First Principles Study of the Photoelectric Properties of Alkaline Earth Metal (Be/Mg/Ca/Sr/Ba)-Doped Monolayers of MoS2.

The energy band structure, density of states, and optical properties of monolayers of MoS2 doped with alkaline earth metals (Be/Mg/Ca/Sr/Ba) are systematically studied based on first principles. The results indicate that all the doped systems have a great potential to be formed and structurally stable. In comparison to monolayer MoS2, doping alkaline earth metals results in lattice distortions in the doped system. Therefore, the recombination of photogenerated hole-electron pairs is suppressed effectively. Simultaneously, the introduction of dopants reduces the band gap of the systems while creating impurity levels. Hence, the likelihood of electron transfer from the valence to the conduction band is enhanced, which means a reduction in the energy required for such a transfer. Moreover, doping monolayer MoS2 with alkaline earth metals increases the static dielectric constant and enhances its polarizability. Notably, the Sr-MoS2 system exhibits the highest value of static permittivity, demonstrating the strongest polarization capability. The doped systems exhibit a red-shifted absorption spectrum in the low-energy region. Consequently, the Be/Mg/Ca-MoS2 systems demonstrate superior visible absorption properties and a favorable band gap, indicating their potential as photo-catalysts for water splitting.

Degradation Profiling of Nardosinone at High Temperature and in Simulated Gastric and Intestinal Fluids.

Nardosinone, a predominant bioactive product from Nardostachys jatamansi DC, is well-known for its promising therapeutic applications, such as being used as a drug on anti-inflammatory, antidepressant, cardioprotective, anti-neuroinflammatory, anti-arrhythmic, anti-periodontitis, etc. However, its stability under varying environmental conditions and its degradation products remain unclear. In this study, four main degradation products, including two previously undescribed compounds [2-deoxokanshone M (64.23%) and 2-deoxokanshone L (1.10%)] and two known compounds [desoxo-narchinol A (2.17%) and isonardosinone (3.44%)], were firstly afforded from the refluxed products of nardosinone in boiling water; their structures were identified using an analysis of the extensive NMR and X-ray diffraction data and the simulation and comparison of electronic circular dichroism spectra. Compared with nardosinone, 2-deoxokanshone M exhibited potent vasodilatory activity without any of the significant anti-neuroinflammatory activity that nardosinone contains. Secondly, UPLC-PDA and UHPLC-DAD/Q-TOF MS analyses on the degradation patterns of nardosinone revealed that nardosinone degraded more easily under high temperatures and in simulated gastric fluid compared with the simulated intestinal fluid. A plausible degradation pathway of nardosinone was finally proposed using nardosinonediol as the initial intermediate and involved multiple chemical reactions, including peroxy ring-opening, keto-enol tautomerization, oxidation, isopropyl cleavage, and pinacol rearrangement. Our findings may supply certain guidance and scientific evidence for the quality control and reasonable application of nardosinone-related products.

Protective effect of dabrafenib on renal ischemia-reperfusion injury in vivo and in vitro.

AIMS: Ischemia-reperfusion injury (IRI) is a major cause of acute kidney injury (AKI), which can lead to poor outcome and increased risk of mortality. Dabrafenib (DAB) is an approved cancer treatment. Little is known about the effect of DAB in prevention or treatment of renal IRI. METHODS: For in vivo experiments, C57BL/6 mice were divided into four groups: sham (no IRI, no DAB), IRI, DAB, and DAB + IRI. IRI was induced by clamping of bilateral renal pedicles for 30 min. For in vitro experiments, HK-2 cells were used to establish the hypoxia/reoxygenation (H/R) injury model, with four groups: control (no H/R, no DAB), H/R, DAB, and DAB + H/R. Renal function and renal histological changes were recorded. Expression of NGAL and KIM-1 proteins and mRNAs were determined by western blotting and qRT-PCR; secretion of inflammatory cytokines (IL-6 and TNF- α) was determined by qRT-PCR; Cell death was determined using the TUNEL assay, measurement of cleaved caspase-3, and flow cytometry. Necroptosis-related proteins were determined by western blotting. RESULTS: In mice, DAB pretreatment improved renal function and also reduced histological injury, inflammation, cell death, and expression of necroptosis-associated proteins. In HK-2 cells, DAB significantly decreased the levels of NGAL and KIM-1, inflammatory cytokines, cell death, and necroptosis-related proteins. CONCLUSION: Our in vitro and in vivo experiments indicated that DAB appears to alleviate renal IRI by suppressing cell death and inhibiting inflammatory responses. DAB has potential use for the clinical prevention and treatment of AKI-induced IRI.

