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Tumor vascular blockade is a promising strategy for adjuvant cancer treatment. In this work, a self-delivery nanomedicine is developed based on a vascular disruptor and photosensitizer for tumor synergistic therapy. Specifically, this nanomedicine (designated as CeCA) is comprised of combretastatin A4 (CA4) and chlorine e6 (Ce6) by self-assembly technique. Among which, CA4 could not only induce tubulin inhibition for chemotherapy but also disrupt the vasculature to cause tumor hemorrhage. Moreover, Ce6 is able to generate lots of singlet oxygen (

This study is devoted to proposing a useful intelligent prediction model to distinguish the severity of COVID-19, to provide a more fair and reasonable reference for assisting clinical diagnostic decision-making. Based on patients' necessary information, pre-existing diseases, symptoms, immune indexes, and complications, this article proposes a prediction model using the Harris hawks optimization (HHO) to optimize the Fuzzy K-nearest neighbor (FKNN), which is called HHO-FKNN. This model is utilized to distinguish the severity of COVID-19. In HHO-FKNN, the purpose of introducing HHO is to optimize the FKNN's optimal parameters and feature subsets simultaneously. Also, based on actual COVID-19 data, we conducted a comparative experiment between HHO-FKNN and several well-known machine learning algorithms, which result shows that not only the proposed HHO-FKNN can obtain better classification performance and higher stability on the four indexes but also screen out the key features that distinguish severe COVID-19 from mild COVID-19. Therefore, we can conclude that the proposed HHO-FKNN model is expected to become a useful tool for COVID-19 prediction.

An efficient copper-catalyzed strategy for the synthesis of α-ketoamides via cross-coupling of methyl ketones and pyridin-2-amines is described. This transformation has provided a simple process for the formation of C−N and C=O bonds to prepare α-ketoamides, which are important substrates and intermediates for the preparation of fine chemicals. The reaction mechanism is investigated, which suggests that the reaction proceeds via a radical pathway.

Although photodynamic therapy (PDT) has been well-known as a promising anti-tumor treatment, its limited therapeutic efficiency remains to be a large challenge. In this study, a carrier free nanomedicine (designated as PyroMor) is developed to greatly initiate cell apoptosis and paraptosis for synergistic cancer therapy. Pyropheophorbide-a (Pyro) and morusin (Mor) are capable of self-assembling into PyroMor, which has been testified to have superiority of improved stability, cellular internalization, and biocompatibility. Because of efficient cellular uptake behavior, PyroMor could induce cellular paraptosis by Mor-caused vacuolation in mitochondria, ER and cytoplasm, contributing to improving the PDT efficacy of Pyro. Therefore, self-delivery PyroMor is able to accomplish synergistic anti-tumor effect via stimulation of cell apoptosis as well as paraptosis. In addition, in vivo studies also clarify that PyroMor presents passive tumor targeting delivery, leading to robust repressive effect on tumor proliferation with negligible systemic toxicity. This strategy of combined cancer therapy by initiating both cell apoptosis and paraptosis extremely benefits to the development of precise and effective cancer therapy in clinic.

With a high incidence and high mortality rate, ovarian cancer presents a challenge for clinical practice. It is thus extremely urgent to investigate new diagnosis and therapy methods for the treatment of ovarian cancer. Ternary copper-based chalcogenide nanomaterials are attractive owing to their near infrared (NIR) response for cancer theranostic fields. However, improving the theranostic efficiency of these nanomaterials is challenging. Herein, CuS-MnS2 nano-flowers were easily synthesized and under NIR irradiation exhibited a relatively high photothermal conversion efficiency of 67.5% and a simultaneous reactive oxygen species (ROS) generation effect. Owing to these outstanding photothermal/photodynamic effects, excellent tumor ablation results could be achieved by the combined use of CuS-MnS2 nano-flowers and 808 nm NIR laser treatments. The main anticancer mechanism of CuS-MnS2 nano-flowers + NIR was likely necroptosis. In addition, the nano-flowers showed remarkable contrast enhancement according to magnetic resonance imaging (MRI). These CuS-MnS2 nano-flowers could thus serve as a promising multifunctional nanotheranostic agent for MRI and as a photothermal/photodynamic cancer therapy agent through necroptosis.

