Microbial Polysaccharides Extracted from Different Mature Muds of the Euganean Thermal District Show Similar Anti-Inflammatory Activity In Vivo.

The Euganean Thermal District, situated in North-East Italy, is one of Europe's largest and oldest thermal centres. The topical application of its therapeutic thermal muds is recognised by the Italian Health System as a beneficial treatment for patients suffering from arthro-rheumatic diseases. Polysaccharides produced by the mud microbiota have been recently identified as anti-inflammatory bioactive molecules. In this paper we analysed the efficacy of Microbial-Polysaccharides (M-PS) derived from mature muds obtained at different maturation temperatures, both within and outside the codified traditional mud maturation range. M-PSs were extracted from six mature muds produced by five spas of the Euganean Thermal District and investigated for their chemical properties, monosaccharide composition and in vivo anti-inflammatory potential, using the zebrafish model organism. Additionally, mature muds were characterized for their microbiota composition using Next-Generation Sequencing. The results showed that all M-PSs exhibit similar anti-inflammatory potential, referable to their comparable chemical composition. This consistency was observed despite changes in cyanobacteria populations, suggesting a possible role of the entire microbial community in shaping the properties of these biomolecules. These findings highlight the importance of scientific research in untangling the origins of the therapeutic efficacy of Euganean Thermal muds in the treatment of chronic inflammatory conditions.

Design of a delivery vehicle chitosan-based self-assembling: controlled release, high hydrophobicity, and safe treatment of plant fungal diseases.

BACKGROUND: Traditional pesticides are poorly water-soluble and suffer from low bioavailability. N-succinyl chitosan (NSCS) is a water-soluble chitosan derivative, has been recently used to encapsulate hydrophobic drugs to improve their bioavailability. However, it remains challenging to synthesize pesticides of a wide variety of water-soluble drugs and to scale up the production in a continuous manner. RESULTS: A synthetic method for preparing water-soluble nanopesticides with a polymer carrier was applied. The bioactive molecule BTL-11 was loaded into hollow NSCS to promote drug delivery, improve solubility and anti-fungal activity. The synthesized nanopesticides had well controlled sizes of 606 nm and the encapsulation rate was 80%. The release kinetics, drug toxicity and drug activity were further evaluated. The inhibitory activity of nanopesticides against Rhizoctonia solani (R. solani) was tested in vivo and in vitro. In vivo against R. solani trials revealed that BTL-11 has excellent control efficiency for cultivated rice leaf and sheath was 79.6 and 76.5%, respectively. By contrast, for BTL-11@NSCS NPs, the anti-fungal ability was strongly released and afforded significant control efficiencies of 85.9 and 81.1%. Those effects were significantly better than that of the agricultural fungicide azoxystrobin (51.5 and 66.5%). The proposed mechanism was validated by successfully predicting the synthesis outcomes. CONCLUSIONS: This study demonstrates that NSCS is a promising biocompatible carrier, which can enhance the efficacy of pesticides, synergistically improve plant disease resistance, protect crop growth, and can be used for the delivery of more insoluble pesticides.

Impact of Processing and Physicochemical Parameter on Hibiscus sabdariffa Calyxes Biomolecules and Antioxidant Activity: From Powder Production to Reconstitution.

Hibiscus sabdariffa is a tropical plant with red calyxes whose anthocyanins, phenols, and antioxidant activity make it attractive to consumers both from a nutritional and medicinal standpoint. Its seasonality, perishability, and anthocyanin instability, led to the setup of stabilization methods comprising drying and powdering. However, its properties can often be altered during these stabilization processes. Treatments such as dehumidified-air-drying, infrared drying, and oven-drying, and their combination showed better quality preservation. Moreover, powder production enables superior biomolecule extractability which can be linked to a higher bioaccessibility. However, the required temperatures for powder production increase the bioactive molecules degradation leading to their antioxidant activity loss. To overcome this issue, ambient or cryogenic grinding could be an excellent method to improve the biomolecule bioavailability and accessibility if the processing steps are well mastered. To be sure to benefit from the final nutritional quality of the powder, such as the antioxidant activity of biomolecules, powders have to offer excellent reconstitutability which is linked to powder physicochemical properties and the reconstitution media. Typically, the finest powder granulometry and using an agitated low-temperature reconstitution media allow for improving anthocyanin extractability and stability. In this review, the relevant physicochemical and processing parameters influencing plant powder features from processing transformation to reconstitution will be presented with a focus on bioactive molecules and antioxidant activity preservation.

