Objective: To investigate the correlation between the osseous structure of temporomandibular joint (TMJ) and three different status of anterior disc location, so that it could guide the clinical diagnosis further. Methods: Fifty-two patients [46 females and 6 males, with an age of (27.8±8.3) years] who treated with MRI and cone beam CT, were recruited from the Temporomandibular Joint Specialist Clinic, The First Affiliated Hospital of Xinjiang Medical University, between March 2018 to December 2021. According to the radiographic findings of the level of anterior disc displacement (ADD) in TMJ, patients were divided into three groups: normal articular disc position (NADP, n=28 TMJs), anterior disc displacement with reduction (ADDWR, n=28 TMJs), and anterior disc displacement without reduction (ADDWoR, n=28 TMJs). In the light of the reconstructed three-dimensional model, ten representative morphological parameters including condylar volume (CV), condylar superficial area (CSA), fossa volume (FV), fossa superficial area (FSA), the proportion of the condylar volume in the articular fossa (CV%), the proportion of the condylar superficial area in the articular fossa (CSA%), superior joint space (SJS), anterior joint space (AJS), posterior joint space (PJS), and medial joint space (MJS), were measured respectively under one-way analysis of variance (ANOVA), Kruskal-Wallis Htest and receiver operator characteristic curve(ROC curve) analyses. Results: CV and CSA values varied significantly in the pathological progression from normal location to irreversible anterior displacement in TMJ. For CV value, NADP group [(1 834.90±667.67) mm3]>ADDWR group [(1 747.34±369.42) mm3]>ADDWoR group [(1 256.29±418.27) mm3] [t=4.31, P(NADP-ADDWoR)<0.001; t=3.66, P(ADDWR-ADDWoR)<0.001], for CSA value, NADP group [(859.27±216.01) mm2]>ADDWR group [(838.23±118.82) mm2]>ADDWoR group [(669.14±150.26) mm2] [t=4.27, P(NADP-ADDWoR)<0.001; t=3.80, P(ADDWR-ADDWoR)<0.001]. The difference of SJS value in NADP group [(2.22±0.88) mm], ADDWR group [(1.94±0.64) mm] and ADDWoR group [(1.45±0.57) mm], was statistically significant [t=4.11, P(NADP-ADDWoR)<0.001; t=2.63, P(ADDWR-ADDWoR)=0.010]. The results of MJS in NADP group [(5.03±1.41) mm], ADDWR group [(3.86±1.32) mm], and ADDWoR group [(4.91±1.65) mm] were significantly different [t=3.00, P(NADP-ADDWR)=0.004; t=2.63, P(ADDWR-ADDWoR)=0.009]. As calculated by the ROC curve analysis, CV, CSA and SJS showed that (AUCCV=0.77, AUCCSA=0.76; AUCSJS=0.76) for the NADP and ADDWoR groups, and (AUCCV=0.80; AUCCSA=0.80; AUCSJS=0.72) for the ADDWR and ADDWoR groups. While the diagnostic accuracy of MJS for the comparison in NADP versus ADDWR and ADDWR versus ADDWoR was respectively AUC(NADP-ADDWR)=0.73, and AUC(ADDWR-ADDWoR)=0.69. Conclusions: CV, CSA, SJS, and MJS were significantly associated with the different disc displacement status, and the condyle in TMJ ADD exhibited three-dimensionally altered dimensions. They could be considered as promising biometric markers to diagnose the ADD status.
