Anatomical consideration of ultrasonography-guided intraoral injection for temporal tendinitis.

Temporal tendinitis is characterized by acute inflammation often resulting from mechanical stress, such as repetitive jaw movements associated with jaw opening and closing and teeth clenching. Treatment for temporal tendinitis typically involves the administration of local anesthetic or corticosteroid injections. However, the complex anatomical structure of the coronoid process, to which the temporalis tendon attaches, located deep within the zygomatic arch, poses challenges for accurate injections. In this study, we aimed to establish guidelines for the safe and effective treatment of temporal tendinitis by using intraoral ultrasonography (US) to identify the anatomical structures surrounding the temporalis tendon and coronoid process. US was performed using an intraoral transducer on 58 volunteers without temporomandibular joint disease. The procedure involved placing the transducer below the occlusal plane of the maxillary second molar. Measurements were taken for the horizontal distance from the anterior border of the coronoid process, observed at the midpoint (MP) of the US images, and the depth of the coronoid process and temporalis muscle from the oral mucosa. The anterior border of the coronoid process was visualized on all US images and classified into three observed patterns at the MP: type A (anterior to the MP, 56.2%), type B (at the MP, 16.1%), and type C (posterior to the MP, 27.7%). The temporalis muscle was located at a mean depth of 3.12 ± 0.68 mm from the oral mucosa. The maxillary second molar is an intraoral landmark for visualizing the anterior border of the coronoid process. The new location information obtained using intraoral US could help identify the safest and most effective injection sites for the treatment of temporal tendinitis.

Anatomical analysis of the intramuscular distribution patterns of the levator scapulae and the clinical implications for pain management.

PURPOSE: The present study aimed to demonstrate the intramuscular nerve distribution of the levator scapulae muscle that is responsible for pain and to use this anatomic data to propose possible injection sites. METHODS: Twenty levator scapulae muscles were dissected from 16 Korean embalmed cadavers. The intramuscular nerve distribution of the levator scapulae muscle was identified by whole-mount nerve staining to preserve and stain the nerve fibers without damage. RESULTS: The posterior ramus of spinal nerves C3, C4, and C5 innervated the levator scapulae muscles. When the origin and insertion of the muscle were set to 0% and 100%, respectively, most of the intramuscular nerve terminals were located between 30 and 70%. This area may correspond to the cricoid cartilage of the sixth cervical vertebra. CONCLUSION: Most intramuscular nerve terminals can be found in the middle and distal portions of the levator scapulae muscle. Our findings improve our understanding of the intramuscular nerve distribution of the levator scapulae muscle and will aid in pain management in clinical practice.

A standardized protocol for needle placement in the infraspinatus muscle: an anatomical perspective.

PURPOSE: This study aimed to evaluate the morphology of the three parts of the infraspinatus muscle based on surface landmarks for precise and effective access, and to propose the most effective fine-wire electrode insertion technique and sites. METHODS: Fifteen Asian fresh cadavers were used. We investigated the probability of the presence of the superior, middle, and inferior parts in each infraspinatus muscle based on surface landmarks. Based on the positional characteristics of the muscle, we determined the needle insertion method and confirmed its effectiveness by dissection. RESULTS: The superior part was mostly observed near the spine of the scapula. The middle part was broadly observed within the infraspinous fossa. The inferior part showed variable location within the infraspinous fossa. The injection accuracy of the superior, middle, and inferior parts in the infraspinatus muscle was 95.8%, 100%, and 91.7%, respectively. Targeting the superior and middle parts for injection of the infraspinatus muscle is relatively more straightforward than targeting the inferior part. Targeting the inferior part of the infraspinatus muscle in this study was more challenging than targeting the superior and middle parts. CONCLUSION: Needling for electromyography should be performed with special care to avoid unintended muscle parts, which could lead to inaccurate data acquisition and affect the conclusions about muscle function.

Sonoanatomy of the platysmal bands: What causes the platysmal band?

