Angiopoietin-like protein 3: a novel potential biomarker for nephrotic syndrome in children.

Background: Angiopoietin-like 3 (ANGPTL3) is a secretory glycoprotein. It has been demonstrated that ANGPTL3 level was upregulated in minimal change nephrotic syndrome (MCNS) kidney tissues. Subsequently, our group found that ANGPTL3 level was closely correlated with nephropathy in vivo and in vitro. Hence, whether ANGPTL3 level could be correlated with the proteinuria level, and assessment of disease severity of nephrotic syndrome (NS) remained to be investigated. This study aimed to analyzed the correlation between the levels of ANGPTL3 in serum and urine of patients with nephrotic syndrome and proteinuria, and assessed the severity of the patients' disease. In future clinical translation, the level of ANGPTL3 in serum, urine will be used as a biomarker to better predict the development of nephrotic syndrome. Methods: A total of 200 NS patients and 80 healthy controls (age, 1-18 years) were admitted to our institution between 2021 and 2022. The etiology of NS included primary nephrotic syndrome (PNS, n = 144) and NS with other causes (n = 56). A total of 280 serum samples and 244 urinary samples were collected to determine ANGPTL3 level using enzyme-linked immunosorbent assay (ELISA). Results: Serum ANGPTL3 and urinary ANGPTL3/Cre were remarkably elevated in NS patients compared with those in healthy controls. Furthermore, serum ANGPTL3 and urinary ANGPTL3/Cre were significantly correlated with proteinuria level. Additionally, multivariate linear regression analysis demonstrated that serum ALB was independently correlated with serum ANGPTL3 and PRO/CR was independently correlated with urinary ANGPTL3/Cre in NS patients. Conclusion: Serum ANGPTL3 and urinary ANGPTL3/Cre showed a promising performance in the diagnosis of NS, and served as novel potential noninvasive biomarkers to assess disease severity of NS. Further exploration of the role of ANGPTL3 level may shed a new light on the treatment of NS.

A monitoring aid for movement disorder rehabilitation / 国际生物医学工程杂志

Objective:To design a motor impairment rehabilitation monitoring aid for the assessment of motor impairment in patients who do not have or have difficulty walking independently.Methods:An assistive device vehicle was designed, equipped with an accelerometer and a six-dimensional force sensor. The normal walking (NW) group and abnormal walking group were set up, in which the abnormal walking group included moderate abnormal walking (MA) group, moderate abnormal walking with the aid of the assistive vehicle (MA-V) group, severe abnormal walking (SA) group, and severe abnormal walking with the aid of the assistive vehicle (SA-V) group. In the MA-V group, the range of knee movement was adjusted from 0 to 30°, and in the SA group, the knee joint was completely unbending. The gait cycles, peak and mean acceleration values of the right and left legs were evaluated by accelerometers, and changes in the upper limb forces were assessed by six-dimensional force transducers.Results:For the moderate impairment group, the difference in gait cycle between the MA and MA-V groups was not statistically significant ( P>0.05), and the gait cycle in the MA-V group was slightly greater than that in the MA group. For the severe injury group, the gait cycle of the SA-V group was lower than that of the SA group, and the difference was statistically significant ( P<0.01). For all abnormal groups, the mean and peak acceleration of the left leg were greater than that of the right leg, and the difference between the peak acceleration of the left leg and that of the right leg was statistically significant ( P<0.05). In the abnormal walking pattern, the mean (absolute) value of the left hand force was greater than that of the right hand, especially in the Z-axis. The standard deviations of the combined forces on the left side for the NW, MA-V, and SA-V groups were 2.759, 8.297, and 13.118 N, respectively. The SA-V group had the highest dispersion in the force scatter plot, while the NW group had a better concentration. Conclusions:An assistive vehicle equipped with an accelerometer and a six-dimensional force sensor was designed to help physicians in the assessment and rehabilitation of motor disorders.

Reproduction, cultural symbolism, and online relationship: Constructing city spatial imagery on TikTok.