From Plants to Wound Dressing and Transdermal Delivery of Bioactive Compounds.

Transdermal delivery devices and wound dressing materials are constantly improved and upgraded with the aim of enhancing their beneficial effects, biocompatibility, biodegradability, and cost effectiveness. Therefore, researchers in the field have shown an increasing interest in using natural compounds as constituents for such systems. Plants, as an important source of so-called "natural products" with an enormous variety and structural diversity that still exceeds the capacity of present-day sciences to define or even discover them, have been part of medicine since ancient times. However, their benefits are just at the beginning of being fully exploited in modern dermal and transdermal delivery systems. Thus, plant-based primary compounds, with or without biological activity, contained in gums and mucilages, traditionally used as gelling and texturing agents in the food industry, are now being explored as valuable and cost-effective natural components in the biomedical field. Their biodegradability, biocompatibility, and non-toxicity compensate for local availability and compositional variations. Also, secondary metabolites, classified based on their chemical structure, are being intensively investigated for their wide pharmacological and toxicological effects. Their impact on medicine is highlighted in detail through the most recent reported studies. Innovative isolation and purification techniques, new drug delivery devices and systems, and advanced evaluation procedures are presented.

Hyaluronic Acid: A Powerful Biomolecule with Wide-Ranging Applications-A Comprehensive Review.

Hyaluronic acid (HA) is a glycosaminoglycan widely distributed in the human body, especially in body fluids and the extracellular matrix of tissues. It plays a crucial role not only in maintaining tissue hydration but also in cellular processes such as proliferation, differentiation, and the inflammatory response. HA has demonstrated its efficacy as a powerful bioactive molecule not only for skin antiaging but also in atherosclerosis, cancer, and other pathological conditions. Due to its biocompatibility, biodegradability, non-toxicity, and non-immunogenicity, several HA-based biomedical products have been developed. There is an increasing focus on optimizing HA production processes to achieve high-quality, efficient, and cost-effective products. This review discusses HA's structure, properties, and production through microbial fermentation. Furthermore, it highlights the bioactive applications of HA in emerging sectors of biomedicine.

Therapeutic Efficacy of a Formulation Prepared with Linum usitatissimum L., Plantago ovata Forssk., and Honey on Uncomplicated Pelvic Inflammatory Disease Analyzed with Machine Learning Techniques.

A single-blind double-dummy randomized study was conducted in diagnosed patients (n = 66) to compare the efficacy of Linseeds (Linum usitatissimum L.), Psyllium (Plantago ovata Forssk.), and honey in uncomplicated pelvic inflammatory disease (uPID) with standard drugs using experimental and computational analysis. The pessary group received placebo capsules orally twice daily plus a per vaginum cotton pessary of powder from linseeds and psyllium seeds, each weighing 3 gm, with honey (5 mL) at bedtime. The standard group received 100 mg of doxycycline twice daily and 400 mg of metronidazole TID orally plus a placebo cotton pessary per vaginum at bedtime for 14 days. The primary outcomes were clinical features of uPID (vaginal discharge, lower abdominal pain (LAP), low backache (LBA), and pelvic tenderness. The secondary outcomes included leucocytes (WBCs) in vaginal discharge on saline microscopy and the SF-12 health questionnaire. In addition, we also classified both (pessary and standard) groups using machine learning models such as Decision Tree (DT), Random Forest (RF), Logistic Regression (LR), and AdaBoost (AB). The pessary group showed a higher percentage reduction than the standard group in abnormal vaginal discharge (87.05% vs. 77.94%), Visual Analogue Scale (VAS)-LAP (80.57% vs. 77.09%), VAS-LBA (74.19% vs. 68.54%), McCormack pain scale (McPS) score for pelvic tenderness (75.39% vs. 67.81%), WBC count of vaginal discharge (87.09% vs. 83.41%) and improvement in SF-12 HRQoL score (94.25% vs. 86.81%). Additionally, our DT 5-fold model achieved the maximum accuracy (61.80%) in the classification. We propose that the pessary group is cost-effective, safer, and more effective as standard drugs for treating uPID and improving the HRQoL of women. Aucubin, Plantamajoside, Herbacetin, secoisolariciresinol diglucoside, Secoisolariciresinol Monoglucoside, and other various natural bioactive molecules of psyllium and linseeds have beneficial effects as they possess anti-inflammatory, antioxidant, antimicrobial, and immunomodulatory properties. The anticipated research work is be a better alternative treatment for genital infections.

