More effective production of human insulin is important, because insulin is the main medication that is used to treat multiple types of diabetes and because many people are suffering from diabetes. The current system of insulin production is based on recombinant DNA technology, and the expression vector is composed of a preproinsulin sequence that is a fused form of an artificial leader peptide and the native proinsulin. It has been reported that the sequence of the leader peptide affects the production of insulin. To analyze how the leader peptide affects the maturation of insulin structurally, we adapted several in silico simulations using 13 artificial proinsulin sequences. Three-dimensional structures of models were predicted and compared. Although their sequences had few differences, the predicted structures were somewhat different. The structures were refined by molecular dynamics simulation, and the energy of each model was estimated. Then, protein-protein docking between the models and trypsin was carried out to compare how efficiently the protease could access the cleavage sites of the proinsulin models. The results showed some concordance with experimental results that have been reported; so, we expect our analysis will be used to predict the optimized sequence of artificial proinsulin for more effective production.
Computer Simulation ; DNA, Recombinant ; Humans* ; Insulin ; Molecular Dynamics Simulation* ; Proinsulin ; Protein Sorting Signals ; Trypsin

BACKGROUND: Anatomic footprint restoration of anterior cruciate ligament (ACL) is recommended during reconstruction surgery. The purpose of this study was to compare and analyze the femoral and tibial tunnel positions of transtibial single bundle (SB) and transportal double bundle (DB) ACL reconstruction using three-dimensional computed tomography (3D-CT). METHODS: In this study, 26 patients who underwent transtibial SB ACL reconstruction and 27 patients with transportal DB ACL reconstruction using hamstring autograft. 3D-CTs were taken within 1 week after the operation. The obtained digital images were then imported into the commercial package Geomagic Studio v10.0. The femoral tunnel positions were evaluated using the quadrant method. The mean, standard deviation, standard error, minimum, maximum, and 95% confidence interval values were determined for each measurement. RESULTS: The femoral tunnel for the SB technique was located 35.07% +/- 5.33% in depth and 16.62% +/- 4.99% in height. The anteromedial (AM) and posterolateral (PL) tunnel of DB technique was located 30.48% +/- 5.02% in depth, 17.12% +/- 5.84% in height and 34.76% +/- 5.87% in depth, 45.55% +/- 6.88% in height, respectively. The tibial tunnel with the SB technique was located 45.43% +/- 4.81% from the anterior margin and 47.62% +/- 2.51% from the medial tibial articular margin. The AM and PL tunnel of the DB technique was located 33.76% +/- 7.83% from the anterior margin, 45.56% +/- 2.71% from the medial tibial articular margin and 53.19% +/- 3.74% from the anterior margin, 46.00% +/- 2.48% from the medial tibial articular margin, respectively. The tibial tunnel position with the transtibial SB technique was located between the AM and PL tunnel positions formed with the transportal DB technique. CONCLUSIONS: Using the 3D-CT measuring method, the location of the tibia tunnel was between the AM and PL footprints, but the center of the femoral tunnel was at more shallow position from the AM bundle footprint when ACL reconstruction was performed by the transtibial SB technique.
Adult ; Anterior Cruciate Ligament Reconstruction/*methods ; *Femur/radiography/surgery ; Humans ; Imaging, Three-Dimensional/*methods ; Knee Joint/physiology ; Male ; Prospective Studies ; Surgery, Computer-Assisted/*methods ; *Tibia/radiography/surgery ; Tomography, X-Ray Computed

Thyroid cancer is one of the most common malignancies of endocrine organs, and its incidence rate has increased steadily over the past several decades. Most differentiated thyroid tumors derived from thyroid epithelial cells exhibit slow-growing cancers, and patients with these tumors can achieve a good prognosis with surgical removal and radioiodine treatment. However, a small proportion of patients present with advanced thyroid cancer and are unusually resistant to current drug treatment modalities. Thyroid tumorigenesis is a complex process that is regulated by the activation of oncogenes, inactivation of tumor suppressors, and alterations in programmed cell death. Mitochondria play an essential role during tumor formation, progression, and metastasis of thyroid cancer. Recent studies have successfully observed the mitochondrial etiology of thyroid carcinogenesis. This review focuses on the recent progress in understanding the molecular mechanisms of thyroid cancer relating to altered mitochondrial metabolism.
Carcinogenesis ; Cell Death ; Epithelial Cells ; Humans ; Incidence ; Metabolism* ; Mitochondria ; Neoplasm Metastasis ; Oncogenes* ; Prognosis ; Quality Control* ; Thyroid Gland* ; Thyroid Neoplasms*

