Metal-organic frameworks for organic transformations by photocatalysis and photothermal catalysis.

Organic transformation by light-driven catalysis, especially, photocatalysis and photothermal catalysis, denoted as photo(thermal) catalysis, is an efficient, green, and economical route to produce value-added compounds. In recent years, owing to their diverse structure types, tunable pore sizes, and abundant active sites, metal-organic framework (MOF)-based photo(thermal) catalysis has attracted broad interest in organic transformations. In this review, we provide a comprehensive and systematic overview of MOF-based photo(thermal) catalysis for organic transformations. First, the general mechanisms, unique advantages, and strategies to improve the performance of MOFs in photo(thermal) catalysis are discussed. Then, outstanding examples of organic transformations over MOF-based photo(thermal) catalysis are introduced according to the reaction type. In addition, several representative advanced characterization techniques used for revealing the charge reaction kinetics and reaction intermediates of MOF-based organic transformations by photo(thermal) catalysis are presented. Finally, the prospects and challenges in this field are proposed. This review aims to inspire the rational design and development of MOF-based materials with improved performance in organic transformations by photocatalysis and photothermal catalysis.

A novel strategy with in vivo characterization, extraction, isolation and activity evaluation for discovery of absorbed anti-inflammatory oligosaccharides from Zhu-Ling decoction.

Zhu-Ling decoction (ZLD), a classical traditional Chinese medicine (TCM) formula, is used for the treatment of chronic kidney diseases. However, the structure and activity of absorbed oligosaccharides (OSs) in ZLD are not clear. In this study, a novel strategy with in vivo characterization, extraction, isolation, activity evaluation was established and applied to identify absorbed anti-inflammatory OSs in ZLD. The results revealed that 30 OSs (22 reducing and 8 non-reducing OSs) and 11 OSs (7 reducing and 4 non-reducing OS) were characterized from ZLD in vitro and in vivo by using UPLC/Q-TOF-MS with PMP derivatization, respectively. Among them, a series of -1 â†’ 3-ß-D-Glcp-OSs were isolated and identified by HPLC-HILIC-UVD-ELSD, SPHPLC-HILIC-RID, monosaccharide composition, MS and 1D/2D-NMR spectroscopy, including laminaritriose, laminaritetraose, laminaripentaose, laminarihexaose, laminariheptaose, laminarioctaose and laminarinonaose. Moreover, the 4 non-reducing absorbed OSs were identified by comparison with reference standards, including sucrose, trehalose, raffinose and stachyose. Among them, laminaritriose, laminaritetraose and laminaripentaose significantly inhibited TNF-α and IL-6 levels in LPS-induced HK-2 cell and exerted significant anti-inflammatory effects via the NF-κB and Akt/mTOR signaling pathways. Together, our work provides a novel strategy for discovery of absorbed anti-inflammatory OSs and broadens new horizons for the discovery of in vivo pharmacodynamic substances in TCM formulas.

Incidence, clinical features, and survival outcomes of primary malignant lacrimal gland tumors: A population-based analysis.

BACKGROUND: Studies on the epidemiological information and prognosis of primary malignant lacrimal gland tumors (MLGTs) are rare for its low occurrence. The goal of our research was to investigate the epidemiological characteristics and survival outcomes of patients with MLGTs. METHODS: Incidence and demographic information of patients with MLGTs were collected from the Surveillance, Epidemiology, and End Results (SEER) database. To identify independent prognostic factors for disease-specific survival (DSS) and overall survival (OS), univariate and multivariate Cox regression analysis were performed. RESULTS: The overall incidence of primary MLGTs from 1975 to 2020 was 0.413/1,000,000 (according to the 2000 American standard population), with a steadily increasing incidence over years. A total of 964 patients with primary MLGTs were diagnosed, with an average age of 59.3 years. Of these, 53.2% were aged ≥60 years, 57.4% were female, and 77.1% were whites. Multivariate Cox regression analysis demonstrated that year of diagnosis, age, sex, histological type, SEER stage, surgery, and chemotherapy were independent prognostic factors of DSS or OS. CONCLUSIONS: Although primary MLGT is rare, its incidence has steadily increased in the past 46 years, and surgery was related to a better prognosis.

Promising Natural Medicines for the Treatment of High-Altitude Illness.