The city on social media has become a hot topic in the study of city communication and city image. From the perspective of spatial theory and the communication characteristics of social media, this paper divides the spatial imagery of TikTok into three spaces: material space-cognitive attention, mental space-mental association, and relational space-emotional involvement. Based on the content analysis of 40 videos, we analyze the process of social media using cognition, association, and emotion as the starting points to increase the material space, expand the mental space, and expand the relational space. We find that spatial imagery can be co-constructed from the material space, mental space, and relational space. Lastly, the model is changed, and the value of using spatial theory to understand how city images are made is talked about.

Gene expression profiles in the brain of phenylketonuria mouse model reversed by the low phenylalanine diet therapy.

To gain insight into the potential protective mechanisms of low phenylalanine diet (LPD) in phenylketonuria (PKU), gene expression profiles were studied in the cerebral cortex and hippocampus of a PKU mouse model (BTBR-Pahenu2). PKU mice were fed with low Phe diet (LPD-PKU group) and normal diet (PKU group). Wild-type mice were treated with normal diet (WT group) as control. After 12 weeks, we detected gene expression in the cerebral cortex and hippocampus of the three groups by RNA-sequencing, and then screened the differentially-expressed genes (DEGs) among the groups by bioinformatics analyses. We found that the transcriptional profiles of both cerebral cortex and hippocampus changed markedly between PKU and WT mice. Furthermore, LPD changed the transcriptional profiles of the cerebral cortex and the hippocampus of PKU mice significantly, especially in the cerebral cortex, with overlaps of genes that changed with the disease and altered by LPD treatment. In the cerebral cortex, hundreds of DEGs enriched in a wide spectrum of biological processes, molecular function, and cellular component, including nervous system development, axon development and guidance, calcium ion binding, modulation of chemical synaptic transmission, and regulation of protein kinase activity. In the hippocampus, the overlapping genes were enriched in positive regulation of long term synaptic, negative regulation of excitatory postsynaptic potential, positive regulation of synapse assembly. Our results showed that genes impaired in PKU and then rescued by LPD might indicate the potential protective capability of LPD in the PKU brain.

End posture analysis and motion planning based on UR3 manipulator puncture navigation / 国际生物医学工程杂志

Objective:To establish a motion planning method for avoiding singularities for manipulator-assisted puncture surgery navigation, and design the corresponding computer program.Methods:According to the actual operation and the need of clinicians, the puncture needle sleeve installed at the end of the UR3 robotic arm was designed, and the kinematics analysis and simulation verification of the robotic arm were performed. A calculation program for solving the movement pose when the puncture needle at the end of the robotic arm reaches the target position, and a motion planning program for avoiding singularities through small-angle rotation were programmed.Results:Six groups of joint angles were randomly selected, and the theoretical coordinates calculated by the program were compared with the actual coordinates. The result showed that the error between the theoretical value and the actual value was small, which proved the correctness of the kinematics model. In the verification experiment, 3 sets of initial poses at random were simulated, the best pose was obtained by the program. Then the pose was transmitted into the control system to control the movement of the robotic arm. The verification experiment results showed that the puncture needle can reach the target point, and the singularity can be effectively avoid by the small-angle rotation of the fixed central axis.Conclusions:The singular point avoidance method based on end posture rotation can effectively avoid the failure of initial target posture motion planning, and it has reference value for the application of manipulator in puncture surgery.

Design and study of nitric oxide portable producing device using continuous discharging arc plasma reaction keeping low energy efficiency for viral pneumonia emergency therapy.

This study investigated the efficiency of a portable nitric oxide (NO) inhalation device through optimizing its design and structure. The portable rescue device could be used in clinical applications in outbreaks of viral pneumonia such as SARS. To reduce energy consumption for battery-powered portable usage, NO micro-channel plasma reactions induced by a continuous discharge arc were employed. A single-use airway tube could be combined with an intubation tube in clinical applications. In the experiment, a switching transistor controlled high frequency DC (12.5 kHz) was used to create a continuous discharge arc between two stainless steel electrodes (1-mm separation) after high-voltage breakthrough. A rotate instrument was employed to change the direction angle between the airflow and discharge arc, tube filled with Calcium hydroxide connected with gas outlet for reducing NO2, gas flow rate and input voltage were evaluated separately with concentration of NO and NO2/NO ratio. Results showed that a 2 L/min air flow direction from the cathode to the anode of electrodes (direction angle was zero) under 4 V input voltages produced 32.5±3.8 ppm NO, and the NO2/NO ratio reduced to less than 10%, stable output of nitric oxide might be convenient and effective for NO inhalation therapy. Modularization of the design produced a portable NO inhalation device that has potential for use in clinical applications as it is low cost, easy to disinfect, consumes low levels of energy and is ready to use.

