The deubiquitinase UCHL3 mediates p300-dependent chemokine signaling in alveolar type II cells to promote pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a chronic, fatal, fibrotic, interstitial lung disease of unknown cause. Despite extensive studies, the underlying mechanisms of IPF development remain unknown. Here, we found that p300 was upregulated in multiple epithelial cells in lung samples from patients with IPF and mouse models of lung fibrosis. Lung fibrosis was significantly diminished by the alveolar type II (ATII) cell-specific deletion of the p300 gene. Moreover, we found that ubiquitin C-terminal hydrolase L3 (UCHL3)-mediated deubiquitination of p300 led to the transcriptional activation of the chemokines Ccl2, Ccl7, and Ccl12 through the cooperative action of p300 and C/EBPß, which consequently promoted M2 macrophage polarization. Selective blockade of p300 activity in ATII cells resulted in the reprogramming of M2 macrophages into antifibrotic macrophages. These findings demonstrate a pivotal role for p300 in the development of lung fibrosis and suggest that p300 could serve as a promising target for IPF treatment.

Therapeutic effects of selective p300 histone acetyl-transferase inhibitor on liver fibrosis.

Liver fibrosis is caused by chronic liver damage and results in the aberrant accumulation of extracellular matrix during disease progression. Despite the identification of the HAT enzyme p300 as a major factor for liver fibrosis, the development of therapeutic agents targeting the regulation of p300 has not been reported. We validated a novel p300 inhibitor (A6) on the improvement of liver fibrosis using two mouse models, mice on a choline-deficient high-fat diet and thioacetamide-treated mice. We demonstrated that pathological hall-marks of liver fibrosis were significantly diminished by A6 treatment through Masson's trichrome and Sirius red staining on liver tissue and found that A6 treatment reduced the expression of matricellular protein genes. We further showed that A6 treatment improved liver fibrosis by reducing the stability of p300 protein via disruption of p300 binding to AKT. Our findings suggest that targeting p300 through the specific inhibitor A6 has potential as a major therapeutic avenue for treating liver fibrosis. [BMB Reports 2023; 56(2): 114-119].

Comparing reliability between 3D imaging and 2D photography for external nasal anthropometry.

This study investigates and compares the reliability and reproducibility of two facial anthropometric methods about external nasal angles, 3D imaging and conventional 2D photography. 2D photograph images and 3D images about external nose of 30 volunteers were taken using digital camera and Morpheus 3D scanner. To evaluate intra-rater reliability, each images were taken over two different days for each subject by the same researcher. To evaluate inter-rater reliability, another researcher took each images for each subject on the first day. The reliability of each method for measuring 4 external nasal angle is obtained using intraclass correlation coefficient (ICC) and compared. Inter-rater and intra-rater reliability of both 3D imaging and 2D photography had excellent agreement in all 4 nasal angles. In the nasofacial angular parameter, Inter-rater ICC, 2D photography was significantly higher than 3D imaging. Result of intra-rater ICC also showed both 3D imaging and 2D photography had good reliability in all 4 nasal angles. Similar to those of inter-rater ICC, nasofacial angular parameter showed statistically significant differences between 3D imaging and 2D photography. In terms of reliability, both 2D and 3D showed appropriate anthropometric results and considering its own advantage, each methods can be used complementarily.

Aucuparin Suppresses Bleomycin-Induced Pulmonary Fibrosis Via Anti-Inflammatory Activity.

Idiopathic pulmonary fibrosis (IPF) is a lung disease that results in scarring of the lungs for an unknown reason. Although many studies have been conducted on IPF, precise mechanisms and treatments have not yet been identified. In this study, we found that aucuparin, a natural product isolated from Sorbus aucuparia, inhibited pulmonary fibrosis in a bleomycin (BLM)-induced lung fibrosis mouse model. In the lung samples of mice treated with aucuparin, the gene expression of inflammation and macrophage activation markers was reduced compared to those treated with BLM alone. Moreover, aucuparin decreased the expression of profibrotic marker genes and increased the expression of antifibrotic marker genes. Finally, we observed that aucuparin significantly suppressed transforming growth factor-ß-induced activation of inflammatory cytokine production and collagen synthesis from macrophages and fibroblasts, respectively. Taken together, these data demonstrate that aucuparin inhibits lung fibrosis via its anti-inflammatory action and support its potential to be a therapeutic drug for IPF treatment.

