Current Status of Cell-Based Therapies for Vitiligo.

Vitiligo is a chronic pigmentary disease with complex etiology, the signs of which are caused by the destruction of melanocytes in the epidermis, leading to the lack of melanin pigment responsible for skin coloration. The treatment of vitiligo, which aims at repigmentation, depends both on the clinical characteristics of the disease as well as on molecular markers that may predict the response to treatment. The aim of this review is to provide an overview of the clinical evidence for vitiligo cell-based therapies taking into account the required procedures and equipment necessary to carry them out as well as their effectiveness in repigmentation, assessed using the percentage of repigmentation of the treated area. This review was conducted by assessing 55 primary clinical studies published in PubMed and ClinicalTrails.gov between 2000 and 2022. This review concludes that the extent of repigmentation, regardless of the treatment method, is highest in stable localized vitiligo patients. Moreover, therapies that combine more than one cell type, such as melanocytes and keratinocytes, or more than one method of treatment, such as the addition of NV-UVB to another treatment, increase the chances of >90% repigmentation. Lastly, this review concludes that various body parts respond differently to all treatments.

Milk Formula Enriched with Sodium Butyrate Influences Small Intestine Contractility in Neonatal Pigs.

Butyrate, a by-product of gut bacteria fermentation as well as the digestion of fat in mother's milk, exerts a wide spectrum of beneficial effects in the gastrointestinal tissues. The present study aimed to determine the effects of sodium butyrate on small intestine contractility in neonatal piglets. Piglets were fed milk formula alone (group C) or milk formula supplemented with sodium butyrate (group B). After a 7-day treatment period, isometric recordings of whole-thickness segments of the duodenum and middle jejunum were obtained by electric field stimulation under the influence of increasing doses of Ach (acetylocholine) in the presence of TTX (tetrodotoxin) and atropine. Moreover, structural properties of the intestinal wall were assessed, together with the expression of cholinergic and muscarinic receptors (M1 and M2). In both intestinal segments (duodenum and middle jejunum), EFS (electric field stimulation) impulses resulted in increased contractility and amplitude of contractions in group B compared to group C. Additionally, exposure to dietary butyrate led to a significant increase in tunica muscularis thickness in the duodenum, while mitotic and apoptotic indices were increased in the middle jejunum. The expression of M1 and M2 receptors in the middle jejunum was significantly higher after butyrate treatment. The results indicate increased cholinergic signaling and small intestinal growth and renewal in response to feeding with milk formula enriched with sodium butyrate in neonatal piglets.

Association between Maternal Periodontitis and Development of Systematic Diseases in Offspring.

Periodontal disease (PD) is one of the most common oral conditions affecting both youths and adults. There are some research works suggesting a high incidence of PD in pregnant women. As an inflammatory disease of bacterial origin, PD may result in the activation of the pathways affecting the course and the pregnancy outcome. The authors, based on the literature review, try to answer the PICO question: Does maternal periodontitis (exposure) influence the incidence of complications rates in pregnancy and the development of systemic diseases in childhood and adult offspring (outcome) in the humans of any race (population) compared to the offspring of mothers with healthy periodontium (comparison)? The authors try to describe the molecular pathways and mechanisms of these interdependencies. There is some evidence that maternal periodontitis may affect the pregnancy course and outcome, resulting in preeclampsia, preterm delivery, vulvovaginitis and low birth weight. It can be suggested that maternal periodontitis may affect offspring epigenome and result in some health consequences in their adult life.

Pre-digestion of the lipids in infant formula affects gut maturation of the preterm pig.

Preterm birth is associated with increased risk of complications, specifically with regards to the gastrointestinal tract. These complications mainly include the maldigestion and malabsorption of nutrients resulting from the immaturity of the small intestine. The current study investigated whether pre-digestion of fat in infant formula would affect the developmental remodeling of the structure of the small intestine mucous membrane. Three groups of premature piglets (corresponding to 30-32 week of human gestation) were used in the study: the first group, not subjected to any treatment and euthanized within 2 hours after caesarian delivery, was used as the control group (PT group), the second group, was fed an infant formula-IF (SPT group), and the third group was fed a lipase pre-hydrolyzed infant formula-hIF (PPT group). Feeding preterm piglets with an infant formula for 14 days stimulated intestinal maturation (in SPT and PPT groups). However, pre-digestion of the infant formula with lipase significantly increased proliferative activity and intensity of apoptosis in the small intestine epithelium, resulting in more rapid enterocyte turnover. The data obtained not only confirm that starting enteral feeding directly after birth stimulates developmental and structural changes in the small intestine, but also highlighted the importance of lipid digestion for enterocyte turnover and speeding up of intestinal maturation in preterm piglets. The latest is of high importance for the proper gut development of preterm children.