Design of a portable nitric oxide rescue device / 国际生物医学工程杂志

Objective:To design a portable NO rescue device that can be used for NO inhalation therapy.Methods:The NO rescue device adopts a modular design, and the key parameters can be easily adjusted. The device uses a low-intensity, high-frequency pulse discharge method to produce NO mixed gas by ionizing dry air at atmospheric pressure, and uses Ca(OH) 2 particles to filter the NO 2 gas in the NO mixed air. Based on the NO rescue device, the effects of airflow direction, gas flow rate and input voltage on the levels of NO and NO 2 in the NO mixed gas were studied. The NO 2 filtering performance of the NO 2 removal device in the device was also studied. Results:When the air flows in from the cathode and flows out from the anode of the reaction chamber, and the flow rate and input voltage respectively were 2 L/min and 4 V, the system had a better performance. At this condition, the volume fraction of NO in the output gas is 3.25×10 -5, and NO 2/NO is about 0.05. Conclusions:The proposed NO rescue device can meet the needs of medical NO gas, and the system has stable performance, portable volume, and low cost, and has broad application prospects in the treatment of pulmonary hypertension and chronic obstructive pulmonary diseases.

Effect of integrin ß1 in the treatment of stress urinary incontinence by electrical stimulation.

The aim of the present study was to investigate the protective effect of integrin ß1 in the treatment of stress urinary incontinence (SUI) by electrical stimulation, and the underlying mechanisms by which electrical stimulation regulates the collagen metabolism of female vaginal wall fibroblasts (FVWFs). FVWFs obtained from the vaginal wall tissue of patients with (Ingelman­Sundberg scale; grade II, n=8; grade III, n=10) or without (n=8) SUI during gynecological operations were isolated by enzymatic digestion and subsequently identified by immunocytochemistry. Following this, cultured FVWFs were treated with an inhibitor of integrin ß1, recombinant human integrin ß1 and electrical stimulation (100 mv/mm, 2 h, 20 Hz), followed by total mRNA and protein extraction. mRNA and protein expression levels of integrin ß1, transforming growth factor (TGF)­ß1 and collagen (COL) I and III in FVWFs were quantified by reverse transcription­quantitative PCR (RT­qPCR) and western blot analysis respectively. Integrin ß1, TGF­ß1 and COL I and III expression levels were decreased in patients with SUI compared with healthy controls, and the grade III group had lower levels than the grade II group. Following electrical stimulation treatment, the expression levels of TGF­ß1, COL I and III were enhanced in the grade II group, but not in the grade III group. Nevertheless, the inhibitor of integrin ß1 reduced the protective effect of electrical stimulation in the grade II group. In addition, electrical stimulation combined with recombinant human integrin ß1 could also protect cells from SUI in the grade III group. The present study provides evidence for the increased degradation of the extracellular matrix and integrin ß1 in the vaginal wall tissues of patients with SUI, and the protective effect of electrical stimulation against SUI via integrin ß1. These results provide a novel mechanism for the treatment of SUI using electrical stimulation.

Clinical utility in infants with suspected monogenic conditions through next-generation sequencing.

