Beneficial Effects of Oxymatrine from Sophora flavescens on Alleviating by Improving Inflammation and Ferroptosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Sophora flavescens is often used in traditional Chinese medicine for skin issues, diarrhea, and vaginal itching (Plant names have been checked with http://www.the plant list.org on Feb 22th, 2024). Oxymatrine (OY), a major bioactive compound from Sophora flavescens, is commonly used in China to treat ulcerative colitis, but its mechanisms are still unclear. AIM OF THE STUDY: Recent studies have found that the crosstalk between ferroptosis and inflammation is an important mechanism in the pathogenesis of UC. The aim of this study was to investigate the potential underlying mechanisms of OY treatment on DSS-induced ulcerative colitis, specifically focusing on the processes of ferroptosis and inflammation. MATERIALS AND METHODS: Bioinformatics methods were used to identify key targets of OY for ferroptosis and inflammation in ulcerative colitis, based on GEO data and FerrDb database. Then, 4% DSS solution was used to induce UC model. OY's impact on morphological changes was assessed using colon views, Hematoxylin and eosin (HE) staining, and transmission electron microscopy (TEM). Ferroptosis phenotype index and inflammations factors were detected by ELISA or chem-bio detection kits The screen out hub related genes about ferroptosis and inflammation were verified by RT-PCR, immunohistochemistry (IHC), immunofluorescence (IF), and western blotting (WB) respectively. RESULTS: Bioinformatics results show that there are 16 key target genes involved in ferroptosis and inflammation interaction of OY treatment for UC, such as IL6, NOS2, IDO1, SOCS1, and DUOX. The results of animal experiments show that OY could depress inflammatory factors (IL-1ß, IL-6, TNF-α, HMGB1, and NLRP3) and reduce iron deposition (Fe2+, GSH, and ferritin). Additionally, OY suppressed the hub genes or proteins expression involved in ferroptosis and inflammation, including IL-1ß, IL-6, NOS2, HIF1A, IDO1, TIMP1, and DUOX2. CONCLUSION: This present study combines bioinformatics, molecular biology, and animal experimental research evidently demonstrated that OY attenuates UC by improving ferroptosis and inflammation, mainly target to the expression of IL-1ß, IL-6, NOS2, HIF1A, IDO1, TIMP1, and DUOX2.

Narazaciclib, a novel multi-kinase inhibitor with potent activity against CSF1R, FLT3 and CDK6, shows strong anti-AML activity in defined preclinical models.

CSF1R is a receptor tyrosine kinase responsible for the growth/survival/polarization of macrophages and overexpressed in some AML patients. We hypothesized that a novel multi-kinase inhibitor (TKi), narazaciclib (HX301/ON123300), with high potency against CSF1R (IC50 ~ 0.285 nM), would have anti-AML effects. We tested this by confirming HX301's high potency against CSF1R (IC50 ~ 0.285 nM), as well as other kinases, e.g. FLT3 (IC50 of ~ 19.77 nM) and CDK6 (0.53 nM). An in vitro proliferation assay showed that narazaciclib has a high growth inhibitory effect in cell cultures where CSF1R or mutant FLT3-ITD variants that may be proliferation drivers, including primary macrophages (IC50 of 72.5 nM) and a subset of AML lines (IC50 < 1.5 µM). In vivo pharmacology modeling of narazaciclib using five AML xenografts resulted in: inhibition of MV4-11 (FLT3-ITD) subcutaneous tumor growth and complete suppression of AM7577-PDX (FLT3-ITD/CSF1Rmed) systemic growth, likely due to the suppression of FLT3-ITD activity; complete suppression of AM8096-PDX (CSF1Rhi/wild-type FLT3) growth, likely due to the inhibition of CSF1R ("a putative driver"); and nonresponse of both AM5512-PDX and AM7407-PDX (wild-type FLT3/CSF1Rlo). Significant leukemia load reductions in bone marrow, where disease originated, were also achieved in both responders (AM7577/AM8096), implicating that HX301 might be a potentially more effective therapy than those only affecting peripheral leukemic cells. Altogether, narazaciclib can potentially be a candidate treatment for a subset of AML with CSF1Rhi and/or mutant FLT3-ITD variants, particularly second generation FLT3 inhibitor resistant variants.

