This study investigates the pharmacokinetics and metabolic characteristics of three marine-derived piericidins as potential drug leads for kidney disease: piericidin A (PA) and its two glycosides (GPAs), glucopiericidin A (GPA) and 13-hydroxyglucopiericidin A (13-OH-GPA). The research aims to facilitate lead selection and optimization for developing a viable preclinical candidate. Rapid absorption of PA and GPAs in mice was observed, characterized by short half-lives and low bioavailability. Glycosides and hydroxyl groups significantly enhanced the absorption rate (13-OH-GPA > GPA > PA). PA and GPAs exhibited metabolic instability in liver microsomes due to Cytochrome P450 enzymes (CYPs) and uridine diphosphoglucuronosyl transferases (UGTs). Glucuronidation emerged as the primary metabolic pathway, with UGT1A7, UGT1A8, UGT1A9, and UGT1A10 demonstrating high elimination rates (30%-70%) for PA and GPAs. This rapid glucuronidation may contribute to the low bioavailability of GPAs. Despite its low bioavailability (2.69%), 13-OH-GPA showed higher kidney distribution (19.8%) compared to PA (10.0%) and GPA (7.3%), suggesting enhanced biological efficacy in kidney diseases. Modifying the C-13 hydroxyl group appears to be a promising approach to improve bioavailability. In conclusion, this study provides valuable metabolic insights for the development and optimization of marine-derived piericidins as potential drug leads for kidney disease.
Animals ; Male ; Mice ; Aquatic Organisms/chemistry* ; Biological Availability ; Cytochrome P-450 Enzyme System/metabolism* ; Glucuronosyltransferase/metabolism* ; Microsomes, Liver/metabolism* ; Molecular Structure ; Biological Products/pharmacokinetics* ; Pyridines/pharmacokinetics*

Objective To investigate the effects of different foot strike patterns during running on Achilles tendon(AT)morphology and mechanical loading.Methods Fourteen habitual rearfoot strike runners and 14 habitual forefoot strike runners were recruited.Morphological characteristics(tendon length,cross-sectional area,and thickness)of the AT were collected using ultrasound imaging.The AT loading characteristics(plantar flexion moment,tendon force,load rate,impulse,and stress)of subjects wearing cushioned running shoes while running at a speed of 10 km/h were collected and calculated using a three-dimensional force measurement treadmill.Results Compared to habitual rearfoot strike runners,habitual forefoot strike runners showed a significant increase in peak plantar flexion moment of ankle joint,AT peak force,average loading rate,and peak loading rate(P<0.05).However,the differences in AT length,cross-sectional area,and thickness between the two groups were not statistically significant(P>0.05).Conclusions Long-term forefoot strike patterns can adaptively enhance the mechanical loading characteristics of the AT during repetitive stretch-shortening cycles.

Objective: To examine the safety and effectiveness of a new stent graft system for endovascular repair of abdominal aortic aneurysm(AAA). Methods: This is a prospective,multi-center,single-arm clinical trial. The patients with AAA treated with a new stent graft system were enrolled at 21 centers from September 2018 to September 2019 in China. Follow-up was performed before discharge, and at 30, 180, 360 days after operation, respectively. The primary safety endpoint was the incidence of major adverse events(MAE) within 30 days. The primary efficacy endpoint was the success rate of AAA treatment at 360 days. Secondary safety endpoints were the incidence of perioperative access complications and acute lower limb ischemia,all-cause mortality, AAA related mortality and incidence of serious adverse events (SAE) at 180 and 360 days. Secondary efficacy endpoints were the incidence of type Ⅰ or Ⅲ endoleak,stent displacement,and conversion to open surgery or re-intervention at 180 and 360 days. Results: One hundred and fifty-six patients were enrolled,including 137 males and 19 females. The age was (68.9±6.9) years (range:48.2 to 84.6 years).Maximum aneurysm diameter was (50.8±11.2) mm (range:25.0 to 85.0 mm),diameter of proximal landing zone was (21.2±2.5) mm (range:17.0 to 29.5 mm),and length of proximal landing zone was (31.4±13.0) mm (range:11.0 to 75.0 mm).The incidence of MAE was 1.3% (2/156) at 30 days,both were all-cause death cases. The success rate of AAA treatment was 88.5% (138/156) at 360 days. No perioperative access complication and acute lower limb ischemia occurred. All-cause mortality was 2.0% (3/154) at 180 days and 2.6% (4/153) at 360 days,and there was no AAA related death. The incidence of SAE was 23.0%(35/152) at 180 days and 30.5%(46/151) at 360 days, and no device-related SAE occurred. The incidence of type Ⅰor Ⅲ endoleak was 3.4% (5/147) at 180 days and 3.5% (5/144) at 360 days. Conclusion: The new stent graft system is easy to operate,and early-term safety and effectiveness results are expected.
Humans ; Middle Aged ; Aged ; Aged, 80 and over ; Prospective Studies ; China ; Ischemia ; Aortic Aneurysm, Abdominal/surgery*