In Situ Characterization of Micro-Vibration in Natural Latex Membrane Resembling Tympanic Membrane Functionally Using Optical Doppler Tomography.

Non-invasive characterization of micro-vibrations in the tympanic membrane (TM) excited by external sound waves is considered as a promising and essential diagnosis in modern otolaryngology. To verify the possibility of measuring and discriminating the vibrating pattern of TM, here we describe a micro-vibration measurement method of latex membrane resembling the TM. The measurements are obtained with an externally generated audio stimuli of 2.0, 2.2, 2.8, 3.1 and 3.2 kHz, and their respective vibrations based tomographic, volumetric and quantitative evaluations were acquired using optical Doppler tomography (ODT). The micro oscillations and structural changes which occurred due to diverse frequencies are measured with sufficient accuracy using a highly sensitive ODT system implied phase subtraction method. The obtained results demonstrated the capability of measuring and analyzing the complex varying micro-vibration of the membrane according to implied sound frequency.

Two Different Views on the World Around Us: The World of Uniformity versus Diversity.

We propose that when individuals believe in fixed traits of personality (entity theorists), they are likely to expect a world of "uniformity." As such, they easily infer a population statistic from a small sample of data with confidence. In contrast, individuals who believe in malleable traits of personality (incremental theorists) are likely to presume a world of "diversity," such that they "hesitate" to infer a population statistic from a similarly sized sample. In four laboratory experiments, we found that compared to incremental theorists, entity theorists estimated a population mean from a sample with a greater level of confidence (Studies 1a and 1b), expected more homogeneity among the entities within a population (Study 2), and perceived an extreme value to be more indicative of an outlier (Study 3). These results suggest that individuals are likely to use their implicit self-theory orientations (entity theory versus incremental theory) to see a population in general as a constitution either of homogeneous or heterogeneous entities.

The RIDA Allergy Screen Versus the Phadiatop Test in 430 Consecutive Patient Specimens.

OBJECTIVE: To compare the performances of the Phadiatop test and the RIDA qLine Allergy in specimens from the South Korean population. METHODS: We divided 430 consecutive patient specimens into 4 groups depending on the test results of the 2 assays. We evaluated the degree of agreement between the assays and used the ImmunoCAP sIgE test to identify the allergen-specific immunoglobulin E (IgE). RESULTS: Agreement between the 2 tests was significant (k = 0.614, P <.001). When tested with the ImmunoCAP allergen-specific immunoglobulin E (sIgE) test, 8 of 48 (16.7%) cases that tested RIDA qLine Allergy positive/Phadiatop negative yielded positive results and 34 of 35 (97.1%) RIDA qLine Allergy negative/Phadiatop positive cases yielded positive results in more than 1 of the 14 tested items. CONCLUSIONS: Our results suggest that the Phadiatop test is more accurate than the RIDA qLine Allergy in discrepant cases.

Impact of obstructive sleep apnea on left atrial functional and structural remodeling beyond obesity.

BACKGROUND: To evaluate the left atrial (LA) volume and function of obese patients with/without obstructive sleep apnea (OSA) and its association with left ventricular (LV) diastolic function independent of obesity. METHODS: LA volumetric and functional parameters were measured by 2-dimensional and strain echocardiography in 49 obese (body mass index ≥ 25 kg/m(2)) subjects (24 non-OSA and 25 OSA). RESULTS: OSA group showed larger maximal LA volume indexed for body surface area, larger volume before atrial contraction, a reduction in the LA passive emptying fraction, and an increase in the LA active emptying fraction with no significant change in LA total emptying fraction. Mitral annular early diastolic velocity (Ea) was significantly reduced, whereas the ratio of mitral valve early diastolic velocity (E) to Ea (E/Ea) and late diastolic velocity (Aa) were significantly increased in OSA group. Although the mean peak late diastolic strain rate had not shown any differences, the LA mean peak systolic strain/strain rate, and mean peak early diastolic strain rate were significantly lower in the OSA group. Apnea-hypopnea index (AHI) of the OSA patients was significantly correlated with E/Ea (r=0.67, p<0.001). There is a significant correlation between LA active emptying volume index and E/Ea (r=0.77, p<0.001), and between LA passive emptying volume index and E/Ea (r=-0.51, p=0.009). CONCLUSION: LA structural and functional remodeling was significantly correlated with the severity of OSA and LV diastolic filling pressure. OSA impaired LA wall compliance and passive contraction independent of obesity.

