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Perfluorinated and polyfluorinated alkyl substances (PFAS), more than 4700 in number, are a group of widely used man-made chemicals that accumulate in living things and the environment over time. They are known as "forever chemicals" because they are extremely persistent in our environment and body. Because PFAS have been widely used for many decades, their presence is evident globally, and their persistence and potential toxicity create concern for animals, humans and environmental health. They can have multiple adverse health effects, such as liver damage, thyroid disease, obesity, fertility problems, and cancer. The most significant source of living exposure to PFAS is dietary intake (food and water), but given massive industrial and domestic use, these substances are now punctually present not only domestically but also in the outdoor environment. For example, livestock and wildlife can be exposed to PFAS through contaminated water, soil, substrate, air, or food. In this review, we have analyzed and exposed the characteristics of PFAS and their various uses and reported data on their presence in the environment, from industrialized to less populated areas. In several areas of the planet, even in areas far from large population centers, the presence of PFAS was confirmed, both in marine and terrestrial animals (organisms). Among the most common PFAS identified are undoubtedly perfluorooctanesulfonate (PFOS) and perfluorooctanoic acid (PFOA), two of the most widely used and, to date, among the most studied in terms of toxicokinetics and toxicodynamics. The objective of this review is to provide insights into the toxic potential of PFAS, their exposure, and related mechanisms. [ABSTRACT FROM AUTHOR]

Simple Summary: Simultaneous exposure to several contaminants can create a cross-linkage that leads to increased fish toxicity. Cadmium (Cd), one of the most common metals detected in the environment, can cause concentration-dependent damage in developing fish. Co-exposure of Cd and other contaminants, such as the pesticide imidacloprid (IMI), can cause developmental damage in zebrafish, particularly to eye cells. In fact, co-exposure to concentrations that are in themselves non-toxic can cause morphological damage accompanied by a sharp increase in apoptosis and cell death in retinal cells, with disruption of the antioxidant mechanism. In the present study, we analyzed the combination of non-toxic concentrations per se, of Cd and a pesticide the imidacloprid (IMI) (10 and 50 μM for Cd and 195 μM for IMI), to highlight early developmental toxicity and possible damage to retinal cells. Co-exposure to Cd and IMI showed a toxic effect in zebrafish larval development, with lowered degrees of survival and hatching, and in some cases the induction of structural alterations and edema. In addition, co-exposure to 50 and 195 μM, respectively, for Cd and IMI, also showed increased apoptosis in eye cells, accompanied by up regulation of genes associated with antioxidant markers (cat, sod1, nrf2 and ho-1). Thus, the present study aims to highlight how the presence of multiple contaminants, even at low concentrations, can be a risk factor in a model of zebrafish (Danio rerio). The presence of other contaminants, such as IMI, can cause an enhancement of the toxic action of Cd on morphological changes in the early life stage of zebrafish, but more importantly disrupt the normal development of the retina, eventually triggering apoptosis. [ABSTRACT FROM AUTHOR]

Endocrine disruptors (EDs) are chemical substances capable of affecting endocrine system functioning and interfering with organ morphogenesis and physiological functions. The development and regeneration of bone tissues have a complex hormonal regulation, and therefore, bone tissue cells can be considered potential targets for endocrine disruptors. In that regard, the aim of this research was to investigate the impact of ED exposure on the inflammatory response and oxidative stress in an experimental model of collagen-induced arthritis (CIA). Arthritis was induced by an emulsion of type II collagen (CII) and complete Freund's adjuvant, which was administered intradermally on days 0 and 21. Mice from day 21 to day 35 received the following EDs by oral gavage: cypermethrin (CP), diethyl phthalate (DEP), vinclozolin (VCZ), 17α-ethinylestradiol (EE), perfluorooctanesulfonic acid (PFOS) and atrazine (ATR). ED exposure caused worsening of clinical signs (erythema and edema in the hind paws), histological and radiographic changes, as well as behavioral deficits, induced by CII injections. Furthermore, ED exposure significantly increased the degree of inflammation and oxidative damage induced by arthritis; this upregulation was more evident after exposure to ATR than to other EDs. The results from our study suggest that exposure to EDs may play a deleterious role in the progression of RA; therefore, exposure to EDs should be limited. [ABSTRACT FROM AUTHOR]

Gastric ulcer or peptic ulcer is a common disease worldwide. Basically, it develops when there is an imbalance between the protective and aggressive factors, especially at the luminal surface of epithelial cells. Thus, there is a constant interest in research new drugs for treatment of gastric ulcer. The snail secretion is a dense mucous, that covers the external surface of the snails, with important functions for the survival of snails. The biological proprieties of snail Helix Aspersa Muller mucus it has been known for centuries to treat human disorders in particular for skin disease. Recently the use of snail mucus has seen a worldwide increase, as a component in cosmetic product and it has been used in particular for the management of wound and skin disorders. In this study we use a murine model of ethanol intragastric administration which has been widely used to test the drugs efficacies and to explore the underlying mechanism for gastric ulcer development. The intragastric ethanol administration causes several mucosal damages and an induction of a severe inflammatory response. Our results show a significant protective effect of snail secretion filtrate in reducing macroscopic and histological lesions, as well the protective effect on mucus content, oxidative stress and inflammatory response. In conclusion this study demonstrate the protective effect of intragastrical snail secretion filtrate, in a model of ethanol-induced gastric ulcer in mice, suggesting its possible useful use in the treatment or prevention of gastric ulcer. [ABSTRACT FROM AUTHOR]

Background: Luteolin has been demonstrated to possess numerous biological effects. However, the effect of luteolin on LPS (Lipopolysaccharides) stimulation in CPEK cells has not been investigated. Hypothesis/Objectives: An in vitro model of atopic canine dermatitis was used to identify the antioxidant effect of luteolin as a new treatment that is capable of improving the conditions of veterinary patients. Methods: CPEK cells were treated with or without luteolin in the presence or absence of LPS. A cell viability assay was performed to test luteolin toxicity and the protective effect of luteolin after LPS stimulation. Additionally, enzyme‐linked immunosorbent assay (ELISA) kits were used to detect the levels of IL‐33, IL‐1β, IL‐6, and IL‐8. Results: Luteolin was capable to significantly decrease levels expression of IL‐33, IL 1β, IL‐6, and IL‐8. Conclusions and clinical importance: Luteolin could be a new pharmacological treatment for canine atopic dermatitis. [ABSTRACT FROM AUTHOR]

Background: Leishmaniasis is a emergent disease characterized by different clinical manifestations in both humans and dogs. Predominant clinical features of cutaneous leishmaniasis are ulcerative painless skin lesions. Several data reported that pain is associated with human and dog leishmaniasis, out with areas of painless ulcerative lesions per se. Actually, current medications used for leishmaniasis management are characterized by several side effects and, in addition, some cases of the disease are refractory to the treatment. On this background it is mandatory the identification of new and safe candidates for designing less toxic and low-cost remedies. Therefore, the search for new leishmanicidal compounds is indispensable. Methods: In the present paper we investigated the effect of orally N-acetyl-L-cysteine (NAC) supplementation at dose of 200 mg/Kg for 10 weeks, in subcutaneous Leishmania (L). amazonensis infected BALB/c mice. And evaluating the effect of NAC on inflammatory response such as TNF-α, IL-6, IL-1β levels, and on thermal and mechanical hyperalgesia. Results: In the present paper we showed how NAC supplementation affected parameters of oxidative stress (GSH, MDA, SOD), inflammation such as cytokines levels (IL-1β, IL-6, TNFα) and mast cell activation and consequently on induced pain, during leishmaniosis in BALB\c mice. Conclusions: The findings of our study provided the scientific data demonstrating that L. amazonensis infection induces inflammation and pain in BALB/c mice that are reversed by administration of NAC. [ABSTRACT FROM AUTHOR]

Periodontal disease is the most common cause of tooth loss in humans, is an inflammatory disease initiated by oral microbial biofilm. Given the involvement of the inflammatory pathway in this type of pathology, the main pharmacological strategy for the treatment of periodontitis, is the inhibition of the inflammatory process in order to prevent tissue destruction and bone resorption, a condition associated with a painful state. To do this, the best class of drugs are Non-steroidal anti-inflammatory drugs (NSAIDs), however, the presence of side effects, especially at the gastrointestinal tract, limits their use for long-term therapy. Recently, some evidence shows that derivatives of NSAIDs capable of releasing hydrogen sulphide exhibit lower collateral effects, particularly at the gastric level. In fact, H2S is an endogenous gaseous mediator with a cytoprotective role at the gastric level. In this study, we have compared the protective effects of ketoprofen with ATB-352, a hydrogen sulfide-releasing derivative of ketoprofen, in an experimental model of periodontitis in rat. Periodontitis was induced by a single intragingival injection of 1 μl LPS (10 μg/μl), Our results show that 14 h after intragingival injection of LPS, there was a high tissue damage associated with bone resorption, and in gingivomucosal tissues there was a significant expression of NF-kb p65 and pro-inflammatory cytokine as well as a higher expression of COX-2 and iNOS, activation of the apoptotic process, and also increased levels of NGF expression, often associated with a higher nociceptive perception. Treatment with ATB-352 at the dose of 20mg\kg, was able to reduce the inflammatory process associated with intragingival LPS injection and also had a positive effect on bone resorption and tissue damage. [ABSTRACT FROM AUTHOR]