Objective To explore the correlation between foot morphology and toe/metatarsophalangeal joint muscle strength. Methods Twenty-six male recreational runners were recruited. Foot length, truncated foot length, foot width, navicular height, dorsum height at 50% of the foot length, metatarsophalangeal joint strength, tensile force of the first and remaining four toes were measured by using digital caliper, metatarsophalangeal joint strength tester and dynameter, respectively. Partial correlations were used to analyze the correlation between foot morphology and foot muscle strength. ResultsWith adjusted age and body mass index (BMI), the foot width in standing position and truncated foot length in sitting and standing position were positively correlated to tensile force of the first toe; the foot length, foot width and truncated foot length were positively correlated to tensile force of the remaining four toes in both positions, and the arch height index in sitting position was negatively associated with tensile force of the remaining four toes; the foot width was positively correlated to metatarsophalangeal joint strength in both positions. Conclusions The longer foot length, foot width, truncated foot length, and the lower arch height in normal range might be related to the larger foot muscle strength. The consideration of the differences in foot morphological characteristics in different positions during the measurement of foot morphology can provide references for predicting foot muscle strength and preventing foot injury.

Objective To investigate the mechanical properties of Achilles tendon (AT) during running under different shoe conditions (minimalist vs conventional shoes). MethodsSixteen healthy male runners with habitual rearfoot strike patterns were recruited to complete the running trials at the speed of 3.16~3.50 m/s under two shoe conditions. The cross-sectional area of the AT was obtained by ultrasound imaging. Sagittal plane ankle kinematics and ground reaction forces were recorded by motion capture system and three-dimensional force platform simultaneously. Mechanical properties of the ankle and AT were calculated. Paired t test was used to compare the effects of two shoe conditions on various parameters (ankle angle, strike angle, AT force, stress, strain, etc). ResultsCompared with conventional shoes, foot inclination angle was significantly reduced by 39.9% with minimalist shoes. Obvious increase in ankle moment, peak AT force, peak AT loading rate, average loading rate, and obvious decrease in time to peak AT force were observed with minimalist shoes. Peak AT stress, peak AT strain and corresponding stress rate, peak strain rate also increased significantly with minimalist shoes. ConclusionsGreater AT loading was observed when runners with habitual rearfoot strike pattern in conventional shoes begin to wear minimalist shoes. Therefore, a gradual transition to minimalist shoes was recommended for them so as to improve the ability to load adaptively.

