Efficacy of a combination of sildenafil and magnesium sulfate in the treatment of persistent pulmonary hypertension of the newborn, and its influence on hemodynamics

Purpose: To investigate the efficacy of the combined use of sildenafil and magnesium sulfate in the treatment of persistent pulmonary hypertension of the newborn (PPHN), and its influence on hemodynamics.Methods: A total of 174 children with persistent pulmonary hypertension who were treated in Ganzhou People’s Hospital, Ganzhou, China were selected and randomly assigned to joint group (JG) and control group (CG), with 87 patients in each group. The CG group received magnesium sulfate, while the JG group received sildenafil plus magnesium sulphate. The respiratory parameters of the children were analyzed using blood gas analyzer, while their hemodynamic indices were evaluated using color Doppler echocardiography. The levels of cytokines and inflammatory factors were determined by enzyme-linked immunosorbent assay (ELISA).Results: Time taken for symptom disappearance, oxygen therapy, and hospitalization period were shorter in JG than in CG (p < 0.05). Post-treatment, the respiratory parameters (PaO2, PaCO2, and SaO2) in both groups s improved, with lower levels of PaO2 and PaCO2, and a higher level of SaO2 in JG (p < 0.05). Following treatment, the levels of systemic vascular resistance (SVR), posterior pulmonary vascular resistance (PVR) and pulmonary artery pressure (PA) in JG were significantly reduced, relative to CG (p < 0.05). Similarly, the expression of endothelin -1 (ET-1), brain natriureticpeptide (BNP), and angiotensin 1 (ANG-1) improved, with lower levels of ET-1 and BNP, and a higher level of ANG-1 in JG (p < 0.05). There was post-treatment reduction as well in IL-6 and TNF-α, with lower levels in JG (p < 0.05). Patients in JG showed higher total treatment effectiveness and a lowerincidence of adverse reactions than those in CG (p < 0.05).Conclusion: The combined use of sildenafil and magnesium sulfate enhances the management of PPHN, ameliorates respiratory parameters, hemodynamics, and levels of cytokines and inflammatory factors. These findings provide evidence-based medical references for a new treatment strategy for PPHN

Upregulation of AKAP12 by demethylation inhibits proliferation and increases chem osensitivity to adriamycin in leukemic cells

Purpose: To elucidate the role of AKAP12 in leukemia cells.Methods: Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blotting (WB) were employed to determine the expression of AKAP12 in leukocyte cell lines, while 5-azacytidine was used to treat the cells, followed by assessment of the expression of AKAP12. After constructing the overexpressing vector pc-AKAP12 and transfecting it into cells or treating the cells with 5-azacytidine, cell counting kit-8 assay (CCK-8) was used to determine cell proliferation. Cloning ability of the cells was evaluated by colony formation assay.  Furthermore, flow cytometry was employed to measure the degrees of cell cycle and cell apoptosis. The effect of AKAP12 on PI3K/AKT were determined by western blot.Results: The results showed that AKAP12 was lowly expressed in lymphocytic leukemia cell lines (p < 0.001), but was reversed by 5-azacytidine. Transfection of AKAP12 or 5-azacytidine treatment increased the expression of AKAP12 in the cells (p > 0.001), inhibited leukemia cell proliferation and clonality, and arrested cell cycle in G1 phase as well as induced apoptosis. In addition, PI3K/AKT signaling pathway was inhibited by AKAP12.Conclusion: AKAP12 is lowly expressed in leukemia cells, and may also play a role in inhibiting leukemia progression by suppressing the activity of PI3K/AKT pathway.Thus, targeting AKAP12 mght be a potential strategy in the management of lukemia

Alcohol Intake and Abnormal Expression of Brf1 in Breast Cancer.

Breast cancer is the most common malignant disease of females. Overall, one woman in every nine will get breast cancer at some time in her life. Epidemiological studies have indicated that alcohol consumption has most consistently been associated with breast cancer risk. However, the mechanism of alcohol-associated breast cancer remains to be addressed. Little is known about the effects of alcohol consumption on Brf1 (TFIIIB-related factor 1) expression and RNA Pol III gene (RNA polymerase III-dependent gene) transcription, which are responsible for protein synthesis and tightly linked to cell proliferation, cell transformation, and tumor development. Emerging evidences have indicated that alcohol induces deregulation of Brf1 and Pol III genes to cause the alterations of cell phenotypes and tumor formation. In this paper, we summarize the progresses regarding alcohol-caused increase in the expression of Brf1 and Pol III genes and analysis of its molecular mechanism of breast cancer. As the earlier and accurate diagnosis approach of breast cancer is not available yet, exploring the molecular mechanism and identifying the biomarker of alcohol-associated breast cancer are especially important. Recent studies have demonstrated that Brf1 is overexpressed in most ER+ (estrogen receptor positive) cases of breast cancer and the change in cellular levels of Brf1 reflects the therapeutic efficacy and prognosis of this disease. It suggests that Brf1 may be a potential diagnosis biomarker and a therapeutic target of alcohol-associated breast cancer

