Hyodeoxycholic acid protects the neurovascular unit against oxygen-glucose deprivation and reoxygenation-induced injury in vitro

Calculus bovis is commonly used for the treatment of stroke in traditional Chinese medicine. Hyodeoxycholic acid(HDCA) is a bioactive compound extracted from calculus bovis. When combined with cholic acid, baicalin and jas-minoidin, HDCA prevents hypoxia-reoxygenation-induced brain injury by suppressing endoplasmic reticulum stress-mediated apoptotic signaling. However, the effects of HDCA in ischemic stroke injury have not yet been studied. Neurovascular unit(NVU) dysfunction occurs in ischemic stroke. Therefore, in this study, we investigated the effects of HDCA on the NVU under ischemic conditions in vitro. We co-cultured primary brain microvascular endothelial cells, neurons and astrocytes using a transwell chamber co-culture system. The NVU was pre-treated with 10.16 or 2.54 μg/mL HDCA for 24 hours before exposure to oxygen-glucose deprivation for 1 hour. The cell counting kit-8 assay was used to detect cell activity. Flow cytometry and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling were used to assess apoptosis. Enzyme-linked immunosorbent assay was used to measure the expression levels of inflammatory cytokines, including interleukin-1β, interleukin-6 and tumor necrosis factor-α, and neurotrophic factors, including brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor. Oxidative stress-related factors, such as superoxide dismutase, nitric oxide, malondialdehyde and γ-glutamyltransferase, were measured using kits. Pretreatment with HDCA significantly decreased blood-brain barrier permeability and neuronal apoptosis, significantly increased transendothelial electrical resistance and γ-glutamyltransferase activity, attenuated oxidative stress damage and the release of inflammatory cytokines, and increased brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor expression. Our findings suggest that HDCA maintains NVU morphological integrity and function by modulating inflammation, oxidation stress, apoptosis, and the expression of neurotrophic factors. Therefore, HDCA may have therapeutic potential in the clinical management of ischemic stroke. This study was approved by the Ethics Committee of Experimental Animals of Beijing University of Chinese Medicine(approval No. BUCM-3-2016040201-2003) in April 2016.

Temporal alterations in pericytes at the acute phase of ischemia/reperfusion in the mouse brain

Pericytes,as the mural cells surrounding the microvasculature,play a critical role in the regulation of microcirculation;however,how these cells respond to ischemic stroke remains unclear.To determine the temporal alterations in pericytes after ischemia/reperfusion,we used the 1-hour middle cerebral artery occlusion model,which was examined at 2,12,and 24 hours after reperfusion.Our results showed that in the reperfused regions,the cerebral blood flow decreased and the infarct volume increased with time.Furthermore,the pericytes in the infarct regions contracted and acted on the vascular endothelial cells within 24 hours after reperfusion.These effects may result in incomplete microcirculation reperfusion and a gradual worsening trend with time in the acute phase.These findings provide strong evidence for explaining the“no-reflow”phenomenon that occurs after recanalization in clinical practice.

Spinocerebellar ataxia type 3 with dopamine-responsive dystonia:A case report

BACKGROUND Spinocerebellar ataxia type 3(SCA3)is a rare neurodegenerative disease with high genetic heterogeneity.SCA3 mainly manifests as progressive cerebellar ataxia accompanied by paralysis of extraocular muscles,dysphagia,lingual fibrillation,pyramidal tract sign,and extrapyramidal system sign.However,it rarely has clinical manifestations similar to Parkinson-like symptoms,and is even rarer in patients sensitive to dopamine.We report a patient initially diagnosed with dopamine-responsive dystonia who was ultimately diagnosed with SCA3 by genetic testing,which was completely different from the initial diagnosis.CASE SUMMARY A 40-year-old Chinese woman was admitted to hospital due to severe inflexibility.At the beginning of the disease,she presented with anxiety and sleep disorder.At the later stage,she presented with gait disorder,which was similar to Parkinson's disease.Her medical history was unremarkable,but her mother,grandmother,and uncle all had similar illnesses and died due to inability to take care of themselves and related complications.Laboratory and imaging examinations showed no abnormalities,but electromyography and electroencephalography revealed delayed somatosensory evoked potentials and slow background rhythm,respectively.Her symptoms fluctuated during the daytime,and we initially diagnosed her with dopamine-responsive dystonia.After treatment with lowdose levodopa,the patient’s symptoms were significantly improved,but the final genetic diagnosis was SCA3.CONCLUSION SCA3 has various clinical phenotypes and needs to be differentiated from Parkinson's syndrome and dopamine-responsive dystonia.

Effect of Majie Pingchuan cataplasm on epithelial-derived cytokines in asthmatic mice based on the"lung-skin-intestine"axis

