Preparation of Dihydromyricetin-Loaded Self-Emulsifying Drug Delivery System and Its Anti-Alcoholism Effect.

Intraperitoneal injection of dihydromyricetin (DMY) has shown promising potential in the treatment of alcoholism. However, its therapeutic effect is limited due to its low solubility, poor stability, and high gut-liver first-pass metabolism, resulting in very low oral bioavailability. In this study, we developed a DMY-loaded self-emulsifying drug delivery system (DMY-SEDDS) to enhance the oral bioavailability and anti-alcoholism effect of DMY. DMY-SEDDS improved the oral absorption of DMY by facilitating lymphatic transport. The area under the concentration-time curve (AUC) of DMY in the DMY-SEDDS group was 4.13-fold higher than in the DMY suspension group. Furthermore, treatment with DMY-SEDDS significantly enhanced the activities of alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH) in the liver of mice (p < 0.05). Interestingly, DMY-SEDDS also increased ADH activity in the stomach of mice with alcoholism (p < 0.01), thereby enhancing ethanol metabolism in the gastrointestinal tract and reducing ethanol absorption into the bloodstream. As a result, the blood alcohol concentration of mice with alcoholism was significantly decreased after DMY-SEDDS treatment (p < 0.01). In the acute alcoholism mice model, compared to saline treatment, DMY-SEDDS prolonged the onset of LORR (loss of righting reflex) (p < 0.05) and significantly shortened the duration of LORR (p < 0.01). Additionally, DMY-SEDDS treatment significantly reduced gastric injury in acute alcoholism mice. Collectively, these findings demonstrate the potential of DMY-SEDDS as a treatment in the treatment of alcoholism.

Role of biochemical markers and autoantibodies in diagnosis of early-stage primary biliary cholangitis.

BACKGROUND: Primary biliary cholangitis (PBC) is a chronic progressive autoimmune cholestatic disease. The main target organ of PBC is the liver, and nonsuppurative inflammation of the small intrahepatic bile ducts may eventually develop into cirrhosis or liver fibrosis. AIM: To explore the clinical characteristics of early-stage PBC, identify PBC in the early clinical stage, and promptly treat and monitor PBC. METHODS: The data of 82 patients with PBC confirmed by pathology at Tianjin Second People's Hospital from January 2013 to November 2021 were collected, and the patients were divided into stage I, stage II, stage III, and stage IV according to the pathological stage. The general data, serum biochemistry, immunoglobulins, and autoimmune antibodies of patients in each stage were retrospectively analyzed. RESULTS: In early-stage (stages I + II) PBC patients, 50.0% of patients had normal alanine aminotransferase (ALT) levels, and 37.5% had normal aspartate aminotransferase (AST) levels. For the remaining patients, the ALT and AST levels were mildly elevated; all of these patients had levels of < 3 times the upper limit of normal values. The AST levels were significantly different among the three groups (stages I + II vs stage III vs stage IV, P < 0.05). In the early stage, 29.2% of patients had normal alkaline phosphatase (ALP) levels. The remaining patients had different degrees of ALP elevation; 6.3% had ALP levels > 5 times the upper limit of normal value. Moreover, γ-glutamyl transferase (GGT) was more robustly elevated, as 29.2% of patients had GGT levels of > 10 times the upper limit of normal value. The ALP values among the three groups were significantly different (P < 0.05). In early stage, the jaundice index did not increase significantly, but it gradually increased with disease progression. However, the above indicators were significantly different (P < 0.05) between the early-stage group and the stage IV group. With the progression of the disease, the levels of albumin and albumin/globulin ratio tended to decrease, and the difference among the three groups was statistically significant (P < 0.05). In early-stage patients, IgM and IgG levels as well as cholesterol levels were mildly elevated, but there were no significant differences among the three groups. Triglyceride levels were normal in the early-stage group, and the differences among the three groups were statistically significant (P < 0.05). The early detection rates of anti-mitochondria antibody (AMA) and AMA-M2 were 66.7% and 45.8%, respectively. The positive rate of anti-sp100 antibodies was significantly higher in patients with stage IV PBC. When AMA and AMA-M2 were negative, in the early stage, the highest autoantibody was anti-nuclear antibody (ANA) (92.3%), and in all ANA patterns, the highest was ANA centromere (38.5%). CONCLUSION: In early-stage PBC patients, ALT and AST levels are normal or mildly elevated, GGT and ALP levels are not elevated in parallel, GGT levels are more robustly elevated, and ALP levels are normal in some patients. When AMA and AMA-M2 are negative, ANA especially ANA centromere positivity suggests the possibility of early PBC. Therefore, in the clinic, significantly elevated GGT levels with or without normal ALP levels and with ANA (particularly ANA centromere) positivity (when AMA and AMA-M2 are negative) may indicate the possibility of early PBC.

