1.Effect and mechanisms of highly active umbilical cord mesenchymal stem cells on aging spleen in elderly tree shrews
Li YE ; Chuan TIAN ; Xiaojuan ZHAO ; Mengdie CHEN ; Qianqian YE ; Qiang LI ; Zhuyin LIAO ; Ye LI ; Xiangqing ZHU ; Guangping RUAN ; Zhixu HE ; Liping SHU ; Xinghua PAN
Chinese Journal of Tissue Engineering Research 2025;29(19):4000-4010
BACKGROUND:Spleen has the functions of blood storage,hematopoiesis,and immunity.With the increase of age,the structural degeneration and functional decline of spleen lead to the impairment of immune system function,thus accelerating the aging process of the body.The treatment of spleen aging in tree shrews with highly active umbilical cord mesenchymal stem cells has not been reported. OBJECTIVE:To explore the intervention effect and mechanism of highly active umbilical cord mesenchymal stem cells on spleen aging in tree shrews. METHODS:Highly active umbilical cord mesenchymal stem cells were isolated,cultured,and obtained from the umbilical cord tissue of newborn tree shrews by caesarean section.The differentiation abilities of adipogenesis,osteogenesis,and chondrogenesis were detected by three-line differentiation kit.Cell cycle and surface markers were detected by flow cytometry.The second generation of highly active umbilical cord mesenchymal stem cells were transfected with Genechem Green Fluorescent Protein with infection complex values of 100,120,140,160,180,and 200,respectively,to screen the best transfection conditions.After transfection,the fourth generation of highly active umbilical cord mesenchymal stem cells was injected into the tail vein of tree shrews in the elderly treatment group.The young control group and the aged model group were not given special treatment.After 4 months of treatment,the spleen tissue was taken and the structure of the spleen was observed by hematoxylin-eosin staining.β-Galactosidase staining was used to detect the activity of aging-related galactosidase.Immunohistochemical staining was used to detect the expression levels of p21 and p53 proteins.Ki67 and PCNA immunofluorescence staining was used to detect cell proliferation activity.Immunofluorescence staining was used to detect the expression levels of spleen autophagy protein molecules Beclin 1 and APG5L/ATG5.Reactive oxygen species fluorescence staining was used to detect the content of reactive oxygen species in spleen tissue.CD3 immunofluorescence staining was used to detect the change of the proportion of total T lymphocytes.The secretion levels of interleukin 1β and transforming growth factor β1 in spleen were detected by enzyme linked immunosorbent assay.The distribution of highly active umbilical cord mesenchymal stem cells labeled with green fluorescent protein in spleen tissue was observed by DAPI double staining of nucleus. RESULTS AND CONCLUSION:(1)Highly active umbilical cord mesenchymal stem cells grew in a short spindle shape with fish-like growth,with a large proportion of G0/G1 phase,and had the potential to differentiate into adipogenesis,osteogenesis,and chondrogenesis.(2)Multiplicity of infection=140 and transfection for 72 hours were the best conditions for labeling tree shrews highly active umbilical cord mesenchymal stem cells with Genechem Green Fluorescent Protein.(3)Compared with the aged model group,in the aged treatment group,the spleen tissue cells of tree shrews were arranged closely,and the area of white pulp was increased(P<0.01);the boundary between red pulp and white pulp was clear;the proportion of germinal centers did not show statistically significant difference(P>0.05).The activity level of galactosidase related to spleen tissue aging was decreased(P<0.001),and the expression levels of aging protein molecules p21 and p53 were down-regulated(P<0.001).The expression levels of proliferation-related molecules Ki67 and PCNA were up-regulated(P<0.001,P<0.05);expression levels of autophagy-related molecules Beclin 1 and APG5L/ATG5 were up-regulated(P<0.001),and the content of reactive oxygen species decreased(P<0.001),and the proportion of CD3+T cells increased(P<0.05).The secretion level of interleukin 1β in the aging-related secretion phenotype decreased(P<0.001);no significant difference was found in transforming growth factor β1 level(P>0.05).Compared with the young control group,the above indexes were significantly different in the elderly treatment group(P<0.05).(4)Green fluorescent cells labeled with green fluorescent protein were observed in spleen tissue of tree shrews the elderly treatment group by frozen tissue section observation.The results show that intravenous infusion of highly active umbilical cord mesenchymal stem cells can migrate to spleen tissue,inhibit the production of reactive oxygen species,down-regulate the expression of aging-related proteins,induce autophagy,promote cell proliferation,reduce chronic inflammation,and then improve the structure and function of spleen tissue.