Mung Bean (Vigna radiata (L.) R. Wilczek) from Burkina Faso Used as Antidiabetic, Antioxidant and Antimicrobial Agent.

Chronic non-communicable diseases are becoming more and more recurrent and require the addition of functional foods in our eating habits. Legumes due to their composition in biomolecules could meet this need. Much used in Chinese medicine, the mung bean arouses interest in Burkina Faso. The objective of this study is to perform phytochemical profiling and to evaluate certain biological properties of the mung bean in its natural or germinated state. Qualitative phytochemical screening was carried out by precipitation and differential staining tests. The antimicrobial activity was tested on in vitro growth by the agar medium diffusion method. DPPH and FRAP methods were used to assess antioxidant activity. The antidiabetic activity of hydroethanolic extracts was evaluated on rats rendered diabetic by streptozotocin, with metformin as a reference molecule. Phytochemistry has revealed the presence of phenolic compounds and derivatives in the mung bean, whether in its natural state (MBN) or in its germinated state (MBG). Only the MBG exhibits antimicrobial activity on 70% of the strains used. It appears that the MBG has a reducing power of the DPPH radical with an IC50 of 28 mg/mL compared to the same extract of the MBN, which had an IC50 of 32.5 mg/mL with a difference (p < 0.05) between the extracts. MBN extracts at a dose of 300 milligrams per kilogram of body weight (mg/kg.bw) showed a reduction (p < 0.0001) in glycaemia and kept the body weight of the animals constant throughout the treatment. In addition, the MBN regulated the level of total cholesterol, tryglicerides of LDL, ASAT, ALAT, urea and creatine. These results show that the mung bean grown in Burkina Faso is a health food, which, integrated into dietary habits, could contribute to the prevention of chronic diseases.

A Kunitz-type inhibitor from tick salivary glands: A promising novel antitumor drug candidate.

Salivary glands are vital structures responsible for successful tick feeding. The saliva of ticks contains numerous active molecules that participate in several physiological processes. A Kunitz-type factor Xa (FXa) inhibitor, similar to the tissue factor pathway inhibitor (TFPI) precursor, was identified in the salivary gland transcriptome of Amblyomma sculptum ticks. The recombinant mature form of this Kunitz-type inhibitor, named Amblyomin-X, displayed anticoagulant, antiangiogenic, and antitumor properties. Amblyomin-X is a protein that inhibits FXa in the blood coagulation cascade and acts via non-hemostatic mechanisms, such as proteasome inhibition. Amblyomin-X selectively induces apoptosis in cancer cells and promotes tumor regression through these mechanisms. Notably, the cytotoxicity of Amblyomin-X seems to be restricted to tumor cells and does not affect non-tumorigenic cells, tissues, and organs, making this recombinant protein an attractive molecule for anticancer therapy. The cytotoxic activity of Amblyomin-X on tumor cells has led to vast exploration into this protein. Here, we summarize the function, action mechanisms, structural features, pharmacokinetics, and biodistribution of this tick Kunitz-type inhibitor recombinant protein as a promising novel antitumor drug candidate.

Nutraceuticals: Focus on Anti-Inflammatory, Anti-Cancer, Antioxidant Properties in Gastrointestinal Tract.

In recent years, nutraceuticals have gained great popularity, owing to their physiological and potential health effects, such as anti-inflammatory, anti-cancer, antioxidant, and prebiotic effects, and their regulation of lipid metabolism. Since the Mediterranean diet is a nutritionally recommended dietary pattern including high-level consumption of nutraceuticals, this review aimed to summarize the main results obtained by our in vitro and in vivo studies on the effects of the major constituents of the Mediterranean diet (i.e., extra virgin olive oil compounds, polyunsaturated fatty acids, and fruit components). Based on experimental studies, the therapeutic purpose of nutraceuticals depends on their bioavailability, solubility, toxicity, and delivery system. This review provides more in-depth knowledge on the effects linked to nutraceuticals administration on human health, focusing the gastrointestinal tract and suggesting specific dietary components for personalized adjuvant therapies.

