Facial synthesis of fluorine-engineered magnetic covalent organic framework for selective and ultrasensitive determination of fipronil, its metabolites and analogs in food samples.

To improve the adsorption affinity and selectivity of fipronils (FPNs), including fipronil, its metabolites and analogs, a magnetic covalent organic framework (Fe3O4@COF-F) with copious fluorine affinity sites was innovatively designed as an adsorbent of magnetic solid-phase extraction (MSPE). The enhanced surface area, pore size, crystallinity of Fe3O4@COF-F and its exponential adsorption capacities (187.3-231.5 mg g-1) towards fipronils were investigated. Combining MSPE with high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS), an analytical method was established for the selective determination of fipronils in milk and milk powder samples. This method achieved high sensitivity (LODs: 0.004-0.075 ng g-1), satisfactory repeatability and accuracy with spiked recoveries ranging from 89.9% to 100.3% (RSDs≤5.1%). Overall, the constructed Fe3O4@COF-F displayed great potential for the selective enrichment of fipronils, which could be ascribed to fluorine­fluorine interaction. This method proposed a feasible and promising strategy for the development of functionalized COF and broadened its application in fluorine containing hazards detection.

Impact of monocarbonyl analogs of curcumin (MACs) C66 and B2BrBC on the expression of diabetes-associated genes in streptozotocin-treated rat pancreatic RIN-m cells-Quantitative RT-PCR array data.

This paper presents a dataset obtained from an RT2-qPCR array analysis of rat pancreatic RIN-m cells treated with two monocarbonyl analogs of curcumin (MACs), C66 and B2BrBC in the presence or absence of streptozotocin (STZ). The array quantified the expression of 84 genes associated with the onset, development, and progression of diabetes. This dataset provides information on the gene expression profiles of pancreatic cells modulated by two specific MACs in a diabetic context. The data can serve as a foundation for developing new hypotheses, designing follow-up experiments, and identifying novel targets for treatment. It can be used to investigate further the molecular mechanisms underlying the therapeutic effects of these MACs and in comparative studies using other experimental antidiabetic compounds.

An In Silico Study on Withania somnifera Bioactives and Curcumin Analogs as Potential Inducers of Smoothened (Smo) Receptor of Sonic Hedgehog (SHH) Pathway to Promote Oligodendrogenesis.

Demyelinating disorder is a subset of neurodegenerative conditions wherein factors such as aging and/or auto-immune attack cause damage and degradation of myelin sheath which enwraps the neuronal axons. Lowered axonal integrity and sub-par conduction of nerve impulses due to impaired action potentials make neurodegeneration imminent as the neurons do not have mitotic ability to replenish their numbers. Oligodendrocytes (OLs) myelinate the axonal segments of neurons and perform neuronal maintenance. Neuroregenerative stem cell therapy exploits this property for remyelination by targeting OL replenishment using in vitro stem cell differentiation protocols for inducing OL lineage cells. But some shortcomings of such protocols are over-reliance on synthetic inducers, lengthy differentiation process, low differentiation efficiency besides being financially expensive. This in silico study sought to identify herbal substitutes of currently available OL-lineage-specific synthetic inducers from a virtual library of curcumin analogs and Withania somnifera bioactives. Smoothened (Smo) receptor belonging to the canonical sonic hedgehog (SHH) signaling pathway promotes in vivo differentiation of OLs as well as their subsequent lineage progression to myelinating OLs. Therefore, we performed pharmacokinetics prediction for the bioactives followed by their molecular docking and molecular dynamics simulation with Smo. From a pool of 1289 curcumin analogs and 80 Withania somnifera-derived bioactives, the best docked ligands were identified as the compounds with PubChem IDs 68815167 and 25880, respectively. Molecular dynamics simulation of these ligands further concluded the Withania somnifera bioactive 25880 to have the best activity with Smo. This compound may be deemed as a potential lead molecule for an agonistic interaction with and activation of Smo to initialize its downstream signaling cascade for enriching OL differentiation.

Anti-cancer activity of capsaicin and its analogs in gynecological cancers.

