Age-associated changes in innate and adaptive immunity: role of the gut microbiota.

Aging is generally regarded as an irreversible process, and its intricate relationship with the immune system has garnered significant attention due to its profound implications for the health and well-being of the aging population. As people age, a multitude of alterations occur within the immune system, affecting both innate and adaptive immunity. In the realm of innate immunity, aging brings about changes in the number and function of various immune cells, including neutrophils, monocytes, and macrophages. Additionally, certain immune pathways, like the cGAS-STING, become activated. These alterations can potentially result in telomere damage, the disruption of cytokine signaling, and impaired recognition of pathogens. The adaptive immune system, too, undergoes a myriad of changes as age advances. These include shifts in the number, frequency, subtype, and function of T cells and B cells. Furthermore, the human gut microbiota undergoes dynamic changes as a part of the aging process. Notably, the interplay between immune changes and gut microbiota highlights the gut's role in modulating immune responses and maintaining immune homeostasis. The gut microbiota of centenarians exhibits characteristics akin to those found in young individuals, setting it apart from the microbiota observed in typical elderly individuals. This review delves into the current understanding of how aging impacts the immune system and suggests potential strategies for reversing aging through interventions in immune factors.

Assessing the potential role of arbuscular mycorrhizal fungi in improving the phytochemical content and antioxidant properties in Gomphrena globosa.

Strategies to increase the secondary metabolite production, obtained from medicinal plants has been the topic of research in recent years. The symbiotic interaction between arbuscular mycorrhizal fungi and plants allows host-fungus pairings to enhance secondary metabolite synthesis. Therefore, the current study investigated the effect of inoculating two distinct AMF species discretely as well as in conjunction on the flower-derived secondary metabolites in Gomphrena globosa. The findings showed that the plants inoculated with combined treatment exhibited higher total phenolic (50.11 mg GAE/g DW), flavonoids (29.67 mg QE/g DW), saponins (122.55 mg DE/g DW), tannins (165.71 TAE/g DW) and terpenoid (8.24 mg LE/g DW) content in the methanolic extract. HPTLC examination showed the existence of kaempferol and benzoic acid with the highest amount (0.90% and 5.83% respectively) observed in the same treatment. FTIR analysis revealed functional group peaks with increased peak intensity in the combination treatment. Higher antioxidant activities such as DPPH (IC50: 401.39 µg/mL), ABTS (IC50: 71.18 µg/mL) and FRAP (8774.73 µM Fe (II) equivalent) were observed in the methanolic extract of combined treatment. To our knowledge, this is the first study on the impact of AMF inoculation on bioactive compounds and antioxidant activities in G. globosa flowers. Moreover, this study could lead to the development of novel pharmaceuticals and herbal remedies for various diseases.

Systematic Review of the Cost-Effectiveness of Home-Based Palliative Care Interventions in Patients with Cancer: A Critical Analysis.

Background: The increased prevalence of cancer and the negative impact of pain on the quality of life of patients underscore the need to implement efficient palliative care interventions and management of pain. The cost-effectiveness of palliative care interventions for cancer, mostly pharmacological and delivered through home-based palliative care services, is unclear. Most of the studies do not take into account indirect costs nor consider variations across different geographical regions. Objective: To describe existing and cutting-edge knowledge on cost-effectiveness or item costs related to palliative home-based care for patients with cancer. We evaluated various costs, including direct medical, non-medical, and indirect costs in different geographical regions and analysed how different options for care affect the patients' quality of life and associated expenses. Methods: This Prospero-registered systematic review (CRD42023404217) adhered to the PRISMA criteria. Following a multistep selection process, we selected 22 articles published between 2013 and 2023 focused on quality of life outcomes and cost-effectiveness of home-based palliative care for cancer patients. Results: Home-based palliative care decreases the number of hospital visits, while its influence on patients quality of life is currently difficult to demonstrate across geographic regions based on available evidence. Overall, home care decreases the costs associated to the palliative care of patients with cancer. The cost structure analysis revealed that besides healthcare costs, informal care expenses and productivity losses represent a significant proportion of overall expenses). In Europe, the direct medical, non-medical, and indirect costs (in purchasing power parity) were on average $1,941, $842, and $1,241, per month per person, respectively. In the USA and Asia, direct medical and indirect costs are on average $1,095 (USA) vs $1,444 (Asia) and $2,192 (USA) vs $1,162 (Asia). Conclusion: In conclusion, the studies reviewed highlight significant cost variations and potential savings associated with palliative home-based care for cancer patients. Home-based palliative care, particularly involving medications, has shown favorable cost-effectiveness compared to hospital care. Specialized palliative home care, psychological interventions, and outpatient services further contribute to overall cost savings. However, the economic impact varies across different geographical contexts and cost categories, emphasizing the need for tailored approaches in palliative care planning and implementation.

