Predicting protein-protein interactions in unbalanced data using the primary structure of proteins

<p>Abstract</p> <p>Background</p> <p>Elucidating protein-protein interactions (PPIs) is essential to constructing protein interaction networks and facilitating our understanding of the general principles of biological systems. Previous studies have revealed that interacting protein pairs can be predicted by their primary structure. Most of these approaches have achieved satisfactory performance on datasets comprising equal number of interacting and non-interacting protein pairs. However, this ratio is highly unbalanced in nature, and these techniques have not been comprehensively evaluated with respect to the effect of the large number of non-interacting pairs in realistic datasets. Moreover, since highly unbalanced distributions usually lead to large datasets, more efficient predictors are desired when handling such challenging tasks.</p> <p>Results</p> <p>This study presents a method for PPI prediction based only on sequence information, which contributes in three aspects. First, we propose a probability-based mechanism for transforming protein sequences into feature vectors. Second, the proposed predictor is designed with an efficient classification algorithm, where the efficiency is essential for handling highly unbalanced datasets. Third, the proposed PPI predictor is assessed with several unbalanced datasets with different positive-to-negative ratios (from 1:1 to 1:15). This analysis provides solid evidence that the degree of dataset imbalance is important to PPI predictors.</p> <p>Conclusions</p> <p>Dealing with data imbalance is a key issue in PPI prediction since there are far fewer interacting protein pairs than non-interacting ones. This article provides a comprehensive study on this issue and develops a practical tool that achieves both good prediction performance and efficiency using only protein sequence information.</p

Anti-Oxidative Abilities of Essential Oils from Atractylodes ovata Rhizome

The rhizome of Atractylodes ovata De Candolle is rich in essential oils, which are usually removed by processing. In this study, anti-oxidative abilities of essential oils and aqueous extracts of A. ovata rhizome were explored, and the influence of processing on the anti-oxidative abilities was examined. Essential oils and aqueous extracts of A. ovata were extracted by boiling water and steam distillation, respectively. Quality of these two A. ovata samples was controlled by HPLC and GC-MS system, and anti-oxidative abilities were then evaluated. Results showed that surface color of A. ovata turned to brown and chemical components were changed by processing. Contents of both atractylon and atractylenolide II decreased in the essential oils, but only the contents of atractylon decreased by processing. Atractylenolide III increased in both A. ovata samples. However, A. ovata essential oils displayed stronger anti-oxidative abilities than aqueous extracts in DPPH-scavenging, TBH-induced lipid peroxidation and catalase activity assays. Moreover, the bioactivity of essential oils from raw A. ovata was stronger than oils from processed A. ovata. On the other hand, cytotoxicity of A. ovata essential oils was stronger than that of aqueous extracts, and was more sensitive on H9C2 cell than NIH-3T3 and WI-38 cells. In contrast, stir-frying processing method increased cytotoxicity of essential oils, but the cytotoxicity was ameliorated when processed with assistant substances. The results suggested that phytochemical components and bioactivity of A. ovata were changed after processing and the essential oils from raw A. ovata showed better anti-oxidative and fewer cytotoxicity effects

Enhanced Differentiation of Three-Gene-Reprogrammed Induced Pluripotent Stem Cells into Adipocytes via Adenoviral-Mediated PGC-1α Overexpression

Induced pluripotent stem cells formed by the introduction of only three factors, Oct4/Sox2/Klf4 (3-gene iPSCs), may provide a safer option for stem cell-based therapy than iPSCs conventionally introduced with four-gene iPSCs. Peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) plays an important role during brown fat development. However, the potential roles of PGC-1α in regulating mitochondrial biogenesis and the differentiation of iPSCs are still unclear. Here, we investigated the effects of adenovirus-mediated PGC-1α overexpression in 3-gene iPSCs. PGC-1α overexpression resulted in increased mitochondrial mass, reactive oxygen species production, and oxygen consumption. Microarray-based bioinformatics showed that the gene expression pattern of PGC-1α-overexpressing 3-gene iPSCs resembled the expression pattern observed in adipocytes. Furthermore, PGC-1α overexpression enhanced adipogenic differentiation and the expression of several brown fat markers, including uncoupling protein-1, cytochrome C, and nuclear respiratory factor-1, whereas it inhibited the expression of the white fat marker uncoupling protein-2. Furthermore, PGC-1α overexpression significantly suppressed osteogenic differentiation. These data demonstrate that PGC-1α directs the differentiation of 3-gene iPSCs into adipocyte-like cells with features of brown fat cells. This may provide a therapeutic strategy for the treatment of mitochondrial disorders and obesity

