This scoping review explores the expression patterns and molecular features of sarcoglycans (SGs) in non-muscle organs, challenging the long-standing assumption that their function is confined to skeletal and cardiac muscle. By analyzing evidence from both animal models and human studies, the review highlights the widespread presence of SG subunits in organs, including the nervous system, glands, adipose tissue, oral mucosa, retina, and other structures, with distinct regional and cell-type-specific patterns. Studies on the central nervous system demonstrate a widespread “spot-like” distribution of SG subunits in neurons and glial cells, implicating their involvement in synaptic organization and neurotransmission. Similarly, SGs maintain cellular integrity and homeostasis in glands and adipose tissue. At the same time, the altered expression of SGs is associated with pathological conditions in the gingival epithelium of the oral mucosa. These findings underscore the multifaceted roles of SGs beyond muscle, suggesting that they may contribute to cellular signaling, membrane stability, and neurovascular coupling. However, significant gaps remain regarding SG post-translational modifications and functional implications in non-muscle organs. Future research integrating molecular, cellular, and functional approaches in animal models and human tissues is essential to fully elucidate these roles and explore their potential as therapeutic targets in various diseases.

The International Journal of Molecular Sciences retracts the article, “Differential Expression of Nitric Oxide Synthase Isoforms nNOS and iNOS in Patients with Non-Segmental Generalized Vitiligo” [...]

Inflammatory bowel diseases (IBDs) represent multifactorial chronic inflammatory conditions of the gastrointestinal tract. The main IBDs are Crohn’s disease (CD) and ulcerative colitis (UC). CD may cause perforation, stricture or transmural inflammation, which can occur discontinuously in the entire gastrointestinal tract (GIT). UC leads to mucosal inflammation as well as mucosal atrophy in the rectum and the colon. Innate immunity is considered the first line of defense against microbial invasion; among Toll-like receptors, TLR2 is the most important for defense against mycobacterial infection. TLR2 has been reported to have a lot of functions in infectious diseases and in other pathologies, such as chronic and acute inflammatory diseases. Alfa-Smooth Muscle Actin (α-SMA) is an important biomarker in IBDs. All myofibroblasts express α-SMA, which has been found to be upregulated in CD and UC. Paraformaldehyde-fixed intestinal tissues, from patients with CD and patients with UC, were analyzed by immunostaining for TLR2 and α-SMA. Our results showed that, in the samples obtained from UC patients with inflamed mucosa, TLR2-positive epithelial cells concentrated on the mucosal surface and scattered immune cells in the connective tissue; furthermore, numerous α-SMA-positive cells (subepithelial myofibroblasts) were detected in the lamina propria and around glands, while some myofibroblasts co-localizing with α-SMA and TLR2 could be inflammatory macrophages. In CD patients, TLR2-positive enterocytes and α-SMA-positive myofibroblasts in the lamina propria of the villus have been observed. In control samples, a low positivity to α-SMA and TLR2 was observed in subepithelial myofibroblasts and scattered immune cells of the lamina propria. These data showed the recall of α-SMA-positive myofibroblasts during the inflammatory state; in addition, TLR2 expression has been observed to change in the intestinal epithelium in IBDs, demonstrating that alterations in the innate system response may contribute to the pathogenesis of these diseases.

In the present study, the inkjet-printing (IJP) technique is used for the development of a planar microwave sensor aimed at the dielectric characterization of biological samples. The proposed sensor consists of two capacitively coupled split-ring resonators (SRRs) fabricated using the microstrip technology. A silver-based conductive ink is deposited by IJP on a conventional 1.6-mm-thick FR4 substrate, thus creating the resonant structure. The experimental analysis is carried out by considering a water–ethanol mixture as a test solution in which the ethanol volume fraction is varied, thereby changing the effective permittivity of the mixture. In this contribution, the authors focused their analysis on the dielectric constant of the solution under test (i.e., the real part of the complex relative permittivity). The water–ethanol mixture is placed into a low-density polyethylene (LDPE) sample vial that is arranged on the surface of the planar sensor. No direct contact is needed between the microwave device and the solution under test. The effect of the ethanol volume fraction change is related to the behavior of the two resonances occurring in the forward transmission coefficient ( ${S}_{21}$ ) of the sensor in the frequency range from 2 to 3 GHz. The permittivity change of the sample under test affects the capacitive coupling between the two SRRs altering the separation between two resonant frequencies. This enables the sensor to differential measurements, thereby improving its robustness. The frequency separation is used to track variations in the ethanol concentration and, thus, the dielectric constant of the solution under test. In addition, a lumped-element equivalent-circuit model is presented, and the changes in the values of the lumped elements with ethanol concentration are estimated and discussed.

