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Bisphenol A promotes cholesterol absorption in Caco-2 cells by up-regulation of NPC1L1 expression
No full textAbstract
Background
Bisphenol A (BPA), an commonly exposed environmental chemicals in humans, has been shown to have a hypercholesterolemic effect with molecular mechanism not clear. Since intestinal cholesterol absorption plays a major role in maintaining total body cholesterol homeostasis, the present study is to investigate whether BPA affects cholesterol absorption in the intestinal Caco-2 cells. Methods: The Caco-2 cells were pretreated with BPA at different concentrations for 24\ua0h and then incubated with radioactive micellar cholesterol for 2\ua0h. The absorption of radioactive cholesterol was quantified by liquid scintillation. The expression of Niemann-Pick C1-like 1 (NPC1L1) and sterol regulatory element binding protein-2 (SREBP-2) was analyzed by Western blot and qPCR.
Results
We found that confluent Caco-2 cells expressed NPC1L1, and the absorption of cholesterol in the cells was inhibited by ezetimibe, a specific inhibitor of NPC1L1. We then pretreated the cells with 0.1\u201310 nM BPA for 24\ua0h and found that BPA at 1 and 10 nM doses promoted cholesterol absorption. In addition, we found that the BPA-induced promotion of cholesterol absorption was associated with significant increase in the levels of NPC1L1 protein and NPC1L1 mRNA. Moreover, the stimulatory effects of BPA on cholesterol absorption and NPC1L1 expression could be prevented by blockade of the SREBP-2 pathway.
Conclusions
This study provides the first evidence that BPA promotes cholesterol absorption in the intestinal cells and the stimulatory effect of BPA is mediated, at least in part, by SREBP-2-NPC1L1 signaling pathway
Increased expression of Cks1 protein is associated with lymph node metastasis and poor prognosis in nasopharyngeal carcinoma
No full textAbstract
Background
The Cks1 protein is an essential factor in regulating cell cycle by mediating the ubiquitination of CDK inhibitor p27
kip1
. It has been reported that aberrant expression of Cks1 and p27
kip1
proteins was found in various tumors and related to initiation and progression of carcinomas. However, the potential roles which Cks1 and p27
KIP1
proteins play in NPC remain unclear. This study aims to examine the expression status of Cks1 and p27
kip1
and their possible prognostic significance in NPC.
Methods
Paraffin-embedded specimens with NPC ( n \u2009=\u2009168) and non-tumor nasopharyngeal tissues ( n \u2009=\u200949) were analyzed by IHC.
Results
Expression of Cks1 increased in NPC tissues compared with non-tumor nasopharyngeal tissues ( P \u2009<\u20090.05), whereas p27
kip1
protein frequently expressed in non-tumor nasopharyngeal tissues compared with NPC tissues ( P \u2009<\u20090.05). There was a significant reverse correlation between Cks1 and p27
kip1
protein expression in NPC ( r \u2009=\u2009\u22120.189, P \u2009<\u20090.05).In addition, Kaplan-Meier survival curve showed that there was a significant tendency of shorter overall survival (OS) in NPC patients with Cks1 positive expression compared to negative ones, especially in patients with lymph node metastasis ( P \u2009<\u20090.001, respectively). But there was no significance between p27
kip1
expression and survival viability of NPC patients. Multivariate Cox regression analysis further identified increased expression of Cks1 was the independent poor prognostic factor for NPC ( p \u2009=\u20090.13).
Conclusion
Our research found expression of Cks1 increased and was inverse to the expression of p27
KIP1
. High expression of Cks1 was significantly associated with lymph node metastasis and survival status in NPC. In addition, the abnormally high level of Cks1 protein was proved to be an independent poor prognostic factor in NPC. These results may provide novel clue for NPC therapy ..
Update on Lysinuric Protein Intolerance, a Multi-faceted Disease Retrospective cohort analysis from birth to adulthood
No full textAbstract
Background
Lysinuric protein intolerance (LPI) is a rare metabolic disease resulting from recessive-inherited mutations in the SLC7A7 gene encoding the cationic amino-acids transporter subunit y
+
LAT1. The disease is characterised by protein-rich food intolerance with secondary urea cycle disorder, but symptoms are heterogeneous ranging from infiltrative lung disease, kidney failure to auto-immune complications. This retrospective study of all cases treated at Necker Hospital (Paris, France) since 1977 describes LPI in both children and adults in order to improve therapeutic management.
