Post-marketing safety concerns with relugolix: a disproportionality analysis of the FDA adverse event reporting system.

BACKGROUND: Relugolix has been used to treat advanced prostate cancer. This study assessed adverse events (AEs) associated with relugolix from the US Food and Drug Administration Adverse Event Reporting System (FAERS). METHODS: Disproportionality analysis, including the reporting odds ratio (ROR), the proportional reporting ratio (PRR), the Bayesian confidence propagation neural network (BCPNN), and the multi-item gamma Poisson shrinker (MGPS) algorithms, were employed to quantify the signals of relugolix-associated AEs. RESULTS: A total of 5,059,213 reports of AEs were collected from the FAERS database, of which 5,662 reports were identified with relugolix as the "primary suspect (PS)". A total of 70 significant disproportionality PTs conforming to the four algorithms were simultaneously retained. Unexpected new AEs, such as erectile dysfunction, gynaecomastia, testicular atrophy, male genital atrophy, libido decreased might also occur. CONCLUSION: This study found potential new AEs signals and might provide important support for clinical monitoring and risk identification of relugolix.

Real-World Disproportionality Analysis of the Food and Drug Administration Adverse Event Reporting System Database for Asciminib.

INTRODUCTION: Asciminib is primarily utilized for treating Philadelphia chromosome-positive chronic myeloid leukemia in its chronic phase among patients harboring the T315I mutation or those who have been previously treated with at least two tyrosine kinase inhibitors. The safety profile of asciminib across a broad patient population over an extended timeframe remains unverified. This study uses a real-world pharmacovigilance database to evaluate the adverse events (AEs) linked with asciminib, providing valuable insights for clinical drug safety. METHODS: Data from the FDA Adverse Event Reporting System (FAERS) database, spanning from October 2021 to December 2023, served as the basis for this analysis. The extent of disproportional events was assessed using sophisticated metrics such as the reporting odds ratio, proportional reporting ratio, information component, and empirical Bayesian geometric mean. RESULTS: Within the specified period, the FAERS database documented 3,913,574 AE reports, with asciminib being associated with 966 incidents. Reactions to asciminib spanned 27 system organ categories. Utilizing four distinct analytical algorithms, 663 significant preferred terms exhibiting disproportional frequencies were identified. Notably, this investigation uncovered 26 significant AEs linked to off-label asciminib use, encompassing conditions such as gynecomastia, nephrotic syndrome, orchitis, pyelonephritis, hepatotoxicity, and pancreatitis. The median onset time for asciminib-related AEs was 52.5 days, ranging from 17 to 122.75 days. CONCLUSION: The study sheds light on additional potential AEs associated with asciminib use, warranting further research to confirm these findings.

A novel isosteviol-based bifunctional squaramide organocatalyst for enantioselective Michael addition of acetylacetone to nitroolefins.

Chiral amine-squaramide is a kind of effective hydrogen bond donor bifunctional catalyst to promote many asymmetric transformations. In this paper, novel chiral tertiary amine-squaramide derived from the natural product of the stevioside was developed and applied into the asymmetric Michael addition of acetylacetone to nitroolefins. This asymmetric reaction performed well, and a series of enantiomerically enriched compounds were obtained in high yields (up to 96%) with excellent enantioselectivities (up to 99% ee).

NaCl induces flocculation and lipid oxidation of soybean oil body emulsions recovered by neutral aqueous extraction.

