Background: Bone morphogenetic protein (BMP) signaling is crucial for osteogenic (OS) differentiation, bone growth, and repair. However, the clinical use of BMPs is limited due to their cost and challenges in delivery. SB4, a potent compound of benzoxazole, is a newly introduced small molecule shown to activate the BMP signaling pathway. In this study, we investigated the effects of SB4 on OS differentiation of adipose-derived mesenchymal stem cells (ADMSCs). Methods: We first examined whether BMP signaling is active in osteoinduced ADMSCs. ADMSCs were treated with SB4 (5 and 10 μM) for 24 hr, and mRNA expression of BMP direct target genes (ID1 and ID3) was analyzed. ADMSCs were then cultured with or without SB4 (10 μM) for 7, 14, and 21 days, followed by Alizarin red staining and real-time polymerase chain reaction analysis of mRNA expression of OS markers RUNX2, BMP2, alkaline phosphatase (ALP), and Osteopontin. To investigate the most effective time period of SB4 in osteogenesis, SB4 was applied every 3.5 days during the 21-day differentiation period. Results: After 24 hr of treatment with SB4 (5 and 10 μM), increased mRNA expression of BMP direct target genes (ID1 and ID3) confirmed that SB4 acts as an active BMP agonist. SB4-treated ADMSCs showed enhanced bone matrix production and increased mRNA expression of RUNX2, BMP2, ALP, and Osteopontin. Increased mRNA expression of OS markers, bone matrix formation, and ALP activity during the first 7 days of SB4 treatment suggested the importance of SB4 at the early stage of differentiation. Conclusions These results indicate that SB4, with potential BMP-like activity, induces OS differentiation of ADMSCs, leading it to serve as a cost-effective BMP agonist for osteogenesis-related research as well as a potential therapeutic agent for bone repair and regeneration.

Purpose: Eosinophilic esophagitis (EoE) is the most well-known eosinophilic gastrointestinal disorder (EGID) characterized by the presence of a high number eosinophils within the esophageal epithelium and the clinical signs. Biopsies of patients with suspected EoE may not show a high number of eosinophils, however the presence of granules may help with the diagnosis. This study aims to evaluate the presence of cell-free eosinophil granules in the esophageal tissue of patients with suspected and confirmed EoE to accelerate the diagnosis and treatment of patients with low eosinophil count. Methods: Fifteen patients with confirmed EoE and 15 suspected of EoE were included in this study. Patients' esophageal tissue biopsies were stained using immunohistochemistry (IHC) to identify eosinophils and their cell-free granules. For testing, anti-major basic protein (MBP) and anti-chemokine receptor type 3 (CCR3) were used as primary antibodies and a double-staining kit containing secondary antibodies conjugated to the enzyme and related chromogens were used. Results: Cell-free granules with different degrees were observed in 53.3% and 93.3% of suspected and confirmed EoE samples, respectively. Furthermore, in esophageal biopsy of 73.3% of patients with suspected and 93.3% of patients with a definitive diagnosis of EoE, basal layer hyperplasia (BLH) was recognized. Conclusion The results of the present study showed that IHC can be applied to detect cell-free eosinophil granules in esophageal tissue. Observation of granules and basal cell hyperplasia in biopsies of suspected EoE patients whose eosinophil count is below the threshold can be valuable findings to make a definitive diagnosis for these patients.

Purpose: Eosinophilic esophagitis (EoE) is the most well-known eosinophilic gastrointestinal disorder (EGID) characterized by the presence of a high number eosinophils within the esophageal epithelium and the clinical signs. Biopsies of patients with suspected EoE may not show a high number of eosinophils, however the presence of granules may help with the diagnosis. This study aims to evaluate the presence of cell-free eosinophil granules in the esophageal tissue of patients with suspected and confirmed EoE to accelerate the diagnosis and treatment of patients with low eosinophil count. Methods: Fifteen patients with confirmed EoE and 15 suspected of EoE were included in this study. Patients' esophageal tissue biopsies were stained using immunohistochemistry (IHC) to identify eosinophils and their cell-free granules. For testing, anti-major basic protein (MBP) and anti-chemokine receptor type 3 (CCR3) were used as primary antibodies and a double-staining kit containing secondary antibodies conjugated to the enzyme and related chromogens were used. Results: Cell-free granules with different degrees were observed in 53.3% and 93.3% of suspected and confirmed EoE samples, respectively. Furthermore, in esophageal biopsy of 73.3% of patients with suspected and 93.3% of patients with a definitive diagnosis of EoE, basal layer hyperplasia (BLH) was recognized. Conclusion The results of the present study showed that IHC can be applied to detect cell-free eosinophil granules in esophageal tissue. Observation of granules and basal cell hyperplasia in biopsies of suspected EoE patients whose eosinophil count is below the threshold can be valuable findings to make a definitive diagnosis for these patients.

