Advancements in the Research of New Modulators of Nitric Oxide Synthases Activity.

Nitric oxide (NO) has been defined as the "miracle molecule" due to its essential pleiotropic role in living systems. Besides its implications in physiologic functions, it is also involved in the development of several disease states, and understanding this ambivalence is crucial for medicinal chemists to develop therapeutic strategies that regulate NO production without compromising its beneficial functions in cell physiology. Although nitric oxide synthase (NOS), i.e., the enzyme deputed to the NO biosynthesis, is a well-recognized druggable target to regulate NO bioavailability, some issues have emerged during the past decades, limiting the progress of NOS modulators in clinical trials. In the present review, we discuss the most promising advancements in the research of small molecules that are able to regulate NOS activity with improved pharmacodynamic and pharmacokinetic profiles, providing an updated framework of this research field that could be useful for the design and development of new NOS modulators.

Conversion of polyploid and alloploid Saccharomyces sensu stricto strains to leu2 mutants by genome DNA editing.

A large number of recombinant plasmids for the yeast Saccharomyces cerevisiae have been constructed and accumulated over the past four decades. It is desirable to apply the recombinant plasmid resources to Saccharomyces sensu stricto species group, which contains an increasing number of natural isolate and industrial strains. The application to the group encounters a difficulty. Natural isolates and industrial strains are exclusively prototrophic and polyploid, whereas direct application of most conventional plasmid resources imposes a prerequisite in host yeast strains of an auxotrophic mutation (i.e., leu2) that is rescued by a selection gene (e.g., LEU2) on the recombinant plasmids. To solve the difficulty, we aimed to generate leu2 mutants from yeast strains belonging to the yeast Saccharomyces sensu stricto species group by DNA editing. First, we modified an all-in-one type CRISPR-Cas9 plasmid pML104 by adding an antibiotic-resistance gene and designing guide sequences to target the LEU2 gene and to enable wide application in this yeast group. Then, the resulting CRISPR-Cas9 plasmids were exploited to seven strains belonging to five species of the group, including natural isolate, industrial, and allopolyploid strains. Colonies having the designed mutations in the gene appeared successfully by introducing the plasmids and assisting oligonucleotides to the strains. Most of the plasmids and resultant leu2- mutants produced in this study will be deposited in several repository organizations. KEY POINTS: • All-in-one type CRISPR-Cas9 plasmids targeting LEU2 gene were designed for broad application to Saccharomyces sensu stricto group species strains • Application of the plasmids generated leu2 mutants from strains including natural isolates, industrial, and allopolyploid strains • The easy conversion to leu2 mutants permits free access to recombinant plasmids having a LEU2 gene.

Flavonoidal alkaloids: Emerging targets for drug discovery from Nature's bounty.

This paper explores the potential of flavonoid alkaloids, a unique class of compounds that contain both flavonoid and alkaloid structures, as emerging targets for drug discovery. These compounds exhibit diverse biological activities, such as anti-inflammatory, anti-cancer, and anti-diabetic effects, which are attributed to the combination of different flavonoid scaffolds and alkaloid groups. Flavonoid alkaloids have attracted researchers' attention due to their diverse structures and important bio-activities. Therefore, this review summarizes recent advances in the extraction, purification, structural characterization, synthesis pathways and biological activities of flavonoid alkaloids from natural sources. Finally, the potential prospects and challenges associated with this class of compounds in pharmacological research are discussed along with details of a mechanistic investigation and future clinical applications in this research field.

Blue healing: marine biopolymers' dual role in diabetic wounds and palliative care.

Chronic Diabetic wounds pose significant challenges in healthcare due to prolonged healing times and increased susceptibility to infections. Traditional wound dressings often fall short in providing an optimal environment for healing. Owing to their biocompatibility and biodegradability, natural polysaccharides present promising wound management alternatives. This review highlights the potential of polysaccharides derived from diverse sources, including marine organisms, in promoting wound healing. While considerable progress has been made in understanding their haemostatic, antimicrobial, and immunomodulatory properties, further research is needed to elucidate their precise mechanisms of action and optimise their therapeutic efficacy. Harnessing the unique characteristics of marine-based polysaccharides holds excellent promise for future advancements in wound care, particularly in the detection and treatment of diabetic wound infections.

