Over-expression and increased activity of cyclooxygenase (COX)-2 induced by smoking has been implicated in the development of cancer. This study aimed to explore the interaction between smoking and ...functional polymorphisms of COX-2 in modulation of gastric cardia adenocarcinoma (GCA) risk.
Three COX-2 polymorphisms, including -1195G>A (rs689466), -765G>C (rs20417), and 587Gly>Arg (rs3218625), were genotyped in 357 GCA patients and 985 controls. In the multivariate logistic regression analysis, we found that the -1195AA, -765GC, and 587Arg/Arg genotypes were associated with increased risk of GCA (OR = 1.50, 95% CI = 1.05-2.13; OR = 2.06, 95% CI = 1.29-3.29 and OR = 1.67, 95% CI = 1.04-2.66, respectively). Haplotype association analysis showed that compared with G(-1195)-G(-765)- G(Gly587Arg), the A(-1195)-C(-765)-A(Gly587Arg) conferred an increased risk of GCA (OR = 2.49, 95% CI = 1.54-4.01). Moreover, significant multiplicative interactions were observed between smoking and these three polymorphisms of -1195G>A, -765G>C, and 587Gly>Arg, even after correction by false discovery rate (FDR) method for multiple comparisons (FDR-P(interaction) = 0.006, 5.239×10(-4) and 0.017, respectively). Similarly, haplotypes incorporating these three polymorphisms also showed significant interaction with smoking in the development of GCA (P for multiplicative interaction = 2.65×10(-6)).
These findings indicated that the functional polymorphisms of COX-2, in interaction with smoking, may play a substantial role in the development of GCA.
Aiming to uncover a shared genetic basis of abdominal obesity and osteoporosis, we performed a bivariate GWAS meta-analysis of femoral neck BMD (FNK-BMD) and trunk fat mass adjusted by trunk lean ...mass (TFM
adj
) in 11,496 subjects from 6 samples, followed by in silico replication in the large-scale UK Biobank (UKB) cohort. A series of functional investigations were conducted on the identified variants. Bivariate GWAS meta-analysis identified two novel pleiotropic loci 12q15 (lead SNP
rs73134637
,
p
= 3.45 × 10
–7
) and 10p14 (lead SNP
rs2892347
,
p
= 2.63 × 10
–7
) that were suggestively associated and that were replicated in the analyses of related traits in the UKB sample (osteoporosis
p
= 0.06 and 0.02, BMI
p
= 0.03 and 4.61 × 10
–3
, N up to 499,520).
Cis
-eQTL analysis demonstrated that allele C at
rs73134637
was positively associated with
IFNG
expression in whole blood (
N
= 369,
p
= 0.04), and allele A at
rs11254759
(10p14,
p
= 9.49 × 10
–7
) was negatively associated with
PRKCQ
expression in visceral adipose tissue (
N
= 313,
p
= 0.04) and in lymphocytes (
N
= 117,
p
= 0.03). As a proof-of-principle experiment, the function of
rs11254759
, which is 235 kb 5′-upstream from
PRKCQ
gene, was investigated by the dual-luciferase reporter assay, which clearly showed that the haplotype carrying
rs11254759
regulated
PRKCQ
expression by upregulating
PRKCQ
promoter activity (
p
= 4.60 × 10
–7
) in an allelic specific manner. Mouse model analysis showed that heterozygous
PRKCQ
deficient mice presented decreased fat mass compared to wild-type control mice (
p
= 3.30 × 10
–3
). Mendelian randomization analysis demonstrated that both FNK-BMD and TFM
adj
were causally associated with fracture risk (
p
= 1.26 × 10
–23
and 1.18 × 10
–11
). Our findings may provide useful insights into the genetic association between osteoporosis and abdominal obesity.
Objectives
To evaluate the effect of real‐time three‐dimensional (3D) ultrasonography (US) in guiding percutaneous nephrostomy (PCN).
Materials and Methods
A hydronephrosis model was devised in which ...the ureters of 16 beagles were obstructed. The beagles were divided equally into groups 1 and 2. In group 1, the PCN was performed using real‐time 3D US guidance, while in group 2 the PCN was guided using two‐dimensional (2D) US. Visualization of the needle tract, length of puncture time and number of puncture times were recorded for the two groups.