Association of Social Support with Rehabilitation Outcome among Older Adults with Hip Fracture Surgery: A Prospective Cohort Study at Post-Acute Care Facility in Asia.

OBJECTIVES: There is growing interest in the role of social support during the recovery after hip fractures. The research to date has been mainly focused on structural support, with few studies concerned with functional support. This study examined the effects of both functional and structural aspects of social support on rehabilitation outcomes among older adults with hip fracture surgery. DESIGN: Prospective cohort study. SETTING AND PARTICIPANTS: Consecutive older adults (≥60 years) with hip fracture surgery who underwent inpatient rehabilitation in a post-acute care facility in Singapore between January 11, 2021, and October 30, 2021 (n = 112). METHODS: We administered the Medical Outcome Study-Social Support Survey (MOS-SSS) to assess perceived functional support of patients and used living arrangement as an indicator for structural support. Participants were followed up over the inpatient stay at the post-acute care facility until discharge; thereafter, rehabilitation efficiency (REy) and rehabilitation effectiveness (REs) were evaluated. Multiple linear regressions were performed to examine the associations of MOS-SSS score and living arrangement with REy and REs, respectively, adjusting for age, gender, ethnicity, comorbidity, body mass index, prefracture function, type of fracture, and length of stay. RESULTS: Perceived functional support had positive associations with rehabilitation outcomes. A 1-unit increase in MOS-SSS total score was associated with 0.15 units (95% CI 0.03-0.3, P = .029) greater gain in physical function after a typical 1-month stay, and 0.21 units (95% CI 0.01-0.41, P = .040) higher achievement in potential functional improvement upon discharge. In contrast, no association was observed between structural support and rehabilitation outcomes. CONCLUSIONS AND IMPLICATIONS: Perceived functional support may significantly impact the recovery of older adults with hip fracture during the inpatient rehabilitation process, independent of structural support. Our findings suggest the potential of incorporating interventions enhancing perceived functional support of patients into the post-acute care model for hip fracture.

Artificially Intelligent Olfaction for Fast and Noninvasive Diagnosis of Bladder Cancer from Urine.

Globally, bladder cancer (BLC) is one of the most common cancers and has a high recurrence and mortality rate. Current clinical diagnostic approaches are either invasive or inaccurate. Here, we report on a cost-efficient, artificially intelligent chemiresistive sensor array made of polyaniline (PANI) derivatives that can noninvasively diagnose BLC at an early stage and maintain postoperative surveillance through ″smelling″ clinical urine samples at room temperature. In clinical trials, 18 healthy controls and 76 BLC patients (60 and 16 at early and advanced stages, respectively) are assessed by the artificial olfactory system. With the assistance of a support vector machine (SVM), very high sensitivity and accuracy from healthy controls are achieved, exceeding those obtained by the current techniques in practice. In addition, the recurrences of both early and advanced stages are diagnosed well, with the effect of confounding factors on the performance of the artificial olfactory system found to have a negligible influence on the diagnostic performance. Overall, this study contributes a novel, noninvasive, easy-to-use, inexpensive, real-time, accurate method for urine disease diagnosis, which can be useful for personalized care/diagnosis and postoperative surveillance, resulting in saving more lives.