Capsicum leaf protein-based bionanocomposite films for packaging application: Effect of corn starch content on film properties.

The addition of corn starch (CS) enhances the interfacial adhesion of the film-forming liquids (FFLs), weakening the internal relative molecular motion. As a result, the rheological properties and zeta potential values of the FFLs were affected. A tight spatial network structure between capsicum leaf protein (CLP), lignocellulose nanocrystals (LNCs) and CS can be formed through intermolecular entanglement and hydrogen bonding interactions. The crystallinity, thermal degradation temperature, tensile strength and water contact angle of the protein-based bionanocomposite films (PBBFs) increased with increasing CS addition. This is due to the transformation of the secondary space structure of the CLP inside the PBBFs and the increase in cohesion. However, the excessive addition of CS forms aggregated clusters on the surface of PBBFs, which increases the surface roughness of PBBFs and causes more light scattering. Therefore, the brightness and yellowness values of the PBBFs increase, and the transmittance decreases.

Effect of moxibustion combined with intraperitoneal injection of benazepril on endoplasmic reticulum stress-related protein phosphorylation in rats with chronic heart failure. / è‰¾ç¸è”åˆè´é‚£æ™®åˆ©å¯¹æ ¢æ€§å¿ƒåŠ›è¡°ç«­å¤§é¼ å¿ƒè‚Œå† è´¨ç½‘åº”æ¿€ç›¸å ³è›‹ç™½ç£·é ¸åŒ–è¡¨è¾¾çš„å½±å“.

OBJECTIVES: To observe the effect of moxibustion at "Xinshu"(BL15) and "Feishu"(BL13) combined with intraperitoneal injection of benazepril on cardiac function and phosphorylation of protein kinase R-like endoplasmic reticulum kinase (PERK) and eukaryotic initiation factor 2α (elF2α) proteins in myocardium of rats with chronic heart failure (CHF), so as to explore its potential mechanism underlying improvement of CHF. METHODS: A total of 42 male SD rats were randomly assigned to blank control (n=10), CHF model (n=7), medication (benazepril, n=8), moxibustion (n=8) and moxibustion+benazepril (n=9) groups, after cardiac ultrasound model identification and elimination of the dead. The CHF model was established by intraperitoneal injection of doxorubicin hydrochloride (DOX), once every week for 6 weeks. Mild moxibustion was applied to bilateral BL15 and BL13 regions for 20 min, once daily for 3 weeks. The rats of the medication group and moxibustion+benazepril group (benazepril was given first, followed by moxibustion) received intraperitoneal injection of benazepril (0.86 mg/kg) solution once daily for 3 weeks . The cardiac ejection fraction (EF) and left ventricular fractional shortening (FS) were measured using echocardiography. Histopathological changes of the cardiac muscle tissue were observed under light microscope after hematoxylin-eosin (H.E.) staining. Serum contents of B-type brain natriuretic peptide (BNP) and angiotensin Ⅱ (AngⅡ) were measured by enzyme-linked immunosorbent assay (ELISA). The expressions of phospho-PERK (p-PERK) and phospho-elF2α (p-elF2α) in the myocardium were detected by Western blot. RESULTS: Compared with the blank control group, the EF and FS of the left cardiac ventricle were significantly decreased (P<0.01), while the contents of serum BNP and AngⅡ, and expression levels of p-PERK and p-eIF2α significantly increased in the model group (P<0.01). In comparison with the model group, both the decreased EF and FS and the increased BNP and AngⅡ contents as well as p-PERK and p-elF2α expression levels were reversed by moxibustion, medication and moxibustion+benazepril (P<0.01). The effects of moxibustion+benazepril were markedly superior to those of simple moxibustion and simple medication in raising the levels of EF and FS rate and in down-regulating the contents of BNP, Ang Ⅱ, levels of p-PERK and p-elF2α (P<0.01, P<0.05). Outcomes of H.E. staining showed irregular arrangement of cardiomyocytes, cell swelling, vacuole and inflammatory infiltration in the model group, which was relatively milder in the 3 treatment groups. The effects of moxibustion+benazepril were superior to those of moxibustion or benazepril. CONCLUSIONS: Moxibustion combined with Benazepril can improve the cardiac function in CHF rats, which may be related to its functions in down-regulating the expression levels of myocardial p-PERK and p-elF2α to inhibit endoplasmic reticulum stress response.