Xueshuantong injection (lyophilized) combined with salvianolate lyophilized injection protects against focal cerebral ischemia/reperfusion injury in rats through attenuation of oxidative stress.

Salvianolate lyophilized injection (SLI) and Xueshuantong injection (lyophilized) (XST) are two herbal standardized preparations that have been widely used in China for the treatment of acute cerebral infarction. In this study, we investigated the neuroprotective effects of SLI combined with XST in a rat model of middle cerebral artery occlusion-reperfusion (MCAO/R). Wistar rats were subjected to 1.5 h of MCAO followed by reperfusion for 3 h, then were treated with SLI or XST alone, or with their combinations via tail vein injection daily for 3 d. Edaravone (EDI, 6 mg·kg-1·d-1) was used as a positive control drug, We showed that administration of a combination of 1X1S (XST 100 mg·kg-1·d-1 plus SLI 21 mg·kg-1·d-1) more effectively protected the ischemic brains than SLI or XST used alone. Administration of 1X1S not only significantly decreased neurological deficit scores and infarct volumes and increased regional cerebral blood flow, but also inhibited the activation of both microglia and astrocytes in the hippocampus. Furthermore, administration of 1X1S significantly decreased the levels of MDA and ROS with concomitant increases in the levels of antioxidant activity (SOD, CAT and GSH) in the brain tissues as compared with SLI and XST used alone. Moreover, administration of 1X1S remarkably upregulated the expression of Nrf-2, HO-1 and NQO-1, and downregulated the expression of Keap1 and facilitated the nuclear translocation of Nrf-2 in the brain tissues as compared with XST used alone. Our study demonstrates that a combination of 1X1S effectively protects MCAO/R injury via suppressing oxidative stress and the Nrf-2/Keap1 pathway.

G protein pathway suppressor 2 (GPS2) acts as a tumor suppressor in liposarcoma.

Liposarcoma(LPS) is the most common type of soft tissue sarcoma accounting for 20 % of all adult sarcomas. However, the molecular pathogenesis of this malignancy is still poorly understood. Here, we showed that GPS2 expression was downregulated in LPS and correlated with the prognosis of this disease. In vitro study showed that knockdown of GPS2 resulted in enhanced proliferation and migration of LPS cell line SW872, without significant influence of cell death. Conclusively, our results suggest that GPS2 may act as a tumor suppressor in LPS and serve as a potential prognosis marker for this disease.

Danhong injection attenuates ischemia/reperfusion-induced brain damage which is associating with Nrf2 levels in vivo and in vitro.

Danhong injection, a Chinese Materia Medica standardized product extracted from Radix Salviae miltiorrhizae and Flos Carthami tinctorii, is used extensively for the treatment of cerebrovascular diseases such as acutely cerebral infarction in clinic. In this study, we further investigated the mechanisms of Danhong injection on cerebral ischemia/reperfusion (I/R) damage relating to Nrf2/ARE signalling pathway in vivo and in vitro. For in vivo experiment, cerebral I/R injury was induced through middle cerebral artery occlusion. Rats were randomly divided into five groups: sham-operated group, I/R injury group, 6 mg/kg edaravone injection (positive control drug) group, 0.9 ml/kg Danhong injection (DHI-L) group, 1.8 ml/kg Danhong injection (DHI-H) group. The neurological score, cerebral infarction and brain edema were assessed while levels of superoxide dismutase (SOD), glutathione (GSH) and malondialdehyde (MDA) in brain tissue were also evaluated. Transcription levels of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), NAD(P)H: quinone oxidoreductase 1 (NQO1) were analysed by real-time polymerase chain reaction. For in vitro experiment, mouse Neuro-2A cells were wounded with H2O2 then cell viability and mRNA transcriptions levels of Nrf2, HO-1, NQO1 were detected. Protein expression level of Nrf2 was assayed by western blotting. The results showed that Danhong injection could ameliorate neurological score, cerebral infarction and brain edema. Also it can increase levels of SOD, GSH and decrease of MDA and upregulate expressions of Nrf2, HO-1, NQO1 in ischemic brain tissue in vivo. What's more, it increased the mRNA transcription of Nrf2 and HO-1 and upregulated protein expression of Nrf2 in vitro. These findings suggested that Danhong injection could prevent I/R-induced brain damage through activating Nrf2/ARE signaling pathway.

