BACKGROUND Gastric neuroendocrine carcinomas(NECs)exhibit aggressive features,such as rapid growth,higher rate of metastasis,and a generally unfavorable prognosis compared to gastric adenocarcinoma.As a result,therape...BACKGROUND Gastric neuroendocrine carcinomas(NECs)exhibit aggressive features,such as rapid growth,higher rate of metastasis,and a generally unfavorable prognosis compared to gastric adenocarcinoma.As a result,therapeutic options for NECs remain limited,contributing to the poor prognosis of patients.Immunotherapy has emerged as a promising treatment strategy and demonstrated the potential to partially improve the survival and prognosis of patients with NECs.Nevertheless,the unique clinical response termed pseudoprogression(PsP)has garnered considerable attention in the context of immunotherapy.CASE SUMMARY Presented here is a case of NEC recurrence five and a half months after radical gastric surgery.The 45-year-old male patient underwent combination treatment involving a PD-1 blocker and tyrosine kinase inhibitors and encountered two instances of PsP during treatment.The patient ultimately achieved a durable treatment response without altering his treatment regimens,resulting in a substantial therapeutic benefit.CONCLUSION This case report aimed to provide the authors’experience with the diagnosis of PsP and treatment strategies for PsP in ongoing immunotherapy.展开更多
Our previous studies showed that the early use of calpain inhibitors reduces calpain activity in multiple brain regions, and that postnatal treatment with calpeptin may lead to cerebellar motor dysfunction. However, i...Our previous studies showed that the early use of calpain inhibitors reduces calpain activity in multiple brain regions, and that postnatal treatment with calpeptin may lead to cerebellar motor dysfunction. However, it remains unclear whether postnatal calpeptin application affects hippocampus-related behaviors. In this study, Sprague-Dawley rats were purchased from the Animal Center of Anhui Medical University of China. For the experiments in the adult stage, rats were intraperitoneally injected with calpeptin, 2 mg/kg, once a day, on postnatal days 7–14. Then on postnatal day 60, the Morris water maze test was used to evaluate spatial learning and memory abilities. The open field test was carried out to assess anxiety-like activities. Phalloidin staining was performed to observe synaptic morphology in the hippocampus. Immunohistochemistry was used to count the number of NeuN-positive cells in the hippocampal CA1 region. DiI was applied to label dendritic spines. Calpeptin administration impaired spatial memory, caused anxiety-like behavior in adulthood, reduced the number and area of apical dendritic spines, and decreased actin polymerization in the hippocampus, but did not affect the number of NeuN-positive cells in the hippocampal CA1 region. For the neonatal experiments, neonatal rats were intraperitoneally injected with calpeptin, 2 mg/kg, on postnatal days 7 and 8. Western blot assay was performed to analyze the protein levels of Akt, Erk, p-Akt, p-Erk1/2, Erk1/2, SCOP, PTEN, mTOR, p-mTOR, CREB and p-CREB in the hippocampus. SCOP expression was increased, and the phosphorylation levels of Akt, mTOR and CREB were reduced in the hippocampus. These findings show that calpeptin administration after birth affects synaptic development in neonatal rats by inhibiting the Akt/mTOR signaling pathway, thereby perturbing hippocampal function. Therefore, calpeptin administration after birth is a risk factor for neurodevelopmental defects.展开更多
It is necessary to explore potent therapeutic agents via regulating gut microbiota and metabolism to combat Parkinson's disease(PD).Dioscin,a bioactive steroidal saponin,shows various activities.However,its effect...It is necessary to explore potent therapeutic agents via regulating gut microbiota and metabolism to combat Parkinson's disease(PD).Dioscin,a bioactive steroidal saponin,shows various activities.However,its effects and mechanisms against PD are limited.In this study,dioscin dramatically alleviated neuroinflammation and oxidative stress,and restored the disorders of mice induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP).16 S rDNA sequencing assay demonstrated that dioscin reversed MPTP-induced gut dysbiosis to decrease Firmicutes-to-Bacteroidetes ratio and the abundances of Enterococcus,Streptococcus,Bacteroides and Lactobacillus genera,which further inhibited bile salt hydrolase(BSH)activity and blocked bile acid(BA)deconjugation.Fecal microbiome