Drug addiction, a disorder characterized by chronic relapse and compulsive drug use, poses a significant threat to public safety and human health. Addictive substances can be categorized as natural, semi-synthetic, or...Drug addiction, a disorder characterized by chronic relapse and compulsive drug use, poses a significant threat to public safety and human health. Addictive substances can be categorized as natural, semi-synthetic, or synthetic based on their origin. Additionally, they can be classified into three groups according to their pharmacological targets: opioids, hallucinogens, and cannabinoids that act on G-protein-coupled receptors (GPCRs);alcohols, nicotine, ketamine, barbiturates, and benzodiazepines (BDZs) that affect ligand-gated ion channel-type receptors;and psychostimulants that interact with monoamine transporters. Current treatments for drug addiction primarily include substitution therapy and non-pharmacological approaches. However, these methods have limitations, particularly in addressing the underlying causes of relapse. Several drugs in clinical trials have demonstrated potential therapeutic effects for addiction to opioids, heroin, cocaine, and other substances. This review examines the origins and pharmacological mechanisms of addiction to naturally-derived psychoactive substances (NPS) and provides an overview of recent advancements in pharmacotherapy for drug addiction.展开更多
Carbon-based perovskite solar cells(C-PSCs)exhibit notable stability and durability.However,the power conversion efficiency(PCE)is significantly hindered by energy level mismatches,which result in interfacial charge t...Carbon-based perovskite solar cells(C-PSCs)exhibit notable stability and durability.However,the power conversion efficiency(PCE)is significantly hindered by energy level mismatches,which result in interfacial charge transport barriers at the electrode-related interfaces.Herein,we report a back electrode that utilizes atomically dispersed metallic cobalt(Co)in carbon nanosheets(Co_1/CN)to adjust the interfacial energy levels.The electrons in the d-orbitals of Co atoms disrupt the electronic symmetry of the carbon nanosheets(CN),inducing a redistribution of the electronic density of states that leads to a downward shift in the Fermi level and a significantly reduced interfacial energy barrier.As a result,the C-PSCs using Co1/CN as back electrodes achieve a notable PCE of 22.61%with exceptional long-term stability,maintaining 94.4%of their initial efficiency after 1000 h of continuous illumination without encapsulation.This work provides a promising universal method to regulate the energy level of carbon electrodes for C-PSCs and paves the way for more efficient,stable,and scalable solar technologies toward commercialization.展开更多
Wastewater-based epidemiology has emerged as a transformative surveillance tool for estimating substance consumption and monitoring disease prevalence,particularly during the COVID-19 pandemic.It enables the populatio...Wastewater-based epidemiology has emerged as a transformative surveillance tool for estimating substance consumption and monitoring disease prevalence,particularly during the COVID-19 pandemic.It enables the population-level monitoring of illicit drug use,pathogen prevalence,and environmental pollutant exposure.In this perspective,we summarize the key challenges specific to the Chinese context:(1)Sampling inconsistencies,necessitating standardized 24-hour composite protocols with high-frequency autosamplers(≤15 min/event)to improve the representativeness of samples.展开更多
In this study,we developed a novel on-line solid phase extraction(SPE)-ultra-high-performance liquid chromatography tandem mass spectrometry(UHPLC-MS/MS)-based analytical method for simultaneously quantifying 12 illic...In this study,we developed a novel on-line solid phase extraction(SPE)-ultra-high-performance liquid chromatography tandem mass spectrometry(UHPLC-MS/MS)-based analytical method for simultaneously quantifying 12 illicit drugs and metabolites(methamphetamine,amphetamine,morphine,codeine,6-monoacetylmorphine,benzoylecgonine,3,4-methylenedioxymethamphetamine,3,4-methylenedioxyamphetamine,cocaine,ketamine,norketamine,and methcathinone)and cotinine(COT)in wastewater samples.The analysis was performed by loading 2 m L of the sample onto an Oasis hydrophilic-lipophilic balance cartridge and using a cleanup step(5%methanol)to eliminate interference with a total run time of 13 min.The isotope-labeled internal standard method was used to quantify the target substances and correct for unavoidable losses and matrix effects during the on-line SPE process.Typical analytical characteristics used for method validation were sensitivity,linearity,precision,repeatability,recovery,and matrix effects.The limit of detection(LOD)and limit of quantification(LOQ)of each target were set at 0.20 ng/L and 0.50 ng/L,respectively.The linearity was between 0.5 ng/L and250 ng/L,except for that of COT.The intra-and inter-day precisions were<10.45%and 25.64%,respectively,and the relative recovery ranged from 83.74%to 162.26%.The method was used to analyze various wastewater samples from 33 cities in China,and the results were compared with the experimental results of identical samples analyzed using off-line SPE.The difference rate was between 19.91%and-20.44%,and the error range could be considered acceptable.These findings showed that on-line SPE is a suitable alternative to off-line SPE for the analysis of illicit drugs in samples.展开更多
AIM: To explore the approaches exerted by mesenchymal stem cells (MSCs) to improve Parkinson’s disease (PD) pathophysiology.METHODS: MSCs were harvested from bone marrow of femoral bones of male rats, grow...AIM: To explore the approaches exerted by mesenchymal stem cells (MSCs) to improve Parkinson’s disease (PD) pathophysiology.METHODS: MSCs were harvested from bone marrow of femoral bones of male rats, grown and propagated in culture. Twenty four ovariectomized animals were classified into 3 groups: Group (1) was control, Groups (2) and (3) were subcutaneously administered with rotenone for 14 d after one month of ovariectomy for induction of PD. Then, Group (2) was left untreated, while Group (3) was treated with single intravenous dose of bone marrow derived MSCs (BM-MSCs). SRY gene was assessed by PCR in brain tissue of the female rats. Serum transforming growth factor beta-1 (TGF-β1), monocyte chemoattractant protein-1 (MCP-1) and brain derived neurotrophic factor (BDNF) levels were assayed by ELISA. Brain dopamine DA level was assayed fluorometrically, while brain tyrosine hydroxylase (TH) and nestin gene expression were detected by semi-quantitative real time PCR. Brain survivin expression was determined by immunohistochemical procedure. Histopathological investigation of brain tissues was also done.RESULTS: BM-MSCs were able to home at the injured brains and elicited significant decrease in serum TGF-β1 (489.7 ± 13.0 vs 691.2 ± 8.0, P < 0.05) and MCP-1 (89.6 ± 2.0 vs 112.1 ± 1.9, P < 0.05) levels associated with significant increase in serum BDNF (3663 ± 17.8 vs 2905 ± 72.9, P < 0.05) and brain DA (874 ± 15.0 vs 599 ± 9.8, P < 0.05) levels as well as brain TH (1.18 ± 0.004 vs 0.54 ± 0.009, P < 0.05) and nestin (1.29 ± 0.005 vs 0.67 ± 0.006, P < 0.05) genes expression levels. In addition to, producing insignificant increase in the number of positive cells for survivin (293.2 ± 15.9 vs 271.5 ± 15.9, P > 0.05) expression. Finally, the brain sections showed intact histological structure of the striatum as a result of treatment with BM-MSCs.CONCLUSION: The current study sheds light on the therapeutic potential of BM-MSCs against PD pathophysiology via multi-mechanistic actions.展开更多