[Microwave radiation induces injury to GC-2spd cells].

OBJECTIVE: To explore the impact of microwave radiation on GC-2spd cells. METHODS: We exposed cultured GC-2spd cells to microwave radiation at the average power densities of 0, 10 and 30 mW/cm2 for 15 minutes and, from I to 24 hours after the exposure, we observed the changes in cell proliferation, histology and ultrastructure, cell apoptosis, and cAMP content by MTIT, light microscopy, electron microscopy, flow cytometry and ELISA. RESULTS: Compared with the control group, the GC-2spd cells showed a significant decrease in proliferation ability at 1 -24 hours after 10 and 30 mW/cm2 microwave radiation, except at 12 hours after 30 mW/cm2 radiation (P <0.05 or P <0.01), with reduced length and number of cell enation and increased intra cytoplasm vacuoles. The rate of cell apoptosis (%) was significantly increased in the 10 and 30 mW/cm2 groups at 6 hours (4.56 +/- 2.09 vs 14.59 +/- 1.09 and 8.48 +/- 1.73, P <0.05 or P <0.01) , with agglutination and margin translocation of chromatins and obvious dilation of endo cytoplasmic reticula. The cAMP content (nmol/g) in the GC-2spd cells was remarkably reduced in the 10 and 30 mW/cm2 groups at 6 and 24 hours (2.77 +/-0.24 vs 1.65+/- 0. 17 and 1.96+/-0.10, 3.02 +/-0.47 vs 2.13 +/-0.33 and 1.69 +/-0.27, P <0.05 or P <0.01). CONCLUSION: Microwave radiation at 10 and 30 mW/cm2 may cause injury to GC-2spd cells, which is manifested by decreased content of intracellular cAMP, reduced activity of cell proliferation, and increased rate of cell apoptosis.

[Effects of xinfuli granule on cardiomyocyte apoptosis in rats with dilated heart failure induced by adriamycin].

OBJECTIVE: To investigate the effects of Xinfuli Granule (XG) on cardiomyocyte apoptosis in rats with adriamycin-induced dilated cardiomyopathy (DCM). METHODS: Seventy-two male SD rats were randomly divided into 6 groups, i.e., the normal control group, the model group, the irbesartan group, the low dose XG group, the medium dose XG group, and the high dose XG group. The DCM heart failure rat model was established using peritoneal injection of ADR. Equal volume of normal saline was injected to those in the normal control group, once per week for 6 consecutive weeks. The medication was started from the 5th week by gastrogavage. XG was dispensed into 0.5 g/mL suspension with distilled water. The XG was administered at the daily dose of 0.675 g/kg, 1.350 g/kg, and 2.700 g/kg to those in the low dose XG group, the medium dose XG group, and the high dose XG group, respectively. Irbesartan was administered to rats in the irbesartan group at the daily dose of 50 mg/kg. Equal volume of normal saline was administered to those in the normal control group and the model group by gastrogavage, once in the morning for 4 consecutive weeks. Myocardial apoptosis was measured by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL), and the expressions of the Bcl-2 and Bax protein of cardiomyocytes were measured by immunohistochemical assay. RESULTS: Compared with the normal control group, the cardiomyocyte apoptosis rate and Bax expression level obviously increased, but the expression of Bcl-2 and the Bcl-2/Bax ratio decreased significantly in the model group (P < 0.05). Compared with the model group, the expression of Bax and the Bcl-2/Bax ratio increased significantly in the high dose XG group and the irbesartan group (P < 0.01). The Bax expression level obviously decreased in all groups except the normal control group (P < 0.01). CONCLUSIONS: XG could obviously attenuate cardiomyocyte apoptosis in the adriamycin-induced DCM rats, and reverse the occurrence and development of heart reconstruction. The underlying mechanism might be related to regulating and controlling the expressions of Bax and Bcl-2.

