Phytonanotherapy for the Treatment of Metabolic Dysfunction-Associated Steatotic Liver Disease.

Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as nonalcoholic fatty liver disease, is a steatotic liver disease associated with metabolic syndrome (MetS), especially obesity, hypertension, diabetes, hyperlipidemia, and hypertriglyceridemia. MASLD in 43-44% of patients can progress to metabolic dysfunction-associated steatohepatitis (MASH), and 7-30% of these cases will progress to liver scarring (cirrhosis). To date, the mechanism of MASLD and its progression is not completely understood and there were no therapeutic strategies specifically tailored for MASLD/MASH until March 2024. The conventional antiobesity and antidiabetic pharmacological approaches used to reduce the progression of MASLD demonstrated favorable peripheral outcomes but insignificant effects on liver histology. Alternatively, phyto-synthesized metal-based nanoparticles (MNPs) are now being explored in the treatment of various liver diseases due to their unique bioactivities and reduced bystander effects. Although phytonanotherapy has not been explored in the clinical treatment of MASLD/MASH, MNPs such as gold NPs (AuNPs) and silver NPs (AgNPs) have been reported to improve metabolic processes by reducing blood glucose levels, body fat, and inflammation. Therefore, these actions suggest that MNPs can potentially be used in the treatment of MASLD/MASH and related metabolic diseases. Further studies are warranted to investigate the feasibility and efficacy of phytonanomedicine before clinical application.

Advances in Nanotechnology towards Development of Silver Nanoparticle-Based Wound-Healing Agents.

Since antiquity, silver-based therapies have been used in wound healing, wound care and management of infections to provide adequate healing. These therapies are associated with certain limitations, such as toxicity, skin discolouration and bacterial resistance, which have limited their use. As a result, new and innovative wound therapies, or strategies to improve the existing therapies, are sought after. Silver nanoparticles (AgNPs) have shown the potential to circumvent the limitations associated with conventional silver-based therapies as described above. AgNPs are effective against a broad spectrum of microorganisms and are less toxic, effective at lower concentrations and produce no skin discolouration. Furthermore, AgNPs can be decorated or coupled with other healing-promoting materials to provide optimum healing. This review details the history and impact of silver-based therapies leading up to AgNPs and AgNP-based nanoformulations in wound healing. It also highlights the properties of AgNPs that aid in wound healing and that make them superior to conventional silver-based wound treatment therapies.

Antitumor activity of phenylene bridged binuclear bis(imino-quinolyl)palladium(II) and platinum(II) complexes.

Antitumor effects of a known bis(imino-quinolyl)palladium(II) complex 1 and its newly synthesized platinum(II) analogue 2 were evaluated against human breast (MCF-7) and human colon (HT-29) cancer cell lines. The complexes gave cytotoxicity profiles that were better than the reference drug cisplatin. The highest cytotoxic activities were pronounced in complex 2 across the two examined cancer cell lines. Both compounds represent potential active drugs based on bimetallic complexes.

Wound healing effects of biogenic gold nanoparticles synthesized using red wine extracts.

Gold nanoparticles (AuNPs) were synthesized using three red wine extracts (RW-Es); by varying temperature, pH, concentrations of RW-Es and gold salt. The RW-AuNPs were characterized by UV-vis, transmission electron microscopy (TEM), dynamic light scattering (DLS), and the Fourier Transform Infra-red Spectroscopy (FT-IR). Their stability was evaluated in water, foetal bovine serum (FBS), phosphate-buffered saline (PBS), and Dulbecco's Modified Eagle Medium (DMEM) by UV-Vis. The effect of the RW-Es and RW-AuNPs on KMST-6 cell cell viability was evaluated by MTT assay; and their wound healing effects were monitored by scratch assay. RW-AuNPs synthesis was observed by colour change, and confirmed by UV-Vis spectrum, with an absorption peak around 550 nm. The hydrodynamic sizes of the RW-AuNPs ranged between 10 and 100 nm. Polyphenols, carboxylic acids, and amino acids are some of functional groups in the RW-Es that were involved in the reduction of RW-AuNPs. The RW-AuNPs were stable in test solutions and showed no cytotoxicity to the KMST-6 cells up to 72 h. AuNPs synthesized from Pinotage and Cabernet Sauvignon enhanced proliferation of KMST-6 cells and showed potential as wound healing agents. Further studies are required to investigate the molecular mechanisms involved in the potential wound-healing effect of the RW-AuNPs.