The Pathogenesis of Eosinophilic Asthma: A Positive Feedback Mechanism That Promotes Th2 Immune Response via Filaggrin Deficiency.

Eosinophilic asthma (EA) is a common subtype of asthma and often progresses to severe disease. In order to understand its pathogenesis, targeted next-generation gene sequencing was performed on 77 Chinese EA patients and 431 Chinese healthy controls to obtain differential genomic variations. Among the 41 Single Nucleotide Polymorphisms (SNPs) screened for mutation sites in more than 3 patients, filaggrin gene FLG rs192116923 T>G and FLG rs75235053 C>G were newly found to be associated with EA patients with atopic dermatitis (AD) (P <0.001) and severe EA (P=0.032), respectively. Filaggrin has been shown to be mainly expressed in epithelial cells and plays an important role in formation of an effective skin barrier. Bioinformatic analysis indicated FLG rs192116923 T>G may increase the binding of Smad3 to transmit TGF-ß1 signaling, and thereby inhibit filaggrin expression, and FLG rs75235053 C>G may add new splicing sites to reduce filaggrin monomers. It has been known that the level of Th2 cytokine IL-4 is increased in EA patients, and IL-4 increases airway epithelial permeability and enhances inflammatory response through some unclear mechanisms. To figure out whether filaggrin is involved in immune responses in asthma, we have treated human respiratory epithelial cell line BEAS-2B cells with IL-4 and found that the expression levels of filaggrin and E-cadherin decreased significantly in a time and dose-dependent manner, suggesting that IL-4 increased airway epithelial permeability by reducing filaggrin and adhesion molecule. In addition, in our study, IL-4 increased the expression of epithel-derived inflammatory cytokines IL-33 and TSLP which further enhanced the Th2 inflammatory response. To investigate the role of filaggrin in development of EA, knockdown filaggrin with siRNA revealed a decrease in E-cadherin levels, which were further down-regulated by IL-4 stimulation. Knockdown of filaggrin alone did not affect the levels of IL-33 and TSLP, but further exacerbated the decrease of IL-33/TSLP caused by IL-4, suggesting that filaggrin may involve in IL-4R signaling pathway to regulate the level of IL-33/TSLP. In conclusion, in the Th2 cytokine milieu of asthma, FLG deficient mutation in airway epithelial cells may increase the epithelial permeability and the expression of IL-33/TSLP which positively feedback the Th2 inflammation response.

Self-assembled micelles enhance the oral delivery of curcumin for the management of alcohol-induced tissue injury.

Curcumin (CUR) shows great potential in the management of alcohol-use disorders. However, the hydrophobicity and poor oral bioavailability result in the limited therapeutic efficacy of CUR against alcohol-induced tissue injury. Here, self-assembled Soluplus® micelles (Ms) were developed for the enhanced oral delivery of CUR. CUR-loaded Soluplus® micelles (CUR-Ms) were prepared using a thin-film hydration method and these micelles displayed nearly spherical shape with an average size of 62.80 ± 1.29 nm. CUR in micelles showed the greater stability, solubility and dissolution than free CUR. With the increased water solubility of CUR-Ms and P glycoprotein inhibition of Soluplus®, the absorption rate constant (Ka) and apparent permeability coefficient (Papp) of CUR-Ms in intestines was respectively 3.50 and 4.10 times higher than that of free CUR. Pharmacokinetic studies showed that CUR-Ms significantly improved the oral bioavailability of CUR. Specifically, the AUC0-∞ and Cmax of CUR-Ms were increased by 9.45 and 47.38 folds compared to free CUR, respectively. In mice with alcohol-induced tissue injury, the oral administration of CUR-Ms greatly reduced oxidative stress, and significantly defended liver and gastric mucosa from alcoholic damages. The results demonstrated CUR-Ms with good oral bioavailability could represent a promising strategy for the management of alcohol-induced tissue injury.

