bluuebunny/crossref_metadata_2025 huggingface dataset:
Fermentation of ginkgo biloba kernel juice using Lactobacillus plantarum Y2 from the ginkgo peel: Fermentation characteristics and evolution of phenolic profiles, antioxidant activities in vitro, and volatile flavor compounds
Authors: Yang Jie , Sun Yue , Chen Jinling , Cheng Yu , Zhang Haoran , Gao Tengqi , Xu Feng , Pan Saikun , Tao Yang , Lu Jing
Published: October 2022

In this study, a strain of Lactobacillus plantarum Y2 was isolated from the ginkgo peel, and showed adequate adaptation to the ginkgo biloba kernel juice. After 48 h of fermentation, the number of viable cells in the stable growth phase was remained at 10.0 Log CFU/mL, while the content of total organic acid increased by 5.86%. Phenolic substances were significantly enriched, and the content of total phenolic substances increased by 9.72%, and the content of total flavonoids after fermentation exceeded 55.33 mg/L, which was 3.6 times that of the unfermented ginkgo juice. The total relative content of volatile flavor compounds increased by 125.48%, and 24 new volatile flavor substances were produced. The content of total sugar, total protein, and total free amino acid decreased to 44.85, 67.51, and 6.88%, respectively. Meanwhile, more than 82.25% of 4′-O-methylpyridoxine was degraded by lactic acid fermentation, and the final concentration in ginkgo biloba kernel juice was lower than 41.53 mg/L. In addition, the antioxidant and antibacterial activities of fermented ginkgo biloba kernel juice were significantly enhanced. These results showed that LAB fermentation could effectively improve the nutritional value and safety of ginkgo biloba kernel juice.
Antioxidant and antidiabetic activities of a polyphenol rich extract obtained from Abelmoschus esculentus (okra) seeds using optimized conditions in microwave-assisted extraction (MAE)
Authors: Woumbo Cerile Ypolyte , Kuate Dieudonné , Metue Tamo Danielle Gaelle , Womeni Hilaire Macaire
Published: October 2022

Functional foods have gained popularity in recent decades. They are exploited for their bioactive compounds like polyphenols, which are highly demanded in cosmetic, pharmaceutical and nutraceutical industries. However, extractive techniques and conditions used up to recently are almost obsolete and must be optimized for higher efficiency. The current study aimed to evaluate the antidiabetic potential of an optimized extract of Abelmoschus esculentus (okra) seeds. The optimal conditions for extracting polyphenolic compounds from okra seeds were determined using Microwave Assisted Extraction (MAE). A Face Center Composite Design (FCCD) was used for optimization. Solvent/dry matter ratio, wavelength and time were considered while the response studied was the polyphenolic content. The extract obtained at optimal conditions was characterized using Thin Layer Chromatography (TLC) and Fourier Transform Infra-Red (FTIR) spectroscopy, then tested for its antioxidant, alpha amylase inhibitory and antidiabetic activities. Response Surface Methodology (RSM) permitted the determination of the optimal conditions for phenols extraction as: microwave power 330 W, with a solvent ratio of 97.04/1 mL/g for 9.5 min of extraction time. The optimized extract showed a phenolic content up to 86.37 ± 1.13 mg GAE/g containing quercetin and catechin as revealed by the TLC. Functional groups characteristic of polyphenols were identified on FTIR spectra, and the extract exhibited good in vitro antioxidant capacities with DPPH (2, 2-diphenyl-1-picrylhydrazyl) radical scavenging capacity and FRAP (Ferric Reducing Antioxidant Power Assay). An IC50 of 3.99 ± 0.15 μg/mL was obtained with the DPPH scavenging test. Alpha amylase inhibitory assay revealed that the optimized okra extract behaved as a non-competitive inhibitor of porcine pancreatic amylase with an IC50 of 484.17 ± 2.33 μg/mL. Antidiabetic activity of the extract was observed in streptozotocin-induced diabetic males Wistar rats, as shown by the fasting blood glucose levels, food intake, changes in body weight and serum lipid profile among others.
Coconut oil and medium-chain fatty acids attenuate high-fat diet-induced obesity in mice through increased thermogenesis by activating brown adipose tissue
Authors: Gao Yunxiao , Liu Yiwen , Han Xue , Zhou Fang , Guo Jielong , Huang Weidong , Zhan Jicheng , You Yilin
Published: October 2022

Coconut oil (CO) and its main ingredients, medium-chain fatty acids (MCFA), present many benefits. Whether MCFA and CO play an equally valuable role in anti-obesity remains unclear. This study compared the anti-obesity effects of CO and MCFA [octanoic acid (C8:0) and decanoic acid (C10:0)] to gain insight into the underlying mechanism. Male C57BL/6J mice were fed either a low-fat diet (LFD) or high-fat diet (100% HFD) replaced with 2.5% MCFA (97.5% HFD + 2.5% MCFA) or 5% CO (95% HFD + 5% CO) for 17 weeks. CO and MCFA ameliorated the HFD-induced abnormal body and adipose depot weights, insulin sensitivity, and energy expenditure (EE), which was associated with brown adipose tissue (BAT) thermogenesis. Furthermore, CO enhanced the expression of thermogenesis markers in BAT, which was consistent with increased BAT activity. CO showed a better effect than MCFA in activating BAT to increase thermogenesis and energy metabolism to combat obesity, which may be attributed to the cooperation of MCFA and other substances in CO. This work provides evidence for the anti-obesity effects of CO, which could be a better alternative to lard in daily diet, rather than pure MCFA.
Effect of natural polyphenols in Chinese herbal medicine on obesity and diabetes: Interactions among gut microbiota, metabolism, and immunity
Authors: Chen Keyu , Gao Zezheng , Ding Qiyou , Tang Cheng , Zhang Haiyu , Zhai Tiangang , Xie Weinan , Jin Zishan , Zhao Linhua , Liu Wenke
Published: October 2022

