The role of immune cell signatures in the pathogenesis of ovarian-related diseases: a causal inference based on mendelian randomization.

BACKGROUND: Immune cells play a pivotal role in maintaining ovarian function. However, the specific contributions of different immune cell phenotypes to the pathogenesis of specific ovarian-related diseases remain poorly understood. We aim to investigate the correlation between 731 immunophenotypes and ovarian-related diseases. MATERIALS AND METHODS: Utilizing publicly available genetic data, we undertook a series of quality control measures to identify instrumental variables (IVs) associated with exposure. Subsequently, we conducted two-sample Mendelian randomization (MR) using inverse variance weighting to explore the causal relationships between 731 immune cell features and six ovarian-related diseases: ovarian cysts, ovarian dysfunction, premature ovarian failure (POF), polycystic ovary syndrome (PCOS), benign neoplasm of ovary, and malignant neoplasm of ovary at the genetic level. Sensitivity analyses, including leave-one-out and other MR analysis models, were performed. Finally, Bayesian colocalization (COLOC) analysis was employed to identify specific co-localized genes, thereby validating the MR results. RESULTS: At the significance level corrected by Bonferroni, four immune phenotypes, including CD25 on IgD- CD38- B cells, were associated with ovarian cysts; four immune phenotypes, including CD39+ CD4+ T cell Absolute Count, were associated with ovarian dysfunction; eight immune phenotypes, including SSC-A on HLA DR+ CD8+ T cells, were associated with POF; five immune phenotypes, including CD20- CD38- B cell Absolute Count, were associated with PCOS; five immune phenotypes, including CD4+ CD8dim T cell Absolute Count, were associated with benign ovarian tumors; and three immune phenotypes, including BAFF-R on IgD- CD38+ B cells, were associated with malignant ovarian tumors. Sensitivity analysis indicated robust results. COLOC analysis identified four immune cell co-localized variants (rs150386792, rs117936291, rs75926368, rs575687159) with ovarian diseases. CONCLUSION: Our study elucidates the close genetic associations between immune cells and six ovarian-related diseases, thereby providing valuable insights for future research endeavors and clinical applications.

The association between childhood adiposity in northeast China and anthropogenic heat flux: A new insight into the comprehensive impact of human activities.

Anthropogenic heat has been reported to have significant health impacts, but research on its association with childhood adiposity is still lacking. In this study, we matched the 2008-2012 average anthropogenic heat flux, as simulated by a grid estimation model using inventory methods, with questionnaire and measurement data of 49,938 children randomly recruited from seven cities in Northeast China in 2012. After adjusting for social demographic and behavioral factors, we used generalized linear mixed-effect models to assess the association between anthropogenic heat flux and adiposity among children. We also examined the effect modification of various social demographic and behavioral confounders. We found that each 10 W/m2 increase in total anthropogenic heat flux and that from the industry source was associated with an increase of 5.82% (95% CI = 0.84%-11.05%) and 6.62% (95% CI = 0.87%-12.70%) in the odds of childhood adiposity. Similarly, the excess rate of adiposity among children were 5.26% (95% CI = -1.33%-12.29%) and 8.51% (95% CI = 2.24%-15.17%) per 1 W/m2 increase in the anthropogenic heat flux from transportation and buildings, and was 7.94% (95% CI = 2.28%-13.91%) per 0.001 W/m2 increase in the anthropogenic heat flux from human metabolism. We also found generally greater effect estimates among female children and children who were exposed to passive smoking during pregnancy, born by caesarean section, non-breastfed/mixed-fed, or lived within 20 m adjacent to the main road. The potential deleterious effect of anthropogenic heat exposure on adiposity among children may make it a new but major threat to be targeted by future mitigation strategies.

The Effects of Acute Exposure to Ammonia on Oxidative Stress, Hematological Parameters, Flesh Quality, and Gill Morphological Changes of the Large Yellow Croaker (Larimichthys crocea).

