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.

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.

Oral microbiota in human health and disease: A perspective.

The evolution of medical knowledge about oral microbiota has increased awareness of its important role for the entire human body health. A wide range of microbial species colonizing the oral cavity interact both with each other and with their host through complex pathways. Usually, these interactions lead to a harmonious coexistence (i.e. eubiosis). However, several factors - including diet, poor oral hygiene, tobacco smoking, and certain medications, among others - can disrupt this weak homeostatic balance (i.e. dysbiosis) with potential implications on both oral (i.e. development of caries and periodontal disease) and systemic health. This article is thus aimed at providing an overview on the importance of oral microbiota in mediating several physiological and pathological conditions affecting human health. In this context, strategies based on oral hygiene and diet as well as the role of probiotics supplementation are discussed.

Crosstalk between the Resident Microbiota and the Immune Cells Regulates Female Genital Tract Health.

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.

Subversion of the Oral Microbiota and Induction of Immune-Mediated Systemic Inflammation with Special Reference to Periodontitis: Current Knowledge and Perspectives.

Under steady-state circumstances, the oral microbiota is in equilibrium with host tissues, thus contributing to local and systemic health. Any interruption of such equilibrium leads to a condition of dysbiosis with the proliferation of oral pathogens able to cause gingivitis and periodontal disease. The mechanisms of periodontitis will be described, mostly emphasizing the noxious effects exerted by oral pathogens on the periodontium either directly or indirectly via the release of an array of mediators, even including pro-inflammatory cytokines, chemokines, and enzymes. The persistence of local inflammation ultimately leads to systemic inflammation; therefore, the link between periodontitis and obesity, diabetes and cardiovascular disease will be elucidated. Some natural compounds, such as polyphenols, prebiotics, and probiotics, will be discussed for their ability to exert anti-inflammatory and anti-oxidant activities in the context of the inflamed buccal cavity and systemically, as well as for their modulation of the altered gum-gut microbiota.

Antibiotic Resistance to Mycobacterium tuberculosis and Potential Use of Natural and Biological Products as Alternative Anti-Mycobacterial Agents.

BACKGROUND: Tuberculosis (TB) is an infectious disease caused by the bacillus Mycobacterium tuberculosis (Mtb). TB treatment is based on the administration of three major antibiotics: isoniazid, rifampicin, and pyrazinamide. However, multi-drug resistant (MDR) Mtb strains are increasing around the world, thus, allowing TB to spread around the world. The stringent response is demonstrated by Mtb strains in order to survive under hostile circumstances, even including exposure to antibiotics. The stringent response is mediated by alarmones, which regulate bacterial replication, transcription and translation. Moreover, the Mtb cell wall contributes to the mechanism of antibiotic resistance along with efflux pump activation and biofilm formation. Immunity over the course of TB is managed by M1-macrophages and M2-macrophages, which regulate the immune response against Mtb infection, with the former exerting inflammatory reactions and the latter promoting an anti-inflammatory profile. T helper 1 cells via secretion of interferon (IFN)-gamma, play a protective role in the course of TB, while T regulatory cells secreting interleukin 10, are anti-inflammatory. Alternative therapeutic options against TB require further discussion. In view of the increasing number of MDR Mtb strains, attempts to replace antibiotics with natural and biological products have been object of intensive investigation. Therefore, in this review the anti-Mtb effects exerted by probiotics, polyphenols, antimicrobial peptides and IFN-gamma will be discussed. All the above cited compounds are endowed either with direct antibacterial activity or with anti-inflammatory and immunomodulating characteristics.

Overview of Candida albicans and Human Papillomavirus (HPV) Infection Agents and their Biomolecular Mechanisms in Promoting Oral Cancer in Pediatric Patients.

Oral carcinoma represents one of the most common malignancies worldwide. Oral squamous cell carcinomas (OSCCs) account over 90% of all oral malignant tumors and are characterized by high mortality in the advanced stages. Early diagnosis is often a challenge for its ambiguous appearance in early stages. Mucosal infection by the human papillomavirus (HPV) is responsible for a growing number of malignancies, particularly cervical cancer and oropharyngeal carcinomas. In addition, Candida albicans (C. albicans), which is the principal fungi involved in the oral cancer development, may induce carcinogenesis through several mechanisms, mainly promoting inflammation. Medical knowledge and research on adolescent/pediatric patients' management and prevention are in continuous evolution. Besides, microbiota can play an important role in maintaining oral health and therefore all human health. The aim of this review is to evaluate epidemiological and pathophysiological characteristics of the several biochemical pathways involved during HPV and C. albicans infections in pediatric dentistry.

Stem Cells: A Historical Review about Biological, Religious, and Ethical Issues.

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.

Focus on HPV Infection and the Molecular Mechanisms of Oral 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 Cannabis Spread throughout the Continents and its Therapeutic Use in History.