Effects of capsaicin loads on the properties of capsicum leaf protein-based nanocellulose composite films.

This study aims to enhance the functionality of conventional protein-based nanocellulose composite films (PNCF) to meet the high demand for natural antimicrobial packaging films. Capsicum leaf protein (CLP) and cellulose nanocrystals (CNCs) extracted from capsicum leaves were used as raw materials. Capsaicin, an essential antibacterial active ingredient in the capsicum plant, was used as an additive. The influence of different capsaicin loads on PNCF physicochemical and material properties was investigated under alkaline conditions. The results show that all film-forming liquids (FFLs) are non-Newtonian fluids with shear thinning behavior. When the capsaicin loading exceeds 20 %, the surface microstructure of PNCF changes from dense lamellar to rod-like. Capsaicin did not alter the PNCF crystal structure, thermal stability or chemical bonding. Capsaicin can be loaded onto the PNCF surface by intermolecular hydrogen bonding reactions with CLP and CNC, preserving capsaicin's biological activity. With increasing capsaicin loads from 0 % to 50 %, the mechanical and hydrophobic properties of PNCF decreased, whereas the diameter of the inhibition zone increased. All PNCFs have UV-blocking properties with potential applications in developing biodegradable food packaging materials. The results of this study provide a theoretical basis for the high-value utilization of capsicum cultivation waste and the preparation of novel PNCF.

Enantioselective sulfur(VI) fluoride exchange reaction of iminosulfur oxydifluorides.

Linkage chemistry and functional molecules derived from the stereogenic sulfur(VI) centre have important applications in organic synthesis, bioconjugation, drug discovery, agrochemicals and polymeric materials. However, existing approaches for the preparation of optically active S(VI)-centred compounds heavily rely on synthetic chiral S(IV) pools, and the reported linkers of S(VI) lack stereocontrol. A modular assembly method, involving sequential ligand exchange at the S(VI) centre with precise control of enantioselectivity, is appealing but remains elusive. Here we report an asymmetric three-dimensional sulfur(VI) fluoride exchange (3D-SuFEx) reaction based on thionyl tetrafluoride gas (SOF4). A key step involves the chiral ligand-induced enantioselective defluorinative substitution of iminosulfur oxydifluorides using organolithium reagents. The resulting optically active sulfonimidoyl fluorides allow for further stereospecific fluoride-exchange by various nucleophiles, thereby establishing a modular platform for the asymmetric SuFEx ligation and the divergent synthesis of optically active S(VI) functional molecules.

Acid-Catalyzed Highly Enantioselective Synthesis of α-Amino Acid Derivatives from Sulfinamides and Alkynes.

An enantioselective difunctionalization of activated alkynes using chiral sulfinamide reagents is developed. It is an atom and chirality transfer process that allows for the modular synthesis of optically active α-amino acid derivatives under mild conditions. The reaction proceeds through an acid-catalyzed [2,3]-sigmatropic rearrangement mechanism with predictable stereochemistry and a broad scope.

Atypical inflammatory kinase IKBKE phosphorylates and inactivates FoxA1 to promote liver tumorigenesis.