BACKGROUND: Regarding reconstruction surgery of the anterior cruciate ligament (ACL), there is still a debate whether to perform a single bundle (SB) or double bundle (DB) reconstruction. The purpose of this study was to analyze and compare the volume and surface area of femoral and tibial tunnels during transtibial SB versus transportal DB ACL reconstruction. METHODS: A consecutive series of 26 patients who underwent trantibial SB ACL reconstruction and 27 patients with transportal DB ACL reconstruction using hamstring autograft from January 2010 to October 2010 were included in this study. Three-dimensional computed tomography (3D-CT) was taken within one week after operation. The CT bone images were segmented with use of Mimics software v14.0. The obtained digital images were then imported in the commercial package Geomagic Studio v10.0 and SketchUp Pro v8.0 for processing. The femoral and tibial tunnel lengths, diameters, volumes and surface areas were evaluated. A comparison between the two groups was performed using the independent-samples t-test. A p-value less than the significance value of 5% (p < 0.05) was considered statistically significant. RESULTS: Regarding femur tunnels, a significant difference was not found between the tunnel volume for SB technique (1,496.51 +/- 396.72 mm3) and the total tunnel volume for DB technique (1,593.81 +/- 469.42 mm3; p = 0.366). However, the total surface area for femoral tunnels was larger in DB technique (919.65 +/- 201.79 mm2) compared to SB technique (810.02 +/- 117.98 mm2; p = 0.004). For tibia tunnels, there was a significant difference between tunnel volume for the SB technique (2,070.43 +/- 565.07 mm3) and the total tunnel volume for the DB technique (2,681.93 +/- 668.09 mm3; p < or = 0.001). The tibial tunnel surface area for the SB technique (958.84 +/- 147.50 mm2) was smaller than the total tunnel surface area for the DB technique (1,493.31 +/- 220.79 mm2; p < or = 0.001). CONCLUSIONS: Although the total femoral tunnel volume was similar between two techniques, the total surface area was larger in the DB technique. For the tibia, both total tunnel volume and the surface area were larger in DB technique.
Adult ; Anterior Cruciate Ligament/injuries/surgery ; Anterior Cruciate Ligament Reconstruction/*methods ; Autografts ; Femur/*radiography/surgery ; Humans ; Imaging, Three-Dimensional ; Male ; Tendon Injuries/*radiography/rehabilitation/surgery ; Tendons/transplantation ; Tibia/*radiography/surgery

Objective: To evaluate the trueness and precision of full-arch scans acquired using five intraoral scanners and investigate the factors associated with the dimensional accuracy of the intraoral scan data. Methods: Nine adult participants (mean age, 34.3 ± 8.3 years) were recruited. Four zirconium spheres (Ø 6 mm) were bonded to the canines and the molars. Following acquisition of reference scans using an industrial-grade scanner, five intraoral scanners, namely i500, CS3600, Trios 3, iTero, and CEREC Omnicam, were used to scan the arches. Linear distances between the four reference spheres were automatically calculated, and linear mixed model analysis was performed to compare the trueness and precision of the intraoral scan data among the different scanners. Results: The absolute mean trueness and precision values for all intraoral scanners were 76.6 ± 79.3 and 56.6 ± 52.4 µm, respectively. The type of scanner and the measured linear distances had significant effects on the accuracy of the intraoral scan data. With regard to trueness, errors in the intermolar dimension and the distance from the canine to the contralateral molar were greater with Omnicam than with the other scanners. With regard to precision, the error in the linear distance from the canine to the molar in the same quadrant was greater with Omnicam and CS3600 than with the other scanners. Conclusions The dimensional accuracy of intraoral scan data may differ significantly according to the type of scanner, with the amount of error in terms of trueness being clinically significant.

Objective: To evaluate the trueness and precision of full-arch scans acquired using five intraoral scanners and investigate the factors associated with the dimensional accuracy of the intraoral scan data. Methods: Nine adult participants (mean age, 34.3 ± 8.3 years) were recruited. Four zirconium spheres (Ø 6 mm) were bonded to the canines and the molars. Following acquisition of reference scans using an industrial-grade scanner, five intraoral scanners, namely i500, CS3600, Trios 3, iTero, and CEREC Omnicam, were used to scan the arches. Linear distances between the four reference spheres were automatically calculated, and linear mixed model analysis was performed to compare the trueness and precision of the intraoral scan data among the different scanners. Results: The absolute mean trueness and precision values for all intraoral scanners were 76.6 ± 79.3 and 56.6 ± 52.4 µm, respectively. The type of scanner and the measured linear distances had significant effects on the accuracy of the intraoral scan data. With regard to trueness, errors in the intermolar dimension and the distance from the canine to the contralateral molar were greater with Omnicam than with the other scanners. With regard to precision, the error in the linear distance from the canine to the molar in the same quadrant was greater with Omnicam and CS3600 than with the other scanners. Conclusions The dimensional accuracy of intraoral scan data may differ significantly according to the type of scanner, with the amount of error in terms of trueness being clinically significant.

