bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of dietary resveratrol on placental function and reproductive performance of late pregnancy sows
Authors: Hu Ruizhi , Tan Jijun , Li Zhanfeng , Wang Long , Shi Mingkun , Li Baizhen , Liu Ming , Yuan Xupeng , He Jianhua , Wu Xiaosong
Published: October 2022

Placental function is vital to the fetal growth of sows, and resveratrol (RES) can protect cells against oxidative stress, which is one of the major factors impairing placental function. This study aimed to investigate the effect of dietary resveratrol (RES) on placental function and reproductive performance during late pregnancy in a sow model from the aspects of oxidative stress, insulin resistance, and gut microbiota. A total of 26 hybrid pregnant sows (Landrace × Yorkshire) with similar parity were randomly allocated into two groups (n = 13) and fed with a basal diet or a diet containing 200 mg/kg of resveratrol from day 85 of gestation until parturition. The dietary supplementation of RES increased the litter weight at parturition by 12.53% (p = 0.145), with ameliorated insulin resistance (HOMA-IR), increased triglyceride (TG) levels, and decreased interleukin (IL)-1β and IL-6 levels in serum (p < 0.05). Moreover, resveratrol increased the placental vascular density (p < 0.05) with the enhanced expression of nutrient transporter genes (SLC2A1 and SLC2A3) and antioxidant genes, such as superoxide dismutase 2 (SOD2) and heme oxygenase-1 (HO-1) but declined the expression of inflammatory genes, such as IL-1β and IL-6 (p < 0.05). The characterization of the fecal microbiota revealed that resveratrol decreased the relative abundance of the Christensensllaceae R-7 group and Ruminococcaceae UCG-008 (p < 0.05), which had a positive linear correlation with the expression of IL-1β and IL-6 (p < 0.05), but had a negative linear correlation with the expression of SOD2, HO-1, SLC2A1, and SCL2A3 genes (p < 0.05). These data demonstrated that dietary supplementation with resveratrol can improve placental function with ameliorated insulin resistance, oxidative stress, and inflammation potentially by regulating Ruminococcaceae UCG-008 and the Christensensllaceae R-7 group in sows.
Lacticaseibacillus rhamnosus HN001 alters the microbiota composition in the cecum but not the feces in a piglet model
Authors: Young Wayne , Maclean Paul , Dunstan Kelly , Ryan Leigh , Peters Jason , Armstrong Kelly , Anderson Rachel , Dewhurst Hilary , van Gendt Melanie , Dilger Ryan N. , Dekker James , Haggarty Neill , Roy Nicole
Published: October 2022

The probiotic Lacticaseibacillus rhamnosus strain HN001 has been shown to have several beneficial health effects for both pediatric and maternal groups, including reduced risk of eczema in infants and gestational diabetes and postnatal depression in mothers. While L. rhamnosus HN001 appears to modify immune and gut barrier biomarkers, its mode of action remains to be fully elucidated. To gain insights into the role of HN001 on the infant microbiome, the impacts of L. rhamnosus HN001 supplementation was studied in 10-day old male piglets that were fed either infant formula, or infant formula with L. rhamnosus HN001 at a low (1.3 × 105 CFU/ml) or high dose (7.9 × 106 CFU/ml) daily for 24 days. The cecal and fecal microbial communities were assessed by shotgun metagenome sequencing and host gene expression in the cecum and colon tissue was assessed by RNA-seq. Piglet fecal samples showed only modest differences between controls and those receiving dietary L. rhamnosus HN001. However, striking differences between the three groups were observed for cecal samples. While total lactobacilli were significantly increased only in the high dose L. rhamnosus HN001 group, both high and low dose groups showed an up to twofold reduction across the Firmicutes phylum and up to fourfold increase in Prevotella compared to controls. Methanobrevibacter was also decreased in HN001 fed piglets. Microbial genes involved in carbohydrate and vitamin metabolism were among those that differed in relative abundance between those with and without L. rhamnosus HN001. Changes in the cecal microbiome were accompanied by increased expression of tight junction pathway genes and decreased autophagy pathway genes in the cecal tissue of piglets fed the higher dose of L. rhamnosus HN001. Our findings showed supplementation with L. rhamnosus HN001 caused substantial changes in the cecal microbiome with likely consequences for key microbial metabolic pathways. Host gene expression changes in the cecum support previous research showing L. rhamnosus HN001 beneficially impacts intestinal barrier function. We show that fecal samples may not adequately reflect microbiome composition higher in the gastrointestinal tract, with the implication that effects of probiotic consumption may be missed by examining only the fecal microbiome.
Effects of post-fermentation on the flavor compounds formation in red sour soup
Authors: Zhou Xiaojie , Zhou Wenhua , He Xiaojie , Deng Yaxin , Li Liangyi , Li Ming , Feng Xuzhong , Zhang Lin , Zhao Liangzhong
Published: October 2022

