Objective This study aimed to comprehensively investigate the potential protective effects and underlying mechanisms of taurine against dihydrotestosterone(DHT)-induced androgenetic alopecia(AGA)in male C57BL/6 mice,w...Objective This study aimed to comprehensively investigate the potential protective effects and underlying mechanisms of taurine against dihydrotestosterone(DHT)-induced androgenetic alopecia(AGA)in male C57BL/6 mice,with a focus on hair follicle cycle modulation,cellular proliferation/apoptosis,and key related signaling pathways.Methods Six-week-old female C57BL/6 mice were initially used to assess the hair growth-promoting potential of taurine.After acclimatization,they were randomly assigned to three groups(n=8):control(regular drinking water),taurine(drinking water containing 1%taurine),and minoxidil(topical 2%minoxidil,positive control).For the AGA study,male C57BL/6 mice were randomly divided into five groups(n=8):control(physiological saline),DHT(model group,1 mg/d DHT),DHT+low-dose taurine(1 mg/d DHT+2 mg/d taurine),DHT+high-dose taurine(1 mg/d DHT+10 mg/d taurine),and DHT+minoxidil(positive control,1 mg/d DHT+topical 2%minoxidil).One day before treatment initiation,dorsal hair was shaved with scissors,and residual hair was removed using a depilatory cream.DHT and taurine were administered via daily intraperitoneal injection.Hair regrowth was assessed by photographing the depilated area at regular intervals and quantified using a four-point grading system(0-3).Dorsal skin samples were collected on day 14 for histological analysis(H&E staining),immunofluorescence staining(Ki67 for proliferation,TUNEL for apoptosis),ELISA(DHT quantification),RT-qPCR,and Western blot analysis to evaluate the expression of key genes and proteins(androgen receptor(AR),transforming growth factor(TGF)‑β1,TGF‑β2,Dickkopf-1(DKK1)).Results In female mice,taurine supplementation significantly accelerated hair growth,with effects comparable to minoxidil.This was evidenced by an earlier transition from pink(telogen)to black(anagen)skin and increased hair growth scores.Histological analysis showed that taurine increased hair follicle count and dermal thickness.Immunofluorescence confirmed enhanced keratinocyte proliferation in the hair matrix.In the DHTinduced AGA model,DHT significantly extended the telogen phase,inhibited hair growth,increased skin DHT content,and induced hair follicle miniaturization.Taurine treatment,particularly at the high dose,effectively counteracted these effects:it promoted the telogen-to-anagen transition and improved hair growth scores.Histomorphometric analysis showed that taurine significantly restored DHT-induced reductions in dermal thickness,hair follicle count,hair bulb depth,and follicle size.Taurine treatment also reduced apoptosis and promoted the proliferation of hair follicle cells,as demonstrated by Ki67 and TUNEL assays.Crucially,RT-qPCR and Western blot analyses revealed that DHT significantly up-regulated the expression of AR,TGF‑β1,TGF‑β2,and DKK1 at both mRNA and protein levels in dorsal skin.Taurine administration markedly down-regulated the expression of these pathogenic factors,bringing them closer to the levels observed in the control group.Conclusion Taurine demonstrates significant efficacy in alleviating DHT-induced AGA in male C57BL/6 mice.Its protective effects are mediated through multi-faceted mechanisms.(1)Promoting hair follicle cycle progression:it accelerates the transition from telogen to anagen,counteracting DHT-induced prolongation of the telogen phase.(2)Modulating cellular dynamics:it stimulates the proliferation of hair matrix keratinocytes and reduces DHT-induced apoptosis within hair follicle cells.(3)Suppressing androgen-driven pathogenic pathways:it downregulates the expression of critical molecules in the AGA pathway,including AR,the cytokines TGF-β1 and TGF-β2,and the Wnt pathway inhibitor DKK1.Given its favorable safety profile and multi-targeted action,taurine emerges as a promising novel therapeutic candidate or adjunct for treating AGA.Further investigation into its clinical potential and precise molecular mechanisms is warranted.This study provides a robust preclinical foundation for considering taurine supplementation or topical application in hair loss management strategies.展开更多
目的研究不同缺失率、不同缺失机制下,MICE(multivariate imputation by chained equations)多重填补的效果,探讨该填补方法的适用情况。方法依托某现况调查的完全数据,使用R软件构造不同缺失率、不同缺失机制的缺失数据。计算列表删除...目的研究不同缺失率、不同缺失机制下,MICE(multivariate imputation by chained equations)多重填补的效果,探讨该填补方法的适用情况。方法依托某现况调查的完全数据,使用R软件构造不同缺失率、不同缺失机制的缺失数据。计算列表删除和MICE多重填补后分析结果的标准偏倚,并进行比较。单独对分类变量计算多重填补后的平均错分率。结果在单变量缺失率分别为10%、20%和30%的随机缺失三种情况下,MICE多重填补表现优良;其他模拟情况下,MICE多重填补相比于列表删除并未表现出明显的优势。对于分类变量,MICE填补后的平均错分率均超过60%。结论对于随机缺失数据,且单变量缺失率不超过30%时,建议采用MICE多重填补进行处理;但对于资料中的分类变量,不建议直接引用MICE填补后的具体数值。展开更多
