bluuebunny/crossref_metadata_2025 huggingface dataset:
The Rise and Fall of Physiological Theories of the Control of Human Eating Behavior
Authors: Levitsky David A. , Barre Laura , Michael John Jeshurun , Zhong Yingyi , He Yitong , Mizia Alyse , Kaila Sahib
Published: May 2022

Kuhns was the first to suggest that theories in science do not develop in small increments but rather in major leaps to paradigms that examine the same question through very different perspectives. Theories on the mechanism responsible for control of human food intake fall into Kuhn’s description. This article describes how the two major theories of the control of food intake in humans, the Glucostatic Theory, and the Lipostatic Theory, showed initial promise as explanations, but later deteriorated with the slow accumulation experimental data. The locus of theories considered eating behavior as a part of physiological system that regulates the storage of energy on the body. We challenge this fundamental belief with data which suggests that we must be ready to accept a major change in the way we think about eating behavior if we are ever to decrease the prevalence of obesity.
Nutrition, Epigenetics, and Major Depressive Disorder: Understanding the Connection
Authors: Ortega Miguel A. , Fraile-Martínez Óscar , García-Montero Cielo , Alvarez-Mon Miguel Angel , Lahera Guillermo , Monserrat Jorge , Llavero-Valero Maria , Mora Fernando , Rodríguez-Jiménez Roberto , Fernandez-Rojo Sonia , Quintero Javier , Alvarez De Mon Melchor
Published: May 2022

Major depressive disorder (MDD) is a complex, multifactorial disorder of rising prevalence and incidence worldwide. Nearly, 280 million of people suffer from this leading cause of disability in the world. Moreover, patients with this condition are frequently co-affected by essential nutrient deficiency. The typical scene with stress and hustle in developed countries tends to be accompanied by eating disorders implying overnutrition from high-carbohydrates and high-fat diets with low micronutrients intake. In fact, currently, coronavirus disease 2019 (COVID-19) pandemic has drawn more attention to this underdiagnosed condition, besides the importance of the nutritional status in shaping immunomodulation, in which minerals, vitamins, or omega 3 polyunsaturated fatty acids (ω-3 PUFA) play an important role. The awareness of nutritional assessment is greater and greater in the patients with depression since antidepressant treatments have such a significant probability of failing. As diet is considered a crucial environmental factor, underlying epigenetic mechanisms that experience an adaptation or consequence on their signaling and expression mechanisms are reviewed. In this study, we included metabolic changes derived from an impairment in cellular processes due to lacking some essential nutrients in diet and therefore in the organism. Finally, aspects related to nutritional interventions and recommendations are also addressed.
Parents’ Modeling During the COVID-19 Pandemic: Influences on Family Members’ Diet Quality and Satisfaction With-Food-Related Life in Dual-Earner Parents With Adolescent Children
Authors: Schnettler Berta , Miranda-Zapata Edgardo , Orellana Ligia , Saracostti Mahia , Poblete Héctor , Lobos Germán , Adasme-Berríos Cristian , