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A severe condition of sepsis can be a complication of necrotizing enterocolitis (NEC), which can occur in premature infants and becomes a medical challenge in the neonatal intensive care unit (NICU). It is a multifactorial intestinal disease (can affect both the small and large intestine) that can lead to ischemia of the intestinal tissues that evolves into acute organ necrosis. One of these factors is that different types of nutrition can influence the onset or the progression of the disease. Cow-milk-based infant formulas have been shown to cause it in premature infants more frequently than human milk. Recently, nutrition has been shown to be beneficial after surgery. Several issues still under study, such as the pathogenesis and the insufficient and often difficult therapeutic approach, as well as the lack of a common and effective prevention strategy, make this disease an enigma in daily clinical practice. Recent studies outlined the emerging role of the host immune system and resident gut microbiota, showing their close connection in NEC pathophysiology. In its initial stages, broad-spectrum antibiotics, bowel rest, and breastfeeding are currently used, as well as probiotics to help the development of the intestinal microbiota and its eubiosis. This paper aims to present the current knowledge and potential fields of research in NEC pathophysiology and therapeutic assessment.

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.

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.

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-kβ) 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.

Ginseng was the most revered of the herbs in ancient times in China, Korea, Japan, America. Ginseng was discovered over 5000 years ago in the mountains of Manchuria, China. References to ginseng are found in books dating back more than two millennia. It is revered by the Chinese people as it is considered a herb for everything use and therefore for a wide range of diseases (currently its Latin name derived from the Greek panacea, meanings, that is, for everything). So, it was used exclusively by the Chinese Emperor's, and they were willing to pay the price without problems. Increasing its fame, ginseng brought a flourishing international trade that allowed Korea to supply China with silk and medicines in exchange for wild ginseng and later along with what grows in America.

Metabolic syndrome (MetS) is a combination of metabolic disorders that concurrently act as factors promoting systemic pathologies such as atherosclerosis or diabetes mellitus. It is now believed to encompass six main interacting conditions: visceral fat, imbalance of lipids (dyslipidemia), hypertension, insulin resistance (with or without impairing both glucose tolerance and fasting blood sugar), and inflammation. In the last 10 years, there has been a progressive interest through scientific research investigations conducted in the field of metabolomics, confirming a trend to evaluate the role of the metabolome, particularly the intestinal one. The intestinal microbiota (IM) is crucial due to the diversity of microorganisms and their abundance. Consequently, IM dysbiosis and its derivate toxic metabolites have been correlated with MetS. By intervening in these two factors (dysbiosis and consequently the metabolome), we can potentially prevent or slow down the clinical effects of the MetS process. This, in turn, may mitigate dysregulations of intestinal microbiota axes, such as the lung axis, thereby potentially alleviating the negative impact on respiratory pathology, such as the chronic obstructive pulmonary disease. However, the biomolecular mechanisms through which the IM influences the host’s metabolism via a dysbiosis metabolome in both normal and pathological conditions are still unclear. In this study, we seek to provide a description of the knowledge to date of the IM and its metabolome and the factors that influence it. Furthermore, we analyze the interactions between the functions of the IM and the pathophysiology of major metabolic diseases via local and systemic metabolome’s relate endotoxemia.

The use of innovative approaches to elucidate the pathophysiological mechanisms of autoimmune diseases, as well as to further study of the factors which can have either a positive or negative effect on the course of the disease, is essential. In this line, the development of new molecular techniques and the creation of the Human Genome Program have allowed access to many more solutions to the difficulties that exist in the identification and characterization of the microbiome, as well as changes due to various factors. Such innovative technologies can rekindle older hypotheses, such as molecular mimicry, allowing us to move from hypothesis to theory and from correlation to causality, particularly regarding autoimmune diseases and dysbiosis of the microbiota. For example, Prevotella copri appears to have a strong association with rheumatoid arthritis; it is expected that this will be confirmed by several scientists, which, in turn, will make it possible to identify other mechanisms that may contribute to the pathophysiology of the disease. This article seeks to identify new clues regarding similar correlations between autoimmune activity and the human microbiota, particularly in relation to qualitative and quantitative microbial variations therein.