2.Bone marrow mesenchymal stem cells improve bone cancer pain by inhibiting p38MAPK phosphorylation and microglia activation
Houming KAN ; Jinzhao HUANG ; Xiaodie GUI ; Wendi TIAN ; Lijun FAN ; Xuetai CHEN ; Xiaotong DING ; Liping CHEN ; Wen SHEN
The Korean Journal of Pain 2025;38(2):116-127
Background:
Bone cancer pain (BCP) is not adequately addressed by current treatment methods, making the exploration of effective management strategies a topic of significant interest. Bone marrow mesenchymal stem cells (BMSCs) seem to be a potential way for managing BCP, yet little is known about the mechanisms underlying the efficacy of this potential treatment.
Methods:
We established the male C57BL/6 mice BCP models. Behavioral tests, X-ray, bone histology, western blotting, and immunofluorescence were used to verify the analgesic effect of BMSCs.
Results:
Intramedullary injection of Lewis lung carcinoma cells into the femur successfully generated the mice BCP models. The number of c-Fos-positive neurons and phosphorylated mitogen-activated protein kinase (MAPK) proteins in the spinal dorsal horn of the BCP mice increased. Intrathecal injection of BMSCs temporarily improved the BCP mice’s mechanical and thermal hyperalgesia without affecting motor function. This effect may be related to inhibiting spinal microglia and p-p38 MAPK activation. The analgesic effect of BMSCs may be related to the homing effect mediated by CXCR4.
Conclusions
Intrathecal injection of BMSCs can temporarily inhibit mechanical and thermal hyperalgesia in BCP mice without affecting motor function. This effect may be related to the inhibition of p-p38 protein expression and the inhibition of microglia but not to p-ERK and p-JNK.
3.Bone marrow mesenchymal stem cells improve bone cancer pain by inhibiting p38MAPK phosphorylation and microglia activation
Houming KAN ; Jinzhao HUANG ; Xiaodie GUI ; Wendi TIAN ; Lijun FAN ; Xuetai CHEN ; Xiaotong DING ; Liping CHEN ; Wen SHEN
The Korean Journal of Pain 2025;38(2):116-127
Background:
Bone cancer pain (BCP) is not adequately addressed by current treatment methods, making the exploration of effective management strategies a topic of significant interest. Bone marrow mesenchymal stem cells (BMSCs) seem to be a potential way for managing BCP, yet little is known about the mechanisms underlying the efficacy of this potential treatment.
Methods:
We established the male C57BL/6 mice BCP models. Behavioral tests, X-ray, bone histology, western blotting, and immunofluorescence were used to verify the analgesic effect of BMSCs.
Results:
Intramedullary injection of Lewis lung carcinoma cells into the femur successfully generated the mice BCP models. The number of c-Fos-positive neurons and phosphorylated mitogen-activated protein kinase (MAPK) proteins in the spinal dorsal horn of the BCP mice increased. Intrathecal injection of BMSCs temporarily improved the BCP mice’s mechanical and thermal hyperalgesia without affecting motor function. This effect may be related to inhibiting spinal microglia and p-p38 MAPK activation. The analgesic effect of BMSCs may be related to the homing effect mediated by CXCR4.
Conclusions
Intrathecal injection of BMSCs can temporarily inhibit mechanical and thermal hyperalgesia in BCP mice without affecting motor function. This effect may be related to the inhibition of p-p38 protein expression and the inhibition of microglia but not to p-ERK and p-JNK.
4.Bone marrow mesenchymal stem cells improve bone cancer pain by inhibiting p38MAPK phosphorylation and microglia activation
Houming KAN ; Jinzhao HUANG ; Xiaodie GUI ; Wendi TIAN ; Lijun FAN ; Xuetai CHEN ; Xiaotong DING ; Liping CHEN ; Wen SHEN
The Korean Journal of Pain 2025;38(2):116-127
Background:
Bone cancer pain (BCP) is not adequately addressed by current treatment methods, making the exploration of effective management strategies a topic of significant interest. Bone marrow mesenchymal stem cells (BMSCs) seem to be a potential way for managing BCP, yet little is known about the mechanisms underlying the efficacy of this potential treatment.
