RELATIONSHIP OF HELICOBACTER PYLORI CAGA AND VACA STATUS TO MORPHOLOGICAL CHANGES OF GASTRIC MUCOSA AND PRIMARY CLARITHROMYCIN RESISTANCE RATE IN PATIENTS WITH CHRONIC GASTRITIS: A CROSS-SECTIONAL STUDY.

OBJECTIVE: The aim: To investigate the relation of H. pylori CagA and VacA status to morphological changes of gastric mucosa and primary clarithromycin resistance rate in patients with chronic gastritis. PATIENTS AND METHODS: Materials and methods: A cross-sectional study was conducted between May 2021 and January 2023, involving 64 patients with H. pylori-associated chronic gastritis. The patients were assigned to two groups according to the H. pylori virulence factors (CagA and VacA) status. The grades of inflammation, activity, atrophy, and metaplasia were determined according to the Houston-updated Sydney system. The identification of H. pylori genetic markers of antibiotic resistance and pathogenicity was performed by the polymerase chain reaction using paraffin stomach biopsies. RESULTS: Results: Patients with CagA- and VacA-positive H. pylori strains had significantly higher grades of inflammation both in the antrum and in the corpus of the stomach, activity of gastritis in the antrum, higher incidence and grade of atrophy in the antrum. Primary resistance to clarithromycin was significantly more prevalent in patients with CagA- and VacA-negative H. pylori strains (58.3% vs. 11.5%, p=0.002). CONCLUSION: Conclusions: Positive CagA and VacA status is related to more severe histopathological changes of gastric mucosa. In contrast, the rate of primary clarithromycin resistance is higher in patients CagA- and VacA-negative H. pylori strains.

Early-life adversity and long-term neurobehavioral outcomes: epigenome as a bridge?

Accumulating evidence suggests that adversities at critical periods in early life, both pre- and postnatal, can lead to neuroendocrine perturbations, including hypothalamic-pituitary-adrenal axis dysregulation and inflammation persisting up to adulthood. This process, commonly referred to as biological embedding, may cause abnormal cognitive and behavioral functioning, including impaired learning, memory, and depressive- and anxiety-like behaviors, as well as neuropsychiatric outcomes in later life. Currently, the regulation of gene activity by epigenetic mechanisms is suggested to be a key player in mediating the link between adverse early-life events and adult neurobehavioral outcomes. Role of particular genes, including those encoding glucocorticoid receptor, brain-derived neurotrophic factor, as well as arginine vasopressin and corticotropin-releasing factor, has been demonstrated in triggering early adversity-associated pathological conditions. This review is focused on the results from human studies highlighting the causal role of epigenetic mechanisms in mediating the link between the adversity during early development, from prenatal stages through infancy, and adult neuropsychiatric outcomes. The modulation of epigenetic pathways involved in biological embedding may provide promising direction toward novel therapeutic strategies against neurological and cognitive dysfunctions in adult life.

Non-genomic transmission of longevity between generations: potential mechanisms and evidence across species.

Accumulating animal and human data indicate that environmental exposures experienced during sensitive developmental periods may strongly influence risk of adult disease. Moreover, the effects triggered by developmental environmental cues can be transgenerationally transmitted, potentially affecting offspring health outcomes. Increasing evidence suggests a central role of epigenetic mechanisms (heritable alterations in gene expression occurring without changes in underlying DNA sequence) in mediating these effects. This review summarizes the findings from animal models, including worms, insects, and rodents, and also from human studies, indicating that lifespan and longevity-associated characteristics can be transmitted across generations via non-genetic factors.

Gut microbiota: A player in aging and a target for anti-aging intervention.

Aging-associated alterations in composition, diversity and functional features of intestinal microbiota are well-described in the modern literature. They are suggested to be caused by an age-related decline in immune system functioning (immunosenescence) and a low-grade chronic inflammation (inflammaging), which accompany many aging-associated pathologies. The microbiota-targeted dietary and probiotic interventions have been shown to favorably affect the host health and aging by an enhancement of antioxidant activity, improving immune homeostasis, suppression of chronic inflammation, regulation of fat deposition and metabolism and prevention of insulin resistance. Recently, a high effectiveness and safety of novel therapeutic application such as fecal microbiota transplantation in the prevention and treatment of age-related pathological conditions including atherosclerosis, type 2 diabetes and Parkinson's disease has been demonstrated. In this review, recent research findings are summarized on the role of gut micribiota in aging processes with emphasis on therapeutic potential of microbiome-targeted interventions in anti-aging medicine.

Anti-aging pharmacology: Promises and pitfalls.

Life expectancy has grown dramatically in modern times. This increase, however, is not accompanied by the same increase in healthspan. Efforts to extend healthspan through pharmacological agents targeting aging-related pathological changes are now in the spotlight of geroscience, the main idea of which is that delaying of aging is far more effective than preventing the particular chronic disorders. Currently, anti-aging pharmacology is a rapidly developing discipline. It is a preventive field of health care, as opposed to conventional medicine which focuses on treating symptoms rather than root causes of illness. A number of pharmacological agents targeting basic aging pathways (i.e., calorie restriction mimetics, autophagy inducers, senolytics etc.) are now under investigation. This review summarizes the literature related to advances, perspectives and challenges in the field of anti-aging pharmacology.