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The purpose of this study is to investigate the characteristics of dentigerous and radicular cysts that occur between deciduous and succeeding permanent teeth and to propose considerations for differential diagnosis of cysts at the treatment planning stage in the outpatient clinic.A total of 87 patients with a cystic lesion located between a deciduous tooth and the succeeding permanent tooth participated in the study. Twelve variables were analyzed to diagnose such a cyst. For data analysis, Fisher's exact test was used to determine the statistical significance of the variables.Of the total 87 patients who participated in this study, 69 were diagnosed with dentigerous cysts and 18 were diagnosed with radicular cysts. Seven of the 12 differential factors analyzed in this study were statistically significant: age, location, symptoms, dental caries, endodontic treatment, delayed eruption, and size.Several criteria can be considered for diagnosis of dentigerous cysts or radicular cysts. Age, location, presence of symptoms and dental caries, previous endodontic treatment, cystic size, and delayed eruption of impacted permanent teeth are reliable factors that should be considered when diagnosing dentigerous and radicular cysts.

A series of oligomeric chain extender-derived AEMs (QPP-b-PSK-w-TMA) are reported for AEMFC and AEMWE. Especially, the QPP-b-PSK-3.5-TMA-based AEMFC showed the highest specific power among the state-of-the-art AEMFCs with noble metal catalysts.

Cerium oxide-containing interlocking interfacial layer improved mechanical adhesion and chemical stability of the interface. For the first time as a hydrocarbon-based membrane, it operated stably for more than 500 hours.

Recent proteomic, metabolomic, and transcriptomic studies have highlighted a connection between changes in mitochondria physiology and cellular pathophysiological mechanisms. Secondary assays to assess the function of these organelles appear fundamental to validate these -omics findings. Although mitochondrial membrane potential is widely recognized as an indicator of mitochondrial activity, high-content imaging-based approaches coupled to multiparametric to measure it have not been established yet. In this paper, we describe a methodology for the unbiased high-throughput quantification of mitochondrial membrane potential in vitro, which is suitable for 2D to 3D models. We successfully used our method to analyze mitochondrial membrane potential in monolayers of human fibroblasts, neural stem cells, spheroids, and isolated muscle fibers. Moreover, by combining automated image analysis and machine learning, we were able to discriminate melanoma cells from macrophages in co-culture and to analyze the subpopulations separately. Our data demonstrated that our method is a widely applicable strategy for large-scale profiling of mitochondrial activity.

Objectives The purpose of this study was to evaluate the clinical and radiographic characteristics of idiopathic bone cavity (IBC) to determine the effect of surgical intervention on the process of healing. Materials and Methods All cases diagnosed with IBC during the period of 2011 to 2020 at our Department of Oral and Maxillofacial Surgery were searched. Ninety cases were retrieved. The features evaluated were sex, age, contour of the lesion, number of teeth involved, site, history of trauma, and postoperative healing pattern. The significance of differences was assessed by Mann-Whitney U test and chi-square test. Results The female:male ratio showed no predilection toward either sex (0.9:0.8). The mean age of the collected sample was 22.05±14.38 years, and the age ranged from 10 to 58 years. All cases presented in the mandible and showed well-circumscribed radiolucency. Margins were either scalloped or round in shape, and the size varied from one tooth to six teeth involvement. Seventy cases involved three or fewer roots. Three cases showed bilateral lesion. Four cases had a history of trauma at the area of the lesion. Fifty-one cases were followed for six months after surgery, and all showed increased bone density at the lesion. Conclusion There is no definitive radiological or clinical feature of IBC. Considering the diversity of clinical and radiological features, such a diagnosis relies primarily on surgical findings of an empty bone cavity with no epithelial lining. Our data suggest that surgical intervention be the first choice of treatment as opposed to observation.

