Ekram Alias

Mitochondrial dysfunction plays a central role in cardiac aging. Damaged mitochondria release excessive free radicals from the electron transport chain (ETC), leading to an increased production of reactive oxygen species (ROS). The accumulation of ROS, together with impaired ROS clearance mechanisms, results in oxidative stress, further disrupts mitochondrial dynamics, and diminishes bioenergetic capacity. Furthermore, the dysfunctional mitochondria exhibit an impaired endogenous antioxidant system, exacerbating this imbalance. These alterations drive the structural and functional deterioration of the aging heart, positioning mitochondria at the center of mechanisms underlying age-associated cardiovascular decline. In this review, we summarize the current evidence on how mitochondrial oxidative stress, mutations on mitochondrial DNA (mtDNA), and disruptions in the fission—fusion balance contribute to cardiomyocyte aging. This review also explores ways to mitigate oxidative stress, particularly with mitochondria-targeted antioxidants, and discusses the emerging potential of mitochondrial transplantation to replace dysfunctional mitochondria.

Introduction: The xanthophyll carotenoid astaxanthin is well-known for its potent antioxidant properties, which are superior to those of other antioxidants such as vitamins C and E. However, this highly hydrophobic compound has low solubility and poor oral bioavailability, limiting its efficacy and clinical application. To address these pharmacokinetic challenges, nanostructured lipid carriers (NLC) have been proposed as potential lipid-based drug carriers for the oral delivery of astaxanthin owing to their excellent biocompatibility, stability, and efficient drug loading capacity. Purpose: In this study, we aimed to develop an NLC using cocoa butter and palm oil for astaxanthin encapsulation, and to optimize the nanoformulation by employing Response Surface Methodology (RSM), a statistical approach. Methods: Three-factor Central Composite Design (CCD) in RSM was used to understand the effect of independent variables on response variables. The size, polydispersity index, and encapsulation efficiency of the astaxanthin-loaded NLC were also characterized. Results: Findings of this study indicated that the mass of cocoa butter, palm oil and Tween 80 influenced the particle size, polydispersity index and zeta potential of NLC. The experimental determination of NLC did not differ significantly from the predicted RSM outcomes with size, polydispersity index and zeta potential of 254.42 ± 3.91 nm, 0.38 ± 0.01 and − 30.54 ± 0.85 mV, respectively. This nanoparticulate system showed an excellent astaxanthin entrapment efficiency of 99.69± 0.0003%. Conclusion: The ideal combination of each composition in the NLC formulation yielded nanoparticles with desirable particle size, polydispersity index, and zeta potential for efficient oral delivery of astaxanthin. Plain Language Summary: Astaxanthin is a natural antioxidant that is much stronger than vitamins C and E. However, it does not dissolve well in water and is poorly absorbed when administered orally, which limits its usefulness. To overcome this drawback, this study explored the use of nanostructured lipid carriers (NLC), which are tiny fat-based particles, to improve astaxanthin movement in the body. An NLC formulation was developed using cocoa butter and palm oil. The optimization process was conducted using a statistical method called Response Surface Methodology (RSM) to determine the best combination of ingredients. Different amounts of cocoa butter, palm oil, and a stabilizer (Tween 80) can affect the size, stability, and ability of the particles to hold astaxanthin. The results also showed that the optimized NLC had a small and uniform size (approximately 254 nm), stable dispersion (zeta potential of − 30.54 mV), and highly efficient astaxanthin trapping (99.69%). In conclusion, we successfully developed an NLC formulation that can efficiently carry astaxanthin, potentially improving its absorption and effectiveness when used as a supplement or medicine.