Paracrine interactions are imperative for the maintenance of adipose tissue intercellular homeostasis, and intracellular organelle dysfunction results in local and systemic alterations in metabolic homeostasis. It is currently accepted that mitochondrial proteotoxic stress activates the mitochondrial unfolded protein response (UPRmt) in vitro and in vivo. The induction of mitochondrial chaperones and proteases during the UPRmt is a key cell-autonomous mechanism of mitochondrial quality control. The UPRmt also affects systemic metabolism through the secretion of cell non-autonomous peptides and cytokines (hereafter, metabokines). Mitochondrial function in adipose tissue plays a pivotal role in whole-body metabolism and human diseases. Despite continuing interest in the role of the UPRmt and quality control pathways of mitochondria in energy metabolism, studies on the roles of the UPRmt and metabokines in white adipose tissue are relatively sparse. Here, we describe the role of the UPRmt in adipose tissue, including adipocytes and resident macrophages, and the interactive roles of cell non-autonomous metabokines, particularly growth differentiation factor 15, in local adipose cellular homeostasis and systemic energy metabolism.

PURPOSE: The purpose of this study was to evaluate the anatomical similarity of three-dimensional (3D) morphometric parameters between right and left knees. MATERIALS AND METHODS: Ten fresh-frozen paired cadaveric knees were tested. Following dissection, footprint areas of the anterior cruciate ligament (ACL) and posterior cruciate ligament (PCL) were measured. Surface scanning was performed using a 3D scanner. Scanned data were reproduced and morphometric parameters were measured on specialized software. After making mirror models, we compared footprint center positions of the ACL and PCL of both sides and calculated the average deviation of 3D alignment between the right- and left-side models. RESULTS: No significant side-to-side differences were found in any morphometric parameters. Bony shapes displayed a side-to-side difference of < 1 mm. Distal femoral and proximal tibial volumes did not present side-to-side differences, either; the average 3D deviations of alignment between the right and left sides were 0.8±0.4/1.1±0.6 mm (distal femur/proximal tibia). Center-to-center distances between the right and left ACL footprints were 2.6/2.7 mm (femur/tibia) for the anteromedial bundle and 2.4/2.8 mm for the posterolateral bundle. They were 1.9/1.5 mm for the anterolateral bundle and 2.2/1.8 mm for the posteromedial bundle of the PCL. CONCLUSIONS: There was a remarkable 3D morphometric similarity between right and left knees. Our results might support the concept of obtaining morphologic reference data from the uninvolved contralateral knee.
Anatomy, Comparative ; Anterior Cruciate Ligament ; Cadaver ; Imaging, Three-Dimensional ; Knee Joint ; Knee ; Posterior Cruciate Ligament

Mitochondrial stress and the dysregulated mitochondrial unfolded protein response (UPRmt) are linked to various diseases, including metabolic disorders, neurodegenerative diseases, and cancer. Mitokines, signaling molecules released by mitochondrial stress response and UPRmt, are crucial mediators of inter-organ communication and influence systemic metabolic and physiological processes. In this review, we provide a comprehensive overview of mitokines, including their regulation by exercise and lifestyle interventions and their implications for various diseases. The endocrine actions of mitokines related to mitochondrial stress and adaptations are highlighted, specifically the broad functions of fibroblast growth factor 21 and growth differentiation factor 15, as well as their specific actions in regulating inter-tissue communication and metabolic homeostasis. Finally, we discuss the potential of physiological and genetic interventions to reduce the hazards associated with dysregulated mitokine signaling and preserve an equilibrium in mitochondrial stress-induced responses. This review provides valuable insights into the mechanisms underlying mitochondrial regulation of health and disease by exploring mitokine interactions and their regulation, which will facilitate the development of targeted therapies and personalized interventions to improve health outcomes and quality of life.

Mitochondrial stress and the dysregulated mitochondrial unfolded protein response (UPRmt) are linked to various diseases, including metabolic disorders, neurodegenerative diseases, and cancer. Mitokines, signaling molecules released by mitochondrial stress response and UPRmt, are crucial mediators of inter-organ communication and influence systemic metabolic and physiological processes. In this review, we provide a comprehensive overview of mitokines, including their regulation by exercise and lifestyle interventions and their implications for various diseases. The endocrine actions of mitokines related to mitochondrial stress and adaptations are highlighted, specifically the broad functions of fibroblast growth factor 21 and growth differentiation factor 15, as well as their specific actions in regulating inter-tissue communication and metabolic homeostasis. Finally, we discuss the potential of physiological and genetic interventions to reduce the hazards associated with dysregulated mitokine signaling and preserve an equilibrium in mitochondrial stress-induced responses. This review provides valuable insights into the mechanisms underlying mitochondrial regulation of health and disease by exploring mitokine interactions and their regulation, which will facilitate the development of targeted therapies and personalized interventions to improve health outcomes and quality of life.