Cardioprotective Role of BGP-15 in Ageing Zucker Diabetic Fatty Rat (ZDF) Model: Extended Mitochondrial Longevity.

Impaired mitochondrial function is associated with several metabolic diseases and health conditions, including insulin resistance and type 2 diabetes (T2DM), as well as ageing. The close relationship between the above-mentioned diseases and cardiovascular disease (CVD) (diabetic cardiomyopathy and age-related cardiovascular diseases) has long been known. Mitochondria have a crucial role: they are a primary source of energy produced in the form of ATP via fatty acid oxidation, tricarboxylic acid (TCA) cycle, and electron transport chain (ETC), and ATP synthase acts as a key regulator of cardiomyocyte survival. Mitochondrial medicine has been increasingly discussed as a promising therapeutic approach in the treatment of CVD. It is well known that vitamin B3 as an NAD+ precursor exists in several forms, e.g., nicotinic acid (niacin) and nicotinamide (NAM). These cofactors are central to cellular homeostasis, mitochondrial respiration, ATP production, and reactive oxygen species generation and inhibition. Increasing evidence suggests that the nicotinic acid derivative BGP-15 ((3-piperidine-2-hydroxy-1-propyl)-nicotinic amidoxime) improves cardiac function by reducing the incidence of arrhythmias and improves diastolic function in different animal models. Our team has valid reasons to assume that these cardioprotective effects of BGP-15 are based on its NAD+ precursor property. Our hypothesis was supported by an animal experiment where ageing ZDF rats were treated with BGP-15 for one year. Haemodynamic variables were measured with echocardiography to detect diabetic cardiomyopathy (DbCM) and age-related CVD as well. In the ZDF group, advanced HF was diagnosed, whereas the BGP-15-treated ZDF group showed diastolic dysfunction only. The significant difference between the two groups was supported by post-mortem Haematoxylin and eosin (HE) and Masson's trichrome staining of cardiac tissues. Moreover, our hypothesis was further confirmed by the significantly elevated Cytochrome c oxidase (MTCO) and ATP synthase activity and expression detected with ELISA and Western blot analysis. To the best of our knowledge, this is the first study to demonstrate the protective effect of BGP-15 on cardiac mitochondrial respiration in an ageing ZDF model.

A Kunitz-type inhibitor from tick salivary glands: a promising novel antitumor drug candidate

Salivary glands are vital structures responsible for successful tick feeding. The saliva of ticks contains numerous active molecules that participate in several physiological processes. A Kunitz-type factor Xa (FXa) inhibitor, similar to the tissue factor pathway inhibitor (TFPI) precursor, was identified in the salivary gland transcriptome of Amblyomma sculptum ticks. The recombinant mature form of this Kunitz-type inhibitor, named Amblyomin-X, displayed anticoagulant, antiangiogenic, and antitumor properties. Amblyomin-X is a protein that inhibits FXa in the blood coagulation cascade and acts via non-hemostatic mechanisms, such as proteasome inhibition. Amblyomin-X selectively induces apoptosis in cancer cells and promotes tumor regression through these mechanisms. Notably, the cytotoxicity of Amblyomin-X seems to be restricted to tumor cells and does not affect non-tumorigenic cells, tissues, and organs, making this recombinant protein an attractive molecule for anticancer therapy. The cytotoxic activity of Amblyomin-X on tumor cells has led to vast exploration into this protein. Here, we summarize the function, action mechanisms, structural features, pharmacokinetics, and biodistribution of this tick Kunitz-type inhibitor recombinant protein as a promising novel antitumor drug candidate.

Valorisation of food agro-industrial by-products: From the past to the present and perspectives.