Bisphosphonate-Related Osteonecrosis of the Jaw (BRONJ) is a pathological condition observed in patients underwent oral surgical procedures during bisphosphonates treatment. Although several studies have focused on the BRONJ, the exact pathophysiological pathways remain still unclear. In this study we aimed to observe the effects of the low-dose bisphosphonates administration on mandibular bone of rats with and without mini-implants application. For this study we used 28 male Wistar rats, divided in in two groups: 1) control group, treated with saline solution (n = 14 rats); 2) ZA group, treated with low dose zoledronic acid (n=14 rats). After 6 weeks of treatment, the half of each group underwent mini-implant application. All rats were sacrificed and their mandibles were analyzed by light microscopy and scanning electron microscopy (SEM). Our data have shown a healthy bone tissue of control group both with and without mini-implant application. In the treated group empty osteocyte lacunae have been observed and they slightly increase in rats with mini-implant application. Although that, no bone exposition has been observed. By that, during low dose zoledronic acid treatment we can observe the presence of empty osteocytes lacunae, also called “primary lesion”, that not seem to be sufficient alone to determine osteonecrosis of the jaw spontaneously or even after mini-implant application.

Crohn's disease (CD) and ulcerative colitis (UC) are both inflammatory bowel diseases (IBD). Unlike UC, which is limited to the mucosa of the colon, CD inflammation is characterized by chronic mucosal ulcerations affecting the entire gastrointestinal tract. Goblet cells (GCs) can be found in some lining epithelia, particularly in the respiratory and digestive tracts. GCs represent the main source of mucin that are the significant components of the mucus layer; hypertrophy of GCs and an increase in mucin production are observed in many enteric infections. The cytoplasm of goblet cells may also contain neuropeptides, such as serotonin, that can be altered in inflammatory bowel disease (IBD). The defense system of the gut is represented by the intestinal mucosal barrier, its protective function is strictly connected to the regulation of the mucus layer and the coordination of the neuro-immune response. Paraformaldehyde-fixed intestinal tissues, obtained from fifteen patients with Crohn's disease, were analyzed by immunostaining for MUC2, MUC4, 5-HT, and VAChT. This study aims to define the link between neuropeptides and mucins in mucous cells and their involvement in the inflammation process. Our results showed in mucous cells of Crohn's disease (CD) patients a high expression of MUC4 and a decrease in the expression of vesicular acetylcholine transporter (VAChT) demonstrating the presence of an inflammatory state.

[This corrects the article DOI: 10.3389/fphar.2016.00273.].

The inkjet printing (IJP) is a highly attractive printing technology, consisting in the deposition of ink layers on flexible or rigid substrates. IJP technology is used in the present study to develop a planar microstrip sensor aimed at the dielectric characterization of biological samples, such as cell cultures. In this contribution we focused on the dielectric constant of the solution under test (i.e., the real part of the complex relative permittivity). The proposed sensor consists of two capacitive coupled ring resonators, which are achieved by printing a silver-based conductive ink on a 1.6-mm thick FR4-substrate. The measurement-based analysis is performed by studying the two resonances occurring in the forward transmission coefficient in the frequency range from 2 GHz to 3 GHz. By considering a water-ethanol mixture as a case study, the developed sensor is successfully validated for dielectric characterization of the material surrounding the prototype itself. No direct contact is required between the microwave transducer and the solution under test. In the present work, the water-ethanol mixture is put into a low-density polyethylene (LDPE) sample vial and placed over the sensor. It is found that the difference between the two resonant frequencies can be used as sensing parameter for monitoring variations in the ethanol concentration and then in the resulting dielectric constant of the solution under test.

