1.Tasquinimod promotes the sensitivity of ovarian cancer cells to cisplatin by down-regulating the HDAC4/p21 pathway
Zhao LI ; Ya-Hong WU ; Ye-Qing GUO ; Xiao-Jia MIN ; Ying LIN
The Korean Journal of Physiology and Pharmacology 2025;29(2):191-204
To investigate whether Tasquinimod can influence cisplatin resistance in drug-resistant ovarian cancer (OC) cell lines by regulating histone deacetylase 4 (HDAC4) or p21, we explored its effects on the cell cycle, and associated mechanisms.RT-PCR and Western blot analyses, flow cytometry, CCK8 assay, and immunofluorescence were utilized to investigate the effects of Tasquinimod on gene expression, cell cycle, apoptosis, viability, and protein levels in OC cells. The results showed that Tasquinimod inhibited cell viability and promoted apoptosis in SKOV3/DDP (cisplatin) and A2780/DDP cells more effectively than DDP alone. In combination with cisplatin, Tasquinimod further enhanced cell apoptosis and reduced cell viability in these cell lines, an effect that could be reversed following HDAC4 overexpression. Tasquinimod treatment down-regulated HDAC4, Bcl-2, and cyclin D1, and CDK4 expression and up-regulated the cleaved-Caspase-3, and p21 expression in SKOV3/DDP and A2780/ DDP cells. Additionally, Tasquinimod inhibited DDP resistance in OC/DDP cells. These effects were similarly observed in OC mouse models treated with Tasquinimod. In conclusion, Tasquinimod can improve OC cells' sensitivity to DDP by down-regulating the HDAC4/p21 axis, offering insights into potential strategies for overcoming cisplatin resistance in OC.
2.Tasquinimod promotes the sensitivity of ovarian cancer cells to cisplatin by down-regulating the HDAC4/p21 pathway
Zhao LI ; Ya-Hong WU ; Ye-Qing GUO ; Xiao-Jia MIN ; Ying LIN
The Korean Journal of Physiology and Pharmacology 2025;29(2):191-204
To investigate whether Tasquinimod can influence cisplatin resistance in drug-resistant ovarian cancer (OC) cell lines by regulating histone deacetylase 4 (HDAC4) or p21, we explored its effects on the cell cycle, and associated mechanisms.RT-PCR and Western blot analyses, flow cytometry, CCK8 assay, and immunofluorescence were utilized to investigate the effects of Tasquinimod on gene expression, cell cycle, apoptosis, viability, and protein levels in OC cells. The results showed that Tasquinimod inhibited cell viability and promoted apoptosis in SKOV3/DDP (cisplatin) and A2780/DDP cells more effectively than DDP alone. In combination with cisplatin, Tasquinimod further enhanced cell apoptosis and reduced cell viability in these cell lines, an effect that could be reversed following HDAC4 overexpression. Tasquinimod treatment down-regulated HDAC4, Bcl-2, and cyclin D1, and CDK4 expression and up-regulated the cleaved-Caspase-3, and p21 expression in SKOV3/DDP and A2780/ DDP cells. Additionally, Tasquinimod inhibited DDP resistance in OC/DDP cells. These effects were similarly observed in OC mouse models treated with Tasquinimod. In conclusion, Tasquinimod can improve OC cells' sensitivity to DDP by down-regulating the HDAC4/p21 axis, offering insights into potential strategies for overcoming cisplatin resistance in OC.
3.Tasquinimod promotes the sensitivity of ovarian cancer cells to cisplatin by down-regulating the HDAC4/p21 pathway
Zhao LI ; Ya-Hong WU ; Ye-Qing GUO ; Xiao-Jia MIN ; Ying LIN
The Korean Journal of Physiology and Pharmacology 2025;29(2):191-204
To investigate whether Tasquinimod can influence cisplatin resistance in drug-resistant ovarian cancer (OC) cell lines by regulating histone deacetylase 4 (HDAC4) or p21, we explored its effects on the cell cycle, and associated mechanisms.RT-PCR and Western blot analyses, flow cytometry, CCK8 assay, and immunofluorescence were utilized to investigate the effects of Tasquinimod on gene expression, cell cycle, apoptosis, viability, and protein levels in OC cells. The results showed that Tasquinimod inhibited cell viability and promoted apoptosis in SKOV3/DDP (cisplatin) and A2780/DDP cells more effectively than DDP alone. In combination with cisplatin, Tasquinimod further enhanced cell apoptosis and reduced cell viability in these cell lines, an effect that could be reversed following HDAC4 overexpression. Tasquinimod treatment down-regulated HDAC4, Bcl-2, and cyclin D1, and CDK4 expression and up-regulated the cleaved-Caspase-3, and p21 expression in SKOV3/DDP and A2780/ DDP cells. Additionally, Tasquinimod inhibited DDP resistance in OC/DDP cells. These effects were similarly observed in OC mouse models treated with Tasquinimod. In conclusion, Tasquinimod can improve OC cells' sensitivity to DDP by down-regulating the HDAC4/p21 axis, offering insights into potential strategies for overcoming cisplatin resistance in OC.