Red Sour Soup (RSS) is a traditional fermented food in China. After two rounds of fermentation, sour soup has a mellow flavor. However, the microbial composition and flavor formation processes in post-fermentation in RSS are unclear. This study investigates the bacteria composition of RSS during the post-fermentation stage (0–180 days) using high-throughput sequencing. The results show that lactic acid bacteria (LAB) are dominant during the post-fermentation process, and their abundance gradually increases with fermentation time. Additionally, gas chromatography-mass spectrometry was used to detect volatile flavor compounds in the post-fermentation process. Seventy-seven volatile flavor compounds were identified, including 24 esters, 14 terpenes, 9 aromatic hydrocarbons, 9 alkanes, 6 heterocyclic compounds, 3 alcohols, 3 acids, 3 ketones, 2 phenols, 2 aldehydes, 1 amine, and 1 other. Esters and aromatic hydrocarbons are the main volatile compounds in RSS during the post-fermentation process. Orthogonal partial least squares screening and correlation analysis derived several significant correlations, including 48 pairs of positive correlations and 19 pairs of negative correlations. Among them, Acetobacter spp., Clostridium spp. and Sporolactobacillus spp. have 15, 14, 20 significant correlation pairs, respectively, and are considered the most important bacterial genera post-fermentation. Volatile substances become abundant with increasing fermentation time. LAB are excessive after more than 120 days but cause a drastic reduction in volatile ester levels. Thus, the post-fermentation time should be restricted to 120 days, which retains the highest concentrations of volatile esters in RSS. Overall, these findings provide a theoretical basis to determine an optimal post-fermentation time duration, and identify essential bacteria for manufacturing high-quality starter material to shorten the RSS post-fermentation processing time.
Lactobacillus improves meat quality in Sunit sheep by affecting mitochondrial biogenesis through the AMPK pathway
Authors: Wang Chenlei , Yan Xinlei , Bai Yanping , Sun Lina , Zhao Lihua , Jin Ye , Su Lin
Published: October 2022

Sunit sheep are famous for their high meat quality, but the meat quality of them has declined due to the change in feeding methods. Lactobacillus has a variety of probiotic effects and is widely used in animal diets to optimize meat quality. This study aimed to investigate the effect of dietary supplementation with different levels of Lactobacillus on meat quality. A total of 24 3-month-old Sunit sheep with an average body weight of 19.03 ± 3.67 kg were randomly divided into control (C), 1% (L1), 2% (L2), and 3% Lactobacillus groups (L3), with 6 sheep in each group. Myofiber characteristics, meat quality, and metabolic enzyme activity were detected. Moreover, the regulatory mechanism of Lactobacillus on meat quality was explored by using Western blotting and real-time Quantitative polymerase chain reaction (RT-qPCR). The results showed that dietary addition of Lactobacillus decreased LDH activity in the Biceps femoris of Sunit sheep (P < 0.05). Compared to the other groups, the 1% Lactobacillus group showed the conversion of myofibers from the glycolytic to the oxidative type, and the increasing b* values (P < 0.05), decreasing shear force and cooking loss of meat (P < 0.05) and the relative gene and protein expression levels of AMPK, PGC-1α, NRF1, TFAM, and COX IV (P < 0.05) in the Biceps femoris were also increased in the 1% Lactobacillus group. Therefore, the addition of Lactobacillus to the diet of Sunit sheep could regulate the AMPK signaling pathway to promote myofiber type conversion, which improves meat quality. This study provided a theoretical and data basis for improving the meat quality of sheep and supplied a novel way of applying Lactobacillus.
Dietary linseed oil affects the polyunsaturated fatty acid and transcriptome profiles in the livers and breast muscles of ducks
Authors: Wang Laidi , Dong Bingqiang , Yang Ting , Zhang Ao , Hu Xiaodan , Wang Zhixiu , Chang Guobin , Chen Guohong
Published: October 2022

Linseed oil, an important source of dietary α-linolenic acid, is used to provide meat enriched in n-3 PUFA. We investigated the effects of dietary linseed oil (0, 0.5, 1, and 2%) on growth performance, meat quality, tissue fatty acid (FA), and transcriptome profiles in ducks. The result showed that dietary linseed oil had no effect on growth performance. Increasing dietary linseed oil enrichment raised n-3 PUFA and linoleic acid (LA) levels in both the liver and breast muscle, but decreased dihomo-gamma-linolenic acid (DGLA) and arachidonic acid (ARA) levels in the liver. The liver n-3 PUFA content was negatively correlated with duck body weight. Transcriptome analysis showed that dietary linseed oil caused hepatic changes in genes (SCD, FADS1, FADS2, and ACOT6) related to the biosynthesis of unsaturated fatty acids. Besides, dietary linseed oil also affected the expression of genes related to PUFAs and downstream metabolites (such as linoleic acid, steroid hormone, progesterone, etc.) metabolic pathways in both liver and breast muscle. Key genes involved in PUFA synthesis and transport pathways were examined by RT-qPCR, and the results verified that hepatic expression levels of FADS1 and FADS2 decreased, and those of FABP4 and FABP5 increased when 2% linseed oil was added. CD36 expression level increased in breast muscle when 2% linseed oil was added. Thus, 2% dietary linseed oil supplementation produces n-3 PUFA-enriched duck products by regulating the PUFA metabolic pathways, which could be advantageous for health-conscious consumers.
Birth and newborn care policies and practices limit breastfeeding at maternity facilities in Vietnam
Authors: Nguyen Tuan T. , Cashin Jennifer , Tran Hoang T. , Hoang Tuan A. , Mathisen Roger , Weissman Amy , Murray John C. S.
Published: October 2022

