Long non-coding RNAs (lncRNAs) have emerged as critical regulators of tumor progression. However, the role and molecular mechanism of lncRNA XIST in gastric cancer is still unknown.
Real-time PCR ...analysis was performed to measure the expression levels of lncRNA XIST in gastric cancer tissues and cell lines, the correlation between lncRNA XIST expression and clinicopathological characteristics and prognosis was analyzed in gastric cancer patients. The biological function of lncRNA XIST on gastric cancer cells were determined both in vitro and in vivo. The regulating relationship between lncRNA XIST and miR-101 was investigated in gastric cancer cells.
lncRNA XIST was significantly up-regulated in gastric cancer tissues and cell lines. Overexpression of lncRNA XIST was markedly associated with larger tumor size, lymph node invasion, distant metastasis and TNM stage in gastric cancer patients. Functionally, knockdown of lncRNA XIST exerted tumor-suppressive effects by inhibiting cell proliferation, migration and invasion in vitro and tumor growth and metastasis in vivo. Furthermore, an inverse relationship between lncRNA XIST and miR-101 was found. Polycomb group protein enhancer of zeste homolog 2 (EZH2), a direct target of miR-101, could mediated the biological effects that lncRNA XIST exerted.
lncRNA XIST is up-regulated and is associated with aggressive tumor phenotypes and patient survival in gastric cancer, and the newly identified lncRNA XIST/miR-101/EZH2 axis could be a potential biomarkers or therapeutic targets for gastric cancer patients.
The object of the study is to identify N-glycan profiling changes associated with gastric cancer and explore the impact of core-fucosylation on biological behaviors of human gastric cancer cells. A ...total of 244 subjects including gastric cancer, gastric ulcer and healthy control were recruited. N-glycan profiling from serum and total proteins in gastric tissues was analyzed by DNA sequencer-assisted fluorophore-assisted capillary electrophoresis. The abundance of total core-fucosylated residues and the expression of enzymes involved in core-fucosylation were analyzed with lectin blot, quantitative reverse transcription-polymerase chain reaction, western blot, Immunohistochemical staining and lectin-histochemical staining. The recombinant plasmids of GDP-fucose transporter and α-1,6-fucosyltransferase (Fut8) were constructed and transfected into gastric cancer cell lines BGC-823 and SGC-7901. CCK-8 and wound healing assay were used to assess the functional impact of core-fucosylation modulation on cell proliferation and migration. Characteristic serum N-glycan profiles were found in gastric cancer. Compared with the healthy control, a trianntenary structure abundance, peak 9 (NA3Fb), was increased significantly in gastric cancer, while the total abundance of core-fucosylated residues (sumfuc) was decreased. Core-fucosylated structures, peak6(NA2F) and peak7(NA2FB) were deceased in gastric tumor tissues when compared with that in adjacent non-tumor tissues. Consistently, lens culinaris agglutinin (LCA)-binding proteins were decreased significantly in sera of gastric cancer, and protein level of Fut8 was decreased significantly in gastric tumor tissues compared with that in adjacent non-tumor tissues. Upregulation of GDP-Tr and Fut8 could inhibit proliferation, but had no significant influence on migration of BGC-823 and SGC-7901 cells. Core-fucosylation is down regulated in gastric cancer. Upregulation of core-fucosylation could inhibit proliferation of the human gastric cancer cells.
The efficacy and safety of stereotactic body radiotherapy (SBRT) plus transcatheter arterial chemoembolization (TACE) versus SBRT or TACE alone(monotherapy) for hepatocellular carcinoma (HCC) ...patients with portal vein tumour thrombus (PVTT) remains controversial. This meta-analysis was performed to provide more powerful evidence for clinical strategies in inoperable HCC with PVTT.
