The Postbiotic Properties of Butyrate in the Modulation of the Gut Microbiota: The Potential of Its Combination with Polyphenols and Dietary Fibers.

The gut microbiota is a diverse bacterial community consisting of approximately 2000 species, predominantly from five phyla: Firmicutes, Bacteroidetes, Actinobacteria, Proteobacteria, and Verrucomicrobia. The microbiota's bacterial species create distinct compounds that impact the host's health, including well-known short-chain fatty acids. These are produced through the breakdown of dietary fibers and fermentation of undigested carbohydrates by the intestinal microbiota. The main short-chain fatty acids consist of acetate, propionate, and butyrate. The concentration of butyrate in mammalian intestines varies depending on the diet. Its main functions are use as an energy source, cell differentiation, reduction in the inflammatory process in the intestine, and defense against oxidative stress. It also plays an epigenetic role in histone deacetylases, thus helping to reduce the risk of colon cancer. Finally, butyrate affects the gut-brain axis by crossing the brain-blood barrier, making it crucial to determine the right concentrations for both local and peripheral effects. In recent years, there has been a significant amount of attention given to the role of dietary polyphenols and fibers in promoting human health. Polyphenols and dietary fibers both play crucial roles in protecting human health and can produce butyrate through gut microbiota fermentation. This paper aims to summarize information on the key summits related to the negative correlation between intestinal microbiota diversity and chronic diseases to guide future research on determining the specific activity of butyrate from polyphenols and dietary fibers that can carry out these vital functions.

Trace Elements in Stenella coeruleoalba: Assessment of Marine Environmental Pollution and Dolphin Health Status.

Heavy metals are environmental contaminants and can easily accumulate and biomagnify in various marine species (fishes and mammalians) at the top of the aquatic food chain. Among marine mammalians, the striped dolphin (Stenella coeruleoalba) is the most abundant cetacean in the Mediterranean Sea and is considered to be a sentinel species to monitor the environmental marine pollution. In this study, the contents of toxic metals and metalloids (Cd, Pb, Hg, and As), micro-elements (Ni, Cr, Cu, Fe, Co, Mn, Se and Zn) and macro-elements (Na, Ca, K, Mg and P) were evaluated by ICP-MS analysis in several organs/tissues (lung, skin, muscle and liver) of Stenella coeruleoalba. The assessment of marine environmental pollution and dolphins health status was carried out through further analysis of the same specific parameters such as the metal pollution index (MPI) and coefficient of condition (K). Finally, the correlation between toxic metals and metalloids and essential micro-elements, expressed as molar ratios, was analyzed to evaluate the detoxifying ability (effectiveness) of Zn, Se and Cu. Data obtained showed the presence of toxic metals and metalloids analyzed in the Stenella coeruleoalba samples but the MPI values suggested a low environmental contamination of the Mediterranean Sea where dolphins lived. The content of micro- and macro-elements was found to be in a normal range for this species and predictive of dolphins good health status, as confirmed by the coefficient of condition K. However, the correlation between toxic and essential metals, expressed as molar ratios, showed that the following toxic metals cannot be detoxified by the essential metals: 66Zn/201Hg, 82Se/201Hg, 63Cu/201Hg and 66Zn/52Cr, 82Se/52Cr, 63Cu/52Cr. Therefore, this study highlights the key role of dolphin Stenella coeruleoalba to assess marine pollution and the importance of analyzing the complete mineral profile to evaluate the animal health status.

Two Olea europea extracts reduce deleterious effects in a model of neurotoxicity: involvement of the endoplasmic reticulum.

Prolonged exposure to lead has been recognized as harmful to human health as it may cause neurotoxic effects including mitochondrial damage, apoptosis, excitotoxicity, and myelin formation alterations, among others. Numerous data have shown that consuming olive oil and its valuable components could reduce neurotoxicity and degenerative conditions. Olive oil is traditionally obtained from olive trees; this plant (Olea europaea L.) is an evergreen fruit tree. In this manuscript two extracts have been used and compared: the extract from the leaves of Olea europaea L., (OE), and the extract derived from OE but with a further sonication process (s-OE). Therefore, the objectives of this experimental work were as follows: 1) To generate an innovative extract; 2) To test both extracts on a model of neurotoxicity of human neurons induced following lead exposure; and 3) To study the mechanisms behind lead-induced neurotoxicity. The results showed that the mechanism involved in the neurotoxicity of lead included dysfunction of the cellular endoplasmic reticulum, which suffered oxidative damage. In addition, in all experiments s-OE was more effective than OE, having greater and better effects against lead-induced damage, and being dissolved in a smaller amount of EtOH that promotes its sustainability.

