miRNA omics reveal neferine induces apoptosis through Ca2+mediated endoplasmic reticulum stress pathway in human endometrial cancer.

BACKGROUND: Endometrial cancer (EC) as one of the most prevalent malignancies in the female reproductive system, usually has a poor diagnosis and unfavorable health effects. Neferine (Nef), derived from the edible and medicinal lotus seed, has been known for its functional activity; however, its anti-cancer mechanism for EC remains elusive. PURPOSE: We explored the potential anti-cancer effects and underlying molecular mechanisms of Nef on EC. METHODS: The cytotoxicity was tested using MTT, and the cell cycle, apoptosis, Ca2+ levels, and the mitochondrial membrane potential (MMP) were observed through flow cytometry. After Nef treatment, differences in miRNA expression were identified using miRNA-seq data. Furthermore, western blot and immunohistochemistry (IHC) were employed to identify the proteins associated with apoptosis in both mice and cells. RESULTS: Nef treatment led to Ishikawa cell apoptosis and blocked cell proliferation in the G2/M phase. In total, 101 significantly different miRNA (p 〈 0.05 and |logFC| 〉 1) were obtained and subjected to GO and KEGG enrichment analysis, which revealed the Ca2+ and PI3K/AKT signaling pathways pertaining to apoptosis. Nef treatment significantly changed intracellular Ca2+ levels and MMP, activating the endoplasmic reticulum stress (ERS) pathway and the expression of key proteins in the mitochondrial pathway. In addition, Nef also inhibited the expression of key proteins in the PI3K/AKT pathway, causing cell apoptosis. Moreover, in mouse tumor tissues, the expression of CHOP, Bcl-2, Caspase 3, Cyto-c, and p-AKT was also consistent with the results in vitro. CONCLUSION: Nef could block the cell cycle and induce the activation of the mitochondrial apoptotic pathway involving the Ca2+-mediated ERS pathway and the PI3K/AKT pathway, thereby inducing apoptosis in EC cells, confirming the potential role of Nef in the prevention and treatment of EC.

Exploring the Potential of Invasive Species Sargassum muticum: Microwave-Assisted Extraction Optimization and Bioactivity Profiling.

Sargassum muticum (SM) poses a serious environmental issue since it is a fast-expanding invasive species occupying key areas of the European shoreline, disrupting the autochthonous algae species, and disturbing the ecosystem. This problem has concerned the general population and the scientific community. Nevertheless, as macroalgae are recognized as a source of bioactive molecules, the abundance of SM presents an opportunity as a raw material. In this work, response surface methodology (RSM) was applied as a tool for the optimization of the extraction of bioactive compounds from SM by microwave-assisted extraction (MAE). Five different parameters were used as target functions: yield, total phenolic content (TPC); and the antioxidant measurements of 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity (DPPH), 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS), and ß-carotene bleaching (BC). After the optimal extraction conditions were determined (time = 14.00 min; pressure = 11.03 bar; ethanol = 33.31%), the chemical composition and bioactivity of the optimum extract was evaluated to appraise its antioxidant capability to scavenge reactive species and as a potential antibacterial, antidiabetic, antiproliferation, and neuroprotective agent. The results lead to the conclusion that MAE crude extract has bioactive properties, being especially active as an antiproliferation agent and as a nitric oxide and superoxide radical scavenger.

Unraveling the Bioactive Potential of Camellia japonica Edible Flowers: Profiling Antioxidant Substances and In Vitro Bioactivity Assessment.

In recent years, the search for novel natural-based ingredients by food and related industries has sparked extensive research aimed at discovering new sources of functional molecules. Camellia japonica, traditionally known as an ornamental plant, has gained attention due to its diverse array of bioactive compounds with potential industrial applications. Although C. japonica flowers are edible, their phytochemical profile has not been thoroughly investigated. In this study, a phenolic profile screening through an HPLC-ESI-QQQ-MS/MS approach was applied to C. japonica flower extracts, revealing a total of 36 compounds, including anthocyanins, curcuminoids, dihydrochalcones, dihydroflavonols, flavonols, flavones, hydroxybenzoic acids, hydroxycinnamic acids, isoflavonoids, stilbenes, and tyrosols. Following extract profiling, their bioactivity was assessed by means of in vitro antioxidant, antimicrobial, cytotoxic, and neuroprotective activities. The results showed a multifaceted high correlation of phenolic compounds with all the tested bioactivities according to Pearson's correlation analysis, unraveling the potential of C. japonica flowers as promising sources of nutraceuticals. Overall, these findings provide insight into the valorization of C. japonica flowers from different unexplored cultivars thus diversifying their industrial outcome.