BACKGROUND: Rare diseases are complex disorders with huge variability in clinical manifestations. Decreasing cost of next-generation sequencing (NGS) tests in recent years made it affordable. We witnessed the diagnostic yield and clinical use of different NGS strategies on a myriad of monogenic disorders in a pediatric setting. METHODS: Next-generation sequencing tests are performed for 98 unrelated Chinese patients within their first year of life, who were admitted to Xin Hua Hospital, affiliated with Shanghai Jiao Tong University School of Medicine, during a 2-year period. RESULTS: Clinical indications for NGS tests included a range of medical concerns. The mean age was 4.4 ± 4.2 months of age for infants undergoing targeting specific (known) disease-causing genes (TRS) analysis, and 4.4 ± 4.3 months of age for whole-exome sequencing (WES) (p > 0.05). A molecular diagnosis is done in 72 infants (73.47%), which finds a relatively high yield with phenotypes of metabolism/homeostasis abnormality (HP: 0001939) (odds ratio, 1.83; 95% CI, 0.56-6.04; p = 0.32) and a significantly low yield with atypical symptoms (without a definite HPO term) (odds ratio, 0.08; 95% CI, 0.01-0.73; p = 0.03). TRS analysis provides molecular yields higher than WES (p = 0.01). Ninety-eight different mutations are discovered in 72 patients. Twenty-seven of them have not been reported previously. Nearly half (43.06%, 31/72) of the patients are found to carry 11 common disorders, mostly being inborn errors of metabolism (IEM) and neurogenetic disorders and all of them are observed through TRS analysis. Eight positive cases are identified through WES, and all of them are sporadic, of highly variable phenotypes and severity. There are 26 patients with negative findings in this study. CONCLUSION: This study provides evidence that NGS can yield high success rates in a tertiary pediatric setting, but suggests that the scope of known Mendelian conditions may be considerably broader than currently recognized.

Research progress of medical nitric oxide production technology / 国际生物医学工程杂志

Nitric oxide is a messenger molecule in the body, which is widely distributed in various tissues of living organisms and participates in regulating the physiological activities of cells. Inhalation of low concentrations of NO can selectively relax the pulmonary blood vessels, which can achieve good results and has been applied in clinical respiratory emergency treatment such as pulmonary hypertension, neonatal hypoxic respiratory failure, acute respiratory distress syndrome (ARDS), etc. At present, in addition to the clinical use of chemical methods to produce NO gas (storage in cylinders), NO can also be generated by discharge. Among them, the pulsed arc discharge can realize the preparation of NO at any time and solve the problems of decompression and storage of conventional NO gas supply. In this paper, the clinical application of NO, discharge technology, and removal methods of nitrogen dioxide (NO2) were reviewed.

Effect of supernatant of mesenchymal stem cells on tumor necrosis factor-α and apoptosis protein caspase-3 in diabetic skin ulcer rat model / 国际生物医学工程杂志

Objective To investigate the supernatant of umbilical cord-derived mesenchymal stem cells (UCMSCs) on tumor necrosis factor-α(TNF-α) and apoptosis protein caspase-3 in diabetic rats model with skin ulcer. Methods 45 Sprague-Dawley rats were randomly divided into control group (acute wounds group), phosphate buffered saline (PBS) group and UCMSCs supernatant group. The diabetic rat model was constructed by injecting with alloxan by tail vein and feeding with high-fat diet. Diabetic skin ulcer (DSU) rat model was constructed by scratching a wound and infusing suspension of Staphylococcus aureus. In the control group, the diabetic rats (n=15) were scratched to form a wound and treated by tail vein injection of 100μl PBS. In the PBS group, DSU rats (n=15) were treated by tail vein injection of 100μl PBS, and then 100μl PBS was dropped at the ulcer site. In the UCMSCs supernatant group, freeze-dried powder of UCMSCs supernatant was dissolved in 200μl PBS, 100μl of which was injected into the tail vein of DSU rats (n=15), and other 100μl was dropped at the ulcer site. After 5 days of the treatments, the levels of serum TNF-αwere detected by radioimmunoassay method, and the expression of TNF-αand caspase-3 in the ulcer tissues of rats was detected by polymerase chain reaction and Western Blot. Results The levels of TNF-αin the PBS group [(35.9±3.7)μg/L] were significantly higher than that of the control group [(11.4±4.9)μg/L] and the UCMSCs group [(14.7±6.6)μg/L] (all P<0.05). The levels of mRNA and protein expression of TNF-αand caspase-3 in the UCMSCs group were significantly lower than those of the PBS group (all P<0.05), and have no significant differences with respect to those of the control group (all P>0.05). Conclusions UCMSCs supernatant treatments can effectively down-regulate the expression of TNF-αand caspase-3 in ulcer tissue of DSU rats, and play an anti-inflammatory and anti-apoptotic effect.

