Treatment with β-sitosterol ameliorates the effects of cerebral ischemia/reperfusion injury by suppressing cholesterol overload, endoplasmic reticulum stress, and apoptosis

β-Sitosterol is a type of phytosterol that occurs naturally in plants.Previous studies have shown that it has anti-oxidant,anti-hyperlipidemic,anti-inflammatory,immunomodulatory,and anti-tumor effects,but it is unknown whetherβ-sitosterol treatment reduces the effects of ischemic stroke.Here we found that,in a mouse model of ischemic stroke induced by middle cerebral artery occlusion,β-sitosterol reduced the volume of cerebral infarction and brain edema,reduced neuronal apoptosis in brain tissue,and alleviated neurological dysfunction;moreover,β-sitosterol increased the activity of oxygen-and glucose-deprived cerebral cortex neurons and reduced apoptosis.Further investigation showed that the neuroprotective effects ofβ-sitosterol may be related to inhibition of endoplasmic reticulum stress caused by intracellular cholesterol accumulation after ischemic stroke.In addition,β-sitosterol showed high affinity for NPC1L1,a key transporter of cholesterol,and antagonized its activity.In conclusion,β-sitosterol may help treat ischemic stroke by inhibiting neuronal intracellular cholesterol overload/endoplasmic reticulum stress/apoptosis signaling pathways.

The Role of IL-2, IL-4, IL-10 and IFN-γ Cytokines Expression in the Microenvironment of Cervical Intraepithelial Neoplasia

Objective: To investigate the role of IL-2, IL-4, IL-10 and IFN-γ cytokines in the microenvironment of cervical intraepithelial neoplasia. Methods: 180 patients participating were enrolled in this trial, where 50 cases are in control group, 50 cases are in low-grade squamous intraepithelial lesion (LSIL) group, 50 cases are in high-grade squamous intraepithelial lesion (HSIL) group, and 30 cases have cervical carcinoma. ELISA methods are used to detect the expression of IL-2, IL-4, IL-10 and IFN-γ in the lavage fluid, and all data is analyzed using one-way analysis of variance. Results: The expression of IL-2 and IFN-γ in cervical lavage fluid gradually decreases with the aggravation of the lesion. The expression of IL-4 and IL-10 increases by the aggravation of pathological changes. There were statistically significant differences in IL-2 level among the four groups. IFN-γ levels are significantly different between the cervical cancer group and the other groups, also between HSIL and LSIL group, and between HSIL and the control group, but no statistically significant difference was observed in IFN-γ e between LSIL and the control group. The expressions of IL-4 and IL-10 between the cervical cancer group and the other groups were significantly different, and also between HSIL and the control group. But there was no statistically significant difference between LSIL and the control group, HSIL and LSIL. Conclusion: The cytokines of IL-2, IL-4, IL-10 and IFN-γ in the microenvironment of the cervix play an important role in the occurrence and development of cervical intraepithelial neoplasia. This study may provide the evidence for diagnosis and treatment of cervical intraepithelial neoplasia.

Research progress of in-situ gelling ophthalmic drug delivery system

Blindness and vision impairment are the most devastating global health problems resulting in a substantial economic and social burden.Delivery of drug to particular parts of the anterior or posterior segment has been a major challenge due to various protective barriers and elimination mechanisms associated with the unique anatomical and physiological nature of the ocular system.Drug administration to the eye by conventional delivery systems results in poor ocular bioavailability(<5%).The designing of a novel approach for a safe,simple,and effective ocular drug delivery is a major concern and requires innovative strategies to combat the problem.Over the past decades,several novel approaches involving different strategies have been developed to improve the ocular delivery system.Among these,the ophthalmic in-situ gel has attained a great attention over the past few years.This review discussed and summarized the recent and the promising research progress of in-situ gelling in ocular drug delivery system.