目的： 本研究通过三维重建图像测量分析3种不同关节盘状态下，颞下颌关节（TMJ）相关骨性结构的改变情况，为临床诊断提供指导。 方法： 对2018年3月至2021年12月就诊于新疆医科大学第一附属医院颞下颌关节专病门诊同时行MRI与锥形束CT检查的52例患者，其中女性46例，男性6例，年龄（27.8±8.3）岁。根据MRI检查结果将纳入研究对象分为关节盘位置正常（NADP）组、可复性关节盘前移位（ADDWR）组及不可复性关节盘前移位（ADDWoR）组，每组各28侧TMJ。对各组锥形束CT资料进行三维重建，根据重建模型分别记录髁突体积（CV）、髁突表面积（CSA）、关节窝体积（FV）、关节窝表面积（FSA）、髁突在关节窝中体积占比（CV%）、髁突在关节窝中表面积占比（CSA%）、关节腔上间隙（SJS）、关节腔前间隙（AJS）、关节腔后间隙（PJS）以及关节腔内侧间隙（MJS）。采用单因素方差分析、Kruskal-Wallis H检验及受试者操作特征曲线（ROC曲线）分析各参数的改变情况。 结果： CV和CSA在关节盘正常至不可复性前移位的病理进展中均发生显著变化（F=10.79，P<0.001；F=10.95，P<0.001）。NADP组和ADDWR组的CV、CSA和SJS［分别为（1 834.90±667.67）和（1 747.34±369.42）mm3，（859.27±216.01）和（838.23±118.82）mm2，（2.22±0.88）和（1.94±0.64）mm］均显著大于ADDWoR组［分别为（1 256.29±418.27）mm3、（669.14±150.26）mm2、（1.45±0.57）mm］（t=4.31，P<0.001；t=3.66，P<0.001；t=4.27，P<0.001；t=3.80，P<0.001；t=4.11，P<0.001；t=2.63，P=0.010）。NADP组MJS［（5.03±1.41）mm］显著高于ADDWR组［（3.86±1.32）mm］（t=3.00，P=0.004），ADDWR组MJS显著高于ADDWoR组［（4.91±1.65）mm］（t=2.63，P=0.009）。ROC曲线分析显示，CV、CSA、SJS对鉴别NADP与ADDWoR的曲线下面积（AUC）值分别为0.77、0.76、0.76，CV、CSA、SJS对鉴别ADDWR与ADDWoR效果的AUC值分别为0.80、0.80、0.72。MJS对鉴别NADP和ADDWR、ADDWR和ADDWoR的AUC值分别为0.73和0.69。 结论： 颞下颌关节盘移位患者的髁突在三维层面上改变明显，CV、CSA、SJS和MJS的变化与不同的关节盘状态显著相关，可作为评价颞下颌关节盘移位准确度较高的测量指标。.

To investigate the levels of nicotinamide-adenine dinucleotide phosphate oxidase 2 (NOX2) in serum and pericardial drainage samples in the early stage after coronary artery bypass grafting (CABG) and determine whether NOX2 is predictive of postoperative atrial fibrillation (POAF).
This prospective pilot study involved 152 adults without history of atrial fibrillation who underwent first-time elective isolated CABG. Serum and pericardial fluid samples were simultaneously obtained from patients at baseline and 4, 12, and 24 h post operation. NOX2 levels were determined using enzyme-linked immunosorbent assays. The heart rhythm of patients was continuously monitored through a Holter monitor until discharge. Logistic regression and receiver-operating characteristic (ROC) curve analyses were performed, as appropriate.
Fifty-one patients (33.6%) experienced in-hospital POAF. NOX2 concentration in serum and pericardial drainage samples was increased after surgery, reached its peak at 12 h, and gradually declined thereafter toward the baseline levels by 24 h. At 12 h, patients with POAF had higher levels of serum NOX2 than those without (3.96 ± 0.35 vs. 3.70 ± 0.75 μg/mL, respectively, p = 0.004). There were no discernible differences in pericardial NOX2 between the 2 groups. Multivariate analysis revealed that serum NOX2 at 12 h post operation was the strongest independent predictor of POAF (odds ratio: 2.179, 95% confidence interval: 1.084-4.377). The area under the ROC curve of the POAF predictive model was 0.732 (95% confidence interval: 0.654-0.801).