Methods of Topical Administration of Drugs and Biological Active Substances for Dental Implants-A Narrative Review.

Dental implants are, nowadays, established surgical devices for the restoration of lost teeth. Considered as an alternative for traditional prosthetic appliances, dental implants surpass them in reliability and patient feedback. Local drug delivery around the implants promotes osseointegration and reduces peri-implantitis. However, there are currently no methods of a multiple, precise topical administration of drugs to the implant area. Engineering coatings on the implants, drug application on carriers during implantation, or gingival pockets do not meet all requirements of dental surgeons. Therefore, there is a need to create porous implants and other medical devices that will allow a multiple drug delivery at a controlled dose and release profile without traumatic treatment. Due to the growing demand for the use of biologically active agents to support dental implant treatment at its various stages (implant placement, long-term use of dental superstructures, treatment of the peri-implant conditions) and due to the proven effectiveness of the topical application of pharmacological biologically active agents to the implant area, the authors would like to present a review and show the methods and devices that can be used by clinicians for local drug administration to facilitate dental implant treatment. Our review concludes that there is a need for research in the field of inventions such as new medical devices or implants with gradient solid-porous structures. These devices, in the future, will enable to perform repeatable, controllable, atraumatic, and repeatable injections of active factors that may affect the improvement of osteointegration and the longer survival of implants, as well as the treatment of peri-implantitis.

Maternal High-Fat Diet Exposure During Gestation and Lactation Affects Intestinal Development in Suckling Rats.

Maternal health and diet influence metabolic status and play a crucial role in the development of metabolic function in offspring and their susceptibility to metabolic diseases in adulthood. The pathogenesis of various metabolic disorders is often associated with impairment in intestinal structure and function. Thus, the aim of the current study was to determine the effects of maternal exposure to a high fat diet (HFD), during gestation and lactation, on small intestinal growth and maturation in rat pups at 21 days old. Female, Wistar Han rats were fed either a breeding diet (BD) or high fat diet (HFD), from mating until the 21st day of lactation. Maternal HFD exposure increased body weight, BMI and adiposity. Compared to the maternal BD, HFD exposure influenced small intestine histomorphometry in a segment-dependent manner, changed the activity of brush border enzymes and had an impact on intestinal contractility via changes in cholinergic signaling. Moreover, offspring from the maternal HFD group had upregulated mRNA expression of cyclooxygenase (COX)-2, which plays a role in the inflammatory process. These results suggest that maternal HFD exposure, during gestation and lactation, programs the intestinal development of the offspring in a direction toward obesity as observed changes are also commonly reported in models of diet-induced obesity. The results also highlight the importance of maternal diet preferences in the process of developmental programming of metabolic diseases.

Gestational Diabetes Mellitus Affects Offspring's Epigenome. Is There a Way to Reduce the Negative Consequences?

Gestational diabetes mellitus (GDM) is the most common pregnancy complication worldwide and may result in short-term and long-term consequences for offspring. The present review highlights evidence of epigenetic programming, mostly from human studies, which occurs in offspring exposed to maternal GDM during different stages of development, paying special attention to the differences in sensitivity of offspring to maternal hyperglycemia as a result of sex-related factors. We also aim to answer the following question: If these epigenetic changes are constant throughout the lifetime of the offspring, how do they present phenotypically?

Correction: The effects of intra-stomach obestatin administration on intestinal contractility in neonatal piglets fed milk formula.

[This corrects the article DOI: 10.1371/journal.pone.0230190.].

The effects of intra-stomach obestatin administration on intestinal contractility in neonatal piglets fed milk formula.

A 23-amino acid peptide named obestatin is derived from the ghrelin gene. The aim of the experiment was to study the effects of enteral obestatin administration for a 6-day period on intestinal contractility in piglets fed milk formula. Pigs were treated with 0.9% NaCl (group C) or varying doses of obestatin: 2 µg/kg body weight (BW) (group O2), 10 µg/kg BW (O10) or 15 µg/kg BW (O15) every 8 hours via a stomach tube. Blood was sampled for assessment of obestatin concentration. Duodenal and middle jejunum whole-thickness preparations were studied in an organ bath for isometric recording under electric field stimulation (EFS) and increasing doses of acetylcholine (ACh), and in the presence of atropine and tetrodotoxin (TTX). Additionally, the measurement of intestinal muscularis layer and the immunodetection of Muscarinic Acetylcholine Receptors (M1 and M2) were performed. In comparison to C animals, the obestatin concentration in blood plasma was significantly increased in groups O10 and O15. In both studied intestinal segments, significant increases in the frequency and amplitude of spontaneous contractions were observed in O15 and C groups. In the duodenum and middle jejunum significant differences in responsiveness to EFS (0.5, 5 and 50 Hz) were observed between the groups. The addition of 10-4 M ACh to the duodenum significantly increased the responsiveness in tissues. In contrast, in the middle jejunum a significant increase in the amplitude of contraction was observed after the addition of 10-9 and 10-6 M ACh (groups O15 and O10, respectively). Pretreatment with atropine and TTX resulted in a significant decrease in the responsiveness of the intestinal preparations from all groups, in both studied segments. The increased contractility was not dependent on the expression of muscarinic receptors. Results indicate the importance of enteral obestatin administration in the regulation of intestinal contractility in neonatal piglets.

