Running Title Research Articles

Differential gene expression between fungal mating types is associated with sequence degeneration Running title: Differential gene expression correlates with sequence degeneration

Differential gene expression between fungal mating types is associated with sequence degeneration Running title: Differential gene expression correlates with sequence degeneration

Estimation and adequacy of dentist supply through the dental care productivity

Running title: Adequacy of dentist supply Objectives: The proper provision of dentists is very important for delivering the dental care that people need. The purpose of this study is to evaluate the adequacy of dentist supply and to predict the proper supply of dentists in Korea for the next 10 years. Methods and materials: Using the data from 2004 to 2017 in the Statictics Korea, the dental needs were measured as days of admission and the annual total dental care hours in 2020, 2023, 2026 and 2030 were predticted using regression analysis. The dental care productivity (average in-office hours) of dentists was analyzed using regression analysis including age, gender, education level and region as a confounder. The annual care hours were predicted according to seven scenarios based on the percentage of women among dentists, post-dentist education levels, the percentage of dentists in the metropolitan area, aging and retirement age. Results: The needed dentist based on the data in the Statictics Korea will be 27, 288 ~ 27, 311 in 2020, 28,104 ~ 28,1785 in 2023, 28,977 ~ 29,124 in 2026, and 30,174 ~ 30,413 in 2030. On the other hand, the number of dentists in Korea will be 26,945 in 2020, 28,813 in 2023, 30,682 in 2026 and 33,173 in 2030. The adequacy index of dentist supply will be -0.01 in 2020 to +0.10 in 2030. Conclusions: Our data showed that dentists will be adequately supplied in Korea for the next 10 years. Overall, the ratio between dentist versus 1,000 Koreans will be increased from 0.5 in 2019 to 0.7 in 2020, which will meet the mean of OECD countries.

Down-regulation of miR-10b represses cell vitality in osteosarcoma and is inversely associated with prognosis via interacting with FAM46C: Running title: MiR-10b/FAM46C axis modulates OS progression

The purpose of this exploration was to detect the biological effects of miR-10b/FAM46C pair on osteosarcoma (OS) development. By accessing to the Gene Expression Omnibus (GEO) database, we achieved expressional profiles of miR-10b and FAM46C. Kaplan-Meier method was applied to determine the overall survival rates of OS patients. MiR-10b mimic/inhibitor were utilized to alter miR-10b expression. Overexpression of FAM46C was induced by pcDNA3.1-FAM46C. QRT-PCR and western blot were conducted to assess the expression levels. Cell counting kit-8 (CCK-8) and transwell assays were employed to evaluate the proliferative, invasive and migratory properties of OS cells. Pearson correlation analysis was performed to confirm the association between miR-10b and FAM46C. Dual-luciferase reporter assay was conducted to determine the target of miR-10b. The overall survival of OS patients was inversely correlated with miR-10b expression. MiR-10b was increased in OS compared with normal controls. Depletion of miR-10b attenuated the proliferation, invasion and migration of MG-63 cells. FAM46C was considered as a target gene of miR-10b and inversely related with miR-10b. Overexpression of FAM46C could inhibit cell growth, invasion and migration in OS; furthermore, it also can enforced the miR-10b inhibitor-induced effects on cell behaviors of OS cells. Down-regulation of miR-10b played a suppressive effect on the cell activity in OS cells, which provides a novel insight into the advance of OS therapeutic therapies.

Using neuroscience techniques to understand and improve design cognition.

Cognitive neuroscience research has traditionally focused on understanding the brain mechanisms that enable cognition by means of experimental laboratory tasks. With a budding literature, there is growing interest in the application of the related methods and findings to real-world settings. In this opinion paper we explore the potential and promise of employing current cognitive neuroscience methodologies in the field of design. We review recent evidence from preliminary studies that have employed such methods toward identifying the neural bases of design thinking and discuss their impact and limitations. Further, we highlight the importance of pairing neuroscience methods with well-established behavioral paradigms during ecologically-valid, real-world design tasks. Experimental investigations that meet these requirements can generate powerful datasets of neurocognitive measures that can offer new insights into the complex cognitive and brain systems enabling design thinking. We argue that this new knowledge can lead to the development and implementation of new techniques toward cultivating and improving design thinking in design education and professional practice.

Themes of advanced information processing in the primate brain.