Ammonia is considered to be the major chemical pollutant causing fish poisoning in aquaculture. This research aimed to evaluate the impact of acute ammonia exposure on the large yellow croaker's meat quality, gill morphology, liver oxidative stress, and hematological parameters. The fish were exposed to total ammonia nitrogen concentrations of 0, 2.96, 5.92, and 8.87 mg/L for 48 h, respectively. The findings demonstrated that all ammonia-exposed fish had higher liver lactate dehydrogenase and glutamic oxalate transaminase activities. The glucose, blood urea nitrogen, and creatinine levels in 8.87 mg/L total ammonia nitrogen (TAN) were higher than other samples. The total protein, albumin, and triglyceride levels in serum decreased significantly in ammonia-exposed samples. After 48 h of ammonia exposure, superoxide dismutase activities showed a 76.1%, 118.0%, and 156.8% increase when fish were exposed to 2.96, 5.92, and 8.87 mg/L TAN, respectively. Catalase activities and glutathione contents were considerably higher (p < 0.05) in all ammonia-treated samples compared to 0 mg/L TAN. The ammonia-treated gill lamellae become thicker, shorter, and curved. Additionally, the ammonia exposure resulted in the accumulation of free amino acids and the loss of nucleotides. The inosine monophosphate and adenosine monophosphate contents in the flesh were decreased after 12 h of exposure to 2.96, 5.92, and 8.87 mg/L ammonia compared to the control group. Overall, large yellow croakers exposed to ammonia for 6 h presented not only changes in serum composition but also oxidative stress, liver and gill tissue damage and flesh quality deterioration.

Effect of different stunning methods on antioxidant status, myofibrillar protein oxidation, and gelation properties of large yellow croaker during postmortem.

Post-mortem muscle biochemical processes play a crucial role on fish fillets quality and they are strictly linked to stunning methods. The improper stunning methods before slaughter could cause the fish to deteriorate more quickly during cold storage. This study aimed to investigate the effect of stunning methods (hit on the head, T1; gill cut, T2; immersion in ice/water slurry, T3; CO2 narcosis, T4; 40% CO2 + 30 % N2 + 30% O2, T5) on myofibrillar proteins (MPs) of large yellow croaker. The results indicated that T2 and T3 samples were significantly damaged compared with other samples, which reflected that the activities of total superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) were significantly damaged during cold storage in T2 and T3 samples. And the gill cut and immersion in ice/water slurry resulted in the generation of protein carbonyl, the decrease of Ca2+-ATPase, free ammonia and protein solubility, and the production of dityrosine during storage. In addition, MPs gel of T2 and T3 samples showed the decrease of water hold capacity (WHC) and whiteness, structure destruction, and water migration. The T4 samples had the least damage of MPs and gel structure during cold storage.

Comparative transcriptome responses of leaf and root tissues to salt stress in wheat strains with different salinity tolerances.

Background: Salinity stress is a major adverse environmental factor that can limit crop yield and restrict normal land use. The selection of salt-tolerant strains and elucidation of the underlying mechanisms by plant breeding scientists are urgently needed to increase agricultural production in arid and semi-arid regions. Results: In this study, we selected the salt-tolerant wheat (Triticum aestivum) strain ST9644 as a model to study differences in expression patterns between salt-tolerant and salt-sensitive strains. High-throughput RNA sequencing resulted in more than 359.10 Gb of clean data from 54 samples, with an average of 6.65 Gb per sample. Compared to the IWGSC reference annotation, we identified 50,096 new genes, 32,923 of which have functional annotations. Comparisons of abundances between salt-tolerant and salt-sensitive strains revealed 3,755, 5,504, and 4,344 genes that were differentially expressed at 0, 6, and 24 h, respectively, in root tissue under salt stress. KEGG pathway analysis of these genes showed that they were enriched for phenylpropanoid biosynthesis (ko00940), cysteine and methionine metabolism (ko00270), and glutathione metabolism (ko00480). We also applied weighted gene co-expression network analysis (WGCNA) analysis to determine the time course of root tissue response to salt stress and found that the acute response lasts >6 h and ends before 12 h. We also identified key alternative splicing factors showing different splicing patterns in salt-sensitive and salt-tolerant strains; however, only few of them were differentially expressed in the two groups. Conclusion: Our results offer a better understanding of wheat salt tolerance and improve wheat breeding.

