1.Effect of Bushen Decoction on Na +-K+ATPase, Ca2 +-Ca2 +ATPase and Succinate Dehydrogenase in Rats with Heart Failure
Wenjing SHI ; Hua ZHOU ; Jingfeng RONG ; Chunyuan YUAN
Chinese Journal of Rehabilitation Theory and Practice 2012;18(6):544-547
Objective To explore the effect of Bushen decoction on Na+-K+ATPase 、Ca2+-Mg2+ATPase and succinate dehydrogenase(SDH) in rats with heart failure. Methods 60 heart failure rats were established by ligating left anterial descending coronary artery. Theywere randomly divided into model group, sham operation group, trimetazidine group, Bushen low-dose group, Bushen middle-dose groupand Bushen high-dose group with 10 rats in each group. They were gavaged 2 weeks after modeling for 8 weeks, hemodynamic changes includingleft ventricular systolic pressure (LVSP), left ventricular diastolic pressure (LVEDP), and the maximum rate left ventricular pressurerised or decreased (±LVdp/dtmax) were recorded as well as the level of Na+-K+ATP ase、Ca2+-Mg2+ATPase and SDH through the spectrophotometer.Results Compared with the sham operation group, the LVSP and + LVdp/dtmax of rats in model group decreased (P<0.05), LVEDPand -LVdp/dtmax increased (P<0.05). After Bushen intervention, contractility and diastolic function of myocardial of rats in middle and highdose group were better than model group (P<0.01), especially in high dose group.
Na+-K+ATP ase、Ca2+-Mg2+ATPase and SDH activity werehigher in Bushen groups than the model group, but lower than the sham operation group. With the increase of the doses, Na+-K+ATP ase、Ca2+-Mg2+ATPase and SDH activity gradually increased. Conclusion Bushen decoction can improve the cardiac function of rats with heartfailure that may be associated with Na+-K+ATPase, Ca2+-Mg2+ATPase and SDH activity.
2.Preliminary study of imaging infarct patterns and pathogenesis in patients with anterior circulation infarction
Guoqing ZHOU ; Yongjun CAO ; Guodong XIAO ; Chunyuan ZHANG ; Heqing ZHAO ; Chunfeng LIU
International Journal of Cerebrovascular Diseases 2010;18(11):813-817
Objective To analyze imaging infarct patterns and features in patients with severe stenosis or occlusion of internal carotid artery (ICA) and middle cerebral artery (MCA)from the point of view of diffusion-weighted imaging (DWI) and to investigate the infarction related mechanism. Methods Eighty-eight patients with acute ischemic stroke who had moderate to severe ICA or MCA stenosis or occlusion confirmed by cerebral angiography were analyzed retrospectively. They were divided into ICA lesion and MCA lesion groups. The infarct patterns were classified as single and multiple according to DWI. The former were reclassified as perforating artery infarct (PAI), pial infarct (PI), watershed infarct, and large infarct. Results There were 11 types of infarct patterns in MCA territories. The DWI multi-infarct pattern accounted for 62.5% of all patients (55/88). PI with watershed infarction appeared more often in the ICA lesion group (11/45, P=0. 040), and PI with PAI appeared more often in the MCA lesion group (10/43, P = 0. 037). Conclusions In patients with cerebral infarction associated with ICA or MCA severe stenosis or occlusion, most of them showed multi-infarct pattern,which suggested the mixed mechanisms such as embolization, hypoperfusion/impaired clearance of emboli, and local perforating branch occlusion were the main mechanisms of the occurrence of cerebral infarction. The main mechanism of cerebral infarction in the ICA lesion group was embolization combined with hypoperfusion/impaired clearance of emboli, while in the MCA lesion group was embolization combined with local perforating branch occlusion.