Here is a review of several empirical examples of information processing that occur in the primate cerebral cortex. These include visual processing, object identification and perception, information encoding, and memory. Also, there is a discussion of the higher scale neural organization, mainly theoretical, which suggests hypotheses on how the brain internally represents objects. Altogether they support the general attributes of the mechanisms of brain computation, such as efficiency, resiliency, data compression, and a modularization of neural function and their pathways. Moreover, the specific neural encoding schemes are expectedly stochastic, abstract and not easily decoded by theoretical or empirical approaches.

Development and psychometric evaluation of the Beliefs about Home Hemodialysis Scale for patients on in-center hemodialysis<span style="font-size: 12px">Running title: Health beliefs and home hemodialysis</span>

Objective There is no valid and reliable instrument that evaluates health beliefs related to home hemodialysis of patients. This study aimed to develop the Beliefs about Home Hemodialysis Scale (BHHS) and evaluate its psychometric properties in a sample of patients on in-center hemodialysis. Methods This methodological study was carried out with 102 patients on in-center hemodialysis. Data were collected by a questionnaire, the Perceived Social Support from Family Scale, and the BHHS. The analysis of data was carried out using descriptive statistics, Mann-Whitney U test, Pearson's correlation coefficients, and psychometric tests. Results The overall content validity index of the scale was satisfactory with 1.00 for relevance and 0.97 for clarity. The exploratory factor analysis yielded a four-factor structure (perceived benefits, perceived barriers toward the environment, perceived barriers toward the procedure, and perceived barriers toward socioeconomic support) accounting for 64.5% of the total variance. The BHHS had acceptable internal consistency (Cronbach's alpha coefficient = 0.69–0.91), test-retest reliability (intraclass correlation coefficient = 0.88–0.95), concurrent validity with the Perceived Social Support from Family Scale scores and known group validity with wanting to start home hemodialysis. Conclusions The initial psychometric testing of the BHHS is favorable. The BHHS is a valid and reliable instrument for assessing the perceived benefits and barriers to home hemodialysis in patients on in-center hemodialysis. The results of this study will gain a better understanding of the beliefs about home hemodialysis of patients and will lead to more effective intervention strategies.

Stop-bang questionnaire: Practical approach to diagnosis of obstructive sleep apnea in roncopathic subjects<span style="font-size:12px">Running title: Practical approach to diagnosis of obstructive sleep apnea in roncopathic subjects</span>

A correlation was established between snoring and obstructive sleep apnea syndrome (OSAS). Although this association is highly prevalent in the general population, OSAS remains largely undiagnosed. The STOP-BANG Questionnaire (SBQ) consists of simple questions with dichotomous answers (yes/no). It is utilized for the preoperative clinical assessment of anesthesiological risk in patients with suspected OSAS, and positive response to ≥3 questions reinforces the diagnostic suspicion. The SBQ survey during an ENT visit in a patient with a rupture may be a reliable, fast, concise, and easy-to-use screening tool to diagnose OSAS. The present study aimed to evaluate the predictability of SBQ during an ENT visit and compare it with the apnea-hypopnea index (AHI) in patients undergoing nocturnal cardiorespiratory monitoring, a gold standard for the diagnosis of OSAS. A population of roncopathic subjects was evaluated using SBQ, ENT assessment, and night-time cardiorespiratory monitoring. SBQ was administered by the ENT specialist during the first visit in the presence of the bed partner. A total of 98 snoring subjects were evaluated. A significant linear correlation was established between AHI and the number of positive responses to SBQ. The present study demonstrated that SBQ can be employed for the diagnosis of OSAS in roncopathic population. Also, a linear correlation was found between the SBQ score and the OSAS grade based on the AHI. The SBQ administered by the ENT specialist is a rapid and reliable screening tool, capable of reducing the national health costs through early and targeted diagnosis.

