Innovative Encapsulation Strategies for Food, Industrial, and Pharmaceutical Applications.

Bioactive metabolites obtained from fruits and vegetables as well as many drugs have various capacities to prevent or treat various ailments. Nevertheless, their efficiency, in vivo, encounter many challenges resulting in lower efficacy as well as different side effects when high doses are used resulting in many challenges for their application. Indeed, demand for effective treatments with no or less unfavorable side effects is rising. Delivering active molecules to a particular site of action within the human body is an example of targeted therapy which remains a challenging field. Developments of nanotechnology and polymer science have great promise for meeting the growing demands of efficient options. Encapsulation of active ingredients in nano-delivery systems has become as a vitally tool for protecting the integrity of critical biochemicals, improving their delivery, enabling their controlled release and maintaining their biological features. Here, we examine a wide range of nano-delivery techniques, such as niosomes, polymeric/solid lipid nanoparticles, nanostructured lipid carriers, and nano-emulsions. The advantages of encapsulation in targeted, synergistic, and supportive therapies are emphasized, along with current progress in its application. Additionally, a revised collection of studies was given, focusing on improving the effectiveness of anticancer medications and addressing the problem of antimicrobial resistance. To sum up, this paper conducted a thorough analysis to determine the efficacy of encapsulation technology in the field of drug discovery and development.

Bioactive compounds from nature: Antioxidants targeting cellular transformation in response to epigenetic perturbations induced by oxidative stress.

Oxidative stress results from a persistent imbalance in oxidation levels that promotes oxidants, playing a crucial role in the early and sustained phases of DNA damage and genomic and epigenetic instability, both of which are intricately linked to the development of tumors. The molecular pathways contributing to carcinogenesis in this context, particularly those related to double-strand and single-strand breaks in DNA, serve as indicators of DNA damage due to oxidation in cancer cases, as well as factors contributing to epigenetic instability through ectopic expressions. Oxidative stress has been considered a therapeutic target for many years, and an increasing number of studies have highlighted the promising effectiveness of natural products in cancer treatment. In this regard, we present significant research on the therapeutic targeting of oxidative stress using natural molecules and underscore the essential role of oxidative stress in cancer. The consequences of stress, especially epigenetic instability, also offer significant therapeutic prospects. In this context, the use of natural epi-drugs capable of modulating and reorganizing the epigenetic network is beginning to emerge remarkably. In this review, we emphasize the close connections between oxidative stress, epigenetic instability, and tumor transformation, while highlighting the role of natural substances as antioxidants and epi-drugs in the anti-tumoral context.

Natural bioactive compounds targeting DNA methyltransferase enzymes in cancer: Mechanisms insights and efficiencies.

The regulation of gene expression is fundamental to health and life and is essentially carried out at the promoter region of the DNA of each gene. Depending on the molecular context, this region may be accessible or non-accessible (possibility of integration of RNA polymerase or not at this region). Among enzymes that control this process, DNA methyltransferase enzymes (DNMTs), are responsible for DNA demethylation at the CpG islands, particularly at the promoter regions, to regulate transcription. The aberrant activity of these enzymes, i.e. their abnormal expression or activity, can result in the repression or overactivation of gene expression. Consequently, this can generate cellular dysregulation leading to instability and tumor development. Several reports highlighted the involvement of DNMTs in human cancers. The inhibition or activation of DNMTs is a promising therapeutic approach in many human cancers. In the present work, we provide a comprehensive and critical summary of natural bioactive molecules as primary inhibitors of DNMTs in human cancers. The active compounds hold the potential to be developed as anti-cancer epidrugs targeting DNMTs.

Bioactive substances of cyanobacteria and microalgae: Sources, metabolism, and anticancer mechanism insights.

Cyanobacteria and microalgae contain various phytochemicals, including bioactive components in the form of secondary metabolites, namely flavonoids, phenolic acids, terpenoids, and tannins, with remarkable anticancer effects. This review highlights the recent advances in bioactive compounds, with potential anticancer activity, produced by cyanobacteria and microalgae. Previous in vitro investigations showed that many of these bioactive compounds exhibit potent effects against different human cancer types, such as leukemia and breast cancers. Multiple mechanisms implicated in the antitumor effect of these compounds were elucidated, including their ability to target cellular, subcellular, and molecular checkpoints linked to cancer development and promotion. Recent findings have highlighted various mechanisms of action of bioactive compounds produced by cyanobacteria and microalgae, including induction of autophagy and apoptosis, inhibition of telomerase and protein kinases, as well as modulation of epigenetic modifications. In vivo investigations have demonstrated a potent anti-angiogenesis effect on solid tumors, as well as a reduction in tumor volume. Some of these compounds were examined in clinical investigations for certain types of cancers, making them potent candidates/scaffolds for antitumor drug development.