Li Li, Lin Lin, Bo Wen, Peng-cheng Zhao, Da-sheng Liu, Guo-ming Pang, Zi-rong Wang, Yong Tan, and Cheng Lu. Promising natural medicines for the treatment of high-altitude illness. High Alt Med Biol. 24:175-185, 2023.-High-altitude illness (HAI) is a dangerous disease characterized by oxidative stress, inflammatory damage and hemodynamic changes in the body that can lead to severe damage to the lungs, heart, and brain. Natural medicines are widely known for their multiple active ingredients and pharmacological effects, which may be important in the treatment of HAI. In this review, we outline the specific types of HAI and the underlying pathological mechanisms and summarize the currently documented natural medicines applied in the treatment of acute mountain sickness and high-altitude cerebral edema, high-altitude pulmonary edema, chronic mountain sickness, and high-altitude pulmonary hypertension. Their sources, types, and medicinal sites are summarized, and their active ingredients, pharmacological effects, related mechanisms, and potential toxicity are discussed. In conclusion, natural medicines, as an acceptable complementary and alternative strategy with fewer side effects and more long-term application, can provide a reference for developing more natural antialtitude sickness medicines in the future and have good application prospects in HAI treatment.

CProMG: controllable protein-oriented molecule generation with desired binding affinity and drug-like properties.

MOTIVATION: Deep learning-based molecule generation becomes a new paradigm of de novo molecule design since it enables fast and directional exploration in the vast chemical space. However, it is still an open issue to generate molecules, which bind to specific proteins with high-binding affinities while owning desired drug-like physicochemical properties. RESULTS: To address these issues, we elaborate a novel framework for controllable protein-oriented molecule generation, named CProMG, which contains a 3D protein embedding module, a dual-view protein encoder, a molecule embedding module, and a novel drug-like molecule decoder. Based on fusing the hierarchical views of proteins, it enhances the representation of protein binding pockets significantly by associating amino acid residues with their comprising atoms. Through jointly embedding molecule sequences, their drug-like properties, and binding affinities w.r.t. proteins, it autoregressively generates novel molecules having specific properties in a controllable manner by measuring the proximity of molecule tokens to protein residues and atoms. The comparison with state-of-the-art deep generative methods demonstrates the superiority of our CProMG. Furthermore, the progressive control of properties demonstrates the effectiveness of CProMG when controlling binding affinity and drug-like properties. After that, the ablation studies reveal how its crucial components contribute to the model respectively, including hierarchical protein views, Laplacian position encoding as well as property control. Last, a case study w.r.t. protein illustrates the novelty of CProMG and the ability to capture crucial interactions between protein pockets and molecules. It's anticipated that this work can boost de novo molecule design. AVAILABILITY AND IMPLEMENTATION: The code and data underlying this article are freely available at https://github.com/lijianing0902/CProMG.

Massive hemothorax secondary to internal jugular vein central venous catheter placement in a patient undergoing spinal surgery complicated by chest trauma: a case report.

BACKGROUND: Placement of a central venous catheter (CVC) is a common procedure for spinal surgery and is relatively safe under ultrasound guidance. CASE PRESENTATION: We report the case of a 56-year-old female who underwent ultrasound-guided placement of an internal jugular vein CVC for fluid replacement during spinal surgery for thoracic vertebral burst compression fracture and multiple rib fractures as a result of a high-altitude fall injury. Hemothorax developed intraoperatively. During a thoracotomy, the tip of the CVC was found within the chest cavity. The presence of chest trauma may impact on clinician's appreciation of the potential complications of internal jugular vein CVC placement. CONCLUSION: The present case demonstrates the need for clinical awareness of the potential complications of CVC placement in patients with chest trauma and the need for adequate training in this technique.

Chemical and metabolic profiling of Codonopsis Radix extract with an integrated strategy using ultra-high-performance liquid chromatography coupled with mass spectrometry.