Sesquiterpenoids and monoterpenoids from the water decoction of Valeriana officinalis L.

Nine previously undescribed compounds including three sesquiterpenoids, three iridoids, two monoterpenoids and a furan fatty acid, along with seventeen known ones, were isolated from the water decoction of roots and rhizomes of Valeriana officinalis L. Structure elucidation of the twenty-six compounds were accomplished by analysis of the extensive spectroscopic data, and the absolute configurations of the nine previously undescribed ones were established by NOESY experiment and the electronic circular dichroism (ECD) simulations. Among them, ß-patchoulene-8-O-ß-D-glucopyranoside, 11-methoxyl-viburtinal, and protocatechuic acid showed anti-neuroinflammatory potentials by significantly inhibiting the secretion of nitric oxide (NO) on BV-2 cells upon LPS stimulation (p < 0.001) without affecting the cell viability.

Santalane-type sesquiterpenoids and isobenzofuranones from cultures of Paraconiothyrium sporulosum YK-03.

Three undescribed santalane-type sesquiterpenoids (parasantalenoic acids A-C) and two undescribed epimeric isobenzofuranones (paraphthalides A and B) were isolated from cultures of the marine mud-associated fungus Paraconiothyrium sporulosum YK-03. Their structures were elucidated by analysis of the extensive spectroscopic and crystal X-ray diffraction data, combined with ECD calculations and comparison. Santalane-type sesquiterpenoids have been firstly found in the Paraconiothyrium species. Parasantalenoic acids A-C represent three rare polyhydroxylated santalane-type sesquiterpenoid carboxylic acids, and parasantalenoic acid A represents the first example of 2-chlorinated santalane-type sesquiterpenoid. A plausible biosynthetic pathway for parasantalenoic acids A-C was proposed. Additionally, the anti-neuroinflammatory activities of parasantalenoic acids A-C were investigated by evaluating their inhibitory effects on nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated BV-2 microglia cells. Among them, parasantalenoic acid C showed significant anti-neuroinflammatory activity with an inhibition of 86.45 ± 2.45% at 10 µM.

Data mining for adverse drug reaction signals of daptomycin based on real-world data: a disproportionality analysis of the US Food and Drug Administration adverse event reporting system.

BACKGROUND: Previous reports on daptomycin's adverse drug reactions (ADRs) have been insufficient, often because of limited data. Pharmacovigilance risk signal detection is innovative and has been applied to the safety monitoring and reevaluation of drugs post-marketing. AIM: The study aimed to promote safe daptomycin prescribing by mining and evaluating the daptomycin ADR signals from the US Food and Drug Administration Adverse Event Reporting System (FAERS). METHOD: A disproportionality analysis (reporting odds ratio ROR and proportional reporting ratio PRR) was utilized for FAERS data mining from the first quarter of 2004 to the second quarter of 2021 (the most recent quarterly data at the time of the study). Preferred Terms of ADR reports were categorized by System Organ Class (SOC) based on the Medical Dictionary for Regulatory Activities. RESULTS: This study retrieved 12,221 cases within the reporting period. A total of 140 repetitive signals were obtained by ROR and PRR, of which 53 new ADR signals were not recorded in the drug labels/datasheets. The top three ADR reports were "blood creatine phosphokinase elevation" (ROR, 56.66, 95% confidence interval (CI) 51.07-62.87, PRR 51.94), "eosinophilic pneumonia" (ROR 696.71, 95%CI 603.21-804.70, PRR 657.57), and "rhabdomyolysis" (ROR 22.85, 95%CI 19.94-26.18, PRR 21.83). The highest ROR of "antimicrobial susceptibility test resistant" was found at 9808.14. Reports of rare adverse events, such as "necrotizing fasciitis and compartment syndrome," have emerged. The significant SOCs were "Infections and Infestations" and "Investigations." CONCLUSION: New daptomycin ADR signals were detected. Clinicians should monitor these potential ADRs in patients receiving daptomycin.