Luteolin: A promising multifunctional natural flavonoid for human diseases.

Natural products are closely associated with human health. Luteolin (LUT), a flavonoid polyphenolic compound, is widely found in fruits, vegetables, flowers, and herbs. It is noteworthy that LUT exhibits a variety of beneficial pharmacological properties and holds significant potential for clinical applications, particularly in antitumor, anti-convulsion, diabetes control, anti-inflammatory, neuroprotection, anti-oxidation, anti-cardiovascular, and other aspects. The potential mechanism of action has been partially elucidated, including the mediation of NF-κB, toll-like receptor, MAPK, Wnt/ß-catenin, PI3K/Akt, AMPK/mTOR, and Nrf-2, among others. The review that aimed to comprehensively consolidate essential information on natural sources, pharmacological effects, therapeutic and preventive potential, as well as potential mechanisms of LUT. The objective is to establish a theoretical basis for the continued development and application of LUT.

Four decades of full-scale nitrous oxide emission inventory in China.

China is among the top nitrous oxide (N2O)-emitting countries, but existing national inventories do not provide full-scale emissions including both natural and anthropogenic sources. We conducted a four-decade (1980-2020) of comprehensive quantification of Chinese N2O inventory using empirical emission factor method for anthropogenic sources and two up-to-date process-based models for natural sources. Total N2O emissions peaked at 2287.4 (1774.8-2799.9) Gg N2O yr-1 in 2018, and agriculture-developed regions, like the East, Northeast, and Central, were the top N2O-emitting regions. Agricultural N2O emissions have started to decrease after 2016 due to the decline of nitrogen fertilization applications, while, industrial and energetic sources have been dramatically increasing after 2005. N2O emissions from agriculture, industry, energy, and waste represented 49.3%, 26.4%, 17.5%, and 6.7% of the anthropogenic emissions in 2020, respectively, which revealed that it is imperative to prioritize N2O emission mitigation in agriculture, industry, and energy. Natural N2O sources, dominated by forests, have been steadily growing from 317.3 (290.3-344.1) Gg N2O yr-1 in 1980 to 376.2 (335.5-407.2) Gg N2O yr-1 in 2020. Our study produces a Full-scale Annual N2O dataset in China (FAN2020), providing emergent counting to refine the current national N2O inventories.

Fructose-induced hyperuricaemia - protection factor or oxidative stress promoter?

Accumulating evidence suggests that dietary fructose may play a role in the hyperuricaemia development, but the precise mechanism remains unclear. Hyperuricaemia is characterised by excessive production and deposition of urate crystals, and the metabolism of fructose has been implicated in the elevation of serum urate levels. The association between fructose intake and the risk of hyperuricaemia is explained by the metabolism of fructose in the liver, small intestine, and kidney. Many studies have confirmed the correlation between fructose consumption and an increased risk of developing hyperuricaemia, but more prospective studies to fully elucidate the role of fructose intake in the pathogenesis of hyperuricaemia are needed. It is important to note that maintaining a balanced diet, and lifestyle is crucial when considering fructose intake. Limiting the consumption of products high in added sugars and maintaining a healthy weight can contribute to reducing the risk of hyperuricaemia and associated health complications.

A systematic review on understanding the mechanistic pathways and clinical aspects of natural CDK inhibitors on cancer progression.: Unlocking cellular and biochemical mechanisms.

Cell division, differentiation, and controlled cell death are all regulated by phosphorylation, a key biological function. This mechanism is controlled by a variety of enzymes, with cyclin-dependent kinases (CDKs) being particularly important in phosphorylating proteins at serine and threonine sites. CDKs, which contain 20 unique components, serve an important role in regulating vital physiological functions such as cell cycle progression and gene transcription. Methodologically, an extensive literature search was performed using reputable databases such as PubMed, Google Scholar, Scopus, and Web of Science. Keywords encompassed "cyclin kinase," "cyclin dependent kinase inhibitors," "CDK inhibitors," "natural products," and "cancer therapy." The inclusion criteria, focused on relevance, publication date, and language, ensured a thorough representation of the most recent research in the field, encompassing articles published from January 2015 to September 2023. Categorization of CDKs into those regulating transcription and those orchestrating cell cycle phases provides a comprehensive understanding of their diverse functions. Ongoing clinical trials featuring CDK inhibitors, notably CDK7 and CDK4/6 inhibitors, illuminate their promising potential in various cancer treatments. This review undertakes a thorough investigation of CDK inhibitors derived from natural (marine, terrestrial, and peptide) sources. The aim of this study is to provide a comprehensive comprehension of the chemical classifications, origins, target CDKs, associated cancer types, and therapeutic applications.