Pharmacological Properties of Trichostatin A, Focusing on the Anticancer Potential: A Comprehensive Review.

Trichostatin A (TSA), a natural derivative of dienohydroxamic acid derived from a fungal metabolite, exhibits various biological activities. It exerts antidiabetic activity and reverses high glucose levels caused by the downregulation of brain-derived neurotrophic factor (BDNF) expression in Schwann cells, anti-inflammatory activity by suppressing the expression of various cytokines, and significant antioxidant activity by suppressing oxidative stress through multiple mechanisms. Most importantly, TSA exhibits potent inhibitory activity against different types of cancer through different pathways. The anticancer activity of TSA appeared in many in vitro and in vivo investigations that involved various cell lines and animal models. Indeed, TSA exhibits anticancer properties alone or in combination with other drugs used in chemotherapy. It induces sensitivity of some human cancers toward chemotherapeutical drugs. TSA also exhibits its action on epigenetic modulators involved in cell transformation, and therefore it is considered an epidrug candidate for cancer therapy. Accordingly, this work presents a comprehensive review of the most recent developments in utilizing this natural compound for the prevention, management, and treatment of various diseases, including cancer, along with the multiple mechanisms of action. In addition, this review summarizes the most recent and relevant literature that deals with the use of TSA as a therapeutic agent against various diseases, emphasizing its anticancer potential and the anticancer molecular mechanisms. Moreover, TSA has not been involved in toxicological effects on normal cells. Furthermore, this work highlights the potential utilization of TSA as a complementary or alternative medicine for preventing and treating cancer, alone or in combination with other anticancer drugs.

Natural Bioactive Compounds Targeting Histone Deacetylases in Human Cancers: Recent Updates.

Cancer is a complex pathology that causes a large number of deaths worldwide. Several risk factors are involved in tumor transformation, including epigenetic factors. These factors are a set of changes that do not affect the DNA sequence, while modifying the gene's expression. Histone modification is an essential mark in maintaining cellular memory and, therefore, loss of this mark can lead to tumor transformation. As these epigenetic changes are reversible, the use of molecules that can restore the functions of the enzymes responsible for the changes is therapeutically necessary. Natural molecules, mainly those isolated from medicinal plants, have demonstrated significant inhibitory properties against enzymes related to histone modifications, particularly histone deacetylases (HDACs). Flavonoids, terpenoids, phenolic acids, and alkaloids exert significant inhibitory effects against HDAC and exhibit promising epi-drug properties. This suggests that epi-drugs against HDAC could prevent and treat various human cancers. Accordingly, the present study aimed to evaluate the pharmacodynamic action of different natural compounds extracted from medicinal plants against the enzymatic activity of HDAC.

Phytochemical properties, biological activities and medicinal use of Centaurium erythraea Rafn.

ETHNOPHARMACOLOGICAL RELEVANCE: Centaurium erythraea is an important medicinal plant in many countries, e.g. Morocco, Algeria, Italy, Spain, Portugal, and countries of Balkan Peninsula. It is used in folk medicine to treat various illnesses. It is also used as an antiapoplectic, anticoagulant, anticholagogue, antipneumonic, hematocathartic, and as a hypotensive agent. AIM OF THE REVIEW: In this review, previous reports on the taxonomy, botanical description, geographic distribution, ethnomedicinal applications, phytochemistry, pharmacological properties, and toxicity of Centaurium erythraea were critically summarized. MATERIALS AND METHODS: Scientific search engines including PubMed, ScienceDirect, SpringerLink, Web of Science, Scopus, Wiley Online, SciFinder, and Google Scholar were consulted to collect data on C. erythraea. The data presented in this work summarized the main reports on C. erythraea phytochemical compounds, ethnomedicinal uses, and pharmacological activities. RESULTS: C. erythraea is used in traditional medicine to treat various diseases such as diabetes, fever, rhinitis, stomach ailments, urinary tract infections, dyspeptic complaints, loss of appetite, and hemorrhoids, and as diuretic. The essential oils and extracts of C. erythraea exhibited numerous biological properties such as antibacterial, antioxidant, antifungal, antileishmanial, anticancer, antidiabetic, anti-inflammatory, insecticidal, diuretic, gastroprotective, hepatoprotective, dermatoprotective, neuroprotective, and inhibitory agent for larval development. Phytochemical characterization of C. erythraea revealed the presence of several classes of secondary metabolites such as xanthonoids, terpenoids, flavonoids, phenolic acids, and fatty acids. CONCLUSIONS: Ethnomedicinal studies demonstrated the use of C. erythraea for the treatment of various disorders. Pharmacological reports showed that C. erythraea especially its aerial parts and roots exhibited potent, and beneficial activities. These findings confirmed the link between the traditional medicinal use and the results of the scientific biological experiments. Considering these results, further investigation using diverse in vivo pharmacological assays are strongly recommended to validate the results of its traditional use. Toxicological tests and pharmacokinetic studies are also required to validate the safety and efficacy of C. erythraea and its bioactive contents.