Prevalence of Helminths in Small Ruminant Farms and Evaluation of Control Practices Used to Counter Anthelmintic Resistance in Southern Italy.

Anthelmintic resistance in small ruminants is a serious worldwide problem. To reduce their spread, it is essential to know the prevalence of helminths on farms and the control practices adopted. As these studies in the Calabria region of southern Italy are fragmentary and outdated, a study on the prevalence of helminths in small ruminant holdings in this area has been conducted. The measures implemented to control helminths were also evaluated through questionnaires administered to farmers. In particular, on 90 farms (45 sheep and 45 goats), 1800 faecal samples from 900 sheep and 900 goats were collected in the spring. Using the FLOTAC dual technique, parasitological examinations demonstrated the presence of gastrointestinal nematodes in 100% of sheep and goat farms, followed by Nematodirus spp. (84.44% sheep and 48.89% goats), Moniezia spp. (73.33% sheep and 35.56% goats), Trichuris ovis (48.89% sheep and 42.22% goats), lungworms (28.89% sheep and 42.22% goats), Strongyloides papillosus (40% sheep and 26.67% goats), Dicrocoelium dendriticum (13.33% sheep and 26.67% goats), Calicophoron daubneyi (6.67% sheep and 31.11% goats), Fasciola hepatica (6.67% sheep and 4.44% goats), and Skrjabinema ovis (4.44% sheep and goats). The questionnaires showed that 82% and 85% of the farmers had applied pasture rotation, and that 93.3% and 86.6% had used anthelmintics in the previous year for sheep and goats, respectively. Only 24.4% of sheep farmers and 11.3% of goat farmers had carried out parasitological tests prior to treatments. The most used classes of anthelmintics were macrocyclic lactones and benzimidazoles, and only in 21.6% and 15.6%, for sheep and goats, respectively, was drug rotation carried out. These results denote that helminths represent a health problem for small ruminants and highlight a lack of knowledge of parasite control strategies among farmers. In these conditions, anthelmintic resistance phenomena could develop over time. Therefore, it is necessary to implement all possible strategies for the control of helminths, and to prevent the spread of anthelmintic resistance phenomena on farms in southern Italy.

Antioxidant Activity and Seasonal Variations in the Composition of Insoluble Fiber from the Cladodes of Opuntia ficus-indica (L.) Miller: Development of New Extraction Procedures to Improve Fiber Yield.

Opuntia ficus-indica (L.) Miller is a plant belonging to the Cactaceae family adapted to live in environments characterized by long periods of drought and arid or desert climates. This plant is characterized by an aerial part composed of structures transformed by branches, called "cladodes", which are essential to reduce excessive perspiration of water and appear covered with thorns. The composition of the cladodes includes water, polysaccharides, fiber, proteins, vitamins, fatty acids, sterols, polyphenols, and minerals. The main purposes of this scientific work are (a) to compare the insoluble fiber (IF) extracted from the cladodes of O. ficus-indica belonging to the same plant but collected in different seasonal periods (winter and summer) and develop new extraction protocols that are able to improve the yield obtained and (b) evaluate the antioxidant potential of the fiber and study possible variations as a result of the extraction protocol chosen. The first objective was achieved (1) by measuring the amount of IF extracted from cladodes harvested in winter and summer (CW and CS, respectively) and (2) by modifying three variables involved in the fiber extraction protocol. To achieve the second objective, the following experiments were carried out: (1) measurement of the antioxidant potential of IF in CW and CS; (2) measurement of cellular reactive oxygen species; (3) measurement of the activity of some antioxidant enzymes; and (4) comparison of the polyphenol content in CW and CS. In conclusion, the results obtained showed that the IF extraction process can be improved, achieving a uniform yield regardless of seasonality; the antioxidant effect may vary depending on the extraction protocol.

Interaction of Flupyradifurone and Deltamethrin, Two Pesticides Commonly Used for Plant Pest Control, in Honeybees.