Physiologically, FoxA1 plays a key role in liver differentiation and development, and pathologically exhibits an oncogenic role in prostate and breast cancers. However, its role and upstream regulation in liver tumorigenesis remain unclear. Here, we demonstrate that FoxA1 acts as a tumor suppressor in liver cancer. Using a CRISPR-based kinome screening approach, noncanonical inflammatory kinase IKBKE has been identified to inhibit FoxA1 transcriptional activity. Notably, IKBKE directly binds to and phosphorylates FoxA1 to reduce its complex formation and DNA interaction, leading to elevated hepatocellular malignancies. Nonphosphorylated mimic Foxa1 knock-in mice markedly delay liver tumorigenesis in hydrodynamic transfection murine models, while phospho-mimic Foxa1 knock-in phenocopy Foxa1 knockout mice to exhibit developmental defects and liver inflammation. Notably, Ikbke knockout delays diethylnitrosamine (DEN)-induced mouse liver tumor development. Together, our findings not only reveal FoxA1 as a bona fide substrate and negative nuclear effector of IKBKE in hepatocellular carcinioma (HCC) but also provide a promising strategy to target IKBEK for HCC therapy.

High-fat diet promotes liver tumorigenesis via palmitoylation and activation of AKT.

OBJECTIVE: Whether and how the PI3K-AKT pathway, a central node of metabolic homeostasis, is responsible for high-fat-induced non-alcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC) remain a mystery. Characterisation of AKT regulation in this setting will provide new strategies to combat HCC. DESIGN: Metabolite library screening disclosed that palmitic acid (PA) could activate AKT. In vivo and in vitro palmitoylation assay were employed to detect AKT palmitoylation. Diverse cell and mouse models, including generation of AKT1C77S and AKT1C224S knock-in cells, Zdhhc17 and Zdhhc24 knockout mice and Akt1C224S knock-in mice were employed. Human liver tissues from patients with NASH and HCC, hydrodynamic transfection mouse model, high-fat/high-cholesterol diet (HFHCD)-induced NASH/HCC mouse model and high-fat and methionine/choline-deficient diet (HFMCD)-induced NASH mouse model were also further explored for our mechanism studies. RESULTS: By screening a metabolite library, PA has been defined to activate AKT by promoting its palmitoyl modification, an essential step for growth factor-induced AKT activation. Biologically, a high-fat diet could promote AKT kinase activity, thereby promoting NASH and liver cancer. Mechanistically, palmitoyl binding anchors AKT to the cell membrane in a PIP3-independent manner, in part by preventing AKT from assembling into an inactive polymer. The palmitoyltransferases ZDHHC17/24 were characterised to palmitoylate AKT to exert oncogenic effects. Interestingly, the anti-obesity drug orlistat or specific penetrating peptides can effectively attenuate AKT palmitoylation and activation by restricting PA synthesis or repressing AKT modification, respectively, thereby antagonising liver tumorigenesis. CONCLUSIONS: Our findings elucidate a novel fine-tuned regulation of AKT by PA-ZDHHC17/24-mediated palmitoylation, and highlight tumour therapeutic strategies by taking PA-restricted diets, limiting PA synthesis, or directly targeting AKT palmitoylation.

Immune infiltration is associated with pan-cancer prognostic biomarker RING finger protein 187.

Cancer is associated with the highest mortality rate globally. While life-saving screening and treatments exist, better awareness is needed. RNF187, an E3 ligase regulating biological processes, belongs to the RING domain-containing E3 ligase family. RNF187 may serve as an oncogene due to abnormal expression in tumors. However, its association with immune infiltration and prognosis across various cancers remains unclear. We searched several databases including TCGA, GTE x, CCLE, TIMER, and GSEA. R software was used to evaluate RNF187 differential expression, survival, pathology stage, DNA methylation, tumor mutational burden (TMB), microsatellite instability (MSI), gene co-expression analysis, mismatch repairs (MMRs), tumor microenvironment (TME), and immune cell infiltration. Clinicopathological data were collected, and immunohistochemistry was used to verify RNF187 expression in tumor tissues. RNF187 expression was up-regulated in various cancers compared to that in normal tissues and associated with poor patient outcomes. Dysregulation of RNF187 expression in multiple cancer types was strongly correlated with DNA methylation, MMR, MSI, and TMB. RNF187 could interact with different immune cells in cancers. Biomarkers associated with RNF187 may be helpful for prognosis and immunology in treating pan-cancer patients.