Results
Sixteen patients diagnosed with LPI (12 males, 4 females, from 9 families) were followed for a mean of 11.4 years (min-max: 0.4-37.0 years). Presenting signs were failure to thrive ( n \u2009=\u20099), gastrointestinal disorders ( n \u2009=\u20092), cytopenia ( n \u2009=\u20096), hyperammonemia ( n \u2009=\u200910) with acute encephalopathy ( n \u2009=\u20094) or developmental disability ( n \u2009=\u20093), and proteinuria ( n \u2009=\u20091). During follow-up, 5 patients presented with acute hyperammonemia, and 8 presented with developmental disability. Kidney disease was observed in all patients: tubulopathy (11/11), proteinuria (4/16) and kidney failure (7/16), which was more common in older patients (mean age of onset 17.7 years, standard deviation 5.33 years), with heterogeneous patterns including a lupus nephritis. We noticed a case of myocardial infarction in a 34-year-old adult. Failure to thrive and signs of haemophagocytic-lymphohistiocytosis were almost constant. Recurrent acute pancreatitis occurred in 2 patients. Ten patients developed an early lung disease. Six died at the mean age of 4 years from pulmonary alveolar proteinosis. This pulmonary involvement was significantly associated with death. Age-adjusted plasma lysine concentrations at diagnosis showed a trend ..
Normal saline versus heparin for patency of central venous catheters in adult patients - a systematic review and meta-analysis
No full textAbstract
Background
Heparin saline (HS) is theoretically superior to normal saline (NS) for maintaining the patency of central venous catheters (CVCs), but the comparative efficacy of them remains controversial. The aim of this systematic review and meta-analysis was to assess the efficacy of NS versus HS in the maintenance of the patency of CVCs in adult patients.
Methods
We searched PubMed, Embase and the Cochrane library databases. Randomized controlled trials (RCTs) evaluating the use of NS vs. HS to maintain the permeability of CVCs among adult patients were included in our meta-analysis. References of relevant papers were reviewed manually. No language restriction was applied. Non-human studies were excluded. Pooled relative risk (RR) was calculated using a Mantel-Haenszel random-effects model. We also performed subgroup analysis examining the effect of the duration of catheter placement on the outcome. All statistical tests were two-sided using a significance level of 0.05.
Results
Ten RCTs involving 7875 subjects (with analysis at patient, catheter, lumen and line access level) were included in this meta-analysis. Whether in terms of pooled or local analysis (RR with 95% confidence interval spans 1), NS can be equally, if not more effective, in keeping the CVCs open. Of studies reporting secondary outcomes (maneuver needed, heparin-induced thrombocytopenia, haemorrhage, central venous thrombosis and catheter-related bloodstream infection), heparinised saline was shown not to be superior to non-heparinised solution. Subgroup analysis in patients with short vs long term CVC placement was consistent with the main outcome partly and in particular for maintenance of catheter patency in patients with a long-term placement i.e. >30\ua0days, the RR was 0.97 ( n \u2009=\u20096589; 95% CI\u2009=\u20090.76 to 1.23; P \u2009=\u20090.796). However, for patients in whom the catheter was in place for <30\ua0days, the RR was 1.52 ( n \u2009=\u20091286; 95% CI\u2009=\u20091.02 to 2.27; P \u2009=\u20090.041).
Conclusions
Based on the results of this meta-analysis, HS is not superior to NS in reducing CVCs occlusion. But in the short term, the use of HS is slightly superior to NS for flushing catheters from a statistical point of view
Effect of perioperative sodium bicarbonate administration on renal function following cardiac surgery for infective endocarditis: a randomized, placebo-controlled trial
No full textAbstract
Background
Patients with infective endocarditis (IE) have an elevated risk of renal dysfunction because of extensive systemic inflammation and use of nephrotoxic antibiotics. In this randomized, placebo-controlled trial, we investigated whether perioperative sodium bicarbonate administration could attenuate postoperative renal dysfunction in patients with IE undergoing cardiac surgery.
