Search

Maillard reaction products (MRPs) play a crucial role in preserving food quality due to their antioxidant capacity. In this study, we isolated and characterized the antioxidant components from MRPs using a xylose-lysine system under optimal conditions. Methylene chloride and ethyl acetate were employed for sequential extractions, and the ethyl acetate phase underwent thin-layer chromatography and silica column separation. The identified compound, 3-hydroxy-4-methyl-2(5 H)-furanone (3H4MFN), was analyzed using FT-IR, GC-MS, and NMR, revealing its volatile nature with a chemical formula of C5H6O3. Further activity analysis demonstrated that 3H4MFN exhibited higher or comparable antioxidant activity to vitamin C (VC) and vitamin B6 (VB6). This newly discovered compound shows potential as a natural antioxidant in cosmetics, food, and nutraceutical applications. Highlight: A novel antioxidant has been identified from MRPs. The structure was determined by NMR, FT-IR and GC-MS. The newly identified compounds showed higher antioxidant activity than Vc and VB6. [ABSTRACT FROM AUTHOR]

Copyright of GeSec: Revista de Gestao e Secretariado is the property of Sindicato das Secretarias e Secretarios do Estado de Sao Paulo (SINSESP) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Allergic rhinitis is an inflammatory disease dependent on immunoglobulin E and causes inflammation of the nasal mucosa, leading to decreased quality of life for affected patients. Since common treatments, including corticosteroids and antihistamines, have temporary therapeutic effects and numerous side effects, investigating natural compounds effective in improving allergic rhinitis with low complications and high efficacy can be significant and necessary. Purpose: This study aims to present a comprehensive and critical evaluation of the effect of natural compounds in improving allergic rhinitis. Methods: Studies were identified through systematic searches of ScienceDirect, PubMed, Scopus, and Web of Sciences databases. Eligibility checks were conducted based on predefined selection criteria. Forty-six articles were included in this study. Results and discussion: Phytochemicals, including flavonoids, alkaloids, terpenoids, and other compounds showed significant anti-inflammatory and antihistaminic effects. These compounds alleviate allergic rhinitis symptoms by inhibiting inflammatory mediators, oxidative stress, apoptosis, and key signaling pathways such as MAPK/NFκB and TLR4/MyD88/NF-κB. Conclusion: Phytochemicals exhibit anti-inflammatory and antioxidant properties, making them. [ABSTRACT FROM AUTHOR]

Background: Cardiomyocyte senescence plays a crucial role as a pathological mechanism in heart failure (HF). However, the exact triggering factors and underlying causes of HF onset and progression are still not fully understood. Objectives: By integrating multi-omics data, this study aimed to determine the genetic associations between cardiomyocyte and HF using cell senescence-related genes (SRGs). Methods: The study utilized the CellAge database and the SenMayo dataset, combined with high-resolution single-cell RNA sequencing (scRNA-seq) data, to identify SRG and examine differences in cardiac cell expression. To explore the causal relationship with HF using Mendelian Randomization (MR). Genetic variations influencing gene expression, DNA methylation, and protein expression (cis-eQTL, cis-mQTL, and cis-pQTL) were analyzed using the two-sample MR (TSMR) and summary-data-based MR (SMR). Additionally, Bayesian colocalization analysis, germline genetic variation, and bulk RNA data were employed to strengthen the reliability of the results. The application potential of therapeutic targets is ultimately assessed by evaluating their druggability. Results: The expression of 39 SRGs in cardiomyocytes was identified. In the discovery set revealed that CDKN1A (OR = 1.09, 95% confidence interval (CI) 1.02–1.15, FDR = 0.048) could be causally related to HF, and the results are also replicated in the validation set (OR = 1.20, 95% confidence interval (CI) 1.10–1.30, FDR <0.0001). Based on the SMR method, CDKN1A was confirmed as a candidate pathogenic gene for HF, and its methylation (cg03714916, cg08179530) was associated with HF risk loci. The result is validated by Bayesian colocalization analysis, genetic variations, and bulk RNA data. The druggability analysis identified two potential therapeutic drugs. Conclusion: Based on multi-omics data, this study uncovered the reciprocal regulation of cardiomyocyte senescence through CDKN1 A, providing potential targets for HF drug development. [ABSTRACT FROM AUTHOR]

Inflammation is a vital immune defense mechanism regulated by Toll‐like receptors (TLRs) and the nuclear factor‐kappa B (NF‐κB) pathway. TANK‐binding kinase 1 (TBK1) is central to immunity and inflammation and influences antiviral responses and cellular processes. However, the precise role of TBK1 in modulating the NF‐κB pathway through interactions with other proteins, such as spleen tyrosine kinase (Syk), remains poorly understood. As dysregulation of TBK1 and NF‐κB can lead to a variety of diseases, they are important therapeutic targets. In this work, inflammatory processes involving the TBK1‐Syk‐NF‐κB pathway were elucidated using lipopolysaccharide (LPS)‐induced macrophages; human embryonic kidney 293 (HEK293) cells overexpressing MyD88, TBK1, and Syk proteins and their mutants; and real‐time polymerase chain reaction (PCR), immunoblotting analyses, and kinase assays. TBK1 was activated in LPS‐, poly I:C‐, and Pam3CSK‐stimulated macrophages. Transcript levels of TNF, NOS2, and IL1B were increased in cells overexpressing TBK1 but not in cells overexpressing TBK1 K38A. The transcription of TNF, NOS2, and IL1B and NF‐κB luciferase activity were inhibited by silencing TBK1 in LPS‐stimulated RAW264.7 cells and MyD88‐transfected HEK293 cells. Syk was the key mediator of the TBK1‐dependent NF‐κB pathway and bound directly to the coiled coil domain of TBK1, which was necessary to activate Syk and the Syk‐p85 pathway. This research advances the understanding of the role of TBK1 in NF‐κB signaling, emphasizing Syk as a key mediator. The interaction between TBK1 and Syk has potential for precise immune modulation that can be applied to treat immune‐related disorders. [ABSTRACT FROM AUTHOR]