Marine-derived Compounds: A Powerful Platform for the Treatment of Alzheimer's Disease.

Alzheimer's disease (AD) is a debilitating form of dementia that primarily affects cholinergic neurons in the brain, significantly reducing an individual's capacity for learning and creative skills and ultimately resulting in an inability to carry out even basic daily tasks. As the elderly population is exponentially increasing, the disease has become a significant concern for society. Therefore, neuroprotective substances have garnered considerable interest in addressing this universal issue. Studies have shown that oxidative damage to neurons contributes to the pathophysiological processes underlying AD progression. In AD, tau phosphorylation and glutamate excitotoxicity may play essential roles, but no permanent cure for AD is available. The existing therapies only manage the early symptoms of AD and often come with numerous side effects and toxicities. To address these challenges, researchers have turned to nature and explored various sources such as plants, animals, and marine organisms. Many historic holy books from different cultures emphasize that adding marine compounds to the regular diet enhances brain function and mitigates its decline. Consequently, researchers have devoted significant time to identifying potentially active neuroprotective substances from marine sources. Marine-derived compounds are gaining recognition due to their abundant supply of diverse chemical compounds with biological and pharmacological potential and unique mechanisms of action. Several studies have reported that plants exhibit multitarget potential in treating AD. In light of this, the current study focuses on marine-derived components with excellent potential for treating this neurodegenerative disease.

Advances in polysaccharides of natural source of anti-diabetes effect and mechanism.

PURPOSE: Diabetes is a chronic disease in metabolic disorder, and the pathology is characterized by insulin resistance and insulin secretion disorder in blood. In current, many studies have revealed that polysaccharides extracted from natural sources with significant anti-diabetic effects. Natural polysaccharides can ameliorate diabetes through different action mechanisms. All these polysaccharides are expected to have an important role in the clinic. METHODS: Existing polysaccharides for the treatment of diabetes are reviewed, and the mechanism of polysaccharides in the treatment of diabetes and its structural characteristics are described in detail. RESULTS: This article introduced the natural polysaccharide through different mechanisms of action in the treatment of diabetes, including oxidative stress, apoptosis, inflammatory response and regulation of intestinal bacteria. Natural polysaccharides can treat of diabetes by regulating signaling pathways is also a research hotspot. In addition, the structural characteristics of polysaccharides were explored. There are some structure-activity relationships between natural polysaccharides and the treatment of diabetes.

Pyrrole: A Decisive Scaffold for the Development of Therapeutic Agents and Structure-Activity Relationship.

An overview of pyrroles as distinct scaffolds with therapeutic potential and the significance of pyrrole derivatives for drug development are provided in this article. It lists instances of naturally occurring pyrrole-containing compounds and describes the sources of pyrroles in nature, including plants and microbes. It also explains the many conventional and modern synthetic methods used to produce pyrroles. The key topics are the biological characteristics, pharmacological behavior, and functional alterations displayed by pyrrole derivatives. It also details how pyrroles are used to treat infectious diseases. It describes infectious disorders resistant to standard treatments and discusses the function of compounds containing pyrroles in combating infectious diseases. Furthermore, the review covers the uses of pyrrole derivatives in treating non-infectious diseases and resistance mechanisms in non-infectious illnesses like cancer, diabetes, and Alzheimer's and Parkinson's diseases. The important discoveries and probable avenues for pyrrole research are finally summarized, along with their significance for medicinal chemists and drug development. A reference from the last two decades is included in this review.

Source identification and exposure risk management for soil arsenic in urban reclamation areas with high background levels: A case study in a coastal reclamation site from the Pearl River Delta, China.

