BACKGROUND: Immunoglobulins (Ig) reactive with α-melanocyte-stimulating hormone (α-MSH), an anorexigenic neuropeptide, are present in humans and were previously associated with eating disorders. In this longitudinal study involving patients with anorexia nervosa (AN), we determined whether α-MSH in serum is bound to IgG and analyzed long-term dynamics of both α-MSH peptide and α-MSH-reactive Ig in relation to changes in BMI and gut microbiota composition.
METHODS: The study included 64 adolescents with a restrictive form of AN, whose serum samples were collected at hospital admission, discharge, and during a 1-year follow-up visit and 41 healthy controls, all females.
RESULTS: We found that in both study groups, approximately 40% of serum α-MSH was reversibly bound to IgG and that levels of α-MSH-reactive IgG but not of α-MSH peptide in patients with AN were low at hospital admission but recovered 1 year later. Total IgG levels were also low at admission. Moreover, BMI-standard deviation score correlated positively with α-MSH IgG in both groups studied but negatively with α-MSH peptide only in controls. Significant correlations between the abundance of specific bacterial taxa in the gut microbiota and α-MSH peptide and IgG levels were found in both study groups, but they were more frequent in controls.
CONCLUSIONS: We conclude that IgG in the blood plays a role as an α-MSH-binding protein, whose characteristics are associated with BMI in both patients with AN and controls. Furthermore, the study suggests that low production of α-MSH-reactive IgG during the starvation phase in patients with AN may be related to altered gut microbiota composition.

The co-occurrence of asthma and obesity is becoming an increasingly common health problem. It became clear that both diseases are closely related, since overweight/obesity are associated with an increased risk of asthma development, and more than half of the subjects with severe or difficult-to-treat asthma are obese. Currently, there are no specific guidelines for the treatment of this group of patients. The mechanisms involved in the asthma-obesity phenotype include low-grade chronic inflammation and changes in pulmonary physiology. However, genetic predispositions, gender differences, comorbid conditions, and gut microbiota also seem to be important. Regulatory peptides affect many processes related to the functioning of the respiratory tract and adipose tissue. Adipokines such as leptin, adiponectin, resistin, and the less studied omentin, chemerin, and visfatin, as well as the gastrointestinal hormones ghrelin, cholecystokinin, glucagon-like peptide-1, and neuropeptides, including substance P or neuropeptide Y, can play a significant role in asthma with obesity. The aim of this article is to provide a concise review of the contribution of particular peptides in inflammatory reactions, obesity, asthma, and a combination of both diseases, as well as emphasize their potential role in the effective treatment of the asthma-obesity phenotype in the future.

BACKGROUND: Current methods of treating male infertility have limited efficiency, since they are aimed to individual stages of the pathogenesis. Preparations based on testicular regulatory polypeptides are the most physiological and universal, owing to a complex effect on the self-regulation of testicular tissue.
OBJECTIVE: To study the delayed efficiency and safety of therapy with Fertiwell in patients with pathospermia and to assess the frequency of conception and pregnancy outcome in their partners based on the collection, analysis and interpretation of medical data.
METHODS: A telephone survey of patients participating in the phase III clinical trial was carried out. The fact of conception in a couple was assessed over a period of 1 to 9 months after completion of therapy, as well as time from completion of the course to conception, pregnancy outcomes, newborn health outcomes.
RESULTS: In the period from 1 to 9 months after completion of therapy, pregnancy occurred in 17 out of 34 couples (50%) in the Fertiwell group and in 13 out of 42 couples (30.95%) in the placebo group. This difference was statistically and clinically significant (p<0.05). All pregnancies resulted in a live birth. The median time from completion of the course to conception was 4 months in Fertiwell group and 6 months in the placebo group. There were no significant differences in anthropometric parameters of newborns between the two groups (p>0.05).
CONCLUSIONS: When using the drug Fertiwell, pregnancy and live birth rate was significantly higher (2.23 times) compared to the control group. There was a trend toward earlier pregnancies in partners of men receiving Fertiwell. Thus, this drug can be recommended for the treatment of men with idiopathic infertility as monotherapy, as well as in combination with assisted reproductive technologies.