3.Changes in circadian gene cryptochrome 2 expression in mouse models of psoriasis and HaCaT cells and their underlying mechanisms
Lingling YAO ; Zengyang YU ; Chunyuan GUO ; Jing ZHOU ; Lian CUI ; Qian YU ; Yingyuan YU ; Xue ZHOU ; Jiangluyi CAI ; Yuling SHI
Chinese Journal of Dermatology 2022;55(9):759-766
Objective:To investigate changes in circadian gene cryptochrome 2 (CRY2) expression in mouse models of psoriasis and HaCaT cells, and to explore underlying mechanisms.Methods:Imiquimod-induced mouse model experiment: 12 C57BL/6 female mice were randomly and equally divided into imiquimod group receiving topical imiquimod treatment for 5 consecutive days and control group receiving no treatment; these mice were sacrificed on day 6, skin tissues were resected from the back of mice, and immunofluorescence staining was performed to determine the CRY2 expression in the epidermis. HaCaT cell transfection experiment: HaCaT cells with small interfering RNA (siRNA) -mediated knockdown of CRY2 served as siRNA-CRY2 group, and siRNA-NC group as control group; 5-ethynyl-2′-deoxyuridine (EdU) staining was performed to evaluate the proliferative activity of the HaCaT cells, real-time fluorescence-based quantitative PCR (qPCR) to determine the mRNA expression of chemokines in the HaCaT cells, and Western blot analysis to determine phosphorylation levels of extracellular signal-regulated kinase 1/2 (ERK1/2) . Tumor necrosis factor-α (TNF-α) -stimulated animal and cell experiments: 12 C57BL/6 female mice were randomly and equally divided into TNF-α group subcutaneously injected with TNF-α solution in the ear for 6 days, and phosphate buffered saline (PBS) group subcutaneously injected with the same amount of PBS; the mice were sacrificed on day 7, skin tissues were resected from the ear of mice, and immunofluorescence staining was conducted to determine the CRY2 expression in the epidermis; CRY2-knockdown HaCaT cells stimulated with 50 ng/ml TNF-α for 12 hours served as siRNA-CRY2 + TNF-α group, and siRNA-NC + TNF-α group as control group; qPCR was performed to determine the mRNA expression of chemokines in HaCaT cells in the above groups. Statistical analysis was carried out by using two-independent-sample t test. Results:Immunofluorescence staining showed that the CRY2 protein expression was significantly lower in the mouse dorsal epidermis in the imiquimod group (0.94 ± 0.23) than in the control group (2.30 ± 0.25, t = 3.99, P = 0.016) . Compared with the siRNA-NC group, the siRNA-CRY2 group showed significantly increased proportions of EdU-positive cells (48.13% ± 10.97% vs. 38.23% ± 0.81%, t = 5.00, P = 0.007) , mRNA expression levels of chemokines CXCL1 and CXCL8, as well as significantly increased phosphorylated (p) -ERK1/2 protein expression levels (all P < 0.05) , while there were no significant differences in the CCL20 mRNA expression or ERK1/2 protein expression between the two groups (both P > 0.05) . Immunofluorescence staining showed significantly decreased CRY2 protein expression level in the mouse ear epidermis in the TNF-α group (0.37 ± 0.34) compared with the PBS group (2.04 ± 0.17, t = 4.38, P = 0.012) ; the relative mRNA expression levels of chemokines CXCL1, CXCL8, and CCL20 in HaCaT cells were significantly higher in the siRNA-CRY2 + TNF-α group than in the siRNA-NC + TNF-α group (all P < 0.05) . Conclusion:CRY2 was markedly underexpressed in psoriasis, which might promote the proliferation of keratinocytes and expression of chemokines CXCL1, CXCL8 and CCL20, and TNF-α might be an upstream cytokine that could downregulate CRY2 expression.
