Therapeutic potential of amitriptyline for paraquat-induced pulmonary fibrosis: Involvement of caveolin-1-mediated anti-epithelial-mesenchymal transition and inhibition of apoptosis.

OBJECTIVE: Treatment of pulmonary fibrosis caused by paraquat (PQ) poisoning remains problematic. Amitriptyline (AMT) has multiple pharmacological effects. Here we investigated the anti-fibrotic effect of AMT on PQ-induced pulmonary fibrosis and its possible mechanism. METHODS: C57BL/6 mice were randomly divided into control, PQ, PQ + AMT and AMT groups. Histopathology of the lungs, blood gas analysis, and levels of hydroxyproline (HYP), transforming growth factor ß1 (TGF-ß1) and interleukin 17 (IL-17) were measured. The siRNA transfection inhibited caveolin-1 in A549 cells, which induced epithelial-mesenchymal transition (EMT) by PQ and followed intervention with AMT. E-cadherin, N-cadherin, α-smooth muscle actin (α-SMA) and caveolin-1 were studied by immunohistochemistry and western blot analysis. The apoptosis rate was measured by flow cytometry. RESULTS: Compared with the PQ group, the PQ + AMT group displayed mild pathological changes in pulmonary fibrosis, lower HYP, IL-17 and TGF- ß1 levels in lung, but high TGF- ß1 in serum. Levels of N-cadherin and α-SMA in the lungs were significantly decreased, but caveolin-1 was increased, while SaO2 and PaO2 levels were higher. Compared with the PQ group, the apoptosis rate, N-cadherin and α-SMA levels in A549 cells were significantly decreased after PQ treatment and high dose AMT intervention (p < 0.01). The expressions of E-cadherin, N-cadherin and α-SMA in the PQ-induced cells transfected with caveolin-1 siRNA or siControl RNA were significantly different (p < 0.01), but the apoptosis rate was unaltered. CONCLUSION: AMT inhibited PQ-induced EMT in A549 cells and improved lung histopathology and oxygenation in mice by up-regulating caveolin-1.

Subtypes of Chinese Shidu parents' (parents who have lost their only child) depressive symptoms and their relationships with resilience and coping styles.

We aimed to examine the subtype classification characteristics of depressive symptoms in Shidu parents (SDPs, parents who have lost their only child) and their associations with resilience and coping styles. The sample comprised 182 SDPs (Mean age = 59.93 ± 7.41 years, 61.5% females). Latent profile analysis and logistic regression analysis were used to analyze the data. Three subgroups of depressive symptoms in SDPs were identified: the depression and pessimism group (38.4%), the low depression symptoms group (30.8%), and the well-adapted group (30.8%). The low depression symptoms group had a lower education level and higher family monthly income than the depression and pessimism group. The low depression symptoms group and the well-adapted group scored significantly higher in resilience, and lower in negative coping style than the depression and pessimism group. The results highlighted that target intervention is needed for SDPs with high education levels, low family monthly income, high negative coping style, and low resilience in the depression and pessimism group.

Measurement Invariance and Intergenerational Parallelism of General Self-Efficacy in Adolescent and Parent Dyads.

General self-efficacy refers to global beliefs about one's capabilities across a variety of tasks or conditions. It is regarded as an important, relatively stable, motivational trait, and is associated with positive outcomes in a wide range of domains. The general self-efficacy scale (GSE) is the most commonly used measure to evaluate general self-efficacy among adults and youths. This study aimed to examine the measurement invariance of the GSE across age groups among adolescent and parent dyads, and to investigate the intergenerational parallelism of general self-efficacy and the moderating roles of parents' gender and family socioeconomic status (SES). Participants were 807 adolescent/parent dyads. Multi-group confirmatory factor analysis revealed that full metric and scalar measurement invariance held. Regression analysis showed that parents' self-efficacy significantly predicted their children's self-efficacy (ß = 0.232, p < 0.001). Multiple regression analysis indicated family SES played a moderating role (ß = 0.066, p < 0.001), although parents' gender did not (ß = -0.053, p = 0.288). The results demonstrated the GSE's measurement invariance across age, and further supported use of the GSE among adults and adolescents. Moreover, our findings provided evidence for the presence of this kind of intergenerational parallelism and the moderating role of family SES.

Fetal outcomes after intentional ingestion of paraquat: A case report.

RATIONALE: Despite the fact that treatment of paraquat poisoning in pregnant women and their fetuses is challenging and raises ethical issues, it is rarely reported in the literature. We report the case of a pregnant woman who took paraquat intentionally. PATIENT CONCERNS: A 36-year-old woman at 38 weeks gestational age, in an apparent suicide attempt, drank 1 mouthful (about 20 ml) of paraquat solution. Ten hours later, her urine dithionate test showed light blue color with a plasma paraquat concentration of 0.547 µg/ml. Six hours after admission, a male infant, whose plasma paraquat concentration was 0.761 µg/ml, together with 0.673 µg/ml in the amniotic fluid measured by high-performance liquid chromatography, was delivered but the woman's lung, liver, and kidney function declined rapidly. DIAGNOSIS: INTERVENTIONS:: Because of placenta previa and multiple organ failure, emergency cesarean section, and panhysterectomy were performed for the pregnant woman. Intravenous injection of antibiotic to prevent infection and dexamethasone 30 mg once a day were administered. Mechanical ventilation was performed for the infant and meropenem and penicillin injection was administered. OUTCOMES: The infant died 33 hours after birth while the mother died on the 3rd day after ingestion. LESSONS: Paraquat can enter the fetus through the placenta and the amniotic fluid via fluid exchange. The pathological changes of fetal organs may relate to gestational age, and the prognosis was very poor in both the mother and the fetus.