Capsaicin is the hot and pungent ingredient of chili peppers. It is a potent pain-relieving agent and is often present in over-the-counter analgesic lotions and creams. Several convergent studies reveal that capsaicin displays growth-suppressive activity in human cancers in vitro and in vivo. Apart from its growth-suppressive activity (as a single agent), capsaicin has been found to sensitize human cancer cells to the pro-apoptotic effects of chemotherapy and radiation. The first part of this book chapter discusses the anti-cancer activity of capsaicin in gynecological cancers in cell culture experiments and mouse models. Out of all gynecological cancers, the anti-cancer activity of capsaicin (and its analogs) has only been investigated in cervical cancers and ovarian cancers. The clinical development of capsaicin as a viable anti-cancer drug has remained challenging due to its poor bioavailability and aqueous solubility properties. In addition, the administration of capsaicin is associated with adverse side effects like gastrointestinal cramps, stomach pain, irritation in the gut, nausea diarrhea and vomiting. Two strategies have been investigated to overcome these drawbacks of capsaicin. The first is to encapsulate capsaicin in sustained release drug delivery systems. The second strategy is to design non-pungent capsaicin analogs which will retain the anti-tumor activity of capsaicin. The second part of this chapter provides an overview of the anti-neoplastic (and chemosensitization activity) of capsaicin analogs and capsaicin-based sustained release formulations in cervical and ovarian cancers. The design of selective non-pungent capsaicin analogs and capsaicin-based polymeric drug delivery systems may foster the hope of novel strategies for the treatment and management of gynecological cancers.

Immune Cell Molecular Pharmacodynamics of Lanreotide in Relation to Treatment Response in Patients with Gastroenteropancreatic Neuroendocrine Tumors.

The CLARINET trial led to the approval of lanreotide for the treatment of patients with gastroenteropancreatic neuroendocrine tumors (NETs). It is hypothesized that lanreotide regulates proliferation, hormone synthesis, and other cellular functions via binding to somatostatin receptors (SSTR1-5) present in NETs. However, our knowledge of how lanreotide affects the immune system is limited. In vitro studies have investigated functional immune response parameters with lanreotide treatment in healthy donor T cell subsets, encompassing the breadth of SSTR expression, apoptosis induction, cytokine production, and activity of transcription factor signaling pathways. In our study, we characterized in vitro immune mechanisms in healthy donor T cells in response to lanreotide. We also studied the in vivo effects by looking at differential gene expression pre- and post-lanreotide therapy in patients with NET. Immune-focused gene and protein expression profiling was performed on peripheral blood samples from 17 NET patients and correlated with clinical response. In vivo, lanreotide therapy showed reduced effects on wnt, T cell receptor (TCR), and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) signaling in CD8+ T cells in responders compared to non-responders. Compared to non-responders, responders showed reduced effects on cytokine and chemokine signaling but greater effects on ubiquitination and proteasome degradation genes. Our results suggest significant lanreotide pharmacodynamic effects on immune function in vivo, which correlate with responses in NET patients. This is not evident from experimental in vitro settings.

Extruded plant protein two-dimensional scaffold structures support myoblast cell growth for potential applications in cultured meat.

Cultured meat has been proposed as a promising alternative to conventional meat products. Five different plant protein blends made from soy (from two different manufacturers), wheat, mung bean, and faba bean, were extruded to form low-moisture meat analogs (LMMA) and were used to assess LMMA scaffold potential for cultured meat application. Extruded LMMAs were characterized using scanning electron microscopy, water-holding capacity, total soluble matter, and mechanical properties. Two-dimensional LMMA scaffolds were seeded with C2C12 skeletal myoblast cells and cultured for 14 days, and cell attachment and morphology were evaluated. All five extrudates exhibited directionality of their fibrous protein structures but to varying degrees. Soy, wheat, mung bean, and faba bean-based LMMA scaffolds initially supported myoblast cell growth. However, after 14 days of culture, the extruded wheat LMMA exhibited superior myoblast cell growth. This may be attributed to the highly aligned fibrous structure of the extruded wheat LMMA as well as its elastic modulus, which closely approximated that of native skeletal muscle. Overall, two-dimensional structures of the extruded plant proteins support cell growth and advance the development of cultured meat.

Amyloid-Driven Allostery.

