Ubiquitin-proteasome pathway-mediated regulation of the Bcl-2 family: effects and therapeutic approaches.

Proteasomal degradation of proteins represents an important regulatory mechanism in maintaining healthy homeostasis in cells. Deregulation of the ubiquitin-proteasome system is associated with various diseases as it controls protein abundance and turnover in cells. Furthermore, proteasomal regulation of protein turnover rate can determine a cell's response to external stimuli. The Bcl-2 family of proteins is an important group of proteins involved in mediating cell survival or cell death in response to external stimuli. Aberrant overexpression of anti-apoptotic proteins or deletion of pro-apoptotic proteins can lead to the development of cancer. Unsurprisingly, proteasomal degradation of Bcl-2 proteins also serves as an important factor regulating the level of Bcl-2 proteins and thereby affecting the functional outcome of cell death. This review aims to highlight the regulation of the Bcl-2 family of proteins with particular emphasis on proteasomal-mediated degradation pathways and the current literature on the therapeutic approaches targeting the proteasome system.

Pharmacological and non-pharmacological interventions in management of peripheral venipuncture-related pain: a randomized clinical trial.

BACKGROUND: Venipuncture is a routine nursing procedure in the pediatric ward for blood collection and transfusion. However, this procedure can cause severe pain and distress if not adequately managed. METHODS: Children aged 3-16 years old were randomized into three groups: EMLA group, distraction group, and combined group. The primary outcome was children's self-reported pain scored using the Wong-Baker FACES® Pain Rating Scale. The parents-reported and observer-reported pain were scored using the Revised Face, Legs, Activity, Cry and Consolability Scale, and children's salivary cortisol levels, heart rate, percutaneous oxygen saturation, venipuncture duration and retaining time of IV cannulas were the secondary outcomes. RESULTS: A total of 299 children (167 male, 55.8%, median age 8.5) were enrolled: EMLA group (n = 103), distraction group(n = 96) and combined group(n = 100). There was no statistical difference in self-reported pain (P = 0.051), parent-reported pain (P = 0.072), and observer-reported pain (P = 0.906) among the three groups. All three interventions can decrease children's pain during IV cannulations. Additionally, the distraction group's salivary cortisol levels were lower than the combined group(P = 0.013). Furthermore, no significant difference was observed in the heart rate(P = 0.844), percutaneous oxygen saturation (P = 0.438), venipuncture duration (p = 0.440) and retaining time of IV cannulas (p = 0.843) among the three groups. CONCLUSIONS: All three groups responded with slight pain during the peripheral venipuncture procedure. Therefore, medical workers in pediatric settings can use the interventions appropriate for their medical resources and availability while involving parents and children's preferences whenever possible. TRIAL REGISTRATION: This trial was registered on https://register. CLINICALTRIALS: gov/ (Gov.ID NCT04275336).

Nursing Management of Abdominal Wound Dehiscence of an Infant With Severe Undernutrition and Peristomal Moisture-Associated Dermatitis After Ileostomy Closure: A Case Study.

BACKGROUND: Abdominal wound dehiscence (AWD) is a costly postoperative complication; its management is particularly challenging for WOC nurses when it occurs secondary to an ostomy closure. CASE: We present a case of AWD secondary to ileostomy closure in Baby Q, a 9-month 19-day-old female infant. A silver wound contact dressing was used on her dehisced wound followed by negative pressure wound therapy and adhesive tape to pull the wound edge together and promote granulation. We used a combination of enteral nutrition, parenteral nutrition, total parenteral nutrition, and total enteral nutrition adjusting the feeding plan stepwise according to her nutritional status. CONCLUSIONS: Malnutrition and severe peristomal skin complications may contribute to the risk of AWD in infants undergoing reversal of a temporary ostomy. Assessing and treating nutritional status and peristomal skin is imperative before performing ostomy closure.

[Research progress on potential targets-mitochondrial dynamics-related proteins in treatment of myocardial ischemia-reperfusion injury].

Acute myocardial infarction(AMI) is still the leading cause of death worldwide. At present, the treatment of AMI is mainly to restore the cardiac blood supply through myocardial reperfusion. With the widespread use of coronary artery bypass grafting and percutaneous coronary intervention(PCI), myocardial reperfusion injury is a major clinical problem. Mitochondrial dysfunction is an important pathological basis for myocardial ischemic injury. Therefore, mitochondria can be used as an important target against myocardial damage. In this article, we would briefly review the physiological functions of mitochondrial dynamics-related proteins as well as their pathological mechanisms and pharmacological interventions in treatment of myocardial ischemia-reperfusion injury.