Women with endometriosis have higher comorbidities: Analysis of domestic data in Taiwan

AbstractEndometriosis, defined by the presence of viable extrauterine endometrial glands and stroma, can grow or bleed cyclically, and possesses characteristics including a destructive, invasive, and metastatic nature. Since endometriosis may result in pelvic inflammation, adhesion, chronic pain, and infertility, and can progress to biologically malignant tumors, it is a long-term major health issue in women of reproductive age. In this review, we analyze the Taiwan domestic research addressing associations between endometriosis and other diseases. Concerning malignant tumors, we identified four studies on the links between endometriosis and ovarian cancer, one on breast cancer, two on endometrial cancer, one on colorectal cancer, and one on other malignancies, as well as one on associations between endometriosis and irritable bowel syndrome, one on links with migraine headache, three on links with pelvic inflammatory diseases, four on links with infertility, four on links with obesity, four on links with chronic liver disease, four on links with rheumatoid arthritis, four on links with chronic renal disease, five on links with diabetes mellitus, and five on links with cardiovascular diseases (hypertension, hyperlipidemia, etc.). The data available to date support that women with endometriosis might be at risk of some chronic illnesses and certain malignancies, although we consider the evidence for some comorbidities to be of low quality, for example, the association between colon cancer and adenomyosis/endometriosis. We still believe that the risk of comorbidity might be higher in women with endometriosis than that we supposed before. More research is needed to determine whether women with endometriosis are really at risk of these comorbidities

Diode Laser Transscleral Cyclophotocoagulation in the Treatment of Refractory Glaucoma with Iris Melanocytoma

Iris melanocytoma is a rare melanocytic nevus with distinctive clinical and pathologic features. Secondary glaucoma may develop rapidly and respond poorly to glaucoma medication in some cases. However, few data are available in the literature with respect to the appropriate treatment for refractory glaucoma associated with iris melanocytoma. Herein, we present a 28-year-old man with blurred vision and an elevated intraocular pressure (IOP) of 40 mmHg in his right eye while on multiple glaucoma medications. A dark brown lobulated iris mass with surrounding small pigmented lesions was noted between the 4 and 5:30 o'clock positions. Sector iridectomy was performed and pathologic examination revealed an iris melanocytoma. After surgery, antiglaucomatous medications still failed to control IOP. The patient then underwent diode laser transscleral cyclophotocoagulation (TSCP). At the last follow-up of 15 months, IOP had returned to normal without the need for medication

Mucolytic Agents and Statins Use is Associated with a Lower Risk of Acute Exacerbations in Patients with Bronchiectasis-Chronic Obstructive Pulmonary Disease Overlap

Background: Bronchiectasis-chronic obstructive pulmonary disease (COPD) overlap (BCO) is a neglected area of trials, and it is not covered by guidelines for clinical practice. Methods: Using the National Health Insurance Research Database of Taiwan, COPD patients with or without bronchiectasis from 2000 to 2009 were enrolled as the BCO and COPD alone cohorts, respectively. Patients followed for &lt;28 days, diagnosed with COPD who were not prescribed with COPD medications, and those diagnosed with bronchiectasis who did not receive a chest X-ray or computed tomography were excluded. The primary endpoints were acute exacerbations and mortality. Results: There were 831 patients in the BCO cohort and 3321 patients in the COPD alone cohort, covering 3763.08 and 17,348.95 person-years, respectively, from 2000 to 2011. The BCO cohort had higher risk for exacerbations (adjusted hazard ratio (HR) 2.26, 95% confidence interval (CI) 1.94&#8315;2.63) and mortality (HR 1.46, 95% CI 1.24&#8315;1.73) than the COPD alone cohort. In the patients overall, the use of statins, macrolides, and mucolytic agents was associated with significantly lower risks of acute exacerbations (statins, HR 0.37, 95% CI 0.29&#8315;0.46; macrolides, HR 0.65, 95% CI 0.45&#8315;0.93; mucolytic agents, HR 0.68, 95% CI 0.59&#8315;0.78). Statins were associated with a significantly lower risk of mortality (HR 0.32, 95% CI 0.25&#8315;0.41). In the BCO group, statins and mucolytic agents use was associated with significantly lower risks of acute exacerbations (statins, HR 0.44, 95% CI 0.29&#8315;0.65; mucolytic agents, HR 0.58, 95% CI 0.45&#8315;0.75). Conclusion: Statins and mucolytic agents use may lower risk of acute exacerbation in patients with BCO