With global prevalence, metabolic diseases, represented by obesity and type 2 diabetes mellitus (T2DM), have a huge burden on human health and medical expenses. It is estimated that obese population has doubled in recent 40 years, and population with diabetes will increase 1.5 times in next 25 years, which has inspired the pursuit of economical and effective prevention and treatment methods. Natural polyphenols are emerging as a class of natural bioactive compounds with potential beneficial effects on the alleviation of obesity and T2DM. In this review, we investigated the network interaction mechanism of “gut microbial disturbance, metabolic disorder, and immune imbalance” in both obesity and T2DM and systemically summarized their multiple targets in the treatment of obesity and T2DM, including enrichment of the beneficial gut microbiota (genera Bifidobacterium, Akkermansia, and Lactobacillus) and upregulation of the levels of gut microbiota-derived metabolites [short-chain fatty acids (SCFAs)] and bile acids (BAs). Moreover, we explored their effect on host glucolipid metabolism, the AMPK pathway, and immune modulation via the inhibition of pro-inflammatory immune cells (M1-like Mϕs, Th1, and Th17 cells); proliferation, recruitment, differentiation, and function; and related cytokines (TNF-α, IL-1β, IL-6, IL-17, and MCP-1). We hope to provide evidence to promote the clinical application of natural polyphenols in the management of obesity and T2DM.
Assessment of self-reported financial toxicity among patients with nasopharyngeal carcinoma undergoing radiotherapy: A cross-sectional study in western China
Authors: Jiang Hua , Mou Wenxuan , Lyu Jianxia , Jiang Luxi , Liu Ying , Zeng Yu , Hu Aiping , Zheng Wei , Jiang Qinghua , Yang Shuang
Published: October 2022

Objective 

Using the Comprehensive Score for Financial Toxicity (COST) tool to measure financial toxicity (FT) among nasopharyngeal cancer (NPC) patients in western China and investigate the association between FT and psychological distress.

Methods

We conducted a cross-sectional study of survivors with NPC in a tertiary oncology hospital in China. FT was assessed using the COST (Chinese version), a validated instrument widely used both at home and abroad. The NCCN Distress Thermometer (DT) was used to measure psychological distress. A multivariate logistic regression model was built to determine factors associated with FT, and the Pearson correlation was used to assess the correlation between COST and DT scores.

Results

Of 210 patients included in this study, the mean FT score was 16.3 (median: 22.5, SD: 9.7), and the prevalence of FT was 66.2% (mild FT: 37.1%, moderate FT: 50.5%, severe FT: 2.4%). Suggested by the logistic regression model, 5 variables were associated with increased FT: unemployed, no commercial insurance, receiving lower annual income, advanced cancer, and receiving targeted therapy. The Pearson correlation showed a significantly moderate correlation between financial toxicity and psychological distress (r= -0.587, P < 0.001).

Conclusion

Patients with nasopharyngeal carcinoma (NPC) in western China demonstrated higher self-reported financial toxicity (FT) associated with factors including unemployed, no commercial insurance, receiving lower annual income, advanced cancer, and receiving targeted therapy. These predictors will help clinicians identify potential patients with FT in advance and conduct effective psychological interventions.
A refractory liver metastatic solid pseudopapillary neoplasm pancreas harbored CTNNB1 mutation showed good response to celecoxib: A case report
Authors: Shang Yu , Zhang Yunkun , Pan Evenki , Yang Peng , Xu Lingling , Sun Jinghua
Published: October 2022

Solid pseudopapillary neoplasm (SPN) of the pancreas is rare relatively low-grade malignant neoplasm and metastasis rarely. Surgical resection is the primary treatment option for primary and metastatic lesions of SPN, and chemotherapy is often ineffective in non-operable SPNs. SPNs are characterized by the presence of somatic CTNNB1 exon 3 mutations, leading to the activation of Wnt/β-catenin/Cox-2 signal pathway. Here, we firstly report that a refractory liver metastatic pancreatic SPN patient after the failure of multi-line chemotherapies benefited from the Cox-2 selective inhibitor (Celecoxib) based on CTNNB1 D32V mutation detected by next-generation sequencing (NGS), achieving a more than 22-month progression-free survival without any adverse events. Our case provides a potential treatment option for liver metastatic SPN patients with CTNNB1 mutations and highlights the application of NGS for the better treatment decision making.
Automated 3D segmentation of the aorta and pulmonary artery for predicting outcomes after thoracoscopic lobectomy in lung cancer patients
Authors: Lee Hsin-Ying , Chung Yu-Jung , Wang Hao-Jen , Chiang Xu-Heng , Chen Li-Wei , Lin Yan-Ting , Lee Yi-Chieh , Hsu Hsao-Hsun , Chang Yeun-Chung , Chen Chung-Ming , Lin Mong-Wei , Chen Jin-Shing
Published: October 2022

Background

Preoperative two-dimensional manual measurement of pulmonary artery diameter in a single-cut axial view computed tomography (CT) image is a commonly used non-invasive prediction method for pulmonary hypertension. However, the accuracy may be unreliable. Thus, this study aimed to evaluate the correlation of short-term surgical outcomes and pulmonary artery/aorta (PA/Ao) diameter ratio measured by automated three-dimensional (3D) segmentation in lung cancer patients who underwent thoracoscopic lobectomy.