Despite the many therapeutic advances, gastric ulcers continue to be prevalent. Natural compounds have been found to play a crucial role in preventing gastric ulcers in various phytochemical studies. The study aimed to investigate the protective effect of alpha-pinene against ethanol-induced gastric ulcers in rats by evaluating its impact on pro-inflammatory cytokines and oxidative stress markers. Male Wistar rats were orally administered alpha-pinene (50 and 100 mg/kg) prior to being induced with gastric ulceration using ethanol, and the gross morphological lesions, pro-inflammatory cytokine levels, and oxidative stress markers in gastric tissues were evaluated. Alpha-pinene treatment reduced gross morphological lesions in comparison to untreated animals. In ethanol-treated rats, alpha-pinene at 50 and 100 mg/kg also reduced oxidative stress, as verified by a decrease in tissue myeloperoxidase activity and malondialdehyde levels. In addition, alpha-pinene at both doses increased GSH and CAT levels compared to the untreated group. Alpha-pinene at both doses also lowered IL-1β and TNF- α production compared to the untreated group. Alpha-pinene may have a beneficial therapeutic role in gastric damage induced by ethanol as it reduces oxidative stress and pro-inflammatory factors. [ABSTRACT FROM AUTHOR]

This work aimed to obtain a phytochemical extract from jambolan leaf using a hydroethanolic solvent and ultrasound-assisted extraction. For this purpose, an experimental design was applied to analyze the effect of process variables related to temperature (30–60 °C), time (10–30 min), and solvent to leaf ratio (5–15 mL g−1), on the extraction mass yield (EMY) and on the yield of phenolic compounds (PCY). The effect of extractor solvent, AE (absolute ethanol), 75E (75% v·v−1 ethanol) and 50E (50% v·v−1), on the chemical characterization of the extracts, antidiabetic and antimicrobial activity, and cell viability, were also evaluated. The application of the highest values of process variables resulted in obtaining the maximum of the response variables (EMY = 9.94 wt% and PCY = 13.01 mg GAE g−1 leaf). A higher content of phenolic compounds and flavonoids was obtained with 50E, which is mainly composed of sinapic, vanillic, trans-caffeic, and quinic acids, which were responsible for the greatest antioxidant potential, antibacterial activity (against Staphylococcus aureus and Pseudomonas aeruginosa), and inhibition of α-amylase. On the other hand, the use of AE allowed us to obtain extracts with higher concentrations of squalene, α-tocopherol, β-sitosterol, and friedelin. From cell viability tests, the extracts are not considered toxic at the concentration tested (100 µg mg−1). [ABSTRACT FROM AUTHOR]

Muscular strength and endurance are vital for physical fitness. While mistletoe extract has shown efficacy in significantly increasing muscle strength and endurance, its accessibility is limited. This study explores combining mistletoe and apple peel extracts as an effective muscle health supplement. Analyses of histology, RNA, and protein in the combined extract-treated mouse group demonstrated significant enhancements in muscle strength and endurance, evidenced by larger muscle fibers, improved mitochondrial function, and a higher ratio of type I and IIa muscle fibers. Combining half doses of each extract resulted in greater improvements than using each extract separately, indicating a synergistic effect. Pathway analysis suggests that the observed synergy arises from complementary mechanisms, with a mistletoe extract-induced decrease in myostatin (MSTN) and an apple peel extract-induced increase in IGF1, leading to a sharp rise in AKT, S6K, and MuRF1, which promote myogenesis, along with a significant increase in PGC-1α, TFAM, and MEF2C, which are critical for mitochondrial biogenesis. This research provides practical insights into developing cost-effective, natural supplements to enhance muscle performance and endurance, with potential applications in athletic performance, improving muscle growth and endurance in children, and addressing age-related muscle decline. [ABSTRACT FROM AUTHOR]

Simple Summary: Cancer chemotherapy is dominated by cytotoxic drugs that non-selectively kill proliferating cells by blocking DNA replication and inducing apoptosis. Some natural anticancer products are less toxic to normal, slow-replicating cells but kill aggressive tumor cells. The combination of two structural isomers of pentacyclic triterpenes, oleanolic acid and ursolic acid, showed potent cytotoxic activity in human breast cancer cells in vitro by inducing cytotoxic autophagy at a significantly lower dose than previously reported. They were nontoxic to breast epithelial cells. Their activity was mainly due to the inhibition of AKT-mediated cell survival and the inhibition of the mammalian target of rapamycin (mTOR) signaling pathway, a central regulator of cell metabolism, growth, and proliferation. The compounds were equally effective against ER+ and triple-negative breast cancer cells. Combining low doses of nontoxic inhibitors of PI3k kinase increased the activities of these compounds. In contrast, inhibition of autophagy by 3-methyl adenine annulled their activity, demonstrating that cytotoxic autophagy may be the dominant mechanism of cell death. These compounds have potential for cancer therapy in neoadjuvant or adjuvant settings. Background: Oleanolic acid (OA) and Ursolic acid (UA) are bioactive triterpenoids. Reported activities vary with the dose used for testing their activities in vitro. Studies using doses of ≥20 µM showed apoptosis activities in cancer cells. However, reported drug levels in circulation achieved by oral administration of UA and OA are ≤2 µM, thus limiting their use for treatment or delivering a combination treatment. Materials and Methods: The present report demonstrates the efficacy of OA, UA, and OA + UA on tumor cell-specific cytotoxicity at low doses (5 µM to 10 µM) in breast cancer (BrCa) cell lines MCF7 and MDA-MB231. Results: The data show that both OA and UA killed BrCa cells at low doses, but were significantly less toxic to MCF-12A, a non-tumorigenic cell line. Moreover, OA + UA at ≤10 µM was lethal to BrCa cells. Mechanistic studies unraveled the significant absence of apoptosis, but their cytotoxicity was due to the induction of excessive autophagy at a OA + UA dose of 5 µM each. A link to drug-induced cytotoxic autophagy was established by demonstrating a lack of their cytotoxicity by silencing the autophagy-targeting genes (ATGs), which prevented OA-, UA-, or OA + UA-induced cell death. Further, UA or OA + UA treatment of BrCa cells caused an inhibition of PI3 kinase-mediated phosphorylation of Akt/mTOR, the key pathways that regulate cancer cell survival, metabolism, and proliferation. Discussion: Combinations of a PI3K inhibitor (LY294002) with OA, UA, or OA + UA synergistically inhibited BrCa cell survival. Therefore, the dominance of cytotoxic autophagy by inhibiting PI3K-mediated autophagy may be the primary mechanism of PTT-induced anticancer activity in BrCa cells. Conclusion: These results suggest it would be worthwhile testing combined OA and UA in clinical settings. [ABSTRACT FROM AUTHOR]