The fields of allostery and amyloid-related pathologies, such as Parkinson's disease (PD), have been extensively explored individually, but less is known about how amyloids control allostery. Recent advancements have revealed that amyloids can drive allosteric effects in both intrinsically disordered proteins, such as alpha-synuclein (αS), and multi-domain signaling proteins, such as protein kinase A (PKA). Amyloid-driven allostery plays a central role in explaining the mechanisms of gain-of-pathological-function mutations in αS (e.g. E46K, which causes early PD onset) and loss-of-physiological-function mutations in PKA (e.g. A211D, which predisposes to tumors). This review highlights allosteric effects of disease-related mutations and how they can cause exposure of amyloidogenic regions, leading to amyloids that are either toxic or cause aberrant signaling. We also discuss multiple potential modulators of these allosteric effects, such as MgATP and kinase substrates, opening future opportunities to improve current pharmacological interventions against αS and PKA-related pathologies. Overall, we show that amyloid-driven allosteric models are useful to explain the mechanisms underlying disease-related mutations.

Computational investigation of novel synthetic analogs of C-1'ß substituted remdesivir against RNA-dependent RNA-polymerase of SARS-CoV-2.

Remdesivir, a C-nucleotide prodrug binds to the viral RNA-dependent-RNA polymerase (RdRp) and inhibits the viral replication by terminating RNA transcription prematurely. It is reported in literature that interaction between the C-1'ß-CN moiety of Remdesivir (RDV) and the Ser861 residue in RdRp enzyme, causes a delayed chain termination during the RNA replication process and is one of the important aspect of its mechanism of action. In the pursuance of increasing the biological activity of RDV and enhancing the SAR studies, against RNA viruses, we have designed its fourteen C1'ß substituted analogs, 10 -23 bearing 4/5-membered heterocyclic rings. The docking and 100 ns molecular dynamics (MD) simulations of 10-23 to the RdRp protein (PDB ID: 7L1F) revealed important interactions between 2',3'-diol, oxo group of phosphoramidate, nitrogen residues of heterocyclic rings of synthetic molecules with Arg555, Arg553, Ser759, Cys622, Asn691, Asp623 amino acid residues of protein. The docking score of 2-ethylbutyl ((S)-(((2R,3S,4R,5R)-5-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-3,4-dihydroxy-5-(1H-1,2,3-triazol-4-yl)tetrahydrofuran-2-yl)methoxy)(phenoxy)phosphoryl)-L-alaninate, 11 was found to be the higher than RDV among 14 new compounds i.e. -5.20 kcal/mol. Out of 3 compounds, 10, 12 and 13 submitted for MD simulations and Molecular Mechanics Poisson-Boltzmann Surface Area (MMPBSA) analysis, trifluoro-oxadiazole derivative, 13 showed higher binding energy as compared to Remdesivir. The predicted ADMET properties of 14 compounds showed their potential for being drug candidates. The present study suggests that substitution at the C1'ß position by 4/5-membered rings plays an important role in the interactions between nucleoside/tide and target protein.

Long-term experience with octreotide and lanreotide for the treatment of gastroenteropancreatic neuroendocrine tumors.

INTRODUCTION: The somatostatin analogs (SSA) octreotide and lanreotide are a mainstay in the treatment of neuroendocrine tumors (NET). The two pivotal trials differed considerably in terms of patient characteristics and are not directly comparable. Further comparative data are lacking. METHODS: This retrospective chart review study included patients with gastroenteropancreatic NET grade 1 or 2 who were treated with octreotide LAR or lanreotide autogel. The main aim was to compare the two SSA based on progression-free survival (PFS) and overall survival (OS) from treatment start. RESULTS: In total, 129 patients were analyzed, 60% (n = 77) had a small intestinal NET and 31% (n = 40) a pancreatic NET. Histologically, 34% (n = 44) had NET G1, 55% (n = 71) a NET G2, and 11% (n = 14) a NET G1/G2 unclassified. Lanreotide was used in 90 patients (70%) and octreotide in 39 patients (30%). Overall, the median PFS was 32.2 months (95% CI 23.0-42.9 months). No PFS difference (p = 0.8) was observed between lanreotide (29.8 months, 95% CI 18.7-48.5 months) and octreotide (36.0 months, 95% CI 23.2-68.2 months). Median OS from treatment start was calculated at 93.5 months (95% CI 71.1-132.9 months). Again, the median OS following lanreotide (113.4 months, 95% CI 62.3-NA months) or after octreotide (90.3 months, 95% CI 71.1-NA months) did not differ significantly (p > 0.9). CONCLUSIONS: Our long-term experience with octreotide and lanreotide in NET did not reveal differences in antitumor effectiveness. This is consistent with previous reports and might suggest that both SSA can be used interchangeably if needed.