Pulmonary arterial hypertension (PAH) is a chronic, progressive disease characterized by an increase in blood pressure in the lungs' arteries. It can occur in a variety of species, including humans, dogs, cats, and horses. To date, PAH has a high mortality rate in both veterinary and human medicine, often due to complications such as heart failure. The complex pathological mechanisms of PAH involve multiple cellular signalling pathways at various levels. IL-6 is a powerful pleiotropic cytokine that regulates several phases of immune response, inflammation, and tissue remodelling. The hypothesis of this study was that the use of an IL-6 antagonist in PAH could interrupt or mitigate the cascade of events that leads to the progression of the disease and the worsening of clinical outcome, as well as tissue remodelling. In this study, we used two pharmacological protocols with an IL-6 receptor antagonist in a monocrotaline-induced PAH model in rats. Our results showed that the use of an IL-6 receptor antagonist had a significant protective effect, ameliorating both haemodynamic parameters, lung and cardiac function, tissue remodelling, and the inflammation associated with PAH. The results of this study suggest that the inhibition IL-6 could be a useful pharmacological strategy in PAH, in both human and veterinary medicine. [Display omitted] [ABSTRACT FROM AUTHOR]

Acute and chronic inflammation responses are important risk factors for vascular remodeling processes such as in atherosclerosis, arteriosclerosis and restenosis. Inflammation and oxidative stress in the intimal region after vascular damage are a key event in the development of neointimal hyperplasia. In this study, we used this model of vascular damage, which involves the complete ligature of the left carotid artery for 14 days, to observe the role of N-palmitoylethanolamine in combination with Polydatin at the dose of 30 mg/kg, on regulation of inflammatory process, and oxidative stress. Palmitoylethanolamide (PEA), an endogenous fatty acid amide belonging to the N-acylethanolamine family, has anti-inflammatory and neuroprotective effects. However, PEA lacks direct capacity to prevent formation of free radicals. Polydatin (PLD) that is a natural precursor of resveratrol has antioxidant activity. Thus, the combination of PEA and PLD could have beneficial effects on inflammatory process and oxidative stress. This model shows that 14 days after carotid artery ligation there is a significant structural change within the vessel, and that there is an important involvement of the inflammatory pathway in the progression of this disease. In this study we demonstrated that PEA/PLD combination treatment reduces vessel damage, adhesion molecules expression such as intercellular adhesion molecules-1(ICAM-1) and vascular cell adhesion molecules-1(V-CAM), proinflammatory cytokines production (Tumor Necrosis Factor alpha (TNF-α) and Interleukin 1 beta (IL-1β), the inducible nitric oxide synthase (iNOS) and Poly (ADP-ribose) polymerase (PAR), formation, Nuclear factor kappa-B expression and apoptosis (BAX, Fas-Ligand) activation. Our results clearly demonstrated that treatment with PEA/PLD 30 mg/Kg is able to reduce vascular damage and attenuates the inflammatory process. [ABSTRACT FROM AUTHOR]

The inflammasome NLRP3 is a molecular pathway activated by a wide range of cellular insults to elicit innate immune defenses through the activation of caspase-1 and the maturation of proinflammatory cytokines, such as IL-1β and IL-18. The expression of NRLP3 is abnormally elevated in numerous human inflammatory diseases, including pulmonary diseases. An injection of carrageenan (CAR) into the pleural cavity triggered an acute inflammatory response, leading to tissue damage, inflammatory exudates, leukocyte infiltration, and increased myeloperoxidase activity. The aim of this study was to assess the effect of the inflammasome blocking agents BAY 11-7082 (30 mg/kg, i.p.) and Brilliant Blue G (BBG) (45.5 mg/kg, i.p.) in a mouse model of CAR-induced pleurisy. Treatment with BAY 11-7082 or BBG 1 h after CAR injection attenuated pulmonary membrane thickening and polymorphonuclear leukocyte infiltration, reduced NF-κB translocation in the nucleus, and inhibited the assembly of the NRLP3/ASC/caspase-1 complex. Treatment with BAY 11-7082 or BBG also down-regulated iNOS, nitrotyrosine, and poly-ADP-ribosyl polymerase expression and inhibited CAR-induced apoptosis. Our results demonstrate that treatment with inflammasome-blocking agents can significantly reduce the development of acute CAR-induced lung injury. [ABSTRACT FROM AUTHOR]

Complex regional pain syndrome type 1 (CRPS-I) is a disabling and frequently chronic condition. It involves the extremities and is a frequent consequence of distal tibia and radius fractures. The inflamed appearance of the affected CRPS-I limb suggests that local production of inflammatory mediators may be implicated in the ensuing etiology. A rodent tibia fracture model, characterized by inflammation, chronic unilateral hindlimb warmth, edema, protein extravasation, allodynia and hyperalgesia resembles the clinical features of patients with acute CRPS-I. N-palmitoylethanolamine (PEA), a member of the family of naturallyoccurring N-acylethanolamines, is well-known for its ability to modulate inflammatory processes and regulate pain sensitivity. However, the large particle size and lipidic nature of PEA may limit its bioavailability and solubility when given orally. Micronized formulations are frequently used to enhance the dissolution rate of drug and reduce its variability of absorption when orally administered. The aim of this study was to assess the effects of a formulation of micronized and ultramicronized PEA (PEA-MPS), given orally in a mouse model of CRPS-I. CD-1 male mice were subjected to distal tibia fracture and divided into two groups: control and treated with PEA-MPS (PEA micronized 300 mg/kg and ultramicronized 600 mg/kg). Sensibility to pain was monitored in all mice throughout the course of the experiment. Twenty-eight days after tibia fracture induction animals were sacrificed and biochemical parameters evaluated. The PEA-MPS-treated group showed an improved healing process, fracture recovery and fibrosis score. PEA-MPS administration decreased mast cell density, nerve growth factor, matrix metalloproteinase 9 and cytokine expression. This treatment also reduced (poly-ADP)ribose polymerase activation, peroxynitrite formation and apoptosis. Our results suggest that PEA-MPS may be a new therapeutic strategy in the treatment of CRPS-I. [ABSTRACT FROM AUTHOR]

The article titled "RETRACTED: Di Paola et al. Assessment of 2-Pentadecyl-2-oxazoline Role on Lipopolysaccharide-Induced Inflammation on Early Stage Development of Zebrafish (Danio rerio)" has been retracted by the journal Life. The retraction was due to concerns regarding the misuse and re-use of Figure 1A in the article. The Editorial Office and Editorial Board decided to retract the article in accordance with MDPI's retraction policy and the Committee on Publication Ethics retraction guidelines. The authors did not agree with the retraction. [Extracted from the article]

R3433 --> The snail secretion is a dense mucous, that covers the external surface of the snails, with important functions for the survival of snails. The biological proprieties of snail Helix aspersa muller mucus it has been known for centuries to treat human disorders in particular for skin disease. Recently the use of snail mucus has seen a worldwide increase, as a component in cosmetic product and it has been used in particular for the management of wound and skin disorders. In this study we use a murine model of excisional wound repair, which has been widely used to test the drugs efficacies. Our results show a significant protective effect of snail secretion filtrate in reducing macroscopic and histological lesions, as well the protective effect on oxidative stress and inflammatory response. In conclusion this study demonstrate the protective effect of snail secretion filtrate, suggesting its possible useful use in the treatment or skin diseases. [ABSTRACT FROM AUTHOR]

