The journal retracts the article “Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Inhibitor as a Novel Therapeutic Tool for Lung Injury” [...]

The journal retracts the article titled “Aggravation of TGFβ1-Smad Pathway and Autoimmune Myocarditis by Fungicide (Tebuconazole) Exposure” [...]

Carnosine (CAR), an endogenous histidine-containing dipeptide, exhibits antioxidant and anti-inflammatory activity in various experimental models; however, its molecular mechanism of action remains poorly understood. Here, we demonstrate that the Michael adduct between CAR and 4-hydroxy-2-nonenal (HNE), which has been detected in previous studies in both in vitro and in vivo settings, mediates its bioactivity, particularly its antioxidant and anti-inflammatory responses, through Nrf2 activation. The CAR-HNE adduct was synthesized and its physicochemical, metabolic, and biological properties were evaluated. CAR-HNE exhibited high stability in biological matrices and retained the ability to transfer HNE to thiol nucleophiles at a slow rate under physiologically relevant conditions, consistent with electrophile-mediated Nrf2 activation. This kinetic behavior limits the cytotoxicity typically associated with free HNE while preserving the redox signaling capacity. CAR-HNE induced dose-dependent Nrf2 activation and NF-κB inhibition in cell-based assays without the hormetic toxicity observed for free HNE. Mechanistically, CAR-HNE may act as a redox-tunable electrophilic reservoir, restoring nucleophilic tone and modulating redox-sensitive transcription factors. In vivo, CAR-HNE attenuated DSS-induced colitis more effectively than equimolar doses of either carnosine or HNE alone. Proteomic analyses revealed modulation of canonical Nrf2-dependent antioxidant pathways. Our findings suggest a conceptual shift in carnosine biology: rather than acting as a classical antioxidant or carbonyl quencher, carnosine functions as a precursor of redox-active electrophilic adducts that transduce anti-inflammatory and antioxidant responses via controlled RCS signaling.

Ulcerative colitis (UC) is a multifactorial inflammatory bowel disease (IBD) with increasing incidence worldwide. Current treatments, including NSAIDs and corticosteroids, provide partial symptom relief but are associated with significant side effects, highlighting the need for novel therapies with improved safety profiles. Given the role of oxidative stress and inflammation in driving tissue damage during colitis, natural compounds with antioxidant and anti-inflammatory properties represent promising therapeutic candidates. Thinned apples (TA), an agricultural byproduct, were identified as a valuable source of polyphenols (TAP) with demonstrated anti-inflammatory and antioxidant activities in a cell-based inflammation model. This study evaluates TAP's therapeutic potential in a DNBS-induced colitis mouse model using label-free quantitative proteomics. Proteomic analysis revealed modulation of key pathways affected by TAP treatment, including: (i) activation of antioxidant defense mechanisms; (ii) reversal of DNBS-induced alterations, specifically ferroptosis and heme-toxicity; (iii) suppression of immune responses; and (iv) attenuation of ulcerative features, with downregulation of proteins involved in coagulation, inflammation, and angiogenesis. Overall, TAP showed significant therapeutic effects by targeting oxidative stress and inflammation, supporting its use as a polyphenol-rich extract in health products for UC. Moreover, repurposing TA as a bioactive extract offers an innovative strategy for industrial applications in therapeutic development.

Hyperhomocysteinemia (HHcy), a metabolic disorder that causes a higher risk of neurovascular disease, is brought on by elevated blood levels of Hcy. Increased production of ROS and neuroinflammation, which result in neuronal damage and ultimately neuronal death, are known consequences of HHcy. The oxidative effect could be neutralized through the consumption of products rich in polyphenols, such as cashew nuts. Therefore, the objective of the study was to investigate the beneficial effect of cashews in an experimental condition of HHcy. HHcy was induced in rats by oral methionine (Meth) administration for 30 days, and cashew nuts at the dose of 100 mg/kg were administered by oral gavage for 30 consecutive days. Our results showed that Meth administration induced oxidative stress, astrocytes, and microglia activation, and neuronal cell death. Daily consumption of cashew nuts was able to counteract oxidative stress by the modulation of the antioxidant NRF-2 pathway and consequent reduction of lipid peroxidation and upregulation of antioxidant enzyme levels, such as GSH and HO-1. At the same way, Cashew nuts reduced neuroinflammatory markers and apoptotic process, as demonstrated by TUNEL assay and Bax and Bcl-2 levels. Thus, the results suggested that the balanced consumption of cashew nuts could have a positive action in the prevention of HHcy-induced disorders.