Triple-negative breast cancer (TNBC) is the most severe form of breast cancer, characterized by the loss of estrogen, progesterone, and human epidermal growth factor receptors. It is caused by various genetic and epigenetic factors, resulting in poor prognosis. Epigenetic changes, such as DNA methylation and histone modification, are the leading mechanisms responsible for TNBC progression and metastasis. This review comprehensively covers the various subtypes of TNBC and their epigenetic causes. In addition, the genetic association of TNBC with all significant genes and signaling pathways linked to the progression of this form of cancer has been enlisted. Furthermore, the possible uses of natural compounds through different mechanistic pathways have also been discussed in detail for the successful management of TNBC. [ABSTRACT FROM AUTHOR]

Through vicinal difunctionalization of nitriles, a successful, innovative strategy for the synthesis of N-alkyl amidines is developed. This methodology capitalizes on commercially available nitriles, alcohols, and sulfonamides. The activation of alcohols by trifluoromethanesulfonic anhydride (Tf2O) plays a pivotal role throughout the entire reaction process. In comparison to existing amidine synthesis methods, this strategy showcases notable advantages, including the avoidance of toxic and hazardous azides, the exclusion of transition metal catalysts, and the use of mild reaction conditions. Importantly, this methodology provides an effective approach for late-stage modification of complex molecules and drugs, holding promise for the construction of molecular libraries in drug discovery. [ABSTRACT FROM AUTHOR]

Cold atmospheric plasma (CAP) is a novel non-thermal technology with significant potential for use in meat processing to prolong shelf life. The objective of the study was to evaluate the efficiency of CAP treatment on the natural microbiota and quality traits of pork stored for 8 days at 4 °C. CAP treatment was applied by employing piezoelectric direct discharge technology to treat pork samples for 0, 3, 6, and 9 min. Reductions of approximately 0.8–1.7 log CFU/g were observed in total viable counts (TVC) and Pseudomonas spp. levels for CAP treatments longer than 3 min, immediately after treatment. A storage study revealed that CAP-treated pork (>6 min) had significantly lower levels of TVC, Pseudomonas spp., and Enterobacteriaceae throughout storage. Regarding quality traits, CAP application for longer than 3 min significantly increased water retention and yellowness and decreased meat redness compared to untreated pork. However, other parameters such as pH, tenderness, and lightness exhibited no statistically significant differences between untreated and CAP-treated pork. Lipid oxidation levels were higher only for the 9-min treatment compared to untreated pork. Our results revealed that CAP is a promising technology that can extend the microbiological shelf life of pork during refrigeration storage. [ABSTRACT FROM AUTHOR]

Cognitive deficits are the main outcome of neurological disorders whose occurrence has risen over the past three decades. Although there are some pharmacologic approaches approved for managing neurological disorders, it remains largely ineffective. Hence, exploring novel nature-based nutraceuticals is a pressing need to alleviate the results of neurodegenerative diseases, such as Alzheimer's disease (AD) and other neurodegenerative disorders. Some triterpenoids and their derivates can be considered potential therapeutics against neurological disorders due to their neuroprotective and cognitive-improving effects. Betulin (B), betulinic acid (BA), and ursolic acid (UA) are pentacyclic triterpenoid compounds with a variety of biological activities, including antioxidative, neuroprotective and anti-inflammatory properties. This review focuses on the therapeutic efficacy and probable molecular mechanisms of triterpenoids in damage prevention to neurons and restoring cognition in neurodegenerative diseases. Considering few studies on this concept, the precise mechanisms that mediate the effect of these compounds in neurodegenerative disorders have remained unknown. The findings can provide sufficient information about the advantages of these compounds against neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Background and objectives: Self-rated health (SRH) serves as an assessment of contentment regarding one’s social, mental, and physical well-being and has been linked to both cardiovascular mortality and morbidity. Nonetheless, the relationship between SRH and medical outcomes in individuals with hypertension unsettled. This research endeavors to pinpoint the determinants that affect SRH in Iranian patients with hypertension. Materials and methods: This cross-sectional study took place in Isfahan, Iran, from November 2018 to August 2019 and involved 886 patients with essential HTN. The data collection methods included a checklist for demographic information and risk factors, blood pressure measurements (systolic and diastolic), the Persian version of the 8-Item Morisky Medication Adherence scale, and a self-rated health questionnaire recommended by the World Health Organization. Independent sample T-test and chi squared test were used for comparison of variables between two groups of SRH. Additionally, multivariable logistic regression was used to analyze the factors influencing self-rated health status. Results: Among 886 participants (mean age 57.8 ± 8.8 years, 71.9% women), 89.62% reported good SRH. Comorbid conditions were significantly associated with poorer SRH (p < 0.05). Notably, higher education (odd ratio (OR) = 1.88, 95% confidence interval (CI) = 1.13–3.11, p = 0.015) and increased income (OR = 4.34, 95% CI = 1.43–13.18, p = 0.010) were identified as positive determinants of good SRH. Conclusion: We concluded that socioeconomic factors (education and income) and comorbid conditions (diabetes, hyperlipidemia, and pulmonary diseases) are risk factors for poor SRH among hypertensive patients. These findings could help planning of health enhancement initiative. [ABSTRACT FROM AUTHOR]