The sarcoglycan sub-complex is a protein system which plays a key role in sarcolemma stabilization during muscle activity consisting of six glycosylated transmembrane proteins. Integrins play a key role in the process of cell adhesion, linking the extracellular matrix to the actin cytoskeleton. Here we have analysed the receptor for thyroid hormone, identified on αvβ3-integrin that has an important role in the activation of non-genomic actions of the hormone. Many non-genomic actions of the thyroid hormone appear to contribute to basal levels of activity of a variety of proteins, including ion pumps, intracellular protein trafficking and protein turnover. The purpose of our research was to study the presence and behaviour of sarcoglycans and integrins on the thyroid gland, in both normal and pathological conditions, for the first time. Our results show a normal fluorescence pattern in patients without pathology, and a reduced fluorescence pattern in patients with thyroid disease. Moreover, colocalization in healthy patients was found in double localization reactions, whereas in patients with Hashimoto’s thyroiditis sarcoglycans did not colocalize with tested integrin. These data could confirm the hypothesis of a close association between sarcoglycans and integrins, which, in pathological condition, are not found contemporarily hypothesizing that each single protein system could have a role in maintaining cell vitality.

Crohn's disease (CD) is a chronic intestinal inflammation considered to be a major entity of inflammatory bowel diseases (IBDs), affecting different segments of the whole gastrointestinal tract. Peripheral serotonin (5-HT), a bioactive amine predominantly produced by gut enterochromaffin cells (ECs), is crucial in gastrointestinal functions, including motility, sensitivity, secretion, and the inflammatory response. These actions are mediated by a large family of serotonin receptors and specialized serotonin transporter (SERT) located on a variety of cell types in the gut. Several studies indicate that intestinal 5-HT signaling is altered in patients with inflammatory bowel disease. Paraformaldehyde-fixed intestinal tissues, obtained from fifteen patients with Crohn's disease were analyzed by immunostaining for serotonin, Langerin/CD207, and alpha-Smooth Muscle Actin (α-SMA). As controls, unaffected (normal) intestinal specimens of seven individuals were investigated. This study aimed to show the expression of serotonin in dendritic cells (DCs) and myofibroblast which have been characterized with Langerin/CD207 and α-SMA, respectively; furthermore, for the first time, we have found the presence of serotonin in goblet cells. Our results show the correlation between different types of intestinal cells in the maintenance of the inflammatory state in CD linked to the recall of myofibroblasts.

The dystrophin-glycoprotein complex is a multimeric system made up of the sarcoglycan sub-complex, the sarcomplasmatic complex and the dystroglycans complex. The sarcoglycan sub-complex stabilizes the sarcolemma during muscle activity and plays a role in force transduction. This protein system is also expressed in the muscle of non-human primates such as chimpanzees and baboons, and its expression changes depending on social ranking. In fact, previous data have shown that all muscle fibers of masseter and sternocleidomastoid muscles of chimpanzees and high- ranking baboons always express sarcoglycans, while middle- and low-ranking baboons are characterized by fibers that are negative for the sarcoglycan sub-complex. Given this information, the aim of the present work was to evaluate the expression of other proteins such as laminin, beta dystroglycan and dystrophin in the sternocleidomastoid muscle of high- and low-ranking baboons. The samples were processed by immunohistochemistry; results show that in high-ranking baboons, all tested proteins were always expressed while in low-ranking baboons, fibers that were negative for sarcoglycans and beta dystroglycan have been observed. No negative fibers for laminin and dystrophin have been found in low-ranking baboons suggesting that only the transmembrane proteins of the dystrophin glycoprotein complex change in their expression and that could be correlated to a phylogenetic arrangement.

Ulcerative colitis is a chronic inflammatory condition of the gastrointestinal tract that can affect people of worldwide. In contrast with Crohn’s disease, that can relate the entire thickness of the bowel wall, the inflammation of ulcerative colitis is limited to the colonic mucosa. Immune cells including activated T cells, plasma cells, mast cells, macrophages, and dendritic cells (DCs) trigger the inflammation. Furthermore, dendritic cells are antigen presenting cells involved in maintaining intestinal immune homeostasis. It has been described an increment of number in DCs colonic mucosa of patients with ulcerative colitis. The immune cells such as antigen-presenting cells can act as autocrine or paracrine modulators. Recent studies showed that dendritic cells synthetized and released classical neurotransmitters as glutamate, dopamine, acetylcholine, and serotonin. Paraformaldehyde-fixed intestinal tissues, obtained from the stricture sites of ten patients with ulcerative colitis were analyzed by immunostaining for Langerin/CD207, serotonin and vesicular acetylcholine transporter. As controls, unaffected (normal) portions of five patients were also investigated. Aim of this study was to characterize for the first time the human gut dendritic cells of ulcerative colitis patients, with Langerin/CD207 that is a c-type lectin expressed by different types of DCs and to colocalize in the same cells the expression of serotonin and vesicular acetylcholine transporter, showing the link between dendritic cells, gut enterochromaffin cells or autonomic nerves in immune activation and generation of intestinal inflammation.