Background/Objective: The tocotrienol-rich fraction (TRF) is a lipid-soluble vitamin that has good antioxidant and anti-inflammatory properties. The TRF is widely studied as a potential treatment for various diseases, including bone diseases. However, its application is limited due to its poor oral bioavailability profile, warranting an innovative approach to overcome its pharmacokinetic limitations. Recently, the nano-hydroxyapatite (nHA) has been investigated as a drug delivery vehicle for various drugs and active compounds owing to its excellent biocompatibility, biodegradability, and osteogenic properties. The nHA is also a well-known biomaterial which has chemical and structural similarities to bone minerals. Hence, we aim to explore the use of the nHA as a potential nanocarrier for the TRF. Methods: In this study, we develop and optimize the formulation of an nHA-encapsulating TRF (nHA/TRF) by employing the response surface methodology (RSM). Results: RSM outcomes reveal that the mass of the nHA, the concentration of the TRF, and the incubation time have a significant effect on the particle size, zeta potential, and encapsulation efficiency of the nHA/TRF. The outcomes for the optimized formulation are not significantly different from the predicted RSM outcomes. The optimized nHA/TRF formulation is freeze-dried and results in an average particle size of ~270 nm, a negative zeta potential value of ~−20 mV, a polydispersity index of <0.4, and an encapsulation efficiency of ~18.1%. Transmission electron microscopy (TEM) shows that the freeze-dried nHA/TRF has a spherical structure. Conclusions: Taken together, the above findings indicate that the nHA may be established as a nanocarrier for efficient delivery of the TRF, as demonstrated by the promising physical properties.

Preclinical research on diabetes and obesity has been carried out in various animal models over the years. These animal models are developed from genetic manipulation that affects their body metabolism, chemical-induced procedures, diet alteration/modifications, or combinations of the aforementioned approaches. The diabetic and obesity animal models have allowed researchers to not only study the pathological aspect of the diseases but also enable them to screen and explore potential therapeutic compounds. Besides several widely known complications such as macrovascular diseases, diabetic neuropathy, nephropathy and retinopathy, type 2 diabetes mellitus is also known to affect bone health. There is also evidence to suggest obesity affects bone health. Therefore, continuous research needs to be conducted to find a remedy or solution to this matter. Previous literature reported evidence of bone loss in animal models of diabetes and obesity. These findings, as highlighted in this review, further augment the suggestion of an inter-relationship between diabetes, obesity and bone loss.

Osteoporosis, a metabolic bone disorder characterized by decreased bone mass per unit volume, poses a significant global health burden due to its association with heightened fracture risk and adverse impacts on patients’ quality of life. This review synthesizes the current understanding of the pathophysiological mechanisms underlying osteoporosis, with a focus on key regulatory pathways governing osteoblast and osteoclast activities. These pathways include RANK/RANKL/OPG, Wingless-int (Wnt)/β-catenin, and Jagged1/Notch1 signaling, alongside the involvement of parathyroid hormone (PTH) signaling, cytokine networks, and kynurenine in bone remodeling. Pharmacotherapeutic interventions targeting these pathways play a pivotal role in osteoporosis management. Anti-resorptive agents, such as bisphosphonates, estrogen replacement therapy/hormone replacement therapy (ERT/HRT), selective estrogen receptor modulators (SERMs), calcitonin, anti-RANKL antibodies, and cathepsin K inhibitors, aim to mitigate bone resorption. Conversely, anabolic agents, including PTH and anti-sclerostin drugs, stimulate bone formation. In addition to pharmacotherapy, nutritional supplementation with calcium, vitamin D, and vitamin K2 holds promise for osteoporosis prevention. However, despite the availability of therapeutic options, a substantial proportion of osteoporotic patients remain untreated, highlighting the need for improved clinical management strategies. This comprehensive review aims to provide clinicians and researchers with a mechanistic understanding of osteoporosis pathogenesis and the therapeutic mechanisms of existing medications. By elucidating these insights, this review seeks to inform evidence-based decision-making and optimize therapeutic outcomes for patients with osteoporosis.

Non-invasive prenatal testing was first discovered in 1988; it was primarily thought to be able to detect common aneuploidies, such as Patau syndrome (T13), Edward Syndrome (T18), and Down syndrome (T21). It comprises a simple technique involving the analysis of cell-free foetal DNA (cffDNA) obtained through maternal serum, using advances in next-generation sequencing. NIPT has shown promise as a simple and low-risk screening test, leading various governments and private organizations worldwide to dedicate significant resources towards its integration into national healthcare initiatives as well as the formation of consortia and research studies aimed at standardizing its implementation. This article aims to review the reliability of NIPT while discussing the current challenges prevalent among different communities worldwide.

