Role of FXR in the development of NAFLD and intervention strategies of small molecules.

Non-alcoholic fatty liver disease (NAFLD) remains a prevailing etiological agent behind hepatocyte diseases like chronic liver disease. The spectrum of processes involved in NAFLD stages includes hepatic steatosis, non-alcoholic fatty liver, and non-alcoholic steatohepatitis (NASH). Without intervention, the progression of NASH can further deteriorate into cirrhosis and ultimately, hepatocellular carcinoma. The cardinal features that characterize NAFLD are insulin resistance, lipogenesis, oxidative stress and inflammation, extracellular matrix deposition and fibrosis. Due to its complex pathogenesis, existing pharmaceutical agents fail to take a curative or ameliorative effect on NAFLD. Consequently, it is imperative to identify novel therapeutic targets and strategies for NAFLD, ideally to improve the aforementioned key features in patients. As an enterohepatic regulator of bile acid homeostasis, lipid metabolism, and inflammation, FarnesoidX receptor (FXR) is an important pharmacological target for the treatment of NAFLD. Manipulating FXR to regulate lipid metabolic signaling pathways is a potential mechanism to mitigate NAFLD. Therefore, elucidating the modulatory character of FXR in regulating lipid metabolism in NAFLD has the potential to yield groundbreaking perspectives for drug design. This review details recent advances in the regulation of lipid depletion in hepatocytes and investigates the pivotal function of FXR in the progress of NAFLD.

Correction: Yan, L., et al. Combined Taurine, Epigallocatechin Gallate and Genistein Therapy Reduces HSC-T6 Cell Proliferation and Modulates the Expression of Fibrogenic Factors. Int. J. Mol. Sci. 2013, 14, 20543-20554.

The authors regret that, during the preparation of our published manuscript "Combined taurine, epigallocatechin gallate and genistein therapy reduces HSC-T6 cell proliferation and modulates the expression of fibrogenic factors" [...].

Plant morphology, physiological characteristics, accumulation of secondary metabolites and antioxidant activities of Prunella vulgaris L. under UV solar exclusion.

BACKGROUND: Prunella vulgaris L. has been an important medicinal plant for the treatment of thyroid gland malfunction and mastitis in China for over 2000 years. There is an urgent need to select effective wavelengths for greenhouse cultivation of P. vulgaris as light is a very important factor in P. vulgaris growth. Here, we described the effects of natural light (control) and UV solar exclusion on the morphological and physiological traits, secondary metabolites contents and antioxidant activities of P. vulgaris. RESULTS: The results showed that UV solar exclusion resulted in remarkable alterations to morphological and biomass traits; significantly reduced the chlorophyll a, chlorophyll b and total chlorophyll contents; significantly enhanced the ratio of chlorophyll a to b; and significantly increased the carotenoid and anthocyanin contents in P. vulgaris. UV solar exclusion significantly increased the catalase (CAT) and peroxidase (POD) activities, increased superoxide dismutase (SOD) and ascorbate peroxidase (APX) activities and slightly decreased the glutathione (GSH) content. UV solar exclusion significantly increased the soluble sugar and H2O2 contents and increased the soluble protein content but significantly decreased the proline content and slightly decreased the MDA content. The secondary metabolite contents (total phenolics, rosmarinic acid, caffeic acid, hyperoside, ursolic acid and oleanolic acid) and in vitro antioxidative properties (DPPH· and ABTS·+scavenging activities) were significantly increased in P. vulgaris spicas under UV solar exclusion. Additionally, the total polysaccharide and total flavonoids contents were slightly increased by UV solar exclusion. The salviaflaside content was significantly reduced by UV solar exclusion. CONCLUSION: Our study demonstrated that P. vulgaris activates several antioxidant defence systems against oxidative damage caused by UV solar exclusion.

Effects of UV-B Radiation on the Content of Bioactive Components and the Antioxidant Activity of Prunella vulgaris L. Spica during Development.