Research progress of medical nitric oxide production technology / 国际生物医学工程杂志

Nitric oxide is a messenger molecule in the body, which is widely distributed in various tissues of living organisms and participates in regulating the physiological activities of cells. Inhalation of low concentrations of NO can selectively relax the pulmonary blood vessels, which can achieve good results and has been applied in clinical respiratory emergency treatment such as pulmonary hypertension, neonatal hypoxic respiratory failure, acute respiratory distress syndrome (ARDS), etc. At present, in addition to the clinical use of chemical methods to produce NO gas (storage in cylinders), NO can also be generated by discharge. Among them, the pulsed arc discharge can realize the preparation of NO at any time and solve the problems of decompression and storage of conventional NO gas supply. In this paper, the clinical application of NO, discharge technology, and removal methods of nitrogen dioxide (NO2) were reviewed.

Simulation of flow field characteristics of cyclic variation of human upper respiratory tract / 国际生物医学工程杂志

Objective To explore the distribution and changes of the upper respiratory tract pressure in the human body under circulatory respiration conditions.Methods An oral-secondary bronchus model was established based on CT images.The pressure distribution at various parts of the model during circulatory respiration and the pressure distribution at the moment of maximum inspiration or expiration were simulated under a respiratory flow of 60 L/min.Results The pressure difference in the upper respiratory tract increased with the respiratory flow.Some positions with special structures,such as pharynx,larynx,trachea,etc.,showed pressure gradient changes,especially between edge of epiglottis to the trachea and upon the bifurcation point of tracheal.Conclusions The air flow motion,including pressure distribution and variation,is related to the anatomy morphological structure of the respiratory tract,and they interactively influence the respiration process.The flow field characteristics of pressure cyclic variation can provide basis for exploring the aerosol deposition and the occurrence and treatment of some respiratory tract diseases.

Mechanical arm assisted lumbar puncture ultrasound scanning control and structural reconstruction / 国际生物医学工程杂志

Objective To design a mechanical arm assisted lumbar puncture ultrasound scanning system to realize automatic scanning imaging of the lumbar vertebrae and visualize the three-dimensional reconstruction of the acquired two-dimensional ultrasound image,so as to obtain the three-dimensional image of the scanning lumbar and provide a basis for path planning and assisted puncture.Methods The main control program of the robotic arm was programmed by C language which can control the robotic arm to scan the lumbar vertebrae of the patient by a clamped ultrasound.The acquired 2D ultrasound image was reconstructed and visualized using a VTK-based 3D reconstruction visualization program.The lumbar vertebrae model reconstruction was conducted by Enovo Medical Model in water and CIRS 034 lumbar vertebral phantom,respectively,and the experimental results were compared and analyzed.Results By using the lumbar puncture ultrasound scanning system,the obtained two-dimensional ultrasound image of the lumbar spine model was clear and the anatomy was basically complete.The results of three-dimensional reconstruction showed that the spinous processes and their gaps of the scanned lumbar model were clearly visible,and the structure was intact,indicating that the system was operating normally and could achieve the expected function.By comparing the reconstruction results of the bent-knee lateral position and prone position,it can be concluded that the body position has an important influence on the reconstruction results of the lumbar spine ultrasound image.The bent-knee lateral position should be used in the follow-up study of lumbar puncture.Conclusions A lumbar puncture ultrasound scanning system assisted by a mechanical arm was proposed.The system can effectively capture the clear ultrasound image of the model and realize the visualization of 3D reconstruction,which can provide a basis for puncture path planning and assisted puncture.

Role of transforming growth factor ß­1 in the pathogenesis of pelvic organ prolapse: A potential therapeutic target.