Unilateral posterior crossbite is a malocclusion disease that involves morpho-functional characteristics of masseter muscle; a normal or increased activity of contralateral muscle and a reduced activity of the ipsilateral muscle during unilateral crossbite have been shown. Since the extracellular matrix plays a key role in in mechano-transduction of transmitting forces during muscle contraction, the aim of the present study was to analyse the behaviour of extracellular matrix in this type of malocclusion through immunofluorescence reactions against laminin, collagen IV, MMP-2 and MMP-9. Our results show an increased expression of Laminin, Collagen IV, and MMP-9 in the contralateral side if compared to the ipsilateral side. No differences have been found in MMP-2 expression between contralateral and ipsilateral muscles. Since the increased expression of Laminin, Collagen IV and MMP-9 is associated with muscle hypertrophy and MMP-2 is associated with muscle atrophy, our results support the existence of a hypertrophic response of contralateral muscle during unilateral posterior crossbite that probably aims to compensate the altered function of the ipsilateral one.

The extracellular matrix of the articular disc in a temporomandibular joint (TMJ) is composed mainly of collagen I and elastin. The collagen is important for resisting tensile forces, while the elastin is responsible to maintain the shape after deformation. We studied the orientation of collagen and elastin in a normal human temporomandibular joint disc by light microscopy, immunofluorescence and scanning electron microscopy. Our results demonstrated that collagen and elastin run parallel to each other in the intermediate zone with an anteroposterior orientation. From here, the orientation of two fibers groups changes into a disordered arrangement in the transition zone. Numerous elastic fibers cross with the collagen fibers, defining an interwoven knitted arrangement. The evaluation of the disc–condyle relationship shows that the medial margin of the articular disc is inserted directly at the superficial layer of the mandibular condylar cartilage. Therefore, the tensile properties of the TMJ disc are expressed in the directions corresponding to the orientation of the collagen fibers, and the complex orientation of elastin with the collagen determines the maintaining of the shape after the stresses by the joint movements. Moreover, the direct anatomical relationship between the articular disc and the mandibular condyle makes a decisive contribution to the understanding of TMJ movements.

Unilateral posterior crossbite is a type of malocclusion that involves morpho-functional characteristics of masticatory muscle, such as the masseter: electrophysiological data have shown that the affected side works less than the contralateral muscle, which shows a normal or increased activity, probably in order to compensate for the affected side. The aim of present work was to measure the diameter and the cross-sectional area of ipsilateral and contralateral muscle fibers to verify if hypertrophy and/or hypotrophy take place in this malocclusion. We used immunofluorescence pictures to measure, using ImageJ software, the diameter and the cross-sectional area of fibers from control and crossbite groups; after that, the data were processed to perform statistical analyses. Results show that the fiber diameters of contralateral muscle are larger than the diameters of ipsilateral and control fibers, and that this difference is statistically significant. No statistically significant difference was found between the fiber diameters of the ipsilateral and control muscles. All these data suggest that, during unilateral posterior crossbite, morphological changes take place in the contralateral masseter muscle, which undergoes hypertrophy, probably to compensate for the low activity of the affected muscle.

Background and objectives: Functional deregulation of dopaminergic midbrain regions is a core feature of schizophrenia pathophysiology. Anatomical research on primates suggests that these regions may be subdivided into distinct, topographically organized functional territories according to their connectivity to the striatum. The aim of the present work was the reconstruction of dopaminergic midbrain subregions in healthy subjects and schizophrenic patients and the evaluation of their structural connectivity profiles. Materials and Methods: A hypothesis-driven connectivity-based parcellation derived from diffusion tractography was applied on 24 healthy subjects and 30 schizophrenic patients to identify distinct territories within the human dopaminergic midbrain in vivo and non-invasively. Results: We identified a tripartite subdivision of dopaminergic midbrain, including limbic, prefrontal and sensorimotor territories. No significant differences in structural features or connectivity were found between subjects and patients. Conclusions: The parcellation scheme proposed herein may help to achieve detailed characterization of structural and functional anomalies of the dopaminergic midbrain in schizophrenic patients.

