The antioxidant effect of salidroside has been proven, but its role in liver injury is poorly understood. In this study, we aimed to evaluate the protective effects and mechanism of salidroside on ...liver injury induced by carbon tetrachloride (CCl
) in vivo. Mice were pretreated with salidroside (60 mg/kg, intraperitoneally injected, i.p.) once per day for 14 consecutive days and then administered with CCl
(15.95 g/kg, i.p.) for 24 h to produce a liver injury model. Salidroside attenuated hepatic transaminase elevation in serum and ameliorated liver steatosis and necrosis, thereby suggesting its protective effect on the liver. Salidroside antagonized CCl
-induced toxicity by equilibrating antioxidation system, thereby inhibiting reactive oxygen species accumulation, and restoring mitochondrial structure and function. Salidroside exerts antioxidant and liver-protective effects by selectively inhibiting the activation of genes, including growth arrest and DNA -damage-inducible 45 α (Gadd45a), mitogen-activated protein kinase 7 (Mapk7), and related RAS viral oncogene homolog 2 (Rras2), which induce oxidative stress in the mitogen-activated protein kinase pathway. These results revealed that salidroside can protect the liver from CCl
-induced injury by resisting oxidative stress and protecting mitochondrial function.
Aberrant metabolisms have been hypothesized to precede the occurrence of hepatocellular carcinoma (HCC), therefore, we investigated biomarkers associated with subsequent HCC in peripheral bloods ...using metabolomic technologies. A cohort of 475 HCC-naïve liver cirrhotic patients were recruited and prospectively followed. A total of 39 patients developed HCC in the follow-up period. Baseline plasma metabolites were explored using untargeted nuclear magnetic resonance. Candidates were then quantified by ultra-performance liquid chromatography. A series of univairiate and multivariate analysis showed that Phenylalanine (Phe) and Glutamine (Gln) levels are associated with time to HCC, independent of viological etiologies and age. A HCC risk score R was then constructed using the polynomial combination of age, Phe and Gln in the units of micromolar (μM):Formula: see text R correlates with the time to HCC significantly (Hazard ratio HR = 2.368, 95% confidence interval CI 1.760-3.187, P < 0.001). An additional cross-sectional analysis showed that Phe and Gln concentrations both correlates with HCC occurrence in the next 3 years (area under the receiver operating characteristic curve AUC = 0.607 and 0.629, P = 0.033 and 0.010 respectively). In conclusion, phenylalanine and glutamine concentrations in the peripheral blood correlate with subsequent HCC.
Boron–nitrogen units were incorporated into thiophene‐fused polycyclic aromatic compounds. Organic field‐effect transistors based on these azaborine compounds were fabricated, demonstrating a novel ...engineering concept of organic semiconductors and providing opportunities of a broad class of BN‐containing compounds for application in future organic electronic devices (see picture; μFET=hole mobility).
Blood exosomes, which are extracellular vesicles secreted by living cells into the circulating blood, are regarded as a relatively noninvasive novel tool for monitoring brain physiology and disease ...states. An increasing number of blood cargo-loaded exosomes are emerging as potential biomarkers for preclinical and clinical Alzheimer's disease. Therefore, we conducted a meta-analysis and systematic review of molecular biomarkers derived from blood exosomes to comprehensively analyze their diagnostic performance in preclinical Alzheimer's disease, mild cognitive impairment, and Alzheimer's disease. We performed a literature search in PubMed, Web of Science, Embase, and Cochrane Library from their inception to August 15, 2020. The research subjects mainly included Alzheimer's disease, mild cognitive impairment, and preclinical Alzheimer's disease. We identified 34 observational studies, of which 15 were included in the quantitative analysis (Newcastle-Ottawa Scale score 5.87 points) and 19 were used in the qualitative analysis. The meta-analysis results showed that core biomarkers including Aβ1-42, P-T181-tau, P-S396-tau, and T-tau were increased in blood neuron-derived exosomes of preclinical Alzheimer's disease, mild cognitive impairment, and Alzheimer's disease patients. Molecules related to additional risk factors that are involved in neuroinflammation (C1q), metabolism disorder (P-S312-IRS-1), neurotrophic deficiency (HGF), vascular injury (VEGF-D), and autophagy-lysosomal system dysfunction (cathepsin D) were also increased. At the gene level, the differential expression of transcription-related factors (REST) and microRNAs (miR-132) also affects RNA splicing, transport, and translation. These pathological changes contribute to neural loss and synaptic dysfunction. The data confirm that the above-mentioned core molecules and additional risk-related factors in blood exosomes can serve as candidate biomarkers for preclinical and clinical Alzheimer's disease. These findings support further development of exosome biomarkers for a clinical blood test for Alzheimer's disease. This meta-analysis was registered at the International Prospective Register of Systematic Reviews (Registration No. CRD4200173498, 28/04/2020).
