Current Knowledge about Gastric Microbiota with Special Emphasis on Helicobacter pylori-Related Gastric Conditions.

The gastric milieu, because of its very low acidic pH, is very harsh for bacterial growth. The discovery of Helicobacter pylori (H.p.) has opened a new avenue for studies on the gastric microbiota, thus indicating that the stomach is not a sterile environment. Nowadays, new technologies of bacterial identification have demonstrated the existence of other microorganisms in the gastric habitat, which play an important role in health and disease. This bacterium possesses an arsenal of compounds which enable its survival but, at the same time, damage the gastric mucosa. Toxins, such as cytotoxin-associated gene A, vacuolar cytotoxin A, lipopolysaccharides, and adhesins, determine an inflammatory status of the gastric mucosa which may become chronic, ultimately leading to a gastric carcinoma. In the initial stage, H.p. persistence alters the gastric microbiota with a condition of dysbiosis, predisposing to inflammation. Probiotics and prebiotics exhibit beneficial effects on H.p. infection, and, among them, anti-inflammatory, antioxidant, and antibacterial activities are the major ones. Moreover, the association of probiotics with prebiotics (synbiotics) to conventional anti-H.p. therapy contributes to a more efficacious eradication of the bacterium. Also, polyphenols, largely present in the vegetal kingdom, have been demonstrated to alleviate H.p.-dependent pathologies, even including the inhibition of tumorigenesis. The gastric microbiota composition in health and disease is described. Then, cellular and molecular mechanisms of H.p.-mediated damage are clarified. Finally, the use of probiotics, prebiotics, and polyphenols in experimental models and in patients infected with H.p. is discussed.

Increased melanomacrophage centres in the liver of reproductively dysfunctional female greater amberjack Seriola dumerili (Risso, 1810).

The greater amberjack Seriola dumerili is a new aquaculture fish that may display reproductive dysfunctions. During extensive follicular atresia, which is a common reproductive dysfunction in females during vitellogenesis, part of the reabsorbed yolk returns to the liver to be metabolized and recycled. Melanomacrophage centres (MMCs) are aggregates of macrophage-like cells that play a role in the destruction, detoxification and recycling of endogenous and exogenous materials, and have been associated with systemic stress. Wild and captive-reared greater amberjack were sampled in the Mediterranean Sea during two different phases of the reproductive cycle. The liver of reproductively dysfunctional captive-reared females sampled during the spawning season showed a high density of both MMCs and apoptotic cells. A weak liver anti-cytochrome P450 monooxygenase 1A immunoreactivity was observed, suggesting that the examined fish were not exposed to environmental pollutants. We propose that the observed increase in MMCs and apoptosis in captive-reared fish was related to the hepatic overload associated to the metabolism of yolk proteins reabsorbed during extensive follicular atresia. Since follicular atresia is a frequent physiological and pathological event in teleosts, we suggest that the reproductive state should be always assessed when MMCs are used as markers of exposure to stress or pollutants.

Molecular and Cellular Substrates for the Friedreich Ataxia. Significance of Contactin Expression and of Antioxidant Administration.

In this study, the neural phenotype is explored in rodent models of the spinocerebellar disorder known as the Friedreich Ataxia (FA), which results from mutations within the gene encoding the Frataxin mitochondrial protein. For this, the M12 line, bearing a targeted mutation, which disrupts the Frataxin gene exon 4 was used, together with the M02 line, which, in addition, is hemizygous for the human Frataxin gene mutation (Pook transgene), implying the occurrence of 82-190 GAA repeats within its first intron. The mutant mice phenotype was compared to the one of wild type littermates in regions undergoing differential profiles of neurogenesis, including the cerebellar cortex and the spinal cord by using neuronal (ß-tubulin) and glial (Glial Fibrillary Acidic Protein) markers as well as the Contactin 1 axonal glycoprotein, involved in neurite growth control. Morphological/morphometric analyses revealed that while in Frataxin mutant mice the neuronal phenotype was significantly counteracted, a glial upregulation occurred at the same time. Furthermore, Contactin 1 downregulation suggested that changes in the underlying gene contributed to the disorder pathogenesis. Therefore, the FA phenotype implies an alteration of the developmental profile of neuronal and glial precursors. Finally, epigallocatechin gallate polyphenol administration counteracted the disorder, indicating protective effects of antioxidant administration.

