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Plants in the genus Pistacia represent valuable natural resources for neuroprotective research based on ethnomedicinal knowledge. While other Pistacia species have been extensively studied, Pistacia falcata ( P. falcata ) has received limited attention. This study aimed to characterise the phenolic compounds in P. falcata extract using HPLC-DAD-MS/MS and evaluate its neuroprotective potential by assessing its ability to inhibit important central nervous system (CNS) enzymes-acetylcholinesterase (AChE) and monoamine oxidases (MAO-A and MAO-B). P. falcata displayed a rich profile of phenolic acids and unique glucuronidated flavonoids, contributing to its potent antioxidant activity (IC50 23.37 ± 0.63 µg/mL). The extract exhibited a stronger inhibitory effect on MAO-B than MAO-A and inhibited AChE (IC50 0.22 ± 0.01 mg/mL). These findings suggest that P. falcata has significant neuroprotective potential, warranting further investigation as a source of functional food and nutraceutical ingredients for managing neurodegenerative diseases.

It is now widely accepted that the reconstructed human epidermis models (OECD TG 439) can be used as a standalone replacement of the in vivo rabbit assay (OECD TG 404) to accurately predict skin irritancy. Many legislations have now introduced the legal requirement to use in vitro methods as the first step. The applicability of these methods to organosilicon-based substances was not evaluated during the validation of this guideline. Therefore, the aim of the current work was to assess the applicability of EpiSkin™ and EpiDerm™ SIT in vitro methods for organosilicons. Ten substances were evaluated, and results were compared with existing rabbit data. The data showed that both test methods failed to accurately predict the in vivo skin irritation potential, with predictive capacities below the minimum test guideline requirements. The two models delivered consistent results in only 60% of the cases. Several hypotheses were explored to explain this high rate of discordance without success. As EpiDerm™ SIT showed 100% sensitivity, a new stepwise testing strategy is proposed for organosilicons consisting of starting with EpiDerm™ SIT, following by EpiSkin™ in case of positive outcome. While keeping protective, this adapted strategy avoids unnecessary animal testing., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 The Dow Chemical Company, The Author(s). Published by Elsevier Inc. All rights reserved.)

This manuscript provides a comprehensive overview of the use of gamma rays, electron beams, and X-rays to improve the safety and quality of cheese. It examines the sources, energy levels, penetration depths, and applications, focusing on the nutritional and safety benefits as well as potential health concerns. Microbial dynamics in cheese are discussed, showing how irradiation doses influence bacterial counts and cheese characteristics. Gamma rays are suitable for bulky cheeses due to their high penetration depth, while electron beams are ideal for surface treatments due to their limited penetration depth. X-rays offer a good balance between penetration depth and energy efficiency. Consumer perception and legal aspects are also addressed, with market acceptance and retail impact assessed. The review demonstrates that irradiation can reduce contamination, extend shelf life, and preserve sensory properties, making it a promising tool for cheese processing. Future research should explore the long-term effects on texture and flavour as well as the economic feasibility of large-scale production, helping the industry to meet the demand for nutritious dairy products., Competing Interests: Conflict of interestThe authors declare no conflicts of interest., (© Association of Food Scientists & Technologists (India) 2025. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Background: The human gut microbiota plays a crucial role in various aspects of health, extending beyond digestion and nutrient absorption. Ganoderma lucidum (Reishi) and Hericium erinaceus (Lion's Mane), traditional medicinal mushrooms, have garnered interest due to their potential to exert positive health effects. The aim of our study was to investigate the molecular impact of Reishi and Lion's Mane on mood regulation through the gut-brain axis., Methods: We utilized a dynamic simulator of the human intestinal microbial ecosystem (SHIME), followed by HPLC-ESI-QTOF-MS/MS and a series of biochemical and molecular assays, including MTT for cell viability, fluorogenic probes for redox balance (ROS and GSH), and Western blot for protein analysis., Results: Chromatographic analysis confirmed the presence of bioactive compounds in both mushrooms, including triterpenoids (ganoderic acids) and polysaccharides in G. lucidum, as well as hericenones and erinacines in H. erinaceus. We observed concentration-dependent changes in metabolic activity and redox balance due to microbiome cell-free supernatant treatment (M-CFSs). M-CFSs also influenced the Nrf2 pathway and activated heat shock proteins, which may confer neuroprotective effects. Notably, M-CFSs upregulated neurotrophic factors such as BDNF, CDNF, and MANF, crucial for neuronal function. Our study revealed alterations in intracellular signaling cascades, most notably the CREB/BDNF pathway. Moreover, the Akt/mTOR and ERK1/2 showed no significant changes, while Akt/GSK3α/β displayed only partial modifications. The overlapping effects of synaptic activity and activation of the gut-brain axis appear to contribute to mood enhancement., Conclusions: These pilot findings suggest a potential role for G. lucidum and H. erinaceus in mood disorder regulation through multifaceted mechanisms involving the gut microbiota. The study underscores the importance of understanding the synergistic interactions between medicinal fungi, gut microbiota, and neural processes to develop novel or preventive strategies for mental health disorders., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier B.V. All rights reserved.)

Two-dimensional (2D) organic-inorganic halide perovskites are solution-processable semiconductors that are promising for optoelectronic applications. Understanding crystallization mechanisms to achieve control over nanostructures is important for optimizing desired properties. Here we introduce a versatile strategy to synthesize spiral microplates of diverse 2D perovskites at the air-water interface through screw-dislocation-driven growth. Spirals of 11 2D perovskite compositions (LA) 2 (A) n -1 Pb n X 3 n +1 with different spacer (LA) cations, A-cations, halide (X) anions, and n -number can be grown. They typically consist of single- or few-layer perovskite step heights but exhibit stacking complexity when multiple dislocations interact. The spiral microplates exhibit the characteristic optical properties (photoluminescence and second-harmonic generation) of the underlying 2D perovskites. Fluorescence-detected circular dichroism imaging shows that the chirality of the spiral center does not translate to the observed chiroptical properties of the microplate, consistent with the length scale of the chiral distortion. This solution growth of perovskite spirals diversifies the perovskite microstructures for optoelectronics and other applications.

Background: Diabetes increases ischemic heart injury via incompletely understood mechanisms. We recently reported that diabetic adipocytes-derived small extracellular vesicles (sEV) exacerbate myocardial reperfusion (MI/R) injury by promoting cardiomyocyte apoptosis. Combining in vitro mechanistic investigation and in vivo proof-concept demonstration, we determined the underlying molecular mechanism responsible for diabetic sEV-induced cardiomyocyte apoptosis after MI/R., Methods and Results: Adult mice were fed a high-fat diet (HFD) for 12 weeks. sEV were isolated from plasma or epididymal adipose tissue. HFD significantly increased the number and size of plasma- and adipocyte-derived sEV. Intramyocardial injection of an equal number of diabetic plasma sEV in nondiabetic hearts significantly increased cardiac apoptosis and exacerbated MI/R-induced cardiac dysfunction. Diabetic plasma sEV significantly activated cardiac caspase 9 but not caspase 8, suggesting that diabetic sEV induces cardiac apoptosis via the mitochondrial pathway. These pathologic alterations were phenotyped by intramyocardial injection of sEV isolated from diabetic adipocytes or HGHL-challenged 3T3L1 adipocytes. To obtain direct evidence that diabetic sEV promotes cardiomyocyte apoptotic cell death, isolated neonatal rat ventricular cardiomyocytes (NRVMs) were treated with sEV and subjected to simulated ischemia/reperfusion (SI/R). Treatment of cardiomyocytes with sEV from diabetic plasma, diabetic adipocytes, or HGHL-challenged 3T3L1 adipocytes significantly enhanced SI/R-induced apoptosis and reduced cell viability. These pathologic effects were replicated by a miR-130b-3p (a molecule increased dramatically in diabetic sEV) mimic and blocked by a miRb-130b-3p inhibitor. Molecular studies identified PGC-1α (i.e. PGC-1α1/-a) as the direct downstream target of miR-130b-3p, whose downregulation causes mitochondrial dysfunction and apoptosis. Finally, treatment with diabetic adipocyte-derived sEV or a miR-130b-3p mimic significantly enhanced mitochondrial reactive oxygen species (ROS) production in SI/R cardiomyocytes. Conversely, treatment with a miR-130b-3p inhibitor or overexpression of PGC-1α extremely attenuated diabetic sEV-induced ROS production., Conclusion: We obtained the first evidence that diabetic sEV promotes oxidative stress and mitochondrial-mediated cardiomyocyte apoptotic cell death, exacerbating MI/R injury. These pathological phenotypes were mediated by miR-130b-3p-induced suppression of PGC-1α expression and subsequent mitochondrial ROS production. Targeting miR-130b-3p mediated cardiomyocyte apoptosis may be a novel strategy for attenuating diabetic exacerbation of MI/R injury., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background/Objectives : We assessed the influence of long-term injection of magnoflorine (MAG) on memory acquisition in mice for the first time. Methods : This isoquinoline alkaloid that belongs to the aporphines was isolated from the roots of Berberis vulgaris by centrifugal partition chromatography (CPC) using a biphasic solvent system composed of chloroform: methanol: water in the ratio 4:3:3 ( v / v / v ) with 20 mM of hydrochloric acid and triethylamine, within 64 min. Results : Our results indicated that long-term injection of MAG 20 mg/kg dose improve the long-term memory acquisition in mice that were evaluated in the passive avoidance (PA) test with no toxicity records. The analysis of brain lysates and animal plasma by HPLC-ESI-QTOF-MS/MS showed the ability of the compound to cross the blood-brain barrier, and an elevated level of phosphatidylcholine PC (14:1(9Z)/14:1(9Z)) with the molecular formula of C 36 H 69 NO 8 P was observed in both treated groups with 10 mg/kg and 20 mg/kg MAG in comparison to the control group. Conclusions : This phenomenon may explain MAG's cognition-enhancing properties as the PC may induce the synthesis and strengthening of neuronal cells. Also, the 7-day-long administration of MAG at 10 mg/kg and 20 mg/kg increased the mean number of parvalbumin (PV)-IR neurons in the hippocampus. Statistically, the largest PV-IR neurons were observed at the 20 mg/kg dose, which may indicate a potential effect of MAG on Ca 2+ metabolism. However, no statistical differences were observed in the mean number of PV-IR nerve fibers in both doses of MAG, regardless of the hippocampal fields. This positive effect of MAG on hippocampal neurons provides further support for the neuroprotective effect of this alkaloid.