Nowadays, old-generation pesticides are released into ecosystems alongside new formulations, giving rise to pharmacological interactions (additive, synergistic, and antagonistic effects). The aim of this study was to evaluate the impact that simultaneous exposure to DMT and FLU doses has on bee health. Groups of twenty honeybees were housed in cages to compose six macro-groups. One group consisted of experimental replicates treated orally with a toxic dose of deltamenthrin (DMT 21.6 mg/L); two other groups were subjected to the oral administration of two toxic doses of flupyradifurone (FLU 50 mg/L and FLU 100 mg/L); and two other groups were intoxicated with a combination of the two pesticides (DMT 21.6 + FLU 50 and DMT 21.6 + FLU 100). The consequences of the pesticides' interactions were highlighted by measuring and comparing data on survival, food consumption, and abnormal behavior. Generally speaking, antagonism between the two pesticides has been demonstrated. The bees were able to survive for up to three days at the lowest dosage of FLU (50 mg/L), with 46% of the subjects still alive; however, the maximum dose (100 mg/L) caused all treated animals to die as early as the second day. When DMT and FLU 50 were administered together, the group that received DMT alone had a lower survival rate. When comparing the survival rates produced by the DMT and FLU 50 combination to those of the group receiving FLU 50 alone, the same was clearly visible. While there was no statistically significant improvement observed when the survival indices of the DMT and FLU 100 combination were compared to those of the group intoxicated with DMT alone, an improvement in survival indices was observed when these were compared with the group intoxicated with FLU 100 alone.

Non-essential heavy metal effects in cardiovascular diseases: an overview of systematic reviews.

Introduction: Cardiovascular diseases (CVDs) are the most important cause of premature death and disability worldwide. Environmental degradation and cardiovascular diseases are two keys to health challenges, characterized by a constant evolution in an industrialized world that exploits natural resources regardless of the consequences for health. The etiological risk factors of CVDs are widely known and include dyslipidemia, obesity, diabetes, and chronic cigarette consumption. However, one component that is often underestimated is exposure to heavy metals. The biological perspective explains that different metals play different roles. They are therefore classified into essential heavy metals, which are present in organisms where they perform important vital functions, especially in various physiological processes, or non-essential heavy metals, with a no biological role but, nonetheless, remain in the environment in which they are absorbed. Although both types of metal ions are many times chemically similar and can bind to the same biological ligands, the attention given today to nonessential metals in several eukaryotic species is starting to raise strong concerns due to an exponential increase in their concentrations. The aim of this systematic review was to assess possible correlations between exposure to nonessential heavy metals and increased incidence of cardiovascular disease, reporting the results of studies published in the last 5 years through March 2023. Methods: The studies includes reviews retrieved from PubMed, Medline, Embase, and Web of Science databases, in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement and following the PICO (Population Intervention Comparison Outcome Population) framework. Results: Eight reviews, including a total of 153 studies, were identified. Seven of these review enlighted the association between CVDs and non-essential heavy metals chronic exposure. Discussion: It is evident that exposure to heavy metals represent a risk factor for CVDs onset. However, further studies are needed to better understand the effects caused by these metals.

Effect of pomegranate (Punica granatum) anthelmintic treatment on milk production in dairy sheep naturally infected with gastrointestinal nematodes.

Anthelmintic drug resistance has proliferated across Europe in sheep gastrointestinal nematodes (GINs). Sheep welfare and health are adversely impacted by these phenomena, which also have an impact on productivity. Finding alternatives for controlling GINs in sheep is thus of utmost importance. In this study, the anthelmintic effectiveness (AE) of a Calabrian ethnoveterinary aqueous macerate based on Punica granatum (whole fruits) was assessed in Comisana pregnant sheep. Furthermore, an examination, both qualitative and quantitative, was conducted on milk. Forty-five sheep were selected for the investigation. The sheep were divided by age, weight, physiological state (pluripara at 20 days before parturition), and eggs per gram of feces (EPG) into three homogeneous groups of 15 animals each: PG received a single oral dosage of P. granatum macerate at a rate of 50 mL per sheep; AG, treated with albendazole, was administered orally at 3.75 mg/kg/bw; and CG received no treatment. Timelines were as follows: D0, treatments, group assignment, fecal sampling, and AE assessment; D7, D14, D21, fecal sampling, and AE evaluation. The FLOTAC technique was used to evaluate the individual GIN fecal egg count (FEC) using a sodium chloride flotation solution (specific gravity = 1.20) and 100 × (1-[T2/C2]) as the formula for evaluating FEC reduction. Following the lambs' weaning, milk was collected on the following days (DL) in order to quantify production: DL35, DL42, DL49, DL56, DL63, DL70, DL77, and DL84. The amount of milk produced by every animal was measured and reported in milliliters (ml) for quantitative evaluations. Using MilkoScan TM fT + foss electric, Denmark, the quality of the milk (casein, lactose, protein concentration, and fat, expressed as a percentage) was assessed. The macerate demonstrated a considerable AE (51.8%). Moreover, its use has resulted in higher milk production rates quantitatively (15.5%) and qualitatively (5.12% protein, 4.12% casein, 4.21% lactose, and 8.18% fat). The study showed that green veterinary pharmacology could be the easiest future approach to counteracting anthelmintic resistance in sheep husbandry.

