Spontaneous Recovery of Traumatic Unilateral Superior Oblique Palsy and Ocular Factors for Predicting Prognosis

Purpose@#This study evaluated the prognosis of patients with traumatic unilateral superior oblique palsy (SOP) and clinical factors associated with spontaneous resolution. @*Methods@#Medical records of patients with traumatic unilateral SOP who visited two hospitals (Yeungnam University Hospital and Daegu Catholic University Medical Center) between January 2015 and June 2020 were reviewed retrospectively. When traumatic unilateral SOP did not recover within at least 1 year of follow-up, no spontaneous resolution was considered. Both traumatic and ocular factors were evaluated to evaluate their association with spontaneous recovery. @*Results@#Fifty-nine patients (mean age, 52.6 years; 48 male patients) were enrolled in this study. The mean interval from trauma to initial presentation was 3.9 months. The mean vertical deviation at initial presentation was 6.34 ± 5.22 prism diopters (PD) (range, 0–25 PD). During the mean 24.1-month follow-up period, 28 patients (47.5%) achieved spontaneous resolution of SOP. Thirteen patients underwent surgical treatment for SOP. Vertical deviation <6 PD at the initial visit and low fundus torsion in the nonparetic eye and both eyes were significantly associated with spontaneous recovery (p < 0.05, logistic regression analysis). Traumatic factors, including the trauma type, presence of intracranial lesion, loss of consciousness, and Glasgow Coma Scale score, were not associated with spontaneous recovery. @*Conclusions@#In this multicenter study, spontaneously recovery was achieved in 47.5% patients with traumatic unilateral SOP. Even mild head trauma can lead to permanent SOP. Ocular factors, including the angle of deviation and fundus torsion, may better predict spontaneous resolution than traumatic factors in patients with traumatic unilateral SOP.

The Association between Level of Control and Exodeviation after the Monocular Occlusion Test in Pediatric Patients with Intermittent Exotropia

Purpose@#We investigated the association between the level of control and exodeviation after the monocular occlusion test (MO) in pediatric patients with intermittent exotropia. @*Methods@#We retrospectively reviewed the records of pediatric patients with intermittent exotropia who visited Yeungnam University Hospital between September 2015 and December 2020. The largest exodeviation obtained before and after 1 hour of MO were compared. The LACTOSE (Look And Cover, then Ten seconds of Observation Scale for Exotropia) control scoring system was used to measure the level of control. Controllability was defined when the patient had the subjective awareness of exotropia and the instinctive ability to correct ocular deviation. @*Results@#Five hundred and three consecutive patients (260 male and 243 female patients; mean age, 7.8 years) were included. In all control scores, exodeviation significantly increased after the MO (p < 0.001). However, the patients with an increase in exodeviation ≥5 prism diopters (PD) after the test did not show any significant association with the control scores. The presence of controllability was significantly associated with an increase of ≥5 PD at near (p = 0.034). @*Conclusions@#Exodeviation showed significant increase after the MO, regardless of the level of control, in pediatric patients with intermittent exotropia. There was no significant association between the control scores and an increase of ≥5 PD after the MO. Patients with controllability were more likely to show increase in exodeviation after the MO.

Effect of Childhood Trauma on the Association Between Stress-Related Psychological Factors and Hair Cortisol Level in Young Adults

