Previous studies have revealed that triglyceride to high-density lipoprotein cholesterol (HDL-C) ratio (henceforth TG/HDL-C) is one of the major risk factors for cardiovascular disease, insulin ...resistance and metabolism syndrome. However, there are fewer investigations of the correlations between the aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio and brachial ankle pulse wave velocity (baPWV). This study was undertaken to investigate the relationship between the AST to ALT ratio and brachial-ankle pulse wave velocity (baPWV) in a Japanese population.
The present study was a cross-sectional study. A total of 646 Japanese men and women without fatty liver, aged 24-84 years old, received a health medical check-up programme including the results from baPWV inspection and various standardized questionnaires in a health examination centre in Japan. Main outcome measures included AST/ALT ratio, baPWV, fatty liver and postmenopausal status. Abdominal ultrasonography was used to diagnose fatty liver. A postmenopausal state was defined as beginning 1 year following the cessation of menses.
After adjusting for potential confounders (age, sex, BMI, SBP, DBP, AST, ALT, GGT, uric acid, fasting glucose, TC, LDL, eGFR, smoking and exercise statuses, fatty liver, alcohol consumption and ABI), a non-linear relationship was detected between AST/ALT and baPWV, which had an inflection point of 5.6. The effect sizes and the confidence intervals on the left and right sides of the inflection point were 12.7 (1.9 to 23.5) and - 16.7 (- 36.8 to 3.3), respectively. Subgroup analysis in participants with excessive alcohol consumption (more than 280 g/week) showed that AST/ALT had a negative correlation with baPWV (β = - 30.7, 95%CI (- 53.1, - 8.4)), and the P value for the interaction was less than 0.05.
The relationship between AST/ALT and baPWV is non-linear. AST/ALT was positively correlated with baPWV when AST/ALT was less than 5.6. In addition, the trend was the opposite in subjects who consumed excessive amounts of alcohol.
A novel kind of ternary nanocomposites, BaTiO3 and NiFe2O4 nanoparticles deposited on reduced graphene oxide nanosheets, was prepared via a three-step method. The phase structure, morphology, ...chemical composition, and magnetic properties were analyzed by powder X-ray diffraction (XRD) technique, field emission scanning electron microscope (FESEM), transmission electron microscopy (TEM), Raman spectroscopy and vibrating sample magnetometry (VSM) while the microwave absorption performance was investigated by vector network analyzer (VNA). The results showed the sample with 30 wt% reduced graphene oxide exhibits the most remarkable microwave absorption properties. The optimal reflection loss can reach −51.1 dB at 9.52 GHz with a coating layer thickness of only 2.9 mm and a broad bandwidth (RL < −10 dB) of 3.12 GHz.
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•A novel kind of ternary nanocomposites was prepared.•The formation mechanism of ternary nanocomposites was discussed.•The ternary nanocomposites possessed excellent microwave absorption properties.