We searched the PubMed, EMBASE, Web of Science, Cochrane Library, China Biology Medicine (CBM), China National Knowledge Infrastructure (CNKI), VIP Journal Integration Platform (VIP), and WanFang databases for eligible studies. We pooled the results of 1- and 2-year overall survival rates (OSRs), objective response rates (ORRs), and adverse events (AEs) between the two groups and performed a subgroup meta-analysis for study type, control group, treatment order, and the interval between SBRT and TACE.
Nine studies with 10 cohorts involving 938 patients were included in our meta-analysis. SBRT plus TACE yielded significantly higher 1-year OSR (RR, 1.5295% CI, 1.33-1.74), 2-year OSR (RR, 2.00 95% CI: 1.48-2.70), ORR (RR = 1.22 95% CI, 1.08-1.37), and a lower progression disease (PD) rate (RR = 0.45 95% CI:0.26-0.79) than monotherapy. No significant differences were detected in CR, PR, SD, or AEs between the two groups. Subgroup analysis regarding study type, control group, and treatment order indicated that compared with monotherapy, the combination of SBRT with TACE was associated with an increase in 1- and 2-year OSRs but not in ORR. In regard to the interval between SBRT and TACE, subgroup analysis found that the combination therapy for patients with an SBRT-TACE interval <28 days was preferable to monotherapy in the 1- and 2-year OSRs, and ORR. However, for patients with an SBRT-TACE interval ≥28 days, no obvious distinctions were observed in the 1-year OSR, 2-year OSR, or ORR between the two groups.
The combination of SBRT with TACE appears to be better than monotherapy in treating HCC with PVTT and should be recommended for inoperable HCC patients with PVTT.
Although various geochemical and geophysical investigations have already indicated a great resource potential in the Xisha area of the South China Sea, the origin of organic matter and molecular ...evidence for tracing the migration of hydrocarbons from deep petroleum reservoirs are still lacking. In this study, systematic organic geochemical analyses, including bulk organic matter parameters and lipid biomarkers were performed for deep sediments from two cores. The C/N ratios and δ13C and δ15N values of organic matter in most of the samples, together with the maxima of short-chain n-alkanoic acids and mid-chain n-alkanols, high abundances of monounsaturated fatty acids C18:1ω9 and C22:1ω13, jointly indicate the dominance of marine organic matter. n-Alkanes in sediments from core GMGS4-XH-W06B are characterized by small unresolved complex mixture (UCMs) humps, high odd/even predominance (OEP) and carbon preference index (CPI) values, clearly exhibiting characteristics of modern sediments. However, the sediments for core GMGS4-XH-W03B are featured with big UCMs, associated with OEP and CPI values around 1.0, showing signatures of petroleum hydrocarbons from high maturity sources. Considering the geologic background, the biomarker signatures are solid evidence for indicating the existence of underlying petroleum reservoirs, and may provide the valuable information for assessing the hydrocarbon resources in the Xisha area.
Global warming and increasing extreme weather have become a severe problem in recent years, posing a significant threat to human health worldwide. Research exploring the link between injury as one of ...the leading causes of death globally and ambient temperature was lacking. Based on the hourly injury emergency ambulance dispatch (IEAD) records from 2019-2021 in the main urban area of Chongqing, this study explored the role of temperature extremes on the pathogenesis of injury by different mechanisms and identified sensitive populations for different mechanisms of injury.
In this study, we collected hourly injury emergency ambulance dispatch (IEAD) records from Chongqing Emergency Dispatch Center in the main urban area of Chongqing from 2019 to 2021, and used a distributed lagged nonlinear model (DLNM) with quasi-Poisson distribution to evaluate the association between ambient temperature and IEADs. And the stratified analysis was performed by gender, age and different injury mechanisms to identify susceptible groups. Finally, the attributable burden of ambient extreme temperatures was also investigated.