Polyphenol Effects on Splenic Cytokine Response in Post-Weaning Contactin 1-Overexpressing Transgenic Mice.

BACKGROUND: In mice, postnatal immune development has previously been investigated, and evidence of a delayed maturation of the adaptive immune response has been detected. METHODS: In this study, the effects of red grape polyphenol oral administration on the murine immune response were explored using pregnant mice (TAG/F3 transgenic and wild type (wt) mice) as the animal model. The study was performed during pregnancy as well as during lactation until postnatal day 8. Suckling pups from polyphenol-administered dams as well as day 30 post-weaning pups (dietary-administered with polyphenols) were used. Polyphenol effects were evaluated, measuring splenic cytokine secretion. RESULTS: Phorbol myristate acetate-activated splenocytes underwent the highest cytokine production at day 30 in both wt and TAG/F3 mice. In the latter, release of interferon (IFN)-γ and tumor necrosis factor (TNF)-α was found to be higher than in the wt counterpart. In this context, polyphenols exerted modulating activities on day 30 TAG/F3 mice, inducing release of interleukin (IL)-10 in hetero mice while abrogating release of IL-2, IFN-γ, TNF-α, IL-6, and IL-4 in homo and hetero mice. CONCLUSION: Polyphenols are able to prevent the development of an inflammatory/allergic profile in postnatal TAG/F3 mice.

The influence of diet on anti-cancer immune responsiveness.

Immunotherapy has matured into standard treatment for several cancers, but much remains to be done to extend the reach of its effectiveness particularly to cancers that are resistant within each indication. This review proposes that nutrition can affect and potentially enhance the immune response against cancer. The general mechanisms that link nutritional principles to immune function and may influence the effectiveness of anticancer immunotherapy are examined. This represents also the premise for a research project aimed at identifying the best diet for immunotherapy enhancement against tumours (D.I.E.T project). Particular attention is turned to the gut microbiota and the impact of its composition on the immune system. Also, the dietary patterns effecting immune function are discussed including the value of adhering to a healthy diets such as the Mediterranean, Veg, Japanese, or a Microbiota-regulating diet, the very low ketogenic diet, which have been demonstrated to lower the risk of developing several cancers and reduce the mortality associated with them. Finally, supplements, as omega-3 and polyphenols, are discussed as potential approaches that could benefit healthy dietary and lifestyle habits in the context of immunotherapy.

Effects of thermal water inhalation in chronic upper respiratory tract infections in elderly and young patients.

BACKGROUND: Chronic upper respiratory tract infections (cURTI) are very frequent illnesses which occur at any age of life. In elderly, cURTI are complicated by immunosenescence, with involvement of lung immune responsiveness. RESULTS: In the present study, 51 elderly (age range: 66-86) and 51 young (age range 24-58) cURTI patients underwent a single cycle (two weeks) of inhalatory therapy with salt-bromide-iodine thermal water in the thermal station "Margherita di Savoia" (Margherita di Savoia, BAT, Italy). Peripheral blood serum cytokines and clinical assessment were performed before therapy (T0) and after six months (T1) and 12 months (T2) from inhalatory treatment. In both elderly and young patients, at baseline an increased release of T helper (h)1-related cytokines [interleukin (IL)-2 and interferon-γ] and of Th2-related cytokine (IL-4) was documented. Inhalatory treatment reduced the excessive secretion of all the above-cited cytokines. IL-10 values were above normality at all times considered in both groups of patients. In addition, an increase in IL-17 and IL-21 serum levels following therapy was observed in both groups of patients. Pro-inflammatory cytokine (IL-1ß, IL-6, IL-8 and tumor necrosis factor-α) baseline values were lower than normal values at T0 in both elderly and young cURTI patients. Their levels increased following inhalatory treatment. Clinically, at T2 a dramatic reduction of frequency of upper respiratory tract infections was recorded in both groups of patients. CONCLUSION: Thermal water inhalation is able to modulate systemic immune response in elderly and young cURTI patients, thus reducing excessive production of Th1 and Th2-related cytokines, on the one hand. On the other hand, increased levels of IL-21 (an inducer of Th17 cells) and of IL-17 may be interpreted as a protective mechanism, which likely leads to neutrophil recruitment in cURTI patients. Also restoration of pro-inflammatory cytokine release following inhalatory therapy may result in microbe eradication. Quite importantly, the maintenance of high levels of IL-10 during the follow-up would suggest a consistent regulatory role of this cytokine in attenuating the pro-inflammatory arm of the immune response.