c-Jun N-terminal kinase signaling in aging.

Aging encompasses a wide array of detrimental effects that compromise physiological functions, elevate the risk of chronic diseases, and impair cognitive abilities. However, the precise underlying mechanisms, particularly the involvement of specific molecular regulatory proteins in the aging process, remain insufficiently understood. Emerging evidence indicates that c-Jun N-terminal kinase (JNK) serves as a potential regulator within the intricate molecular clock governing aging-related processes. JNK demonstrates the ability to diminish telomerase reverse transcriptase activity, elevate ß-galactosidase activity, and induce telomere shortening, thereby contributing to immune system aging. Moreover, the circadian rhythm protein is implicated in JNK-mediated aging. Through this comprehensive review, we meticulously elucidate the intricate regulatory mechanisms orchestrated by JNK signaling in aging processes, offering unprecedented molecular insights with significant implications and highlighting potential therapeutic targets. We also explore the translational impact of targeting JNK signaling for interventions aimed at extending healthspan and promoting longevity.

Amaranth and buckwheat grains: Nutritional profile, development of functional foods, their pre-clinical cum clinical aspects and enrichment in feed.

The resurgence of interest in amaranth and buckwheat as nutrient-rich and versatile grains has incited extensive research aimed at exploring their potential benefits for sustainable agriculture and human nutrition. Amaranth is renowned for its gluten-free nature and exceptional nutritional profile, offering high-quality proteins, fiber, minerals, and bioactive compounds. Similarly, buckwheat is recognized for its functional and nutraceutical properties, offering a plethora of health benefits attributed to its diverse array of biologically active constituents; flavonoids, phytosterols, and antioxidants. This comprehensive review comprehends the existing understanding of the composition, anti-nutritional factors, biological activity, and potential application of these grains, emphasizing their pivotal role in addressing global food insecurity. Developed functional foods using these grains are having enhanced physicochemical properties, mineral content, phenolic content and overall sensory acceptability. In addition, the consumption of developed functional food products proved their health benefits against various type of anomalies. Moreover, enrichment of both grains in the animal feeds also showing positive health benefits.

Discovery of a 6-Aminobenzo[b]thiophene 1,1-Dioxide Derivative (K2071) with a Signal Transducer and Activator of Transcription 3 Inhibitory, Antimitotic, and Senotherapeutic Activities.