4.Severity Assessment Parameters and Diagnostic Technologies of Obstructive Sleep Apnea
Zhuo-Zhi FU ; Ya-Cen WU ; Mei-Xi LI ; Ping-Ping YIN ; Hai-Jun LIN ; Fu ZHANG ; Yu-Xiang YANG
Progress in Biochemistry and Biophysics 2025;52(1):147-161
Obstructive sleep apnea (OSA) is an increasingly widespread sleep-breathing disordered disease, and is an independent risk factor for many high-risk chronic diseases such as hypertension, coronary heart disease, stroke, arrhythmias and diabetes, which is potentially fatal. The key to the prevention and treatment of OSA is early diagnosis and treatment, so the assessment and diagnostic technologies of OSA have become a research hotspot. This paper reviews the research progresses of severity assessment parameters and diagnostic technologies of OSA, and discusses their future development trends. In terms of severity assessment parameters of OSA, apnea hypopnea index (AHI), as the gold standard, together with the percentage of duration of apnea hypopnea (AH%), lowest oxygen saturation (LSpO2), heart rate variability (HRV), oxygen desaturation index (ODI) and the emerging biomarkers, constitute a multi-dimensional evaluation system. Specifically, the AHI, which measures the frequency of sleep respiratory events per hour, does not fully reflect the patients’ overall sleep quality or the extent of their daytime functional impairments. To address this limitation, the AH%, which measures the proportion of the entire sleep cycle affected by apneas and hypopneas, deepens our understanding of the impact on sleep quality. The LSpO2 plays a critical role in highlighting the potential severe hypoxic episodes during sleep, while the HRV offers a different perspective by analyzing the fluctuations in heart rate thereby revealing the activity of the autonomic nervous system. The ODI provides a direct and objective measure of patients’ nocturnal oxygenation stability by calculating the number of desaturation events per hour, and the biomarkers offers novel insights into the diagnosis and management of OSA, and fosters the development of more precise and tailored OSA therapeutic strategies. In terms of diagnostic techniques of OSA, the standardized questionnaire and Epworth sleepiness scale (ESS) is a simple and effective method for preliminary screening of OSA, and the polysomnography (PSG) which is based on recording multiple physiological signals stands for gold standard, but it has limitations of complex operations, high costs and inconvenience. As a convenient alternative, the home sleep apnea testing (HSAT) allows patients to monitor their sleep with simplified equipment in the comfort of their own homes, and the cardiopulmonary coupling (CPC) offers a minimal version that simply analyzes the electrocardiogram (ECG) signals. As an emerging diagnostic technology of OSA, machine learning (ML) and artificial intelligence (AI) adeptly pinpoint respiratory incidents and expose delicate physiological changes, thus casting new light on the diagnostic approach to OSA. In addition, imaging examination utilizes detailed visual representations of the airway’s structure and assists in recognizing structural abnormalities that may result in obstructed airways, while sound monitoring technology records and analyzes snoring and breathing sounds to detect the condition subtly, and thus further expands our medical diagnostic toolkit. As for the future development directions, it can be predicted that interdisciplinary integrated researches, the construction of personalized diagnosis and treatment models, and the popularization of high-tech in clinical applications will become the development trends in the field of OSA evaluation and diagnosis.