The female genital tract (FGT) performs several functions related to reproduction, but due to its direct exposure to the external environment, it may suffer microbial infections. Both the upper (uterus and cervix) and lower (vagina) FGT are covered by an epithelium, and contain immune cells (macrophages, dendritic cells, T and B lymphocytes) that afford a robust protection to the host. Its upper and the lower part differ in terms of Lactobacillus spp., which are dominant in the vagina. An alteration of the physiological equilibrium between the local microbiota and immune cells leads to a condition of dysbiosis which, in turn, may account for the outcome of FGT infection. Aerobic vaginitis, bacterial vaginosis, and Chlamydia trachomatis are the most frequent infections, and can lead to severe complications in reproduction and pregnancy. The use of natural products, such as probiotics, polyphenols, and lactoferrin in the course of FGT infections is an issue of current investigation. In spite of positive results, more research is needed to define the most appropriate administration, according to the type of patient.

This article is intended to deepen our knowledge to date regarding the functions of the resident microbiota/microbiome in the urinary system for human health and disease. First, we sought to report the general characteristics (composition and stability) of the normal urinary system microbiota in the different anatomical sites in relation to some factors such as the effect of age, gender and diet, analyzing in detail the functions and the composition of the microbiota in the light of current knowledge. Several pieces of evidence suggest the importance of preserving the micro-ecosystem of the urinary system, and in some cases their relationship with diseases is important for maintaining human health is well understood. The female and male reproductive microbiota have mainly been studied over the past decade. In the past, the arrest was thought to have taken place in a sterile environment. Microorganisms of the microbiota form biofilms, three-dimensional structures, that differ in the reproductive organs and interact with both gametes and the embryo as well as with maternal tissues. These biofilms from the reproductive system also interact with others, such as that of the gastrointestinal tract. Reduction in its diversity intestinal microbiota can disrupt estrogen metabolism and affect the reproductive microbiota. It is therefore understood that its quantitative and qualitative identification is important for microbiota, but also the study of the structures formed by the microorganisms. A dysbiosis with local or systemic causes can lead to serious diseases. The role of probiotics in maintaining microbial population harmony (eubiosis) and preventing certain pathologies of the urinary and reproductive system was also investigated. A negative variation in the qualitative and quantitative composition of certain strains of microorganisms (dysbiosis) due to local or systemic causes can even lead to serious diseases. The role of probiotics in maintaining the healthy balance of microorganism populations (eubiosis), and thus in the prevention of certain pathologies of the urinary and reproductive system, has also been studied.

Several studies have shown that the gut microbiota influences behavior and, in turn, changes in the immune system associated with symptoms of depression or anxiety disorder may be mirrored by corresponding changes in the gut microbiota. Although the composition/function of the intestinal microbiota appears to affect the central nervous system (CNS) activities through multiple mechanisms, accurate epidemiological evidence that clearly explains the connection between the CNS pathology and the intestinal dysbiosis is not yet available. The enteric nervous system (ENS) is a separate branch of the autonomic nervous system (ANS) and the largest part of the peripheral nervous system (PNS). It is composed of a vast and complex network of neurons which communicate via several neuromodulators and neurotransmitters, like those found in the CNS. Interestingly, despite its tight connections to both the PNS and ANS, the ENS is also capable of some independent activities. This concept, together with the suggested role played by intestinal microorganisms and the metabolome in the onset and progression of CNS neurological (neurodegenerative, autoimmune) and psychopathological (depression, anxiety disorders, autism) diseases, explains the large number of investigations exploring the functional role and the physiopathological implications of the gut microbiota/brain axis.