6-Nitrobenzo[b]thiophene 1,1-dioxide (Stattic) is a potent signal transducer and activator of the transcription 3 (STAT3) inhibitor developed originally for anticancer therapy. However, Stattic harbors several STAT3 inhibition-independent biological effects. To improve the properties of Stattic, we prepared a series of analogues derived from 6-aminobenzo[b]thiophene 1,1-dioxide, a compound directly obtained from the reduction of Stattic, that includes a methoxybenzylamino derivative (K2071) with optimized physicochemical characteristics, including the ability to cross the blood-brain barrier. Besides inhibiting the interleukin-6-stimulated activity of STAT3 mediated by tyrosine 705 phosphorylation, K2071 also showed cytotoxicity against a set of human glioblastoma-derived cell lines. In contrast to the core compound, a part of K2071 cytotoxicity reflected a STAT3 inhibition-independent block of mitotic progression in the prophase, affecting mitotic spindle formation, indicating that K2071 also acts as a mitotic poison. Compared to Stattic, K2071 was significantly less thiol-reactive. In addition, K2071 affected cell migration, suppressed cell proliferation in tumor spheroids, exerted cytotoxicity for glioblastoma temozolomide-induced senescent cells, and inhibited the secretion of the proinflammatory cytokine monocyte chemoattractant protein 1 (MCP-1) in senescent cells. Importantly, K2071 was well tolerated in mice, lacking manifestations of acute toxicity. The structure-activity relationship analysis of the K2071 molecule revealed the necessity of the para-substituted methoxyphenyl motif for antimitotic but not overall cytotoxic activity of its derivatives. Altogether, these results indicate that compound K2071 is a novel Stattic-derived STAT3 inhibitor and a mitotic poison with anticancer and senotherapeutic properties that is effective on glioblastoma cells and may be further developed as an agent for glioblastoma therapy.

Trends in the Treatment of Chronic Wounds.

Chronic wounds remain one of the significant burdens to health across the world, mainly in view of diabetes and its natural consequences. This category of lesions includes pressure ulcers, vascular diseases, and surgery-related wounds, which affect millions and pose a major challenge to the healthcare industry. The paper reviews the various physiological mechanisms of wound healing, factors that impede it, and some new treatments emerging at this moment. In contrast, current developments include surgical and non-surgical alternatives like topical dressings, medicated formulations, and skin substitutes. Advanced wound care today covers tissue-engineered skin substitutes, 3D-printed wound dressings, topical medicated formulations, and growth factor-based therapies. These are non-invasive, biocompatible methods that are cost-effective, userfriendly, and more conducive to natural healing than traditional therapies. Hydrogel dressings have high water content to create a moist environment that encourages healing. They also reflect excellent physicochemical and biological properties, which enhance autolytic debridement and reduction of pain due to the moisture retention, biocompatibility, and non-toxicity conferred. Tissue-engineered skin substitutes, comprising allogeneic or autologous cells, wound-healing enhancement bioengineered allogeneic cellular therapies are like the natural skin and encourage regeneration. 3D printing allows the production of customized dressings to aid in better treatment. Newer therapies, including bioengineered allogeneic cellular therapies and fish skin grafting, require more clinical trials to confirm safety and efficacy. With such innovations in wound healing technologies and therapies, the future looks quite promising in managing chronic wounds, enhancing healing, reducing healthcare expenditure, and promoting a better quality of life for patients.

Drosophila melanogaster as a model organism for screening acetylcholinesterase reactivators.

The widely used insecticide chlorpyrifos (CP) is known to inhibit acetylcholinesterase (AChE) activity attributed to result in various neurological disorders and acetylcholine-dependent organ functions including heart, skeletal muscle, lung, gastrointestinal tract, and central nervous systems. Enzyme reactivators, such as oximes, are known to restore AChE activity and mitigate adverse effects. The identification of compounds that reactivate AChE constitute agents with important therapeutic beneficial effects in cases of pesticide poisoning. However, the screening of novel drugs using traditional models may raise ethical concerns. This study aimed to investigate the potential of Drosophila melanogaster as a model organism for screening AChE reactivators, with a focus on organophosphate poisoning. The efficacy of several oximes, including pralidoxime, trimedoxime, obidoxime, methoxime, HI-6, K027, and K048, against CP-induced AChE activity inhibition in D. melanogaster was determined in silico, in vitro, and in vivo experiments. Molecular docking studies indicated a strong interaction between studied oximes and the active-site gorge of AChE. Data showed that selected oximes (100 µM) are effective in the reactivation of AChE inhibited by CP (10 µM) in vitro. Finally, in vivo investigations demonstrated that selected oximes, pralidoxime and K048 (1.5 ppm), reversed the locomotor deficits, inhibition of AChE activity as well as lowered the mortality rates induced by CP (0.75 ppm). Our findings contribute to utilization of D. melanogaster as a robust model for determination of actions of identified new AChE inhibitory agents with more effective therapeutic properties that those currently in use in the clinical practice in treatment of AChE associated disorders.

