1.Erratum: Author correction to "The novel ER stress inducer Sec C triggers apoptosis by sulfating ER cysteine residues and degrading YAP via ER stress in pancreatic cancer cells" Acta Pharm Sin B 12 (2022) 210-227.
Junxia WANG ; Minghua CHEN ; Mengyan WANG ; Wenxia ZHAO ; Conghui ZHANG ; Xiujun LIU ; Meilian CAI ; Yuhan QIU ; Tianshu ZHANG ; Huimin ZHOU ; Wuli ZHAO ; Shuyi SI ; Rongguang SHAO
Acta Pharmaceutica Sinica B 2025;15(2):1208-1209
[This corrects the article DOI: 10.1016/j.apsb.2021.07.004.].
2.PCBP1-mediated regulation of iron homeostasis suppresses ferroptosis against cadmium-induced neurotoxicity in mouse neuroblastoma cells
Sheng JIE ; Rui TIAN ; Yuchen QU ; Li TIAN ; Jia XIE ; Mengyan CHEN ; Mindi HE ; Zhengping YU ; Huifeng PI ; Ping DENG
Journal of Army Medical University 2025;47(19):2315-2326
Objective To investigate the role of poly(rC)-binding protein 1(PCBP1)in cadmium(Cd)-induced ferroptosis in mouse neuroblastoma Neuro-2a(N2A)cells.Methods N2A cells were exposed to a concentration gradient of CdCl?(0,1,2,4 μmol/L)for 72 h.Cell viability was assessed by trypan blue staining.Western blotting was employed to detect the expression of ferroptosis-related proteins(GPX4,HMOX1,ACSL4)and PCBP1.Intracellular Fe2? level and lipid peroxidation were detected using FerroOrange and BODIPY581/591 C11 probes,respectively.Ferrostatin-1(Fer-1),a ferroptosis inhibitor,was applied to confirm the critical role of ferroptosis in Cd-induced cytotoxicity.Molecular docking was performed to elucidate the interaction between PCBP1 and ferritin,as well as the binding sites of Cd2?.PCBP1 overexpression plasmid was further constructed for functional validation.Results Cd exposure suppressed cell viability in N2A cells in a dose-dependent manner(P<0.01),significantly down-regulated GPX4 expression(P<0.05),up-regulated HMOX1 expression(P<0.01),and induced Fe2? overload and lipid peroxidation(P<0.01).Molecular docking revealed that Cd2? directly bound to the KH2 domain of PCBP1 and then co-localized on the outer surface of ferritin heavy chain.Overexpression of PCBP1 markedly reversed Cd-induced Fe2? accumulation,GPX4 down-regulation,lipid peroxidation,and cell death.Conclusion Cd exposure disrupts PCBP1-mediated iron homeostasis via transcriptional suppression and competitive displacement of metal ions,and then synergistically drives Fe2? overload-triggered ferroptosis cascades,ultimately leading to neurotoxicity.Targeting PCBP1-mediated iron homeostasis can effectively mitigate Cd-induced neurotoxicity,and may serve as a novel therapeutic strategy.
3.Clinical study on the"Stomach Three Needles"for preventing highly emetogenic chemotherapy-induced acute nausea and vomiting in breast cancer patients
Mengyan LIN ; Wenwu WANG ; Fangfeng LIN ; Shuping SHI ; Jie LIN ; Biyin CHEN
China Modern Doctor 2025;63(31):8-11,30
Objective To observe the effectiveness and safety of the"Stomach Three Needles"in preventing acute chemotherapy-induced nausea and vomiting(CINV)in patients with breast cancer.Methods Seventy patients with breast cancer who received highly emetogenic chemotherapy(HEC)and were admitted to the Third People's Hospital Affiliated to Fujian University of Traditional Chinese Medicine from January 2023 to May 2025 were selected as research subjects.They were divided into treatment group(35 cases)and control group(35 cases)according to the random number table method.The treatment group received"Stomach Three Needles"combined with triple-drug prophylactic antiemetic therapy,while the patients in control group were given triple-drug prophylactic antiemetic therapy alone.The severity of nausea and vomiting symptoms during the acute phase,functional living index-emesis(FLIE),and adverse reactions between two groups of patients were compared.Results The severity grades of acute-phase nausea and vomiting symptoms in treatment group were all lower than those in control group(P<0.05).The complete response rate and total effective rate of acute-phase nausea and vomiting in treatment group were significantly higher than those in control group(P<0.05).The FLIE score of the patients in treatment group was significantly higher than that in control group(P<0.05).There was no statistically significant difference in the occurrence of adverse reactions such as headache,fatigue,constipation,and abdominal distension between two groups of patients(P>0.05).Conclusion The"Stomach Three Needles"combined with triple-drug prophylactic antiemetic therapy can effectively reduce the incidence and severity of acute CINV in breast cancer patients,improve their quality of life,and has good safety.It is worthy of clinical promotion.