Serum NOX2 may be useful in the identification of POAF. Larger studies are warranted to substantiate these findings.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common human enzyme defect that affects more than 500 million people worldwide. Individuals affected with G6PD deficiency may occasionally suffer mild-to-severe chronic hemolytic anemia. Chronic non-spherocytic hemolytic anemia (CNSHA) is a potential result of the Class I G6PD variants. This comparative computational study attempted to correct the defect in variants structure by docking the AG1 molecule to selected Class I G6PD variants [G6PDNashville (Arg393His), G6PDAlhambra (Val394Leu), and G6PDDurham (Lys238Arg)] at the dimer interface and structural NADP+ binding site. It was followed by an analysis of the enzyme conformations before and after binding to the AG1 molecule using the molecular dynamics simulation (MDS) approach, while the severity of CNSHA was determined via root-mean-square deviation (RMSD), root-mean-square fluctuation (RMSF), hydrogen bonds, salt bridges, radius of gyration (Rg), solvent accessible surface area analysis (SASA), and principal component analysis (PCA). The results revealed that G6PDNashville (Arg393His) and G6PDDurham (Lys238Arg) had lost the direct contact with structural NADP+ and salt bridges at Glu419 - Arg427 and Glu206 - Lys407 were disrupted in all selected variants. Furthermore, the AG1 molecule re-stabilized the enzyme structure by restoring the missing interactions. Bioinformatics approaches were also used to conduct a detailed structural analysis of the G6PD enzyme at a molecular level to understand the implications of these variants toward enzyme function. Our findings suggest that despite the lack of treatment for G6PDD to date, AG1 remains a novel molecule that promotes activation in a variety of G6PD variants.

Objective To investigate the protective effects of an angiotensin-converting enzyme inhibitor after inducing oxidative stress on keloid fibroblasts. Methods Primary keloid fibroblasts were isolated and cultured by enzyme digestion combined with the tissue adhesion method in vitro, and the third to fifth generations of cells were selected for the experiment. For 24 hours, keloid fibroblasts were treated with different concentrations of hydrogen peroxide. Different concentrations of angiotensin-converting enzyme inhibitor were added to the keloid fibroblast culture medium, and then the cells were treated with hydrogen peroxide for 24 hours. Results With the increase of hydrogen peroxide concentration, the growth of keloid fibroblasts was inhibited and the levels of malondialdehyde, superoxide dismutase, and reactive oxygen species increased gradually, accompanied by an increase in the expression of nicotinamide adenine dinucleotide phosphate oxidase and collagen I mRNA. The expression of nicotinamide adenine dinucleotide phosphate oxidase-mRNA in keloid fibroblasts and the formation of reactive oxygen species in keloid fibroblasts were induced by different concentrations of angiotensin II, and the most significant effect was at 10-5 mmol/mL. The effects of diphenyleneiodonium chloride (NOX inhibitor), N-acetylcysteine (reactive oxygen species inhibitor) and nicotinamide adenine dinucleotide phosphate oxidase (NADPH oxidase) RNA treatment on angiotensin II-induced nicotinamide adenine dinucleotide phosphate oxidase and collagen I increased significantly. Hydrogen peroxide and angiotensin II alone or combined can induce NADPH oxidase and reactive oxygen species expression in keloid fibroblasts. When the angiotensin-converting enzyme inhibitor was added, the expression of NADPH oxidase and reactive oxygen species in keloid induced by hydrogen peroxide and angiotensin II could be inhibited. Conclusion Oxidative stress can lead to increased expression of reactive oxygen species, NADPH oxidase and collagen I in keloid fibroblasts, suggesting oxidative stress mediates the migration of human keloid fibroblasts and extracellular matrix synthesis.

Ruta chalepensis L., commonly known as Shazab in Saudi Arabia, is one of the famous culinary plants belonging to the Rutaceae family. It is commonly used in ethnomedicine in treating numerous diseases. This study was performed to characterize the essential oil isolated from Saudi species using a relatively new advanced headspace solid-phase microextraction technique. Following that, the antioxidant activity of the extracted oil was assessed using in vitro techniques such as the DPPH and nitric oxide scavenging tests, as well as the reducing power FRAP study and the molecular docking tool. The essential oil yield of the dried plant was 0.83% (v/w). Gas chromatography joined with a mass spectrometer was used to determine the chemical composition of the pale-yellow essential oil. Sixty-eight constituents were detected, representing 97.70% of the total oil content. The major constituents were aliphatic ketones dominated by 2-undecanone (37.30%) and 2-nonanone (20.00%), with minor constituents of mono and sesquiterpenoids chemical classes. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase is one of the major causes of many contemporary diseases due to its ability to create a reactive oxygen species (ROS). Thus, molecular docking was used to confirm that some oil phytoconstituents have good docking scores compared to the standard antioxidant drug (Vitamin C), indicating great binding compatibility between the (NADPH) oxidase receptor site and the ligand. In conclusion, our findings suggest that the oil could be used safely and as a cost-effective remedy in treating various modern diseases caused by free radical formation.

