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Many features of deadly human cervical cancers (HCCs) still require elucidation. Among HCC-derived cell lines, here we used the C4-I one since its quantitative gene expression pattern most closely mimics invasive HCCs, including protein kinase-Cζ (PKCζ) overexpression. Via proteomic, bioinformatic, and biochemical approaches we identified 31 and 33 proteins co-immunoprecipitating with PKCζ from nuclear membranes (NMs) of, respectively, untreated or VP-16-exposed C4-I cells. Such proteins belonged to eight functional groups, whose compositions and relative sizes changed with either context. Of the 56 proteins identified, only eight were shared between the two subproteomes, including Bcl10. Surprisingly, proteins known to associate with Bcl10, like Carma1/3 and Malt1, in so-called CBM signalosomes were absent. Notably, in VP-16-treated C4-I cells, PKCζ•Bcl10 complexes increasingly accrued at NMs, where PKCζ phosphorylated Bcl10, as PKCζ also did in vitro and in cell-free systems, both processes being thwarted by interfering RNA (iRNA) PKCζ depletion. Caspase-3 was associated with PKCζ•Bcl10 complexes and proteolyzed PKCζ leading to its inactivation/destruction; both events were prevented by Bcl10 iRNA suppression. Thus, PKCζ's molecular interactions and functional roles changed strikingly according to the untreated or apoptogen-treated cells context, and by complexing with Bcl10, PKCζ surprisingly favored its own demise, which suggests both proteins as HCCs therapeutic targets.

PURPOSE. To determine if sleep deprivation induces dry eye through altering peroxisome proliferator-activated receptor alpha (PPARa) expression in mice. METHODS. The ''stick over water'' sleep deprivation-induced dry eye (SDE) model evaluated PPARa involvement in inducing this condition. Scanning electron microscopy (SEM) examined microvilli morphology in superficial corneal epithelial cells (SCECs) in SDE and PPARa À/À mice. Quantitative RT-PCR (qRT-PCR) and Western blot (WB) or immunostaining evaluated PPARa, carnitine palmitoyl transferase 1a (CPT1a), and transient receptor potential vanilloid 6 (TRPV6) expression levels and Ezrin phosphorylation status. Hematoxylin-eosin and Oil Red O staining characterized meibomian gland morphology and corneal lipid accumulation, respectively. Phenol red cotton threads measured tear production. In cultured corneal epithelial sheets, qRT-PCR, WB, and SEM determined the individual effects of fenofibrate and MK886 (PPARa agonist and antagonist, respectively) on PPARa, TRPV6 expression, and SCEC microvilli morphology. RESULTS. Corneal epithelial lipid accumulation, microvilli morphologic changes, and decreased tear production were associated with marked declines in PPARa, CPT1a, and TRPV6 expression levels as well as Ezrin phosphorylation status, whereas meibomian glands were unaltered in SDE mice. These effects of SDE mice mimicked those in their nonstressed PPARa À/À counterpart. Topical application of fenofibrate reversed these effects in SDE corneas. In cultured corneal epithelial sheets, fenofibrate increased PPARa and TRPV6 gene and protein expression levels and restored microvilli morphology, whereas MK886 attenuated these changes. CONCLUSIONS. Sleep deprivation induces dry eye through abnormal SCEC microvilli morphology, which is caused by sequential downregulation of PPARa, TRPV6 expression, and Ezrin phosphorylation status in mice.

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Purpose: To detect lung metastases, we conducted a retrospective study to improve patient prognosis.Methods: Hypertension patients with ocular metastases (OM group; n = 58) and without metastases (NM group; n = 1,217) were selected from individuals with lung cancer admitted to our hospital from April 2005 to October 2019. The clinical characteristics were compared by Student's t-test and chi-square test. Independent risk factors were identified by binary logistic regression, and their diagnostic value evaluated by receiver operating characteristic curve analysis.Results: Age and sex did not differ significantly between OM and NM groups; There were significant differences in pathological type and treatment. Adenocarcinoma was the main pathological type in the OM group (67.24%), while squamous cell carcinoma was the largest proportion (46.43%) in the NM group, followed by adenocarcinoma (34.10%). The OM group were treated with chemotherapy (55.17%), while the NM group received both chemotherapy (39.93%) and surgical treatment (37.06%). Significant differences were detected in the concentrations of cancer antigen (CA)−125, CA-199, CA-153, alpha fetoprotein (AFP), carcinoembryonic antigen (CEA), cytokeratin fraction 21-1 (CYFRA21-1), total prostate-specific antigen, alkaline phosphatase, and hemoglobin (Student's t-test). Binary logistic regression analysis indicated that CA-199, CA-153, AFP, CEA, and CYRFA21-1 were independent risk factors for lung cancer metastasis. AFP (98.3%) and CEA (89.3%) exhibited the highest sensitivity and specificity, respectively, while CYRFA21-1 had the highest area under the ROC curve value (0.875), with sensitivity and specificity values of 77.6 and 87.0%, respectively. Hence, CYFRA21-1 had the best diagnostic value.

Purpose In gestational diabetes (GDM), abnormalities occur not only in glucose metabolism, but also in lipid metabolism. Adiponectin (ADPN) plays an important role in the regulation of lipid metabolism. In this paper, the role and mechanism of ADPN in GDM are discussed. Methods GDM model was formed in pregnant mice induced by high-fat diet and streptozotocin, and blood glucose level was detected after ADPN treatment. The levels of TG, TC, HDL-C, and LDL-C in blood lipid of mice were detected by biochemical apparatus. HE staining was used to detect the placenta damage in mice. The expression of oxidative stressrelated indexes in placental tissues was also detected by ELISA. Placental iron deposition was detected by Prussian blue staining. Redox capacity of placental tissue was detected by ELISA. Western blot was used to detect the expression of ferroptosis-related proteins in placental tissues. The expression of ADPN in placenta and peripheral blood was detected by ELISA, and the expression of ADPNR, downstream CPT-1, and GLUT4 of placenta were detected by RT-qPCR and western blot. Subsequently, trophoblast cells were induced by palmitic acid and glucose, and the cell activity was detected by CCK-8. The results in animal experiments were verified in cell experiments by RT-qPCR, western blot, and fluorescence labeling of iron ions. Finally, ADPN and CPT-1 inhibitor PM were given to trophoblast cells to further explore the mechanism.Results ADPN inhibited blood glucose and lipid levels in GDM mice. ADPN inhibited oxidation/peroxide imbalanceinduced ferroptosis in placental tissues of GDM mice. ADPN inhibited the expression of CPT-1 and GLUT4 in placental tissues of GDM mice. This result was also confirmed in cell experiments, and this process may be achieved by regulating CPT-1. Conclusions ADPN ameliorated placental injury in GDM by correcting fatty acid oxidation/peroxide imbalance-induced ferroptosis via restoration of CPT-1 activity.

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