CD4+ROR γ t++ and Tregs in a Mouse Model of Diet-Induced Nonalcoholic Steatohepatitis.

BACKGROUND AND AIMS: Inflammatory mediators that cross-talk in different metabolically active organs are thought to play a crucial role in the pathogenesis of Nonalcoholic Steatohepatitis (NASH). This study was aimed at investigating the CD4+RORγt+ T-helper cells and their counterpart, the CD4+CD25+FOXP3+ regulatory T cells in the liver, subcutaneous adipose tissue (SAT), and abdominal adipose tissue (AAT) in a high fat diet (HFD) mouse model. METHODS: C57BL6 mice were fed a HFD or a normal diet (ND). Liver enzymes, metabolic parameters, and liver histology were assessed. The expression of CD4+RORγt+ cells and regulatory T cells in different organs (blood, liver, AAT, and SAT) were analyzed by flow cytometry. Cytokine and adipokine tissue expression were studied by RT-PCR. RESULTS: Mice fed a HFD developed NASH and metabolic alterations compared to normal diet. CD4+RORγt++ cells were significantly increased in the liver and the AAT while an increase of regulatory T cells was observed in the SAT of mice fed HFD compared to ND. Inflammatory cytokines were also upregulated. CONCLUSIONS: CD4+RORγt++ cells and regulatory T cells are altered in NASH with a site-specific pattern and correlate with the severity of the disease. These site-specific differences are associated with increased cytokine expression.

Current View on Major Natural Compounds Endowed with Antibacterial and Antiviral Effects.

Nowadays, infectious diseases of bacterial and viral origins represent a serious medical problem worldwide. In fact, the development of antibiotic resistance is responsible for the emergence of bacterial strains that are refractory even to new classes of antibiotics. Furthermore, the recent COVID-19 pandemic suggests that new viruses can emerge and spread all over the world. The increase in infectious diseases depends on multiple factors, including malnutrition, massive migration of population from developing to industrialized areas, and alteration of the human microbiota. Alternative treatments to conventional antibiotics and antiviral drugs have intensively been explored. In this regard, plants and marine organisms represent an immense source of products, such as polyphenols, alkaloids, lanthipeptides, and terpenoids, which possess antibacterial and antiviral activities. Their main mechanisms of action involve modifications of bacterial cell membranes, with the formation of pores, the release of cellular content, and the inhibition of bacterial adherence to host cells, as well as of the efflux pump. Natural antivirals can interfere with viral replication and spreading, protecting the host with the enhanced production of interferon. Of note, these antivirals are not free of side effects, and their administration to humans needs more research in terms of safety. Preclinical research with natural antibacterial and antiviral compounds confirms their effects against bacteria and viruses, but there are still only a few clinical trials. Therefore, their full exploitation and more intensive clinical studies represent the next steps to be pursued in this area of medicine.

Associations between "Cancer Risk", "Inflammation" and "Metabolic Syndrome": A Scoping Review.

BACKGROUND: Individuals with metabolic syndrome exhibit simultaneously pro-thrombotic and pro-inflammatory conditions which more probably can lead to cardiovascular diseases progression, type 2 diabetes mellitus, and some types of cancer. The present scoping review is aimed at highlighting the association between cancer risk, inflammation, and metabolic syndrome. METHODS: A search strategy was performed, mixing keywords and MeSH terms, such as "Cancer Risk", "Inflammation", "Metabolic Syndrome", "Oncogenesis", and "Oxidative Stress", and matching them through Boolean operators. A total of 20 manuscripts were screened for the present study. Among the selected papers, we identified some associations with breast cancer, colorectal cancer, esophageal adenocarcinoma, hepatocellular carcinoma (HCC), and cancer in general. CONCLUSIONS: Cancer and its related progression may also depend also on a latent chronic inflammatory condition associated with other concomitant conditions, including type 2 diabetes mellitus, metabolic syndrome, and obesity. Therefore, prevention may potentially help individuals to protect themselves from cancer.

A Bird's-Eye View of the Pathophysiologic Role of the Human Urobiota in Health and Disease: Can We Modulate It?

