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Alcoholic liver disease (ALD) is characterized by hepatocyte damage, inflammatory cell activation, and increased intestinal permeability leading to the clinical manifestations of alcoholic hepatitis. Selected members of the family of microRNAs (miRNAs) are affected by alcohol, resulting in an abnormal miRNA profile in the liver and circulation in ALD. Increasing evidence suggests that miRNAs that regulate inflammation, lipid metabolism and promote cancer are affected by excessive alcohol administration in mouse models of ALD. This communication highlights recent findings in miRNA expression and functions as they relate to the pathogenesis of ALD. The cell‐specific distribution of miRNAs, as well as the significance of circulating extracellular miRNAs, is discussed as potential biomarkers. Finally, the prospects of miRNA‐based therapies are evaluated in ALD.

Alcoholic liver disease (ALD) is characterized by hepatocyte damage, inflammatory cell activation, and increased intestinal permeability leading to the clinical manifestations of alcoholic hepatitis. Selected members of the family of microRNAs (miRNAs) are affected by alcohol, resulting in an abnormal miRNA profile in the liver and circulation in ALD. Increasing evidence suggests that miRNAs that regulate inflammation, lipid metabolism and promote cancer are affected by excessive alcohol administration in mouse models of ALD. This communication highlights recent findings in miRNA expression and functions as they relate to the pathogenesis of ALD. The cell‐specific distribution of miRNAs, as well as the significance of circulating extracellular miRNAs, is discussed as potential biomarkers. Finally, the prospects of miRNA‐based therapies are evaluated in ALD.

Percutaneous ethanol injection (PEI) was applied to 162 lesions in 133 patients with hepatocellular carcinomas (HCC) 3 cm or less in diameter (small HCC) between Aug. 1983 and Apr. 1992. Histological findings in resected specimen for which PEI had previously been performed before surgery showed that PEI could completely necrotize an HCC of 32 mm in diameter. The antitumoral effect by PEI could correctly be evaluated by enhanced CT. The 1-, 3-, 5- and 7-year survival rates after PEI calculated by the Kaplan-Meier method were 95.9%, 60.5%, 36.9% and 21.7%, respectively. The survival rate of post-PEI patients with I or II grade in clinical stage was better than that of those with III. Recurrence occurred in hepatic areas different from the original lesion in 27.8% in one year and 63.6% in three years after PEI, rates quite similar to those of recurrence after surgical resection for HCCs of 3 cm or less in diameter. For such recurrence, PEI alone was then repeated in half of the 76 patients. Complications caused by PEI were not serious and did not necessitate intensive care. Because of its anti-tumor therapeutic effect and minimal damage to the liver, PEI might be considered a viable alternative to surgery for most patients with small HCC.

Percutaneous ethanol injection (PEI) was applied to 162 lesions in 133 patients with hepatocellular carcinomas (HCC) 3 cm or less in diameter (small HCC) between Aug. 1983 and Apr. 1992. Histological findings in resected specimen for which PEI had previously been performed before surgery showed that PEI could completely necrotize an HCC of 32 mm in diameter. The antitumoral effect by PEI could correctly be evaluated by enhanced CT. The 1-, 3-, 5- and 7-year survival rates after PEI calculated by the Kaplan-Meier method were 95.9%, 60.5%, 36.9% and 21.7%, respectively. The survival rate of post-PEI patients with I or II grade in clinical stage was better than that of those with III. Recurrence occurred in hepatic areas different from the original lesion in 27.8% in one year and 63.6% in three years after PEI, rates quite similar to those of recurrence after surgical resection for HCCs of 3 cm or less in diameter. For such recurrence, PEI alone was then repeated in half of the 76 patients. Complications caused by PEI were not serious and did not necessitate intensive care. Because of its anti-tumor therapeutic effect and minimal damage to the liver, PEI might be considered a viable alternative to surgery for most patients with small HCC.

“Low expectation of success” is proposed as a factor in relation to problem behavior in the comprehensive theoretical model of problem behavior (CTMPB). Based on the framework of CTMPB, this study aimed to further examine the association between confidence in the future (including parental confidence in the adolescent future and adolescent self-confidence in the future in this study) and problem behavior. A nationwide representative sample data from the China Education Panel Survey (CEPS) were used in this study. A total of 8328 middle school students and their parents were included. Among the students, 4081 (49.0%) were boys, the mean age was 14.53 years (SD = 0.70); among the parents, 3908 (46.9%) were male, the mean age was 41.15 years (SD = 5.14). The results reveal that parental confidence in adolescent future (PCAF) can play a role in adolescent problem behavior through adolescent perceived parental confidence in adolescent future (APPCAF) and adolescent self-confidence in the future (ASF). Low levels of both PCAF and ASF are vulnerability risk factors in adolescent problem behavior. Lowering PCAF and ASF might increase the likelihood of engaging in problem behavior. However, this study was based on cross-sectional data only and is required to be supported by further experimental or longitudinal studies.