transplantation test showed that the anti-PD effect of dioscin was gut microbiota-dependent.In addition,non-targeted fecal metabolomics assays revealed many differential metabolites in adjusting steroid biosynthesis and primary bile acid biosynthesis.Moreover,targeted bile acid metabolomics assay indicated that dioscin increased the levels of ursodeoxycholic acid,tauroursodeoxycholic acid,taurodeoxycholic acid and bmuricholic acid in feces and serum.In addition,ursodeoxycholic acid administration markedly improved the protective effects of dioscin against PD in mice.Mechanistic test indicated that dioscin significantly up-regulated the levels of takeda G protein-coupled receptor 5(TGR5),glucagon-like peptide-1 receptor(GLP-1R),GLP-1,superoxide dismutase(SOD),and down-regulated NADPH oxidases 2(NOX2)and nuclear factor-kappaB(NF-kB)levels.Our data indicated that dioscin ameliorated PD phenotype by restoring gut dysbiosis and regulating bile acid-mediated oxidative stress and neuroinflammation via targeting GLP-1 signal in MPTP-induced PD mice,suggesting that the compound should be considered as a prebiotic agent to treat PD in the future.展开更多
Nine major cell populations among 46,716 cells were identified in mouse intestinal ischemia‒reperfusion(II/R)injury by single-cell RNA sequencing.For enterocyte cells,11 subclusters were found,in which enterocyte clus...Nine major cell populations among 46,716 cells were identified in mouse intestinal ischemia‒reperfusion(II/R)injury by single-cell RNA sequencing.For enterocyte cells,11 subclusters were found,in which enterocyte cluster 1(EC1),enterocyte cluster 3(EC3),and enterocyte cluster 8(EC8)were newly discovered cells in ischemia 45 min/reperfusion 720 min(I 45 min/R 720 min)group.EC1 and EC3 played roles in digestion and absorption,and EC8 played a role in cell junctions.For TA cells,after ischemia 45 min/reperfusion 90 min(I 45 min/R 90 min),many TA cells at the stage of proliferation were identified.For Paneth cells,Paneth cluster 3 was observed in the resting state of normal jejunum.After I 45 min/R 90 min,three new subsets were found,in which Paneth cluster 1 had good antigen presentation activity.The main functions of goblet cells were to synthesize and secrete mucus,and a novel subcluster(goblet cluster 5)with highly proliferative ability was discovered in I 45 min/R 90 min group.As a major part of immune system,the changes in T cells with important roles were clarified.Notably,enterocyte cells secreted Guca2b to interact with Gucy2c receptor on the membranes of stem cells,TA cells,Paneth cells,and goblet cells to elicit intercellular communication.One marker known as glutathione S-transferase mu 3(GSTM3)affected intestinal mucosal barrier function by adjusting mitogen-activated protein kinases(MAPK)signaling during II/R injury.The data on the heterogeneity of intestinal cells,cellular communication and the mechanism of GSTM3 provide a cellular basis for treating II/R injury.展开更多
The quality of Chinese materia medica(CMM)is a challenging and focused topic in the modernization of traditional Chinese medicine(TCM).A profound comprehension of the morphology,structure,active constituents,and dynam...The quality of Chinese materia medica(CMM)is a challenging and focused topic in the modernization of traditional Chinese medicine(TCM).A profound comprehension of the morphology,structure,active constituents,and dynamic changes during the whole process of CMM growth is essential,which needs highly precise contemporary techniques for in-depth elucidation.Magnetic resonance imaging(MRI)is a cutting-edge tool integrating the benefits of both nuclear magnetic resonance(NMR)spectroscopy and imaging technology.With real-time,non-destructive,and in situ detection capabilities,MRI has been previously used for monitoring internal and external structures of plants alongside compounds during physiological processes in vivo.Here,factors involved in the holistic quality evaluation of CMMs were investigated.Given the applications of MRI in various plants,several representative CMMs were used as examples to demonstrate a methodology of quality visualization by MRI,embodying holistically monitoring the real-time macroscopic morphology,mesoscopic structure,and microscopic metabolites nondestructively in situ.Taken together,the review not only presents a pioneering application mode for utilizing MRI for CMM quality visualization but also holds promise for advancing the quality control and evaluation of CMMs.展开更多
基金Wu Jieping Medical Foundation,No.320.6750.2021-02-113.