Codonopsis radix was commonly used as food materials or herbal medicines in many countries. However, the comprehensive analysis of chemical constituents, and in vivo xenobiotics of Codonopsis radix remain unclear. In the present study, an integrated strategy with feature-based molecular networking using ultra-high-performance liquid chromatography coupled with mass spectrometry was established to systematically screen the chemical constituents and the in vivo xenobiotics of Codonopsis radix. A step-by-step manner based on a composition database, visual structure classification, discriminant ions, and metabolite software prediction was proposed to overcome the complexities due to the similar structure of chemical constituents and metabolites of Codonopsis radix. As a result, 103 compounds were tentatively characterized, 20 of which were identified by reference standards. Besides, a total of 50 xenobiotics were detected in vivo, including 26 prototypes and 24 metabolites, while the metabolic features of the pyrrolidine alkaloids were elucidated for the first time. The metabolism reactions of pyrrolidine alkaloids and sesquiterpene lactones included oxidation, methylation, hydration, hydrogenation, demethylation, glucuronidation, and sulfation. This study provided a generally applicable approach to the comprehensive investigation of the chemical and metabolic profile of traditional Chinese medicine and offered reasonable guidelines for further screening of quality control indicators and pharmacodynamics mechanism of Codonopsis radix.

Research Progress in Competitive Purine Antagonists.

Purine, one of the nucleotides, is an important substance for the metabolism and regulation of the body. Purine plays a key role not only in the composition of coenzymes but also in the supply of energy. Since purine was artificially synthesized, it has always been an important scaffold for respiratory diseases, cardiovascular diseases, and anti- tumor and anti-viral drugs. In addition to being widely used as competitive antagonists in the treatment of diseases, purines can be used in combination with other drugs and as precursors to benefit human life. Unfortunately, few new discoveries have been made in recent years. In this article, purine drugs in the market have been classified according to their different targets. In addition, their mechanism of action and structure-activity relationship have also been introduced. This paper provides details of the signaling pathways through which purine drugs can bind to the respective receptors on the surface of cells and cause consequent reactions within the cell, which finally affect the targeted diseases. The various receptors and biological reactions involved in the signaling for respective disease targets within the cells are discussed in detail.

Simultaneous determination of multiple constituents of Qi-Lin pill by UPLC-MS/MS: Applications to pharmacokinetics and testicular tissue distribution in rats.

Qi-Lin pill (QLP) is an effective traditional Chinese medicine prescription (TCMP) that has been used for the treatment of the oligoasthenozoospermia in China. Recently, some articles described the pharmacological effects of QLP and multiple ingredients in QLP contribute to its effects. However, the pharmacokinetic and target tissue distribution data of QLP are still unknown. In the present study, according to the Bioanalytical Method Validation Guidance of FDA, a sensitive and selective UPLC-MS/MS method was developed and validated for simultaneous determination of multiple constituents in rat plasma and testicular tissue, including morusimic acid A, codonopyrridium B, magnoflorine, emodin, 2,3,5,4'-tetrahydroxystilbene-2-O-ß-D-glucoside (THSG), ecliptasaponin A, paeoniflorin, albiflorin, gallic acid, danshensu, salvianolic acid A, catechin, isosinensetin, nobiletin, formononetin, calycosin, icariside II, icariin and epimedin C. For 19 analytes, the LLOQs reached 0.01-4 ng/mL. And all calibration curves showed favorable linearity (r ≥ 0.9903) in linear ranges. The intra-day and inter-day precision (relative standard deviation) for all analytes was less than 14.92 %, and the accuracies (as relative error) were in the range of - 6.44 % to 6.22 %. Extraction recoveries and matrix effects of analytes and IS were acceptable. All analytes were stable during the assay and storage in plasma samples. The method was successfully applied for the pharmacokinetics and testis distribution of multiple chemical constituents in QLP after a single oral dose. As a result, high exposure of danshensu, gallic acid, paeoniflorin and albiflorin were observed in rat plasma and testicular tissue. Among the flavonoids, isosinensetin and nobiletin had high exposure in testicular tissue. Moreover, alleviation of progesterone reduction was evaluated in H2O2-induced R2C leydig cells, and danshensu, gallic acid, paeoniflorin, albiflorin and nobiletin showed potent activity. Therefore, these five components were considered to be the effective components of QLP due to their relatively high exposure in vivo and biological activity. This finding also provided relevant information on action mechanism of QLP in the treatment of oligoasthenozoospermia.

Sinusoidal-amplitude binary phase mask and its application in achieving an ultra-long optical needle.