OBJECTIVE To explore the potential effect and mechanisms of protopanaxadiol deriva.tive 1-(3,4-dimethoxyphenethyl)-3-(3-dehydroxyl-20(s)-protopa-naxadiol-3 b-yl)-urea(DDPU) in the treatment of Alzheimer disease.METHOD...OBJECTIVE To explore the potential effect and mechanisms of protopanaxadiol deriva.tive 1-(3,4-dimethoxyphenethyl)-3-(3-dehydroxyl-20(s)-protopa-naxadiol-3 b-yl)-urea(DDPU) in the treatment of Alzheimer disease.METHODS ELISA assay was performed in both HEK293-APPswe and CHO-APP cells to demonstrate the efficacy of DDPU in reducing Ab level.SH-SY5 Y,primary neurons and astrocyte cellswereused to study the regulation of DDPU against the signaling pathways involved in Aβ/ER-stress pathology.APP/PS1 transgenic mice wereusedto study the regulation of DDPU against ADL and cognitive deficits.APP/PS1 transgenic mice were randomly placed into three groups(n=10):The two 6-month transgenic groups were administrated with 30 mg·kg^(-1) DDPU or vehicle and the 6-month non-transgenic group was administrated with vehicle for 100 days by intraperitonealinjec.tion.After 100-day administration,nest construction assay and Morris water maze(MWM) assay were applied to evaluate the daily living activities and cognitive abilities of the mice with continuous DDPU treatment.Upon completion of behavior assays,mice were euthanized,and the brains were removed and bisected in mid-sagittal plane.The right hemispheres were frozen and stored at-80°C,and the left hemispheres were fixed in 4% paraformaldehyde.RESULTS DDPU effectively improved learning and memory impairments in APP/PS1 transgenic mice,and the underlying mechanisms have been inten.sively investigated.DDPU reduced Ab production by inhibiting the PERK/eIF2 a signaling-mediated BACE1 translation,while promoted Ab clearance as a PI3K inhibitor thus negatively regulating PI3K/AKT/mTOR signaling in promotion of autophagy.Moreover,DDPU also exhibited neuroprotective effect by attenuating ER stress.Therefore,all findings have clearly demonstrated the crosstalk between Ab and ER stress,and confirmed that targeting ER stress should be a potential target for innovative anti-AD drug development,while highlighted the potential of DDPU in the treatment of AD.展开更多
The objective was to evaluate the toxicity effect of gossypol on ultrastructure of mouse testis and the expression of Bax mRNA and Bcl-2 mRNA of sperm cells in mice. Forty-eight male mice were randomly divided into fo...The objective was to evaluate the toxicity effect of gossypol on ultrastructure of mouse testis and the expression of Bax mRNA and Bcl-2 mRNA of sperm cells in mice. Forty-eight male mice were randomly divided into four groups： control group, L-group （30 mg-kgt. d）, M-group （60 mg·kg-1 ·d） and H-group （120 mg·kg-1· d） and were orally administrated with gossypol diluted by sodium carboxymethyl cellulose （SCC） or SCC （control group） for 20 days. On the 21st day, all the mice were killed and ultrastructure changes of testis were observed by TEM. mRNA expression of Bax and Bcl-2 in testis was measured by semiquantitative RT-PCR. The results showed that the testicular ultrastructure in three treated groups was gradually damaged, according to the dosage of gossypol and cellular structure disordered and organdie degenerated, manifesting vacuolation of mitochondria, expansion of endoplasmie reticulum, mRNA expression of Bcl-2 in testis significantly increased （p〈0.05） in L-group and then significantly decreased （p〈0.05, p〈0.01） in M-group and H-group compared with that in the control group; mRNA expression of Bcl-2 in M-group and H-group significantly decreased （p〈0.05, p〈0.01） than that in L-group and Bcl-2 mRNA expression in H-group showed a significant decrease （p〈0.05） compared with that in M-group. On the other hand, mRNA expression of Bax significant increased （p〈0.05,p〈0.01） in M-group and H-group than that in the control group. The ratio of Bcl-2/Bax significantly reduced 07〈0.05, p〈0.01） in the treated group than that in the control group and was found to be an obvious dose-dependent. It demonstrated that the gnssypol could induce the changes on ultrastructure of mice testis, down-regulate mRNA expression of Bcl-2 and up-regnlate mRNA expression of Bax, which indicated that sperm ceils were induced apoptosis.展开更多
The serum levels of IL-12 and IL-10 in mice after infected with Babesia microti （B. microti） and Babesia rodhaini （B. rodhaini） were examined. Collected the mice serum and examined the concentration of IL-12 and I...The serum levels of IL-12 and IL-10 in mice after infected with Babesia microti （B. microti） and Babesia rodhaini （B. rodhaini） were examined. Collected the mice serum and examined the concentration of IL-12 and IL-10 by using ELISA after infection with B. microti and B. rodhaini at 0, 3, 6, 9, 12, 18, 24, 36, 72, 96 h in mice. The results showed that B. microti infection resulted in IL-12 increasing, which peaked at 3 and 24 h after the infection, while same infection did not induce a significant change in IL-10 compared to uninfected mice. When mice were infected with B. rodhaini, any significant changes were not decteted both in IL-12 and IL-10 in comparison with uninfected animals during the period of 3-72 h after infection. Instead, a significant decline in IL-12 and IL-10 was found compared to uninfected mice 96 h after infection with B. rodhaini. It indicates that the mutagenetic cytokine is IL-12 in the serum of mice after infection with B. microti, and no any significant changes were detected in both IL-12 and IL-10 from 0 to 72 h after infected with B. rodhaini.展开更多
OBJECTIVE To study the protective effect of potassium 2-(l-hydroxypentyl)-benzoate(PHPB) on hippocampal neurons,synapses and dystrophic axons in APP/PS1 mice.METHODS Ten-month-old male APP/PS1 transgenic mice and age-...OBJECTIVE To study the protective effect of potassium 2-(l-hydroxypentyl)-benzoate(PHPB) on hippocampal neurons,synapses and dystrophic axons in APP/PS1 mice.METHODS Ten-month-old male APP/PS1 transgenic mice and age-matched wild-type mice were randomly divided into three groups:wild-type group(WT Con group,n=10),APP/PS1 group(Tg Con group,n=10) and PHPB treated APP/PS1 group(PHPB group,n=10).PHPB group received 30 mg · kg-1 PHPB by oral gavage once daily for 3 months.WT Con group and Tg Con group received the same volume of water.Three months later,mice were sacrificed for biochemical and pathological testing such as transmission electron microscopy,Golgi staining and Western boltting analysis.RESULTS Under the transmission electron microscope,most hippocampal neurons and subcel ular organel es in WT Con group exhibited normal morphology.However,the degenerative changes were observed in Tg Con group such as nuclear fragmentation,mitochondrial swelling,ribosomes detachment and autophagic vacuoles accumulation.The hippocampal synapses number and the thickness of postsynaptic density(PSD) were significantly decreased in Tg Con group compared with the WT Con group(P<0.05).After PHPB treatment,the degenerative changes in APP/PS1 mice were alleviated to some extent.The synapse number has been elevated significantly(P<0.05) and the PSD has been thickened as well.Golgi staining showed that the spine density of secondary and tertiary apical dendritic branches was significantly decreased in CA1 and DG areas of Tg Con group(P<0.05).Sholl analysis revealed a decrease of dendritic complexity in Tg Con group compared with WT Con group(P<0.05).These abnormalities were alleviated to some extent after PHPB treatment.Western blotting study showed that the protein levels of synaptic marker PSD-95 and synaptophysin were significantly decreased in the hippocampus of Tg Con group(P<0.05).A significant increase of PSD-95(P<0.05) and a slight increase of SYP were observed after the PHPB treatment.Besides,we found a significant increase in the ratio of LC3-Ⅱ/LC3-Ⅰ in Tg Con group compared with the WT Con group(P<0.01) and the relevant improvement after PHPB treatment(P<0.05),which showed the regulatory effect of PHPB on autophagy impairment.CONCLUSION PHPB showed protective effects on hippocampal neurons,synapses and dystrophic axons in APP/PS1 mice,which might help explain its role on cognitive improvement in Alzheimer disease treatment.展开更多
OBJECTIVE To explore whether J24924could prevent the development of pristane-induced lupus in a mouse model,and whether it could protect renal and lower the cardiovascular risk.METHODS The effect of J24924 was assesse...OBJECTIVE To explore whether J24924could prevent the development of pristane-induced lupus in a mouse model,and whether it could protect renal and lower the cardiovascular risk.METHODS The effect of J24924 was assessed in female BALB/c mice intraperitoneal injected with 0.5 m L of pristane,and serum autoantibodies were tested every month,blood pressure wasmeasured every 2 months,while serum inflammatory markers,spleen pathologic characteristics,renal injury and vascular function were observed at 6 month.RESULTS J24924 could decrease serum autoantibodies and serum inflammatory markers in the SLE mice and improved the spleen pathologic characteristics,and at the same time improved the renal injury and decreased inflammatory responses in kidneys,reduced blood pressure and improved vascular endothelial function.Western blotting assays revealed that inhibition for the activation of NF-κB and Rho/ROCKs signaling pathways and the downstream signaling molecules might be the potential mechanisms of J24924.CONCLUSION Our findings suggestthat therapy of J24924 may be a strategy to prevent SLE and ameliorate associated kidney and cardiovascular complications.展开更多
Tisplatin is one of the valuable icancer agents against several types of neoplasm. However, nephrotoxicity is the major adverse effect representing in cisplatin therapy. In this study, the animal tests detecting prote...Tisplatin is one of the valuable icancer agents against several types of neoplasm. However, nephrotoxicity is the major adverse effect representing in cisplatin therapy. In this study, the animal tests detecting protective effects of a natural compound, Decursin, on cisplatin-induced nephrotoxicity were examined by using in vivo model. Pretreatment Decursin 10, 20 and 40 mg · kg^-1 at 48, 24 and 6 h, and administration of a single dose of Cisplatin 5.2 mg · kg^-1. Nephrotoxicity was evaluated by serum BUN and creatinine examination. There was significant difference in body weights, serum BUN and creatinine levels of the normal group. Based on the new understanding of the protective mechanisms of cisplatin-induced nephrotocivity, new strategies can be developed to prevent renal injury or to enhance recovery after cisplatin treatment.展开更多
OBJECTIVE Propane-2-sulfonic acid octadec-9-enyl-amide(N15),an analogue of oleoylethanolamide(OEA),is a novel PPARα/γdual agonist.Our previous studies verified the positive effects of OEA on the acute and delayed st...OBJECTIVE Propane-2-sulfonic acid octadec-9-enyl-amide(N15),an analogue of oleoylethanolamide(OEA),is a novel PPARα/γdual agonist.Our previous studies verified the positive effects of OEA on the acute and delayed stages of cerebral ischaemia.However,it is not clear whether N15 is effective against ischaemic cerebral injury.In the present study,male Kunming mice were subjected to middle cerebral artery occlusion(MCAO).METHODS To evaluate its preventive effects,N15(50,100 or 200 mg·kg-1,ip)was administered for3 d before ischaemia.To evaluate its therapeutic effects,N15(200 mg·kg-1,ip)was administered 1 h before reperfusion or 0,1,2 or 4 h after reperfusion.Neurological deficit scores,infarct volume and the degree of brain oedema were determined at 24 h after reperfusion.Blood brain