[Discrimination of Honey Varieties Based on Amino Acid Derivative Fluorescence Method Combining with Multilinear Pattern Recognition].

Assessing the authenticity about the botanical and geographical origins of food is an important content for food safety research. Amino acids are the most important nutrients of honey. The types and contents of amino acids are different in various honey samples. Thus they can be used as one of the important parameters to discriminate the honey variety and quality. In this article, amino acids in honey were first derived with formaldehyde and acetyl acetone solution. In the following step, three-dimensional fluorescence spectrums combing with multidimensional pattern recognition methods were used to distinguish the kinds of honey. Five kinds of honey (total 150 honey samples) from different botanicals were studied in this research. Before fluorescence detection, the effect of the amount of derivation reagent, the time of reaction, temperature and pH to the derivation progress of honey samples were first studied. Research showed that the fluorescence intensity of derivatives of honey was the strongest when the amount of derivation reagent was 4.0 mL, the time of reaction being 2 h, pH being 4 and the temperature being 100 ℃. The derivatives of honey were then scanned with three-dimensional fluorescence spectrometry. The collection of fluorescence intensity values occurred within excitation-emission ranges of 300~500 and 380~580 nm. A 150×41×101 cube matrix data sets can be acquired. The three-dimensional fluorescence data sets were decomposed with multilinear pattern recognition methods, such as multilinear principal components analysis (M-PCA), self-weight alternative trilinear decomposition (SWATLD) and multilinear partial least squares discriminant analysis (N-PLS-DA) methods. All of these multilinear pattern recognition methods showed the clustering tendency for five different kinds of honey. Compared with the other two methods, N-PLS-DA got more accurate and reliable classification results because it made full use of all the fluorescence information of the derivative honey samples. Its total recognition rate reached 88%. The result is acceptable for the complexity of the honey samples. It showed this method could be applied to identify the varieties of honey. Compared with the chromatographic analysis method, this method is relatively simpler and more sensitivity. It avoided the chromatographic separation and reduced the consumption of organic solvent. Thus it can be regarded as a kind of relatively green honey classification method. This research will provide a new idea to directly fluorescence analyze for no or weak fluorescence natural substances.

Metachronous primary esophageal squamous cell carcinoma and duodenal adenocarcinoma: A case report and review of literature.

BACKGROUND: The prevalence of multiple primary malignant neoplasms (MPMNs) is increasing in parallel with the incidence of malignancies, the continual improvement of diagnostic models, and the extended life of patients with tumors, especially those of the digestive system. However, the co-existence of MPMNs and duodenal adenocarcinoma (DA) is rarely reported. In addition, there is a lack of comprehensive analysis of MPMNs regarding multi-omics and the tumor microenvironment (TME). CASE SUMMARY: In this article, we report the case of a 56-year-old man who presented with a complaint of chest discomfort and abdominal distension. The patient was diagnosed with metachronous esophageal squamous cell carcinoma and DA in the Department of Oncology. He underwent radical resection and chemotherapy for the esophageal tumor, as well as chemotherapy combined with a programmed death-1 inhibitor for the duodenal tumor. The overall survival was 16.6 mo. Extensive evaluation of the multi-omics and microenvironment features of primary and metastatic tumors was conducted to: (1) Identify the reasons responsible for the poor prognosis and treatment resistance in this case; and (2) Offer novel diagnostic and therapeutic approaches for MPMNs. This case demonstrated that the development of a second malignancy may be independent of the location of the first tumor. Thus, tumor recurrence (including metastases) should be distinguished from the second primary for an accurate diagnosis of MPMNs. CONCLUSION: Multi-omics characteristics and the TME may facilitate treatment selection, improve efficacy, and assist in the prediction of prognosis.

Ovarian sex cord stromal tumours: analysis of the clinical and sonographic characteristics of different histopathologic subtypes.