Food is one of the factors with the highest impact on human health. Today, attention is paid not only to food properties such as energy provision and palatability but also to functional aspects including phytochemical, antioxidant properties, etc. Massaman and spicy basil leaf curries are famous Thai food dishes with a good harmony of flavor and taste, derived from multiple herbs and spices, including galangal rhizomes, chili pods, garlic bulbs, peppers, shallots, and coriander seeds, that provide an array of health benefits. The characterization of phytochemicals detected by LC-ESI-QTOF-MS/MS identified 99 components (Masaman) and 62 components (spicy basil leaf curry) such as quininic acid, hydroxycinnamic acid, luteolin, kaempferol, catechin, eugenol, betulinic acid, and gingerol. The cynaroside and luteolin-7-O-glucoside found in spicy basil leaf curry play a key role in antioxidant activities and were found at a significantly higher concentration than in Massaman curry. Phenolic and flavonoid compounds generally exhibit a bitter and astringent taste, but all the panelists scored both curries higher than 7 out of 9, confirming their acceptable flavor. Results suggest that the Massaman and spicy basil leaves contain various phytochemicals at different levels and may be further used as functional ingredients and nutraceutical products. [ABSTRACT FROM AUTHOR]

The complement factor C5a is a core effector product of complement activation. C5a, acting through its receptors C5aR1 and C5aR2, exerts pleiotropic immunomodulatory functions in myeloid cells, which is vital for host defense against pathogens. Pattern-recognition receptors (PRRs) are similarly expressed by immune cells as detectors of pathogen-associated molecular patterns. Although there is evidence of cross talk between complement and PRR signaling pathways, knowledge of the full potential for C5a-PRR interaction is limited. In this study, we comprehensively investigated how C5a signaling through C5a receptors can modulate diverse PRR-mediated cytokine responses in human primary monocyte-derived macrophages and observed a powerful, concentration-dependent bidirectional effect of C5a on PRR activities. Unexpectedly, C5a synergized with Dectin-1, Mincle, and STING in macrophages to a much greater extent than TLRs. Notably, we also identified that selective Dectin-1 activation using depleted zymosan triggered macrophages to generate cell-intrinsic C5a, which acted on intracellular and cell surface C5aR1, to help sustain mitochondrial ROS generation, up-regulate TNFa production, and enhance fungal killing. This study adds further evidence to the holistic functions of C5a as a central immunomodulator and important orchestrator of pathogen sensing and killing by phagocytes. [ABSTRACT FROM AUTHOR]

Astrocytes have an important role in neuronal maturation and synapse function in the brain. The interplay between astrocytes and neurons is found to be altered in many neurodevelopmental disorders, including fragile X syndrome (FXS) that is the most common inherited cause of intellectual disability and autism spectrum disorder. Transcriptional, functional, and metabolic alterations in Fmr1 knockout mouse astrocytes, human FXS stem cell-derived astrocytes as well as in in vivo models suggest autonomous effects of astrocytes in the neurobiology of FXS. Abnormalities associated with FXS astrocytes include differentiation of central nervous system cell populations, maturation and regulation of synapses, and synaptic glutamate balance. Recently, FXS-specific changes were found more widely in astrocyte functioning, such as regulation of inflammatory pathways and maintenance of lipid homeostasis. Changes of FXS astrocytes impact the brain homeostasis and function both during development and in the adult brain and offer opportunities for novel types of approaches for intervention. [ABSTRACT FROM AUTHOR]

Peripheral nerve injuries lead to severe functional impairments and long recovery times, with limited effectiveness and accessibility of current treatments. This has increased interest in natural bioactive compounds, such as ursolic acid (UA). Our study evaluated the effect of an oleolyte rich in UA from white grape pomace (WGPO) on neuronal regeneration in mice with induced sciatic nerve resection, administered concurrently with the induced damage (the WGPO group) and 10 days prior (the PRE-WGPO group). The experiment was monitored at two-time points (4 and 10 days) after injury. After 10 days, the WGPO group demonstrated a reduction in muscle atrophy, evidenced by an increased number and diameter of muscle fibers and a decreased Atrogin-1 and Murf-1 expression relative to the denervated control. It was also observed that 85.7% of neuromuscular junctions (NMJs) were fully innervated, as indicated by the colocalization of α-bungarotoxin and synaptophysin, along with the significant modulation of Oct-6 and S-100. The PRE-WGPO group showed a more beneficial effect on nerve fiber reformation, with a significant increase in myelin protein zero and 95.2% fully innervated NMJs, and a pro-hypertrophic effect in resting non-denervated muscles. Our findings suggest WGPO as a potential treatment for various conditions that require the repair of nerve and muscle injuries. [ABSTRACT FROM AUTHOR]