Methamphetamine is one of the most prevalent drugs abused in the world.Methamphetamine abusers usually present with hyperpyrexia (39℃),hallucination and other psychiatric symptoms.However,the detailed mechanism under...Methamphetamine is one of the most prevalent drugs abused in the world.Methamphetamine abusers usually present with hyperpyrexia (39℃),hallucination and other psychiatric symptoms.However,the detailed mechanism underlying its neurotoxic action remains elusive.This study investigated the effects of methamphetamine + 39℃ on primary cortical neurons from the cortex of embryonic Sprague-Dawley rats.Primary cortex neurons were exposed to 1 mM methamphetamine + 39℃.Propidium iodide staining and lactate dehydrogenase release detection showed that methamphetamine + 39℃ triggered obvious necrosis-like death in cultured primary cortical neurons,which could be partially inhibited by receptor-interacting protein-1 (RIP1) inhibitor Necrostatin-1 partially.Western blot assay results showed that there were increases in the expressions of receptor-interacting protein-3 (RIP3) and mixed lineage kinase domain-like protein (MLKL) in the primary cortical neurons treated with 1 mM methamphetamine + 39℃ for 3 hours.After pre-treatment with RIP3 inhibitor GSK’872,propidium iodide staining and lactate dehydrogenase release detection showed that neuronal necrosis rate was significantly decreased;RIP3 and MLKL protein expression significantly decreased.Immunohistochemistry staining results also showed that the expressions of RIP3 and MLKL were up-regulated in brain specimens from humans who had died of methamphetamine abuse.Taken together,the above results suggest that methamphetamine + 39℃ can induce RIP3/MLKL regulated necroptosis,thereby resulting in neurotoxicity.The study protocol was approved by the Medical Ethics Committee of the Third Xiangya Hospital of Central South University,China (approval numbers: 2017-S026 and 2017-S033) on March 7,2017.展开更多
Objective: To study the effect of citric acid given alone or combined with atropine on brain oxidative stress, neuronal injury, liver damage, and DNA damage of peripheral blood lymphocytes induced in the rat by acute ...Objective: To study the effect of citric acid given alone or combined with atropine on brain oxidative stress, neuronal injury, liver damage, and DNA damage of peripheral blood lymphocytes induced in the rat by acute malathion exposure. Methods: Rats were received intraperitoneal(i.p.) injection of malathion 150 mg/kg along with citric acid(200 or 400 mg/kg, orally), atropine(1 mg/kg, i.p.) or citric acid 200 mg/kg+atropine 1 mg/kg and euthanized 4 h later. Results: Malathion resulted in increased lipid peroxidation(malondialdehyde) and nitric oxide concentrations accompanied with a decrease in brain reduced glutathione, glutathione peroxidase(GPx) activity, total antioxidant capacity(TAC) and glucose concentrations. Paraoxonase-1, acetylcholinesterase(ACh E) and butyrylcholinesterase activities decreased in brain as well. Liver aspartate aminotransferase and alanine aminotransferase activities were raised. The Comet assay showed increased DNA damage of peripheral blood lymphocytes. Histological damage and increased expression of inducible nitric oxide synthase(i NOS) were observed in brain and liver. Citric acid resulted in decreased brain lipid peroxidation and nitric oxide. Meanwhile, glutathione, GPx activity, TAC capacity and brain glucose level increased. Brain ACh E increased but PON1 and butyrylcholinesterase activities decreased by citric acid. Liver enzymes, the percentage of damaged blood lymphocytes, histopathological alterations and i NOS expression in brain and liver was decreased by citric acid. Meanwhile, rats treated with atropine showed decreased brain MDA, nitrite but increased GPx activity, TAC, ACh E and glucose. The drug also decreased DNA damage of peripheral blood lymphocytes, histopathological alterations and i NOS expression in brain and liver. Conclusions: The study demonstrates a beneficial effect for citric acid upon brain oxidative stress, neuronal injury, liver and DNA damage due to acute malathion exposure.展开更多
In this study, concentrations of Cr, Mn, Ni, Cu, Zn, Cd and Pb were determined in road dusts collected from different locations in Dhaka to assess source, contamination status and health risk. Energy-dispersive X-ray ...In this study, concentrations of Cr, Mn, Ni, Cu, Zn, Cd and Pb were determined in road dusts collected from different locations in Dhaka to assess source, contamination status and health risk. Energy-dispersive X-ray fluorescence spectroscopy and energy-dispersive X-ray spectroscopy were used to determine Cr, Mn, Ni, Cu, Zn, Cd and Pb and their mean concentrations were 162.27 ± 29.46, 721.18 ± 180.14, 35.65 ± 12.55, 104.56 ± 128.33, 515.32 ± 321.90,BDL, and 342.82 ± 591.20 mg/kg, respectively. Among the heavy metals, highest concentrations of Cu, Zn and Pb were found at urban sites-7(municipal waste dumping) and 8(medical waste incineration). Highest concentration of Cr followed by Cu and Zn was found at site-5(Tejgaon, urban). Principal component analysis revealed that anthropogenic activities are the potential sources for Cr, Ni, Cu, Zn and Pb while earth crust for Mn. Pollution index and pollution load index results suggested that all the sites were contaminated and/or degraded by Cr, Cu, Zn and Pb except sites-9(urban), 10(sub-urban), 11(rural) while sites-7 and 8(urban) were extremely degraded. For noncarcinogenic health risk, hazard quotient values for dermal were higher compared to that of inhalation/ingestion. Though hazard index values were less than 1 at all the sites, these were at least one order of magnitude higher for children group than that of adult group, thus the children group may face more noncarcinogenic health risk at sites -7 and 8. Values of incremental lifetime cancer risk were from 10to 10showed no carcinogenic health risk by road dusts contaminated with the heavy metals.展开更多
Objective:To investigate the effect of two extracts of Bougainvillea spectabilis(B. spectabilis) flowers with yellow and pink/purple on brain oxidative stress and neuronal damage caused in rats by systemic rotenone in...Objective:To investigate the effect of two extracts of Bougainvillea spectabilis(B. spectabilis) flowers with yellow and pink/purple on brain oxidative stress and neuronal damage caused in rats by systemic rotenone injection. Methods:Rotenone 1.5 mg/kg was given three times per week alone or in combination with B. spectabilis flowers extracts(25 mg or 50 mg) via the subcutaneous route for 2 weeks. Brain concentrations of the lipid peroxidation marker malondialdehyde(MDA),reduced glutathione,nitric oxide(nitrite),the pro-inflammatory cytokine interleukin-1beta(Il-1β) as well as butyrylcholinesterase,and paraoxonase-1(PON-1) activities,were determined. Histopathology and caspase-3 immunohistochemistry were also performed. Results:Rotenone resulted in significant increases of brain MDA(the product of lipid peroxidation),and nitric oxide content along with decreased brain reduced glutathione. There were also marked and significant inhibition of brain PON-1 and BCh E activities and increased Il-1β in brain of rotenone-treated rats. B. spectabilis flowers extract itself resulted in brain oxidative stress increasing both lipid peroxidation and nitrite content whilst inhibiting PON-1 activity. The yellow flowers extract inhibited BCh E activity and increased brain Il-1β. When given to rotenone-treated rats,B. spectabilis extracts,however,decreased lipid peroxidation while their low administered doses increased brain GSH. Brain nitrite decreased by the pink extract but showed further increase by the yellow extract. Either extract,however,caused further inhibition of PON-1 activity while the yellow extract resulted in further inhibition of BChE activity. Histopathological studies indicated that both extracts protected against brain,liver and kidney damage caused by the toxicant. Conclusions:These data indicate that B. spectabilis flowers extracts exert protective effect against the toxic effects of rotenone on brain,liver and kidney. B. spectabilis flowers extracts decreased brain lipid peroxidation and prevented neuronal death due to rotenone and might thus prove the value in treatment of Parkinson's disease.展开更多
Objective: To investigate the effect of the prostaglandin E1 analogue misoprostol on oxidative stress and neurodegeration caused by subcutaneous rotenone administration in rats. Methods:Rotenone was administered in a ...Objective: To investigate the effect of the prostaglandin E1 analogue misoprostol on oxidative stress and neurodegeration caused by subcutaneous rotenone administration in rats. Methods:Rotenone was administered in a dose of 1.5 mg/kg every other day for 2 weeks. Starting from the 1 st day of rotenone injection, rats were subcutaneously treated with misoprostol at doses of10, 100 or 1 000 μg/kg. Rats were evaluated for brain lipid peroxidation(malondialdehyde:MDA), reduced glutathione(GSH), nitric oxide(NO) levels, and paraoxonase-1(PON-1) activity.The concentrations of the anti-apoptotic protein B cell/lymphoma-2(Bcl-2) were determined in the striatum. Histopathologic examination and the expression of inducible nitric oxide synthase(iNOS) in the cerebral cortex and striatum were also performed. Results: Compared with the vehicle-treated group, rotenone caused a significant increase in brain lipid proxidation(MDA)by 61%(P<0.05) accompanied by an increase in NO by 73.1%(P<0.05) and a decrease in GSH concentration by 29.4%(P<0.05). In addition, brain PON-1 activity significantly decreased by63.0%(P<0.05) and striatal Bcl-2 significantly decreased by 27.9%(P<0.05) with respect to the corresponding control value. Brain sections from rotenone treated rats showed extensive dark pyknotic and apoptotic nuclei in neurons, shrunken cytoplasm and perineuronal vacuolation.Rotenone also caused pronounced expression of iNOS in the cerebral cortex and striatum.Treatment with misoprostol at doses of 100 and 1 000 μg/kg resulted in decreased brain MDA(by 16.5%-23.0%)(P<0.05) and NO levels(by 37.1%-40.7%)(P<0.05) and increased GSH concentrations(by 18.8%-30.1%)(P<0.05). PON-1 activity was significantly increased by80.0%-114.8%(P<0.05) by misoprostol at 100 and 1 000 μg/kg, respectively. In addition,misoprostol treatment restored striatal Bcl-2 concentrations to its normal value. Misoprostol treatment resulted in markedly reduced brain injury and decreased iNOS expression in the cerebral cortex and striatum of rotenone intoxicated rats. Conclusions: These data suggest that misoprostol prevents the rotenone-induced neurodegeneration in rat brain by reducing brain oxidative stress.展开更多
Objective:To determine the delta-9-tetrahydrocannabinol(THC)content of cannabis seizures in Egypt.Methods:Unheated and heated extracts of cannabis seizures were prepared from the dried flowering tops and leaves(mariju...Objective:To determine the delta-9-tetrahydrocannabinol(THC)content of cannabis seizures in Egypt.Methods:Unheated and heated extracts of cannabis seizures were prepared from the dried flowering tops and leaves(marijuana)or from the resin(hashish)and subjected to analysis using high performance liquid chromatography(HPLC).Results:The heated resin extract had the peak of THC in a relative ratio of 31.34%,while extracting the resin directly without heating contained only 18.34%of THC.On the other hand,marijuana showed minimum percentage of THC at 11.188% on heating and 9.55% without heating.Conclusions:These results indicate the high potency of the abused cannabis plant in the illicit Egyptian market.展开更多
Parkinson's disease(PD) is one of the most prevalent neurodegenerative diseases which typically affects individuals over 65 years. Although the symptomatology is predominantly motor, neuropsychiatric manifestation...Parkinson's disease(PD) is one of the most prevalent neurodegenerative diseases which typically affects individuals over 65 years. Although the symptomatology is predominantly motor, neuropsychiatric manifestations, e.g., depression, apathy, anxiety, and cognitive impairment occur in the course of the illness and can have a great impact on the quality of life in these patients. Parkinson's disease is commonly comorbid with depression with prevalence rates of depression, generally higher than those reported in general population. Depression in PD is frequently underestimated andconsequently undertreated, which have significant effects on the quality of life in these patients. The neurobiology of depression in PD is complex and involves alterations in dopaminergic, serotonergic, noradrenergic and possibly other neurotransmitter systems which are affected in the course of the disease. The tricyclic antidepressants and the selective serotonin reuptake inhibitors are the two classes of antidepressant drugs used for depressive symptoms in PD. Several published studies suggested that both classes are of comparable efficacy. Other serotonergic antidepressants, e.g., nefazodone and trazodone have also been of benefit. Meanwhile, there are limited data available on other drugs but these suggest a benefit from the serotonin and noradrenaline reuptake inhibitors such as mirtazapine, venlafaxine, atomoxetine and duloxetine. Some of the drugs used in symptomatic treatment of PD, e.g., the irreversible selective inhibitors of the enzyme monoamine oxidase-B, rasagiline and selegiline as well as the dopamine receptor agonist pramipexole are likely to have direct antidepressant activity independent of their motor improving action. This would make these drugs an attractive option in depressed subjects with PD. The aim of this review is to provide an updated data on the prevalence, clinical features of depression in subjects with PD. The effects of antiparkinsonian and antidepressant drugs on depressive symptoms in these patients are also discussed.展开更多
Objective Neonatal exposure to propofol has been reported to cause neurotoxicity and neurocognitive decline in adulthood;however,the underlying mechanism has not been established.Methods SD rats were exposed to propof...Objective Neonatal exposure to propofol has been reported to cause neurotoxicity and neurocognitive decline in adulthood;however,the underlying mechanism has not been established.Methods SD rats were exposed to propofol on postnatal day 7(PND-7).Double-immunofluorescence staining was used to assess neurogenesis in the hippocampal dentate gyrus(DG).The expression of pAkt and p27 were measured by western blotting.The Morris water maze,novel object recognition test,and object location test were used to evaluate neurocognitive function 2-month-old rats.Results Phosphorylation of Akt was inhibited,while p27 expression was enhanced after neonatal exposure to propofol.Propofol also inhibited proliferation of neural stem cells(NSCs)and decreased differentiation to neurons and astroglia.Moreover,the neurocognitive function in 2-month-old rats was weakened.Of significance,intra-hippocampal injection of the Akt activator,SC79,attenuated the inhibition of p-AKT and increase of p27 expression.SC79 also rescued the propofol-induced inhibition of NSC proliferation and differentiation.The propofol-induced neurocognition deficit was also partially reversed by SC79.Conclusion Taken together,these results suggest that neurogenesis is hindered by neonatal propofol exposure.Specifically,neonatal propofol exposure was shown to suppress the proliferation and differentiation of NSCs by inhibiting Akt/p27 signaling pathway.展开更多
There had been no standardized rules for citing ethical Kampo products used in clinical trials in journal articles. Although the name of a Kampo manufacturer was described in 77.9% of research articles, the name and r...There had been no standardized rules for citing ethical Kampo products used in clinical trials in journal articles. Although the name of a Kampo manufacturer was described in 77.9% of research articles, the name and ratios of crude drug components of Kampo formulas were not described in 77.5% of these papers. Considering the importance of proper characterization of interventions in the Consolidated Standards of Reporting Trials (CONSORT) checklist, we hereby propose the use of the Standards of Reporting Kampo Products (STORK) website, http://mpdb.nibiohn.go.jp/stork, as a reference for Kampo products. This will provide an official source on the internet for verified information on individual Kampo formulations for citation purposes in clinical research articles.展开更多