The prevalence of early and exclusive breastfeeding in Vietnam remains sub-optimal. The objective of this study was to determine factors associated with early initiation of breastfeeding (EIBF) and exclusive breastfeeding for the first 3 days after birth (EBF3D). We conducted a population-based, cross-sectional survey of 726 mothers with children aged 0–11 months in two provinces and one municipality from May to July 2020. Multinomial logistic regression was used to examine factors associated with EIBF and EBF3D. The prevalence of EIBF was 39.7% and EBF3D 18.0%. The EIBF prevalence is positively associated with immediate and uninterrupted skin-to-skin contact (SSC) for 10–29 min (aOR: 2.55; 95% CI: 1.49, 4.37), 30–59 min (aOR: 4.15; 95% CI: 2.08, 8.27), 60–80 min (aOR: 4.35; 95% CI: 1.50, 12.6), or ≥90 min (aOR: 5.87; 95% CI: 3.14, 10.98). EIBF was negatively associated with cesarean birth (aOR: 0.24; 95% CI: 0.11, 0.51), bringing infant formula to the birth facility (aOR: 0.49; 95% CI: 0.30, 0.78), purchased it after arrival (aOR: 0.37; 95% CI: 0.24, 0.60), or did both (aOR: 0.43; 95% CI: 0.21, 0.89). EBF3D was negatively associated with cesarean section birth (aOR: 0.15; 95% CI: 0.06, 0.39), vaginal birth with episiotomy (aOR: 0.40; 95% CI: 0.18, 0.88), bringing formula to the maternity facility (aOR: 0.03; 95% CI: 0.01, 0.07), purchased it after arrival (aOR: 0.02; 95% CI: 0.01, 0.06) or did both (aOR: 0.04; 95% CI: 0.02, 0.10). Receiving counseling from any source was not significantly associated with early breastfeeding practices. Policy and health service delivery interventions should be directed at eliminating infant formula from birthing environments, reducing unnecessary cesarean sections and episiotomies, providing immediate and uninterrupted SSC for all births, and improving breastfeeding counseling and support.
Did the sweetness of beverages change with the Chilean Food Labeling and Marketing Law? A before and after study
Authors: Rebolledo Natalia , Bercholz Maxime , Corvalán Camila , Ng Shu Wen , Taillie Lindsey Smith
Published: October 2022

There has been a rapid proliferation of policies around the globe to reduce sugar consumption, yet there is little understanding as to whether these policies have led to changes in the overall sweetness of products, which is essential for understanding long-term effects on food preferences and intake. For example, the implementation of Chile’s Law on Food Labeling and Advertising led to decreases in the sugar content of non-alcoholic packaged beverages and increases in non-nutritive sweeteners (NNS) use in these beverages. Given that NNS have greater sweetness intensity than sugars, it is unclear what was the net effect of these changes on the sweetness of purchased beverages. Using longitudinal household purchase data (n > 2,000 households), we measured the changes in the sweetness of beverage purchases after implementing the first phase of the Chilean law and examine if there were differences by key family sociodemographic variables. We developed three sweetness indices: (1) NNS sweetness, including the sweetness of the six NNS most consumed by Chileans; (2) total sugars sweetness, including the sweetness from total sugars; and (3) total sweetness, combining the sweetness from NNS and sugars. Using fixed-effects models, we compared the observed post-law purchases to a counterfactual based on pre-law trends. We found that NNS sweetness increased relative to the counterfactual, while total sugars sweetness decreased after the law. However, the absolute changes in NNS sweetness were almost entirely offset by the decreases in total sugar sweetness, leading to no change in the total sweetness of beverage purchases. Additionally, there were no differences in the sweetness changes by family sociodemographics. Our findings indicate that Chilean consumers are exposed to similar sweetness levels in their beverages after the law. Future research should explore whether sweetness also remained consistent in dietary intake.
Traditional uses, phytochemistry, pharmacology and toxicology of garlic (Allium sativum), a storehouse of diverse phytochemicals: A review of research from the last decade focusing on health and nutritional implications
Authors: Tudu Champa Keeya , Dutta Tusheema , Ghorai Mimosa , Biswas Protha , Samanta Dipu , Oleksak Patrik , Jha Niraj Kumar , Kumar Manoj , Radha  , Proćków Jarosław , Pérez de la Lastra José M. , Dey Abhijit
Published: October 2022

Allium sativum L. (Garlic) is a fragrant herb and tuber-derived spice that is one of the most sought-after botanicals, used as a culinary and ethnomedicine for a variety of diseases around the world. An array of pharmacological attributes such as antioxidant, hypoglycemic, anti-inflammatory, antihyperlipidemic, anticancer, antimicrobial, and hepatoprotective activities of this species have been established by previous studies. A. sativum houses many sulfur-containing phytochemical compounds such as allicin, diallyl disulfide (DADS), vinyldithiins, ajoenes (E-ajoene, Z-ajoene), diallyl trisulfide (DATS), micronutrient selenium (Se) etc. Organosulfur compounds are correlated with modulations in its antioxidant properties. The garlic compounds have also been recorded as promising immune-boosters or act as potent immunostimulants. A. sativum helps to treat cardiovascular ailments, neoplastic growth, rheumatism, diabetes, intestinal worms, flatulence, colic, dysentery, liver diseases, facial paralysis, tuberculosis, bronchitis, high blood pressure, and several other diseases. The present review aims to comprehensively enumerate the ethnobotanical and pharmacological aspects of A. sativum with notes on its phytochemistry, ethnopharmacology, toxicological aspects, and clinical studies from the retrieved literature from the last decade with notes on recent breakthroughs and bottlenecks. Future directions related to garlic research is also discussed.
Paternal preconceptional diet enriched with n-3 polyunsaturated fatty acids affects offspring brain function in mice
Authors: Li Muhan , Shi Qiaoyu , Jiang Xueyi , Liu Xuanyi , Han Wei , Fan Xiuqin , Li Ping , Qi Kemin
Published: October 2022