The risk for total IEADs increased significantly at high temperature (32 °C) compared with optimal temperature (9 °C) (CRR: 1.210; 95%CI1.127,1.300). The risks of traffic accident injury (CRR: 1.346; 95%CI1.167,1.552), beating injury (CRR: 1.508; 95%CI1.165,1.952), fall-height injury (CRR: 1.871; 95%CI1.196-2.926) and injury of sharp penetration (CRR: 2.112; 95%CI1.388-3.213) were significantly increased. At low temperature (7 °C), the risk of fall injury (CRR: 1.220; 95% CI 1.063,1.400) increased significantly. Lag for 24 hours at extreme low temperature (5 °C), the risk of 18-45 years (RR: 1.016; 95%CI1.009,1.024) and over 60 years of age (RR: 1.019; 95%CI1.011,1.025) increased significantly. The effect of 0 h delay in extreme high temperature (36 °C) on males aged 18-45 years (RR: 1.115; 95%CI1.071,1.162) and 46-59 years (RR: 1.069; 95%CI1.023,1.115) had significant impact on injury risk.
This study showed that ambient temperature was significantly related to the risk of injury, and different mechanisms of injury were affected differently by extreme temperature. The increasing risk of traffic accident injury, beating injury, fall-height injury and sharp penetrating injury was associated with extreme heat, while fall injury was associated with extreme cold. The risk of injury in high temperature environment was mainly concentrated in males and young adults. The results of this study can help to identify the sensitive population with different injury mechanisms in extreme temperature environment, and provide reference for public health emergency departments to respond to relevant strategies in extreme temperature environment to minimize the potential risk to the public.
IntroductionDry eye (DE) is a multifactorial ocular surface disease causing considerable medical, social and financial implications. Currently, there is no recognised long-term, effective treatment ...to alleviate DE. Clinical evidence shows that electroacupuncture (EA) can improve DE symptoms, tear secretion and tear film stability, but it remains controversial whether it is just a placebo effect. We aim to provide solid clinical evidence for the EA treatment of DE.Methods and analysisThis is a multicentre, randomised, sham-controlled trial. A total of 168 patients with DE will be enrolled and randomly assigned to EA or sham EA groups to receive 4-week consecutive treatments and follow-up for 24 weeks. The primary outcome is the change in the non-invasive tear break-up time (NIBUT) from baseline to week 4. The secondary outcomes include tear meniscus height, the Schirmer I test, corneal and conjunctival sensation, the ocular surface disease index, corneal fluorescein staining, the numerical rating scale and the Chinese DE-related quality of life scale.Ethics and disseminationThe trial protocol and informed consent were approved by the Ethics Committee of Yueyang Hospital of Integrated Traditional Chinese and Western Medicine Affiliated to Shanghai University of Traditional Chinese Medicine (identifier: 2021–119), Shanghai Eye Disease Prevention and Treatment Center (identifier: 2022SQ003) and Eye and ENT Hospital of Fudan University (identifier: 2022014).Trial registration numberNCT05552820.
The vagina provides a characteristic low‐Na+ and low‐pH fluid microenvironment that is considered generally protective. Previous studies have shown that various types of epithelial cells harbor the ...capacity of intracellular pH (pHi) regulation. However, it remains elusive whether vaginal epithelium could actively regulate pHi by transporting acid–base ions. In this study, we verified that after transient exposure to NH4Cl, the pHi values could rapidly recover from acidification via Na+‐H+ exchanger (NHE), Na+‐HCO3− cotransporter (NBC), and carbonic anhydrase in human vaginal epithelial cell line VK2/E6E7. Positive expression of the main acid–base transporters including NHE1‐2, NBCe1‐2, and NBCn1 mRNA was also detected in VK2/E6E7 cells. Moreover, the in vivo study further showed that interfering with the function of V‐type H+‐ATPase, NHE or NBC expressed in vagina impaired vaginal luminal pH homeostasis in rats. Taken together, our study reveals the property of pH regulation in vaginal epithelial cells, which might provide novel insights into the potential role of vaginal epithelium in the formation of the vaginal acidic microenvironment.
This study demonstrated that after transient intracellular acidification, the vaginal epithelial cells could modulate the intracellular pH from a relatively acid level to the resting level via various kinds of transporters and enzyme. Moreover, vaginal luminal pH could also be regulated by the acid–base carriers in vivo, revealing an active pH regulatory characteristic of vaginal epithelia.