Primary and metastatic tumors of the nervous system represent a diverse group of neoplasms, each characterized by distinct biological features, prognostic outcomes, and therapeutic approaches. Due to their molecular complexity and heterogeneity, nervous system cancers (NSCs) pose significant clinical challenges. For decades, plants and their natural products with established anticancer properties have played a pivotal role in the treatment of various medical conditions, including cancers. Anthraquinone derivatives, a class of tricyclic secondary metabolites, are found in several botanical families, such as Fabaceae , Polygonaceae , Rhamnaceae , and Rubiaceae . In a comprehensive review, recent advancements in the anticancer properties of 1,8-dihydroanthraquinone derivatives-such as emodin, aloe-emodin, hypericin, chrysophanol, rhein, and physcion-were analyzed. These compounds have been studied extensively, both used individually and in combination with other chemotherapeutic agents, using in vitro and in vivo models of nervous system tumors. It was demonstrated that 1,8-dihydroanthraquinone derivatives induce apoptosis and necrosis in cancerous cells, intercalate into DNA, disrupting transcription and replication in rapidly dividing cells, and alter ROS levels, leading to oxidative stress that damages tumor cells. Additionally, they can influence signaling pathways involved in oncogenesis, such as MAPK, PI3K/Akt, or others crucial for the survival and the proliferation of NSC cells. The exploration of 1,8-dihydroanthraquinone derivatives aims to develop novel therapies that could overcome resistance and improve cancer patients' outcomes.

Adonis tianschanica is a lesser-known plant species belonging to the genus Adonis that grows in Kazakhstan. The aim of this study was to characterize the composition of the ethanolic, water, and hydroethanolic extracts from the aerial parts of A. tianschanica by HPLC-ESI-QTOF-MS/MS to isolate the major compound isoquercitrin by HSCCC (High-Speed Counter-Current Chromatography) and to determine the cytotoxicity and anti-inflammatory potential of the extracts produced with this plant. Fingerprinting of the analyzed extracts showed the presence of a multitude of metabolites comprising polyphenols, organic acids, and coumarins, and only trace quantities of cardiac glycosides in the analyzed samples. Flavonoids were certainly the best-represented group, with kaempferol, quercetin, and their derivatives as the major components of the extracts. Key findings in this paper were that the ethanol: water (50:50 v / v ) extract of A. tianschanica and its major compound isoquercitrin were able to reduce the production of NO induced by LPS, in addition to demonstrating anti-inflammatory effects by reducing cytokines such as IL-6, TNF-α, and IL-1β.

Objective: Health care costs are disproportionately concentrated among a small number of patients. We sought to identify variables associated with high-cost patients and high hospital concentration of high-cost patients and to examine associations with short-term outcomes in head and neck cancer (HNCA) surgery., Study Design: The Nationwide Inpatient Sample was used to identify 170,577 patients who underwent HNCA surgery in 2001-2011. High-cost patients were defined as patients whose costs of care were in the top decile, and high-concentration hospitals were defined as those whose percentage of high-cost patients was in the top decile., Methods: Multivariable regression was used to evaluate associations between cost and patient and hospital variables, postoperative complications, and in-hospital mortality., Results: Costs associated with high-cost patients were 4.47-fold greater than the remaining 90% of patients. High-concentration hospitals treated 36% of all high-cost patients. High-cost patients were more likely to be non-white (OR = 2.08 [1.45-2.97]), have oral cavity cancer (OR = 1.21 [1.05-1.39]), advanced comorbidity (OR = 1.53 [1.31-1.77]), Medicaid (OR = 1.93 [1.62-2.31]) or self-pay payor status (OR = 1.72 [1.38-2.14]), income>50th percentile (OR = 1.25 [1.05-1.51]), undergo major procedures (OR = 3.52 [3.07-4.05]) and have non-routine discharge (OR = 7.50 [6.01-9.35]). High-concentration hospitals were more likely to be teaching hospitals (OR = 3.14 [1.64-6.05]) and less likely to be urban (OR = 0.20 [0.04-0.93]). After controlling for all other variables, high-cost patients were associated with an increased odds of mortality (OR = 8.00 [5.89-10.85]) and postoperative complications (OR = 5.88 [5.18-6.68]). High-concentration hospitals were associated with an increased odds of postoperative complications (OR = 1.31 [1.08-1.61]) but were not associated with increased mortality (OR = 0.98 [0.67-1.44])., Conclusions: High-cost HNCA surgical patients are associated with increased postoperative morbidity and mortality, and are disproportionately concentrated at teaching hospitals., Level of Evidence: 4 Laryngoscope, 134:4971-4978, 2024., (© 2024 The American Laryngological, Rhinological and Otological Society, Inc.)

Both postmortem toxicological and medical-forensic examinations are very important in the case of analyzing various types of chemical substances. Hydroxyzine (HZ) is a first-generation antihistamine drug with a sedative effect that disrupts cognitive function and affects the ability to drive motor vehicles. Enzymatic oxidation of the hydroxy-methyl group to the carboxyl group leads to the formation of its main metabolite-cetirizine (CZ). CZ is the active substance of antiallergic drugs. Because it does not cross the BBB (blood-brain barrier) easily, it is less likely to cause drowsiness or affect memory and impair cognitive function. Therefore, in criminal studies, it is often important what medication had been taken by a person involved, e.g., in a car accident, HZ or CZ. The analysis of both antihistamine drugs is challenging, as usually very low concentrations of the compound of interest need to be determined. Thus, an ultra-sensitive UHPLC-QqQ-MS/MS method was developed for simultaneous determination of HZ and CZ in biological fluid samples. The lower limit of quantification (LOQ) for HZ and CZ was calculated as 0.345 and 0.3696 ng/mL, respectively. Together with a reduced sample volume to 200 μL, it makes the developed method suitable for a sensitive multidrug forensic toxicological analysis. Samples were extracted with simple and fast liquid-liquid extraction (ethyl acetate, pH 9). The present method for the determination of HZ and CZ in human blood proved to be simple, fast, selective, and sensitive. The quantification by LC-MS/MS was successfully applied to the samples coming from 28 authentic biological fluids (blood, urine, vitreous humor, bile and stomach content), both antemortem and postmortem. The performed studies confirm that the developed method is characterized by a high extraction efficiency. Its accuracy, reproducibility, simplicity, and selectivity suggest its application in clinical, toxicological, and forensic laboratories., (© 2024. The Author(s).)

Selected phenotypes of dried maca ( Lepidium peruvianum ) hypocotyls and supercritical CO 2 extract (USPlus ® ) of saw palmetto ( Serenoa repens ) were used to determine their targeted, cytotoxic action in prostate cancer cells. Fingerprinting by HPLC-MS and PCA analysis showed compositional differences in glucosinolates, amides, macamides, and other alkaloids, which varied based on the color and the size of hypocotyls. These phytochemical differences translated into a higher antioxidant potential of red maca than black maca samples. The greatest COX-2 inhibition was demonstrated with a combination of red maca: saw palmetto (67%:33%) and red maca: saw palmetto: black maca (25%:50%:25%). The LNCaP androgen-dependent prostate cancer cell line was the most sensitive to the three-component mixture of black, red maca, and saw palmetto treatment. This combination provided the most abundant set of high-activity metabolites, and is worthy of consideration in further clinical applications and future in-depth study.

