Impact of surgery on survival in breast cancer with bone metastases only: a SEER database retrospective analysis.

BACKGROUND: It was controversial to operate on the primary site of breast cancer (BC) with bone metastasis only. We investigated the impact of surgery on BC patients with bone metastases via a SEER database retrospective analysis. METHODS: A total of 2917 BC cases with bone metastasis, first diagnosed between 2010 and 2015 in the Surveillance, Epidemiology, and Results Database (SEER) of National Cancer Institute were selected. We assessed the effect of different surgical procedures on survival and prognosis. RESULTS: Compared with the non-surgical group, the primary tumor surgical group showed longer median survival time (χ2 = 146.023, P < 0.001), and the breast-conserving subgroup showed the highest median survival time of 70 months (χ2 = 157.117, P < 0.001). Compared with the non-surgery group, the median overall survival (OS) of primary surgery group was longer (HR = 0.525, 95%CI = 0.467-0.590, P < 0.001), and the breast-conserving subgroup showed the longest median operative OS (HR = 0.394, 95%CI = 0.325-0.478, P < 0.001). CONCLUSION: This study showed that primary surgery could improve the median survival time and OS of BC patients with bone metastasis. Moreover, under the condition of low tumor burden, breast conserving surgery was a better choice.

Favorable Prognostic Impact of Cathepsin H (CTSH) High Expression in Thyroid Carcinoma.

BACKGROUND: Presently, no study reported the function of cathepsin H (CTSH) in thyroid carcinoma (THCA). The aim of present study was to initially explore the factors affecting CTSH expression, and association between CTSH expression and survival rate in THCA. METHODS: We explored mRNA expression of CTSH in normal and BRCA tissues, and evaluated prognostic impact of CTSH expression on the overall survival of THCA patients. Then, related factors influencing CTSH mRNA expression in THCA were analyzed. Functional enrichment analysis was performed to reveal the potential function of CTSH involved in THCA. We also constructed PPI network among co-expressed genes of CTSH to determine hub genes, followed by association analysis on hub genes with CTSH. RESULTS: (1) CTSH mRNA was highly expressed in THCA compared with normal group (P<0.001). High expression of CTSH was conducive to the overall survival of THCA patients (P=0.0027). CTSH was then determined as an independent prognostic factor in THCA (P=0.024). (2) The mRNA expression of CTSH was statistically related to patient's histological type, N stage, T stage, tumor stage and sample type (all P<0.001). CTSH copy number variation and methylation also influenced its mRNA expression (all P<0.001). (3) Pathway analysis indicated that CTSH mainly participated in cancer-related pathways, such as hedgehog signaling pathway, cytokine-cytokine receptor interaction and JAK-STAT signaling pathway (all P<0.05). (4) The top 10 co-expressed genes in whole PPI network showed significant correlation with CTSH expression (all P<0.001). CONCLUSION: CTSH higher expression was observed in THCA, which caused a good prognosis of patients. CTSH expression might be regulated by multiple factors including clinical characteristic, methylation, copy number and other genes. This study demonstrated the clinical significance of CTSH in THCA, as well as revealed the potential pathway associated with CTSH involved in thyroid cancer.

Microstructure abnormity in the optic nerve of type 1 diabetic rats revealed by diffusion tensor imaging study.

Diabetic retinopathy (DR) is one of a major complication of type 1 diabetes mellitus (T1DM) and a leading cause of blindness. Evidence of animal study has shown that it is not only a microvasucular lesion of the eye, but also a neurodegeneration disease of the visual system. However, the in vivo imaging evidence of axonal degeneration in the diabetic optic nerve is scarce. Diffusion tensor imaging (DTI) technique has been proved to be an effective tool to track the integrity of the nerve fibers in the central nervous system. In this study, type 1 diabetes was induced by intraperitoneally injecting a single dose of streptozotocin (STZ) into Sprague-Dawley rats. DTI combined with histological assessments was carried out on the optic nerve to clarify the microstructural alterations underlying DTI indices changes at 4 weeks (4 w), 8 weeks (8 w) and 12 weeks (12 w) after STZ induction. The retinal changes were analyzed by pathological evaluations at 4 weeks (4 w) and 12 weeks (12 w) after STZ induction. DTI results showed significantly decreased mean diffusivity (MD) and axial diffusivity (Da) in diabetic optic nerve compared to controls at 12 w. Atrophy in diabetic nerves was monitored by high resolution T2-weighted images. Axonal degeneration without myelin loss of the optic nerve was confirmed by histological examination. Moreover, there are positive correlations between decreased diffusivities (MD and Da) in the optic nerve and reduced total axolemmal area. The diabetic rats showed intense glial activity since 4 w and thinning of the thickness in inner plexiform layer and nerve fiber layer at 12 w in the retina. In conclusion, DTI could in vivo monitor the progression of optic nerve degeneration in diabetes and the findings in our study would help supply axonal protection for DR in preclinical practice.