Abducens nerve palsy complicated by inferior petrosal sinus septic thrombosis due to mastoiditis.

We present a very rare case of a 29-month-old boy with acute onset right abducens nerve palsy complicated by inferior petrosal sinus septic thrombosis due to mastoiditis without petrous apicitis. Four months after mastoidectomy, the patient fully recovered from an esotropia of 30 prism diopters and an abduction limitation (-4) in his right eye.

Comparative computation of orbital volume from axial and coronal CT using three-dimensional image analysis.

PURPOSE: Volume measurements calculated from axial and coronal CT scans were compared to determine which method more accurately determines orbital volume. METHODS: Thirty facial CT scans were used to measure 30 normal orbits using an image analysis program (Dextroscope, Singapore). The 3-dimensional volumes determined from axial scans and coronal scans were analyzed. The coronal scan volume measurements were further subdivided based on anterior limit criteria (termed C1 and C2). Three novel cephalometric angular measurements of the anterior orbital aperture were calculated and used to analyze the volumetric methodologies described above. RESULTS: The calculated orbital volume was greatest on axial scan, 25.6 +/- 2.4 ml, followed by volume based on coronal calculations with C1 delimitation (23.8 +/- 2.9 ml) and C2 delimitation (16.6 +/- 2.2 ml). We measured 3 novel orbital aperture angles on sagittal 3-dimensional reconstruction images, anterovertical, posterovertical, and horizontal orbital aperture angles that are related to the volume measurement underestimation. CONCLUSION: The orbital volume from coronal scans is underestimated compared with that from the axial scans, and the criterion for anterior limit of measurement can affect volume determination. Three novel cephalometric angle measurements may account for inaccuracies in orbital volume measurements.

Three-dimensional analysis of zygomatic-maxillary complex fracture patterns.

Zygomatic-maxillary (ZMC) complex fractures are a common consequence of facial trauma. In this retrospective study, we present a novel method of ZMC fracture pattern analysis, utilizing three-dimensional visualization of computed tomography (CT) images to record displacement of the malar eminence in a three-dimensional coordinate plane. The pattern of fracture was then correlated with treatment outcome. Facial CT scans were obtained from 29 patients with unilateral ZMC fractures and 30 subjects without fractures and analyzed. Briefly, displacement of the malar eminence (ME) on the fractured side was measured in medial-lateral (x), superior-inferior (y), and anterior-posterior (z) dimensions, as well as Euclidean distance, by comparison to ME location on the unfractured side. Baseline natural variance in asymmetry was accounted for by comparing ME location on the left and right sides in subjects without fractures. Patients who required open reduction and internal fixation (ORIF) to repair the ZMC fracture alone had significantly greater cumulative ME displacements than patients who did not require ORIF (p = 0.02). Additionally, patients with a high fracture score of 3, 4, or 5 (assigned based on severity displacement in each dimension) had significantly higher rates of ORIF than patients with a low fracture score of 0, 1, or 2 (p = 0.05). Severe displacement in one or more dimensions was associated with higher rates of ORIF than seen in patients with only neutral or mild displacements in all dimensions (p = 0.05). Severe x displacement was most strongly correlated with surgical intervention (p = 0.02). Overall, orbital floor repair was less strongly associated with most displacement measures than ZMC repair alone; however, patients requiring orbital floor repair had greater Euclidean ME displacements than patients who did not require orbital floor repair (p = 0.02). Fracture severity, as determined by multiple parameters in this novel evaluation system, is associated with higher rates of ORIF in patients with unilateral ZMC fractures. Determination of ZMC fracture pattern may thus be informative when considering treatment options.