Metal halide perovskites are an important class of semiconductors now being implemented as photovoltaic absorbers and explored for light emission, among other device applications. The semiconducting properties of halide perovskites are deeply intertwined with their composition and structure. Specifically the symmetry, tilting, and distortions of the metal halide octahedra impact the band structure and other optoelectronic properties. In this review, we examine the various compositions of monovalent A-site cations in three-dimensional (3D) halide perovskites AMX 3 (M = divalent metal; X = halide). We focus on how the A-site cation templates the inorganic metal-halide perovskite framework, resulting in changes in the crystal structure symmetry, as well as M-X bonding parameters, summarized in a comprehensive table of AMX 3 structures. The A-site cation motion, effects of alloying, and 2D Ruddlesden-Popper perovskite structures with unique A-site cations are further overviewed. Correlations are shown between these A-site cation dominated structural parameters and the resulting optoelectronic properties such as band gap. This review should serve as a reference for the A-site cation structural chemistry of metal halide perovskites and inspire continued research into less explored metal halide perovskite compositions and structures., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Introduction: Helicobacter pylori infection is a major issue worldwide, with widespread prevalence, combined with its link to gastritis, peptic ulcers, gastric cancer, and mucosa-associated lymphoid tissue (MALT) lymphoma. Meanwhile, effectiveness of current treatment protocols is limited by increasing antibiotic resistance and patient compliance issues due to long regimens and side effects. Plukenetia volubilis , or sacha inchi, is a valuable source of bioactive molecules. However, studies on its antimicrobial activity, especially against H. pylori , are lacking., Methods: In this study, the anti- H. pylori activity of P. volubilis leaves water extract was explored using in vitro and in silico approaches. High-Performance Liquid Chromatography coupled to Electrospray Ionisation and Quadrupole Time-of-Flight Mass Spectrometry (HPLC-ESI- QTOF-MS-MS) analysis of the water extract from the leaves was used to characterise the chemical composition of the plant and allowed identification of some flavonoids, such as astragalin, and some phenolic compounds. Then, high-speed counter current chromatography (HSCCC) was used to fractionate the ethyl acetate partition obtained from the water extract from the leaves., Results and Discussion: The presence of flavonoids derived from kaempferol was confirmed and astragalin was isolated for the first time in P. volubilis . The P. volubilis water infusion, ethyl acetate extract and the isolated astragalin exhibited anti-bacterial activity against H. pylori J99 and two clinical isolates (e.g., minimum inhibitory concentrations of 0.53, 0.51 and 0.49 μg/mL, respectively, for clarithromycin-resistant clinical isolate SSR366). Then, using molecular docking for potential protein targets for H. pylori , it was verified that astragalin could interact with these proteins by in silico analysis., Conclusion: These findings highlight that P. volubilis and astragalin produce a bacteriostatic activity against H. pylori and may have potential to be used in treatment against H. pylori , after further research., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Tan, Scortecci, Cabral De Medeiros, Kukula-Koch, Butler, Smith and Boylan.)

Lepidium peruvianum -an edible herbaceous biennial plant distributed in the Andes-has been used for centuries as food and as a natural medicine in treating hormonal disorders, as an antidepressant, and as an anti-osteoporotic agent. The presented study aims to prove its beneficial cosmetic and chemopreventive properties by testing the antiradical, whitening, cytotoxic, and anticancer properties of differently colored phenotypes that were extracted using three solvents: methanol, water, and chloroform, with the help of the chemometric approach to provide evidence on the impact of single glucosinolanes (seven identified compounds in the HPLC-ESI-QTOF-MS/MS analysis) on the biological activity of the total extracts. The tested extracts exhibited moderate antiradical activity, with the methanolic extract from yellow and grey maca phenotypes scavenging 49.9 ± 8.96% and 48.8% ± 0.44% of DPPH radical solution at a concentration of 1 mg/mL, respectively. Grey maca was the most active tyrosinase inhibitor, with 72.86 ± 3.42% of the enzyme activity calculated for the water extract and 75.66 ± 6.21% for the chloroform extract. The studies in cells showed no cytotoxicity towards the human keratinocyte line HaCaT in all studied extracts and a marked inhibition of cell viability towards the G361 melanoma cell line, which the presence of pent-4-enylglucosinolate, glucotropaeolin, and glucoalyssin in the samples could have caused. Given all biological activity tests combined, the three mentioned compounds were shown to be the most significant positive contributors to the results obtained, and the grey maca water extract was found to be the best source of the former compound among the tested samples.

Background: The rate of primary surgery for human papillomavirus-related oropharynx cancer (HPVOPC) has recently declined, while utilization of transoral robotic surgery (TORS) has lagged at community cancer centers (CCs). We hypothesize that differences in overall survival (OS) exist between patients undergoing surgery for HPVOPC at CCs and low (<15 TORS/year; LVACs) and high (≥15 TORS/year; HVACS) TORS volume academic centers., Methods: Cases from the US National Cancer Database with a diagnosis of HPVOPC from 2010-2019 that underwent primary surgical treatment were included. Trends in TORS utilization, rates of positive surgical margins (PMs), quality of adjuvant treatment and 5-year OS were compared between CCs, LVACs and HVACs., Results: 5,406 cases met study criteria. A significantly lower proportion of cases at CCs utilized TORS than at LVACs or HVACs (26.2% vs 44.0% vs 73.9%, respectively, p < .001). The rate of PMs was significantly higher at CCs than at LVACs or HVACs (25.7% vs 15.3% vs 9.2%, p < .001). A greater proportion of cases undergoing adjuvant radiotherapy (RT) received prolonged courses (23.6% vs 13.1% vs 8.8%, p < .001) or excessive doses (16.5% vs 11.5% vs 8.7%, p < .001) of RT at CCs than at LVACs or HVACs, respectively. 5-year OS was lowest at CCs (85.2%, 95%CI: 81.7-88.2%), intermediate at LVACs (88.9%, 95%CI: 87.2-90.4%), and highest at HVACs (91.4%, 95%CI: 89.5-92.9%; pLR<0.01)., Conclusions: Significant differences in the type and quality of surgical and adjuvant treatment for HPVOPC exist between facility types based on TORS volume. Overall survival was lowest at CCs, intermediate at LVACs and highest at HVACs., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Plants are a rich source of secondary metabolites, among which phenolics are the most abundant. To date, over 8000 various polyphenolic compounds have been identified in plant species, among which phenolic acids, flavonoids, coumarins, stilbenes and lignans are the most important ones. Acne is one of the most commonly treated dermatological diseases, among which acne vulgaris and rosacea are the most frequently diagnosed. In the scientific literature, there is a lack of a detailed scientific presentation and discussion on the importance of plant phenolics in the treatment of the most common specific skin diseases, e.g., acne. Therefore, the aim of this review is to gather, present and discuss the current state of knowledge on the activity of various plant phenolics towards the prevention and treatment of acne, including in vitro, in vivo and human studies. It was revealed that because of their significant antibacterial, anti-inflammatory and antioxidant activities, phenolic compounds may be used in the treatment of various types of acne, individually as well as in combination with commonly used drugs like clindamycin and benzoyl peroxide. Among the various phenolics that have been tested, EGCG, quercetin and nobiletin seem to be the most promising ones; however, more studies, especially clinical trials, are needed to fully evaluate their efficacy in treating acne.

The genus Vaccinium is represented by shrubs growing in a temperate climate that have been used for ages as traditional remedies in the treatment of digestive problems, in diabetes, renal stones or as antiseptics due to the presence of polyphenols (anthocyanins, flavonoids and tannins) in their fruits and leaves. Recent studies confirm their marked potential in the treatment of skin disorders and as skin care cosmetics. The aim of this review is to present the role of Vaccinium spp. as cosmetic products, highlight their potential and prove the biological properties exerted by the extracts from different species that can be useful for the preparation of innovative cosmetics. In the manuscript both skin care and therapeutic applications of the representatives of this gender will be discussed that include the antioxidant, skin lightening, UV-protective, antimicrobial, anti-inflammatory, and chemopreventive properties to shed new light on these underestimated plants.

From ancient times to the present day, fermentation has been utilized not only for food preservation but also for enhancing the nutritional and functional properties of foods. This process is influenced by numerous factors, including the type of microorganisms used, substrate composition, pH, time, and temperature, all of which can significantly alter the characteristics of the final product. Depending on the parameters, fermentation enhances the bioactive content of the products and imparts the necessary properties, such as antioxidant characteristics, for the products to be considered functional. The enhancement of these properties, particularly antioxidant activity, enriches foods with bioactive compounds and functional attributes, contributing to improved health benefits. Through a review of recent research, this study elucidates how different fermentation processes can enhance the bioavailability and efficacy of antioxidants, thereby improving the nutritional and functional qualities of foods. This study investigated the multifaceted effects of fermentation on antioxidant properties by exploring various types and conditions of fermentation. It highlights specific examples from dairy products and other food categories as well as the valorization of food waste and byproducts. The findings underscore the potential of fermentation as a sustainable method to produce health-promoting foods with elevated antioxidant activities, offering new perspectives for food science and technology.

Colostrum is a nutritious milk synthesized by mammals during the postpartum period, and its rich bioactive components has led to a global increase in the consumption of bovine colostrum as a supplement. Bovine colostrum contains key components such as immunoglobulins, oligosaccharides, lactoferrin and lysozyme. It is a special supplement source due to its natural, high bioavailability and high concentrations of growth factors. Growth factors are critical to many physiological functions, and considering its presence in the colostrum, further research must be conducted on its safe application in many bodily disorders. Growth factors contribute to wound healing, muscle and bone development, and supporting growth in children. Additionally, the molecular mechanisms have been explored, highlighting the growth factors roles in cell proliferation, tissue regeneration, and the regulation of immune responses. These findings are crucial for understanding the potential health effects of bovine colostrum, ensuring its safe use, and forming a basis for future clinical applications. This review article examines the growth factors concentration in bovine colostrum, their benefits, clinical studies, and molecular mechanisms.