BACKGROUND: The platysmal band is created by the platysma muscle, a thin superficial muscle that covers the entire neck and the lower part of the face. The platysmal band appears at the anterior and posterior borders of the muscle. To date, no definite pathophysiology has been established. Here, we observed a lack of knowledge of the anatomy of the platysma muscle using ultrasonography in this study. METHODS: We conducted a descriptive, prospective study observing the platysmal band in resting and contraction states to reveal muscle changes. Twenty-four participants (aged 23-57 years) with anterior and posterior neck bands underwent ultrasonography in resting and contracted states. Ten cadavers were studied aged 67-85 years to measure the thickness of the platysma muscle at 12 points: horizontally (medial, middle, lateral) and vertically (inferior mandibular margin, hyoid bone, cricoid cartilage, superior margin of clavicle). RESULTS: The anterior and posterior borders of the platysma muscle were thicker than the middle of the platysma muscle when in a contracted state, and the muscle also had a convex shape when contracted. The thickness of the platysma muscle was not significantly different over 12 points in the resting state. During contraction, the platysma muscles contracted in the medial and lateral margins of the muscle, which was more significant in the posterior bands. CONCLUSION: The anterior and posterior platysmal bands are related to muscle thickness during contraction. These observations support the change in platysmal band treatment only at the anterior and posterior border of the muscle.

Three-dimensional topography of facial soft tissues for the safer and effective threading procedures.

INTRODUCTION: To reduce complications caused by the procedure, the target layer for thread lifting should be the superficial fat or superficial musculoaponeurotic system of the face. The aim of this study was to establish the thicknesses of the facial skin and superficial fat using a 3D scanning system to provide basic clinical data for thread lifting. MATERIAL AND METHODS: Thirty fixed Korean and Thai cadavers (male: 17, female: 13) were used. The depths of the skin and superficial fat were measured using a three dimensional (3D) structured-light scanner. Facial images of both undissected and removed skin and superficial fat were taken with the 3D scanner. The paths from the temple and the front of the tragus to the infraorbital, perioral, cheek, and mental areas were displayed on the 3D image. The thickness along the path was measured by calculating the difference between the undissected and dissected 3D images. RESULTS: The means and standard deviations of thicknesses of the skin and superficial fat were 2.1 ± 0.4 mm and 5.2 ± 1.9 mm in the 11 pathways. The facial skin became thicker going toward the lower aspect of the face from temple to infraorbtial and perioral regions. The thickness of the superficial fat around the marionette line showed the biggest change. CONCLUSIONS: The present findings indicate that a 3D scanning system can yield crucial anatomical information about the thickness of the facial skin and superficial fat for use in various minimally invasive clinical procedures including thread lifting.

Clinical anatomy considerations on the muscular and vascular components of the midface by ultrasonographic imaging.

The first signs of face aging appear in the midface, so procedures such as botulinum toxin and filler injections are performed there. However, no guidelines based on clinical anatomy describing the muscular and vascular components in vivo have been published. The aim of this research was to describe the depths of the midface muscles and the locations of vessels using ultrasonographic (US) imaging. US was applied at 12 landmarks on the midface in 88 volunteers (49 males and 39 females; 19-36 years) to detect sex differences in the depths of muscles and the locations of the vessels. The depths of the orbicularis oculi (OOc), levator labii superioris alaeque nasi (LLSAN), and zygomaticus minor (Zmi) differed significantly with sex at P7 (p = 0.001) and P8 (p = 0.017), P1 (p = 0.028), and P4 (p = 0.035), respectively. The facial artery, facial vein, angular artery, angular vein, and perforator vessels were found at P9, P2 and P10, P1, P1 and P5, and P8, P11 and P12, respectively. The findings indicate that the depths of the OOc, LLSAN, and Zmi muscles differ between the sexes and that the vessels appear at specific landmarks. This information could help in developing anatomical guidelines for several procedures.

Anatomical guide for botulinum neurotoxin injection: Application to cosmetic shoulder contouring, pain syndromes, and cervical dystonia.