Perspective: on the future of fecal microbiota transplantation.

Fecal Microbiota Transplantation (FMT) has shown to possess impressive potential benefit for a wide range of clinical indications. Due to its inherent safety issues and efficacy constraints, the use of personalized FMT analogs could be a promising avenue. The development of such analogs will require a detailed understanding of their functionality, encompassing not only microbe-host interactions of the microbial taxa that are involved, but also of the ecological dimensions of the analogs and an overview of the gastrointestinal sites where these relevant microbial interactions take place. Moreover, characterization of taxa that have been lost due to diminished exposure to beneficial microbes, as a consequence of Western lifestyle, may lead to creation of future FMT analogs with the capacity to restore functionalities that we have lost.

Sulfamoylated Estradiol Analogs Targeting the Actin and Microtubule Cytoskeletons Demonstrate Anti-Cancer Properties In Vitro and In Ovo.

The microtubule-disrupting agent 2-methoxyestradiol (2-ME) displays anti-tumor and anti-angiogenic properties, but its clinical development is halted due to poor pharmacokinetics. We therefore designed two 2-ME analogs in silico-an ESE-15-one and an ESE-16 one-with improved pharmacological properties. We investigated the effects of these compounds on the cytoskeleton in vitro, and their anti-angiogenic and anti-metastatic properties in ovo. Time-lapse fluorescent microscopy revealed that sub-lethal doses of the compounds disrupted microtubule dynamics. Phalloidin fluorescent staining of treated cervical (HeLa), metastatic breast (MDA-MB-231) cancer, and human umbilical vein endothelial cells (HUVECs) displayed thickened, stabilized actin stress fibers after 2 h, which rearranged into a peripheral radial pattern by 24 h. Cofilin phosphorylation and phosphorylated ezrin/radixin/moesin complexes appeared to regulate this actin response. These signaling pathways overlap with anti-angiogenic, extra-cellular communication and adhesion pathways. Sub-lethal concentrations of the compounds retarded both cellular migration and invasion. Anti-angiogenic and extra-cellular matrix signaling was evident with TIMP2 and P-VEGF receptor-2 upregulation. ESE-15-one and ESE-16 exhibited anti-tumor and anti-metastatic properties in vivo, using the chick chorioallantoic membrane assay. In conclusion, the sulfamoylated 2-ME analogs displayed promising anti-tumor, anti-metastatic, and anti-angiogenic properties. Future studies will assess the compounds for myeloproliferative effects, as seen in clinical applications of other drugs in this class.

Engineering a Bifunctional Fusion Purine/Pyrimidine Nucleoside Phosphorylase for the Production of Nucleoside Analogs.

Nucleoside phosphorylases (NPs) are pivotal enzymes in the salvage pathway, catalyzing the reversible phosphorolysis of nucleosides to produce nucleobases and α-D-ribose 1-phosphate. Due to their efficiency in catalyzing nucleoside synthesis from purine or pyrimidine bases, these enzymes hold significant industrial importance in the production of nucleoside-based drugs. Given that the thermodynamic equilibrium for purine NPs (PNPs) is favorable for nucleoside synthesis-unlike pyrimidine NPs (PyNPs, UP, and TP)-multi-enzymatic systems combining PNPs with PyNPs, UPs, or TPs are commonly employed in the synthesis of nucleoside analogs. In this study, we report the first development of two engineered bifunctional fusion enzymes, created through the genetic fusion of purine nucleoside phosphorylase I (PNP I) and thymidine phosphorylase (TP) from Thermus thermophilus. These fusion constructs, PNP I/TP-His and TP/PNP I-His, provide an innovative one-pot, single-step alternative to traditional multi-enzymatic synthesis approaches. Interestingly, both fusion enzymes retain phosphorolytic activity for both purine and pyrimidine nucleosides, demonstrating significant activity at elevated temperatures (60-90 °C) and within a pH range of 6-8. Additionally, both enzymes exhibit high thermal stability, maintaining approximately 80-100% of their activity when incubated at 60-80 °C over extended periods. Furthermore, the transglycosylation capabilities of the fusion enzymes were explored, demonstrating successful catalysis between purine (2'-deoxy)ribonucleosides and pyrimidine bases, and vice versa. To optimize reaction conditions, the effects of pH and temperature on transglycosylation activity were systematically examined. Finally, as a proof of concept, these fusion enzymes were successfully employed in the synthesis of various purine and pyrimidine ribonucleoside and 2'-deoxyribonucleoside analogs, underscoring their potential as versatile biocatalysts in nucleoside-based drug synthesis.