Objective@#Relationship between hair cortisol concentration (HCC) and stress-related psychological measures are inconclusive, possibly due to overlooked heterogeneity regarding childhood trauma and a lack of comprehensive research on stress-related psychological factors. This study aims to compare young adults without history of childhood trauma to young adults who experienced childhood trauma using HCC and various stress-related psychological factors, as well as investigate the impacts of childhood trauma on the association between HCC and stress-related psychological measures. @*Methods@#A total of 206 young, healthy adults were recruited. We divided participants into two groups depending on whether or not they had suffered moderate-to-severe childhood trauma (CT+ and CT-) and compared HCC and various stress-related psychological measures between groups. Using multiple linear regression analyses, we assessed the associations between HCC and stress-related psychological measures for each group. @*Results@#We found no difference between the groups in HCC or the reported number of stressful life events in the past year; however, CT+ individuals reported higher stress perception, more depressive and anxiety-related symptoms, and more difficulties in emotion regulation than CT- individuals. HCC was associated with emotion dysregulation among the CT- individuals, but not among the CT+ individuals. @*Conclusion@#These findings suggest that history of childhood trauma should be considered in studies using HCC as a biomarker for stress in young adults. Furthermore, HCC might be a useful biomarker of stress and stress-related emotion dysregulation in individuals without moderate-to-severe childhood trauma.

Surgical Outcomes of Medial Rectus Recession and Lateral Rectus Resection for Large-angle Deviations of Acute Acquired Concomitant Esotropia

Purpose@#This study aimed to evaluate the surgical outcomes of unilateral medial rectus recession and lateral rectus resection (R&R) for patients with large-angle deviations of acute acquired concomitant esotropia (AACE) without a neurological disease. Further, we have also suggested the surgical dosage of R&R for large-angle deviations of AACE. @*Methods@#This was a retrospective study of patients with AACE who underwent surgery and followed up after surgery for at least 6 months between September 2016 and March 2020. Among them, patients with ocular deviations of ≥30 prism diopters (PD) who underwent unilateral R&R were included. @*Results@#Seventeen patients with AACE were enrolled in this study (mean age, 23.5 years; four females). The mean amount of deviation was 40.00 PD at distance and near (range, 30–55 PD). Fifteen patients (88.2%) had myopia. The mean interval between the initial visit and surgery was 7.7 months (range, 4–20 months). All included patients had resolved diplopia after the surgery. Most patients with decreased stereoacuity displayed stereoacuity recovery after surgical treatment. At the final visit (mean follow-up period, 12.8 months), the mean angle of esodeviation was 0.82 PD (range, 6–0 PD) at distance and 0.47 PD (range, 4–0 PD) near. No patient displayed over-correction or adduction limitations in the operated eye. @*Conclusions@#The unilateral R&R procedure presented favorable surgical outcomes for patients with large-angle deviations of AACE. These results and proposed surgical dosage guidelines may be useful for surgeons in planning the surgical treatment of large-angle deviations of AACE.

Autophagy-Related Protein MAP1LC3C Plays a Crucial Role in Odontogenic Differentiation of Human Dental Pulp Cells

BACKGROUND@#Autophagy plays important roles in odontogenic differentiation of dental pulp cells (DPCs) in the developmental stage of tooth bud. Few studies have reported the role of autophagy during reparative dentin formation process. The objective of this study was to discover gene expression pattern correlated to autophagy and their role during odontogenic differentiation process in DPCs. @*METHODS@#After tooth cavities were prepared on the mesial surface of lower first molar crown of rats. Odontogenic differentiation and reparative dentin formation were assessed based on detection of morphology change with hematoxylin and eosin staining. @*RESULTS@#After tooth cavities were prepared on the mesial surface of lower first molar crown of rats, odontogenic differentiation and reparative dentin formation were assessed based on detection of morphology change with hematoxylin and eosin staining and dentin sialophosphoprotein (DSPP), whereas autophagy inhibitor 3-methyladenine (3MA) reversed. @*Results@#of quantitative polymerized chain reaction array of autophagosome formation related genes revealed that GABARAPL2 was prominently upregulated while expression of other ATG8 family members were moderately increased after tooth cavity preparation. In addition, human DPCs incubated in differentiation medium predominantly upregulated MAP1LC3C, which selectively decreased by 3MA but not by autophagy enhancer trehalose. Knock-down of MAP1LC3C using shRNA resulted in strong downregulation of dentin matrix protein 1 and DSPP as well-known odontogenic marker compared to knock-down of MAP1LC3B during odontogenic differentiation process of human DPCs. @*CONCLUSION@#Our results suggest that MAP1LC3C plays a crucial role in odontogenic differentiation of human DPCs via regulating autophagic flux.