ABSTRACT Acute and chronic lung injuries are characterized by a large amount of ROS, pro‐inflammatory leukocytes and ferroptosis, resulting in alveolar injury. Nowadays, there is great interest in the bioactive compounds obtained from the waste products deriving from agriculture and the food industry. Thinned young apples are particularly rich in polyphenols, more than 10‐fold with respect to harvested apples, and have antioxidant and anti‐inflammatory activities. Therefore, the aim of this study is to investigate whether modulation of ferroptosis biomarkers by thinned apple polyphenols (TAP) extract was able to reduce lung injuries in two experimental model: acute lung injury (ALI) and bleomycin‐induced idiopathic pulmonary fibrosis (IPF). Our results demonstrated that TAP extract was able to inhibit the ferroptosis, modulating the main biomarkers: malondialdehyde, NADPH oxidase‐4, glutathione peroxidase 4 and ferritin heavy chain 1. This modulation is probably due to Nrf2 activation, negative regulator of ferroptosis, by TAP extract and consequently activating the production of antioxidant enzymes. This induced histological alteration, cytokines release and fibrosis in the alveoli and lung parenchyma. Collectively, these results demonstrated that TAP extract was able to reduce ferroptosis in acute and chronic lung injury models, suggesting it as a potential biomarker for early diagnosis and intervention timely.

Progressive degeneration of the nervous system is a hallmark of neurological diseases. Recent research highlights gut microbiota metabolites like Trimethylamine N-oxide (TMAO)-derived from dietary betaine, carnitine, phosphatidylcholine, and choline-as key players. TMAO and its precursor TMA cross the blood-brain barrier, modulating behavior, neurogenesis, and brain development. Elevated TMAO promotes pro-inflammatory pathways, linking it to metabolic, vascular, and neurological risks. However, its role is complex with studies suggesting neuroprotective roles and variability influenced by diet, dysbiosis, renal function, and FMO3 genetics. Although preclinical and clinical data exhibit some variability, this very heterogeneity underscores our review's value in analyzing both the challenges and strengths of TMAO, providing a comprehensive overview. Therefore, this review summarizes the multifaceted role of TMAO in neurological disorders, the challenges to validation, and its promising potential as a dynamic biomarker. In conclusion, incorporating TMAO into multimarker panels places it at the forefront of precision neurology, transforming gut-brain axis research into tools for early screening, risk stratification, and intervention, before irreversible neurodegeneration.

The journal retracts the article titled "Ultramicronized Palmitoylethanolamide and Paracetamol, a New Association to Relieve Hyperalgesia and Pain in a Sciatic Nerve Injury Model in Rat" [...].

The journal retracts the article titled “Role of Etanercept and Infliximab on Nociceptive Changes Induced by the Experimental Model of Fibromyalgia” [...]

In the original publication [...].

The journal retracts the article “Environmental risk assessment of mixture of COVID-19 treating pharmaceutical drugs in zebrafish early life stage (Danio rerio)” [...]

In the original publication [...].