Vitamin D in Cancer Prevention and Treatment: A Review of Epidemiological, Preclinical, and Cellular Studies.

BACKGROUND: Inhibition of human carcinomas has previously been linked to vitamin D due to its effects on cancer cell proliferation, migration, angiogenesis, and apoptosis induction. The anticancer activity of vitamin D has been confirmed by several studies, which have shown that increased cancer incidence is associated with decreased vitamin D and that dietary supplementation of vitamin D slows down the growth of xenografted tumors in mice. Vitamin D inhibits the growth of cancer cells by the induction of apoptosis as well as by arresting the cells at the G0/G1 (or) G2/M phase of the cell cycle. Aim and Key Scientific Concepts of the Review: The purpose of this article is to thoroughly review the existing information and discuss and debate to conclude whether vitamin D could be used as an agent to prevent/treat cancers. The existing empirical data have demonstrated that vitamin D can also work in the absence of vitamin D receptors (VDRs), indicating the presence of multiple mechanisms of action for this sunshine vitamin. Polymorphism in the VDR is known to play a key role in tumor cell metastasis and drug resistance. Although there is evidence that vitamin D has both therapeutic and cancer-preventive properties, numerous uncertainties and concerns regarding its use in cancer treatment still exist. These include (a) increased calcium levels in individuals receiving therapeutic doses of vitamin D to suppress the growth of cancer cells; (b) hyperglycemia induction in certain vitamin D-treated study participants; (c) a dearth of evidence showing preventive or therapeutic benefits of cancer in clinical trials; (d) very weak support from proof-of-principle studies; and (e) the inability of vitamin D alone to treat advanced cancers. Addressing these concerns, more potent and less toxic vitamin D analogs have been created, and these are presently undergoing clinical trial evaluation. To provide key information regarding the functions of vitamin D and VDRs, this review provided details of significant advancements in the functional analysis of vitamin D and its analogs and VDR polymorphisms associated with cancers.

Spinning a Sustainable Future: Electrospun Polysaccharide-Protein Fibers for Plant-Based Meat Innovation.

This study aims to evaluate the feasibility of producing electrospun fibers by combining polysaccharides, zein, and poly(ethylene oxide) (PEO) to simulate the fibers applied in plant-based meat analogs. The rheological properties of biopolymer solutions were evaluated, and the electrospun fibers were characterized according to their morphology, structural interactions, and thermal analysis. The results indicated that the fibers prepared in a ratio of 90:10 of zein/carrageenan from the mixture of a solution containing 23 wt.% of zein with a solution containing 1 wt.% of carrageenan and with the addition of 1 wt.% of PEO presented a promising structure for application as fibers in meat analogs because they have a more hydrophilic surface. Thus, they have good moisture retention. In addition, they have good thermal stability at high temperatures, which is crucial to achieve a consistent and pleasant texture. Furthermore, it was observed that adding zein and PEO helps with the spinnability of the polysaccharides, producing fibers with good homogeneity.

Synthesis, Biological Activity, and Molecular-Docking Studies of New Brassinosteroid Analogs.