Study of penetration mechanism of labrasol on rabbit cornea by Ussing chamber, RT-PCR assay, Western blot and immunohistochemistry

Labrasol, as a non-ionic surfactant, can enhance the permeation and absorption of drugs, and is extensively used in topical, transdermal, and oral pharmaceutical preparations as an emulsifier and absorption enhancer. Recent studies in our laboratory have indicated that labrasol has a strong absorption enhancing effect on different types of drugs in vitro and in vivo. This study was performed to further elucidate the action mechanism of labrasol on the corneal penetration. In this research, the fluorescein sodium, a marker of passive paracellular transport of tight junction, was selected as the model drug to assess the effect of labrasol on in vitro corneal permeability. To investigate the continuous and real-time influence of labrasol on the membrane permeability and integrity, the Ussing chamber system was applied to monitor the electrophysiological parameters. And, furthermore, we elucidated the effect of labrasol on excised cornea at the molecular level by application of RT-PCR, Western blot, and immunohistochemical staining. The results indicated that labrasol obviously enhance the transcorneal permeability of fluorescein sodium, and the enhancement was realized by interacting with and down-regulating the associated proteins, such as Factin, claudin-1 and β-catenin, which were contributed to cell-cell connections, respectively.

Low Temperature Direct Synthesis of Strontium Titanate Powder

Low temperature direct synthesis (LTDS) involves the preparation of a base solution of Sr^(2+),and the mixing of base solution with tetrabutyl titanate solution.LTDS is an advantageous method because it does not require the complex hydrothermal facilities and it can prevent the agglomeration in calcinations of other liquid methods.In our work,we adopted LTDS method to prepare the nano strontium titanate powders,and characterize them by XRD,FT-IR and TGA.The influences of preparation temperature and solvents on grain size and lattice parameters were investigated.The results show that preparation temperature can slightly change the lattice parameters of grain,while solvents also play important roles in the preparation.

Introduction Performance and Application Evaluation of Leafy Ornamental Vegetables in Kunming City

[Objectives]This study was conducted to enrich the plant resource of ornamental vegetables in Kunming. [Methods]15 leafy vegetables were selected as test materials in this study. This study investigated the biological characteristics of the 15 ornamental vegetables by introduction trial and grey correlation analysis. In addition,we discussed the application of ornamental vegetables in urban agriculture. [Results]The grey correlation values of 11 ornamental vegetables were greater than 0. 6. The grey correlation values of other four ornamental vegetables were less than 0. 5. Among them,the grey correlation of Beta vulgaris L. var. cicla L. was 0. 94,which have the highest appreciation evaluation. The second appreciation evaluation belonged to rainbow leafy Beta vulgaris L. var. cicla L. with grey correlation of 0. 88. [Conclusions] In short,there are nine ornamental vegetables could be applied in the urban agriculture of Kunming,and there are six ornamental vegetables must be further investigated by cultivation experiment,to understand their cultivation characteristics and key points of management.

Prognosis of synchronous endometrial and ovarian cancer based on the PROMISE molecular system

To the Editor:Synchronous endometrial and ovarian cancer(SEOC)was found in approximately 5%of endometrial cancer(EC)patients and 10%of ovarian cancer patients.[1]In the case of concurrent coexistence of endometrial and ovarian carcinomas,there are two scenarios:two independent primary tumors(IPTs)or ECs with ovarian metastases,which have different prognoses and treatment response.Previous studies have shown that endometrioid tumors classified as IPTs had a better prognosis than those classified as FIGO stage IIIA endometrial cancers(IIIA-ECs)(86%vs.58%5-year survival rates).

Proteolytic processing of SDF-1α by matrix metalloproteinase-2 impairs CXCR4 signaling and reduces neural progenitor cell migration