BACKGROUND: Ovarian sex cord stromal tumours (OSCSTs) are rare ovarian tumours and include different histopathologic subtypes. This study aimed to analyse the clinical and sonographic characteristics of different histopathologic OSCST subtypes. METHODS: A total of 63 patients with surgically proven OSCSTs were enrolled in this retrospective study to analyse their clinical and sonographic features. Ultrasound examinations and predictive models were performed before surgery. The clinical and sonographic findings were compared according to the type of OSCST based on the histopathological diagnosis. RESULTS: The mean age of 63 patients was 52.17 years (range: 17-78 years). Eighteen patients experienced irregular vaginal bleeding (28.57% 18/63), 7 patients exhibited abnormal body hair (11.11%). 2 patients (3.17%) showed an increased level of CA125, and 25 patients (39.68%, 25/63) showed an increased level of testosterone. Forty-two patients had ovarian thecoma-fibroma groups (OTFGs). Six patients had Sertoli-Leydig cell tumours (S-LCTs), 4 patients had Leydig cell tumours (LCTs), 8 patients had ovarian granulosa cell tumours (OGCTs), 2 patients had ovarian steroid cell tumours, not otherwise specified (OSCTs-NOS), and one patient had sclerosing stromal tumours (SSTs). The mean diameter of the tumour was 47.9 mm (range: 10-258 mm). Forty-seven masses were hypoechoic (74.60%). Twenty-eight masses had posterior echo attenuation, 22 masses exhibited abundant Doppler flow signals (34.92%), and one patient had ascites (1.59%). The diagnostic accuracy of the Simple Rules (SR) and the Assessment of Different NEoplasias in the adneXa (ADNEX) model in distinguishing benign and malignant OSCSTs was 44% (30/63) and 84% (53/63), respectively. The diagnostic accuracy of the SR for OTFGs, S-LCTs & LCTs & OSCTs-NOS, OGCTs, and SSTs was 47.6% (20/42), 16.67% (2/12), 100% (8/8), and 0% (0/1), respectively. The diagnostic accuracy of the ADNEX model for OTFGs, S-LCTs & LCTs & OSCTs-NOS, OGCTs, and SSTs was 93% (31/42), 58.33% (7/12), 75% (6/8), and 100% (1/1), respectively. CONCLUSIONS: OSCSTs generally appear as a solid mass on ultrasound. Posterior echo attenuation indicates an OTFG. A solid mass with abundant Doppler flow signals indicates an S-LCT, LCT, OSCT-NOS or OGCT. Current predictive models are not very effective, but symptoms, sonographic features and serum hormones are helpful for diagnosis.

Trimethylamine N-Oxide increases soluble fms-like tyrosine Kinase-1 in human placenta via NADPH oxidase dependent ROS accumulation.

BACKGROUNDS: Preeclampsia (PE) is characterized as placental vascular disturbance and excessive secretion of soluble fms-like tyrosine kinase 1 (sFlt-1) into the maternal circulation. Trimethylamine N-oxide (TMAO, a gut microbe-derived metabolite) is strongly associated with various cardiovascular and cerebrovascular diseases. Recently, we observe that higher maternal circulating TMAO and sFlt-1 in patients with PE. The aims of the present study are to explore the effects of TMAO on placental sFlt-1 production and the underlying mechanism in human placenta. METHODS: Human placental explants, human placental primary trophoblasts and the extravillous trophoblasts (EVT) cell line (HRT-8/SVneo) were exposured to various concentrations of TMAO (100, 150, 300, and 600 µM). The mRNA expression and protein secretion of sFlt-1 in placental explants, primary trophoblasts and HRT-8/SVneo cells were determined with qPCR and ELISA, respectively. The levels of intracellular reactive oxygen species (ROS) production in primary trophoblasts and HRT-8/SVneo cells were measured by peroxide-sensitive fluorescent probe dichlorofluorescein diacetate. RESULTS: Exposure of placental explants, primary trophoblasts and HRT-8/SVneo cells to TMAO significantly enhanced sFlt-1 at both mRNA and protein levels in a dose dependent manner. Moreover, inhibition of NADPH oxidase with apocynin significantly attenuated TMAO-induced ROS production in primary trophoblasts and HRT-8/SVneo, and suppressed sFlt-1 secretion in placental explants, primary trophoblasts and HRT-8/SVneo. CONCLUSIONS: Our findings indicated the NADPH oxidase dependent ROS pathway played a critical role in mediating TMAO-induced sFlt-1 generation in human placenta. TMAO may become a potential novel target for pharmacological or dietary interventions to reduce the risk of developing PE.

Retraction Note to: Ambient air pollution and adverse birth outcomes: a systematic review and meta-analysis.