The role and potential of computer-aided drug discovery strategies in the discovery of novel antimicrobials.

Antimicrobial resistance (AMR) has become more of a concern in recent decades, particularly in infections associated with global public health threats. The development of new antibiotics is crucial to ensuring infection control and eradicating AMR. Although drug discovery and development are essential processes in the transformation of a drug candidate from the laboratory to the bedside, they are often very complicated, expensive, and time-consuming. The pharmaceutical sector is continuously innovating strategies to reduce research costs and accelerate the development of new drug candidates. Computer-aided drug discovery (CADD) has emerged as a powerful and promising technology that renews the hope of researchers for the faster identification, design, and development of cheaper, less resource-intensive, and more efficient drug candidates. In this review, we discuss an overview of AMR, the potential, and limitations of CADD in AMR drug discovery, and case studies of the successful application of this technique in the rapid identification of various drug candidates. This review will aid in achieving a better understanding of available CADD techniques in the discovery of novel drug candidates against resistant pathogens and other infectious agents.

Ehretia Species Phytoconstituents as Potential Lead Compounds against Klebsiella pneumoniae Carbapenemase: A Computational Approach.

The evolution of antibiotic-resistant carbapenemase has negatively impacted the management of critical healthcare-associated infections. K. pneumoniae carbapenemase-2- (KPC-2-) expressing bacteria have developed resistance to conventional therapeutic options, including those used as a last resort for life-threatening diseases. In this study, Ehretia species phytoconstituents were screened for their potential to inhibit KPC-2 protein using in silico approaches. Molecular docking was used to identify strong KPC-2 protein binding phytoconstituents retrieved from the literature. The best-docked conformation of the ligands was selected based on their glide energy and binding interactions. To determine their binding free energies, these hit compounds were subjected to molecular mechanics with generalized born and surface area (MM-GBSA) in the PRIME module. Pharmacological assessments of the ligands were performed to evaluate their drug-likeness. Molecular dynamic (MD) simulations were used to analyze the conformational stability of the selected druglike compounds within the active site of the KPC-2 protein. Overall, a total of 69 phytoconstituents were compiled from the literature. Fourteen of these compounds exhibited a stronger binding affinity for the protein target than the reference drugs. Four of these top hit compounds, DB09, DB12, DB28, and DB66, revealed the highest efficacy in terms of drug-likeness properties. The MD simulation established that among the druglike compounds, DB66 attained stable conformations after 150 ns simulation in the active site of the protein. We concluded that DB66 from Ehretia species could play a significant role in therapeutic efforts against KPC-2-expressing bacteria.

Anticancer, Antioxidant, and Catalytic Activities of Green Synthesized Gold Nanoparticles Using Avocado Seed Aqueous Extract.