Mechanisms of tissue factor induction by Porphyromonas gingivalis in human endothelial cells

Associations between periodontal infection and cardiovascular disease have been documented. Porphyromonas gingivalis is a well-established periodontal pathogen, and tissue factor (TF) is a key initiator of the coagulation cascade. In this context, P. gingivalis has been reported to enhance TF expression in human endothelial cells. The present study investigated the underlying mechanisms of TF induction by P. gingivalis in human umbilical vein endothelial cells. P. gingivalis increased TF expression in a dose- and time-dependent manner. Not only live bacteria but also glutaraldehyde-fixed bacteria increased TF expression to the same extent. However, sonicates of P. gingivalis did not induce TF expression. Cytochalasin D and SMIFH2, which are inhibitors of actin polymerization and actin nucleation, respectively, inhibited the TF expression induced by P. gingivalis. Finally, TF production was decreased or increased in the presence of various signaling inhibitors, including mitogen-activated protein kinases. These results suggest that P. gingivalis induces endothelial TF expression by a bacterial internalization-dependent mechanism and through diverse signal transduction mechanisms.

Autophagy-Related Protein MAP1LC3C Plays a Crucial Role in Odontogenic Differentiation of Human Dental Pulp Cells

BACKGROUND@#Autophagy plays important roles in odontogenic differentiation of dental pulp cells (DPCs) in the developmental stage of tooth bud. Few studies have reported the role of autophagy during reparative dentin formation process. The objective of this study was to discover gene expression pattern correlated to autophagy and their role during odontogenic differentiation process in DPCs. @*METHODS@#After tooth cavities were prepared on the mesial surface of lower first molar crown of rats. Odontogenic differentiation and reparative dentin formation were assessed based on detection of morphology change with hematoxylin and eosin staining. @*RESULTS@#After tooth cavities were prepared on the mesial surface of lower first molar crown of rats, odontogenic differentiation and reparative dentin formation were assessed based on detection of morphology change with hematoxylin and eosin staining and dentin sialophosphoprotein (DSPP), whereas autophagy inhibitor 3-methyladenine (3MA) reversed. @*Results@#of quantitative polymerized chain reaction array of autophagosome formation related genes revealed that GABARAPL2 was prominently upregulated while expression of other ATG8 family members were moderately increased after tooth cavity preparation. In addition, human DPCs incubated in differentiation medium predominantly upregulated MAP1LC3C, which selectively decreased by 3MA but not by autophagy enhancer trehalose. Knock-down of MAP1LC3C using shRNA resulted in strong downregulation of dentin matrix protein 1 and DSPP as well-known odontogenic marker compared to knock-down of MAP1LC3B during odontogenic differentiation process of human DPCs. @*CONCLUSION@#Our results suggest that MAP1LC3C plays a crucial role in odontogenic differentiation of human DPCs via regulating autophagic flux.

Surgical Outcomes of Medial Rectus Recession and Lateral Rectus Resection for Large-angle Deviations of Acute Acquired Concomitant Esotropia