Recent studies demonstrate that paternal nutrition prior to conception may determine offspring development and health through epigenetic modification. This study aims to investigate the effects of paternal supplementation of n-3 polyunsaturated fatty acids (n-3 PUFAs) on the brain development and function, and associated gene imprinting in the offspring. Three to four-week-old male C57BL/6J mice (founder) were fed with an n-3 PUFA-deficient diet (n-3 D), and two n-3 PUFA supplementation diets – a normal n-3 PUFA content diet (n-3 N) and a high n-3 PUFA content diet (n-3 H) for 12 weeks. Then they were mated to 10-week-old virgin female C57BL/6J mice to generate the offspring. The results showed that paternal n-3 PUFA supplementation in preconception reduced the anxiety- and depressive-like behavior, and improved sociability, learning and memory in the offspring, along with increased synaptic number, upregulated expressions of neuron specific enolase, myelin basic protein, glial fibrillary acidic protein, brain-derived neurotrophic factor in the hippocampus and cerebral cortex, and altered expressions of genes associated with mitochondria biogenesis, fusion, fission and autophagy. Furthermore, with paternal n-3 PUFA supplementation, the expression of imprinted gene Snrpn was downregulated both in testes of the founder mice and their offspring, but upregulated in the cerebral cortex and hippocampus, with altered DNA methylation in its differentially methylated region. The data suggest that higher paternal intake of n-3 PUFAs in preconception may help to maintain optimal brain development and function in the offspring, and further raise the possibility of paternal nutritional intervention for mental health issues in subsequent generations.
Comparison of nutritional composition between plant-based drinks and cow’s milk
Authors: Walther Barbara , Guggisberg Dominik , Badertscher René , Egger Lotti , Portmann Reto , Dubois Sébastien , Haldimann Max , Kopf-Bolanz Katrin , Rhyn Peter , Zoller Otmar , Veraguth Rosmarie , Rezzi Serge
Published: October 2022

The high decline in liquid milk consumption in Western countries has been compensated by the increased consumption of processed dairy products and the rapidly increasing number of new plant-based beverages constantly introduced in the market, advertised as milk substitutes and placed on shelves near milk products. To provide better understanding about the nutritional value of these drinks compared with cow’s milk, 27 plant-based drinks of 8 different species and two milk samples were purchased from two big retailers in Switzerland, and their composition regarding protein, carbohydrate, fat, vitamin, and mineral contents and residue load [glyphosate, aminomethylphosphonic acid (AMPA), and arsenic] was analyzed quantitatively and qualitatively. Energy and nutrient intakes were calculated and compared with the dietary reference values for Germany, Austria and Switzerland (D-A-CH). In addition, the digestible indispensable amino acid score (DIAAS) was calculated to estimate the quality of the proteins. Milk contained more energy; fat; carbohydrate; vitamins C, B2, B12, and A; biotin; pantothenic acid; calcium; phosphorus; and iodine than most plant-based drinks. Soy drinks provided slightly more protein and markedly more vitamins B1 and B6, folic acid, and vitamins E and D2 (with supplemented vitamin D2) and K1, magnesium, manganese, iron, and copper than milk and the other plant-based drinks. However, with the exception of cow’s milk and soy drinks, which had > 3% protein, most milk alternatives contained ≤ 1% protein; therefore, they cannot be considered good protein sources. In regard to protein quality, milk was outstanding compared with all plant-based drinks and exhibited higher calculated DIAASs. Our results show that the analyzed plant-based drinks are not real alternatives to milk in terms of nutrient composition, even if the actual fortification is taken into account. Improved fortification is still an issue and can be optimized using the most bioavailable and soluble derivatives. Complete replacement of milk with plant-based drinks without adjusting the overall diet can lead to deficiencies of certain important nutrients in the long term.
Is intraoperative ultrasound more efficient than magnetic resonance in neurosurgical oncology? An exploratory cost-effectiveness analysis
Authors: Mosteiro Alejandra , Di Somma Alberto , Ramos Pedro Roldán , Ferrés Abel , De Rosa Andrea , González-Ortiz Sofía , Enseñat Joaquim , González Jose Juan
Published: October 2022

Objective

Intraoperative imaging is a chief asset in neurosurgical oncology, it improves the extent of resection and postoperative outcomes. Imaging devices have evolved considerably, in particular ultrasound (iUS) and magnetic resonance (iMR). Although iUS is regarded as a more economically convenient and yet effective asset, no formal comparison between the efficiency of iUS and iMR in neurosurgical oncology has been performed.

Methods

A cost-effectiveness analysis comparing two single-center prospectively collected surgical cohorts, classified according to the intraoperative imaging used. iMR (2013-2016) and iUS (2021-2022) groups comprised low- and high-grade gliomas, with a maximal safe resection intention. Units of health gain were gross total resection and equal or increased Karnofsky performance status. Surgical and health costs were considered for analysis. The incremental cost-effectiveness ratio (ICER) was calculated for the two intervention alternatives. The cost-utility graphic and the evolution of surgical duration with the gained experience were also analyzed.

Results

50 patients followed an iMR-assisted operation, while 17 underwent an iUS-guided surgery. Gross total resection was achieved in 70% with iMR and in 60% with iUS. Median postoperative Karnofsky was similar in both group (KPS 90). Health costs were € 3,220 higher with iMR, and so were surgical-related costs (€ 1,976 higher). The ICER was € 322 per complete resection obtained with iMR, and € 644 per KPS gained or maintained with iMR. When only surgical-related costs were analyzed, ICER was € 198 per complete resection with iMR and € 395 per KPS gained or maintained.

Conclusion

This is an unprecedented but preliminary cost-effectiveness analysis of the two most common intraoperative imaging devices in neurosurgical oncology. iMR, although being costlier and time-consuming, seems cost-effective in terms of complete resection rates and postoperative performance status. However, the differences between both techniques are small. Possibly, iMR and iUS are complementary aids during the resection: iUS real-time images assist while advancing towards the tumor limits, informing about the distance to relevant landmarks and correcting neuronavigation inaccuracy due to brain shift. Yet, at the end of resection, it is the iMR that reliably corroborates whether residual tumor remains.
Association of inflammatory markers with survival in patients with advanced gastric cancer treated with immune checkpoint inhibitors combined with chemotherapy as first line treatment
Authors: Wan Mingyu , Ding Yongfeng , Mao Chenyu , Ma Xiaolu , Li Ning , Xiao Cheng , Qian Jiong , Jiang Haiping , Zheng Yulong , Wu Luntao , Teng Lisong , Xu Nong
Published: October 2022

Background

The emergence of immune checkpoint inhibitors has changed the landscape of first-line treatment of patients with advanced gastric cancer. Currently, the prognostic significance of inflammatory markers in first-line immunotherapy combined with chemotherapy for gastric cancer is currently unclear. This study aimed to identify inflammatory markers with potential to predict treatment outcome in advanced gastric cancer patients receiving immunotherapy combined with chemotherapy.