The temporomandibular joint (TMJ) is a bilateral synovial articulation stabilized by several anatomical structures such as ligaments. The existence of articular capsule reinforcement structures have been described in the lateral and medial sides of disc which have been defined as collateral ligaments, lateral and medial. Despite that, some macroscopic observations support that these collateral ligaments do not belong to the articular capsule but they belong to the disc. By that, the aim of the present work was to evaluate morphological aspects of TMJ from cadaveric frozen heads by histological and immunofluorescence techniques in order to verify the origin and insertion of lateral and medial collateral ligaments. Results show that both lateral and medial ligaments origin from the disc and insert directly to the articular cartilage of mandibula condyle. These data open a new approach in the study of human TMJ.

The orthodontic tooth movement is the last step of several biological processes that take place after the application of external forces. During this process, dental pulp tissue is subjected to structural and protein expression modifications in order to maintain their integrity and functional morphology. The purpose of the present work was to perform an in vivo study, evaluating protein expression modifications in the human dental pulp of patients that have undergone orthodontic tooth movement due to pre-calibrated light force application for 30 days. Dental pulp samples were extracted from molars and premolars of the control group and after 7 and 30 days of treatment; the samples were then processed for immunofluorescence reactions using antibodies against fibronectin, collagen I and vascular endothelial growth factor (VEGF). Our results show that, after 7 days of treatment, all tested proteins change their pattern expression and will reset after 30 days. These data demonstrate that the dental pulp does not involve any irreversible iatrogenic alterations, supporting the efficacy and safety of using pre-calibrated force application to induce orthodontic tooth movement in clinical practice.

The periodontal ligament (PDL) is a highly vascularized connective tissue surrounding the root of a tooth. In particular, the PDL is continuously exposed to mechanical stresses during the phases of mastication, and it provides physical, sensory, and trophic functions. It is known that the application of orthodontic force creates a change in periodontal structures. In fact, these forces generate a pressure on the ligament that closes the vessels. The aim of this study is to observe the modifications of vascular endothelial growth factor (VEGF) in the PDL and extracellular matrix proteins after application of a pre-calibrated and constant orthodontic force at different phases of treatment. We used a 50-g NiTi coiled spring and in vivo samples of PDL of maxillary and mandibular premolars of patients subjected to orthodontic treatment. These teeth were extracted at 1, 7, 14, 21, and 30 days, respectively, by application of force. The extraction of the PDL was effectuated by scarifying the radicular surface on the pressure and tension sides. The mechanical stress induced by the application of force caused an increase in the reactive type of metabolism of extracellular matrix proteins and modulation of neoangiogenesis until restoration.

Dental pulp is formed by connective tissue and it is localized in cavity of tooth. In the den- tal pulp is verified all defensive processes so as in all connective tissues. This tissue is continu- ously exposed to mechanical stresses during the phases of orthodontic therapy [1]. The progres- sion of the inflammatory process in human pulp fibroblasts apparently depends on stimulation by neuropeptides and production of inflammatory cytokines. A recent report described apop- tosis in dental pulp tissues of rats undergoing orthodontic treatment [2]. The literature shows conflicting results for correlation of pulpal changes incident to orthodontic force. Some reports suggested permanent damage to pulpal tissue from orthodontic force, but others claimed no significant long-lasting effects on the pulp [2]. However tissue reactions incident to orthodon- tic tooth movement depend mainly on the pattern of stress-strain distribution in the paraden- tal tissue. In recent years, the alterations in pulpal vasculature and blood flow in response to orthodontic force have gained much attention. The clinical impact of these studies was to deter- mine whether any alterations in pulpal tissue could jeopardize the long-term vitality of the teeth. In this study we analyzed in vivo human samples of dental pulp of 18 subjects, sched- uled for orthodontic treatment at the Department of Dentistry of Messina University. The pre- molars were subjected to a buccally directed tipping force (50 g) with Nickel Titanium closed coil spring (American Orthodontics). On dental pulp samples, after extraction of the premolars,were monitored by analysis of the expression of different proteins that compose it and by anal- ysis of Vascular Endothelial Growth Factor (VEGF). We have demonstrated an initial decrease in blood flow at 7 days, followed by an increase in blood flow at 28 days.