Older people in rural China have a lower risk of depression than those in Western countries. Low socioeconomic status showed a "dose-response" relationship with depression, and social supports were much more common, which were protective for depression. Further exploration of Chinese culture and tradition may yield universal insights into preventive factors for depression in older people.
The conversion of life-threatening viruses into live but avirulent vaccines represents a revolution in vaccinology. In a proof-of-principle study, we expanded the genetic code of the genome of influenza A virus via a transgenic cell line containing orthogonal translation machinery. This generated premature termination codon (PTC)-harboring viruses that exerted full infectivity but were replication-incompetent in conventional cells. Genome-wide optimization of the sites for incorporation of multiple PTCs resulted in highly reproductive and genetically stable progeny viruses in transgenic cells. In mouse, ferret, and guinea pig models, vaccination with PTC viruses elicited robust humoral, mucosal, and T cell-mediated immunity against antigenically distinct influenza viruses and even neutralized existing infecting strains. The methods presented here may become a general approach for generating live virus vaccines that can be adapted to almost any virus.
BackgroundAlthough an abundance of evidence has indicated that tumor-associated macrophages (TAMs) are associated with a favorable prognosis in patients with colon cancer, it is still unknown how TAMs exert a protective effect. This study examined whether TAMs are involved in hepatic metastasis of colon cancer.Materials and methodsOne hundred and sixty cases of pathologically-confirmed specimens were obtained from colon carcinoma patients with TNM stage IIIB and IV between January 1997 and July 2004 at the Cancer Center of Sun Yat-Sen University. The density of macrophages in the invasive front (CD68TFHotspot) was scored with an immunohistochemical assay. The relationship between the CD68TFHotspot and the clinicopathologic parameters, the potential of hepatic metastasis, and the 5-year survival rate were analyzed.ResultsTAMs were associated with the incidence of hepatic metastasis and the 5-year survival rate in patients with colon cancers. Both univariate and multivariate analyses revealed that the CD68TFHotspot was independently prognostic of survival. A higher 5-year survival rate among patients with stage IIIB after radical resection occurred in patients with a higher macrophage infiltration in the invasive front (81.0%) than in those with a lower macrophage infiltration (48.6%). Most importantly, the CD68TFHotspot was associated with both the potential of hepatic metastasis and the interval between colon resection and the occurrence of hepatic metastasis.ConclusionThis study showed evidence that TAMs infiltrated in the invasive front are associated with improvement in both hepatic metastasis and overall survival in colon cancer, implying that TAMs have protective potential in colon cancers and might serve as a novel therapeutic target.
In this study, β2-AR level was found to be up-regulated in MCF-7 cells overexpressing Her2 (MCF-7/Her2). Correlation of β2-AR level with Her2 status was demonstrated in breast cancer tissue samples. Constitutive phosphorylation of ERK, mRNA expression up-regulation of catecholamine-synthesis enzymes, and increased epinephrine release were detected in MCF-7/Her2 cells. β2-AR expression induced by epinephrine and involvement of ERK signaling were validated. The data indicate that Her2 overexpression and excessive phosphorylation of ERK cause epinephrine autocrine release from breast cancer cells, resulting in up-regulation of β2-AR expression. The data also showed that catecholamine prominently stimulated Her2 mRNA expression and promoter activity. The activation and nuclear translocation of STAT3 triggered by isoproterenol were observed. Enhanced binding activities of STAT3 to the Her2 promoter after isoproterenol stimulation were verified. Using STAT3 shRNA and dominant negative STAT3 mutant, the role of STAT3 in isoproterenol-induced Her2 expression was further confirmed. The data support a model where β2-AR and Her2 comprise a positive feedback loop in human breast cancer cells.
A I M : To i n v e s t i g a t e t h e e f f e c t o f a d m i s s i o n hypertriglyceridemia (HTG) on the episodes of severe acute pancreatitis (SAP).
METHODS:One hundred and seventy-six patients with SAP were divided into HTG group (n = 45) and control group (n = 131) according to admission triglyceride (TG) ≥ 5.65 mmol/L and < 5.65 mmol/L, respectively. Demographics, etiology, underlying diseases, biochemical parameters, Ranson' s score, acute physiology and chronic heath evaluation Ⅱ (APACHE Ⅱ) score, Balthazar's computed tomography ( C T ) s c o r e , c o m p l i c a t i o n s a n d m o r t a l i ty w e r e compared. Correlation between admission TG and 24-h APACHE Ⅱ score was analyzed. RESULTS: SAP patients with HTG were younger (40.8 ± 9.3 years vs 52.6 ± 13.4 years, P < 0.05) with higher etiology rate of overeating, high-fat diet (40.0% vs 14.5%, P < 0.05) and alcohol abuse (46.7% vs 23.7%, P < 0.01), incidence rate of hypocalcemia (86.7% vs 63.4%, P < 0.01) and hypoalbuminemia (84.4% vs 60.3%, P < 0.01), 24-h APACHE Ⅱ score (13.6 ± 5.7 vs 10.7 ± 4.6, P < 0.01) and admission serum glucose (17.7 ± 7.7 vs 13.4 ± 6.1, P < 0.01), complication rate of renal failure (51.1% vs 16.8%, P < 0.01), shock (37.9% vs 14.5%, P < 0.01) and infection (37.4% vs 18.3%, P < 0.01) and mortality (13.1% vs 9.1%, P < 0.01). Logistic regression analysis showed a positive correlation between admission TG and 24-h APACHE Ⅱ score (r = 0 .509, P = 0.004).
SUMMARY
The gastrointestinal (GI) epithelium is a highly regenerative tissue with the potential to provide a renewable source of insulin+ cells after undergoing cellular reprogramming. Here, we show that cells of the antral stomach have a previously unappreciated propensity for conversion into functional insulin-secreting cells. Native antral endocrine cells share a surprising degree of transcriptional similarity with pancreatic β cells, and expression of β cell reprogramming factors in vivo converts antral cells efficiently into insulin+ cells with close molecular and functional similarity to β cells. Induced GI insulin+ cells can suppress hyperglycemia in a diabetic mouse model for at least 6 months and regenerate rapidly after ablation. Reprogramming of antral stomach cells assembled into bioengineered mini-organs in vitro yielded transplantable units that also suppressed hyperglycemia in diabetic mice, highlighting the potential for development of engineered stomach tissues as a renewable source of functional β cells for glycemic control.
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