Methods

This retrospective study enrolled untreated advanced or metastatic gastric or gastro-esophageal junction cancer patients from 5 clinical trials (the clinical trial cohort) and the real world (the real-word cohort). Inflammatory markers included in the analysis included neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), systemic inflammation index (SII), and derived neutrophil-to-lymphocyte ratio (dNLR). Receiver operating characteristic (ROC) curves were constructed to identify optimal cut-off values. The prognostic potential of the markers was determined using Kaplan–Meier analysis, univariate and multivariate Cox-regression analyses in the clinical trial cohort and the findings were validated in the real-world cohort.

Results

In the clinical trial cohort (n=45), MLR, PLR and SII were associated with PFS but not OS (All P<0.05), while dNLR was not correlated with PFS or OS. Only NLR was associated with PFS and OS and identified as an independent prognostic predictor in the univariate and multivariate analyses. The prognostic value of NLR was validated in the real-world cohort (n=55).

Conclusions

NLR was a strong predictor of PFS and OS in patients with advanced gastric cancer receiving immune checkpoint inhibitors combined with chemotherapy. Further prospective studies are required to validate our results.
Bladder paraganglioma, gastrointestinal stromal tumor, and SDHB germline mutation in a patient with Carney-Stratakis syndrome: A case report and literature review
Authors: Shi Yihang , Ding Li , Mo Chengqiang , Luo Yanji , Huang Shaoqing , Cai Shirong , Xia Yanzhe , Zhang Xinhua
Published: October 2022

Background

Carney-Stratakis syndrome (CSS) is a rare dyad of paraganglioma (PGL)/pheochromocytoma (PHEO) and gastrointestinal stromal tumor (GIST). PGLs are neuroendocrine tumors of neural crest origin which are mostly found in the head, neck, and retroperitoneal space. GISTs are the most common mesenchymal tumors of the digestive tract, usually caused by KIT/PDGFRA mutations. Here, we reported a case of CSS with unusual bladder PGL and succinate dehydrogenase (SDH) deficient GIST due to a germline mutation in SDH-subunit B (SDHB) gene.

Case presentation

A 39-year-old female patient initially diagnosed with gastric GIST and isolated pelvic metastasis was eventually found to be CSS with bladder PGL and SDH-deficient GIST after surgery. This patient underwent resection of gastric and bladder tumors, and postoperative pathology confirmed the diagnosis of CSS. According to the next-generation sequencing (NGS), the patient carried a germline mutation in the SDHB gene, which was the cause of the disorder. The patient had no tumor recurrence with regular follow-up in 10 months.

Conclusions

CSS is an autosomal genetic disorder with no gender difference in incidence, and PGLs are more frequent than GISTs. SDH germline mutation is the molecular biological mechanism of CSS while the most common type is SDHB mutation. The unique mechanism of tumorigenesis including hypoxia and hypermethylation caused by SDH deficiency renders target therapy with tyrosine kinase inhibitors ineffective, therefore complete surgical resection is the optimal treatment in the absence of tumor metastases.
Effects of probiotic supplementation on related side effects after chemoradiotherapy in cancer patients
Authors: Lu Yongkai , Luo Xiaoqin , Yang Di , Li Yi , Gong Tuotuo , Li Binglin , Cheng Jian , Chen Ruijuan , Guo Xin , Yuan Wei
Published: October 2022

Objectives

Chemotherapy and radiotherapy generally cause serious adverse side effects in cancer patients, thereby affecting subsequent treatment. Numerous studies have shown that taking probiotics is an option for preventing and treating these side effects. In this investigation, a meta-analysis of the effects of oral probiotics on side effects brought on by radiotherapy, chemotherapy, or chemoradiotherapy treatment will be carried out.

Methods

Two researchers independently and carefully reviewed all pertinent studies that were published before June 30, 2022 and were accessible on PubMed, Embase, Cochrane Library, and the Web of Science. Moreover, the Cochrane Collaboration’s Tool was used to evaluate the risk of bias. Utilizing Review Manager software version 5.4, data were retrieved from eligible studies to evaluate their merits and determine odds ratios (OR) and 95% confidence intervals (CIs) (RevMan 5.4).

Results

2 097 patients from 16 randomized controlled trials were extracted, and standard meta-analysis methods were used to examine the data. Compared with the placebo groups, oral probiotics significantly reduced the side effects caused by radiotherapy and chemotherapy on various types of cancer, such as head and neck cancer, pelvic and abdominal cancer, breast cancer, lung cancer, etc. (OR: 0.31, 95% CI: 0.20 – 0.48; P < 0.005). Further analysis found that the incidence of diarrhea in patients with pelvic and abdominal cancers (OR: 0.32, 95% CI: 0.16 - 0.65; P < 0.005) and the frequency of oral mucositis in patients with head and neck tumors were also significantly lower (OR: 0.28, 95% CI: 0.18 - 0.43; P < 0.005) after the oral administration of probiotics. This suggests that probiotics have a positive influence on the treatment of side effects after chemoradiotherapy. Additionally, a funnel plot revealed that there was no significant publication bias in this study.