barrier(BBB)disruption was evaluated by Evans blue(EB)leakage at 6 h after reperfusion.The activation/inflammatory responses of microglia were detected using immunohistochemistry and Western blotting.RESULTS N15 pretreatment improved neurological dysfunction,reduced infarct volume and alleviated brain oedema in a dose-dependent manner;the most effective dose was 200 mg·kg-1.The therapeutic time window was within 2 h after reperfusion.Moreover,N15was more potent in the treatment of cerebral ischaemia injury than OEA.N15 treatment preserved the BBB integrity and suppressed the activation of microglia.N15 inhibited inflammatory cytokine expression not only in MCAO mice but also in lipopolysaccharide(LPS)-stimulated BV-2microglial cells.Moreover,N15 decreased the phosphorylation levels of NF-κBp65,STAT3,and ERK1/2 both in vivo and in vitro.CONCLUSION Our findings demonstrated that N15 exerts neuroprotective effects and was more potent than OEA.Additionally,the neuroprotective effects of N15 on cerebral ischaemia may be attributed to its anti-inflammatory properties,at least in part,by enhancing PPARα/γdual signalling and inhibiting the activation of the NF-κB,STAT3,and ERK1/2 signalling pathways.These findings suggest that N15 may be a potential therapeutic choice for the prevention and treatment of ischaemic stroke.展开更多
Aim To study the influence of SiniSan on the Tryptophan- kynurenine（TRP-KYN）pathway, the activity and content of the key metabolism enzyme indoleamine2, 3-dioxygenase （IDO）. Methods The mice model was established ...Aim To study the influence of SiniSan on the Tryptophan- kynurenine（TRP-KYN）pathway, the activity and content of the key metabolism enzyme indoleamine2, 3-dioxygenase （IDO）. Methods The mice model was established by intraperitoneal injection LPS （ 1 mg · kg^-1 ）. Using ELISA to detect the contents of IFN-γin serum. The content of Tryptophan and kynurenine in brain tissue were detected by using HPLC-MS/MS technique. The mRNA expression level of IDO in brain tissue was detected by using real-time PCR. Results 4 hours after the LPS injection, the immobility time of model group mice prolonged. The content of IFN-~/in serum increased significantly （P 〈 0.05）. Meanwhile, the activity of IDO in brain tissue and the mRNA expression level of IDO increased. SiniSan could short the immobility time of mice, reduced the content of IFN-γin serum （P 〈 0.05）. It could also inhibit the activity of IDO and the expression of mRNA（P 〈 0.01 ）. Conclusion SiniSan blocks the pathway of IDO activation, inhibit the activity of IDO and reduce the content of it. SiniSan produces antidepressant effect by adjusting the TRP-KYN metabolism.展开更多
Aim Some indirect evidences indicate a possible correlation between oxidative stress and motion sick- ness. The aim of this research was to investigate whether oxidative stress contributing to motion sickness in mice ...Aim Some indirect evidences indicate a possible correlation between oxidative stress and motion sick- ness. The aim of this research was to investigate whether oxidative stress contributing to motion sickness in mice or not. Methods We examined the mRNA levels of peroxiredoxin 6 （PRDX6） , catalase and enzyme superoxide dis- mutase 1 （SOD1）; reactive oxygen species （ROS）; total antioxidant capacity and SOD activity in different brain regions after rotary stimulation. Mice motion sickness index was recorded after rotation when pretreated with pa- raquat, vitamin C or vitamin E. Results The R0S level and antioxidant capacity were both increased in cerebel- lum plus brainstem （CB） after rotation, a critical region determines motion sickness. However, manipulation of ox- idants or antioxidants using pharmacological method in vivo had no influence on motion sickness index in mice. Conclusion Oxidative stress is not involved in the development of motion sickness in mice.展开更多
Objective To clarify the differences in cardiac structure,cardiac function,and myocardial metabolism in type 2 diabetes mellitus mice with obesity or non-obesity and to elucidate the key molecular mechanisms leading t...Objective To clarify the differences in cardiac structure,cardiac function,and myocardial metabolism in type 2 diabetes mellitus mice with obesity or non-obesity and to elucidate the key molecular mechanisms leading to this difference.Methods Db/db mice and low-dose STZ injection combined with HFD-induced diabetes mellitus mice were used in this study as the model of type 2 diabetes mellitus with obesity or non-obesity.展开更多
OBJECTIVE To evaluate whether ginsenoside Rb1 has antiepileptic effects on pen⁃tylenetetrazole(PTZ)-induced epileptic mice via intranasal therapeutic administration.METHODS Rb1 monoclonal antibody was used to observe ...OBJECTIVE To evaluate whether ginsenoside Rb1 has antiepileptic effects on pen⁃tylenetetrazole(PTZ)-induced epileptic mice via intranasal therapeutic administration.METHODS Rb1 monoclonal antibody was used to observe the distribution of Rb120 mg·kg-1 in mouse brain tissues under different administration routes and to explore the feasibility of intranasal Rb1.PTZ was injected intraperitoneally into healthy ICR mice every 48 hours to construct a tonic-clonic epileptic model.Then Rb120 or 40 mg·kg-1 or valproate 300 mg·kg-1 or saline was administered intranasally for 30 d,and PTZ was continued every five days to imitate occa⁃sional convulsions in the clinic.Racine scale(RCS)and wireless electroencephalogram(EEG)monitoring were used to assess the presence and severity of