The green lacewing Chrysopa formosa as a potential biocontrol agent for managing Spodoptera frugiperda and Spodoptera litura.

Understanding predator-prey interactions is essential for successful pest management by using predators, especially for the suppression of novel invasive pest. The green lacewing Chrysopa formosa is a promising polyphagous predator that is widely used in the biocontrol of various pests in China, but information on the control efficiency of this predator against the seriously invasive pest Spodoptera frugiperda and native Spodoptera litura is limited. Here we evaluated the predation efficiency of C. formosa adults on eggs and first- to third-instar larvae of S. frugiperda and S. litura through functional response experiments and determined the consumption capacity and prey preference of this chrysopid. Adults of C. formosa had a high consumption of eggs and earlier instar larvae of both prey species, and displayed a type II functional response on all prey stages. Attack rates of the chrysopid on different prey stages were statistically similar, but the handling time increased notably as the prey developed. The highest predation efficiency and shortest-handling time were observed for C. formosa feeding on Spodoptera eggs, followed by the first-instar larvae. C. formosa exhibited a significant preference for S. litura over S. frugiperda in a two-prey system. In addition, we summarized the functional response and predation efficiency of several chrysopids against noctuid pests and made a comparison with the results obtained from C. formosa. These results indicate that C. formosa has potential as an agent for biological control of noctuid pests, particularly for the newly invasive pest S. frugiperda in China.

Development of Zein/tannic acid nanoparticles as antioxidants for oxidation inhibition of blackberry seed oil emulsions.

The zein-tannic acid nanoparticles (ZTNPs) were developed as antioxidants for oxidation inhibition of blackberry seed oils. These particles were spherical with an average diameter below 200 nm. The results of structural characterization indicated that tannic acid was bound to zein by electrostatic, hydrophobic, and hydrogen bonding interactions, resulting in the conformational changes of zein. The antioxidant capacity of zein was significantly improved by binding of tannic acid, which suggested ZTNPs had a 2-Phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl 3-Oxide (PTIO) radical scavenging rate as high as 77.5 % at pH 4. Moreover, ZTNPs at pH 7 exhibited a higher thermal stability and better resistance to emulsion lipid oxidation. They inhibited the formation of ROOH and TBARS of blackberry seed oil emulsions during storage by covering at the oil-water interface with an adsorption rate of approximately 100 %, forming a dense particle film to reduce the oxygen content and prevent the continuation of the oxidation process.

Analyzing the interactions of mRNAs, miRNAs and lncRNAs to predict ceRNA networks in bovine cystic follicular granulosa cells.

Cross-talk between competitive endogenous RNAs (ceRNAs) may play a critical role in revealing potential mechanism of bovine follicular cysts. Ovarian cyst has always been an intractable scientific problem and has led to considerable economic losses to bovine breeding industry. However, its pathogenesis and molecular mechanisms are still not well understood. Here, this study aimed to investigate the role of non-coding RNAs (ncRNAs) and the ceRNA networks in bovine follicular cyst. Whole transcriptome sequencing of bovine follicular granulosa cells (GCs) was conducted to obtain the expression profiles of mRNAs, lncRNAs and miRNAs. The results for the identified expressions of 8,003 mRNAs, 579 lncRNAs and 205 miRNAs were often altered between cystic and normal follicular GCs. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed on these differentially expressed mRNAs. Furthermore, the ceRNA network combining mRNAs, miRNAs, and lncRNAs using several bioinformatics methods based on co-expression analysis between the differentially expressed RNAs was conducted. Finally, the lncRNA NONBTAT027373.1-miR-664b-HSD17B7 pathway was verified by dual-luciferase reporting assay and RNA binding protein immunoprecipitation (RIP) assay. LncRNA NONBTAT027373.1 sponged miR-664b in GCs and prevented miR-664b from binding to the HSD17B7 3'-UTR. These results indicated that genes and lncRNAs related to steroid hormone synthesis and energy metabolism could play important roles in the formation of bovine cystic follicles through the ceRNA mechanism and represent candidate targets for further research. This can be used as a practical guideline for promoting healthy and highly efficient development in the bovine industry.