Simple Summary: Natural compounds are often an important source of biologically active molecules, which can find important applications in the treatment or pharmacological prevention of several pathologies. Silibinin is a natural polyphenolic flavonoid that is extracted from plant milk thistle, Silybum marianum. Silibinin has been reported to have antioxidant and immunomodulatory and anti-inflammatory activities. In horses, in particular, inflammation secondary to bacterial infection or translocation is one of the most frequent causes of morbidity and mortality. The aim of this study was to test the effect of silibinin on lipopolysaccharide (LPS)-induced inflammatory response in equine peripheral blood mononuclear cells (PBMCs). Taken together, our results showed an interesting prospective in therapeutic use of silibinin in equine inflammatory disease. Furthermore, the results from this study support the evidence of use equine PBMCs as an in vitro model to study inflammatory and immune response and for drug screening into the target specie. Although inflammation is an important physiological response, it plays a prominent role in several diseases across the mammalian species. In horses, in particular, inflammation secondary to bacterial infection or translocation is one of the most frequent causes of morbidity and mortality. Research in new molecules with anti-inflammatory and immunomodulatory proprieties and safe use profile is constantly an active field; natural compounds are an important source of molecules with peculiar properties such as antioxidants, anti-inflammatory and immune modulating. Silibinin, a natural polyphenolic flavonoid, extracted from plant milk thistle, Silybum marianum, has been reported to have actions such as antioxidant immunomodulatory and anti-inflammatory. The aim of this study was to test the effect of silibinin on lipopolysaccharide (LPS)-induced inflammatory response in equine peripheral blood mononuclear cells (PBMCs). Our results showed the protective effect of silibinin 10 μM and 50 μM in equine PBMCs stimulated with LPS. Silibilinin was able to prevent the LPS induced increased levels of TNF-α, IL-1β, IL-6 and IL-8. The results from this study on LPS-stimulated equine PBMCs showed that silibinin could be a useful pharmacological approach in treatment or prevention of several inflammatory conditions in horse. [ABSTRACT FROM AUTHOR]

Simple Summary: The objective of this study was to evaluate the levels and potential bioaccumulation of vanadium (V), chromium (Cr), cobalt (Co), copper (Cu), zinc (Zn), cadmium (Cd), lead (Pb), and bismuth (Bi) in horses from the industrial risk area of Sicily (Italy). Different biological substrates (whole blood, serum, tail, and mane) and samples of hay, concentrate, and water were analyzed. Pearson's test was applied to evaluate the correlation of mineral concentrations between whole blood and serum, and between tail and mane. The results showed statistical differences in tested mineral elements among the biological substrates. Minerals had a non-homogenous distribution in the organism, showing different concentrations in the biological substrates. The objective of this study was to evaluate the levels and the potential bioaccumulation of vanadium (V), chromium (Cr), cobalt (Co), copper (Cu), zinc (Zn), cadmium (Cd), lead (Pb), and bismuth (Bi) in horses from the industrial risk area of Sicily (Italy). Different biological substrates (whole blood, serum; tail and mane) and samples of hay, concentrate and water provided to the horses were processed by means of Thermo Scientific iCAP-Q ICP–MS spectrometer for mineral concentration. One-way analysis of variance (ANOVA) was applied to show the differences in various trace elements in the biological substrates. Pearson's test was applied to evaluate the correlation of mineral concentrations between whole blood and serum; and tail and mane. The results showed statistical differences of tested mineral elements among biological substrates; Cr whole blood concentrations were negatively correlated with serum concentrations and a positive correlation between whole blood and serum was observed for Cd and Bi. This latter also showed a positive correlation between mane and tail. The concentrations of V, Cr, and Pb in tail with serum and whole blood samples were negatively correlated, while the concentrations of Cd in tail and serum samples were positively correlated. Minerals had a non-homogenous distribution in the organism, showing different concentrations in the biological substrates. [ABSTRACT FROM AUTHOR]

Simple Summary: Canine osteoarthritis is a chronic degenerative joint disease and a major cause of elective euthanasia. The disorder increasingly limits joint motion, might cause lameness as well as pain, and impacts quality of life. An unmet need remains for safe and effective therapies for osteoarthritis. Palmitoyl-glucosamine and curcumin are used in animal nutrition. A co-micronized formulation, with the two substances being jointly processed to reduce their particle size and increase the extent to which they can be absorbed, is currently available on the European market. The present study investigated if this formulation could relieve joint pain and benefit mobility. Two well-established rat models of inflammation and osteoarthritis pain were used. Results from the first set of experiments showed that the dietary supplement relieved experimentally induced paw edema, infiltration of inflammatory cells, and decreased sensitivity to painful stimuli (thermal hyperalgesia). In the osteoarthritis model, the supplement proved to protect joint cartilage against degradation and successfully address neuropathic pain (i.e., pain from normally non-painful stimuli). Locomotor function recovered by 45% under supplement administration. The present findings suggest that the dietary supplement with palmitoyl-glucosamine co-micronized with curcumin might help manage osteoarthritis. Chronic mixed pain and orthopedic dysfunction are the most frequently associated consequences of canine osteoarthritis (OA). An unmet need remains for safe and effective therapies for OA. Palmitoyl-glucosamine (PGA) and curcumin are safe and naturally occurring compounds whose use is limited by poor bioavailability. Micronization is an established technique to increase bioavailability. The aim of this study was to investigate if the dietary supplementation with PGA co-micronized with curcumin (PGA-Cur, 2:1 ratio by mass) could limit pathologic process in two well-established rat models of inflammation and OA pain, i.e., subplantar carrageenan (CAR) and knee injection of sodium monoiodoacetate (MIA), respectively. In CAR-injected animals, a single dose of PGA-cur significantly reduced paw edema and hyperalgesia, as well as tissue damage and neutrophil infiltration. The repeated administration of PGA-Cur three times per week for 21 days, starting the third day after MIA injection resulted in a significant anti-allodynic effect. Protection against cartilage damage and recovery of locomotor function by 45% were also recorded. Finally, PGA-cur significantly counteracted MIA-induced increase in serum levels of TNF-α, IL-1β, NGF, as well as metalloproteases 1, 3, and 9. All the effects of PGA-Cur were superior compared to the compounds used singly. PGA-Cur emerged as a useful dietary intervention for OA. [ABSTRACT FROM AUTHOR]

Traumatic brain injury (TBI) is a shocking disease frequently followed by behavioral disabilities, including risk of cerebral atrophy and dementia. N-formylpeptide receptor 1 (FPR1) is expressed in cells and neurons in the central nervous system. It is involved in inflammatory processes and during the differentiation process in the neural stem cells. We investigate the effect of the absence of Fpr1 gene expression in mice subjected to TBI from the early stage of acute inflammation to neurogenesis and systematic behavioral testing four weeks after injury. C57BL/6 animals and Fpr1 KO mice were subjected to TBI and sacrificed 24 h or four weeks after injury. Twenty-four hours after injury, TBI Fpr1 KO mice showed reduced histological impairment, tissue damage and acute inflammation (MAPK activation, NF-κB signaling induction, NRLP3 inflammasome pathway activation and oxidative stress increase). Conversely, four weeks after TBI, the Fpr1 KO mice showed reduced survival of the proliferated cells in the Dentate Gyrus compared to the WT group. Behavioral analysis confirmed this trend. Moreover, TBI Fpr1 KO animals displayed reduced neural differentiation (evaluated by beta-III tubulin expression) and upregulation of astrocyte differentiation (evaluated by GFAP expression). Collectively, our study reports that, immediately after TBI, Fpr1 increased acute inflammation, while after four weeks, Fpr1 promoted neurogenesis. [ABSTRACT FROM AUTHOR]

Simple Summary: This paper reports the efficacy of Ultramicronized Palmitoylethanolamide (PEA-um) supplementation for four show-jumping horses with lameness and joint disease. Joint disease is often associated with inflammatory states and pain that lead to lameness or impairment in athletic performances. PEA-um is a nutraceutical compound that is well-known for its anti-inflammatory and analgesic proprieties, and is widely used in human medicine and small animal veterinary medicine. Although it includes a small number of cases, our study describes for the first time the efficacy of the use of PEA-um in horses. PEA-um was introduced to the normal diet of four horses with non-responsive lameness and significant impairment of athletic performance. After four months of PEA-um supplementation, all horses showed remissions of lameness that led to their reintroduction into showjumping competitions without disease recurrence. Therefore, despite the small number of cases included in this study, the observations suggest that PEA-um may be beneficial in the maintenance of joint disease in athletic horses. Background: Four show jumping horses were evaluated for non-responsive lameness, which caused their withdrawal from show jumping competitions. The clinical evaluation was performed by radiographic examination, flexion tests, diagnostic anesthesia and lameness evaluation using the American Association of Equine Practitioners (AAEP) scale. The diagnoses were a case of navicular syndrome, a complicated case of chronic navicular syndrome and arthrosis of the distal interphalangeal joint of the right anterior limb and two cases of distal intertarsal joint arthritis. Nutraceuticals are often an important management strategy or coadjutant of pharmacological therapies in joint disease. Ultramicronized Palmitoylethanolamide (PEA-um) is an endogenous fatty acid amide that is well-known for its anti-inflammatory and analgesic proprieties widely used in human medicine and small animal veterinary medicine. Although it includes a small number of cases, our study describes for the first time the efficacy of the use of PEA-um in horses. The four horses with non-responsive lameness and significant impairment in athletic performance were daily treated with PEA-um into their normal diet. After four months of PEA-um supplementation, all horses showed remissions of lameness that led to their reintroduction into showjumping competitions without disease recurrence. Therefore, despite the small number of cases included in this study, these observations suggest a good prospective for developing a controlled experiment to test PEA in a larger cohort of horses. [ABSTRACT FROM AUTHOR]