BACKGROUND: Soybean oil bodies (SOB) are naturally pre-emulsified lipid droplets recovered directly from soybean seeds. Almost all food emulsions contain salts. However, it was not clear how the incorporation of salts affected the physicochemical stability of SOB. RESULTS: This study investigated the effect of NaCl (0-1.2%) on the physical and oxidative stability of SOB emulsions under neutral (pH 7) and acidic (pH 3) conditions. In the presence of NaCl, the SOB emulsion (pH 7) showed strong flocculation during storage due to electrostatic screening. The NaCl-induced flocculation of SOB was attenuated at pH 3, which may be due to the difference in conformation or interaction of the protein interfaces covering SOB at different pH values. The increase in ionic strength or acid conditioning treatment resulted in a remarkable increase in the stability of SOB emulsions against coalescence. The confocal laser scanning microscopy images also confirmed the NaCl-induced changes in the flocculation/coalescence properties of SOB. The oxidative behavior tests indicated that SOB emulsions containing NaCl were more susceptible to lipid oxidation but protein oxidation was inhibited due to electrostatic screening, which reduced pro-oxidant accessibility of unadsorbed proteins in the emulsion. This oxidative behavior was attenuated at pH 3. CONCLUSION: The incorporation of NaCl significantly reduced the physical and oxidative stability of the SOB emulsion, and acidic pH mitigated NaCl-induced flocculation and lipid oxidation of SOB. © 2021 Society of Chemical Industry.

Synthesis of Five-Membered Cyclic Guanidines via Cascade [3 + 2] Cycloaddition of α-Haloamides with Organo-cyanamides.

The convenient preparation of N2-unprotected five-membered cyclic guanidines was achieved through a cascade [3 + 2] cycloaddition between organo-cyanamides and α-haloamides under mild conditions in good to excellent yields (up to 99%). The corresponding cyclic guanidines could be easily transformed into hydantoins via hydrolysis.

Ensemble Dictionary Learning for Single Image Deblurring via Low-Rank Regularization.

Sparse representation is a powerful statistical technique that has been widely utilized in image restoration applications. In this paper, an improved sparse representation model regularized by a low-rank constraint is proposed for single image deblurring. The key motivation for the proposed model lies in the observation that natural images are full of self-repetitive structures and they can be represented by similar patterns. However, as input images contain noise, blur, and other visual artifacts, extracting nonlocal similarities only with patch clustering algorithms is insufficient. In this paper, we first propose an ensemble dictionary learning method to represent different similar patterns. Then, low-rank embedded regularization is directly imposed on inputs to regularize the desired solution space which favors natural and sharp structures. The proposed method can be optimized by alternatively solving nuclear norm minimization and l 1 norm minimization problems to achieve higher restoration quality. Experimental comparisons validate the superior results of the proposed method compared with other deblurring algorithms in terms of visual quality and quantitative metrics.

Defocus Blur Detection and Estimation from Imaging Sensors.

Sparse representation has been proven to be a very effective technique for various image restoration applications. In this paper, an improved sparse representation based method is proposed to detect and estimate defocus blur of imaging sensors. Considering the fact that the patterns usually vary remarkably across different images or different patches in a single image, it is unstable and time-consuming for sparse representation over an over-complete dictionary. We propose an adaptive domain selection scheme to prelearn a set of compact dictionaries and adaptively select the optimal dictionary to each image patch. Then, with nonlocal structure similarity, the proposed method learns nonzero-mean coefficients' distributions that are much more closer to the real ones. More accurate sparse coefficients can be obtained and further improve the performance of results. Experimental results validate that the proposed method outperforms existing defocus blur estimation approaches, both qualitatively and quantitatively.

Broad-Spectrum Antimicrobial Activity and Low Cytotoxicity against Human Cells of a Peptide Derived from Bovine αS1-Casein.