Light-dependent protochlorophyllide oxidoreductase (LPOR) is a chlorophyll synthetase that catalyzes the reduction of protochlorophyllide (Pchlide) to chlorophyllide (Chlide) with indispensable roles in regulating photosynthesis processes. A recent study confirmed that thylakoid lipids (TL) were able to allosterically enhance modulator-induced LPOR activation. However, the allosteric modulation mechanism of LPOR by these compounds remains unclear. Herein, we integrated multiple computational approaches to explore the potential cavities in the Arabidopsis thaliana LPOR and an allosteric site around the helix-G region where high affinity for phosphatidyl glycerol (PG) was identified. Adopting accelerated molecular dynamics simulation for different LPOR states, we rigorously analyzed binary LPOR/PG and ternary LPOR/NADPH/PG complexes in terms of their dynamics, energetics, and attainable allosteric regulation. Our findings clarify the experimental observation of increased NADPH binding affinity for LPOR with PGs. Moreover, the simulations indicated that allosteric regulators targeting LPOR favor a mechanism involving lid opening upon binding to an allosteric hinge pocket mechanism. This understanding paves the way for designing novel LPOR activators and expanding the applications of LPOR.

OBJECTIVE: Morphologic study is a common approach in the field of anterior disc displacement (ADD) pathology; however, analysis based on 3D reconstructive imaging has not been investigated. This study investigated the association between ADD and the status of the mandibular condyle and articular fossa.
METHODS: Thirty-four patients were divided into a normal articular disc position (NADP) group, an ADD with reduction (ADDwR) group, and an ADD without reduction (ADDwoR) group. Images reconstructed were used to determine multiple grouped comparisons of these three different types of disc position, and the diagnostic efficacy for the morphologic parameters with significant grouped difference was analyzed to assess.
RESULTS: The condylar volume and condylar superficial area of the NADP, ADDwR, and ADDwoR groups exhibited obvious changes (P < .05). A multivariate logistic ordinal regression model showed that the condylar volume (odds ratio [OR], 1.011; regression coefficient [RC] = .011, P = .018), superior joint space (OR, 8.817; RC = 2.177; P < .001), and medial joint space (OR, 1.492; RC = 0.400; P = .047) had a significantly positive impact on the groups.
CONCLUSIONS: The mandibular condyle and articular fossa in temporomandibular joint ADD exhibited altered dimensions. The condylar volume, condylar superficial area, superior joint space, and medial joint space could be considered as promising biometric markers for assessing ADD, and were investigated in this current pilot study. (Quintessence Int 2023;54:156-166; doi: 10.3290/j.qi.b3512027).

Morphological study is a common approach in the field of anterior disc displacement (ADD) pathology; however, analysis based on three-dimensional reconstructive imaging has not been investigated. This study investigated the association between ADD and the status of the mandibular condyle and articular fossa.
Thirty-four patients were divided into three groups: normal articular disc position (NADP), anterior disc displacement with reduction (ADDwR), and anterior disc displacement without reduction (ADDwoR). Multiple grouped comparisons of three different disc statuses were performed by Kruskal-Wallis H test and variance analysis respectively. Receiver-operating characteristic curve was plotted to assess the diagnostic efficacy of the morphological parameters. Multivariate logistic regression analysis was used to investigate the interfering factors of ADD.