Simple Summary: Aflatoxin B1 (AFB1) is a mycotoxin commonly present in feed, characterized by several toxic effects. AFB1 has been described as being responsible for naturally occurring animal kidney disorders. In addition, AFB1 seems to have a neurotoxical effect that leads to memory impairment behavior. AFB1 toxicity involves the induction of the oxidative stress pathway, rising lipid peroxidation, and it decreases antioxidant enzyme levels. Hence, in our research, we wanted to evaluate the potential protective effects of quercetin in AFB1-mediated toxicity in the brain and the ameliorative effect on behavioral alterations. This antioxidant effect of quercetin in the brains of AFB1-intoxicated mice is reflected in better cognitive and spatial memory capacity, as well as a better profile of anxiety and lethargy disorders. In conclusion, our study suggests that quercetin exerts a preventive role against oxidative stress by promoting antioxidative defense systems and limiting lipid peroxidation. Aflatoxin B1 (AFB1) is a mycotoxin commonly present in feed, characterized by several toxic effects. AFB1 seems to have a neurotoxical effect that leads to memory impairment behavior. AFB1 toxicity involves the induction of the oxidative stress pathway, rising lipid peroxidation, and it decreases antioxidant enzyme levels. Hence, in our research, we wanted to evaluate the potential protective effects of quercetin 30 mg/kg in AFB1-mediated toxicity in the brain and the ameliorative effect on behavioral alterations. Oral supplementation with quercetin increased glutathione peroxidase (GSH) levels, superoxidedismutase (SOD) activity and catalase (CAT) in the brain, and it reduced lipid peroxidation in AFB1-treated mice. This antioxidant effect of quercetin in the brains of AFB1-intoxicated mice is reflected in better cognitive and spatial memory capacity, as well as a better profile of anxiety and lethargy disorders. In conclusion, our study suggests that quercetin exerts a preventive role against oxidative stress by promoting antioxidative defense systems and limiting lipid peroxidation. [ABSTRACT FROM AUTHOR]

Simple Summary: Leishmaniasis is a multisystemic zoonotic disease with several symptoms, and treating this disease is a great challenge for veterinary medicine. Artemisinin derivatives are currently the most widely used drugs for the treatment of malaria, especially for their excellent safety profile and low cost. Artesunate is a more stable derivative of its precursor, artemisin, and has been shown to be a pluripotent agent with different pharmacological actions. In this study, we evaluated the role of neuroinflammation in leishmaniasis and its correlation with pain and sickness behavior, and the anti-inflammatory and neuroprotective effects of artesunate in a murine model of Leishmania amazonensis infection in BALB/c mice. The results from this study indicate that artesunate is a good candidate for treatment and/or as an adjuvant in anti- leishmaniasis therapy, and for preventing and alleviating leishmaniasis-induced pain and neuroinflammation. Background: Leishmaniasis is a multisystemic zoonotic disease with several symptoms, including neurological disorders. Leishmaniasis is accompanied by an increase in nociceptive behaviors, linked to the presence of a chronic inflammatory state, in both peripheral tissue and the central nervous system. Artesunate is a more stable derivative of its precursor artemisin and has been shown to be a pluripotent agent with different pharmacological actions. Methods: In this study, we investigated the effects of artesunate in Leishmaniaamazonensi- infected BALB/c mice, evaluating its effectiveness in reducing inflammation, neuroinflammation, and nociceptive and sickness behaviors. Results: Our results demonstrate a significant increase in pain sensitivity and sickness behaviors after L. amazonensis infection. Moreover, the infection induced a significant increase in inflammatory response at both the paw and spinal cord level. Treatment with artesunate was able to induce a significant decrease in tissue inflammation and neuroinflammation and thus induce a significant decrease in pain sensitivity and sickness behaviors. Conclusions: The results from this study indicate that artesunate is a good candidate for treatment and/or as an adjuvant in leishmanicidal therapy, and to prevent and alleviate leishmaniasis-induced pain and neuroinflammation and thereby improve the quality of life of leishmaniasis patients. [ABSTRACT FROM AUTHOR]

Simple Summary: Laparoscopy is a minimally invasive surgical technique used to explore and treat conditions within the abdomen. In equids, this procedure is generally performed standing, with animals sedated and restrained in stocks. Laparoscopic ovariectomy in equids has gained popularity as it avoids the risk of general anaesthesia, greatly improves visualisation and manipulation of the ovary and its blood supply, reduces the recovery period, and provides a superior aesthetic result. Indications for ovariectomy include neutering, fertility problems, ovarian tumours, hematomas or cysts, disorders of sexual development, and the elimination of undesirable behaviour related to oestrus. During the procedure, pain management is achieved with a combination of systemic or loco-regional anaesthesia. The objective of this systematic review was to evaluate studies in the equine veterinary literature, published between 2003 and 2023, in which loco-regional anaesthesia was used during standing laparoscopic ovariectomy in equids to assess the different drugs, techniques, and outcomes. Laparoscopic ovariectomy is generally performed with equids in the standing position, with the animals heavily sedated and restrained in stocks. This procedure may be quite painful, and it is essential first to manage intraoperative pain to complete the surgery, respecting the animal's welfare and, at the same time, ensuring the safety of the operators. Laparoscopy requires multiple small incisions to introduce the instruments, with one to two incisions enlarged sufficiently to remove the ovary. The surgical procedure must be associated with effective pain control, usually obtained with loco-regional anaesthesia, mesovarian injection, mesovaric or ovarian topical anaesthesia, and epidural anaesthesia. This systematic review aims to discuss articles published from 2003 to 2023 on treating loco-regional anaesthesia in standing laparoscopic ovariectomy in association with an evaluation of pain. The literature review was undertaken according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines on three databases (NCBI-PubMed, Web of Science, and SciVerse Scopus). Despite the collected papers numbering 36, we identified only five eligible papers, demonstrating that few studies are performed in order to evaluate the quality of analgesia with loco-regional anaesthesia in standing laparoscopic ovariectomy in equids. The authors of this systematic review agree that the association of injectable and epidural anaesthesia is the best solution to manage intraoperative pain in standing laparoscopic ovariectomy in equids. [ABSTRACT FROM AUTHOR]

Simple Summary: Fourier Transform Infrared Spectroscopy (FTIR) is a rapid, cost-effective, and routinely used tool for milk analysis that can be easily applied to the classification of valuable dairy products such as Podolica milk. In the work herein presented, we applied machine learning to rapidly classify the FTIR datasets of milk from different bovine breeds. We were able to successfully recognize non-Podolica milk with 86% sensitivity and 100% specificity, demonstrating that the combination of these tools might be used in the future for the rapid classification of milk from different bovine breeds. The Podolica cattle breed is widespread in southern Italy, and its productivity is characterized by low yields and an extraordinary quality of milk and meats. Most of the milk produced is transformed into "Caciocavallo Podolico" cheese, which is made with 100% Podolica milk. Fourier Transform Infrared Spectroscopy (FTIR) is the technique that, in this research work, was applied together with machine learning to discriminate 100% Podolica milk from contamination of other Calabrian cattle breeds. The analysis on the test set produced a misclassification percentage of 6.7%. Among the 15 non-Podolica samples in the test set, 2 were misclassified and recognized as Podolica milk even though the milk was from other species. The correct classification rate improved to 100% when the same method was applied to the recognition of Podolica and Pezzata Rossa milk produced by the same farm. Furthermore, this technique was tested for the recognition of Podolica milk mixed with milk from other bovine species. The multivariate model and the respective confusion matrices obtained showed that all the 14 Podolica samples (test set) mixed with 40% non-Podolica milk were correctly classified. In addition, Pezzata Rossa milk produced by the same farm was detected as a contaminant in Podolica milk from the same farm down to concentrations as little as 5% with a 100% correct classification rate in the test set. The method described yielded higher accuracy values when applied to the discrimination of milks from different breeds belonging to the same farm. One of the reasons for this phenomenon could be linked to the elimination of the environmental variable. However, the results obtained in this work demonstrate the possibility of using FTIR to discriminate between milks from different breeds. [ABSTRACT FROM AUTHOR]