INTRODUCTION: This study proposes an ideal botulinum toxin injection point of the trapezius muscle for shoulder line contouring, pain management, and functional impairment. This study describes the intramuscular nerve branching in the trapezius muscle, providing essential information for botulinum neurotoxin injection. METHOD: A modified Sihler's method was performed on the trapezius muscles (16 specimens). The intramuscular arborization areas were elucidated regarding the external occipital protuberance superiorly, spinous process of the 12th thoracic vertebra inferiorly and acromion of the scapula. RESULT: The intramuscular neural distribution for the superior, middle, and inferior regions of the trapezius muscle had the greatest arborized patterns in the horizontal 1/5-2/5 and vertical 2/10-4/10 sections, the horizontal 1/5-3/5 and vertical 4/10-5/10 sections, and the horizontal 1/5-2/5 and vertical 5/10-7/10 sections, respectively. DISCUSSION: We propose that BoNT treatments should be directed to the horizontal 1/5-2/5 and vertical 2/10-4/10 sections of the superior trapezius, the horizontal 1/5-3/5 and vertical 4/10-5/10 sections of the middle trapezius and the horizontal 1/5-2/5 and vertical 5/10-7/10 sections of the inferior trapezius. Additionally, injective treatment at the horizontal 2/5-3/5 and vertical 2/10-4/10 nerve entry points should be avoided to prevent nerve trunk damage causing paralysis. According to our guidelines, clinicians can ensure minimal dose injections and fewer adverse effects in botulinum neurotoxin injective treatment.

Guidelines for botulinum neurotoxin injections in piriformis syndrome.

BACKGROUND: The piriformis muscle is normally involved in piriformis syndrome and can be treated with botulinum neurotoxin using several different injection methods. However, definitive injection guidelines for the muscle have not been reported previously. AIMS: This study aimed to determine the ideal area for injections based on the intramuscular nerve distribution as obtained using a modified Sihler's staining technique. MATERIALS AND METHODS: A modified Sihler's method was applied to the piriformis muscle in 15 specimens. The intramuscular arborization areas were identified based on two anatomical landmarks: (a) the lateral border of the sacrum bone and (b) the greater trochanter. RESULTS: The nerve entry point for both piriformis muscles was found in the area between the lateral border of the sacrum and one-fifth of the distance toward the greater trochanter. The intramuscular nerve distribution for the piriformis muscle had the largest arborization patterns between one-fifth and two-fifths of the distance from the sacrum to the greater trochanter. The piriformis muscle was tendinous from two-fifths of the distance to the greater trochanter. DISCUSSION: This study has yielded suggested optimal injection locations for the piriformis muscle relative to external anatomical landmarks. CONCLUSION: Clinicians can use these guidelines to ensure the effectiveness of not only botulinum neurotoxin injections but also other agents such as steroids, anesthetics, and normal saline. These guidelines will also help to avoid adverse outcomes of injection treatments.

Three-Dimensional Evaluation of the Depressor Anguli Oris and Depressor Labii Inferioris for Botulinum Toxin Injections.

BACKGROUND: Botulinum toxin type A (BoNT-A) injection administered at an inappropriate site or depth can produce an unwanted change in facial animation because the depressor anguli oris (DAO) and depressor labii inferioris (DLI) muscles are partially overlapped. Therefore, simple BoNT-A injection guidelines, based on 3-dimensional (3D) facial anatomic references and landmarks, would be very useful. OBJECTIVES: The aim of this study was to establish novel BoNT-A injection guidelines that include the soft tissue thickness at the lower perioral region. Data were acquired with a 3D scanning system combined with dissections in order to obtain accurate injection sites and depths for the DAO and DLI. METHODS: 3D scans of the facial skin, superficial fat, and facial muscle surface were performed in 45 embalmed cadavers. The thicknesses of the skin and subcutaneous layer were calculated automatically from superimposed images at each of 5 reference points (P) in the perioral region. RESULTS: In every case (100%), P3 and P5 were located in the DLI and DAO areas, respectively (45/45). Therefore, we defined P3 as the "DLI point" and P5 as the "DAO point." The soft tissue thicknesses at the DLI and DAO points were 6.4 [1.7] mm and 6.7 [1.8] mm, respectively. CONCLUSIONS: The P3 and P5 described in this study are effective guidelines that only target the DLI and DAO. Clinicians, specifically, can easily use facial landmarks, such as the cheilion and pupil, to assign the DLI and DAO points without any measurement or palpation of the modiolus.