The condylar volume (CV) and condylar superficial area (CSA) in the NADP, ADDwR, and ADDwoR groups exhibited obvious changes (P < 0.05). Both CV and superior joint space (SJS) presented a good diagnostic accuracy for NADP-ADDwoR [area under the curve (AUC)CV = 0.813; AUCSJS = 0.855)], and ADDwR-ADDwoR (AUCCV = 0.858; AUCSJS = 0.801). CSA presented a good diagnostic accuracy for ADDwR-ADDwoR (AUC = 0.813). A multivariate logistic ordinal regression model showed that the CV [odds ratio (OR) = 1.011; regression coefficient (RC) = 0.011, P = 0.018], SJS (OR, 8.817; RC = 2.177; P < 0.001), and medial joint space (MJS) (OR, 1.492; RC = 0.400; P = 0.047) had a significantly impact on the groups.
CV, CSA, SJS, and MJS were significantly associated with the different disc status, and the condyle in ADD exhibited 3-dimensionally altered dimensions. They could be considered as promising biometric markers to assess the ADD.

Several natural mutants of the human G6PD enzyme exist and have been reported. Because the enzymatic activities of many mutants are different from that of the wildtype, the genetic polymorphism of G6PD plays an important role in the synthesis of nucleic acids via ribulose-5-phosphate and formation of reduced NADP in response to oxidative stress. G6PD mutations leading to its deficiency result in the neonatal jaundice and acute hemolytic anemia in human. Herein, we demonstrate the molecular dynamics simulations of the wildtype G6PD and its three mutants to monitor the effect of mutations on dynamics and stability of the protein. These mutants are Chatham (A335T), Nashville (R393H), Alhambra (V394L), among which R393H and V394L lie closer to binding site of structural NADP+. MD analysis including RMSD, RMSF and protein secondary structure revealed that decrease in the stability of mutants is key factor for loss of their activity. The results demonstrated that mutations in the G6PD sequence resulted in altered structural stability and hence functional changes in enzymes. Also, the binding site, of structural NADP+, which is far away from the catalytic site plays an important role in protein stability and folding. Mutation at this site causes changes in structural stability and hence functional deviations in enzyme structure reflecting the importance of structural NADP+ binding site. The calculation of binding free energy by post processing end state method of Molecular Mechanics Poisson Boltzmann SurfaceArea (MM-PBSA) has inferred that ligand binding in wildtype is favorable as compared to mutants which represent destabilised protein structure due to mutation that in turn may hinder the normal physiological function. Exploring individual components of free energy revealed that the van der Waals energy component representing non-polar/hydrophobic energy contribution act as a dominant factor in case of ligand binding. Our study also provides an insight in identifying the key inhibitory site in G6PD and its mutants which can be exploited to use them as a target for developing new inhibitors in rational drug design.

Live cyanobacteria and algae integrated onto an extracellular electrode can generate a light-induced current (i.e., a photocurrent). Although the photocurrent is expected to be correlated with the redox environment of the photosynthetic cells, the relationship between the photocurrent and the cellular redox state is poorly understood. Here, we investigated the effect of the reduced nicotinamide adenine dinucleotide phosphate [NADP(H)] redox level of cyanobacterial cells (before light exposure) on the photocurrent using several mutants (Δzwf, Δgnd, and ΔglgP) deficient in the oxidative pentose phosphate (OPP) pathway, which is the metabolic pathway that produces NADPH in darkness. The NAD(P)H redox level and photocurrent in the cyanobacterium Synechocystis sp. PCC 6803 were measured noninvasively. Dysfunction of the OPP pathway led to oxidation of the photosynthetic NADPH pool in darkness. In addition, photocurrent induction was retarded and the current density was lower in Δzwf, Δgnd, and ΔglgP than in wild-type cells. Exogenously added glucose compensated the phenotype of ΔglgP and drove the OPP pathway in the mutant, resulting in an increase in the photocurrent. The results indicated that NADPH accumulated by the OPP pathway before illumination is a key factor for the generation of a photocurrent. In addition, measuring the photocurrent can be a non-invasive approach to estimate the cellular redox level related to NADP(H) pool in cyanobacteria.