The effects of UV-B radiation on the content of bioactive components and the antioxidant activity of Prunella vulgaris L. spica during development were studied. The experimental design involved two levels of UV-B radiation intensity (0 and 120 µW cm-2 nm-1). The results showed that the contents of total flavonoids, rosmarinic acid, caffeic acid and hyperoside, as well as the antioxidant capacities (DPPH● and ABTS•+ scavenging activities), in the spicas significantly decreased during spica development. The content of salviaflaside in the spicas significantly increased during development. The highest contents of total flavonoids, rosmarinic acid, and caffeic acid and the highest antioxidant activities were found in spicas in the full-flowering stage, while the highest content of hyperoside was found in spicas in the bud stage. In addition, the highest content of salviaflaside was found in spicas in the mature-fruiting stage. UV-B radiation significantly promoted the synthesis of secondary metabolites, increased the contents of the main bioactive components in the three developmental stages of isolated dried spicas, and significantly increased the DPPH● and ABTS•+ scavenging activities of P. vulgaris spicas in the mature-fruiting stage. Moreover, the total flavonoids content was positively correlated with the DPPH● and ABTS•+ scavenging activities, and the correlation with the DPPH● scavenging activity was very strong. This result shows that the highest contents of the main bioactive components in the spicas were not all found in the same developmental stages of P. vulgaris. Our research revealed that the best stage for harvesting P. vulgaris spica was between the bud stage and the full-flowering stage since harvesting at this point provides a higher content of bioactive components and a higher antioxidant capacity, which is relevant for medicinal applications.

[Effects of different drying methods on quality of Gastrodiae Rhizoma].

Different drying methods, including drying in the sun, sulphur fumigation, hot air drying, microwave drying, infrared drying and various coupling techniques,were used to dry fresh Gastrodiae Rhizoma. Characteristics, extracts and the contents of active components of all samples were compared to investigate the effects of different drying methods on quality of Gastrodiae Rhizoma. The results showed that the characteristics of the samples would be better with use of sulphur fumigation, hot air drying, and hot air-microwave drying. Different drying methods had little effects on extracts. Among them, the extract content was higher after hot air drying. The stilbene glycosides would transformation and the contents of Gastrodiae Rhizoma polysaccharides would decline with use of sulphur fumigation, microwave drying and infrared drying. In the comprehensive analysis of characteristics, content of active components, production cost and other factors, hot air drying or hot air-microwave drying was recommended as the first choice.

Approach based on high-performance liquid chromatography fingerprint coupled with multivariate statistical analysis for the quality evaluation of Gastrodia Rhizoma.

Gastrodia Rhizoma is a Traditional Chinese Medicine applied in the treatment of stroke, numbness of limb, headache and dizziness. However, its clinical effect is threatened by sulfur-fumigation used in the process of storage. This article employs content determination coupled with high-performance liquid chromatography fingerprint to investigate the effect of sulfur-fumigation on Gastrodia Rhizoma so as to evaluate the quality of Gastrodia Rhizoma. The result was that most active ingredient in Gastrodia Rhizoma decreased after sulfur-fumigation and the fingerprints analyzed by mathematical statistics between sulfur-fumigated Gastrodia Rhizoma and unfumigated Gastrodia Rhizoma have substantial differences, which reveals that sulfur-fumigation has a significant influence on the quality of Gastrodia Rhizoma. The conclusion of hierarchical clustering analysis, principal component analysis and partial least squares could validate each other, which implies that the method of mathematical statistics applied for assessing the quality of Gastrodia Rhizoma is effective and stable. The method not only affords a viable strategy for distinguishing Gastrodia Rhizoma whether sulfur-fumigated or not and assessment of the quality of Gastrodia Rhizoma, but also provides a reference for other herbal medicine that suffers from sulfur-fumigation.

Flavonoids and Organic Acids Affect Phase II Metabolism based on the Regulation of UGT1A1 Expression and Function.

BACKGROUND: Exogenous substances modulate metabolism by regulating the expression and function of UDP-glycosyltransferases (UGTs). However, the exact mechanism in the intestine was rarely understood. Herein, we explored the effects of representative flavonoids and organic acids on the regulation of UGT1A1. METHODS: MTT assays and western blot analysis were used to explore the effect of polyphenols. X-ray diffraction was used to reveal the catalytic mechanisms of UGTs. RESULTS: MTT assays showed that these compounds basically had no cytotoxicity, even in concentrations up to 200 µM. Then, through western blot assays, UGT1A1 expression was increased after being treated with liquiritigenin and caffeic acid. Furthermore, liquiritigenin and caffeic acid enhanced the nuclear translocation of Nrf2. Moreover, a 2.5-Å crystal structure of the complex containing UGTs C-terminal domain and organic acid was solved, and the UDPGA binding pocket could be occupied by organic acid, suggesting the enzyme activity might be impaired by organic acid. CONCLUSION: Above all, liquiritigenin and caffeic acid maintained the metabolism balance by upregulating the expression of UGT1A1 via Nrf2 activation and inhibiting the enzyme activity in Caco-2 cells.