The mechanisms of postacute medical conditions and unexplained symptoms after SARS-CoV-2 infection [Long Covid (LC)] are incompletely understood. There is growing evidence that viral persistence, immune dysregulation, and T cell dysfunction may play major roles. We performed whole-body positron emission tomography imaging in a well-characterized cohort of 24 participants at time points ranging from 27 to 910 days after acute SARS-CoV-2 infection using the radiopharmaceutical agent [ 18 F]F-AraG, a selective tracer that allows for anatomical quantitation of activated T lymphocytes. Tracer uptake in the postacute COVID-19 group, which included those with and without continuing symptoms, was higher compared with prepandemic controls in many regions, including the brain stem, spinal cord, bone marrow, nasopharyngeal and hilar lymphoid tissue, cardiopulmonary tissues, and gut wall. T cell activation in the spinal cord and gut wall was associated with the presence of LC symptoms. In addition, tracer uptake in lung tissue was higher in those with persistent pulmonary symptoms specifically. Increased T cell activation in these tissues was also observed in many individuals without LC. Given the high [ 18 F]F-AraG uptake detected in the gut, we obtained colorectal tissue for in situ hybridization of SARS-CoV-2 RNA and immunohistochemical studies in a subset of five participants with LC symptoms. We identified intracellular SARS-CoV-2 single-stranded spike protein-encoding RNA in rectosigmoid lamina propria tissue in all five participants and double-stranded spike protein-encoding RNA in three participants up to 676 days after initial COVID-19, suggesting that tissue viral persistence could be associated with long-term immunologic perturbations.

2D hybrid organic-inorganic halide perovskites emerge as a new class of 2D semiconductors with the potential to combine excellent optoelectronic properties with symmetry-enabled properties such as ferroelectricity. Although many lead-based ferroelectric 2D halide perovskites are reported, there is yet to be a conclusive report of ferroelectricity in tin-based 2D perovskites. Here, the structures and properties of a new series of 2D Dion-Jacobson (DJ) Sn perovskites: (4AMP)SnI 4 , (4AMP)(MA)Sn 2 I 7 , and (4AMP)(FA)Sn 2 I 7 (4AMP = 4-(aminomethyl)piperidinium, MA = methylammonium, and FA = formamidinium), are reported. Structural characterization reveals that (4AMP)SnI 4 is polar with in-plane spontaneous polarization whereas (4AMP)(MA)Sn 2 I 7 and (4AMP)(FA)Sn 2 I 7 are centrosymmetric. Further, (4AMP)SnI 4 displays second harmonic generation (SHG) and polarization-electric field hysteresis measurements confirm it is ferroelectric with a spontaneous polarization of 10.0 µC cm -2 at room temperature. (4AMP)SnI 4 transitions into a centrosymmetric structure above 367 K. As the first direct experimental observation of the spontaneous ferroelectric polarization of a Sn-based 2D hybrid perovskite, this work opens up environmentally friendly 2D tin halide perovskites for ferroelectricity and other physical property studies., (© 2024 The Authors. Advanced Materials published by Wiley‐VCH GmbH.)

Background: Studies have shown lower overall survival for patients with head and neck cancer treated at low-volume or community cancer centers. As the incidence of human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma steadily rises in the United States, we hypothesized that a greater proportion of patients with HPV-related oropharyngeal squamous cell carcinoma is being treated at community cancer centers, with a shift toward primary nonsurgical treatment., Methods: This cohort study included patients from the US National Cancer Database who received a diagnosis of HPV-related oropharyngeal squamous cell carcinoma from 2010 to 2019 and underwent treatment at a community cancer center or academic cancer center. The proportion of patients with HPV-related oropharyngeal squamous cell carcinoma treated at community cancer centers and receiving primary nonsurgical treatment was analyzed over time. Four-year overall survival was compared between community cancer centers and academic cancer centers., Results: The majority (67.4%) of 20 298 patients were treated at an academic cancer center, yet the proportion of patients treated at community cancer centers increased by 10% from 2010 to 2019 (P < .01 for trend). The proportion of patients undergoing primary nonsurgical treatment increased from 62.1% to 73.7% from 2010 to 2019 (P < .01 for trend), and patients were statistically significantly more likely to undergo nonsurgical treatment at community cancer centers than at academic cancer centers (adjusted odds ratio = 1.20, 95% confidence interval = 1.18 to 1.22). Treatment at community cancer centers was associated with worse survival overall (adjusted hazard ratio = 1.19, 95% confidence interval = 1.09 to 1.31), specifically for patients receiving primary nonsurgical treatment (adjusted hazard ratio = 1.22, 95% confidence interval = 1.11 to 1.34)., Conclusions: Treatment of HPV-related oropharyngeal squamous cell carcinoma has recently shifted to community cancer centers, with an increase in the proportion of nonsurgical treatment and worse overall survival at these centers compared with academic cancer centers. Concentration of care for HPV-related oropharyngeal squamous cell carcinoma at academic cancer centers and dedicated head and neck cancer centers may increase access to all available treatment modalities and improve survival., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

The Stachys L. genus has been widely used in traditional medicine in many countries throughout the world. The study aimed to investigate the chemical composition and bioactivity of the hydroethanolic extract (50% v/v) obtained by ultrasonication from the aerial flowering parts of Stachys sylvatica L. (SSE) collected in Almaty region (Southern Kazakhstan). According to RP-HPLC/PDA analysis the leading metabolites of the SSE belonged to polyphenols: chlorogenic acid and its isomers (2.34 mg/g dry extract) and luteolin derivatives (1.49 mg/g dry extract), while HPLC-ESI-QTOF-MS/MS-based qualitative fingerprinting revealed the presence of 17 metabolites, mainly chlorogenic acid and its isomers, flavonoid glycosides, and verbascoside with its derivatives. GC-MS analysis of the volatile metabolites showed mainly the presence of diterpenoids and fatty acid esters. A reduction in the viability of nematodes Rhabditis sp. was obtained for the SSE concentration of 3.3 mg/mL, while 11.1 mg/mL showed activity comparable to albendazole. The SSE exhibited higher activity against Gram-positive (MIC = 0.5-2 mg/mL) than Gram-negative bacteria and yeast (MIC = 8 mg/mL), exerting bactericidal and fungicidal effects but with no sporicidal activity. The SSE showed some antiviral activity against HCoV-229E replicating in MRC-5 and good protection against the cytopathic effect induced by HHV-1 in VERO. The SSE was moderately cytotoxic towards human cervical adenocarcinoma (H1HeLa) cells (CC 50 of 0.127 mg/mL after 72 h). This study provides novel information on the SSE extract composition and its biological activity, especially in the context of the SSE as a promising candidate for further antiparasitic studies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Mukhamedsadykova, Kasela, Kozhanova, Sakipova, Kukuła-Koch, Józefczyk, Świątek, Rajtar, Iwan, Kołodziej, Ludwiczuk, Kadyrbayeva, Kuntubek, Mamatova, Bogucka-Kocka and Malm.)

Fermentation is used not only to preserve food but also to enhance its beneficial effects on human health and achieve functional foods. This study aimed to investigate how different treatments (spontaneous fermentation or fermentation with the use of starter culture) affect phenolic content, antioxidant potential, and cholinesterase inhibitory activity in different kale cultivars: 'Halbhoner Grüner Krauser', 'Scarlet', and 'Nero di Toscana'. Chosen samples were further tested for their protective potential against the Caco-2 cell line. HPLC-MS analysis revealed that the fermentation affected the composition of polyphenolic compounds, leading to an increase in the content of rutin, kaempferol, sinapinic, and protocatechuic acids. In general, kale cultivars demonstrated various antioxidant activities, and fermentation led to an increase in total phenolic content and antioxidant activity. Fermentation boosted anti-cholinesterase activity most profoundly in 'Nero di Toscana'. Extracts of spontaneously fermented 'Scarlet' (SS) and 'Nero di Toscana' (NTS) showed cytoprotective properties, as revealed by the malondialdehyde (MDA), lactate dehydrogenase (LDH), superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) assays. Additionally, strong anti-inflammatory activity of NTS was shown by decreased release of cytokines IL-1β and TNF-α. Collectively, the conducted studies suggest fermented kale cultivars as a potential source for functional foods.