文摘BACKGROUND Gastric neuroendocrine carcinomas(NECs)exhibit aggressive features,such as rapid growth,higher rate of metastasis,and a generally unfavorable prognosis compared to gastric adenocarcinoma.As a result,therapeutic options for NECs remain limited,contributing to the poor prognosis of patients.Immunotherapy has emerged as a promising treatment strategy and demonstrated the potential to partially improve the survival and prognosis of patients with NECs.Nevertheless,the unique clinical response termed pseudoprogression(PsP)has garnered considerable attention in the context of immunotherapy.CASE SUMMARY Presented here is a case of NEC recurrence five and a half months after radical gastric surgery.The 45-year-old male patient underwent combination treatment involving a PD-1 blocker and tyrosine kinase inhibitors and encountered two instances of PsP during treatment.The patient ultimately achieved a durable treatment response without altering his treatment regimens,resulting in a substantial therapeutic benefit.CONCLUSION This case report aimed to provide the authors’experience with the diagnosis of PsP and treatment strategies for PsP in ongoing immunotherapy.
基金supported by the National Natural Science Foundation of China,No.81601181,81673716(to GZ)the Natural Science Foundation of Anhui Province of China,No.1808085J15(to GZ)the Natural Science Research Project of Anhui Province of China,No.KJ2016A417(to GZ)
文摘Our previous studies showed that the early use of calpain inhibitors reduces calpain activity in multiple brain regions, and that postnatal treatment with calpeptin may lead to cerebellar motor dysfunction. However, it remains unclear whether postnatal calpeptin application affects hippocampus-related behaviors. In this study, Sprague-Dawley rats were purchased from the Animal Center of Anhui Medical University of China. For the experiments in the adult stage, rats were intraperitoneally injected with calpeptin, 2 mg/kg, once a day, on postnatal days 7–14. Then on postnatal day 60, the Morris water maze test was used to evaluate spatial learning and memory abilities. The open field test was carried out to assess anxiety-like activities. Phalloidin staining was performed to observe synaptic morphology in the hippocampus. Immunohistochemistry was used to count the number of NeuN-positive cells in the hippocampal CA1 region. DiI was applied to label dendritic spines. Calpeptin administration impaired spatial memory, caused anxiety-like behavior in adulthood, reduced the number and area of apical dendritic spines, and decreased actin polymerization in the hippocampus, but did not affect the number of NeuN-positive cells in the hippocampal CA1 region. For the neonatal experiments, neonatal rats were intraperitoneally injected with calpeptin, 2 mg/kg, on postnatal days 7 and 8. Western blot assay was performed to analyze the protein levels of Akt, Erk, p-Akt, p-Erk1/2, Erk1/2, SCOP, PTEN, mTOR, p-mTOR, CREB and p-CREB in the hippocampus. SCOP expression was increased, and the phosphorylation levels of Akt, mTOR and CREB were reduced in the hippocampus. These findings show that calpeptin administration after birth affects synaptic development in neonatal rats by inhibiting the Akt/mTOR signaling pathway, thereby perturbing hippocampal function. Therefore, calpeptin administration after birth is a risk factor for neurodevelopmental defects.
基金funding from the Spring City Plan:The High-Level Talent Promotion and Training Project of Kunming and the Independent Research Fund of Yunnan Characteristic Plant Extraction Laboratory(Grant No.:2022YKZY001).