The primary objective of this study was to improve our understanding of the antimicrobial mechanism of protein-derived peptides and to provide evidence for protein-derived peptides as food bio-preservatives by examining the antimicrobial activities, low cytotoxicity, stabilities, and mechanism of Cp1 (LRLKKYKVPQL). In this study, the protein-derived peptide Cp1 was synthesized from bovine αS1-casein, and its potential use as a food biopreservative was indicated by the higher cell selectivity shown by 11-residue peptide towards bacterial cells than human RBCs. It also showed broad-spectrum antimicrobial activity, with minimum inhibitory concentrations (MICs) of 64⁻640 µM against both gram-positive and gram-negative bacteria. The peptide had low hemolytic activity (23.54%, 512 µM) as well as cytotoxicity. The results of fluorescence spectroscopy, flow cytometry, and electron microscopy experiments indicated that Cp1 exerted its activity by permeabilizing the microbial membrane and destroying cell membrane integrity. We found that Cp1 had broad-spectrum antimicrobial activity, low hemolytic activity, and cytotoxicity. The results also revealed that Cp1 could cause cell death by permeabilizing the cell membrane and disrupting membrane integrity. Overall, the findings presented in this study improve our understanding of the antimicrobial potency of Cp1 and provided evidence of the antimicrobial mechanisms of Cp1. The peptide Cp1 could have potential applications as a food biopreservative.

A Novel Fluorescent Probe for the Highly Selective and Sensitive Detection of Palladium in Aqueous Medium.

Based on the Pd0-catalyzed Tsuji-Trost allylic oxidative insertion reaction, we developed a fluorescent probe PdL1 for sensing Pd0. As expected, probe PdL1 exhibited high selectivity and excellent sensitivity in both absorbance and fluorescence detection of Pd0 in CH3CH2OH/PBS (10 mM, pH = 7.4, 6:4, v/v) solution. The detection limit was calculated to be as low as 15 nM, which can meet the selective requirements for practical application.

The effects of shRNA-mediated gene silencing of transcription factor SNAI1 on the biological phenotypes of breast cancer cell line MCF-7.

To research the effects of silencing transcription factor SNAI1 on the in vitro biological phenotypes of breast cancer cell line MCF-7, based on the gene sequence of SNAI1, we linked shRNA with the green fluorescent protein-expressing eukaryotic expression vector pGCsilencer™ U6/Neo/GFP, and transfected it into MCF-7 cells. The SNAI1 gene-silencing effect was authenticated by RT-PCR and immunofluorescence. We then examined the effect of gene silencing on the expression of epithelial and mesenchymal markers and on their biological phenotypes of the target cells. Finally, we explained that SNAI1 was bound to E-cadherin in MCF-7 cells by ChIP. Silencing SNAI1 upregulated the expression of epithelial markers claudin-4, claudin-7, and E-cadherin, while expression of the mesenchymal marker matrix metalloproteinase-2 was downregulated. The capacity for proliferation, migration, and invasion was diminished. SNAI1 binds to the E-cadherin gene promoter and inhibits its transcription. We can conclude that silencing gene SNAI1 inhibits expression of properties that are associated with the malignant phenotype of MCF-7 cells and reverses the epithelial-mesenchymal transition process by regulating relevant target gene E-cadherin.

Ultraselective electrochemiluminescence biosensor based on locked nucleic acid modified toehold-mediated strand displacement reaction and junction-probe.

Locked nucleic acid (LNA) is applied in toehold-mediated strand displacement reaction (TMSDR) to develop a junction-probe electrochemiluminescence (ECL) biosensor for single-nucleotide polymorphism (SNP) detection in the BRCA1 gene related to breast cancer. More than 65-fold signal difference can be observed with perfectly matched target sequence to single-base mismatched sequence under the same conditions, indicating good selectivity of the ECL biosensor.

Preparation of shell-core fiber-encapsulated Lactobacillus rhamnosus 1.0320 using coaxial electrospinning.

In this study, shell-core fibers were successfully prepared by using Eudragit S100 (ES100) and poly(vinyl alcohol) (PVA)/pectin (PEC) through coaxial electrospinning technology. The electrospun fiber was characterized by attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR) and X-ray diffraction (XRD). Thermo-gravimetric analysis (TGA) showed that the coaxial electrospun fiber encapsulated with Lactobacillus rhamnosus 1.0320 (L. rhamnosus) had higher thermal stability than the electrospun fiber prepared by uniaxial electrospinning. L. rhamnosus encapsulated by coaxial electrospun fiber maintained 90.07% and 91.96% survivability in simulated gastric and intestinal fluids. After continuous simulated gastrointestinal fluid treatment, the survival rate of L. rhamnosus encapsulated by coaxial electrospun fiber was 81.40%. The results indicate that shell-core fiber-encapsulated probiotics can improve the tolerance of probiotics to the harsh environment of gastrointestinal tract. The fiber prepared in this study can be applied to the preparation of functional fermented food such as probiotic yogurt fermentation in the future.