Purpose: Eosinophilic esophagitis (EoE) is the most well-known eosinophilic gastrointestinal disorder (EGID) characterized by the presence of a high number eosinophils within the esophageal epithelium and the clinical signs. Biopsies of patients with suspected EoE may not show a high number of eosinophils, however the presence of granules may help with the diagnosis. This study aims to evaluate the presence of cell-free eosinophil granules in the esophageal tissue of patients with suspected and confirmed EoE to accelerate the diagnosis and treatment of patients with low eosinophil count. Methods: Fifteen patients with confirmed EoE and 15 suspected of EoE were included in this study. Patients' esophageal tissue biopsies were stained using immunohistochemistry (IHC) to identify eosinophils and their cell-free granules. For testing, anti-major basic protein (MBP) and anti-chemokine receptor type 3 (CCR3) were used as primary antibodies and a double-staining kit containing secondary antibodies conjugated to the enzyme and related chromogens were used. Results: Cell-free granules with different degrees were observed in 53.3% and 93.3% of suspected and confirmed EoE samples, respectively. Furthermore, in esophageal biopsy of 73.3% of patients with suspected and 93.3% of patients with a definitive diagnosis of EoE, basal layer hyperplasia (BLH) was recognized. Conclusion The results of the present study showed that IHC can be applied to detect cell-free eosinophil granules in esophageal tissue. Observation of granules and basal cell hyperplasia in biopsies of suspected EoE patients whose eosinophil count is below the threshold can be valuable findings to make a definitive diagnosis for these patients.

Purpose: Eosinophilic esophagitis (EoE) is the most well-known eosinophilic gastrointestinal disorder (EGID) characterized by the presence of a high number eosinophils within the esophageal epithelium and the clinical signs. Biopsies of patients with suspected EoE may not show a high number of eosinophils, however the presence of granules may help with the diagnosis. This study aims to evaluate the presence of cell-free eosinophil granules in the esophageal tissue of patients with suspected and confirmed EoE to accelerate the diagnosis and treatment of patients with low eosinophil count. Methods: Fifteen patients with confirmed EoE and 15 suspected of EoE were included in this study. Patients' esophageal tissue biopsies were stained using immunohistochemistry (IHC) to identify eosinophils and their cell-free granules. For testing, anti-major basic protein (MBP) and anti-chemokine receptor type 3 (CCR3) were used as primary antibodies and a double-staining kit containing secondary antibodies conjugated to the enzyme and related chromogens were used. Results: Cell-free granules with different degrees were observed in 53.3% and 93.3% of suspected and confirmed EoE samples, respectively. Furthermore, in esophageal biopsy of 73.3% of patients with suspected and 93.3% of patients with a definitive diagnosis of EoE, basal layer hyperplasia (BLH) was recognized. Conclusion The results of the present study showed that IHC can be applied to detect cell-free eosinophil granules in esophageal tissue. Observation of granules and basal cell hyperplasia in biopsies of suspected EoE patients whose eosinophil count is below the threshold can be valuable findings to make a definitive diagnosis for these patients.

Purpose: Eosinophilic esophagitis (EoE) is the most well-known eosinophilic gastrointestinal disorder (EGID) characterized by the presence of a high number eosinophils within the esophageal epithelium and the clinical signs. Biopsies of patients with suspected EoE may not show a high number of eosinophils, however the presence of granules may help with the diagnosis. This study aims to evaluate the presence of cell-free eosinophil granules in the esophageal tissue of patients with suspected and confirmed EoE to accelerate the diagnosis and treatment of patients with low eosinophil count. Methods: Fifteen patients with confirmed EoE and 15 suspected of EoE were included in this study. Patients' esophageal tissue biopsies were stained using immunohistochemistry (IHC) to identify eosinophils and their cell-free granules. For testing, anti-major basic protein (MBP) and anti-chemokine receptor type 3 (CCR3) were used as primary antibodies and a double-staining kit containing secondary antibodies conjugated to the enzyme and related chromogens were used. Results: Cell-free granules with different degrees were observed in 53.3% and 93.3% of suspected and confirmed EoE samples, respectively. Furthermore, in esophageal biopsy of 73.3% of patients with suspected and 93.3% of patients with a definitive diagnosis of EoE, basal layer hyperplasia (BLH) was recognized. Conclusion The results of the present study showed that IHC can be applied to detect cell-free eosinophil granules in esophageal tissue. Observation of granules and basal cell hyperplasia in biopsies of suspected EoE patients whose eosinophil count is below the threshold can be valuable findings to make a definitive diagnosis for these patients.

