ABSTRACT
BACKGROUND: Numerous studies highlight the critical role that neural histamine plays in feeding behavior, which is controlled by central histamine H3 and H1 receptors. This is the fundamental motivation for the increased interest in creating histamine H3 receptor antagonists as anti-obesity medications. On the other hand, multiple other neurotransmitter systems have been identified as pharmacotherapeutic targets for obesity, including sigma-2 receptor systems. Interestingly, in our previous studies in the rat excessive eating model, we demonstrated a significant reduction in the development of obesity using dual histamine H3/sigma-2 receptor ligands. Moreover, we showed that compound KSK-94 (structural analog of Abbott's A-331440) reduced the number of calories consumed, and thus acted as an anorectic compound. Therefore, in this study, we extended the previous research and studied the influence of KSK-94 on adipose tissue collected from animals from our previous experiment. METHODS: Visceral adipose tissue was collected from four groups of rats (standard diet + vehicle, palatable diet + vehicle, palatable diet + KSK-94, and palatable diet + bupropion/naltrexone) and subjected to biochemical, histopathological, and immunohistochemical studies. RESULTS: The obtained results clearly indicate that compound KSK-94 prevented the hypertrophy and inflammation of visceral adipose tissue, normalized the levels of leptin, resistin and saved the total reduction capacity of adipose tissue, being more effective than bupropion/naltrexon in these aspects. Moreover, KSK-94 may induce browning of visceral white adipose tissue. CONCLUSION: Our study suggests that dual compounds with a receptor profile like KSK-94, i.e., targeting histamine H3 receptor and, to a lesser extent, sigma-2 receptor, could be attractive therapeutic options for patients at risk of developing obesity or with obesity and some metabolic disorders. However, more studies are required to determine its safety profile and the exact mechanism of action of KSK-94.
ABSTRACT
PURPOSE: Natural plant raw materials, previously underestimated in therapeutics, are becoming the subject of research for new applications in medicine. In our research, the hydroalcoholic extract of Isatis tinctoria leaf, rich in flavonoid compounds such as vicenin-2 and quercetin, was examined as a potential antidiabetic and neuroprotective agent. METHODS: The effect of the extract and its main flavonoid compounds on protein glycation, alpha-glucosidase activity, and acetylcholinesterase activity was tested. In vitro, in the mouse hippocampal neuronal cell line and in vivo, using a mouse model, the safety of the extract was screened for. RESULTS: Our experiments demonstrated significant inhibition of protein glycation, alpha-glucosidase activity, acetylcholinesterase activity, and ß-amyloid aggregation by the extract, in a concentration-dependent manner. The extract had a strong reducing effect and did not exhibit cytotoxicity up to a concentration of 25 mg/mL. Intraperitoneal administration of the extract to mice did not have negative effects on body mass, locomotor activity, coordination, and liver cell integrity. CONCLUSIONS: Our research sheds new light on this raw material and deepens knowledge of its activity. This may result in the recognition of its therapeutic effects and even in its introduction in the modern treatment of diseases characterized by pathological changes associated with hyperglycemia, oxidation, and inflammation.
Subject(s)
Hypoglycemic Agents , Neuroprotective Agents , Plant Extracts , Plant Leaves , Animals , Plant Extracts/pharmacology , Mice , Neuroprotective Agents/pharmacology , Neuroprotective Agents/isolation & purification , Hypoglycemic Agents/pharmacology , Plant Leaves/chemistry , Male , Cell Line , Amyloid beta-Peptides , Flavonoids/pharmacology , Flavonoids/isolation & purification , Acetylcholinesterase/metabolism , Phytochemicals/pharmacology , Phytochemicals/isolation & purification , Glycoside Hydrolase Inhibitors/pharmacology , Hippocampus/drug effects , Neurons/drug effects , alpha-Glucosidases/metabolismABSTRACT
The amphibian taxon includes three orders that present different morphological characteristics: Anura, Caudata, and Apoda. Their skin has a crucial role: it acts as an immune organ constituting a physical, chemical, immunological, and microbiological barrier to pathogen insult and conducts essential physiological processes. Amphibians have developed specialized features to protect the vulnerable skin barrier, including a glandular network beneath the skin surface that can produce antimicrobial and toxic substances, thus contributing to the defense against pathogens and predators. This study aims to characterize Langerhans cells in the skin of Lithobates catesbeianus (order: Anura; Shaw, 1802), Amphiuma means (order: Caudata; Garden, 1821), and Typhlonectes natans (order: Apoda; Fischer, 1880) with the following antibodies: Langerin/CD207 (c-type lectin), Major Histocompatibility Complex (MHC)II, and Toll-like receptor (TLR)2 (expressed by different types of DCs). Our results showed Langerhans cells positive for Langerin CD/207 in the epidermis of the three species; moreover, some antigen-presenting cells (APCs) in the connective tissue expressed TLR2 and MHCII. The distribution of the Langerhans cells is very similar in the three amphibians examined, despite their different habitats. A greater knowledge of the amphibian immune system could be useful to better understand the phylogeny of vertebrates and to safeguard amphibians from population declines. Furthermore, the similarities between amphibians' and human skin concerning immunological features may be useful in both biology and translational medicine.