4.Clinical study on the"Stomach Three Needles"for preventing highly emetogenic chemotherapy-induced acute nausea and vomiting in breast cancer patients
Mengyan LIN ; Wenwu WANG ; Fangfeng LIN ; Shuping SHI ; Jie LIN ; Biyin CHEN
China Modern Doctor 2025;63(31):8-11,30
Objective To observe the effectiveness and safety of the"Stomach Three Needles"in preventing acute chemotherapy-induced nausea and vomiting(CINV)in patients with breast cancer.Methods Seventy patients with breast cancer who received highly emetogenic chemotherapy(HEC)and were admitted to the Third People's Hospital Affiliated to Fujian University of Traditional Chinese Medicine from January 2023 to May 2025 were selected as research subjects.They were divided into treatment group(35 cases)and control group(35 cases)according to the random number table method.The treatment group received"Stomach Three Needles"combined with triple-drug prophylactic antiemetic therapy,while the patients in control group were given triple-drug prophylactic antiemetic therapy alone.The severity of nausea and vomiting symptoms during the acute phase,functional living index-emesis(FLIE),and adverse reactions between two groups of patients were compared.Results The severity grades of acute-phase nausea and vomiting symptoms in treatment group were all lower than those in control group(P<0.05).The complete response rate and total effective rate of acute-phase nausea and vomiting in treatment group were significantly higher than those in control group(P<0.05).The FLIE score of the patients in treatment group was significantly higher than that in control group(P<0.05).There was no statistically significant difference in the occurrence of adverse reactions such as headache,fatigue,constipation,and abdominal distension between two groups of patients(P>0.05).Conclusion The"Stomach Three Needles"combined with triple-drug prophylactic antiemetic therapy can effectively reduce the incidence and severity of acute CINV in breast cancer patients,improve their quality of life,and has good safety.It is worthy of clinical promotion.
5.Construction of Dmd Gene Mutant Mice and Phenotype Verification in Muscle and Immune Systems
Min LIANG ; Yang GUO ; Jinjin WANG ; Mengyan ZHU ; Jun CHI ; Yanjuan CHEN ; Chengji WANG ; Zhilan YU ; Ruling SHEN
Laboratory Animal and Comparative Medicine 2024;44(1):42-51
Objective The aim is to utilize CRISPR/Cas9 gene editing technology to construct Dmd gene mutant mice with a point mutation in exon 23 of the Dmd gene. Subsequently, the phenotypic changes of the mice in muscles and immune systems are analyzed and verified, providing an evaluation model for Duchenne muscular dystrophy and other related diseases.MethodsBased on the sequence characteristics of exon 23 of the Dmd gene, small guide RNA (sgRNA) was designed and synthesized. Cas9 mRNA, sgRNA fragments, and oligo donor DNA were microinjected into fertilized eggs of C57BL/6J mice. After transferring the fertilized eggs to surrogate mice, F0 generation mice were born. After mating with F0 generation mice, offspring mice were obtained, and Dmd gene positive mutant (DmdMu/+) mice were obtained after genotype identification. Male hemizygous DmdMu/+(DmdMu/Y) mice were selected for phenotype validation. The body weight of live 3- and 9-month-old mice were recorded. Muscle tension was evaluated through the grid test. Hearts and semitendinosus muscles were collected, and the histopathological changes were observed using HE staining. Further, the expression of Dmd protein in muscle tissue of 9-month-old mice was analyzed by Western blotting.An acute inflammation model was established in DmdMu/Y mice using lipopolysaccharide induction. Peripheral