Mitochondrial DNA (mtDNA) has been identified as a significant genetic biomarker in disease, cancer and evolution. Mitochondria function as modulators for regulating cellular metabolism. In the ...clinic, mtDNA variations (mutations/single nucleotide polymorphisms) and dysregulation of mitochondria-encoded genes are associated with survival outcomes among cancer patients. On the other hand, nuclear-encoded genes have been found to regulate mitochondria-encoded gene expression, in turn regulating mitochondrial homeostasis. These observations suggest that the crosstalk between the nuclear genome and mitochondrial genome is important for cellular function. Therefore, this review summarizes the significant mechanisms and functional roles of mtDNA variations (DNA level) and mtDNA-encoded genes (RNA and protein levels) in cancers and discusses new mechanisms of crosstalk between mtDNA and the nuclear genome.
Members of the polypeptide
-acetylgalactosaminyltransferase (GALNT) family function as the initiating enzymes that catalyze mucin-type O-glycosylation of proteins, and their dysregulated expression ...can alter cancer cell behaviors such as de novo occurrence, proliferation, migration, metastasis, and drug resistance. Recent studies have demonstrated that one of the family's members, GALNT14, is aberrantly expressed in multiple cancers and involved in a variety of biological functions. Moreover, the single nucleotide polymorphisms (SNPs) of
-rs9679162 have been shown to predict therapeutic outcomes in patients with hepatocellular carcinoma as well as several other different types of gastrointestinal cancer. This review summarizes the structural features of GANLT14, its functional roles, and the predictive values of
genotypes and enzyme levels in multiple cancers receiving distinct anticancer therapies.
Time-frequency analysis (TFA) technique is an effective approach to capture the changing dynamic in a nonstationary signal. However, the commonly adopted TFA techniques are inadequate in dealing with ...signals having a strong nonstationary characteristic or multicomponent signals having close frequency components. To overcome this shortcoming, a new TFA technique applying a polynomial chirplet transform (PCT) in association with a synchroextracting transform (SET) is proposed in this paper. It is shown that the energy concentration of the time-frequency representation (TFR) of a strong frequency-modulated signal from a PCT transform can be further enhanced by an SET transform. The technique can also be employed to accurately extract the signal components of a multicomponent nonstationary signal with close frequency components by adopting an iterative process. It is found that the TFR calculated from the proposed technique matches well with the ideal TFR, which demonstrates the superiority of the current technique in dealing with nonstationary signals having rapidly changing dynamics. Results from the analysis of the experimental data under varying speed conditions confirm the validity of the proposed technique in dealing with nonstationary signals from practical sources.
The Chinese citrus fly, Bactrocera minax, is a notorious univoltine pest that causes damage to citrus. B. minax enters obligatory pupal diapause in each generation to resist harsh environmental ...conditions in winter. Despite the enormous efforts that have been made in the past decade, the understanding of pupal diapause of B. minax is currently still fragmentary. In this study, the 20-hydroxyecdysone solution and ethanol solvent was injected into newly-formed pupae to obtain non-diapause- (ND) and diapause-destined (D) pupae, respectively, and a comparative proteomics analysis between ND and D pupae was performed 1 and 15 d after injection. A total of 3,255 proteins were identified, of which 190 and 463 were found to be differentially abundant proteins (DAPs) in ND1 vs D1 and ND15 vs D15 comparisons, respectively. The reliability and accuracy of LFQ method was validated by qRT-PCR. Functional analyses of DAPs, including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment, and protein-protein interaction (PPI) network construction, were conducted. The results revealed that the diapause program of B. minax is closely associated with several physiological activities, such as phosphorylation, chitin biosynthesis, autophagy, signaling pathways, endocytosis, skeletal muscle formation, protein metabolism, and core metabolic pathways of carbohydrate, amino acid, and lipid conversion. The findings of this study provide insights into diapause program of B. minax and lay a basis for further investigation into its underlying molecular mechanisms.
Alpha-lipoic acid, epalrestat, and mecobalamin are widely used as monotherapies for diabetic peripheral neuropathy. However, whether a triple-combination therapy with these three drugs is superior to ...monotherapy or dual therapy remains debatable.
Nine randomized controlled trials were identified through a search on electronic databases such as PubMed, Web of Science, and Cochrane Library. The trial participants (N = 1153) were divided into the experimental group who received the triple-combination therapy and the control group who received conventional or dual therapy with the aforementioned drugs.
Therapeutic outcomes were better in the experimental group than in the control group (odds ratio: 3.74; 95 % confidence interval: 2.57–5.45; I2 = 0 %; p < 0.00001). No statistic difference was noted in adverse effects. Compared with the control group, the experimental group exhibited significant improvements in median motor nerve conduction velocity (MNCV), sensory nerve conduction velocity (SNCV), peroneal MNCV, peroneal SNCV, and vibration perception thresholds (VPT) in the left and right lower limbs. In the control group, a subgroup analysis by treatment strategy revealed similar improvements in total efficacy, MNCV, and SNCV.
For diabetic peripheral neuropathy, the triple-combination therapy may be more effective than monotherapy or dual therapy.
•DPN is the most common complication of DM.•ALA + MC + epalrestat might be an effective and safety treatment procedure.
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