The present study aimed to reveal the metabolic alterations of the extracellular matrix (ECM) in uterosacral ligament (USL) with pelvic organ prolapse (POP) and to explore the role of transforming growth factor­ß1 (TGF­ß1) in pathogenesis of POP. For this purpse, 60 participants who underwent hysterectomy for benign indications were enrolled, 30 of which had symptomatic POP (grade II, III or IV) and composed the POP group, and the other 30 had asymptomatic POP (grade I or less) and served as the controls. Collagen fibers, elastin,matrix metalloproteinase (MMP)­2/9, tissue inhibitor of matrix metalloproteinases (TIMP)­2 and TGF­ß1 were examined by Masson's trichrome staining, immunohistochemistry and RT-qPCR using USL biopsies. In vitro, human USL fibroblasts (hUSLFs) were primary cultured, pre-treated with recombinant TGF­ß1 (0, 5, or 10 ng/ml) and then subjected to cyclic mechanical stretching (CMS; 0 or 5,333 µÎµ strain). Changes in the expression levels of collagen type I/III, elastin, TIMP­2, MMP­2/9 and Smad were detected. Our results revealed that at the tissue level, the expression of collagen fibers, elastin, TIMP­2 and TGF­ß1 was significantly reduced in the POP group, while the activities of MMP­2/9 were significantly upregulated, compared with the control group. Statistical analysis indicated that the mRNA expression of TGF­ß1 inversely correlated with the severity of POP partially. Our in vitro experimental data demonstrated that a CMS of 5333 µÎµ strain promoted the degradation of ECM proteins, inhibited the synthesis of TIMP­2, and upregulated the proteolytic activities of MMP­2/9. Pre-treatment with TGF­ß1 attenuated the loss of ECM by stimulating the synthesis of TIMP­2 and inhibiting the activities of MMP­2/9 through the TGF­ß1/Smad3 signaling pathway. On the whole, our data indicate that the reduced anabolism and increased catabolism of ECM proteins in USL are the pathological characteristics of POP. TGF­ß1 not only has a specific value in predicting the severity of POP, but should also be considered as a novel therapeutic target for POP.

Research progress of low energy laser irradiation in hyperlipidemia treatment / 国际生物医学工程杂志

Hyperlipidemia is one of the most important risk factors of human atherosclerosis and cardiaccerebral vascular disease.The number of hyperlipidemia in China increased year by year and showed a younger trend.The current treatments for hyperlipidemia include drug therapy,physical exercise,diet prevention,liposuction surgery and low-energy laser therapy,etc.Many researches showed that low intensity laser irradiation has a certain curative effect on hyperlipidemia.The aim of this paper is to provide a new idea and method for the future treatment of dyslipidemia by reviewing the anti-hyperlipidemia methods and mechanism of low energy laser irradiation treatment.

A light source for rectal cancer photodynamic therapy based on wireless power supply / 国际生物医学工程杂志

Objective To develop a light source system for the treatment of rectal cancer photodynamic therapy based on magnetic coupling resonant wireless power supply technology.Methods The proposed system consists of the implant and the external power supply device.The implant includes a light source and a resonant receiving coil.The light source is a 650 nm LED.The light source and the receiving coil were encapsulated with transparent epoxy to benefit the implantation and biocompatibility.The external power supply device was based on the magnetic coupling resonant technology,and the frequencies of the high frequency inverter and the natural frequency of the transmitting coil and the receiving coil were set at the same resonant frequency to ensure the efficient transmission of energy.Results The power density range of the light source is 3～22 mW/cm2 in the vertical distance range of 50～ 180 mm to the plane of the transmitting coil.Conclusions In the proposed light source system,the LED was separated from the power source.The size of the implant is small enough to be implanted,and the external power source can provide a real-time and stable energy supply for the implant.

Effect of different time windows and interventions on skin pressure ulcers and ischemia-reperfusion injury in rats / 南方医科大学学报

