The study was performed to analyze the proteomic profiling of doxorubicin-treated H9c2 cardiomyocytes in order to identify novel protein biomarkers associated with doxorubicin-induced cardiomyopathy. The protein profiling of H9c2 cells in response to doxorubicin at an apoptosis-induced concentration of 0.5 μM were compared using iTRAQ analysis. Western-blot analysis was used to confirm differentially expressed proteins identified in the proteomic study. A total of 22 differently expressed proteins were identified in doxorubicin-treated H9c2 cells including 15 up-regulated and 7 down-regulated proteins. Gene Ontology (GO) analysis revealed that 10 altered proteins were enriched in the process of apoptosis. We further validated the expression of cathepsin B and its possible regulator nuclear factor kappa B (NF-κB) in H9c2 cells were increased during doxorubicin treatment using Western-blots. Differentially expressed proteins might provide clues to clarify novel mechanisms underlying doxorubicin-induced cardiomyopathy. Our results also suggest that increased cathepsin B expression might be associated with NF-κB up-regulation, and the exact mechanisms need to be clarified.
This community-based cross-sectional study examined alcohol use and HIV risks among a sample of predominantly ethnic males in Yunnan Province, China. Information about alcohol use, sexual behavior, sex after drinking, and HIV infection was collected using face-to-face interviews and blood testing. Out of 497 potential male participants, 382 males agreed to participate in this study. Of these males, 70% were ethnic minorities, 74.1% were currently married, 95.5% were sexually experienced, 27.5% had used drugs, and 6% were HIV-infected. Over 81% were current drinkers and 55.7% started drinking before the age of 18. Among current drinkers, 44.5% drank daily and 31.9% had drunk heavily in the past 30 days. Baijiu (a Chinese liquor distilled from sorghum with an ethanol content of at least 40%) was the preferred drink of choice. Excessive alcohol use was associated with being an ethnic Jingpo (OR = 1.96), being a smoker (OR = 2.09) and having multiple lifetime sex partners (OR = 1.55). Over 21% reported having ever engaged in sex after drinking. Those who were aged 26 to 35 (OR = 3.80), started drinking before age 18 (OR = 2.14), who were heavy drinkers (OR = 1.99), or who had ever used drugs (OR = 2.00) were more likely to have ever engaged in sex after drinking. Health education programs for alcohol abuse and unwanted outcomes, particularly the risk of HIV, are urgently needed for ethnic males in Yunnan.
Disposal of sputum from patients with pulmonary tuberculosis (TB) who are treated at home is an important aspect of preventing the spread of TB. However, few studies have examined disposal of sputum by patients with TB who are treated at home. Patients with pulmonary TB who are treated at home were surveyed regarding sputum handling and supervision. A cross-sectional survey of a representative sample of patients with pulmonary TB who are treated at home was conducted in Shandong Province. Participants were individuals with TB who had been registered with a local agency responsible for TB control. Participants completed a questionnaire with both qualitative and quantitative questions. How sputum was handled was determined and factors associated with sputum disposal were analyzed using a non-parametric test, logistic regression, and content analysis. Responses were received from 720 participants. Patients expectorated sputum 4.56 ± 10.367 times a day, and 68.6% of patients responded that they correctly disposed of their sputum. Supervision as part of TB control focused on the efforts of health agencies and paid little attention to waste management by patients. A non-parametric test showed that sputum disposal was significantly associated with gender, age, education, sputum smear results, attitudes toward waste management, and attitudes toward supervision (all p < 0.05). Logistic regression analysis showed that gender (OR = 0.482, 95% CI: 0.329-0.704), sputum smear results (OR = 1.300, 95% CI: 1.037-1.629), and level of education (OR = 0.685, 95% CI: 0.528-0.889) were associated with receipt of TB health education (all p < 0.05). Sputum handling by and supervision of patients with pulmonary TB who are treated at home is severely wanting. From a policy perspective, special attention should be given to the definition, details, and methods of supervision of waste management by patients with TB to give them relevant health education and enhance their willingness to be supervised. A financial incentive should be provided to health workers supervising management of TB-related waste.
MLS128 is an anti-carbohydrate monoclonal antibody (mAb) that binds three or two consecutive Tn-antigens. MLS128 bound 110-210 kDa glycoproteins (GPs) and inhibited the growth of LS180 and HT29 colon and MCF-7 breast cancer cells. One possible mechanism of MLS128's inhibition of growth may be via insulin-like growth factor-I receptor (IGF-IR) down-regulation (Morita et al. BioSci Trends. 2009; 3:32-37). The current study examined the role of IGF-IR signaling in the growth of colon cancer cells and its possible interaction with MLS128-induced inhibition of cell growth in LS180, LS174T, and HT29 human colon cancer cells treated with MLS128 or anti-IGF-IR 1H7. Both MLS128 and 1H7 treatment significantly inhibited the growth of colon cancer cells. All three colon cancer cell lines expressed IGF-IR. Their growth was in part IGF-I dependent, but inhibition by MLS128 was independent of IGF-IR signaling. All of the colon cancer cell lines expressed an 110 kDa GP for MLS128 binding, but MCF-7 cells expressed MLS128-detectable bands with higher molecular masses. 1H7 treatments caused down-regulation of IGF-IR but did not affect 110 kDa GP levels. MLS128 treatments resulted in partial disappearance of the 110 kDa band but did not affect IGF-IR levels. Western blotting analyses of colon and breast cancer cell lysates revealed that colon and breast cancer cells differed significantly in patterns of expression of growth-related molecules while colon cancer cells were similar but distinctive. In conclusion, MLS128 inhibited the growth of colon cancer cells by binding to the 110 kDa GP receptor. Inhibition of growth by MLS128 did not appear to affect IGF-IR signaling and instead only affected other growth signaling pathways.
