Prenatal High-Sucrose Diet Induced Vascular Dysfunction of Renal Interlobar Arteries in the Offspring via PPARγ-RXRg-ROS/Akt Signaling.

SCOPE: Prenatal nutrition imbalance correlates with developmental origin of cardiovascular diseases; however whether maternal high-sucrose diet (HS) during pregnancy causes vascular damage in renal interlobar arteries (RIA) from offspring still keeps unclear. METHODS AND RESULTS: Pregnant rats are fed with normal drinking water or 20% high-sucrose solution during the whole gestational period. Swollen mitochondria and distributed myofilaments are observed in vascular smooth muscle cells of RIA exposed to prenatal HS. Maternal HS increases phenylephrine (PE)-induced vasoconstriction in the RIA from adult offspring. NG-Nitro-l-arginine (L-Name) causes obvious vascular tension in response to PE in offspring from control group, not in HS. RNA-Seq of RIA is performed to reveal that the gene retinoid X receptor g (RXRg) is significantly decreased in the HS group, which could affect vascular function via interacting with PPARγ pathway. By preincubation of RIA with apocynin (NADPH inhibitor) or capivasertib (Akt inhibitor), the results indicate that ROS and Akt are the vital important factors to affect the vascular function of RIA exposure to prenatal HS. CONCLUSION: Maternal HS during the pregnancy increases PE-mediated vasoconstriction of RIA from adult offspring, which is mainly related to the enhanced Akt and ROS regulated by the weakened PPARγ-RXRg.

Highly expressed FYN promotes the progression of placenta accreta by activating STAT3, p38, and JNK signaling pathways.

Placenta accreta is an abnormality of the placenta caused by the chorionic villi invading the muscular layer, which can cause serious bleeding, infection, shock, bladder invasion, uterine perforation, and even death. However, the etiology of placental accreta is not entirely clear. In the present study, high-throughput sequencing results showed that FYN is highly expressed in the placental accreta position in the placenta accreta group and is a key regulator of cell invasion and migration. Therefore, we aimed to evaluate the role and potential molecular mechanism of FYN in placenta accreta. The results showed that FYN was highly expressed in the placenta tissues of the placenta accreta group. Furthermore, the levels of phosphorylated STAT3, p38, and JNK in the placenta accreta group were remarkably increased compared with those in the control group. In addition, FYN knockdown considerably decreased the migration and invasion rates of trophoblast cells (HTR8/SVneo) and inhibited the levels of phosphorylated STAT3, p38, and JNK. After subsequently blocking these signaling pathways, the invasion and migration abilities of HTR8/SVneo cells were substantially decreased. In conclusion, FYN may promote excessive trophocyte cell invasion by activating STAT3, p38, and JNK pathways and can be a new target for placenta accreta prevention and treatment.

Neutrophil count is a useful marker to predict the severity of preeclampsia.

BACKGROUND: At present, pre-eclampsia is a growing concern and still a diagnostic challenge for obstetricians. AIMS: This study aimed to evaluate whether the relationship of second trimester of pregnancy neutrophil count differed among pregnancies with mild preeclampsia, severe preeclampsia, and healthy status and explore whether or not neutrophil count in the second trimester of pregnancy would be useful as new predictors of subsequent preeclampsia. PATIENTS AND METHODS: This study involved 933 pregnancies from 1 January 2018 to 30 January 2021, comprising 396 healthy pregnancies, 222 pregnancies with mild preeclampsia, and 315 pregnancies with severe preeclampsia. The relationship between preeclampsia and neutrophil count was analyzed by multiple logistic regression. In addition, maternal placental tissues of three groups were immunohistochemically stained for myeloperoxidase (MPO). RESULTS: Neutrophil count was significantly higher in pregnancies with preeclampsia (including pregnancies with mild and severe preeclampsia) than that in healthy pregnancies. The neutrophil count level was prominently higher in patients with severe preeclampsia compared with those with mild preeclampsia (p < .001). The neutrophil count level was significantly positively associated with preeclampsia after adjusting for gestational week at time of blood sampling, BMI, and age (ß:1.23; 95%CI:1.09-1.36; p < .0001). In addition, MPO expressions of placental tissues in preeclamptic groups were significantly increased than these in healthy pregnant controls (p < .05). CONCLUSIONS: Increased neutrophil count in the second trimester of pregnancy was significantly positively associated with preeclampsia. Hence, neutrophil count plays a role in predicting the severity of preeclampsia. At the same time, it may be an independent predictor of subsequent preeclampsia.Abbreviations: BMI: body mass index; MPO: myeloperoxidase.

Applications of Aptamer-Bound Nanomaterials in Cancer Therapy.

Cancer is still a major disease that threatens human life. Although traditional cancer treatment methods are widely used, they still have many disadvantages. Aptamers, owing to their small size, low toxicity, good specificity, and excellent biocompatibility, have been widely applied in biomedical areas. Therefore, the combination of nanomaterials with aptamers offers a new method for cancer treatment. First, we briefly introduce the situation of cancer treatment and aptamers. Then, we discuss the application of aptamers in breast cancer treatment, lung cancer treatment, and other cancer treatment methods. Finally, perspectives on challenges and future applications of aptamers in cancer therapy are discussed.