Purpose@#This study aimed to evaluate the surgical outcomes of unilateral medial rectus recession and lateral rectus resection (R&R) for patients with large-angle deviations of acute acquired concomitant esotropia (AACE) without a neurological disease. Further, we have also suggested the surgical dosage of R&R for large-angle deviations of AACE. @*Methods@#This was a retrospective study of patients with AACE who underwent surgery and followed up after surgery for at least 6 months between September 2016 and March 2020. Among them, patients with ocular deviations of ≥30 prism diopters (PD) who underwent unilateral R&R were included. @*Results@#Seventeen patients with AACE were enrolled in this study (mean age, 23.5 years; four females). The mean amount of deviation was 40.00 PD at distance and near (range, 30–55 PD). Fifteen patients (88.2%) had myopia. The mean interval between the initial visit and surgery was 7.7 months (range, 4–20 months). All included patients had resolved diplopia after the surgery. Most patients with decreased stereoacuity displayed stereoacuity recovery after surgical treatment. At the final visit (mean follow-up period, 12.8 months), the mean angle of esodeviation was 0.82 PD (range, 6–0 PD) at distance and 0.47 PD (range, 4–0 PD) near. No patient displayed over-correction or adduction limitations in the operated eye. @*Conclusions@#The unilateral R&R procedure presented favorable surgical outcomes for patients with large-angle deviations of AACE. These results and proposed surgical dosage guidelines may be useful for surgeons in planning the surgical treatment of large-angle deviations of AACE.

Mechanisms of tissue factor induction by Porphyromonas gingivalis in human endothelial cells

Associations between periodontal infection and cardiovascular disease have been documented. Porphyromonas gingivalis is a well-established periodontal pathogen, and tissue factor (TF) is a key initiator of the coagulation cascade. In this context, P. gingivalis has been reported to enhance TF expression in human endothelial cells. The present study investigated the underlying mechanisms of TF induction by P. gingivalis in human umbilical vein endothelial cells. P. gingivalis increased TF expression in a dose- and time-dependent manner. Not only live bacteria but also glutaraldehyde-fixed bacteria increased TF expression to the same extent. However, sonicates of P. gingivalis did not induce TF expression. Cytochalasin D and SMIFH2, which are inhibitors of actin polymerization and actin nucleation, respectively, inhibited the TF expression induced by P. gingivalis. Finally, TF production was decreased or increased in the presence of various signaling inhibitors, including mitogen-activated protein kinases. These results suggest that P. gingivalis induces endothelial TF expression by a bacterial internalization-dependent mechanism and through diverse signal transduction mechanisms.

Acquired Strabismus and Diplopia as Initial Presentation Signs of Hyperthyroidism and Thyroid Eye Disease

PURPOSE: We evaluated the clinical characteristics of patients who recently acquired strabismus and diplopia as the initial presentations of hyperthyroidism and thyroid eye disease (TED).METHODS: The medical records of patients with acquired strabismus and diplopia who visited our clinic for evaluation between January 2017 and December 2018 were retrospectively reviewed; patients diagnosed initially with hyperthyroidism and TED were included in this study.RESULTS: A total of 410 patients were referred to our clinic for the evaluation and treatment of diplopia. Among these patients, 12 (2.9%, 12/410) showed acquired strabismus and diplopia as the initial presentation signs of hyperthyroidism and TED. The mean age of onset of diplopia was 54.7 years (range, 18–78 years). Nine patients (75%, 9/12) were male. Six male patients were active smokers at the initial presentation. Hypotropia was the most common type of strabismus (83.3%, 10/12). The mean angle of hypodeviation was 17.5 prism diopters (PD) (range, 4–40 PD). One patient showed exotropia with hypotropia and one patient showed esotropia with a bilateral up gaze limitation. Four male patients (all active smokers) underwent strabismus surgery, and one female patient underwent orbital decompression surgery.CONCLUSIONS: The incidence of acquired strabismus and diplopia as the initial presentation sign of hyperthyroidism was predominant in male patients. Hypotropia was the most common type of strabismus. Male patients who smoked were more likely to show progression to a severe clinical course than female patients.