The general bone anabolic effect of photobiomodulation (PBM) is largely accepted. As a result, PBM therapy is expected to be beneficial in the medical fields of dentistry and bone healing. However, most of the previous in vitro studies on PBM and bone metabolism were performed with single-cell cultures of osteoclast-lineage cells or osteoblast-lineage cells. In the present study, the bone-modulating effects of PBM were evaluated in an in vitro osteoblast/osteoclast co-culture system. Mouse bone marrow-derived macrophages (BMMs) and mouse calvarial pre-osteoblasts cells were purified and used as precursor cells for osteoclasts and osteoblasts, respectively. The PBM effects on single-cell culture of osteoclasts or osteoblasts as well as co-culture were examined by 1.2 J/cm2 low-level Ga-Al-As laser (λ = 808 ± 3 nm, 80 mW, and 80 mA; spot size, 1cm2; NDLux, Seoul, Korea) irradiation for 30 s at daily intervals throughout culture period. At the end of culture, the osteoclast differentiation and osteoblast differentiation were assessed by TRAP staining and ALP staining, respectively. The expressions of osteoclastogenic cytokines were evaluated by RT-PCR and Western blot analyses. Under the single-cell culture condition, PBM enhanced osteoblast differentiation but had minor effects on osteoclast differentiation. However, in the co-culture condition, its osteoblastogenic effect was maintained, and osteoclast differentiation was substantially reduced. Subsequent RT-PCR analyses and western blot results revealed marked reduction in receptor activator of NF-κB ligand (RANKL) expression and elevation in osteoprotegerin (OPG) expression by PBM in co-cultured cells. More importantly, these alterations in RANKL/OPG levels were not observed under the single-cell culture conditions. Our results highlight the different effects of PBM on bone cells based on culture conditions. Further, our findings suggest the indirect anti-osteoclastogenic effect of PBM, which is accompanied by a decrease in RANKL expression and an increase in OPG expression.

BACKGROUND/AIMS Teeth in a jaw fracture line, because of the presence of the periodontal ligament, may communicate with the oral cavity. There are no guidelines for the management of teeth in mandibular fracture lines. The aim of this study was to investigate the factors related to dental problems with teeth involved in mandibular fracture lines and to determine the best treatment option. MATERIAL AND METHODS This retrospective study was based on the medical and radiographic records of patients with mandibular fractures. The relationships among the patient's age, gender, smoking history, amount of bony displacement, surgery, trauma-surgery period, apical involvement, tooth mobility, and periodontal status were investigated. Group comparisons were performed using the chi-squared test, Fisher's exact test, and Mann-Whitney U-test. RESULT A total of 238 patients (247 fracture lines) with mandibular fractures including a tooth in the line of the fracture were examined. Post-operative dental complications occurred in 42 cases (17.0%). Extraction of related teeth occurred in 34 cases (80.9%) compared to eight cases (19.0%) related to root canal therapy. This study defined "dental problem" as "a case with a tooth extracted or endodontically treated after trauma." The variables associated with an increased risk of dental problems were the amount of bony displacement (p

The durability of the membrane electrode assembly (MEA) is one of the important requirements for the successful commercialization of anion exchange membrane fuel cells (AEMFCs). While chemical stabilities of the components (the catalyst, membrane, and ionomer) have been assessed by ex situ tests, the degradation mode of the components in a single-cell is still not fully understood. Herein, the degradation of a MEA based on an ionomer having a polycarbazole main chain and a trimethyl ammonium side group was systematically investigated for a single-cell level under constant current conditions. The degradations of the catalyst, membrane, and ionomer were compared by in situ electrochemical and ex situ post-mortem analyses. The catalyst and ionomer in the cathode showed significant degradation, whereas the membrane was relatively durable, suggesting that the formation of a strong alkaline environment in the cathode catalyst layer is a major cause of the performance fade. The use of an alkaline-stable ionomer with an N,N-dimethylhexylamine group, which is designed based on density functional theory (DFT) calculations, in the cathode catalyst layer leads to 87% durability improvement. This work enhances the understanding of the key factors affecting the durability of AEMFCs under real operation and suggests practical strategies toward higher durability.