4.Value of brain 18F-FDG PET/CT in the preoperative localization of epileptogenic foci in refractory epilepsy patients with negative MRI
Chunyuan ZENG ; Hailing ZHOU ; Zhiqiang TAN ; Guixian TANG ; Huanhua WU ; Biao WU ; Yongjin TANG ; Xueying LING ; Qiang GUO ; Hao XU
Chinese Journal of Nuclear Medicine and Molecular Imaging 2024;44(4):196-201
Objective:To evaluate the value of 18F-FDG PET/CT for preoperative localization of epileptogenic foci in refractory epilepsy patients with negative MRI. Methods:Clinical data (550 lobes) of 55 epilepsy patients (38 males, 17 females, age (20.0±8.1) years) with negative MRI who underwent preoperative 18F-FDG PET/CT-MRI between January 2014 and June 2020 at the First Affiliated Hospital of Jinan University were retrospectively analyzed. The sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) of 18F-FDG PET/CT, video electroencephalogram (VEEG), PET/CT+ VEEG and PET/CT-VEEG for localizing epileptogenic foci were calculated using stereoelectroencephalography (SEEG) and the outcomes of at least 1 year of postoperative follow-up as reference standards. χ2 test was used to compare the efficiencies of different examination modalities for unilobar, multilobar and all patients. Results:The correct lateralization rate of epileptogenic foci was 92.6%(25/27) using PET/CT. The sensitivity, specificity, accuracy, PPV and NPV of PET/CT for localization of epileptogenic foci were 65.1%(54/83), 77.9%(364/467), 76.0%(418/550), 34.4%(54/157) and 92.6%(364/393), respectively. The sensitivities of PET/CT-VEEG for localization of epileptogenic foci in all patients and patients with multilobar epilepsy were higher than those of VEEG alone (75.9%(63/83) vs 45.8%(38/83), 68.6%(35/51) vs 31.4%(16/51); χ2 values: 15.80, 14.16, both P<0.001). The specificities of PET/CT+ VEEG for localization of epileptogenic foci in all patients and patients with unilobar epilepsy were higher than those of VEEG alone (97.6%(456/467) vs 94.6%(442/467), 97.9%(282/288) vs 94.1%(271/288); χ2 values: 5.66, 5.48; P values: 0.017, 0.019). The sensitivity of PET/CT-VEEG (PET/CT and VEEG concordance) for localization of epileptogenic foci was higher than that of PET/CT+ VEEG (PET/CT and VEEG discordance) (8/9 vs 28.4%(21/74); χ2=10.40, P=0.001), and its specificity and accuracy were higher than those of PET/CT-VEEG (PET/CT and VEEG discordance) (93.4%(57/61) vs 71.7%(291/406), 92.9%(65/70) vs 72.1%(346/480); χ2 values: 13.23, 13.96; both P<0.001). Conclusions:18F-FDG PET/CT can localize and lateralize epileptogenic foci in patients with negative MRI. The combination of 18F-FDG PET/CT and VEEG improves the sensitivity, specificity, and accuracy for epileptogenic foci detection. 18F-FDG PET/CT is more accurate in detecting epileptogenic foci when it is concordant with VEEG.