Plant peptides are a new frontier in plant biology, owing to their key regulatory roles in plant growth, development, and stress responses. Synthetic peptides are promising biological agents that can be used to improve crop growth and protection in an environmentally sustainable manner. Plant regulatory peptides identified in pioneering research, including systemin, PSK, HypSys, RALPH, AtPep1, CLV3, TDIF, CLE, and RGF/GLV/CLEL, hold promise for crop improvement as potent regulators of plant growth and defense. Mass spectrometry and bioinformatics are greatly facilitating the discovery and identification of new plant peptides. The biological functions of most novel plant peptides remain to be elucidated. Bioassays are an essential part in studying the biological activity of identified and putative plant peptides. Root growth assays and cultivated plant cell cultures are widely used to evaluate the regulatory potential of plant peptides during growth, differentiation, and stress reactions. These bioassays can be used as universal approaches for screening peptides from different plant species. Development of high-throughput bioassays can facilitate the screening of large numbers of identified and putative plant peptides, which have recently been discovered but remain uncharacterized for biological activity.

OBJECTIVE: To investigate the specific mechanisms of action of Fertiwell in a mouse model of D-galactose-induced aging of the reproductive system.
METHODS: C57BL/6J mice were randomized into four groups: intact mice (control group), a group of mice with artificial accelerated aging treated with D-galactose alone (Gal), D-galactose followed by Fertiwell (PP), and D-galactose followed by a combination of L-carnitine and acetyl-L-carnitine (LC). The artificial accelerated aging of reproductive system was induced by daily intraperitoneal administration of D-galactose at a dose of 100 mg/kg for 8 weeks. After the end of therapy in all groups, the characteristics of sperm, the level of serum testosterone, immunohistochemical parameters, and the expression of specific proteins were evaluated.
RESULTS: Fertiwell had a pronounced therapeutic effect on testicular tissues and spermatozoa, restored testosterone levels to normal values, and, in addition, was more effective protector against oxidative stress in the reproductive system compared to L-carnitine and acetyl-L-carnitine, which are widely used in male infertility. Fertiwell at a dose of 1 mg/kg allowed to significantly increase the number of motile spermatozoa to 67.4+/-3.1%, which was comparable to indicators in the intact group. The introduction of the Fertiwell positively affected the activity of mitochondria, which was also expressed in an increase in sperm motility. In addition, Fertiwell restored the intracellular level of ROS to the values of the control group and reduced the number of TUNEL+ cells (with fragmented DNA) to the level of intact control. Thus, Fertiwell, containing testis polypeptides, has a complex effect on reproductive function, leading to a change in gene expression, an increase in protein synthesis, the prevention of DNA damage in the testicular tissue, and an increase in mitochondrial activity in testicular tissue and spermatozoa of the vas deferens, which leads to the subsequent improvement of testicular function.

Enteroendocrine cells (ECs) in the insect midgut respond to physiological changes in the intestine by releasing multiple peptides to control food intake, gastrointestinal activity and systemic metabolism. Here, we performed a comprehensive mapping of ECs producing different regulatory peptides in the larval midgut of Bombyx mori. In total, we identified 20 peptide genes expressed in different ECs in specific regions of the midgut. Transcript-specific in situ hybridisation combined with antibody staining revealed approximately 30 subsets of ECs, each producing a unique peptide or a combination of several different peptides. Functional significance of this diversity and specific roles of different enteroendocrine peptides are largely unknown. Results of this study highlight the importance of the midgut as a major endocrine/paracrine source of regulatory molecules in insects and provide important information to clarify functions of ECs during larval feeding and development.