The effectiveness of Q6 and PIPER 6-year-old models on quantification of the change of child sitting posture with AEB and its impact on child's injures in frontal crash.

OBJECTIVE: Automatic Emergency Braking (AEB) has a direct impact on the effectiveness of the restraint systems in providing protection toward child occupants. The objective is to evaluate the effectiveness of Q6 and PIPER 6-year-old models in predicting the kinematic responses of child models, and further to quantify and analyze the child injuries during a frontal crash with and without AEB. METHODS: The finite element model of a booster seat has been validated through a full vehicle test. Based on the validated finite element model, two sled test finite element models for the rear seat booster seat with Q6 and PIPER 6-year-old models were constructed. AEB condition was imposed on above the two models and the kinematic responses of sitting posture including head, neck and chest have been compared in detail. The peak head displacement and neck curvature of Q6 dummy and PIPER 6-year-old models have been compared with the test data from child volunteers. Based on the child model with better predictive capability for kinematic response under AEB, child injuries were evaluated and analyzed for the 50 km/h frontal crash test with and without AEB. Last, this study discussed the effects of internal neck and chest structure difference between Q6 and PIPER 6-year-old models on child kinematic response and the injury risks. RESULTS: Under AEB condition, PIPER 6-year-old model has higher head displacement and lower trunk displacement than Q6 dummy model, and the peak head displacement and neck curvature of PIPER 6-year-old model are similar to the test data of child volunteers. During the 50 km/h frontal crash simulation with pre-crash AEB, the HIC15, Head acceleration 3 ms, Nij decrease 43.7%, 19.6% and 28.8%, respectively and the chest deflection increases 15.5% compared to the simulation without AEB. CONCLUSIONS: This study shows that PIPER 6-year-old model is more suitable for the quantification of sitting posture change under AEB due to its higher biofidelity. The pre-crash AEB can substantially reduce the head, neck injuries. But it also increases the chest injury due to the chest pre-compression. Future efforts are recommended to lower the child chest injury by integrating AEB with active pre-tensioning seatbelts.

Ponicidin-induced conformational changes of HSP90 regulates the MAPK pathway to relieve ulcerative colitis.

ETHNOPHARMACOLOGICAL RELEVANCE: Ulcerative colitis (UC) is a recurring chronic intestinal disease that can be debilitating and in severe cases, may further lead to cancer. However, all these treatment techniques still suffer from drug dependence, adverse effects and poor patient compliance. Therefore, there is an urgent need to seek new therapeutic strategies. In traditional Chinese medicine, Rabdosia rubescens (Hemsl.) H.Hara has the effects of clearing heat-toxin and promoting blood circulation to relieve pain, it is wildly used for treating inflammatory diseases such as sore throats and tonsillitis. Ponicidin is an important molecule for the anti-inflammatory effects of Rabdosia rubescens, but it has not been studied in the treatment of colitis. HSP90 is the most critical regulator in the development and progression of inflammatory diseases such as UC. AIM OF THE STUDY: The aim of this study was to explore the anti-inflammatory activity of ponicidin and its mechanism of effect in vitro and in vivo, as well as to identify the target proteins on which ponicidin may interact. MATERIAL AND METHODS: 2.5% (w/v) dextran sulfate sodium (DSS) was used to induce C57BL/6 mice to form an ulcerative colitis model, and then 5 mg/kg and 10 mg/kg ponicidin was given for treatment, while the Rabdosia rubescens extract group and Rabdosia rubescens diterpene extract group were set up for comparison of the efficacy of ponicidin. At the end of modeling and drug administration, mouse colon tissues were taken, and the length of colon was counted, inflammatory factors and inflammatory signaling pathways were detected. RAW264.7 cells were induced to form cell inflammation model with 1 µg/mL Lipopolysaccharide (LPS) for 24 h. 1 µM, 2 µM and 4 µM ponicidin were given at the same time, and after the end of the modeling and administration of the drug, the inflammatory factors and inflammatory signaling pathways were detected by qRT-PCR, western blotting, immunofluorescence and other methods. In vitro, target angling and combined with mass spectrometry were used to search for relevant targets of ponicidin, while isothermal titration calorimetry (ITC), protease degradation experiments and molecular dynamics simulations were used for further confirmation of the mode of action and site of action between ponicidin and target proteins. RESULTS: Ponicidin can alleviate DSS and LPS-induced inflammation by inhibiting the MAPK signaling pathway at the cellular and animal levels. In vitro, we confirmed that ponicidin can interact with the middle domain of HSP90 and induce the conformational changes in the N-terminal domain. CONCLUSION: These innovative efforts identified the molecular target of ponicidin in the treatment of UC and revealed the molecular mechanism of its interaction with HSP90.