5.Tasquinimod promotes the sensitivity of ovarian cancer cells to cisplatin by down-regulating the HDAC4/p21 pathway
Zhao LI ; Ya-Hong WU ; Ye-Qing GUO ; Xiao-Jia MIN ; Ying LIN
The Korean Journal of Physiology and Pharmacology 2025;29(2):191-204
To investigate whether Tasquinimod can influence cisplatin resistance in drug-resistant ovarian cancer (OC) cell lines by regulating histone deacetylase 4 (HDAC4) or p21, we explored its effects on the cell cycle, and associated mechanisms.RT-PCR and Western blot analyses, flow cytometry, CCK8 assay, and immunofluorescence were utilized to investigate the effects of Tasquinimod on gene expression, cell cycle, apoptosis, viability, and protein levels in OC cells. The results showed that Tasquinimod inhibited cell viability and promoted apoptosis in SKOV3/DDP (cisplatin) and A2780/DDP cells more effectively than DDP alone. In combination with cisplatin, Tasquinimod further enhanced cell apoptosis and reduced cell viability in these cell lines, an effect that could be reversed following HDAC4 overexpression. Tasquinimod treatment down-regulated HDAC4, Bcl-2, and cyclin D1, and CDK4 expression and up-regulated the cleaved-Caspase-3, and p21 expression in SKOV3/DDP and A2780/ DDP cells. Additionally, Tasquinimod inhibited DDP resistance in OC/DDP cells. These effects were similarly observed in OC mouse models treated with Tasquinimod. In conclusion, Tasquinimod can improve OC cells' sensitivity to DDP by down-regulating the HDAC4/p21 axis, offering insights into potential strategies for overcoming cisplatin resistance in OC.
6.Tasquinimod promotes the sensitivity of ovarian cancer cells to cisplatin by down-regulating the HDAC4/p21 pathway
Zhao LI ; Ya-Hong WU ; Ye-Qing GUO ; Xiao-Jia MIN ; Ying LIN
The Korean Journal of Physiology and Pharmacology 2025;29(2):191-204
To investigate whether Tasquinimod can influence cisplatin resistance in drug-resistant ovarian cancer (OC) cell lines by regulating histone deacetylase 4 (HDAC4) or p21, we explored its effects on the cell cycle, and associated mechanisms.RT-PCR and Western blot analyses, flow cytometry, CCK8 assay, and immunofluorescence were utilized to investigate the effects of Tasquinimod on gene expression, cell cycle, apoptosis, viability, and protein levels in OC cells. The results showed that Tasquinimod inhibited cell viability and promoted apoptosis in SKOV3/DDP (cisplatin) and A2780/DDP cells more effectively than DDP alone. In combination with cisplatin, Tasquinimod further enhanced cell apoptosis and reduced cell viability in these cell lines, an effect that could be reversed following HDAC4 overexpression. Tasquinimod treatment down-regulated HDAC4, Bcl-2, and cyclin D1, and CDK4 expression and up-regulated the cleaved-Caspase-3, and p21 expression in SKOV3/DDP and A2780/ DDP cells. Additionally, Tasquinimod inhibited DDP resistance in OC/DDP cells. These effects were similarly observed in OC mouse models treated with Tasquinimod. In conclusion, Tasquinimod can improve OC cells' sensitivity to DDP by down-regulating the HDAC4/p21 axis, offering insights into potential strategies for overcoming cisplatin resistance in OC.
7.Expression of the D930020B18Rik gene in the mouse testis during spermatogenesis:Characteristics and potential role
Yong WU ; Wen-Lin CHANG ; Yuan TIAN ; Ming YE ; Ya-Wei ZHANG ; Zeng ZHANG
National Journal of Andrology 2024;30(1):9-17
Objective:To investigate the expression pattern of the D930020B18Rik gene in the testis of the mouse in different stages of development and its possible role in spermatogenesis.Methods:Using gene expression profile microarray,we identified highly ex-pressed D930020B18Rik in the mouse testis and analyzed the expression pattern of the gene by qPCR,immunohistochemistry,Western blot and immunofluorescence staining,and verified its function and molecular mechanism using bioinformatics analysis,dual-luciferase reporter assay and cell cycle synchronization.Results:The expression of the D930020B18Rik gene remained low in the testis of the mouse and mainly localized in the cytoplasm of spermatogonia during the first 2 postnatal weeks(PNW),increased from the 3rd PNW to sexual maturity,localized in the cytoplasm of spermatogonia and the nuclei of round and elongated spermatids,but was absent in the nuclei of mature sperm.Phylogenetic analysis showed that the D930020B18Rik protein sequence was highly conserved in mammals.Gene set enrichment analysis indicated that D930020B18Rik and its homologous protein might be involved in regulating spermatogenesis of mammals by participating in nucleoplasmic condensation(normalized enrichment score[NES]=1.652,P<0.01,false discov-ery rate[FDR]=0.153),meiosis(NES=1.960,P<0.01,FDR=0.001)and formation of microtubule cytoskeleton during mitosis(NES=1.903,P<0.01,FDR=0.009).Dual-luciferase reporter assay revealed that the transcription factors klf5 and foxo1 could identify and bind D930020B18Rik promoters and perform the function of positive or negative transcriptional regulation.Conclusion:The D930020B18Rik gene is expressed in the mouse testis in a time-and location-specific manner,highly associated with spermiogenesis,mainly localized in the nuclei of germ cells,and may be involved in the meiosis of spermatocytes and spermiogenesis.