In recent years, bone loss and its associated diseases have become a significant public health concern due to increased disability, morbidity, and mortality. Oxidative stress and bone loss are correlated, where oxidative stress suppresses osteoblast activity, resulting in compromised homeostasis between bone formation and resorption. This event causes upregulation of bone remodeling turnover rate with an increased risk of fractures and bone loss. Therefore, supplementation of antioxidants can be proposed to reduce oxidative stress, facilitate the bone remodeling process, suppress the initiation of bone diseases, and improve bone health. Astaxanthin (3,3′-dihydroxy-4-4′-diketo-β-β carotene), a potent antioxidant belonging to the xanthophylls family, is a potential ROS scavenger and could be a promising therapeutic nutraceutical possessing various pharmacological properties. In bone, astaxanthin enhances osteoblast differentiation, osteocytes numbers, and/or differentiation, inhibits osteoclast differentiation, cartilage degradation markers, and increases bone mineral density, expression of osteogenic markers, while reducing bone loss. In this review, we presented the up-to-date findings of the potential anabolic effects of astaxanthin on bone health in vitro, animal, and human studies by providing comprehensive evidence for its future clinical application, especially in treating bone diseases.

MicroRNAs are short, single-stranded ribonucleic acids expressed endogenously in the body to regulate gene expression at the post-translational level, with exogenous microRNA offering an attractive approach to therapy. Among the myriad microRNA candidates involved in controlling bone homeostasis and remodeling, microRNA 21 (miR21) is the most abundant. This paper discusses the studies conducted on the role and mechanism of human miR21 (hsa-miR21) in the regulation of bones and the various pathways mediated by miR21, and explores the feasibility of employing exogenous miR21 as a strategy for promoting osteogenesis. From the literature review, it was clear that miR21 plays a dual role in bone metabolism by regulating both bone formation and bone resorption. There is substantial evidence to date from both in vitro and in vivo studies that exogenous miR21 can successfully accelerate new bone synthesis in the context of bone loss due to injury or osteoporosis. This supports the exploration of applications of exogenous miR21 in bone regenerative therapy in the future.

Astaxanthin (3,3′-dihydroxy-4,4′-diketo-β-β carotene), which belongs to the xanthophyll class, has shown potential biological activity in in vitro and in vivo models including as a potent antioxidant, anti-lipid peroxidation and cardiovascular disease prevention agent. It is mainly extracted from an alga, Haematococcus pluvialis. As a highly lipid-soluble carotenoid, astaxanthin has been shown to have poor oral bioavailability, which limits its clinical applications. Recently, there have been several suggestions and the development of various types of nano-formulation, loaded with astaxanthin to enhance their bioavailability. The employment of nanoemulsions, liposomes, solid lipid nanoparticles, chitosan-based and PLGA-based nanoparticles as delivery vehicles of astaxanthin for nutritional supplementation purposes has proven a higher oral bioavailability of astaxanthin. In this review, we highlight the pharmacological properties, pharmacokinetics profiles and current developments of the nano-formulations of astaxanthin for its oral delivery that are believed to be beneficial for future applications. The limitations and future recommendations are also discussed in this review.

Changes in mitochondrial bioenergetics are believed to take place during osteoclastogenesis. This study aims to assess changes in mitochondrial bioenergetics and reactive oxygen species (ROS) levels during polyethylene (PE)-induced osteoclastogenesis in vitro. For this purpose, RAW264.7 cells were cultured for nine days and allowed to differentiate into osteoclasts in the presence of PE and RANKL. The total TRAP-positive cells, resorption activity, expression of osteoclast marker genes, ROS level, mitochondrial bioenergetics, glycolysis, and substrate utilization were measured. The effect of tocotrienols-rich fraction (TRF) treatment (50 ng/mL) on those parameters during PE-induced osteoclastogenesis was also studied. During PE-induced osteoclastogenesis, as depicted by an increase in TRAP-positive cells and gene expression of osteoclast-related markers, higher proton leak, higher extracellular acidification rate (ECAR), as well as higher levels of ROS and NADPH oxidases (NOXs) were observed in the differentiated cells. The oxidation level of some substrates in the differentiated group was higher than in other groups. TRF treatment significantly reduced the number of TRAP-positive osteoclasts, bone resorption activity, and ROS levels, as well as modulating the gene expression of antioxidant-related genes and mitochondrial function. In conclusion, changes in mitochondrial bioenergetics and substrate utilization were observed during PE-induced osteoclastogenesis, while TRF treatment modulated these changes.