We previously identified a unique nucleus,the cerebrospinal fluid(CSF)-contacting nucleus.This study aims to understand its gene architecture and preliminarily suggest its functions.The results showed that there were ...We previously identified a unique nucleus,the cerebrospinal fluid(CSF)-contacting nucleus.This study aims to understand its gene architecture and preliminarily suggest its functions.The results showed that there were about 19,666 genes in this nucleus,of which 913 were distinct from the dorsal raphe nucleus(non-CSF contacting).The top 40 highly-expressed genes are mainly related to energy metabolism,protein synthesis,transport,secretion,and hydrolysis.The main neurotransmitter is 5-HT.The receptors of 5-HT and GABA are abundant.The channels for Cl–,Na+,K+,and Ca2+are routinely expressed.The signaling molecules associated with the CaMK,JAK,and MAPK pathways were identified accurately.In particular,the channels of transient receptor potential associated with nociceptors and the solute carrier superfamily members associated with cell membrane transport were significantly expressed.The relationship between the main genes of the nucleus and life activities is preliminarily verified.展开更多
Microglia-mediated neuroinflammation is considered a pathological feature of Parkinson's disease.Triggering receptor expressed on myeloid cell-1(TREM-1)can amplify the inherent immune response,and crucially,regula...Microglia-mediated neuroinflammation is considered a pathological feature of Parkinson's disease.Triggering receptor expressed on myeloid cell-1(TREM-1)can amplify the inherent immune response,and crucially,regulate inflammation.In this study,we found marked elevation of serum soluble TREM-1 in patients with Parkinson's disease that positively correlated with Parkinson's disease severity and dyskinesia.In a mouse model of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinson's disease,we found that microglial TREM-1 expression also increased in the substantia nigra.Further,TREM-1 knockout alleviated dyskinesia in a mouse model of Parkinson's disease and reduced dopaminergic neuronal injury.Meanwhile,TREM-1 knockout attenuated the neuroinflammatory response,dopaminergic neuronal injury,and neutrophil migration.Next,we established an in vitro 1-methyl-4-phenyl-pyridine-induced BV2 microglia model of Parkinson's disease and treated the cells with the TREM-1 inhibitory peptide LP17.We found that LP17 treatment reduced apoptosis of dopaminergic neurons and neutrophil migration.Moreover,inhibition of neutrophil TREM-1 activation diminished dopaminergic neuronal apoptosis induced by lipopolysaccharide.TREM-1 can activate the downstream CARD9/NF-κB proinflammatory pathway via interaction with SYK.These findings suggest that TREM-1 may play a key role in mediating the damage to dopaminergic neurons in Parkinson's disease by regulating the interaction between microglia and peripheral neutrophils.展开更多
In traditional Chinese medicine(TCM),Euphorbia fischeriana Steud(E.fischeriana)and Euphorbia ebracteolata Hayata(E.ebracteolata),commonly referred to as“Langdu”,are widely extensively utilized for treating lymphatic...In traditional Chinese medicine(TCM),Euphorbia fischeriana Steud(E.fischeriana)and Euphorbia ebracteolata Hayata(E.ebracteolata),commonly referred to as“Langdu”,are widely extensively utilized for treating lymphatic tuberculosis and ringworm[1].Both plant species are perennial herbaceous plants mainly distributed in northeastern China,Mongolia,Russia(Siberia),and Republic of Korea[2].There have been many reports on the chemical constituents and pharmacological effects of the two plant species,which has made more and more researchers realize that there may be differences between E.fischeriana and E.ebracteolata.In some cases,long-term improper use of herbal medicines can even lead to life-threatening conditions[3,4].Therefore,it is essential to employ an effective technology to differentiate between these two plants based on their chemical constituents and biological activities,so as to reduce the harm caused by the mixing and misuse of medicinal materials.Therefore,the present paper describes a study of the differences between E.ebracteolata and E.fischeriana,using untargeted plant metabolomics and biological activity evaluations.This study aims to provide valuable insight into their equivalence and potential interchangeability in TCM and clinical medication.展开更多
2,6-Dichloro-1,4-benzoquinone(2,6-DCBQ), an emerging water disinfection by-product, is widely detected in water resources. However, its potential effects on the reproductive system are largely unknown. Here, we invest...2,6-Dichloro-1,4-benzoquinone(2,6-DCBQ), an emerging water disinfection by-product, is widely detected in water resources. However, its potential effects on the reproductive system are largely unknown. Here, we investigated the long-term effects of 2,6-DCBQ on gonadal development by exposing zebrafish from 15 to 180 days postfertilization(dpf). Following exposure to 2,6-DCBQ(20 and 100 μg/L), female-specific effects including delayed puberty onset, retarded ovarian growth and breakdown of the zona radiata were observed, resulting in subfertility in adult females. Adverse effects in folliculogenesis disappeared two months after cessation of 2,6-DCBQ administration. In contrast, no adverse impacts were noted in male testes. The effects on females were associated with significant reduction in 17 β-estradiol(E2) level, suggesting a role for 2,6-DCBQ in anti-estrogenic activity. E2 level change in blood was further supported by dysregulated expression of genes( cyp19a1a, fshb, kiss3, esr2b, vtg1, and vtg3) related to the hypothalamic-pituitary-gonad-liver(HPGL) axis. The present study demonstrates for the first time that 2,6-DCBQ induces reproductive impairments in female zebrafish through disrupting 17 β-estradiol level.展开更多
Dear Editor,Depending on the perceived threat in the environment,organisms can express a broad spectrum of behaviors,ranging from exploration to defensive behaviors[1,2],such as fear response and avoidance.Generalizat...Dear Editor,Depending on the perceived threat in the environment,organisms can express a broad spectrum of behaviors,ranging from exploration to defensive behaviors[1,2],such as fear response and avoidance.Generalization of fear memory can generate anxiety-related disorders that afflict 10%-30%of individuals worldwide,especially during the epidemic situation[3,4].展开更多
Cannabis sativa has long been known for its psychotropic effect. Only recently with the discovery of the cannabinoid receptors, their endogenous legends and the enzymes responsible for their synthesis and degradation,...Cannabis sativa has long been known for its psychotropic effect. Only recently with the discovery of the cannabinoid receptors, their endogenous legends and the enzymes responsible for their synthesis and degradation, the role of this ‘endocannabinoid system’ in different pathophysiologic processes is beginning to be delineated. There is evidence that CB1 receptor stimulation with synthetic cannabinoids or Cannabis sativa extracts rich in ?9-tetrahydrocannabinol inhibit gastric acid secretion in humans and in experimental animals. This is specially seen when gastric acid secretion is stimulated by pentagastrin, carbachol or 2 deoxy-D-glucose. Cannabis and/or cannabinoids protect the gastric mucosa against noxious challenge with non-steroidal anti-inflammatory drugs, ethanol as well as against stress induced mucosal damage. Cannabis/cannabinoids might protect the gastric mucosa by virtue of its antisecretory, antioxidant, anti-inflammatory, and vasodilator properties.展开更多
基金supported by the National Natural Science Foundation of China(No.82373836).