Methods:
We established the male C57BL/6 mice BCP models. Behavioral tests, X-ray, bone histology, western blotting, and immunofluorescence were used to verify the analgesic effect of BMSCs.
Results:
Intramedullary injection of Lewis lung carcinoma cells into the femur successfully generated the mice BCP models. The number of c-Fos-positive neurons and phosphorylated mitogen-activated protein kinase (MAPK) proteins in the spinal dorsal horn of the BCP mice increased. Intrathecal injection of BMSCs temporarily improved the BCP mice’s mechanical and thermal hyperalgesia without affecting motor function. This effect may be related to inhibiting spinal microglia and p-p38 MAPK activation. The analgesic effect of BMSCs may be related to the homing effect mediated by CXCR4.
Conclusions
Intrathecal injection of BMSCs can temporarily inhibit mechanical and thermal hyperalgesia in BCP mice without affecting motor function. This effect may be related to the inhibition of p-p38 protein expression and the inhibition of microglia but not to p-ERK and p-JNK.
5.Bone marrow mesenchymal stem cells improve bone cancer pain by inhibiting p38MAPK phosphorylation and microglia activation
Houming KAN ; Jinzhao HUANG ; Xiaodie GUI ; Wendi TIAN ; Lijun FAN ; Xuetai CHEN ; Xiaotong DING ; Liping CHEN ; Wen SHEN
The Korean Journal of Pain 2025;38(2):116-127
Background:
Bone cancer pain (BCP) is not adequately addressed by current treatment methods, making the exploration of effective management strategies a topic of significant interest. Bone marrow mesenchymal stem cells (BMSCs) seem to be a potential way for managing BCP, yet little is known about the mechanisms underlying the efficacy of this potential treatment.
Methods:
We established the male C57BL/6 mice BCP models. Behavioral tests, X-ray, bone histology, western blotting, and immunofluorescence were used to verify the analgesic effect of BMSCs.
Results:
Intramedullary injection of Lewis lung carcinoma cells into the femur successfully generated the mice BCP models. The number of c-Fos-positive neurons and phosphorylated mitogen-activated protein kinase (MAPK) proteins in the spinal dorsal horn of the BCP mice increased. Intrathecal injection of BMSCs temporarily improved the BCP mice’s mechanical and thermal hyperalgesia without affecting motor function. This effect may be related to inhibiting spinal microglia and p-p38 MAPK activation. The analgesic effect of BMSCs may be related to the homing effect mediated by CXCR4.
Conclusions
Intrathecal injection of BMSCs can temporarily inhibit mechanical and thermal hyperalgesia in BCP mice without affecting motor function. This effect may be related to the inhibition of p-p38 protein expression and the inhibition of microglia but not to p-ERK and p-JNK.
6.Bone marrow mesenchymal stem cells improve bone cancer pain by inhibiting p38MAPK phosphorylation and microglia activation
Houming KAN ; Jinzhao HUANG ; Xiaodie GUI ; Wendi TIAN ; Lijun FAN ; Xuetai CHEN ; Xiaotong DING ; Liping CHEN ; Wen SHEN
The Korean Journal of Pain 2025;38(2):116-127
Background:
Bone cancer pain (BCP) is not adequately addressed by current treatment methods, making the exploration of effective management strategies a topic of significant interest. Bone marrow mesenchymal stem cells (BMSCs) seem to be a potential way for managing BCP, yet little is known about the mechanisms underlying the efficacy of this potential treatment.
Methods:
We established the male C57BL/6 mice BCP models. Behavioral tests, X-ray, bone histology, western blotting, and immunofluorescence were used to verify the analgesic effect of BMSCs.
Results:
Intramedullary injection of Lewis lung carcinoma cells into the femur successfully generated the mice BCP models. The number of c-Fos-positive neurons and phosphorylated mitogen-activated protein kinase (MAPK) proteins in the spinal dorsal horn of the BCP mice increased. Intrathecal injection of BMSCs temporarily improved the BCP mice’s mechanical and thermal hyperalgesia without affecting motor function. This effect may be related to inhibiting spinal microglia and p-p38 MAPK activation. The analgesic effect of BMSCs may be related to the homing effect mediated by CXCR4.