Immune-Related lncRNAs with WGCNA Identified the Function of SNHG10 in HBV-Related Hepatocellular Carcinoma.

Objective: The hepatitis B virus (HBV) infection led to hepatitis, which was one of common reasons for hepatocellular carcinoma (HCC). The immune microenvironment alteration played a crucial role in this process. The study aimed to identify immune-related long noncoding RNAs (lncRNAs) in HBV-related HCC and explore potential mechanisms. Methods: In total, 1,072 immune-related genes (IRGs) were enriched in different co-expression modules with weighted gene co-expression network analysis (WGCNA) combining the corresponding clinical features in HBV-related HCC. The immune-related lncRNAs were selected from the crucial co-expression model based on the correlation analysis with IRGs. The immune-related lncRNAs were furtherly used to construct prognostic signature by the Cox proportional hazards regression and Lasso regression. Furthermore, the proliferation and migration ability of lncRNA SNHG10 were verified in vitro. Results: A total of nine co-expression modules were identified by WGCNA of which the "red" co-expression module was most correlated with various clinical characteristics. Additionally, the IRGs in this module were significantly enriched in multiple immune-related pathways. The twelve immune-related lncRNAs prognostic signature (HAND2-AS1, LINC00844, SNHG10, MALAT1, LINC00460, LBX2-AS1, MIR31HG, SEMA6A-AS1, LINC1278, LINC00514, CTBP-AS2, and LINC00205) was constructed. The risk score was an independent risk factor in HBV-related HCC and verified by principal components analysis (PCA), nomogram, and PCR between different cell lines. Moreover, the proportion of immune cells were significantly different between high-risk score group and low-risk score group. The malignant behavior of Hep3B was significantly different between si-lncRNA SNHG10 and control group. Conclusions: The immune-related lncRNAs prognostic signature provided some potential biomarkers and molecular mechanisms in HBV-related HCC.

Hulless Black Barley as a Carrier of Probiotics and a Supplement Rich in Phenolics Targeting Against H2O2-Induced Oxidative Injuries in Human Hepatocarcinoma Cells.

Lactic acid bacteria can provide benefits to human beings and transform phenolic substances to improve their potential functionality. It was of interest to develop black barley as a carrier of probiotics and nutraceutical supplement rich in more antioxidants. Due to fermentation, bacterial counting and free phenolic content in black barley increased to 9.54 ± 0.22 log cfu/mL and 5.61 ± 0.02 mg GAE/mL, respectively. Eleven phenolic compounds, including nine isoflavones and two nitrogenous compounds were characterized using UPLC-QTOF-MS, among which epicatechin, hordatine, and pelargonidin aglycone were largely enriched. Moreover, free phenolic extracts from fermented barley (F-BPE) played a greater role in scavenging DPPH radicals, reducing Fe3+ to Fe2+, and increasing oxygen radical absorbance capacity, compared phenolic extracts from unfermented barley [UF-BPE (1.94-, 1.71-, and 1.35-fold at maximum for F-BPE vs. UF-BPE, respectively)]. In hepatocarcinoma cells, F-BPE also better inhibited ROS production and improved cell viability, cell membrane integrity, SOD activity, and non-enzymatic antioxidant GSH redox status (2.85-, 3.28-, 2.05-, 6.42-, and 3.99-fold at maximum for F-BPE vs. UF-BPE, respectively).

The Role of Tumor Deposits in Predicting the Efficacy of Chemotherapy in Stage III Colon Cancer.