Background: The widely variable clinical manifestations of SARS-CoV2 disease (COVID-19) range from asymptomatic infections to multiple organ failure and death. Among the organs affected is the heart. This does not only affect people who already have previous cardiovascular problems, but also healthy people. This is a reason not to overlook any symptoms or to perform targeted examinations, even if apparently unrelated to the heart, for quick recognition and timely therapy. Aim of the study: This review recapitulates the current state of knowledge on the potential mechanisms and manifestation of myocarditis in patients with COVID-19 infection. Methods: A web-based search of published data was performed for all relevant studies on patients diagnosed with a COVID-19-induced acute myocarditis, and a total of 50 reports were included. The analysis of the studies evaluated highlights a male predominance, with the average age of patients being 55 years. The most common presenting symptoms included fever, shortness of breath, cough, and chest pain. Among ECG changes, non-specific ST-segment and T-wave amplitude alterations and ventricular tachycardia episodes were reported. Finally, we wanted to use a general evaluation without distinguishing between various countries, taking into consideration only the peer or reviewer, regardless of the declared value of the journals that have been published. Results and critical findings: The most common presenting symptoms included fever, shortness of breath, cough, and chest pain. Among ECG changes, non-specific ST-segment and T-wave amplitude alterations and ventricular tachycardia episodes were reported. In most patients, elevated levels of cardiac and inflammatory biomarkers were measured. Left ventricular dysfunction and hypokinesis were commonly exhibited symptoms. Cardiac Magnetic Resonance Imaging (CMRI) confirmed the diagnosis of myocarditis with features of cardiac edema and cardiac injury. Nine patients underwent histopathological examination. Treatment with corticosteroids and immunoglobulins was the most applied strategy following the administration of antivirals. Discussion: Despite the exponentially growing knowledge on the management of COVID-19 infection, current available data on SARS-CoV2-correlated myocarditis are still limited, and several difficulties may be encountered in the differential diagnosis of acute myocarditis in the context of COVID-19 disease. Conclusions: While diagnostic criteria and evaluation strategies for myocarditis are well described, no guidelines for the diagnosis and treatment of myocarditis in COVID-19 patients have yet been established. Therefore, further research is needed to advance the understanding of this disease process and define the most appropriate strategic approach in these patients.

The human body is colonized from the birth by a large number of microorganisms. This will constitute a real “functional microbial organ” that is fundamental for homeostasis and therefore for health in humans. Those microorganisms. The microbial populations that colonize humans creating a specific ecosystem they have been collectively referred to as “human microbiota” or “human normal microflora”. The microbiota play an important pathophysiological role in the various locations of the human body. This article focuses on one of the most important, that is the enteric microbiota. The composition (quantitative and qualitative) of microbes is analyzed in relation to age and environment during the course of human life. It also highlights eubiosis and dysbiosis as key terms for its role in health and disease. Finally, it analyzes its bi-directional relationship with the microbiota of the lungs, skin and that of the brain, and consequently for the whole central and peripheral nervous system for the maintenance of health in the human body.