Ionizing radiation interacts with the immune system and induces molecular damage in the cellular milieu by generating reactive oxygen species (ROS) leading to cell death. The present study was performed to investigate the protective efficacy of N‐acetyl‐L‐tryptophan (NAT) against gamma‐radiation‐induced cell death in murine macrophage J774A.1 cells. The radioprotective efficacy of NAT was evaluated in terms of cell survivability, effect on antioxidant enzyme activity, and free radicals inhibition. Radioprotective efficacy of NAT pretreatment to irradiated cells was assessed via cell cycle progression, mitochondrial membrane potential (MMP) perturbation, and apoptosis regulation using flow cytometry. Results of the study demonstrated significant radioprotective efficacy (>80%) of NAT in irradiated cells as estimated by sulforhodamine B (SRB), MTT, and clonogenic assay. Significant (p < 0.001) reduction in ROS, xanthine oxidase, and mitochondrial superoxide levels along with increment in catalase, glutathione‐s‐transferase, glutathione, and ATPase activities in NAT pretreated plus irradiated cells was observed as compared to the gamma‐irradiated cells. Further, significant (p < 0.001) stabilization of MMP and reduction in apoptosis was also observed in NAT pretreated plus irradiated cells as compared to irradiated cells that not pretreated with NAT. The current study demonstrates that NAT pretreatment to irradiated cells protects against gamma radiation‐induced cell death by reducing oxidative stress, stabilizing MMP, and inhibiting apoptosis. These observations conclusively highlight the potential of developing NAT as a prospective radioprotective agent upon further validation using in‐depth preclinical assessment in cellular and animal models. [ABSTRACT FROM AUTHOR]

Neurofilaments (NFs) are the most abundant component of mature neurons, that interconnect with actin and microtubules to form the cytoskeleton. Specifically expressed in the nervous system, NFs present the particularity within the Intermediate Filament family of being formed by four subunits, the neurofilament light (NF-L), medium (NF-M), heavy (NF-H) proteins and a-internexin or peripherin. Here, we review the current knowledge on NF proteins and neurofilaments, from their domain structures and their model of assembly to the dynamics of their transport and degradation along the axon. The formation of the filament and its behaviour are regulated by various determinants, including post-transcriptional (miRNA and RBP proteins) and post-translational (phosphorylation and ubiquitination) modifiers. Altogether, the complex set of modifications enable the neuron to establish a stable but elastic NF array constituting the structural scaffold of the axon, while permitting the local expression of NF proteins and providing the dynamics necessary to fulfil local demands and respond to stimuli and injury. Thus, in addition to their roles in mechano-resistance, radial axonal outgrowth and nerve conduction, NFs control microtubule dynamics, organelle distribution and neurotransmission at the synapse. We discuss how the studies of neurodegenerative diseases with NF aggregation shed light on the biology of NFs. In particular, the NEFL and NEFH genes are mutated in Charcot-Marie-Tooth (CMT) disease, the most common inherited neurological disorder of the peripheral nervous system. The clinical features of the CMT forms (axonal CMT2E, CMT2CC; demyelinating CMT1F; intermediate I-CMT) with symptoms affecting the central nervous system (CNS) will allow us to further investigate the physiological roles of NFs in the brain. Thus, NF-CMT mouse models exhibit various degrees of sensory-motor deficits associated with CNS symptoms. Cellular systems brought findings regarding the dominant effect of NF-L mutants on NF aggregation and transport, although these have been recently challenged. Neurofilament detection without NF-L in recessive CMT is puzzling, calling for a reexamination of the current model in which NF-L is indispensable for NF assembly. Overall, we discuss how the fundamental and translational fields are feeding each-other to increase but also challenge our knowledge of NF biology, and to develop therapeutic avenues for CMT and neurodegenerative diseases with NF aggregation. [ABSTRACT FROM AUTHOR]

Background: Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by two main pathological mechanisms, mostly hyperphosphorylated tau and amyloid-β toxicity. Although many studies focus on these basic mechanisms, ferroptosis draws attention as an important pathway responsible for neurodegeneration in AD. There is no definitive treatment for AD but alternative phytochemicals to drugs come into prominence. Betulin is usually obtained from the birch tree. It is an abundant triterpene and has a high antioxidant capacity. Isthmin-1 (ISM1) is a secreted adipokine. Objective: In this study, we investigated the potential treatment of AD in the ferroptosis-ISM1-betulin triangle. Methods: For this, we created an AD model with okadaic acid (200 ng/kg)) in 36 Wistar albino male rats and treated with betulin (20 mg/kg/day, i.p). We evaluated ISM1 gene expression, iron accumulation, and total oxidative metabolism parameters (TAS, TOS, OSI) in hippocampal tissue. We analyzed cognitive recovery in AD with Morris Water Maze Test and general locomotor activity, explore, and anti-anxiolytic effect with Open Field Test. Results: We compared the obtained data with metabolic and genetic results. In conclusion, betulin may have a role in neuronal ferroptotic mechanisms by reducing iron accumulation by ISM1 regulation. Conclusions: Betulin may have a role in neuronal ferroptotic mechanisms by reducing iron accumulation by ISM1 regulation. Although this study suggests the corrective effect of betulin and ISM1 on cognitive gain and anxiety, it is the first study to show the total antioxidant capacity of betulin in AD. [ABSTRACT FROM AUTHOR]

The most frequent cause of hospitalization in adults over 65 in Western nations is acute decompensation of heart failure (ADHF). Due to the high death rate, it places a heavy load on healthcare systems as well as people. The present study's objective was to ascertain the connection between polymorphisms in the Glutathione S-transferase Mu 1 (GSTM1) gene and heartfailure-reduced ejection fraction (HFrEF) patients. Sixty patients with a mean age of 25-94 were taken from both genders after the clinical diagnosis by a specialist to cases who were referred to the Ibn Al-Baitar Specialized Center for Cardiac Surgery and Ramadi Teaching Hospital, and thirty apparently healthy people were taken as a control. Blood and serum containing EDTA were drawn from sick and healthy people to extract DNA for multiplex PCR detection of the GSTM1 polymorphism. The GSTM1 genotype was found in 23 (38.33%) and the null gene in 37 (61.66%) of the 60 ADHF patients. Of 30 healthy people, 8 (26.66%) had the GSTM1 gene and 22 (73.33%) had the null gene. According to the present study, the etiology of acute decompensated heart failure (ADHF) and the antioxidant null gene (GSTM1) are related. The present study has been achieved to determine the relationship between the presence of the antioxidant gene (GSTM1) and the incidence of ADHF with reduced ejection fraction for research and therapeutic purposes, which opens new spaces in the treatment of the mentioned condition. [ABSTRACT FROM AUTHOR]