Synthesis and in vitro assessment of the reactivation profile of clinically available oximes on the acetylcholinesterase model inhibited by A-230 nerve agent surrogate.

The risk of the use of toxic chemicals for unlawful acts has been a matter of concern for different governments and multilateral agencies. The Organisation for the Prohibition of Chemical Weapons (OPCW), which oversees the implementation of the Chemical Weapons Convention (CWC), considering recent events employing chemical warfare agents as means of assassination, has recently included in the CWC "Annex on Chemicals" some organophosphorus compounds that are regarded as acting in a similar fashion to the classical G- and V-series of nerve agents, inhibiting the pivotal enzyme acetylcholinesterase. Therefore, knowledge of the activity of the pyridinium oximes, the sole class of clinically available acetylcholinesterase reactivators to date, is plainly justified. In this paper, continuing our research efforts in medicinal chemistry on this class of toxic chemicals, we synthesized an A-230 nerve agent surrogate and applied a modified Ellman's assay to evaluate its ability to inhibit our enzymatic model, acetylcholinesterase from Electrophorus eel, and if the clinically available antidotes are able to rescue the enzyme activity for the purpose of relating the findings to the previously disclosed in silico data for the authentic nerve agent and other studies with similar A-series surrogates. Our experimental data indicates that pralidoxime is the most efficient compound for reactivating acetylcholinesterase inhibited by A-230 surrogate, which is the opposite of the in silico data previously disclosed.

Quantification of oxidative stress markers in the blood sera following subacute administration of different oximes in rats.

Oxidative stress status, as a disruption of redox homeostasis, in the blood sera of Wistar rats caused by repeated application of selected acetylcholinesterase reactivators - asoxime, obidoxime, K027, K048, K074, and K075 were evaluated. Throughout this study, each oxime in a dose of 0.1 of LD50/kg im was given 2x/week for 4 weeks. Then, seven days after the last oximes' application, markers of lipid peroxidation (malondialdehyde, MDA), and protein oxidation (advanced oxidation protein products, AOPP), as well as the activity of antioxidant enzymes (catalase, CAT, superoxide dismutase, SOD, reduced glutathione, GSH, and oxidized glutathione, GSSG), were determined. Oxidative stress parameters, MDA and AOPP were significantly highest in the K048-, K074- and K075-treated groups (p < 0.001). The activity of CAT was significantly elevated in the obidoxime-treated group (p < 0.05), while treatment with K027, K048, and K074 induced high elevation in SOD levels (p < 0.01, p < 0.001). Interestingly, the activity of GSH in each oxime-treated group was significantly elevated. Unlike, treatment with obidoxime caused elevation in GSSG levels (p < 0.01). As a continuation of our previously published data, these results assure that applied oximes following subacute treatment ameliorated the oxidative status and further adverse systemic toxic effects in rats.

Selected fruit pomaces: Nutritional profile, health benefits, and applications in functional foods and feeds.

The utmost objective of every nation is to achieve zero hunger and ensure the health and well-being of its population. However, in impoverished nations, particularly in rural areas, such issues persist on a daily basis. Currently, there is a growing demand for fruit consumption due to their potential health benefits. Surprisingly, their most prevalent by-product is pomace, which is produced in millions of tonnes and is usually discarded as waste after processing or consumption. Even food produced with these kinds of raw resources can contribute to the objective of eradicating world hunger. Owing to these advantages, scientists have begun evaluating the nutritional content of various fruit pomace varieties as well as the chemical composition in different bioactive constituents, which have significant health benefits and can be used to formulate a variety of food products with notable nutraceutical and functional potential. So, the purpose of this review is to understand the existing familiarity of nutritional and phytochemical composition of selected fruit pomaces, those derived from pineapple, orange, grape, apple, and tomato. Furthermore, this article covers pre-clinical and clinical investigations conducted on the selected fruit pomace extracts and/or powder forms and its incorporation into food products and animal feed. Adding fruit pomaces reduces the glycemic index, increases the fibre content and total polyphenolic contents, and reduces the cooking loss, etc. In animal feeds, incorporating fruit pomaces improves the antioxidant enzyme activities, humoral immune system, and growth performance and reduces methane emission.