For a long time, urine has been considered sterile in physiological conditions, thanks to the particular structure of the urinary tract and the production of uromodulin or Tamm-Horsfall protein (THP) by it. More recently, thanks to the development and use of new technologies, i.e., next-generation sequencing and expanded urine culture, the identification of a microbial community in the urine, the so-called urobiota, became possible. Major phyla detected in the urine are represented by Firmicutes, Bacteroidetes, Proteobacteria, and Actinobacteria. Particularly, the female urobiota is largely represented by Lactobacillus spp., which are very active against urinary pathogenic Escherichia (E.) coli (UPEC) strains via the generation of lactic acid and hydrogen peroxide. Gut dysbiosis accounts for recurrent urinary tract infections (UTIs), so-called gut-bladder axis syndrome with the formation of intracellular bacterial communities in the course of acute cystitis. However, other chronic urinary tract infections are caused by bacterial strains of intestinal derivation. Monomicrobial and polymicrobial infections account for the outcome of acute and chronic UTIs, even including prostatitis and chronic pelvic pain. E. coli isolates have been shown to be more invasive and resistant to antibiotics. Probiotics, fecal microbial transplantation, phage therapy, antimicrobial peptides, and immune-mediated therapies, even including vaccines for the treatment of UTIs, will be described.

Blood Microbiota and Its Products: Mechanisms of Interference with Host Cells and Clinical Outcomes.

In healthy conditions, blood was considered a sterile environment until the development of new analytical approaches that allowed for the detection of circulating bacterial ribosomal DNA. Currently, debate exists on the origin of the blood microbiota. According to advanced research using dark field microscopy, fluorescent in situ hybridization, flow cytometry, and electron microscopy, so-called microbiota have been detected in the blood. Conversely, others have reported no evidence of a common blood microbiota. Then, it was hypothesized that blood microbiota may derive from distant sites, e.g., the gut or external contamination of blood samples. Alteration of the blood microbiota's equilibrium may lead to dysbiosis and, in certain cases, disease. Cardiovascular, respiratory, hepatic, kidney, neoplastic, and immune diseases have been associated with the presence of Gram-positive and Gram-negative bacteria and/or their products in the blood. For instance, lipopolysaccharides (LPSs) and endotoxins may contribute to tissue damage, fueling chronic inflammation. Blood bacteria can interact with immune cells, especially with monocytes that engulf microorganisms and T lymphocytes via spontaneous binding to their membranes. Moreover, LPSs, extracellular vesicles, and outer membrane vesicles interact with red blood cells and immune cells, reaching distant organs. This review aims to describe the composition of blood microbiota in healthy individuals and those with disease conditions. Furthermore, special emphasis is placed on the interaction of blood microbiota with host cells to better understand disease mechanisms.

Exploitation of Natural By-Products for the Promotion of Healthy Outcomes in Humans: Special Focus on Antioxidant and Anti-Inflammatory Mechanisms and Modulation of the Gut Microbiota.

Daily, a lot of food is wasted, and vegetables, fruit, and cereals as well as marine products represent the major sources of unwanted by-products. The sustainability, waste recovery, and revalorization of food by-products have been proposed as the main goals of the so-called circular economy. In fact, food wastes are enriched in by-products endowed with beneficial effects on human health. Grape, olives, vegetables, and rice contain different compounds, such as polyphenols, dietary fibers, polysaccharides, vitamins, and proteins, which exert antioxidant and anti-inflammatory activities, inhibiting pro-oxidant genes and the Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-kß) pathway, as demonstrated by in vitro and in vivo experiments. Dietary fibers act upon the gut microbiota, expanding beneficial bacteria, which contribute to healthy outcomes. Furthermore, marine foods, even including microalgae, arthropods, and wastes of fish, are rich in carotenoids, polyphenols, polyunsaturated fatty acids, proteins, and chitooligosaccharides, which afford antioxidant and anti-inflammatory protection. The present review will cover the major by-products derived from food wastes, describing the mechanisms of action involved in the antioxidant and anti-inflammatory activities, as well as the modulation of the gut microbiota. The effects of some by-products have also been explored in clinical trials, while others, such as marine by-products, need more investigation for their full exploitation as bioactive compounds in humans.