BACKGROUND: Cannabis sativa L. (C. sativa) is a plant whose use as a therapeutic agent shares its origins with the first Far East's human societies. Cannabis has been used not only for recreational purposes but as food to obtain textile fibers, to produce hemp paper, to treat many physical and mental disorders. AIM: This review aims to provide a complete assessment of the deep knowledge of the cannabis psychoactive effects and medicinal properties in the course of history covering i.) The empirical use of the seeds and the inflorescences to treat many physical ailments by the ancient Oriental physicians' ii.) The current use of cannabis as a therapeutic agent after the discovery of its key psychoactive constituent and the human endogenous endocannabinoid system. METHODS: This study was performed through a detailed analysis of the studies on the historical significance and medical applications of Cannabis sativa by using international scientific databases, historical and medical books, ancient Greek and Chinese manuscripts translations, library and statistical data from government reports and texts from the National Library of Greece (Stavros Niarchos Foundation), from the School of Health Sciences of the National and Kapodistrian University of Athens (Greece). We selected papers and texts focusing on a historical point of view about the medical importance of the plant and its applications for a therapeutic purpose in the past. RESULTS AND CONCLUSION: Through a detailed analysis of the available resources about the origins of C. sativa, we found that its use by ancient civilizations as a source of food and textile fibers dates back over 10,000 years, while its therapeutic applications have been improved over the centuries, from the ancient East medicine of the 2nd and 1st millennium B.C. to the more recent introduction in the Western world after the 1st century A.D. In the 20th and 21st centuries, Cannabis and its derivatives have been considered as a menace and banned throughout the world, but nowadays, they are still the most widely consumed illicit drugs all over the world. Its legalization in some jurisdictions has been accompanied by new lines of research to investigate its possible applications for medical and therapeutic purposes.

Oral Cancer: A Historical Review.

Aim: This historical medical literature review aims at understanding the evolution of the medical existence of oral cancer over times, particularly better comprehending if the apparent lower prevalence of this type of cancer in antiquity is a real value due to the absence of modern environmental and lifestyle factors or it is linked to a misinterpretation of ancient foreign terms found in ancient medical texts regarding oral neoplasms. Methods: The databases MedLne, PubMed, Web of Science, Elsevier's EMBASE.com, Cochrane Review, National Library of Greece (Stavros Niarchos Foundation, Athens) and the Library of the School of Health Sciences of the National and Kapodistrian University of Athens (Greece) were extensively searched for relevant studies published during the past century on the history of oral cancer and its treatment from antiquity to modern times, in addition to the WHO website to analyse the latest epidemiological data. In addition, we included historical books on the topic of interest and original sources. Results: Historical references reveal that the cradle of the oral oncology was in ancient Egypt, the Asian continent and Greece and cancer management was confined to an approximate surgical practice, in order to remove abnormal masses and avoid bleeding with cauterization. In the Medieval Age, little progress occurred in medicine in general, oral cancers management included. It is only from the Renaissance to modern times that knowledge about its pathophysiological mechanisms and histopathology and its surgical and pharmacological treatment approaches became increasingly deep all over the world, evolving to the actual integrated treatment. Despite the abundant literature exploring oncology in past civilizations, the real prevalence of oral cancer in antiquity is much less known; but a literature analysis cannot exclude a consistent prevalence of this cancer in past populations, probably with a likely lower incidence than today, because many descriptions of its aggressiveness were found in ancient medical texts, but it is still difficult to be sure that each single description of oral masses could be associated to cancer, particularly for what concerns the period before the Middle Ages. Conclusions: Modern oncologists and oral surgeons must learn a lot from their historic counterparts in order to avoid past unsuccessful efforts to treatment oral malignancies. Several descriptions of oral cancers in the antiquity that we found let us think that this disease might be linked to mechanisms not strictly dependent on environmental risk factors, and this might guide future research on oral cavity treatments towards strategical cellular and molecular techniques.

Gastric Cancer in History: A Perspective Interdisciplinary Study.

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.

Antiviral properties of antineoplastic drugs. From herpes simplex-1 disappearance to a wide antiviral action: a serendipity case report.

Herein we report the clinical case of a 46 year old female affected by lung cancer and cerebral metastases who showed, one month after the beginning of an oncologic therapy with vinorelbine and cisplatin, the complete remission of periodic (every 15 days) recurrences of herpetic mouth lesions. More than one year after the disappearance of the herpetic lesions, no further evidence of them were found. Subsequently, specific laboratory investigations, together with another case report that is presently in process, showed that vinorelbine, aside from its well known antineoplastic properties, also exerts a powerful antiviral action.

[Dentistry oral hygiene and endocarditis. Pathophysiology and prophylactic therapy]. / Rischio di endocarditi infettive correlate a trattamenti odontoiatrici e di igiene orale.

Infectious endocarditis is a cardiac pathology of bacterial, viral or more rarely mycotic origin developing on the surfaces of the endocardium or heart valves. Predisposing conditions are congenital malformations of the heart or valvular acquired alterations, as well as the presence of a valvular prosthesis. The microorganisms involved in the etiology and pathogenesis of the damage of such infection (bacterias, viruses or yeasts) determine the formation of the endocardic vegetations typical of this condition. Such lesions can be located on the valvular or the parietal endocardium and sometimes on the endothelium of a great artery. In despite of the elevated standards of instrumental investigations and therapeutic protocols, the bacterial endocarditis represents a pathology of wide interest, scientific and social, due to its high rate of incidence, morbility and mortality. Still now infectious endocarditis causes death in 20-30% of the patients. Although the significant progress on prevention of the infectious diseases and of the cross infections in dentistry practice, from the tartar ablation up to the oncologic oral surgery, still now the skills of oral hygiene and dentistry represent a potential threat for the development of an infectious endocarditis in predisposed patients. The authors, on the base of the revision of the literature and of their own clinical experience, show the etiology, pathophysiology and the clinical pictures related to such complex disease.