Retraction Note to: J Zhejiang Univ-Sci B (Biomed & Biotechnol) 2019 20(3):238-252. https://doi.org/10.1631/jzus.B1800122. The authors have retracted this article (Guo et al., 2019) because some data from the original literature had not been converted to appropriate units in the paper, which resulted in deviation of the meta-analysis results. For example, for the forest plot used to examine associations between PM10 exposure and the risk of adverse birth outcomes, the estimates from Brauer et al. (2008), Pedersen et al. (2013), Zhao et al. (2015), and Hansen et al. (2006) were on the originally reported scales of 1 µg/m3, 10 µg/m3, 10 µg/m3, and Inter Quartile Range, respectively. None of these estimates had been converted to 20 µg/m3 increase scale that was stated in the article. Similar problem exists in the analysis on associations between NO2 exposure and risk of adverse birth outcomes. Therefore, the results of the meta-analysis are misleading. All authors have agreed to this retraction and express their deepest apologies to the original authors, publishers, and readers.

Ambient air pollution and adverse birth outcomes: a systematic review and meta-analysis.

Several reviews have assessed the relationship between exposure to ambient air pollution and adverse birth outcomes during pregnancy, but the results remain controversial. The objective of this study was to assess this correlation quantitatively and to explore sources of heterogeneity. We included all published case-control or cohort studies that evaluated the correlation between ambient air pollution and low birth weight (LBW), preterm birth (PTB), and small for gestational age (SGA). Analytical methods and inclusion criteria were provided on the PROSPERO website (CRD42018085816). We evaluated pooled effects and heterogeneity. Subgroup analyses (grouped by exposure period, study settings, study design, exposure types, data source, Newcastle-Ottawa quality score (NOS), and adjustment for smoking or meteorological factors) were also conducted and publication bias was examined. The risk of bias in systematic reviews (ROBIS) tool was used to evaluate the overall risk of bias in this review. Forty studies met the inclusion criteria. We observed pooled odds ratios (ORs) of 1.03-1.21 for LBW and 0.97-1.06 for PTB when mothers were exposed to CO, NO2, NOx, O3, PM2.5, PM10, or SO2 throughout their pregnancy. For SGA, the pooled estimate was 1.02 in relation to NO2 concentrations. Subgroup analysis and sensitivity analysis decreased the heterogeneity to some extent, such as the subgroups of continuous measures (OR=0.98 (0.97-0.99), I2=0.0%) and NOS>7 (OR=0.98 (0.97-0.99), I2=0.0%) in evaluating the association between PTB and NO2. This review was completed with a low risk of bias. High concentrations of air pollution were significantly related to the higher risk of adverse birth outcomes. However, the sources of heterogeneity among studies should be further explored.

A CdII -Based Metal-Organic Framework with pcu Topology as Turn-On Fluorescent Sensor for Al3.

A new metal-organic framework (MOF) {[Cd2 (bbib)2 (ndc)2 ]⋅2DMF}n (JXUST-1) (bbib=1,3-bis(benzimidazolyl)benzene, H2 ndc=1,4-naphthalenedicarboxylic acid, DMF=N,N-dimethylformamide) has been solvothermally synthesized and characterized by single-crystal X-ray diffraction, PXRD, TGA, IR and elemental analysis. JXUST-1 exhibits a three-dimensional 6-connected pcu topology with a Schläfli symbol {412 .63 } constructed by [Cd2 (CO2 )3 ] secondary building units. Fluorescence studies show that this MOF can sensitively and selectively recognize Al3+ via a fluorescence enhancement effect, and the detection limit is 0.048 ppm. Furthermore, JXUST-1 displays relatively good thermal and chemical stabilities as well as reusability. All these results suggest JXUST-1 to be a highly selective and recyclable luminescent sensing material for the detection of Al3+ .

Determination of daunomycin in human plasma and urine by using an interference-free analysis of excitation-emission matrix fluorescence data with second-order calibration.

Daunorubicin (DNR) is a significant antineoplastic antibiotic, which is usually applied to a chemotherapy of acute lymphatic and myelogenous leukaemia. Unfortunately, cardiotoxicity research in animals has indicated that DNR is cardiotoxic. Therefore, it is important to quantify DNR in biological fluids. A new algorithm, the alternating fitting residue (AFR) method, and the traditional parallel factor analysis (PARAFAC) have been utilized to directly determine DNR in human plasma and urine. These methodologies fully exploit the second-order advantage of the employed three-way fluorescence data, allowing the analyte concentrations to be quantified even in the presence of unknown fluorescent interferents. Furthermore, in contrast to PARAFAC, more satisfactory results were gained with AFR.

Detection of adulteration in acetonitrile using near infrared spectroscopy coupled with pattern recognition techniques.