Phytochemical Analysis and Study of Antioxidant, Anticandidal, and Antibacterial Activities of Teucrium polium subsp. polium and Micromeria graeca (Lamiaceae) Essential Oils from Northern Morocco.

The protection of agricultural crops and the preservation of the organoleptic and health qualities of food products represent a major challenge for the agricultural and agro-food industries. Essential oils have received greater attention as alternatives to replace the control strategies based on pesticides against phytopathogenic bacteria and synthetic compounds in food preservation. The aims of this work were to study the chemical composition of Teucrium polium subsp. polium and Micromeria graeca essential oils and to examine their antioxidant and antimicrobial effects. To carry out this work, the chemical composition of the essential oil was determined using gas chromatography (GC) with the detection feature of mass spectrometry (MS). Subsequently, the antioxidant activity was investigated by DPPH and FRAPS assays. The antimicrobial effect was studied against phytopathogenic and foodborne pathogenic bacteria using the disc and the microdilution methods. Our results showed that GC-MS analysis of EOs allowed the identification of 30 compounds in T. polium EO (TPpEO), while 5 compounds were identified in M. graeca EO (MGEO). TPpEO had as major compounds ß-pinene (19.82%) and germacrene D (18.33%), while geranial (36.93%) and z-citral (18.25%) were the main components of MGEO. The most potent activity was obtained from MGEO (IC50 = 189.7 ± 2.62 µg/mL) compared to TPpEO (IC50 = 208.33 ± 3.51 µg/mL. For the FRAP test, the highest reducing power was obtained from 1.32 ± 0.1 mg AAE/g of TPpEO compared to MGEO 0.51 ± 0.13 mg AAE/g of EO. Both EOs exhibited varying degrees of antibacterial activities against all the tested strains with inhibition zones in the range of 9.33 ± 0.57 mm to >65 mm and MIC values from 0.19 to 12.5 mg/mL. However, MGEO exhibits an interesting anticandidal effect with inhibition zone 44.33 ± 0.57 mm. The findings of this research establish the riches of EOs on volatile compounds, their important antioxidant activity, and their antimicrobial effect against the bacteria tested.

Genomic Diversity and Hotspot Mutations in 30,983 SARS-CoV-2 Genomes: Moving Toward a Universal Vaccine for the "Confined Virus"?

The COVID-19 pandemic has been ongoing since its onset in late November 2019 in Wuhan, China. Understanding and monitoring the genetic evolution of the virus, its geographical characteristics, and its stability are particularly important for controlling the spread of the disease and especially for the development of a universal vaccine covering all circulating strains. From this perspective, we analyzed 30,983 complete SARS-CoV-2 genomes from 79 countries located in the six continents and collected from 24 December 2019, to 13 May 2020, according to the GISAID database. Our analysis revealed the presence of 3206 variant sites, with a uniform distribution of mutation types in different geographic areas. Remarkably, a low frequency of recurrent mutations has been observed; only 169 mutations (5.27%) had a prevalence greater than 1% of genomes. Nevertheless, fourteen non-synonymous hotspot mutations (>10%) have been identified at different locations along the viral genome; eight in ORF1ab polyprotein (in nsp2, nsp3, transmembrane domain, RdRp, helicase, exonuclease, and endoribonuclease), three in nucleocapsid protein, and one in each of three proteins: Spike, ORF3a, and ORF8. Moreover, 36 non-synonymous mutations were identified in the receptor-binding domain (RBD) of the spike protein with a low prevalence (<1%) across all genomes, of which only four could potentially enhance the binding of the SARS-CoV-2 spike protein to the human ACE2 receptor. These results along with intra-genomic divergence of SARS-CoV-2 could indicate that unlike the influenza virus or HIV viruses, SARS-CoV-2 has a low mutation rate which makes the development of an effective global vaccine very likely.