Materials and methods

We included 383 consecutive lung cancer patients with thin-slice CT images who underwent lobectomy at a single institute between January 1, 2011 and December 31, 2019. Automated 3D segmentation models were used for 3D vascular reconstruction and measurement of the average diameters of Ao and PA. Propensity-score matching incorporating age, Charlson comorbidity index, and lobectomy performed by uniportal VATS was used to compare clinical outcomes in patients with PA/Ao ratio ≥1 and those <1.

Results

Our segmentation method measured 29 (7.57%) patients with a PA/Ao ratio ≥1. After propensity-score matching, a higher overall postoperative complication classified by the Clavien–Dindo classification (p = 0.016) were noted in patients with 3D PA/Ao diameter ratio ≥1 than those of <1. By multivariate logistic regression, patients with a 3D PA/Ao ratio ≥ 1 (p = 0.013) and tumor diameter > 3 cm (p = 0.002) both significantly predict the incidence of postoperative complications.

Conclusions

Pulmonary artery/aorta diameter ratio ≥ 1 measured by automated 3D segmentation may predict postoperative complications in lung cancer patients who underwent lobectomy.
Mono- and biallelic germline variants of DNA glycosylase genes in colon adenomatous polyposis families from two continents
Authors: Olkinuora Alisa Petriina , Mayordomo Andrea Constanza , Kauppinen Anni Katariina , Cerliani María Belén , Coraglio Mariana , Collia Ávila Karina , Gutiérrez Alejandro , Alvarez Karin , Cassana Alessandra , Lopéz-Köstner Francisco , Jauk Federico , García-Rivello Hernán , Ristimäki Ari , Koskenvuo Laura , Lepistö Anna , Nieminen Taina Tuulikki , Vaccaro Carlos Alberto , Pavicic Walter Hernán , Peltomäki Päivi
Published: October 2022

Recently, biallelic germline variants of the DNA glycosylase genes MUTYH and NTHL1 were linked to polyposis susceptibility. Significant fractions remain without a molecular explanation, warranting searches for underlying causes. We used exome sequencing to investigate clinically well-defined adenomatous polyposis cases and families from Finland (N=34), Chile (N=21), and Argentina (N=12), all with known susceptibility genes excluded. Nine index cases (13%) revealed germline variants with proven or possible pathogenicity in the DNA glycosylase genes, involving NEIL1 (mono- or biallelic) in 3 cases, MUTYH (monoallelic) in 3 cases, NTHL1 (biallelic) in 1 case, and OGG1 (monoallelic) in 2 cases. NTHL1 was affected with the well-established, pathogenic c.268C>T, p.(Gln90Ter) variant. A recurrent heterozygous NEIL1 c.506G>A, p.(Gly169Asp) variant was observed in two families. In a Finnish family, the variant occurred in trans with a truncating NEIL1 variant (c.821delT). In an Argentine family, the variant co-occurred with a genomic deletion of exons 2 – 11 of PMS2. Mutational signatures in tumor tissues complied with biological functions reported for NEIL1. Our results suggest that germline variants in DNA glycosylase genes may occur in a non-negligible proportion of unexplained colon polyposis cases and may predispose to tumor development.
Establishment of a nomogram for predicting lymph node metastasis in patients with early gastric cancer after endoscopic submucosal dissection
Authors: Zhang Xin , Yang Dejun , Wei Ziran , Yan Ronglin , Zhang Zhengwei , Huang Hejing , Wang Weijun
Published: October 2022

Background

Endoscopic submucosal dissection (ESD) has been accepted as the standard treatment for the appropriate indication of early gastric cancer (EGC). Determining the risk of lymph node metastasis (LNM) is critical for the following treatment selection after ESD. This study aimed to develop a predictive model to quantify the probability of LNM in EGC to help minimize the invasive procedures.

Methods

A total of 952 patients with EGC who underwent radical gastrectomy were retrospectively reviewed. LASSO regression was used to help screen the potential risk factors. Multivariate logistic regression was used to establish a predictive nomogram, which was subjected to discrimination and calibration evaluation, bootstrapping internal validation, and decision curve analysis.

Results

Results of multivariate analyses revealed that gender, fecal occult blood test, CEA, CA19-9, histologic differentiation grade, lymphovascular invasion, depth of infiltration, and Ki67 labeling index were independent prognostic factors for LNM. The nomogram had good discriminatory performance, with a concordance index of 0.816 (95% CI 0.781–0.853). The validation dataset yielded a corrected concordance index of 0.805 (95% CI 0.770–0.842). High agreements between ideal curves and calibration curves were observed.

Conclusions

The nomogram is clinically useful for predicting LNM after ESD in EGC, which is beneficial to identifying patients who are at low risk for LNM and would benefit from avoiding an unnecessary gastrectomy.
Apatinib combined with PD-1 antibody for third-line or later treatment of advanced gastric cancer
Authors: Cui Qingli , Mao Yuefeng , Wu Daoyuan , Hu Yanhui , Ma Dongyang , Zhang LiHan , Liu Huaimin
Published: October 2022

Background

Both apatinib and programmed death 1 (PD-1) monoclonal antibody (mAb) monotherapy have been licensed in China for the third-line treatment of advanced gastric cancer (AGC). However, whether the combination could improve the prognosis of patients with AGC after second-line treatment has not been evaluated.

Methods

We retrospectively screened 892 patients with AGC who received third-line or later treatment from June 2016 to July 2021 at the Affiliated Cancer Hospital of Zhengzhou University and second People’s Hospital of Pingdingshan. 166 patients who received apatinib plus PD-1 mAb, apatinib, or PD-1 mAb were included. Based on medical records and follow-up data, we analyzed the efficacy and safety of these three treatment options.