Proteomic study of localized tissue necrosis by Naja atra venom.

Naja atra bites often result in immediate and severe illness. The venom of N. atra contains a complex mixture of toxins that can cause significant damage to the patient's skin tissue. If left untreated, this condition can progress to localized necrosis, potentially resulting in impairment or even amputation in severe cases. Despite the known effects of the venom, the exact mechanisms underlying this tissue necrosis are not fully understood. This study aimed to investigate the protein components responsible for tissue necrosis induced by N. atra venom at both the organism-wide and molecular levels. To achieve this, venom was injected into Bama miniature pigs to cause ulcers, and exudate samples were collected at various time points after injection. Label-free proteomics analysis identified 1119, 1016, 938, 864, and 855 proteins in the exudate at 6, 12, 24, 36, and 48 h post-injection, respectively. Further analysis revealed 431 differentially expressed proteins, with S100A8, MMP-2, MIF, and IDH2 identified as proteins associated with local tissue necrosis. In this study, we established a Bama miniature pig model for N. atra venom injection and performed proteomic analysis of the wound exudate, which provides important insights into the molecular pathology of snakebite-induced tissue necrosis and potential theoretical bases for clinical treatment. Proteomic data from this study can be accessed through ProteomeXchange using the identifier PXD052498.

Time-dependent absorption of TiO2 optical thin films under pulsed and continuous wave 790 nm laser irradiation.

The time-dependent absorption at 790 nm of TiO2 films prepared by ion-beam sputtering (IBS) and electron-beam evaporation (EBE) was measured. The pump source was a Ti:sapphire oscillator that was operated in CW and pulsed (50 fs) modes. The absorption coefficient of the IBS film under CW illumination was 8 cm-1, independent of time and power. Under pulsed illumination, there was evidence of three-photon absorption, and the total absorption increased 10-fold over time at the highest measured irradiance. The absorption of the EBE film had higher initial absorption (∼24 cm-1) and increased under both CW and pulsed illumination with time. An electron state model based on band-to-band excitation and electron trapping is presented that explains the observed results. The implications for laser-induced damage of oxide coatings are discussed.

Combined taurine, epigallocatechin gallate and genistein therapy reduces HSC-T6 cell proliferation and modulates the expression of fibrogenic factors.

Hepatic fibrogenesis involves the activation of hepatic stellate cells (HSCs), which synthesize excess extracellular matrix and contribute to the development of liver fibrosis. In a prior study we tested the effect of combined treatment with taurine, epigallocatechin gallate and genistein on the development of alcohol-induced liver fibrosis in vitro. In this study, the biological activity of the combination of these molecules was assessed by measuring its effect on cell proliferation, fibrosis-related gene expression, and proteomic expression profiling in the activated HSC cell line, HSC-T6. HSC-T6 cells were incubated with different concentrations of the drug combination taurine, epigallocatechin gallate and genistein. Cell proliferation was evaluated by MTT assay. Transforming growth factor ß1 (TGF-ß1), collagen type I (Col-I), matrix metalloproteinase-2 (MMP-2), and tissue inhibitor of metalloproteinases 1 and 2 (TIMP-1 and TIMP-2) mRNA were analyzed by semi-quantitative reverse-transcription PCR. Proteomic profiling of HSC-T6 cells was also performed by SELDI-TOF-MS. Combined drug treatment significantly inhibited cell proliferation and TGF-ß1, Col-I, TIMP-1 and TIMP-2 mRNA expression in activated HSC-T6 cells, while the expression of MMP-2 mRNA increased. A total of 176 protein m/z peaks were identified. The intensities of 10 protein peaks were downregulated and two protein peaks were upregulated in HSC-T6 cells after combined drug treatment. In conclusion, combined drug treatment with taurine, epigallocatechin gallate and genistein can inhibit HSC proliferation, and impact fibrosis-related gene and protein expression. The antifibrotic effects of this drug combination may be due to its effects on the expression of fibrogenic genes.