Optical needle has become a hot research topic in recent years, due to the excellent properties and potential applications. To achieve a sub-diffraction optical needle, there are three common methods including planar diffractive lenses, reflective mirrors or axicons, and high-NA objective lenses with the designed phase or amplitude elements. Here, we propose a new kind of designed phase and amplitude element called the sinusoidal-amplitude binary phase mask (SA-BPM), which modulates the amplitude and phase distributions of the incident vector optical fields (VOFs) simultaneously. Based on Richards-Wolf vector diffraction integral, the corresponding parameters of SA-BPM and the optimal optical needle length are calculated by exhaustive method and genetic algorithm. We further upgrade the SA-BPM by adding a Gaussian function in the amplitude modulation, and design the Gaussian SA-BPM (GSA-BPM). We find that the ultra-long optical needles are achieved with the SA-BPM and GSA-BPM, and the depth of focus of the optical needles are improved by 30%-70% compared with the case of binary phase mask. Such SA-BPM and GSA-BPM we proposed have great potential for manipulation and utilization of the ultra-long optical needles.

Investigation of the effects of high cervical spinal cord electrical stimulation on improving neurological dysfunction and its potential mechanism in rats with traumatic brain injury.

To explore the effects of high cervical spinal cord electrical stimulation (cSCS) on the recovery of neurological function and its possible mechanism in rats with traumatic brain injury (TBI). 72 rats were randomly divided into: (1) a sham group; (2) a traumatic brain injury (TBI) group; (3) a TBI+cSCS group; (4) a LY294002+TBI+cSCS group. The degree of neurological dysfunction was evaluated by modified Neurological severity score (mNSS). The pathological changes of the brain tissue in the injured area were observed by HE staining, and the apoptosis of neuron cells were observed by TUNEL staining. The expressions of BDNF and VEGFmRNA were detected by polymerase chain reaction (PCR), and the expressions of p-AKT, AKT, Bcl-2, Bax and caspase-3 proteins were detected by western blot. Compared with that of the TBI and LY294002+TBI+cSCS groups, the mNSS of the TBI+cSCS group were significantly lower on day 3 and 7 ( P <0.05). Compared with that in the TBI and LY294002+TBI+cSCS groups, the apoptosis of neuron cells in the TBI+cSCS group decreased significantly ( P < 0.05). Compared with the TBI and LY294002+TBI+cSCS group, the expression of Bcl-2 protein increased and the expressions of Bax and Caspase-3 proteins decreased in the TBI+cSCS group ( P < 0.05). Compared with that in the TBI and LY294002+TBI+cSCS groups, the intensity of p-Akt/Akt in the TBI+cSCS group increased ( P < 0.05). We found that cSCS had a protective effect on neuron cells after craniocerebral injury and could improve neurological dysfunction in rats, the mechanism of which might be that cSCS made the PI3K/Akt pathway more active after TBI.

MLGL-MP: a Multi-Label Graph Learning framework enhanced by pathway interdependence for Metabolic Pathway prediction.

MOTIVATION: During lead compound optimization, it is crucial to identify pathways where a drug-like compound is metabolized. Recently, machine learning-based methods have achieved inspiring progress to predict potential metabolic pathways for drug-like compounds. However, they neglect the knowledge that metabolic pathways are dependent on each other. Moreover, they are inadequate to elucidate why compounds participate in specific pathways. RESULTS: To address these issues, we propose a novel Multi-Label Graph Learning framework of Metabolic Pathway prediction boosted by pathway interdependence, called MLGL-MP, which contains a compound encoder, a pathway encoder and a multi-label predictor. The compound encoder learns compound embedding representations by graph neural networks. After constructing a pathway dependence graph by re-trained word embeddings and pathway co-occurrences, the pathway encoder learns pathway embeddings by graph convolutional networks. Moreover, after adapting the compound embedding space into the pathway embedding space, the multi-label predictor measures the proximity of two spaces to discriminate which pathways a compound participates in. The comparison with state-of-the-art methods on KEGG pathways demonstrates the superiority of our MLGL-MP. Also, the ablation studies reveal how its three components contribute to the model, including the pathway dependence, the adapter between compound embeddings and pathway embeddings, as well as the pre-training strategy. Furthermore, a case study illustrates the interpretability of MLGL-MP by indicating crucial substructures in a compound, which are significantly associated with the attending metabolic pathways. It is anticipated that this work can boost metabolic pathway predictions in drug discovery. AVAILABILITY AND IMPLEMENTATION: The code and data underlying this article are freely available at https://github.com/dubingxue/MLGL-MP.