Genistein alleviates lead-induced neurotoxicity in vitro and in vivo: Involvement of multiple signaling pathways.

Lead (Pb) is a ubiquitous environmental and industrial pollutant. It induces neurotoxicity and cell death by disrupting the pro- and anti-oxidative balance; however, the mechanisms of its toxicity have yet to be fully understood. The soy-derived isoflavonoid, genistein (GEN), was reported to possess neuroprotective and antioxidative properties. The present study investigated the molecular mechanisms of Pb-induced neurotoxicity in vivo and in vitro, addressing the efficacy of GEN in protecting against Pb-induced toxicity. Pb exposure was associated with reduction of cell viability and cell apoptosis, concomitant with reactive oxygen species (ROS) generation in vitro, and pre-treatment with GEN markedly ameliorated the Pb-induced oxidative injury by increasing the expression of key antioxidant enzymes and the antioxidant transcription factor, nuclear factor erythroid 2 p45-related factor 2 (Nrf2). Next, PKC-α activation was found after Pb exposure in vitro and pretreatment with GEN attenuated Pb-induced ROS generation by PKC-α inhibition. MAPK-NF-κB activation triggered by Pb was also inhibited by GEN. In summary, our study establishes that GEN alleviates Pb-induced impairment in spatial memory, and reduces cell apoptosis caused by Pb exposure and GEN protects neurons from Pb-induced neurotoxicity by downstream activation of antioxidant and anti-apoptotic pathways via regulation of Nrf2 and MAPK-NF-κB signaling.

[Relationship between recurrent spontaneous abortion and the level of interferon-γ and interleukin-4 in peripheral blood and gingival crevicular fluid of patients with chronic periodontitis].

OBJECTIVE: To investigate the relationship between recurrent spontaneous abortion (RSA) and the level of interferon-γ (IFN-γ) and interleukin-4 (IL-4) in peripheral blood and gingival crevicular fluid of patients with chronic periodontitis. METHODS: Fifty pregnant women with recurrent spontaneous abortion (gestational age: 5 - 28 weeks) and 40 pregnant women (gestational age: 39 - 41 weeks) were included and their periodontal status was examined. The level of IFN-γ and IL-4 in gingival crevicular fluid and peripheral blood was detected by enzyme-linked immunosorbent assay. RESULTS: Nine RSA women and 5 in control group had periodontitis. The prevalence of periodontitis in RSA group was 18% (9/50) and 13% (5/40) in the control group (P < 0.05). The probing depth, attachment loss and bleeding index in RSA group were higher than those in the control group (P < 0.05). The level of IFN-γ was (52.98 ± 17.56) ng/L in gingival crevicular fluid of RSA group and (25.25 ± 7.93) ng/L in control group (P < 0.01). The level of IL-4 was (15.43 ± 1.77) ng/L in gingival crevicular fluid of RSA group and (19.62 ± 4.04) ng/L in control group (P < 0.01). The content of IFN-γ was (27.79 ± 3.59) ng/L in peripheral blood of RSA group and (18.39 ± 2.65) ng/L in control group (P < 0.05). The content of IL-4 was (15.88 ± 0.95) ng/L in peripheral blood of RSA group and (22.98 ± 4.30) ng/L in control group (P < 0.001). The content of cytokines in gingival crevicular fluid and peripheral blood in the same group was positively related (r > 0.8, P < 0.001). CONCLUSIONS: Pregnant women of RSA have a higher chance of getting periodontitis. The change in the level of cytokines in periodontal tissue could result in excursion of maternal intrauterine immune environment to T-helper 1 (Th1). Periodontitis was related to RSA.