Bergamot Polyphenolic Fraction for the Control of Flupyradifurone-Induced Poisoning in Honeybees.

Flupyradifurone (FLU) is a butenolide insecticide that has come onto the market relatively recently. It is used in agriculture to control aphids, psyllids, and whiteflies. Toxicity studies have decreed its low toxicity to honeybees. However, recent research has challenged these claims; oral exposure to the pesticide can lead to behavioral abnormalities and in the worst cases, lethal phenomena. Compounds with antioxidant activity, such as flavonoids and polyphenols, have been shown to protect against the toxic effects of pesticides. The aim of this research was to evaluate the possible protective effect of the bergamot polyphenolic fraction (BPF) against behavioral abnormalities and lethality induced by toxic doses of FLU orally administered to honeybees under laboratory conditions. Honeybees were assigned to experimental groups in which two toxic doses of FLU, 50 mg/L and 100 mg/L were administered. In other replicates, three doses (1, 2 and 5 mg/kg) of the bergamot polyphenolic fraction (BPF) were added to the above toxic doses. In the experimental groups intoxicated with FLU at the highest dose tested, all caged subjects (20 individuals) died within the second day of administration. The survival probability of the groups to which the BPF was added was compared to that of the groups to which only the toxic doses of FLU were administered. The mortality rate in the BPF groups was statistically lower (p < 0.05) than in the intoxicated groups; in addition, a lower percentage of individuals exhibited behavioral abnormalities. According to this research, the ingestion of the BPF attenuates the harmful effects of FLU. Further studies are needed before proposing BPF incorporation into the honeybees' diet, but there already seem to be beneficial effects associated with its intake.

The dangerous "West Coast Swing" by hyperglycaemia and chronic stress in the mouse hippocampus: Role of kynurenine catabolism.

Growing epidemiological studies highlight a bi-directional relationship between depressive symptoms and diabetes mellitus. However, the detrimental impact of their co-existence on mental health suggests the need to treat this comorbidity as a separate entity rather than the two different pathologies. Herein, we characterized the peculiar mechanisms activated in mouse hippocampus from the concurrent development of hyperglycaemia, characterizing the different diabetes subtypes, and chronic stress, recognized as a possible factor predisposing to major depression. Our work demonstrates that kynurenine overproduction, leading to apoptosis in the hippocampus, is triggered in a different way depending on hyperglycaemia or chronic stress. Indeed, in the former, kynurenine appears produced by infiltered macrophages whereas, in the latter, peripheral kynurenine preferentially promotes resident microglia activation. In this scenario, QA, derived from kynurenine catabolism, appears a key mediator causing glutamatergic synapse dysfunction and apoptosis, thus contributing to brain atrophy. We demonstrated that the coexistence of hyperglycaemia and chronic stress worsened hippocampal damage through alternative mechanisms, such as GLUT-4 and BDNF down-expression, denoting mitochondrial dysfunction and apoptosis on one hand and evoking the compromission of neurogenesis on the other. Overall, in the degeneration of neurovascular unit, hyperglycaemia and chronic stress interacted each other as the partners of a "West Coast Swing" in which the leading role can be assumed alternatively by each partner of the dance. The comprehension of these mechanisms can open novel perspectives in the management of diabetic/depressed patients, but also in the understanding the pathogenesis of other neurodegenerative disease characterized by the compromission of hippocampal function.

The potential effect of natural antioxidants on endothelial dysfunction associated with arterial hypertension.