Urbanization involving the excavation and reuse of arsenic-bearing geological materials may pose human health risks. We investigated the distribution and sources of soil arsenic at a coastal reclamation site in the Pearl River Delta, China, and proposed risk management strategies. Analysis of 899 soil samples revealed an average of 58.97 mg/kg arsenic, with a maximum of 1450 mg/kg, mainly in fill material obtained from a local island. Integrative analysis combining reclamation history, regional geology, and bedrock mineralogy conclusively identified hydrothermally altered arsenic-bearing sulfide minerals within extensively fractured bedrock as the primary source of arsenic. Physical weathering and anthropogenic rock blasting produced discrete arsenic-rich particles that were directly transported into soils during land reclamation and accumulated to potential hazardous levels. Oral, dermal, and inhalation pathways were identified as primary exposures for future populations. Integrated engineering and institutional controls, coupled with long-term monitoring, were recommended to mitigate risks. The results highlight the importance of identifying specific geogenic and anthropogenic sources that contribute to heavy metal enrichment of soils in reclaimed areas where native bedrock naturally contains elevated level of metals, supporting evidence-based best practices for risk management and future land use.

Nano-Hydroxyapatite Isolation and Characterisation of Echinometra mathaei from the Persian Gulf.

The study focuses on the preparation and characterisation (physicochemical and mechanical) of hydroxyapatite [Ca10(PO4)6(OH)2] (HA) from sea urchin, Echinometra mathaei. Therefore, nano-sized HA prepared from sea urchin shells were collected from beaches of the Persian Gulf in Iran. Sea urchin shells were found a source of calcium carbonate in the form of aragonite (calcite) that crystallised in an organic matrix. HA is one of the polymers used in coating the nanoparticles extracted from various sources. The calcined aragonite converted to nanosized hydroxyapatite powder by chemical reaction with orthophosphoric acid while maintaining stoichiometry, Ca/P = 1.667 at 80°C. To determine the purity of the nano-hydroxyapatite (nHA) numerous analytical procedures were used. Fourier transforms infrared spectroscopy (FTIR) confirmed the presence of the peak of 961 cm-1 is related to the symmetric tensile band of the P-O bond, and the peak of 1038 cm-1 and 1091 cm-1 is related to the tensile solid absorption of the PO4 as functional groups of nHA. The nanocrystalline HA can be observed from the SEM images. Thermogravimetric analysis (TGA-DTA) demonstrates the thermal stability of nHA powder. The results show successful isolation and characterisation study of this crucial nano-material shows it is valuable in biomedical applications, particularly in bone tissue engineering. Indeed, its fabrication is easy and economical.

Persea americana extract protects intestinal tissue from Eimeria papillata-induced murine Infection.

Coccidiosis is the most prevalent disease-causing widespread economic loss among farm and domestic animals. Currently, several drugs are available for the control of this disease but resistance has been confirmed for all of them. There is an urgent need, therefore, for the identification of new sources as alternative treatments to control coccidiosis. The present work aimed to study the effect of the Persea americana extract (PAE) as an anti-coccidial, anti-oxidant, and anti-apoptotic modulator during murine intestinal Eimeria papillata infection. A total of 25 male mice were divided into five groups, as follows: Group1: Non-infected-non-treated (negative control), Group2: Non-infected-treated group with PAE (500 mg/kg b.w). Group3: Infected-non-treated (positive control), Group4: Infected-treated group with PAE (500 mg/kg b.w.), and Group5: Infected-treated group with Amprolium (120 mg/kg b.w.). Groups (3-5) were orally inoculated with 1 × 103 sporulated E. papillata oocysts. After 60 min of infection, groups (4 and 5) were treated for 5 consecutive days with the recommended doses of PAE and amprolium. The fact that PAE has an anti-coccidial efficacy against intestinal E. papillata infection in mice has been clarified by the reduction of fecal oocyst output on the 5th day post-infection by about 85.41%. Moreover, there is a significant reduction in the size of each parasite stage in the jejunal tissues of the infected-treated group with PAE. PAE counteracted the E. papillata-induced loss of glutathione peroxidase (GPx), superoxide dismutase (SOD), and total antioxidant capacity (TCA). E. papillata infection also induced an increase in the apoptotic cells expressed by caspase-3 which modulated after PAE treatment. Moreover, the mRNA expression of the goblet cell response gene, mucin (MUC2), was upregulated from 0.50 to 1.20-fold after treatment with PAE. Based on our results, PAE is a promising medicinal plant with anti-coccidial, anti-oxidant, and anti-apoptotic activities and could be used as a food additive.