Measurements of orbital volume change using computed tomography in isolated orbital blowout fractures.

OBJECTIVES: To measure the orbital volume of unilateral pure blowout fractures with computed tomography before and after surgery and to compare 3-dimensional (3-D) imaging systems. METHODS: Twenty-four patients were evaluated with facial computed tomographic scans before and after surgery. Both the orbital volume and the displaced soft tissue volume were measured by 2 operators using 2 different 3-D software programs (Vitrea; Vital Images Inc, Minnetonka, Minnesota; and Dextroscope; Bracco AMT Inc, Princeton, NJ). RESULTS: The mean (SD) normal orbital volumes calculated by Vitrea and Dextroscope were 25.5 (2.4) mL and 24.8 (3.0) mL, respectively. The average preoperative orbital volumes were 28.3 (2.3) mL and 27.6 (3.1) mL, while the postoperative volumes were 25.8 (2.5) mL and 24.9 (3.0) mL. Vitrea showed that the average volume of displaced orbital soft tissue was 2.8 (1.9) mL before surgery and that it was reduced to 0.3 (1.3) mL after surgery, while Dextroscope showed that the average displaced orbital soft tissue was 2.9 (1.4) mL before surgery and that it was reduced to 0.1 (1.2) mL after surgery. There was no statistical difference between the 3-D analysis programs. CONCLUSIONS: Consistent volume measurements can be obtained using different 3-D image analysis programs. Measuring preoperative and postoperative volume changes and postoperative reduction can ensure a good surgical result and thereby decrease the incidence of enophthalmos.

Modified technique for endoscopic endonasal reduction of medial orbital wall fracture using a resorbable panel.

PURPOSE: To describe a modified technique using resorbable panel for endoscopic endonasal reduction of medial orbital wall fracture. METHODS: A prospective, small interventional case series involving 2 patients with medial orbital wall fractures that were treated with the modified technique. Postoperatively, patients were evaluated for visual acuity, enophthalmos, extraocular motility, and diplopia. RESULT: Both patients recovered completely without any residual eye symptoms or complications, and postoperative CT showed a completely resolved medial orbital wall. CONCLUSION: The modified technique for endoscopic endonasal reduction using a resorbable panel was effective for the reconstruction of orbital wall fractures, without complications. The modified technique may be expected to have advantages over the conventional endoscopic approach using a Silastic sheet and Merocel because it does not require long-term nasal packing, and the resorbable panel supports the orbital contents longer.

Expression of glucocorticoid receptor mRNAs in glucocorticoid-resistant nasal polyps.

Glucocorticoids (GCs) are the most effective group of medications available to treat inflammation. Although most patients with inflammation respond to GC, a small group of patients exhibit persistent GC-resistance with prolonged inflammation. Previously, it was proposed that the GC-resistance is caused by low amount of human GC receptor (hGRalpha) and/or excessive presence of a GC receptor isoform, hGRbeta that was generated from alternative splicing of the hGR message. We have tested this hypothesis by investigating correlation between the expression pattern of hGR mRNAs in patients with inflammatory nasal polyps and the effectiveness of GC treatment.? We have performed reverse transcription PCR analysis of mRNAs coding each hGRalpha and hGRbeta in nasal tissues.? hGRalpha mRNA was more expressed in patients with nasal polyps than in normal subjects. However, the elevated hGRalphamRNA expression was decreased after GC treatment. Compared with hGRalpha mRNA expression, level of hGRbeta mRNA expression was very low in all groups. In patients, hGRbetamRNA was expressed at a similar level regardless of GC efficacy, indicating that there is no correlation between the GC sensitivity and the expression level of hGRbeta mRNA. Thus, persistent GC-resistance is not associated with low expression of hGRa or over- expression of hGRbeta.