Changes in Exodeviation after the Monocular Occlusion Test in Adult Patients with Intermittent Exotropia and Its Association with the Level of Control

Purpose@#We investigated the changes in ocular deviation after the monocular occlusion test in adults with intermittent exotropia and evaluated its association with the level of control. @*Methods@#We retrospectively enrolled adults (aged ≥18 years) with intermittent exotropia who visited our clinic between September 2015 and May 2019. Patients with basic intermittent exotropia with a distant deviation within 10 prism diopters (PD) of the near deviation were included. The largest ocular deviations obtained before and after 1 hour of monocular occlusion were compared. The level of control was measured using the LACTOSE (Look and Cover, then Ten seconds of Observation Scale for Exotropia) control scoring system. @*Results@#Forty-six consecutive adult patients (28 males, 18 females; mean age, 34.3 years) were enrolled. The mean ocular deviation was 36.3 PD (range, 18 to 5 PD) at distant fixation and 38.5 PD (range, 18 to 80 PD) at near fixation, which increased significantly to 38.5 PD (p = 0.043) and 41.1 PD (p = 0.011), respectively, after monocular occlusion. The mean ocular deviation increased ≥5 PD in 14 (30.4%) and 15 (32.6%) patients at distant and near fixation, respectively. The level of control was measured in 30 patients. A higher degree of near control was significantly associated with an increase of ≥5 PD in near fixation after the test (p = 0.009 for a near control score ≤2). @*Conclusions@#The monocular occlusion test may help to determine the largest ocular deviation in adults with intermittent exotropia. Approximately one-third of patients exhibited an increase in ocular deviation ≥5 PD. Patients exhibiting good control were more likely to manifest an increase in the ocular deviation.

Dramatic Decrease in Ocular Deviation 1 Day before Surgery in Patients with Intermittent Exotropia

Purpose@#To evaluate the clinical characteristics of patients with intermittent exotropia who exhibited a dramatic decrease in ocular deviation 1 day before surgery. @*Methods@#This study retrospectively enrolled patients with intermittent exotropia who underwent surgery between Decem-ber 2013 and December 2019. Those who exhibited a decrease in ocular alignment ≥10 prism diopters (PD) at the last exam-ination (1 day before surgery) compared with the largest previous angle of deviation were included. A monocular occlusion test was performed to re-confirm the largest angle of ocular deviation. @*Results@#Among 547 patients with intermittent exotropia, 10 (six females; mean age, 8.6 years) exhibited a dramatic de-crease in ocular deviation before impending surgery. The mean largest angle of deviation was 31.0 PD (range, 20 to 50 PD) at distance and 34.5 PD (range, 20 to 55 PD) at near. The mean control scores using the LACTOSE (Look and Cover then Ten Seconds of Observation Scale for Exotropia) scoring system were 2.5 at distance, 1.8 at near, and 4.3 when combined. Mean ocular deviation prior to the impending surgery decreased to 7.4 PD (range, 0 to 10 PD) at distance and 6.2 PD (range, -10 to 10 PD) at near. The largest angle of ocular deviation was re-confirmed using the monocular occlusion test in all patients. All patients underwent surgery as planned, and none exhibited postoperative overcorrection. @*Conclusions@#A relatively small number of patients with intermittent exotropia exhibited a dramatic decrease in ocular align-ment 1 day before surgery but demonstrated a relatively better level of control. The monocular occlusion test was helpful in re-confirming the largest angle of ocular deviation.

Changes in Esodeviation after Inferior Oblique Recession in Patients with Refractive Accommodative Esotropia and Inferior Oblique Overaction

Purpose@#To evaluate the changes in esodeviation after inferior oblique (IO) recession in patients with refractive accommoda-tive esotropia and IO overaction. @*Methods@#Graded IO recession was performed in 68 patients who were diagnosed with refractive accommodative esotropia with IO overaction. The patients were followed for at least 3 months after surgery and the angle of esodeviation with cor-rection was evaluated at distance and near at each follow-up evaluation. The patients were divided into two groups: patients who underwent unilateral IO recession (UIO-Rec) and patients who underwent bilateral IO recession (BIO-Rec). The change in esodeviation after surgery was compared between the two groups. @*Results@#A total of 68 patients were enrolled in this study, with 38 patients in the UIO-Rec group and 30 in the BIO-Rec group.In the UIO-Rec group, there was no statistically significant difference in esodeviation before and after surgery. In the BIO-Rec group, esodeviation at distance increased significantly 1 day postoperatively (p = 0.033). However, esodeviation returned to the preoperative value one week after surgery (p = 0.665). Changes in esodeviation at distance were significantly greater in the BIO-Rec group than in the UIO-Rec group one day after surgery (p = 0.044). @*Conclusions@#Bilateral IO-weakening surgery induced a transient increase in esodeviation in patients with refractive accom-modative esotropia. However, we found no evidence that well-controlled esotropia with corrected hyperopia became de-compensated after IO-weakening surgery, as induced esodeviation was minor and temporary.