A porphysome-based photodynamic O2 economizer (P-PAT) is prepared for hypoxic tumor therapy. The self-assembled porphyrin bilayers of P-PAT possess high loading capacity to atovaquone (ATO) (nearly 70%), which could restrain mitochondrial respiration to relieve hypoxia and enhance photodynamic therapy.

In this work, fluorinated graphene nanoscrolls (FGN) were synthesized via facile chemical methods under simple and mild conditions. Interestingly, the formation of the featured FGN was significantly solvent sensitive. Experimental results indicated that in the presence of aprotic solvent, for example, N,N dimethylformamide (DMF), the reaction system inclined to form the interesting FGN nanostructures. The structure and morphology of the prepared FGN were detailed characterized by atomic force microscopy (AFM), transmission electron microscopy (TEM), scanning electron microscopy (SEM) and X-ray diffraction (XRD) etc. The obtained FGN was used as a cathode material for primary lithium ion batteries with superior discharge specific capacity (eg. 979.3 mAhg-1), stable discharge platform and high energy density (eg. 2287.9 Wh kg-1), which fosters it a high density, low cost and durable candidate for cathode material for lithium ion batteries..

In this work, novel graphene/In2O3 (GR/In2O3) nanocubes were prepared via one-pot solvothermal treatment, reduction reaction, and successive annealing technology at 600 &deg, C step by step. Interestingly, In2O3 with featured cubic morphology was observed to grow on multi-layered graphene nanosheets, forming novel GR/In2O3 nanocubes. The resulting nanocomposites were characterized using transmission electron microscopy (TEM), scanning electron microscopy (SEM), X-ray diffraction spectroscopy (XRD), etc. Further investigations demonstrated that a selective electrochemical sensor based on the prepared GR/In2O3 nanocubes can be achieved. By using the prepared GR/In2O3-based electrochemical sensor, the enantioselective and chem-selective performance, as well as the optimal conditions for L-Lysine detection in Camellia nitidissima Chi, were evaluated. The experimental results revealed that the GR/In2O3 nanocube-based electrochemical sensor showed good chiral recognition features for L-lysine in Camellia nitidissima Chi with a linear range of 0.23&ndash, 30 &mu, mol&middot, L&minus, 1, together with selectivity and anti-interference properties for other different amino acids in Camellia nitidissima Chi.

In this work, novel graphene/In2O3 (GR/In2O3) nanocubes were prepared via one-pot solvothermal treatment, reduction reaction, and successive annealing technology at 600 °C step by step. Interestingly, In2O3 with featured cubic morphology was observed to grow on multi-layered graphene nanosheets, forming novel GR/In2O3 nanocubes. The resulting nanocomposites were characterized using transmission electron microscopy (TEM), scanning electron microscopy (SEM), X-ray diffraction spectroscopy (XRD), etc. Further investigations demonstrated that a selective electrochemical sensor based on the prepared GR/In2O3 nanocubes can be achieved. By using the prepared GR/In2O3-based electrochemical sensor, the enantioselective and chem-selective performance, as well as the optimal conditions for L-Lysine detection in Camellia nitidissima Chi, were evaluated. The experimental results revealed that the GR/In2O3 nanocube-based electrochemical sensor showed good chiral recognition features for L-lysine in Camellia nitidissima Chi with a linear range of 0.23–30 μmol·L−1, together with selectivity and anti-interference properties for other different amino acids in Camellia nitidissima Chi.

