The excessive formation of reactive oxygen species (ROS) and impairment of defensive antioxidant systems leads to a condition known as oxidative stress. The main source of free radicals responsible for oxidative stress is mitochondrial respiration. The deleterious effects of ROS on cellular biomolecules, including DNA, is a well-known phenomenon that can disrupt mitochondrial function and contribute to cellular damage and death, and the subsequent development of various disease processes. In this review, we summarize the most important findings that implicated mitochondrial oxidative stress in a wide variety of pathologies from Alzheimer disease (AD) to autoimmune type 1 diabetes. This review also discusses attempts to affect oxidative stress as a therapeutic avenue.

Numerous harmful factors that affect the human body from birth to old age cause many disturbances, e.g., in the structure of the genome, inducing cell apoptosis and their degeneration, which leads to the development of many diseases, including cancer. Among the factors leading to pathological processes, microbes, viruses, gene dysregulation and immune system disorders have been described. The function of a protective agent may be played by lactoferrin as a “miracle molecule”, an endogenous protein with a number of favorable antimicrobial, antiviral, antioxidant, immunostimulatory and binding DNA properties. The purpose of this article is to present the broad spectrum of properties and the role that lactoferrin plays in protecting human cells at all stages of life.

Structural abnormalities causing DNA modifications of the ethene and propanoadducts can lead to mutations and permanent damage to human genetic material. Such changes may cause premature aging and cell degeneration and death as well as severe impairment of tissue and organ function. This may lead to the development of various diseases, including cancer. In response to a damage, cells have developed defense mechanisms aimed at preventing disease and repairing damaged genetic material or diverting it into apoptosis. All of the mechanisms described above are part of the repertoire of action of Lactoferrin—an endogenous protein that contains iron in its structure, which gives it numerous antibacterial, antiviral, antifungal and anticancer properties. The aim of the article is to synthetically present the new and innovative role of lactoferrin in the protection of human genetic material against internal and external damage, described by the modulation mechanisms of the cell cycle at all its levels and the mechanisms of its repair.

Background: The clinical treatment of various types of pain relies upon the use of opioid analgesics. However most of them produce, in addition to the analgesic effect, several side effects such as the development of dependence and addiction as well as sedation, dysphoria, and constipation. One solution to these problems are chimeric compounds in which the opioid pharmacophore is hybridized with another type of compound to incease antinociceptive effects. Neurotensin-induced antinociception is not mediated through the opioid system. Therefore, hybridizing neurotensin with opioid elements may result in a potent synergistic antinociceptor.Results: Using the known structure-activity relationships of neurotensin we have synthesized a new chimeric opioid-neurotensin compound PK20 which is characterized by a very strong antinociceptive potency. The observation that the opioid antagonist naltrexone did not completely reverse the antinociceptive effect, indicates the partial involvement of the nonopioid component in PK20 in the produced analgesia.Conclusions: The opioid-neurotensin hybrid analogue PK20, in which opioid and neurotensin pharmacophores overlap partially, expresses high antinociceptive tail-flick effects after central as well as peripheral applications.

To address the different types of pain (e.g. acute, chronic, neuropathic) different classes of medications, mainly non-steroidal anti-inflammatory drugs and narcotics (opioids), are used. More specifically, the alleviation or treatment of moderate to severe pain states commonly invokes the use of opioids. Unfortunately, their chronic administration induces various undesirable side effects, such as for example physical dependence and tolerance. One strategy to overcome these major side effects and to prolong the antinociceptive efficiency of the applied drugs involves the creation of multifunctional compounds which contain hybridized structures. Combination of opioid agonist and antagonist pharmacophores in a single chemical entity has been considered and extensively investigated, but opioids have also been combined with other bioactive neurotransmitters and peptide hormones that are involved in pain perception (e.g. substance P, neurotensin, cholecystokinin, cannabinoids, melanocortin ligands, etc.). Such novel chimeras (also called designed multiple ligands or twin/triplet drugs), may interact independently with their respective receptors and potentially result in more effective antinociceptive properties. The designed multiple ligands presented in this work include opioid-non-opioid peptide dimer analogs, mixed peptidic- non-peptidic bifunctional ligands and dual non-peptidic dimers. The main focus herein is placed on the design and biological evaluation of these multiple opioid compounds, rather than the synthetic approach and preparation.