The results of studies on the antioxidant effect of a number of peptide drugs, which is manifested at various levels, ranging from cells to the whole body, in adulthood and during aging, under the influence of extreme environmental factors, indicate the important role of low-molecular peptides in the mechanisms of regulating homeostasis during aging. The antioxidant properties of regulatory peptides are shown in experiments both on intact sexually mature animals, and especially clearly during aging or the action of extreme environmental factors (hypoxia, hypokinesia). A number of the studied substances (AEDG, KE) have a membrane-stabilizing effect, preventing osmotic and acid hemolysis of red blood cells and reducing the level of extra-erythrocyte hemoglobin and total peroxidase activity in blood plasma. It is shown that the studied peptides are able to have a neuroprotective effect by stabilizing the activity of enzymes (neprilysin, an insulin degrading enzyme) that play an important role in the catabolism of beta-amyloid, and prevent its accumulation in concentrations toxic to cells. The involvement of regulatory peptides with antioxidant properties on the expression of genes that ensure the stabilization of mitochondrial membranes, the functioning of the electron transport chain and the activity of antioxidant enzymes is considered.
Приведенные в работе результаты исследований об антиоксидантном действии ряда пептидных препаратов, которое наблюдается на различных уровнях, начиная от клеточного до организма в целом, свидетельствуют о важной роли низкомолекулярных пептидов в механизмах регуляции гомеостаза при старении. Антиоксидантные свойства регуляторных пептидов проявляются в экспериментах как на интактных половозрелых животных, так и особенно наглядно при старении или действии экстремальных факторов внешней среды (гипоксия, гипокинезия). Ряд исследуемых пептидов (AEDG, KE) оказывают мембраностабилизирующее действие, препятствуя осмотическому и кислотному гемолизу эритроцитов и снижая уровень содержания внеэритроцитарного гемоглобина и суммарной пероксидазной активности в плазме крови. Показано, что исследуемые пептиды способны оказывать нейропротекторный эффект путем стабилизации активности ферментов (неприлизин, инсулин деградирующий фермент), играющих важную роль в катаболизме β-амилоида, и препятствовать его накоплению в мозге. Рассматривается участие регуляторных пептидов, обладающих антиоксидантными свойствами, на экспрессию генов, обеспечивающих стабилизацию митохондриальных мембран, функционирование электрон-транспортной цепи и активность антиоксидантных ферментов.

Numerous regulatory peptides play a critical role in the pathogenesis of airway inflammation, airflow obstruction and hyperresponsiveness, which are hallmarks of asthma. Some of them exacerbate asthma symptoms, such as neuropeptide Y and tachykinins, while others have ameliorating properties, such as nociception, neurotensin or β-defensin 2. Interacting with peptide receptors located in the lungs or on immune cells opens up new therapeutic possibilities for the treatment of asthma, especially when it is resistant to available therapies. This article provides a concise review of the most important and current findings regarding the involvement of regulatory peptides in asthma pathology.

Aging is associated with a decline in the erectile capacity and sexual motivation. Emerging new therapy for the treatment of these age-related pathologies in men is the use of the regulatory peptides. We validated the use of HLDF-6-amide (Thr-Gly-Glu-Hse-His-Arg-NH2) as a potential modulator of sexual performance in aged male rats. Behavioral tests, including the standard parameters of sexual behavior, were performed longitudinally at 20 and 26 months of age. The effects of HLDF-6-amide administered daily at 300 μg/kg for 3 week on the levels of sex hormones and the activity of antioxidant enzymes and indicators of inflammation were evaluated. HLDF-6-amide administration increased the copulative activity of the 20-month-old male rats. This effect of HLDF-6-amide was more pronounced in the 26-month-old rats. Although HLDF-6-amide did not have the effect on the levels of circulating testosterone and estradiol, it reduced the activity of leukocyte elastase and glutathione-S-peroxidase, suggesting that the peptide has anti-inflammatory and antioxidant properties. Therefore, this study shows that HLDF-6-amide has the positive impact on sexual activity in this rodent model, representing a new therapeutic approach for improving sexual performance in older men.

Some pri-miRNAs can code for short peptides called micropeptides (miPEPs) and it has been suggested that these peptides positively regulate the accumulation of their associated miRNAs. Recent data further support this model and point towards the potential for miPEPs to be used in the agricultural sector to improve crop agronomic traits.