Much work has been dedicated to the quest to determine the structure-activity relationship in synthetic brassinosteroid (BR) analogs. Recently, it has been reported that analogs with phenyl or benzoate groups in the alkyl chain present activities comparable to those shown by natural BRs, depending on the nature of the substituent in the aromatic ring. However, as it is well known that the activity depends on the structure of the whole molecule, in this work, we have synthesized a series of compounds with the same substituted benzoate in the alkyl chain and a hydroxyl group at C3. The main goal was to compare the activities with analogs with -OH at C2 and C3. Additionally, a molecular-docking study and molecular dynamics simulations were performed to establish a correlation between the experimental and theoretical results. The synthesis of eight new BR analogs was described. All the analogs were fully characterized by spectroscopical methods. The bioactivity of these analogs was assessed using the rice lamina inclination test (RLIT) and the inhibition of the root and hypocotyl elongation of Arabidopsis thaliana. The results of the RLIT indicate that at the lowest tested concentration (1 × 10-8 M), in the BR analogs in which the aromatic ring was substituted at the para position with methoxy, the I and CN substituents were more active than brassinolide (50-72%) and 2-3 times more active than those analogs in which the substituent group was F, Cl or Br atoms. However, at the highest concentrations, brassinolide was the most active compound, and the structure-activity relationship changed. On the other hand, the results of the A. thaliana root sensitivity assay show that brassinolide and the analogs with I and CN as substituents on the benzoyl group were the most active compounds. These results are in line with those obtained via the RLIT. A comparison of these results with those obtained for similar analogs that had a hydroxyl group at C2 indicates the importance of considering the whole structure. The molecular-docking results indicate that all the analogs adopted a brassinolide-like orientation, while the stabilizing effect of the benzoate group on the interactions with the receptor complex provided energy binding values ranging between -10.17 and -13.17 kcal mol-1, where the analog with a nitrile group was the compound that achieved better contact with the amino acids present in the active site.

The Aryl Hydrocarbon Receptor and Its Crosstalk: A Chemopreventive Target of Naturally Occurring and Modified Phytochemicals.

The aryl hydrocarbon receptor (AhR) is an environmentally sensitive transcription factor (TF) historically associated with carcinogenesis initiation via the activation of numerous carcinogens. Nowadays, the AhR has been attributed to multiple endogenous functions to maintain cellular homeostasis. Moreover, crosstalk, often reciprocal, has been found between the AhR and several other TFs, particularly estrogen receptors (ERs) and nuclear factor erythroid 2-related factor-2 (Nrf2). Adequate modulation of these signaling pathways seems to be an attractive strategy for cancer chemoprevention. Several naturally occurring and synthetically modified AhR or ER ligands and Nrf2 modulators have been described. Sulfur-containing derivatives of glucosinolates, such as indole-3-carbinol (I3C), and stilbene derivatives are particularly interesting in this context. I3C and its condensation product, 3,3'-diindolylmethane (DIM), are classic examples of blocking agents that increase drug-metabolizing enzyme activity through activation of the AhR. Still, they also affect multiple essential signaling pathways in preventing hormone-dependent cancer. Resveratrol is a competitive antagonist of several classic AhR ligands. Its analogs, with ortho-methoxy substituents, exert stronger antiproliferative and proapoptotic activity. In addition, they modulate AhR activity and estrogen metabolism. Their activity seems related to a number of methoxy groups introduced into the stilbene structure. This review summarizes the data on the chemopreventive potential of these classes of phytochemicals, in the context of AhR and its crosstalk modulation.

Cytotoxic impacts of seven alternative bisphenols on human in vitro cellular models.

Bisphenols (BPs), common in plastics, coatings, and resins, are under scrutiny for potential endocrine disruption. Despite banning bisphenol A (BPA), its perceived safer alternatives may still pose health risks, urging thorough studies on their toxicity mechanisms. This study aimed to investigate the cellular toxicity of the top seven most commonly used BPs, bisphenol S (BPS), bisphenol F (BPF), bisphenol AF (BPAF), bisphenol P (BPP), bisphenol AP (BPAP), bisphenol B (BPB), bisphenol E (BPE) in eight different relevant human in vitro cell models: liver (HepaRG), intestinal (Caco-2), breast (T47D), brain (HMC-3), lungs (MRC-5), kidney (HEK293), endothelial (HMEC-1), and skin (HEK-001) cell lines. BPE manifested the highest cytotoxicity in Caco-2 cells, presenting an EC50 value of roughly 0.2 µM (95% confidence interval). In contrast, HEK293 and HepaRG cells demonstrated significant resilience to BPS (EC50 > 1000 µM). BPAF, BPP, and BPAP had consistently low EC50 values across cell lines (6-27.9 µM, 0.6-134.7 µM, and 3.6-178.8 µM), indicating elevated toxicity. After 24 h, all bisphenols adhered to nominal concentrations except BPAF, BPP, and BPS. BPP's concentration notably decreased (30.82 ± 5.53% of nominal value). The results revealed diverse effects of bisphenol analogs on different cell types. These findings emphasized the considerable cytotoxic potential of specific bisphenol analogs across various human cell models, underlining the necessity for a re-evaluation of their safety and regulatory standards.

