Lipid-Based Delivery Systems for Flavonoids and Flavonolignans: Liposomes, Nanoemulsions, and Solid Lipid Nanoparticles.

Herbal chemicals with a long history in medicine have attracted a lot of attention. Flavonolignans and flavonoids are considered as two classes of the above-mentioned compounds with different functional groups which exhibit several therapeutic capabilities such as antimicrobial, anti-inflammatory, antioxidant, antidiabetic, and anticancer activities. Based on the studies, high hydrophobic properties of the aforementioned compounds limit their bioavailability inside the human body and restrict their wide application. Nanoscale formulations such as solid lipid nanoparticles, liposomes, and other types of lipid-based delivery systems have been introduced to overcome the above-mentioned challenges. This approach allows the aforementioned hydrophobic therapeutic compounds to be encapsulated between hydrophobic structures, resulting in improving their bioavailability. The above-mentioned enhanced delivery system improves delivery to the targeted sites and reduces the daily required dosage. Lowering the required daily dose improves the performance of the drug by diminishing its side effects on non-targeted tissues. The present study aims to highlight the recent improvements in implementing lipid-based nanocarriers to deliver flavonolignans and flavonoids.

Next-Generation Hydrogels as Biomaterials for Biomedical Applications: Exploring the Role of Curcumin.

Since the first report on the pharmacological activity of curcumin in 1949, enormous amounts of research have reported diverse activities for this natural polyphenol found in the dietary spice turmeric. However, curcumin has not yet been used for human application as an approved drug. The clinical translation of curcumin has been hampered due to its low solubility and bioavailability. The improvement in bioavailability and solubility of curcumin can be achieved by its formulation using drug delivery systems. Hydrogels with their biocompatibility and low toxicity effects have shown a substantial impact on the successful formulation of hydrophobic drugs for human clinical trials. This review focuses on hydrogel-based delivery systems for curcumin and describes its applications as anti-cancer as well as wound healing agents.

Tannic acid: a versatile polyphenol for design of biomedical hydrogels.

Tannic acid (TA), a natural polyphenol, is a hydrolysable amphiphilic tannin derivative of gallic acid with several galloyl groups in its structure. Tannic acid interacts with various organic, inorganic, hydrophilic, and hydrophobic materials such as proteins and polysaccharides via hydrogen bonding, electrostatic, coordinative bonding, and hydrophobic interactions. Tannic acid has been studied for various biomedical applications as a natural crosslinker with anti-inflammatory, antibacterial, and anticancer activities. In this review, we focus on TA-based hydrogels for biomaterials engineering to help biomaterials scientists and engineers better realize TA's potential in the design and fabrication of novel hydrogel biomaterials. The interactions of TA with various natural or synthetic compounds are deliberated, discussing parameters that affect TA-material interactions thus providing a fundamental set of criteria for utilizing TA in hydrogels for tissue healing and regeneration. The review also discusses the merits and demerits of using TA in developing hydrogels either through direct incorporation in the hydrogel formulation or indirectly via immersing the final product in a TA solution. In general, TA is a natural bioactive molecule with diverse potential for engineering biomedical hydrogels.

Interleukin-12 Plasmid DNA Delivery by N-[(2-Hydroxy-3-trimethylammonium)propyl]chitosan-Based Nanoparticles.

Cationic polysaccharides are capable of forming polyplexes with nucleic acids and are considered promising polymeric gene carriers. The objective of this study was to evaluate the transfection efficiency and cytotoxicity of N-[(2-hydroxy-3-trimethylammonium)propyl] chitosan salt (HTCS), a quaternary ammonium derivative of chitosan (CS), which benefits from non-ionizable positive charges. In this work, HTCS with a full quaternization of amino groups and a molar mass of 130,000 g·mol-1 was synthesized to use for delivery of a plasmid encoding the interleukin-12 (IL-12) gene. Thus, a polyplex based on HTCS and the IL-12 plasmid was prepared and then was characterized in terms of particle size, zeta potential, plasmid condensation ability, and protection of the plasmid against enzymatic degradation. We showed that HTCS was able to condense the IL-12 plasmid by the formation of polyplexes in the range of 74.5 ± 0.75 nm. The level of hIL-12 production following the transfection of the cells with HTCS polyplexes at a C/P ratio of 8:1 was around 4.8- and 2.2-fold higher than with CS and polyethylenimine polyplexes, respectively. These findings highlight the role of HTCS in the formation of polyplexes for the efficient delivery of plasmid DNA.