Insight into the effect of different nanocellulose types on protein-based bionanocomposite film properties.

This paper investigates the effect of five different types of nanocellulose on the properties of protein-based bionanocomposite films (PBBFs) and the mechanism of action. The results show that TEMPO-oxidized nanocellulose (TNC) PBBFs have the smoothest surface structure. This is because some hydroxyl groups in TNC are converted to carboxyl groups, increasing hydrogen bonding and cross-linking with proteins. Bacterial nanocellulose (BNC) PBBFs have the highest crystallinity. Filamentous BNC can form an interlocking network with protein, promoting effective stress transfer in the PBBFs with maximum tensile strength. The PBBFs of lignin nanocellulose (LNC) have superior elasticity due to the presence of lignin, which gives them the greatest creep properties. The PBBFs of cellulose nanocrystals (CNCs) have the largest water contact angle. This is because the small particle size of CNC can be uniformly distributed in the protein matrix. The different types of nanocellulose differ in their microscopic morphology and the number of hydroxyl groups and hydrogen bonding sites on their surfaces. Therefore, there are differences in the spatial distribution and the degree of intermolecular cross-linking of different types of nanocellulose in the protein matrix. This is the main reason for the differences in the material properties of PBBFs.

Quercetin and AMPK: A Dynamic Duo in Alleviating MG-Induced Inflammation via the AMPK/SIRT1/NF-κB Pathway.

Mycoplasma gallisepticum (MG) is recognized as a principal causative agent of avian chronic respiratory disease, inflicting substantial economic losses upon the poultry industry. However, the extensive use of conventional antibiotics has resulted in the emergence of drug resistance and various challenges in their clinical application. Consequently, there is an urgent need to identify effective therapeutic agents for the prevention and treatment of mycoplasma-induced respiratory disease in avian species. AMP-activated protein kinase (AMPK) holds significant importance as a regulator of cellular energy metabolism and possesses the capacity to exert an anti-inflammatory effect by virtue of its downstream protein, SIRT1. This pathway has shown promise in counteracting the inflammatory responses triggered by pathogenic infections, thus providing a novel target for studying infectious inflammation. Quercetin possesses anti-inflammatory activity and has garnered attention as a potential alternative to antibiotics. However, there exists a gap in knowledge concerning the impact of this activation on MG-induced inflammatory damage. To address this knowledge gap, we employed AlphaFold2 prediction, molecular docking, and kinetic simulation methods to perform a systematic analysis. As expected, we found that both quercetin and the AMPK activator AICAR activate the chicken AMPKγ1 subunit in a similar manner, which was further validated at the cellular level. Our project aims to unravel the underlying mechanisms of quercetin's action as an agonist of AMPK against the inflammatory damage induced by MG infection. Accordingly, we evaluated the effects of quercetin on the prevention and treatment of air sac injury, lung morphology, immunohistochemistry, AMPK/SIRT1/NF-κB pathway activity, and inflammatory factors in MG-infected chickens. The results confirmed that quercetin effectively inhibits the secretion of pro-inflammatory cytokines such as IL-1ß, TNF-α, and IL-6, leading to improved respiratory inflammation injury. Furthermore, quercetin was shown to enhance the levels of phosphorylated AMPK and SIRT1 while reducing the levels of phosphorylated P65 and pro-inflammatory factors. In conclusion, our study identifies the AMPK cascade signaling pathway as a novel cellular mediator responsible for quercetin's ability to counter MG-induced inflammatory damage. This finding highlights the potential significance of this pathway as an important target for anti-inflammatory drug research in the context of avian respiratory diseases.