文摘Drug addiction, a disorder characterized by chronic relapse and compulsive drug use, poses a significant threat to public safety and human health. Addictive substances can be categorized as natural, semi-synthetic, or synthetic based on their origin. Additionally, they can be classified into three groups according to their pharmacological targets: opioids, hallucinogens, and cannabinoids that act on G-protein-coupled receptors (GPCRs);alcohols, nicotine, ketamine, barbiturates, and benzodiazepines (BDZs) that affect ligand-gated ion channel-type receptors;and psychostimulants that interact with monoamine transporters. Current treatments for drug addiction primarily include substitution therapy and non-pharmacological approaches. However, these methods have limitations, particularly in addressing the underlying causes of relapse. Several drugs in clinical trials have demonstrated potential therapeutic effects for addiction to opioids, heroin, cocaine, and other substances. This review examines the origins and pharmacological mechanisms of addiction to naturally-derived psychoactive substances (NPS) and provides an overview of recent advancements in pharmacotherapy for drug addiction.
基金supported by the National Natural Science Foundation of China(22109019,52272193)Fundamental Research Funds for the Central Universities(DUT22LAB602,DUT23RC(3)002)。
文摘Carbon-based perovskite solar cells(C-PSCs)exhibit notable stability and durability.However,the power conversion efficiency(PCE)is significantly hindered by energy level mismatches,which result in interfacial charge transport barriers at the electrode-related interfaces.Herein,we report a back electrode that utilizes atomically dispersed metallic cobalt(Co)in carbon nanosheets(Co_1/CN)to adjust the interfacial energy levels.The electrons in the d-orbitals of Co atoms disrupt the electronic symmetry of the carbon nanosheets(CN),inducing a redistribution of the electronic density of states that leads to a downward shift in the Fermi level and a significantly reduced interfacial energy barrier.As a result,the C-PSCs using Co1/CN as back electrodes achieve a notable PCE of 22.61%with exceptional long-term stability,maintaining 94.4%of their initial efficiency after 1000 h of continuous illumination without encapsulation.This work provides a promising universal method to regulate the energy level of carbon electrodes for C-PSCs and paves the way for more efficient,stable,and scalable solar technologies toward commercialization.
基金supported by the National Natural Science Foundation of China(Grant no.42307534)Discovery Project(DP220101790)+1 种基金The University of Queensland ScholarshipAustralian Research Council Discovery Project(DP220101790).
文摘Wastewater-based epidemiology has emerged as a transformative surveillance tool for estimating substance consumption and monitoring disease prevalence,particularly during the COVID-19 pandemic.It enables the population-level monitoring of illicit drug use,pathogen prevalence,and environmental pollutant exposure.In this perspective,we summarize the key challenges specific to the Chinese context:(1)Sampling inconsistencies,necessitating standardized 24-hour composite protocols with high-frequency autosamplers(≤15 min/event)to improve the representativeness of samples.
基金supported by the National Key Research and Development Program of China(Grant No.:2018YFC0807402)the National Natural Science Foundation of China(Grant No.:82073810)。
文摘In this study,we developed a novel on-line solid phase extraction(SPE)-ultra-high-performance liquid chromatography tandem mass spectrometry(UHPLC-MS/MS)-based analytical method for simultaneously quantifying 12 illicit drugs and metabolites(methamphetamine,amphetamine,morphine,codeine,6-monoacetylmorphine,benzoylecgonine,3,4-methylenedioxymethamphetamine,3,4-methylenedioxyamphetamine,cocaine,ketamine,norketamine,and methcathinone)and cotinine(COT)in wastewater samples.The analysis was performed by loading 2 m L of the sample onto an Oasis hydrophilic-lipophilic balance cartridge and using a cleanup step(5%methanol)to eliminate interference with a total run time of 13 min.The isotope-labeled internal standard method was used to quantify the target substances and correct for unavoidable losses and matrix effects during the on-line SPE process.Typical analytical characteristics used for method validation were sensitivity,linearity,precision,repeatability,recovery,and matrix effects.The limit of detection(LOD)and limit of quantification(LOQ)of each target were set at 0.20 ng/L and 0.50 ng/L,respectively.The linearity was between 0.5 ng/L and250 ng/L,except for that of COT.The intra-and inter-day precisions were<10.45%and 25.64%,respectively,and the relative recovery ranged from 83.74%to 162.26%.The method was used to analyze various wastewater samples from 33 cities in China,and the results were compared with the experimental results of identical samples analyzed using off-line SPE.The difference rate was between 19.91%and-20.44%,and the error range could be considered acceptable.These findings showed that on-line SPE is a suitable alternative to off-line SPE for the analysis of illicit drugs in samples.
文摘AIM: To explore the approaches exerted by mesenchymal stem cells (MSCs) to improve Parkinson’s disease (PD) pathophysiology.METHODS: MSCs were harvested from bone marrow of femoral bones of male rats, grown and propagated in culture. Twenty four ovariectomized animals were classified into 3 groups: Group (1) was control, Groups (2) and (3) were subcutaneously administered with rotenone for 14 d after one month of ovariectomy for induction of PD. Then, Group (2) was left untreated, while Group (3) was treated with single intravenous dose of bone marrow derived MSCs (BM-MSCs). SRY gene was assessed by PCR in brain tissue of the female rats. Serum transforming growth factor beta-1 (TGF-β1), monocyte chemoattractant protein-1 (MCP-1) and brain derived neurotrophic factor (BDNF) levels were assayed by ELISA. Brain dopamine DA level was assayed fluorometrically, while brain tyrosine hydroxylase (TH) and nestin gene expression were detected by semi-quantitative real time PCR. Brain survivin expression was determined by immunohistochemical procedure. Histopathological investigation of brain tissues was also done.RESULTS: BM-MSCs were able to home at the injured brains and elicited significant decrease in serum TGF-β1 (489.7 ± 13.0 vs 691.2 ± 8.0, P < 0.05) and MCP-1 (89.6 ± 2.0 vs 112.1 ± 1.9, P < 0.05) levels associated with significant increase in serum BDNF (3663 ± 17.8 vs 2905 ± 72.9, P < 0.05) and brain DA (874 ± 15.0 vs 599 ± 9.8, P < 0.05) levels as well as brain TH (1.18 ± 0.004 vs 0.54 ± 0.009, P < 0.05) and nestin (1.29 ± 0.005 vs 0.67 ± 0.006, P < 0.05) genes expression levels. In addition to, producing insignificant increase in the number of positive cells for survivin (293.2 ± 15.9 vs 271.5 ± 15.9, P > 0.05) expression. Finally, the brain sections showed intact histological structure of the striatum as a result of treatment with BM-MSCs.CONCLUSION: The current study sheds light on the therapeutic potential of BM-MSCs against PD pathophysiology via multi-mechanistic actions.