SCOPE:Valproic acid (VPA) postnatal exposure in mice results in behavioral impairment, aberrant sensitivity to sensory stimuli, and self-harming behavior, hallmarks of autism. According to previous reports, Coriolus versicolor (CV) has a protective effect on the brain. The goal of the current investigation was to assess how CV affected the neurobehavioral and metabolic changes caused by VPA in mice. METHODS AND RESULTS:Mice pups were injected with VPA at 14 days of age and orally administered CV at a dose of 200 mg/kg daily from 14 to 40 days of age. Mice pups were placed through behavioral tests during the trial to evaluate motor skill growth, nociceptive response, locomotion, anxiety, and cognition. Following behavioral testing, mice were killed, and the brain was removed and subjected to biochemical analyses (glutathione, malondialdehyde, and nitric oxide) and histopathological analysis. Additionally, to further investigate the role of the TLR-4/Myd88/NF-κB signaling pathway, we examined the modulation of this pathway and the alteration in gamma-amino butyric acid (GABA) production using Western blot analysis. CONCLUSION:According to our research, CV daily administration greatly reduced behavioral alteration, reversed the disorganization of the cerebellum and hippocampus, and significantly improved the VPA-induced neuroinflammation via the TLR-4/Myd88/NF-κB signaling cascade.

The journal retracts the article, “Formyl Peptide Receptor 1 Signaling in Acute Inflammation and Neural Differentiation Induced by Traumatic Brain Injury” [...]

Fibromyalgia (FM) is a disorder characterized by chronic widespread musculoskeletal pain, and it is often accompanied by fatigue, sleep disturbance, and cognitive dysfunction. Although pathophysiology is multifactorial, increasing evidence highlights the pivotal role of oxidative stress and mitochondrial dysfunction in the development of this condition. In particular, the Nrf2/HO-1/NQO1 antioxidant axis plays a crucial role in counteracting oxidative damage and maintaining cellular homeostasis. Boswellia (BS) is a genus of plants in the Burseraceae family, which includes around twenty species found across sub-Saharan Africa, the Arabian Peninsula, and the Indian subcontinent. In Ayurvedic medicine, it has traditionally been used in the treatment of diabetes, fever, as well as certain cardiovascular, dermatological, and neurological conditions. Boswellic acids are thought to possess anti-inflammatory, anti-rheumatic, and pain-relieving properties. The purpose of this study was to investigate the beneficial effects of BS extract in a murine model of reserpine-induced FM. Following reserpine administration, markers of oxidative stress, neuroinflammation, and behavioral changes including mechanical allodynia, hyperalgesia, anxiety, and depression-like behaviors were significantly increased. Daily oral administration of BS at a dose of 100 mg/kg effectively restored these pathological changes. BS oral supplementation, by preventing microglia and astrocyte activation, as demonstrated by decreased GFAP and Iba-1 expression, BS decreased neurological inflammation and restored neurotransmitter levels such as norepinephrine, dopamine and serotonin. Futhermore, improved antioxidant defenses by increasing nuclear translocation of Nrf2 and subsequent expression of its downstream targets, HO-1 and NQO1, limiting lipid peroxidation and ROS production. According to behavioral tests, BS significantly reduced the emotional deficit and mechanical sensitivity linked to FM. Our findings indicate that BS integration has neuroprotective effects, acting on oxidative stress and neuroinflammation, and suggesting that it is a viable natural strategy for managing FM symptoms.

In the original publication [...].

Background/Objectives Obesity is a major public health concern, significantly elevating the risk of developing comorbid conditions such as type 2 diabetes mellitus and cardio-vascular diseases, while also shortening life expectancy. Currently, metabolic and bariatric surgery (MBS) is one of the most effective long-term interventions for achieving substantial weight loss, alongside notable improvements in overall quality of life. However, evidence suggests that these procedures may negatively affect bone health, leading to an increased risk of fractures. This systematic review and meta-analysis aim to assess the role of Osteopontin (OPN) as a potential biomarker for predicting both persistent inflammation and bone deterioration following MBS. Methods A comprehensive search of scientific databases including PubMed (MEDLINE), Embase (OVID), and Web of Science, covering literature up to January 31, 2024, identified 6 studies that met the inclusion criteria for the systematic review. For the meta-analysis, data from 5 studies measuring circulating OPN levels pre- and post-surgery were pooled. Results The combined analysis revealed a significant increase in OPN levels after MBS compared to baseline (OR: 24.56; 95 % CI: 13.30–35.81; p < 0.0001). Conclusions These findings suggest that OPN may serve as a valuable biomarker for monitoring inflammation and assessing the risk of bone-related complications in patients following MBS.