Cerenkov Luminescence Tomography for In Vivo Radiopharmaceutical Imaging

Cerenkov luminescence imaging (CLI) is a cost-effective molecular imaging tool for biomedical applications of radiotracers. The introduction of Cerenkov luminescence tomography (CLT) relative to planar CLI can be compared to the development of X-ray CT based on radiography. With CLT, quantitative and localized analysis of a radiopharmaceutical distribution becomes feasible. In this contribution, a feasibility study of in vivo radiopharmaceutical imaging in heterogeneous medium is presented. Coupled with a multimodal in vivo imaging system, this CLT reconstruction method allows precise anatomical registration of the positron probe in heterogeneous tissues and facilitates the more widespread application of radiotracers. Source distribution inside the small animal is obtained from CLT reconstruction. The experimental results demonstrated that CLT can be employed as an available in vivo tomographic imaging of charged particle emitters in a heterogeneous medium

Association of hypoglycaemia with the risks of arrhythmia and mortality in individuals with diabetes - a systematic review and meta-analysis

BackgroundHypoglycaemia has been linked to an increased risk of cardiac arrhythmias by causing autonomic and metabolic alterations, which may be associated with detrimental outcomes in individuals with diabetes(IWD), such as cardiovascular diseases (CVDs) and mortality, especially in multimorbid or frail people. However, such relationships in this population have not been thoroughly investigated. For this reason, we conducted a systematic review and meta-analysis.MethodsRelevant papers published on PubMed, Embase, Cochrane, Web of Knowledge, Scopus, and CINHAL complete from inception to December 22, 2022 were routinely searched without regard for language. All of the selected articles included odds ratio, hazard ratio, or relative risk statistics, as well as data for estimating the connection of hypoglycaemia with cardiac arrhythmia, CVD-induced death, or total death in IWD. Regardless of the heterogeneity assessed by the I2 statistic, pooled relative risks (RRs) and 95% confidence intervals (CI) were obtained using random-effects models.ResultsAfter deleting duplicates and closely evaluating all screened citations, we chose 60 studies with totally 5,960,224 participants for this analysis. Fourteen studies were included in the arrhythmia risk analysis, and 50 in the analysis of all-cause mortality. Hypoglycaemic patients had significantly higher risks of arrhythmia occurrence (RR 1.42, 95%CI 1.21-1.68), CVD-induced death (RR 1.59, 95% CI 1.24-2.04), and all-cause mortality (RR 1.68, 95% CI 1.49-1.90) compared to euglycaemic patients with significant heterogeneity.ConclusionHypoglycaemic individuals are more susceptible to develop cardiac arrhythmias and die, but evidence of potential causal linkages beyond statistical associations must await proof by additional specifically well planned research that controls for all potential remaining confounding factors

Regulation of High-Temperature Stress Response by Small RNAs

Temperature extremes constitute one of the most common environmental stresses that adversely affect the growth and development of plants. Transcriptional regulation of temperature stress responses, particularly involving protein-coding gene networks, has been intensively studied in recent years. High-throughput sequencing technologies enabled the detection of a great number of small RNAs that have been found to change during and following temperature stress. The precise molecular action of some of these has been elucidated in detail. In the present chapter, we summarize the current understanding of small RNA-mediated modulation of high- temperature stress-regulatory pathways including basal stress responses, acclimation, and thermo-memory. We gather evidence that suggests that small RNA network changes, involving multiple upregulated and downregulated small RNAs, balance the trade-off between growth/development and stress responses, in order to ensure successful adaptation. We highlight specific characteristics of small RNA-based tem- perature stress regulation in crop plants. Finally, we explore the perspectives of the use of small RNAs in breeding to improve stress tolerance, which may be relevant for agriculture in the near future

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

TBP Is Differentially Regulated by c-Jun N-Terminal Kinase 1 (JNK1) and JNK2 through Elk-1, Controlling c-Jun Expression and Cell Proliferation

Emerging evidence supports the idea that the c-Jun N-terminal kinases (JNKs) possess overlapping but distinct functions. The potential roles of the ubiquitously expressed JNK1 and JNK2 in regulating expression of the central transcription initiation factor, TATA-binding protein (TBP), were examined. Relative to wild-type fibroblasts, TBP was decreased in Jnk1(−/−) cells and increased in Jnk2(−/−) cells. Similarly, reduction of JNK1 in human hepatoma cells decreased TBP expression, whereas reduction of JNK2 enhanced it. JNK-mediated regulation of TBP expression occurs at the transcriptional level through their ability to target Elk-1, which directly regulates the TBP promoter in response to epidermal growth factor stimulation. JNK1 increases, whereas JNK2 decreases, the phosphorylation state of Elk-1, which differentially affects Elk-1 occupancy at a defined site within the TBP promoter. These JNK-mediated alterations in TBP expression, alone, serve to regulate c-Jun expression and fibroblast proliferation rates. These studies uncovered several new molecular events that distinguish the functions of JNK1 and JNK2 that are critical for their regulation of cellular proliferation