Results

Patients received apatinib plus PD-1 mAb (n=49), apatinib monotherapy (n=63), or PD-1 mAb monotherapy (n=54). Apatinib plus PD-1 mAb showed significantly longer progression-free survival (PFS) and overall surivival (OS) compared with the apatinib monotherapy (PFS: 5.5 months versus 3.0 months; p=0.002; OS: 10 months versus 7.6 months; p=0.011) or PD-1 mAb monotherapy (PFS: 5.5 months versus 2.3 months; p=0.017; OS: 10 months versus 6.5 months; p=0.004). Apatinib plus PD-1 mAb showed higher ORR and DCR than the apatinib and PD-1 mAb monotherapy (ORR: 34.7% versus 6.3% versus 9.3%; p=0.001; DCR: 75.5% versus 44.4% versus 40.7%; p=0.001). Further subgroup analysis for PFS and OS shown consistent efficacy in most subgroups with apatinib plus PD-1 mAb versus apatinib monotherapy or PD-1 mAb monotherapy. Multivariate analyses suggested that apatinib plus PD-1 mAb was significantly associated with better PFS and OS. Most of the treatment-related toxicities were mild and tolerable.

Conclusion

Compared with the monotherapy of either apatinib or PD-1 mAb, apatinib plus PD-1 mAb treatment yielded longer PFS and OS, and achieved significant higher ORR and DCR.
Study on the changes of CT texture parameters before and after HCC treatment in the efficacy evaluation and survival predication of patients with HCC
Authors: Zhou Wei , Lv Yinzhang , Hu Xuemei , Luo Yan , Li Jiali , Zhu Haidan , Hai Yucheng
Published: October 2022

Objective

To investigate texture parameters of contrast-enhanced computed tomography (CT) images before and after transarterial chemoembolization (TACE) as a tool for assessing the therapeutic response and survival predication in hepatocellular carcinoma (HCC).

Materials and methods

Data of 77 HCC patients who underwent three-phase dynamic contrast-enhanced CT examination within 4 weeks before and 4–8 weeks after TACE were collected and efficacy evaluation was performed according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST) standard. The remission group consisted of 31 patients (12 with complete remission+19 with partial remission), while the non-remission group consisted of 46 patients (27 with stable disease+19 with progressive disease). Full-volume manual delineation of the region of interest (ROI) and texture analysis of the ROI were performed on the CT images using FireVoxel software. Changes in the 48 texture parameters from three-phase CT images before and after TACE were calculated and compared between the two groups. The receiver operating characteristic (ROC) curve and the areas under the curve (AUC) were used to analyze the diagnostic performance of texture parameters. A multifactorial Cox model was used for predicting survival. The C-indices of texture parameter difference values with predictive value, texture features model, and texture features combined with mRECIST in predicting OS were compared with those of mRECIST.

Results

A total of 41 changes in texture parameters were statistically significant between the remission and non-remission groups. The receiver operating characteristic (ROC) curve showed that the AUC of changes in the 90th percentile in the arterial phase was the largest at 0.842. When the cut-off value was 70.50, the Youden index was the largest (0.621), and the sensitivity and specificity were 0.710 and 0.911, respectively. Three changes in texture parameters were independent factors associated with patient survival, with a hazard of 0.173, 2.068, and 1.940, respectively. The C-index of the OS predicted by the texture features model was not statistically different from that of the mRECIST (0.695 vs. 0.668, p=0.493). While the C-indices of skewness in the portal venous phase combined with mRECIST (0.729, p=0.015), skewness in the delayed phase combined with mRECIST (0.715, p=0.044), and skewness in both two phases combined with mRECIST (0.728, p=0.017) were statistically different.

Conclusion

Changes in the texture parameters of CT images before and after TACE treatment can be used to obtain relevant grayscale histogram parameters for evaluating the early efficacy of TACE in HCC treatment. And the texture analysis combined with mRECIST may be superior to the mRECIST alone in predicting survival in HCC after TACE treatment.
The sternum reconstruction: Present and future perspectives
Authors: Aramini Beatrice , Masciale Valentina , Radaelli Lorenzo Federico Zini , Sgarzani Rossella , Dominici Massimo , Stella Franco
Published: October 2022

Sternectomy is a procedure mainly used for removing tumor masses infiltrating the sternum or treating infections. Moreover, the removal of the sternum involves the additional challenge of performing a functional reconstruction. Fortunately, various approaches have been proposed for improving the operation and outcome of reconstruction, including allograft transplantation, using novel materials, and developing innovative surgical approaches, which promise to enhance the quality of life for the patient. This review will highlight the surgical approaches to sternum reconstruction and the new perspectives in the current literature.
Case report: Pulmonary hypertensive crisis leading to cardiac arrest during endoscopic evaluation in a 6-year-old boy with autism, severe malnutrition, and undiagnosed scurvy
Authors: Quinn Laura A. , Gilley Stephanie P. , Ta Allison D. , Frank Benjamin S. , Foley Carolyn B. , Moore Jaime M.
Published: October 2022