PURPOSE: To evaluate the role of tumor deposits (TDs) in predicting the efficacy of chemotherapy in stage III colon cancer. METHODS: Using the SEER∗Stat software Version 8.3.6, we started with a national cohort of colon cancer cases diagnosed between 2004 and 2016. We used the χ2 (Chi-square) test to compare differences between different categorical variables according to the number of TDs. The Cox proportional hazards regression model was used to determine the independent association of different clinical and pathological variables with CSS, which were adjusted for other significant prognostic factors. RESULTS: We have identified 29,017 patients diagnosed with stage III colon cancer from the SEER database. The results of multivariate analyses showed that patients with the receipt of chemotherapy had 54.7% decreased risk of cancer-specific mortality compared with those not (HR = 0.453, 95% CI = 0.425-0.483, P < 0.0001) in the no-TD group; In the 1-2-TD group, patients with the receipt of chemotherapy had 56.8% decreased risk of cancer-specific mortality compared with those not (HR = 0.432, 95% CI = 0.364-0.512, P < 0.0001); In the ≥3-TD group, patients with the receipt of chemotherapy had 51.8% decreased risk of cancer-specific mortality compared with those not (HR = 0.482, 95% CI = 0.389-0.597, P < 0.0001). CONCLUSIONS: Our study demonstrated that the presence of TDs was associated with a dismal prognosis and high number of TDs would also contribute to the worse survival of colon cancer. High number of TDs did not affect the survival benefit of chemotherapy in stage III colon cancer.

Gene Signature and Identification of Clinical Trait-Related m6 A Regulators in Pancreatic Cancer.

Pancreatic cancer (PC) has a very poor prognosis and is usually diagnosed only at an advanced stage. The discovery of new biomarkers for PC will help in early diagnosis and a better prognosis for patients. Recently, N6-methyladenosine (m6A) RNA modifications and their regulators have been implicated in the development of many cancers. To investigate the functions and mechanisms of m6A modifications in the development of PC, 19 m6A regulators, including m6A-methyltransferases (ZC3H13, RBM15/15B, WTAP, KIAA1429, and METTL3/14), demethylases (FTO and ALKBH5), and binding proteins (YTHDF1/2/3, YTHDC1/2, IGF2BP1/2/3, HNRNPC, and HNRNPA2B1) were analyzed in 178 PC tissues from the cancer genome atlas (TCGA) database. The results were verified in PC cell lines Mia-PaCa-2, BXPC-3, and the control cell line HDE-CT. The m6A regulators-based sample clusters were significantly related to overall survival (OS). Further, lasso regression identified a six-m6A-regulator-signature prognostic model (KIAA1429, HNRNPC, METTL3, YTHDF1, IGF2BP2, and IGF2BP3). Model-based high-risk and low-risk groups were significantly correlated with OS and clinical traits (pathologic M, N, and clinical stages and vital status). The risk signature was verified as an independent prognostic marker for patients with PC. Finally, gene set enrichment analysis revealed m6A regulators (KIAA1429, HNRNPC, and IGF2BP2) were related to multiple biological behaviors in PC, including adipocytokine signaling, the well vs. poorly differentiated tumor pathway, tumor metastasis pathway, epithelial mesenchymal transition pathway, gemcitabine resistance pathway, and stemness pathway. In summary, the m6A regulatory factors which related to clinical characteristics can be involved in the malignant progression of PC, and the constructed risk markers may be a promising prognostic biomarker that can guide the individualized treatment of PC patients.

Comparative Study of Microbiological Monitoring Results from Three Types of Sampling Methods after Gastrointestinal Endoscope Reprocessing.