Text mining analysis of teachers' reports on student suicide in South Korea.

A teacher as a suicide prevention gatekeeper has an important role in identifying suicide risks and warning signs in students. After a student's suicide, teachers in Korea have to write a student suicide case report based on their direct and indirect observations. In particular, the section 'characteristic of student suicide' of this report contains valuable information about the suicide; however, it is unstructured, and thus cannot be analyzed using conventional statistical methods. We aimed to identify the characteristics of observed Korean students, who have committed suicide, using text mining techniques as well as to improve our understanding of suicidal behaviors in the school contexts. Therefore, a series of text mining techniques: topic analysis, word correlation, and word frequency analysis, in three problem categories: health, school, and family problems, were used to analyze the characteristics of student suicides. Topic analysis showed that only 30% of the student suicide case reports identified problematic student characteristics related to suicide. Correlations between words showed that words in one problem category were often correlated with words in other problem categories. Frequency word analysis showed that the three problem categories varied across gender and school levels. These results provide interesting insights into the characteristics of suicides among Korean students and important implications for suicide intervention in the education field.

Three-Dimensional Territory and Depth of the Corrugator Supercilii: Application to Botulinum Neurotoxin Injection.

This study aimed to determine the three-dimensional (3D) territory and depth of the corrugator supercilii muscle (CSM) using a 3D structured-light scanner. Thirty-two hemifaces from Korean and Thai embalmed cadavers were used in this study, and 35 healthy young Korean subjects also participated. A 3D analysis of the CSM territory and depth was performed using a structured-light 3D scanner. The most frequently observed locations of the CSM identified in the cadaver were confirmed in healthy young subjects using a real-time two-dimensional B-mode ultrasonography system. The CSM was present in all of the cadavers and healthy young subjects at the intersection point between the vertical line passing through the medial canthus and the horizontal line passing through the glabella (Point #6). The CSM was located on the medial side of the lateral limbus in most cases. The most-medial and most-lateral origin points were at depths of 5.7 ± 1.4 mm (mean ± SD) and 6.6 ± 1.4 mm, respectively; the corresponding depths of the insertion points were 5.4 ± 1.4 mm and 5.6 ± 2.1 mm, respectively. The origin and insertion points of the CSM were at similar depths. The injection depth should be around 4 mm for botulinum neurotoxin (BoNT) injections into the CSM. Point #6 could be regarded as an effective target point for managing the glabellar frown line and preventing palpebral ptosis when injecting BoNT into the CSM. Clin. Anat., 33:795-803, 2020. © 2019 Wiley Periodicals, Inc.

A novel anatomical consideration on the exposed segment of the facial artery.

An understanding of the location and depth of the facial artery (FA) is essential in aesthetic surgery and various cosmetic procedures. The purpose of this study was to clarify the three-dimensional (3D) topography of the exposed segment (ES) of the FA and to provide information to help minimize complications during clinical procedures. From 50 embalmed adult cadavers, the undissected and dissected hemifaces were scanned and reconstructed using the 3D scanner. Then the topographic location of the ES was identified and measured from the superimposed the 3D images. The ES was observed in 82% of the whole specimens. The exposure patterns of the ES were examined, and classified into three types: Type I, one site exposed pattern (74%); Type II, two sites exposed pattern (8%); and Type III, nonexposed pattern (18%). The extent of the ES was located at 2.2 mm above and 4.2 mm below the cheilion (Ch)-otobasion inferius line, and 20.0 to 25.2 mm from the Ch on the lateral aspect. In the frontal view, the average distance from the mid-pupillary line to the ES was 7.1 mm, and from the lateral canthal line to the ES was 6.1 mm. The ES was 7.6 mm below the skin surface. The results of this study will help to provide safe guidelines for filler injections as well as selecting the safe regions in various clinical procedures. Clin. Anat. 33:257-264, 2020. © 2019 Wiley Periodicals, Inc.