Covid-19 Related Knowledge, Attitude and Practices in a Southeastern City in Nigeria: A Cross-Sectional Survey

Although guidelines and recommendations for the prevention of COVID-19 are in place, it is vital to assess how well people know and practice them, as well as people’s attitude towards these measures to inform robust interventions. This study examined COVID-19 related knowledge, attitude, and preventive practices (KAP) among adult residents of the city of Onitsha in South-Eastern Nigeria. We conducted a cross-sectional survey of 140 adult residents of Onitsha city in March 2020 before the lockdown. Descriptive and inferential statistics were used to describe COVID-19 KAP, information gaps and needs, and associations between KAP and demographic characteristics. About 60.7% of respondents had high COVID-19 knowledge, 56.4% had a good attitude towards COVID-19 management, and 53.6% adopted good COVID-19 prevention practices. Participants with bachelor/postgraduate degrees had higher than average COVID-19 knowledge (15.42±0.57, p<0.0001), attitude (1.11±0.10, p<0.0025), and prevention practice (5.02±0.32 p<0.0005) scores. Over half of the participants correctly identified virus as the cause of COVID-19 (60%, p<0.01) and knew that COVID-19 could be transmitted through contaminated surfaces (59.3%, p<0.05) and infected droplets (58.6%, p<0.05). About three-quarters of the participants (75%, p<.0001) indicated needing more information on COVID-19 compared to only a quarter (25%, p<.0001) that stated that they experienced no gap in information. A moderate proportion of our study population had high COVID-19 KAP scores. Our study findings can inform future COVID-19 program planning to ensure a more targeted and effective intervention strategy to prevent and control the disease spread among residents of Onitsha city. Running Title: COVID-19 Related Knowledge, Attitude and Practice (KAP)

Pancreas glucagon immunolocalization in the scorpion mud turtle, kinosternon scorpioides Running title: pancreas glucagon immunolocalization in turtle

Pancreas glucagon immunolocalization in the scorpion mud turtle, kinosternon scorpioides Running title: pancreas glucagon immunolocalization in turtle

Comparison of Lidocaine, and Lidocaine-Neostigmine for Epidural Analgesia in Dogs

ABSTRACT Objectives: Evaluate and compare the analgesic effect of epidural lidocaine and lidocaine- neostigmine combination in dogs. Methods: Six healthy dogs of mixed breed weighing 12–15 kg were selected for this study. All dogs received all treatments in a cross-over design with at least a one-week interval. Dogs were premeditated with Xylazine (0.5 mg/kg) and general anesthesia was induced with thiopental sodium (12.5 mg/kg) to perform the lumbosacral puncture. Epidural analgesia was done using either 6 mg/kg of lidocaine 2% or a combination of 6 mg/kg of Lidocaine 2%, with 10 µg/kg neostigmine. The degree of analgesia was evaluated using a numerical rating scale. Analgesia was defined as lack of response to pinprick test and pressure from hemostat clamp and was performed after one hour of epidural injection, and thereafter every 10 min until complete recovery. Heart rate (HR), respiratory rate (RR), and rectal temperature (RT) were recorded before (baseline, 0) and at every 10 min until a complete recovery was observed. Results: HR, RR and RT did not differ between treatments at any time point. The lidocaine–neostigmine combination produced a significant (P < 0.05) longer duration of analgesia than lidocaine alone. The addition of neostigmine resulted in a significantly longer duration of analgesia. Co-administration of epidural neostigmine and lignocaine appears to be a useful technique for postoperative analgesia as it increases the duration of analgesia Conclusion: Adding neostigmine to epidural administered lidocaine in dogs increases the analgesic effect on both hind limbs and perineal region. Short running title: Lidocaine-neostigmine epidural in the dog.

Nucleotide, ribonucleotide and ribonucleoside binding belongs to differentially expressed genes in porcine epithelial oviductal cells during longterm primary cultivation

Abstract The oviduct play a crucial role in reproductive process, through facilitating successful embryo growth and conception. Oviduct activity is orchestrated by various factors, depending on cyclic dynamics, which crucially affect the success of reproductive function. The morphological modifications of oviducts in response to the female reproductive cycle are well established. However, detailed characterization at the molecular level is still needed. The present study, employed primary in vitro cell cultures and high-throughput transcriptome analysis via an Affymetrix microarray approach, described nucleotide, ribonucleotide and ribonucleoside binding patterns at a molecular level in oviduct epithelial cells (OECs). 222 genes were targeted belonging to four gene ontology biological process terms (GO BP): “adenyl nucleotide binding”, “adenyl ribonucleotide binding”, “ribonucleotide binding”, “ribonucleoside binding”, which showed the greatest variability in the level of mRNA expression during of long-term cultivation. In this group of genes, special attention was paid to those showing the greatest variability in relation to the reference measurement, including OASL, PIM1, ACTA2 and ABCA1. Running title: Oviductal nucleotide and nucleoside binding patterns