GC-MS Analysis, Antioxidant and Antimicrobial Activities of Achillea Odorata Subsp. Pectinata and Ruta Montana Essential Oils and Their Potential Use as Food Preservatives.

In order to discover new natural resources with biological properties, the chemical composition, the antioxidant and antimicrobial activities, and the potential use as food preservative of essential oils of Moroccan Achillea odorata subsp. pectinata (AOpEO) and Ruta montana (RMEO) were studied. Gas chromatography-mass spectrometry (GC-MS) analysis revealed the presence of 21 and 25 compounds in AOpEO and RMEO, respectively. The results showed that the major compounds of AOpEO are camphor (45.01%), bornyl acetate (15.07%), borneol (11.33%), ß-eudesmol (4.74%), camphene (3.58%), and 1.8-cineole (eucalyptol) (2.96%), whereas 2-undecanone (63.97%), camphor (3.82%) and cyclopropanecarboxylic acid (3.66%) were the main components of RMEO. The antioxidant activities were evaluated by diphenylpicrylhydraziyl radical (DPPH) and reducing power assays. The antimicrobial activities of essential oils were tested against bacterial strains and food contaminant yeast using agar disc diffusion and microdilution methods. A significant antimicrobial activity of AOpEO was observed against Bacillus subtilis, Proteus mirabilis and Candida albicans, compared to RMEO. The efficacy of AOpEO was also evaluated in model food systems (cabbage and barley) artificially inoculated during storage. The results found that the adding of a minimal inhibitory concentration (MIC) and 4× MIC were potent in decreasing the Proteus mirabilis growth in food model systems. Our findings suggested that AOpEO may be potentially used as an alternative food preservative.

Computational Analysis of IDH1, IDH2, and TP53 Mutations in Low-Grade Gliomas Including Oligodendrogliomas and Astrocytomas.

INTRODUCTION: The emergence of new omics approaches, such as genomic algorithms to identify tumor mutations and molecular modeling tools to predict the three-dimensional structure of proteins, has facilitated the understanding of the dynamic mechanisms involved in the pathogenesis of low-grade gliomas including oligodendrogliomas and astrocytomas. METHODS: In this study, we targeted known mutations involved in low-grade gliomas, starting with the sequencing of genomic regions encompassing exon 4 of isocitrate dehydrogenase 1 (IDH1) and isocitrate dehydrogenase 2 (IDH2) and the four exons (5-6 and 7-8) of TP53 from 32 samples, followed by computational analysis to study the impact of these mutations on the structure and function of 3 proteins IDH1, IDH2, and p53. RESULTS: We obtain a mutation that has an effect on the catalytic site of the protein IDH1 as R132H and on the catalytic site of the protein IDH2 as R172M. Other mutations at p53 have been identified as K305N, which is a pathogenic mutation; R175 H, which is a benign mutation; and R158G, which disrupts the structural conformation of the tumor suppressor protein. CONCLUSION: In low-grade gliomas, mutations in IDH1, IDH2, and TP53 may be the key to tumor progression because they have an effect on the function of the protein such as mutations R132H in IDH1 and R172M in IDH2, which change the function of the enzyme alpha-ketoglutarate, or R158G in TP53, which affects the structure of the generated protein, thus their importance in understanding gliomagenesis and for more accurate diagnosis complementary to the anatomical pathology tests.

Thermophilic bacteria in Moroccan hot springs, salt marshes and desert soils

The diversity of thermophilic bacteria was investigated in four hot springs, three salt marshes and 12 desert sites in Morocco. Two hundred and forty (240) thermophilic bacteria were recovered, identified and characterized. All isolates were Gram positive, rod-shaped, spore forming and halotolerant. Based on BOXA1R-PCR and 16S rRNA gene sequencing, the recovered isolates were dominated by the genus Bacillus (97.5%) represented by B. licheniformis (119), B. aerius (44), B. sonorensis (33), B. subtilis (subsp. spizizenii (2) and subsp. inaquosurum (6)), B. amyloliquefaciens (subsp. amyloliquefaciens (4) and subsp. plantarum (4)), B. tequilensis (3), B. pumilus (3) and Bacillus sp. (19). Only six isolates (2.5%) belonged to the genus Aeribacillus represented by A. pallidus (4) and Aeribacillus sp. (2). In this study, B. aerius and B. tequilensis are described for the first time as thermophilic bacteria. Moreover, 71.25%, 50.41% and 5.41% of total strains exhibited high amylolytic, proteolytic or cellulolytic activity respectively.