Arterial hypertension represents a leading cause of cardiovascular morbidity and mortality worldwide, and the identification of effective solutions for treating the early stages of elevated blood pressure (BP) is still a relevant issue for cardiovascular risk prevention. The pathophysiological basis for the occurrence of elevated BP and the onset of arterial hypertension have been widely studied in recent years. In addition, consistent progress in the development of novel, powerful, antihypertensive drugs and their appropriate applications in controlling BP have increased our potential for successfully managing disease states characterized by abnormal blood pressure. However, the mechanisms responsible for the disruption of endogenous mechanisms contributing to the maintenance of BP within a normal range are yet to be fully clarified. Recently, evidence has shown that several natural antioxidants containing active ingredients originating from natural plant extracts, used alone or in combination, may represent a valid solution for counteracting the development of arterial hypertension. In particular, there is evidence to show that natural antioxidants may enhance the viability of endothelial cells undergoing oxidative damage, an effect that could play a crucial role in the pathophysiological events accompanying the early stages of arterial hypertension. The present review aims to reassess the role of oxidative stress on endothelial dysfunction in the onset and progression of arterial hypertension and that of natural antioxidants in covering several unmet needs in the treatment of such diseases.

The protective effect of Bergamot Polyphenolic Fraction on reno-cardiac damage induced by DOCA-salt and unilateral renal artery ligation in rats.

To date, the complex pathological interactions between renal and cardiovascular systems represent a real global epidemic in both developed and developing countries. In this context, renovascular hypertension (RVH) remains among the most prevalent, but also potentially reversible, risk factor for numerous reno-cardiac diseases in humans and pets. Here, we investigated the anti-inflammatory and reno-cardiac protective effects of a polyphenol-rich fraction of bergamot (BPF) in an experimental model of hypertension induced by unilateral renal artery ligation. Adult male Wistar rats underwent unilateral renal artery ligation and treatment with deoxycorticosterone acetate (DOCA) (20 mg/kg, s.c.), twice a week for a period of 4 weeks, and 1% sodium chloride (NaCl) water (n = 10). A subgroup of hypertensive rats received BPF (100 mg/kg/day for 28 consecutive days, n = 10) by gavage. Another group of animals was treated with a sub-cutaneous injection of vehicle (that served as control, n = 8). Unilateral renal artery ligation followed by treatment with DOCA and 1% NaCl water resulted in a significant increase in mean arterial blood pressure (MAP; p< 0.05. vs CTRL) which strongly increased the resistive index (RI; p<0.05 vs CTRL) of contralateral renal artery flow and kidney volume after 4 weeks (p<0.001 vs CTRL). Renal dysfunction also led to a dysfunction of cardiac tissue strain associated with overt dyssynchrony in cardiac wall motion when compared to CTRL group, as shown by the increased time-to-peak (T2P; p<0.05) and the decreased whole peak capacity (Pk; p<0.01) in displacement and strain rate (p<0.05, respectively) in longitudinal motion. Consequently, the hearts of RAL DOCA-Salt rats showed a larger time delay between the fastest and the lowest region (Maximum Opposite Wall Delay-MOWD) when compared to CTRL group (p<0.05 in displacement and p <0.01 in strain rate). Furthermore, a significant increase in the levels of the circulating pro-inflammatory cytokines and chemokines (p< 0.05 for IL-12(40), p< 0.01 for GM-CSF, KC, IL-13, and TNF- α) and in the NGAL expression of the ligated kidney (p< 0.001) was observed compared to CTRL group. Interestingly, this pathological condition is prevented by BPF treatment. In particular, BPF treatment prevents the increase of blood pressure in RAL DOCA-Salt rats (p< 0.05) and exerts a protective effect on the volume of the contralateral kidney (p <0.01). Moreover, BPF ameliorates cardiac tissue strain dysfunction by increasing Pk in displacement (p <0.01) and reducing the T2P in strain rate motion (p<0.05). These latter effects significantly improve MOWD (p <0.05) preventing the overt dyssynchrony in cardiac wall motion. Finally, the reno-cardiac protective effect of BPF was associated with a significant reduction in serum level of some pro-inflammatory cytokines and chemokines (p<0.05 for KC and IL-12(40), p<0.01 for GM-CSF, IL-13, and TNF- α) restoring physiological levels of renal neutrophil gelatinase-associated lipocalin (NGAL, p<0.05) protein of the tethered kidney. In conclusion, the present results show, for the first time, that BPF promotes an efficient renovascular protection preventing the progression of inflammation and reno-cardiac damage. Overall, these data point to a potential clinical and veterinary role of dietary supplementation with the polyphenol-rich fraction of citrus bergamot in counteracting hypertension-induced reno-cardiac syndrome.

Protective Role of Bergamot Polyphenolic Fraction (BPF) against Deltamethrin Toxicity in Honeybees (Apis mellifera).