ABSTRACT
The striped dolphin (Stenella coeruleoalba) is a medium-sized pelagic dolphin with a single external nasal opening (blowhole) located in the rostral and dorsal regions of the skull. The nasal cavity is divided into three sections: the olfactory, respiratory, and vestibular areas. The surface epithelium lining the regio vestibularis is the first tissue in the nose to be directly affected by environmental antigens. Cetaceans have a significant amount of mucosa-associated lymphoid tissue (MALT) located throughout their bodies. The lymphoid tissue found in the nasal mucosa is known as nose- or nasopharynx-associated lymphoid tissue (NALT). NALT has not yet been studied in dolphins, but it has been identified and documented in humans and laboratory rodents. This study utilized toll-like receptor 2 (TLR2), CD4, Langerin/CD207, and inducible nitric oxide synthase to characterize, for the first time, immune cells in the mucosal regio vestibularis of the S. coeruleoalba nasal cavity using confocal microscopy immunofluorescence techniques. The findings revealed scattered immune cells immunoreactive to the tested antibodies, present in both the epithelial tissue lining the nasal cavity vestibulum and the underlying connective tissue. This study enhances our comprehension of the immune system of cetaceans. RESEARCH HIGHLIGHTS: This study provides new insights into NALT in S. coeruleoalba. This research deepens the knowledge of the skin of cetaceans.
Subject(s)
Immunohistochemistry , Lymphoid Tissue , Nasal Cavity , Stenella , Animals , Nasal Cavity/anatomy & histology , Lymphoid Tissue/anatomy & histology , Stenella/anatomy & histology , Nasal Mucosa , Microscopy, Confocal , Nitric Oxide Synthase Type II/metabolism , CD4 Antigens/metabolism , CD4 Antigens/analysis , Dolphins/anatomy & histologyABSTRACT
Crohn's disease (CD) and ulcerative colitis (UC) are both inflammatory bowel diseases (IBD). Unlike UC, which is limited to the mucosa of the colon, CD inflammation is characterized by chronic mucosal ulcerations affecting the entire gastrointestinal tract. Goblet cells (GCs) can be found in some lining epithelia, particularly in the respiratory and digestive tracts. GCs represent the main source of mucin that are the significant components of the mucus layer; hypertrophy of GCs and an increase in mucin production are observed in many enteric infections. The cytoplasm of goblet cells may also contain neuropeptides, such as serotonin, that can be altered in inflammatory bowel disease (IBD). The defense system of the gut is represented by the intestinal mucosal barrier, its protective function is strictly connected to the regulation of the mucus layer and the coordination of the neuro-immune response. Paraformaldehyde-fixed intestinal tissues, obtained from fifteen patients with Crohn's disease, were analyzed by immunostaining for MUC2, MUC4, 5-HT, and VAChT. This study aims to define the link between neuropeptides and mucins in mucous cells and their involvement in the inflammation process. Our results showed in mucous cells of Crohn's disease (CD) patients a high expression of MUC4 and a decrease in the expression of vesicular acetylcholine transporter (VAChT) demonstrating the presence of an inflammatory state.