Background: Various microorganisms such as bacteria, virus, and fungi can infect humans and cause not just a simple infection but septic conditions, organ dysfunction, and precancerous conditions or cancer involving various organ systems. After the discovery of the microscope, it was easier to discover and study such microorganisms, as in the case of Helicobacter pylori, a pathogen that was seen in the distant era of the nineteenth century but without being recognized as such. It took 100 years to later discover the pathogenesis and the cancer that this bacterium can cause. Since it was discovered, until today, there has been a continuous search for the understanding of its pathogenetic mechanisms, and the therapeutic approach is continuously updated. Methods: We investigated how diagnosis and therapy were dealt with in the past and how researchers sought to understand, exactly, the pathogenetic biomolecular mechanisms of H. pylori, from the genesis of the infection to the current knowledge, with an analysis of carcinogenic mechanisms in the stomach. We have examined the scientific evolution of the knowledge of the disease over these 40 years in the gastroenterological and pharmacological fields. This was possible through a search in the databases of Medline, the WHO website, the Centers for Disease Control and Prevention (CDC) website, PubMed, and Web of Science to analyze the earlier and the latest data regarding H. pylori. Results: With the scientific discoveries over time, thanks to an increasing number of progressions in scientific research in the analysis of the gastric mucosa, the role of Helicobacter pylori in peptic ulcer, carcinogenesis, and in some forms of gastric lymphoma was revealed. Furthermore, over the years, the biomolecular mechanism involvement in some diseases has also been noted (such as cardiovascular ones), which could affect patients positive for H. pylori. Conclusions: Thanks to scientific and technological advances, the role of the bacterium H. pylori in carcinogenesis has been discovered and demonstrated, and new prospective research is currently attempting to investigate the role of other factors in the stomach and other organs. Cancer from H. pylori infection had a high incidence rate compared to various types of cancer, but in recent years, it is improving thanks to the techniques developed in the detection of the bacterium and the evolution of therapies. Thus, although it has become an increasingly treatable disease, there is still continuous ongoing research in the field of treatment for resistance and pharma compliance. Furthermore, in this field, probiotic therapy is considered a valid adjuvant.

Poor diet, obesity and a sedentary lifestyle have a significant impact on natural microbiota disorders; specifically, the intestinal one. This in turn can lead to a multitude of organ dysfunctions. The gut microbiota contains more than 500 species of bacteria and constitutes 95% of the total number of cells in the human body, thus contributing significantly to the host’s resistance to infectious diseases. Nowadays, consumers have turned to purchased foods, especially those containing probiotic bacteria or prebiotics, that constitute some of the functional food market, which is constantly expanding. Indeed, there are many products available that incorporate probiotics, such as yogurt, cheese, juices, jams, cookies, salami sausages, mayonnaise, nutritional supplements, etc. The probiotics are microorganisms that, when taken in sufficient amounts, contribute positively to the health of the host and are the focus of interest for both scientific studies and commercial companies. Thus, in the last decade, the introduction of DNA sequencing technologies with subsequent bioinformatics processing contributes to the in-depth characterization of the vast biodiversity of the gut microbiota, their composition, their connection with the physiological function—known as homeostasis—of the human organism, and their involvement in several diseases. Therefore, in this study, we highlighted the extensive investigation of current scientific research for the association of those types of functional foods containing probiotics and prebiotics in the diet and the composition of the intestinal microbiota. As a result, this study can form the foundation for a new research path based on reliable data from the literature, acting a guide in the continuous effort to monitor the rapid developments in this field.

A growing interest in creating advanced biomaterials with specific physical and chemical properties is currently being observed. These high-standard materials must be capable to integrate into biological environments such as the oral cavity or other anatomical regions in the human body. Given these requirements, ceramic biomaterials offer a feasible solution in terms of mechanical strength, biological functionality, and biocompatibility. In this review, the fundamental physical, chemical, and mechanical properties of the main ceramic biomaterials and ceramic nanocomposites are drawn, along with some primary related applications in biomedical fields, such as orthopedics, dentistry, and regenerative medicine. Furthermore, an in-depth focus on bone-tissue engineering and biomimetic ceramic scaffold design and fabrication is presented.

Fever represents an elevation of body temperature, that exerts a protective effect against pathogens. Innate immune cells and neurons are implicated in the regulation of body temperature. Pathogen-associated molecular patterns, i.e., lipopolysaccharides from Gram-negative bacteria and peptidoglycan and lipoteichoic acid from Gram-positive bacteria are exogenous pyrogens, that bind to Toll-like receptors on immune and non-immune cells. The subsequent release of pro-inflammatory cytokines [interleukin-1 (IL-1), IL-6 and Tumor necrosis factor-alpha] and their passage through the brain trigger the febrile response. In fact, neurons of the pre-optic area produce prostaglandin E2 (PGE2), that, in turn, bind to the PGE2 receptors; thus, generating fever. Apart from classical non-steroidal anti-inflammatory drugs, i.e., aspirin and acetaminophen, various botanicals are currently used as antipyretic agents and, therefore, their mechanisms of action will be elucidated.