Dexamethasone: Insights into Pharmacological Aspects, Therapeutic Mechanisms, and Delivery Systems.

Dexamethasone (DEX) has been widely used to treat a variety of diseases, including autoimmune diseases, allergies, ocular disorders, cancer, and, more recently, COVID-19. However, DEX usage is often restricted in the clinic due to its poor water solubility. When administered through a systemic route, it can elicit severe side effects, such as hypertension, peptic ulcers, hyperglycemia, and hydro-electrolytic disorders. There is currently much interest in developing efficient DEX-loaded nanoformulations that ameliorate adverse disease effects inhibiting advancements in scientific research. Various nanoparticles have been developed to selectively deliver drugs without destroying healthy cells or organs in recent years. In the present review, we have summarized some of the most attractive applications of DEX-loaded delivery systems, including liposomes, polymers, hydrogels, nanofibers, silica, calcium phosphate, and hydroxyapatite. This review provides our readers with a broad spectrum of nanomedicine approaches to deliver DEX safely.

Diosgenin: Mechanistic Insights on its Anti-inflammatory Effects.

Diosgenin (DG), a well-known steroid saponin, has shown anti-inflammatory effects. This review was aimed to discuss all published literature concerning the anti-inflammatory effects of diosgenin. Based on the modulatory impact of DG on the NF-κB pathway, its supplementation is associated with downregulation of the NF-κB pathway and TGF-ß, resulting in inhibition of inflammation. It appears that upstream modulators of NF-κB signaling pathways such as Tlrs and downstream mediators include iNOS and COX-2, leading to the inhibition of the inflammatory response and development of pathological conditions. Due to the low toxicity of the herbal compounds, the risk of the side effects of DG use for the management of inflammatory disorders such as asthma, rheumatism, rhinitis, and arthritis is lower than that of synthetic glucocorticoids. It has been shown that regulation of NF-κB and oxidative stress signaling pathways by DG is beneficial against cardiotoxicity induced by chemotherapeutic agents such as doxorubicin.

Isoforms of autophagy-related proteins: role in glioma progression and therapy resistance.

Autophagy is the process of recycling and utilization of degraded organelles and macromolecules in the cell compartments formed during the fusion of autophagosomes with lysosomes. During autophagy induction the healthy and tumor cells adapt themselves to harsh conditions such as cellular stress or insufficient supply of nutrients in the cell environment to maintain their homeostasis. Autophagy is currently seen as a form of programmed cell death along with apoptosis and necroptosis. In recent years multiple studies have considered the autophagy as a potential mechanism of anticancer therapy in malignant glioma. Although, subsequent steps in autophagy development are known and well-described, on molecular level the mechanism of autophagosome initiation and maturation using autophagy-related proteins is under investigation. This article reviews current state about the mechanism of autophagy, its molecular pathways and the most recent studies on roles of autophagy-related proteins and their isoforms in glioma progression and its treatment.

Chitosan: A versatile bio-platform for breast cancer theranostics.

