Suppressing Organic Bromine but Promoting Bromate: Is the Ultraviolet/Ozone Process a Double-Edged Sword for the Toxicity of Wastewater to Mammalian Cells?

Brominated byproducts and toxicity generation are critical issues for ozone application to wastewater containing bromide. This study demonstrated that ultraviolet/ozone (UV/O3, 100 mJ/cm2, 1 mg-O3/mg-DOC) reduced the cytotoxicity of wastewater from 14.2 mg of pentol/L produced by ozonation to 4.3 mg of pentol/L (1 mg/L bromide, pH 7.0). The genotoxicity was also reduced from 1.65 to 0.17 µg-4-NQO/L by UV/O3. Compared with that of O3 alone, adsorbable organic bromine was reduced from 25.8 to 5.3 µg/L by UV/O3, but bromate increased from 32.9 to 71.4 µg/L. The UV/O3 process enhanced the removal of pre-existing precursors (highly unsaturated and phenolic compounds and poly aromatic hydrocarbons), while new precursors were generated, yet the combined effect of UV/O3 on precursors did not result in a significant change in toxicity. Instead, UV radiation inhibited HOBr concentration through both rapid O3 decomposition to reduce HOBr production and decomposition of the formed HOBr, thus suppressing the AOBr formation. However, the hydroxyl radical-dominated pathway in UV/O3 led to a significant increase of bromate. Considering both organic bromine and bromate, the UV/O3 process effectively controlled both cytotoxicity and genotoxicity of wastewater to mammalian cells, even though an emphasis should be also placed on managing elevated bromate. Futhermore, other end points are needed to evaluate the toxicity outcomes of the UV/O3 process.

Renal interstitial fibrotic assessment using non-Gaussian diffusion kurtosis imaging in a rat model of hyperuricemia.

BACKGROUND: To investigate the feasibility of Diffusion Kurtosis Imaging (DKI) in assessing renal interstitial fibrosis induced by hyperuricemia. METHODS: A hyperuricemia rat model was established, and the rats were randomly split into the hyperuricemia (HUA), allopurinol (AP), and AP + empagliflozin (AP + EM) groups (n = 19 per group). Also, the normal rats were selected as controls (CON, n = 19). DKI was performed before treatment (baseline) and on days 1, 3, 5, 7, and 9 days after treatment. The DKI indicators, including mean kurtosis (MK), fractional anisotropy (FA), and mean diffusivity (MD) of the cortex (CO), outer stripe of the outer medulla (OS), and inner stripe of the outer medulla (IS) were acquired. Additionally, hematoxylin and eosin (H&E) staining, Masson trichrome staining, and nuclear factor kappa B (NF-κB) immunostaining were used to reveal renal histopathological changes at baseline, 1, 5, and 9 days after treatment. RESULTS: The HUA, AP, and AP + EM group MKOS and MKIS values gradually increased during this study. The HUA group exhibited the highest MK value in outer medulla. Except for the CON group, all the groups showed a decreasing trend in the FA and MD values of outer medulla. The HUA group exhibited the lowest FA and MD values. The MKOS and MKIS values were positively correlated with Masson's trichrome staining results (r = 0.687, P < 0.001 and r = 0.604, P = 0.001, respectively). The MDOS and FAIS were negatively correlated with Masson's trichrome staining (r = -626, P < 0.0014 and r = -0.468, P = 0.01, respectively). CONCLUSION: DKI may be a non-invasive method for monitoring renal interstitial fibrosis induced by hyperuricemia.

New Insight into Utilization of Fish By-Product Proteins and Their Skin Health Promoting Effects.

In regions reliant on fisheries for livelihoods, a significant number of fish by-products are generated annually due to processing. These discarded parts contain valuable biological resources, such as proteins, fish oils, and trace elements, thus holding enormous potential for reutilization. In recent years, fish by-product proteins have been widely utilized in skincare products due to their rich collagen content, biosafety, and biocompatibility. This review summarizes the research into and applications of fish by-product proteins in skin health, including alleviating oxidative stress and skin inflammation, reducing DNA damage, mitigating melanin production, improving skin hydration, slowing skin matrix degradation, and promoting synthesis. Additionally, the possibility of improving skin health by improving the abundance of gut microbiota is also discussed. This review underscores the importance of fish by-product proteins in the fisheries, food processing, cosmetics, and biomedical industries.