Conclusions

Probiotics may help to reduce the occurrence of cancer therapy-related side effects, especially oral mucositis in head and neck tumors and diarrhea in patients with pelvic and abdominal tumors. However, given the small number of clinical trials involved, additional randomized, double-blind, multicentric trials in a larger population are required. This paper may assist researchers in improving trial design in the selection of probiotic strains and selecting appropriate patients who may benefit from probiotic treatments.
Navigating the contested borders between myelodysplastic syndrome and acute myeloid leukemia
Authors: Ambinder Alexander J. , DeZern Amy E.
Published: October 2022

Myelodysplastic syndrome and acute myeloid leukemia are heterogeneous myeloid neoplasms which arise from the accumulation of mutations in a myeloid stem cell or progenitor that confer survival or growth advantages. These disease processes are formally differentiated by clinical, laboratory, and morphological presentations, especially with regard to the preponderance of blasts in the peripheral blood or bone marrow (AML); however, they are closely associated through their shared lineage as well as their existence on a spectrum with some cases of MDS displaying increased blasts, a feature that reflects more AML-like behavior, and the propensity for MDS to transform into AML. It is increasingly recognized that the distinctions between these two entities result from the divergent patterns of genetic alterations that drive each of them. Mutations in genes related to chromatin-remodeling and the spliceosome are seen in both MDS and AML arising out of antecedent MDS, while mutations in genes related to signaling pathways such as RAS or FLT3 are more typically seen in AML or otherwise are a harbinger of transformation. In this review, we focus on the insights into the biological and genetic distinctions and similarities between MDS and AML that are now used to refine clinical prognostication, guide disease management, and to inform development of novel therapeutic approaches.
High expressions of CD10, FAP and GPR77 in CAFs are associated with chemoresistance and worse prognosis in gastric cancer
Authors: Tong Yilin , Zhao Zehua , Zhang Jianjun , Wang Wentao , Zhu Yanmei
Published: October 2022

Introduction

As neoadjuvant chemotherapy (NCT) has been successfully introduced in gastric cancer (GC), more biomarkers are needed to evaluate the efficacy. Cancer-associated fibroblasts (CAFs) is associated with chemoresistance and prognosis. Three biomarkers, CD10, fibroblast activation protein-α (FAP) and G-protein-coupled receptor 77 (GPR77), have been proved to express in CAFs. However, their predictive values for efficacy of NCT and prognosis in gastric cancer is unknown.

Methods

Totally, specimens of 171 locally advanced gastric cancer patients who underwent NCT and D2 radical gastrectomy and matched preoperative biopsy specimens were retrospectively analyzed. Tumor regression grade (TRG) is reevaluated according to Mandard TRG. Expressions of CD10, FAP and GPR77 in CAFs before NCT (pre-) and after NCT (post-) were evaluated by immunohistochemistry. Survival curves on overall survival (OS) were obtained by Kaplan-Meier method, and differences were analyzed by log-rank test. Associations between categorical variables were explored by chi-square test or Fisher’s exact method. Univariable and multivariate analyses were performed by logistic regression model and Cox proportional hazard regression model.

Results

High expressions of post-CD10, post-FAP, post-GPR77 and pre-CD10 were related to worse TRG (all p<0.05). In multivariable analysis, post- and pre-FAP were independent predictive factors to TRG (p<0.010). Post-CD10 (p=0.032) and post-FAP (p=0.013) were related to OS in univariable analysis, but none of biomarkers were independent prognostic factors in multivariable analysis.

Conclusions

Expressions of CD10, FAP and GPR77 in CAFs were related to chemoresistance and overall survival, and these biomarkers have predictive values for tumor regression and prognosis in locally advanced gastric cancer patients.
An analysis of sexual dimorphism in the tumor microenvironment of colorectal cancer
Authors: Geddes Andrea E. , Ray Anita  L. , Nofchissey Robert A. , Esmaeili Azadeh , Saunders Apryl , Bender Dawn E. , Khan Maaz , Aravindan Sheeja , Ahrendsen Jared T. , Li Min , Fung Kar-Ming , Jayaraman Muralidharan , Yang Jingxuan , Booth Kristina K. , Dunn Gary D. , Carter Steven N. , Morris Katherine T.
Published: October 2022

Women with colorectal cancer (CRC) have survival advantages over men, yet the underlying mechanisms are unclear. T cell infiltration within the CRC tumor microenvironment (TME) correlates strongly with survival. We hypothesized that women with CRC have increased T cell infiltration and differential gene expression in the TME compared to men. Tissue microarrays comprising primary tumor, tumor infiltrated lymph nodes, and uninvolved colon were created from CRC patients. Proportions of CD4 positive (CD4+) and CD8 positive (CD8+) T cells were identified using immunohistochemistry. TME immune- and cancer-related genetic expression from primary and metastatic CRC tumor were also evaluated via the NanoStringIO360 panel and The Cancer Genome Atlas Project database. CD4+ was higher in tumor samples from women compared to men (22.04% vs. 10.26%, p=0.002) and also in lymph node samples (39.54% vs. 8.56%, p=0.001). CD8+ was increased in uninvolved colon from women compared to men (59.40% vs. 43.61%, p=0.015), and in stage I/II tumors compared to III/IV in all patients (37.01% vs. 23.91%, p=0.009). Top CD8+ tertile patients survived longer compared to the bottom (43.9 months vs. 25.3 months, p=0.007). Differential gene expression was observed in pathways related to Treg function, T cell activity, and T cell exhaustion, amongst several others, in women compared to men. Thus, significant sexual dimorphism exists in the TME that could contribute to survival advantages observed in female patients with CRC.
New insights into the characteristics of DRAK2 and its role in apoptosis: From molecular mechanisms to clinically applied potential
Authors: Zheng Youwei , Li Xinchao , Kuang Lirun , Wang Yong
Published: October 2022