The technical deficiencies in traditional medical imagining methods limit the study of
Ankle ; Ankle Joint ; Biomechanical Phenomena ; Range of Motion, Articular ; Technology

The research progress in fatigue protocols and biomechanics of lower extremity and its relationship with injury induced by exercise-induced fatigue was reviewed in this paper. At present, fatigue protocols can be divided into the traditional fatigue-induced protocol and the functional fatigue-induced protocol under laboratory condition. The former mainly includes power-cycling model, treadmill run model and step-ups model, while the latter is closer to what is experienced during competition, which is usually shown as multidirectional movements. In addition, the biomechanical measures of exercise-induced fatigue mainly include kinematics, ground reaction force, joint mechanics and electromyography. Different fatigue protocols do not uniformly produce alterations in lower limb biomechanical factors. The refinement of fatigue protocols and specific indicators should be considered in future studies, in order to compare the induced effects of fatigue protocols and provide references for the selection of fatigue protocols in laboratory tests. Meanwhile, the relationship between the response of brain-nerve system and the activation of musculoskeletal system for specific athletic task should be focused, so as to understand the difference of biomechanical mechanisms between fatigue protocols and further explore the effect of exercise-induced fatigue on sports injuries.

Objective By establishing the intervention mode of 12-week gait retraining (GR) (with the specific aim of changing the habitual running gait), to determine the changes of vertical ground reaction force (vGRF), kinematics and dynamics of hip, knee, ankle joints, as well as stiffness of lower limbs in running before and after GR, and to explore the influence of running posture transformation on impact force and lower limb biomechanics. Methods Vicon motion capture system and Kistler 3D force measurement platform were used to collect the GRF and marker track of 30 runners (15 in experimental group and 15 in control group) before and after GR with the minimalist shoes at a speed of 12 km/h±5%. Results A total of 17 subjects (9 in experimental group and 8 in control group) completed the GR. After GR, the maximum loading rate of both groups decreased significantly, and the maximum loading rate of experimental group was lower than that of control group. The foot strike angle in experimental group decreased significantly after GR, and the plantarflexion angle and hip joint angular extension velocity increased in both groups. The force moment of ankle joint increased in experimental group, and the stiffness of lower limbs was significantly improved in both groups. Conclusions A 12-week GR exercise intervention model was successfully established, with 78% conversion rate (from rearfoot strike to forefoot strike). GR can effectively avoid the peak of impact force, reduce the maximum loading rate, increase the lower limb stiffness, and thus reduce or even avoid the risk of running injury caused by impact force and may provide a possibility for the improvement of running economy.

Objective To examine the effects of shoe cushioning on impact characteristics, kinematics and dynamics of lower extremities before and after neuromuscular fatigue during drop landing. Methods Fifteen trained male athletes were required to execute three successful trials of drop landing from a 60-cm platform before and after fatigue protocol. The impact force, loading rate, lower extremity kinematics, joint moment, joint stiffness were compared. Results Before fatigue, highly-cushioned shoes reduced the loading rate at heel before fatigue, and the time to peak loading rate of heel was significantly shorter than that of control shoes. After fatigue, highly-cushioned shoes significantly reduced the peak impact force and loading rate at heel, loading rate at forefoot. Meanwhile the time to peak impact force and peak loading rate at heel were significantly longer, and the contact and minimum angle of ankle were significantly greater. No significant changes were found in lower extremity stiffness, peak moment and joint stiffness of ankle. Conclusions In the situation where neuromuscular activity is reduced, highly-cushioned shoes can effectively attenuate the impact, thereby helping to avoid or reduce the potential impact damage after fatigue.

Achilles tendon is the key structure to connect the heel and foot plantar flexors and transmit the force from the leg triceps muscle, which is the key to storing and releasing energy storage during running and jumping. At present, the primary causes of Achilles tendon injury are non-homologous loading during stance phase and deficient recovery after overload. However, the relevant measures to prevent Achilles tendon injury cannot achieve full recovery. This paper reviewed the research progress of Achilles tendon’s motor function and its application in biomechanics domestically and internationally, reconsidering the role of Achilles tendon in human running and jumping which included anatomical structure of the Achilles tendon, the relationship between internal force and external force, and the effective training program. The key for future research on motor function of Achilles tendon is to improve its mechanical properties, keep the increased load in a better range and ultimately improve motion performance and reduce sports injury from the source.