Objective:To observe the effect of MJPC cataplasm on the content of epithelial-derived cytokines in lung,skin and intestine of asthmatic mice.Methods:C57/BL6 female mice were randomly divided into four groups:control group,asthma model group,dexamethasone group and MJPC cataplasm group.Ovalbumin sensitized and challenged asthmatic mouse models were established.The spleen index was calculated,and HE staining was used to observe the pathological change in lung tissues.The ova-specific IgE in the mouse serum and the content of TSLP in lung,skin and intestine were detected by enzyme-linked immunosorbent assay(ELISA).The expressions of TSLP mRNA and IL-33 mRNA in skin and intestinal tissue were detected by qRT-PCR.Results:Compared with the control group,the spleen index of mice in asthma model group was increased.Vascular congestion and edema,inflammatory cell infiltration and bronchial wall thickening were observed.The expressions of IgE in the mouse serum were significantly increased,and the content of TSLP in lung and skin tissue increased,but that in intestine tissue did not change significantly.The expression of TSLP mRNA was up-regulated in skin and intestinal tissues.The expression of IL-33 mRNA was up-regulated in skin tissue,but not in intestine,and the differences were statistically significant(P<0.05);Compared with the model group,MJPC cataplasm could decrease the spleen index and the expression of IgE in the mouse serum,improve the pathological damage of lung tissue in asthmatic mice,reduce the content of TSLP in lung,skin and intestinal tissue,increased the expression of TSLP mRNA in skin tissue,and down-regulate the expression of Il-33 mRNA in skin tissue and the expression of TSLP mRNA and IL-33 mRNA expression in intestinal tissue(P<0.05).Pearson correlation coefficient(r)of the content of TSLP between lung and skin was 0.689,that between lung and intestinal was-0.163,and that between skin and intestinal was-0.163,and the differences were not statistically significant(P>0.05).Conclusion:MJPC cataplasm improve airway inflammation by inhibiting the content of epithelial-derived cytokines on the"lung-skin-intestine"axis of asthmatic mice,and achieve the effect of treating asthm.

The enlightenment and application of“Laxative method used in early stage of Febrile Disease”in treating COVID-19

The theory of the TCM laxative method is rich in content.Doctors of past dynasties have used it to treat febrile diseases.And the theory of“Laxative method used in early stage of Febrile Disease”has been praised by later generations.It advocates chasing away evil influence early and paying attention to the laxative method to prevent the spread of disease.the Novel Coronavirus(COVID-19)Infectious Pneumonia belongs to the category of"epidemic"in traditional Chinese medicine.The reasonable application of the cathartic is an important way to provide a way out for evil.However,don’t be blind to use laxative method,you should get it at the right time.The treatment of COVID-19 has different solution at different stages.You should adapt to the changes of the disease to use cathartic.A case in here is attached for reference.

MnS–MnO heterogeneous nanocube@N,S-doped carbon as a highly efficient bifunctional water splitting electrocatalyst

A stable,efficient,and economical bifunctional electrolytic catalyst would be incredibly beneficial for the development of hydrogen production by electrocatalytic water splitting.In this study,we synthesized a novel MnS–MnO heterogeneous nanocube@N,S-doped carbon(MnS–MnO@NSC).MnS–MnO nanocubes possess rich heterogeneous interfaces and plentiful catalytic active sites to promote electrochemical reactions,while the N,S-doped carbon shell possesses excellent conductivity and catalytic properties and protects the nanocubes.MnS–MnO@NSC exhibited excellent electrochemical properties as an effective bifunctional electrocatalyst for the hydrogen evolution reaction(HER)and oxygen evolution reaction(OER)in KOH solution.In the HER,the overpotential was as low as 124 mV at a current density of 10 mA·cm^(-2)while in the OER,it was only 340 mV at 100 mA·cm^(-2)under the same conditions.In addition,a MnS–MnO@NSC||MnS–MnO@NSC electrolyzer exhibited almost comparable activity and higher steadiness than those exhibited by the state-of-the-art Pt/C||RuO_(2)/C system for full water splitting in KOH solution.

Development of an enzyme-linked immunosorbent assay using specific monoclonal antibodies against theacrine and its application

Tbeacrine （1,3,7,9-tetramethyluric acid）, a purine alkaloid similar to caffeine in its chemical structure, is isolated from edible Camellia assamica vat. kucha and has various pharmacological activities including hypnotic effects, anti-depressant effects, anti-inflammatory and analgesic effects, and a protective effect against stress-provoked liver damage. A rapid and simple assay is required to quantify theacrine in biological samples for pharmacokinetic studies in small animals. This study aimed to establish an enzyme-linked immunosorbent assay （ELISA） for theacrine quantification in blood. Herein, we successfully obtained monoclonal antibodies （MAbs） against theacrine, MAbs C11B5, and developed an ELISA method for the fast determination of theacrine in mouse blood. The range for calibration of theacrine by ELISA was 0.156-100 μg mL-1. The half maximum inhibitory concentration （IC50） value was 1.55 μg mL-1. The ELISA method lays a good foundation for the further research.

Finite-temperature ductility-brittleness and electronic structures of Al_(n)Sc(n=1,2 and 3)

Finite-temperature ductility-brittleness and electronic structures of Al_(3)Sc,Al_(2)Sc and AlSc are studied comparatively by first-principles calculations and ab initio molecular dynamics.Results show that Al_(3)Sc and Al_(2)Sc are brittle at both ground state and finite temperatures,while AlSc possesses a significantly superior ductility.At ground state,AlSc is ductile from Pugh's and Poisson's criteria,while it is brittle in Pettifor's model.The ductility of all Al_(3)Sc,Al_(2)Sc and AISc improves greatly with the elevated temperature.Especially,the Cauchy pressure of AlSc undergoes a transition from negative to positive.At T>600 K,AlSc is unequivocally classified as ductile from all criteria considered.In all compounds,the Al-Al bond originated from s-p and p-p orbital hybridizations,and the Al-Sc bond dominated by p-d covalent hybridization,are the first and second strongest chemical bonds,respectively.To explain the difference in mechanical properties,the mean bond strength(MBS)is introduced in this work.The weaker Al-Al bond in AlSc,leading to a smaller MBS,could be the origin of the softer elastic stiffness and superior intrinsic ductility.The longer length of the Al-Al bond in AlSc is responsible for its weaker bond strength.Furthermore,the enhanced metallicity of the Al-Al bond in AlSc would also contribute to its exceptional ductility.The longer length of the Al-Al bond in AISc is responsible for its weaker bond strength.Furthermore,the enhanced metallicity of the Al-Al bond in AlSc would also contribute to its exceptional ductility.