“Low expectation of success” is proposed as a factor in relation to problem behavior in the comprehensive theoretical model of problem behavior (CTMPB). Based on the framework of CTMPB, this study aimed to further examine the association between confidence in the future (including parental confidence in the adolescent future and adolescent self-confidence in the future in this study) and problem behavior. A nationwide representative sample data from the China Education Panel Survey (CEPS) were used in this study. A total of 8328 middle school students and their parents were included. Among the students, 4081 (49.0%) were boys, the mean age was 14.53 years (SD = 0.70); among the parents, 3908 (46.9%) were male, the mean age was 41.15 years (SD = 5.14). The results reveal that parental confidence in adolescent future (PCAF) can play a role in adolescent problem behavior through adolescent perceived parental confidence in adolescent future (APPCAF) and adolescent self-confidence in the future (ASF). Low levels of both PCAF and ASF are vulnerability risk factors in adolescent problem behavior. Lowering PCAF and ASF might increase the likelihood of engaging in problem behavior. However, this study was based on cross-sectional data only and is required to be supported by further experimental or longitudinal studies.

To examine the combined hepatotoxic and nephrotoxic effects of cadmium and ethanol, rats maintained on an ethanol containing liquid diet (5% w/w) were given cadmium either acutely (3 x 1 mg/kg IP) or subacutely (about 14 mg/kg/day PO for 6 weeks). Parameters tested were cadmium, zinc and copper contents of blood and various organs, metallothionein (MT) contents, polysome profile of liver and kidneys, serum SDH and GPT levels and creatinine clearance. Ethanol reduced the hepatic MT contents without altering the polysome profile and the zinc and copper contents. Cadmium on the other hand raised the MT contents in liver and kidneys. This effect of cadmium predominated in the combined treatment. Morphological examination and functional tests (SDH, GPT, creatinine clearance) indicate that cadmium does not enhance the toxic effects of ethanol, and vice versa.

To examine the combined hepatotoxic and nephrotoxic effects of cadmium and ethanol, rats maintained on an ethanol containing liquid diet (5% w/w) were given cadmium either acutely (3 x 1 mg/kg IP) or subacutely (about 14 mg/kg/day PO for 6 weeks). Parameters tested were cadmium, zinc and copper contents of blood and various organs, metallothionein (MT) contents, polysome profile of liver and kidneys, serum SDH and GPT levels and creatinine clearance. Ethanol reduced the hepatic MT contents without altering the polysome profile and the zinc and copper contents. Cadmium on the other hand raised the MT contents in liver and kidneys. This effect of cadmium predominated in the combined treatment. Morphological examination and functional tests (SDH, GPT, creatinine clearance) indicate that cadmium does not enhance the toxic effects of ethanol, and vice versa.

Humans are exposed to complex mixtures of phthalates. Gestational exposure to phthalates has been linked to preeclampsia and preterm birth through potential pathways such as endocrine disruption, oxidative stress, and inflammation. Eicosanoids are bioactive signaling lipids that are related to a variety of homeostatic and inflammatory processes. We investigated associations between urinary phthalates and their mixtures with plasma eicosanoid levels during pregnancy using the PROTECT cohort in Puerto Rico (N = 655). After adjusting for covariates, we estimated pair-wise associations between the geometric mean of individual phthalate metabolite concentrations across pregnancy and eicosanoid biomarkers using multivariable linear regression. We used bootstrapping of adaptive elastic net regression (adENET) to evaluate phthalate mixtures associated with eicosanoids and subsequently create environmental risk scores (ERS) to represent weighted sums of phthalate exposure for each individual. After adjusting for false-discovery, in single-pollutant analysis, 14 of 20 phthalate metabolites or parent compound indices showed significant and primarily negative associations with multiple eicosanoids. In our mixture analysis, associations with several metabolites of low molecular weight phthalates - DEP, DBP, and DIBP - became prominent. Additionally, MEHHTP and MECPTP, metabolites of a new phthalate replacement, DEHTP, were selected as important predictors for determining the concentrations of multiple eicosanoids from different pathway groups. A unit increase in phthalate ERS derived from bootstrapping of adENET was positively associated with several eicosanoids mainly from Cytochrome P450 pathway. For example, an increase in ERS was associated with 11(S)-HETE (β = 1.6, 95% CI: 0.020, 3.180), (±)11,12-DHET (β = 2.045, 95% CI: 0.250, 3.840), 20(S)-HETE (β = 0.813, 95% CI: 0.147, 1.479), and 9 s-HODE (β = 2.381, 95% CI: 0.657, 4.104). Gestational exposure to phthalates and phthalate mixtures were associated with eicosanoid levels during pregnancy. Results from the mixture analyses underscore the complexity of physiological impacts of phthalate exposure and call for further in-depth studies to examine these relationships.