The therapeutic discretion in cases of peri-implantitis should take into account the limits and advantages of specific therapeutic itineraries tailored according to each clinical case and each individual patient. This type of oral pathology emphasizes the complex classification and diagnostic issues coupled with the need for targeted treatments, in light of the oral peri-implant microbiota changes. This review highlights the current indications for the non-surgical treatment of peri-implantitis, describing the specific therapeutic efficacy of different approaches and discussing the more appropriate application of single non-invasive therapies The non-surgical treatment choice with antiseptics or antibiotics (single or combined, local, or systemic) for short courses should be considered on a case-by-case basis to minimize the incidence of side effects and concomitantly avoid disease progression.

During the last decades, metal-based biomaterials have been extensively explored to be used as biocompatible metals for biomedical applications, owing to their superior mechanical properties and corrosion resistance. Consequently, for long-term implanted medical devices, to assure the biomaterials’ reliability, functionality, and biocompatibility, studying the various bio-tribological damage mechanisms to obtain the optimum properties is one of the most important goals. In this review, we consider the most important metal-based biomaterials such as stainless steel, alloys of titanium (Ti), cobalt-chromium (Co-Cr), and Nichel-Titatium (Ni-Ti), as well Magnesium (Mg) alloys and with Tantalum (Ta), emphasizing their characteristics, clinical applications, and deterioration over time. The influence of metal elements on biological safety, including significant effects of metal-based biomaterials in dentistry were discussed, considering the perspectives of surface, mechanical properties, corrosion behaviors, including interactions, bio-mechanisms with tissues, and oral environments. In addition, the role of the oral microbiota was explored due to its role in this erosion condition, in order to further understand the mechanism of metal-based biomaterials implanted on the microflora balance of aerobic and anaerobic bacteria in an oral environment.

Stem cells can be used to replace damaged cells or regenerate organs and have broadened our knowledge of the development and progression of certain diseases. Despite significant advances in understanding stem cell biology, several problems limit their use. These problems are related not only to the growth of tumors in animal models and their rejection in transplant cases but also to ethical and social issues about the use of embryonic cells. The ethical-scientific debate on this type of cells has taken on great interest both for their application in regenerative medicine and for the potential possibilities in the field of cell and gene therapy. Different points of view often have the expression of a perception that depends on scientific goals or opportunities or on religious traditions and beliefs. Therefore, as the questions and doubts about when life begins, so do the answers for the use of these cells as therapy or otherwise. So, in addition to the origin of stem cells, there are currently some social bioethical (such as political and legislative issues) and religious dilemmas. The purpose of the study is aimed at being a narrative on the history of stem cells and the evolution of their use to date, as well as to clarify the bioethical position of the various religions today in comparison with the social ones regarding the research and use of embryonic and adult ones. Hence, their biological hypostasis regarding the concepts of “conception” and “fertilization” and their development and therapeutic use compared to those of the main theological doctrines.