A Review of Foods of Plant Origin as Sources of Vitamins with Proven Activity in Oxidative Stress Prevention according to EFSA Scientific Evidence.

Beyond their nutritional benefits, vitamins could decrease the risk of chronic diseases due to their potent antioxidant capacity. The present work is aimed at reviewing the state of the art regarding (1) the vitamins involved in oxidative stress prevention in accordance with the requirements established by the European Food Safety Authority (EFSA) and (2) the foods of plant origin that are sources of those vitamins and have potential benefits against oxidative stress in humans. According to the European regulations based on EFSA scientific evidence, riboflavin, vitamin C, and vitamin E are those vitamins subjected to the approved health claim "contribute to the protection of cells from oxidative stress". Scientific studies conducted in humans with some natural food sources of riboflavin (almonds, wheat germ, mushrooms, oat bran), vitamin C (guava, kale, black currant, Brussels sprouts, broccoli, orange), and vitamin E (hazelnuts, almonds, peanuts, pistachio nuts, extra virgin olive oil, dates, rye) have been performed and published in the literature. However, no food of plant origin has obtained a favorable EFSA opinion to substantiate the approval of health claims related to its potential properties related to oxidative stress prevention. Further studies (concretely, well-controlled human intervention studies) must be carried out in accordance with EFSA requirements to provide the highest level of scientific evidence that could demonstrate the potential relationship between foods of plant origin and antioxidant capacity. This review could be useful for the scientific community to study the application of health claims referring to the antioxidant capacity potentially exerted by foods of plant origin.

Natural Sources of Food Colorants as Potential Substitutes for Artificial Additives.

In recent years, the demand of healthier food products and products made with natural ingredients has increased overwhelmingly, led by the awareness of human beings of the influence of food on their health, as well as by the evidence of side effects generated by different ingredients such as some additives. This is the case for several artificial colorants, especially azo colorants, which have been related to the development of allergic reactions, attention deficit and hyperactivity disorder. All the above has focused the attention of researchers on obtaining colorants from natural sources that do not present a risk for consumption and, on the contrary, show biological activity. The most representative compounds that present colorant capacity found in nature are anthocyanins, anthraquinones, betalains, carotenoids and chlorophylls. Therefore, the present review summarizes research published in the last 15 years (2008-2023) in different databases (PubMed, Scopus, Web of Science and ScienceDirect) encompassing various natural sources of these colorant compounds, referring to their obtention, identification, some of the efforts made for improvements in their stability and their incorporation in different food matrices. In this way, this review evidences the promising path of development of natural colorants for the replacement of their artificial counterparts.

Natural waste-derived nano photocatalysts for azo dye degradation.

Due to their widespread application in water purification, there is a significant interest in synthesising nanoscale photocatalysts. Nanophotocatalysts are primarily manufactured through chemical methods, which can lead to side effects like pollution, high-energy usage, and even health issues. To address these issues, "green synthesis" was developed, which involves using plant extracts as reductants or capping agents rather than industrial chemical agents. Green fabrication has the benefits of costs less, pollution reduction, environmental protection and human health safety, compared to the traditional methods. This article summarises recent advances in the environmentally friendly synthesis of various nanophotocatalysts employed in the degradation of azo dyes. This study compiles critical findings on natural and artificial methods to achieve the goal. Green synthesis is constrained by the time and place of production and issues with low purity and poor yield, reflecting the complexity of plants' geographical and seasonal distributions and their compositions. However, green photocatalyst synthesis provides additional growth opportunities and potential uses.

Quantifying the contributions of natural and anthropogenic dust sources in Shanxi Province, northern China.

