Current Pharmaceutical Design - Volume 29, Issue 39, 2023

Polyhydroxyalkanoates (PHAs) have been a current research topic for many years. PHAs are biopolymers produced by bacteria under unfavorable growth conditions. They are biomaterials that exhibit a variety of properties, including biocompatibility, biodegradability, and high mechanical strength, making them suitable for future applications. This review aimed to provide general information on PHAs, such as their structure, classification, and parameters that affect the production process. In addition, the most commonly used bacterial strains that produce PHAs are highlighted, and details are provided on the type of carbon source used and how to optimize the parameters for bioprocesses. PHAs present a challenge to researchers because a variety of parameters affect biosynthesis, including the variety of carbon sources, bacterial strains, and culture media. Nevertheless, PHAs represent an opportunity to replace plastics, because they can be produced quickly and at a relatively low cost. With growing environmental concerns and declining oil reserves, polyhydroxyalkanoates are a potential replacement for nonbiodegradable polymers. Therefore, the study of PHA production remains a hot topic, as many substrates can be used as carbon sources. Both researchers and industry are interested in facilitating the production, commercialization, and application of PHAs as potential replacements for nonbiodegradable polymers. The fact that they are biocompatible, environmentally biodegradable, and adaptable makes PHAs one of the most important materials available in the market. They are preferred in various industries, such as agriculture (for bioremediation of oil-polluted sites, minimizing the toxicity of pollutants, and environmental impact) or medicine (as medical devices). The various bioprocess technologies mentioned earlier will be further investigated, such as the carbon source (to obtain a biopolymer with the lowest possible cost, such as glucose, various fatty acids, and especially renewable sources), pretreatment of the substrate (to increase the availability of the carbon source), and supplementation of the growth environment with different substances and minerals). Consequently, the study of PHA production remains a current topic because many substrates can be used as carbon sources. Obtaining PHA from renewable substrates (waste oil, coffee grounds, plant husks, etc.) contributes significantly to reducing PHA costs. Therefore, in this review, pure bacterial cultures (Bacillus megaterium, Ralstonia eutropha, Cupriavidus necator, and Pseudomonas putida) have been investigated for their potential to utilize by-products as cheap feedstocks. The advantage of these bioprocesses is that a significant amount of PHA can be obtained using renewable carbon sources. The main disadvantage is that the chemical structure of the obtained biopolymer cannot be determined in advance, as is the case with bioprocesses using a conventional carbon source. Polyhydroxyalkanoates are materials that can be used in many fields, such as the medical field (skin grafts, implantable medical devices, scaffolds, drug-controlled release devices), agriculture (for polluted water cleaning), cosmetics and food (biodegradable packaging, gentle biosurfactants with suitable skin for cosmetics), and industry (production of biodegradable biopolymers that replace conventional plastic). Nonetheless, PHA biopolymers continue to be researched and improved and play an important role in various industrial sectors. The properties of this material allow its use as a biodegradable material in the cosmetics industry (for packaging), in the production of biodegradable plastics, or in biomedical engineering, as various prostheses or implantable scaffolds.

Photodynamic therapy (PDT) is an innovative, non-invasive method of treating cancer that uses light-activated photosensitizers to create reactive oxygen species (ROS). However, challenges associated with the limited penetration depth of light and the need for precise control over photosensitizer activation have hindered its clinical translation. Nanomedicine, particularly gold nanobiostructures, offers promising solutions to overcome these limitations. This paper reviews the advancements in PDT and nanomedicine, focusing on applying antibody-modified gold nanobiostructures as multifunctional platforms for enhanced PDT efficacy and improved cancer treatment outcomes. The size, shape, and composition of gold nanobiostructures can significantly influence their PDT efficacy, making synthetic procedures crucial. Functionalizing the surface of gold nanobiostructures with various molecules, such as antibodies or targeting agents, bonding agents, PDT agents, photothermal therapy (PTT) agents, chemo-agents, immunotherapy agents, and imaging agents, allows composition modification. Integrating gold nanobiostructures with PDT holds immense potential for targeted cancer therapy. Antibody-modified gold nanobiostructures, in particular, have gained significant attention due to their tunable plasmonic characteristics, biocompatibility, and surface functionalization capabilities. These multifunctional nanosystems possess unique properties that enhance the efficacy of PDT, including improved light absorption, targeted delivery, and enhanced ROS generation. Passive and active targeting of gold nanobiostructures can enhance their localization near cancer cells, leading to efficient eradication of tumor tissues upon light irradiation. Future research and clinical studies will continue to explore the potential of gold nanobiostructures in PDT for personalized and effective cancer therapy. The synthesis, functionalization, and characterization of gold nanobiostructures, their interaction with light, and their impact on photosensitizers' photophysical and photochemical properties, are important areas of investigation. Strategies to enhance targeting efficiency and the evaluation of gold nanobiostructures in vitro and in vivo studies will further advance their application in PDT. The integrating antibody-modified gold nanobiostructures in PDT represents a promising strategy for targeted cancer therapy. These multifunctional nanosystems possess unique properties that enhance PDT efficacy, including improved light absorption, targeted delivery, and enhanced ROS generation. Continued research and development in this field will contribute to the advancement of personalized and effective cancer treatment approaches.