Background: Animal models of sciatic nerve injury are commonly used to study neuropathic pain as well as axon regeneration. Inflammation/immune response at the site of nerve lesion is known to be an essential trigger of the pathological changes that have a critical impact on nerve repair and regeneration; moreover, the damage to peripheral nerve can cause a loss of sensory function and produces a persistent neuropathic pain. N-Acylethanolamines (NAEs) involve a family of lipid molecules existent in animal and plant, of which is N-palmitoylethanolamide (PEA) that arouses great attention owing to its anti-inflammatory, analgesic, and neuroprotective activities. The modulation of specific amidases for NAEs (and in particular NAE-hydrolyzing acid amidase NAAA, which is more selective for PEA) could be a condition to preserve its levels. Here, we investigated, in a mice model of sciatic nerve crush, the effect of 2-pentadecyl-2-oxazoline (PEA-OXA) the oxazoline of PEA that reportedly modulates activity of NAAA.Methods: In this experimental model, the mice, following the sciatic nerve crush, were treated daily with PEA-OXA at a dose of 10 mg\kg for 14 days. Therefore, we evaluated the effects of PEA-OXA on the degree of injury, on the inhibition of neuropathic pain, and on the inflammatory process, as in the improvement of reparative processes and therefore in the restoration of locomotor function.Results: Our results showed that PEA-OXA (10 mg/kg) treatment, daily, for 14 days after sciatic nerve crush, have an anti-inflammatory and neuroprotective effect and moreover have an analgesic protective effect on hypersensitivity, and improve the functional recovery after nerve crush.Conclusions: Therefore, treatment with PEA-OXA as a whole has shown a protective effect, which makes it a powerful candidate for the treatment of peripheral nerve injury and neuropathic pain. [ABSTRACT FROM AUTHOR]

Purpose: Inflammatory corneal diseases such as bacterial keratitis provoke severe injury to the visual functions and physical structure, leading to opaqueness, wounding, damage to the cornea, and even long-lasting vision loss. Usually antioxidant substances have been of great attention as candidate therapies in the management of keratitis in both humans and animals. Based on the findings, the aim of our research was to examine the effects of Tempol (4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl), a membrane-permeable free radical scavenger with exclusive antioxidant properties, on in vitro model of eye inflammation of rabbit corneal cells stimulated with lipopolysaccharide (LPS) (Seruminstitute Rabbit Cornea). Methods: The cells were pretreated with Tempol and incubated with LPS for 24 h. LPS stimulation triggered increased cellular mortality, oxidative stress, cytokine levels expression of tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6, and also enhanced prostaglandin E2 (PGE2) levels and cyclooxygenase-2 (COX-2) expression. Results: Pretreatment with Tempol (3 mM) significantly increased cell viability and antioxidant activity as well as decreased reactive oxygen species production, cytokines, PGE2 levels, and COX-2 expression. Conclusions: Taken together, Tempol could be a new therapeutic strategy for management of ocular inflammatory disorders for clinical and veterinary use. [ABSTRACT FROM AUTHOR]

Graphical abstract Abstract Inflammatory bowel disease is characterised by intricate immune cell interactions with tissue cells and such cross-talks can become deregulated. The formyl peptide receptor 1 (Fpr1) is expressed by both immune and stromal cells including epithelial cells. We evaluated the development of the physiopathology of the DNBS induced colitis in Fpr1 KO mice on the C57BL/6 genetic background compared to C57BL/6 genetic background animals. We have assessed both macroscopic and histological markers of the diseased, together with the immunohistochemical and molecular changes. DNBS-treated Fpr1 KO mice showed a i) reduction in weight loss, ii) lower extent of colon injury and iii) an increase in MPO activity. Molecular analyses indicated that in absence of Fpr1 there was reduced NF-κB translocation into the nucleus, cytokines levels, FOXP3 and GATA3, CD4, CD8 and CD45 expression as well as a dysregulation of TGF-β signalling. In addition, the colon of DNBS-injected Fpr1 KO mice displayed a lower degree of expression of Bax and higher expression of Bcl-2 compared correspondent WT mice. Finally, intravital microscopy investigation of the microcirculation post-DNBS instillation revealed a lower degree of neutrophil-endothelial cell rolling and adhesion - mediated by P-selectin and ICAM-1 – in Fpr1 KO mice. All the main outcome in the study have a P-value, statistical significance of evidence, less than 0.05. We provide evidence for an important pathogenic role of mouse Fpr1 in experimental colitis, an outcome effected through modulation of immune cell recruitment together with a modulation of local cellular activation and survival. [ABSTRACT FROM AUTHOR]

Myocarditis is an inflammatory cardiac disorder and the primary cause of heart failure in young adults. Its origins can be attributed to various factors, including bacterial or viral infections, exposure to toxins or drugs, endocrine disruptors (EDs), and autoimmune processes. Tebuconazole (TEB), which is a member of the triazole fungicide family, is utilized to safeguard agricultural crop plants against fungal pathogens. Although TEB poses serious threats to mammal health, the information about how it induces toxic effects through various pathways, particularly in autoimmune diseases, are still limited. Thus, the aim of this paper was to evaluate the effect of TEB exposure in autoimmune myocarditis (AM). To induce AM, rats were immunized with porcine cardiac myosin and exposed to TEB for 21 days. Thereafter, animals were sacrificed, and histological, biochemical, and molecular analyses were performed. TEB exposure increased heart weight, systolic blood pressure and heart rate already augmented by AM. Additionally, it significantly increased creatine phosphokinase heart (CK-MB), creatine phosphokinase (CPK), cardiac troponin T (cTnT), and cardiac troponin I (cTnI), as compared to the control. From the histological perspective, TEB exacerbates the histological damage induced by AM (necrosis, inflammation and cell infiltration) and increased fibrosis and collagen deposition. TEB exposure strongly increased pro-inflammatory cytokines and prooxidant levels (O2−, H2O2, NO2−, lipid peroxidation) and reduced antioxidant enzyme levels, which were already dysregulated by AM. Additionally, TEB increased NOX-4 expression and the TGFβ1-Smads pathway already activated by AM. Overall, our results showed that TEB exposure strongly aggravated the cardiotoxicity induced by AM. [ABSTRACT FROM AUTHOR]

Myocardial ischemia/reperfusion injury (MIRI) is the principal cause of death and occurs after prolonged blockage of the coronary arteries. Diabetes represents one of the main factors aggravating myocardial injury. Restoring blood flow is the first intervention against a heart attack, although reperfusion process could cause additional damage, such as the overproduction of reacting oxygen species (ROS). In recent years, açaí berry has gained international attention as a functional food due to its antioxidant and anti-inflammatory properties; not only that but this fruit has shown glucose-lowering effects. Therefore, this study was designed to evaluate the cardioprotective effects of açaí berry on the inflammatory and oxidative responses associated with diabetic MIRI. Diabetes was induced in rats by a single intravenous inoculation of streptozotocin (60 mg/kg) and allowed to develop for 60 days. MIRI was induced by occlusion of the left anterior descending coronary artery for 30 min followed by 2 h of reperfusion. Açaí (200 mg/kg) was administered 5 min before the end of ischemia and 1 h after reperfusion. In this study, we clearly demonstrated that açaí treatment was able to reduce biomarkers of myocardial damage, infarct size, and apoptotic process. Moreover, açaí administrations reduced inflammatory and oxidative response, modulating Nf-kB and Nrf2 pathways. These results suggest that açai berry supplementation could represent a useful strategy for pathological events associated to MIRI. [ABSTRACT FROM AUTHOR]

Endometriosis (EMS) is a gynecological disease characterized by inflammation, oxidative stress, and apoptosis dysregulation. This study aims to evaluate the effect of Boswellia serrata gum resin extract (BS) on the endometriotic lesions in a rat model of endometriosis. We divided female rats into three groups, including Sham, EMS, EMS + BS. In the EMS and EMS + BS groups, pathology was induced and after 7 days by the abdominal high-frequency ultrasound (hfUS) analysis the presence of the endometriotic lesions was confirmed. Subsequently, the EMS + BS group was administered with BS (100 mg/Kg) daily for another 7 days. At the end of the experiment, the hfUS analysis was repeated and the animals were sacrificed to evaluate the size and histoarchitecture of the endometriotic implants. Pelvic ultrasound showed increased size of the endometriotic lesions in the Endo group, while BS administration reduced the lesion size. The macroscopic analysis confirmed the reduced area and volume of the endometriotic lesions of the EMS + BS group. The histological analysis showed reduced characteristic of ectopic stroma and glands in the animals treated with BS. Western blot analyses were conducted to evaluate the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. BS increases the expression of Nfr2 in the nucleus and the expression of its downstream antioxidant proteins NQO-1 and HO-1. Moreover, it reduced lipid peroxidation and increased glutathione (GSH) levels, and glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities. BS administration also restored the impaired apoptotic pathway in the lesions by reducing Bcl-2 expression and increasing Bax and cleaved caspase 9 levels. The BS apoptotic effect was also confirmed by the cleavage of PARP, another specific marker of apoptosis, and by the TUNEL assay. Our results show that BS administration resulted in an effective and coordinated suppression of Endo owing to its antioxidant and antiapoptotic activities. [ABSTRACT FROM AUTHOR]