Food agro-industrial by-products mainly include peels, seeds, stems, bagasse, kernels, and husk, derived during food processing. Due to their overproduction and the lack of sustainable management, such by-products have been conventionally rejected and wasted in landfills, being the principal strategy for their treatment, but nowadays, this strategy has been associated with several environmental, social and economic issues. Hence, we focused on the use of different consolidated biotechnological processes and methodologies as suitable strategies for food by-products management and valorisation, highlighting them as potential bioresources because they still gather high compositional and nutritional value, owing to their richness in functional and bioactive molecules with human health benefits. Food by-products could be utilised for the development of new food ingredients or products for human consumption, promoting their integral valorisation and reincorporation to the food supply chain within the circular bioeconomy concept, creating revenue streams, business and job opportunities. In this review, the main goal was to provide a general overview of the food agro-industrial by-products utilised throughout the years, improving global sustainability and human nutrition, emphasising the importance of biowaste valorisation as well as the methodologies employed for the recovery of value-added molecules.

Current Perspectives on the Physiological Activities of Fermented Soybean-Derived Cheonggukjang.

Cheonggukjang (CGJ, fermented soybean paste), a traditional Korean fermented dish, has recently emerged as a functional food that improves blood circulation and intestinal regulation. Considering that excessive consumption of refined salt is associated with increased incidence of gastric cancer, high blood pressure, and stroke in Koreans, consuming CGJ may be desirable, as it can be made without salt, unlike other pastes. Soybeans in CGJ are fermented by Bacillus strains (B. subtilis or B. licheniformis), Lactobacillus spp., Leuconostoc spp., and Enterococcus faecium, which weaken the activity of putrefactive bacteria in the intestines, act as antibacterial agents against pathogens, and facilitate the excretion of harmful substances. Studies on CGJ have either focused on improving product quality or evaluating the bioactive substances contained in CGJ. The fermentation process of CGJ results in the production of enzymes and various physiologically active substances that are not found in raw soybeans, including dietary fiber, phospholipids, isoflavones (e.g., genistein and daidzein), phenolic acids, saponins, trypsin inhibitors, and phytic acids. These components prevent atherosclerosis, oxidative stress-mediated heart disease and inflammation, obesity, diabetes, senile dementia, cancer (e.g., breast and lung), and osteoporosis. They have also been shown to have thrombolytic, blood pressure-lowering, lipid-lowering, antimutagenic, immunostimulatory, anti-allergic, antibacterial, anti-atopic dermatitis, anti-androgenetic alopecia, and anti-asthmatic activities, as well as skin improvement properties. In this review, we examined the physiological activities of CGJ and confirmed its potential as a functional food.

Application of Ketoreductase in Asymmetric Synthesis of Pharmaceuticals and Bioactive Molecules: An Update (2018-2020).

With the rapid development of genomic DNA sequencing, recombinant DNA expression, and protein engineering, biocatalysis has been increasingly and widely adopted in the synthesis of pharmaceuticals, bioactive molecules, fine chemicals, and agrochemicals. In this review, we have summarized the most recent advances achieved (2018-2020) in the research area of ketoreductase (KRED)-catalyzed asymmetric synthesis of chiral secondary alcohol intermediates to pharmaceuticals and bioactive molecules. In the first part, synthesis of chiral alcohols with one stereocenter through the bioreduction of four different ketone classes, namely acyclic aliphatic ketones, benzyl or phenylethyl ketones, cyclic aliphatic ketones, and aryl ketones, is discussed. In the second part, KRED-catalyzed dynamic reductive kinetic resolution and reductive desymmetrization are presented for the synthesis of chiral alcohols with two contiguous stereocenters.

Dietary Epicatechin, A Novel Anti-aging Bioactive Small Molecule.

Epicatechin (EC), a flavonoid present in various foods including cocoa, dark chocolate, berries, and tea, has recently been reported to promote general health and survival of old mice fed a standard chow diet. This is considered a novel discovery in the field of identifying natural compounds to extend lifespan, given that presumably popular anti-aging natural agents including resveratrol, green tea extract, and curcumin had failed in extending the lifespan of standard chow-diet-fed mice. However, the anti-aging mechanism of EC is not fully understood, thus impeding the potential application of this natural compound in improving a healthy lifespan in humans. In this review, we first summarized the main dietary sources that contain a significant amount of EC and recent research regarding the absorption, metabolism and distribution of EC in humans and rodents. The review is then focused on the anti-aging effects of EC in cultured cells, animals and humans with the possible physiological, cellular and molecular mechanisms underlying its lifespan-extending effects.