Pediatric gastroenterologists are often responsible for the evaluation of malnutrition in the setting of selective eating. Endoscopic evaluation for conditions including eosinophilic esophagitis and celiac disease can help to identify and treat mucosal disease contributing to food selectivity. However, undiagnosed micronutrient deficiencies can cause cardiovascular derangements that significantly increase a patient's anesthetic risk. Vitamin C deficiency in particular, alone or in combination with severe malnutrition, is associated with a severe but reversible form of pulmonary arterial hypertension that, while life threatening in the acute phase, may significantly improve within days of starting ascorbic acid replacement therapy. Here we present a case of a 6-year-old boy with autism spectrum disorder (ASD), severe malnutrition, and undiagnosed chronic vitamin C deficiency who developed a pulmonary hypertensive crisis after induction of general anesthesia leading to cardiac arrest during endoscopic evaluation. While the association between food selectivity among youth with neurodevelopmental differences and vitamin C deficiency is well-described, and pulmonary hypertension is a recognized rare complication of scurvy, extant literature has not addressed next steps to improve patient outcomes. Using this case report as a foundation, we discuss specific patient populations to screen and treat for micronutrient deficiencies prior to anesthesia and propose a novel clinical algorithm for pre-anesthesia risk stratification and mitigation in patients specifically at risk for scurvy and associated pulmonary hypertension.
Case Report: Congenital disseminated tuberculosis neonate born to tuberculosis- COVID-19 mother
Authors: Risan Nelly Amalia , Febrianda Rilda Dwi , Nataprawira Heda Melinda
Published: October 2022

We report a case of a 26-day-old male neonate with high suggestive of congenital disseminated tuberculosis (TB) [tuberculous meningitis (TBM), pulmonary TB, and ocular TB] at term, low birth weight born cesarean section from a confirmed COVID-19 and pulmonary TB mother who hospitalized in the isolation room and never seen her son for three weeks. The baby had a fever for two weeks after birth and a history of seizures. A nasopharyngeal swab for RT-PCR SARS-CoV-2 yielded a negative result. He was initially diagnosed as having a sepsis-like syndrome and then hospitalized. Chest x-ray revealed bilateral infiltrate, cerebrospinal fluid analysis (CSF) showed clear, cell count was 9 with dominant mononuclear cell, and gastric lavages did not yield acid-fast bacilli. X-pert MTB/RIF from gastric lavage specimen detected Mycobacterium tuberculosis rifampicin sensitive. Anti-tuberculosis drugs for TBM were started. Abdominal sonography identified multiple hypoechoic nodules in the liver and spleen. Neuroimaging studies did not identify hydrocephalus, meningeal enhancement, infarct, or tuberculoma. A Video-EEG examination showed electrical seizure after initiation of phenobarbital. Video-EEG evaluation showed no epileptiform discharge. Upon follow-up, he showed slightly delayed motor development, pan-uveitis, retinal detachment, and cataracts. We assumed that ocular TB resulted from a paradoxical reaction following TB treatment. Retinal detachment was improved and lens replacement was done.
Comprehensibility of a personalized medication overview compared to usual-care prescription drug labels
Authors: Schackmann Laura , van Dijk Liset , Brabers Anne E. M. , Zwier Sandra , Koster Ellen S. , Vervloet Marcia
Published: October 2022

Poor understanding of prescription drug label (PDL) instructions can lead to medication errors, suboptimal treatment (side) effects, and non-adherence. A personalized medication hard-copy overview listing PDL instructions and visual information may support patients in their medication use. This study aimed to investigate the comprehensibility of PDL instructions on a personalized medication overview compared to usual-care PDL instructions presented on a medication box. A hypothetical-online-experiment was set up, comparing groups of respondents exposed vs not exposed to the medication overview and who received PDL instructions for three, five, or eight medications. Participants were divided randomly in six groups. Online questionnaires were sent to a stratified sample of 900 members from the Nivel Dutch Healthcare Consumer Panel. Outcome measures included comprehension of instructions for medication use, e.g. how often, dose timing, usage advice and warnings for a medication with simple use instructions (omeprazol) and more complex use instructions (levodopa/carbidopa (L/C)). To analyze differences between experimental conditions ANOVA testing was used. 604 respondents (net response 67%) completed the questionnaires. Respondents exposed (E) to the overview gave a higher proportion of correct answers compared to non-exposed (NE) respondents for usage advice (L/C: mean 0.83, SD 0.4 E; 0.03, SD 0.2 NE, p < 0.001; omeprazol: mean 0.85, SD 0.4 E; 0.10, SD 0.3 NE, p < 0.001). Both groups gave the same proportion of correct answers (mean 0.80, SD 0.4, p = 1.0) for dose timing of omeprazol. More NE respondents gave correct answers for how often (mean 0.85, SD 0.4 NE; mean 0.76, SD 0.4 E, p = 0.02) and dose timing (mean 0.92, SD 0.3 NE; mean 0.86, SD 0.4 E, p = 0.04) of L/C. No differences were found regarding number of medications nor were interaction effects found between the number of medications and information type. As a medication overview contains additional information, it can be a good addition in supporting patients in their medication use compared to usual-care PDLs. Future research should focus on identifying patient groups who might benefit more from a medication overview, by testing the effect of such overview on this group.
Molecular docking and biochemical validation of (-)-syringaresinol-4-O-β-D-apiofuranosyl-(1→2)-β-D-glucopyranoside binding to an allosteric site in monoamine transporters
Authors: Liu Hanhe , Wu Yingyao , Li Chan , Tang Qingfa , Zhang Yuan-Wei
Published: October 2022