We previously identified a causal link between a rare patient mutation in DISC1 (disrupted-in-schizophrenia 1) and synaptic deficits in cortical neurons differentiated from isogenic patient-derived ...induced pluripotent stem cells (iPSCs). Here we find that transcripts related to phosphodiesterase 4 (PDE4) signaling are significantly elevated in human cortical neurons differentiated from iPSCs with the DISC1 mutation and that inhibition of PDE4 or activation of the cAMP signaling pathway functionally rescues synaptic deficits. We further generated a knock-in mouse line harboring the same patient mutation in the Disc1 gene. Heterozygous Disc1 mutant mice exhibit elevated levels of PDE4s and synaptic abnormalities in the brain, and social and cognitive behavioral deficits. Pharmacological inhibition of the PDE4 signaling pathway rescues these synaptic, social and cognitive behavioral abnormalities. Our study shows that patient-derived isogenic iPSC and humanized mouse disease models are integral and complementary for translational studies with a better understanding of underlying molecular mechanisms.
Tumor-associated macrophages (TAMs) are associated with poor outcomes in multiple solid cancers and play important roles in cancer progression. Epithelial-mesenchymal transition (EMT) may account for ...metastasis and recurrence. However, the association between TAMs and EMT is not clarified in triple-negative breast cancer (TNBC). The aim of this study was to investigate the effects of TAMs on EMT in TNBC.
We studied specimens from 278 patients with TNBC. TAMs marker cluster of differentiation 163 and EMT-related marker E-cadherin were detected by immunohistochemistry in TNBC tissues, and their clinical significance was evaluated from the patients' medical records.
TNBC patients with polarized cluster of differentiation 163+ TAMs infiltration and low level of E-cadherin had a significantly higher risk of aggressive features, including recurrence, histologic differentiation, and lymph node metastasis. Infiltration of TAMs was also negatively correlated with E-cadherin in TNBC tissues. Multivariate analysis indicated that infiltration of TAMs and low expression of E-cadherin were independent prognostic factors of overall survival and disease-free survival in TNBC patients.
High infiltration of TAMs was associated with low expression of E-cadherin and could be used as an unfavorable prognostic factor for patients with TNBC.
Asthma is a common heterogeneous respiratory disease characterized by airway inflammation and airway hyperresponsiveness (AHR) which is associated with abnormality in smooth muscle contractility. The ...epithelial cell-derived cytokine IL-25 is implicated in type 2 immune pathology including asthma, whereas the underlying mechanisms have not been fully elucidated. This study aims to investigate the effects of IL-25 on mouse tracheal smooth muscle contractility and elucidate the cellular mechanisms. Incubation with IL-25 augmented the contraction of mouse tracheal smooth muscles, which could be suppressed by the L-type voltage-dependent Ca
channel (L-VDCC) blocker nifedipine. Furthermore, IL-25 enhanced the cytosolic Ca
signals and triggered up-regulation of α1C L-VDCC (Ca
1.2) in primary cultured mouse tracheal smooth muscle cells. Knocking down IL-17RA/IL-17RB receptors or inhibiting the transforming growth factor-β-activated kinase 1 (TAK1)-tumor progression locus 2 (TPL2)-MAPK kinase 1/2 (MEK1/2)-ERK1/2-activating protein-1 (AP-1) signaling pathways suppressed the IL-25-elicited up-regulation of Ca
1.2 and hyperreactivity in tracheal smooth muscles. Moreover, inhibition of TPL2, ERK1/2 or L-VDCC alleviated the AHR symptom induced by IL-25 in a murine model. This study revealed that IL-25 potentiated the contraction of tracheal smooth muscle and evoked AHR via activation of TPL2-ERK1/2-Ca
1.2 signaling, providing novel targets for the treatment of asthma with a high-IL-25 phenotype.
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