Designing two-dimensional halide perovskites for high-performance optoelectronic applications requires deep understanding of the structure-property relationship that governs their excitonic behaviors. However, a design framework that considers both intra and interlayer structures modified by the A-site and spacer cations, respectively, has not been developed. Here, we use pressure to synergistically tune the intra and interlayer structures and uncover the structural modulations that result in improved optoelectronic performance. Under applied pressure, (BA) 2 (GA)Pb 2 I 7 exhibits a 72-fold boost of photoluminescence and 10-fold increase of photoconductivity. Based on the observed structural change, we introduce a structural descriptor χ that describes both the intra and interlayer characteristics and establish a general quantitative relationship between χ and photoluminescence quantum yield: smaller χ correlates with minimized trapped excitons and more efficient emission from free excitons. Building on this principle, we design a perovskite (CMA) 2 (FA)Pb 2 I 7 that exhibits a small χ and an impressive photoluminescence quantum yield of 59.3%., (© 2024. The Author(s).)

Many people around the world suffer from neurodegenerative diseases associated with cognitive impairment. As life expectancy increases, this number is steadily rising. Therefore, it is extremely important to search for new treatment strategies and to discover new substances with potential neuroprotective and/or cognition-enhancing effects. This study focuses on investigating the potential of astragaloside IV (AIV), a triterpenoid saponin with proven acetylcholinesterase (AChE)-inhibiting activity naturally occurring in the root of Astragalus mongholicus , to attenuate memory impairment. Scopolamine (SCOP), an antagonist of muscarinic cholinergic receptors, and lipopolysaccharide (LPS), a trigger of neuroinflammation, were used to impair memory processes in the passive avoidance (PA) test in mice. This memory impairment in SCOP-treated mice was attenuated by prior intraperitoneal (ip) administration of AIV at a dose of 25 mg/kg. The attenuation of memory impairment by LPS was not observed. It can therefore be assumed that AIV does not reverse memory impairment by anti-inflammatory mechanisms, although this needs to be further verified. All doses of AIV tested did not affect baseline locomotor activity in mice. In the post mortem analysis by mass spectrometry of the body tissue of the mice, the highest content of AIV was found in the kidneys, then in the spleen and liver, and the lowest in the brain.

Only some of the nutrients consumed with food are able to be absorbed from the gastrointestinal (GI) tract and enter the systemic circulation (blood). Because some elements are essential minerals for humans, their beneficial effect on the body depends significantly on their bioavailable amount (the fraction that can be absorbed and used by the organism). The term bioavailability, which is very often used to describe the part of nutrients that is able to be absorbed, is influenced by various factors of exogenous and endogenous origin. The main purpose of the study was to assess the relative bioavailability of Cr from selected dietary supplements in the presence of various types of diets, which significantly influence the level of bioavailability. The research was performed using a previously developed and optimized two-stage in vitro digestion model using cellulose dialysis tubes of food rations with the addition of pharmaceutical products. Cr was determined using the ICP-OES and GF-AAS methods, depending on its concentration in particular fractions. The determined relative bioavailability ranged between 2.97 and 3.70%. The results of the study revealed that the type of diet, the chemical form of the molecule, and the pharmaceutical form of preparations have a significant influence on the bioavailability of Cr.

Alpinia officinarum is a representative of the Zingiberaceae family, which is known for its wide use in the food and pharmaceutical industries also due to its precious pharmacological potential. The major aim of the present study was to evaluate the influence of thermal treatment on the composition of the rhizome of Alpinia officinarum and its antioxidant activity. The fresh rhizome was subjected to various thermal treatment processes-boiling, frying and microwave heating during various time intervals-and their composition and antioxidant activity were determined using chromatographic (HPLC - High Performance Liquid Chromatography and HPLC-MS - High Performance Liquid Chromatography Mass Spectrometry) and spectrophotometric (DPPH and TPC - Total Phenolic Content) methods. Pinobanksin was the main compound found in the extract of the fresh rhizome (537.79 mg/kg), followed by galangin (197.7 mg/kg) and zingerone (185.5 mg/kg). The effect of thermal treatment on the rhizome composition was varied. In general, thermal processing significantly decreased the content of active compounds in the rhizome. However, there were some exceptions-boiling for 4 min significantly increased the content of pinobanksin (1162.4 mg/kg) and galangin (280.7 mg/kg), and microwave processing for 4 min increased the content of pinocembrin (213 mg/kg). It was found that boiling and microwave treatment significantly increased the antioxidant activity of the processed rhizomes.

Species distribution models and maps from large-scale biodiversity data are necessary for conservation management. One current issue is that biodiversity data are prone to taxonomic misclassifications. Methods to account for these misclassifications in multi-species distribution models have assumed that the classification probabilities are constant throughout the study. In reality, classification probabilities are likely to vary with several covariates. Failure to account for such heterogeneity can lead to biased prediction of species distributions. Here, we present a general multi-species distribution model that accounts for heterogeneity in the classification process. The proposed model assumes a multinomial generalised linear model for the classification confusion matrix. We compare the performance of the heterogeneous classification model to that of the homogeneous classification model by assessing how well they estimate the parameters in the model and their predictive performance on hold-out samples. We applied the model to gull data from Norway, Denmark and Finland, obtained from the Global Biodiversity Information Facility. Our simulation study showed that accounting for heterogeneity in the classification process increased the precision of true species' identity predictions by 30% and accuracy and recall by 6%. Since all the models in this study accounted for misclassification of some sort, there was no significant effect of accounting for heterogeneity in the classification process on the inference about the ecological process. Applying the model framework to the gull dataset did not improve the predictive performance between the homogeneous and heterogeneous models (with parametric distributions) due to the smaller misclassified sample sizes. However, when machine learning predictive scores were used as weights to inform the species distribution models about the classification process, the precision increased by 70%. We recommend multiple multinomial regression to be used to model the variation in the classification process when the data contains relatively larger misclassified samples. Machine learning prediction scores should be used when the data contains relatively smaller misclassified samples., Competing Interests: The authors declare no conflict of interest., (© 2024 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd.)

Fruit peels might be a valuable source of active ingredients for cosmetics, leading to more sustainable usage of plant by-products. The aim of the study was to evaluate the phytochemical content and selected biological properties of hydroglycolic extracts from peels and pulps of Annona cherimola , Diospyros kaki , Cydonia oblonga , and Fortunella margarita as potential cosmetic ingredients. Peel and pulp extracts were compared for their antiradical activity (using DPPH and ABTS radical scavenging assays), skin-lightening potential (tyrosinase inhibitory assay), sun protection factor (SPF), and cytotoxicity toward human fibroblast, keratinocyte, and melanoma cell lines. The total content of polyphenols and/or flavonoids was significantly higher in peel than in pulp extracts, and the composition of particular active compounds was also markedly different. The HPLC-MS fingerprinting revealed the presence of catechin, epicatechin and rutoside in the peel of D. kaki , whereas kaempferol glucoside and procyanidin A were present only in the pulp. In A. cherimola , catechin, epicatechin and rutoside were identified only in the peel of the fruit, whereas procyanidins were traced only in the pulp extracts. Quercetin and luteolinidin were found to be characteristic compounds of F. margarita peel extract. Naringenin and hesperidin were found only in the pulp of F. margarita . The most significant compositional variety between the peel and pulp extracts was observed for C. oblonga : Peel extracts contained a higher number of active components (e.g., vicenin-2, kaempferol rutinoside, or kaempferol galactoside) than pulp extract. The radical scavenging potential of peel extracts was higher than of the pulp extracts. D. kaki and F. margarita peel and pulp extracts inhibited mushroom and murine tyrosinases at comparable levels. The C. oblonga pulp extract was a more potent mushroom tyrosinase inhibitor than the peel extract. Peel extract of A. cherimola inhibited mushroom tyrosinase but activated the murine enzyme. F. margarita pulp and peel extracts showed the highest in vitro SPF. A. cherimola , D. kaki , and F. margarita extracts were not cytotoxic for fibroblasts and keratinocytes up to a concentration of 2% ( v/v ) and the peel extracts were cytotoxic for A375 melanoma cells. To summarize, peel extracts from all analyzed fruit showed comparable or better cosmetic-related properties than pulp extracts and might be considered multifunctional active ingredients of skin lightening, anti-aging, and protective cosmetics.