The pathogenic role of the immune system in erectile dysfunction and Peyronie's disease: focusing on immunopathophysiology and potential therapeutic strategies.

INTRODUCTION: Erectile dysfunction (ED) represents the major cause of male sexual dysfunction, which is often associated with obesity, diabetes mellitus, atherosclerotic cardiovascular disease, and cigarette smoking. Peyronie's disease is a chronic disorder associated with irreversible fibrotic damage of the tunica albuginea leading to ED, painful erection, coital disturbance, and physical and social complaints. Both conditions are characterized by chronic inflammation, oxidative stress, and significant changes in intracavernous hydrodynamics. In this scenario, oxidized lipoproteins, M1-polarized macrophages, proinflammatory cytokines (such as the tumor necrosis factor α), endothelial nitric oxide synthase, penile smooth muscle cells, and toll-like receptors represent the main triggers of the inflammatory process in ED. Phosphodiesterase-5 inhibitors are the most common treatment for ED. This treatment is used intermittently, as it is conceived as a symptomatic and not curative therapy. Moreover, not all patients respond to phosphodiesterase-5 inhibitors (35%-85%), particularly those with dysmetabolic phenotypes. Additional or alternative treatments are therefore desirable, mostly in refractory cases. OBJECTIVES: In this review, we describe the immune-mediated pathogenesis of ED and Peyronie's disease (PD). In our literature search we placed particular emphasis on potentially practical therapeutic approaches, including natural products (such as polyphenols), due to their anti-inflammatory and antioxidant activities, stem cell therapy, and platelet-derived preparations. METHODS: We searched PubMed/MEDLINE, Web of Science, Scopus, Cochrane Library, Google Scholar, and institutional websites. Original studies, narrative reviews, systematic reviews, and meta-analyses written in English were searched, screened, and selected. RESULTS: In animal models of ED and PD, therapeutic approaches, including anti-inflammatory and antioxidant agents, stem cell therapy, and platelet-derived preparations, have provided positive results, including improved penile function, reduced inflammation and oxidative stress, and promotion of tissue repair. However, clinical evidence of improvement in human patients is still insufficient. CONCLUSION: Promising results for treating ED and PD have been shown in preclinical and pilot clinical studies, but specific clinical trials are needed to validate the efficacy of these therapeutic approaches in men with ED.

Healthy Diets and Lifestyles in the World: Mediterranean and Blue Zone People Live Longer. Special Focus on Gut Microbiota and Some Food Components.

Longevity has been associated with healthy lifestyles, including some dietary regimens, such as the Mediterranean diet (MedDiet) and the Blue Zone (BZ) diets. MedDiet relies on a large consumption of fruit, vegetables, cereals, and extra-virgin olive oil, with less red meat and fat intake. Four major BZ have been recognized in the world, namely, Ogliastra in Sardinia (Italy), Ikaria (Greece), the Peninsula of Nicoya (Costa Rica), and Okinawa (Japan). Extreme longevity in these areas has been associated with correct lifestyles and dietary regimens. Fibers, polyphenols, beta-glucans, and unsaturated fatty acids represent the major constituents of both MedDiet and BZ diets, given their anti-inflammatory and antioxidant activities. Particularly, inhibition of the NF-kB pathway, with a reduced release of pro-inflammatory cytokines, and induction of T regulatory cells, with the production of the anti-inflammatory cytokine, interleukin- 10, are the main mechanisms that prevent or attenuate the "inflammaging." Notably, consistent physical activity, intense social interactions, and an optimistic attitude contribute to longevity in BZD areas. Commonalities and differences between MedDIet and BZ diets will be outlined, with special reference to microbiota and food components, which may contribute to longevity.

Current Views about the Inflammatory Damage Triggered by Bacterial Superantigens and Experimental Attempts to Neutralize Superantigen-Mediated Toxic Effects with Natural and Biological Products.