The structural basis of conserved residue variant effect on enzyme activity of UGT2B15.

UDP-glucuronosyltransferase 2B15 (UGT2B15) is a crucial phase II drug-metabolizing enzyme, which glucuronidates various compounds, including clinical drugs and hormones. Mutants might affect glucuronidation, leading to a disruption of drug metabolism in vivo and decrease of therapeutic effect. Here, we mainly analyzed two representative mutants, H401P and L446S, on UGT2B15 activity using glucuronidation assays, molecular dynamic (MD) simulation and X-ray diffraction methods. The enzyme activity of L446S obviously increased six-fold than the wild type, although the enzyme activities of P191L, T374A, and H401P were lost apparently. Furthermore, we used MD simulations to calculate the energy change in the catalytic process of H401P and L446S, and the results indicated the free binding energies of H401P mutant to oxazepam and UDPGA were -30.98 ± 1.00 kcal/mol and -36.42 ± 1.04 kcal/mol, respectively, increased obviously compared to wild type, suggesting the mutation on position 401 had a crucial effect on the catalysis. Moreover, the three-dimensional structure of UGT2B15 C-terminal domain L446S was determined through protein crystallography and X-ray diffraction technology and the results suggested that one more hydrogen bonding between S446 and K410 was formed in the S446 crystal structure, compared to the wild type. Isothermal titration calorimetry assay further revealed the Kd values of C-terminal domain of UGT2B15 harbored L446S towards the cofactor UDPGA was similar to the value of wild type. Above all, our results pointed out that H401P and L446S affected the enzyme activity by different mechanism. Our work provided a helpful mechanism for variance explained in the UGTs catalyzation process.

Comprehensive evaluation of urban water supply security based on the VIKOR-TOPSIS method.

To determine the security status of urban water supplies, a comprehensive evaluation model of urban water supply security based on the VIKOR and TOPSIS models is proposed. The comprehensive evaluation value K is obtained as the evaluation result, and the larger K is, the higher the safety of the urban water supply. The results show that the security of the water supply in Tianjin increased from 0.2300 in 2015 to 0.8026 in 2018. Although it slightly decreased to 0.5439 in 2019, it was still at a high level and increased to 0.7508 in 2020. The urban water transmission and distribution status, the service level of the water supply industry, and the status of sewage treatment play positive roles in affecting the safety of the water supply in Tianjin, and the status of urban water sources and the urban water use status are the main factors that reduced the safety of the urban water supply. According to the results of an obstacle degree model and the actual conditions in the study area, it is suggested that Tianjin should continue to focus on the development of water resources and the utilization of unconventional water sources and actively promote the construction of a water-saving society.

Environmental quality assessment and spatial spillover effects of three urban agglomerations in China: A Meta-EBM approach.

The new development form of urban agglomeration has greatly promoted economic and social progress in recent years, but it is also facing severe environmental pollution problems. Understanding the status quo of environmental efficiency in urban agglomerations and its leading driving forces is an important prerequisite for formulating energy conservation and emission reduction policies. This research uses the Meta Epsilon Based Measure (Meta-EBM) model to measure the environmental emission efficiency of the Beijing-Tianjin-Hebei（BTH）, Yangtze River Delta (YRD) and Pearl River Delta (PRD) urban agglomerations in China from 2014 to 2018 so as to improve on the inability of traditional Data Envelopment Analysis (DEA) to combine linear and non-linear characteristics, and employs Moran's I index and spatial econometric methods to analyze their spatial dependence and main driving factors. The results demonstrate that the overall environmental efficiency of the three major urban agglomerations in the five years from 2014 to 2018 presents a wave-like development and then tends to be flat. The itemized efficiency of economic outputs has maintained a relatively high level with the environmental output index exhibiting the best efficiency for industrial wastewater, followed by industrial sulfur dioxide (SO2). The scores of the two indicators for inhalable fine particle emissions (PM2.5) and industrial smoke and dust in each urban agglomeration are not ideal, and there are obvious differences between regions. Among them, YRD and PRD are relatively inferior. From the perspective of spatial spillover effects, various indicators show diverse characteristics at different development stages of the regions. Population and Normalized Difference Vegetation Index (NDVI) have a positive effect on environmental efficiency, while both Gross Domestic Product (GDP) per capita and transportation tend to show greater negative effects on regional environmental optimization. This study proposes countermeasures as follows. Each urban agglomeration should set up measures suitable to local conditions and give full play to their location advantages. They can also use space radiation to promote sector economic development and optimize urban environmental benefits.