blood from the submandibular vein was collected, and the changes in the proportion of neutrophils and monocytes were detected by flow cytometry.Results The results of genome sequencing and Western blotting confirmed the successful construction of Dmd gene point mutant mice (DmdMu/+ mice). Dmd protein expression was not detected in skeletal muscle and myocardium of DmdMu/+ mice, and it was significantly reduced compared to wild-type C57BL/6J mice (P<0.05). Compared with wild-type mice of the same background, DmdMu/Y mice at 3 and 9 months of age showed significant weight loss (P<0.01) and decreased muscle tension (P<0.05). 9-month-old DmdMu/Y mice exhibited significant pathological changes in skeletal muscle and myocardium, including widening of intermuscular space. Under normal condition, compared with wild-type mice, the proportion of neutrophils and monocytes in the peripheral blood of 3-month-old DmdMu/Y mice was significantly lower than that of wild-type mice (P<0.01). After lipopolysaccharide stimulation, the proportion of neutrophils in peripheral blood of 3-month-old DmdMu/Y mice remained significantly lower compared to that of wild-type mice (P<0.01). The proportion of neutrophils in peripheral blood of 9-month-old DmdMu/Y mice significantly decreased after lipopolysaccharide induction (P<0.01), with a trend of change observed in monocytes between groups.Conclusion The successful construction of the Dmd gene mutant mouse model has confirmed the vital function of Dmd gene in maintaining normal muscle tissue morphology and muscle tone. It preliminarily indicated that Dmd gene deletion could significantly reduce the proportion of neutrophils in peripheral blood, offering a new perspective for the study of immune system alterations in Duchenne muscular dystrophy patients.
6.Status quo of preterm infants′ feeding difficulties at weaning and self-feeding transition stage and its influencing factors
Die CHEN ; Wentao PENG ; Mengyan TANG ; Xiaomei LIU
Chinese Journal of Child Health Care 2024;32(1):21-25
【Objective】 To investigate the prevalence and influencing factors of feeding difficulties in preterm infants at weaning and self-feeding transition stage, so as to provide a scientific basis for the management of feeding preterm infants. 【Methods】 Preterm infants at corrected age of 6 - 24 months were recruited from the Department of Child Health of five maternal and child health hospital of Chengdu from April to May 2021, and were surveyed by using the Chinese Version of the Montreal Children Hospital Feeding Scale (MCF-FS) and the self-designed questionnaire on the influencing factors of feeding difficulties. Then the status quo of feeding difficulties and its influencing factors were analyzed. 【Results】 The prevalence rate of feeding difficulties in 231 preterm infants was 32%. Among them, the prevalence rate of mild, moderate and severe feeding difficulties was 15.2%, 7.8% and 9.1%, respectively. Binary Logistic stepwise regression analysis indicated that food allergy (OR=4.253, 95%CI: 1.430 - 12.649), anxious mood of caregivers (OR=6.064, 95%CI: 2.998 - 12.268), tease or chase during eating(OR=2.873, 95%CI: 1.382 - 5.970), recreational activities at eating (OR=2.328, 95%CI: 1.115 - 4.860), and forced feeding (OR=2.772, 95%CI: 1.239 - 6.198) were positively associated with feeding difficulty of preterm infants(P<0.05). 【Conclusion】 Feeding difficulties in the weaning and self-feeding transition period of preterm infants are prevalent, so the guidance should focus on premature infants with food allergy, anxious caregivers and improper feeding behaviors, and appropriate interventions should be taken to promote scientific feeding.