The present study aimed to investigate the effect of sinomenine hydrochloride (SIN) on cell survival/proliferation in the human hepatoma cell line Huh7, as well as determine the underlying mechanisms. Three different doses of SIN, 140, 280 and 560 µM, were tested. Cellular apoptosis and cell cycle distribution were analyzed by flow cytometry. Western blotting was used to determine protein levels of the apoptosis-associated regulators, cleaved caspase 3, B-cell lymphoma-2 (Bcl-2)-associated X protein (Bax), Bcl-2 homologous antagonist/killer (Bak) and Bcl-extra large (Bcl-xl), as well as the cell cycle-related regulators, p21 and p27. It was observed that the three doses of SIN were able to suppress Huh7 cell survival/proliferation, and efficiently induce cellular apoptosis as well as multiphase cell cycle arrest. Mechanistically, SIN treatment upregulated the levels of the pro-apoptotic regulators, cleaved caspase 3 and Bax, and downregulated the level of anti-apoptotic Bcl-xl. Additionally, SIN treatment also increased the protein levels of p21 and p27, as two regulators functioning to slow cell cycle progression. Taken together, the present studied indicated SIN to be a promising compound for the treatment of hepatocellular carcinoma, based on its apparent effect in modulating cell apoptosis and the cell cycle in Huh7 cells in vitro.

Fluoride (F) exposure was widely reported to be associated with renal diseases. Since absorbed F enters the organism from drinking water mostly through the gastrointestinal tract, investigating changes of gut microbes may have profound implications for the prevention of chronic F exposure because increasing evidence supported the existence of the gut-kidney axis. In the present study, we aimed to explore the potential positive effects of probiotics on high F exposure-induced renal lesions and dysfunction in mice by the modulation of the colonic microbiota. Mice were fed with normal (Ctrl group) or sodium-fluoride (F and Prob groups; 100 mg/L sodium fluoride (NaF)) drinking water with or without Lactobaillus johnsonii BS15, a probiotic strain proven to be preventive for F exposure. Mice fed with sodium-fluoride drinking water alone exhibited renal tissue damages, decreased the renal antioxidant capability and dysfunction. In contrast, L. johnsonii BS15 reversed these F-induced renal changes. 16S rRNA gene sequencing shows that L. johnsonii BS15 alleviated the increased community diversity (Shannon diversity) and richness index (number of observed features) as well as the distured structure of colon microbiota in F-exposed mice. A total of 13 OTUs with increased relative abundance were identified as the keystone OTUs in F-exposed mice based on the analysis of degree of co-occurrence and abundance of OTUs. Moreover, Spearman’s rank correlation shows that the 13 keystone OTUs had negative effect on renal health and intestinal integrity. L. johnsonii BS15 reversed four of keystone OTUs (OTU 5, OTU 794, OTU 1035, and OTU 868) changes which might be related to the underlying protected mechanism of L. johnsonii BS15 against F-induced renal damages.

With a high incidence and high mortality rate, ovarian cancer presents a challenge for clinical practice. It is thus extremely urgent to investigate new diagnosis and therapy methods for the treatment of ovarian cancer. Ternary copper-based chalcogenide nanomaterials are attractive owing to their near infrared (NIR) response for cancer theranostic fields. However, improving the theranostic efficiency of these nanomaterials is challenging. Herein, CuS-MnS2 nano-flowers were easily synthesized and under NIR irradiation exhibited a relatively high photothermal conversion efficiency of 67.5% and a simultaneous reactive oxygen species (ROS) generation effect. Owing to these outstanding photothermal/photodynamic effects, excellent tumor ablation results could be achieved by the combined use of CuS-MnS2 nano-flowers and 808 nm NIR laser treatments. The main anticancer mechanism of CuS-MnS2 nano-flowers + NIR was likely necroptosis. In addition, the nano-flowers showed remarkable contrast enhancement according to magnetic resonance imaging (MRI). These CuS-MnS2 nano-flowers could thus serve as a promising multifunctional nanotheranostic agent for MRI and as a photothermal/photodynamic cancer therapy agent through necroptosis.