Post-harvest storage of natural almonds is a critical step, as it can cause the onset of microbial contamination and modify polyphenolic composition of almond skin, potentially altering the antioxidant capacity and overall, the health effects of the native product. This study aims to evaluate the impact of different post-harvest storage conditions on the microbiological stability, polyphenolic profile, and antioxidant activity of natural almonds (Prunus dulcis cv. "Fascionello"). Natural almonds were obtained from Consorzio Mandorla di Avola and stored under three conditions: light exposure at room temperature (RT), dark at RT, and dark at 4°C, monitoring temperature and relative humidity. Samples were analyzed at four time points (T0, T3, T6, and T9 months). Microbiological stability was assessed using standard plate-counting techniques; polyphenolic content was determined through spectrophotometric assays and RP-LC-DAD-ESI-MS/MS analysis, whereas the antioxidant activity was evaluated using different spectrophotometric and spectrofluorimetric assays including DPPH, TEAC, FRAP, and ORAC assays. Chemometric analyses were performed to compare polyphenolic changes across different storage conditions over time. Temperature remained stable with moderate variations, indicating a well-controlled environment, while humidity exhibits significant fluctuations, likely influenced by external factors. No significant microbial contamination was detected throughout storage, confirming the microbiological safety of natural almonds. The polyphenolic content significantly decreased within the first 3 months, particularly under dark conditions at RT. However, a recovery phase was observed at 6 months, with cold-stored almonds retaining the highest levels of total polyphenols and flavonoids. The antioxidant activity of almond skin extracts correlated with polyphenolic content, showing an initial decline followed by stabilization under refrigerated storage. Hierarchical clustering analyses highlighted distinct polyphenolic expression patterns based on storage conditions and time points. Post-harvest storage conditions significantly impact the polyphenolic profile and antioxidant properties of natural almonds. For short-term storage (≤6 months), RT with controlled light exposure is sufficient to preserve polyphenols, whereas cold and dark conditions are recommended to maintain bioactive compound stability and antioxidant potential for long-term storage (>6 months). These findings provide valuable insights for optimizing storage strategies in the food, nutraceutical, and pharmaceutical industries.

Background/Objectives: Traumatic brain injury (TBI) disrupts both the intestinal epithelium and blood-brain barrier (BBB), contributing to oxidative stress, neuroinflammation, and behavioral impairments. Vitis vinifera leaf (VVL) extract possesses antioxidant and anti-inflammatory properties, but its protective effects on the brain-gut axis following TBI remain unclear. This study aimed to evaluate whether VVL supplementation preserves barrier integrity and improves neurobehavioral outcomes after TBI. Methods: A murine model of TBI was used, with animals receiving daily oral supplementation of the VVL extract. Neurobehavioral performance was assessed through behavioral testing, while histopathological examinations, biochemical assays, and gene expression profiling were performed to evaluate neuronal and intestinal integrity, antioxidant defense, and inflammatory responses. Results: VVL supplementation significantly alleviated anxiety- and depression-like behaviors and preserved the structural integrity of neuronal and intestinal tissues. Antioxidant defense mechanisms were strengthened, as shown by increased catalase and superoxide dismutase activities, together with upregulation of Nrf2 and HO-1 expression. Tight junction proteins, including ZO-1 and occludin, were upregulated in both brain and gut tissues, reflecting improved barrier integrity. Furthermore, VVL markedly reduced pro-inflammatory cytokine expression. Conclusions: VVL extract confers dual protection of the gut and brain barriers after TBI by enhancing endogenous antioxidant defenses, maintaining tight junction integrity, and suppressing inflammation. These findings suggest that VVL may represent a natural therapeutic strategy to mitigate oxidative stress, neuroinflammation, and behavioral dysfunctions associated with TBI.