Orbital Infarction Syndrome after Thrombectomy for Internal Carotid Artery Occlusion

Purpose@#To report a case of orbital infarction syndrome after thrombectomy for internal carotid artery (ICA) occlusion.Case summary: A 69-year-old female with a history of diabetes mellitus and hypertension was referred to our clinic because of acute right ocular pain and visual disturbance. The patient had a history of a right middle cerebral artery territory infarction following right ICA occlusion and her ocular symptoms developed 6 hours after thrombectomy treatment. The visual acuity was hand motion in the right eye and 20/20 in the left eye. Pupil dilation and a relative afferent pupillary defect were seen in her right eye.There was ptosis of the right eyelid, and the ocular motility examination showed all gaze limitations in the right eye. In fundus examinations, multiple white focal ischemic retinal lesions were observed in the right eye suggesting branch retinal artery occlusion. Slit lamp examination showed chemosis in the right eye. The patient was diagnosed with ocular infarction syndrome due to micro-thromboembolism of the ophthalmic artery which developed after the thrombectomy. @*Conclusions@#Orbital infarction syndrome can occur after thrombectomy. Therefore, it is necessary to consider the development of orbital infarction when patients present with sudden-onset ocular pain, visual loss, and ocular movement limitations after the procedure.

Surgical Outcomes of Patients with Intermittent Exotropia Exhibiting High Hyperopia and Emmetropia

Purpose@#We analyzed the clinical factors and surgical outcomes of patients with intermittent exotropia exhibiting high hyperopia and emmetropia. @*Methods@#Patients with intermittent exotropia who underwent strabismus surgery and were followed-up for at least one year between April 1999 and January 2018 were retrospectively reviewed. The patients were divided into two groups according to their preoperative spherical equivalent refractive error (SERE): a high hyperopia group (≥+4.00 diopters [D], group 1) and an emmetropia group (+0.50 to -0.50 D, group 2). The surgical outcomes of the groups were compared. @*Results@#We enrolled 74 patients, of whom 24 and 50 were included in groups 1 and 2, respectively. In group 1, the mean SERE was +5.00 D (+4.00 to +8.00 D) in the more affected eye and +2.81 D (+0.00 to +7.25 D) in the better eye. In group 1, the changes in SERE at one year after surgery were as follows: +1.24 D in the worse eye and +0.90 D in the better eye (both, p < 0.001). The mean exodeviation at one day postoperatively for distance and near were -1.25 prism diopters (PD) and 0.21 PD, respectively, in group 1, and -4.62 PD and -2.16 PD in group 2. Thus, group 1 exhibited less exodeviation in terms of both distance and near than did group 2 on day one postoperatively. However, no significant group difference was evident at one year postoperatively. @*Conclusions@#The surgical outcomes of intermittent exotropia patients with high hyperopia did not differ from those of patients with emmetropia.