Hydrosulfonylation of Unactivated Alkenes and Alkynes by Halogen-Atom Transfer (XAT) Cleavage of SVI-F Bond.

A photochemical halogen-atom transfer (XAT) method for generating sulfonyl radicals from aryl sulfonyl fluorides has been developed. It allows the hydrosulfonylation of unactivated alkenes, which was challenging to achieve through our previous single-electron transfer route. This reaction has excellent functional group tolerance and substrate scope under mild conditions.

Synthesis of Sulfoximines by Copper-Catalyzed Oxidative Coupling of Sulfinamides and Aryl Boronic Acids.

A novel copper-catalyzed cross-coupling reaction of sulfinamides and aryl boronic acids is developed. The reaction is highly chemoselective and stereospecific, which allows mild synthesis of optically pure sulfoximines with broad scope and functional group tolerance. The utility of this method is demonstrated by the asymmetric synthesis of pharmaceutical intermediates.

Potentilla sericea stress-responsive spermine synthase PsSPMS enhances cadmium tolerance in Arabidopsis thaliana.

Potentilla sericea is resistant and tolerates rough management. It is an excellent garden groundcover for ecological restoration and soil consolidation for slope protection. Polyamines have functions such as promoting tissue growth and physiological resistance, while spermine synthase catalyzes the production of spermine. The PsSPMS gene from Potentilla sericea was cloned and transformed into Arabidopsis thaliana to study the response of transgenic Arabidopsis thaliana to cadmium stress. The results showed that the contents of spermidine, spermine as well as glutathione were higher in PsSPMS overexpressing Arabidopsis thaliana than the control, while the contents of putrescine were less than the control. Net photosynthetic rate, stomatal conductance, chlorophyll content, water use efficiency, electron transfer rate, PSII-related parameters, proline content, superoxide dismutase, and glutathione reductase activities were higher in PsSPMS overexpressing Arabidopsis thaliana than the control, while malondialdehyde, superoxide anion, and hydrogen peroxide contents were lower than the control. Correlation analysis showed significant differences between the indicators (P < 0.05 and P < 0.01). Expression of AtSPMS, AtSPD3, AtGSH2 and AtGR in transgenic Arabidopsis thaliana was higher than that of the control. Therefore, this study provides a genetic reference for the cultivation of cadmium-tolerant plants through genetic engineering and lays the foundation for further research on cadmium-tolerant Potentilla sericea.

Perfect Talbot self-imaging effect of aperiodic gratings.

We propose and investigate a class of aperiodic grating structure which can achieve perfect Talbot effect under certain conditions. The aperiodic grating structure is obtained by the superposition of two or more sine terms. In the case of two sine terms, the Talbot effect can be realized when the period ratio of two terms is arbitrary. While in the case of more than two sine terms, the period ratios of each term must meet certain extra conditions. The theory has been further verified by numerical simulations. It expands the field of Talbot effect and is of potential significance for subsequent research applications such as optical imaging and measurement.

Turning sulfonyl and sulfonimidoyl fluoride electrophiles into sulfur(VI) radicals for alkene ligation.

Sulfonyl and sulfonimidoyl fluorides are versatile substrates in organic synthesis and medicinal chemistry. However, they have been exclusively used as S(VI)+ electrophiles for defluorinative ligations. Converting sulfonyl and sulfonimidoyl fluorides to S(VI) radicals is challenging and underexplored due to the strong bond dissociation energy of SVI-F and high reduction potentials, but once achieved would enable dramatically expanded synthetic utility and downstream applications. In this report, we disclose a general platform to address this issue through cooperative organosuperbase activation and photoredox catalysis. Vinyl sulfones and sulfoximines are obtained with excellent E selectivity under mild conditions by coupling reactions with alkenes. The synthetic utility of this method in the preparation of functional polymers and dyes is also demonstrated.

Photothermal-Magnetic Synergistic Effects in an Electrocatalyst for Efficient Water Splitting under Optical-Magnetic Fields.