OBJECTIVE: Compare the effects of three sampling methods on the microbiological monitoring results after reprocessing of gastrointestinal endoscopes, providing scientific basis for improving the monitoring quality of gastrointestinal endoscope cleaning and disinfection. METHOD: Gastrointestinal endoscopes after reprocessing were selected randomly at the gastrointestinal endoscopy center of a tertiary hospital in Shanghai from October 2018 to February 2019. The endoscopes selected were all sampled in three different methods under continuous sampling and intermittent sampling respectively. Methods used includes, the biopsy channel group (Group A), the entire channel group (Group B), and the disc brush group (Group C). Then the colony forming units (CFU/piece) were counted in the laboratory. RESULTS: A total of 12 endoscopes were sampled by using continuous sampling approach, in which the detection rate of bacteria in disc brush group (33.3%) and entire channel group (33.3%) was higher than biopsy channel group (8.3%). Among the 12 endoscopes sampled with intermittent approach, the detection rate of bacteria from high to low was the disc brush group (50%), the entire channel group (41.7%), and the biopsy channel group (8.3%). CONCLUSION: Different sampling methods will lead to the difference of microbiological culture results after reprocessing of gastrointestinal endoscope, indicating that the improved sampling method is beneficial to objectively reflect the endoscope cleaning and disinfection effect, and improve the monitoring quality of endoscope disinfection.

Reactive ion etching for fabrication of biofunctional titanium nanostructures.

One of the major problems with the bone implant surfaces after surgery is the competition of host and bacterial cells to adhere to the implant surfaces. To keep the implants safe against implant-associated infections, the implant surface may be decorated with bactericidal nanostructures. Therefore, fabrication of nanostructures on biomaterials is of growing interest. Here, we systematically studied the effects of different processing parameters of inductively coupled plasma reactive ion etching (ICP RIE) on the Ti nanostructures. The resultant Ti surfaces were characterized by using scanning electron microscopy and contact angle measurements. The specimens etched using different chamber pressures were chosen for measurement of the mechanical properties using nanoindentation. The etched surfaces revealed various morphologies, from flat porous structures to relatively rough surfaces consisting of nanopillars with diameters between 26.4 ± 7.0 nm and 76.0 ± 24.4 nm and lengths between 0.5 ± 0.1 µm and 5.2 ± 0.3 µm. The wettability of the surfaces widely varied in the entire range of hydrophilicity. The structures obtained at higher chamber pressure showed enhanced mechanical properties. The bactericidal behavior of selected surfaces was assessed against Staphylococcus aureus and Escherichia coli bacteria while their cytocompatibility was evaluated with murine preosteoblasts. The findings indicated the potential of such ICP RIE Ti structures to incorporate both bactericidal and osteogenic activity, and pointed out that optimization of the process conditions is essential to maximize these biofunctionalities.

Anti-tumor efficacy of phellamurin in osteosarcoma cells: Involvement of the PI3K/AKT/mTOR pathway.

The extracts of Phellodendron amurense (P. amurense) have been shown to contain many active ingredients e.g. flavone glycosides and to exert a wide range of physiological activities including anti-tumor activity. However, the effects of phellamurin (Phe), a plant flavonone glycoside from the leaves of P. amurense, on osteosarcoma (OS) have never been reported. The effects of Phe on cell viability and apoptosis were evaluated by MTT assay and flow cytometry analysis, respectively. Western blot analysis was performed to detect the protein levels of phosphorylated phosphatidylinositol 3 kinase (PI3K) (p-PI3K), phosphorylated protein kinase B (AKT) (p-AKT), AKT, phosphorylated mammalian target of rapamycin (mTOR) (p-mTOR), and mTOR. We found that Phe suppressed the viability and promoted apoptosis in OS cells in a dose-dependent manner. Notably, Phe repressed the PI3K/AKT/mTOR pathway in OS cells. LY294002 effectively inhibited the PI3K/AKT/mTOR signaling pathway, repressed cell viability and induced apoptosis in OS cells. Activation of PI3K/AKT/mTOR pathway by 740Y-P abolished the effects of Phe on the viability and apoptosis of OS cells. We also found that Phe repressed OS tumor growth and inhibited the PI3K/AKT/mTOR pathway in vivo. In conclusion, Phe suppressed the viability and induced apoptosis in OS cells, at least, partially by inhibiting the PI3K/AKT/mTOR pathway. Our study suggested that Phe might be a new and potential chemotherapeutic agent for the treatment of OS.

Ribophorin II potentiates P-glycoprotein- and ABCG2-mediated multidrug resistance via activating ERK pathway in gastric cancer.