Disposal of agricultural waste has a negative impact on the environment and human health and may contribute to the greenhouse effect. The field of nanotechnology could provide alternative solutions to upcycle agricultural wastes in a safer manner into high-end value products. Organic waste from plants contain biomaterials that could serve as reducing and capping agents in the synthesis of nanomaterials with enhanced activities for use in biomedical and environmental applications. Persea americana (avocado) is a fruit with a high nutritional value; however, despite its rich phytochemical profile, its seed is often discarded as waste. Therefore, this study aimed to upcycle avocado seeds through the synthesis of gold nanoparticles (AuNPs) and evaluate their anticancer, antioxidant, and catalytic activities. The biosynthesis of avocado seed extract (AvoSE)-mediated AuNPs (AvoSE-AuNPs) was achieved following the optimization of various reaction parameters, including pH, temperature, extract, and gold salt concentrations. The AvoSE-AuNPs were poly-dispersed and anisotropic, with average core and hydrodynamic sizes of 14 ± 3.7 and 101.39 ± 1.4 nm, respectively. The AvoSE-AuNPs showed excellent antioxidant potential in terms of ferric reducing antioxidant power (343.88 ± 0.001 µmolAAE/L), 2,2-diphenyl-1-picrylhydrazyl (128.80 ± 0.0159 µmolTE/L), and oxygen radical absorbance capacity (1822.02 ± 12.6338 µmolTE/L); significantly reduced the viability of Caco-2 and PC-3 cells in a dose-dependent manner; and efficiently reduced 4-nitrophenol (4-NP) to 4-aminophenol. This study demonstrated how avocado seeds, an agricultural waste, can be used as sources of new bioactive materials for the synthesis of AuNPs, which have excellent antioxidant, anticancer, and catalytic activities, showing AvoSE-AuNPs' versatility in various applications. In addition, the AvoSE-AuNPs exhibited good stability and recyclability during the catalytic activity, which is significant because some of the primary issues with the use of metallic NPs as catalysts are around the cost-effectiveness, recovery, and reusability of the catalyst.

Dichlorido[2-(phenyl-imino-meth-yl)quinoline-N,N']palladium(II).

In the title complex, [PdCl(2)(C(16)H(12)N(2))], the Pd(II) ion is coordinated by two N atoms [Pd-N 2.039 (2), 2.073 (2) Å] from a bidentate ligand and two chloride anions [Pd-Cl 2.2655 (7), 2.2991 (7) Å] in a distorted square-planar geometry. In the crystal, π-π inter-actions between the six-membered rings of the quinoline fragments [centroid-centroid distances = 3.815 (5), 3.824 (5) Å] link two mol-ecules into centrosymmetric dimers.

Antimicrobial Effects of Gum Arabic-Silver Nanoparticles against Oral Pathogens.

Dental caries is considered one of the most prevalent oral diseases worldwide, with a high rate of morbidity among populations. It is a chronic infectious disease with a multifactorial etiology that leads to the destruction of the dental tissues. Due to their antimicrobial, anti-inflammatory, antifungal, and antioxidant properties; silver nanoparticles (AgNPs) are incorporated in dental products to help prevent infectious oral diseases. In this study, the antimicrobial effects of AgNPs synthesized using Gum Arabic extracts (GAE) were examined. The GA-AgNPs were synthesized and characterized using ultraviolet-visible (UV-Vis) spectrophotometer, dynamic light scattering (DLS), transmission electron microscopy (TEM), and Fourier transform infrared (FTIR) spectroscopy. The antimicrobial activity of the GA-AgNPs was evaluated on Streptococcus sanguinis (S. sanguinis), Streptococcus mutans (S. mutans), Lactobacillus acidophilus (L. acidophilus), and Candida albicans (C. albicans) using agar disc diffusion and microdilution assays. The antibiofilm of GA-AgNPs was evaluated on the surface of human tooth enamel that had been exposed to S. mutans with and without the GA-AgNPs using scanning electron microscopy (SEM). GA-AgNPs were spherical in shape with a particle size distribution between 4 and 26 nm. The GA-AgNPs exhibited antimicrobial activity against all the tested oral microbes, with GA-AgNPs_0.4g having higher antimicrobial activity. The GA-AgNPs_0.4g inhibited S. mutans adhesion and biofilm formation on the surface of the tooth enamel. Therefore, this study supports the prospective implementation of the plant extract-mediated AgNPs in dental healthcare.

A Label-Free Gold Nanoparticles-Based Optical Aptasensor for the Detection of Retinol Binding Protein 4.