Xueshuantong injection combined with Salvianolate lyophilized injection improves the synaptic plasticity against focal cerebral ischemia/reperfusion injury in rats through PI3K/AKT/mTOR and RhoA/ROCK pathways.

The combined use of two or more different drugs can better promote nerve recovery and its prognosis for treatment of stroke. Salvianolate lyophilized injection (SLI) made from the aqueous extraction of salvia miltiorrhiza and Xueshuantong injection (lyophilized) (XST) made from the Panax Notoginseng extraction are two herbal standardized preparations that have been widely used in China for the treatment of ischemic stroke. In this study, we investigated the neuroprotective effects of XST combined with SLI in the recovery stage of middle cerebral artery occlusion / reperfusion (MCAO/R) injury rat. Wistar rats were subjects to MCAO/R, then were treated with SLI or XST alone, or with their combination (1X1S) via tail injection daily for 14 days. The pathological status of the brain was detected by neurological deficit scores, TTC, regional cerebral blood flow and Nissl staining. Golgi-Cox staining was used to assess dendritic, axonal and synaptic remodeling. The expression of MAP-2, ß-Tubulin, PSD95, SYN, BDNF and VEGF were analyzed by western blotting and immunofluorescence. The results showed that administration of 1X1S not only significantly decreased neurological scores and infarct volumes, but also increased regional cerebral blood flow, strengthened dendritic and synaptic remodeling compared with XST, SLI used alone. And the mechanism of combined of 1X1S to exert neuroprotection may be associated with PI3K/ AKT/ mTOR and RhoA/ROCK2 pathways. Overall, these findings suggest that combination of XST and SLI promotes dendritic spine density and synaptic plasticity via upregulation of the PI3K/ AKT/ mTOR pathways and inhabitation the RhoA/ROCK2 signaling pathway in rat with MCAO/R, showing its multiple-action-multiple-target efficacy and suggest a potential new strategy for ischemia.

Neuroprotective effects of scutellarin against hypoxic-ischemic-induced cerebral injury via augmentation of antioxidant defense capacity.

An increasing number of studies has indicated that hypoxic-ischemic-induced cerebral injury is partly mediated via oxidative stress. Recent researches have focused on searching for drug and herbal manipulations to protect against hypoxic-ischemic-induced oxidative cell damage. Scutellarin is a flavonoid derived from the Erigeron breviscapus (vant.) and has been reported to exhibit neuroprotective properties. However, its precise mechanism, particularly its antioxidation mechanism, remains elusive. In the present study, we investigated the neuroprotective effects of scutellarin on middle cerebral artery occlusion (MCAO)-induced brain damage in rats, and oxygen-glucose deprivation (OGD)-induced toxicity in primary culture of rat cortical neurons. In vivo, intraperitoneal injections of scutellarin (20 and 60 mg/kg) improved the neurological score and diminished the percentage of brain infarct volume. At the same time, scutellarin significantly increased superoxide dismutase (SOD), catalase (CAT) activities and glutathione (GSH) level in ischemic brain tissues, enhancing endogenous antioxidant activity. Moreover, pretreatment of scutellarin (25, 50 and 100 µM) protected neurons against lethal stimuli, decreased the percentage of apoptotic cells and inhibited reactive oxygen species (ROS) generation in OGD-induced primary cortical neurons in vitro. These results suggest that the preventive and therapeutic potential of scutellarin in cerebral injury patients is, at least in part, ascribed to augmentation of cellular antioxidant defense capacity.

Effects of salvianolate lyophilized injection combined with Xueshuantong injection in regulation of BBB function in a co-culture model of endothelial cells and pericytes.