OBJECTIVES: To investigate the effect of auriculotherapy on reducing labor anxiety. METHODS: In this randomized clinical trial, 166 nulliparous pregnant women admitted to the Labor Ward of Izadi Hospital in Qom, Iran were included and assigned to two groups by randomized block design. In the intervention group (83 cases), auriculotherapy in "Shenmen, Thalamic, Zero, Brain, and Brain stem" was performed in dilatations of 4, 6 and 8 cm, between the contractions for 30 s in both ears at interval 1 h. While the control group received routine care. The Spielberger Inventory were completed pre- and post-interventions. RESULTS: The auriculotherapy was effective to reduce anxiety state in the intervention group compared to the control group (P=0.001). The score of state anxiety in the intervention group reduced for 7.0, 8.0 and 11.0 U in 4, 6, and 8 cm dilatations after the intervention. The score of trait anxiety in the intervention group reduced for 3.8, 4.0 and 8.3 U in 4, 6, and 8 cm dilatations after the intervention. There was no significant difference of delivery mode and newborns' weight and Apgar score between groups (P>0.05). No adverse postpartum outcome such as hemorrhage has been observed in both groups. CONCLUSION Since most women are anxious during labor, it seems that auriculotherapy can be an easy and safe method to reduce labor anxiety. (Trial registration No. irct20121230011944n4).
Anxiety/therapy* ; Auriculotherapy/methods* ; Female ; Humans ; Infant, Newborn ; Labor, Obstetric ; Pregnancy ; Pregnant Women ; Research Design

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus found in China in 2019. The disease caused by SARS-CoV-2, coronavirus disease 2019 (COVID-19), has been found to be closely related to the cells that secrete angiotensin-converting enzyme 2 (ACE2). ACE2 is involved in the renin-angiotensin system and is widely secreted in several tissues, including the testis, which has raised concerns because organs with high expression of the ACE2 receptor are susceptible to infection. Analyses have shown that in testicular cells, such as spermatogonia, seminiferous duct cells, Sertoli cells, and Leydig cells, there is a high expression level of ACE2. Therefore, SARS-CoV-2 may damage male reproductive tissues and cause infertility. Since male infertility is an important problem, scientists are evaluating whether COVID-19 may influence male infertility through the ACE2 receptor.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus found in China in 2019. The disease caused by SARS-CoV-2, coronavirus disease 2019 (COVID-19), has been found to be closely related to the cells that secrete angiotensin-converting enzyme 2 (ACE2). ACE2 is involved in the renin-angiotensin system and is widely secreted in several tissues, including the testis, which has raised concerns because organs with high expression of the ACE2 receptor are susceptible to infection. Analyses have shown that in testicular cells, such as spermatogonia, seminiferous duct cells, Sertoli cells, and Leydig cells, there is a high expression level of ACE2. Therefore, SARS-CoV-2 may damage male reproductive tissues and cause infertility. Since male infertility is an important problem, scientists are evaluating whether COVID-19 may influence male infertility through the ACE2 receptor.

Objective: Post-traumatic stress disorder (PTSD) and chronic pain often co-occur. Studies have shown an interaction between pain and PTSD. In this narrative review, we aim to support conducting comprehensive studies by describing PTSD, pain and determining whether opioidergic system, its agonist and antagonist manipulation could positively or negatively affect PTSD symptoms and concurrent pain. Methods: Term searches was done in Google Scholar, Scopus, ScienceDirect, Web of Science and PubMed databases as well as hand searching in key resource journals from 1979–2019. Results: There are a lot of contradictions and disputes when endogenous opioidergic system and opioidergic antagonist system are studied in PTSD patients. Exogenous morphine administration in PTSD patients can decrease the symptoms of PTSD but it doesn’t have a pain reduction effect to an acceptable level. Beta-endorphin as an endogenous opioid is effective in pain reduction in the moment of events but after minutes to hours, the endorphins withdrawal syndrome leads to exaggerated intrusive thoughts and flashbacks of PTSD, which exacerbate the pain. It has also been shown that naloxone, as an opioidergic antagonist, can reduce or increase the PTSD symptoms and its associated pain. Conclusion Data suggest different roles of opioidergic system and their antagonist in pain control and mood in PTSD. However, further investigations need to be done in order to reveal the role of endogenous opioidergic system and opioidergic antagonist system as a mediator in PTSD patients suffering from acute or chronic pain.