Self-emulsifying Drug Delivery System Improve Oral Bioavailability: Role of Excipients and Physico-chemical Characterization.

Self-emulsifying drug delivery system (SEDDS) is a kind of solid or liquid formulation composed of drugs, oil, surfactant and cosurfactant. It could form a fine emulsion (micro/nano) in the gastrointestinal tract after oral administration. Later on, the formed emulsion is absorbed through the lymphatic pathway. The oral bioavailability of drugs in SEDDS would be improved for bypassing the first-pass effect of the liver. Therefore, SEDDS has become a vital strategy to increase the oral bioavailability of poor watersoluble drugs. In addition, there is no aqueous phase in SEDDS, thus SEDDS is a homogeneous system, consequently being suitable for large-scale production and more stable than conventional emulsion. However, the role of formulation aspects in the biological property of SEDDS is not fully clear. In order to prepare the satisfying SEDDS to improve oral drug bioavailability, we need to fully understand the various factors that affect the in vivo behavior of SEDDS. In this review, we would explore the role of ingredient (drugs, oils, surfactant and cosurfactant) of SEDDS in increasing oral drug bioavailability. We would also discuss the effect of physicochemical property (particle size and zeta potential) of SEDDS on the oral drug bioavailability enhancement. This review would provide an approach to develop a rational SEDDS to improving oral drug bioavailability. Lay Summary: Self-emulsifying drug-delivery system (SEDDS) has been proven to be promising in ameliorating the oral bioavailability of poor water-soluble drugs. This review highlighted the influence of excipients and physicochemical property of SEDDS on the formation of emulsion and the oral absorption of drugs in the body.

Clinical characteristics and biomarkers analysis of asthma inflammatory phenotypes.

Aim: Asthma inflammatory phenotypes facilitate treatment, their clinical characteristics and biomarkers were analyzed. Materials & methods: A total of 176 asthmatics were divided into eosinophilic asthma (EA), neutrophilic asthma (NA), paucigranulocytic asthma and mixed-granulocytic asthma by induced sputum. Results: EA, NA and paucigranulocytic asthma patients were 65 (36.9%), 31 (17.6%) and 75 (42.6%). Sputum IL-5 and IL-13, blood IL-13, fractional exhaled nitric oxide (FeNO) were related to EA, the areas under the receiver operating characteristic curve were 0.790, 0.846, 0.828, 0.830, combined FeNO with blood IL-13 was 0.872. Sputum and blood IL-8, blood IL-17 were related to NA, their area under the receiver operating characteristic curve was 0.939, 0.844, 0.821, combined blood IL-8 with IL-17 was 0.882. Conclusion: Blood IL-13 and FeNO, blood IL-8 and IL-17 were alternative biomarkers of EA and NA, respectively.

Entropy and Confidence-Based Undersampling Boosting Random Forests for Imbalanced Problems.

In this article, we propose a novel entropy and confidence-based undersampling boosting (ECUBoost) framework to solve imbalanced problems. The boosting-based ensemble is combined with a new undersampling method to improve the generalization performance. To avoid losing informative samples during the data preprocessing of the boosting-based ensemble, both confidence and entropy are used in ECUBoost as benchmarks to ensure the validity and structural distribution of the majority samples during the undersampling. Furthermore, different from other iterative dynamic resampling methods, ECUBoost based on confidence can be applied to algorithms without iterations such as decision trees. Meanwhile, random forests are used as base classifiers in ECUBoost. Furthermore, experimental results on both artificial data sets and KEEL data sets prove the effectiveness of the proposed method.

Geometric Structural Ensemble Learning for Imbalanced Problems.