Comparative effectiveness and safety of inhaled corticosteroid plus long-acting β₂-agonist fixed-dose combinations vs. long-acting muscarinic antagonist in bronchiectasis

This study aimed to evaluate the effectiveness and safety of fixed-dose combination (FDC) inhaled corticosteroids/long-acting β2-agonists (ICS/LABA) in bronchiectasis. A retrospective cohort study analyzed electronic medical records of bronchiectasis patients initiating ICS/LABA FDC or LAMA between 2007 and 2021. All bronchiectasis diagnoses were made by radiologists using high-resolution computed tomography. Of the 1,736 patients, 1,281 took ICS/LABA FDC and 455 LAMA. Among the 694 propensity score matched patients, ICS/LABA FDC had comparable outcomes to LAMA, with HRs of 1.22 (95% CI 0.81–1.83) for hospitalized respiratory infection, 1.06 (95% CI 0.84–1.33) for acute exacerbation, and 1.06 (95% CI 0.66–1.02) for all-cause hospitalization. Beclomethasone/formoterol (BEC/FOR) or budesonide/formoterol (BUD/FOR) led to a lower risk of acute exacerbation compared to fluticasone/salmeterol (FLU/SAL) (BEC/FOR HR 0.59, 95% CI 0.43–0.81; BUD/FOR HR 0.68, 95% CI 0.50–0.93). BEC/FOR resulted in lower risks of hospitalized respiratory infection (HR 0.48, 95% 0.26–0.86) and all-cause hospitalization (HR 0.55, 95% 0.37–0.80) compared to FLU/SAL. Our findings provide important evidence on the effectiveness and safety of ICS/LABA FDC compared with LAMA for bronchiectasis. BEC/FOR and BUD/FOR were associated with better outcomes than FLU/SAL.</p

Silicon Quantum Dot Nanoparticles with Antifouling Coatings for Immunostaining on Live Cancer Cells

Fluorescent silicon quantum dots (SiQDs) have shown a great potential as antiphotobleaching, nontoxic and biodegradable labels for various in vitro and in vivo applications. However, fabricating SiQDs with high water-solubility and high photoluminescence quantum yield (PLQY) remains a challenge. Furthermore, for targeted imaging, their surface chemistry has to be capable of conjugating to antibodies, as well as sufficiently antifouling. Herein, antibody-conjugated SiQD nanoparticles (SiQD-NPs) with antifouling coatings composed of bovine serum albumin (BSA) and polyethylene glycol (PEG) are demonstrated for immunostaining on live cancer cells. The monodisperse SiQD-NPs of diameter about 130 nm are synthesized by a novel top-down method, including electrochemical etching, photochemical hydrosilylation, high energy ball milling, and “selective-etching” in HNO₃ and HF. Subsequently, the BSA and PEG are covalently grafted on to the SiQD-NP surface through presynthesized chemical linkers, resulting in a stable, hydrophilic, and antifouling organic capping layer with isothiocyanates as the terminal functional groups for facile conjugation to the antibodies. The in vitro cell viability assay reveals that the BSA-coated SiQD-NPs had exceptional biocompatibility, with minimal cytotoxicity at concentration up to 1600 μg mL^–1. Under 365 nm excitation, the SiQD-NP colloid emits bright reddish photoluminescence with PLQY = 45–55% in organic solvent and 5–10% in aqueous buffer. Finally, through confocal fluorescent imaging and flow cytometry analysis, the anti-HER2 conjugated SiQD-NPs show obvious specific binding to the HER2-overexpressing SKOV3 cells and negligible nonspecific binding to the HER2-nonexpressing CHO cells. Under similar experimental conditions, the immunofluorescence results obtained with the SiQD-NPs are comparable to those using conventional fluorescein isothiocyanate (FITC)