Albizia julibrissin Durazz is one of the most common herbs used for depression and anxiety treatment, but its mechanism of action as an antidepressant or anxiolytic drug have not been fully understood. We previously isolated and identified one lignan glycoside compound from Albizia Julibrissin Durazz, (-)-syringaresinol-4-O-β-D-apiofuranosyl-(1→2)-β-D-glucopyranoside (SAG), that inhibited all three monoamine transporters with a mechanism of action different from that of the conventional antidepressants. In this study, we generated homology models for human dopamine transporter and human norepinephrine transporter, based on the X-ray structure of Drosophila dopamine transporter, and conducted the molecular docking of SAG to all three human monoamine transporters. Our computational results indicated that SAG binds to an allosteric site (S2) that has been demonstrated to be formed by an aromatic pocket positioned in the scaffold domain in the extracellular vestibule connected to the central site (S1) in these monoamine transporters. In addition, we demonstrated that SAG stabilizes a conformation of serotonin transporter with both the extracellular and cytoplasmic pathways closed. Furthermore, we performed mutagenesis of the residues in both the allosteric and orthosteric sites to biochemically validate SAG binding in all three monoamine transporters. Our results are consistent with the molecular docking calculation and support the association of SAG with the allosteric site. We expect that this herbal molecule could become a lead compound for the development of new therapeutic agents with a novel mechanism of action.
Synthesis and appraisal of dalbergin-loaded PLGA nanoparticles modified with galactose against hepatocellular carcinoma: In-vitro, pharmacokinetic, and in-silico studies
Authors: Gautam Anurag Kumar , Kumar Pranesh , Maity Biswanath , Routholla Ganesh , Ghosh Balaram , Chidambaram Kumarappan , Begum M. Yasmin , Al Fatease Adel , Rajinikanth P.S. , Singh Sanjay , Saha Sudipta , M. R. Vijayakumar
Published: October 2022

Hepatocellular carcinoma (HCC) is a common malignancy which affects a substantial number of individuals all over the globe. It is the third primary cause of death among persons with neoplasm and has the fifth largest mortality rate among men and the seventh highest mortality rate among women. Dalbergin (DL) is described to be effective in breast cancer via changing mRNA levels of apoptosis-related proteins. DL belongs to neoflavonoids, a drug category with low solubility and poor bioavailability. We created a synthetic version of this naturally occurring chemical, DL, and then analyzed it using 1H-NMR, 13C-NMR, and LC-MS. We also made PLGA nanoparticles and then coated them with galactose. The design of experiment software was used to optimize DL-loaded galactose-modified PLGA nanoparticles. The optimized DL-nanoformulations (DLF) and DL-modified nanoformulations (DLMF) were analyzed for particle size, polydispersity index, shape, and potential interactions. In-vitro experiments on liver cancer cell lines (HepG2) are used to validate the anti-proliferative efficacy of the modified DLMF. The in-vitro research on HepG2 cell lines also demonstrated cellular accumulation of DLF and DLMF by FITC level. The in-vitro result suggested that DLMF has high therapeutic effectiveness against HCC. In-vivo pharmacokinetics and bio-distribution experiments revealed that DLMF excelled pristine DL in terms of pharmacokinetic performance and targeted delivery, which is related to galactose’s targeting activity on the asialoglycoprotein receptor (ASGPR) in hepatic cells. Additionally, we performed an in-silico study of DL on caspase 3 and 9 proteins, and the results were found to be −6.7 kcal/mol and −6.6 kcal/mol, respectively. Our in-silico analysis revealed that the DL had strong apoptotic properties against HCC.
The anticancer effects of curcumin and clinical research progress on its effects on esophageal cancer
Authors: Wang Shimeng , Gao Xinliang , Li Jialin , Wei Shixiong , Shao Yifeng , Yin Yipeng , Zhang Duo , Tang Mingbo
Published: October 2022

Esophageal cancer (EC) is a common tumor of the gastrointestinal system and a major threat to human health. The etiology and incidence of EC vary depending on the type of pathology. Owing to the unique physiological structure of the esophagus and the poor biological behavior of EC, the treatment modalities available are limited, and the prognosis of patients is relatively poor. Curcumin is a type of natural phytochemical belonging to the class of phenolic compounds. It exerts favorable anticancer effects on various cancers. A growing body of evidence indicates that curcumin suppresses tumor development and progression by inhibiting tumor cell proliferation, invasion, and migration, thus inducing apoptosis, regulating microRNA expression, reversing multidrug resistance, and inducing sensitivity to the therapeutic effect of chemoradiotherapy. Multiple cellular molecules, growth factors, and genes encoding proteins participating in different signaling pathways interact with each other to contribute to the complex and orderly anticancer effect. The efficacy and safety of curcumin have been established in preclinical studies for EC and clinical trials for other cancers. However, the low bioavailability of curcumin limits its clinical application. Therefore, the modification of curcumin analogs, the combination of curcumin with other drugs or therapies, and the use of novel nanocarriers have been widely investigated to improve the clinical effects of curcumin in EC.
Modified Qing’e Formula protects against UV-induced skin oxidative damage via the activation of Nrf2/ARE defensive pathway
Authors: Zhu Shan , Qin Wenxiao , Liu Tao , Liu Tao , Ma Hongfei , Hu Cunyu , Yue Xiaofeng , Yan Yiqi , Lv Yingshuang , Wang Zijing , Zhao Zhiyue , Wang Xiang , Liu Yan , Xia Qingmei , Zhang Han , Li Nan
Published: October 2022