Gastric Metastasis of Primary Lung Cancer: Case Report and Systematic Review With Pooled Analysis.

Background: Gastric metastasis from lung cancer (GMLC) is a rare occurrence. The clinicopathological characteristics, outcomes, and prognostic factors remain largely elusive. Methods: We conducted a systematic review on case reports and case series of GMLC by scanning MEDLINE, Embase, and ISI Web of Knowledge. Data involving the clinicopathological features, treatment, and outcomes were extracted and analyzed. Survival analysis was performed using Kaplan-Meier method. The Cox proportional hazards regression model was used to identify potential prognostic factors associated with survival. Furthermore, a case of metastatic gastric adenocarcinoma of pulmonary origin with epidermal growth factor receptor (EGFR) L858R+T790M mutation was also described and included. Results: Seventy-eight records involving 114 cases (including ours) were finally included. The median age on admission was 65 years with a male predominance of 79.8%. Lung adenocarcinoma (42.1%), located in the right upper lobe (30.3%), was the most frequent primary tumor. Bleeding (36.7%) and abdominal pain (35.8%) were the two most common symptoms. Endoscopically, gastric lesions were typically presented as elevated lesions with or without volcano-like ulceration, or ulcerative lesions, mostly involving the gastric corpus. The median overall survival time and survival time after diagnosis of metastatic cancer were 11 months [95% confidence interval (CI): 7-14] and 4.5 months (95% CI: 3-9), respectively. The survival analyses revealed that surgical interventions (including lung surgery and/or abdominal surgery) and systemic therapy (including chemotherapy, radiotherapy, and/or targeted therapy) seemed to be positive prognostic factors for both overall survival and survival after diagnosis of metastatic cancer. Conclusions: Clinicians should be alerted to the occurrence of gastric metastasis in lung cancer patients. Comprehensive evaluation and appropriate treatment for specific patients may improve the survival rate of GMLC patients.

Physicochemical properties and bioactivity of polysaccharides from Isaria cicadae Miquel with different extraction processes: effects on gut microbiota and immune response in mice.

The effect of different extraction processes on the physicochemical characterization, digestibility, antioxidant activity and prebiotic activity of Isaria cicadae Miquel (ICM) fruiting body polysaccharides was studied. Furthermore, the effect of ultrasound-assisted extraction of ICM (U-ICM) on gut microbiota, the intestinal barrier and immune response was deeply explored. This study found that ICMs showed high indigestibility in both α-amylase and artificial gastric juice, indicating that ICMs have the potential as dietary fiber. In contrast, U-ICM had the best antioxidant activity and prebiotic potential. Meanwhile, there was a structure-activity relationship between the antioxidant activity of ICMs and the content of uronic acid, arabinose and galactose. When healthy mice were fed U-ICM for 42 days, the relative abundances of Lactobacillus, Akkermansia, and Bacteroides were found to increase significantly, while that of Clostridium decreased significantly. Meanwhile, U-ICM significantly promotes the expression of tight junction protein and the production of cytokines, indicating that U-ICM had the function of enhancing the intestinal barrier and regulating the host immune response. In conclusion, U-ICM as dietary fiber has the potential to be developed as a gut health-promoting prebiotic component or functional food. This research provided a valuable resource for further exploring the structure-activity relationship and prebiotic activity of ICMs.

Lactobacillus plantarum 23-1 improves intestinal inflammation and barrier function through the TLR4/NF-κB signaling pathway in obese mice.