Background: The impact of inhaled corticosteroid (ICS) in the interaction between asthma, COVID-19 and COVID-19 associated outcomes remain largely unknown. The objective of this study is to investigate the risk of COVID-19 and its related outcomes in patients with asthma using and not using inhaled corticosteroid (ICS). Methods: We used the TriNetX Network, a global federated network that comprises 55 healthcare organizations (HCO) in the United States, to conduct a retrospective cohort study. Patients with a diagnosis of asthma with and without ICS between January 2020 and December 2022 were included. Propensity score matching was used to match the case cohorts. Risks of COVID-19 incidence and medical utilizations were evaluated. Results: Out of 64,587 asthmatic patients with ICS and without ICS, asthmatic patients with ICS had a higher incidence of COVID-19 (Hazard ratio, HR: 1.383, 95% confidence interval, CI: 1.330–1.437). On the contrary, asthmatic patients with ICS revealed a significantly lower risk of hospitalization (HR: 0.664, 95% CI: 0.647–0.681), emergency department visits (HR: 0.774, 95% CI: 0.755–0.793), and mortality (HR:0.834, 95% CI:0.740–0.939). In addition, subgroup or sensitivity analyses were also conducted to examine the result of different vaccination status, disease severity, or COVID-19 virus variants. Conclusion: For asthmatic patients using ICS, risk of COVID-19 was significantly higher than non-users. The observed association could provide potential guidance for primary care physicians regarding the risk of COVID-19 in asthmatic patients. [ABSTRACT FROM AUTHOR]

This study investigated the potential bioactive properties of white cheeses produced in different regions of Turkey, including their potential antioxidant, antihypertensive, antidiabetic, antimicrobial, and anticancer activities. The cheese samples were analyzed both before and after in vitro digestion. The study found that all cheese samples exhibited significant angiotensin‐converting enzyme inhibition activity both before (45.5%–70.1% for 0.03 g cheese/mL) and after in vitro digestion (25.5%–63.5% for 0.0167 g cheese/mL), whereas α‐amylase inhibition activity was present in all samples (in the range of 5.1%–50.0% for 3.0 × 10−5 g cheese/mL) but disappeared after digestion, and α‐glucosidase inhibition activity was only detected after in vitro digestion (from 20.5% to 60.4% for 5.6 × 10−5 g cheese/mL), indicating potential antidiabetic properties. However, antimicrobial and anticancer activities were not observed in any of the samples. The results also suggest that the bioactivity potential of white cheese may vary depending on the region of production, as cheeses from the Marmara region exhibited high α‐glucosidase inhibition activity after digestion. In conclusion, while white cheese is a valuable addition to the diet due to its high nutritional value and potential health benefits. This study revealed the bioactive potential of ripened white cheese and in vivo investigations of the cheese components would better show their possible benefits. Practical Application: Although the bioactivity potentials varied among the ripened white cheese samples produced in different regions of Turkey, a consistent trend was observed in terms of their presence or absence. Our research revealed that all ripened cheese samples demonstrated significant potential antioxidant and antihypertensive activities, as well as potential antidiabetic properties. Moreover, it can be interpreted that ripened white cheese has the potential to reduce the digestion of carbohydrates when consumed with carbohydrate‐rich foods. Although the present results provide limited practical findings directly applicable to the industry, if the data and information obtained from this study are further explored and further studies delving into specific mechanisms of bioactive components could emerge. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is a complex malignancy responsible for the second-highest cancer deaths worldwide. TGF-β maintains normal cellular homeostasis by inhibiting the cell cycle and inducing apoptosis, but its elevated level is correlated with colorectal cancer progression, as TGF-β is a master regulator of the epithelial-to-mesenchymal transition, a critical step of metastasis. Tumors, including CRC, use elevated TGF-β levels to avoid immune surveillance by modulating immune cell differentiation, proliferation, and effector function. Presently, the treatment of advanced CRC is mainly based on chemotherapy, with multiple adverse effects. Thus, there is a need to develop alternate tactics because CRC continue to be mostly resistant to the present therapeutic regimen. TGF-β blockade has emerged as a promising therapeutic target in cancer therapy. Blocking TGF-β with phytochemicals and other molecules, such as antisense oligonucleotides, monoclonal antibodies, and bifunctional traps, alone or in combination, may be a safer and more effective way to treat CRC. Furthermore, combination immunotherapy comprising TGF-β blockers and immune checkpoint inhibitors is gaining popularity because both molecules work synergistically to suppress the immune system. Here, we summarize the current understanding of TGF-β as a therapeutic target for managing CRC and its context-dependent tumor-promoting or tumor-suppressing nature. [ABSTRACT FROM AUTHOR]

Breast cancer is currently the most common malignancy and has a high mortality rate. Ginsenosides, the primary bioactive constituents of ginseng, have been shown to be highly effective against breast cancer both in vitro and in vivo. This study aims to comprehensively understand the mechanisms underlying the antineoplastic effects of ginsenosides on breast cancer. Through meticulous bibliometric analysis and an exhaustive review of pertinent research, we explore and summarize the mechanism of action of ginsenosides in treating breast cancer, including inducing apoptosis, autophagy, inhibiting epithelialmesenchymal transition and metastasis, and regulating miRNA and lncRNA. This scholarly endeavor not only provides novel prospects for the application of ginsenosides in the treatment of breast cancer but also suggests future research directions for researchers. [ABSTRACT FROM AUTHOR]