Bioactive sulforaphane from cruciferous vegetables: advances in biosynthesis, metabolism, bioavailability, delivery, health benefits, and applications.

Chronic inflammation-induced diseases (CID) are the dominant cause of death worldwide, contributing to over half of all global deaths. Sulforaphane (SFN) derived from cruciferous vegetables has been extensively studied for its multiple functional benefits in alleviating CID. This work comprehensively reviewed the biosynthesis, metabolism, bioavailability, delivery, health benefits, and applications of SFN and its potential mechanisms against CID (e.g., cancer, obesity, type 2 diabetes, et al.), and neurological disorders based on a decade of research. SFN exerts its biological functions through the hydrolysis of glucosinolates by gut microbiota, and exhibits rapid metabolism and excretion characteristics via metabolization of mercapturic acid pathway. Microencapsulation is an important way to improve the stability and targeted delivery of SFN. The health benefits of SNF against CID are attributed to the multiple regulatory mechanisms including modulating oxidative stress, inflammation, apoptosis, immune response, and intestinal homeostasis. The clinical applications of SFN and related formulations show promising potential; however, further exploration is required regarding the sources, dosages, toxicity profiles, and stability of SFN. Together, SFN is a natural product with great potential for development and application, which is crucial for the development of functional food and pharmaceutical industries.

Extraction, purification and anticancer activity studies on triterpenes from pomegranate peel.

Pomegranate peel is the by-product of pomegranate processing, which contains a lot of triterpene compounds. In this study, the total triterpenes of pomegranate peel (TPP) were extracted using an ultrasonic-assisted ethanol extraction method under optimal conditions, purified using D-101 macroporous resin to obtain a purity of 75.28%. The triterpenes in TPP were mainly pentacyclic triterpenes determined by LC-MS/MS. Network pharmacological analysis predicted that the anticancer targets were closely related to the MAPK pathway. The in vitro results showed that TPP could inhibit cell proliferation, promote apoptosis, reduce mitochondrial membrane potential and increase ROS levels. The western blot results indicated that the expression levels of the apoptotic proteins Bax, Bcl-2, cytochrome C, cleaved caspase-3 and cleaved caspase-9 were increased. In addition, the protein expression of the MAPK pathway predicted by network pharmacology also changed significantly. These results provided that TPP has potential for adjuvant therapy of tumors.

Potential application of carduma (Cetengraulis mysticetus) and plumuda (Opisthonema spp.) fish paste for the development of a leberkäse (liver loaf) fish product: Physicochemical and functional properties.

This study investigated the potential use of fish paste from two pelagic species (Cetengraulis mysticetus or carduma in Colombia and Opisthonema sp. or plumuda in Colombia), either separately or combined, as a substitute for external fat sources in a Leberkäse product. Three stages were analyzed, evaluating biometric proportions, body performance, and meat batters containing different concentrations of fish pastes. Physicochemical and instrumental characterization analyses were performed to determine the effect of the type of fish paste and the level of its inclusion in the final product. Results showed that plumuda fish paste had higher protein and ash content than carduma fish paste, and the inclusion of carduma fish paste in meat batters led to a greater loss of liquid and lower emulsion and gel stability values. The study also established selection criteria for the two pelagic fish species that could be useful for the fishing industry. Overall, the study demonstrated that Leberkäse can be produced using these pelagic species with a relatively simple processing technology.

Correction: Chakraborty et al. Bromelain a Potential Bioactive Compound: A Comprehensive Overview from a Pharmacological Perspective. Life 2021, 11, 317.

The authors were not aware of errors made in one small subsection (Section 6.17. Antidiarrheal Effect, including the data in the table of effects) of this paper [...].

The Impact of Vitamin D and Its Dietary Supplementation in Breast Cancer Prevention: An Integrative Review.

Vitamin D deficiency is currently a significant public health issue closely linked to numerous diseases, such as breast cancer. This study aims to determine the estimated optimal serum levels of vitamin D to have a protective effect against breast cancer, in addition to exploring the biological mechanisms and risk factors involved. A literature search of articles published in the last 5 years was conducted, and simple statistical analyses using mean and standard deviation were performed to calculate the average concentration of vitamin D from different available studies. It has been observed that serum levels of vitamin D ≥ 40.26 ng/mL ± 14.19 ng/mL could exert a protective effect against breast cancer. Additionally, various biological mechanisms, such as those related to the immune system, and risk factors like diet implicated in this relationship were elucidated. Consequently, it can be concluded that proper serum levels of vitamin D may have a protective effect against breast cancer, and dietary supplementation may be an appropriate procedure to achieve these optimal vitamin D concentrations.