Methods
Seventy patients randomly received sodium chloride ( n \u2009=\u200935) or sodium bicarbonate ( n \u2009=\u200935). Sodium bicarbonate was administered as a 0.5\ua0mmol/kg loading dose for 1\ua0h commencing with anesthetic induction, followed by a 0.15\ua0mmol/kg/h infusion for 23\ua0h. The primary outcome was peak serum creatinine (SCr) level during the first 48\ua0h postoperatively. The incidence of acute kidney injury, SCr level, estimated glomerular filtration rate, and major morbidity endpoints were assessed postoperatively.
Results
The peak SCr during the first 48\ua0h postoperatively (bicarbonate vs. control: 1.01 (0.74, 1.37) mg/dl vs. 0.88 (0.76, 1.27) mg/dl, P \u2009=\u20090.474) and the incidence of acute kidney injury (bicarbonate vs. control: 29% vs. 23%, P \u2009=\u20090.584) were similar in both groups. The postoperative increase in SCr above baseline was greater in the bicarbonate group than in the control group on postoperative day 2 (0.21 (0.07, 0.33) mg/dl vs. 0.06 (0.00, 0.23) mg/dl, P \u2009=\u20090.028) and postoperative day 5 (0.23 (0.08, 0.36) mg/dl vs. 0.06 (0.00, 0.23) mg/dl, P \u2009=\u20090.017).
Conclusions
Perioperative sodium bicarbonate administration had no favorable impact on postoperative renal function and outcomes in patients with IE undergoing cardiac surgery. Instead, it was associated with possibly harmful renal effects, illustrated by a greater increase in SCr postoperatively, compared to control.
Trial registration
ClinicalTrials.gov, NCT01920126 . Registered on 31 July 2013
Optimization of microwave-assisted extraction of zerumbone from Zingiber zerumbet L. rhizome and evaluation of antiproliferative activity of optimized extracts
No full textAbstract
Background
The extraction of bioactive compounds from herbal materials requires optimization in order to recover the highest active dose. Response surface methodology was used to optimize variables affecting the microwave extraction of zerumbone from Zingiber zerumbet using the Box\u2013Behnken design. The influence of variables, such as ethanol concentration\ua0(X
1
), microwave power\ua0(X
2
), irradiation time\ua0(X
3
), and liquid-to-solid ratio\ua0(X
4
), on the extraction of zerumbone was modeled using a second-order regression equation. The antiproliferative activity of optimized and non-optimized extracts was evaluated against the HeLa cancer cell line using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay.
Results
Two linear parameters, X
1
and X
4
, and their quadratic parameters were highly significant at the P\ua0<\ua00.01 level. Two interaction parameters, X
1
X
4
and X
2
X
3
were significant, whereas interactions of X
1
X
2
, X
1
X
3
, X
2
X
4
and X
3
X
4
were insignificant (P\ua0>\ua00.05). The optimum microwave extraction conditions were as follows: ethanol concentration, 44%; microwave power, 518\ua0W; irradiation time, 38.5\ua0s; and liquid-to-solid ratio, 38\ua0mL/g. Under these conditions, the maximum zerumbone yield was 5.88\ua0mg/g DM, which was similar to the predicted value (5.946\ua0mg/g DM). Optimized and non-optimized Z. zerumbet rhizome extracts exhibited significant antiproliferative activity against HeLa cancer cells, with half-maximal inhibitory concentration (IC
50
) values of 4.3 and 7.8\ua0\u3bcg/mL, respectively, compared with 1.68\ua0\u3bcg/mL for the anticancer drug cisplatin. When the extract concentration increased from 4.3 to 16.0\ua0\u3bcg/mL, the inhibition of cancer cell growth increased from 50.0 to 79.5%.
..
Presence of zoonotic Cryptosporidium scrofarum, Giardia duodenalis assemblage A and Enterocytozoon bieneusi genotypes in captive Eurasian wild boars (Sus scrofa) in China: potential for zoonotic transmission
No full textAbstract
Background
Cryptosporidium spp . , Giardia duodenalis and Enterocytozoon bieneusi are the main causal pathogens of gastrointestinal disease. However, there are limited reports about the prevalence of these organisms in captive Eurasian wild boars worldwide. Therefore, we examined the occurrence and identified the species/assemblages/genotypes of these pathogens in captive Eurasian wild boars, and estimated the zoonotic potential.