Lung cancer accounts for the most cancer-related deaths in the world. Our previous study suggested the improved survival of lung cancer patients, mainly female patients, with subsequent metachronous ...primary breast cancer. However, whether the survival advantages of the two primaries are associated with patients' sex and the specific breast cancer is unclear. Whether male lung cancer patients with another primary may encounter the same survival advantage as female patients is also uncertain. The uncertainty hinders these patients from the potential benefit of lung cancer clinical trial. A total of 343 male lung adenocarcinoma patients with subsequent bladder papillary transitional cell carcinoma (LCBC), 1539 lung adenocarcinoma patients with prior bladder papillary transitional cell carcinoma (BCLC), 1181 lung adenocarcinoma patients with subsequent prostate adenocarcinoma (LCPC), 7426 lung adenocarcinoma patients with prior prostate adenocarcinoma (PCLC), and patients with single bladder/prostate/lung (SLC) cancer were identified from the Surveillance, Epidemiology, and End Results. Patients were classified into simultaneous two primary cancer (sTPC), metachronous two primary cancer 1 (mTPC1), or mTPC2 groups when interval time between two cancers was within 6 months, between 7 and 60 months, or over 60 months, respectively. Propensity matching score program was executed to match the two primary cancers with single primary. Cox regression and competing risk regression were performed to identify confounders associated with all-cause and cancer-specific survival, respectively. The major cancer-related and non-cancer-related death in the two primaries were lung cancer and heart disease, respectively. Median overall survival times since lung primary of LCBC and SLC were 97 and 17 months, respectively, and incidence of all-cause and cancer-specific death in LCBC since lung malignancy was significantly lower (Coef. - 1.24, 95% CI - 1.49 to 0.99; SHR 0.42, 95% CI 0.33-0.53). Among the categorized groups, prognosis values of sTPC and mTPC2 groups were not statically different from that of the matched single lung cancer, whereas increased overall survival time and decreased incidence of all-cause and cancer-specific death relative to the matched patients were observed in mTPC1 group (H.R 0.28, 95% CI 0.19-0.41; SHR 0.33, 95% CI 0.23-0.47). Similar prognosis of LCPC relative to SLC was also observed. Furthermore, a generally improved survival relative to SLC was observed in PCLC (median survival times of PCLC and SLC were 17 and 12 months, respectively; Coef. - 0.32, 95% CI - 0.43 to 0.22; SHR 0.77, 95% CI 0.69-0.85), whereas prognosis of BCLC was similar to the matched ones. These results hinted that survival of lung cancer patients might vary with prior cancer history. Further analysis among groups with the two primaries suggested that advanced bladder cancer was not associated with prognosis of patients with LCBC and BCLC. On the contrary, advanced prostate cancer was associated with all-cause and cancer-specific death in patients with PCLC but not in patients with LCPC. Compared with patients with single lung cancer, male lung cancer patients with subsequent bladder/prostate primary over 6 months experienced generally improved survival. These results were similar to our previous study regarding female lung cancer patients with another breast primary. On the contrary, male lung cancer patients with prior primary malignancy encountered varied prognosis: improved survival relative to single lung primary was observed in lung cancer with prior prostate cancer, whereas prognosis of lung cancer with prior bladder cancer was not different. Therefore, great attention was required to characterize prognosis of lung cancer patients with another primary in advance, which was essential to eliminate the potential bias when these patients were included into the clinical trials.
Changes in intestinal microecology during acute liver failure (ALF) directly affect the occurrence and development of the disease. The study aimed to investigate the relationship between the ...intestinal microbiota and the key immune cells. Fecal microbiota transplantation (FMT) was used to determine whether ALF can balance Th17/Treg cytokines. The relationship between gut microbiota and clinical indicators was analyzed. BALB/c mice were treated with D-galactosamine (D-GalN) to induce a murine ALF model. FMT to D-GalN mice was conducted to test for liver function indicators. Results showed that the proportions of Lachnospiraceae, Prevotella, S24-7, Odoribacter and Rikenellaceae in D-GalN mice with intestinal microbiota disorder were restored after FMT. Further, CIA analysis showed that bacteria had a covariant relationship with clinical indicators. Microbiota could account for changes in 49.9% of the overall clinical indicators. Adonis analysis showed that Ruminococcus, and Enterococcus have a greater impact on clinical indicators. FMT down-regulated the expression of IL-17A, TNF-α, and TGF-β, while up-regulated IL-10 and IL-22. Transplantation of feces from Saccharomyces boulardii donor mice improved GalN-induced liver damage. These findings indicate that FMT attenuates D-GalN-induced liver damage in mice, and a clinical trial is required to validate the relevance of our findings in humans, and to test whether this therapeutic approach is effective for patients with ALF.
Nonalcoholic steatohepatitis (NASH) is one of the most common liver diseases and has no safe and effective drug for treatment. We have previously reported the function of blueberry, but the effective ...monomer and related molecular mechanism remain unclear.
The monomer of blueberry was examined by ultra performance liquid chromatography-mass spectrometry (UPLC-MS). The NASH cell model was constructed by exposing HepG2 cells to free fatty acids. The NASH mouse model was induced by a high-fat diet for 12 weeks. NASH cell and mouse models were treated with different concentrations of blueberry monomers. The molecular mechanism was studied by Oil Red O staining, ELISA, enzyme activity, haematoxylin-eosin (H&E) staining, immunohistochemistry, immunofluorescence, western blot, RNA sequencing, and qRT-PCR.