Value addition of mango kernel for development and characterization of starch with starch nanoparticles for packaging applications.

The present research was conducted to explore the potential of mango kernel starch from the Chaunsa variety to develop starch and starch nanoparticles (SNPs) based films. The investigation included starch isolation from mango kernel followed by the preparation of SNPs by acid hydrolysis and a thorough examination of various physicochemical properties for film formation. The properties of SNPs were found to be distinctly different from those of native starch. SNPs exhibited an aggregated form with an irregular surface, whereas native starch had an oval and elongated shape with a smooth surface. X-ray diffraction (XRD) analysis confirmed that the starch type in SNPs was of the A-type. Additionally, the pasting properties of SNPs were minimal due to the acid hydrolysis process. SNP-based composite film was developed with (5 %) SNP concentration added. This successful incorporation of SNPs enhanced biodegradability, with complete degradation occurring within three weeks. Moreover, the composite films displayed increased burst strength, measuring 1303.51 ± 73.7 g, and lower water vapor transmission rates (WVTR) at (7.40 ± 0.50) × 10-3 g per square meter per second and reduced water solubility at 35.32 ± 3.0 %. This development represents a significant advancement in the field of eco-friendly packaging materials.

RETRACTED: Ali et al. A Novel Herbal Hydrogel Formulation of Moringa oleifera for Wound Healing. Plants 2021, 10, 25.

The journal retracts the article, "A Novel Herbal Hydrogel Formulation of Moringa oleifera for Wound Healing" [...].

Deoxynivalenol induces cell senescence in RAW264.7 macrophages via HIF-1α-mediated activation of the p53/p21 pathway.

Deoxynivalenol (DON), a potent mycotoxin, exhibits strong immunotoxicity and poses a significant threat to human and animal health. Cell senescence has been implicated in the immunomodulatory effects of DON; however, the potential of DON to induce cell senescence remains inadequately explored. Emerging evidence suggests that hypoxia-inducible factor-1α (HIF-1α) serves as a crucial target of mycotoxins and is closely involved in cell senescence. To investigate this potential, we employed the RAW264.7 macrophage model and treated the cells with varying concentrations of DON (2-8 µM) for 24 h. Transcriptome analysis revealed that 2365 genes were significantly upregulation while 2405 genes were significantly decreased after exposure to DON. KEGG pathway enrichment analysis demonstrated substantial enrichment in pathways associated with cellular senescence and hypoxia. Remarkably, we observed a rapid and sustained increase in HIF-1α expression following DON treatment. DON induced cell senescence through the activation of the p53/p21WAF1/CIP1 (p21) and p16INK4A (p16) pathways, while also upregulating the expression of nuclear factor-κB, leading to the secretion of senescence-associated secretory phenotype (SASP) factors, including IL-6, IL-8, and CCL2. Crucially, HIF-1α positively regulated the expression of p53, p21, and p16, as well as the secretion of SASP factors. Additionally, DON induced cell cycle arrest at the S phase, enhanced the activity of the senescence biomarker senescence-associated ß-galactosidase, and disrupted cell morphology, characterized by mitochondrial damage. Our study elucidates that DON induces cell senescence in RAW264.7 macrophages by modulating the HIF-1α/p53/p21 pathway. These findings provide valuable insights for the accurate prevention of DON-induced immunotoxicity and associated diseases.

Injectable nano-in situ-thermosensitive-hydrogels based on halofuginone and silver for postoperative treatment against triple-negative breast cancer.