<p><b>OBJECTIVE</b>To observe the effect of different time windows and interventions on skin pressure ulcers and ischemia-reperfusion (I/R) injury in rats.</p><p><b>METHODS</b>Sixty?eight SD rats were randomly divided into blank control group (n=4) and model group (n=64). The rats in the model group were randomly divided into group A (n=32) without intervention and group B (n=32) with post?conditioning. The degree of skin compression, neutrophil infiltration and serum levels of free radicals were observed in the rats after compression for 2, 4, 6, and 8 h (8 rats at each time point).</p><p><b>RESULTS</b>A significant difference was found in the severity of skin damage among the control group, group A, and group B (P=0.001), and the injury was milder in group B than in group A. Severe skin lesions occurred in 2 rats after skin compression for 6 h, as compared with 6 after compression for 8 h (P=0.043), but in none of the rats after compression for 2 or 4. Seventeen rats in group B and 15 in group A showed grade 1 neutrophil infiltration in the skin lesions, and 8 rats in group B and 10 in group A showed grade II neutrophil infiltration (P=0.002). Neutrophil infiltration was the mildest in rats with a 2?h compression, and exacerbated progressively and significantly as the compression time extended (P=0.027). With the prolongation of the intervention time, the rats in both groups A and B showed decreased SOD and increased MDA and NO levels, and overall the I/R injury was milder in 2? and 4?h compression groups than in 6? and 8?h compression groups. The level of serum SOD was significantly higher and MDA and NO levels were significantly higher in group B than in group A (P<0.05).</p><p><b>CONCLUSION</b>Ischemic post?conditioning can relieve I/R injury in acute pressure ulcer in rats. The effective time window for intervention is within 6 h of ischemia, and the effect of ischemic post-conditioning is optimal within 2 h. Ischemic post?conditioning can alleviate free radical injury and inflammation caused by I/R injury.</p>

Therapeutic Effects of Punicalagin Against Ovarian Carcinoma Cells in Association With ß-Catenin Signaling Inhibition.

AIM: The aim of this study was to investigate the effects of punicalagin, a polyphenol isolated from Punica granatum, on human A2780 ovarian cancer cells in vitro. METHODS: The viability of human A2780 ovarian cells was evaluated using Cell Counting Kit-8 assay. Cell cycle was detected with flow cytometry analysis. The protein expression levels of Bcl-2, Bax, ß-catenin, cyclin D1, survivin, tissue inhibitor of metalloproteinase (TIMP)-2, and TIMP-3 were measured using Western blot analysis. Matrix metalloproteinase (MMP)-2 and MMP-9 activity was determined with gelatin zymography. Wound healing assay was used to determine cell migration. RESULTS: Punicalagin inhibited the cell viability of A2780 cells in a dose- and time-dependent manner, and the cell cycle of A2780 cells was arrested in G1/S phase transition. The treatment also induced apoptosis as shown by the up-regulation of Bax and down-regulation of Bcl-2. On the other hand, punicalagin treatment increased the expressions of TIMP-2 and TIMP-3, decreased the activities of MMP-2 and MMP-9, and inhibited cell migration. In addition, the ß-catenin pathway was suppressed as shown by the down-regulations of ß-catenin and its downstream factors including cyclin D1 and survivin. CONCLUSIONS: Punicalagin may have cancer-chemopreventive as well as cancer-chemotherapeutic effects against human ovarian cancer in humans through the inhibition of ß-catenin signaling pathway.

Role of mechanical strain-activated PI3K/Akt signaling pathway in pelvic organ prolapse.

Mechanical loading on pelvic supports contributes to pelvic organ prolapse (POP). However, the underlying mechanisms remain to be elucidated. Our previous study identified that mechanical strain induced oxidative stress (OS) and promoted apoptosis and senescence in pelvic support fibroblasts. The aim of the present study is to investigate the molecular signaling pathway linking mechanical force with POP. Using a four­point bending device, human uterosacral ligament fibroblasts (hUSLF) were exposed to mechanical tensile strain at a frequency of 0.3 Hz and intensity of 5333 µÎµ, in the presence or absence of LY294002. The applied mechanical strain on hUSLF resulted in apoptosis and senescence, and decreased expression of procollagen type I α1. Mechanical strain activated phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/Akt signaling and resulted in downregulated expression of glutathione peroxidase 1 and Mn­superoxide dismutase, and accumulation of intracellular reactive oxygen species. These effects were blocked by administration of LY294002. Furthermore, it was demonstrated that PI3K/Akt was activated in the uterosacral ligaments of POP patients, and that OS was increased and collagen type I production reduced. The results from the present study suggest that mechanical strain promotes apoptosis and senescence, and reduces collagen type I production via activation of PI3K/Akt-mediated OS signaling pathway in hUSLF. This process may be involved in the pathogenesis of POP as it results in relaxation and dysfunction of pelvic supports.