Coenzyme and cofactor metabolism belongs to biochemical processes significantly regulated in human granulosa cells collected after IVF during long-term primary in vitro culture

Abstract Granulosa cells (GCs) provide the microenvironment necessary for the development of the follicle and the maturation of the oocyte. GCs are associated with reproductive system function and the maintenance of pregnancy by participating in the synthesis of steroid hormones. Many authors point to new ways of using GCs in regenerative medicine and indicate the significant plasticity of this cell population, suggesting that GCs can undergo a transdifferentiation process. Employing primary in vitro cell cultures and high-throughput transcriptome analysis via Affymetrix microarrays, this study describes groups of genes associated with enzymatic reactions. 52 genes were identified belonging to four gene ontology biological process terms (GO BP): “coenzyme biosynthetic process”, “coenzyme metabolic process”, “cofactor biosynthetic process” and “cofactor metabolic process”. All identified genes showed reduction in the level of mRNA expression during long-term in vitro cultivation. Significanthe transcriptomic profile variability was exhibited for the genes (ELOVL5, ELOVL6 and GPAM) involved in enzymatic regulation of fatty acid metabolism. Running title: Enzymatic regulation in granulosa cells

Ultrastructural variability of macrophages in the wall of selected aorto-coronary bypass grafts

Abstract Macrophages, detected as CD68+ cells, are considered to have marked contribution to aorto-coronary grafts disease. The purpose of this study was to find any ultrastructural differences in CD68+ cells between arterial and venous aorto-coronary grafts. The surplus segments of radial artery (RA) and saphenous vein (SV) were obtained from 50 patients with the mean age of 63.4±9.2 years who undergo elective coronary artery bypass grafting (CABG). The vascular segments were analyzed by means of both light (to assess number and distribution of macrophages within their walls) and transmission electron microscopy (to evaluate ultrastructure of CD68+ cells in the vessel layers). Histological analysis revealed that not only more macrophages (median (25th; 75th percentile)) were found on the transverse sections of veins (95 (67; 135)) than arteries (66 (43; 108)) (p&lt;0.05) but also at least of 50% of them were found in the tunica intima and tunica media in SV while only 30% in RA. TEM studies showed that biological activity of macrophages depended on CD68+ location and was irrespective of the vessel type. Those found in the tunica intima and tunica media presented ultrastructure typical for active cells rich in numerous lysosomes, well developed rough endoplasmic reticulum and Golgi apparatus whereas adventitial macrophages for unreactive residual cells. Ultrastructural characteristics of both forms of macrophages infiltrating wall of aorto-coronary grafts is similar irrespective of the vessel type. More active cells in the inner layers of the venous conduits may contribute to their inferior outcomes compared to the arteries. Running title: Macrophages and aorto-coronary grafts

Evidence for existence of molecular stemness markers in porcine ovarian follicular granulosa cells

Abstract Granulosa cells (GCs) are important component of the follicle, a principal functional unit of the ovary. They undergo highly dynamic changes during folliculogenesis and play a vital role in oocyte’s maturation. Recently, it has been shown that GCs also exhibit stem cell properties, since they express OCT-4, Nanog, Sox-2, which are markers of pluripotency, as well as several mesenchymal stem cell markers, such as CD29, CD44, CD90, CD105, CD117 or CD166. In addition, GCs are able to differentiate towards neurogenic, chondrogenic and osteogenic lineages. Since the use of embryonic stem cells in regenerative medicine is burdened with ethical concerns and the risk of immune rejection or teratoma formation, adult stem cells are emerging as a promising alternative. GCs especially seem to provide a promising source of stem cells, since they are easily obtainable during assisted reproduction techniques. In order to better understand the genetic changes taking place in proliferating granulosa cells cultured in vitro, we isolated GCs from 40 prepubertal gilts and cultured them in vitro for 168 h. After 24, 48, 72, 96, 120, 144 and 168 h of cultivation the total RNA was extracted, reverse transcription was conducted and RT-qPCR reaction was performed. We observed that CD44, CD90 and IGF1 were upregulated after the cultivation, whereas CD105 and LIF were downregulated. Collectively, our results confirm stemness potential of porcine GCs and provide an insight into the transcriptome changes during in vitro cultivation. Running title: Molecular stemness markers in porcine granulosa cells

Overview of methods of isolation, cultivation and genetic profiling on human umbilical cord stem cells