Hippocampal activation of 5-HT1B receptors and BDNF production by vagus nerve stimulation in rats under chronic restraint stress.

A growing body of evidence shows that the electrical stimulation of the vagus nerve can improve mental illness including depression. Here, we investigated whether the vagus nerve stimulation (VNS) is involved in regulating the responsiveness of hippocampal neurons in rats under chronic restraint stress (CRS). c-Fos protein signals were detected 2 hr after VNS in 5-HT1A receptor-positive neurons in the dorsal raphe nucleus (DRN) as well as in the nucleus tractus solitarius (NTS). Chronic VNS was performed on a daily basis for 2 weeks using an implanted microelectrode in rats that had undergone CRS for 2 weeks. We found that the levels of both 5-HT1B receptors and phospho-Erk1/2 were decreased in parallel in the hippocampal neurons of CRS animals and then increased to the baseline levels by chronic VNS. Hippocampal induction of 5-HT1B receptors and phospho-Erk1/2 by VNS was diminished after the injection of 5,7-dihydroxytryptamine (5,7-DHT), a neurotoxin of serotonergic neurons, into the DRN. Hippocampal production of brain-derived neurotrophic factor (BDNF) was also upregulated by VNS, but the treatment of 5,7-DHT abrogated the effects of VNS on BDNF induction. VNS in CRS animals improved the behavioral scores in forced swimming test (FST) compared to sham-stimulated control. Our results suggest that VNS-mediated serotonergic input via 5-HT1B receptors into the hippocampal neurons may activate BDNF pathway and improve depressive-like behaviors in CRS animals.

Regional thickness of facial skin and superficial fat: Application to the minimally invasive procedures.

Various recently introduced minimally invasive treatment modalities are now widely used for enhancing the aging face. In a special, filler is used to increase the volume of tissue, and so understanding the regional thickness and distribution of the facial superficial fat is essential for optimizing minimally invasive procedures. The aim of this study was to establish the overall facial skin and superficial fat thicknesses using a three-dimensional (3D) scanning system. From 53 adult Korean and Thai embalmed adult cadavers, the undissected and serially-dissected facial specimens were scanned and reconstructed. The facial skin and superficial fat thicknesses on seven facial regions were calculated from the superimposed images. The facial skin tended to become thicker in the order of the radix and dorsum, and the temple, supraorbital, forehead, perioral, cheek, and infraorbital areas. The skin was thinnest at radix and dorsum (1.51 ± 0.55 mm), and thickest in infraorbital region (1.97 ± 0.84 mm). The facial superficial fat thickness tended to increase in the order of the radix and dorsum, supraorbital, forehead, temple, cheek, infraorbital, and perioral regions. The superficial fat was thinnest at the radix and dorsum (1.61 ± 1.07 mm), and thickest in the perioral region (5.14 ± 3.31 mm). The facial superficial fat thickness tended to increase in the order of the radix and dorsum, supraorbital, forehead, temple, cheek, infraorbital, and perioral regions. The present findings indicate that 3D scanning system can yield crucial anatomical information about depths of the facial skin and superficial fat layers for utilization in various clinical procedures. Clin. Anat. 32:1008-1018, 2019. © 2019 Wiley Periodicals, Inc.

Ultrasonography of the internal architecture of the superficial part of the masseter muscle in vivo.

It is unclear whether the deep inferior tendon (DIT) is equally present in vivo, and little anatomical information is available regarding the existence and morphology of the DIT in healthy young subjects. The aim of this study was to characterize the DIT of the masseter muscle in healthy young subjects using ultrasonography and to compare the morphology of this tendon with previously reported data for healthy young subjects in order to provide the most-effective injection methods for botulinum neurotoxin treatments of masseteric hypertrophy. This study investigated two fresh cadavers and 30 healthy subjects. Ultrasonography scanning in both longitudinal and transverse directions was applied to the masseter muscle. The DIT within the superficial part of the masseter was observed in both the fresh cadavers and the living subjects. The posterior region of the masseter muscle was compartmentalized (entirely covered) by the DIT in 26.7% of the specimens. The superficial part of the masseter muscle was divided by the DIT transversely and longitudinally into the superficial and deep muscle bellies in 35% and 38.3% of the specimens, respectively. The present findings suggest applying a DIT-based injection technique under guidance by ultrasonography prior to treating masseteric hypertrophy. Clin. Anat. 32:446-452, 2019. © 2019 Wiley Periodicals, Inc.