With cancer being a leading cause of death globally, there is an urgent need to improve therapeutic strategies and identify effective chemotherapeutics. This study aims to highlight the potential of crocetin, a natural product derived from certain plants, as an anticancer agent. It was  conducted an extensive review of the existing literature to gather and analyze the most recent data on the chemical properties of crocetin and its observed effects in various in vitro and in vivo studies. The study  particularly focused on studies that examined crocetin's impact on cell cycle dynamics, apoptosis, caspases and antioxidant enzyme levels, tumor angiogenesis, inflammation, and overall tumor growth. Crocetin exhibited diverse anti-tumorigenic activities including inhibition of tumor cell proliferation, apoptosis induction, angiogenesis suppression, and potentiation of chemotherapy. Multiple cellular and molecular pathways such as the PI3K/Akt, MAPK and NF-κB were modulated by it. Crocetin demonstrates promising anti-cancer properties and offers potential as an adjunctive or alternative therapy in oncology. More large-scale, rigorously designed clinical trials are needed to establish therapeutic protocols and ascertain the comprehensive benefits and safety profile of crocetin in diverse cancer types., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Previously, we demonstrated that palmatine (PALM) - an isoquinoline alkaloid from Berberis sibrica radix, exerted antiseizure activity in the pentylenetetrazole (PTZ)-induced seizure assay in larval zebrafish. The aim of the present study was to more precisely characterize PALM as a potential anticonvulsant drug candidate. A range of zebrafish and mouse seizure/epilepsy models were applied in the investigation. Immunostaining analysis was conducted to assess the changes in mouse brains, while in silico molecular modelling was performed to determine potential targets for PALM. Accordingly, PALM had anticonvulsant effect in ethyl 2-ketopent-4-enoate (EKP)-induced seizure assay in zebrafish larvae as well as in the 6 Hz-induced psychomotor seizure threshold and timed infusion PTZ tests in mice. The protective effect in the EKP-induced seizure assay was confirmed in the local field potential recordings. PALM did not affect seizures in the gabra1a knockout line of zebrafish larvae. In the scn1Lab -/- zebrafish line, pretreatment with PALM potentiated seizure-like behaviour of larvae. Repetitive treatment with PALM, however, did not reduce development of PTZ-induced seizure activity nor prevent the loss of parvalbumin-interneurons in the hippocampus of the PTZ kindled mice. In silico molecular modelling revealed that the noted anticonvulsant effect of PALM in EKP-induced seizure assay might result from its interactions with glutamic acid decarboxylase and/or via AMPA receptor non-competitive antagonism. Our study has demonstrated the anticonvulsant activity of PALM in some experimental models of seizures, including a model of pharmacoresistant seizures induced by EKP. These results indicate that PALM might be a suitable new drug candidate but the precise mechanism of its anticonvulsant activity has to be determined., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Sprays are used both in workplace and consumer settings. Although spraying has advantages, such as uniform distribution of substances on surfaces in a highly efficient manner, it is often associated with a high inhalation burden. For an adequate risk assessment, this exposure has to be reliably quantified. Exposure models of varying complexity are available, which are applicable to spray applications. However, a need for improvement has been identified. In this contribution, a simple 2-box approach is suggested for the assessment of the time-weighted averaged exposure concentration (TWA) using a minimum of input data. At the moment, the model is restricted to binary spray liquids composed of a non-volatile fraction and volatile solvents. The model output can be refined by introducing correction factors based on the classification and categorization of two key parameters, the droplet size class and the vapor pressure class of the solvent, or by using a data set of experimentally determined airborne release fractions related to the used spray equipment. A comparison of model results with measured data collected at real workplaces showed that this simple model based on readily available input parameters is very useful for screening purposes. The generic 2-box spray model without refinement overestimates the measurements of the considered scenarios in approximately 50% of the cases by more than a factor of 100. The generic 2-box model performs better for room spraying than for surface spraying, as the airborne fraction in the latter case is clearly overestimated. This conservatism of the prediction was significantly reduced when correction factors or experimentally determined airborne release fractions were used in addition to the generic input parameters. The resulting predictions still overestimate the exposure (ratio tool estimate to measured TWA > 10) or they are accurate (ratio 0.5-10). If the available information on boundary conditions (application type, equipment) does not justify the usage of airborne release fraction, room spraying should be used resulting in the highest exposure estimate. The model scope may be extended to (semi)volatile substances. However, acceptance may be compromised by the limited availability of measured data for this group of substances and thus may have limited potency to evaluate the model prediction., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Hahn, Schwarz, Nowak, Schwarz, Meyer and Koch.)

Moringa oleifera Lam. (Moringaceae) is a species of tree with an increasing utility, occurring naturally mainly in Pakistan and northern India. M. oleifera is currently cultivated in Africa, South America, Asia and the Middle East. The usage of its leaves, seed oil, bark, fruits, flowers and roots has positive opinions of FDA (American Food and Drug Administration), EFSA (European Food Safety Authority) and CosIng (Cosmetic Ingredients database). The chemical composition of M. oleifera is dominated by: proteins (consisting mainly of amino acids such as arginine or serine), fatty acids (omega-3 and omega-6), vitamins (vitamin A, B and C and tocopherols), mineral salts (including several bioelements, such as calcium, magnesium, sodium, and potassium), valuable polyphenolic compounds from the group of phenolic acids (e.g., gallic acid, ferulic acid) and flavonoids (e.g., myricetin, rutoside, and kaempferol). The raw materials show antioxidant, hepatoprotective, anti-inflammatory and antimicrobial properties. Dietary supplements and alimentary products containing M. oleifera are recommended as health-promoting and "novel food" preparations. The main purpose of this work was a review of the latest scientific literature on M. oleifera , with particular emphasis on the studies focusing on its chemical composition, biological activity and safety. Moreover, the review tends to discuss the results of biotechnological studies using this material and the agronomical significance., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Klimek-Szczykutowicz, Gaweł-Bęben, Rutka, Blicharska, Tatarczak-Michalewska, Kulik-Siarek, Kukula-Koch, Malinowska and Szopa.)

Plectranthus scutellarioides (L.) R.Br. is a medicinal plant that has long been used in traditional medicine to treat conditions such as abscesses, ulcers, and ear and eye infections. It is known to have a wide range of biological properties, such as antibacterial, antioxidant, antifungal, anti-inflammatory, anti-diabetic and anti-cancer effects. In this study, we established in vitro cultures from both the aerial parts and roots of Plectranthus scutellarioides . Subsequently, we compared the basic phytochemical profile of the obtained extracts and conducted a biological analysis to assess their potential for inducing apoptosis in breast (MCF-7) and lung (A549) cancer cells. Phytochemical analysis by HPLC-MS revealed the presence of compounds belonging to phenolic acids (ferulic, syringic, vanillic, rosmarinic, chlorogenic, caffeic, coumaric, dihydroxybenzoic acids), flavonoids (eriodyctiol and cirsimaritin), and terpenes such as 6,11,12,14,16-Pentahydroxy-3,17diacetyl-8,11,13-abietatrien-7-one, 6,11,12,14,16-Pentahydroxy-3,17-diacetyl5,8,11,13-abietatetraen-7-one, and 3,6,12-Trihydroxy-2-acetyl-8,12-abietadien7,11,14-trione. The results show that both extracts have a cytotoxic and genotoxic effect against MCF-7 and A549 cancer cells, with a different degree of sensitivity. It was also shown that both extracts can induce apoptosis by altering the expression of apoptotic genes ( Bax , Bcl-2 , TP53 , Fas, and TNFSF10 ), reducing mitochondrial membrane potential, increasing ROS levels, and increasing DNA damage. In addition, it has been shown that the tested extracts can alter blood coagulation parameters. Our results indicate that extracts from in vitro cultures of Plectranthus scutellarioides aerial parts and roots have promising therapeutic application, but further research is needed to better understand the mechanisms of their action in the in vitro model.

Gentiopicroside (GPS) is a leading component of several plant species from the Gentianaceae botanical family. As a compound with plenty of biological activities and a component of herbal drugs, GPS has an important role in the regulation of physiological processes in humans. The results of recently published scientific studies underline a meaningful role of this molecule as an active factor in metabolic pathways and mechanisms, which may have an influence in the treatment of different diseases, including digestive tract disorders, malignant changes, neurological disorders, microbial infections, bone formation disorders, inflammatory conditions, and others. This review aims to collect previously published reports on the biological properties of GPS as a single compound that were confirmed by in vitro and in vivo studies, and to draw attention to the newly discovered role of this bitter-tasting secoiridoid. Thanks to these properties, the research on this substance could be revisited.

The compositional tunability of 2D metal halide perovskites enables exploration of diverse semiconducting materials with different structural features. However, rationally tuning the 2D perovskite structures to target physical properties for specific applications remains challenging, especially for lead-free perovskites. Here, we study the effect of the interplay of the B-site (Ge, Sn, and Pb), A-site (cesium, methylammonium, and formamidinium), and spacer cations on the structure and optical properties of a new series of 2D Ruddlesden-Popper perovskites using the previously unreported spacer cation 4-bromo-2-fluorobenzylammonium (4Br2FBZ). We report eight new crystal structures and study the consequence of varying the B-site (Pb, Sn, Ge) and dimension ( n = 1, 2, vs 3D). Dimension strongly influences local distortion and structural symmetry, and the increased octahedral tilting and lone pair effects in Ge perovskites lead to a polar n = 2 perovskite that exhibits second harmonic generation, (4Br2FBZ) 2 (Cs)Ge 2 I 7 . In contrast, the analogous Sn and Pb perovskites remain centrosymmetric, but the B-site metal influences the photoluminescence properties. The Pb perovskites exhibit broad, defect-mediated emission at low temperature, whereas the Sn perovskites show purely excitonic emission over the entire temperature range, but the carrier recombination dynamics depend on dimensionality and dark excitonic states. Wholistic understanding of these differences that arise based on cations and dimensionality can guide the rational materials design of 2D perovskites for targeting physical properties for optoelectronic applications based on the interplay of cations and the connectivity of the inorganic framework.