Metabolomics analyses of serum metabolites perturbations associated with Naja atra bite.

Naja atra bite is one of the most common severe snakebites in emergency departments. Unfortunately, the pathophysiological changes caused by Naja atra bite are unclear due to the lack of good animal models. In this study, an animal model of Naja atra bite in Guangxi Bama miniature pigs was established by intramuscular injection at 2 mg/kg of Naja atra venom, and serum metabolites were systematically analyzed using untargeted metabolomic and targeted metabolomic approaches. Untargeted metabolomic analysis revealed that 5045 chromatographic peaks were obtained in ESI+ and 3871 chromatographic peaks were obtained in ESI-. Screening in ESI+ modes and ESI- modes identified 22 and 36 differential metabolites compared to controls. The presence of 8 core metabolites of glutamine, arginine, proline, leucine, phenylalanine, inosine, thymidine and hippuric acid in the process of Naja atra bite was verified by targeted metabolomics significant difference (P<0.05). At the same time, during the verification process of the serum clinical samples with Naja atra bite, we found that the contents of three metabolites of proline, phenylalanine and inosine in the serum of the patients were significantly different from those of the normal human serum (P<0.05). By conducting functional analysis of core and metabolic pathway analysis, we revealed a potential correlation between changes in key metabolites after the Naja atra bite and the resulting pathophysiological alterations, and our research aims to establish a theoretical foundation for the prompt diagnosis and treatment of Naja atra bite.

Corrigendum: Effects of meteorological factors and atmospheric pollution on hand, foot, and mouth disease in Urumqi Region.

[This corrects the article DOI: 10.3389/fpubh.2022.913169.].

Glutamine ameliorates Bungarus multicinctus venom-induced lung and heart injury through HSP70: NF-κB p65 and P53/PUMA signaling pathways involved.

Background: Bungarus multicinctus is one of the most dangerous venomous snakes prone to cardiopulmonary damage with extremely high mortality. In our previous work, we found that glutamine (Gln) and glutamine synthetase (GS) in pig serum were significantly reduced after Bungarus multicinctus bite. In the present study, to explore whether there is a link between the pathogenesis of cardiopulmonary injury and Gln metabolic changes induced by Bungarus multicinctus venom. We investigated the effect of Gln supplementation on the lung and heart function after snakebite. Methods: We supplemented different concentrations of Gln to mice that were envenomated by Bungarus multicinctus to observe the biological behavior, survival rate, hematological and pathological changes. Gln was supplemented immediately or one hour after the venom injection, and then changes in Gln metabolism were analyzed. Subsequently, to further explore the protective mechanism of glutamine on tissue damage, we measured the expression of heat-shock protein70 (HSP70), NF-κB P65, P53/PUMA by western blotting and real-time polymerase in the lung and heart. Results: Gln supplementation delayed the envenoming symptoms, reduced mortality, and alleviated the histopathological changes in the heart and lung of mice bitten by Bungarus multicinctus. Additionally, Gln increased the activity of glutamine synthetase (GS), glutamate dehydrogenase (GDH) and glutaminase (GLS) in serum. It also balanced the transporter SLC7A11 expression in heart and lung tissues. Bungarus multicinctus venom induced the NF-κB nuclear translocation in the lung, while the HO-1 expression was suppressed. At the same time, venom activated the P53/PUMA signaling pathway and the BAX expression in the heart. Gln treatment reversed the above phenomenon and increased HSP70 expression. Conclusion: Gln alleviated the glutamine metabolism disorder and cardiopulmonary damage caused by Bungarus multicinctus venom. It may protect lungs and heart against venom by promoting the expression of HSP70, inhibiting the activation of NF-κB and P53/PUMA, thereby delaying the process of snake venom and reducing mortality. The present results indicate that Gln could be a potential treatment for Bungarus multicinctus bite.