Glucocorticoids are widely used in clinical practice for the treatment of many immune-mediated and inflammatory diseases, and glucocorticoid-induced osteoporosis (GIO) is the most common type of secondary osteoporosis. Epimedium is one of the most commonly used traditional Chinese medicines for treating osteoporosis. In the present study, we systematically analysed the metabonomic characteristics of GIO model rats and elucidated the therapeutic effect of Epimedium by using a 1H NMR-based metabonomic approach in conjunction with multivariate data analysis. Rats in treatment and model groups were injected with dexamethasone (0.1mg/kg/day) for 5 weeks. Simultaneously, two treatment groups were orally administered Epimedium (10g/kg/day) or Alendronate (1.2mg/kg/day) for 5 weeks. In GIO model rats, lipid and lactate levels in serum were increased, while creatine/creatinine, PC/GPC, taurine, glycine and β-glucose levels were decreased. In urine, GIO rats had higher levels of phenylacetylglycine but lower levels of 2-oxoglutarate, citrate, creatine/creatinine, taurine, PC/GPC and hippurate than controls. Epimedium reversed the aforementioned metabolic alterations in multiple metabolic pathways involved in energy, lipid, amino acid and phospholipid metabolism and gut microbiota derangement. Our results indicated that Epimedium had significant effects in the prevention and treatment of osteoporosis. It is concluded that 1H NMR metabonomics is a useful method for studying the metabolic effects of traditional Chinese medicine from a systematic and holistic view.

In this work, highly uniform cubic germanium/husk-derived graphene nanocomposites (Ge/GR nanocubes) were synthesized via facile chemical methods. The structure and composition of the prepared Ge/GR nanocubes were characterized by transmission electron microscopy (TEM), scanning electron microscopy (SEM), X-ray diffraction (XRD) and energy dispersive X-ray spectroscopy (EDX) etc., confirming a homogeneous distribution of Ge nanocubes (30–90 nm in size) on few-layered graphene nanosheets. Further investigations showed that the prepared novel Ge/GR nanocubes could combine both photocatalytical advantages of Ge nanocubes and graphene nanosheets for Sudan I purification with optimal removal efficiency of 98.1% in wide concentration range (0.25–4.0 mg/mL) at mild conditions. The prepared high active photocatalyst can be used for five consecutive runs. By using husk-derived graphite microcrystalline as the starting material of graphene, the cost of the Ge/GR nanocubes was obvious decreased, which fosters it a high active, low cost and durable candidate for azo dye removal in water.

Interstitial lung disease is the most common complication of systemic sclerosis (SSc) and is associated with a high rate of mortality. Due to the complex pathogenesis of SSc, the therapies currently available remain limited. In the present study, the effect of asiatic acid (AA) on SSc-associated pulmonary fibrosis (PF) and its association with the transforming growth factor-β1 (TGF-β1)/Smad2/3 signaling pathway were evaluated. A hypochlorous acid (HOCl)-induced model of SSc was used to evaluate the therapeutic effect of AA on PF in SSc, where AA was administered to SSc mice by gavage. PF was alleviated in the AA-treated SSc mice groups when examined under light microscopy. In addition, there was a decrease in histopathological progression and collagen in the lungs. AA significantly reduced expression of type I collagen in the lungs of mice with SSc. It also significantly suppressed α-smooth muscle actin expression, which attenuated the conversion of fibroblasts into muscle fibroblasts. These AA-associated antifibrosis and anti-immune effects were mediated through the significant downregulation of advanced oxidation protein product, E-selectin, and anti-DNA topoisomerase-1 autoantibody levels in the serum. Furthermore, the expression levels of TGF-β1 and the phosphorylated-Smad2/3/Smad2/3 ratios in AA-treated SSc mice were similar to the control. The presence of pulmonary inflammation and fibrosis was confirmed in the HOCl-induced SSc mice and the results demonstrated that selective inhibition of reactive oxygen species prevented PF. By focusing on the classical TGF-β1/Smad2/3 signaling pathway, a mechanism of action of AA was identified to be associated with the inhibition of Smad2/3 activation through negative regulation of Smad2/3 phosphorylation.