Abstract Stem cells possess unique properties, such as self-renewal ability or differentiation capacity into more specialized cells, which makes them particularly relevant for regenerative medicine and cellular therapies. Although embryonic stem cells (ESCs) are capable of differentiation into all cell lineages, their utilization is associated with ethical concerns since they are obtained from embryos. Furthermore, ESCs may form teratomas or cause immune rejection in the clinical setting. Therefore, an effort has been made to utilize stem cells derived from adult tissues, especially mesenchymal stem cells (MSCs). A particularly attractive source of MSCs is the human umbilical cord, which is typically discarded after birth and considered a medical waste, therefore the acquisition of the cells is not associated with any health risk for a patient. Moreover, umbilical cord-derived MSCs do not express MHCII, thus they exhibit reduced immunogenicity. MSCs have been isolated from all compartments of umbilical cord, however the Wharton’s jelly-derived MSCs (WJ-M-SCs) are the most clinically utilizable. There are two techniques of UC-MSCs isolation: the enzymatic and explant procedures. The explant method involves cell outgrowth of tissue pieces placed into plastic culture vessel after mechanical splitting, whereas the enzymatic technique involves minced tissue digestion in an enzymatic solution. In vitro culture conditions of the isolated cells are highly variable among the researchers, however the most commonly performed molecular assays are homogenous and include: RT-qPCR, flow cytometry and immunocytochemistry. Running title: Human umbilical cord stem cells isolation, cultivation and genetic profiling

Battling Glioblastoma: A Novel Tyrosine Kinase Inhibitor with Multi-Dimensional Anti-Tumor Effect (Running Title: Cancer Cells Death Signalling Activation).

Glioblastoma (GB), a grade IV glioma, with high heterogeneity and chemoresistance, obligates a multidimensional antagonist to debilitate its competence. Considering the previous reports on thioesters as antitumor compounds, this paper investigates on use of this densely functionalized sulphur rich molecule as a potent anti-GB agent. Bio-evaluation of 12 novel compounds, containing α-thioether ketone and orthothioester functionalities, identified that five analogs exhibited better cytotoxic profile compared to standard drug cisplatin. Detailed toxicity studies of top compound were evaluated in two cell lines, using cell viability test, apoptotic activity, oxidative stress and caspase activation and RNA-sequencing analysis, to obtain a comprehensive molecular profile of drug activity. The most effective molecule presented half maximal inhibitory concentration (IC50) values of 27 μM and 23 μM against U87 and LN229 GB cells, respectively. Same compound effectively weakened various angiogenic pathways, mainly MAPK and JAK-STAT pathways, downregulating VEGF. Transcriptome analysis identified significant promotion of apoptotic genes, and genes involved in cell cycle arrest, with concurrent inhibition of various tyrosine kinase cascades and stress response genes. Docking and immunoblotting studies suggest EGFR as a strong target of the orthothioester identified. Therefore, orthothioesters can potentially serve as a multi-dimensional chemotherapeutic possessing strong cytotoxic, anti-angiogenic and chemo-sensitization activity, challenging glioblastoma pathogenesis.

Innovations in Curriculum Designs Do Not Guarantee Students’ Patient-Centered Attitudes Running Title: Curricula and Patient-Centered Attitudes

ABSTRACT Background Medical schools all around the world are engaged in curricular reforms aimed at fostering patient- and learner-centeredness, implementing curricular transformations in order to counterbalance the erosion of humanistic and professional values and the loss of idealism of recent graduate physicians. In Brazil, medical schools are facing the challenge of redesigning medical curricula towards more learner-centered and patient-centered approaches, stimulated by recent national medical education guidelines. However, desirable outcomes towards medical education have not been fully achieved. Aim To access medical students’ attitudes and determine predictors of medical students’ patient-centered attitudes among students from different curricular designs (traditional, innovative and advanced). Methods Medical students from 1st to 6th year from 21 Brazilian medical schools participating in the project for evaluating change and trends proposed by the Brazilian Association of Medical Education, with different stages of curricular designs (traditional, innovative and advanced), answered the Brazilian version of the Patient–Practitioner Orientation Scale (B-PPOS) and a questionnaire with curricular and sociodemographic variables. Results Brazilian medical students care more than they share information, power and responsibility (p &lt; 0.001; d = 0.599). They are more concerned with the psychosocial context than with patient’s perspective (p &lt; 0.001; d = 0.797) and share more power and responsibility than understanding (p &lt; 0.001, d = 0.455). Female gender (B = 0.180), students from public schools (B = 0.132), year of medical training (B = 0.021), preference for future medical practice in public services (B = 0.053) and extracurricular activities (B = 0.068) were predictors of patient-centered attitudes among medical students (p &lt; 0.05). Meanwhile, the father’s educational level and choice to study surgical specialties (p &lt; 0.05) were predictors of less patient-centered attitudes among students. Different curricular designs were not associated with students’ patient-centered attitudes (p &gt; 0.05). Conclusion tant predictors of patient-centered attitudes among medical students. Further research should investigate the direct influence of faculty professionalism development programs on students’ patient centered-attitudes.