The combined use of two or more different drugs can better promote nerve recovery and its prognosis for treatment of stroke. The salvianolate lyophilized injection (SLI) and Xueshuantong Injection (XST) are two standardized Chinese medicine injections which have been widely used in the treatment of cerebrovascular diseases. Salvianolic acid B (Sal B) and Notoginsenoside R1 (NR1) is respectively one of the active constituents of SLI and XST, which have certain effects on stroke. In this study, we established a co-culture of endothelial cells and pericytes for oxygen-glucose deprivation/reperfusion (OGD/R) injury model to study the effects of SLI and Sal B or XST and NR1 alone, or with their combinations (1S1X) in regulation of BBB function. The results showed that compared with the OGD/R group, treatment with SLI, XST and SalB and NR1 can significantly increase the TEER, reduce the permeability of Na-Flu, enhance the expression of tight junctions (TJs) between cells, and stabilize the basement membrane (BM) composition. In addition, the combination of 1S1X is superior to the XST or SLI alone in enhancing the TJs between cells and stabilizing the BM. And the active components SalB and NR1 can play a strong role in these two aspects, even with the whole effects. Furthermore, the study showed that XST, Sal B and NR1 increases in Ang-1and Tie2, while decrease in Ang-2 and VEGF protein expressions. Overall, these findings suggest that SLI combined with XST (1X1S) has protective effects on co-culture of endothelial cells and pericytes after OGD/R. Moreover, its protective effect might be associated with increase of TJs and BMs through activation of Ang/Tie-2 system signaling pathway.

Anti-inflammatory activity of salvianolic acid B in microglia contributes to its neuroprotective effect.

This study examined whether Salvianolic acid B (Sal B), a major active component of Chinese herb Radix Salviae Miltiorrhizae, may exert an anti-inflammatory effect in microglia and may be neuroprotective by regulating microglial activation. Our results showed that Sal B significantly reduced the production of nitric oxide (NO), tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta) and reactive oxygen species (ROS) induced by lipopolysaccharide (LPS) treatment in rat primary microglia in a dose-dependent manner. Sal B had no effects on ATP-dependent IL-1beta release and interferon (IFN)-gamma-induced NO production. Sal B also suppressed LPS-induced inducible nitric oxide synthase (iNOS), TNF-alpha, and IL-1beta mRNA expression, which was accompanied by inhibiting transcription factor NF-kappaB activation. Sal B could protect neurons through inhibition of microglial activation in a microglia-neuron coculture system. In conclusion, these data demonstrate that anti-inflammatory activity of Sal B in microglia contributes to its neuroprotective effect and suggest that it may be useful for preventing microglia-mediated neuroinflammation.

A novel low-cost electrode for recording the local field potential of freely moving rat's brain.

Local field potentials (LFPs) are involved in almost all cognitive activities of animals. Several kinds of recording electrodes are used for recording LFPs in freely moving animals, including commercial and homemade electrodes. However, commercial recording electrodes are expensive, and their relatively fixed size often causes a steric hindrance effect, especially when combining deep brain stimulation (DBS) with LFP recording, which may not always satisfy the aim of researchers. Currently, an increasing number of researchers are designing their own recording electrodes to lower research costs. Nevertheless, there is no simple universal method to produce low-cost recording electrodes with a specific size according to the target brain area. Thus, we developed a simple method for quickly producing low-cost multiple-channel recording electrodes. To inspect the effectiveness of our self-designed electrode, LFPs were recorded in a Parkinson's disease (PD) rat model, and an electrical stimulation electrode was implanted into the subthalamic nucleus to verify the space-saving ability of the self-designed recording electrode. The results showed that <30 min was needed to prepare an electrode and that the electrode materials cost <5 dollars. Further investigations showed that our electrode successfully recorded the beta oscillations (12-40 Hz) in the PD rat model. Thus, this method will greatly reduce the cost of recording electrodes and save time for researchers. Additionally, the small size of the electrode will further facilitate DBS research.

Xueshuantong for Injection (Lyophilized, ) Alleviates Streptozotocin-Induced Diabetic Retinopathy in Rats.