5.Tumor necrosis factor α-mediated low expression of fatty acid desaturase 2 in psoriasis
Xue ZHOU ; Zengyang YU ; Youdong CHEN ; Chunyuan GUO ; Qian YU ; Yifan HU ; Lingling YAO ; Yuling SHI
Chinese Journal of Dermatology 2022;55(9):752-758
Objective:To investigate the expression of fatty acid desaturase 2 (FADS2) in psoriatic skin lesions, as well as its regulatory factors.Methods:FADS2 expression in psoriatic skin lesions was analyzed by using the dataset GDS4602 in Gene Expression Omnibus (GEO) database. Skin tissues were obtained from the back of 5 C57BL/6 mouse models of imiquimod-induced psoriasis, normal skin of 4 patients without psoriasis or other immune skin diseases, lesions of 4 patients with psoriasis before and after 10-week treatment with infliximab, as well as lesions of 3 patients with psoriasis before and after 12-week treatment with secukinumab in Shanghai Skin Disease Hospital. FADS2 expression was determined by both immunohistochemical staining and Western blot analysis in the epidermis of mouse skin tissues, and by immunohistochemical staining in that of human skin tissues. In vitro cultured human immortalized keratinocytes (HaCaT) were divided into several groups to be treated with 50 ng/ml tumor necrosis factor-α (TNF-α) alone for 0, 6, 12 and 24 hours respectively, 200 ng/ml interleukin-17A (IL-17A) alone for 0, 6 and 12 hours respectively, or treated with 50 ng/ml TNF-α and 5 μmol/L BAY 11-7082 (a nuclear factor-κB pathway inhibitor) for 6 hours (TNF-α+ BAY 11-7082 6 h group) , and the cells receiving normal culture served as the control group. After the above treatment, real-time fluorescence-based quantitative PCR (qPCR) and Western blot analysis were conducted to determine the mRNA and protein expression of FADS2 respectively. Statistical analysis was carried out by using one-way analysis of variance and t test. Results:Analysis of the dataset GDS4602 showed that the FADS2 mRNA expression was significantly lower in the lesional and non-lesional skin tissues from the patients with psoriasis (0.656 ± 0.475, 1.503 ± 1.062, respectively) than in the normal skin tissues (2.035 ± 1.226; F = 55.17, 3.07, P < 0.001, = 0.012, respectively) , and was significantly lower in the lesional skin tissues than in the non-lesional skin tissues from the patients with psoriasis ( F = 26.27, P < 0.001) . Western blot analysis and immunohistochemical staining both showed significantly decreased FADS2 protein expression in the mouse skin tissues in the imiquimod group (gray-value ratio: 0.463 ± 0.172; fluorescence intensity: 21.840 ± 3.125) compared with the normal control group (gray-value ratio: 1.000, t = 7.00, P = 0.002; fluorescence intensity: 30.720 ± 6.850, t = 3.15, P = 0.035) . Compared with the skin lesions before treatment, the FADS2 protein expression significantly increased in the skin lesions from the patients with psoriasis after 10-week treatment with infliximab (43.775± 3.342 vs. 27.950 ±1.218, t = -6.95, P = 0.006) , but was not significantly changed in the skin lesions from the patients with psoriasis after 12-week treatment with secukinumab (28.667 ± 3.402 vs. 31.933 ± 2.987, t = 2.72, P = 0.113) . qPCR revealed that the FADS2 mRNA expression significantly decreased in HaCaT cells in the TNF-α 6 h group and TNF-α 12 h group compared with the TNF-α 0 h group ( P = 0.002, 0.003, respectively) , while there was no significant change in the FADS2 mRNA expression in the IL-17A 6 h group and IL-17A 12 h group compared with the IL-17A 0 h group ( P = 0.849, 0.961, respectively) . The FADS2 mRNA expression significantly decreased in HaCaT cells in the TNF-α 6 h group (0.682 ± 0.132) compared with the control group (1.000, t = 4.82, P = 0.017) , but significantly increased in the TNF-α + BAY 11-7082 6 h group (1.541 ± 0.525) compared with the TNF-α 6 h group ( t = -3.58, P = 0.037) . Western blot analysis revealed significantly decreased FADS2 protein expression in HaCaT cells in the TNF-α 24 h group compared with the TNF-α 0 h group ( F = 6.24, P = 0.013) . Conclusion:FADS2 expression was downregulated in psoriatic lesions, which may be related to TNF-α.
