration of PLPs with trastuzumab (Trz), a HER2-targeted therapeutic used in the treatment of various cancers, results in specific targeting and uptake of Trz-PLPs into HER2-overexpressing breast cancer cells. By simultaneously decorating PLPs with Trz and UbV.7.2, we now show that these particles are also internalized by HER2-positive cells, thus providing a means for intracellular delivery of the biologic in a controlled fashion. Internalized particles retain USP7 inhibition activity of UbV.7.2 and alter the metabolic and proteomic landscapes of these cells. This study demonstrates that the λ "designer nanoparticles" represent a powerful system for the intracellular delivery of biologics in a defined dose.

Biosynthesized Silver Nanoparticles from Eruca sativa Miller Leaf Extract Exhibits Antibacterial, Antioxidant, Anti-Quorum-Sensing, Antibiofilm, and Anti-Metastatic Activities.

Worldwide, the primary problem today is the proliferation of cancer and secondary bacterial infections caused by biofilms, as they are the principal causes of death due to the lack of effective drugs. A great deal of biological activities of silver nanoparticles (AgNPs) have made them a brilliant choice for the development of new drugs in recent years. The present study was conducted to evaluate the anticancer, antibacterial, anti-QS, and antibiofilm effects of AgNPs synthesized from Eruca sativa (E. sativa) leaf extract. The ultraviolet–visible (UV–Vis) spectra showed a peak of surface plasmon resonance at 424 nm λmax, which corresponded to AgNP formation. The Fourier transform infrared spectroscopy (FT-IR) confirmed that biological moieties are involved for the development of AgNPs. Moreover, transmission electron microscopy (TEM) analyses confirmed the spherical shape and uniform size (8.11 to 15 nm) of the AgNPs. In human lung cancer cells (A549), the anticancer potential of AgNPs was examined by the MTT [3-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay, scratch assay, and invasion assay. The results indicated that AgNPs inhibit the migration of A549 cells. The synthesized AgNPs showed MIC values of 12.5 µg/mL against Chromobacterium violaceum (C. violaceum) and 25 µg/mL against Pseudomonas aeruginosa (P. aeruginosa), which demonstrated their antibacterial abilities. Biological compounds that disable the QS system are being investigated as potential strategies for preventing bacterial infections. Thus, we analyzed the potential effectiveness of synthesized AgNPs in inhibiting QS-regulated virulence factors and biofilm formation in both strains of bacteria. In C. violaceum, the synthesized AgNPs significantly inhibited both violacein (85.18% at 1/2 × MIC) and acyl homoserine lactone (78.76% at 1/2 × MIC). QS inhibitory activity was also demonstrated in P. aeruginosa at a sub-MIC concentration (1/2 × MIC) by a reduction in pyocyanin activity (68.83%), total protease (68.50%), LasA activity (63.91%), and LasB activity (56.40%). Additionally, the exopolysaccharide production was significantly reduced in both C. violaceum (65.79% at 1/2 × MIC) and P. aeruginosa (57.65% at 1/2 × MIC). The formation of biofilm was also significantly inhibited at 1/2 × MIC in C. violaceum (76.49%) and in P. aeruginosa (65.31%). Moreover, a GC–MS analysis confirmed the presence of different classes of bioactive phytochemical constituents present in the leaf extract of E. sativa. On the basis of our results, we conclude that biologically synthesized AgNPs showed numerous multifunctional properties and have the potential to be used against human cancer and bacterial biofilm-related infections.

A Preliminary Nuclear Magnetic Resonance Metabolomics Study Identifies Metabolites that Could Serve as Diagnostic Markers of Major Depressive Disorder.

The evaluation of metabolites that are directly involved in the physiological process, few steps short of phenotypical manifestation, remains vital for unravelling the biological moieties involved in the development of the (MDD) and in predicting its treatment outcome. Eight (8) urine and serum samples each obtained from consenting healthy controls (HC), twenty-five (25) urine and serum samples each from first episode treatment naïve MDD (TNMDD) patients, and twenty (22) urine and serum samples each s from treatment naïve MDD patients 2 weeks after SSRI treatment (TWMDD) were analysed for metabolites using proton nuclear magnetic resonance (1HNMR) spectroscopy. The evaluation of patients' samples was carried out using Partial Least Squares Discriminant Analysis (PLS-DA) and Orthogonal Partial Least Square- Discriminant Analysis (OPLSDA) models. In the serum, decreased levels of lactate, glucose, glutamine, creatinine, acetate, valine, alanine, and fatty acid and an increased level of acetone and choline in TNMDD or TWMDD irrespective of whether an OPLSDA or PLSDA evaluation was used were identified. A test for statistical validations of these models was successful. Only some changes in serum metabolite levels between HC and TNMDD identified in this study have potential values in the diagnosis of MDD. These changes included decreased levels of lactate, glutamine, creatinine, valine, alanine, and fatty acid, as well as an increased level of acetone and choline in TNMDD. The diagnostic value of these changes in metabolites was maintained in samples from TWMDD patients, thus reaffirming the diagnostic nature of these metabolites for MDD.

Biogenically structural and morphological engineering of Trigonella foenum-graecum mediated SnO2 nanoparticles with enhanced photocatalytic and antimicrobial activities

The increasing water pollution and infectious diseases in the current globalization are the signals for the high demand of advanced materials for their treatment in near future. In this regard, the present work presents an advanced, easy and low-cost biogenic process for the synthesis of Trigonella foenum-graecum@SnO2 as a photocatalyst and an antimicrobial agent. The particles are characterized through X-ray diffractometer, scanning electron microscope, transmission electron microscope, Fourier infrared transform spectrometer and UV–Visible spectrometer. Debye Scherrer, Williamson–Hall and the Modified Debye Scherrer equations give an average crystallite size of about 10 nm. FTIR spectrum shows the presence of many biological and organic moieties in the Trigonella foenum-graecum extract acting as both capping and reducing agent, and various functional groups such as carboxyl, hydroxyl, fat and alcohol, are observed on the surface of Trigonella foenum-graecum mediated SnO2 nanoparticles. The larger bandgap of SnO2 nanoparticles (2.60 eV) as compared to its bulk counterpart (3.60 eV) is attributed to the quantum confinement of its excitons. SEM and TEM analysis show nanosized spherical particles with a clear frame of the passivating agent. SnO2 nanoparticles are found to be an efficient photocatalyst in the degradation of toxic Coralene Red dye with degradation efficiency of 100% and high photodegradation rate-constant of 9.65 × 10−3 min−1. As an antimicrobial mediator, the SnO2 nanoparticles are effective against E. coli (gram-negative) and B. subtilis (gram-positive) with different zones of clearance.