TLR4/NF-κB signaling pathway gene single nucleotide polymorphisms alter gene expression levels and affect ARDS occurrence and prognosis outcomes.

BACKGROUND: To study the occurrence and prognosis of acute respiratory distress syndrome (ARDS) using single nucleotide polymorphisms (SNPs) of TNF-α rs1800629, IL-6 rs1800796, and MyD88 rs7744 loci in the TLR4/NF-κB pathway. METHODS: Genotypes were analyzed for TNF-α rs1800629, IL-6 rs1800796, and MyD88 rs7744 loci. Plasma TNF-α and IL-6 levels and MyD88 mRNA expression in peripheral blood mononuclear cells (PBMCs) of 300 ARDS patients and 300 non-ARDS patients (control group) were examined. The patients were followed up for 60 days, and the prognosis outcome was recorded. RESULTS: The TNF-α rs1800629 locus A allele and the IL-6 rs1800796 locus G allele were found to be risk factors for ARDS (adjusted OR = 1.452, 95% CI: 1.211-1.689, P < .001 and adjusted OR = 1.205, 95% CI: 1.058-1.358, P = .005, respectively). The G allele at MyD88 rs7744 locus was a protective factor against ARDS (adjusted OR = 0.748, 95% CI: 0.631-0.876, P < .001). Compared with the other groups, homozygotes for TNF-α rs1800629, IL-6 rs1800796, and MyD88 rs7744 loci had higher expression levels, of which homozygotes for TNF-α rs1800629 and IL-6 rs1800796 loci had lower 60-day survival rates, while MyD88 rs7744 locus homozygotes had a higher 60-day survival rate. CONCLUSION: The effect of TNF-α rs1800629, IL-6 rs1800796, and MyD88 rs7744 SNPs on gene expression level is a likely cause of ARDS occurrence and poor prognosis.

Correlations of IL-17 and NF-κB gene polymorphisms with susceptibility and prognosis in acute respiratory distress syndrome in a chinese population.

The present study was performed to investigate the association between interleukin-17 (IL-17) and nuclear factor κB (NF-κB) gene polymorphisms and the risk and prognosis of acute respiratory distress syndrome (ARDS) in a Chinese population. A total of 210 Chinese patients with ARDS were selected as the study group, 210 individuals who were identified as at-risk patients but did not meet criteria for ARDS were recruited as the control group. Three single nucleotide polymorphisms (SNPs) of IL-17, including rs763780 (A>G), rs2275913 (G>A), rs8193036 (C>T) and NF-κB1 gene rs3774934 (G>A) loci were examined by Sanger sequencing technique in the peripheral blood of all subjects. Patients were followed for 30-day survival. The IL-17 rs763780 and NF-κB1 rs3774934 SNPs had no impact on ARDS risk and prognosis of ARDS (P>0.05). Compared with individuals carrying the wild-type GG genotype of rs2275913 at IL-17, the AA-homozygous and GA- heterozygous individuals were protected from the development of ARDS. Consistently, a decreased 30-day mortality risk was found among A-allele carriers of rs2275913 at IL-17 (p<0.05). For IL-17 rs8193036 SNP, the homozygote TT genotype and heterozygote CT genotypes were associated with increased ARDS susceptibility and 30-day mortality risk (P<0.05). Besides, decreased IL-17 levels were found in A-allele carriers of IL-17 rs2275913, whereas individuals carrying T-allele of IL-17 rs8193036 were found to have significantly increased levels of IL-17 (P<0.05). Our results suggested that two functional polymorphisms of IL-17, rs2275913 and rs8193036 were associated with ARDS risk and prognosis, indicating that the two genetic variants might act as possible markers for the prediction of ARDS risk and development.

Relationship between CIP2A expression, and prognosis and MDR-related proteins in patients with advanced gastric cancer.

CIP2A is highly expressed in a variety of malignancies. We determined the expression and clinical significance of CIP2A in patients with advanced gastric cancer. CIP2A protein was expressed in 25 of 37 cancer tissue specimens. There was no correlation between CIP2A and PGP, GST-π, Topo-II, and LRP expression. Survival analysis showed significant differences between the survival rate of the CIP2A protein-positive and -negative groups (χ(2)=4.509, P=0.034), but the degree of positive expression was unrelated to survival time (χ(2)=4.639, P=0.098). CIP2A expression may have no prospective value for optimizing chemotherapy regimens, but it can be an indicator for patient prognosis.