7.Current status and progress of Parkinson disease treatment
Qiuxia CHEN ; Mengyan LI ; Ting WANG
Chinese Journal of Behavioral Medicine and Brain Science 2024;33(9):807-812
Parkinson disease (PD) is a chronic progressive neurodegenerative disorder that typically leads to motor impairments (such as increased muscle tone, resting tremors, bradykinesia and postural instability) and various non-motor symptoms (including sleep disturbances, anxiety, depression, cognitive impairments and autonomic nervous system dysfunction). Currently, symptomatic treatment primarily relies on medication, but non-pharmacological approaches are also crucial, such as psychological interventions, rehabilitation therapies, neurostimulation techniques, biosensors and monitoring technologies. However, these are all symptomatic treatments, as PD cannot be completely cured at present and there are many limitations. Nevertheless, some promising new therapies such as optogenetics, drug delivery systems, stem cell therapy, gene therapy, immunotherapy, neuroprotection, and interventions to improve gut microbiota imbalance offer hope for alleviating PD symptoms and potentially making a cure for PD achievable in the future. This article provides an overview of the current status and recent advancements in both pharmacological and non-pharmacological treatments for Parkinson disease, as well as prospects for future promising therapeutic technologies.
8.Effect of Probiotics on Bile Acid Metabolism via FXR-FGF19 Pathway in Patients With Choledocholithiasis
Lüwang YE ; Cong WANG ; Junwei FAN ; Ting JIANG ; Mengyan DU ; Weigang CHEN ; Fang LIU
Chinese Journal of Gastroenterology 2024;29(1):10-14
Background:Recurrence after stone removal is common in patients with choledocholithiasis.Recent studies have indicated that dysbiosis in gut microbiota plays an important role in the formation of cholesterol gallstones.Aims:To explore the effect of probiotics supplementation on serum lipopolysaccharide(LPS)and the indicators of bile acid metabolism in patients with a high risk of cholesterol gallstone formation.Methods:Sixty choledocholithiasis patients undergoing ERCP lithotomy were recruited at the First Affiliated Hospital of Shihezi University from June 2021 to June 2023.Bile and stool samples were collected for bacterial culture.Then the patients were randomly allocated into two groups:patients in control group received conventional supportive therapy after calculus removal,while those in probiotics intervention group were given oral bifid triple viable enteric capsule 420 mg,twice a day for 6 months based on conventional therapy.Changes in serum levels of LPS,the cell wall component of Gram-negative bacteria,fibroblast growth factor 19(FGF19),the key molecule in bile acid metabolism,and cholesterol 7α-hydroxylase(CYP7A1),the rate-limiting enzyme of bile acid synthesis,were determined and compared between the two groups.Results:Escherichia coli and Klebsiella pneumoniae were the main pathogens in bile and stool of patients with choledocholithiasis.Six months after ERCP lithotomy,the serum levels of LPS and FGF19 were decreased,and the serum level of CYP7A1 was increased in both groups(all P<0.05),especially in probiotics intervention group(all P<0.05).Conclusions:Oral probiotics supplementation can reduce the serum LPS level and modulate the canonical pathway of enterohepatic circulation of bile acids--farnesoid X receptor(FXR)-FGF19 pathway in high-risk patients of cholesterol gallstone formation.These alterations reduce the cholesterol supersaturation in bile and inhibit the probability of cholesterol gallstone formation.