Cytoplasmic serine/threonine Pim kinases have emerged as important modulators of immune regulation and oncology. However, their regulatory roles in bone remodeling remain obscure. Here, we aimed to determine the roles of Pim kinases in periodontal disease (PD), focusing on the regulation of osteoclastogenesis and bone resorptive activity. We investigated Pim kinases expression in PD by analyzing data from the online Gene Expression Omnibus database and using ligature-induced periodontitis mouse model. The expression of Pim kinases during receptor activator of nuclear factor kB ligand (RANKL)-induced osteoclastogenesis was assessed in mouse bone marrow-derived macrophages (BMMs) using reverse transcription polymerase chain reaction. Osteoclast differentiation and bone resorption activity were respectively verified by tartrate-resistant acid phosphatase staining and dentin disc-based bone resorption assays. We silenced and overexpressed Pim-2 using small interfering RNA (siRNA) and retroviral vector, respectively, to investigate the molecular mechanisms underlying Pim-2 regulation in RANKL-induced osteoclastogenesis and bone resorption activity. Upregulated expression of Pim-2 was observed in both patients with PD and periodontitis-affected mouse gingival tissues. siRNA-mediated silencing of Pim-2 in BMMs diminished RANKL-induced resorptive activity without affecting osteoclastogenesis. Moreover, RANKL-triggered stimulation of a3 isoform, which is a subunit of vacuolar-type ATPase, was selectively attenuated in BMMs on silencing Pim-2. The overexpression of Pim-2 with a retroviral vector stimulated the a3 subunit, thus inducing bone resorption activity. Taken together, these results suggest that Pim-2 acts as a major modulator of osteoclastic activity by regulating a3 isoform expression in PD.

Acacetin, which is present in damiana (Turnera diffusa ) and black locust (Robinia pseudoacacia ), has several pharmacologic activities such as antioxidant, anti-inflammatory, and anti-proliferative effects on cancer cells. However, the effect of acacetin on head and neck cancers has not been clearly established. This study aimed to examine the effects of acacetin on cell growth and apoptosis induction in FaDu human pharyngeal carcinoma cells. These were investigated by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay, Live/Dead cell assay, 4′,6-diamidino-2-phenylindole dihydrochloride staining, caspase-3 and caspase-7 activation assay, and immunoblotting in FaDu cells. Acacetin induced FaDu cell death in a dose-dependent manner, with an estimated IC50 value of 41.9 µM, without affecting the viability of L-929 mouse fibroblasts as normal cells. Acacetin treatment resulted in nuclear condensation in the FaDu cells. It promoted the proteolytic cleavage of procaspase-3, -7, -8, and -9 with increasing amounts of the cleaved caspase isoforms in FaDu cells. Acacetin-induced apoptosis in FaDu cells was mediated by the expression of Fas and activation of caspase-8, caspase-3, and poly (ADP-ribose) polymerase. Immunoblotting showed downregulation of the anti-apoptotic mitochondrial proteins Bcl-2 and Bcl-xL, but upregulation of the mitochondria-dependent pro-apoptotic proteins Bax and Badin FaDu cells after acacetin treatment. These findings indicate that acacetin inhibits cell proliferation and induces apoptotic cell death in FaDu human pharyngeal carcinoma cells via both the death receptor-mediated extrinsic apoptotic pathway and the mitochondria-mediated intrinsic apoptotic pathway.

Objectives The purpose of this study was to identify the characteristics of supernumerary teeth, analyze the associated complications, and to present new clinical knowledge on surgical interventions for supernumerary teeth. Study Design This retrospective cohort study was based on the medical records and radiographic records of patients who underwent surgical extraction of supernumerary teeth. The relationships among the patient's age, gender, anatomic features of supernumerary teeth, and presence and type of complications (i.e., spacing, rotation, delayed eruption of the adjacent tooth, cyst formation.) were investigated. The groups were compared by using the Mann-Whitney U test, the Kolmogorov-Smirnov test, and multiple logistic regression analysis (P Results The study population consisted of 705 participants who underwent extraction for 1036 supernumerary teeth. The mean age of the participants was 11.5 years, and 73.5% of the participants were males. The complication rate was 55.6%. Variables associated with an increased risk of complications were the patient's age, dentition, tuberculate shape, and horizontal direction of eruption (P Conclusions An increase in the patient's age or abnormalities in the shape and direction of eruption of supernumerary teeth was associated with complications. These parameters should be considered while formulating the treatment plan.

