Circadian rhythm-related factors of PER and CRY family genes function as novel therapeutic targets and prognostic biomarkers in lung adenocarcinoma.

The period (PER) and cryptochrome (CRY) families play critical roles in circadian rhythms. The imbalance of circadian factors may lead to the occurrence of cancer. Expressions of PER and CRY family members decrease in various cancers. Nevertheless, expression levels, genetic variations, and molecular mechanisms of PER and CRY family members in lung adenocarcinoma (LUAD) and their correlations with prognoses and immune infiltration in LUAD patients are still unclear. In this study, to identify their biological functions in LUAD development, comprehensive high-throughput techniques were applied to analyze the relationships of expressions of PER and CRY family members with genetic variations, molecular mechanisms, and immune infiltration. The present results showed that transcription levels of PER1 and CRY2 in LUAD were significantly downregulated. High expression levels of PER2, PER3, CRY1, and CRY2 indicated longer overall survival. Some cancer signaling pathways were related to PER and CRY family members, such as cell-cycle, histidine metabolism, and progesterone-mediated oocyte maturation pathways. Expressions of PER and CRY family members significantly affected the infiltration of different immune cells. In conclusion, our findings may help better understand the molecular basis of LUAD, and provide new perspectives of PER and CRY family members as novel biomarkers for LUAD.

Contribution of PGR genetic polymorphisms to the pathogenesis of endometrial cancer: A meta-analysis.

OBJECTIVE: The aim of this meta-analysis is to identify whether two common genetic polymorphisms (rs1042838 G > T and rs10895068 C > T) in the PGR gene may contribute to the pathogenesis of endometrial cancer. MATERIALS AND METHODS: The MEDLINE (1966 ~ 2013), the Cochrane Library Database (Issue 12, 2013), EMBASE (1980 ~ 2013), CINAHL (1982 ~ 2013), Web of Science (1945 ~ 2013) and the Chinese Biomedical Database (CBM) (1982 ~ 2013) were searched without language restrictions. Meta-analyses were conducted using the STATA software (Version 12.0, Stata Corporation, College Station, Texas, USA). We calculated odds ratio (OR) and its 95% confidence interval (95% CI) to estimate the relationships between PGR genetic polymorphisms and the pathogenesis of endometrial cancer. RESULTS: Six studies with a total of 6,285 patients with endometrial cancer and 12,120 control subjects met the inclusion criteria for the meta-analysis. Our findings suggested that PGR rs1042838 polymorphism was significantly correlated with an increased risk of endometrial cancer (T allele vs. G allele: OR = 1.23, 95% CI: 1.07 ~ 1.42, P = 0.005; GT + TT vs. GG: OR = 1.21, 95% CI: 1.06 ~ 1.40, P = 0.006; TT vs. GG + GT: OR = 1.65, 95% CI: 1.09 ~ 2.49, P = 0.017; TT vs. GG: OR = 1.72, 95% CI: 1.12 ~ 2.65, P = 0.013; TT vs. GT: OR = 1.42, 95% CI: 1.01 ~ 2.00, P = 0.044, respectively). We also observed positive associations between PGR rs10895068 polymorphism and the pathogenesis of endometrial cancer (T allele vs. C allele: OR = 1.15, 95% CI: 1.02 ~ 1.29, P = 0.027; CT + TT vs. CC: OR = 1.14, 95% CI: 1.00 ~ 1.29, P = 0.045, respectively). CONCLUSION: Ethnicity-stratified analysis indicated that rs1042838 and rs10895068 polymorphisms in the PGR gene might be strongly related to the pathogenesis of endometrial cancer among Caucasians and mixed populations (all P < 0.05). In conclusion, our findings provide empirical evidence that PGR rs1042838 and rs10895068 polymorphisms may be involved in the pathogenesis of endometrial cancer.

Relationship of adiponectin and resistin levels in umbilical serum, maternal serum and placenta with neonatal birth weight.