Small intestinal development in suckling rats after enteral obestatin administration.

This study investigated the effect of enteral administration of obestatin on the development of small intestine, as well as oxidative stress markers and trancriptomic profile of gastrointestinal genes. Suckling rats were assigned to 3 groups treated with: C-saline solution; OL-obestatin (125 nmol/kg BW); OH-obestatin (250 nmol/kg BW) administered twice daily, from the 14th to the 21st day of life. Enteral administration of obestatin in both studied doses had no effect neither on the body weight of animals nor the BMI calculated in the day of euthanasia. Compared to the control group (C), treatment with obestatin resulted in significant changes in the histometry of the small intestinal wall as well as intestinal epithelial cell remodeling. The observed changes and their possible implications for intestinal development were dependent on the dosage of peptide. The enteral administration of high dose (OH) of obestatin significantly decreased its expression in the stomach and increased markers of oxidative stress. The gene profile revealed MAPK3 (mitogen-activated protein kinase-3) as the key regulator gene for obestatin action in the gastrointestinal track. In conclusion, we have showed that enteral administration of obestatin influences the gut mucosa remodeling. It is also suggested that the administration of high dose (OH) has inhibitory effect on the intestinal maturation of suckling rats.

Maternal High-Fat Diet During Pregnancy and Lactation has Opposite Effects on Gonadal Expression of Leptin and Leptin Receptor in Rat Dams and Their Offspring.

This study investigated the effect of a high-fat (HF) diet on protein expression of leptin and its receptor in the gonads of dams and their offspring. Female Wistar rats were fed a HF diet (30% fat) or a standard breeding (BD) diet (5% fat) during pregnancy and lactation. At 21 days of lactation, mothers and both sexes of prepubertal offspring were killed by decapitation. The protein expression of leptin and its receptor was assayed by Western blot and immunohistochemistry in gonadal, periovarian, and epididymal white adipose tissue (WAT). We demonstrated that leptin protein expression in ovary, and both leptin and ObRb expression in periovarian WAT was decreased in HF dams compared with BD animals. Immunohistochemistry showed lower leptin expression in growing antral follicles and corpora lutea of HF dams. Conversely, in both gonads and epididymal WAT of HF offspring, leptin and its receptor were significantly higher expressed compared with BD. Immunolocalization of leptin system in HF offspring gonads showed higher expression in growing and antral follicles of the ovary, seminiferous tubules, and interstitial tissue of testes. In conclusion, high gonadal and gonadal-WAT expression of leptin system was observed in the offspring of dams fed a HF diet during pregnancy and lactation.

Small intestine motility development in newborn mammals.

Since the beginning of the 20th century, researchers have been working to improve the understanding of gastrointestinal motility. The first major discovery was the observation of a migrating myoelectric complex that turned out to be a universal occurrence among vertebrates. Further inquires resulted in a detailed description of its development during different stages of ontogeny. Some time before that, a cornerstone had been laid for a breakthrough that would come years later. That cornerstone came in the form of interstitial cells of Cajal whose true role could not be discerned until the discovery of a CD117 receptor - their main marker. With the ability to precisely mark interstitial cells of Cajal, a wave of subsequent new experiments and observations connected them to the occurrence of slow waves and allowed an understanding of the mechanism responsible for their generation. Some of these findings suggested that Cajal cells might have a role in the development of several motility disorders thus opening an avenue of research that requires the usage of both traditional and advanced diagnostic methods.

The biological role of a-ketoglutaric acid in physiological processes and its therapeutic potential.

In this article we present the results of recent studies on the mechanism of action and biological role of α-ketoglutaric acid (AKG) in animals including developmental period of life. AKG is an intermediate in the Krebs cycle, which generates energy for life processes. Administration of AKG has been shown to be beneficial for proper development and function of the skeletal system during growth of young organisms, as well as in adulthood. In the form of a dietary supplement it also contributes to inhibition of osteoporosis in women. Moreover, it promotes the growth of muscle mass and accelerates wound healing. AKG has a significant impact on the morphology of the gastrointestinal tract in healthy animals and animals with damaged gastrointestinal tract mucosa. It is also a promising substance for the treatment of patients with short bowel syndrome, as it stimulates beneficial changes in intestinal morphology. Recent research has also revealed that AKG has neuroprotective effects.