Pesticide-induced poisoning phenomena are a serious problem for beekeeping and can cause large losses of honeybee populations due to acute and sub-acute poisoning. The reduced responsiveness of honeybees to the damage caused by pesticides used in agriculture can be traced back to a general qualitative and quantitative impoverishment of the nectar resources of terrestrial ecosystems. Malnutrition is associated with a decline in the functionality of the immune system and the systems that are delegated to the detoxification of the organism. This research aimed to verify whether bergamot polyphenolic extract (BPF) could have protective effects against poisoning by the pyrethroid pesticide deltamethrin. The studies were conducted with caged honeybees under controlled conditions. Sub-lethal doses of pesticides and related treatments for BPF were administered. At a dose of 21.6 mg/L, deltamethrin caused mortality in all treated subjects (20 caged honeybees) after one day of administration. The groups where BPF (1 mg/kg) was added to the toxic solution recorded the survival of honeybees by up to three days. Comparing the honeybees of the groups in which the BPF-deltamethrin association was added to the normal diet (sugar solution) with those in which deltamethrin alone was added to the normal diet, the BPF group had a statistically significant reduction in the honeybee mortality rate (p ≤ 0.05) and a greater consumption of food. Therefore, it can be argued that the inclusion of BPF and its constituent antioxidants in the honeybee diet reduces toxicity and oxidative stress caused by oral intake of deltamethrin. Furthermore, it can be argued that BPF administration could compensate for metabolic energy deficits often induced by the effects of malnutrition caused by environmental degradation and standard beekeeping practices.

Chemical Profile of Essential Oils of Selected Lamiaceae Plants and In Vitro Activity for Varroosis Control in Honeybees (Apis mellifera).

The most significant ectoparasitic mite of honeybees, Varroa destructor, has a detrimental effect on bee health and honey output. The principal strategy used by the control programs is the application of synthetic acaricides. All of this has resulted in drug resistance, which is now a major worry for beekeeping. As a result, research on alternate products and techniques for mite management is now required. The aim of this study was to determine whether essential oils (EOs) extracted from botanical species of Lamiacae, typical of the Calabria region of Southern Italy, could reduce the population of the mite V. destructor. Among the best-known genera of the Lamiaceae family are oregano, rosemary and thyme, whose EOs were employed in this study. By steam distillation, the EOs were extracted from Origanum vulgare subsp. viridulum (Martrin-Donos) Nyman, Thymus capitatus Hoffmanns. and Link, Thymus longicaulis C.Presl and Salvia rosmarinus Schleid. plant species harvested directly on the Calabrian territory in their balsamic time. Each EO went to the test in vitro (contact toxicity) against V. destructor. Fifty adult female mites, five for each EO and the positive and negative control, were used in each experimental replicate. The positive controls comprised five individuals treated to Amitraz dilute in acetone, and the negative controls included five individuals exposed to acetone alone. To create the working solution to be tested (50 µL/tube), the EOs were diluted (0.5 mg/mL, 1 mg/mL, 2 mg/mL and 4 mg/mL) in HPLC-grade acetone. After 1 h of exposure, mite mortality was manually assessed. Origanum vulgare subsp. viridulum, Thymus capitatus and Thymus longicaulis were the EOs with the highest levels of efficiency at 2 mg/mL, neutralizing (dead + inactivated), 94%, 92% and 94% of parasites, respectively. Salvia rosmarinus EO gave a lower efficacy, resulting in a percentage of 38%. Interestingly, no adverse effects were highlighted in toxicity tests on honeybees. These results show that these OEs of the Lamiaceae family have antiparasitic action on V. destructor. Therefore, they could be used, individually or combined, to exploit the synergistic effect for a more sustainable control of this parasite mite in honeybee farms.

Plants and Their Derivatives as Promising Therapeutics for Sustainable Control of Honeybee (Apis mellifera) Pathogens.

The most important pollinator for agricultural crops is the Western honeybee (Apis mellifera). During the winter and summer seasons, diseases and stresses of various kinds endanger honeybee numbers and production, resulting in expenses for beekeepers and detrimental effects on agriculture and ecosystems. Researchers are continually in search of therapies for honeybees using the resources of microbiology, molecular biology, and chemistry to combat diseases and improve the overall health of these important pollinating insects. Among the most investigated and most promising solutions are medicinal plants and their derivatives. The health of animals and their ability to fight disease can be supported by natural products (NPs) derived from living organisms such as plants and microbes. NPs contain substances that can reduce the effects of diseases by promoting immunity or directly suppressing pathogens, and parasites. This literature review summarises the advances that the scientific community has achieved over the years regarding veterinary treatments in beekeeping through the use of NPs. Their impact on the prevention and control of honeybee diseases is investigated both in trials that have been conducted in the laboratory and field studies.