Dust storms have direct or indirect impacts on climate change and human health. Identifying and quantifying natural/anthropogenic dust sources can facilitate effective prevention and control of dust events. Based on surface real-time PM10 monitoring data, satellite remote sensing and the HYSPLIT model, this study determined the specific timing, coverage and sources of dust events in Shanxi Province, Northern China. Thus, a composite fingerprinting technique was established to quantify potential dust sources and dust contributions of single dust events. The dust oxidation model was validated, indicating that the composite fingerprinting technique was well suited to the study region. The results show that natural dust sources (67%) contributed more to the study region than anthropogenic dust sources. They were mainly from the northwest and north of the study region. Particularly, the contributions of Taiyuan (TY) and Linfen (LF) accounted for the largest (82%) and smallest (55%) proportions, respectively, both exceeding 50%. Anthropogenic dust sources contributed 33%, mainly from the east and south of the study region. The contribution of anthropogenic dust sources increased in the study region from north to south. In terms of potential dust sources, the Tengger Desert and Badain Jaran Desert (TDBD) contributed the most (26%), followed by the Otindag Sandy Land (OL) (22%). The Taklimakan Desert (TD) contributed the least (2%). The Middle Farmland region of the Hexi Corridor (HMF) in the west (15%) had the largest proportion of anthropogenic dust sources. Differences in the regional contribution of potential dust sources mainly resulted from winter winds, surface drought severity and particle size. At an insignificant distance from the study region, the contribution of potential dust sources was larger in the west than in the east and increased from south to north overall. These methods and findings can contribute to improving the ecological environment in Northern China.

Green chemistry production of biopolymeric film-derived biomaterial prepared using natural alginate and vanillin compounds for application as a biocurative.

The present work presents the results obtained in the production of vanillin-doped alginate biopolymeric film using green chemistry methodology. Alginate dressings are already a therapeutic reality, but they act only by maintaining the appropriate environment for healing. In order to improve their properties, the incorporation of vanillin was proposed due to its antioxidant and antimicrobial potential. Different biopolymeric films were produced employing the experiment planning through response surface analysis, which allowed determining the best region for a medium value of solubility and high degree of swelling. This region refers to values above 0.07 g of CaCl2 and concentrations above 0.024 g of vanillin, triggering solubility between 25 and 30% and a degree of swelling above 100% and with fixed values of alginate (0.85 g). Such data are related to experiments (A), (B), and (C) listed in Table 1. Regarding the optimization of the process, the normal boundary intersection (NBI) method allowed the analysis of concave regions, predicting the optimal points and generating the Pareto chart with equidistant limits. The antimicrobial test allowed observing the antimicrobial activity against Escherichia coli and Pseudomonas aeruginosa microorganisms from the biopolymeric films, as well as a solution of vanillin with calcium chloride and glycerol obtaining a halo of inhibition only in the presence of vanillin, and there was no significant difference between the results obtained in the experiments (A) and (B). The thermal analyses showed that the material has thermal stability in the ideal temperature range (~ 25 °C) for application as a biocurative. We preliminarily concluded that the alginate biopolymeric film doped with vanillin prepared using green chemical methodology presents antimicrobial properties and thermal stability that indicate its potential use as biocurative.

Drug Delivery Application of Functional Nanomaterials Synthesized Using Natural Sources.

Nanomaterials (NMs) synthesized from natural sources have been attracting greater attention, due to their intrinsic advantages including biocompatibility, stimuli-responsive property, nontoxicity, cost-effectiveness, and non-immunogenic characteristics in the biological environment. Among various biomedical applications, a breakthrough has been achieved in the development of drug delivery systems (DDS). Biocompatibility is necessary for treating a disease safely without any adverse effects. Some components in DDS respond to the physiological environment, such as pH, temperature, and functional group at the target, which facilitates targeted drug release. NM-based DDS is being applied for treating cancer, arthritis, cardiovascular diseases, and dermal and ophthalmic diseases. Metal nanomaterials and carbon quantum dots are synthesized and stabilized using functional molecules extracted from natural sources. Polymers, mucilage and gums, exosomes, and molecules with biological activities are directly derived from natural sources. In DDS, these functional components have been used as drug carriers, imaging agents, targeting moieties, and super disintegrants. Plant extracts, biowaste, biomass, and microorganisms have been used as the natural source for obtaining these NMs. This review highlights the natural sources, synthesis, and application of metallic materials, polymeric materials, carbon dots, mucilage and gums, and exosomes in DDS. Aside from that, challenges and future perspectives on using natural resources for DDS are also discussed.