6.In vitro study on the sealing effect of different shapes of cuff tracheal tubes under the lowest safe pressure
Chunyuan ZHAO ; Ling HUANG ; Zi WEI ; Long CHANG ; Jing LIN ; Chunfeng ZHOU
Chinese Critical Care Medicine 2024;36(1):28-32
Objective:To compare the effectiveness of cylindrical-shaped and conical-shaped cuff catheters for airway closure using different pressure measurement methods at the lowest safe pressure and to guide the clinical application.Methods:Twenty-four patients with endotracheal intubation admitted to the intensive care unit (ICU) of Guangxi Medical University Cancer Hospital from December 2021 to January 2022 were enrolled. Leakage test in vitro was performed on the secretion on the patients' cuff. The needle and plunger from 20 mL syringe was separated, the syringe was sealed with adhesive, and the syringe nozzle was filled thoroughly to create a tracheal model. Consecutively, both cylindrical-shaped and conical-shaped cuff catheters were inserted into the simulated trachea, and the cuff pressure was calibrated to 20 cmH 2O (1 cmH 2O≈0.098 kPa) before commencing the experiment. The viscosity of the secretion on the patients' cuff was classified (grade Ⅰ was watery subglottic secretion, grade Ⅱ was thick subglottic secretion, grade Ⅲ was gel-like subglottic secretion), and the same viscosity secretion was injected into the catheter cuff. Utilizing a self-control approach, intermittent pressure measurement was initially conducted on both the cylindrical-shaped and conical-shaped cuff by improved pressure measurement method (intermittent pressure measurement group), followed by continuous pressure measurement experiment (continuous pressure measurement group). The leakage volume of the three viscosity subglottic secretions and the values of cuff pressure measurement of different shaped cuff catheters at 4, 6, 8 hours of inflation were recorded. Results:A total of 180 retention samples were extracted from 24 patients with tracheal intubation during ventilation, with 90 samples in each of the two groups using different pressure measurement methods, and 30 samples of retention materials with different viscosities in each group. In the intermittent pressure measurement group, at 4 hours of inflation, all samples of secretion with grade Ⅰ and grade Ⅱ on cylindrical-shaped cuff leaked, while 3 samples of secretion with grade Ⅲ also leaked. For conical-shaped cuff, 28 samples of secretion with grade Ⅰ leaked, only 2 samples of secretion with grade Ⅱ leaked, and there was no leak for secretion with grade Ⅲ. At 6 hours of inflation, all samples of the three viscosity secretions on different shaped cuffs leaked. The leakage was gradually increased with the prolongation of inflation time. In the continuous pressure measurement group, at 4 hours of inflation, all samples of secretion with grade Ⅰ on cylindrical-shaped cuff leaked, while 29 samples of secretion with grade Ⅱ leaked, and there was no leak for secretion with grade Ⅲ. For the conical-shaped cuff, 26 samples of secretion with grade Ⅰ leaked, and there was no leak for secretion with grade Ⅱ and grade Ⅲ. At 6 hours of inflation, the conical-shaped cuff still had no leak for secretion with grade Ⅲ. As the inflation time prolonged, the leakage of subglottic secretion on different shaped cuffs in both groups was gradually increased. At 8 hours of inflation, all samples experienced leakage, but the leakage of subglottic secretion on different shaped cuffs in the continuous pressure measurement group was significantly reduced as compared with the intermittent pressure measurement group [leakage for secretion with grade Ⅲ (mL): 1.00 (0.00, 1.25) vs. 2.00 (1.00, 2.00) on the cylindrical-shaped cuff, 1.00 (0.00, 1.00) vs. 2.00 (2.00, 2.00) on the conical-shaped cuff, both P < 0.01]. The values of pressure measurement of cuffs with different shapes at different time points of inflation in the continuous pressure measurement group were within the set range (20-21 cmH 2O). The cuff pressure at 4 hours of inflation in the intermittent pressure measurement group was significantly lower than the initial value (cmH 2O: 18.3±0.6 vs. 20.0±0.0 in the cylindrical-shaped cuff, 18.4±0.6 vs. 20.0±0.0 in the conical-shaped cuff, both P < 0.01), and the cuff pressure in both shaped cuffs showed a significant decrease tendency as inflation time prolonged. However, there was no statistically significant difference in values of pressure measurement between the different shaped cuff catheters. Conclusions:Continuous pressure monitoring devices can maintain the effective sealing of conical-shaped cuff catheters at the lowest safe pressure. When using an improved pressure measurement method for intermittent pressure measurement and/or using a cylindrical cuff catheter, the target pressure should be set at 25-30 cmH 2O, and the cuff pressure should be adjusted regularly.