Retinol-binding protein 4 (RBP4) has been implicated in insulin resistance in rodents and humans with obesity and T2DM, making it a potential biomarker for the early diagnosis of T2DM. However, diagnostic tools for low-level detection of RBP4 are still lagging behind. Therefore, there is an urgent need for the development of T2DM diagnostics that are rapid, cost-effective and that can be used at the point-of-care (POC). Recently, nano-enabled biosensors integrating highly selective optical detection techniques and specificity of aptamers have been widely developed for the rapid detection of various targets. This study reports on the development of a rapid gold nanoparticles (AuNPs)-based aptasensor for the detection of RBP4. The retinol-binding protein aptamer (RBP-A) is adsorbed on the surface of the AuNPs through van der Waals and hydrophobic interactions, stabilizing the AuNPs against sodium chloride (NaCl)-induced aggregation. Upon the addition of RBP4, the RBP-A binds to RBP4 and detaches from the surface of the AuNPs, leaving the AuNPs unprotected. Addition of NaCl causes aggregation of AuNPs, leading to a visible colour change of the AuNPs solution from ruby red to purple/blue. The test result was available within 5 min and the assay had a limit of detection of 90.76 ± 2.81 nM. This study demonstrates the successful development of a simple yet effective, specific, and colorimetric rapid assay for RBP4 detection.

Nanotechnology-Based Strategies for Effective and Rapid Detection of SARS-CoV-2.

The coronavirus disease 2019 (COVID-19) pandemic has gained worldwide attention and has prompted the development of innovative diagnostics, therapeutics, and vaccines to mitigate the pandemic. Diagnostic methods based on reverse transcriptase-polymerase chain reaction (RT-PCR) technology are the gold standard in the fight against COVID-19. However, this test might not be easily accessible in low-resource settings for the early detection and diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The lack of access to well-equipped clinical laboratories, requirement for the high level of technical competence, and the cost of the RT-PCR test are the major limitations. Moreover, RT-PCR is unsuitable for application at the point-of-care testing (PoCT) as it is time-consuming and lab-based. Due to emerging mutations of the virus and the burden it has placed on the health care systems, there is a growing urgency to develop sensitive, selective, and rapid diagnostic devices for COVID-19. Nanotechnology has emerged as a versatile technology in the production of reliable diagnostic tools for various diseases and offers new opportunities for the development of COVID-19 diagnostic systems. This review summarizes some of the nano-enabled diagnostic systems that were explored for the detection of SARS-CoV-2. It highlights how the unique physicochemical properties of nanoparticles were exploited in the development of novel colorimetric assays and biosensors for COVID-19 at the PoCT. The potential to improve the efficiency of the current assays, as well as the challenges associated with the development of these innovative diagnostic tools, are also discussed.

Peptide-functionalized nanoparticles for the selective induction of apoptosis in target cells.

AIM: The study developed a prohibitin (PHB) targeted nanotherapy for selective induction of apoptosis in target cells. METHODS: Gold nanoparticles (AuNPs) were bifunctionalized with adipose homing and proapoptotic peptides. The efficacy and mode of cell death induced by the AuNPs were investigated in vitro on three cancer cell lines. RESULTS: The antiproliferative activity of PHB-targeted bifunctionalized AuNPs was more pronounced on cells that express the PHB receptor, and demonstrated receptor-mediated targeting and selectivity. The bifunctionalized AuNPs induced cell death by apoptosis. CONCLUSION: The PHB-targeted nanotherapy under study could potentially be used for treatment of diseases that are characterized by overexpression of PHB. As such, further investigations will be conducted in vivo.

Strain-dependent stimulation of growth in leptin-treated obese db/db mice.

Leptin increases the proliferation of various cell types in vitro, and we reported that background strain influences the metabolic responses to leptin in db/db mice, which express short-form, but not long-form, leptin receptors. Here, we examined the effects of leptin on growth of young C57BL/Ks, C57BL/6J, and C57BL/3J db/db mice. Intraperitoneal infusions of 20 micro g leptin/d for 26 d increased the food intake of C57BL/6J mice by 15% (P < 0.01), but had no effect in C57BL/Ks db/db mice. Leptin-infused C57BL/6J db/db mice gained more weight ( approximately 20%; P < 0.04) than PBS-infused controls. The increased weight was sustained after leptin infusion ended. Leptin had no effect on weight gain or food intake of C57BL/3J db/db mice, which only express the soluble leptin receptor. A single leptin injection increased MAPK phosphorylation in liver by 40% (P < 0.001) and that in muscle tissues by 20% (P < 0.001) in C57BL/6J mice, but did not change phosphorylation in C57BL/3J db/db mice. These results suggest that leptin increases the weight gain of C57BL/6J db/db mice by activating the MAPK pathway through a mechanism that is dependent on short-form leptin receptors. This response may be masked by activation of the long-form receptor in wild-type animals that lose body fat during leptin treatment.