Breast cancer is considered one of the utmost neoplastic diseases globally, with a high death rate of patients. Over the last decades, many approaches have been studied to early diagnose and treat it, such as chemotherapy, hormone therapy, immunotherapy, and MRI and biomarker tests; do not show the optimal efficacy. These existing approaches are accompanied by severe side effects, thus recognizing these challenges, a great effort has been done to find out the new remedies for breast cancer. Main finding: Nanotechnology opened a new horizon to the treatment of breast cancer. Many nanoparticulate platforms for the diagnosis of involved biomarkers and delivering antineoplastic drugs are under either clinical trials or just approved by the Food and Drug Administration (FDA). It is well known that natural phytochemicals are successfully useful to treat breast cancer because these natural compounds are safer, available, cheaper, and have less toxic effects. Chitosan is a biocompatible and biodegradable polymer. Further, it has outstanding features, like chemical functional groups that can easily modify our interest with an exceptional choice of promising applications. Abundant studies were directed to assess the chitosan derivative-based nanoformulation's abilities in delivering varieties of drugs. However, the role of chitosan in diagnostics and theranostics not be obligated. The present servey will discuss the application of chitosan as an anticancer drug carrier such as tamoxifen, doxorubicin, paclitaxel, docetaxel, etc. and also, its role as a theranostics (i.e. photo-responsive and thermo-responsive) moieties. The therapeutic and theranostic potential of chitosan in cancer is promising and it seems that to have a good potential to get to the clinic.

Editing SOX Genes by CRISPR-Cas: Current Insights and Future Perspectives.

Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) and its associated proteins (Cas) is an adaptive immune system in archaea and most bacteria. By repurposing these systems for use in eukaryote cells, a substantial revolution has arisen in the genome engineering field. In recent years, CRISPR-Cas technology was rapidly developed and different types of DNA or RNA sequence editors, gene activator or repressor, and epigenome modulators established. The versatility and feasibility of CRISPR-Cas technology has introduced this system as the most suitable tool for discovering and studying the mechanism of specific genes and also for generating appropriate cell and animal models. SOX genes play crucial roles in development processes and stemness. To elucidate the exact roles of SOX factors and their partners in tissue hemostasis and cell regeneration, generating appropriate in vitro and in vivo models is crucial. In line with these premises, CRISPR-Cas technology is a promising tool for studying different family members of SOX transcription factors. In this review, we aim to highlight the importance of CRISPR-Cas and summarize the applications of this novel, promising technology in studying and decoding the function of different members of the SOX gene family.

Photodynamic therapy for leishmaniasis: Recent advances and future trends.

Leishmaniasis has infected more than 12 million people worldwide. This neglected tropical disease, causing 20,000-30,000 deaths per year, is a global health problem. The emergence of resistant parasites and serious side effects of conventional therapies has led to the search for less toxic and non-invasive alternative treatments. Photodynamic therapy is a promising therapeutic strategy to produce reactive oxygen species for the treatment of leishmaniasis. In this regard, natural and synthetic photosensitizers such as curcumin, hypericin, 5-aminolevulinic acid, phthalocyanines, phenothiazines, porphyrins, chlorins and nanoparticles have been applied. In this review, the recent advances on using photodynamic therapy for treating Leishmania species have been reviewed.

Evaluation of Bacillus velezensis for Biological Control of Rhizoctonia solani in Bean by Alginate/Gelatin Encapsulation Supplemented with Nanoparticles.

Plant growth promoting rhizobacteria (PGPR) are a group of bacteria that can increase plant growth; but due to unfavorable environmental conditions, PGPR are biologically unstable and their survival rates in soil are limited. Therefore, the suitable application of PGPR as a plant growth stimulation is one of the significant challenges in agriculture. This study presents an intelligent formulation based on Bacillus velezensis VRU1 encapsulation enriched with nanoparticles that was able to control Rhizoctonia solani on the bean. The spherical structure of the capsule was observed based on the Scanning Electron Microscope image. Results indicated that with increasing gelatin concentration, the swelling ratio and moisture content were increased; and since the highest encapsulation efficiency and bacterial release were observed at a gelatin concentration of 1.5%, this concentration was considered in mixture with alginate for encapsulation. The application of this formulation which is based on encapsulation and nanotechnology appears to be a promising technique to deliver PGPR in soil and is more effective for plants.