Anion conducting polymers (ACPs) are essential materials for alkaline electrochemical energy technology such as anion-exchange membrane fuel cells (AEMFCs) and water electrolysers (AEMWEs). The aforementioned polymers are promising alternatives for proton exchange membrane-based systems due to the possibility of using platinum group metal-free electrocatalysts. However, there are still no reliable ACPs possessing the desired performance and stability, which is a major challenge for developing alkaline energy systems. Herein, we highlight an anion-exchange membrane and ionomer based on quaternised poly-carbazole (QPC-TMA) with a rigid ether-free and curved backbone structure comprised of carbazole monomers. The developed ACP exhibits excellent ionic conductivity, as well as chemical and mechanical stability. Moreover, the AEMFC using QPC-TMA shows excellent performance (1.61 W cm−2) compared with the other best-performing AEMFCs. In addition, the AEMWE using QPC-TMA demonstrates outstanding stability and state-of-the-art performance (3.5 A cm−2 at 1.9 V), which is the first report of an AEMWE that outperforms the best-performing proton-exchange membrane water electrolysers.

Installed in Ganhyun Park, Wonju-si, South Korea, the 404 Skybridge is the longest pedestrian bridge in Korea, planned as a three-dimensional cable suspension bridge with a main span length of 380m. The location of the installation lies about 100m above from the ground level, on a slope of the mountain which presents very difficult construction condition.The three-dimensional cable suspension bridge is a challenge to construct but capable to achieve slender girders to have strong horizontal rigidity, without using separate wind resisting cables. By implementing the 3D angle of the cables much larger than the general three-dimensional suspension bridge, the horizontal rigidity of the girders enhanced, and flutter wind speed increased.At the start of the 404 Skybridge, Skywalk was constructed to provide scenery of the Ganhyun Park.

Background and Objectives: Malignant glioblastoma (GBM) is caused by abnormal proliferation of glial cells, which are found in the brain. The therapeutic effects of surgical treatment, radiation therapy, and chemo-therapy against GBM are relatively poor compared with their effects against other tumors. Luteolin is abundant in peanut shells and is also found in herbs and other plants, such as thyme, green pepper, and celery. Luteolin is known to be effective against obesity and metabolic syndrome. The anti-inflammatory, and anti-cancer activities of luteolin have been investigated. Most studies have focused on the antioxidant and anti-inflammatory effects of luteolin, which is a natural flavonoid. However, the association between the induction of apoptosis by luteolin in GBM and autophagy has not yet been investigated. This study thus aimed to confirm the occurrence of luteolin-induced apoptosis and autophagy in GBM cells and to assess their relationship. Materials and Methods: A172 and U-373MG glioblastoma cell lines were used for this experiment. We confirmed the apoptosis effect of Luteolin on GBM cells using methods such as 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, immunofluorescence, Flow cytometry (FACS) western blot, and real-time quantitative PCR (qPCR). Results: In the luteolin-treated A172 and U-373MG cells, cell viability decreased in a concentration- and time-dependent manner. In addition, in A172 and U-373MG cells treated with luteolin at concentrations greater than 100 μM, nuclear fragmentation, which is a typical morphological change characterizing apoptosis, as well as fragmentation of caspase-3 and Poly (ADP-ribose) polymerase (PARP), which are apoptosis-related factors, were observed. Autophagy was induced after treatment with at least 50 μM luteolin. Inhibition of autophagy using 3MA allowed for a low concentration of luteolin to more effectively induce apoptosis in A172 and U-373MG cells. Conclusions: Results showed that luteolin induces apoptosis and autophagy and that the luteolin-induced autophagy promotes cell survival. Therefore, an appropriate combination therapy involving luteolin and an autophagy inhibitor is expected to improve the prognosis of GBM treatment.

The purpose of this study was to evaluate risk factors and symptoms in cemento-osseous dysplasia (COD) patients.In this study, 62 patients who were diagnosed histologically with COD were investigated from 2010 to 2020 at the author's institution. We compared clinical and radiological characteristics of symptomatic and asymptomatic patients. The factors were sex, age, lesion size, site, radiologic stage of lesion, apical involvement, sign of infection, and history of tooth extraction. Statistical analysis was performed using Fisher's exact test and the chi-square test.COD was more prevalent in female patients. With the exception of three cases, all were focal COD. The majority of patients presented with symptoms when the lesion was smaller than 1.5 cm in size. Symptoms were observed when the apex of the tooth was included in the lesion or there was a local infection around the lesion. The history of tooth extraction and previous endodontic treatment were evaluated, and history was not a significant predictor for the onset of symptoms.In this study, risk factors associated with symptomatic patients were size of lesion, apical involvement, and local infection.