基金funded by the National Natural Science Foundation of China,No.81971891(to KX),81571939(to KX),81772134(to KX),81772024(to JY),and 81860781(to FXL)the Key Research and Development Program of Hunan Province of China,No.2018SK2091(to KX)+1 种基金the Natural Science Foundation of Hunan Province of China,No.2017JJ2339(to JY)the Wu Jie-Ping Medical Foundation of the Minister of Health of China,No.320.6750.14118(to KX)
文摘Methamphetamine is one of the most prevalent drugs abused in the world.Methamphetamine abusers usually present with hyperpyrexia (39℃),hallucination and other psychiatric symptoms.However,the detailed mechanism underlying its neurotoxic action remains elusive.This study investigated the effects of methamphetamine + 39℃ on primary cortical neurons from the cortex of embryonic Sprague-Dawley rats.Primary cortex neurons were exposed to 1 mM methamphetamine + 39℃.Propidium iodide staining and lactate dehydrogenase release detection showed that methamphetamine + 39℃ triggered obvious necrosis-like death in cultured primary cortical neurons,which could be partially inhibited by receptor-interacting protein-1 (RIP1) inhibitor Necrostatin-1 partially.Western blot assay results showed that there were increases in the expressions of receptor-interacting protein-3 (RIP3) and mixed lineage kinase domain-like protein (MLKL) in the primary cortical neurons treated with 1 mM methamphetamine + 39℃ for 3 hours.After pre-treatment with RIP3 inhibitor GSK’872,propidium iodide staining and lactate dehydrogenase release detection showed that neuronal necrosis rate was significantly decreased;RIP3 and MLKL protein expression significantly decreased.Immunohistochemistry staining results also showed that the expressions of RIP3 and MLKL were up-regulated in brain specimens from humans who had died of methamphetamine abuse.Taken together,the above results suggest that methamphetamine + 39℃ can induce RIP3/MLKL regulated necroptosis,thereby resulting in neurotoxicity.The study protocol was approved by the Medical Ethics Committee of the Third Xiangya Hospital of Central South University,China (approval numbers: 2017-S026 and 2017-S033) on March 7,2017.
文摘Objective: To study the effect of citric acid given alone or combined with atropine on brain oxidative stress, neuronal injury, liver damage, and DNA damage of peripheral blood lymphocytes induced in the rat by acute malathion exposure. Methods: Rats were received intraperitoneal(i.p.) injection of malathion 150 mg/kg along with citric acid(200 or 400 mg/kg, orally), atropine(1 mg/kg, i.p.) or citric acid 200 mg/kg+atropine 1 mg/kg and euthanized 4 h later. Results: Malathion resulted in increased lipid peroxidation(malondialdehyde) and nitric oxide concentrations accompanied with a decrease in brain reduced glutathione, glutathione peroxidase(GPx) activity, total antioxidant capacity(TAC) and glucose concentrations. Paraoxonase-1, acetylcholinesterase(ACh E) and butyrylcholinesterase activities decreased in brain as well. Liver aspartate aminotransferase and alanine aminotransferase activities were raised. The Comet assay showed increased DNA damage of peripheral blood lymphocytes. Histological damage and increased expression of inducible nitric oxide synthase(i NOS) were observed in brain and liver. Citric acid resulted in decreased brain lipid peroxidation and nitric oxide. Meanwhile, glutathione, GPx activity, TAC capacity and brain glucose level increased. Brain ACh E increased but PON1 and butyrylcholinesterase activities decreased by citric acid. Liver enzymes, the percentage of damaged blood lymphocytes, histopathological alterations and i NOS expression in brain and liver was decreased by citric acid. Meanwhile, rats treated with atropine showed decreased brain MDA, nitrite but increased GPx activity, TAC, ACh E and glucose. The drug also decreased DNA damage of peripheral blood lymphocytes, histopathological alterations and i NOS expression in brain and liver. Conclusions: The study demonstrates a beneficial effect for citric acid upon brain oxidative stress, neuronal injury, liver and DNA damage due to acute malathion exposure.
基金the financial support by the National Natural Science Foundation of China (42042050, U2005207)Natural Science Foundation of Fujian Province, China (2020J0141)。
文摘In this study, concentrations of Cr, Mn, Ni, Cu, Zn, Cd and Pb were determined in road dusts collected from different locations in Dhaka to assess source, contamination status and health risk. Energy-dispersive X-ray fluorescence spectroscopy and energy-dispersive X-ray spectroscopy were used to determine Cr, Mn, Ni, Cu, Zn, Cd and Pb and their mean concentrations were 162.27 ± 29.46, 721.18 ± 180.14, 35.65 ± 12.55, 104.56 ± 128.33, 515.32 ± 321.90,BDL, and 342.82 ± 591.20 mg/kg, respectively. Among the heavy metals, highest concentrations of Cu, Zn and Pb were found at urban sites-7(municipal waste dumping) and 8(medical waste incineration). Highest concentration of Cr followed by Cu and Zn was found at site-5(Tejgaon, urban). Principal component analysis revealed that anthropogenic activities are the potential sources for Cr, Ni, Cu, Zn and Pb while earth crust for Mn. Pollution index and pollution load index results suggested that all the sites were contaminated and/or degraded by Cr, Cu, Zn and Pb except sites-9(urban), 10(sub-urban), 11(rural) while sites-7 and 8(urban) were extremely degraded. For noncarcinogenic health risk, hazard quotient values for dermal were higher compared to that of inhalation/ingestion. Though hazard index values were less than 1 at all the sites, these were at least one order of magnitude higher for children group than that of adult group, thus the children group may face more noncarcinogenic health risk at sites -7 and 8. Values of incremental lifetime cancer risk were from 10to 10showed no carcinogenic health risk by road dusts contaminated with the heavy metals.
文摘Objective:To investigate the effect of two extracts of Bougainvillea spectabilis(B. spectabilis) flowers with yellow and pink/purple on brain oxidative stress and neuronal damage caused in rats by systemic rotenone injection. Methods:Rotenone 1.5 mg/kg was given three times per week alone or in combination with B. spectabilis flowers extracts(25 mg or 50 mg) via the subcutaneous route for 2 weeks. Brain concentrations of the lipid peroxidation marker malondialdehyde(MDA),reduced glutathione,nitric oxide(nitrite),the pro-inflammatory cytokine interleukin-1beta(Il-1β) as well as butyrylcholinesterase,and paraoxonase-1(PON-1) activities,were determined. Histopathology and caspase-3 immunohistochemistry were also performed. Results:Rotenone resulted in significant increases of brain MDA(the product of lipid peroxidation),and nitric oxide content along with decreased brain reduced glutathione. There were also marked and significant inhibition of brain PON-1 and BCh E activities and increased Il-1β in brain of rotenone-treated rats. B. spectabilis flowers extract itself resulted in brain oxidative stress increasing both lipid peroxidation and nitrite content whilst inhibiting PON-1 activity. The yellow flowers extract inhibited BCh E activity and increased brain Il-1β. When given to rotenone-treated rats,B. spectabilis extracts,however,decreased lipid peroxidation while their low administered doses increased brain GSH. Brain nitrite decreased by the pink extract but showed further increase by the yellow extract. Either extract,however,caused further inhibition of PON-1 activity while the yellow extract resulted in further inhibition of BChE activity. Histopathological studies indicated that both extracts protected against brain,liver and kidney damage caused by the toxicant. Conclusions:These data indicate that B. spectabilis flowers extracts exert protective effect against the toxic effects of rotenone on brain,liver and kidney. B. spectabilis flowers extracts decreased brain lipid peroxidation and prevented neuronal death due to rotenone and might thus prove the value in treatment of Parkinson's disease.