Postoperative distant metastasis and high recurrence rate causes a dilemma in treating triple-negative breast cancer (TNBC) owing to its unforeseeable invasion into various organs or tissues. The wealth of nutrition provided by vascular may facilitate the proliferation and angiogenesis of cancer cells, which further enhance the rates of postoperative metastasis and recurrence. Chemotherapy, as a systemic postoperative adjuvant therapy, is generally applied to diminish recurrence and metastasis of TNBC. Herein, an halofuginone-silver nano thermosensitive hydrogel (HTPM&AgNPs-gel) was prepared via a physical swelling method. The in vitro anticancer efficacy of HTPM&AgNPs-gel was analyzed by investigating cell proliferation, migration, invasion, and angiogenesis capacity. Furthermore, the in vivo anti-cancer activity of HTPM&AgNPs-gel was further appraised through the tumor suppression, anti-metastatic, anti-angiogenic, and anti-inflammatory ability. The optimized HTPM&AgNPs-gel, a thermosensitive hydrogel, showed excellent properties, including syringeability, swelling behavior, and a sustained release effect without hemolysis. In addition, HTPM&AgNPs-gel was confirmed to effectively inhibit the proliferation, migration, invasion, and angiogenesis of MDA-MB-231 cells. An evaluation of the in vivo anti-tumor efficacy demonstrated that HTPM&AgNPs-gel showed a stronger tumor inhibition rate (68.17%) than did HTPM-gel or AgNPs-gel used alone and exhibited outstanding biocompatibility. Notably, HTPM&AgNPs-gel also inhibited lung metastasis induced by residual tumor tissue after surgery and further blocked angiogenesis-related inflammatory responses. Taken together, the suppression of inflammation by interdicting the blood vessels adjoining the tumor and inhibiting angiogenesis is a potential strategy to attenuate the recurrence and metastasis of TNBC. HTPM&AgNPs-gel is a promising anticancer agent for TNBC as a local postoperative treatment.

The mechanism of arbuscular mycorrhizal fungi-alleviated manganese toxicity in plants: A review.

The development of the mining industry and the overuse of inorganic fertilizers have led to an excess of manganese (Mn) in the soil, thereby, contaminating the soil environment and people's health. On heavy metal-contaminated soils, the combined arbuscular mycorrhizal fungi (AMF)-phytoremediation technique becomes a hotspot because of its environmentally friendly, in situ remediation. AMF inoculation often leads to a decrease in host Mn acquisition, which provides a basis for its application in phytoremediation of contaminated soils. Moreover, the utilization value of native AMF is greater than that of exotic AMF, because native AMF can adapt better to Mn-contaminated soils. In addition to the fact that AMF enhance plant Mn tolerance responses such as regionalization, organic matter chelation, limiting uptake and efflux, and so on, AMF also develop plant-independent fungal pathways such as direct biosorption of Mn by mycorrhizal hyphae, fungal Mn transporter genes, and sequestration of Mn by mycorrhizal hyphae, glomalin, and arbuscule-containing root cortical cells, which together mitigate excessive Mn toxicity to plants. Clarifying AMF-plant interactions under Mn stress will provide support for utilizing AMF as a phytoremediation in Mn-contaminated soils. The review reveals in detail how AMF develop its own mechanisms for responding to excess Mn and how AMF enhance plant Mn tolerance, accompanied by perspectives for future research.

The role of cellular senescence in neurodegenerative diseases.

Increasing evidence has revealed that cellular senescence drives NDs, including Alzheimer's disease (AD) and Parkinson's disease. Different senescent cell populations secrete senescence-associated secretory phenotypes (SASP), including matrix metalloproteinase-3, interleukin (IL)-1α, IL-6, and IL-8, which can harm adjacent microglia. Moreover, these cells possess high expression levels of senescence hallmarks (p16 and p21) and elevated senescence-associated ß-galactosidase activity in in vitro and in vivo ND models. These senescence phenotypes contribute to the deposition of ß-amyloid and tau-protein tangles. Selective clearance of senescent cells and SASP regulation by inhibiting p38/mitogen-activated protein kinase and nuclear factor kappa B signaling attenuate ß-amyloid load and prevent tau-protein tangle deposition, thereby improving cognitive performance in AD mouse models. In addition, telomere shortening, a cellular senescence biomarker, is associated with increased ND risks. Telomere dysfunction causes cellular senescence, stimulating IL-6, tumor necrosis factor-α, and IL-1ß secretions. The forced expression of telomerase activators prevents cellular senescence, yielding considerable neuroprotective effects. This review elucidates the mechanism of cellular senescence in ND pathogenesis, suggesting strategies to eliminate or restore senescent cells to a normal phenotype for treating such diseases.