Correlation between Cycling Power and Muscle Thickness in Cyclists.

The aim of this study was to determine the correlation between muscle thickness (MT) and cycling power in varsity cyclists using ultrasonography (US) and to identify any differences in MT between short- and long-distance cyclists. Twelve cyclists participated in this study. Real-time two-dimensional B-mode US was used to measure the MT in the anterior thigh, anterior lower leg, and trunk, especially in the abdominal and lumbar regions. A cycle ergometer was used to measure cycling power parameters such as maximum anaerobic power (over 5 s), mean anaerobic power (over 30 s), and aerobic power (over 3 min). This study was approved by the Ethics Committee of Korea National Sports University. There was a significant relationship between the MT and cycling power for the rectus femoris (RF) and vastus lateralis (VL) in the thigh, the rectus abdominis (RA) in the abdominal region, and the erector spinae (ES) in the lower back. The MT values of the RF, VL, and ES were strongly associated with the maximum and mean anaerobic power. There were significant differences between short- and long-distance cyclists in the MT of the RF in the thigh, the RA, the external abdominal oblique, the internal abdominal oblique, and the transverse abdominis muscle in the abdomen. We suggest that training programs attempting to improve cycling performance focus on improving the VL and ES via resistance weight or cycle training and also the core muscles for short-distance cyclists. Clin. Anat. 31:899-906, 2018. © 2018 Wiley Periodicals, Inc.

Positional relationship between the pectoralis major and external abdominal oblique muscles for consideration during dual-plane breast augmentation.

During dual plane breast augmentation (DPBA), the costal origin of the pectoralis major (the PM) should be cut to ensure appropriate coverage and positioning of an implant. However, surgeons sometimes make inappropriate planar incisions and insufficient muscular incisions because the external abdominal oblique (the EAO) muscle partially overlaps the lateral portion of the PM. The goal of this study was to clarify the positional relationship between the PM and EAO with the aim of improving the accuracy of implant and muscular incisions during DPBA. Forty sides of 20 embalmed and fresh cadavers were dissected. The midline and midclavicular line (MCL) were used as reference lines for measurements. We clarified the overlapping patterns between the PM and EAO, and measured the distances from the MCL to the borders of those two muscles. The costal part of the PM originated from the 5th (25%), 6th (70%), or 7th rib (5%), respectively. The distances from the MCL to the lateral border of the PM at the 4th, 5th, and 6th ribs were 49.8 mm, 30.5 mm, and 6.3 mm, respectively. In 90% of the specimens, the PM and the EAO overlapped near the MCL. The width of the overlapping portion between the PM and EAO was about 25 mm. This study is one of the first to suggest an innovative approach for explaining the positional relationships between the PM and EAO. Our findings can be useful for surgeons attempting to produce optimal outcomes in DPBA, especially in procedures that involve patients of different races. Clin. Anat. 31:339-346, 2018. © 2018 Wiley Periodicals, Inc.

Classification of unusual insertion of the pectoralis minor muscle.