The bioaccessibility of zinc (Zn), calcium (Ca), magnesium (Mg), and selenium (Se) from various nuts (Brazil nuts, walnuts, peanuts, almonds, cashews, pecans, hazelnuts, macadamia nuts, and pistachios) was assessed using a simulated two-phase model of enzymatic digestion in vitro. The levels of Zn, Mg, and Ca were determined by atomic absorption spectrometry, and Se was measured by inductively coupled plasma-mass spectrometry. All tested nuts were good sources of Mg, and most, except macadamia nuts, were also good sources of Zn (the standard portion covers over 15% of NRV-R (UE) 1924/2006). Brazil nuts had the highest Se content. Almonds and Brazil nuts were rich in Ca. Se demonstrated the highest bioaccessibility from nuts (27.7% to 70.65%), whereas Ca exhibited the lowest bioaccessibility (below 9%). Pistachios had the highest Zn bioavailability, while cashews excelled in Mg bioaccessibility. Macadamia and pistachios were top for Ca bioaccessibility, and Brazil nuts for Se. Bioaccessibility is positively correlated with fat (for Zn: r = 0.23), carbohydrates (for Mg: 0.44; for Ca: 0.35), and sugar content (for Zn: r = 0.36; for Mg: 0.46; for Ca: 0.40).

Emodin-8- O -glucoside (E-8- O -G) is a glycosylated derivative of emodin that exhibits numerous biological activities, including immunomodulatory, anti-inflammatory, antioxidant, hepatoprotective, or anticancer activities. However, there are no reports on the activity of E-8- O -G against cancers of the nervous system. Therefore, the aim of the study was to investigate the antiproliferative and cytotoxic effect of E-8- O -G in the SK-N-AS neuroblastoma, T98G human glioblastoma, and C6 mouse glioblastoma cancer cells. As a source of E-8- O -G the methanolic extract from the aerial parts of Reynoutria japonica Houtt. (Polygonaceae) was used. Thanks to the application of centrifugal partition chromatography (CPC) operated in the descending mode using a mixture of petroleum ether:ethyl acetate:methanol:water (4:5:4:5 v / v / v / v ) and a subsequent purification with preparative HPLC, E-8- O -G was obtained in high purity in a sufficient quantity for the bioactivity tests. Assessment of the cancer cell viability and proliferation were performed with the MTT (3-(bromide 4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium), CTG (CellTiter-Glo ® ) and BrdU (5-bromo-2'-deoxyuridine) assays, respectively. E-8- O -G inhibits the viability and proliferation of SK-N-AS neuroblastoma, T98G human glioblastoma multiforme, and C6 mouse glioblastoma cells dose-dependently. E-8- O -G seems to be a promising natural antitumor compound in the therapy of nervous system tumors.

Breast cancer (BC) is the most common malignancy among women worldwide. In recent years, significant progress has been made in BC therapy. However, serious side effects resulting from the use of standard chemotherapeutic drugs, as well as the phenomenon of multidrug resistance (MDR), limit the effectiveness of approved therapies. Advanced research in the BC area is necessary to create more effective and safer forms of therapy to improve the outlook for individuals diagnosed with this aggressive neoplasm. For decades, plants and natural products with anticancer properties have been successfully utilized in treating various medical conditions. Anthraquinone derivatives are tricyclic secondary metabolites of natural origin that have been identified in plants, lichens, and fungi. They represent a few botanical families, e.g., Rhamnaceae, Rubiaceae, Fabaceae, Polygonaceae, and others. The review comprehensively covers and analyzes the most recent advances in the anticancer activity of 1,8-dihydroanthraquinone derivatives (emodin, aloe-emodin, hypericin, chrysophanol, rhein, and physcion) applied both individually, or in combination with other chemotherapeutic agents, in in vitro and in vivo BC models. The application of nanoparticles for in vitro and in vivo evidence in the context of 1,8-dihydroanthraquinone derivatives was also described.

Gastric cancer is the most common cancer and remains the leading cause of cancer death worldwide. In this study, the anticancer action of magnoflorine isolated via counter-current chromatography from the methanolic extract of Berberis vulgaris root against gastric cancer in models of primary ACC-201 and AGS and metastatic MKN-74 and NCI-N87 cell lines was analyzed. Cell viability and proliferation were tested through the use of MTT and BrdU tests, respectively. Cell cycle progression and apoptosis were evaluated using flow cytometry. The interaction of magnoflorine and docetaxel has been examined through isobolographic analysis. Moreover, potential toxicity was verified in zebrafish in an in vivo model. Gastric cancer cell lines revealed different responses to magnoflorine treatment with regard to viability/proliferation, apoptosis induction and cell cycle inhibition without any undesirable changes in the development of larval zebrafish at the tested concentrations. What is more, magnoflorine in combination with docetaxel produced an additive pharmacological interaction in all studied gastric cancer cell lines, which may suggest a complementary mechanism of action of both compounds. Taken together, these findings provide a foundation for the possibility of magnoflorine as a potential therapeutic approach for gastric cancer and merits further investigation, which may pave the way for clinical uses of magnoflorine.

Ginger ( Zingiber officinale Rosc.) is a plant known all over the world that is used as a spice and as an ingredient in drinks, dietary supplements, and cosmetics. The growing availability of its fresh rhizomes makes it even more likely to be used in the diet, mainly due to its beneficial health properties and high content of polyphenols (gingerols and shogaols). The main goal and motivation of the authors was to assess the bioavailability of active substances contained in the extract from ginger rhizomes in the presence of various types of diets using the in vitro digestion method, enabling simulation of the processes occurring during the digestion and absorption of metabolites in the small intestine. For the qualitative and quantitative analyses, the HPLC-MS (High Performance Liquid Chromatography-Mass Spectrometry) and HPLC (High Performance Liquid Chromatography) techniques were used, respectively. Based on the obtained results, it was found that the best bioavailability of the selected ginger polyphenols (6-gingerol, 8-gingerdione, 8-shogaol, and 10-gingerdione) was estimated for a high-fiber diet, while the weakest results were obtained for standard and basic diets. In the case of the high-fiber diet, the bioavailability of the mentioned compounds was estimated as 33.3, 21.4, 6.73, and 21.0%, while for the basic diet, it was only 21.3, 5.3, 2.0, and 1.0%, respectively.

Introduction: Capparis cartilaginea Decne. (CC) originates from the dry regions of Asia and the Mediterranean basin. In traditional medicine, tea of CC leaves is commonly used to treat inflammatory conditions such as rheumatism, arthritis, and gout. Due to the limited studies on the phytochemistry and biological activity of CC compared to other members of the Capparaceae family, this work aims to: 1) Identify the chemical composition of CC extract and 2) Investigate the potential anti-inflammatory effect of CC extract, tea and the isolated compounds. Methods: To guarantee aim 1, high-speed countercurrent chromatography (HSCC) method; Nuclear Magnetic Resonance (NMR) and High-Performance Liquid Chromatography coupled to Electrospray Ionisation and Quadrupole Time-of-Flight Mass Spectrometry (HPLC-ESIQTOF-MS/MS) were employed for this purpose. To guarantee aim 2, we studied the effect of the isolated flavonoids on matrix metalloproteinases (MMPs) -9 and -2 in murine macrophages. Molecular docking was initially performed to assess the binding affinity of the isolated flavonoids to the active site of MMP-9. Results and discussion: In silico model was a powerful tool to predict the compounds that could strongly bind and inhibit MMPs. CC extract and tea have shown to possess a significant antioxidant and anti-inflammatory effect, which can partially explain their traditional medicinal use., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Alsharif, Hante, Govoni, Verli, Kukula-Koch, Jose Santos-Martinez and Boylan.)

This article presents the results of studies investigating the effect of red kale ( Brassica oleracea L. ssp. acephala L. var. sabellica ) extract on cancer cells (HT-29). The cytotoxicity of the red kale extract was assessed using MTT and LDH assays, while qRT-PCR was employed to analyze the expression of genes associated with the p53 signaling pathway to elucidate the effect of the extract on cancer cells. Furthermore, HPLC-ESI-QTOF-MS/MS was applied to identify bioactive compounds present in red kale. The obtained results indicated that red kale extract reduced the viability and suppressed the proliferation of HT-29 cells (the IC 50 value of 60.8 µg/mL). Additionally, mRNA expression analysis revealed significant upregulation of several genes, i.e., casp9 , mapk10 , mapk11 , fas , kat2 b , and ubd , suggesting the induction of cell apoptosis through the caspase-dependent pathway. Interestingly, the study revealed a decrease in the expression of genes including cdk2 and cdk4 encoding cell cycle-related proteins, which may lead to cell cycle arrest. Furthermore, the study identified certain bioactive compounds, such as sinigrin, spirostanol, hesperetin and usambarensine, which could potentially contribute to the apoptotic effect of red kale extracts. However, further investigations are necessary to elucidate the specific role of these individual compounds in the anti-cancer process.