Exposure to ultraviolet (UV) light triggers the rapid generation and accumulation of reactive oxygen species (ROS) in skin cells, which increases oxidative stress damage and leads to photoaging. Nuclear factor E2-related factor 2 (Nrf2) modulates the antioxidant defense of skin cells against environmental factors, especially ultraviolet radiation. Natural products that target Nrf2-regulated antioxidant reactions are promising candidates for anti-photoaging. The aim of this study was to investigate the protective effect of Modified Qing’e Formula (MQEF) on UV-induced skin oxidative damage and its molecular mechanisms. In this study, the photoaging models of human keratinocytes (HaCaT) and ICR mice were established by UV irradiation. In vitro models showed that MQEF displayed potent antioxidant activity, significantly increased cell viability and reduced apoptosis and excess ROS levels. Meanwhile, the knockdown of Nrf2 reversed the antioxidant and anti-apoptotic effects of MQEF. In vivo experiments indicated that MQEF could protect the skin against UV-exposed injury which manifested by water loss, sensitivity, tanning, wrinkling, and breakage of collagen and elastic fibers. The application of MQEF effectively increased the activity of antioxidant enzymes and reduced the content of malondialdehyde (MDA) in mice. In addition, MQEF was able to activate Nrf2 nuclear translocation in mouse skin tissue. In summary, MQEF may attenuate UV-induced photoaging by upregulating Nrf2 expression and enhancing antioxidant damage capacity. MQEF may be a potential candidate to prevent UV-induced photoaging by restoring redox homeostasis.
MMPP promotes adipogenesis and glucose uptake via binding to the PPARγ ligand binding domain in 3T3-L1 MBX cells
Authors: Kim Na-Yeon , Lim Chae-Min , Park Hyo-Min , Kim Jinju , Pham Thu-Huyen , Yang Young , Lee Hee Pom , Hong Jin Tae , Yoon Do-Young
Published: October 2022

Peroxisome proliferator-activated receptor-gamma (PPARγ) is a transcription factor involved in adipogenesis, and its transcriptional activity depends on its ligands. Thiazolidinediones (TZDs), well-known PPARγ agonists, are drugs that improve insulin resistance in type 2 diabetes. However, TZDs are associated with severe adverse effects. As current therapies are not well designed, novel PPARγ agonists have been investigated in adipocytes. (E)-2-methoxy-4-(3-(4-methoxyphenyl) prop-1-en-1-yl) phenol (MMPP) is known to have anti-arthritic, anti-inflammatory, and anti-cancer effects. In this study, we demonstrated the adipogenic effects of MMPP on the regulation of PPARγ transcriptional activity during adipocyte differentiation in vitro. MMPP treatment increased PPARγ transcriptional activity, and molecular docking studies revealed that MMPP binds directly to the PPARγ ligand binding domain. MMPP and rosiglitazone showed similar binding affinities to the PPARγ. MMPP significantly promoted lipid accumulation in adipocyte cells and increased the expression of C/EBPβ and the levels of p-AKT, p-GSK3, and p-AMPKα at an early stage. MMPP enhanced the expression of adipogenic markers such as PPARγ, C/EBPα, FAS, ACC, GLUT4, FABP4 and adiponectin in the late stage. MMPP also improved insulin sensitivity by increasing glucose uptake. Thus, MMPP, as a PPARγ agonist, may be a potential drug for type 2 diabetes and metabolic disorders, which may help increase adipogenesis and insulin sensitivity.
Inhibition of colon cancer K-RasG13D mutation reduces cancer cell proliferation but promotes stemness and inflammation via RAS/ERK pathway
Authors: Qi Yan , Zou Hong , Zhao XiaoHui , Kapeleris Joanna , Monteiro Michael , Li Feng , Xu Zhi Ping , Deng Yizhen , Wu Yanheng , Tang Ying , Gu Wenyi
Published: October 2022

K-Ras is a well-studied oncogene, and its mutation is frequently found in epithelial cancers like pancreas, lung, and colorectal cancers. Cancer cells harboring K-Ras mutations are difficult to treat due to the drug resistance and metastasis properties. Cancer stem cells (CSCs) are believed the major cause of chemotherapeutic resistance and responsible for tumor recurrence and metastasis. But how K-Ras mutation affects CSCs and inflammation is not clear. Here, we compared two colon cancer cell lines, HCT-116 and HT-29, with the former being K-RasG13D mutant and the latter being wildtype. We found that HCT-116 cells treated with a K-Ras mutation inhibitor S7333 formed significantly more tumor spheroids than the untreated control, while the wild type of HT-29 cells remained unchanged. However, the size of tumor spheroids was smaller than the untreated controls, indicating their proliferation was suppressed after S7333 treatment. Consistent with this, the expressions of stem genes Lgr5 and CD133 significantly increased and the expression of self-renewal gene TGF-β1 also increased. The flow cytometry analysis indicated that the expression of stem surface marker CD133 increased in the treated HCT-116 cells. To understand the pathway through which the G13D mutation induced the effects, we studied both RAS/ERK and PI3K/Akt pathways using specific inhibitors SCH772984 and BEZ235. The results indicated that RAS/ERK rather than PI3K/Akt pathway was involved. As CSCs play the initial role in cancer development and the inflammation is a vital step during tumor initiation, we analyzed the correlation between increased stemness and inflammation. We found a close correlation of increased Lgr5 and CD133 with proinflammatory factors like IL-17, IL-22, and IL-23. Together, our findings suggest that K-RasG13D mutation promotes cancer cell growth but decreases cancer stemness and inflammation thus tumorigenesis and metastasis potential in colon cancer. Inhibition of this mutation reverses the process. Therefore, care needs be taken when employing targeted therapies to K-RasG13D mutations in clinics.
Species richness and asynchrony maintain the stability of primary productivity against seasonal climatic variability
Authors: Zhang Ze , Hautier Yann , Bao Tiejun , Yang Jie , Qing Hua , Liu Zhongling , Wang Min , Li Taoke , Yan Mei , Zhang Guanglin
Published: October 2022