Presumed Ischemic Unilateral Oculomotor Nerve Palsy Developing after a Snake Bite

Purpose@#We report a patient with presumed ischemic unilateral oculomotor nerve palsy developing after a snake bite on the right finger.Case summary: A 58-year-old male visited our emergency department complaining of right ptosis and binocular diplopia that had developed after a snake bite. He had been bitten on a finger of the right hand by an unidentified snake about 6 hours prior to symptom onset. He lacked neurological symptoms such as headache, nausea, vomiting, or an altered consciousness level. The right hand exhibited severe swelling, oozing, and inflammation. The visual acuity was 20/25 in both eyes. Ptosis was evident in the right eye. Both pupils responded normally to light and near stimulation. Extraocular examination revealed movement limitations in all right-eye gaze fields except abduction. A serological test revealed coagulopathy. Pyridostigmine was prescribed, but the ocular symptoms did not immediately improve; however, they did improve gradually during follow-up. At 8 months after the initial visit, the patient exhibited an ortho primary gaze with an adduction limitation of -1. No aberrant regeneration was apparent. @*Conclusions@#Unilateral oculomotor nerve palsy can develop after a snake bite, possibly attributable to microvascular ischemia caused by coagulopathy.

L-ascorbic acid induces apoptosis in human laryngeal epidermoid Hep-2 cells by modulating the nuclear factor kappa-light-chain-enhancer of activated B cells/ mitogen-activated protein kinase/Akt signaling pathway

L-ascorbic acid (L-AA; vitamin C) induces apoptosis in cancer cells. This study aimed to elucidate the molecular mechanisms of L-AA-induced apoptosis in human laryngeal epidermoid carcinoma Hep-2 cells. L-AA suppressed the viability of Hep-2 cells and induced apoptosis, as shown by the cleavage and condensation of nuclear chromatin and increased number of Annexin V-positive cells. L-AA decreased Bcl-2 protein expression but upregulated Bax protein levels. In addition, cytochrome c release from the mitochondria into the cytosol and activation of caspase-9, -8, and -3 were enhanced by L-AA treatment. Furthermore, apoptosis-inducing factor (AIF) and endonuclease G (EndoG) were translocated into the nucleus during apoptosis of L-AA-treated Hep-2 cells. L-AA effectively inhibited the constitutive nuclear factor-κB (NF-κB) activation and attenuated the nuclear expression of the p65 subunit of NF-κB. Interestingly, L-AA treatment of Hep-2 cells markedly activated Akt and mitogen-activated protein kinase (MAPK; extracellular signal-regulated kinase 1/2, p38, and c-Jun N-terminal kinase [JNK]) and and LY294002 (Akt inhibitor), SB203580 (p38 inhibitor) or SP600125 (a JNK inhibitor) decreased the levels of Annexin V-positive cells. These results suggested that L-AA induces the apoptosis of Hep-2 cells via the nuclear translocation of AIF and EndoG by modulating the Bcl- 2 family and MAPK/Akt signaling pathways.

Green tea polyphenol (–)-epigallocatechin-3-gallate prevents ultraviolet-induced apoptosis in PC12 cells

Green tea polyphenol (–)-epigallocatechin-3-gallate (EGCG) is a potent antioxidant with protective effects against neurotoxicity. However, it is currently unclear whether EGCG protects neuronal cells against radiation-induced damage. Therefore, the objective of this study was to investigate the effects of EGCG on ultraviolet (UV)-induced oxidative stress and apoptosis in PC12 cells. The effects of UV irradiation included apoptotic cell death, which was associated with DNA fragmentation, reactive oxygen species (ROS) production, enhanced caspase-3 and caspase-9 activity, and poly (ADP-ribose) polymerase cleavage. UV irradiation also increased the Bax/Bcl-2 ratio and mitochondrial pathway-associated cytochrome c expression. However, pretreatment with EGCG before UV exposure markedly decreased UV-induced DNA fragmentation and ROS production. Furthermore, the UV irradiationinduced increase in Bax/Bcl-2 ratio, cytochrome c upregulation, and caspase-3 and caspase-9 activation were each ameliorated by EGCG pretreatment. Additionally, EGCG suppressed UV-induced phosphorylation of p38 and rescued UV-downregulated phosphorylation of ERK. Taken together, these results suggest that EGCG prevents UV irradiationinduced apoptosis in PC12 cells by scavenging ROS and inhibiting the mitochondrial pathways known to play a crucial role in apoptosis. In addition, EGCG inhibits UV-induced apoptosis via JNK inactivation and ERK activation in PC12 cells. Thus, EGCG represents a potential neuroprotective agent that could be applied to prevent neuronal cell death induced by UV irradiation.