OBJECTIVE: Adiponectin and resistin have been postulated to play a role in the regulation of energy metabolism during pregnancy. However, relationship of adiponectin and resistin levels in umbilical serum, maternal serum and placenta with neonatal birth weight remains to be poorly understood. The purpose of the study was to clarify the correlations between adiponectin and resistin levels and neonatal birth weight. METHODS: Enzyme immunoassay was used to measure the adiponectin and resistin levels in maternal and umbilical serum from 40 normal pregnant women (control group), 30 women with macrosomia (macrosomia group) and 30 women with fetal growth restriction (FGR group). Immunohistochemistry was used to measure adiponectin and resistin levels in placenta. RESULTS: Serum adiponectin and resistin levels were significantly increased in control women compared with that in macrosomia mothers, but significantly decreased compared with that in FGR mothers. The levels of adiponectin and resistin in control babies were significantly higher than that in macrosomic babies, whereas significantly lower than that in FGR babies. The placental expressions of adiponectin and resistin in macrosomia, control and FGR group were gradually elevated, and there was a significant difference between them. Umbilical serum adiponectin levels and placental adiponectin expression were inversely correlated with birth weight. Umbilical serum levels and placental expression of resistin had positive correlation with maternal serum resistin and negative correlation with birth weight. In addition, maternal serum resistin levels were inversely correlated with birth weight. CONCLUSION: It is suggested that adiponectin and resistin play an important role in controlling body weight and may be related to the occurrence of fetal macrosomia and FGR.

Relationship of adiponectin and resistin levels in umbilical and maternal serum with fetal macrosomia.

AIM: Adiponectin and resistin are novel hormones secreted by human adipocytes and mononuclear cells, which have been postulated to play roles in the regulation of energy metabolism during pregnancy. However, correlations between adiponectin and resistin levels in umbilical and maternal serum and fetal macrosomia remain poorly understood. The purpose of this study was to clarify the relationship of adiponectin and resistin levels in umbilical and maternal serum with fetal macrosomia. METHODS: Serum adiponectin and resistin levels were prospectively measured by enzyme immunoassay in 70 mothers and their 70 neonates. The study group included 30 neonates with macrosomia and the control group included 40 neonates that were appropriate for gestational age. The correlations of cord serum adiponectin and resistin with maternal serum adiponectin and resistin, birth weight, body mass index (BMI), and placental weight were analyzed. RESULTS: Serum adiponectin and resistin levels were significantly decreased in macrosomic mothers compared with those in control women. The levels of adiponectin and resistin were diminished in macrosomic babies in comparison with control newborns. Umbilical serum adiponectin levels were inversely correlated with birth weight, newborn BMI, and placental weight, but not with maternal serum adiponectin levels. Umbilical serum resistin levels had a positive correlation with maternal serum resistin and a negative correlation with birth weight, newborn BMI, and placental weight. In addition, maternal serum resistin levels were inversely correlated with newborn birth weight. CONCLUSION: It is suggested that adiponectin and resistin play important roles in controlling body weight and may be related to the occurrence of fetal macrosomia.

[Relationship of adiponectin and visfatin with fetus intrauterine growth].

OBJECTIVE: To explore the correlation between adipocyte factors (adiponectin and visfatin) and fetus intrauterine growth. METHODS: Enzyme immunoassay was used to measure the adiponectin and visfatin levels in maternal and umbilical serum from 14 women with fetal growth restriction (FGR group), 14 women with macrosomia (macrosomia group) and 14 normal pregnant women (control group). The correlations of cord serum adiponectin and visfatin with maternal serum adiponectin and visfatin were analyzed. RESULTS: (1) Serum visfatin levels in FGR mothers [(41.4 +/- 5.5)] microg/L were significantly higher than that in control women [(34.7 +/- 4.9) microg/L] and macrosomia mothers [(37.3 +/- 4.4) microg/L; P < 0.01, P < 0.05]. Serum adiponectin levels in macrosomia mothers [(4.1 +/- 1.3) mg/L] were significantly lower than that in control women [(6.6 +/- 1.5) mg/L] and FGR mothers [(6.4 +/- 1.3) mg/L; P < 0.01]. (2) Serum visfatin levels in FGR babies [(58.1 +/- 7.6) microg/L] were significantly increased than that in control newborns [(42.6 +/- 7.8) microg/L] and macrosomia babies [(48.5 +/- 9.1) microg/L; P < 0.01, P < 0.05]. Serum adiponectin levels in macrosomia babies [(6.5 +/- 1.3) mg/L] were significantly decreased than that in control newborns [(7.7 +/- 1.5) mg/L] and FGR babies [(7.7 +/- 1.0) mg/L; P < 0.05, P < 0.05]. (3) Maternal serum visfatin levels were positively correlated with umbilical serum visfatin levels (r = 0.720, P < 0.01). Umbilical serum adiponectin levels were higher than that in maternal serum, but there were no relationship between them (r = 0.301, P > 0.05). CONCLUSION: The changes of visfatin and adiponectin levels may be related to the occurrence of FGR and fetal macrosomia.

[Effects of glucagon like peptide-1 treatment on the alveolar capillary basal lamina in Otsuka Long-Evans Tokushima Fatty rats].