A critical role for mitochondrial dysfunction has been shown in the pathogenesis of fibromyalgia. It is a chronic pain syndrome characterized by neuroinflammation and impaired oxidative balance in the central nervous system. Boswellia serrata (BS), a natural polyphenol, is a well-known able to influence the mitochondrial metabolism. The objective of this study was to evaluate the mitochondrial dysfunction and biogenesis in fibromyalgia and their modulation by BS. To induce the model reserpine (1 mg/Kg) was subcutaneously administered for three consecutive days and BS (100 mg/Kg) was given orally for twenty-one days. BS reduced pain like behaviors in reserpine-injected rats and the astrocytes activation in the dorsal horn of the spinal cord and prefrontal cortex that are recognized as key regions associated with the neuropathic pain. Vulnerability to neuroinflammation and impaired neuronal plasticity have been described as consequences of mitochondrial dysfunction. BS administration increased PGC-1α expression in the nucleus of spinal cord and brain tissues, promoting the expression of regulatory genes for mitochondrial biogenesis (NRF-1, Tfam and UCP2) and cellular antioxidant defence mechanisms (catalase, SOD2 and Prdx 3). According with these data BS reduced lipid peroxidation and the GSSG/GSH ratio and increased SOD activity in the same tissues. Our results also showed that BS administration mitigates cytochrome-c leakage by promoting mitochondrial function and supported the movement of PGC-1α protein into the nucleus restoring the quality control of mitochondria. Additionally, BS reduced Drp1 and Fis1, preventing both mitochondrial fission and cell death, and increased the expression of Mfn2 protein, facilitating mitochondrial fusion. Overall, our results showed important mitochondrial dysfunction in central nervous system in fibromyalgia syndrome and the role of BS in restoring mitochondrial dynamics. [Display omitted] • BS reduced glial cells activation in spinal cord and brain tissue induced by FM. • BS reduced oxidative stress in spinal cord and brain tissue induced by FM. • BS reduced cytochrome c release in spinal cord and brain tissue induced by FM. • BS reduced mitochondrial dysfunction in spinal cord and brain tissue induced by FM. [ABSTRACT FROM AUTHOR]

Endocrine-disrupting substances (EDS) are common and pervasive in our environment and pose a serious risk to both human and animal health. Endocrine-disrupting compounds (EDCs) have been associated with a variety of detrimental human health effects, including respiratory issues, as a result of their ability to disrupt cell physiology. Vinclozolin ((RS)-3-(3,5-Dichlorophenyl)-5-methyl-5-vinyloxazolidine-2,4-dione) is a common dicarboximide fungicide used to treat plant diseases. Several studies have analyzed the effects of vinclozolin exposure on the reproductive system, but less is known about its effect on other organs such as the lung. Mice were exposed for 28 days to orally administered vinclozolin at a dose of 100 mg/kg. Vinclozolin exposure induced histological alterations and collagen depositions in the lung. Additionally, vinclozolin induced inflammation and oxidative stress that led to lung apoptosis. Our study demonstrates for the first time that the toxicological effects of vinclozolin are not limited to the reproductive system but also involve other organs such as the lung. [ABSTRACT FROM AUTHOR]

Vinclozolin is one of the most used fungicides in the control of fungi in fruits, vegetables, and ornamental plants. The effects of its exposure on different organs have been described, but information regarding its relevance to vinclozolin-induced nephrotoxicity is largely missing. This study focuses on the potential mechanism of vinclozolin-induced nephrotoxicity. CD1 male mice were administered vinclozolin (100 mg/kg) by oral gavage for 28 days. Vinclozolin administration decreased body weight over the treatment period and at the end of the experiment, increased the ratio of kidney weight to body weight and increased serum urea nitrogen and creatinine contents. Vinclozolin also induced histopathological alterations, including tubular dilatation and necrosis and impaired the integrity of the renal-tubular architecture and kidney fibrosis. The analyses conducted showed that vinclozolin administration altered the mRNA levels of mitochondrial function-related proteins (SIRT3, SIRT1, PGC-1α, TFAM, NRF1, VDAC-1, and Cyt c) and oxidative stress (increased lipid peroxidation and decreased total antioxidative capacity, catalase, and superoxide dismutase activities, glutathione levels, and glutathione peroxidase activity) in the kidneys. Furthermore, vinclozolin induced toxicity that altered Nrf2 signalling and the related proteins (HO-1 and NQO-1). Vinclozolin administration also affected both the extrinsic and intrinsic apoptotic pathways, upregulating the expression of proapoptotic factors (Bax, Caspase 3, and FasL) and downregulating antiapoptotic factor (Bcl-2) levels. This study suggests that vinclozolin induced nephrotoxicity by disrupting the transcription of mitochondrial function-related factors, the Nrf2 signalling pathway, and the extrinsic and intrinsic apoptotic pathways. [ABSTRACT FROM AUTHOR]

Acute lung injury (ALI) is a common and devastating clinical disorder with a high mortality rate and no specific therapy. The pathophysiology of ALI is characterized by increased alveolar/capillary permeability, lung inflammation, oxidative stress and structural damage to lung tissues, which can progress to acute respiratory distress syndrome (ARDS). Adelmidrol (ADM), an analogue of palmitoylethanolamide (PEA), is known for its anti-inflammatory and antioxidant functions, which are mainly due to down-modulating mast cells (MCs) and promoting endogenous antioxidant defense. The aim of this study is to evaluate the protective effects of ADM in a mice model of ALI, induced by intratracheal administration of lipopolysaccharide (LPS) at the dose of 5 mg/kg. ADM 2% was administered by aerosol 1 and 6 h after LPS instillation. In this study, we clearly demonstrated that ADM reduced lung damage and airway infiltration induced by LPS instillation. At the same time, ADM counteracted the increase in MC number and the expression of specific markers of MC activation, i.e., chymase and tryptase. Moreover, ADM reduced oxidative stress by upregulating antioxidant enzymes as well as modulating the Nf-kB pathway and the resulting pro-inflammatory cytokine release. These results suggest that ADM could be a potential candidate in the management of ALI. [ABSTRACT FROM AUTHOR]

The second-most common cause of dementia is vascular dementia (VaD). The majority of VaD patients experience cognitive impairment, which is brought on by oxidative stress and changes in autophagic function, which ultimately result in neuronal impairment and death. In this study, we examine a novel method for reversing VaD-induced changes brought on by açai berry supplementation in a VaD mouse model. The purpose of this study was to examine the impact of açai berries on the molecular mechanisms underlying VaD in a mouse model of the disease that was created by repeated ischemia–reperfusion (IR) of the whole bilateral carotid artery. Here, we found that açai berry was able to reduce VaD-induced behavioral alteration, as well as hippocampal death, in CA1 and CA3 regions. These effects are probably due to the modulation of nuclear factor erythroid 2-related factor 2 (Nrf-2) and Beclin-1, suggesting a possible crosstalk between these molecular pathways. In conclusion, the protective effects of açai berry could be a good supplementation in the future for the management of vascular dementia. [ABSTRACT FROM AUTHOR]

(1) Background: Multiple contaminations of several mycotoxins have been detected in human and veterinary food and feed worldwide. To date, a number of studies on the combined effects of mycotoxins have been conducted on cell and animal models, but very limited studies have been done on aquatic organisms. (2) The purpose of the present study was to evaluate the combined toxic effects of Aflatoxin B1 (AFB1) and Fumonisin B1 (FB1) on zebrafish (Danio rerio) embryos. (3) Results: Our results showed that the combination of AFB1 and FB1 at nontoxic concentrations exerted a negative effect on the lethal endpoints analyzed, such as survival, hatching, and heart rate. In addition, the mixture of mycotoxins caused an increase in the levels of enzymes and proteins involved in the antioxidant process, such as superoxide dismutase (SOD) and catalase (CAT), both in terms of protein levels and gene expression, as well as an increase in the levels of the detoxification enzymes glutathione s-transferases (GST) and cytochromes P450 (CYP450). Furthermore, we showed that the mycotoxin mixture induced an increase in pro-apoptotic proteins such as bax and caspase 3, and at the same time reduced the gene expression of the anti-apoptotic bcl-2 protein. Finally, a significant decrease in thyroid function was observed in terms of triiodothyronine (T3), thyroxine (T4), and vitellogenin (VTG) levels. (4) Conclusion: We can say that the mixture of mycotoxins carries a greater risk factor than individual presences. There is a greater need for effective detoxification methods to control and reduce the toxicity of multiple mycotoxins and reduce the toxicity of multiple mycotoxins in feed and throughout the food chain. [ABSTRACT FROM AUTHOR]