As a natural active ingredient, lactic acid bacteria have potential anti-inflammatory effects. In this study, male C57BL/6J mice were given a high-fat diet (HFD) to establish an obese mouse model. Lactobacillus plantarum 23-1 (LP23-1) with prebiotic characteristics was intervened for 8 weeks to evaluate its remission effect on obese animals and related mechanisms. The effects of LP23-1 on lipid accumulation and intestinal inflammation in HFD-fed mice were systematically evaluated by detecting lipid accumulation, blood lipid level, pathological changes in the liver and small intestine, oxidative stress and inflammatory cell level, lipid transport-related gene expression, the inflammatory signaling pathway, and intestinal tight junction (TJ) mRNA and protein expression. The results showed that LP23-1 could significantly reduce the body weight and fat index of HFD-fed mice, improve the lipid levels of serum and liver, reduce the histopathological damage to the liver and small intestine, and alleviate oxidative stress and inflammatory response caused by obesity. In addition, reverse transcription-polymerase chain reaction and western blot analysis showed that LP23-1 could regulate the mRNA expression of lipid transport-related genes; activate the TLR4/NF-κB signaling pathway; reduce intestinal inflammation; improve the mRNA and protein expression of intestinal TJ proteins zona occludens-1 (ZO-1), occludin, claudin-1, and Muc2; repair intestinal mucosal injury; and enhance intestinal barrier function. The aforementioned results showed that LP23-1 through the TLR4/NF-κB signaling pathway and intestinal barrier function reduced obesity symptoms. This study provided new insights into the mechanism of LP23-1 in reducing obesity and provided a theoretical basis for developing new functional foods.

Effects of Soybean Oil Body as a Milk Fat Substitute on Ice Cream: Physicochemical, Sensory and Digestive Properties.

Soybean oil body (SOB) has potential as a milk fat substitute due to its ideal emulsification, stability and potential biological activity. In this study, SOB was used as a milk fat substitute to prepare ice cream, expecting to reduce the content of saturated fatty acid and improve the quality defects of ice cream products caused by the poor stability of milk fat at low temperatures. This study investigated the effect of SOB as a milk fat substitute (the substitution amount was 10-50%) on ice cream through apparent viscosity, particle size, overrun, melting, texture, sensory and digestive properties. The results show SOB substitution for milk fat significantly increased the apparent viscosity and droplet uniformity and decreased the particle size of the ice cream mixes, indicating that there were lots of intermolecular interactions to improve ice cream stability. In addition, ice cream with 30% to 50% SOB substitution had better melting properties and texture characteristics. The ice cream with 40% SOB substitution had the highest overall acceptability. Furthermore, SOB substitution for milk fat increased unsaturated fatty acid content in ice cream and fatty acid release during digestion, which had potential health benefits for consumers. Therefore, SOB as a milk fat substitute may be an effective way to improve the nutritional value and quality characteristics of dairy products.

Lactobacillus plantarum Combined with Galactooligosaccharides Supplement: A Neuroprotective Regimen Against Neurodegeneration and Memory Impairment by Regulating Short-Chain Fatty Acids and the c-Jun N-Terminal Kinase Signaling Pathway in Mice.

Probiotics and prebiotics have received attention in alleviating neurodegenerative diseases. Lactobacillus plantarum (L. plantarum) 69-2 was combined with galactooligosaccharides (GOS) and supplemented in a d-galactose (d-gal)-induced neurodegeneration and memory impairment mice model to explore its effects on the brain and the regulation of short-chain fatty acids. The results showed that the L. plantarum-GOS supplementation inhibited d-gal-induced oxidative stress and increased the brain's nuclear factor erythroid 2-related factor 2 (Nrf2) levels. Butyrate, a metabolite of the gut microbiota regulated by L. plantarum combined with GOS, inhibits p-JNK expression, downregulates pro-apoptotic proteins expression and the activation of inflammatory mediators, and upregulates synaptic protein expression. This might be a potential mechanism for L. plantarum 69-2 combined with GOS supplementation to alleviate d-gal-induced neurodegeneration and memory impairment. This study sheds new light on the development of aging-related neuroprotective dietary supplements based on the gut-brain axis.