As a member of the death-associated protein kinase (DAPK) family, DAP kinase-associated apoptosis-inducing kinase 2 (DRAK2) performs apoptosis-related functions. Compelling evidence suggests that DRAK2 is involved in regulating the activation of T lymphocytes as well as pancreatic β-cell apoptosis in type I diabetes. In addition, DRAK2 has been shown to be involved in the development of related tumor and non-tumor diseases through a variety of mechanisms, including exacerbation of alcoholic fatty liver disease (NAFLD) through SRSF6-associated RNA selective splicing mechanism, regulation of chronic lymphocytic leukemia and acute myeloid leukemia, and progression of colorectal cancer. This review focuses on the structure, function, and upstream pathways of DRAK2 and discusses the potential and challenges associated with the clinical application of DRAK2-based small-molecule inhibitors, with the aim of advancing DRAK2 research.
Knockout of ABC transporters by CRISPR/Cas9 contributes to reliable and accurate transporter substrate identification for drug discovery
Authors: Feng Dongyan , Zhong Guorui , Zuo Qingxia , Wan Yanbin , Xu Wanqing , He Changsheng , Lin Cailing , Huang Dongchao , Chen Feng , Huang Lizhen
Published: October 2022

It is essential to explore the relationship between drugs and transporters in the process of drug development. Strong background signals in nonhuman MDCK or LLC-PK1 cells and overlapping interference of inhibitors or RNAi in human Caco-2 cells mean that an ideal alternative could be to knock out specific transporter genes in Caco-2 cells. However, the application of gene knockout (KO) to Caco-2 cells is challenging because it is still inefficient to obtain rapidly growing Caco-2 subclones with double-allele KO through long-term monoclonal cultivation. Herein, CRISPR/Cas9, a low cost but more efficient and precise gene editing technology, was utilized to singly or doubly knockout the P-gp, BCRP, and MRP2 genes in Caco-2 cells. By combining this with single cell expansion, rapidly growing transporter-deficient subclones were successfully screened and established. Bidirectional transport assays with probe substrates and three protease inhibitors indicated that more reliable and detailed data could be drawn easily with these KO Caco-2 models. The six robust KO Caco-2 subclones could contribute to efficient in vitro drug transport research.
Eldecalcitol prevents muscle loss by suppressing PI3K/AKT/FOXOs pathway in orchiectomized mice
Authors: Zhang Haichao , Ke Zheng , Dong Shuangshuang , Du Yanping , Tang Wenjing , Chen Minmin , Yu Weijia , Cheng Qun
Published: October 2022

Elderly male patients are susceptible to develop osteoporosis and sarcopenia, especially those with fragility fractures, hypogonadism, and prostate cancer with androgen deprivation therapy. However, at present, very few treatments are available for men with sarcopenia. Previous preclinical studies in ovariectomized rats have shown the promising effects of eldecalcitol in ameliorating the bone strength and muscle atrophy. We thus investigated the effects of eldecalcitol on androgen-deficient male mice. Six-week-old male mice underwent orchiectomy (ORX) or sham surgery. Mice were randomly divided into 4 groups (n = 12/per group), including 1) sham mice, 2) ORX group, 3) ORX eldecalcitol 30 ng/kg, and 4) ORX eldecalcitol 50 ng/kg. Eldecalcitol increased bone mass and strength of femur in ORX mice. Eldecalcitol 30 ng/kg dose completely rescued ORX-induced muscle weakness. The RT-qPCR showed that eldecalcitol enhanced the mRNA levels of type I and IIa fibers. The expression levels of MuRF1 and Atrogin-1 of gastrocnemius in the eldecalcitol groups were much lower than that of the ORX group. It is assumed that eldecalcitol potentially acts via PI3K/AKT/FOXOs signaling pathway. These findings provide evidence for evaluating eldecalcitol as an investigational treatment for male patients with sarcopenia and osteoporosis.
BCATc inhibitor 2 ameliorated mitochondrial dysfunction and apoptosis in oleic acid-induced non-alcoholic fatty liver disease model
Authors: Lu Zhuo , Sun Gui-Feng , Pan Xiao-An , Qu Xin-Hui , Yang Ping , Chen Zhi-Ping , Han Xiao-Jian , Wang Tao
Published: October 2022

Nonalcoholic fatty liver disease (NAFLD) is a prevalent hepatic disease in the world. Disorders of branched chain amino acid (BCAA) metabolism is involved in various diseases. In this study, we aim to explore the role of BCAA metabolism in the development of NAFLD and the protective effect of BCATc Inhibitor 2, an inhibitor of cytosolic branched chain amino acid transaminase, against NAFLD as well as its underlying mechanism. It was found that oleic acid induced lipid accumulation and apoptosis in HepG2 and LO2 cells. Supplementation of BCAAs further aggravated oleic acid-induced lipid accumulation and apoptosis. In contrast, treatment of BCATc Inhibitor 2 ameliorated oleic acid-induced lipid accumulation and apoptosis. Molecularly, supplementation of BCAAs or treatment of BCATc Inhibitor 2 up-regulated or down-regulated the expression of SREBP1 and lipogenesis-related genes without affecting lipolysis-related genes. BCATc Inhibitor 2 maintained mitochondrial function by ameliorating oleic acid-induced mitochondrial ROS generation and mitochondrial membrane potential disruption. In addition, BCATc Inhibitor 2 treatment alleviated oleic acid-induced activation of JNK and AKT signaling pathway and Bcl2/Bax/Caspase axis. In conclusion, our results indicate BCAA metabolism is involved in NAFLD and BCATc Inhibitor 2 protects against oleic acid-induced lipid accumulation and apoptosis. These findings suggest that BCATc Inhibitor 2 is a promising candidate drug for the treatment of NAFLD.
Mangiferin promotes osteogenic differentiation and alleviates osteoporosis in the ovariectomized mouse via the AXL/ERK5 pathway
Authors: He Jinwen , Wang Xingwen , Zhao Dacheng , Geng Bin , Xia Yayi
Published: October 2022