The human intestine is colonized by a huge number of microorganisms from the moment of birth. This set of microorganisms found throughout the human body, is called the microbiota; the microbiome indicates the totality of genes that the microbiota can express, i.e., its genetic heritage. Thus, microbiota participates in and influences the proper functioning of the organism. The microbiota is unique for each person; it differs in the types of microorganisms it contains, the number of each microorganism, and the ratio between them, but mainly it changes over time and under the influence of many factors. Therefore, the correct functioning of the human body depends not only on the expression of its genes but also on the expression of the genes of the microorganisms it coexists with. This fact makes clear the enormous interest of community science in studying the relationship of the human microbiota with human health and the incidence of disease. The microbiota is like a unique personalized “mold” for each person; it differs quantitatively and qualitatively for the microorganisms it contains together with the relationship between them, and it changes over time and under the influence of many factors. We are attempting to modulate the microbial components in the human intestinal microbiota over time to provide positive feedback on the health of the host, from intestinal diseases to cancer. These interventions to modulate the intestinal microbiota as well as to identify the relative microbiome (genetic analysis) can range from dietary (with adjuvant prebiotics or probiotics) to fecal transplantation. This article researches the recent advances in these strategies by exploring their advantages and limitations. Furthermore, we aim to understand the relationship between intestinal dysbiosis and pathologies, through the research of resident microbiota, that would allow the personalization of the therapeutic antibiotic strategy.

Botulinum toxins or neurotoxins (BoNTs) are the most potent neurotoxins known, and are currently extensively studied, not only for their potential lethality, but also for their possible therapeutic and cosmetic uses. Currently, seven types of antigenically distinct toxins are known and characterized, produced by a rod-shaped bacterium, Clostridium botulinum. Human poisoning by botulism (presenting with severe neuromuscular paralytic disease) is usually caused by toxins A, B, E, and F type. Poisoning from contaminated food preparations is the most common cause of noniatrogenic botulism. The spores are highly resistant to heat but are easily destroyed at 80 °C for thirty minutes. Type A and B toxins are resistant to digestion by the enzymes of the gastrointestinal system. After their entry, BoNTs irreversibly bind to cholinergic nerve endings and block the release of acetylcholine from the synapses. In contrast, in wound botulism, the neurotoxin is instead product by the growth of C. botulium in infected tissues. The contamination by BoNT inhalation does not occur by a natural route but it is certainly the most dangerous. It can be caused by the dispersion of the botulinum toxin in the atmosphere in the form of an aerosol and therefore can be deliberately used for bioterrorist purposes (e.g., during CBRN (chemical, biological, radiological, and nuclear) unconventional events). In addition, BoNTs are currently used to treat a variety of diseases or alleviate their symptoms, such as the onabotulinumtoxinA for migraine attacks and for cosmetic use. Indeed, this paper aims to report on updated knowledge of BoNTs, both their toxicological mechanisms and their pharmacological action.

Current medical knowledge and research on patients’ management are still evolving, and several protocols on minimizing risk of infection by Candida spp. among the population have developed. The aim of this work is to review the epidemiological and biomolecular characteristics and the various histopathological carcinogenesis hypothesis mechanisms that can occur during Candida albicans infections. Current evidence from the literature on the role of C. albicans during potentially malignant oral disorders and oral cancer has been sought. Thus, these biomolecular processes can give or contribute to benign lesions, also in precancerous or cancerous situations. Alongside this, the physiological microorganism oral flora (microbiota) can play a crucial role in maintaining oral health during those infections and therefore avoid carcinogenesis.

This study is focused on the epidemiological characteristics and biomolecular mechanisms that lead to the development of precancerous and cancerous conditions of oral lesions related to Human Papilloma Virus (HPV) infections. Current evidence from the literature demonstrates the role of HPV in potentially malignant oral disorders. Therefore, the underlying biomolecular processes can give arise, or contribute to, benign lesions as well as to oral carcinogenesis.

The recent COVID-19 pandemic promoted efforts to better understand the organization of the respiratory microbiome and its evolution from birth to adulthood and how it interacts with external pathogens and the host immune system. This review aims to deepen understanding of the essential physiological functions of the resident microbiome of the respiratory system on human health and diseases. First, the general characteristics of the normal microbiota in the different anatomical sites of the airways have been reported in relation to some factors such as the effect of age, diet and others on its composition and stability. Second, we analyze in detail the functions and composition and the correct functionality of the microbiome in the light of current knowledge. Several studies suggest the importance of preserving the micro-ecosystem of commensal, symbiotic and pathogenic microbes of the respiratory system, and, more recently, its relationship with the intestinal microbiome, and how it also leads to the maintenance of human health, has become better understood.