The stability of grassland communities informs us about the ability of grasslands to provide reliable services despite environmental fluctuations. There is large evidence that higher plant diversity and asynchrony among species stabilizes grassland primary productivity against interannual climate variability. Whether biodiversity and asynchrony among species and functional groups stabilize grassland productivity against seasonal climate variability remains unknown. Here, using 29-year monitoring of a temperate grassland, we found lower community temporal stability with higher seasonal climate variability (temperature and precipitation). This was due to a combination of processes including related species richness, species asynchrony, functional group asynchrony and dominant species stability. Among those processes, functional group asynchrony had the strongest contribution to community compensatory dynamics and community stability. Based on a long-term study spanning 29 years, our results indicate that biodiversity and compensatory dynamics a key for the stable provision of grassland function against increasing seasonal climate variability.
Accuracy of genomic selection for alfalfa biomass yield in two full-sib populations
Authors: He Xiaofan , Zhang Fan , He Fei , Shen Yuhua , Yu Long-Xi , Zhang Tiejun , Kang Junmei
Published: October 2022

Alfalfa (Medicago sativa) is one of the most important leguminous forages, widely planted in temperate and subtropical regions. As a homozygous tetraploid, its complex genetic background limits genetic improvement of biomass yield attributes through conventional breeding methods. Genomic selection (GS) could improve breeding efficiency by using high-density molecular markers that cover the whole genome to assess genomic breeding values. In this study, two full-sib F1 populations, consisting of 149 and 392 individual plants (P149 and P392), were constructed using parents with differences in yield traits, and the yield traits of the F1 populations were measured for several years in multiple environments. Comparisons of individual yields were greatly affected by environments, and the best linear unbiased prediction (BLUP) could accurately represent the original yield data. The two hybrid F1 populations were genotyped using GBS and RAD-seq techniques, respectively, and 47,367 and 161,170 SNP markers were identified. To develop yield prediction models for a single location and across locations, genotypic and phenotypic data from alfalfa yields in multiple environments were combined with various prediction models. The prediction accuracies of the F1 population, including 149 individuals, were 0.11 to 0.70, and those of the F1 population, consisting of 392 individuals, were 0.14 to 0.67. The BayesC and RF models had the highest average prediction accuracy of 0.60 for two F1 populations. The accuracy of the prediction models for P392 was higher than that of P149. By analyzing multiple prediction models, moderate prediction accuracies are obtained, although accuracies will likely decline across multiple locations. Our study provided evidence that GS can accelerate the improvement of alfalfa yield traits.
Mycorrhizal inoculation effects on growth and the mycobiome of poplar on two phytomanaged sites after 7-year-short rotation coppicing
Authors: Ciadamidaro Lisa , Pfendler Stéphane , Girardclos Olivier , Zappelini Cyril , Binet Philippe , Bert Valerie , Khasa Damase , Blaudez Damien , Chalot Michel
Published: October 2022

Aims

Afforestation of trace-element contaminated soils, notably with fast growing trees, has been demonstrated to be an attractive option for bioremediation due to the lower costs and dispersion of contaminants than conventional cleanup methods. Mycorrhizal fungi form symbiotic associations with plants, contributing to their tolerance towards toxic elements and actively participating to the biorestoration processes. The aim of this study was to deepen our understanding on the effects of mycorrhizal inoculation on plant development and fungal community at two trace-element contaminated sites (Pierrelaye and Fresnes-sur-Escaut, France) planted with poplar (Populus trichocarpa x Populus maximowiczii).

Methods

The 2 sites were divided into 4 replicated field blocks with a final plant density of 2200 tree h-1. Half of the trees were inoculated with a commercial inoculum made of a mix of mycorrhizal species. The sites presented different physico-chemical characteristics (e.g., texture: sandy soil versus silty-loam soil and organic matter: 5.7% versus 3.4% for Pierrelaye and Fresnes-sur-Escaut, respectively) and various trace element contamination levels.

Results

After 7 years of plantation, inoculation showed a significant positive effect on poplar biomass production at the two sites. Fungal composition study demonstrated a predominance of the phylum Ascomycota at both sites, with a dominance of Geopora Arenicola and Mortierella elongata, and a higher proportion of ectomycorrhizal and endophytic fungi (with the highest values observed in Fresnes-sur-Escaut: 45% and 28% for ECM and endophytic fungi, respectively), well known for their capacity to have positive effects on plant development in stressful conditions. Furthermore, Pierrelaye site showed higher frequency (%) of mycorrhizal tips for ectomycorrhizal fungi (ECM) and higher intensity (%) of mycorrhizal root cortex colonization for arbuscular mycorrhizal fungi (AMF) than Fresnes-sur-Escaut site, which translates in a higher level of diversity.

Conclusions

Finally, this study demonstrated that this biofertilization approach could be recommended as an appropriate phytomanagement strategy, due to its capacity to significantly improve poplar productivity without any perturbations in soil mycobiomes.
Abortion and euthanasia: Explanatory factors of an association in Thanatos. Analysis of the European Values Study
Authors: Silvestre Maria , Aristegui Iratxe , Beloki Usue
Published: October 2022

The European Values Study (EVS), and also the World Values Survey (WVS), have for decades included a question that asks about the degree of justification of different behaviors and actions, including abortion and euthanasia. Our research aims to study which factors influence the abortion/euthanasia association in Spain and whether this association is also observed in other countries. A factor analysis of the Spanish sample shows that a number of items related to sexuality and death tend to cluster together. This factor could be called “Eros-Thanatos,” and includes the justification of abortion and euthanasia, in terms of ideological consistency. The analysis shows that in Spain, as well as in Europe generally, not being a religious person is the principal factor associated with the greater justification of abortion and euthanasia. The article analyses whether this association in the Spanish data is something that can be generalized to other European countries or whether, on the contrary, there are factors such as culture and the historical past of the countries that modify the relationship. Correspondence analyses applied to different questions in the questionnaire show that it is possible to establish different dividing lines in Europe according to the values of its citizens, shaping a north-south axis and a west-east axis, in which the processes of secularization in Western Europe or the rise in institutional religion in the former Soviet republics might lie behind.