Critical review on anti-inflammation effects of saponins and their molecular mechanisms.

This review highlights the increasing interest in one of the natural compounds called saponins, for their potential therapeutic applications in addressing inflammation which is a key factor in various chronic diseases. It delves into the molecular mechanisms responsible for the anti-inflammatory effects of these amphiphilic compounds, prevalent in plant-based foods and marine organisms. Their structures vary with soap-like properties influencing historical uses in traditional medicine and sparking renewed scientific interest. Recent research focuses on their potential in chronic inflammatory diseases, unveiling molecular actions such as NF-κB and MAPK pathway regulation and COX/LOX enzyme inhibition. Saponin-containing sources like Panax ginseng and soybeans suggest novel anti-inflammatory therapies. The review explores their emerging role in shaping the gut microbiome, influencing composition and activity, and contributing to anti-inflammatory effects. Specific examples, such as Panax notoginseng and Gynostemma pentaphyllum, illustrate the intricate relationship between saponins, the gut microbiome, and their collective impact on immune regulation and metabolic health. Despite promising findings, the review emphasizes the need for further research to comprehend the mechanisms behind anti-inflammatory effects and their interactions with the gut microbiome, underscoring the crucial role of a balanced gut microbiome for optimal health and positioning saponins as potential dietary interventions for managing chronic inflammatory conditions.

Recent developments and emerging trends in dietary vitamin D sources and biological conversion.

This review elaborates on biochemical characteristics, in vivo metabolism, biological conversion through UV irradiation, as well as dietary fortification of vitamin D. Recent innovations in vitamin D utilization, including nanoencapsulation, direct or indirect addition, emulsion, ultrasound, microwave processing, CRISPR-Cas9 genome editing, as well as UV photoconversion, were summarized. Mushrooms, eggs, yeasts, as well as seafood, such as Barramundi and Atlantic salmon, were typical representatives of original natural food materials for vitamin D bioconversion in relevant research. The critical session thereof referred to the 295 nm UV-B irradiation triggering biological fortification of vitamin D2 and vitamin D3, which occurred in ergosterol from mushrooms, and cholesterol from egg yolk, respectively. The schematic biosynthesis of vitamin D precursors in yeasts regulated miscellaneous enzymes were clearly demonstrated. These summarized pathways played a role as a theoretical primer for vitamin D bioconversion when the UV irradiation technique is concerned. Besides, tomatoes had become the latest potential vitamin D sources after genetic modification. The safety consideration for vitamin D fortified functional food was discussed either. Further research is required to fill the gap of investigating optimized factors like types of eggs, meat, and grain, boarder range of wavelength, and dosage in UV irradiation. Vitamin D has a great potential market in the field of functional food development.

Comprehensive review on signaling pathways of dietary saponins in cancer cells suppression.

Nutrigenomics utilizes high-throughput genomic technologies to reveal changes in gene and protein levels. Excitingly, ever-growing body of scientific findings has provided sufficient evidence about the interplay between diet and genes. Cutting-edge research and advancements in genomics, epigenetics and metabolomics have deepened our understanding on the role of dietary factors in the inhibition of carcinogenesis and metastasis. Dietary saponins, a type of triterpene glycosides, are generally found in Platycodon grandifloras, Dioscorea oppositifolia, asparagus, legumes, and sea cucumber. Wealth of information has started to shed light on pleiotropic mechanistic roles of dietary saponins in cancer prevention and inhibition. In this review, we have attempted to summarize the in vitro research of dietary saponins in the last two decades by searching common databases such as Google Scholar, PubMed, Scopus, and Web of Science. The results showed that dietary saponins exerted anti-cancer activities via regulation of apoptosis, autophagy, arrest cell cycle, anti-proliferation, anti-metastasis, and anti-angiogenesis, by regulation of several critical signaling pathways, including MAPK, PI3K/Akt/mTOR, NF-κB, and VEGF/VEGFR. However, there is no data about the dosage of dietary saponins for practical anti-cancer effects in human bodies. Extensive clinical studies are needed to confirm the effectiveness of dietary saponins for further commercial and medical applications.

Insights into health promoting effects and myochemical profiles of pine mushroom Tricholoma matsutake.