Preparation of Magnesium Hydroxide Flame Retardant from Hydromagnesite and Enhance the Flame Retardant Performance of EVA.

In this study, hydromagnesite, a rare natural hydrated alkaline magnesium carbonate, was used to synthesize magnesium hydroxide (MH) as a flame retardant for ethylene-vinyl acetate (EVA) to enhance its fire resistance and smoke suppression. Various concentrations of sodium hydroxide (NaOH) were used to alter the morphology and the flame-retardant efficiency of synthesized MH. EVA/MH composites were prepared through melt blending, and the influence of NaOH on the flame retardancy and mechanical properties was investigated by means of the limiting oxygen index (LOI), cone calorimeter test (CCT) and tensile test. The flame retardancy results demonstrated that composites exhibited remarkably improved flame retardant properties after introducing MH, reflected by an increase in the LOI value from 20% for neat EVA to roughly 38%. Additionally, the peak of heat release rate (pHRR), the total heat release (THR) and the peak of the smoke production rate for EVA3 were decreased by 37.6%, 20.7% and 44.4% compared with neat EVA, respectively. In the meantime, increasing char residues were also observed. The incorporation of different MH concentrations had a limited effect on the mechanical properties of the EVA/MH composites.

Research Progress of Graphene Nano-Electromechanical Resonant Sensors-A Review.

Graphene nano-electromechanical resonant sensors have wide application in areas such as seawater desalination, new energy, biotechnology, and aerospace due to their small size, light weight, and high sensitivity and resolution. This review first introduces the physical and chemical properties of graphene and the research progress of four preparation processes of graphene. Next, the principle prototype of graphene resonators is analyzed, and three main methods for analyzing the vibration characteristics of a graphene resonant sheet are described: molecular structural mechanics, non-local elastic theory and molecular dynamics. Then, this paper reviews research on graphene resonator preparation, discussing the working mechanism and research status of the development of graphene resonant mass sensors, pressure sensors and inertial sensors. Finally, the difficulties in developing graphene nano-electromechanical resonant sensors are outlined and the future trend of these sensors is described.

Hyperbaric oxygen via mediating SIRT1-induced deacetylation of HMGB1 improved cReperfusion inj/reperfusion injury.

Ischemic stroke leads to severe neurological dysfunction in adults. Hyperbaric oxygen (HBO) induces tolerance to cReperfusion inj/reperfusion (I/R) injury. Therefore, our aims were to investigate whether SIRT1 participates in regulatingin the neuro-protective effect of HBO in a cerebral I/R model and its mechanism. Mice N2a cells were used to construct an oxygen deprivation/reperfusion (OGD/R) model to simulate in vitro brain I/R injury and to evaluate the role of HBO in OGD/R stimulated cells. Cell proliferation was detected using MTT, and apoptosis was determined by flow cytometry. ELISA was used to measure the concentration of TNF-α, IL-1ß and IL-6 related inflammatory factors. RT-qPCR and western blot assays were performed to test the expression of SIRT1. Immunoprecipitation was used to detect acetylation of HMGB1. Expression of SIRT1 was obviously reduced after OGD/R treatment in N2a cells, while SIRT1 was obviously enhanced in HBO treated cells. Moreover, knockdown of SIRT1 induced neuro-inflammation damage in cells and HBO effectively improved the inflammatory response in OGD/R treated cells by affecting SIRT1 levels. Furthermore, HBO induced the deacetylation of HMGB1 via regulating SIRT1. Interestingly, HBO via regulating the SIRT1-induced HMGB1 deacetylation and suppressing MMP-9 improved ischemic brain injury. HBO regulated ischemic brain injury via regulation of SIRT1-induced HMGB1 deacetylation, making it a potential treatment for ischemic brain injury treatment.

[Molecular mechanism of Fagopyri Dibotryis Rhizoma in treatment of acute lung injury based on network pharmacology and in vitro experiments].