Nuclear receptors (NRs) form a family of druggable transcription factors that are regulated by ligand binding to orchestrate multifaceted physiological functions, including reproduction, immunity, metabolism, and growth. NRs represent attractive and valid targets for the management and treatment of a vast array of ailments. Pentacyclic triterpenes (PTs) are ubiquitously distributed natural products in medicinal and aromatic plants, of which ursolic acid (UA) is an extensively studied member, due to its diverse bio-pertinent activities against different cancers, inflammation, aging, obesity, diabetes, dyslipidemia, and liver injury. In fact, PTs share a common lipophilic structure that resembles NRs' endogenous ligands. Herein, we present a review of the literature on UA's effect on NRs, showcasing the resulting health benefits and potential therapeutic outcomes. De facto, UA exhibited numerous pharmacodynamic effects on PPAR, LXR, FXR, and PXR, resulting in remarkable anti-inflammatory, anti-hyperlipidemic, and hepatoprotective properties, by lowering lipid accumulation in hepatocytes and mitigating non-alcoholic steatohepatitis (NASH) and its subsequent liver fibrosis. Furthermore, UA reversed valproate and rifampicin-induced hepatic lipid accumulation. Additionally, UA showed great promise for the treatment of autoimmune inflammatory diseases such as multiple sclerosis and autoimmune arthritis by antagonizing RORγ. UA exhibited antiproliferative effects against skin, prostate, and breast cancers, partially via PPARα and RORγ pathways. Herein, for the first time, we explore and provide insights into UA bioactivity with respect to NR modulation. [ABSTRACT FROM AUTHOR]

Eclipta prostrata L. (EPL), a medicinal plant, is widely utilized in the central highlands of Vietnam. This study aims to assess the chemical profile and potential medical effects of an EPL extract rich in flavonoids. A total of 36 secondary metabolites were identified from the EPL extract through GC-MS and UHPLC-UV analysis. Among them, 15 volatile compounds and several phenolic and flavonoid chemicals, including salicylic acid, epicatechin gallate, isovitexin, and apigetrin, were reported in EPL extract for the first time. This herbal extract demonstrated moderate inhibition against α-amylase and α-glucosidase, and high anti-oxidant and anti-acetylcholinesterase activities (IC50 = 76.8 ± 0.8 μg/mL). These promising attributes can be likely attributed to the high levels of major compounds, including wedelolactone (1), chlorogenic acid (3), epicatechin gallate (6), salicylic acid (8), isovitexin (9), apigetrin (11), and myricetin (12). These findings align with the traditional use of EPL for enhancing memory and cognitive function, as well as its potential benefits in diabetes management. The results of the molecular docking study reveal that the major identified compounds (1, 6, 9, and 11) showed a more effective acetylcholinesterase inhibitory effect than berberine chloride, with good binding energy (DS values, −12.3 to −14.3 kcal/mol) and acceptable values of RMSD (1.02–1.67 Å). Additionally, almost all the identified major compounds exhibited good ADMET properties within the required limits. [ABSTRACT FROM AUTHOR]

This study investigated the tenderizing and flavor-enhancing effects of koji, a fermented grain cultured with a single microorganism, on chicken breasts during curing. Chicken breasts were cured with different ingredients, including 4% (w/w) curing agent (GC), 5% (w/w) Aspergillus oryzae with rice (FR), A. oryzae with soybean (FS), and Bacillus subtilis with soybean (BS) for 4 h at 4 °C prior to cooking. After the superheated steam procedure, all samples were cooked in a convection oven, and their physicochemical properties were analyzed. Koji-treated samples exhibited significantly higher expressible moisture due to the degradation of the protein matrix (p < 0.05). Texture profile analysis showed that the tenderness of koji-treated samples was significantly higher than that of GC (p < 0.05). Furthermore, koji-treated samples were regarded as tenderer, and they were preferred over GC (p < 0.05) in the sensory evaluation. Principal attributes analysis revealed that the overall preference for koji-treated samples was highly correlated with umami, juiciness, and tenderness (p < 0.05). Overall, this study provides insights into applying koji as a potential curing treatment to improve the eating quality of chicken breasts. Koji can be used as a novel technology in the food industry to improve taste and tenderness simultaneously. [ABSTRACT FROM AUTHOR]

The paper presents results of studying the kinematics of the ionized gas in the galaxy of the Large Magellanic Cloud type NGC 7292 obtained with the 2.5-m telescope of the Caucasian Mountain Observatory (CMO SAI MSU) and the 6-m BTA telescope of the Special Astrophysical Observatory (SAO RAS). Analysis of the velocity fields of the ionized and neutral hydrogen showed that the kinematic center of NGC 7292 located at the center of the bar, northwest of the photometric center of the galaxy (the southeastern end of the bar) previously taken as the center of NGC 7292. In addition to the circular rotation of the gas, the radial motions associated with the bar play a significant role in the kinematics of the disk. The observed perturbations of the gaseous-disk kinematics induced by the ongoing star formation do not exceed those caused by the bar. It is possible that part of the non-circular motions (at the southeastern end of the bar which is the brightest H II region) may be related to the effects of the capture of a dwarf companion or a gaseous cloud. [ABSTRACT FROM AUTHOR]