Tricholoma matsutake (TM) is a valuable edible mushroom that has attracted increasing attention due to its potential medicinal values and functional uses. However, the chemical composition and molecular mechanisms behinds TM are not specifically summarized yet. Hence, this review aims to systematically analyze the research progress on the characterization of chemical compositions and the reported health effects of TM in the last 20 years. The myochemical profiles of TM consist of proteins with amino acids, fatty acids, nucleic acids with their derivatives, polysaccharides, minerals, volatile components, phenolic compounds, and steroids. The bioactive substances in TM exert their health effects mainly by regulating body immunity and restoring the balance of the redox system. NF-κB signaling pathway and its downstream cytokines such as TNF-α and IL-6 are the key molecular mechanisms. In addition, MAPK, PI3K-Akt, and JAK-STAT are also involved. NF-κB, MAPK, and PI3K-Akt are also highly related to cancer regulation and thus TM has great anticancer potential. Considering that most studies have only investigated the dosage and inhibition rate of TM on cancer cell lines, more extensive studies need to focus on the specific molecular mechanisms behind these anticancer effects in the future.

Review of the recent developments in metabolomics-based phytochemical research.

Phytochemicals are important bioactive components present in natural products. Although the health benefits of many food products are well-known and accepted as a common knowledge, the identity of the main bioactive molecules and the mechanism by which they interact in the body of human are often unknown. It was only in the last 30 years when the field of metabolomics had matured that the identification of such molecules with bioactivity has been made possible through the development of instruments to separate and computational techniques to characterize complex samples. This in turn has enabled in vitro studies to quantify the biological activity of the respective phytochemical either in mice models or in humans. In this review, the importance of key dietary phytochemicals such as phenolic acids, flavonoids, carotenoids, resveratrol, curcumin, and capsaicinoids are discussed together with their potential functions for human health. Untargeted metabolomics, in particular, liquid chromatography mass spectrometry, is the most used method to isolate, identify and profile bioactive compounds in the study of phytochemicals in foods. The application of metabolomics in drug discovery is a common practice nowadays and has boosted the drug and/or supplement manufacturing sector. HighlightsPhytochemicals are beneficial compounds for human healthPhytochemicals are plant-based bioactive and obtainable from natural productsUntargeted metabolomics has boosted the discovery of phytochemicals from foodTargeted metabolomics is key in the authentication and screening of phytochemicalsMetabolomics of phytochemicals is reshaping the road to drug and supplement manufacture.

Molecular Mechanisms of Bioactive Nutrients Promoting Health through Gut Microbiota.

Many food components (such as phytochemicals, complex carbohydrates, proteins, fats, vitamins, minerals, etc [...].

Network Pharmacology and Bioinformatics Study of Geniposide Regulating Oxidative Stress in Colorectal Cancer.

This study aims to identify the mechanism of geniposide regulating oxidative stress in colorectal cancer (CRC) through network pharmacology and bioinformatics analysis. Targets of geniposide, oxidative stress-related targets and targets related to CRC were applied from databases. The hub genes for geniposide regulating oxidative stress in CRC were identified with the protein-protein interaction (PPI) network. Furthermore, we applied Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment to analyze the hub genes from a macro perspective. We verified the hub genes by molecular docking, GEPIA, HPA and starBase database. We identified five hub genes: IL1B, GSK3B, NOS3, RELA and CDK4. GO analysis results suggested that the anti-colorectal cancer effect of geniposide by regulating oxidative stress is possibly related to the influence of multiple biological processes, including response to temperature stimulus, response to alkaloid, nitric oxide biosynthetic process, nitric oxide metabolic process, reactive nitrogen species metabolic process, cellular response to peptide, etc. KEGG enrichment analysis results indicated that the PI3K-Akt signaling pathway, IL-17 signaling pathway, p53 signaling pathway, NF-κB signaling pathway and NOD-like receptor signaling pathway are likely to be the significant pathways. Molecular docking results showed that the geniposide had a good binding activity with the hub genes. This study demonstrates that geniposide can regulate oxidative stress in CRC, and induction of oxidative stress is one of the possible mechanisms of anti-recurrence and metastasis effects of geniposide against CRC.