The classification on imbalanced data sets is a great challenge in machine learning. In this paper, a geometric structural ensemble (GSE) learning framework is proposed to address the issue. It is known that the traditional ensemble methods train and combine a series of basic classifiers according to various weights, which might lack the geometric meaning. Oppositely, the GSE partitions and eliminates redundant majority samples by generating hyper-sphere through the Euclidean metric and learns basic classifiers to enclose the minority samples, which achieves higher efficiency in the training process and seems easier to understand. In detail, the current weak classifier builds boundaries between the majority and the minority samples and removes the former. Then, the remaining samples are used to train the next. When the training process is done, all of the majority samples could be cleaned and the combination of all basic classifiers is obtained. To further improve the generalization, two relaxation techniques are proposed. Theoretically, the computational complexity of GSE could approach O(ndlog(nmin)log(n maj)) . The comprehensive experiments validate both the effectiveness and efficiency of GSE.

Analysis of lncRNA Expression in Patients With Eosinophilic and Neutrophilic Asthma Focusing on LNC_000127.

Long non-coding RNA (lncRNA) is important in many diseases. Some studies have shown that lncRNA affects the pathogenesis of systemic inflammation of asthma. lncRNA regulates gene transcription, protein expression, and epigenetic regulation. However, lncRNAs associated with different airway phenotypes, such as eosinophilic (Eos) and neutrophilic (Neu) asthma have not been identified. The goal of this study was to determine the differences in circulating lncRNA signatures in Eos and Neu samples. Using RNA-sequencing (RNA-seq), lncRNA expression was evaluated in peripheral whole blood samples among Eos patients, Neu patients, and healthy individuals (Control). Bioinformatic analysis was used to predict relevant biological pathways. Quantitative PCR (qPCR) was used to measure gene expression in whole blood samples, Jurkat cells, and human CD4+ T cells. Finally, a novel lncRNA, LNC_000127, was inhibited by transfection of Jurkat cells with a lentiviral vector, and the effect was examined by Human Asthma RT2 Profiler™ PCR Array and western blotting. Compared to control samples, Eos samples contained 190 unique lncRNAs and Neu samples had 166 unique lncRNAs (difference ≥2-fold). KEGG pathway annotation data and GO terms revealed that different lncRNAs are involved in different mechanisms. LNC_000127, was highly expressed in Eos samples before treatment; its expression was increased in Jurkat cells and human CD4+ T cells following stimulation with PMA/CD28. Subsequent analyses revealed that LNC_000127 functions in the Th2 inflammation pathway. The results suggest that lncRNAs are involved in different phenotypes of asthma. Whether the different phenotypes of asthma can be recognized based on these lncRNAs (as biomarkers) requires further analysis. Targeting LNC_000127 may be effective for reducing Th2 inflammation in Eos asthma.

Peripheral whole blood lncRNA expression analysis in patients with eosinophilic asthma.

Long noncoding RNA (lncRNA) plays roles in many diseases including asthma. Several lncRNAs function in the early differentiation of T-helper cells. lncRNA controls gene transcription, protein expression, and epigenetic regulation. Of the 4 asthma phenotypes, eosinophilic asthma (EA) is the most common. However, the lncRNAs associated with eosinophilic asthma have yet to be identified.We designed a study to identify the circulating lncRNA signature in EA samples. We tested whether significant differences in lncRNA expression were observed between blood samples from patients with EA and healthy individuals (control). Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed for the lncRNA-mRNA (messenger RNA) co-expression network. lncRNA expression was measured using quantitative real-time PCR (polymerase chain reaction).A total of 41 dysregulated lncRNAs and 762 dysregulated mRNAs (difference ≥ 2-fold) were found in EA compared to control samples. GO terms and KEGG pathway annotation data revealed that several lncRNAs are significantly associated with EA. KEGG pathway annotation indicated that the pathways most enriched in EA were measles, T cell receptor signaling pathway, peroxisome proliferator activated-receptors (PPAR) signaling pathway, Fc gamma R-mediated phagocytosis, NF (nuclear factor) kappa B signaling pathway, chemokine signaling pathway, and primary immunodeficiency. Using qRT-PCR, lncRNA was confirmed to differ significantly between EA and control samples.The results presented here show that several lncRNAs may take part in the immune regulation of EA. Whether these lncRNAs can be used as biomarkers needs further study.