Biopolymers for Biological Control of Plant Pathogens: Advances in Microencapsulation of Beneficial Microorganisms.

The use of biofertilizers, including biocontrol agents such as Pseudomonas and Bacillus in agriculture can increase soil characteristics and plant acquisition of nutrients and enhancement the efficiency of manure and mineral fertilizer. Despite the problems that liquid and solid formulations have in maintaining the viability of microbial agents, encapsulation can improve their application with extended shelf-life, and controlled release from formulations. Research into novel formulation methods especially encapsulation techniques has increased in recent years due to the mounting demand for microbial biological control. The application of polymeric materials in agriculture has developed recently as a replacement for traditional materials and considered an improvement in technological processes in the growing of crops. This study aims to overview of types of biopolymers and methods used for encapsulation of living biological control agents, especially microbial organisms.

Antidiabetic Properties of Curcumin: Insights on New Mechanisms.

Plant extracts have been used to treat a wide range of human diseases. Curcumin, a bioactive polyphenol derived from Curcuma longa L., exhibits therapeutic effects against diabetes while only negligible adverse effects have been observed. Antioxidant and anti-inflammatory properties of curcumin are the main and well-recognized pharmacological effects that might explain its antidiabetic effects. Additionally, curcumin may regulate novel signaling molecules and enzymes involved in the pathophysiology of diabetes, including glucagon-like peptide-1, dipeptidyl peptidase-4, glucose transporters, alpha-glycosidase, alpha-amylase, and peroxisome proliferator-activated receptor gamma (PPARγ). Recent findings from in vitro and in vivo studies on novel signaling pathways involved in the potential beneficial effects of curcumin for the treatment of diabetes are discussed in this review.

Small nucleolar RNA host genes promoting epithelial-mesenchymal transition lead cancer progression and metastasis.

The small nucleolar RNA host genes (SNHGs) belong to the long non-coding RNAs and are reported to be able to influence all three levels of cellular information-bearing molecules, that is, DNA, RNA, and proteins, resulting in the generation of complex phenomena. As the host genes of the small nucleolar RNAs (snoRNAs), they are commonly localized in the nucleolus, where they exert multiple regulatory functions orchestrating cellular homeostasis and differentiation as well as metastasis and chemoresistance. Indeed, worldwide literature has reported their involvement in the epithelial-mesenchymal transition (EMT) of different histotypes of cancer, being able to exploit peculiar features, for example, the possibility to act both in the nucleus and the cytoplasm. Moreover, SNHGs regulation is a fundamental topic to better understand their role in tumor progression albeit such mechanism is still debated. Here, we reviewed the biological functions of SNHGs in particular in the EMT process and discussed the perspectives for new cancer therapies.

Paving the Road Toward Exploiting the Therapeutic Effects of Ginsenosides: An Emphasis on Autophagy and Endoplasmic Reticulum Stress.

Programmed cell death processes such as apoptosis and autophagy strongly contribute to the onset and progression of cancer. Along with these lines, modulation of cell death mechanisms to combat cancer cells and elimination of resistance to apoptosis is of great interest. It appears that modulation of autophagy and endoplasmic reticulum (ER) stress with specific agents would be beneficial in the treatment of several disorders. Interestingly, it has been suggested that herbal natural products may be suitable candidates for the modulation of these processes due to few side effects and significant therapeutic potential. Ginsenosides are derivatives of ginseng and exert modulatory effects on the molecular mechanisms associated with autophagy and ER stress. Ginsenosides act as smart phytochemicals that confer their effects by up-regulating ATG proteins and converting LC3-I to -II, which results in maturation of autophagosomes. Not only do ginsenosides promote autophagy but they also possess protective and therapeutic properties due to their capacity to modulate ER stress and up- and down-regulate and/or dephosphorylate UPR transducers such as IRE1, PERK, and ATF6. Thus, it would appear that ginsenosides are promising agents to potentially restore tissue malfunction and possibly eliminate cancer.

The role of nanotechnology in current COVID-19 outbreak.