Background: Gastric adenocarcinoma is the fourth most common type of cancer and the second leading cause of cancer death in the world. Despite abundant traces of an ancient history, the comprehension of its pathogenic mechanisms is rather recent and continuously updated. Methods: We investigated about how the ancient civilizations tried to understand the exactly physiopathology of gastric cancer, from the time when they could not examine deeply the histological and pathophysiologic aspects of the disease, but they just based their knowledge on a visual analysis of the signs and consequences of such disease. We examined the historical evolving knowledge of the disease along the centuries on the gastroenterological, pharmacological, and surgical fields, defining how gastric cancer became an increasingly curable disease. Results: Cancer was known in the ancient world. Ancient people did not know exactly the causes but the climatic, hygienic, and food conditions were the first to be considered over time, also taking into consideration supernatural negative influences. During the Renaissance, a tumultuous time of scientific discoveries started, thanks to an increasing number of autopsies made on cadavers and to the progressions in visual analysis of the stomach mucosa throughout endoscopy. From the first gastric surgery in 1879, many steps forward have been made and, today, gastric cancer is regarded as a more curable disease; one important discovery in this field has been the revelation of the role of Helicobacter pylori in the peptic ulcer disease (PUD) and in some forms of gastric lymphoma. Conclusions: Gastric cancer has the fourth highest incidence of various cancers worldwide and is ranked second as a cause of cancer-related death. It exists from the antiquity and a lot of hypotheses have been developed about its etiology during the centuries, influencing its therapy. During the 20th century, thanks to the scientific and technological progresses the causes of the cancer have been discovered and the role of the bacterium Helicobacter pylori has been demonstrated, and new perspective research are currently trying to investigate the role of other microorganisms in gastric physiopathology, as well as its possible modulation by probiotics.

Aims: There are many reasons for the increase in post-operative mortality and morbidity in patients undergoing surgery. In fact, an activated inflammatory state before cardiac surgery, can potentially worsen the patient’s prognosis and the effects of this preoperative inflammatory state in the medium-term remains unknown. Methods: There were 470 consecutive patients who underwent cardiac surgery, and were divided in three groups according to the median values of preoperative C-reactive protein (CRP) and fibrinogen (FBG): The first group was the low inflammatory status group (LIS) with 161 patients (CRP < 0.39 mg/dL and FBG < 366 mg/dL); the second was the medium inflammatory status group (MIS) with 150 patients (CRP < 0.39 mg/dL and FBG ≥ 366 mg/dL or CRP ≥ 0.39 mg/dL and FBG < 366 mg/dL,); and the third was the high inflammatory status group (HIS) with 159 patients (CRP ≥ 0.39 mg/dL and FBG ≥ 366 mg/dL,). Results: The parameters to be considered for the patients before surgery were similar between the three groups except, however, for age, left ventricular ejection fraction (LVEF) and the presence of arterial hypertension. The operative mortality was not significantly different between the groups (LIS = 2.5%, MIS = 6%, HIS = 6.9%, p = 0.16) while mortality for sepsis was significantly different (LIS = 0%, MIS = 1.3%, HIS = 3.7%, p = 0.03). The infections were more frequent in the HIS group (p = 0.0002). The HIS group resulted in an independent risk factor for infections (relative risk (RR) = 3.1, confidence interval (CI) = 1.2−7.9, p = 0.02). During the 48-months follow-up, survival was lower for the HIS patients. This HIS group (RR = 2.39, CI = 1.03−5.53, p = 0.05) and LVEF (RR = 0.96, CI = 0.92−0.99, p = 0.04) resulted in independent risk factors for mortality during the follow-up. Conclusions: The patients undergoing cardiac surgery with a preoperative highly activated inflammatory status are at a higher risk of post-operative infections. Furthermore, during the intermediate follow-up, the preoperative highly activated inflammatory status and LVEF resulted in independent risk factors for mortality.

