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In the second edition of this Special Issue, several promising antitumor strategies have been presented in addition to those reported in the first edition, in which several compounds (acetylcorynoline, BaP1, sarco/endoplasmic reticulum calcium ATPase inhibitors, neuropeptide Y, neuropeptide Y antagonists, neurokinin-1 receptor antagonists) exerting antitumor effects against colorectal cancer, papillary thyroid carcinoma, cholangiocarcinoma, Ewing sarcoma, liver cancer, and breast cancer were reported [...].

Interindividual variability in analgesic response is at least partly due to well-characterized polymorphisms that are associated with opioid dosing and adverse outcomes. The Clinical Pharmacogenetics Implementation Consortium (CPIC) has put forward recommendations for the CYP2D6 phenotype, but the list of studied drug-gene pairs continues to grow. This clinical trial randomized chronic pain patients ( n = 60), referred from primary care to pain unit care into two opioid prescribing arms, one guided by CYP2D6 , μ-opioid receptor ( OPRM1 ), and catechol-O-methyl transferase ( COMT ) genotypes vs. one with clinical routine. The genotype-guided treatment reduced pain intensity (76 vs. 59 mm, p < 0.01) by improving pain relief (28 vs. 48 mm, p < 0.05), increased quality of life (43 vs. 56 mm p < 0.001), and lowered the incidence of clinically relevant adverse events (3 [1-5] vs. 1 [0-2], p < 0.01) and 42% opioid dose (35 [22-61] vs. 60 [40-80] mg/day, p < 0.05) as opposed to usual prescribing arm. The final health utility score was significantly higher (0.71 [0.58-0.82] vs. 0.51 [0.13-0.67] controls, p < 0.05) by improving sleepiness and depression comorbidity, with a significant reduction of 30-34% for headache, dry mouth, nervousness, and constipation. A large-scale implementation analysis could help clinical translation, together with a pharmaco-economic evaluation.

Harmful alcohol use is responsible for a group of disorders collectively named alcohol use disorders (AUDs), according to the DSM-5 classification. The damage induced by alcohol depends on the amount, time, and consumption patterns (continuous and heavy episodic drinking). It affects individual global well-being and social and familial environments with variable impact. Alcohol addiction manifests with different degrees of organ and mental health detriment for the individual, exhibiting two main traits: compulsive drinking and negative emotional states occurring at withdrawal, frequently causing relapse episodes. Numerous individual and living conditions, including the concomitant use of other psychoactive substances, lie in the complexity of AUD. Ethanol and its metabolites directly impact the tissues and may cause local damage or alter the homeostasis of brain neurotransmission, immunity scaffolding, or cell repair biochemical pathways. Brain modulator and neurotransmitter-assembled neurocircuitries govern reward, reinforcement, social interaction, and consumption of alcohol behaviors in an intertwined manner. Experimental evidence supports the participation of neurotensin (NT) in preclinical models of alcohol addiction. For example, NT neurons in the central nucleus of the amygdala projecting to the parabrachial nucleus strengthen alcohol consumption and preference. In addition, the levels of NT in the frontal cortex were found to be lower in rats bred to prefer alcohol to water in a free alcohol-water choice compared to wild-type animals. NT receptors 1 and 2 seem to be involved in alcohol consumption and alcohol effects in several models of knockout mice. This review aims to present an updated picture of the role of NT systems in alcohol addiction and the possible use of nonpeptide ligands modulating the activity of the NT system, applied to experimental animal models of harmful drinking behavior mimicking alcohol addiction leading to health ruin in humans.

Obesity/overweight are important health problems due to metabolic complications. Dysregulation of peptides exerting orexigenic/anorexigenic effects must be investigated in-depth to understand the mechanisms involved in feeding behaviour. One of the most important and studied orexigenic peptides is galanin (GAL). The aim of this review is to update the mechanisms of action and physiological roles played by the GAL family of peptides (GAL, GAL-like peptide, GAL message-associated peptide, alarin) in the control of food intake and to review the involvement of these peptides in metabolic diseases and food intake disorders in experimental animal models and humans. The interaction between GAL and NPY in feeding and energy metabolism, the relationships between GAL and other substances involved in food intake mechanisms, the potential pharmacological strategies to treat food intake disorders and obesity and the possible clinical applications will be mentioned and discussed. Some research lines are suggested to be developed in the future, such as studies focused on GAL receptor/neuropeptide Y Y 1 receptor interactions in hypothalamic and extra-hypothalamic nuclei and sexual differences regarding the expression of GAL in feeding behaviour. It is also important to study the possible GAL resistance in obese individuals to better understand the molecular mechanisms by which GAL regulates insulin/glucose metabolism. GAL does not exert a pivotal role in weight regulation and food intake, but this role is crucial in fat intake and also exerts an important action by regulating the activity of other key compounds under conditions of stress/altered diet.