Mangiferin is a xanthone glucoside extracted from multiple plants, which has been shown to inhibit bone resorption and alleviate osteoporosis. However, the effect of purified Mangiferin on osteoporosis and its specific mechanisms is unknown. This study aimed to explore whether Mangiferin can promote osteogenic differentiation and alleviate osteoporosis in ovariectomized (OVX) mice and explore the potential mechanisms. Different concentrations and durations of Mangiferin were applied to MC3T3-E1 cells. The optimal concentration and duration of Mangiferin were determined by evaluating the cell viability via cell count kit-8 (CCK-8). The gene and protein expressions of AXL, ERK5, and osteogenic differentiation markers, including BMP2, Collagen1, OPN, Osterix, and Runx2, were detected using western blotting, qRT-PCR, immunofluorescence, and flow cytometry. Mangiferin was administered to OVX mice, and the severity of osteoporosis was evaluated by H and E staining, immunohistochemistry (IHC), microscopic computed-tomography (micro-CT) scanning, western blotting, and immunofluorescence of bone tissue. We found that Mangiferin promoted osteogenic differentiation in a dose-dependent manner at concentrations less than 30 μM. The 30 μM Mangiferin significantly upregulated the expression of AXL, ERK5, and osteogenic differentiation, including the ALP activity, percentage of alizarin red, and the levels of osteogenic differentiation markers. However, these expression levels decreased when AXL was knocked down in MC3T3-E1 cells and it could not be rescued by Mangiferin. Mangiferin relieved osteoporosis in OVX mice without causing severe organ damage. This study concluded that Mangiferin promoted osteogenic differentiation of MC3T3-E1 cells and alleviated osteoporosis in OVX mice. The potential mechanism was via the AXL/ERK5 pathway.
Wnt-pathway inhibitors with selective activity against triple-negative breast cancer: From thienopyrimidine to quinazoline inhibitors
Authors: Boudou Cédric , Mattio Luce , Koval Alexey , Soulard Valentin , Katanaev Vladimir L.
Published: October 2022

The Wnt-pathway has a critical role in development and tissue homeostasis and has attracted increased attention to develop anticancer drugs due to its aberrant activation in many cancers. In this study, we identified a novel small molecule series with a thienopyrimidine scaffold acting as a downstream inhibitor of the β-catenin-dependent Wnt-pathway. This novel chemotype was investigated using Wnt-dependent triple-negative breast cancer (TNBC) cell lines. Structure activity relationship (SAR) exploration led to identification of low micromolar compounds such as 5a, 5d, 5e and a novel series with quinazoline scaffold such as 9d. Further investigation showed translation of activity to inhibit cancer survival of HCC1395 and MDA-MB-468 TNBC cell lines without affecting a non-cancerous breast epithelial cell line MCF10a. This anti-proliferative effect was synergistic to docetaxel treatment. Collectively, we identified novel chemotypes acting as a downstream inhibitor of β-catenin-dependent Wnt-pathway that could expand therapeutic options to manage TNBC.
Parthenolide promotes expansion of Nestin+ progenitor cells via Shh modulation and contributes to post-injury cerebellar replenishment
Authors: Jinling Dong , Liyuan Feng , Wenying Fu , Yuting Huang , Xiangyu Tang , Xiuning Huang , Yu Tang , Qianliang Ming , Linming Guo , Ning Gao , Peng Li
Published: October 2022

Background: Regeneration of injuries occurring in the central nervous system is extremely difficult. Studies have shown that the developing cerebellum can be repopulated by a group of Nestin-expressing progenitors (NEPs) after irradiation injury, suggesting that modulating the mobilization of NEPs is beneficial to promoting nerve regeneration. To date, however, effect of exogenous pharmaceutical agonist on NEPs mobilization remains unknown. Parthenolide (PTL), a sesquiterpene lactone isolated from shoots of feverfew. Although it has been shown to possess several pharmacological activities and is considered to have potential therapeutic effects on the regeneration of peripheral nerve injury, its efficacy in promoting central nervous system (CNS) regeneration is unclear. In this study, we aimed to elucidate the role and possible mechanism of PTL on regeneration in injured CNS after irradiation using a developing cerebellum model.

Methods: We investigated the radioprotective effects of PTL on the developing cerebellum by immunoblotting as well as immunofluorescence staining and ROS detection in vivo and in vitro experiments, and then determined the effects of PTL on NEPs in Nestin CFP and Nestin GFP fluorescent mice. Inducible lineage tracing analysis was used in Nestin-CreERT2×ROSA26-LSL YFP mice to label and track the fate of NEPs in the cerebellum after irradiation. Combined with cell biology and molecular biology techniques to determine changes in various cellular components in the cerebellum and possible mechanisms of PTL on NEPs mobilization in the injured developing cerebellum.

Results: We found that PTL could attenuate radiation-induced acute injury of granule neuron progenitors (GNPs) in irradiated cerebellar external granule layer (EGL) by alleviating apoptosis through regulation of the cells’ redox state. Moreover, PTL increased cerebellar Shh production and secretion by inhibiting the PI3K/AKT pathway, thus promoting expansion of NEPs, which is the compensatory replenishment of granule neurons after radiation damage.

Conclusion: Collectively, our results indicate that activation and expansion of NEPs are critical for regeneration of the injured cerebellum, and that PTL is a promising drug candidate to influence this process.