In this paper, near infrared spectroscopy (NIR) in cooperation with the pattern recognition techniques were used to determine the type of neat acetonitrile and the adulteration in acetonitrile. NIR spectra were collected between 400 nm and 2498 nm. The experimental data were first subjected to analysis of principal component analysis (PCA) to reveal significant differences and potential patterns between samples. Then support vector machine (SVM) were applied to develop classification models and the best parameter combination was selected by grid search. Under the best parameter combination, the classification accuracy rates of three types of neat acetonitrile reached 87.5%, and 100% for the adulteration with different concentration levels. The results showed that NIR spectroscopy combined with SVM could be utilized for determining the potential adulterants including water, ethanol, isopropyl alcohol, acrylonitrile, methanol, and by-products associated with the production of acetonitrile.

Simultaneous and Direct Determination of Vancomycin and Cephalexin in Human Plasma by Using HPLC-DAD Coupled with Second-Order Calibration Algorithms.

A simple, rapid, and sensitive method for the simultaneous determination of vancomycin and cephalexin in human plasma was developed by using HPLC-DAD with second-order calibration algorithms. Instead of a completely chromatographic separation, mathematical separation was performed by using two trilinear decomposition algorithms, that is, PARAFAC-alternative least squares (PARAFAC-ALSs) and self-weight-alternative-trilinear-decomposition- (SWATLD-) coupled high-performance liquid chromatography with DAD detection. The average recoveries attained from PARAFAC-ALS and SWATLD with the factor number of 4 (N = 4) were 101 ± 5% and 102 ± 4% for vancomycin, and 96 ± 3% and 97 ± 3% for cephalexininde in real human samples, respectively. The statistical comparison between PARAFAC-ALS and SWATLD is demonstrated to be similar. The results indicated that the combination of HPLC-DAD detection with second-order calibration algorithms is a powerful tool to quantify the analytes of interest from overlapped chromatographic profiles for complex analysis of drugs in plasma.

Estimating the chemical rank of three-way data arrays by a simple linear transform incorporating Monte Carlo simulation.

Estimating an appropriate chemical rank of a three-way data array is very important to second-order calibration. In this paper, a simple linear transform incorporating Monte Carlo simulation approach (LTMC) to estimate the chemical rank of a three-way data array was suggested. The new method determines the chemical rank through performing a simple linear transform procedure on the original cube matrix to produce two subspaces by singular value decomposition. One of two subspaces is derived from the original three-way data array itself and the other is derived from a new three-way data array produced by the linear transformation of the original one. Projection technique incorporating the Monte Carlo approach acts as distinguishing criterion to choose the appropriate component number of the system. Simulated three-way trilinear data arrays with different noise types (homoscedastic and heteroscedastic), various noise level as well as high collinearity are used to illustrate the feasibility of the new method. The results have shown that the new method could yield accurate results with different conditions appended. The feasibility of the new method is also confirmed by two real arrays, HPLC-DAD data and excitation-emission fluorescent data. All the results are compared with the other three factor-determining methods: factor indicator function (IND), core consistency diagnostic (CORCONDIA) and two-mode subspace comparison (TMSC) approach. It shows that the newly proposed algorithm can objectively and quickly determine the chemical rank to fit the trilinear model.

Interference-free determination of fluoroquinolone antibiotics in plasma by using excitation-emission matrix fluorescence coupled with second-order calibration algorithms.

Fluoroquinolones or so-called second-generation quinolones, in particular, ofloxacin (OFL), norfloxacin (NOR), and enoxacin (ENO), with therapeutic advantages possess strongly overlapped fluorescence spectra. In this paper, two strategies were proposed for simultaneous direct determination of OFL, NOR and ENO in plasma by combining fluorescence excitation-emission matrix (EEM) with second-order calibration based on the alternating trilinear decomposition algorithm (ATLD) and parallel factor analysis (PARAFAC). The results showed that both algorithms could solve the problem of serious fluorescence spectral overlapping of the sought-for analytes even in the presence of uncalibrated interferents. However, ATLD has advantages of being insensitive to overestimated component number and fast convergence. The results by using ATLD with an estimated component number of five were reasonably acceptable for clinical analysis. The average recoveries of OFL, NOR and ENO in synthetic samples were 99.7+/-2.4, 101.5+/-2.4 and 97.3+/-3.8%, respectively; the average recoveries of OFL, NOR and ENO in complex plasma were 94.3+/-2.6, 85.6+/-3.3 and 103.3+/-3.0%, respectively.