Results
In group 1, score for visualization of the needle tract, length of puncture time and number of puncture times were 3, 7.3 ± 3.1 s and one time, respectively. In group 2, the respective results were 1.4 ± 0.5, 21.4 ± 5.8 s and 2.1 ± 0.6 times. The visualization of needle tract in group 1 was superior to that in group 2, and length of puncture time and number of puncture times were both lower in group 1 than in group 2.
Conclusions
Real‐time 3D US‐guided PCN is superior to 2D US‐guided PCN in terms of visualization of needle tract and the targeted pelvicalyceal system, leading to quick puncture. Real‐time 3D US‐guided puncture of the kidney holds great promise for clinical implementation in PCN.
The effects of Ca2+ sparks on cerebral artery smooth muscle cells (CASMCs) and airway smooth muscle cells (ASMCs) tone, as well as the underlying mechanisms, are not clear. In this investigation, we ...elucidated the underlying mechanisms of the distinct effects of Ca2+ sparks on cerebral artery smooth muscle cells (CASMCs) and airway smooth muscle cells (ASMCs) tone. In CASMCs, owing to the functional loss of Ca2+-activated Cl- (Clca) channels, Ca2+ sparks activated large-conductance Ca2+-activated K+ channels (BKs), resulting in a decreases in tone against a spontaneous depolarization-caused high tone in the resting state. In ASMCs, Ca2+ sparks induced relaxation through BKs and contraction via Clca channels. However, the integrated result was contraction because Ca2+ sparks activated BKs prior to Clca channels and Clca channels-induced depolarization was larger than BKs-caused hyperpolarization. However, the effects of Ca2+ sparks on both cell types were determined by L-type voltage-dependent Ca2+ channels (LVDCCs). In addition, compared with ASMCs, CASMCs had great and higher amplitude Ca2+ sparks, a higher density of BKs, and higher Ca2+ and voltage sensitivity of BKs. These differences enhanced the ability of Ca2+ sparks to decrease CASMC and to increase ASMC tone. The higher Ca2+ and voltage sensitivity of BKs in CASMCs than ASMCs were determined by the β1 subunits. Moreover, Ca2+ sparks showed the similar effects on human CASMC and ASMC tone. In conclusions, Ca2+ sparks decrease CASMC tone and increase ASMC tone, mediated by BKs and Clca channels, respectively, and finally determined by LVDCCs.
The soil bacterium
ATCC 27456 produces a number of polyketide natural products. Among them is NFAT-133, an inhibitor of the nuclear factor of activated T cells (NFAT) that suppresses interleukin-2 ...(IL-2) expression and T cell proliferation. Biosynthetic gene inactivation in the ATCC 27456 strain revealed the ability of this strain to produce other polyketide compounds including analogues of NFAT-133. Consequently, seven new derivatives of NFAT-133, TM-129-TM-135, together with a known compound, panowamycin A, were isolated from the culture broth of
ATCC 27456 Δ
. Their chemical structures were elucidated on the basis of their HRESIMS, 1D and 2D NMR spectroscopy, and ECD calculation and spectral data. NFAT-133, TM-132, TM-135, and panowamycin A showed no antibacterial activity or cytotoxicity, but weakly reduced the production of LPS-induced nitric oxide in RAW264.7 cells in a dose-dependent manner. A revised chemical structure of panowamycin A and proposed modes of formation of the new NFAT-133 analogues are also presented.