8.Effects of Zuogui Jiangtang Tongmai Recipe on necroptosis pathway in a rat model of type 2 diabetes mellitus complicated with cerebral infarction
Yu-Zhe CAI ; Ding-Xiang LI ; Yi-Xuan LIU ; Zheng LUO ; Jing-Jing YANG ; Han-Lin LEI ; Ya-Nan ZHANG ; Qin WU ; Jing CHEN ; Yi-Hui DENG
Chinese Traditional Patent Medicine 2024;46(9):2936-2942
AIM To investigate the effects of Zuogui Jiangtang Tongmai Recipe on necroptosis pathway in a rat model of type 2 diabetes mellitus(T2DM)complicated with cerebral infarction(CI).METHODS The SD rats were randomly divided into the sham operation group,the model group,the metformin group(0.045 g/kg),and the low,medium and high dose Zuogui Jiangtang Tongmai Recipe groups(6.5,13,26 g/kg),with 9 rats in each group.In contrast to rats of the sham operation group,rats of the other groups were given 4 weeks feeding of high-sugar and high-fat diet combined with intraperitoneal injection of streptozotocin to establish a T2DM rat model with one week stable blood glucose,followed by gavage of corresponding drugs 3 days before the establishment of the middle cerebral artery occlusion(MCAO)model.After 7 days of administration,the rats had their CI injury assessed by mNSS method and TTC staining;their level of blood glucose detected by blood glucose meter;their levels of glycated serum protein,serum TNF-α and IL-1β detected by ELISA;their cerebral mRNA expressions of FADD,RIPK1,RIPK3 and MLKL detected by RT-qPCR;and their cerebral protein expressions of FADD,p-RIPK1,p-RIPK3 and p-MLKL detected by Western blot.RESULTS Compared with the sham operation group,the model group displayed increased levels of blood glucose value,glycosylated serum protein,neurological function score,cerebral infarction volume,cerebral FADD,RIPK1,RIPK3 and MLKL mRNA expressions,cerebral FADD,p-RIPK1,p-RIPK3 and p-MLKL protein expressions,serum TNF-α and IL-1β levels(P<0.01);and more disordered and morphologically diverse neurons with smaller nucleus.Compared with the model group,the groups intervened with medium or high dose Zuogui Jiangtang Tongmai Recipe,or metformin shared improvement in terms of the aforementioned indices(P<0.05,P<0.01);and more neurons with regular morphology neat arrangement,and reduced cell gap.CONCLUSION Zuogui Jiangtang Tongmai Recipe can improve the neurological dysfunction of the rat model of T2DM complicated with CI,which may associate with the inhibited activation of necroptosis signaling pathway.
9.A survey on the knowledge of Helicobacter pylori infection diagnosis and treatment among medical staff from general hospitals in Hainan Province
Hui ZHOU ; Guoning CHEN ; Yang GUO ; Yan TAN ; Cheng LAN ; Donghan WU ; Zhanliang MA ; Peng CHENG ; Cuiyi MO ; Ming WANG ; Peiyuan LI ; Ya LIN ; Yongqiang YANG ; Junling HAN ; Zhai CHEN ; Changling LIN ; Zhaona WU ; Shengxiong CHEN ; Zhengyi CHEN ; Xiaoxi HUANG
Chinese Journal of Digestion 2024;44(4):223-233
Objective:To investigate the knowledge of Sixth Chinese national consensus report on the management of Helicobacter pylori infection ( treatment excluded) (hereinafter referred to as sixth national consensus) and 2022 Chinese national clinical practice guideline on Helicobacter pylori eradication treatment (hereinafter referred to as the guideline)among medical staff from general hospitals in Hainan. Methods:From February 20 to May 7, 2023, a questionnaire survey on the diagnosis and treatment of Helicobacter pylori ( H. pylori) infection was conducted among 1 463 medical staff from 15 general hospitals in Hainan Province. The questionnaire was drawn up according to the sixth national consensus and the guideline, covering knowledge of 6 sections, induding H. pylori related diseases, detection of H. pylori, eradication, prevention and influence factors of eradication of H. pylori, etc. Chi-square test was used for statistical analysis. Results:A total of 1 463 valid questionnaires were collected with the effective responsive rate of 100.00%.The 1 463 subjects included 225 gastroenterologists and 1 238 other medical staff(including 503 physicians from other departments, 264 surgeons and 471 medical technologists and pharmacists). About 78.67%(177/225)of gastroenterologists agreed that the overall infection rate of H. pylori in China was more than 20%, the awareness rate was higher than that of other