文摘Objective: To investigate the effect of the prostaglandin E1 analogue misoprostol on oxidative stress and neurodegeration caused by subcutaneous rotenone administration in rats. Methods:Rotenone was administered in a dose of 1.5 mg/kg every other day for 2 weeks. Starting from the 1 st day of rotenone injection, rats were subcutaneously treated with misoprostol at doses of10, 100 or 1 000 μg/kg. Rats were evaluated for brain lipid peroxidation(malondialdehyde:MDA), reduced glutathione(GSH), nitric oxide(NO) levels, and paraoxonase-1(PON-1) activity.The concentrations of the anti-apoptotic protein B cell/lymphoma-2(Bcl-2) were determined in the striatum. Histopathologic examination and the expression of inducible nitric oxide synthase(iNOS) in the cerebral cortex and striatum were also performed. Results: Compared with the vehicle-treated group, rotenone caused a significant increase in brain lipid proxidation(MDA)by 61%(P<0.05) accompanied by an increase in NO by 73.1%(P<0.05) and a decrease in GSH concentration by 29.4%(P<0.05). In addition, brain PON-1 activity significantly decreased by63.0%(P<0.05) and striatal Bcl-2 significantly decreased by 27.9%(P<0.05) with respect to the corresponding control value. Brain sections from rotenone treated rats showed extensive dark pyknotic and apoptotic nuclei in neurons, shrunken cytoplasm and perineuronal vacuolation.Rotenone also caused pronounced expression of iNOS in the cerebral cortex and striatum.Treatment with misoprostol at doses of 100 and 1 000 μg/kg resulted in decreased brain MDA(by 16.5%-23.0%)(P<0.05) and NO levels(by 37.1%-40.7%)(P<0.05) and increased GSH concentrations(by 18.8%-30.1%)(P<0.05). PON-1 activity was significantly increased by80.0%-114.8%(P<0.05) by misoprostol at 100 and 1 000 μg/kg, respectively. In addition,misoprostol treatment restored striatal Bcl-2 concentrations to its normal value. Misoprostol treatment resulted in markedly reduced brain injury and decreased iNOS expression in the cerebral cortex and striatum of rotenone intoxicated rats. Conclusions: These data suggest that misoprostol prevents the rotenone-induced neurodegeneration in rat brain by reducing brain oxidative stress.
文摘Objective:To determine the delta-9-tetrahydrocannabinol(THC)content of cannabis seizures in Egypt.Methods:Unheated and heated extracts of cannabis seizures were prepared from the dried flowering tops and leaves(marijuana)or from the resin(hashish)and subjected to analysis using high performance liquid chromatography(HPLC).Results:The heated resin extract had the peak of THC in a relative ratio of 31.34%,while extracting the resin directly without heating contained only 18.34%of THC.On the other hand,marijuana showed minimum percentage of THC at 11.188% on heating and 9.55% without heating.Conclusions:These results indicate the high potency of the abused cannabis plant in the illicit Egyptian market.
文摘Parkinson's disease(PD) is one of the most prevalent neurodegenerative diseases which typically affects individuals over 65 years. Although the symptomatology is predominantly motor, neuropsychiatric manifestations, e.g., depression, apathy, anxiety, and cognitive impairment occur in the course of the illness and can have a great impact on the quality of life in these patients. Parkinson's disease is commonly comorbid with depression with prevalence rates of depression, generally higher than those reported in general population. Depression in PD is frequently underestimated andconsequently undertreated, which have significant effects on the quality of life in these patients. The neurobiology of depression in PD is complex and involves alterations in dopaminergic, serotonergic, noradrenergic and possibly other neurotransmitter systems which are affected in the course of the disease. The tricyclic antidepressants and the selective serotonin reuptake inhibitors are the two classes of antidepressant drugs used for depressive symptoms in PD. Several published studies suggested that both classes are of comparable efficacy. Other serotonergic antidepressants, e.g., nefazodone and trazodone have also been of benefit. Meanwhile, there are limited data available on other drugs but these suggest a benefit from the serotonin and noradrenaline reuptake inhibitors such as mirtazapine, venlafaxine, atomoxetine and duloxetine. Some of the drugs used in symptomatic treatment of PD, e.g., the irreversible selective inhibitors of the enzyme monoamine oxidase-B, rasagiline and selegiline as well as the dopamine receptor agonist pramipexole are likely to have direct antidepressant activity independent of their motor improving action. This would make these drugs an attractive option in depressed subjects with PD. The aim of this review is to provide an updated data on the prevalence, clinical features of depression in subjects with PD. The effects of antiparkinsonian and antidepressant drugs on depressive symptoms in these patients are also discussed.
基金funded by the Natural Science Foundation of Beijing[7212023]Beijing Municipal Administration of Hospitals’Youth Programme[QML20200102]+2 种基金the National Natural Science Foundation of China[82071180]to MHHthe Innovation Training Program for College Students in Jiangsu Province[201910313054Y]to SYYthe Natural Science Foundation of Jiangsu Province[BK20191464]to WYQ
文摘Objective Neonatal exposure to propofol has been reported to cause neurotoxicity and neurocognitive decline in adulthood;however,the underlying mechanism has not been established.Methods SD rats were exposed to propofol on postnatal day 7(PND-7).Double-immunofluorescence staining was used to assess neurogenesis in the hippocampal dentate gyrus(DG).The expression of pAkt and p27 were measured by western blotting.The Morris water maze,novel object recognition test,and object location test were used to evaluate neurocognitive function 2-month-old rats.Results Phosphorylation of Akt was inhibited,while p27 expression was enhanced after neonatal exposure to propofol.Propofol also inhibited proliferation of neural stem cells(NSCs)and decreased differentiation to neurons and astroglia.Moreover,the neurocognitive function in 2-month-old rats was weakened.Of significance,intra-hippocampal injection of the Akt activator,SC79,attenuated the inhibition of p-AKT and increase of p27 expression.SC79 also rescued the propofol-induced inhibition of NSC proliferation and differentiation.The propofol-induced neurocognition deficit was also partially reversed by SC79.Conclusion Taken together,these results suggest that neurogenesis is hindered by neonatal propofol exposure.Specifically,neonatal propofol exposure was shown to suppress the proliferation and differentiation of NSCs by inhibiting Akt/p27 signaling pathway.
文摘There had been no standardized rules for citing ethical Kampo products used in clinical trials in journal articles. Although the name of a Kampo manufacturer was described in 77.9% of research articles, the name and ratios of crude drug components of Kampo formulas were not described in 77.5% of these papers. Considering the importance of proper characterization of interventions in the Consolidated Standards of Reporting Trials (CONSORT) checklist, we hereby propose the use of the Standards of Reporting Kampo Products (STORK) website, http://mpdb.nibiohn.go.jp/stork, as a reference for Kampo products. This will provide an official source on the internet for verified information on individual Kampo formulations for citation purposes in clinical research articles.