We identified one of the main monomer of blueberry as tectorigenin (TEC). Cyanidin-3-O glucoside (C3G) and TEC could significantly inhibit the formation of lipid droplets in steatosis hepatocytes, and the effect of TEC on the formation of lipid droplets was significantly higher than that of C3G. TEC can promote cell proliferation and inhibit the release of inflammatory mediators in NASH cell model. Additionally, TEC administration provided a protective role against high-fat diets induced lipid damage, and suppressed lipid accumulation. In NASH mouse model, TEC can activate autophagy, inhibit pyroptosis and the release of inflammatory mediators. In NASH cell model, TEC inhibited pyroptosis by stimulating autophagy. Then, small RNA sequencing revealed that TEC up-regulated the expression of tRF-47-58ZZJQJYSWRYVMMV5BO (tRF-47). The knockdown of tRF-47 blunted the beneficial effects of TEC on NASH in vitro, including inhibition of autophagy, activation of pyroptosis and release of inflammatory factors. Similarly, suppression of tRF-47 promoted the lipid injury and lipid deposition in vivo.
These results demonstrated that tRF-47-mediated autophagy and pyroptosis plays a vital role in the function of TEC to treat NASH, suggesting that TEC may be a promising drug for the treatment of NASH.
Abstract
The appeal to enroll patients with primary breast and lung cancer in clinical trials is increasing, but survival of these two primary cancers remains to be elucidated. This study analyzed ...the prognosis of primary breast duct carcinoma with subsequent lung adenocarcinoma (BCLA) and primary breast duct carcinoma with prior lung adenocarcinoma (LABC). Cohorts of 3,515 patients with BCLA and 654 patients with LABC were identified from the Surveillance, Epidemiology, and End Results database. Patients were classified into simultaneous two primary cancer (sTPC), metachronous two primary cancer (mTPC1), or mTPC2 groups when the interval times between breast and lung cancer were within 6 months, between 7 and 60 months, or over 60 months, respectively. The propensity score matching program (PSM) was applied to determine the survival of BCLA/LABC relative to single breast/lung cancer. Cox proportional hazard regression model and competing risk modes were performed to identify confounders associated with all-cause and cancer-specific death, respectively. Survival of patients with LABC/BCLA relative to single breast/lung cancer was accessed via median survival time. The survival of patients with BCLA/LABC was generally poor compared with the survival of those with single breast cancer. The PSM-estimated HR in the sTPC group with BCLA and in the mTPC1 and mTPC2 groups with LABC were 0.75 (95% CI 0.62–0.90), 0.52 (95% CI 0.27–0.98), and 0.36 (95% CI 0.20–0.65), respectively, whereas the SHRs were 0.80 (95% CI 0.66–0.97), 0.68 (95% CI 0.34–1.34), and 0.46 (95% CI 0.27–0.80), respectively, compared with those in the single lung cancer group. By contrast, the survival rates of the remaining patients did not differ. The median survival times since secondary malignancy were 42, 23, and 20 months in the sTPC, mTPC1, and mTPC2 groups with BCLA, respectively, and 18, 60, and 180 months in those with LABC, respectively. For patients with BCLA, the adjusted Cox regression suggested incidences of all-cause deaths in mTPC1group were statically higher than those in sTPC group, whereas the incidences of all-cause and cancer-specific death in the mTPC1 and mTPC2 groups were statistically lower than those in the sTPC group. The prognosis of patients with breast cancer and subsequent lung cancer of over 18 months was not significantly different than that of single lung cancer, which supported the profound appeal to increase the involvement of these two primary cancers in potential beneficial clinical trials. For patients with lung cancer and prior breast cancer of within 6 months and subsequent breast cancer of over 18 months, prognosis was improved relative to single lung cancer. Therefore, additional attention is needed to eliminate the potential bias may when these patients are recruited in the clinical trials.