Photoimmunotherapy (PIT) is an emerging therapeutic approach that integrates phototherapy and immunotherapy to eliminate primary tumors under an appropriate dosage of local light irradiation, while simultaneously preventing tumor metastasis and recurrence by activating the host antitumor immune response. Tumor-responsive dynamic nanoassemblies (TDNs) have evolved from being a mere curiosity to a promising platform for high-performance PIT. However, the dynamic nano-bio interaction between TDNs and tumor microenvironment remains poorly understood, which shall be critical for precise control of TDNs assembling/disassembling behavior and superior PIT efficacy. To deepen the understanding of the structure–function relationship of TDNs, this review introduces the rational design, nano-bio interactions, and controllable functionalities of cutting-edge TDNs for enhanced PIT. Moreover, the synergetic mechanism between TDNs-based PIT and immunomodulatory agents-mediated immunomodulation is particularly emphasized. Finally, the challenges and future perspectives in this emerging field are assessed. [ABSTRACT FROM AUTHOR]

The tumor microenvironment (TME) plays an important role in the development of tumors. Immunoregulatory cells and cytokines facilitate cancer cells to avoid immune surveillance. Overexpression of immune checkpoint molecules such as CTLA-4 and PD-1/PD-L1 inhibits immune function and enables cancer cells to avoid clearance by the immune system. Thus, minimizing tumor immunosuppression could be an important strategy for cancer therapy. Currently, many immune checkpoint-targeted drugs, such as PD-1/PD-L1 inhibitors, have been approved for marketing and have shown unique advantages in the clinical treatment of cancers. The concept of "strengthening resistance to eliminate pathogenic factors" in traditional Chinese medicine (TCM) is consistent with the immunotherapy of cancer. According to previous studies, the role of TCM in tumor immunotherapy is mainly associated with the positive regulation of natural killer cells, CD8/CD4 T cells, dendritic cells, M2 macrophages, interleukin-2, tumor necrosis factor- α , and IFN- γ , as well as with the negative regulation of Tregs, myeloid-derived suppressor cells, cancer-associated fibroblasts, PD-1/PD-L1, transforming growth factor- β , and tumor necrosis factor- β. This paper summarizes the current research on the effect of TCM targeting the TME, and further introduces the research progress on studying the effects of TCM on immune checkpoints. Modern pharmacological studies have demonstrated that TCM can directly or indirectly affect the TME by inhibiting the overexpression of immune checkpoint molecules and enhancing the efficacy of tumor immunotherapy. TCM with immunomodulatory stimulation could be the key factor to achieve benefits from immunotherapy for patients with non-inflammatory, or "cold", tumors. [ABSTRACT FROM AUTHOR]

Obesity has been regarded as one of the major health problems worldwide. Studies demonstrated that ursolic acid (UA) can significantly ameliorate the progress of obesity. However, whether the effect of UA on obesity depends on the regulation of gut microbiota and metabolism is uncertain. To investigate the regulatory role of UA in obese mice from the perspective of intestinal microbiome and metabolomics analyses, an obese mice model was established with a highfat diet, and the effect of UA on obesity was evaluated. The alterations of gut microbiota and metabolism related to obesity were evaluated by bioinformatic analysis. The results of the gut microbiota analysis showed that UA intervention could shift the Firmicutes to Bacteroidetes ratio at the phylum level and increase in the genera of Lactobacillus, Bacteroides, and Akkermansia. Additionally, metabolomics analysis showed that the beneficial influence of UA on obesity partly depended on amino acid metabolism. The current study demonstrated the roles of UA in the anti-obesity process, which depends in part on alterations in the gut microbiota and metabolism. Therefore, our findings highlight the potential therapeutic effect of UA on the improvement of diet-induced obesity in humans. [ABSTRACT FROM AUTHOR]

Few studies have reported the therapeutic effects of Korean red ginseng (KRG) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the positive effects of KRG on other viruses have been reported and the effects of KRG on pulmonary inflammatory diseases have also been studied. Therefore, this study investigated the therapeutic effects of KRG-water extract (KRG-WE) in a pseudo-type SARS-CoV-2 (PSV)-induced lung injury model. Constructing the pseudovirus, human angiotensin-converting enzyme 2 (hACE2) transgenic mice were infected via intranasal injection that had been orally administered with KRG-WE for six weeks. After 7-days post infection (dpi), the antiviral effects of KRG-WE were confirmed, followed by real-time polymerase chain reaction (PCR), western blot analysis, flow cytometric analysis, and an enzyme-linked immunoassay (ELISA). KRG-WE significantly inhibited an increase in immunoglobulin caused by PSV. Furthermore, KRG-WE effectively suppressed alveolar macrophages (AMs) inside the lungs and helped normalize the population of other immune cells. In addition, virus-induced gene expression and inflammatory signals such as nuclear factor-kappa B and other upstream molecules were downregulated. Moreover, KRG-WE also normalized gene expression and protein activity in the spleen. In conclusion, KRG-WE reduced AMs, normalized the immune response, and decreased the expression of inflammatory genes and activation of signaling pathway phosphorylation, thereby exhibiting anti-inflammatory effects and attenuating lung damage. [ABSTRACT FROM AUTHOR]

The aim of this review is to investigate the basic principles of red meat cooking technologies, including traditional and modern methods, and their effects on the physical, thermal, mechanical, sensory, and microbial characteristics of red meat. Cooking methods were categorized into two categories: traditional (cooking in the oven and frying) and modern (ohmic, sous vide, and microwave cooking). When red meat is subjected to high temperatures during food manufacturing, it undergoes changes in its engineering and quality attributes. The quality standards of meat products are associated with several attributes that are determined by food technologists and consumers based on their preferences. Cooking improves the palatability of meat in terms of tenderness, flavor, and juiciness, in addition to eliminating pathogenic microorganisms. The process of meat packaging is one of the important processes that extend the life span of meat and increase its shelf life due to non-exposure to oxygen during cooking and ease of handling without being exposed to microbial contamination. This review highlights the significance of meat cooking mathematical modeling in understanding heat and mass transfer phenomena, reducing costs, and maintaining meat quality. The critical overview considers various production aspects/quality and proposed methods, such as, but not limited to, hurdle technology, for the mass production of meat. [ABSTRACT FROM AUTHOR]