7.The effect of vitrectomy combined total versus fovea-sparing peeling of internal limiting membrane for myopic foveoschisis
Hailong HE ; Yuxin FANG ; Zhenyu LIU ; Chunyuan ZHOU ; Haicheng SHE ; Xiuhua WAN ; Zibing JIN
Chinese Journal of Ocular Fundus Diseases 2022;38(10):823-828
Objective:To systematically evaluate the effect of pars plana vitrectomy (PPV) combined total peeling of internal limiting membrane (ILM) versus fovea-sparing peeling of ILM for myopic foveoschisis.Methods:A evidence-based medicine study. Chinese and English as search terms for myopic foveoschisis, vitrectomy, and peeling of internal limiting membrane were used to search literature in China National Knowledge Infrastructure, Wanfang database, VIP database, PubMed of National Library of Medicine, Medline, Embase, and Cochrane Library. The high myopic macular schisis was selected as the research object, the intervention method was PPV combined with complete ILM peeling and combined with foveal preservation ILM peeling surgery clinical control study between Jan 1, 2010, and Jun 31, 2021. Incomplete or irrelevant literature and review literature were excluded. The method of Newcastle-Ottawa Scale system was used to evaluate the included literature. The literature was meta-analyzed by RevMan5.3 software. The mean difference ( MD) and a confidence interval ( CI) of 95% were used to describe the effect sizes of continuous data, fixed effects model was performed. The data including the best corrected visual acuity (BCVA), central fovea thickness (CFT), and postoperative macular hole (MH) were analyzed. Results:In those databases, 232 articles based search stratery were totally retrieved, and 10 articles (417 eyes) were finally included for meta-analysis with 245 eyes for PPV combined total peeling of ILM and 172 eyes for PPV combined fovea-sparing peeling of ILM. Meta-analysis results showed there was no significant difference in BCVA and CFT between the two groups (BCVA: MD=0.05, 95% CI 0.00-0.11; P>0.05; CFT: MD=-4.79, 95% CI -18.69-9.11, P>0.05). It was compared with the incidence of MH, the difference was statistically significant (odds ratio=5.70, 95% CI 2.22-14.61, P<0.05). Conclusion:BCVA and CFT could be improved by PPV combined total and fovea-sparing peeling of ILM for myopic foveoschisis; compared with complete ILM peeling, the incidence of MH was lower after foveal-sparing ILM peeling.
8.Comparison of Biomechanical Stability for Tile Type C Unstable Pelvic Fractures Fixed by Different Approaches
Min LIU ; Xiaosai ZHOU ; Liangle LIU ; Juncheng WANG ; Weiliang WANG ; Chunyuan CAI ; Dongsheng ZHANG
Journal of Medical Biomechanics 2018;33(5):E423-E428
Objective To compare the biomechanical stability of different fixation methods for unstable pelvic fractures, so as to provide references for clinical treatment. Methods An unstable pelvic fracture model (Tile C) with the sacroiliac joint dislocation at one side and the pubic rami fracture was constructed via three-dimensional finite element method. In the front of the pelvis, the fracture models were fixed with anterior pelvic Stoppa approach (ASA),subcutaneous anterior pelvic approach (APA), anterior pelvic ilioinguinal approach (AIA) and anterior pelvic external fixation (AEF),and the rear was fixed with sacroiliac joint screw (SIJS)and posterior tension-band plate (PTP). The Von Mises stress and strain distributions of fracture models fixed by different combinations of fixation approaches were analyzed under simulated standing conditions. Results After the models were applied with 500 N vertical load, the maximum stresses at the fracture sites were all reduced, which were smaller than 10 MPa in the front of the pelvis. The maximum stress at the anterior and posterior part of implants in sequence was ASA<AIA<AEF<APA, and the average displacement under the same stress in sequence was ASA<AIA<AEF<APA. Meanwhile, the maximum stresses at the sacroiliac joint and the posterior part of implants in PTP group were significant smaller than those in SIJS group, and the maximum total displacement and vertical displacement in PTP group were also smaller than those in SIJS group. Conclusions Unstable pelvic fractures could be significantly improved when the fracture was fixed by implants in eight combined methods. However, the overall biomechanical properties of the AIA groups were superior to those of the AEF groups and the APA groups. The stability of PTP groups in the treatment of posterior injury was better than that of SIJS groups.