Therapeutic Potential of Equol: A Comprehensive Review.

Equol (4',7-isoflavandiol), is a phytoestrogenic compound, which is synthesized from parent molecule diadzein by intestinal bacterial flora. It is among one of the most extensively researched molecule due to its high affinity towards estrogen receptors. Its enantiomeric form S-equol has been explored in the treatment of estrogen/androgen mediated diseases. Various therapeutic applications such as anti-cancer, cardioprotective, antidiabetic, antiosteoporosis, anti-ageing, and neuroprotective efficacy are attributed to it. This review explored major studies related to biochemistry and pharmacological applications of equol for human health.

Dental Pulp Stem Cells: Advances to Applications.

Dental pulp stem cells (DPSCs) have a high capacity for differentiation and the ability to regenerate a dentin/pulp-like complex. Numerous studies have provided evidence of DPSCs' differentiation capacity, such as in neurogenesis, adipogenesis, osteogenesis, chondrogenesis, angiogenesis, and dentinogenesis. The molecular mechanisms and functions of DPSCs' differentiation process are affected by growth factors and scaffolds. For example, growth factors such as basic fibroblast growth factor (bFGF), transforming growth factor-ß (TGF-ß), nerve growth factor (NGF), platelet-derived growth factor (PDGF), and bone morphogenic proteins (BMPs) influence DPSC fate, including in differentiation, cell proliferation, and wound healing. In addition, several types of scaffolds, such as collagen, hydrogel, decellularized bioscaffold, and nanofibrous spongy microspheres, have been used to characterize DPSC cellular attachment, migration, proliferation, differentiation, and functions. An appropriate combination of growth factors and scaffolds can enhance the differentiation capacity of DPSCs, in terms of optimizing not only dental-related expression but also dental pulp morphology. For a cell-based clinical approach, focus has been placed on the tissue engineering triad [cells/bioactive molecules (growth factors)/scaffolds] to characterize DPSCs. It is clear that a deep understanding of the mechanisms of stem cells, including their aging, self-renewal, microenvironmental homeostasis, and differentiation correlated with cell activity, the energy for which is provided from mitochondria, should provide new approaches for DPSC research and therapeutics. Mitochondrial functions and dynamics are related to the direction of stem cell differentiation, including glycolysis, oxidative phosphorylation, mitochondrial metabolism, mitochondrial transcription factor A (TFAM), mitochondrial elongation, and mitochondrial fusion and fission proteins. This review summarizes the effects of major growth factors and scaffolds for regenerating dentin/pulp-like complexes, as well as elucidating mitochondrial properties of DPSCs for the development of advanced applications research.

BioMOF@cellulose fabric composites for bioactive molecule delivery.

This work describes in situ synthesis and application of the zinc glutamate Bio Metal-Organic Framework (BioMOF) supported on cellulose fabrics as a dual material for nitric oxide (NO) and 5-fluorouracil (5FU) controlled delivery for wound and/or skin cancer therapy. In situ synthesis of BioMOF on the cotton fabric was successfully achieved and the incorporation of NO and 5FU was studied. We have observed that BioMOF doped with FeII metal ions has a beneficial impact on NO incorporation. The products obtained were analyzed with X-ray powder diffraction (XRPD), Fourier-Transform Infrared Spectroscopy-Attenuated Total Reflectance (FTIR-ATR), Field Emission Scanning Electron Microscopy (FESEM), Diffuse Reflectance UV-Vis-NIR spectrometer, X-Ray pHotoelectron Spectroscopy (XPS), Thermogravimetric Analysis (TGA), N2 adsorption analysis, Transition UV-Visible spectroscopy, and Gas Chromatography-Mass Spectroscopy (GC-MS). Moreover, antibacterial and anticancer activity in melanoma skin cell was carried out in order to prove the biological activity of the drug-loaded BioMOF on treated cellulose fabrics. These studies are indicative of the potential of BioMOF@cellulose fabric composites for the controlled delivery of bioactive molecules on the wound and/or cancer.