OBJECTIVE: To investigate the ameliorate effect and underlying mechanism of Xueshuantong for Injection (Lyophilized, , XST) in streptozocin (STZ)-induced diabetic retinopathy (DR) rats. METHODS: Diabetes mellitus (DM) model was induced by intraperitoneal (i.p.) injection of STZ (60 mg/kg) in Sprague-Dawley rats. Diabetic rats were randomized into 3 groups (n=10) according to a random number table, including DM, XST50 and XST100 groups. XST treatment groups were daily i.p. injected with 50 or 100 mg/kg XST for 60 days, respectively. The control and DM groups were given i.p. injection with saline. Blood glucose level and body weight were recorded every week. Histological changes in the retina tissues were observed with hematoxylin-eosin staining. Apoptosis and inflammation related factors, including cleaved caspase-3, glial fifibrillary acidic protein (GFAP), tumor necrosis factor-α (TNF-α) and intercellular cell adhesion molecule-1 (ICAM-1) were detected by Western blot or real-time polymerase chain reaction. Then, the levels of advanced glycation end product (AGE) and its receptor (RAGE) were investigated. Tight junctions proteins (Zonula occludens-1 (ZO-1), Occludin and Claudin-5) of blood-retinal barrier were detected by Western blot. The levels of retinal fifibrosis, transforming growth factor-ß1 (TGF-ß1)-Smad2/3 signaling pathway were evaluated at last. RESULTS: There was no signifificant difference in the body weight and blood glucose level between XST and DM groups (P>0.05). Compared with the DM group, XST treatment signifificantly increased the retinal thickness of rats (P<0.05 or P<0.01), and suppressed cleaved caspase-3 expression (P<0.01). XST increased the protein expressions of ZO-1, Occludin and Claudin-5 and decreased the mRNA expressions of matrix metalloproteinase 2 (MMP-2) and MMP-9 (P<0.05 or P<0.01). Moreover, XST signifificantly reduced the productions of AGE and RAGE proteins in the retina of rats (P<0.05 or P<0.01), suppressed the over-expression of TNF-α, and decreased the elevated level of ICAM-1 in retina of rats (P<0.05 or P<0.01). XST signifificantly reduced the levels of α-smooth muscle actin (α-SMA), connective tissue growth factor (CTGF), TGF-ß1 and phosphorylation of Smad2/3 protein in rats (P<0.05 or P<0.01). CONCLUSIONS: XST had protective effects on DR with possible mechanisms of inhibiting the inflammation and apoptosis, up-regulating the expression of tight junction proteins, suppressing the productions of AGE and RAGE proteins, and blocking the TGF-ß/Smad2/3 signaling pathway. XST treatment might play a role for the future therapeutic strategy against DR.

Histology and molecular pathology of iliotibial tract contracture in patients with gluteal muscle contracture.

The present study aimed to examine the pathologic changes of the iliotibial tract and discusses its relationship with gluteal muscle contracture. Samples of contractual iliotibial tracts were collected from six patients with contractures of the gluteal muscles and iliotibial tracts during their surgical treatment. Samples of normal iliotibial tracts were collected from six patients receiving surgeries for avascular necrosis of the femoral head who had no contractures of the gluteal muscles and iliotibial tracts. The tissue samples were stained using Hematoxylin and Eosin (H&E), Masson's trichrome, and Sirius Red. The mRNA and protein levels of various tissue repair genes were determined using quantitative real-time PCR and Western blotting. Both the normal and contractual iliotibial tracts consisted of type I and III collagens. The contractual iliotibial tracts had a significantly higher proportion of type III collagen in comparison with the normal iliotibial tracts. The mRNA expression levels and protein levels of tissue repair genes TGFß 1, bFGF, and matrix metalloproteinase-1 (MMP-1) in the contractual iliotibial tracts were up-regulated in comparison with that in the normal iliotibial tracts. However, the mRNA expression levels and protein levels of tissue inhibitors of metalloproteinase-1 (TIMP) in the contractual iliotibial tracts were down-regulated in comparison with that in the normal iliotibial tracts. The contractures of both the gluteal muscles and the iliotibial tracts share similar histology and molecular pathology. Our results indicate that iliotibial tract contracture is secondary to the gluteal muscle contracture and is a constant tissue repair process.

Shuxuetong injection protects cerebral microvascular endothelial cells against oxygen-glucose deprivation reperfusion.