Plant-based Meat Analogs: Perspectives on Their Meatiness, Nutritional Profile, Environmental Sustainability, Acceptance and Challenges.

PURPOSE OF REVIEW: Plant-based meat analogs (PBMAs) have been the subject of interest over the past few years due to consumers' demand for environmentally friendly, healthful, and non-animal-based foods. A better comprehension of the composition, structure, texture, nutrition, and sustainability of these PBMAs is necessary. RECENT FINDINGS: This review articulates the protein sources and composition of PBMAs and their "meatiness" with respect to texture, structure, and flavor enhancement. The components used in the analogs, such as unsaturated fats, fibers, vitamins, minerals, carbohydrates, and plant-based oils enriching their nutritional profile, are described. The study identifies the environmental and sustainability impact of PBMAs, as crucial to the survival and maintenance of biodiversity. More studies are warranted to scope and underscore the significance of the analogs and comprehend the texture or structure-function relationships. Further product development and testing thereof may ultimately result in quality meat analogs that respect meat taste, health and acceptance of consumers, environmental sustainability, animal welfare, and current challenges.

Determination of deoxynivalenol (DON) by a label-free electrochemical immunosensor based on NiFe PBA nanozymes.

Deoxynivalenol (DON) contamination in food products significantly threatens human health, necessitating a reliable and sensitive detection method. This study aims to develop a simple, low-cost, and effective electrochemical immunoassay method for detecting DON based on the nickel­iron bimetallic Prussian blue analog (NiFe PBA). The NiFe PBA nanozymes with high peroxidase-like activity were synthesized using an environmentally friendly chemical precipitation method. In the presence of hydrogen peroxide (H2O2), the current change of thionine oxidation initiated by NiFe PBA nanozymes can be exploited to diagnose DON. Under optimal conditions, the proposed method achieved quantitative detection of DON in the range of 10-107 pg mL-1 with a detection limit of 4.5 pg mL-1 (S/N = 3), demonstrating excellent selectivity, reproducibility, and stability. In addition, the DON immunosensor provides satisfactory results for the detection in real samples, demonstrating the feasibility of the proposed sensor in detecting of DON in such products.

Discovery and synthesis of novel glyrrhizin-analogs containing furanoylpiperazine and the activity against myocardial injury in sepsis.

The signaling pathway mediated by high mobility group protein B1 (HMGB1) plays a key role in myocardial injury during sepsis. Glyrrhizin (GL) is a natural product that inhibits HMGB1 biological activities through forming GL-HMGB1 complex; the research shows its aglycone (GA) is the main pharmacophore binding to HMGB1, while the glycosyl mainly altering its pharmacokinetic properties and enhances the stability of the complex. GL is often metabolized to GA in the gastrointestinal tract, which has a lower efficacy in the treatment of HMGB1-mediated diseases. To obtain the GL analogs with higher activity and better pharmacokinetic properties, 24 GL analogs were synthesized by simplification the glycosyl of GL. Among all the compounds, compound 11 with furanoylpiperazine was screened. The pharmacokinetics experiments showed that compound 11 is converted to 11a in vivo, and 11 serves as its prodrug. Compound 11a displayed a lower cytotoxicity to RAW264.7 cells and three types of cardiomyocyte lines, with IC50 > 800 µM. In the anti-inflammatory assay, 11a not only strongly inhibited NO production (IC50 5.73 µM), but also down-regulated the levels of HMGB1, IL-1ß and TNF-α in a dose-dependent manner; in the anti-oxidative stress assay, compound 11a reduced the level of ROS and increased the MMP in H9c2 cells. More importantly, in the myocardial injury model of septic mice, compound 11a not only alleviated the symptom of myocardial injury by reducing inflammatory infiltration and oxidative stress, but also improved the myocardial blood supply by shrinking the inner diameter of the left ventricle and increasing the ejection fraction (EF) more dramatically (155.8 %); meanwhile, compound 11a adjusted myocardial enzymes in serum of septic mice. In addition, in molecular docking experiments, compound 11a showed stronger HMGB1 binding ability than GL. In summary, compound 11 is a prodrug, which can be converted to 11a in vivo. And compound 11a has a good activity against septic myocardial injury, as well as improving the myocardial blood supply function. This suggests compound 11 is a potential drug candidate for the treatment of septic myocardial injury and deserves further investigate.