COVID-19 has recently become one of the most challenging pandemics of the last century with deadly outcomes and a high rate of reproduction number. It emphasizes the critical need for the designing of efficient vaccines to prevent virus infection, early and fast diagnosis by the high sensitivity and selectivity diagnostic kits, and effective antiviral and protective therapeutics to decline and eliminate the viral load and side effects derived from tissue damages. Therefore, non-toxic antiviral nanoparticles (NPs) have been under development for clinical application to prevent and treat COVID-19. NPs showed great promise to provide nano vaccines against viral infections. Here, we discuss the potentials of NPs that may be applied as a drug itself or as a platform for the aim of drug and vaccine repurposing and development. Meanwhile, the advanced strategies based on NPs to detect viruses will be described with the goal of encouraging scientists to design effective and cost-benefit nanoplatforms for prevention, diagnosis, and treatment.

Biological and Therapeutic Effects of Troxerutin: Molecular Signaling Pathways Come into View.

Flavonoids consist a wide range of naturally occurring compounds which are exclusively found in different fruits and vegetables. These medicinal herbs have a number of favourable biological and therapeutic activities such as antioxidant, neuroprotective, renoprotective, anti-inflammatory, anti-diabetic and anti-tumor. Troxerutin, also known as vitamin P4, is a naturally occurring flavonoid which is isolated from tea, coffee and cereal grains as well as vegetables. It has a variety of valuable pharmacological and therapeutic activities including antioxidant, anti-inflammatory, anti-diabetic and anti-tumor. These pharmacological impacts have been demonstrated in in vitro and in vivo studies. Also, clinical trials have revealed the efficacy of troxerutin for management of phlebocholosis and hemorrhoidal diseases. In the present review, we focus on the therapeutic effects and biological activities of troxerutin as well as its molecular signaling pathways.

Anti-Inflammatory Activity of Melatonin: a Focus on the Role of NLRP3 Inflammasome.

Melatonin is a hormone of the pineal gland that contributes to the regulation of physiological activities, such as sleep, circadian rhythm, and neuroendocrine processes. Melatonin is found in several plants and has pharmacological activities including antioxidant, anti-inflammatory, hepatoprotective, cardioprotective, and neuroprotective. It also has shown therapeutic efficacy in treatment of cancer and diabetes. Melatonin affects several molecular pathways to exert its protective effects. The NLRP3 inflammasome is considered a novel target of melatonin. This inflammasome contributes to enhanced level of IL-1ß, caspase-1 activation, and pyroptosis stimulation. The function of NLRP3 inflammasome has been explored in various diseases, including cancer, diabetes, and neurological disorders. By inhibiting NLRP3, melatonin diminishes inflammation and influences various molecular pathways, such as SIRT1, microRNA, long non-coding RNA, and Wnt/ß-catenin. Here, we discuss these molecular pathways and suggest that melatonin-induced inhibition of NLRP3 should be advanced in disease therapy.

Anti-tumor activity of resveratrol against gastric cancer: a review of recent advances with an emphasis on molecular pathways.

Gastric cancer (GC) is one of the most common cancers with high malignancy. In spite of the great development in diagnostic tools and application of anti-tumor drugs, we have not witnessed a significant increase in the survival time of patients with GC. Multiple studies have revealed that Wnt, Nrf2, MAPK, and PI3K/Akt signaling pathways are involved in GC invasion. Besides, long non-coding RNAs and microRNAs function as upstream mediators in GC malignancy. GC cells have acquired resistance to currently applied anti-tumor drugs. Besides, combination therapy is associated with higher anti-tumor activity. Resveratrol (Res) is a non-flavonoid polyphenol with high anti-tumor activity used in treatment of various cancers. A number of studies have demonstrated the potential of Res in regulation of molecular pathways involved in cancer malignancy. At the present review, we show that Res targets a variety of signaling pathways to induce apoptotic cell death and simultaneously, to inhibit the migration and metastasis of GC cells.