The Effects of Andrographis paniculata (Burm.F.) Wall. Ex Nees and Andrographolide on Neuroinflammation in the Treatment of Neurodegenerative Diseases.

Neurodegenerative diseases (NDs) affect millions of people worldwide, and to date, Alzheimer's and Parkinson's diseases are the most common NDs. Of the many risk factors for neurodegeneration, the aging process has the most significant impact, to the extent that it is tempting to consider neurodegenerative disease as a manifestation of accelerated aging. However, genetic and environmental factors determine the course of neurodegenerative disease progression. It has been proposed that environmental stimuli influence neuroplasticity. Some clinical studies have shown that healthy lifestyles and the administration of nutraceuticals containing bioactive molecules possessing antioxidant and anti-inflammatory properties have a preventive impact or mitigate symptoms in previously diagnosed patients. Despite ongoing research efforts, the therapies currently used for the treatment of NDs provide only marginal therapeutic benefits; therefore, the focus is now directly on the search for natural products that could be valuable tools in combating these diseases, including the natural compound Andrographis paniculata (Ap) and its main constituent, andrographolide (Andro). Preclinical studies have shown that the aqueous extract of Ap can modulate neuroinflammatory and neurodegenerative responses, reducing inflammatory markers and oxidative stress in various NDs. Therefore, in this review, we will focus on the molecular mechanisms by which Ap and Andro can modulate the processes of neurodegeneration and neuroinflammation, which are significant causes of neuronal death and cognitive decline.

Thermoresponsive M1 macrophage-derived hybrid nanovesicles for improved in vivo tumor targeting.

Despite the efforts and advances done in the last few decades, cancer still remains one of the main leading causes of death worldwide. Nanomedicine and in particular extracellular vesicles are one of the most potent tools to improve the effectiveness of anticancer therapies. In these attempts, the aim of this work is to realize a hybrid nanosystem through the fusion between the M1 macrophages-derived extracellular vesicles (EVs-M1) and thermoresponsive liposomes, in order to obtain a drug delivery system able to exploit the intrinsic tumor targeting capability of immune cells reflected on EVs and thermoresponsiveness of synthetic nanovesicles. The obtained nanocarrier has been physicochemically characterized, and the hybridization process has been validated by cytofluorimetric analysis, while the thermoresponsiveness was in vitro confirmed through the use of a fluorescent probe. Tumor targeting features of hybrid nanovesicles were in vivo investigated on melanoma-induced mice model monitoring the accumulation in tumor site through live imaging and confirmed by cytofluorimetric analysis, showing higher targeting properties of hybrid nanosystem compared to both liposomes and native EVs. These promising results confirmed the ability of this nanosystem to combine the advantages of both nanotechnologies, also highlighting their potential use as effective and safe personalized anticancer nanomedicine.

Protective Role of an Extract Waste Product from Citrus bergamia in an In Vitro Model of Neurodegeneration.

A balanced diet, rich in fruits and vegetables and ensuring the intake of natural products, has been shown to reduce or prevent the occurrence of many chronic diseases. However, the choice to consume large quantities of fruits and vegetables leads to an increase in the amount of waste, which can cause an alteration in environmental sustainability. To date, the concept of a "byproduct" has evolved, now being understood as a waste product from which it is still possible obtain useful compounds. Byproducts in the agricultural sector are a rich source of bioactive compounds, capable of possessing a second life, decreasing the amount of waste products, the disposal costs, and environmental pollution. A promising and well-known citrus of the Mediterranean diet is the bergamot (Citrus bergamia, Risso et Poiteau). The composition of bergamot is known, and the rich presence of phenolic compounds and essential oils has justified the countless beneficial properties found, including anti-inflammatory, antioxidant, anti-cholesterolemic, and protective activity for the immune system, heart failure, and coronary heart diseases. The industrial processing of bergamot fruits leads to the formation of bergamot juice and bergamot oil. The solid residues, referred to as "pastazzo", are normally used as feed for livestock or pectin production. The fiber of bergamot (BF) can be obtained from pastazzo and could exert an interesting effect thanks to its content of polyphenols. The aims of this work were twofold: (a) to have more information (composition, polyphenol and flavonoid content, antioxidant activity, etc.) on BF powder and (b) to verify the effects of BF on an in vitro model of neurotoxicity induced by treatment with amyloid beta protein (Aß). In particular, a study of cell lines was carried out on both neurons and oligodendrocytes, to measure the involvement of the glia and compare it with that of the neurons. The results obtained showed that BF powder contains polyphenols and flavonoids and that it is able to exercise an antioxidant property. Moreover, BF exerts a protective action on the damage induced by treatment with Aß, and this defense is found in experiments on the cell viability, on the accumulation of reactive oxygen species, on the involvement of the expression of caspase-3, and on necrotic or apoptotic death. In all these results, oligodendrocytes were always more sensitive and fragile than neurons. Further experiments are needed, and if this trend is confirmed, BF could be used in AD; at the same time, it could help to avoid the accumulation of waste products.