The present study explored the mechanism of Fagopyri Dibotryis Rhizoma(FDR) and its main active components in the treatment of acute lung injury(ALI) based on the network pharmacology and the in vitro experiments. The main active components of FDR were obtained from the TCMSP database and screened by oral bioavailability and drug-likeness. The related target proteins of FDR were retrieved from the PubChem database, and the target genes related to ALI were screened out from the GeneCards database. A protein-protein interaction(PPI) network of compound target proteins and ALI target genes was constructed using STRING 11.0. Ingenuity Pathway Analysis(IPA) platform was used to analyze the common pathways of the potential compound target proteins of FDR and ALI target genes, thereby predicting the key targets and potential signaling pathways of FDR for the treatment of ALI. Finally, the potential pathways and key targets were verified by the in vitro experiments of lipopolysaccharide-induced RAW264.7 cells intervened by epicatechin(EC), the active component of FDR. The results of network pharmacology showed that 15 potential active components such as EC, procyanidin B1, and luteolin presumedly functioned in the treatment of ALI through nuclear transcription factor-κB(NF-κB) signaling pathway, transforming growth factor-ß(TGF-ß) signaling pathway, and adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK) signaling pathway through key targets, such as RELA(P65). The results of in vitro experiments showed that 25 µmol·L~(-1) EC had no toxicity to cells and could inhibit the expression of the p65-phosphorylated protein in the NF-κB signaling pathway to down-regulate the expression of downstream inflammatory cytokines, including tumor necrosis factor-α(TNF-α), IL-1ß and nitric oxide(NO), and up-regulate the expression of IL-10. These results suggested that the therapeutic efficacy of FDR on ALI was achieved by inhibiting the phosphorylation of p65 protein in the NF-κB signaling pathway and down-regulating the level of proinflammatory cytokines downstream of the signaling pathways.

Adjuvant treatment with Angong Niuhuang pills in treating traumatic brain damage: a meta-analysis of randomized controlled trials.

BACKGROUND: The Angong Niuhuang pill (ANP) has been widely used in the adjuvant treatment of patients with traumatic brain injury (TBI). However, the efficacy and adverse reactions of this drug are controversial. In this study, it was aimed to evaluate the effectiveness and safety of ANP on patients with TBI by a systematic review and meta-analysis of randomized controlled trials (RCTs). METHODS: PubMed, Embase, Cochrane Library, Chinese Biomedicine Database (CBM), China National Knowledge Infrastructure (CNKI), Chinese Scientific Journals Database (VIP), and Wangfang databases were systematically searched from their establishment until June 2020. RCTs of ANP treating TBI were enrolled. Odds risk (OR) was used to assess the total effective rate and safety and mean difference (MD) and 95% confidence interval (CI) were used to assess the quantitative data. Tthe included literature's quality was evaluated by RevMan 5.3. The sensitivity and publication bias was evaluated by Stata 16.0. RESULTS: Twelve studies were identified in this systematic review, including 1,568 participants. The metaanalysis results suggested that ANP combined with routine treatment obviously improved the postoperative GCS [MD =1.97, 95% CI (1.22, 2.72), P<0.01] and GOS [OR =2.28, 95% CI (1.60, 3.22), P<0.01] of patients with TBI. ANP also increased Mg2+ concentration and decreased pulmonary infection. In addition, ANP significantly reduced NSE, gastrointestinal bleeding, and liver and kidney function damage. CONCLUSIONS: Based on limited evidence, ANP adjuvant therapy may have a clinical benefit in improving the prognosis of patients with TBI and reducing the associated complications. At the same time, more studies with larger sample sizes and high quality are required to determine the safety and effectiveness of ANP adjuvant therapy.

Diffraction properties and applications of spatially structured optical fields with fractal amplitude masks.

With fractal amplitude masks of the Sierpinski carpet and Sierpinski triangle, we theoretically and experimentally present the diffraction properties and applications of spatially structured optical fields, including the vector optical field, vortex optical field, and vortex vector optical field. The diffraction patterns of the vector optical fields exhibit self-similarity, and the characteristics of the vector optical fields are maintained in every diffraction peak. The diffraction patterns of the vortex optical fields and vortex vector optical fields exhibit triangular lattice arrays, and the vortex topological charge can be determined by the number of peak spots in the triangular lattice array. We hope these diffraction properties with fractal amplitude masks can be applied not only in detecting topological charges of spatially structured optical fields, but also in generating flexibly controlled diffraction patterns and lattice arrays, which may be useful in optical machining, optical trapping, and information transmission.