Oleic acid decreases the expression of a cholesterol transport-related protein (NPC1L1) by the induction of endoplasmic reticulum stress in CaCo-2 cells

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The reported data indicate that oleic acid (OA) decreases cholesterol absorption. To explore the underlying mechanisms, the effects of OA on the expression of cholesterol transport-related proteins (NPC1L1, ABCG5/8, ACAT2, MTP) and the unfolded protein response (UPR) pathway were studied in CaCo-2 enterocytes by incubating CaCo-2 cells with taurocholate micelles or taurocholate micelles containing different concentrations of OA (0.25–1.0 mM). We show that OA effectively induces XBP1 mRNA splicing, a key component of the UPR signaling, and the expression of BiP and mature ATF6 proteins in a concentration-dependent manner, leading to the induction of endoplasmic reticulum (ER) stress and activation of the UPR. Interestingly, OA decreases NPC1L1 expression in a dose-dependent manner while it has no effects on ABCG5 and MTP mRNA level or SREBP-2, ABCG8, and ACAT2 protein level. In CaCo- (..) (AU)

Oleic acid decreases the expression of a cholesterol transport-related protein (NPC1L1) by the induction of endoplasmic reticulum stress in CaCo-2 cells.

The reported data indicate that oleic acid (OA) decreases cholesterol absorption. To explore the underlying mechanisms, the effects of OA on the expression of cholesterol transport-related proteins (NPC1L1, ABCG5/8, ACAT2, MTP) and the unfolded protein response (UPR) pathway were studied in CaCo-2 enterocytes by incubating CaCo-2 cells with taurocholate micelles or taurocholate micelles containing different concentrations of OA (0.25-1.0 mM). We show that OA effectively induces XBP1 mRNA splicing, a key component of the UPR signaling, and the expression of BiP and mature ATF6 proteins in a concentration-dependent manner, leading to the induction of endoplasmic reticulum (ER) stress and activation of the UPR. Interestingly, OA decreases NPC1L1 expression in a dose-dependent manner while it has no effects on ABCG5 and MTP mRNA level or SREBP-2, ABCG8, and ACAT2 protein level. In CaCo-2 cells treated with 1.0 mM OA, both the NPC1L1 mRNA level and the NPC1L1 protein expression in brush-border membrane fractions were decreased by 39% and 37%, respectively (P < 0.01). A dose of 1 mM dithiothreitol (DTT), a positive control for ER stress induction, also decreases NPC1L1 mRNA and protein expression by 27% and 23%, respectively (P < 0.05). Furthermore, 4-phenyl-butyric acid, an UPR inhibitor, blocks OA- and DTT-induced reduction on NPC1L1 mRNA and protein levels. The results suggest that OA down-regulates NPC1L1 mRNA and protein expression via the induction of the UPR, which may play an important role in reducing intestinal cholesterol absorption.

Cholesterol overloading leads to hepatic L02 cell damage through activation of the unfolded protein response.

Reported data indicate that cholesterol loading in the liver can cause hepatic injury. To explore the possible mechanisms of cell damage resulting from cholesterol overloading in hepatocytes, cell apoptosis, the unfolded protein response (UPR) and the correlation between them were assessed in the cholesterol-overloaded normal human hepatic cell line L02. L02 cells were incubated with 200 microg/ ml of low density lipoprotein (LDL) for 24 h with or without 20 microg/ml 58035, an inhibitor of acyl-CoA:cholesterol acyltransferase (ACAT). In the LDL+58035 group, the intracellular cholesterol level was dramatically increased, which was measured by an enzymatic combined high performance liquid chromatography assay. Expression of immunoglobulin-binding protein, X-box binding protein 1, activating transcription factor 6, activating transcription factor 4, CCAAT/enhancer-binding protein homologous protein-10, markers of endoplasmic reticulum stress (ERS)/ UPR, were up-regulated as determined using reverse transcription-polymerase chain reaction (RT-PCR) or Western blot analysis. The rate of cell apoptic death increased 21.3+/-2.4%. Meanwhile, the active caspase-3 protein expression was increased 8.4-fold compared to the active caspase-3 protein expression in the controls. Furthermore, 4-phenylbutyric acid, an inhibitor of UPR, partly reduced cell apoptosis and activation of caspase-3. This study suggests that cholesterol overloading in hepatic L02 cells induces ERS and activates the UPR which, in part, leads to the apoptotic damage of cells.