Dental caries severely hinders efficient access to adequate energy in wildlife. Different food supplies will develop characteristic plaque, and the microorganisms of these plaque are closely related ...to dental health. Here, plaque samples from panda cubs with caries and caries-free were collected for 16S rRNA high-throughput sequencing. All sequences clustered into 337 operational taxonomic units (OTUs; 97% identity), representing 268 independent species belonging to 189 genera, 98 families, 51 orders, 24 classes, and 13 phyla. Two groups shared 218 OTUs, indicating the presence of a core plaque microbiome. α diversity analysis showed that the microbial diversity in plaques with caries exceeded that of caries-free. The dominant phyla of plaque microbiota included Proteobacteria, Bacteroidetes, Firmicutes, Fusobacteria, and Actinobacteria. The dominant genera included
,
,
,
,
,
,
,
,
and
. β diversity analysis showed that the plaque microbial community structure was different between two groups. Using LEfSe analysis, 19 differentially abundant taxa were identified as potential biomarkers. Finally, function predictions analysis showed All the energy related metabolic pathways on KEGG level 2 were enriched in caries-active group. Consistent with the mainstream caries-causing narrative, our results illuminate the lack of information regarding the oral microflora composition and function within giant panda cubs.
It has been reported that celecoxib, a cyclooxygenase-2 (COX-2)-selective nonsteroidal anti-inflammatory drug (NSAID), regulates the radiosensitivity of several cancer cells. BCCIP (BRCA2 and CDKN1A ...interacting protein) plays a critical role in maintaining the critical functions of p53 in tumor suppression and response to therapy. However, whether the effect of celecoxib on the radiosensitivity of colorectal cancer (CRC) cells is dependent on BCCIP is largely unclear. In this study, we found that celecoxib enhanced the radiosensitivity of HeLa (a human cervical carcinoma cell line), A549 (a human lung carcinoma cell line), and HCT116 cells (a human CRC cells line). Among these cells, COX-2 expression was undetected in HCT116 cells. Treatment with celecoxib significantly increased BCCIP expression in COX-2 negative HCT116 cells. Knockdown of BCCIP obviously abrogated the enhanced radiosensitivity of HCT116 cells induced by celecoxib. A combination of celecoxib and irradiation treatment induced much more γ-H2AX foci formation, higher levels of radiation injury-related proteins phosphorylation, G2/M arrest, apoptosis, and p53 and p21 expression, and lower levels of Cyclin B1 in HCT116 cells than those in cells treated with irradiation alone. However, these changes were undetected in BCCIP-silenced HCT116 cells. Therefore, these data suggest that BCCIP gene may be a radiosensitivity-related gene in CRC. Celecoxib affects the functions of p53 and inhibits the recovery from the irradiation-induced injury by up-regulating the expression of BCCIP, and subsequently regulates the expressions of genes such as p21 and Cyclin B1 to enhance the radiosensitivity of HCT116 cells in a COX-2 independent manner.
Background
Globally, are skincare practices and skin injuries in extremely preterm infants comparable? This study describes skin injuries, variation in skincare practices and investigates any ...association between them.
Methods
A web-based survey was conducted between February 2019 and August 2021. Quantifying skin injuries and describing skincare practices in extremely preterm infants were the main outcomes. The association between skin injuries and skincare practices was established using binary multivariable logistic regression adjusted for regions.
Results
Responses from 848 neonatal intensive care units, representing all geographic regions and income status groups were received. Diaper dermatitis (331/840, 39%) and medical adhesive-related skin injuries (319/838, 38%) were the most common injuries. Following a local skincare guideline reduced skin injuries medical adhesive-related injuries: adjusted odds ratios (aOR) = 0.63, 95% confidence interval (CI) = 0.45–0.88; perineal injuries: aOR = 0.66, 95% CI = 0.45–0.96; local skin infections: OR = 0.41, 95% CI = 0.26–0.65; chemical burns: OR = 0.46, 95% CI = 0.26–0.83; thermal burns: OR = 0.51, 95% CI = 0.27–0.96. Performing skin assessments at least every four hours reduced skin injuries (abrasion: aOR = 0.48, 95% CI = 0.33–0.67; pressure: aOR = 0.51, 95% CI = 0.34–0.78; diaper dermatitis: aOR = 0.71, 95% CI = 0.51–0.99; perineal: aOR = 0.52, 95% CI = 0.36–0.75). Regional and resource settings-based variations in skin injuries and skincare practices were observed.
Conclusions
Skin injuries were common in extremely preterm infants. Consistency in practice and improved surveillance appears to reduce the occurrence of these injuries. Better evidence regarding optimal practices is needed to reduce skin injuries and minimize practice variations.
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