9.Study on influencing factors for falls risks score in the elderly
Sihang FANG ; Dizhi LIU ; Chunyuan JIA ; Danni GAO ; Liang SUN ; Xiaoquan ZHU ; Qi ZHOU ; Ze YANG ; Wei XU ; Yuan LYU ; Guofang PANG ; Caiyou HU ; Huiping YUAN
Chinese Journal of Geriatrics 2024;43(11):1481-1485
Objective:To investigate the factors influencing fall risk scores in elderly individuals.Methods:A total of 4 419 individuals were randomly selected using the cluster sampling method from Beijing, Nanning(Guangxi), and Yinchuan(Ningxia).Data on demographic characteristics and fall-related incidents were gathered and analyzed for their correlation with fall risk scores.Results:The fall risk score showed significant associations with various factors, such as the history of falls within one year( β=-3.607, 95% CI: -3.881 to -3.332), care methods( β=2.442, 95% CI: 2.226 to 2.658), exercise( β=0.714, 95% CI: 0.443 to 0.986), retirement( β=-0.585, 95% CI: -0.819 to -0.351), age( β=0.173, 95% CI: 0.159 to 0.187), and use of walking aids( β=-3.737, 95% CI: -4.054 to -3.421). Conclusions:Fall risk scores in older adults are influenced by a variety of factors.Factors such as no history of falls within the past year, living independently, engaging in physical activity, and being employed may contribute to lower fall risk scores in older adults.
10.Novel discovery of schisandrin A regulating the interplay of autophagy and apoptosis in oligoasthenospermia by targeting SCF/c-kit and TRPV1 via biosensors.
Lijuan MA ; Boyi LI ; Jinchen MA ; Chunyuan WU ; Nan LI ; Kailin ZHOU ; Yun YAN ; Mingshuang LI ; Xiaoyan HU ; Hao YAN ; Qi WANG ; Yanfei ZHENG ; Zhisheng WU
Acta Pharmaceutica Sinica B 2023;13(6):2765-2777
Oligoasthenospermia is the primary cause of infertility. However, there are still enormous challenges in the screening of critical candidates and targets of oligoasthenospermia owing to its complex mechanism. In this study, stem cell factor (SCF), c-kit, and transient receptor potential vanilloid 1 (TRPV1) biosensors were successfully established and applied to studying apoptosis and autophagy mechanisms. Interestingly, the detection limit reached 2.787 × 10-15 g/L, and the quantitative limit reached 1.0 × 10-13 g/L. Furthermore, biosensors were used to investigate the interplay between autophagy and apoptosis. Schisandrin A is an excellent candidate to form a system with c-kit similar to SCF/c-kit with a detection constant (KD) of 5.701 × 10-11 mol/L, whereas it had no affinity for SCF. In addition, it also inhibited autophagy in oligoasthenospermia through antagonizing TRPV1 with a KD of up to 4.181 × 10-10 mol/L. In addition, in vivo and in vitro experiments were highly consistent with the biosensor. In summary, high-potency schisandrin A and two potential targets were identified, through which schisandrin A could reverse the apoptosis caused by excessive autophagy during oligoasthenospermia. Our study provides promising insights into the discovery of effective compounds and potential targets via a well-established in vitro-in vivo strategy.