In the area of Emergency Room (ER), many patients present criteria compatible with a SIRS, but only some of them have an associated infection. The new definition of sepsis by the European Society of Intensive Care Medicine and the Society of Critical Care Medicine (2016), revolutionizes precedent criteria, overcoming the concept of SIRS and clearly distinguishing the infection with the patient’s physiological response from the symptoms of sepsis. Another fundamental change concerns the recognition method: The use of SOFA (Sequential-Sepsis Related-Organ Failure Assessment Score) as reference score for organ damage assessment. Also, the use of the qSOFA is based on the use of three objective parameters: Altered level of consciousness (GCS 18 mg/dL in despite of an adequate volume resuscitation. Then, patient first management is mainly based on: (1) Recognition of the potentially septic patient (sepsis protocol-qSOFA); (2) Laboratory investigations; (3) Empirical antibiotic therapy in patients with sepsis and septic shock. With this in mind, the authors discuss the most important aspects of the sepsis in both adults and infants, and also consider the possible treatment according current guidelines. In addition, the possible role of some nutraceuticals as supportive therapy in septic patient is also discussed.

Background: In the pre-Hellenistic period, the concept of medicine was not well-defined. Usually, a disease was considered as a divine punishment and its treatment was devolved to the priests who asked for healing from the divinities. The only job that could be compared to medical practice was a kind of itinerant medicine, derived from the Egyptian therapeutic tradition based only on practical experience and performed by people that knew a number of remedies, mostly vegetable, but without any theoretical bases about the possible mechanisms of action. Opinions about the human nature (naturalistic thinking) and the origin of the illness and heal were the basis of Greek medicine practiced by ancient priests of Asclepius. However, with the evolution of the thought for the continuous research of “κόσμος” (world) knowledge, philosophy woulld become an integral part of medicine and its evolution. This close relationship between philosophy and medicine is confirmed by the Greek physician Galen in the era of the Roman Empire. Methods: Philosophical thought looked for world knowledge starting from mathematics, physics, astronomy, chemistry, medicine, psychology, metaphysics, sociology, and ethics. We must keep in mind that, according to the ancient people, the physicians could not heal the patients without the aid of a “divine God” until medicine, thanks to the Hippocratic practice, became more independent from the supernatural, and contemporary, ethical, and professional. Many physicians were philosophers, as confirmed by their views of life, such as Hippocrates of Cos, Aristotle (hailed as the father of comparative anatomy and physiology), Pythagoras of Samos, Alcmaeon of Croton, Empedocles, Praxagoras, Erasistratus, Galen, and others, including Asclepiades of Bithynia (atomists affinity). Asclepiades, a Greek physician born in Prusa, studied in Athens and Alexandria. His thought was influenced by Democritus’ theories, refusing extensively the Hippocratic ideas that diseases are a result of mood imbalance. Results: Differing from the current Hippocratic idea, only in extreme cases he prescribed medications and bloodletting, two of the most-used therapies of that time. He usually prescribed therapies based on the Epicurean thought, then consisting of walks and music, massages, and thermal baths. He anticipated the modern idea of the body consisting of atoms, and believed that between the atoms exist empty spaces called pores. As the founder of the so called Methodist School, he was the first to divide acute and chronic diseases, and thought that body weakness was dependent on the excessive width of the pores, while their excessive shrinkage determines fever. According to his student Caelius Aurelianus he was the first to adopt tracheotomy as an emergency therapy for diphtheria. Conclusions: Although it is very difficult to reconstruct the theories of Asclepiades of Bithynia because of the lack of original texts, this paper attempts to focus his role and his thought in affirming the Greek medical practice in ancient Rome and to highlight his modernity.