Multidrug resistance (MDR) is a critical reason of cancer chemotherapy failure. Ribophorin II (RPN2) has emerged as a vital regulator of MDR in multiple cancers including gastric cancer (GC). However, the roles and molecular mechanisms of RPN2 in MDR have not been well featured till now. The present study aimed to explore the roles and molecular mechanisms of RPN2 in MDR of drug-resistant GC cells. Results showed that the expressions of RPN2, multidrug resistance 1 (MDR1), and ATP binding cassette subfamily G member 2 (ABCG2) were upregulated in SGC7901/DDP and SGC7901/VCR cells. Knockdown of RPN2 alleviated MDR through downregulating MDR1 and ABCG2 expressions in SGC7901/DDP and SGC7901/VCR cells. RPN2 depletion inhibited the activation of MEK/ERK pathway. RPN2 overexpression enhanced MDR by upregulating P-glycoprotein (P-gp) and ABCG2 protein expressions in SGC7901/DDP or SGC7901/VCR cells, while this effect of RPN2 was abrogated by ERK knockdown or treatment with ERK inhibitor PD98059. Our findings suggested that RPN2 potentiated P-gp- and ABCG2-mediated MDR via activating MEK/ERK pathway in GC, hinting the critical values of RPN2 in ameliorating MDR and providing a promising target for GC therapy.

miR-4262, low level of which predicts poor prognosis, targets proto-oncogene CD163 to suppress cell proliferation and invasion in gastric cancer.

BACKGROUND: miR-4262 was identified as a tumor promoter in several cancers, but its exact role in gastric carcinoma is still largely unknown. METHODS: The expression of miR-4262 was detected in gastric cancer tissues. Different concentrations of miR-4262 mimic and miR-4262 antagomir were respectively transfected into primary gastric carcinoma cells. After incubation for 72 h, the overexpression efficiencies were confirmed by qPCR, cell proliferation was detected with the CCK-8 assay, cell apoptosis was detected by using the PI/Annexin V Cell Apoptosis Kit, and cell invasion was detected with the Transwell invasion assay. The molecular mechanisms underlying the action of miR-4262 in gastric carcinoma cells were also explored. RESULTS: In this study, we found that miR-4262 was significantly downregulated in gastric tissue from gastric cancer patients compared with that from the control group. Moreover, the level of miR-4262 was significantly lower in advanced gastric carcinoma. Additionally, lower level of miR-4262 was correlated with poorer prognosis and lower survival rate in gastric cancer patients. Then, different concentrations of miR-4262 mimic and miR-4262 antagomir were transfected into primary gastric carcinoma cells, respectively. The results showed that miR-4262 mimic suppressed proliferation and invasion and promoted cell apoptosis in a dose-dependent manner in gastric carcinoma cells. In contrast, miR-4262 antagomir increased proliferation and invasion and decreased cell apoptosis in a dose-dependent manner in gastric carcinoma cells. Furthermore, miR-4262 could directly target and suppress the expression of the proto-oncogene CD163. CONCLUSION: Our findings indicate that lower level of miR-4262 predicts poorer prognosis in gastric patients, and miR-4262 can target proto-oncogene CD163 to suppress gastric cancer cell proliferation and invasion.

Differential expression of microRNA-411 and 376c is associated with hypertension in pregnancy