Shuxuetong injection composed of leech (Hirudo nipponica Whitman) and earthworm (Pheretima aspergillum) has been used for the clinical treatment of acute stroke for many years in China. However, the precise neuroprotective mechanism of Shuxuetong injection remains poorly understood. Here, cerebral microvascular endothelial cells (bEnd.3) were incubated in glucose-free Dulbecco's modified Eagle's medium containing 95% N2/5% CO2 for 6 hours, followed by high-glucose medium containing 95% O2 and 5% CO2 for 18 hours to establish an oxygen-glucose deprivation/reperfusion model. This in vitro cell model was administered Shuxuetong injection at 1/32, 1/64, and 1/128 concentrations (diluted 32-, 64-, and 128-times). Cell Counting Kit-8 assay was used to evaluate cell viability. A fluorescence method was used to measure lactate dehydrogenase, and a fluorescence microplate reader used to detect intracellular reactive oxygen species. A fluorescent probe was also used to measure mitochondrial superoxide production. A cell resistance meter was used to measure transepithelial resistance and examine integrity of monolayer cells. The fluorescein isothiocyanate-dextran test was performed to examine blood-brain barrier permeability. Real-time reverse transcription polymerase chain reaction was performed to analyze mRNA expression levels of tumor necrosis factor alpha, interleukin-1ß, interleukin-6, and inducible nitric oxide synthase. Western blot assay was performed to analyze expression of caspase-3, intercellular adhesion molecule 1, vascular cell adhesion molecule 1, occludin, vascular endothelial growth factor, cleaved caspase-3, B-cell lymphoma 2, phosphorylated extracellular signal-regulated protein kinase, extracellular signal-regulated protein kinase, nuclear factor-κB p65, I kappa B alpha, phosphorylated I kappa B alpha, I kappa B kinase, phosphorylated I kappa B kinase, claudin-5, and zonula occludens-1. Our results show that Shuxuetong injection increases bEnd.3 cell viability and B-cell lymphoma 2 expression, reduces cleaved caspase-3 expression, inhibits production of reactive oxygen species and mitochondrial superoxide, suppresses expression of tumor necrosis factor alpha, interleukin-1ß, interleukin-6, inducible nitric oxide synthase mRNA, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1, markedly increases transepithelial resistance, decreases blood-brain barrier permeability, upregulates claudin-5, occludin, and zonula occludens-1 expression, reduces nuclear factor-κB p65 and vascular endothelial growth factor expression, and reduces I kappa B alpha, extracellular signal-regulated protein kinase 1/2, and I kappa B kinase phosphorylation levels. Overall, these findings suggest that Shuxuetong injection has protective effects on brain microvascular endothelial cells after oxygen-glucose deprivation/reperfusion. Moreover, its protective effect is associated with reduction of mitochondrial superoxide production, inhibition of the inflammatory response, and inhibition of vascular endothelial growth factor, extracellular signal-regulated protein kinase 1/2, and the nuclear factor-κB p65 signaling pathway.

[Effects of combined addition of organic materials with zinc fertilizer on zinc availability and transformation in calcareous soil]. / æœ‰æœºç‰©æ–™ä¸Žé”Œè‚¥é æ–½å¯¹çŸ³ç°æ€§åœŸå£¤é”Œæœ‰æ•ˆæ€§åŠå½¢æ€è½¬åŒ–çš„å½±å“.

To investigate the changes of Zn availability and transformation in calcareous soil, orga-nic materials (maize straw, biofertilizer, fulvic acids, and chicken manure) were thoroughly mixed with the soils amended with Zn fertilizer in the nylon net bags and buried in a field. Results showed that compared with control (neither Zn nor organic materials), Zn fertilizer alone and combined addition with organic materials significantly increased soil total Zn concentration (7.2%-13.8%) and DTPA-Zn concentration (2.1-2.8 folds). For the Zn amended treatments, the contributions of organic amendments to soil total Zn and DTPA-Zn concentration decreased in the order of chicken manure > biofertilizer > maize straw > fulvic acids. The highest conversion rate of exogenous Zn into DTPA-Zn occurred in the treatments with straw and biofertilizer. In comparison with single Zn application, combination of Zn fertilizer with organic materials increased soil organic matter and stimulated more Zn weakly bound to organic matter, enhanced mobility factor and reduced distribution index of Zn in soil. The differences in soil Zn availability and transformation among the combinations of Zn fertilizer and organic materials were likely linked to the inherent properties of organic materials such as maturity degree and Zn content. Considering the environment safety and cost reduction, combining Zn fertilizer and straw return was the best practice to enhance Zn availability in the Zn-deficient calcareous soil, although its contribution to Zn availability was less than the combination of biofertilizer or chicken manure with Zn fertilizer.