The slow oxygen evolution reaction (OER) limits water splitting, and external fields can help improve it. However, the effect of a single external field on the OER is limited and unsatisfactory. Furthermore, the mechanism by which external fields improve the OER is unclear, particularly in the presence of multiple fields. Herein, a strategy is proposed for enhancing the OER activity of a catalyst using the combined effect of an optical-magnetic field, and the mechanism of catalytic activity enhancement is studied. Under the optical-magnetic field, Co3 O4 reduces the resistance by increasing the catalyst temperature. Meanwhile, CoFe2 O4 further reduces the resistance via the negative magnetoresistance effect, thus decreasing the resistance from 16 to 7.0 Ω. Additionally, CoFe2 O4 acts as a spin polarizer, and electron polarization results in a parallel arrangement of oxygen atoms, which increases the kinetics of the OER under the magnetic field. Benefiting from the optical and magnetic response design, Co3 O4 /CoFe2 O4 @Ni foam requires an overpotential of 172.4 mV to reach a current density of 10 mA cm-2 under an optical-magnetic field, which is significantly higher than those of recently reported state-of-the-art transition-metal-based catalysts.

Risk factors for the recurrence in pulmonary tuberculosis patients with massive hemoptysis.

OBJECTIVES: To evaluate the outcomes of bronchial artery embolization (BAE) for the treatment of massive hemoptysis in patients with pulmonary tuberculosis and identify risk factors that influence recurrence. METHODS: A total of 81 patients with massive hemoptysis who underwent BAE between January 2014 and December 2017 were retrospectively reviewed. All of the patients had either a history of pulmonary tuberculosis or a current diagnosis of pulmonary tuberculosis. Follow-up ranged from 18 to 66 months. RESULTS: Hemoptysis was stopped or markedly decreased, with subsequent clinical improvement in 73 patients, while 11 patients experienced recurrence during the follow-up period. Systemic-pulmonary shunts and clinical failure showed a statistically significant correlation with the recurrence rate. The cumulative non-recurrence rate was 95.3% for 3 months and 81.9% for more than 24 months. Complications were common (12.5%), but self-limiting. CONCLUSIONS: BAE is a safe and effective treatment option for the control of massive hemoptysis in pulmonary tuberculosis patients. Systemic-pulmonary shunts and clinical failure are the risk factors for recurrence.

High fat diet induces brain injury and neuronal apoptosis via down-regulating 3-ß hydroxycholesterol 24 reductase (DHCR24).

Hyperlipidemia (HLP) is one of the risk factors for memory impairment and cognitive impairment. However, its pathological molecular mechanism remained unclear. 3ß-hydroxysterol Δ24- reductase (DHCR24) is a key enzyme in cholesterol synthesis and has been reported to decrease in the affected areas in the brain of neurodegenerative disorders. In this study, hyperlipidemic mouse model was established to study the effect of high blood lipid on brain. The data obtained from HPLC analysis demonstrated that the cholesterol level in the brain of mice with hyperlipidemia was significantly elevated compared to the control group. While the pathological damages were observed in both cerebral cortex and hippocampus in the brain of hyperlipidemic mice. Furthermore, the protein level of DHCR24 was downregulated accompanied by elevated ubiquitination level in the hyperlipidemic mice brain. The mouse neuroblastoma cells N2a were exposed to the excess cholesterol loading, the cells underwent apoptosis and the mRNA and protein of DHCR24 in cholesterol-loaded N2a cells were significantly reduced. In addition, the expression level of endoplasmic reticulum stress marker protein (Bip and Chop) was markedly increased in response to the cholesterol loading. More importantly, overexpression of DHCR24 in N2a reversed neuronal apoptosis induced by the cholesterol loading. Conclusively, these findings suggested that hyperlipidemia could cause brain tissue injuries via down-regulating DHCR24, and overexpression of DHCR24 may alleviate hyperlipidemia-induced neuronal cells damage by reversing the endoplasmic reticulum stress-mediated apoptosis.