Conclusions
Intrathecal injection of BMSCs can temporarily inhibit mechanical and thermal hyperalgesia in BCP mice without affecting motor function. This effect may be related to the inhibition of p-p38 protein expression and the inhibition of microglia but not to p-ERK and p-JNK.
7.Translation and psychometric evaluation of Cumulative Ambulation Score in elderly inpatients
Yuqi LIANG ; Min ZOU ; Bingjie TIAN ; Yiyan LIU ; Hua CHEN ; Ping WANG ; Liping JIANG
Chinese Journal of Practical Nursing 2024;40(18):1418-1423
Objective:To translate the Cumulated Ambulation Score (CAS) into Chinese and test its reliability and validity in elderly inpatients, to provide a basis for assessing elderly inpatients′ basic mobility during hospitalization.Methods:This was a cross-sectional study. After obtaining the authorization of the original author, the Chinese version of CAS was formed by WHO′s cross-cultural translation process. A total of 414 hospitalized elderly inpatients from Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, and Shanghai Yangpu District Kongjiang Hospital were selected between March and September 2021. Cronbach′s α coefficient was used to test internal consistency, linear weighted Kappa was employed to assess inter-rater reliability, and concurrent validity was examined using items related to mobility of Barthel Index scores as a reference standard.Results:Of the 414 patients, 221 were males and 193 were females, and the patients aged (76.67 ± 9.98) years old; 122 cases (29.5%) had a perfect score of 6 with normal basic mobility, 89 cases (21.5%) had a score of 0 with complete loss of mobility, and the remaining 203 patients had a score of 1-5 with varying degrees of reduced mobility. The Chinese version of CAS demonstrated good assessment performance for basic mobility in elderly inpatients with a Cronbach′s α coefficient of 0.952. Weighted Kappa values for individual items and total scores showed excellent agreement among raters (>0.85), while concurrent validity yielded a value of 0.935 ( P<0.01) when compared with Barthel Index scores.Total score of CAS was significantly correlated with item scores and total score of Barthel index ( r values were 0.423 to 0.944, all P<0.01). Conclusions:The Chinese version of CAS has good reliability and validity. The items are concise, clear and easy to understand. It is suitable as a preliminary screening tool for clinical departments to evaluate the basic mobility of elderly inpatients.
8.Hematopoietic aging: Cellular, molecular, and related mechanisms
Li YE ; Chuan TIAN ; Ye LI ; Hang PAN ; Jinxiu HU ; Liping SHU ; Xinghua PAN
Chinese Medical Journal 2024;137(11):1303-1312
Aging is accompanied by significant inhibition of hematopoietic and immune system function and disruption of bone marrow structure. Aging-related alterations in the inflammatory response, immunity, and stem cell niches are at the root of hematopoietic aging. Understanding the molecular mechanisms underlying hematopoietic and bone marrow aging can aid the clinical treatment of aging-related diseases. In particular, it is unknown how the niche reprograms hematopoietic stem cells (HSCs) in an age-dependent manner to maintain normal hematopoiesis in elderly individuals. Recently, specific inhibitors and blood exchange methods have been shown to reshape the hematopoietic niche and reverse hematopoietic aging. Here, we present the latest scientific discoveries related to hematopoietic aging and hematopoietic system rejuvenation, discuss the relationships between hematopoietic niche aging and HSC aging, and describe related studies on stem cell-mediated regulation of hematopoietic aging, aiming to provide new ideas for further study.