The synthesis and accumulation of collagen play an important role in the formation and progression of hypoxic pulmonary hypertension. Baicalin has been reported to prevent bleomycin-induced pulmonary fibrosis. However, the role of baicalin in the treatment of pulmonary hypertension remains unknown. A disintegrin and metalloprotease with thrombospondin type-1 motif (ADAMTS-1) is a secreted enzyme that acts on a wide variety of extracellular matrix (ECM) substrates associated with vascular diseases. In this study, we aimed to investigate the effects of baicalin on the synthesis of collagen I in rats with pulmonary hypertension induced by hypoxia and the changes in ADAMTS-1 expression. A total of 24 Sprague Dawley rats were randomly assigned to 3 groups as follows: the control group (C), the hypoxia group (H) and the hypoxia + baicalin group (B). The rats in groups H and B were kept in a normobaric hypoxic chamber for 4 weeks, and the rats in group C were exposed to room air. We measured the hemodynamic indexes, including mean pulmonary artery pressure (mPAP), mean systemic (carotid) artery pressure (mSAP), and then calculated the mass ratio of right ventricle to left ventricle plus septum [RV/(LV + S)] to reflect the extent of right ventricular hypertrophy. We measured the mRNA and protein expression levels of type I collagen, type III collagen and ADAMTS-1 by hybridization in situ, and immunohistochemistry and western blot analysis, respectively. The results revealed that treatment with baicalin significantly reduced pulmonary artery pressure and attenuated the remodeling of the pulmonary artery under hypoxic conditions by increasing the expression of ADAMTS-1, so that the synthesis of type I collagen and its mRNA expression were inhibited. In conclusion, baicalin effectively inhibits the synthesis of collagen I in pulmonary arteries and this is associated with an increase in the expression of ADAMTS-1. Thus, treatment with baicalin may be an effective method for lowering pulmonary artery pressure and preventing pulmonary artery remodeling.

Chronic cold stress can trigger biochemical and physiological changes in living organisms, which leads to a rapid loss of homeostasis. However, the biochemical responses of the organism to chronic cold stress are unclear. In this study, we systematically analysed the metabonomic changes under chronic cold stress by using a (1)H NMR-based metabonomics approach in conjunction with clinical biochemistry assessments. We found that chronic cold exposure caused significant elevation in the levels of lipoproteins (HDL, LDL), lactate, acetoacetate, creatine, creatinine, choline metabolites (GPC, PC and betaine), TMAO and taurine but reduction in the levels of VLDL, glutamine, glycine and glycerol in plasma. Increased levels in urinary TCA cycle intermediates (2-ocoglutarate and citrate), acetoacetate, taurine, TMAO, betaine and hippurate were also found in model rats, together with the reduction of creatinine and tryptophan levels. The results indicated that chronic cold stress caused widespread metabolic changes involved in lipid and energy metabolism, gluconeogenesis, the TCA cycle, and gut microbiota disorders, accompanied with hepatic and renal dysfunction. These findings provide a comprehensive insight into the biochemical consequences and metabolic responses to chronic cold stress in rats.

Vascular endothelial apoptosis and dysfunction have a crucial role in triggering pathological vascular remodeling of hypoxia‑induced pulmonary arterial hypertension (PAH). Fibroblast growth factor (FGF)21, an endocrine regulator, has recently been reported to protect cardiac endothelial cells from damage and suppress inflammatory responses. In addition, FGF21 is reported to be involved in endoplasmic reticulum stress (ERS). Previous studies have suggested that ERS participates in the development of PAH, and attenuation of ERS could be an effective therapeutic strategy for the protection of pulmonary arteries. However, whether FGF21 has a protective function via suppression of ERS in pulmonary arterial endothelial cells in hypoxia remains unclear. The present study aimed to explore whether FGF21 could reduce the hypoxia‑induced apoptosis of human pulmonary arterial endothelial cells (HPAECs) and prevent endothelial dysfunction via the inhibition of ERS. HPAECs were divided into six groups: Normoxia, hypoxia, hypoxia plus FGF21, hypoxia plus salubrinal (an ERS inhibitor), hypoxia plus tunicamycin (an ERS agonist), and hypoxia plus tunicamycin plus FGF21. The endoplasmic reticulum ultrastructure in HPAECs was assessed by transmission electron microscopy, and proliferation and apoptosis were examined by cell counting kit‑8 and terminal deoxyribonucleotide transferase‑mediated dUTP nick end‑labelling assays, respectively. The expression levels of ERS‑related proteins, including binding immunoglobulin protein (BiP), protein kinase R‑like endoplasmic reticulum kinase (PERK), phosphorylated (p‑) PERK, transcription factor C/EBP homologous protein (CHOP), B‑cell lymphoma-2 (Bcl‑2) and caspase‑4 were detected by western blotting. Transwell migration chamber assays were performed, and the concentration of nitric oxide (NO)/endothelin‑1 (ET‑1) in the culture medium was determined to examine endothelial function. The results revealed that hypoxia increased the % of apoptotic cells and diminished the viability of HPAECs, accompanied by an upregulation of ERS‑dependent apoptosis by increasing the expression of the proapoptotic caspase‑4 and decreasing the antiapoptotic Bcl‑2. Additionally, hypoxia upregulated the expression of representative proteins in the PERK branch of ERS, including BiP, p‑PERK and CHOP, while it downregulated the expression of PERK. Furthermore, the secretion of NO/ET‑1 and the migration rate of HPAECs were downregulated under conditions of hypoxia. FGF21 significantly attenuated the hypoxia‑induced apoptosis and dysfunction of HPAECs through alleviating the aforementioned changes in ERS‑dependent signaling pathways. In conclusion, ERS may be a crucial mechanism in the hypoxia‑induced apoptosis and endothelial dysfunction of HPAECs. FGF21 may attenuate the hypoxia‑induced apoptosis and dysfunction of HPAECs through alleviating ERS, via the PERK/CHOP signaling pathway and inhibition of caspase‑4 expression.

