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Multiple biological activities of coenzyme Q10 have been demonstrated, opening up opportunities for research and development. However, the biological action of potassium polyacrylate and its effect on the mitochondrial permeability transition pores are both poorly understood. Therefore, this study investigated the in vitro antioxidative potential of potassium polyacrylate (PCK) and coenzyme Q10 (CoQ10) and their effects on mitochondrial permeability transition pores. In vitro antioxidant and angiotensin-converting enzyme inhibitory activities were assessed using standard methods, and lipid peroxidation was also determined. Mitochondrial swelling was evaluated as the change in absorbance under succinate-energized conditions. Cytochrome c release and mitochondrial ATPase activity were assessed. The results showed that PCK and CoQ10 significantly scavenged DPPH and nitric oxide radicals in a concentration-dependent manner and demonstrated a better ferricreducing antioxidant potential. PCK exhibited a high DPPH radical scavenging ability with the lowest IC50 value of 54.05 µg/mL while CoQ10 exhibited higher reducing power with the IC50 value of 82.14 µg/mL.Both were also found to inhibit angiotensin-converting enzyme activity. In addition, PCK and CoQ10 significantly (p<0.05) prevented lipid peroxidation, modulated the opening of mitochondrial permeability transition (mPT) pores and caused no significant release of cytochrome c. However, CoQ10 showed a mild inductive effect on mPT pores at higher concentrations. PCK and CoQ10 also increased mitochondrial ATPase activity. The results of this study suggest that both PCK and CoQ10 may be helpful in the treatment of diseases such as neurological disorders where excessive apoptosis is associated with excessive tissue degradation. [ABSTRACT FROM AUTHOR]

The recent advancements in messenger ribonucleic acid (mRNA) vaccine development have vastly enhanced their use as alternatives to conventional vaccines in the prevention of various infectious diseases and treatment of several types of cancers. This is mainly due to their remarkable ability to stimulate specific immune responses with minimal clinical side effects. This review gives a detailed overview of mRNA vaccines currently in use or at various stages of development, the recent advancements in mRNA vaccine development, and the challenges encountered in their development. Future perspectives on this technology are also discussed., (© 2023 IOP Publishing Ltd.)

Background: Sarcocephalus pobeguinii (Hua ex Pobég) is used in folk medicine to treat oxidative-stress related diseases, thereby warranting the investigation of its anticancer and anti-inflammatory properties. In our previous study, the leaf extract of S. pobeguinii induced significant cytotoxic effect against several cancerous cells with high selectivity indexes towards non-cancerous cells. Aim: The current study aims to isolate natural compounds from S. pobeguinii , and to evaluate their cytotoxicity, selectivity and anti-inflammatory effects as well as searching for potential target proteins of bioactive compounds. Methods: Natural compounds were isolated from leaf, fruit and bark extracts of S. pobeguinii and their chemical structures were elucidated using appropriate spectroscopic methods. The antiproliferative effect of isolated compounds was determined on four human cancerous cells (MCF-7, HepG2, Caco-2 and A549 cells) and non-cancerous Vero cells. Additionally, the anti-inflammatory activity of these compounds was determined by evaluating the nitric oxide (NO) production inhibitory potential and the 15-lipoxygenase (15-LOX) inhibitory activity. Furthermore, molecular docking studies were carried out on six putative target proteins found in common signaling pathways of inflammation and cancer. Results: Hederagenin ( 2 ), quinovic acid 3-O-[α-D-quinovopyranoside] ( 6 ) and quinovic acid 3-O-[β-D-quinovopyranoside] ( 9 ) exhibited significant cytotoxic effect against all cancerous cells, and they induced apoptosis in MCF-7 cells by increasing caspase-3/-7 activity. ( 6 ) showed the highest efficacy against all cancerous cells with poor selectivity (except for A549 cells) towards non-cancerous Vero cells; while ( 2 ) showed the highest selectivity warranting its potential safety as a chemotherapeutic agent. Moreover, ( 6 ) and ( 9 ) significantly inhibited NO production in LPS-stimulated RAW 264.7 cells which could mainly be attributed to their high cytotoxic effect. Besides, the mixture nauclealatifoline G and naucleofficine D ( 1 ), hederagenin ( 2 ) and chletric acid ( 3 ) were active against 15-LOX as compared to quercetin. Docking results showed that JAK2 and COX-2, with the highest binding scores, are the potential molecular targets involved in the antiproliferative and anti-inflammatory effects of bioactive compounds. Conclusion: Overall, hederagenin ( 2 ), which selectively killed cancer cells with additional anti-inflammatory effect, is the most prominent lead compound which may be further investigated as a drug candidate to tackle cancer progression., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Mfotie Njoya, Ndemangou, Akinyelu, Munvera, Chukwuma, Mkounga, Mashele, Makhafola and McGaw.)