Boundary-Eliminated Pseudoinverse Linear Discriminant for Imbalanced Problems.

Existing learning models for classification of imbalanced data sets can be grouped as either boundary-based or nonboundary-based depending on whether a decision hyperplane is used in the learning process. The focus of this paper is a new approach that leverages the advantage of both approaches. Specifically, our new model partitions the input space into three parts by creating two additional boundaries in the training process, and then makes the final decision based on a heuristic measurement between the test sample and a subset of selected training samples. Since the original hyperplane used by the underlying original classifier will be eliminated, the proposed model is named the boundary-eliminated (BE) model. Additionally, the pseudoinverse linear discriminant (PILD) is adopted for the BE model so as to obtain a novel classifier abbreviated as BEPILD. Experiments validate both the effectiveness and the efficiency of BEPILD, compared with 13 state-of-the-art classification methods, based on 31 imbalanced and 7 standard data sets.

Stereodivergent Synthesis of Chromanones and Flavanones via Intramolecular Benzoin Reaction.

The strategy of stereodivergent reactions on racemic mixtures (stereodivergent RRM) was employed for the first time in intramolecular benzoin reactions and led to the rapid access of chromanones/flavanones with two consecutive stereocenters. The easily separable stereoisomers of the products were obtained with moderate to excellent enantioselectivities in a single step. Catechol type additives proved crucial in achieving the desired diastereo- and enantioselectivities.

Prevention and Management of Adverse Reactions Induced by Iodinated Contrast Media.

Iodinated radiocontrast media (IRCM) is widely used in current clinical practice. Although IRCM is generally safe, serious adverse drug reactions (ADRs) may still occur. IRCM-induced ADRs may be subdivided into chemotoxic and hypersensitivity reactions. Several factors have been shown to be associated with an increased risk of ADRs, including previous contrast media reactions, history of asthma and allergic disease, etc. Contrast media with lower osmolality is generally recommended for at-risk patients to prevent ADRs. Current premedication prophylaxis in at-risk patients may reduce the risk of ADRs. However, there is still a lack of consensus on the prophylactic role of premedication. Contrast-induced nephropathy (CIN) is another component of IRCM-related ADRs. Hydration remains the mainstay of CIN prophylaxis in at-risk patients. Despite several preventive measures, ADRs may still occur. Treatment strategies for potential contrast reactions are also summarised in this article. This article summarises the pathophysiology, epidemiology and risk factors of ADRs with emphasis on prevention and treatment strategies. This will allow readers to understand the rationale behind appropriate patient preparation for diagnostic imaging involving IRCM.

Bloating and distention in irritable bowel syndrome: the role of gas production and visceral sensation after lactose ingestion in a population with lactase deficiency.

OBJECTIVES: Bloating and distention are often attributed to dietary factors by patients with irritable bowel syndrome (IBS). This study examined the effects of gas production and visceral hypersensitivity on digestive symptoms after lactose ingestion in a population with lactase deficiency. METHODS: IBS patients (n=277) and healthy controls (HCs, n=64) underwent a 20-g lactose hydrogen breath test (LHBT) with evaluation of hydrogen gas production and lactose intolerance (LI) symptoms. Abdominal distention (199 IBS, 40 HCs) was measured during LHBT. Rectal sensitivity (74 IBS, 64 HCs) was assessed by barostat studies. RESULTS: Hydrogen production and distention were similar in IBS patients and HCs during LHBT; however, LI was more frequent in IBS (53.8 vs. 28.1%, P<0.001), especially bloating (39.0% vs. 14.1%, P<0.001) and borborygmi (39.0 vs. 21.9%, P=0.010). Only 59.0% of patients with bloating had distention. No correlation was observed between girth increment and bloating (P=0.585). IBS patients had lower rectal sensory thresholds (P=0.001). Multivariate analysis indicated that hydrogen production increased bloating (odds ratio (OR) 2.19, 95% confidence interval (CI) 1.09-4.39, P=0.028) and borborygmi (OR 12.37, 95% CI 3.34-45.83, P<0.001) but not distention (P=0.673). Visceral hypersensitivity was associated with bloating (OR 6.61, 95% CI 1.75-25.00, P=0.005) and total symptom score (OR 3.78, 95% CI 1.30-10.99, P=0.014). CONCLUSIONS: Gas production and visceral hypersensitivity both contribute to digestive symptoms, especially bloating and borborygmi, in IBS patients after lactose ingestion. Objective abdominal distention is not correlated with subjective bloating.