To explore the effect of mild hypothermia (35ºC) on breast cancer cells adhesion to vascular endothelial cells, a parallel plant flow chamber was used to observe the adhesion of human breast cancer cells MDA-MB-231 to endothelial cells Eahy926 under physiological flow at 35ºC and 37ºC, as well as the role of intercellular adhesion molecule 1 (ICAM-1) in this process. Further, the effect of mild hypothermia (35ºC) on migration of MDA-MB-231 was also studied. Our results show that mild hypothermia can inhibit the adhesion of tumor cells to endothelial cells and ICAM-1 plays an important role in this process. However, mild hypothermia inhibits breast cancer cell adhesion in a way independent on the change of ICAM-1 expression under our experimental conditions. Mild hypothermia can weaken the chemotaxis of breast cancer cells while it has no obvious effect on unidirectonal migration capacity. These results suggest that mild hypothermia could be used as a potentially adjunct treatment combined with surgery to decrease tumor cell adhesion and migration.
Our previous study demonstrated that the peroxisome proliferator-activated receptor (PPAR) γ agonist, pioglitazone (PIO), may be cardioprotective against ischemia-reperfusion injury; however, modulation of p42/p44 extracellular signal-regulated kinases (ERK1/2) and cyclooxygenase (COX)-2 by PIO in the myocardium with respect to ischemiareperfusion (I/R) is only partially understood. We determined if PIO reduces I/R-induced apoptosis in cardiomyocytes, and whether or not this protective effect is due to modulation of ERK1/2 and COX-2. Sixty male Sprague-Dawley rats were randomized and assigned GW9662; and I/R + PD98059. Rats underwent 30 min of myocardial ischemia and 120 min of reperfusion, and then hearts were harvested for analysis. RT-PCR and Western blotting were performed to detect expression of ERK1/2 and COX-2. The number of TUNEL-positive cardiomyocytes and NEC in the PIO groups (5 and 10 mg•kg–1•day–1) was much lower than the I/R group. The cardioprotective effect of PIO was abrogated by PD98059 and GW9662. Phosphorylation of ERK1/2 and COX-2 was increased in the PIO-treated group compared with the I/R group. GW9662 reversed the expression of ERK1/2 and COX 2 phosphorylation induced by PIO. PD98059 reversed the expression of COX-2 induced by PIO. PIO was shown to be cardioprotective in an I/R injury model in rats via inhibition of cardiomyocyte apoptosis. PIO limited the infarct size in a PPAR-γ-dependent manner. These results show that PIO triggers the MAPK signaling pathway involving ERK1/2 using COX-2 as the downstream target.
Current patches made from macromolecular compounds or composix for tension-free herniorrhaphy are still unsatisfactory in biocompatibility. The ideal patch should be a biological patch with good biocompatibility. Herein allograft patches modified by tissue engineering were used in tension-free herniorrhaphy of swines. Tough membrane tissues from swine were modified with patented tissue engineering techniques to develop allograft patches for tension-free herniorrhaphy. Histological, and physical tests of the allograft patch were performed subsequently, which revealed that the allograft patch was sufficient and satisfactory for tension-free herniorrhaphy. The allograft patches were next used in tension-free herniorrhaphy of abdominal external hernia models of swines and and tumor necrosis factor α (TNF-α) were determined preoperatively and postoperatively. Local pathological changes were recorded postoperatively in swines. In vivo application of the allograft patches revealed that there were no significant serous cellular immune responses in swines, and inflammation induced by allograft patches was significantly lower compared to polypropylene patches, the allograft patches gradually degenerated and new collagen fibers appeared. Abdominal external hernias were cured with allograft patches and without relapse. The modified allograft patch with satisfactory biocompatibility was eligible and sufficient in tension-free herniorrhaphy of swine. Clinical trials should be performed for further evaluation of the allograft patch.
Hypertension ranks among the most important disease challenges on a global scale. Here, a novel hypothesis is presented which implicates angiotensinogen, i.e. the precursor protein for the hypertensive peptide angiotensin II, as a key culprit in the pathogenesis of hypertension. This hypothesis more precisely entails that intracellular angiotensinogen binds and thereby inactivates the retinoblastoma tumor suppressor protein (RB), consequently leading to an inflammatory and hyperproliferative state that significantly contributes to pathologically increasing blood pressure. Accordingly, a conceivable antihypertensive strategy could comprise RBderived compounds that neutralize angiotensinogen.