Bufalin-Mediated Regulation of Cell Signaling Pathways in Different Cancers: Spotlight on JAK/STAT, Wnt/ß-Catenin, mTOR, TRAIL/TRAIL-R, and Non-Coding RNAs.

The renaissance of research into natural products has unequivocally and paradigmatically shifted our knowledge about the significant role of natural products in cancer chemoprevention. Bufalin is a pharmacologically active molecule isolated from the skin of the toad Bufo gargarizans or Bufo melanostictus. Bufalin has characteristically unique properties to regulate multiple molecular targets and can be used to harness multi-targeted therapeutic regimes against different cancers. There is burgeoning evidence related to functional roles of signaling cascades in carcinogenesis and metastasis. Bufalin has been reported to regulate pleiotropically a myriad of signal transduction cascades in various cancers. Importantly, bufalin mechanistically regulated JAK/STAT, Wnt/ß-Catenin, mTOR, TRAIL/TRAIL-R, EGFR, and c-MET pathways. Furthermore, bufalin-mediated modulation of non-coding RNAs in different cancers has also started to gain tremendous momentum. Similarly, bufalin-mediated targeting of tumor microenvironments and tumor macrophages is an area of exciting research and we have only started to scratch the surface of the complicated nature of molecular oncology. Cell culture studies and animal models provide proof-of-concept for the impetus role of bufalin in the inhibition of carcinogenesis and metastasis. Bufalin-related clinical studies are insufficient and interdisciplinary researchers require detailed analysis of the existing knowledge gaps.

Critical review on anti-obesity effects of phytochemicals through Wnt/ß-catenin signaling pathway.

Phytochemicals have been used as one of the sources for the development of anti-obesity drugs. Plants are rich in a variety of bioactive compounds including polyphenols, saponins and terpenes. Phytochemicals inhibit adipocyte differentiation by inhibiting the transcription and translation of adipogenesis transcription factors such as C/EBPα and PPARγ. It has been proved that phytochemicals inhibit the genes and proteins associated with adipogenesis and lipid accumulation by activating Wnt/ß-catenin signaling pathway. The activation of Wnt/ß-catenin signaling pathway by phytochemicals is multi-target regulation, including the regulation of pathway critical factor ß-catenin and its target gene, the downregulation of destruction complex, and the up-regulation of Wnt ligands, its cell surface receptor and Wnt antagonist. In this review, the literature on the anti-obesity effect of phytochemicals through Wnt/ß-catenin signaling pathway is collected from Google Scholar, Scopus, PubMed, and Web of Science, and summarizes the regulation mechanism of phytochemicals in this pathway. As one of the alternative methods of weight loss drugs, Phytochemicals inhibit adipogenesis through Wnt/ß-catenin signaling pathway. More progress in relevant fields may pose phytochemicals as the main source of anti-obesity treatment.

New insights into anti-diabetes effects and molecular mechanisms of dietary saponins.

Diabetes mellitus (DM) is a long-term metabolic disorder that manifests as chronic hyperglycemia and impaired insulin, bringing a heavy load on the global health care system. Considering the inevitable side effects of conventional anti-diabetic drugs, saponins-rich natural products exert promising therapeutic properties to serve as safer and more cost-effective alternatives for DM management. Herein, this review systematically summarized the research progress on the anti-diabetic properties of dietary saponins and their underlying molecular mechanisms in the past 20 years. Dietary saponins possessed the multidirectional anti-diabetic capabilities by concurrent regulation of various signaling pathways, such as IRS-1/PI3K/Akt, AMPK, Nrf2/ARE, NF-κB-NLRP3, SREBP-1c, and PPARγ, in liver, pancreas, gut, and skeletal muscle. However, the industrialization and commercialization of dietary saponin-based drugs are confronted with a significant challenge due to the low bioavailability and lack of the standardization. Hence, in-depth evaluations in pharmacological profile, function-structure interaction, drug-signal pathway interrelation are essential for developing dietary saponins-based anti-diabetic treatments in the future.

Application of vibrational spectroscopic techniques for determination of thermal degradation of frying oils and fats: a review.