Genetic Deletion of Syndecan-4 Alters Body Composition, Metabolic Phenotypes, and the Function of Metabolic Tissues in Female Mice Fed A High-Fat Diet.

Syndecans are transmembrane proteoglycans that, like integrins, bind to components of the extracellular matrix. Previously, we showed significant associations of genetic variants in the Syndecan-4 (SDC4) gene with intra-abdominal fat, fasting plasma glucose levels, and insulin sensitivity index in children, and with fasting serum triglyceride levels in healthy elderly subjects. An independent study also reported a correlation between SDC4 and the risk of coronary artery disease in middle-aged patients. Here, we investigated whether deletion of Sdc4 promotes metabolic derangements associated with diet-induced obesity by feeding homozygous male and female Sdc4-deficient (Sdc4-/-) mice and their age-matched wild-type (WT) mice a high-fat diet (HFD). We found that WT and Sdc4-/- mice gained similar weight. However, while no differences were observed in males, HFD-fed female Sdc4-/- mice exhibited a higher percentage of body fat mass than controls and displayed increased levels of plasma total cholesterol, triglyceride, and glucose, as well as reduced whole-body insulin sensitivity. Additionally, they had an increased adipocyte size and macrophage infiltration in the visceral adipose tissue, and higher triglyceride and fatty acid synthase levels in the liver. Together with our previous human genetic findings, these results provide evidence of an evolutionarily conserved role of SDC4 in adiposity and its complications.

Human Dental Pulp Stem Cells: recent findings and current research

Abstract Prevalence of neurodegenerative diseases, most of which are life threatening and incurable, is an increasing clinical problem. To date, studies have demonstrated a superior proliferation rate of dental pulp stem cells (DPSCs) compared to other mesenchymal stem cells in vitro. DPSCs has recently been recognized as a novel treatment strategy for neurodegenerative disease, due to their advanced potential for neurogenic differentiation. The oral cavity has been described as a promising source of dental pulp stem cells. DPSCs are widely used in regenerative dentistry holding alternative capacity for osteogenic differentiation and therefore new promises for tissue and whole tooth regeneration. Dental stem cell banking offers a plentiful source of stem cells representing great potential for cell reprogramming and thus cell therapy. Recently, the association of pulp stem cells with three – dimensional scaffold templates allows for building up naturally derived implants. This review introduces to unique properties of DPSCs and biological factors influencing mineralization, proliferation and differentiation of pulp stem cells. Latest research studies are compared in terms of effectiveness and limitations of techniques for the isolation of pulp stem cells, including the enzymatic digestion and the explant culture methods. Moreover, a short overview of most recent findings and clinical application of DPSCs is proffered including progress of current research and limitations still to be addressed in the nearest future. Finally, the article presents new advances in the area of regenerative dentistry and regenerative medicine, including three dimensional printing and three dimensional analysis, emerged to deepen studies under procedures to replace the non patient specific artificial implants. Running title: DPSCs - review

Current clinical applications of adipose-derived stem cells in humans and animals

Abstract Adipose derived stem cells are a type of mesenchymal stem cell that, because of their straightforward isolation procedure and ready availability, have been intensively studied in the recent years regarding their possible clinical applications. Additionally, ADSCs have the ability to differentiate into tri-germ lineages, as well as exhibit paracrine activity. Their capacity to differentiate into many different cell lineages such as osteocytes, adipocytes, neural cells, vascular endothelial cells, cardiomyocytes, pancreatic cells, and hepatocytes, has granted them a significant place in consideration for tissue engineering and for their application in regenerative medicine. Moreover, their endocrine activity has a great impact upon therapies as it grants immunosuppressive properties and low immunogenicity. Running title: Clinical applications of ADSCs