Cancer and COVID-19 have been deemed as world health concerns due to the millions of lives that they have claimed over the years. Extensive efforts have been made to develop sophisticated, site-specific, and safe strategies that can effectively diagnose, prevent, manage, and treat these diseases. These strategies involve the implementation of metal nanoparticles and metal oxides such as gold, silver, iron oxide, titanium oxide, zinc oxide, and copper oxide, formulated through nanotechnology as alternative anticancer or antiviral therapeutics or drug delivery systems. This review provides a perspective on metal nanoparticles and their potential application in cancer and COVID-19 treatments. The data of published studies were critically analysed to expose the potential therapeutic relevance of green synthesized metal nanoparticles in cancer and COVID-19. Although various research reports highlight the great potential of metal and metal oxide nanoparticles as alternative nanotherapeutics, issues of nanotoxicity, complex methods of preparation, biodegradability, and clearance are lingering challenges for the successful clinical application of the NPs. Thus, future innovations include fabricating metal nanoparticles with eco-friendly materials, tailor making them with optimal therapeutics for specific disease targeting, and in vitro and in vivo evaluation of safety, therapeutic efficiency, pharmacokinetics, and biodistribution.

Introduction: In recent years, plant-mediated synthesis of silver nanoparticles has evolved as a promising alternative to traditional synthesis methods. In addition to producing silver nanoparticles with diverse biomedical potential, the biosynthesis approach is known to be inexpensive, rapid, and environmentally friendly., Objective: This study was aimed at synthesizing silver nanoparticles using ethanolic stem and root bark extracts of Khaya grandifoliola and highlighting the biomedical potential of the nanoparticles by evaluating their antioxidant, antidiabetic and anticholinesterase effects in vitro., Methods: Silver nanoparticles were prepared using ethanolic stem and root bark extracts of K. grandifoliola as precursors. The biogenic silver nanoparticles were characterized using UV-visible spectroscopy, fourier transform infrared spectroscopy, scanning electron microscopy and energydispersive X-ray analysis. Furthermore, 2,2-Diphenyl-1-picrylhydrazyl radical scavenging, ferric ion reducing antioxidant power, and nitric oxide scavenging assays were used to determine the antioxidant property of the nanoparticles. The antidiabetic potential of the nanoparticles was determined by evaluating their inhibitory effect on the activity of α-amylase and α-glucosidase. The anticholinesterase potential of the nanoparticles was determined by assessing their inhibitory effect on the activity of acetylcholinesterase and butyrylcholinesterase., Results: UV-visible spectroscopy showed surface plasmon resonance bands between 425 and 450 nm. Scanning electron microscopy revealed almost round nanoparticles with a maximum size of 91 nm. Fourier transform infrared spectroscopy affirmed the role of the phytoconstituents present in K. grandifoliola as reducing and stabilizing agents. The biogenic silver nanoparticles showed remarkable antioxidant, antidiabetic, and anticholinesterase effects., Conclusion: Biogenic silver nanoparticles could be useful in biomedical and pharmacological applications., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Different ethnomedical benefits have been documented on different parts of Ackee ( Blighia sapida ); however, their roles in ameliorating oxidative damages are not well established. CdCl 2 inhibitory effects on some oxidative-stress biomarkers and ameliorative potentials of Ackee leaves (AL) and arils (AS) methanolic extracts were studied using Drosophila melanogaster as a model. One to 3-day-old D. melanogaster flies were orally exposed to different concentrations of CdCl 2 in their diet for 7 days. The fly's survival profile and negative geotaxis assays were subsequently analysed. Methanolic extracts of AL and AS treatments showed negative geotaxis behaviour, and extracts were able to ameliorate the effect of Cd 2+ on catalase and GST activities and increase total thiol and GSH levels, while it reduced the H 2 O 2 generation ( p ≤ 0.05) when compared to the control. Furthermore, Cd 2+ exhibited noncompetitive and uncompetitive enzyme inhibition on catalase and GST activities, respectively, which may have resulted in the formation of Enzyme-substrate-Cd 2+ transition complexes, thus inhibiting the conversion of substrate to product. This study, thus, suggests that the Cd 2+ mechanism of toxicity was associated with oxidative damage, as evidenced by the alteration in the oxidative stress-antioxidant imbalance, and that the AL and AS extracts possess essential phytochemicals that could alleviate possibly deleterious oxidative damage effects of environmental pollutants such as CdCl 2 . Thus, Ackee plant parts possess essential phytonutrients which could serve as valuable resources in heavy metal toxicity management., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright © 2022 Omodele Ibraheem et al.)