Lactobacillus paracasei 24 Attenuates Lipid Accumulation in High-Fat Diet-Induced Obese Mice by Regulating the Gut Microbiota.

Obesity has become a worldwide public health problem. Lactic acid bacteria have attracted extensive attention for alleviating obesity and fat accumulation. This study aimed to evaluate the alleviating effects of Lactobacillus paracasei 24 (LP24) on lipid accumulation in an obese mouse model induced by a high-fat diet (HFD). The results showed that LP24 treatment significantly reduced body weight and fat deposition in HFD mice, improved blood lipid levels and liver steatosis, reduced liver oxidative stress injury and the inflammatory response, and regulated fat metabolism-related factors. Moreover, LP24 regulated the abundance and diversity of the gut microbiota, reduced the abundance of Firmicutes and the ratio of Firmicutes/Bacteroidetes (F/B), and increased the abundance of Akkermansia. In summary, LP24 regulates lipid metabolism by activating the expression level of related genes and regulating the gut microbiota through the gut-liver axis to attenuate the development of obesity. This study provides a theoretical basis for probiotics to regulate gut microbiota to reduce lipid accumulation.

Reproducibility and Validity of a Semi-Quantitative Food Frequency Questionnaire for Assessing Dietary Intake of Vegetarians and Omnivores in Harbin, China.

This study aims to evaluate the reproducibility and validity of a semi-quantitative food frequency questionnaire (SQFFQ) developed for vegetarians and omnivores in Harbin, China. Participants (36 vegetarians and 64 omnivores) administered SQFFQ at baseline (SQFFQ1) and six months later (SQFFQ2) to assess the reproducibility. The 24 h recalls (24 HRs) for three consecutive days were completed between the administrations of two SQFFQs to determine the validity. For reproducibility, Pearson correlation coefficients between SQFFQ1 and SQFFQ2 for vegetarians and omnivores were 0.45~0.88 and 0.44~0.84, respectively. For validity, unadjusted Pearson correlation coefficients were 0.46~0.83 with an average of 0.63 and 0.43~0.86 with an average of 0.61, respectively; energy-adjusted Pearson correlation coefficients were 0.43~0.82 with an average of 0.61 and 0.40~0.85 with an average of 0.59, respectively. Majority of the correlation coefficients for food groups and macronutrients decreased or remained unchanged after energy adjustment. Furthermore, all correlations were statistically significant (p < 0.05). Bland−Altman plots also showed reasonably acceptable agreement between the two methods. In conclusion, the SQFFQ developed in this study has reasonably acceptable reproducibility and validity.

Soybean-Oil-Body-Substituted Low-Fat Ice Cream with Different Homogenization Pressure, Pasteurization Condition, and Process Sequence: Physicochemical Properties, Texture, and Storage Stability.

The purpose of this research was to explore the impacts of different homogenization pressures, pasteurization conditions, and process sequence on the physical and chemical properties of soybean oil body (SOB)-substituted low-fat ice cream as well as the storage stability of SOB-substituted ice cream under these process parameters. With the increase of homogenization pressure (10-30 MPa), the increase of pasteurization temperature (65 °C for 30 min-85 °C for 15 min), and the addition of SOB before homogenization, the overrun and apparent viscosity of ice cream increased significantly, and the particle size, hardness, and melting rate decreased significantly. Thus, frozen dairy products of desired quality and condition could be obtained by optimizing process parameters. In addition, the SOB ice cream showed better storage stability, which was reflected in lower melting rate and hardness and more stable microstructure compared with the full-milk-fat ice cream. This study opened up new ideas for the application of SOB and the development of nutritious and healthy ice cream. Meanwhile, this research supplied a conceptual basis for the processing and quality optimization of SOB ice cream.