Diagnostic accuracy of glioma pseudoprogression identification with positron emission tomography imaging: a systematic review and meta-analysis.

Background: Positron emission tomography (PET) imaging is a promising molecular neuroimaging technique and has been proposed as one of the criteria for glioma management. However, there is some controversy concerning the diagnostic accuracy of PET using different radiotracers to differentiate between glioma pseudoprogression (PsP) and true progression (TPR). The purpose of this meta-analysis was to systematically evaluate the methodological quality and clinical value of original studies for distinguishing PsP from TPR in glioma. Methods: The Medline, Web of Science, Embase, Cochrane Library, and ClinicalTrials.gov were searched from inception until September 1, 2022. Retrieved clinical studies only investigated the PsP cases but did not include the cases of radiation necrosis or other treatment-related changes. Eligible studies were screened for data extraction and evaluated by 2 independent reviewers using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool. A random effects model was used to describe summary receiver operating characteristics. Meta-regression and subgroup analyses were applied to identify any sources of heterogeneity. Results: The meta-analysis included 20 studies, comprising 317 (30.9%) patients with PsP and 708 (69.1%) with TPR. The summary sensitivity and specificity of general PET for identifying PsP were 0.86 [95% confidence interval (CI): 0.77-0.91] and 0.84 (95% CI: 0.79-0.88), respectively. The statistical heterogeneity was explained by sample size, study design, World Health Organization (WHO) grade, gold standard, and radiotracer type. The summary sensitivity and specificity of O-(2-18F-fluoroethyl)-L-tyrosine (18F-FET PET) were 0.80 (95% CI: 0.68-0.88) and 0.81 (95% CI: 0.75-0.85), respectively. The maximum tumor-to-brain ratio (TBRmax) and the mean tumor-to-brain ratio (TBRmean) both showed excellent diagnostic performance in 18F-FET studies, the summary sensitivity was 0.83 (95% CI: 0.72-0.91) and 0.79 (95% CI: 0.65-0.98), respectively, and the specificity was 0.76 (95% CI: 0.68-0.84) and 0.78 (95% CI: 0.64-0.88), respectively. Conclusions: PET imaging is generally accurate in identifying glioma PsP. Considering the credibility of meta-evidence and the practicability of using radiotracer, 18F-FET PET holds the highest clinical value, while TBRmax and TBRmean should be regarded as reliable parameters. PET used with the radiotracers and multiple-parameter combinations of PET with magnetic resonance imaging (MRI) and radiomics analysis have broad research and application prospects, whose diagnostic values for identifying glioma PsP warrant further investigation.

[Clusterin is a potential serum marker of hepatic carcinoma].

OBJECTIVE: To determine the differentially expressed serum proteins in patients with hepatoma carcinoma and identify a putative diagnostic marker. METHOD: The isobaric tags for relative and absolute quantitation (iTRAQ) labeling method and LC-MALDI-TOF/TOF MS detection method were used to quantify serum proteins in hepatocellular carcinoma patients (n =20) and healthy individuals (n =20). Real-time reverse transcription-polymerase chain reaction was used to verify the differentially expressed proteins by analyzing the corresponding mRNA expression levels in the hepatic carcinoma and healthy hepatocyte samples, as well as in 30 pairs of patient-matched hepatic carcinoma and adjacent normal tissue samples. Western blot analysis was used to verify the protein expression in hepatic carcinoma cells. RESULT: Fifty-one proteins were significantly differentially expressed between the hepatic carcinoma group and healthy controls. The iTRAQ protein profile showed that the serum level of clusterin was significantly lower in hepatoma carcinoma patients. The mRNA level of clusterin was 20-fold lower in hepatic carcinoma cells than in healthy hepatocytes, and was 2.38-fold lower in hepatoma tissues than that in adjacent normal tissues. The clusterin protein levels were significantly lower in hepatic carcinoma cells (8.06 vs normal hepatocytes: 27.81; P less than 0.01). CONCLUSION: The serum expression of clusterin is significantly decreased in both serum and tissues of hepatic carcinoma patients. The relationship between hepatic carcinoma and clusterin should be evaluated in future studies.