seizure.Immunofluorescence(IF)was performed after drug treatment to evalu⁃ate the effect of Rb1 on brain neuron,microglia and astrocyte in epileptic mice.RESULTS Rb1 had specific binding with anti-Rb1 in the brain under different administration routes,and intrana⁃sal Rb1 was able to enter the brain and play a therapeutic role(P<0.01).PTZ-injured mice pre⁃sented body mass loss,higher seizure stage and shorter seizure latency.At the same time,epilep⁃tic waves,mainly spikes,were detected by wire⁃less EEG.Compared with PTZ group,intranasal Rb1 increased mice weight(P<0.01)and seizure latency(P<0.05),reduced seizure stage(P<0.01)and EEG spikes.In addition,Rb1 significantly reduced neuron loss(P<0.01)indicated by NeuN staining and decreased the number of acti⁃vated microglia(P<0.01)indicated by Iba-1 staining in the cortex and CA1 area of hippocam⁃pus.Moreover,Rb1 reduced the decrease of GLT-1 and GS expression(P<0.05)induced by PTZ.CONCLUTION Intranasal Rb1 has anti-epi⁃leptic effects on PTZ mice.Moreover,Intranasal Rb1 affects the functions of neurons,astrocytes and microglia through regulating the expression of GLT and GS in astrocytes,which may be related to its anti-epileptic effect.展开更多
基金supported by grants from The National Natural Science Foundation of China(31772690)the Natural Science Foundation of Shanxi Province(201701D121106)PhD Research Startup Foundation of Changzhi Medical College(BS202308)。
文摘Objective This study aimed to comprehensively investigate the potential protective effects and underlying mechanisms of taurine against dihydrotestosterone(DHT)-induced androgenetic alopecia(AGA)in male C57BL/6 mice,with a focus on hair follicle cycle modulation,cellular proliferation/apoptosis,and key related signaling pathways.Methods Six-week-old female C57BL/6 mice were initially used to assess the hair growth-promoting potential of taurine.After acclimatization,they were randomly assigned to three groups(n=8):control(regular drinking water),taurine(drinking water containing 1%taurine),and minoxidil(topical 2%minoxidil,positive control).For the AGA study,male C57BL/6 mice were randomly divided into five groups(n=8):control(physiological saline),DHT(model group,1 mg/d DHT),DHT+low-dose taurine(1 mg/d DHT+2 mg/d taurine),DHT+high-dose taurine(1 mg/d DHT+10 mg/d taurine),and DHT+minoxidil(positive control,1 mg/d DHT+topical 2%minoxidil).One day before treatment initiation,dorsal hair was shaved with scissors,and residual hair was removed using a depilatory cream.DHT and taurine were administered via daily intraperitoneal injection.Hair regrowth was assessed by photographing the depilated area at regular intervals and quantified using a four-point grading system(0-3).Dorsal skin samples were collected on day 14 for histological analysis(H&E staining),immunofluorescence staining(Ki67 for proliferation,TUNEL for apoptosis),ELISA(DHT quantification),RT-qPCR,and Western blot analysis to evaluate the expression of key genes and proteins(androgen receptor(AR),transforming growth factor(TGF)‑β1,TGF‑β2,Dickkopf-1(DKK1)).Results In female mice,taurine supplementation significantly accelerated hair growth,with effects comparable to minoxidil.This was evidenced by an earlier transition from pink(telogen)to black(anagen)skin and increased hair growth scores.Histological analysis showed that taurine increased hair follicle count and dermal thickness.Immunofluorescence confirmed enhanced keratinocyte proliferation in the hair matrix.In the DHTinduced AGA model,DHT significantly extended the telogen phase,inhibited hair growth,increased skin DHT content,and induced hair follicle miniaturization.Taurine treatment,particularly at the high dose,effectively counteracted these effects:it promoted the telogen-to-anagen transition and improved hair growth scores.Histomorphometric analysis showed that taurine significantly restored DHT-induced reductions in dermal thickness,hair follicle count,hair bulb depth,and follicle size.Taurine treatment also reduced apoptosis and promoted the proliferation of hair follicle cells,as demonstrated by Ki67 and TUNEL assays.Crucially,RT-qPCR and Western blot analyses revealed that DHT significantly up-regulated the expression of AR,TGF‑β1,TGF‑β2,and DKK1 at both mRNA and protein levels in dorsal skin.Taurine administration markedly down-regulated the expression of these pathogenic factors,bringing them closer to the levels observed in the control group.Conclusion Taurine demonstrates significant efficacy in alleviating DHT-induced AGA in male C57BL/6 mice.Its protective effects are mediated through multi-faceted mechanisms.(1)Promoting hair follicle cycle progression:it accelerates the transition from telogen to anagen,counteracting DHT-induced prolongation of the telogen phase.(2)Modulating cellular dynamics:it stimulates the proliferation of hair matrix keratinocytes and reduces DHT-induced apoptosis within hair follicle cells.(3)Suppressing androgen-driven pathogenic pathways:it downregulates the expression of critical molecules in the AGA pathway,including AR,the cytokines TGF-β1 and TGF-β2,and the Wnt pathway inhibitor DKK1.Given its favorable safety profile and multi-targeted action,taurine emerges as a promising novel therapeutic candidate or adjunct for treating AGA.Further investigation into its clinical potential and precise molecular mechanisms is warranted.This study provides a robust preclinical foundation for considering taurine supplementation or topical application in hair loss management strategies.