medical staff (physicians from other departments 65.41%(329/503), surgeons 61.74%(163/264), medical technologists and pharmacists 60.30%(284/471); the following datas were sorted by this position), and the difference was statistically significant ( χ2=30.97, P<0.001). About 51.11%(115/225) of gastroenterologists considered that H. pylori serological antibody test could not be used as a diagnostic method for current infection, the awareness rate was higher than that of other medical staff(22.07%(111/503), 14.02%(37/264), 12.31%(58/471)), and the difference was statistically significant( χ2 =152.66, P<0.001). Proton pump inhibitor and potassium-competitive acid blocker should be discontinued for 2 weeks, and antibiotics and bismuth should be discontinued for 4 weeks before urea breath test, and the awareness rates of gastroenterologists were higher than those of other medical staff (38.67%(87/225) vs. 23.26%(117/503), 19.70%(52/264), 18.47%(87/471); 60.89%(137/225) vs. 26.64%(134/503), 25.76%(68/264), 23.78%(112/471)), and the differences were statistically significant ( χ2 =133.70 and 165.51, both P<0.001). For refractory H. pylori infection, 98.67%(222/225)of gastroenterologists agreed with the individualized diagnosis and treatment of H. pylori infection should be guided by bacterial culture, antibiotic susceptibility test or drug resistance gene test, and the awareness rate was higher than that of other medical staff (91.85%(462/503), 93.56%(247/264), 93.21%(439/471)), and the difference was statistically significant( χ2=20.55, P=0.002). About 70.67% (159/225) of gastroenterologists recommended a bismuth containing quadruple regimen, 80.44% (181/225) supported a 10 to 14 day H. pylori eradication course, and the awareness rates were higher than other medical staff (46.92%(236/503), 33.33%(88/264), 32.91%(155/471); 67.20%(338/503), 59.09%(156/264), 53.93%(254/471)), and the differences were statistically significant ( χ2=111.25 and 59.99, both P<0.001). The understanding rates of the sixth national consensus and the guideline in gastroenterologists was 85.33% (192/225), which was higher than that of other medical staff (64.21%(323/503), 66.67%(176/264), 57.96%(273/471)), and the difference was statistically significant ( χ2=85.47, P<0.001). Conclusions:Gastroenterologists from general hospitals in Hainan Province have a better understanding of the sixth national consensus and the guideline than other medical staff. However, there is still a lack of deep understanding of the sixth national consensus and the guideline, and it is necessary to further strengthen the learning and application of the sixth national consensus and the guideline.
10.Development of portable medical oxygen purity analyzer
Lin-Xia LI ; Jun-Bo GAO ; Rong FAN ; Ting WU ; Ya-Jiao XU ; Yan-Qi LIU ; Jin MA ; Yun-Ying WANG
Chinese Medical Equipment Journal 2024;45(3):36-40
Objective To develop a portable medical oxygen purity analyzer capable of real-time detection of multi-compo-nent gases in medical oxygen or aviation oxygen to ensure the safety of oxygen consumption.Methods The portable medical oxygen purity analyzer with STM3F103RC as the main controller involved in a management module,an oxygen detection module,a carbon monoxide/chlorine detection module,a flow/carbon dioxide detection module and a dew point detection module as its hardware components,which had its human-machine interface programmed with DGUS supervision,control and data acquisition(SCADA)software and system program developed with C language under Keil MDK environment.The performance verification of the analyzer developed was carried out in terms of oxygen detection error and stability and errors for measuring carbon monoxide,chlorine and carbon dioxide.Results The analyzer showed high precision when used to detect oxygen with high volume fraction,with long-term stability and the absolute error restrained within±0.1%;the erros for measuring carbon monoxide,chlorine and carbon dioxide were all limited within±5%FS to meet the desired requirements.Condusion The portable medical oxygen purity analyzer developed with high precision,stability and portability can be used for detection of medical oxygen and aviation oxygen.[Chinese Medical Equipment Journal,2024,45(3):36-40]

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