Subject(s)
Colitis, Ulcerative , Crohn Disease , Inflammatory Bowel Diseases , Neuropeptides , Humans , Crohn Disease/metabolism , Mucins/metabolism , Goblet Cells/metabolism , Inflammatory Bowel Diseases/metabolism , Colitis, Ulcerative/metabolism , Intestinal Mucosa/metabolism , Inflammation/metabolism , Neuropeptides/metabolismABSTRACT
The internal defense system of mollusks represents an efficient protection against pathogens and parasites, involving several biological immune processes, such as phagocytosis, encapsulation, cytotoxicity, and antigenic recognition of self/non-self. Mollusks possess professional, migratory, and circulating cells that play a key role in the defense of the organism, the hemocytes. Several studies have been performed on hemocytes from different mollusks, but, to date, these cells are still scarcely explored. Different hemocyte populations have been found, according to the presence or absence of granules, size, and the species of mollusks studied. Our study aims to deepen the knowledge of the hemocytes of the gastropod Aplysia depilans using morphological techniques and light and confocal microscopy, testing Toll-like receptor 2, inducible nitric oxide synthetase, and nicotinic acetylcholine receptor alpha 7 subunit. Our results show two hemocyte populations distinguishable by size, and presence/absence of granules in the cytoplasm, strongly positive for the antibodies tested, suggesting for the first time the presence of these receptors on the surface of sea hare hemocytes by immunohistochemistry. These data help in the understanding of the immune system of this gastropod, providing additional data for comprehending the evolution of the defense response in metazoan phylogenesis.
Subject(s)
Aplysia , Gastropoda , Animals , Hemocytes , Mollusca , PhagocytosisABSTRACT
Heterotis niloticus is a basal teleost, belonging to the Osteoglossidae family, which is widespread in many parts of Africa. The digestive tract of H. niloticus presents similar characteristics to those of higher vertebrates, exhibiting a gizzard-like stomach and lymphoid aggregates in the intestinal lamina propria. The adaptive immune system of teleost fish is linked with each of their mucosal body surfaces. In fish, the gut-associated lymphoid tissue (GALT) is generally a diffuse immune system that represents an important line of defense against those pathogens inhabiting the external environment that can enter through food. The GALT comprises intraepithelial lymphocytes, which reside in the epithelial layer, and lamina propria leukocytes, which consist of lymphocytes, macrophages, granulocytes, and dendritic-like cells. This study aims to characterize, for the first time, the leukocytes present in the GALT of H. niloticus, by confocal immuno- fluorescence techniques, using specific antibodies: toll-like receptor 2, major histocompatibility complex class II, S100 protein, serotonin, CD4, langerin, and inducible nitric oxide synthetase. Our results show massive aggregates of immune cells in the thickness of the submucosa, arranged in circumscribed oval-shaped structures that are morphologically similar to the isolated lymphoid follicles present in birds and mammals, thus expanding our knowledge about the intestinal immunity shown by this fish.
Subject(s)
Intestinal Mucosa , Intestines , Animals , Immunohistochemistry , Fishes , Lymphoid Tissue , MammalsABSTRACT
The immune system of teleosts offers many ideas to deepen the immune mechanisms and cells in general. The use of zebrafish as an experimental model is increased in recent years, thanks to its genetic and anatomical characteristics. It is known that several natural compounds exert an action on the immune system, boosting it. Spirulina, a non-toxic blue-green alga, has been declared a superfood for its peculiar biological activities. In this study, we test the immunostimulant effect of spirulina on zebrafish liver macrophages by immunohistochemical analysis using optical and confocal microscopy. Our results have shown an increase in the number of macrophages after feeding with spirulina, furthermore, this natural 'superfood' can induce macrophages aggregation. These data not only provide information on the possible effect of this alga as a complementary feed on the immune cells of teleost, but also improve the knowledge of the immune mechanisms of vertebrates.
Subject(s)
Spirulina , Zebrafish , Animals , Spirulina/chemistry , Liver , MacrophagesABSTRACT
Hemp seed flour (HSF) is a by-product of the hemp oil production process and is a valuable source of protein, dietary fiber, minerals, and vitamins. In line with sustainable food production and a circular economy, this research aimed to utilize HSF as fortifying ingredient in the production of gnocchi, a typical Italian potato-based fresh pasta, and to investigate the effects of the addition on the quality and consumers' acceptability of the enriched products. Three formulations have been developed using 5-20% HSF in substitution of soft wheat flour. Nutritional value, cooking quality, color, texture and sensory profile, and the consumers' acceptability of gnocchi samples were evaluated, as well as the functional properties of pure and composite flours and the HSF aroma compounds. HSF addition allowed to enhance the nutritional value of gnocchi, gaining the nutritional claim of "source of fiber" in case of formulations with ≥10% of HSF. Moreover, the fortified gnocchi had a high technological quality in terms of cooking loss, cooking resistance and textural properties, and average sensory quality; however, the vegetable and hemp odor and the bitter taste make them not well appreciated by consumers highlighting the need for improving the HSF sensory quality for consumers' satisfaction.