OBJECTIVE: To observe and quantitatively analyze the effect of glucagon like peptide-1 (GLP-1) on the alveolar capillary basal lamina in spontaneous type 2 diabetes mellitus animal model Otsuka Long-Evans Tokushima Fatty (OLETF) rats. METHODS: Experimental rats were divided into three groups: OLETF group, GLP-1-treated group (OLETF/G group), and Long-Evans Tokushima Otsuka group (LETO group) as control. The ultrastructure and thickness of the alveolar capillary basal lamina in the rats were examined by transmission electron microscopy and morphometry methods. RESULTS: The fused basal lamina (F-BL) of the alveolar capillary endothelium and type I epithelial basal lamina, and the alveolar capillary endothelium basal lamina (Cap-BL) were thickened in OLETF rats than those of LETO rats [(110.60+/-14.14) nm vs (57.30+/-11.08) nm, and (118.40+/-19.12) nm vs (66.80+/-8.63) nm, P<0.01]. F-BL and Cap-BL were thinned in the OLETF/G group as compared with OLETF group [(79.70+/-5.44) nm vs (110.60+/-14.14) nm and (69.80 +/-3.32) nm vs (118.40+/-19.12) nm, P<0.01]. CONCLUSION: Our studies suggest the existence of ultrastructural changes of alveolar capillary basal lamina in OLETF rats. GLP-1 intervention decreases the damage of alveolar capillary basal lamina in OLETF rats.

[The clinicopathological features of early renal amyloidosis].

OBJECTIVE: To investigate the clinicopathological manifestations of early renal amyloidosis (AL) and its diagnostic criteria. METHODS: Fifteen cases with early renal amyloidosis admitted from 1994 to 2001 were collected from the hospital, and their clinical and pathological features were reviewed. Of them, the initial diagnoses were not made by depending findings from the light microscopy (LM) and immunofluorescense (IF), but confirmed by electron microscopy (EM) afterwards. Immuno-electron microscopy (IEM) were applied for amyloidosis typing. RESULTS: Most patients of early renal AL were in the middle to old age. Nephrotic syndrome was the most prominent symptoms and signs accompanying with rare microscopic hematuria and hypertension. Most of them had a normal renal function. Pathological examinations of renal biopsies using LM and IF showed mild mesangial proliferation and mild thickening of glomerular basement membrane (GBM). Immunoglobulins and complements were negative or only scanty in certain cases, but in all cases there was a light chain protein deposition homogeously. There were 4 cases of minimal change glomerulopathy, 5 cases of mild mesangial proliferative glomerulonephritis, 5 cases of stage I membranous nephropathy, and 1 case of cast nephropathy diagnosed with LM. The amyloid fibrils (diameter 8 - 10 nm) were randomly distributed in the mesangium, along GBM and at the arteriolar wall under EM. Additionally, Congo red staining was positive. IEM demonstrated that amyloid fibrils labeled with colloid gold was combined with a kind of light chain protein which was confirmed as the light chain type of AL. CONCLUSIONS: The diagnosis of early renal AL was occasionally neglected by depending only findings of LM and LF. However, special amyloid fibrils can be detected using EM. EM observation is an indispensable technique for the diagnosis of early renal AL and the typing of AL may further be determined by using IEM.

[Pathological features of light chain nephropathy].

OBJECTIVE: To investigate the pathologic features and diagnostic algorithm of light chain nephropathy (LCN). METHODS: Seven cases of LCN were studied by light microscopy, electron microscopy and immunolabeling of light chains (kappa, lambda) by immunofluorescence and immunoelectron microscopy. RESULTS: The histopathology of 7 cases by light microscopy was variable, with 3 cases showing nodular glomerulosclerosis, 1 case showing mild to moderate mesangial proliferation, and 3 cases showing cast nephropathy with minimal glomerular change. Immunofluorescence study revealed positive staining of a single type of light chain in mesangium (nodular pattern) or along glomerular basement membrane (linear), along tubular basement membrane and around arteriolar walls in all the 7 cases. Ultrastructurally, electron-dense granular deposits were identified in mesangium, subendothelial aspect of glomerular basement membrane, outer aspect of tubular basement membrane and arteriolar walls. Immunogold labeling of light chains showed distinct labeling of a single type light chain in the granular electron-dense materials (5 cases being kappa-positive and 2 being lambda-positive). CONCLUSIONS: LCN typically shows nodular glomerulosclerosis. The ultrastructural change is characteristic and important for diagnosis. Immunolabeling of light chains by immunofluorescence and immunoelectron microscopy carries further diagnostic value, especially in cases with minimal light microscopic change.