Intranasal Application of Budesonide Attenuates Lipopolysaccharide-Induced Acute Lung Injury by Suppressing Nucleotide-Binding Oligomerization Domain-Like Receptor Family, Pyrin Domain-Containing 3 Inflammasome Activation in Mice.

AIM: To investigate the protective effects of budesonide against lipopolysaccharide- (LPS-) induced acute lung injury (ALI) in a murine model and its underlying mechanism. METHODS: Adult male C57BL/6 mice were divided into three groups: control, ALI, and ALI + budesonide groups. LPS (5 mg/kg) was intratracheally injected to induce ALI in mice. Budesonide (0.5 mg/kg) was intranasally given 1 h before LPS administration in the ALI + budesonide group. Twelve hours after LPS administration, all mice were sacrificed. Hematoxylin-eosin staining and pathological scores were used to evaluate pathological injury. Bronchoalveolar lavage was performed. The numbers of total cells, neutrophils, and macrophages in the bronchoalveolar lavage fluid (BALF) were counted. Enzyme-linked immunosorbent assay was employed to detect the proinflammatory cytokines in BALF and serum, including tumor necrosis factor- (TNF-) α, monocyte chemoattractant protein- (MCP-) 1, and interleukin- (IL-) 1ß. The expression of the nucleotide-binding oligomerization domain-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome was detected by western blotting. A lethal dose of LPS (40 mg/kg, intraperitoneally) was injected to evaluate the effects of budesonide on survival rates. RESULTS: Budesonide pretreatment dramatically attenuated pathological injury and reduced pathological scores in mice with ALI. Budesonide pretreatment obviously reduced the numbers of total cells, neutrophils, and macrophages in the BALF of mice with ALI. Additionally, budesonide dramatically reduced TNF-α and MCP-1 expression in the BALF and serum of mice with ALI. Budesonide significantly suppressed NLRP3 and pro-caspase-1 expression in the lung and reduced IL-1ß content in the BALF, indicating that budesonide inhibited the activation of the NLRP3 inflammasome. Furthermore, we found that budesonide improved the survival rates of mice with ALI receiving a lethal dose of LPS. CONCLUSION: Suppression of NLRP3 inflammasome activation in mice via budesonide attenuated lung injury induced by LPS in mice with ALI.

Effects of integrin-targeted photodynamic therapy on pancreatic carcinoma cell.

AIM: To investigate the effects of photodynamic therapy with quantum dots-arginine-glycine-aspartic acid (RGD) probe as photosensitizer on the proliferation and apoptosis of pancreatic carcinoma cells. METHODS: Construction of quantum dots-RGD probe as photosensitizer for integrin-targeted photodynamic therapy was accomplished. After cells were treated with photodynamic therapy (PDT), the proliferation of SW1990 cells were measured by methyl thiazolyl tetrazolium assay. Morphologic changes, cell cycle retardance and apoptosis were observed under fluoroscope and flow cytometry. The expression of myeloid cell leukemia-1 (Mcl-1), protein kinase B (Akt) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) mRNA were detected by reverse transcription-polymerase chain reaction. The amount of reactive oxygen species were also evaluated by fluorescence probe. RESULTS: The photodynamic therapy with quantum dots-RGD probe as photosensitizer significantly inhibited cell proliferation (P < 0.01). Apoptotic cells and morphologic changes could be found under optical microscope. The FCM revealed PDT group had more significant cell apoptosis rate compared to control cells (F = 130.617, P < 0.01) and cell cycle G0/G1 and S retardance (P < 0.05) compared to control cells. The expression of Mcl-1 and Akt mRNA were down-regulated, while expression of TRAIL mRNA was up-regulated after cells treated with PDT. PDT group had more significant number of cells producing reactive oxygen species compared to control cells (F = 3262.559, P < 0.01). CONCLUSION: The photodynamic therapy with quantum dots-RGD probe as photosensitizer significantly inhibits cell proliferation and increases apoptosis in SW1990 cells.