Neural stem cells and neural progenitor cells(NPCs)exist throughout life and are mobilized to replace neurons,astrocytes and oligodendrocytes after injury.Str-omal cell-derived factor 1(SDF-1,now named CXCL12)and its receptor CXCR4,an α-chemokine receptor,are critical for NPC migration into damaged areas of the brain.Our previous studies demonstrated that immune activated and/or HIV-1-infected human monocyte-derived-macrophages(MDMs)induced a substantial increase of SDF-1 production by human astrocytes.However,matrix metalloproteinase(MMP)-2,a protein up-regulated in HIV-1-infected macrophages,is able to cleave four amino acids from the N-terminus of SDF-1,resulting in a truncated SDF-1(5-67).In this study,we investigate the diverse signaling and function induced by SDF-1α and SDF-1(5-67)in human cortical NPCs.SDF-1(5-67)was generated by incubating human recombinant SDF-1α with MMP-2 followed by protein determination via mass spectrometry,Western blotting and ELISA.SDF-1α induced time-dependent phosphorylation of extracellular signal-regulated kinases(ERK)1/2,Akt-1,and diminished cyclic adenosine monophosphate(cAMP).In contrast,SDF-1(5-67)failed to induce these signaling.SDF-1α activation of CXCR4 induced migration of NPCs,an effect that is dependent on ERK1/2 and Akt-1 pathways;whereas SDF-1(5-67)failed to induce NPC migration.This observation provides evidence that MMP-2 may affect NPC migration through post-translational processing of SDF-1α.

Directed migration of human neural progenitor cells to interleukin-1βis promoted by chemokines stromal cell-derived factor-1 and monocyte chemotactic factor-1 in mouse brains

Background:Neurogenesis,including the proliferation,migration and differentiation of neural progenitor cells(NPCs),is impaired in HIV-1 associated dementia(HAD).We previously demonstrated HIV-1-infected macrophages(HIV-MDM)regulate stromal cell-derived factor 1(SDF-1)production in astrocytes through Interleukin-1β(IL-1β).Chemokines are known to induce NPC migration;however,it remains unclear how chemokines produced in inflammation regulate NPC migration.Methods:The secretion of SDF-1 and Monocyte chemotactic preotein-1(MCP-1)in astrocytes upon IL-1βstimulation was measured by ELISA assay.Human NPCs were injected parallel along with IL-1β,SDF-1 or MCP-1 intracranially into basal ganglion 1 mm apart in SCID mice,and immunofluorescent staining was used to study the survival and migration of injected human NPCs.Results:SDF-1 and MCP-1 are secreted by astrocytes upon IL-1βstimulation in a time-dependent manner.Injected human NPCs survived in SCID mice and migrated towards sites of IL-1β,SDF-1 and MCP-1 injection.Conclusions:In conclusion,chemokines SDF-1 or MCP-1 secreted by astrocytes in the presence of IL-1βinjection are attractive to NPCs injected into SCID mouse brains,suggesting that SDF-1 and MCP-1 play important roles in NPC migration during neuroinflammation.

Comparison of two methods for evaluating lower urinary tract symptoms in cervical cancer patients following radical hysterectomy

Objective:To compare the degree of agreement and consistency of urodynamic studies(UDS)with low urinary tract symptoms(LUTS)questionnaires for evaluating LUTS in cervical cancer patients following radical hysterectomy(RH)and pelvic lymphadenectomy.Methods:From January 2012 to March 2015,204 cervical cancer patients who underwent RH in 13 hospitals were evaluated using the Incontinence Questionnaire-Female Lower Urinary Tract Symptoms(ICIQ-FLUTS)and the Overactive Bladder Symptom Score(OABSS).Urodynamic tests were also performed on these patients during the same period.Results:Study participants’age ranged from 23 to 75 years,with a mean(standard deviation)of 48.0±9.3 years.Using questionnaires,the prevalence of patients with LUTS symptoms,including storage symptoms,voiding symptoms,stress urinary incontinence(SUI)and overactive bladder(OAB)was 86.3%,77.0%,62.7%,52.9%and 14.7%,respectively.For UDS,the corresponding prevalence was 89.7%,70.1%,66.7%,46.6%and 13.2%,respectively.The diagnostic concordance of questionnaires and UDS for storage symptoms,voiding symptoms,SUI and OAB was 79.9%,66.7%,66.7%,57.4%and 79.9%,respectively.For voiding symptoms,the correlation coefficient was 0.272,which was higher than that of storage symptoms,SUI and OAB.