Simple Summary: Canine atopic dermatitis (cAD) is a clinical syndrome characterized by inflammatory and allergic manifestations. Recent studies have demonstrated that cAD has many common characteristics with human AD and this assertion is derived from the assumption that domestic dogs share the environment with their owners. Several therapeutic approaches can be used in the management of cAD; in our research, we used the mucus secreted by Helix aspersa Muller. To clarify the development of cAD, we employed cell lines of canine epidermal keratinocytes (CPEK). Our results highlight the anti-inflammatory capacity of mucus in reducing the inflammatory process produced during cAD. Atopic dermatitis (AD) is an inflammatory and allergic disease, whose multifactorial etiopathogenesis is the consequence of the link between the genetic, immunological and environmental components. The complexity and difficulty in understanding the causes that trigger or exacerbate this pathology makes it difficult, once diagnosed, to proceed with a targeted and effective therapeutic process. Today, the new frontiers of research look to natural and innovative treatments to counteract the different manifestations of dermatitis. From this point of view, the mucus secreted by Helix aspersa Muller has proven, since ancient times, to be able to neutralize skin diseases. To study canine atopic dermatitis (cAD), we used cell lines of canine epidermal keratinocytes (CPEK) that are optimal to understand the biological reactivity of keratinocytes in vitro. The data obtained from our study demonstrate the anti-inflammatory capacity of snail secretion filtrate (SSF) in counteracting the production of proinflammatory cytokines produced during cAD, highlighting the opportunities for further studies to be able to identify new, natural and safe treatments for cAD and to open new frontiers for veterinarians and owners. [ABSTRACT FROM AUTHOR]

Fibromyalgia (FMS) is a persistent syndrome marked by widespread musculoskeletal pain and behavioural symptoms. Given the hypothesis linking FMS aetiology to mitochondrial dysfunction and oxidative stress, we examined the biochemical correlation among these factors by studying specific proteins associated with mitochondrial homeostasis in muscle. Additionally, this study investigated the role of Boswellia serrata gum resin extract (BS), known for its various functions, including the potent induction of antioxidant enzymes, in determining protective or reparative mechanisms in the muscle cells. Sprague–Dawley rats were injected with reserpine to induce FMS. These animals exhibited moderate changes in hind limb skeletal muscles, experiencing mobility difficulties. Additionally, there were noteworthy morphological and ultrastructural alterations, along with the expression of myogenin, mitochondrial enzymes and oxidative stress markers in the gastrocnemius muscle. Interestingly, BS demonstrated a reduction in spontaneous motor activity difficulties. Moreover, BS showed a positive impact on musculoskeletal morphostructural aspects, as well as a decrease in oxidative stress and mitochondrial alterations. In particular, BS restored the mRNA expression of citrate synthase and cytochrome-c oxidase subunit II and the activity of electron transfer chain complexes. BS also influenced mitochondrial biogenesis, upregulating PGC-1α expression and the related transcription factors (Nrf1, Tfam, Nrf2, FOXO3a, SIRT3, GCLC, NQO1, SOD2 and GPx4), oxidative stress (lipid peroxidation, GSH levels and GSH-Px activity) and mitochondrial dynamics and function (Mnf2 expression and CoQ10 levels). Overall, this study underlined the key role of the mitochondrial alteration in FMS and that BS had a very high antioxidant effect in these organelles and also in the cells. [Display omitted] • FMS induced musculoskeletal morphostructural alteration. • FMS reduced myogenin expression. • FMS impaired mitochondrial biogenesis in muscle. • FMS increased oxidative stress in muscle. • FMS impaired mitochondrial dynamics and function in muscle. [ABSTRACT FROM AUTHOR]

Endocrine disruptors (EDs) pose significant risks to human and environmental health, with potential implications for neurotoxicity. This study investigates the synergistic neurotoxic effects of perfluorooctane sulfonate (PFOS) and glyphosate (GLY), two ubiquitous EDs, using SHSY5Y neuronal and C6 astrocytic cell lines. While individual exposures to PFOS and glyphosate at non-toxic concentrations did not induce significant changes, their combination resulted in a marked increase in oxidative stress and neuroinflammatory responses. Specifically, the co-exposure led to elevated levels of interleukin-6, tumor necrosis factor alpha, and interferon gamma, along with reduced interleukin-10 expression, indicative of heightened neuroinflammatory processes. These findings underscore the importance of considering the synergistic interactions of EDs in assessing neurotoxic risks and highlight the urgent need for further research to mitigate the adverse effects of these compounds on neurological health. • Neurotoxic synergy: PFOS & glyphosate. • Oxidative stress escalation: Co-exposure. • Heightened neuroinflammation: PFOS & glyphosate. • Cytokine imbalance: Interleukin-10 reduced. • Research urgency: Mitigate ED neurotoxicity. [ABSTRACT FROM AUTHOR]

Endometriosis is usually associated with inflammation and chronic pelvic pain. This paper focuses the attention on the anti-inflammatory, anti-oxidant and analgesic effects of cannabidiol (CBD) and on its potential role in endometriosis. We employed an in vivo model of endometriosis and administered CBD daily by gavage. CBD administration strongly reduced lesions diameter, volume and area. In particular, it was able to modify lesion morphology, reducing epithelial glands and stroma. CBD showed anti-oxidant effects reducing lipid peroxidation, the expression of Nox-1 and Nox-4 enzymes. CBD restored the oxidative equilibrium of the endogenous cellular defense as showed by the SOD activity and the GSH levels in the lesions. CBD also showed important antifibrotic effects as showed by the Masson trichrome staining and by downregulated expression of MMP-9, iNOS and TGF-β. CBD was able to reduce inflammation both in the harvested lesions, as showed by the increased Ikb-α and reduced COX2 cytosolic expressions and reduced NFkB nuclear localization, and in the peritoneal fluids as showed by the decreased TNF-α, PGE2 and IL-1α levels. CBD has important analgesic effects as showed by the reduced mast cells recruitment in the spinal cord and the reduced release of neuro-sensitizing and pro-inflammatory mediators. In conclusion, the collected data showed that CBD has an effective and coordinated effects in endometriosis suppression. [ABSTRACT FROM AUTHOR]

Traumatic brain injury (TBI) disrupts the blood–brain barrier (BBB). Vascular endothelial growth factor (VEGF) is believed to play a key role in TBI and to be overexpressed in the absence of apolipoprotein E (ApoE). Bevacizumab, a VEGF inhibitor, demonstrated neuroprotective activity in several models of TBI. However, the effects of bevacizumab on Apo-E deficient mice are not well studied. The present study aimed to evaluate VEGF expression and the effects of bevacizumab on BBB and neuroinflammation in ApoE−/− mice undergoing TBI. Furthermore, for the first time, this study evaluates the effects of bevacizumab on the long-term consequences of TBI, such as atherosclerosis. The results showed that motor deficits induced by controlled cortical impact (CCI) were accompanied by increased brain edema and VEGF expression. Treatment with bevacizumab significantly improved motor deficits and significantly decreased VEGF levels, as well as brain edema compared to the control group. Furthermore, the results showed that bevacizumab preserves the integrity of the BBB and reduces the neuroinflammation induced by TBI. Regarding the effects of bevacizumab on atherosclerosis, it was observed for the first time that its ability to modulate VEGF in the acute phase of head injury prevents the acceleration of atherosclerosis. Therefore, the present study demonstrates not only the neuroprotective activity of bevacizumab but also its action on the vascular consequences related to TBI. [ABSTRACT FROM AUTHOR]

Low back pain (LBP) management is an important clinical issue. Inadequate LBP control has consequences on the mental and physical health of patients. Thus, acquiring new information on LBP mechanism would increase the available therapeutic tools. Resveratrol is a natural compound with many beneficial effects. In this study, we investigated the role of resveratrol on behavioral changes, inflammation and oxidative stress induced by LBP. Ten microliters of Complete Freund's adjuvant (CFA) was injected in the lumbar intervertebral disk of Sprague Dawley rats to induce degeneration, and resveratrol was administered daily. Behavioral analyses were performed on day zero, three, five and seven, and the animals were sacrificed to evaluate the molecular pathways involved. Resveratrol administration alleviated hyperalgesia, motor disfunction and allodynia. Resveratrol administration significantly reduced the loss of notochordal cells and degenerative changes in the intervertebral disk. From the molecular point of view, resveratrol reduced the 5th/6th lumbar (L5–6) spinal activation of the WNT pathway, reducing the expression of WNT3a and cysteine-rich domain frizzled (FZ)8 and the accumulation of cytosolic and nuclear β-catenin. Moreover, resveratrol reduced the levels of TNF-α and IL-18 that are target genes strictly downstream of the WNT/β-catenin pathway. It also showed important anti-inflammatory activities by reducing the activation of the NFkB pathway, the expression of iNOS and COX-2, and the levels of PGE2 in the lumbar spinal cord. Moreover, resveratrol reduced the oxidative stress associated with inflammation and pain, as shown by the observed reduced lipid peroxidation and increased GSH, SOD, and CAT activities. Therefore, resveratrol administration controlled the WNT/β-catenin pathway and the related inflammatory and oxidative alterations, thus alleviating the behavioral changes induced by LBP. [ABSTRACT FROM AUTHOR]