文摘目的研究不同缺失率、不同缺失机制下,MICE(multivariate imputation by chained equations)多重填补的效果,探讨该填补方法的适用情况。方法依托某现况调查的完全数据,使用R软件构造不同缺失率、不同缺失机制的缺失数据。计算列表删除和MICE多重填补后分析结果的标准偏倚,并进行比较。单独对分类变量计算多重填补后的平均错分率。结果在单变量缺失率分别为10%、20%和30%的随机缺失三种情况下,MICE多重填补表现优良;其他模拟情况下,MICE多重填补相比于列表删除并未表现出明显的优势。对于分类变量,MICE填补后的平均错分率均超过60%。结论对于随机缺失数据,且单变量缺失率不超过30%时,建议采用MICE多重填补进行处理;但对于资料中的分类变量,不建议直接引用MICE填补后的具体数值。
基金supported by National Natural Science Foundation of China(81220108025,81473141) NSFC-TRF collaboration projects(81561148011,DBG5980001)+3 种基金 Drug Innovation Project of SIMM(CASIMM0120154035) Personalized Medicine-Molecular Signature-based Drug Discovery and Development, Strategic Priority Research Program of Chinese Academy of Sciences (XDA12040303) the Project Funded by the Priority Aca-demic Program Development of Jiangsu Higher Education Institutions (Integration of Chinese and Western Medi-cine17KJA350002) National Natural Science Foundation for Young Scientists of China (81703806)
文摘OBJECTIVE To explore the potential effect and mechanisms of protopanaxadiol deriva.tive 1-(3,4-dimethoxyphenethyl)-3-(3-dehydroxyl-20(s)-protopa-naxadiol-3 b-yl)-urea(DDPU) in the treatment of Alzheimer disease.METHODS ELISA assay was performed in both HEK293-APPswe and CHO-APP cells to demonstrate the efficacy of DDPU in reducing Ab level.SH-SY5 Y,primary neurons and astrocyte cellswereused to study the regulation of DDPU against the signaling pathways involved in Aβ/ER-stress pathology.APP/PS1 transgenic mice wereusedto study the regulation of DDPU against ADL and cognitive deficits.APP/PS1 transgenic mice were randomly placed into three groups(n=10):The two 6-month transgenic groups were administrated with 30 mg·kg^(-1) DDPU or vehicle and the 6-month non-transgenic group was administrated with vehicle for 100 days by intraperitonealinjec.tion.After 100-day administration,nest construction assay and Morris water maze(MWM) assay were applied to evaluate the daily living activities and cognitive abilities of the mice with continuous DDPU treatment.Upon completion of behavior assays,mice were euthanized,and the brains were removed and bisected in mid-sagittal plane.The right hemispheres were frozen and stored at-80°C,and the left hemispheres were fixed in 4% paraformaldehyde.RESULTS DDPU effectively improved learning and memory impairments in APP/PS1 transgenic mice,and the underlying mechanisms have been inten.sively investigated.DDPU reduced Ab production by inhibiting the PERK/eIF2 a signaling-mediated BACE1 translation,while promoted Ab clearance as a PI3K inhibitor thus negatively regulating PI3K/AKT/mTOR signaling in promotion of autophagy.Moreover,DDPU also exhibited neuroprotective effect by attenuating ER stress.Therefore,all findings have clearly demonstrated the crosstalk between Ab and ER stress,and confirmed that targeting ER stress should be a potential target for innovative anti-AD drug development,while highlighted the potential of DDPU in the treatment of AD.
文摘The objective was to evaluate the toxicity effect of gossypol on ultrastructure of mouse testis and the expression of Bax mRNA and Bcl-2 mRNA of sperm cells in mice. Forty-eight male mice were randomly divided into four groups： control group, L-group （30 mg-kgt. d）, M-group （60 mg·kg-1 ·d） and H-group （120 mg·kg-1· d） and were orally administrated with gossypol diluted by sodium carboxymethyl cellulose （SCC） or SCC （control group） for 20 days. On the 21st day, all the mice were killed and ultrastructure changes of testis were observed by TEM. mRNA expression of Bax and Bcl-2 in testis was measured by semiquantitative RT-PCR. The results showed that the testicular ultrastructure in three treated groups was gradually damaged, according to the dosage of gossypol and cellular structure disordered and organdie degenerated, manifesting vacuolation of mitochondria, expansion of endoplasmie reticulum, mRNA expression of Bcl-2 in testis significantly increased （p〈0.05） in L-group and then significantly decreased （p〈0.05, p〈0.01） in M-group and H-group compared with that in the control group; mRNA expression of Bcl-2 in M-group and H-group significantly decreased （p〈0.05, p〈0.01） than that in L-group and Bcl-2 mRNA expression in H-group showed a significant decrease （p〈0.05） compared with that in M-group. On the other hand, mRNA expression of Bax significant increased （p〈0.05,p〈0.01） in M-group and H-group than that in the control group. The ratio of Bcl-2/Bax significantly reduced 07〈0.05, p〈0.01） in the treated group than that in the control group and was found to be an obvious dose-dependent. It demonstrated that the gnssypol could induce the changes on ultrastructure of mice testis, down-regulate mRNA expression of Bcl-2 and up-regnlate mRNA expression of Bax, which indicated that sperm ceils were induced apoptosis.
文摘The serum levels of IL-12 and IL-10 in mice after infected with Babesia microti （B. microti） and Babesia rodhaini （B. rodhaini） were examined. Collected the mice serum and examined the concentration of IL-12 and IL-10 by using ELISA after infection with B. microti and B. rodhaini at 0, 3, 6, 9, 12, 18, 24, 36, 72, 96 h in mice. The results showed that B. microti infection resulted in IL-12 increasing, which peaked at 3 and 24 h after the infection, while same infection did not induce a significant change in IL-10 compared to uninfected mice. When mice were infected with B. rodhaini, any significant changes were not decteted both in IL-12 and IL-10 in comparison with uninfected animals during the period of 3-72 h after infection. Instead, a significant decline in IL-12 and IL-10 was found compared to uninfected mice 96 h after infection with B. rodhaini. It indicates that the mutagenetic cytokine is IL-12 in the serum of mice after infection with B. microti, and no any significant changes were detected in both IL-12 and IL-10 from 0 to 72 h after infected with B. rodhaini.