Advances in nanomedicine have seen the adaptation of nanoparticles (NPs) for subcellular delivery for enhanced therapeutic impact and reduced side effects. The pivotal role of the mitochondria in apoptosis and their potential as a target in cancers enables selective induction of cancer cell death. In this study, we examined the mitochondrial targeted delivery of betulinic acid (BA) by the mitochondriotropic TPP + -functionalized epigallocatechin gallate (EGCG)-capped gold NPs (AuNPs), comparing the impact of polyethylene glycol (PEG) and poly-L-lysine-graft-polyethylene glycol (PLL-g-PEG) copolymer on delivery efficacy. This included the assessment of their cellular uptake, mitochondrial localization and efficacy as therapeutic delivery platforms for BA in the human Caco-2, HeLa and MCF-7 cancer cell lines. These mitochondrial-targeted nanocomplexes demonstrated significant inhibition of cancer cell growth, with targeted nanocomplexes recording IC 50 values in the range of 3.12-13.2 µM compared to that of the free BA (9.74-36.31 µM) in vitro, demonstrating the merit of mitochondrial targeting. Their mechanisms of action implicated high amplitude mitochondrial depolarization, caspases 3/7 activation, with an associated arrest at the G0/G1 phase of the cell cycle. This nano-delivery system is a potentially viable platform for mitochondrial-targeted delivery of BA and highlights mitochondrial targeting as an option in cancer therapy.

The mitochondria have recently become a novel target in the treatment of cancer. Targeted delivery by nanoparticles (NPs) has shown potential in enhancing existing therapeutic principles. With toxicity remaining a recurring issue, the green synthesis of inorganic NPs and modification with polymers may help to improve stability and biocompatibility. We synthesized epigallocatechin gallate (EGCG)-capped gold NPs (AuNPs), and functionalized with poly-D-lysine grafted polyethylene glycol (PDL-g-PEG), and the mitochondrial targeting triphenylphosphonium cation, and thereafter assessed their mitochondrial delivery capacity of paclitaxel in cancer cells in vitro . This PDL-g-PEG coated EGCG-AuNPs were further assessed for their laminin receptor avidity and mitochondrial localisation potential, upon functionalisation with the delocalised cation, triphenylphosphine. The laminin receptor dependent uptake and mitochondrial localisation of targeted T-Au(PDL-g-PEG) NPs were confirmed by ICP-OES and fluorescent microscopy. Their delivery of paclitaxel to the mitochondria of cancer cells elicited significant cytotoxicity especially in the human cervical carcinoma (HeLa) cell line, compared to the untargeted T-Au(PDL-g-PEG) and free drugs. Mechanistic studies implicated caspase dependent apoptosis as the mechanism of cell death. Our findings demonstrate the capacity of T-Au-[PDL-PEG] NPs to preferentially localize in the tumour mitochondria, and confirms the potential impact of subcellular targeting, especially to the mitochondria in cancer cells for an improvement in the therapeutic indices of these drugs.