Several anthropogenic products in wastewater are considered a threat to the aquatic environment. In addition to common industrial pollutants, levels of pharmaceuticals have been increasingly found in the environment in recent years, which may present a strong risk to the aquatic species that live there. The constant consumption of biologically active chemicals for human health has been matched by an increase in the leaking of these compounds in natural habitats over the last two decades. This study is aimed at evaluating the developmental toxicity of fotemustine in the ecological environment. Zebrafish embryos were exposed to doses of 25, 50 and 100 µg/mL from 4 h post-fertilization to 120 h. This study confirms that fotemustine exposure at 50 and 100 µg/mL affects the survival and hatching rate, morphology score and body length. Additionally, it significantly disturbs the antioxidant defense system and increases ROS in zebrafish larvae. From the molecular point of view, fotemustine exposure strongly induces apoptosis, endoplasmic reticulum stress (ERS) and the Wnt signaling pathway. [ABSTRACT FROM AUTHOR]

Lipopolysaccharide (LPS), or bacterial endotoxin, is an important virulence factor in several human and animal pathologies. Oxazoline of Palmitoylethanolamide (PEAOXA) has shown strong anti-inflammatory activity in several animal models. LPS was applied for 24 h to zebrafish embryos to induce inflammation, and then the anti-inflammatory action of PEAOXA was evaluated for the first time in the zebrafish model (Danio rerio). Different concentrations of PEAOXA were tested for toxicity on zebrafish embryonic development; only the highest concentration of 30 mg/L showed toxic effects. Quantitative RT-PCR was applied to detect Tumor necrosis factor-α, Interleukin 1β, 6, and 8, and members of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB). Exposure to LPS induced an increase in pro-inflammatory cytokines (tumor necrosis factor and interleukin 1, 6, and 8) in both gene and protein expression, as well as an increase of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) and the nuclear factor kappa light polypeptide enhancer in B-cells inhibitor (IκBα) gene expression. Furthermore, acute LPS exposure also induced an increase in tryptase release, related to mast cell activity, and in the production of apoptosis-related proteins (caspase 3, bax, and bcl-2). Treatment with PEAOXA 10 mg/L significantly counteracts LPS-induced inflammation in terms of cytokine expression and decreases tryptase release and the apoptosis pathway. [ABSTRACT FROM AUTHOR]

Background/Aims: Atrazine (ATR) is the second most widely used herbicide, after glyphosate, that is used to stop pre- and post-emergence broadleaf and grassy weeds. In 2007, it was included in the class of endocrine disruptors due to the impact its exposure had on human health. Occasional ATR exposure at work has been linked to an increased risk of respiratory problems, but the molecular mechanisms underlying this relationship has not yet been fully elucidated. Methods: Mice were exposed to an aerosol containing ATR. In particular ATR aerosol was prepared by dissolving 250 mg of ATR in a vehicle made with saline and 10% DMSO. Seven days after the aerosol exposure, the mice were sacrificed and lung tissue, bronchoalveolar lavage fluid (BALF), and blood samples were collected for histology and biochemical analysis. Results: ATR inhalation induces a generalized state of oxidative/nitrosative stress that leads to an increase in cytokines production and to a physiologically unstable antioxidant defense response evaluated by the alteration of Nrf-2 pathways. Moreover, it stimulates autophagy through Beclin 1/Lc3 expressions and increases lipid peroxidation and apoptosis. All these effects culminate in serious alterations in the tissue architecture of the lungs and to an increase in mucus production and mast cells degranulation. Conclusion: Our study shows, for the first time, the impact of ATR inhalation on lung tissue. This could represent the first step to also recognize this substance as a problematic air pollutant as well as a soil and water contaminant. [ABSTRACT FROM AUTHOR]

Vinclozolin (VCZ) is a widely used fungicide in agriculture, especially in fruits and wine. Various studies have detailed the effects of VCZ exposure on different organs, but no information is available on its effects on brain tissues. This paper investigated the effects of VCZ exposure on the oxidative stress and mitochondrial dysfunction in brain tissue. C57BL/6 mice were exposed to VCZ (100 mg/kg) by oral gavage for 28 days. Mitochondrial homeostasis, often known as mitochondrial quality control, involves a range of processes, including mitochondrial biogenesis, mitochondrial fusion and fission, mitophagy and autophagy. VCZ administration modified the mRNA expression levels of Sirt1, Sirt3, PGC-1α, TFAM, Nrf1, VDAC-1 and Cyt c in brain tissue, as compared to control animals (CTR). The analyses also showed increased oxidative stress, in particular VCZ administration reduced SOD and CAT activities and GSH levels while increased T-AOC levels and lipid peroxidation. Additionally, brain tissues from VCZ group showed DNA oxidation (increased PARP-1 immunostaining) and apoptosis (increased TUNEL+ cells, increased expression of Bax mRNA level and reduced Bcl-2 levels). Western blot and immunohistochemical analyses showed increased mitophagic pathway with the accumulation of PINK1 and Parkin in mitochondria. Additionally, autophagic pathway was also increased with the increased expression and colocalization of LC3 with Neun and GFAP. Overall, this study showed that chronic VCZ exposure impaired mitochondrial homeostasis and increased oxidative stress in brain tissues. [Display omitted] • VCZ exposure induced mitochondrial dysfunction in brain. • VCZ exposure induced oxidative stress in brain. • VCZ exposure increased apoptosis in brain. • VCZ exposure increased mitophagy in brain. [ABSTRACT FROM AUTHOR]

Background/Aims: Oxidative stress plays a key role in aging, which in turn represents a substantial risk factor for brain injuries. The aim of the present study was to investigate the differences in physiological and biochemical changes in the brain during injury-related inflammation and oxidative stress, comparing young and old mice. Methods: Young and old mice were subjected to focal cerebral ischemia induced by transient middle cerebral artery occlusion or to traumatic brain injury performed by a controlled cortical impactor. At the end of both experiments, mice were sacrificed 24h after injuries and brains were collected to perform biochemical analysis. Results: In both ischemic stroke and traumatic brain injury, aging has not only led to damage-induced worsening of motor function and behavioural changes but also increased of infarct area compared to young animals. Moreover, aged mice show increased evidence of oxidative stress and reduced antioxidant capacity when compared to younger animals, as demonstrated by Nrf2-Keap1 signalling pathway and lower expression of antioxidant enzymes, such as HO-1, SOD-1 and GSH-Px. Additionally, brain tissues collected from elderly mice showed an increased IκB-a degradation into the cytoplasm and consequently NF-κB translocation into the nucleus, compared to young mice subjected to same injuries. The elderly mice showed significantly higher levels of iNOS and CoX-2 expression than the young mice, as well as higher levels of inflammatory cytokines such as TNFa, IL-1ß, and IL-6 after MCAO and TBI. Conclusion: Preserving and keeping the NRF-2 pathway active counteracts the onset of oxidative stress and consequent inflammation after ischemic and traumatic brain insult, particularly in the elderly. Not only that, NRF-2 pathway could represent a possible therapeutic target in the management of brain injuries. [ABSTRACT FROM AUTHOR]

Simple Summary: Antimicrobials represent useful tools to fight bacterial infections that could harm human and animal health. Antimicrobial resistance occurs naturally or can be induced by the misuse of antibiotics. Its occurrence limits the efficiency of antibiotics and therefore the possibility to treat infections effectively. This can lead to an increasing severity of infectious diseases in humans and animals. Here, we describe the development of a workflow that provides a qualitative representation of the antimicrobial genes that are translated into proteins. Since proteins are ultimately the real effectors, the method herein described demonstrates that those genes are effectively enhancing antimicrobial resistance (AMR). The presented method is independent of any amplification step and provides useful information on the dynamics of the biochemical functions accomplished by the raw milk bacterial consortium. The environment, including animals and animal products, is colonized by bacterial species that are typical and specific of every different ecological niche. Natural and human-related ecological pressure promotes the selection and expression of genes related to antimicrobial resistance (AMR). These genes might be present in a bacterial consortium but might not necessarily be expressed. Their expression could be induced by the presence of antimicrobial compounds that could originate from a given ecological niche or from human activity. In this work, we applied (meta)proteomics analysis of bacterial compartment of raw milk in order to obtain a method that provides a measurement of circulating AMR involved proteins and gathers information about the whole bacterial composition. Results from milk analysis revealed the presence of 29 proteins/proteoforms linked to AMR. The detection of mainly β-lactamases suggests the possibility of using the milk microbiome as a bioindicator for the investigation of AMR. Moreover, it was possible to achieve a culture-free qualitative and functional analysis of raw milk bacterial consortia. [ABSTRACT FROM AUTHOR]