ABSTRACT
In December 2019, a new single-stranded RNA coronavirus, SARS-CoV-2, appeared in China and quickly spread around the world leading to a pandemic. Infection with SARS-CoV-2 generates symptoms ranging from asymptomatic to severe, occasionally requiring hospitalization in intensive care units, and, in more severe cases, leading to death. Scientists and researchers around the world have made a real race against time to develop various vaccines to slow down and stop the spread of the virus. In addition to conventional viral vector vaccines, new generation mRNA vaccines, BNT152b2 (Comirnaty) and mRNA-1273 (Spikevax), have been developed respectively by Pfizer/BioNTech and Moderna. These vaccines act on immune cells to induce an immune response with the production of specific antibodies against Spike protein of SARS-CoV-2, and to stimulate the differentiation of T and B memory cells. The objective of this review is to provide a detailed picture of the validity of these new vaccines and the safety of vaccination. Not only was the immunogenic effect of mRNA vaccines evaluated, but also the psychosocial impact they had on the population. The data collected show that this type of vaccine can also be an excellent candidate for future treatment and eradication of possible new pathologies with viral and non-viral etiology.
Subject(s)
COVID-19 Vaccines , COVID-19 , Immunogenicity, Vaccine , Vaccination , Humans , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , COVID-19 Vaccines/immunology , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Vaccination/psychologyABSTRACT
The immune system is highly dynamic and susceptible to many alterations throughout pregnancy. Since December 2019, a pandemic caused by coronavirus disease 19 (COVID-19) has swept the globe. To contain the spread of COVID-19, immediate measures such as quarantine and isolation were implemented. These containment measures have contributed to exacerbate situations of anxiety and stress, especially in pregnant women, who are already particularly anxious about their condition. Alterations in the psychological state of pregnant women are related to alterations in the immune system, which is more vulnerable under stress. COVID-19 could therefore find fertile soil in these individuals and risk more severe forms. Normally a controlled dietary regimen is followed during pregnancy, but the use of particular vitamins and micronutrients can help counteract depressive-anxiety states and stress, can improve the immune system, and provide an additional weapon in the defense against COVID-19 to bring the pregnancy to fruition. This review aims to gather data on the impact of COVID-19 on the immune system and psychological condition of pregnant women and to assess whether some micronutrients can improve their psychophysical symptoms.
Subject(s)
COVID-19 , Pandemics , Anxiety/psychology , COVID-19/epidemiology , Depression/diagnosis , Depression/epidemiology , Female , Humans , Immune System , Micronutrients , Pregnancy , Pregnant Women/psychology , SARS-CoV-2 , Stress, Psychological/psychologyABSTRACT
In recent years, the use of natural compounds as adjuvant treatments and alternatives to traditional pharmacological therapies has become increasingly popular. These compounds have a wide range of biological effects, such as: antioxidant, anti-aging, hypocholesterolizing, hypoglycemic, antitumoral, antidepressant, anxiolytic activity, etc. Almost all of these compounds are easily available and are contained in different foods. At the end of 2019 the Coronavirus SARS-CoV-2 appeared in China and quickly spread throughout the world, causing a pandemic. The most common symptoms of this infection are dry cough, fever, dyspnea, and in severe cases bilateral interstitial pneumonia, with consequences that can lead to death. The nations, in trying to prevent the spread of infection, have imposed social distancing and lockdown measures on their citizens. This had a strong psychological-social impact, leading to phobic, anxious and depressive states. Pharmacological therapy could be accompanied by treatment with several natural compounds, such as vitamins, baicalein, zinc and essential oils. These compounds possess marked immunostimulant activity, strengthening the immune response and mitigating interactions between the virus and the host cell. They also have an antidepressant effect, acting on certain neurotransmitters.
Subject(s)
COVID-19 Drug Treatment , Humans , SARS-CoV-2 , Adjuvants, Immunologic/pharmacology , Communicable Disease Control , Antidepressive Agents/pharmacologyABSTRACT
The Olea europaea L. is a very well-known and widely used plant, especially for its nutritional qualities. Its extracts from leaves and fruits are widely used in contrasting and preventing various pathologies. In this review, the collected data highlight important chemical analyses and biological effects of this plant extracts. It exhibits cholesterol-lowering, hypoglycemic, cytotoxic, antibacterial, neuroprotective, antioxidant, anti-inflammatory and hypotensive activities. The results show that extracts from O. europaea could be used as a food additive in the supplementary treatment of many diseases.