Evaluating the hypolipidemic effect of garlic essential oil encapsulated in a novel double-layer delivery system.

The limited application of garlic essential oil (GEO) is attributed to its pungent taste, poor water solubility and low bioavailability. Liposomes are nontoxic, biodegradable and biocompatible, and ß-cyclodextrin can inhibit undesirable odors and improve the stability and bioavailability. Thus a promising dual-layer GEO ß-cyclodextrin inclusion compound liposome (GEO-DCL) delivery system with both advantages was designed and prepared in this study. Experimental results indicated that the encapsulation efficiency of GEO-DCLs was 5% higher than that of GEO liposomes (GEO-CLs), reaching more than 88%. In vitro release experiment showed that the release rate of GEO in GEO-DCLs was 40% lower than that of GEO-CLs after incubation in gastric juice for 6-h, indicating that the stability of GEO-DCLs was better than GEO-CLs. Evaluation of the effects of GEO-DCLs on lowering blood lipid levels in hypercholesterolemia mice. GEO-DCLs could reduce the weight and fat deposition in hypercholesterolemia mice. Inhibiting the increase of TC, LDL-C, and decrease of HDL-C in mice. The degree of liver injury was decreased, the number of round lipid droplets in liver cytoplasm was reduced, and the growth of fat cells was inhibited. The lipid-lowering effects of GEO-DCLs were dose-dependent. GEO-DCL can improve the bioavailability of GEO and improve dyslipidemia. Based on GEO's efficacy in lowering blood lipids, this study developed a kind of GEO-DCL compound pomegranate juice beverage with good taste, miscibility and double effect of reducing blood lipids. This study lays a foundation for the application of GEO in the field of functional food.

Myco-remediation of plastic pollution: current knowledge and future prospects.

To date, enumerable fungi have been reported to participate in the biodegradation of several notorious plastic materials following their isolation from soil of plastic-dumping sites, marine water, waste of mulch films, landfills, plant parts and gut of wax moth. The general mechanism begins with formation of hydrophobin and biofilm proceding to secretion of specific plastic degarding enzymes (peroxidase, hydrolase, protease and urease), penetration of three dimensional substrates and mineralization of plastic polymers into harmless products. As a result, several synthetic polymers including polyethylene, polystyrene, polypropylene, polyvinyl chloride, polyurethane and/or bio-degradable plastics have been validated to deteriorate within months through the action of a wide variety of fungal strains predominantly Ascomycota (Alternaria, Aspergillus, Cladosporium, Fusarium, Penicillium spp.). Understanding the potential and mode of operation of these organisms is thus of prime importance inspiring us to furnish an up to date view on all the presently known fungal strains claimed to mitigate the plastic waste problem. Future research henceforth needs to be directed towards metagenomic approach to distinguish polymer degrading microbial diversity followed by bio-augmentation to build fascinating future of waste disposal.

A review for cancer treatment with mushroom metabolites through targeting mitochondrial signaling pathway: In vitro and in vivo evaluations, clinical studies and future prospects for mycomedicine.

Resistance to apoptosis stands as a roadblock to the successful pharmacological execution of anticancer drug effect. A comprehensive insight into apoptotic signaling pathways and an understanding of the mechanisms of apoptosis resistance are crucial to unveil new drug targets. At this juncture, researchers are heading towards natural sources in particular, mushroom as their potential drugs leads to being the reliable source of potent bioactive compounds. Given the continuous increase in cancer cases, the potent anticancer efficacy of mushrooms has inevitably become a fascinating object to researchers due to their higher safety margin and multitarget. This review aimed to collect and summarize all the available scientific data on mushrooms from their extracts to bioactive molecules in order to suggest their anticancer attributes via a mitochondrion -mediated intrinsic signaling mechanism. Compiled data revealed that bioactive components of mushrooms including polysaccharides, sterols and terpenoids as well as extracts prepared using 15 different solvents from 53 species could be effective in the supportive treatment of 20 various cancers. The underlying therapeutic mechanisms of the studied mushrooms are explored in this review through diverse and complementary investigations: in vitro assays, pre-clinical studies and clinical randomized controlled trials. The processes mainly involved were ROS production, mitochondrial membrane dysfunction, and action of caspase 3, caspase 9, XIAP, cIAP, p53, Bax, and Bcl-2. In summary, the study provides facts pertaining to the potential beneficial effect of mushroom extracts and their active compounds against various types of cancer and is shedding light on the underlying targeted signaling pathways.