Findings
Of 357 fecal samples collected from captive Eurasian wild boars in China, 155 (43.4%) were infected with Cryptosporidium , G. duodenalis and/or E. bieneusi . The infection rates significantly differed in different areas, but did not differ between wild boars kept indoors and outdoors. Three (0.8%), 11 (3.1%) and 147 (41.2%) fecal samples were positive for Cryptosporidium , G. duodenalis and E. bieneusi , respectively. Sequence analysis of SSU rRNA gene revealed that all of the Cryptosporidium strains belonged to C. scrofarum . Based on the sequence analysis of the \u3b2-giardia gene of G. duodenalis , assemblages E and A were characterized. Fourteen E. bieneusi genotypes comprising five novel (WildBoar 7\u201311) and eight known (EbpC, F, CHG19, CHC5, PigEBITS5, D, RWSH4, SC02) genotypes were identified by ITS sequencing. EbpC was the most frequent genotype, detected in 85 specimens. Phylogenetic analysis revealed that all 14 genotypes belonged to Group 1.
Conclusions
This first report on the occurrence of Cryptosporidium , G. duodenalis and E. bieneusi in captive wild boars in China indicates that the presence of zoonotic species/assemblages/genotypes poses a threat to public health. The findings suggest that wild boars could be a significant source of human infection and water pollution
Positive solutions for a class of fractional 3-point boundary value problems at resonance
No full textAbstract
In this paper, we study the nonlocal fractional differential equation:
{
D
0
+
\u3b1
u
(
t
)
+
f
(
t
,
u
(
t
)
)
=
0
,
0
<
t
<
1
,
u
(
0
)
=
0
,
u
(
1
)
=
\u3b7
u
(
\u3be
)
,
where
1
<
\u3b1
<
2
,
0
<
\u3be
<
1
,
\u3b7
\u3be
\u3b1
\u2212
1
=
1
,
D
0
..
The dangers of parathyroid biopsy
No full textAbstract
Background
We report an unusual case of a 66-year-old female with a suspicious thoracic outlet mass presenting with severe biochemical hyperparathyroidism and classic hypercalcemic symptoms of renal and bone involvement.
Case Presentation
There was clinical suspicion for parathyroid carcinoma, further supported by intra-operative findings. However, the final pathology described a primary hyperceullar parathyroid lesion with pathognomonic changes secondary to fine-needle aspiration (FNA) biopsy, along with a separate parathyroid lesion likely resulting from seeding along the needle tract. Upon further review, record of a remote FNA was discovered. This case highlights the complications associated with parathyroid FNA resulting in a diagnostic challenge and raising the possibility of malignancy.
Conclusions
We therefore recommend to take caution when there is a prior parathyroid FNA, as it can present with the risks of a secondary lesion from seeding and increase resemblance of malignancy both clinically and through pathologic diagnosis
Severe obesity, emotions and eating habits: a case-control study
No full textAbstract
Background
Obesity has a multifaceted etiology that involves genetic, biological and behavioral factors, body growth, eating habits, energy expenditure and the function of adipose tissue. The present study aimed to expand upon knowledge about the relationships among obesity, emotions and eating habits in severely obese individuals using a case-control method.
Methods
The subject group consisted of 112 individuals (81 females and 31 males) receiving a permanent disability pension primarily for obesity. The control subjects were randomly selected from the same area and were receiving a disability pension for a different primary illness. The controls were matched with the subjects by the place of residence, sex, age, the time since the pension was granted and occupation. Psychiatric interviews were conducted on all participants. The results were analyzed using the chi-squared test (\u3c7
2
-test) and the percent distribution. The subject and control groups were compared using the t-test for paired variables. Conditional logistic regression analysis was also conducted.
Results
The emotional state of eating was significantly associated with quarrels and feelings of loneliness. The subjects suffered from night eating syndrome, which was associated with an increased risk of early retirement. Binge eating syndrome was observed more frequently in the study group. The subjects reported feeling increased hunger compared with the controls. A significant percentage of the subjects had a body mass index of\u2009\u2265\u200940. No differences in eating habits were observed between the groups.
Conclusion
This study provides information on the relationship between emotions and eating habits in obesity, which is a rarely studied topic. We believe that our study provides a novel and necessary overview of the associations among severe obesity, emotions and eating habits