Deep fried foods are popular among consumers due to their unique taste and texture. During the process of deep-frying, oil is subjected to a high temperature that results into the generation of harmful compounds. The repeated usage of frying oil is a common exercise and associated with various health hazards. Thus, determination of frying oil quality is a critical practice to follow. The chemical methods employed to determine the quality of frying oil are destructive and require large amount of harmful chemical, thus researchers are exploring the application of various vibrational spectroscopic techniques for this purpose. The first part of this review provides a detailed insight into fundamental theoretical aspects of two main vibrational spectroscopic techniques (infrared and Raman spectroscopy) and chemical alteration in frying oils under thermal stress. While in the following parts, the application of near-infrared (NIR) and Fourier transform infrared (FTIR) and Raman spectroscopy for evaluating the quality of various frying oils and fats under thermal stress has been discussed. It is anticipated that this review paper can serve as a reference source for impending research in this field.

Anthocyanin supplement as a dietary strategy in cancer prevention and management: A comprehensive review.

Anthocyanins are natural pigments proven to be beneficial in the vast majority of health problems with no side effects. In this review, the latest progress on the cancer prevention and management of anthocyanins in treating cancers ranked in the top 5 of incidence and mortality was summarized, and the interaction and corresponding mechanisms were established based on a systematic review of electronic libraries. Several studies have revealed that anthocyanins have positive impact on human health with anti-cancer capacity. This review aimed to accumulate the evidence on the anti-cancer effects of anthocyanins, corresponding mechanisms and limitation of anthocyanins on cancer prevention and management. Notably, this review updated the latest studies on cancer prevention and management of anthocyanins and also inputted the future perspectives and the demanding questions for the possible contribution of anthocyanins as anti-cancer adjuvant.

Ferroptosis Related Immunomodulatory Effect of a Novel Extracellular Polysaccharides from Marine Fungus Aureobasidium melanogenum.

Marine fungi represent an important and sustainable resource, from which the search for novel biological substances for application in the pharmacy or food industry offers great potential. In our research, novel polysaccharide (AUM-1) was obtained from marine Aureobasidium melanogenum SCAU-266 were obtained and the molecular weight of AUM-1 was determined to be 8000 Da with 97.30% of glucose, 1.9% of mannose, and 0.08% galactose, owing to a potential backbone of α-D-Glcp-(1→2)-α-D-Manp-(1→4)-α-D-Glcp-(1→6)-(SO3-)-4-α-D-Glcp-(1→6)-1-ß-D-Glcp-1→2)-α-D-Glcp-(1→6)-ß-D-Glcp-1→6)-α-D-Glcp-1→4)-α-D-Glcp-6→1)-[α-D-Glcp-4]26→1)-α-D-Glcp and two side chains that consisted of α-D-Glcp-1 and α-D-Glcp-(1→6)-α-D-Glcp residues. The immunomodulatory effect of AUM-1 was identified. Then, the potential molecular mechanism by which AUM-1 may be connected to ferroptosis was indicated by metabonomics, and the expression of COX2, SLC7A11, GPX4, ACSL4, FTH1, and ROS were further verified. Thus, we first speculated that AUM-1 has a potential effect on the ferroptosis-related immunomodulatory property in RAW 264.7 cells by adjusting the expression of GPX4, regulated glutathione (oxidative), directly causing lipid peroxidation owing to the higher ROS level through the glutamate metabolism and TCA cycle. Thus, the ferroptosis related immunomodulatory effect of AUM-1 was obtained.

Effective and repeatable chromatographic separation of 5 nucleotides in infant formula milk powder by ion-pair high-performance liquid chromatography-ultraviolet.

A robust method using HPLC-UV was developed to improve the accuracy and repeatability of a quantitative method to detect 5 nucleotides (cytidine-monophosphate, uridine monophosphate, adenosine monophosphate, guanine monophosphate, and inosine monophosphate) in infant formulas. The results showed that efficient separation could not be achieved without strict conditions. The proposed method displayed a strong linear relationship (R2 > 0.9999) of single nucleotide in infant formula milk powder in the range of 10 to 1,000 mg/kg, a steady recovery (80.0% ∼110.0%) with relative standard deviation from 0.5% to 3.5%, under strict conditions of hydrophilic C18 column with di-isopropyl at 62.5 ± 2.5°C (± standard deviation), 0.65 ± 0.1 mg/mL tetrabutylammonium bisulfate, and mobile phase of pH of 2.75 ± 0.02. By applying this method on a series of milk products in the Chinese market, we found a few of them exceeded the legal limits of nucleotides.