Mesenchymal stem cell-derived exosomes: a promising vector in treatment for diabetes and its microvascular complications.

Mesenchymal stem cell-derived exosomes (MSC-exos) are phospholipid bimolecular vesicles containing various materials, and they mediate crosstalk among cells. MSC-exos can maintain glucose homeostasis and delay the progression of diabetes and its microvascular complications through multiple mechanisms, such as by improving ß-cell viability and insulin resistance as well as through multiple signal transduction pathways. However, related knowledge has not yet been systematically summarized. Therefore, we reviewed the applications and relevant mechanisms of MSC-exos in treatments for diabetes and its microvascular complications, particularly treatments for improving islet ß-cells viability, insulin resistance, diabetic nephropathy, and retinopathy.

First trimester serum PAPP-A is associated with placenta accreta: a retrospective study.

PURPOSE: Our objective of this study was to investigate whether first trimester serum pregnancy-associated plasma protein-A (PAPP-A) differed amongst pregnancies with placenta previa-accreta and non-adherent placenta previa and healthy pregnancies by a retrospective cohort analysis. METHODS: A total of 177 pregnant females were included in the study, as follows: 35 cases of placenta previa-accreta, 30 cases of non-adherent placenta previa, and 112 cases of BMI and age matched, healthy pregnant controls. PAPP-A multiples of the median (MoM) were acquired from laboratory data files in 1 January 2017-30 September 2019. The probable maternal serum biochemical predictor of placenta accreta was analyzed by using multiple logistic regression analysis. RESULTS: PAPP-A MoM of placenta previa-accreta group was significantly higher than those of the non-adherent placenta previa group and control group (p = 0.009 < 0.05, p < 0.001). Serum PAPP-A was found to be significantly positively associated with placenta accreta after adjusted gestational week at time of blood sampling, BMI, age, smoking, and previous cesarean section history (OR: 3.51; 95% CI: 1.77-6.94; p = 0.0003 < 0.05). In addition, smoking (OR: 9.17; 95% CI: 1.69-49.62; p = 0.010 < 0.05) and previous cesarean section history (OR: 2.75; 95% CI: 1.23-6.17; p = 0.014 < 0.05) were also significantly associated with placenta accreta. CONCLUSION: Increased first trimester serum PAPP-A was significantly positively associated with placenta accreta, suggesting that the potential role of PAPP-A in identifying pregnancies at high risk for placenta accreta. Smoking and previous cesarean section history may be the risk factors for accreta in placenta previa patients.

Ultra-Sensitive Dopamine Sensor Using Stable Black Phosphorus Quantum Dots.

The use of various optical methods for detection of dopamine (DA), such as colorimetry, fluorometry, surface-enhanced Raman spectroscopy (SERS), and electrochemiluminescence (ECL), has progressively matured over the past decade. However, the development of a simple, inexpensive, and quick detection method for dopamine still remains a challenge. Herein, we used stable black phosphorus quantum dots (BPQDs) for sensitive and selective detection of dopamine by UV-Vis spectroscopy. The initial UV-Vis absorption peaks of the BPQDs in aqueous solution were effectively quenched upon the addition of DA. The quenching efficiency was proportional to the concentration of DA within the range of 1 nM to 70 nM or 1 nM to 1250 nM (encompassing physiological DA concentrations) with a low detection limit of 0.33 nM (pH 5˜9). This optical analysis method provides a platform for the detection of dopamine, which has many advantages such as high sensitivity, selectivity, stability, low cost, non-toxicity, and so on.

Characteristic of HPV Integration in the Genome and Transcriptome of Cervical Cancer Tissues.

High-risk HPV is clearly associated with cervical cancer. HPV integration has been confirmed to promote carcinogenesis in the previous studies. In our study, a total of 285 DNA breakpoints and 287 RNA breakpoints were collected. We analyzed the characteristic of HPV integration in the DNA and RNA samples. The results revealed that the patterns of HPV integration in RNA and DNA samples differ significantly. FHIT, KLF5, and LINC00392 were the hotspot genes integrated by HPV in the DNA samples. RAD51B, CASC8, CASC21, ERBB2, TP63, TEX41, RAP2B, and MYC were the hotspot genes integrated by HPV in RNA samples. Breakpoints of DNA samples were significantly prone to the region of INTRON (P < 0.01, Chi-squared test), whereas in the RNA samples, the breakpoints were prone to EXON. Pathway analysis had revealed that the breakpoints of RNA samples were enriched in the pathways of transcriptional misregulation in cancer, cancer pathway, and pathway of adherens junction. Breakpoints of DNA samples were enriched in the pathway of cholinergic synapse. In summary, our data helped to gain insights into the HPV integration sites in DNA and RNA samples of cervical cancer. It had provided theoretical basis for understanding the mechanism of tumorigenesis from the perspective of HPV integration in the HPV-associated cervical cancers.