Superantigens, i.e., staphylococcal enterotoxins and toxic shock syndrome toxin-1, interact with T cells in a different manner in comparison to conventional antigens. In fact, they activate a larger contingent of T lymphocytes, binding outside the peptide-binding groove of the major histocompatibility complex class II. Involvement of many T cells by superantigens leads to a massive release of pro-inflammatory cytokines, such as interleukin (IL)-1, IL-2, IL-6, tumor necrosis factor-alpha and interferon-gamma. Such a storm of mediators has been shown to account for tissue damage, multiorgan failure and shock. Besides conventional drugs and biotherapeutics, experiments with natural and biological products have been undertaken to attenuate the toxic effects exerted by superantigens. In this review, emphasis will be placed on polyphenols, probiotics, beta-glucans and antimicrobial peptides. In fact, these substances share a common functional denominator, since they skew the immune response toward an anti-inflammatory profile, thus mitigating the cytokine wave evoked by superantigens. However, clinical applications of these products are still scarce, and more trials are needed to validate their usefulness in humans.

Long-acting glucagon-like peptide 1 receptor agonists boost erectile function in men with type 2 diabetes mellitus complaining of erectile dysfunction: A retrospective cohort study.

INTRODUCTION: The pharmacological management of erectile dysfunction (ED) in type 2 diabetes (T2D) is challenging as ED has a multifactorial etiology. The therapeutic potential of certain antihyperglycemic medications, such as glucagon-like peptide 1 receptor agonists (GLP-1RAs), has yet to be entirely studied in this setting. MATERIAL AND METHODS: A retrospective cohort study was conducted on 108 outpatients (median age 60 [56, 65] years) with T2D complaining of ED. Data were extracted from a database referring to patients with a 1-year follow-up on stable treatment with metformin alone (n = 45) and GLP-1RAs as an add-on to metformin (n = 63). Erectile function was assessed by the 5-item International Index of Erectile Function (IIEF5) at baseline and after 1 year of stable treatment . Values were compared between baseline (T0) and after 12 months of treatment (T12). RESULTS: ED was confirmed in all at baseline, with an IIEF5 score range between 13 and 19 points. After 12 months of treatment, glucose management was better in patients treated with GLP-1RAs plus metformin (HbA1c T0: 8.3 ± 0.2 vs. HbA1c T12: 7% ± 0.3%, p < 0.0001) than in those on metformin alone (HbA1c T0: 7 ± 0.5 vs. HbA1c T12: 7.3 ± 0.4, p = 0.0007). GLP-1RAs plus metformin over metformin alone resulted in a significant weight loss (-5.82 ± 0.69 kg, p < 0.0001), reduction in waist circumference (-4.99 ± 0.6 cm, p < 0.0001), improvement in HbA1c (-0.56% ± 0.13%, p < 0.0001), and fasting plasma glucose (-25.54 ± 3.09 mg/dL, p < 0.0001), increase in total (+41.41 ± 6.11 ng/dL, p < 0.0001) and free (0.44 ± 0.09 ng/dL, p < 0.0001) testosterone levels, and gain in self-reported erectile function (IIEF5 score: +2.26 ± 0.26, p < 0.0001). The gain in the IIEF5 score was more relevant in patients with higher baseline IIEF5 score (estimated coefficient: 0.16 ± 0.08, p = 0.045), those having carotid stenosis (0.50 ± 0.24, p = 0.045), and showing weight loss from baseline (-0.08 ± 0.03, p = 0.013). The leading determinant of the final IIEF5 score was a 1-year treatment with GLP-1RAs plus metformin over metformin alone (2.74 ± 0.53, p < 0.0001). DISCUSSION: GLP-1RAs plus metformin over metformin alone improved ED regardless of different background characteristics of patients and partially irrespective of therapeutic targets achieved after 12 months of treatment. GLP-1RAs may have induced positive vasculature effects, resulting in improved erectile function in T2D. CONCLUSION: Due to the retrospective nature of the study, a potential cause-effect relationship between the use of GLP-1RAs plus metformin over metformin alone in improving ED cannot be verified and confirmed. Randomized clinical trials are needed to provide evidence supporting the use of GLP-1RAs for treating ED in T2D.

Current View on How Human Gut Microbiota Mediate Metabolic and Pharmacological Activity of Panax ginseng. A Scoping Review.

Panax ginseng is one of the most important remedies in ancient Eastern medicine. In the modern Western world, its reputation started to grow towards the end of the XIX century, but the rather approximate understanding of action mechanisms did not provide sufficient information for an appropriate use. Nowadays, Panax ginseng is frequently used in some pathological conditions, but the comprehension of its potential beneficial effects is still incomplete. The purpose of this study is to highlight the most recent knowledge on mechanisms and effects of ginseng active ingredients on the intestinal microbiota. The human microbiota takes part in the immune and metabolic balance and serves as the most important regulator for the control of local pathogens. This delicate role requires a complex interaction and reflects the interconnection with the brain- and the liver-axes. Thus, by exerting their beneficial effects through the intestinal microbiota, the active ingredients of Panax ginseng (glycosides and their metabolites) might help to ameliorate both specific intestinal conditions as well as the whole organism's homeostasis.