Imino-phosphine palladium(II) and platinum(II) complexes: synthesis, molecular structures and evaluation as antitumor agents.

The imino-phosphine ligands L1 and L2 were prepared via condensation reaction of 2-(diphenylphosphino)benzaldehyde with substituted anilines and obtained in very good yields. An equimolar reaction of L1 and L2 with either PdCl2(cod) or PtCl2(cod) gave new palladium(II) and platinum(II) complexes 1-4. The compounds were characterized by elemental analysis, IR, (1)H and (31)P NMR spectroscopy. The molecular structures of 2, 3 and 4 were confirmed by X-ray crystallography. All the three molecular structures crystallized in monoclinic C2/c space system. The coordination geometry around the palladium and platinum atoms in respective structures exhibited distorted square planar geometry at the metal centers. The complexes were evaluated in vitro for their cytotoxic activity against human breast (MCF-7) and human colon (HT-29) cancer cells, and they exhibited growth inhibitory activities and selectivity that were superior to the standard compound cisplatin.

Hyperleptinemia and reduced TNF-alpha secretion cause resistance of db/db mice to endotoxin.

Leptin deficiency in ob/ob mice increases susceptibility to endotoxic shock, whereas leptin pretreatment protects them against LPS-induced lethality. Lack of the long-form leptin receptor (Ob-Rb) in db/db mice causes resistance. We tested the effects of LPS in C57BL/6J db(3J)/db(3J) (BL/3J) mice, which express only the circulating leptin receptors, compared with C57BL/6J db/db (BL/6J) mice, which express all short-form and circulating isoforms of the leptin receptor. Intraperitoneal injections of LPS significantly decreased rectal temperature and increased leptin, corticosterone, and free TNF-alpha in fed and fasted BL/3J and BL/6J mice. TNF-alpha was increased three- and fourfold in BL/3J and BL/6J, respectively. LPS (100 microg) caused 50% mortality of fasted BL/6J mice but caused no mortality in fasted BL/3J mice. Pretreatment of fasted BL/3J mice with 30 microg leptin prevented the drop in rectal temperature, blunted the increase in corticosterone, but had no effect on TNF-alpha induced by 100 microg LPS. Taken together, these data provide evidence that fasted BL/3J mice are more resistant than BL/6J mice to LPS toxicity, presumably due to the absence of leptin receptors in BL/3J mice. This resistance may be due to high levels of free leptin cross-reacting with other cytokine receptors.

Effects of a high-fat diet and strain on hypothalamic gene expression in rats.

OBJECTIVE: This study was designed to investigate whether dietary fat and genetic background might differentially alter the expression of hypothalamic genes involved in food intake. RESEARCH METHODS AND PROCEDURES: Three-month-old Osborne-Mendel (OM) and S5B/Pl rats were fed either a high-fat or a low-fat diet for 14 days. mRNA for neuropeptide Y (NPY), corticotrophin-releasing hormone, NPY Y-1 receptor and Y-5 receptor, and serotonin 2c (5-HT2c) receptors were measured using Northern blotting or ribonuclease protection assays. RESULTS: OM rats showed an increased expression of NPY and corticotrophin-releasing hormone compared with S5B/Pl rats. The expression of NPY-Y1 and -Y5 receptor mRNA was significantly higher in the hypothalamus of OM rats compared with S5B/Pl rats. The expression of 5HT-2c receptor mRNA was significantly reduced in both strains of rats eating a high-fat diet when compared with the animals eating the low-fat diet. DISCUSSION: These data suggest that over activity of the NPY system may contribute to the development of obesity in OM rats and that expression of the 5HT-2c receptor gene may be modulated by dietary fat.