Phytochemical compounds with promising biological activities from Ascophyllum nodosum extracts using microwave-assisted extraction.

Phytochemical-rich antioxidant extracts were obtained from Ascophyllum nodosum (AN) using microwave-assisted extraction (MAE). Critical extraction factors such as time, pressure, and ethanol concentration were optimized by response surface methodology with a circumscribed central composite design. Under the optimal MAE conditions (3 min, 10.4 bar, 46.8 % ethanol), the maximum recovery of phytochemical compounds (polyphenols and fucoxanthin) with improved antioxidant activity from AN was obtained. In addition, the optimized AN extract showed significant biological activities as it was able to scavenge reactive oxygen and nitrogen species, inhibit central nervous system-related enzymes, and exhibit cytotoxic activity against different cancer cell lines. In addition, the optimized AN extract showed antimicrobial, and anti-quorum sensing activities, indicating that this extract could offer direct and indirect protection against infection by pathogenic microorganisms. This work demonstrated that the sustainably obtained AN extract could be an emerging, non-toxic, and natural ingredient with potential to be included in different applications.

Comprehensive analysis of pigment alterations and associated flavor development in strip and needle green teas.

Strip/needle green teas (SGT/NGT) processed using innovative technologies are in high demand; however, mechanisms behind their color and flavor have not been comprehensively studied. We aimed to reveal the dynamics of major pigmented components (carotenoids, lipids, flavonoids, and Maillard products) and their contributions to the flavor of green teas. The total content of flavonoids in SGT and NGT were 255 ± 4.51 and 201 ± 3.91 mg·g-1, respectively; these values are slightly lower than that in fresh leaves (FLs), resulting in a fresh and sweet aftertaste. In average, carotene content in SGT/NGT (24.8 µg·g-1) was higher than in FL (17.4 µg·g-1), whilst xanthophyll content (603 µg·g-1) decreased to one-half of that in FL (310 µg·g-1). Among the 218 primary metabolites, glutamine, glutamic acid, and arginine were found to accumulate and were dominate contributors for the umami and sweet taste. Notably, more than 96 volatiles were screened and revealed their correlations with carotenoids, lipids, and amino acids. Overall, the synergism between pigments and their non-enzymatic derivates' contribution to GT characterized flavor was illustrated.

Sustainable and Green Synthesis of Iron Nanoparticles Supported on Natural Clays via Palm Waste Extract for Catalytic Oxidation of Crocein Orange G Mono Azoic Dye.

In this study, the removal of Crocein Orange G dye (COG) from aqueous solution was investigated using an innovative green catalyst to overcome problems with chemical techniques. Clay bentonite El Hamma (HB)-supported nanoscale zero-valent iron (NZVI) was used as a heterogeneous Fenton-like catalyst for the oxidation of harmful COG. Palm waste extract was herein used as a reducing and capping agent to synthesize NZVI, and HB clay was employed, which was obtained from the El Hamma bentonite deposit in the Gabes province of Tunisia. HB and HB-NZVI were characterized by various techniques such as scanning electron microscopy (SEM), transmission electron microscopy (TEM), Brunauer, Emmett, and Teller (BET), Fourier transform infrared spectroscopy (FTIR), dynamic light scattering (DLS), X-ray diffraction (XRD), and zeta potential. Under optimal conditions, total degradation of COG was attained within 180 min. Kinetic studies showed that the dye degradation rate followed well the pseudo-second-order model. The apparent activation energy was 33.11 kJ/mol, which is typical of a physically controlled reaction. The degradation pathways and mineralization study revealed that the adsorption-Fenton-like reaction was the principal mechanism that demonstrated 100% degradation efficiency of COG even after three successive runs. Obtained results suggest that HB-NZVI is an affective heterogeneous catalyst for the degradation of COG by H2O2 and may constitute a sustainable green catalyst for azoic dye removal from industrial wastewaters.

Opuntia ficus-indica (L.) Mill. - anticancer properties and phytochemicals: current trends and future perspectives.