Background: Over the past decade, there has been a surge in the number of mitochondrialactive therapeutics for conditions ranging from cancer to aging. Subcellular targeting interventions can modulate adverse intracellular processes unique to the compartments within the cell. However, there is a dearth of reviews focusing on mitochondrial nano-delivery, and this review seeks to fill this gap with regards to nanotherapeutics of the mitochondria., Methods: Besides its potential for a higher therapeutic index than targeting at the tissue and cell levels, subcellular targeting takes into account the limitations of systemic drug administration and significantly improves pharmacokinetics. Hence, an extensive literature review was undertaken and salient information was compiled in this review., Results: From literature, it was evident that nanoparticles with their tunable physicochemical properties have shown potential for efficient therapeutic delivery, with several nanomedicines already approved by the FDA and others in clinical trials. However, strategies for the development of nanomedicines for subcellular targeting are still emerging, with an increased understanding of dysfunctional molecular processes advancing the development of treatment modules. For optimal delivery, the design of an ideal carrier for subcellular delivery must consider the features of the diseased microenvironment. The functional and structural features of the mitochondria in the diseased state are highlighted and potential nano-delivery interventions for treatment and diagnosis are discussed., Conclusion: This review provides an insight into recent advances in subcellular targeting, with a focus on en route barriers to subcellular targeting. The impact of mitochondrial dysfunction in the aetiology of certain diseases is highlighted, and potential therapeutic sites are identified., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The biodegradable polymer, poly(lactide-co-glycolide) is a popular polymer of choice in many nanotherapeutic studies. Herein, we report on the synthesis and evaluation of four chitosan stabilized poly(lactide-co-glycolide) nanoparticles with and without coating with gold, and the targeting ligand, folic acid, as potential non-viral gene delivery vectors. The poly(lactide-co-glycolide) nanoparticles were synthesized via nanoprecipitation/solvent evaporation method in conjunction with the surface functionalizing folic acid and chitosan. The physiochemical properties (morphology, particle size, zeta potential, folic acid/chitosan presence, DNA binding), and biological properties (nuclease protection, in vitro cytotoxicity and transfection potential in human kidney, hepatocellular carcinoma and breast adenocarcinoma cells), of all four gene bound nanoparticles were evaluated. Gel retardation assays confirmed that all the nanoparticles were able to successfully bind the reporter plasmid, pCMV-luc DNA at varying weight ratios. The gold-folate-poly(lactide-co-glycolide) nanoplexes with the highest binding efficiency (w/w ratio 4:1), best protected the plasmid DNA as evidenced from the nuclease protection assays. Furthermore, these nanoplexes presented as spherical particles with an average particle size of 199.4 nm and zeta potential of 35.7 mV. Folic acid and chitosan functionalization of the nanoparticles was confirmed by attenuated total reflection-Fourier transform infrared spectroscopy. All nanoplexes maintained over 90% cell viability in all cell lines investigated. Interestingly, the gold-folate-poly(lactide-co-glycolide) nanoplexes showed a greater transgene activity in the hepatic and breast cancer cells compared to the other nanocomplexes in the same cell lines. The favorable size, colloidal stability, low cytotoxicity, significant transgene expression, and nuclease protection ability in vitro, all provide support for the use of gold-folate-poly(lactide-co-glycolide) nanoplexes in future gene therapy applications.