Background: Zapnometinib is an oral, non-ATP-competitive, small-molecule inhibitor of MEK1/MEK2 with immunomodulatory and antiviral properties. We aimed to investigate the safety and efficacy of zapnometinib in patients with COVID-19., Methods: In this randomised, double-blind, placebo-controlled, multicentre, proof-of-concept, phase 2 trial, we recruited hospitalised adults with moderate or severe COVID-19 from 18 hospitals in Germany, India, Romania, South Africa, and Spain. Those requiring ICU admission or ventilator support at screening or randomisation were excluded. Patients were randomly assigned (1:1) to receive oral zapnometinib (900 mg on Day 1; 600 mg on Days 2-6) or matching placebo, on top of standard of care. Randomisation, stratified by baseline clinical severity status (CSS 3 or 4, measured on a 7-point ordinal scale), was done using Interactive Response Technology. Patients, investigators, and the sponsor were masked to treatment allocation. The primary endpoint was CSS at Day 15 and was conducted on the full analysis set (FAS: all patients who were randomised to the study, received at least one dose of study medication and had at least one post-dose assessment of CSS, as randomised). Safety analyses were conducted on the safety analysis set (all study participants who received at least one dose of study medication, as treated). This study is registered at ClinicalTrials.gov (NCT04776044) and EudraCT (2020-004206-59)., Findings: The trial was terminated early as the emergence of the Omicron variant impacted recruitment. Between 12th April 2021 and 9th August 2022, 104 of the planned 220 patients were enrolled and randomly assigned, 103 were treated, and 101 were included in the FAS (zapnometinib: n = 50; placebo: n = 51). The primary outcome was not significantly different between the two groups, but patients on zapnometinib had higher odds of improved CSS versus placebo (odds ratio [OR] 1.54 [95% CI 0.72-3.33]; p = 0.26). Predefined subgroup analyses identified trends for improved CSS in patients with severe disease at baseline (OR 2.57 [0.76-8.88]; p = 0.13) and non-Omicron variants (OR 2.36 [0.85-6.71]; p = 0.10); the p value of the CSS subgroup by Treatment interaction term in the model was p = 0.28. The frequency and intensity of adverse events was low and similar between arms. Twenty (39.2%) patients treated with zapnometinib experienced adverse events compared with eighteen (34.6%) patients treated with placebo. One patient receiving zapnometinib and two patients receiving placebo died during the study. None of the deaths were considered related to study medication., Interpretation: These results provide proof-of-concept for the innovative approach of targeting the Raf/MEK/ERK pathway in patients with hospitalised moderate/severe COVID-19. Further clinical studies will be required to evaluate the clinical benefit of zapnometinib in this and other indications., Funding: Atriva Therapeutics GmbH and the Federal Ministry of Education and Research, Germany., Competing Interests: G.R. reports personal fees from Astra Zeneca, Atriva Therapeutics, Boehringer Ingelheim, GSK, Insmed, MSD, Sanofi, Novartis, and Pfizer for consultancy during advisory board meetings, and personal fees from Astra Zeneca, Berlin Chemie, BMS, Boehringer Ingelheim, Chiesi, Essex Pharma, Grifols, GSK, Insmed, MSD, Roche, Sanofi, Solvay, Takeda, Novartis, Pfizer and Vertex for lectures including service on speakers’ bureaux. S.S., M.B., and T.O. are employees of Atriva Therapeutics. H.P. and G.M. have nothing to declare. O.S. reports investigator fees from Atriva Therapeutics, Algernon Pharmaceuticals, Atea Pharmaceuticals, Diffusion Pharmaceuticals, Regeneron Pharmaceuticals, PureTech, Celltrion Inc., and Adagio Therapeutics. W.K. reports payment from Atriva Therapeutics to provide statistical support during the RESPIRE study. D.N. reports payment, funded by Atriva Therapeutics, as an employee of the contract research organisation that supported the RESPIRE study. O.P. reports grants to his institution from the Federal Ministry of Education and Research, Germany (Bundesministerium für Bildung und Forschung; BMBF), personal fees for consulting from Atriva Therapeutics, receipt of equipment and materials to his institution from Atriva Therapeutics and is a shareholder of Atriva Therapeutics. A.T. reports consulting fees from Pfizer and Janssen, and payment/honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events, and participation in a Data Safety Monitoring Board or Advisory Board, from Pfizer, Janssen, and Biomerieux. M.W. reports grants from the Deutsche Forschungsgemeinschaft, BMBF, Deutsche Gesellschaft für Pneumologie, European Respiratory Society, Marie Curie Foundation, Else Kröner Fresenius Stiftung, Capnetz Stiftung, Bayer Health Care, Biotest, and Pantherna, consulting fees from Insmed, Pantherna, Pherecydes, Aptarion, Glaxo Smith Kline, Inflarx, and Biotest, and payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from Astra Zeneca, Insmed, Chiesi, Novartis, Teva, Actelion, Boehringer Ingelheim, Glaxo Smith Kline, Biotest, Bayer Health Care. M.W. also holds relevant patents: EPO 12181535.1: IL-27 for modulation of immune response in acute lung injury (2012), WO/2010/094491: Means for inhibiting the expression of Ang-2 (2010), DE 102020116249.9: Camostat/Niclosamide cotreatment in SARS-CoV-2 infected human lung cells (2020/21), and PCT/EP2021/075627: New medical use of cystic fibrosis transmembrane conductance regulator (CFTR) modulators (2021)., (© 2023 Atriva Therapeutics GmbH, Martinsried, Germany.)

The acetylcholinesterase-inhibitory potential of the oleanane-type triterpenes and their glycosides from thebark of Terminalia arjuna (Combreatceae), i.e.,arjunic acid, arjunolic acid, arjungenin, arjunglucoside I, sericic acid and arjunetin, is presented. The studies are based on in silico pharmacokinetic and biomimetic studies, acetylcholinesterase (AChE)-inhibitory activity tests and molecular-docking research. Based on the calculated pharmacokinetic parameters, arjunetin and arjunglucoside I are indicated as able to cross the blood-brain barrier. The compounds of interest exhibit a marked acetylcholinesterase inhibitory potential, which was tested in the TLC bioautography test. The longest time to reach brain equilibrium is observed for both the arjunic and arjunolic acids and the shortest one for arjunetin. All of the compounds exhibit a high and relatively similar magnitude of binding energies, varying from ca. -15 to -13 kcal/mol. The superposition of the most favorable positions of all ligands interacting with AChE is analyzed. The correlation between the experimentally determined IC 50 values and the steric parameters of the molecules is investigated. The inhibition of the enzyme by the analyzed compounds shows their potential to be used as cognition-enhancing agents. For the most potent compound (arjunglucoside I; ARG), the kinetics of AChE inhibition were tested. The Michaelis-Menten constant (Km) for the hydrolysis of the acetylthiocholine iodide substrate was calculated to be 0.011 mM.

Introduction: A yield of ≥18 nodes from neck dissection has been shown to be associated with improved locoregional recurrence rates and survival. We sought to determine factors associated with lymph node yields below this threshold., Materials and Methods: A retrospective review of patients who underwent neck dissection as part of definitive surgical treatment for mucosal head and neck squamous cell carcinoma (SCC) between January 2015 and December 2018 at an academic tertiary referral center was performed. Patients with a history of prior radiation or neck dissection were excluded., Results: There were 412 neck dissections performed in 323 patients. Specimens containing <18 nodes decreased from 16.2% in 2015-2016 to 7.4% of neck dissections in 2017-2018. The proportion of neck dissections removing <3 levels decreased from 9.1% of neck dissections in 2015-2016 to 4.0% in 2017-2018. Multivariable regression analysis demonstrated that dissection of ≥3 levels (OR = 0.2 [0.1-0.4]) and neck dissection in 2017-2018 compared to 2015-2016 (OR = 0.4 [0.2-0.8]) were significantly associated with a lower odds of <18 nodes. Stage, site, race, sex, human papillomavirus status, positive nodes, surgeon volume, and pathologist volume were not associated with neck dissection specimens with <18 nodes, after controlling for all other variables., Conclusions: Increased recognition of the importance of node count as a quality indicator, and the extent of neck dissection is associated with increased nodal yield from neck dissection. These data suggest that node count can be used as a quality measure of neck dissection for mucosal SCC., Level of Evidence: 4 Laryngoscope, 133:2160-2165, 2023., (© 2022 The American Laryngological, Rhinological and Otological Society, Inc.)

Oleanolic acid (OA), as a ubiquitous compound in the plant kingdom, is studied for both its neuroprotective and neurotoxic properties. The mechanism of acetylcholinesterase (AChE) inhibitory potential of OA is investigated using molecular dynamic simulations (MD) and docking as well as biomimetic tests. Moreover, the in vitro SH-SY5Y human neuroblastoma cells and the in vivo zebrafish model were used. The inhibitory potential towards the AChE enzyme is examined using the TLC-bioautography assay (the IC 50 value is 9.22 μM). The CH-π interactions between the central fragment of the ligand molecule and the aromatic cluster created by the His440, Phe288, Phe290, Phe330, Phe331, Tyr121, Tyr334, Trp84, and Trp279 side chains are observed. The results of the in vitro tests using the SH-SY5Y cells indicate that the viability rate is reduced to 71.5%, 61%, and 43% at the concentrations of 100 µg/mL, 300 µg/mL, and 1000 µg/mL, respectively, after 48 h of incubation, whereas cytotoxicity against the tested cell line with the IC 50 value is 714.32 ± 32.40 µg/mL. The in vivo tests on the zebrafish prove that there is no difference between the control and experimental groups regarding the mortality rate and morphology ( p > 0.05).