Predicting Factors of Worse Prognosis in COVID-19: Results from a Cross-sectional Study on 52 Inpatients Admitted to the Internal Medicine Department.

BACKGROUND: The initial phases of the COVID-19 pandemic posed a real need for clinicians to identify patients at risk of poor prognosis as soon as possible after hospital admission. AIM: The study aimed to assess the role of baseline anamnestic information, clinical parameters, instrumental examination, and serum biomarkers in predicting adverse outcomes of COVID-19 in a hospital setting of Internal Medicine. METHODS: Fifty-two inpatients consecutively admitted to the Unit of Internal Medicine "Baccelli," Azienda Ospedaliero - Universitaria Policlinico of Bari (February 1 - May 31, 2021) due to confirmed COVID-19 were grouped into two categories based on the specific outcome: good prognosis (n=44), patients discharged at home after the acute phase of the infection; poor prognosis, a composite outcome of deaths and intensive care requirements (n=8). Data were extracted from medical records of patients who provided written informed consent to participate. RESULTS: The two study groups had similar demographic, anthropometric, clinical, and radiological characteristics. Higher interleukin 6 (IL-6) levels and leucocyte count, and lower free triiodothyronine (fT3) levels were found in patients with poor than those with good prognosis. Higher IL-6 levels and leucocyte count, lower fT3 concentration, and pre-existing hypercholesterolemia were independent risk factors of poor outcomes in our study population. A predicting risk score, built by assigning one point if fT3 < 2 pg/mL, IL-6 >25 pg/mL, and leucocyte count >7,000 n/mm3, revealed that patients totalizing at least 2 points by applying the predicting score had a considerably higher risk of poor prognosis than those with scoring <2 points [OR 24.35 (1.32; 448), p = 0.03]. The weight of pre-existing hypercholesterolemia did not change the risk estimation. CONCLUSION: Four specific baseline variables, one anamnestic (pre-existing hypercholesterolemia) and three laboratory parameters (leucocyte count, IL-6, and fT3), were significantly associated with poor prognosis as independent risk factors. To prevent adverse outcomes, the updated 4-point score could be useful in identifying at-risk patients, highlighting the need for specific trials to estimate the safety and efficacy of targeted treatments.

Functional foods and nutraceuticals as therapeutic tools for the treatment of diet-related diseases.

In Western societies, the incidence of diet-related diseases is progressively increasing due to greater availability of hypercaloric food and a sedentary lifestyle. Obesity, diabetes, atherosclerosis, and neurodegeneration are major diet-related pathologies that share a common pathogenic denominator of low-grade inflammation. Functional foods and nutraceuticals may represent a novel therapeutic approach to prevent or attenuate diet-related disease in view of their ability to exert anti-inflammatory responses. In particular, activation of intestinal T regulatory cells and homeostatic regulation of the gut microbiota have the potential to reduce low-grade inflammation in diet-related diseases. In this review, clinical applications of polyphenol-rich functional foods and nutraceuticals in postprandial inflammation, obesity, and ageing will be discussed. We have placed special emphasis on polyphenols since they are broadly distributed in plants.

The interaction between gut microbiota and age-related changes in immune function and inflammation.

Intestinal microbiota and gut immune systems interact each other, maintaining a condition of homeostasis in the context of the intestinal habitat. However, both systems undergo modifications in elderly, thus accounting for a low grade inflammatory status which, in turn, may evolve toward more severe pathological conditions such as inflammatory bowel disease and colon rectal cancer. In addition, in western societies dietary habits may negatively influence the microbiota composition, also altering gut immune response which is per se impaired in elderly. In order to prevent the outcome of aged-related disease, supplementation of nutraceuticals able to correct abnormalities of both immune system and microbiota has become more frequent than in the past. In this respect, a better identification of components of the aged microbiota as well as a deeper analysis of gut mucosal immunity function should be pursued.