9.Study on Mechanism of Somatostatin Analogue Octreotide in Protecting Against Lung Injury in Mice With Severe Acute Pancreatitis
Mengqi ZHAO ; Mengyan CUI ; Sumin CHEN ; Yingying LU ; Qiaoli JIANG
Chinese Journal of Gastroenterology 2023;28(6):326-334
Background:Acute lung injury(ALI)is the most common organ dysfunction in severe acute pancreatitis(SAP).Somatostatin analogue octreotide is a common used drug in acute pancreatitis.Aims:To explore the protective mechanism of octreotide on lung injury in SAP mice.Methods:In the first part,the experimental mice were randomly assigned into four groups.SAP model was induced by caerulin and lipopolysaccharide,and the mice were sacrificed 24 hours,48 hours and 72 hours after establishment.HE staining was used to observe the pathological score of pancreas and lung.Serum amylase and lung tissue myeloperoxidase(MPO)activity were detected.Real-time quantitative PCR was used to detect mRNA expressions of pyroptosis-related molecules apoptosis-associated speck-like protein containing a CARD(ASC),caspase-1,Gasdermin D(GSDMD),interleukin(IL)-1β,IL-18 and inflammatory factors IL-6,tumor necrosis factor(TNF)-α,high mobility group protein B1(HMGB1)in lung tissue.Western blotting was used to detect protein expressions of NOD-like receptor thermal protein domain associated protein 3(NLRP3),caspase-1,GSDMD and IL-1β in lung tissue.In the second part,mice were randomly divided into control group,SAP group,and octreotide group.HE staining was used to observe the pathological score of pancreas and lung.Serum amylase and lung tissue MPO activity were detected.Real-time quantitative PCR was used to detect mRNA expressions of pyroptosis-related molecules caspase-1,ASC,IL-1β,IL-18 and inflammatory factors IL-6,TNF-α,HMGB1.Immunofluorescence was used to detect protein expressions of NLRP3,caspase-1,GSDMD,ASC,IL-1β in lung tissue.Results:In the first part,compared with control group,pathological score of pancreas and lung tissue,serum amylase and MPO activity were significantly increased in SAP group(all P<0.05),mRNA expressions of pyroptosis-related molecules caspase-1,ASC,GSDMD,IL-1β,IL-18 and inflammatory factors IL-6,TNF-α,HMGB1 were significantly increased(all P<0.05),protein expressions of NLRP3,caspase-1,GSDMD and IL-1β in lung tissue were significantly increased(all P<0.05),especially in 24 hours after establishment group.In the second part,compared with SAP group,pathological score of pancreas and lung tissue,serum amylase were significantly decreased in octreotide group(all P<0.05),mRNA expressions of pyroptosis-related molecules caspase-1,ASC,IL-1β,IL-18 and inflammatory factors IL-6,TNF-α,HMGB1 were significantly decreased in lung tissue in octreotide group(all P<0.05),protein expressions of NLRP3,caspase-1,GSDMD,ASC and IL-1β in lung tissue were significantly decreased(all P<0.05).Conclusions:Cell pyroptosis is involved in the occurrence and development of lung injury in SAP mice,and octreotide may attenuate lung injury in SAP mice by inhibiting pyroptosis.
10.The novel ER stress inducer Sec C triggers apoptosis by sulfating ER cysteine residues and degrading YAP via ER stress in pancreatic cancer cells.
Junxia WANG ; Minghua CHEN ; Mengyan WANG ; Wenxia ZHAO ; Conghui ZHANG ; Xiujun LIU ; Meilian CAI ; Yuhan QIU ; Tianshu ZHANG ; Huimin ZHOU ; Wuli ZHAO ; Shuyi SI ; Rongguang SHAO
Acta Pharmaceutica Sinica B 2022;12(1):210-227
Pancreatic adenocarcinoma (PAAD) is one of the most lethal malignancies. Although gemcitabine (GEM) is a standard treatment for PAAD, resistance limits its application and therapy. Secoemestrin C (Sec C) is a natural compound from the endophytic fungus Emericella, and its anticancer activity has not been investigated since it was isolated. Our research is the first to indicate that Sec C is a broad-spectrum anticancer agent and could exhibit potently similar anticancer activity both in GEM-resistant and GEM-sensitive PAAD cells. Interestingly, Sec C exerted a rapid growth-inhibiting effect (80% death at 6 h), which might be beneficial for patients who need rapid tumor shrinkage before surgery. Liquid chromatography/mass spectrometry and N-acetyl-l-cysteine (NAC) reverse assays show that Sec C sulfates cysteines to disrupt disulfide-bonds formation in endoplasmic reticulum (ER) proteins to cause protein misfolding, leading to ER stress and disorder of lipid biosynthesis. Microarray data and subsequent assays show that ER stress-mediated ER-associated degradation (ERAD) ubiquitinates and downregulates YAP to enhance ER stress via destruction complex (YAP-Axin-GSK-βTrCP), which also elucidates a unique degrading style for YAP. Potent anticancer activity in GEM-resistant cells and low toxicity make Sec C a promising anti-PAAD candidate.

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