Changes in Exodeviation after the Monocular Occlusion Test in Adult Patients with Intermittent Exotropia and Its Association with the Level of Control

Purpose@#We investigated the changes in ocular deviation after the monocular occlusion test in adults with intermittent exotropia and evaluated its association with the level of control. @*Methods@#We retrospectively enrolled adults (aged ≥18 years) with intermittent exotropia who visited our clinic between September 2015 and May 2019. Patients with basic intermittent exotropia with a distant deviation within 10 prism diopters (PD) of the near deviation were included. The largest ocular deviations obtained before and after 1 hour of monocular occlusion were compared. The level of control was measured using the LACTOSE (Look and Cover, then Ten seconds of Observation Scale for Exotropia) control scoring system. @*Results@#Forty-six consecutive adult patients (28 males, 18 females; mean age, 34.3 years) were enrolled. The mean ocular deviation was 36.3 PD (range, 18 to 5 PD) at distant fixation and 38.5 PD (range, 18 to 80 PD) at near fixation, which increased significantly to 38.5 PD (p = 0.043) and 41.1 PD (p = 0.011), respectively, after monocular occlusion. The mean ocular deviation increased ≥5 PD in 14 (30.4%) and 15 (32.6%) patients at distant and near fixation, respectively. The level of control was measured in 30 patients. A higher degree of near control was significantly associated with an increase of ≥5 PD in near fixation after the test (p = 0.009 for a near control score ≤2). @*Conclusions@#The monocular occlusion test may help to determine the largest ocular deviation in adults with intermittent exotropia. Approximately one-third of patients exhibited an increase in ocular deviation ≥5 PD. Patients exhibiting good control were more likely to manifest an increase in the ocular deviation.

L-ascorbic acid induces apoptosis in human laryngeal epidermoid Hep-2 cells by modulating the nuclear factor kappa-light-chain-enhancer of activated B cells/ mitogen-activated protein kinase/Akt signaling pathway

L-ascorbic acid (L-AA; vitamin C) induces apoptosis in cancer cells. This study aimed to elucidate the molecular mechanisms of L-AA-induced apoptosis in human laryngeal epidermoid carcinoma Hep-2 cells. L-AA suppressed the viability of Hep-2 cells and induced apoptosis, as shown by the cleavage and condensation of nuclear chromatin and increased number of Annexin V-positive cells. L-AA decreased Bcl-2 protein expression but upregulated Bax protein levels. In addition, cytochrome c release from the mitochondria into the cytosol and activation of caspase-9, -8, and -3 were enhanced by L-AA treatment. Furthermore, apoptosis-inducing factor (AIF) and endonuclease G (EndoG) were translocated into the nucleus during apoptosis of L-AA-treated Hep-2 cells. L-AA effectively inhibited the constitutive nuclear factor-κB (NF-κB) activation and attenuated the nuclear expression of the p65 subunit of NF-κB. Interestingly, L-AA treatment of Hep-2 cells markedly activated Akt and mitogen-activated protein kinase (MAPK; extracellular signal-regulated kinase 1/2, p38, and c-Jun N-terminal kinase [JNK]) and and LY294002 (Akt inhibitor), SB203580 (p38 inhibitor) or SP600125 (a JNK inhibitor) decreased the levels of Annexin V-positive cells. These results suggested that L-AA induces the apoptosis of Hep-2 cells via the nuclear translocation of AIF and EndoG by modulating the Bcl- 2 family and MAPK/Akt signaling pathways.