基金National Natural Sciences Foundation of China(8147320081673420)CAMS InnovationFund for Medical Sciences (2017-I2M-2-004).
文摘OBJECTIVE To study the protective effect of potassium 2-(l-hydroxypentyl)-benzoate(PHPB) on hippocampal neurons,synapses and dystrophic axons in APP/PS1 mice.METHODS Ten-month-old male APP/PS1 transgenic mice and age-matched wild-type mice were randomly divided into three groups:wild-type group(WT Con group,n=10),APP/PS1 group(Tg Con group,n=10) and PHPB treated APP/PS1 group(PHPB group,n=10).PHPB group received 30 mg · kg-1 PHPB by oral gavage once daily for 3 months.WT Con group and Tg Con group received the same volume of water.Three months later,mice were sacrificed for biochemical and pathological testing such as transmission electron microscopy,Golgi staining and Western boltting analysis.RESULTS Under the transmission electron microscope,most hippocampal neurons and subcel ular organel es in WT Con group exhibited normal morphology.However,the degenerative changes were observed in Tg Con group such as nuclear fragmentation,mitochondrial swelling,ribosomes detachment and autophagic vacuoles accumulation.The hippocampal synapses number and the thickness of postsynaptic density(PSD) were significantly decreased in Tg Con group compared with the WT Con group(P<0.05).After PHPB treatment,the degenerative changes in APP/PS1 mice were alleviated to some extent.The synapse number has been elevated significantly(P<0.05) and the PSD has been thickened as well.Golgi staining showed that the spine density of secondary and tertiary apical dendritic branches was significantly decreased in CA1 and DG areas of Tg Con group(P<0.05).Sholl analysis revealed a decrease of dendritic complexity in Tg Con group compared with WT Con group(P<0.05).These abnormalities were alleviated to some extent after PHPB treatment.Western blotting study showed that the protein levels of synaptic marker PSD-95 and synaptophysin were significantly decreased in the hippocampus of Tg Con group(P<0.05).A significant increase of PSD-95(P<0.05) and a slight increase of SYP were observed after the PHPB treatment.Besides,we found a significant increase in the ratio of LC3-Ⅱ/LC3-Ⅰ in Tg Con group compared with the WT Con group(P<0.01) and the relevant improvement after PHPB treatment(P<0.05),which showed the regulatory effect of PHPB on autophagy impairment.CONCLUSION PHPB showed protective effects on hippocampal neurons,synapses and dystrophic axons in APP/PS1 mice,which might help explain its role on cognitive improvement in Alzheimer disease treatment.
基金The project supported by National Science and Technology Major Project(2013ZX09103001-008,2013ZX09402203)the National Natural Science Foundation of China(81573645)
文摘OBJECTIVE To explore whether J24924could prevent the development of pristane-induced lupus in a mouse model,and whether it could protect renal and lower the cardiovascular risk.METHODS The effect of J24924 was assessed in female BALB/c mice intraperitoneal injected with 0.5 m L of pristane,and serum autoantibodies were tested every month,blood pressure wasmeasured every 2 months,while serum inflammatory markers,spleen pathologic characteristics,renal injury and vascular function were observed at 6 month.RESULTS J24924 could decrease serum autoantibodies and serum inflammatory markers in the SLE mice and improved the spleen pathologic characteristics,and at the same time improved the renal injury and decreased inflammatory responses in kidneys,reduced blood pressure and improved vascular endothelial function.Western blotting assays revealed that inhibition for the activation of NF-κB and Rho/ROCKs signaling pathways and the downstream signaling molecules might be the potential mechanisms of J24924.CONCLUSION Our findings suggestthat therapy of J24924 may be a strategy to prevent SLE and ameliorate associated kidney and cardiovascular complications.
文摘Tisplatin is one of the valuable icancer agents against several types of neoplasm. However, nephrotoxicity is the major adverse effect representing in cisplatin therapy. In this study, the animal tests detecting protective effects of a natural compound, Decursin, on cisplatin-induced nephrotoxicity were examined by using in vivo model. Pretreatment Decursin 10, 20 and 40 mg · kg^-1 at 48, 24 and 6 h, and administration of a single dose of Cisplatin 5.2 mg · kg^-1. Nephrotoxicity was evaluated by serum BUN and creatinine examination. There was significant difference in body weights, serum BUN and creatinine levels of the normal group. Based on the new understanding of the protective mechanisms of cisplatin-induced nephrotocivity, new strategies can be developed to prevent renal injury or to enhance recovery after cisplatin treatment.
基金The project supported by National Natural Sciences Foundation of China(81373407)the Natural Science Foundation of Fujian Province(2016D018)
文摘OBJECTIVE Propane-2-sulfonic acid octadec-9-enyl-amide(N15),an analogue of oleoylethanolamide(OEA),is a novel PPARα/γdual agonist.Our previous studies verified the positive effects of OEA on the acute and delayed stages of cerebral ischaemia.However,it is not clear whether N15 is effective against ischaemic cerebral injury.In the present study,male Kunming mice were subjected to middle cerebral artery occlusion(MCAO).METHODS To evaluate its preventive effects,N15(50,100 or 200 mg·kg-1,ip)was administered for3 d before ischaemia.To evaluate its therapeutic effects,N15(200 mg·kg-1,ip)was administered 1 h before reperfusion or 0,1,2 or 4 h after reperfusion.Neurological deficit scores,infarct volume and the degree of brain oedema were determined at 24 h after reperfusion.Blood brain barrier(BBB)disruption was evaluated by Evans blue(EB)leakage at 6 h after reperfusion.The activation/inflammatory responses of microglia were detected using immunohistochemistry and Western blotting.RESULTS N15 pretreatment improved neurological dysfunction,reduced infarct volume and alleviated brain oedema in a dose-dependent manner;the most effective dose was 200 mg·kg-1.The therapeutic time window was within 2 h after reperfusion.Moreover,N15was more potent in the treatment of cerebral ischaemia injury than OEA.N15 treatment preserved the BBB integrity and suppressed the activation of microglia.N15 inhibited inflammatory cytokine expression not only in MCAO mice but also in lipopolysaccharide(LPS)-stimulated BV-2microglial cells.Moreover,N15 decreased the phosphorylation levels of NF-κBp65,STAT3,and ERK1/2 both in vivo and in vitro.CONCLUSION Our findings demonstrated that N15 exerts neuroprotective effects and was more potent than OEA.Additionally,the neuroprotective effects of N15 on cerebral ischaemia may be attributed to its anti-inflammatory properties,at least in part,by enhancing PPARα/γdual signalling and inhibiting the activation of the NF-κB,STAT3,and ERK1/2 signalling pathways.These findings suggest that N15 may be a potential therapeutic choice for the prevention and treatment of ischaemic stroke.