文摘It is necessary to explore potent therapeutic agents via regulating gut microbiota and metabolism to combat Parkinson's disease(PD).Dioscin,a bioactive steroidal saponin,shows various activities.However,its effects and mechanisms against PD are limited.In this study,dioscin dramatically alleviated neuroinflammation and oxidative stress,and restored the disorders of mice induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP).16 S rDNA sequencing assay demonstrated that dioscin reversed MPTP-induced gut dysbiosis to decrease Firmicutes-to-Bacteroidetes ratio and the abundances of Enterococcus,Streptococcus,Bacteroides and Lactobacillus genera,which further inhibited bile salt hydrolase(BSH)activity and blocked bile acid(BA)deconjugation.Fecal microbiome transplantation test showed that the anti-PD effect of dioscin was gut microbiota-dependent.In addition,non-targeted fecal metabolomics assays revealed many differential metabolites in adjusting steroid biosynthesis and primary bile acid biosynthesis.Moreover,targeted bile acid metabolomics assay indicated that dioscin increased the levels of ursodeoxycholic acid,tauroursodeoxycholic acid,taurodeoxycholic acid and bmuricholic acid in feces and serum.In addition,ursodeoxycholic acid administration markedly improved the protective effects of dioscin against PD in mice.Mechanistic test indicated that dioscin significantly up-regulated the levels of takeda G protein-coupled receptor 5(TGR5),glucagon-like peptide-1 receptor(GLP-1R),GLP-1,superoxide dismutase(SOD),and down-regulated NADPH oxidases 2(NOX2)and nuclear factor-kappaB(NF-kB)levels.Our data indicated that dioscin ameliorated PD phenotype by restoring gut dysbiosis and regulating bile acid-mediated oxidative stress and neuroinflammation via targeting GLP-1 signal in MPTP-induced PD mice,suggesting that the compound should be considered as a prebiotic agent to treat PD in the future.
文摘Nine major cell populations among 46,716 cells were identified in mouse intestinal ischemia‒reperfusion(II/R)injury by single-cell RNA sequencing.For enterocyte cells,11 subclusters were found,in which enterocyte cluster 1(EC1),enterocyte cluster 3(EC3),and enterocyte cluster 8(EC8)were newly discovered cells in ischemia 45 min/reperfusion 720 min(I 45 min/R 720 min)group.EC1 and EC3 played roles in digestion and absorption,and EC8 played a role in cell junctions.For TA cells,after ischemia 45 min/reperfusion 90 min(I 45 min/R 90 min),many TA cells at the stage of proliferation were identified.For Paneth cells,Paneth cluster 3 was observed in the resting state of normal jejunum.After I 45 min/R 90 min,three new subsets were found,in which Paneth cluster 1 had good antigen presentation activity.The main functions of goblet cells were to synthesize and secrete mucus,and a novel subcluster(goblet cluster 5)with highly proliferative ability was discovered in I 45 min/R 90 min group.As a major part of immune system,the changes in T cells with important roles were clarified.Notably,enterocyte cells secreted Guca2b to interact with Gucy2c receptor on the membranes of stem cells,TA cells,Paneth cells,and goblet cells to elicit intercellular communication.One marker known as glutathione S-transferase mu 3(GSTM3)affected intestinal mucosal barrier function by adjusting mitogen-activated protein kinases(MAPK)signaling during II/R injury.The data on the heterogeneity of intestinal cells,cellular communication and the mechanism of GSTM3 provide a cellular basis for treating II/R injury.
基金supported by Plans for Major Provincial Science&Technology Projects,China(Grant No.:202303a0702005)the National Natural Science Foundation of China(Grant Nos.:U19A2009 and 82304881)+1 种基金the Key Natural Science Research Projects in Anhui Universities,China(Grant Nos.:2022AH050484 and 2022AH010036)the Collaborative Innovation Project,China(Grant Nos.:GXXT-2019-043 and GXXT-2019-049).
文摘The quality of Chinese materia medica(CMM)is a challenging and focused topic in the modernization of traditional Chinese medicine(TCM).A profound comprehension of the morphology,structure,active constituents,and dynamic changes during the whole process of CMM growth is essential,which needs highly precise contemporary techniques for in-depth elucidation.Magnetic resonance imaging(MRI)is a cutting-edge tool integrating the benefits of both nuclear magnetic resonance(NMR)spectroscopy and imaging technology.With real-time,non-destructive,and in situ detection capabilities,MRI has been previously used for monitoring internal and external structures of plants alongside compounds during physiological processes in vivo.Here,factors involved in the holistic quality evaluation of CMMs were investigated.Given the applications of MRI in various plants,several representative CMMs were used as examples to demonstrate a methodology of quality visualization by MRI,embodying holistically monitoring the real-time macroscopic morphology,mesoscopic structure,and microscopic metabolites nondestructively in situ.Taken together,the review not only presents a pioneering application mode for utilizing MRI for CMM quality visualization but also holds promise for advancing the quality control and evaluation of CMMs.