Background: Insulin resistance is one of the main factors that lead to the development of type 2 diabetes mellitus (T2DM). The effect of alkaloids on insulin resistance has been extensively examined according to multiple scientific researches. Objective: In this work, we aimed to summarize the interesting results from preclinical and clinical studies that assessed the effects of natural alkaloids (berberine, nigelladine A, piperine, trigonelline, capsaicin, nuciferine, evodiamine, mahanine, and magnoflorine) on impaired insulin sensitivity and worsened insulin resistance, which play a pivotal role in the pathogenesis of type 2 diabetes. Methods: In the current review, PubMed, ScienceDirect, Springer, and Google Scholar databases were used. The inclusion criteria were based on the following keywords and phrases: insulin sensitivity, insulin resistance, alkaloids and insulin resistance, alkaloids and type 2 diabetes, mechanisms of action, and alkaloids. Results: The outcomes reported in this review demonstrated that the selected alkaloids increased insulin sensitivity and reduced insulin resistance in vitro and in vivo evidence, as well as in clinical trials, through improving insulin-signaling transduction mainly in hepatocytes, myocytes, and adipocytes, both at cellular and molecular levels. Insulin signaling components (InsR, IRS-1, PI3K, Akt, etc.), protein kinases and phosphatases, receptors, ion channels, cytokines, adipokines, and microRNAs, are influenced by alkaloids at transcriptional and translational levels, also in terms of function (activity and/or phosphorylation). Multiple perturbations associated with insulin resistance, such as ectopic lipid accumulation, inflammation, ER stress, oxidative stress, mitochondrial dysfunction, gut microbiota dysbiosis, and β-cell failure, are reversed after treatment with alkaloids. Furthermore, various indices and tests are employed to assess insulin resistance, including the Matsuda index, insulin sensitivity index (ISI), oral glucose tolerance test (OGTT), and insulin tolerance test (ITT), which are all enhanced by alkaloids. These improvements extend to fasting blood glucose, fasting insulin, and HbA1c levels as well. Additionally, the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) and the Homeostasis Model Assessment of β-cell function (HOMA-β) are recognized as robust markers of insulin sensitivity and β-cell function, and it is noteworthy that alkaloids also lead to improvements in these two markers. Conclusion: Based on the findings of the current review, alkaloids may serve as both preventive and curative agents for metabolic disorders, specifically type 2 diabetes. Nonetheless, there is an urgent need for additional clinical trials to explore the potential benefits of alkaloids in both healthy individuals and those with type 2 diabetes. Additionally, it is crucial to assess any possible side effects and interactions with antidiabetic drugs.

One-third of people will be diagnosed with cancer at some point in their lives, making it the second leading cause of death globally each year after cardiovascular disease. The complex anticancer molecular mechanisms have been understood clearly with the advent of improved genomic, proteomic, and bioinformatics. Our understanding of the complex interplay between numerous genes and regulatory genetic components within cells explaining how this might lead to malignant phenotypes has greatly expanded. It was discovered that epigenetic resistance and a lack of multitargeting drugs were highlighted as major barriers to cancer treatment, spurring the search for innovative anticancer treatments. It was discovered that epigenetic resistance and a lack of multitargeting drugs were highlighted as major barriers to cancer treatment, spurring the search for innovative anticancer treatments. Many popular anticancer drugs, including irinotecan, vincristine, etoposide, and paclitaxel, have botanical origins. Actinomycin D and mitomycin C come from bacteria, while bleomycin and curacin come from marine creatures. However, there is a lack of research evaluating the potential of algae-based anticancer treatments, especially in terms of their molecular mechanisms. Despite increasing interest in the former, and the promise of the compounds to treat tumours that have been resistant to existing treatment, pharmaceutical development of these compounds has lagged. Thus, the current review focuses on the key algal sources that have been exploited as anticancer therapeutic leads, including their biological origins, phytochemistry, and the challenges involved in converting such leads into effective anticancer drugs.

Orthodontic treatment typically requires an extended duration of 1-2 years to complete the treatment. Accelerating the rate of tooth movement during orthodontic treatment is essential for shortening the overall treatment duration. After the completion of orthodontic treatment, a prominent concern arises in the form of orthodontic relapse, where the teeth tend to revert to their original positions. This issue affects approximately 60% of the global population, underscoring the importance of implementing effective measures to address orthodontic relapse. An approach in this regard involves the targeted administration of herbal and synthetic drugs applied directly to the specific area of interest to facilitate tooth movement and prevent orthodontic relapse. Apart from this, researchers are investigating the feasibility of utilizing different types of nanoparticles to improve the process of orthodontic tooth movement. In recent years, there has been a noticeable increase in the number of studies examining the effects of various drugs on orthodontics. However, the currently available literature does not provide significant evidence relating to orthodontic tooth movement. In this review, the authors provide valuable information about the drugs and nanomaterials that are capable of further enhancing the rate of orthodontic tooth movement and reducing the risk of orthodontic relapse. However, a notable hurdle remains, i.e., there is no marketed formulation available that can enhance orthodontic tooth movement and reduce treatment time. Therefore, researchers should try herbal-synthetic approaches to achieve a synergistic effect that can enhance orthodontic tooth movement. In this nutshell, there is an urgent need to develop a non-invasive, patient-compliant, and cost-effective formulation that will provide quality treatment and ultimately reduce the treatment time. Another critical issue is orthodontic relapse, which can be addressed by employing drugs that slow down osteoclastogenesis, thereby preventing tooth movement after treatment. Nevertheless, extensive research is still required to overcome this challenge in the future.