Preeclampsia is a major reason of morbidity and mortality in pregnant women and perinatal fetus. Hence, it is of prime importance that diagnostic markers are defined to predict chances of preeclampsia in pregnant women. It has been previously shown that microRNA (miRNA)-376c expression is decreased in the placenta of preeclampsia patients at term. Even though this decrease was not mimicked in the placenta at the pre-term stage, miR-376c expression was decreased in the plasma of these patients as early as the second trimester. Plasma and placenta specimens were obtained from pregnant women having unifetal gestation undergoing perinatal care between January 2014 and December 2016 (n=49). Early trimester placentas were collected from patients undergoing terminated pregnancies through dilation and curettage procedure. Our results showed that in addition to miR-376c, miR-441 levels were decreased in the placenta of preeclampsia patients, and this decrease occurred both at pre-term and at term. This decrease is also mimicked in the plasma levels at both early and late weeks of pregnancy, highlighting that miR-441 levels can serve as a diagnostic marker of risk of preeclampsia in pregnant women. Overexpression of the miR-441, as well as miR-376c, promoted cell viability, migration, and invasion in the human immortalized cytotrophoblast cell line HTR8/SVneo, indicating that their decrease in pregnant women would result in anomalous apoptosis and functional imbalance resulting in premature abortion and other complications. MiR-441 level can thus potentially serve as diagnostic marker of preeclampsia in pregnant women.

Pain control for patients with hepatocellular carcinoma undergoing CT-guided percutaneous microwave ablation.

BACKGROUND: Hepatic percutaneous microwave ablation (MWA) is usually performed in patients under conscious sedation. Nonetheless, many patients reported pain during the procedure. The current study investigated the safety and effectiveness of analgesia given at personalized dosage during the MWA procedure. METHODS: A total of 100 patients with hepatocellular carcinomas (HCCs) were included in this study. These patients underwent CT-guided percutaneous MWA between February and October 2017. Patients were randomized into two groups: Experimental group (n = 50) and Control group (n = 50). Patients in the Control group were given 5 mg of morphine intravenously, followed by 10 mg of morphine injected subcutaneously 30 min before surgery. Patients in the Experimental group were given a personalized dosage of morphine during the procedure when the Visual Analogue Scale (VAS) was ≥4. Other clinical and treatment parameters were also analysed. RESULTS: A significantly less amount of morphine (p < 0.001) was used in the experimental group (7.18 ± 1.65 mg) than in the control group (17.40 ± 2.52 mg). No significant differences were found in the number of patients who needed to discontinue the surgery (p = 0.242). Other clinical parameters including heart rate, systolic and diastolic blood pressures at various time points were comparable. Importantly, a lower VAS was reported in the experimental group, indicating a lower pain intensity experienced by patients during the procedure. CONCLUSION: The administration of personalized dosage of morphine to HCC patients undergoing percutaneous MWA is an effective and safe procedure for pain control.

Effectiveness and safety of CT-guided percutaneous radiofrequency ablation of adrenal metastases.

OBJECTIVE: The imaging-guided percutaneous radiofrequency (RF) ablation of adrenal metastases is a relatively new treatment procedure, compared to the more widespread application of the technique for the treatment of liver and renal cancers. The present study aims to evaluate the safety and efficacy of the CT-guided percutaneous RF ablation of adrenal metastases in a cohort of patients. METHODS: 33 patients with 38 adrenal metastases who received percutaneous CT-guided RF ablation between 2012 to 2015 were retrospectively reviewed. The average diameter of the treated adrenal metastases was 3.0 ± 1.6 cm. The treatment outcomes, including presence of residual tumours, technical success rate, recurrence rate, and complications, were evaluated. Patients were followed up for every 3 months to monitor the progression of the disease. RESULTS: Postoperative CT images showed the lack of tumour enhancement in 30 tumours (30/38 tumours, technical success rate = 78.9%), and residual disease was found in 7 tumours (7/37 tumours, 18.9%). The rate of residual disease was significantly lower in the group with tumour size <3 cm than the group with tumour size ≥3 cm (p = 0.025). The severe complication rate was 4.3%, and the mild complication rate was 48%, with intraoperative hypertensive crisis as the most frequently observed complication (27.3%). The follow-up data showed that 76.3% of patients had recurrence-free survival in 27.4 months. CONCLUSION: The current study demonstrated that radiofrequency ablation is a relatively safe and effective treatment for controlling adrenal metastases, especially for patients with tumour size <3 cm. Advances in knowledge: Surgical resection of the adrenal metastases was advocated as one of the treatment options for patients. The present study showed that radiofrequency ablation is a relatively safe and effective treatment for controlling adrenal metastases.