Background Baicalin has been reported to have anti-fibrosis effect; however, its mechanism still remains to be elucidated. Adenosine A2a receptor (A2aR) is a novel inflammation regulator, and transforming growth factor-β1 (TGF-β1)-induced extracellular signal regulated kinase1/2 (ERK1/2) signaling pathway plays an important role in idiopathic pulmonary fibrosis (IPF). This study was to explore the relationship of A2aR and TGF-β1-induced ERK1/2 in bleomycin (BLM)-induced pulmonary fibrosis in mice, and to investigate whether A2aR mediate the anti-fibrosis effect of Baicalin on BLM-induced pulmonary fibrosis. Methods The A2aR−/− and A2aR+/+ mice were respectively divided into three groups: control group, model group, baicalin group. Pulmonary fibrosis was induced in mice of model groups by intratracheal instillation of bleomycin, and baicalin was administered in mice of baicalin groups daily for 28 days. Histopathological and ultrastructural changes of lung tissues were evaluated. Lung coefficient and the levels of hydroxyproline (HYP) in lung tissues were measured at the same time. The levels of serum TGF-β1 were measured by ELISA. The expression of TGF-β1, ERK1/2, p-ERK1/2 and A2aR were detected by western blot and immunohistochemical staining techniques. Results Severe lung fibrosis was observed in the bleomycin-treated mice on day 28. The histopathological findings and collagen content of lung tissues were much severer/higher in A2aR−/− mice than in A2aR+/+ mice. We also showed that TGF-β1 and p-ERK1/2 were upregulated in bleomycin-treated mice and expressed higher in A2aR−/− mice compared to A2aR+/+ mice. Besides, bleomycin-treated A2aR+/+ mice had increased A2aR level in lungs. However, long-term treatment with baicalin in A2aR−/− and A2aR+/+ mice significantly ameliorated the histopathological changes in lungs. Moreover, Increased TGF-β1 and p-ERK1/2 expressions in bleomycin-treated A2aR−/− and A2aR+/+ mice were obviously diminished by baicalin. The baicalin-treated A2aR−/− mice had severer lung fibrosis and higher expressions of TGF-β1 and p-ERK1/2 than A2aR+/+ mice. Baicalin has also upregulated the expression of A2aR in A2aR+/+ mice. Conclusions Genetic inactivation of A2aR exacerbated the pathological processes of bleomycin-induced pulmonary fibrosis. Together, baicalin could inhibit BLM-induced pulmonary fibrosis by upregulating A2aR, suggesting A2aR as a therapeutic target of baicalin for the treatment of pulmonary fibrosis.