Background The purpose of this study was to review the clinical features of oromaxillofacial infections in patients presenting to a hospital emergency ward, to identify the key factors affecting the requirement for hospitalization, and the potential risk factors predisposing to a prolonged length of hospital stay. Methods A retrospective medical record review of the 598 patients treated for oromaxillofacial infection from 2013 to 2017 at the oral and maxillofacial surgery department, Yangsan Pusan National University Hospital, was conducted. The following information was collected from each patient: sex, age, past medical history, site of infection, etiology, admission or outpatient care, level of C-reactive protein (mg/dL), fascial spaces involved, treatment method, and duration of hospitalization. Chi-squared tests were used to identify risk factors, which were further analyzed using multivariable logistic regression. Results A total of 606 patients were eligible for inclusion in the study, of which eight were excluded due to having incomplete charts; thus, 598 patients were included: 55% were male, mean patient age was 47.1 ± 19.9 years, and 12.9% of patients were diabetic. Furthermore, 71.2% of patients had infection originating in the mandible; the most common tooth of origin was lower posterior, and 29.8% of patients were hospitalized. Risk factors for hospital admission were elderly patients with concurrent disease, elevated C-reactive protein level, and multiple-space infection in the oromaxillofacial area. The duration of hospitalization was correlated with both diabetes and age. Conclusions The requirement for hospital admission is determined by the severity of the infection; even severe infections, once treated with appropriate surgery, have no relation to the length of hospital stay. The important risk factors for increased duration of hospitalization are diabetes mellitus and older age. The understanding of risk factors associated with a prolonged hospital stay during the treatment of oromaxillofacial infection will aid in treatment planning as well as highlight the importance of adequate diabetes control in patients at risk of such infection.

Objective The aim of this study was to investigate the incidence of hypesthesia in patients with facial bone fractures and to identify the relationships between posttraumatic hypesthesia and risk factors, including general and fracture-related characteristics. Study Design A total of 437 patients who underwent surgery for facial bone fractures were included. Clinical neurosensory testing was performed at different time points (immediately after trauma and 1 week, 1 month, and 6 months after surgery). The results of these assessments were compared with regard to characteristics and fracture sites. Results The hypesthesia incidences were highest in the mandible (19.1%), maxilla (18.3%), and orbit (8.5%). Sensation was recovered by 97.3% of all patients by 6 months after surgery. Risk factors for hypesthesia were direct nerve injury (P = .002), distance (≤10 mm) between the fracture and nerve foramen (P = .002), the amount of bony displacement (P = .035), and age (P = .004). There were significant differences among the fracture sites. Conclusions Posttraumatic hypesthesia increased temporarily after surgery, but most patients recovered by 6 months postoperatively. Recovery from postoperative hypesthesia was related to the fracture site and pattern. Cases in which the patient did not recover involved direct nerve injury.

In this study, a fiber-optic remote temperature sensor (FRTS) for real-time temperature measurements in a spent nuclear fuel pool is developed. The proposed FRTS consists of a fiber-optic temperature-sensing probe and an optical time-domain reflectometer (OTDR). The probe of an FRTS consists of silicone oil, a fiber channel (FC) terminator, a single-mode optical fiber, and a copper metal cap. Silicone oil is employed as a temperature-sensing material owing to its temperature-dependent refractive index. The optical powers of the reflected light signals (Fresnel reflection), which are generated at the interface between the silicone oil and the core of a single-mode optical fiber in the distal end of the sensing probe, are measured. The temperature of the water was measured in 5 ℃ increments ranging from 10 to 70 ℃, using a fabricated FRTS and an OTDR. The proposed FRTS could be used to effectively monitor the water temperature of a spent nuclear fuel pool (SNFP) at a nuclear power plant (NPP).

In this study, we developed a scintillating fiber phantom dosimeter (SFPD) that can measure the transverse and longitudinal dose distributions of a Co-60 teletherapy source. The SFPD system is composed of organic scintillating fibers, polymethyl methacrylate (PMMA) phantoms, and a complementary metal–oxide–semiconductor (CMOS) sensor camera. When the phantom dosimeter is irradiated with gamma rays from a Co-60 teletherapy source, scintillating lights are emitted from the scintillating fibers inserted in the phantom dosimeter. The scintillating images are measured using a CMOS camera in real time and analyzed using an image processing program. The proposed phantom dosimeter has many advantages such as real-time measurement, easy calibration, and immunity to electromagnetic interference. In addition, it can measure complex dose distributions more precisely, because it has a high spatial resolution due to the small size of organic scintillating fibers. To evaluate the performance of the proposed phantom dosimeter, transverse and longitudinal dose distributions are measured using the CMOS sensor camera. Dose distributions are measured according to the field sizes and compared to the results obtained using an EBT3 film and MCNPX calculations.