Anticancer and Anti-Metastatic Role of Thymoquinone: Regulation of Oncogenic Signaling Cascades by Thymoquinone.

Cancer is a life-threatening and multifaceted disease. Pioneering research works in the past three decades have mechanistically disentangled intertwined signaling networks which play contributory roles in carcinogenesis and metastasis. Phenomenal strides have been made in leveraging our scientific knowledge altogether to a new level of maturity. Rapidly accumulating wealth of information has underlined a myriad of transduction cascades which can be pharmaceutically exploited for cancer prevention/inhibition. Natural products serve as a treasure trove and compel interdisciplinary researchers to study the cancer chemopreventive roles of wide-ranging natural products in cell culture and preclinical studies. Experimental research related to thymoquinone has gradually gained momentum because of the extra-ordinary cancer chemopreventive multifunctionalities of thymoquinone. In this mini-review, we provide an overview of different cell signaling cascades reported to be regulated by thymoquinone for cancer chemoprevention. Essentially, thymoquinone efficacy has also been notably studied in animal models, which advocates for a rationale-based transition of thymoquinone from the pre-clinical pipeline to clinical trials.

Regulation of Cell-Signaling Pathways by Berbamine in Different Cancers.

Natural product research is a cornerstone of the architectural framework of clinical medicine. Berbamine is a natural, potent, pharmacologically active biomolecule isolated from Berberis amurensis. Berbamine has been shown to modulate different oncogenic cell-signaling pathways in different cancers. In this review, we comprehensively analyze how berbamine modulates deregulated pathways (JAK/STAT, CAMKII/c-Myc) in various cancers. We systematically analyze how berbamine induces activation of the TGF/SMAD pathway for the effective inhibition of cancer progression. We also summarize different nanotechnological strategies currently being used for proficient delivery of berbamine to the target sites. Berbamine has also been reported to demonstrate potent anti-cancer and anti-metastatic effects in tumor-bearing mice. The regulation of non-coding RNAs by berbamine is insufficiently studied, and future studies must converge on the identification of target non-coding RNAs. A better understanding of the regulatory role of berbamine in the modulation of non-coding RNAs and cell-signaling pathways will be advantageous in the effective translation of laboratory findings to clinically effective therapeutics.

Jatrorrhizine Improves Endothelial Function in Diabetes and Obesity through Suppression of Endoplasmic Reticulum Stress.

Jatrorrhizine (JAT) is one of the major bioactive protoberberine alkaloids found in rhizoma coptidis, which has hypoglycemic and hypolipidemic potential. This study aimed to evaluate the vasoprotective effects of JAT in diabetes and obesity and the underlying mechanism involved. Mouse aortas, carotid arteries and human umbilical cord vein endothelial cells (HUVECs) were treated with risk factors (high glucose or tunicamycin) with and without JAT ex vivo and in vitro. Furthermore, aortas were obtained from mice with chronic treatment: (1) control; (2) diet-induced obese (DIO) mice fed a high-fat diet (45% kcal% fat) for 15 weeks; and (3) DIO mice orally administered JAT at 50 mg/kg/day for the last 5 weeks. High glucose or endoplasmic reticulum (ER) stress inducer tunicamycin impaired acetylcholine-induced endothelium-dependent relaxations (EDRs) in mouse aortas, induced oxidative stress in carotid arteries and HUVECs, downregulated phosphorylations of Akt at Ser473 and eNOS at Ser1177 and enhanced ER stress in mouse aortas and HUVECs, and these impairments were reversed by cotreatment with JAT. JAT increased NO release in high-glucose-treated mouse aortas and HUVECs. In addition, chronic JAT treatment restored endothelial function with EDRs comparable to the control, increased Akt/eNOS phosphorylation, and attenuated ER stress and oxidative stress in aortas from DIO mice. Blood pressure, glucose sensitivity, fatty liver and its morphological change, as well as plasma levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) and plasma lipid profile, were also normalized by JAT treatment. Collectively, our data may be the first to reveal the vasoprotective effect of JAT that ameliorates endothelial dysfunction in diabetes and obesity through enhancement of the Akt/eNOS pathway and NO bioavailability, as well as suppression of ER stress and oxidative stress.