基金supported by the National Natural Science Foundation of China,2021 Original Exploration Program recommended by experts(82150007)the Natural Science Foundation of Jiangsu Province(BK20190987)and the Chinese Postdoctoral Science Foundation(2018M642328).
文摘We previously identified a unique nucleus,the cerebrospinal fluid(CSF)-contacting nucleus.This study aims to understand its gene architecture and preliminarily suggest its functions.The results showed that there were about 19,666 genes in this nucleus,of which 913 were distinct from the dorsal raphe nucleus(non-CSF contacting).The top 40 highly-expressed genes are mainly related to energy metabolism,protein synthesis,transport,secretion,and hydrolysis.The main neurotransmitter is 5-HT.The receptors of 5-HT and GABA are abundant.The channels for Cl–,Na+,K+,and Ca2+are routinely expressed.The signaling molecules associated with the CaMK,JAK,and MAPK pathways were identified accurately.In particular,the channels of transient receptor potential associated with nociceptors and the solute carrier superfamily members associated with cell membrane transport were significantly expressed.The relationship between the main genes of the nucleus and life activities is preliminarily verified.
基金supported by the National Natural Science Foundation of China,Nos.82271257(to YZ)and 82071228(to YZ)Qing Lan Project(to YZ)+1 种基金Open Competition Grant of Xuzhou Medical University(to YZ)Postgraduate Research&Practice Innovation Program of Jiangsu Province,No.KYCX21_2705(to TS)。
文摘Microglia-mediated neuroinflammation is considered a pathological feature of Parkinson's disease.Triggering receptor expressed on myeloid cell-1(TREM-1)can amplify the inherent immune response,and crucially,regulate inflammation.In this study,we found marked elevation of serum soluble TREM-1 in patients with Parkinson's disease that positively correlated with Parkinson's disease severity and dyskinesia.In a mouse model of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinson's disease,we found that microglial TREM-1 expression also increased in the substantia nigra.Further,TREM-1 knockout alleviated dyskinesia in a mouse model of Parkinson's disease and reduced dopaminergic neuronal injury.Meanwhile,TREM-1 knockout attenuated the neuroinflammatory response,dopaminergic neuronal injury,and neutrophil migration.Next,we established an in vitro 1-methyl-4-phenyl-pyridine-induced BV2 microglia model of Parkinson's disease and treated the cells with the TREM-1 inhibitory peptide LP17.We found that LP17 treatment reduced apoptosis of dopaminergic neurons and neutrophil migration.Moreover,inhibition of neutrophil TREM-1 activation diminished dopaminergic neuronal apoptosis induced by lipopolysaccharide.TREM-1 can activate the downstream CARD9/NF-κB proinflammatory pathway via interaction with SYK.These findings suggest that TREM-1 may play a key role in mediating the damage to dopaminergic neurons in Parkinson's disease by regulating the interaction between microglia and peripheral neutrophils.
基金supported by the National Natural Science Foundation of China(Grant No.:81573694)the Science Foundation of the Educational Department of Liaoning Province,China(Grant No.:LJKZ0920)。
文摘In traditional Chinese medicine(TCM),Euphorbia fischeriana Steud(E.fischeriana)and Euphorbia ebracteolata Hayata(E.ebracteolata),commonly referred to as“Langdu”,are widely extensively utilized for treating lymphatic tuberculosis and ringworm[1].Both plant species are perennial herbaceous plants mainly distributed in northeastern China,Mongolia,Russia(Siberia),and Republic of Korea[2].There have been many reports on the chemical constituents and pharmacological effects of the two plant species,which has made more and more researchers realize that there may be differences between E.fischeriana and E.ebracteolata.In some cases,long-term improper use of herbal medicines can even lead to life-threatening conditions[3,4].Therefore,it is essential to employ an effective technology to differentiate between these two plants based on their chemical constituents and biological activities,so as to reduce the harm caused by the mixing and misuse of medicinal materials.Therefore,the present paper describes a study of the differences between E.ebracteolata and E.fischeriana,using untargeted plant metabolomics and biological activity evaluations.This study aims to provide valuable insight into their equivalence and potential interchangeability in TCM and clinical medication.
基金supported by Xuzhou Medical University start-up grant for excellent scientists (Nos. RC20552044, RC20552054)the Natural Science Research of the Jiangsu Higher Education Institutions (Nos. 21KJB330007, 21KJB320001)。
文摘2,6-Dichloro-1,4-benzoquinone(2,6-DCBQ), an emerging water disinfection by-product, is widely detected in water resources. However, its potential effects on the reproductive system are largely unknown. Here, we investigated the long-term effects of 2,6-DCBQ on gonadal development by exposing zebrafish from 15 to 180 days postfertilization(dpf). Following exposure to 2,6-DCBQ(20 and 100 μg/L), female-specific effects including delayed puberty onset, retarded ovarian growth and breakdown of the zona radiata were observed, resulting in subfertility in adult females. Adverse effects in folliculogenesis disappeared two months after cessation of 2,6-DCBQ administration. In contrast, no adverse impacts were noted in male testes. The effects on females were associated with significant reduction in 17 β-estradiol(E2) level, suggesting a role for 2,6-DCBQ in anti-estrogenic activity. E2 level change in blood was further supported by dysregulated expression of genes( cyp19a1a, fshb, kiss3, esr2b, vtg1, and vtg3) related to the hypothalamic-pituitary-gonad-liver(HPGL) axis. The present study demonstrates for the first time that 2,6-DCBQ induces reproductive impairments in female zebrafish through disrupting 17 β-estradiol level.
基金supported by grants from the National Natural Science Foundation of China(81870852 and 82171199)the Qing Lan Project of Jiangsu Province,the Education Department of Jiangsu Province(18KJA320007)+3 种基金the Natural Science Foundation of Jiangsu Province(BK20181146 and BK20210911)the Postgraduate Research&Practice Innovation Program of Jiangsu Province(KYCX21_2706,KYCX21_2703,and YCX21_2717)the Program on Basic Research Projects of Xuzhou City(KC21048)the Special Funds for Anesthesia Medical Research of Jiangsu Medical Association SYH-32021-0040(2021035).
文摘Dear Editor,Depending on the perceived threat in the environment,organisms can express a broad spectrum of behaviors,ranging from exploration to defensive behaviors[1,2],such as fear response and avoidance.Generalization of fear memory can generate anxiety-related disorders that afflict 10%-30%of individuals worldwide,especially during the epidemic situation[3,4].
基金supported by the National Research Centre(No.10001004)
文摘Cannabis sativa has long been known for its psychotropic effect. Only recently with the discovery of the cannabinoid receptors, their endogenous legends and the enzymes responsible for their synthesis and degradation, the role of this ‘endocannabinoid system’ in different pathophysiologic processes is beginning to be delineated. There is evidence that CB1 receptor stimulation with synthetic cannabinoids or Cannabis sativa extracts rich in ?9-tetrahydrocannabinol inhibit gastric acid secretion in humans and in experimental animals. This is specially seen when gastric acid secretion is stimulated by pentagastrin, carbachol or 2 deoxy-D-glucose. Cannabis and/or cannabinoids protect the gastric mucosa against noxious challenge with non-steroidal anti-inflammatory drugs, ethanol as well as against stress induced mucosal damage. Cannabis/cannabinoids might protect the gastric mucosa by virtue of its antisecretory, antioxidant, anti-inflammatory, and vasodilator properties.