Severe global cerebral ischemia-induced programmed necrosis of hippocampal CA1 neurons in rat is prevented by 3-methyladenine: a widely used inhibitor of autophagy.

The true programmed mechanisms of delayed neuronal death induced by global cerebral ischemia/reperfusion injury remain incompletely characterized. Autophagic cell death and programmed necrosis are 2 kinds of programmed cell death distinct from apoptosis. Here, we studied the death mechanisms of hippocampal cornu ammonis 1 neuronal death after a 20-minute severe global ischemia/reperfusion injury in young adult rats and the effects of 3-methyladenine (3-MA), a widely used inhibitor of autophagy. The morphological changes detected by electron microscopy, together with the activation of autophagy, transferase-mediated UTP nick end-labeling-positive neurons, and delayed death, demonstrated that cornu ammonis 1 neuronal death induced in this paradigm was programmed necrosis. No significant activation of caspase-3 after injury was detected by Western blot and immunohistochemistry. Treatment with 3-MA provided time-dependent protection against cornu ammonis 1 neuronal death at 7 days of reperfusion when it was administered before ischemia; administration 60 minutes after reperfusion was not beneficial. The redistribution of the lysosomal enzyme cathepsin B after injury was inhibited by 3-MA administered before ischemia, suggesting that this might be another important mechanism for the protective effect of 3-MA in ischemic neuronal injury.

Synthesis and biological activity of trans-tiliroside derivatives as potent anti-diabetic agents.

A set of novel trans-tiliroside derivatives were synthesized. The structures of the derivatives were identified by their IR, 1H-NMR, and MS spectra analysis. Their anti-diabetic activities were evaluated on the insulin resistant (IR) HepG2 cell model. As a result, compounds 7a, 7c, 7h, and trans-tiliroside exhibited significant glucose consumption-enhancing effects in IR-HepG2 cells compared with the positive control (metformin). This research provides useful clues for further design and discovery of anti-diabetic agents.

Bicyclol attenuates oxidative stress and neuronal damage following transient forebrain ischemia in mouse cortex and hippocampus.

To assess its potential neuroprotective effect against ischemia/reperfusion (IR) injury in mice, bicyclol was administered intragastrically once a day for 3 days. After 6h of bicyclol pretreatment on the third day, forebrain ischemia was induced for 1h by bilateral occlusion of the carotid arteries. After different times of reperfusion, the histopathological changes and the levels of mitochondria-generated reactive oxygen species (ROS), malondialdehyde (MDA) and the activity of superoxide dismutase (SOD) in the cortex and hippocampus were measured. We found that extensive neuronal death occurred in the cortex and the CA1 area of the hippocampus at day 7 after IR and that bicyclol significantly attenuated IR-induced neuronal death in a dose-dependent manner. We also found that pretreatment with bicyclol dose dependently decreased the generation of ROS and the MDA content and reduced the compensatory increase in SOD activity in the cortex and hippocampus at 4h of reperfusion. These results suggest that bicyclol protects the mouse brain against cerebral IR injury by attenuating oxidative stress and lipid peroxidation.