Nonalcoholic steatohepatitis (NASH) is liver inflammation and a major threat to public health. Several pharmaceutical agents have been used for NASH therapy but their high-rate side effects limit the ...use. Blueberry juice and probiotics (BP) have anti-inflammation and antibacterial properties, and may be potential candidates for NASH therapy. To understand the molecular mechanism, Sprague Dawley rats were used to create NASH models and received different treatments. Liver tissues were examined using HE (hematoxylin and eosin) and ORO (Oil Red O) stain, and serum biochemical indices were measured. The levels of peroxisome proliferators-activated receptor (PPAR)-α, sterol regulatory element binding protein-1c (SREBP-1c), Patatin-like phospholipase domain-containing protein 3 (PNPLA-3), inflammatory cytokines and apoptosis biomarkers in liver tissues were measured by qRT-PCR and Western blot. HE and ORO analysis indicated that the hepatocytes were seriously damaged with more and larger lipid droplets in NASH models while BP reduced the number and size of lipid droplets (
< 0.05). Meanwhile, BP increased the levels of SOD (superoxide dismutase), GSH (reduced glutathione) and HDL-C (high-density lipoprotein cholesterol), and reduced the levels of AST (aspartate aminotransferase), ALT (alanine aminotransferase), TG (triglycerides), LDL-C (low-density lipoprotein cholesterol) and MDA (malondialdehyde) in NASH models (
< 0.05). BP increased the level of PPAR-α (Peroxisome proliferator-activated receptor α), and reduced the levels of SREBP-1c (sterol regulatory element binding protein-1c) and PNPLA-3 (Patatin-like phospholipase domain-containing protein 3) (
< 0.05). BP reduced hepatic inflammation and apoptosis by affecting IL-6 (interleukin 6), TNF-α (Tumor necrosis factor α), caspase-3 and Bcl-2 in NASH models. Furthermore, PPAR-α inhibitor increased the level of SREBP-1c and PNPLA-3. Therefore, BP prevents NASH progression by affecting SREBP-1c/PNPLA-3 pathway via PPAR-α.
Nonalcoholic fatty liver disease (NAFLD) is the most prevalent liver disease and is characterized by excessive fat accumulation. Kaili Sour Soup, a food typical of Guizhou Province, is believed to ...have significant health benefits. Thus, we aimed to identify and assess the impact of Kaili Sour Soup on NAFLD and its underlying mechanism using integrative proteomic and lipidomic analysis.
A high-fat diet and male Wistar rats were used to construct a NAFLD rat model. Haematoxylin and eosin (HE) and Oil Red O staining analyses were used to perform the histologic examination. Proteomic analysis was utilized to systematically identify the global protein profile in NAFLD with and without Kaili Sour Soup treatment. Western blot assays were used to verify the expression of proteins screened by proteomic analysis. Lipidomic analysis was performed to screen lipid metabolism in NAFLD with and without Kaili Sour Soup treatment.
Kaili Sour Soup alleviated high-fat diet (HFD)-induced fatty liver and had a normalizing effect on physiological and biochemical indicators of NAFLD, including body weight, liver weight, liver index, total cholesterol (TC), triglyceride (TG), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and insulin resistance level of homeostasis model assessment (HOMA-IR). Kaili Sour Soup decreased the levels of 13 proteins (Tmem44, Rnaseh2b, Gstm6l, LOC100910877, Rufy4, Slc12a2, Pcif1, P4503A1, Sult1e1, Nop53, AABR07065656.4, AABR07065789.3) that were upregulated by HFD and increased the levels of 3 proteins (Sult1c2, Sult1c2a, Snrnp48) that were downregulated by HFD. Kaili Sour Soup attenuated the HFD-induced increase in acyl carnitine (AcCa) and enhanced the HFD-induced decreases in gangliosides (GM3) and lysophosphatidylserine (LPS) in the NAFLD rat model.
Altogether, this study revealed that Kaili Sour Soup attenuated HFD-induced fatty liver and systematically identified abnormal proteins and lipids involved in the role of Kaili Sour Soup in a NAFLD rat model.
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