Pathophysiological Aspects of Muscle Atrophy and Osteopenia Induced by Chronic Constriction Injury (CCI) of the Sciatic Nerve in Rats.

Skeletal muscle atrophy is a condition characterized by a loss of muscle mass and muscle strength caused by an imbalance between protein synthesis and protein degradation. Muscle atrophy is often associated with a loss of bone mass manifesting as osteoporosis. The aim of this study was to evaluate if chronic constriction injury (CCI) of the sciatic nerve in rats can be a valid model to study muscle atrophy and consequent osteoporosis. Body weight and body composition were assessed weekly. Magnetic resonance imaging (MRI) was performed on day zero before ligation and day 28 before sacrifice. Catabolic markers were assessed via Western blot and Quantitative Real-time PCR. After the sacrifice, a morphological analysis of the gastrocnemius muscle and Micro-Computed Tomography (Micro-CT) on the tibia bone were performed. Rats that underwent CCI had a lower body weight increase on day 28 compared to the naive group of rats (p < 0.001). Increases in lean body mass and fat mass were also significantly lower in the CCI group (p < 0.001). The weight of skeletal muscles was found to be significantly lower in the ipsilateral hindlimb compared to that of contralateral muscles; furthermore, the cross-sectional area of muscle fibers decreased significantly in the ipsilateral gastrocnemius. The CCI of the sciatic nerve induced a statistically significant increase in autophagic and UPS (Ubiquitin Proteasome System) markers and a statistically significant increase in Pax-7 (Paired Box-7) expression. Micro-CT showed a statistically significant decrease in the bone parameters of the ipsilateral tibial bone. Chronic nerve constriction appeared to be a valid model for inducing the condition of muscle atrophy, also causing changes in bone microstructure and leading to osteoporosis. Therefore, sciatic nerve constriction could be a valid approach to study muscle-bone crosstalk and to identify new strategies to prevent osteosarcopenia.

Phytochemical Composition and Pharmacological Efficacy Evaluation of Calamintha nepeta, Calamintha sylvatica, Lavandula austroapennina and Mentha piperita Essential Oils for the Control of Honeybee (Apis mellifera) Varroosis.

Varroa destructor is currently considered the parasite that causes the greatest damage and economic losses to honeybee farms. Its presence is often associated with that of viral and bacterial pathogens, which ultimately leads to colony collapse. Careful control of the parasitic load is therefore necessary to avoid the onset of these events. Although chemical treatments are often in easily and quickly administered formulations, in recent years, there have been increasingly frequent reports of the onset of drug resistance phenomena, which must lead to reconsidering their use. Furthermore, chemical compounds can easily accumulate in the food matrices of the hive, with possible risks for the final consumer. In such a condition, it is imperative to find alternative treatment solutions. Essential oils (EOs) prove to be promising candidates due to their good efficacy and good environmental biodegradability. In this study, the acaricidal efficacy of the EOs of Calamintha sylvatica Bromf., Calamintha nepeta Savi, Lavandula austroapennina N.G. Passal. Tundis & Upson and Mentha piperita L., extracted from botanical species belonging to the Lamiaceae family, was evaluated. The test chosen for the evaluation was residual toxicity by contact. The examined EOs were diluted in Acetone to a concentration of 2, 1 and 0.5 mg/mL. At the highest concentration, the EOs demonstrated an acaricidal activity equal to 52% for C. nepeta, 60% for C. sylvatica, 80% for L. austroapennina and 68% for M. piperita. Of the EOs tested, therefore, Lavender proves to be a good candidate for subsequent evaluations in semi-field and field studies.