文摘Aim To study the influence of SiniSan on the Tryptophan- kynurenine（TRP-KYN）pathway, the activity and content of the key metabolism enzyme indoleamine2, 3-dioxygenase （IDO）. Methods The mice model was established by intraperitoneal injection LPS （ 1 mg · kg^-1 ）. Using ELISA to detect the contents of IFN-γin serum. The content of Tryptophan and kynurenine in brain tissue were detected by using HPLC-MS/MS technique. The mRNA expression level of IDO in brain tissue was detected by using real-time PCR. Results 4 hours after the LPS injection, the immobility time of model group mice prolonged. The content of IFN-~/in serum increased significantly （P 〈 0.05）. Meanwhile, the activity of IDO in brain tissue and the mRNA expression level of IDO increased. SiniSan could short the immobility time of mice, reduced the content of IFN-γin serum （P 〈 0.05）. It could also inhibit the activity of IDO and the expression of mRNA（P 〈 0.01 ）. Conclusion SiniSan blocks the pathway of IDO activation, inhibit the activity of IDO and reduce the content of it. SiniSan produces antidepressant effect by adjusting the TRP-KYN metabolism.
文摘Aim Some indirect evidences indicate a possible correlation between oxidative stress and motion sick- ness. The aim of this research was to investigate whether oxidative stress contributing to motion sickness in mice or not. Methods We examined the mRNA levels of peroxiredoxin 6 （PRDX6） , catalase and enzyme superoxide dis- mutase 1 （SOD1）; reactive oxygen species （ROS）; total antioxidant capacity and SOD activity in different brain regions after rotary stimulation. Mice motion sickness index was recorded after rotation when pretreated with pa- raquat, vitamin C or vitamin E. Results The R0S level and antioxidant capacity were both increased in cerebel- lum plus brainstem （CB） after rotation, a critical region determines motion sickness. However, manipulation of ox- idants or antioxidants using pharmacological method in vivo had no influence on motion sickness index in mice. Conclusion Oxidative stress is not involved in the development of motion sickness in mice.
文摘Objective To clarify the differences in cardiac structure,cardiac function,and myocardial metabolism in type 2 diabetes mellitus mice with obesity or non-obesity and to elucidate the key molecular mechanisms leading to this difference.Methods Db/db mice and low-dose STZ injection combined with HFD-induced diabetes mellitus mice were used in this study as the model of type 2 diabetes mellitus with obesity or non-obesity.
文摘OBJECTIVE To evaluate whether ginsenoside Rb1 has antiepileptic effects on pen⁃tylenetetrazole(PTZ)-induced epileptic mice via intranasal therapeutic administration.METHODS Rb1 monoclonal antibody was used to observe the distribution of Rb120 mg·kg-1 in mouse brain tissues under different administration routes and to explore the feasibility of intranasal Rb1.PTZ was injected intraperitoneally into healthy ICR mice every 48 hours to construct a tonic-clonic epileptic model.Then Rb120 or 40 mg·kg-1 or valproate 300 mg·kg-1 or saline was administered intranasally for 30 d,and PTZ was continued every five days to imitate occa⁃sional convulsions in the clinic.Racine scale(RCS)and wireless electroencephalogram(EEG)monitoring were used to assess the presence and severity of seizure.Immunofluorescence(IF)was performed after drug treatment to evalu⁃ate the effect of Rb1 on brain neuron,microglia and astrocyte in epileptic mice.RESULTS Rb1 had specific binding with anti-Rb1 in the brain under different administration routes,and intrana⁃sal Rb1 was able to enter the brain and play a therapeutic role(P<0.01).PTZ-injured mice pre⁃sented body mass loss,higher seizure stage and shorter seizure latency.At the same time,epilep⁃tic waves,mainly spikes,were detected by wire⁃less EEG.Compared with PTZ group,intranasal Rb1 increased mice weight(P<0.01)and seizure latency(P<0.05),reduced seizure stage(P<0.01)and EEG spikes.In addition,Rb1 significantly reduced neuron loss(P<0.01)indicated by NeuN staining and decreased the number of acti⁃vated microglia(P<0.01)indicated by Iba-1 staining in the cortex and CA1 area of hippocam⁃pus.Moreover,Rb1 reduced the decrease of GLT-1 and GS expression(P<0.05)induced by PTZ.CONCLUTION Intranasal Rb1 has anti-epi⁃leptic effects on PTZ mice.Moreover,Intranasal Rb1 affects the functions of neurons,astrocytes and microglia through regulating the expression of GLT and GS in astrocytes,which may be related to its anti-epileptic effect.