Baicalin has a protective effect on hypoxia-induced pulmonary hypertension in rats, but the mechanism of this effect remains unclear. Thus, investigating the potential mechanism of this effect was the aim of the present study. Model rats that display hypoxic pulmonary hypertension and cor pulmonale under control conditions were successfully generated. We measured a series of indicators to observe the levels of pulmonary arterial hypertension, pulmonary arteriole remodeling, and right ventricular remodeling. We assessed the activation of p38 mitogen-activated protein kinase (MAPK) in the pulmonary arteriole walls and pulmonary tissue homogenates using immunohistochemistry and western blot analyses, respectively. The matrix metalloproteinase- (MMP-) 9 protein and mRNA levels in the pulmonary arteriole walls were measured using immunohistochemistry and in situ hybridization. Our results demonstrated that baicalin not only reduced p38 MAPK activation in both the pulmonary arteriole walls and tissue homogenates but also downregulated the protein and mRNA expression levels of MMP-9 in the pulmonary arteriole walls. This downregulation was accompanied by the attenuation of pulmonary hypertension, arteriole remodeling, and right ventricular remodeling. These results suggest that baicalin may attenuate pulmonary hypertension and cor pulmonale, which are induced by chronic hypoxia, by downregulating the p38 MAPK/MMP-9 pathway.

The present study aimed to investigate the therapeutic effect of monoammonium glycyrrhizinate (MAG) on lipopolysaccharide- (LPS-) induced acute lung injury (ALI) in mice and possible mechanism. Acute lung injury was induced in BALB/c mice by intratracheal instillation of LPS, and MAG was injected intraperitoneally 1 h prior to LPS administration. After ALI, the histopathology of lungs, lung wet/dry weight ratio, protein concentration, and inflammatory cells in the bronchoalveolar lavage fluid (BALF) were determined. The levels of tumor necrosis factor-α(TNF-α) and interleukin-1β(IL-1β) in the BALF were measured by ELISA. The activation of NF-κB p65 and IκB-αof lung homogenate was detected by Western blot. Pretreatment with MAG attenuated lung histopathological damage induced by LPS and decreased lung wet/dry weight ratio and the concentrations of protein in BALF. At the same time, MAG reduced the number of inflammatory cells in lung and inhibited the production of TNF-αand IL-1βin BALF. Furthermore, we demonstrated that MAG suppressed activation of NF-κB signaling pathway induced by LPS in lung. The results suggested that the therapeutic mechanism of MAG on ALI may be attributed to the inhibition of NF-κB signaling pathway. Monoammonium glycyrrhizinate may be a potential therapeutic reagent for ALI.

To study the metabolic changes of pancreatic extracts from insulin-resistant rats induced by fructose feeding using nuclear magnetic resonance ¹H spectroscopy (¹H NMR).Sixteen Wistar rats were divided equally into control group and model group and given water and 10% fructose water for 8 weeks, respectively. The pancreatic tissues were then obtained for H NMR spectra analysis and principal component analysis (PCA).Compared with the control rats, the rats in the model group showed significantly increased creatine, betaine/TMAO, taurine, glycine and myo-inositol and decreased levels of lipids, lactate, glutamate, choline and GPC/PC.¹H NMR and pattern recognition can define the metabolic characteristics of the pancreatic tissue extracts from insulin-resistant rats and provide reliable metabolic evidence for studying the mechanisms of insulin resistance at the molecular level.

Esophageal carcinoma (EC) is one of the most common malignant tumors. EC survival has remained disappointingly low because of the high malignancy of esophageal cancer and the lack of obvious clinical symptoms at an early stage. Early diagnosis is often difficult because the small tumor nodules are frequently missed. Metabonomics based on high-resolution magic-angle spinning (HRMAS) NMR has been popular for tumor detection because it is highly sensitive, provides rich biochemical information and requires no sample pretreatment. (1)H HRMAS spectra of non-involved adjacent esophageal tissues and of well differentiated and moderately differentiated esophageal carcinoma tumors were recorded and analyzed by use of multivariate and statistical analysis techniques. Moderately differentiated EC tumors were found to have increased total choline, alanine, and glutamate and reduced creatine, myo-inositol, and taurine compared with non-involved adjacent tissues. Moreover, clear differences between the metabonomic profiles of EC tissues enabled tumor differentiation. Furthermore, the integral Gly/MI ratio for samples of different tissue types were statistically significantly different; this was sufficient both for distinguishing non-involved tissues from esophageal carcinoma and for classification of well differentiated and moderately differentiated EC tumors.