Hepatoprotective effects of fruits pulp, seed, and peel against chemical-induced toxicity: Insights from in vivo studies.

The liver is a vital organ in human physiology positioned in the upper right quadrant of the peritoneal cavity, which plats a critical role in metabolic processes, detoxification of various substances and overall homeostasis. Along with these critical functions, hepatic diseases impose as significant global health threat. Liver illness is the cause of two million fatalities every year, or 4% of all deaths. Traditionally, healthcare providers have prescribed antibacterial and antiviral medications to address liver illness. Nephrotoxicity is a frequently observed negative reaction to drugs, with the majority of such events happening in individuals who have advanced cirrhosis. Thus, recognizing this gap, there is a dire need of exploration of pharmaceutical alterative for hepatic diseases, with special focus on their efficacy and reduced toxicity. Fruits have long been known to therapeutic impact on human health, thus exploration of fruits components namely pulp, seeds and peels containing phytochemicals have emerged as a promising avenue for hepatoprotective interventions. Thus, review comprehends the information about worldwide burden of chemical induced toxicity and injuries as well as highlight the on-going challenges in hepatic disease management. It also shed light on the valuable contributions fruit parts and their phytocompounds obtained from different components of fruits. Fruit pulp, especially when rich in flavonoids, has demonstrated significant potential in animal model studies. It has been observed to enhance the activity of antioxidant enzymes and reduce the expression of pro-inflammatory markers. The methanolic and ethanolic extracts have demonstrated the most favorable outcomes. Further, this review also discusses about the safety assessments of fruits extracts for their utilization as hepatoprotective agents.

AP-1 and SP1 trans-activate the expression of hepatic CYP1A1 and CYP2A6 in the bioactivation of AFB1 in chicken.

Dietary exposure to aflatoxin B1 (AFB1) is harmful to the health and performance of domestic animals. The hepatic cytochrome P450s (CYPs), CYP1A1 and CYP2A6, are the primary enzymes responsible for the bioactivation of AFB1 to the highly toxic exo-AFB1-8,9-epoxide (AFBO) in chicks. However, the transcriptional regulation mechanism of these CYP genes in the liver of chicks in AFB1 metabolism remains unknown. Dual-luciferase reporter assay, bioinformatics and site-directed mutation results indicated that specificity protein 1 (SP1) and activator protein-1 (AP-1) motifs were located in the core region -1,063/-948, -606/-541 of the CYP1A1 promoter as well as -636/-595, -503/-462, -147/-1 of the CYP2A6 promoter. Furthermore, overexpression and decoy oligodeoxynucleotide technologies demonstrated that SP1 and AP-1 were pivotal transcriptional activators regulating the promoter activity of CYP1A1 and CYP2A6. Moreover, bioactivation of AFB1 to AFBO could be increased by upregulation of CYP1A1 and CYP2A6 expression, which was trans-activated owing to the upregulalion of AP-1, rather than SP1, stimulated by AFB1-induced reactive oxygen species. Additionally, nano-selenium could reduce ROS, downregulate AP-1 expression and then decrease the expression of CYP1A1 and CYP2A6, thus alleviating the toxicity of AFB1. In conclusion, AP-1 and SP1 played important roles in the transactivation of CYP1A1 and CYP2A6 expression and further bioactivated AFB1 to AFBO in chicken liver, which could provide novel targets for the remediation of aflatoxicosis in chicks.