Cancer is a leading cause of mortality worldwide, and conventional cancer therapies such as chemotherapy and radiotherapy often result in undesirable and adverse effects. Natural products have emerged as a promising alternative for cancer treatment, with comparatively fewer side effects reported. Opuntia ficus-indica (L.) Mill., a member of the Cactaceae family, contains a diverse array of phytochemicals, including flavonoids, polyphenols, betalains, and tannins, which have been shown to exhibit potent anticancer properties. Various parts of the Opuntia plant, including the fruits, stems/cladodes, and roots, have demonstrated cytotoxic effects against malignant cell lines in numerous studies. This review comprehensively summarizes the anticancer attributes of the phytochemicals found in Opuntia ficus-indica (L.) Mill., highlighting their potential as natural cancer prevention and treatment agents. Bibliometric metric analysis of PubMed and Scopus-retrieved data using VOSviewer as well as QDA analysis provide further insights and niche to be explored. Most anticancer studies on Opuntia ficus-indica and its purified metabolites are related to colorectal/colon cancer, followed by melanoma and breast cancer. Very little attention has been paid to leukemia, thyroid, endometrial, liver, and prostate cancer, and it could be considered an opportunity for researchers to explore O. ficus-indica and its metabolites against these cancers. The most notable mechanisms expressed and validated in those studies are apoptosis, cell cycle arrest (G0/G1 and G2/M), Bcl-2 modulation, antiproliferative, oxidative stress-mediated mechanisms, and cytochrome c. We have also observed that cladodes and fruits of O. ficus-indica have been more studied than other plant parts, which again opens the opportunity for the researchers to explore. Further, cell line-based studies dominated, and very few studies were related to animal-based experiments. The Zebrafish model is another platform to explore. However, it seems like more in-depth studies are required to ascertain clinical utility of this biosustainable resource O. ficus-indica.

Antifungal action and targeted mechanism of Bio fabricated zinc oxide (ZnO) nanoparticles against Ascochytafabae.

The current work focuses on analysing the structural, optical, and anti-fungal efficacy of ZnO nanoparticles using well diffusion agar methods and minimum inhibitory concentration (MIC). ZnO nanoparticles were created using the sol gel method. To check the synthesized material's spatial and optical characteristics, XRD, UV, and RAMAN studies were performed. The median diameter of produced nanostructures is in the region of nanometre, according to XRD measurements. Results from Raman Spectroscopy for the nanostructure are provided, together with comparisons to current development theory and reliable experimental data. The band gap of the zinc oxide sample is found by graphing (h) 2versus input photon energy and gradually decreasing the linear component of the (h) 2 to zero. The band gap energy is expressed by the line's intersection with the energy axis. Calculations show that the energy band gap is 3.22eV.The fungus Ascochytafabae is in control of the Phaseolus vulgaris L. (beans) blight disease. It mostly affects the plant's stem, leaves, and fruits. Phaseolus vulgaris plant leaf with Ascochytafabae infection was isolated, and ZnO nanoparticle effects were observed. It emerged that the synthesized ZnO nanoparticles were highly efficient against Ascochytafabae. By using the well diffusion method and an absolute concentration of ZnO nanoparticles, the maximum inhibitory concentration was 15.0 ± 0.2 mm.

Challenges in the Application of Circular Economy Models to Agricultural By-Products: Pesticides in Spain as a Case Study.

The income and residue production from agriculture has a strong impact in Spain. A circular economy and a bioeconomy are two alternative sustainable models that include the revalorization of agri-food by-products to recover healthy biomolecules. However, most crops are conventional, implying the use of pesticides. Hence, the reutilization of agri-food by-products may involve the accumulation of pesticides. Even though the waste-to-bioproducts trend has been widely studied, the potential accumulation of pesticides during by-product revalorization has been scarcely assessed. Therefore, in this study, the most common pesticides found in eight highly productive crops in Spain are evaluated according to the available published data, mainly from EFSA reports. Among these, oranges, berries and peppers showed an increasing tendency regarding pesticide exceedances. In addition, the adverse effects of pesticides on human and animal health and the environment were considered. Finally, a safety assessment was developed to understand if the reutilization of citrus peels to recover ascorbic acid (AA) would represent a risk to human health. The results obtained seem to indicate the safety of this by-product to recover AA concentrations to avoid scurvy (45 mg/day) and improve health (200 mg/day). Therefore, this work evaluates the potential risk of pesticide exposure through the revalorization of agri-food by-products using peels from citruses, one of the major agricultural crops in Spain, as a case study.