The purpose of this study was to investigate the accuracy of the airway volume measurement by a Regression Neural Network-based deep-learning model. A set of manually outlined airway data was set to build the algorithm for fully automatic segmentation of a deep learning process. Manual landmarks of the airway were determined by one examiner using a mid-sagittal plane of cone-beam computed tomography (CBCT) images of 315 patients. Clinical dataset-based training with data augmentation was conducted. Based on the annotated landmarks, the airway passage was measured and segmented. The accuracy of our model was confirmed by measuring the following between the examiner and the program: (1) a difference in volume of nasopharynx, oropharynx, and hypopharynx, and (2) the Euclidean distance. For the agreement analysis, 61 samples were extracted and compared. The correlation test showed a range of good to excellent reliability. A difference between volumes were analyzed using regression analysis. The slope of the two measurements was close to 1 and showed a linear regression correlation (r2 = 0.975, slope = 1.02, p &lt, 0.001). These results indicate that fully automatic segmentation of the airway is possible by training via deep learning of artificial intelligence. Additionally, a high correlation between manual data and deep learning data was estimated.

Background Stability of the grafted bone volume is one of the important factors to the success of alveolar bone grafts. For this, platelet-rich plasma (PRP) or fibrin sealant is mixed with the bone graft material. Bio-Oss® is a protein-free bovine mineral commonly used in bone graft procedures. The grafting particles are commonly combined with a standard fibrin sealant (Tisseel®) to fabricate a plastic implantable product. The purpose of this experiment was to evaluate the efficacy of fibrin sealant (Tisseel®) in bone regeneration performance in a rabbit maxillary sinus model. Methods A total of five 3.5 kg weight New Zealand white rabbits were used for the study. After elevating the sinus membrane in both maxillary sinus cavities, Bio-Oss® mixed with normal saline (group 1) was filled into the right side, and Tisseel® mixed Bio-Oss® (group 2) was inserted into the other side. The bone mineral density and bone volume were analyzed with microscopic computed tomography (micro-CT) and histomorphometric 12 weeks after application. Results Histologically, new bone formation rate was 14.8%, and grafted bone rate was 70.5% in group 1. In group 2, they were 18.5% and 60.4%, respectively. According to micro-CT analysis, bone mineral density (mg/cm3, BMD) was 2.5% larger in group 1. Conclusions The findings from this study suggest that, although the difference in the bone formation between group 1 and group 2 appears to be insignificant, group 2 had an advantage in using smaller amount of bone substances to achieve the reliable bone formation.

The general bone anabolic effect of photobiomodulation (PBM) is largely accepted. As a result, PBM therapy is expected to be beneficial in the medical fields of dentistry and bone healing. However, most of the previous in vitro studies on PBM and bone metabolism were performed with single-cell cultures of osteoclast-lineage cells or osteoblast-lineage cells. In the present study, the bone-modulating effects of PBM were evaluated in an in vitro osteoblast/osteoclast co-culture system. Mouse bone marrow-derived macrophages (BMMs) and mouse calvarial pre-osteoblasts cells were purified and used as precursor cells for osteoclasts and osteoblasts, respectively. The PBM effects on single-cell culture of osteoclasts or osteoblasts as well as co-culture were examined by 1.2 J/cm

Contact sites between mitochondria and endoplasmic reticulum (ER) are points in which the two organelles are in close proximity. Due to their structural and functional complexity, their exploitation as pharmacological targets has never been considered so far. Notwithstanding, the number of compounds described to target proteins residing at these interfaces either directly or indirectly is rising. Here we provide original insight into mitochondria–ER contact sites (MERCs), with a comprehensive overview of the current MERCs pharmacology. Importantly, we discuss the considerable potential of MERCs to become a druggable target for the development of novel therapeutic strategies.