PURPOSE: The pectoralis minor muscle (PMi) generally originates from the third, fourth, and fifth ribs and inserts on the medial and superior margins of the anterior portion of the coracoid process. Variations in the shape and attachment point of the PMi could cause discomfort in the shoulders. The aim of this study was to observe the types of morphological insertion patterns and attachment sites of the PMi. METHODS: Seventy-four sides of fresh, embalmed Korean (42 sides; mean age 78 years) and Thai (32 sides; mean age 78 years) cadavers were dissected to analyze the morphological insertion types and attachment sites of the PMi. RESULTS: Unusual insertion patterns were evident in about 23% of the samples. When the portion of the PMi tendon ran over the coracoid process, the most common attachment site was the glenohumeral joint capsule. We also confirmed the attachment of the PMi to the clavicle. Costal attachments of the PMi that extend from the second rib to the fourth rib were observed frequently as well. CONCLUSIONS: Unusual insertion patterns of the PMi are common. Some authors consider that tendon attachment to the joint capsule can cause shoulder pain. In addition, the PMi tendon could be utilized in acromioclavicular joint reconstruction. Surgeons need to be aware of the possibility of a PMi variant being found during surgery even when this is not visible in magnetic resonance or ultrasound imaging.

DNA damage-induced apoptosis suppressor (DDIAS), a novel target of NFATc1, is associated with cisplatin resistance in lung cancer.

In a previous study, we reported that DNA damage induced apoptosis suppressor (DDIAS; hNoxin), a human homolog of mouse Noxin, functions as an anti-apoptotic protein in response to DNA repair. Here we reveal that DDIAS is a target gene of nuclear factor of activated T cells 2 (NFATc1) and is associated with cisplatin resistance in lung cancer cells. In the DDIAS promoter analysis, we found that NFATc1 activated the transcription of DDIAS through binding to NFAT consensus sequences in the DDIAS promoter. In addition, tissue array immunostaining revealed a correlation between DDIAS and NFATc1 expression in human lung tumors. NFATc1 knockdown or treatment with the NFAT inhibitor cyclosporine A induced apoptosis and led to growth inhibition of lung cancer cells, indicating the functional relevance of both the proteins. In contrast, DDIAS overexpression overcame this NFATc1 knockdown-induced growth inhibition, supporting the cancer-specific role of DDIAS as a target gene of NFATc1. NFATc1 or DDIAS inhibition clearly enhanced apoptosis induced by cisplatin in NCI-H1703 and A549 cells. Conversely, DDIAS overexpression rescued NCI-H1703 cells from cisplatin-mediated cell death and caspase-3/7 activation. These results suggest that NFATc1-induced DDIAS expression contributes to cisplatin resistance, and targeting DDIAS or NFATc1 impairs the mechanism regulating cisplatin resistance in lung cancer cells. Taken together, DDIAS is a target of NFATc1 and is associated with cisplatin resistance in lung cancer cells.

N,N-disubstituted azines attenuate LPS-mediated neuroinflammation in microglia and neuronal apoptosis via inhibiting MAPK signaling pathways.

BACKGROUND: Activated microglia interact with astrocytes and neuronal cells to induce neuroinflammation, which can contribute to the pathogenesis and progression of Alzheimer's and Parkinson's disease. To identify the most effective anti-neuroinflammatory agent, we designed and synthesized a family of 13 new azine derivatives and investigated their anti-neuroinflammatory activities in LPS-activated BV-2 microglial cells. RESULTS: Out of 13 derivatives, compound 3 [4,4'-(1E,1'E,3E,3'E)-3,3'-(hydrazine-1,2-diylidene) bis-(prop-1-ene-1-yl-3-ylidene) bis-(2-methoxyphenol)] exhibited excellent anti-neuroinflammatory activities (IC50 = 12.47 µM), which protected neurons from microglia-mediated neurotoxicity. Specifically, the anti-neuroinflammatory effects of compound 3 inhibited MAPK signaling pathways through the inhibition of p38 and JNK mediated signaling and the production of pro-inflammatory cytokines, and inflammatory mediators. Additionally, compound 3 strongly exhibited neuroprotective effect by inhibiting LPS-mediated necrosis and apoptosis. Preliminary SAR analysis suggests that the presence of methoxyphenol and the substitution pattern within hydrazine may influence the anti-neuroinflammatory activity. FACS analysis also strongly supports the neuroprotective effect of compound 3. CONCLUSIONS: Based on our results, the compound 3 exhibited excellent anti-neuroinflammatory activity against LPS-activated microglia, which resulted in the inhibition of neuronal apoptosis and neuronal degeneration.