9.Effects of a 15-days complete fast on dual cognitive control functioning—Evidence from an ERPs
Chao WANG ; Haibo QIN ; Ziqing CAO ; Liping TIAN ; Yuan JIANG ; Zhongquan DAI ; Lizhong CHI ; Bin WU
Space Medicine & Medical Engineering 2024;35(4):209-215,221
Objective In the future,during the landing and exploration of near-Earth planets(e.g.,Mars,Jupiter,etc.),astronauts may take the initiative to start fasting to reduce the amount of load;and it is even more likely that astronauts will take the initiative to fast in the process of manned deep-space exploration in the future,or they may enter a dormant low-metabolism state to save the amount of load to enable the spaceship to fly for a longer period,and to locate in a deeper and farther position.The ability of an individual to maintain cognitive ability and respond appropriately over a period in a long-term fasting state is important for survival.Therefore,the present study focused on investigating the effects of 15 days of complete fasting on dual cognitive control function and its neural mechanisms.Methods Twenty-four healthy volunteers were recruited to participate in the fasting experiment.Behavioral and electroencephalographic data from the AX-CPT Task were collected with event-related potentials(ERP)to assess the effects of 15 days of complete fasting on dual cognitive control in 16 volunteers.Results(1)Behavioral outcomes had significant main effects on response time[F(1,15)=99.41,P?0.001,η2p=0.87]and error rate[F(1,15)=7.75,P=0.014,η2p=0.34],and BX trials were significantly lower than AY trials for both response time and error rate.(2)EEG results were significant for a cue type main effect on P3b[F(1,15)=16.43,P=0.001,η2p=0.52],with cue B inducing a more positive wave amplitude than cue A,and a cue type main effect on CNV[F(1,15)=10.72,P=0.005,η2p=0.42],with cue A evoking a more negative amplitude than cue B,and a significant main effect of trial type on N2[F(1,15)=6.90,P=0.019,η2p=0.32],with BX trials inducing more negative wave amplitudes than AY trials.All these results suggest that volunteers tend to use proactive control processing.Conclusion The 15-days complete fasting experiment did not significantly affect the dual cognitive control function of the volunteers,suggesting that the volunteers also had sufficient cognitive resources to perform cognitive control during the 15-days complete fasting state.This helps to understand further the relationship between long-term fasting and the processing mode of dual cognitive control and provides theoretical support and reference basis for the survival and work of astronauts actively fasting during the future near-Earth planet landing or even deep space exploration.
10.Efficacy observation of clinical medication guided by genetic testing of antipsychotic drugs in patients with schizophrenia
Haiyan WANG ; Jianfeng CAO ; Liping FU ; Liangcheng XIANG ; Tao TIAN ; Jixiang WANG ; Ming SHI ; Xiaojun LI ; Chunguang TANG
Sichuan Mental Health 2024;37(5):420-426
Background Results of genetic testing for antipsychotic drugs can guide the rational use of drugs in clinical practice and help improve the clinical symptoms of patients with schizophrenia.However,there is currently limited evidence in China regarding the impact of genetic testing results on medication adherence,social function and drug side effects of antipsychotic drug treatment.Objective To explore the improvement of clinical symptoms,medication adherence and social function in patients with schizophrenia under the guidance of antipsychotic drug gene testing results and examine the safety of drug treatment,so as to provide references for ifor precise treatment of schizophrenia patients.Methods Patients with acute schizophrenia who received hospitalization at Dazhou Minkang Hospital from July 2019 to August 2021 as well as met the diagnostic criteria of the International Classification of Diseases,tenth edition(ICD-10)were selected as research subjects(n=144).Based on random number table,subjects were divided into study group and control group,with 72 cases in each group.Control group received drug treatment based on the doctor's clinical experience,while study group received drug treatment based on the results of gene testing for antipsychotic drug.Both treatments lasted for 12 weeks.At baseline as well as 2,4,8 and 12 weeks after treatment,Positive and Negative Syndrome Scale(PANSS),8-item Morisky Medication Adherence Scale(MMAS-8),Social Functional Rating Scale(SFRS)and Treatment Emergent Symptom Scale(TESS)were adopted for assessment.Result Time effect and group effect of the reducing rate of PANSS,MMAS-8 and SFRS scores in the groups were statistically significant(Ftime=95.251,6.650,14.101,Fgroup=38.055,58.175,128.221,P<0.01).The interaction effect of the reduction rates of MMAS-8 scores in two groups was statistically significant(Finteraction=5.837,P<0.01).The group effect and interaction effect of the severity scores of drug side effects and patient pain scores in two groups were statistically significant(Fgroup=7.553,81.533,Finteraction=8.693,9.322,P<0.01).Conclusion In terms of improving clinical symptom relief,medication adherence,social function and drug side effects,medication for patients with schizophrenia guided by genetic testing of antipsychotic drugs may be more effective than that relying on medication based on clinical experience.

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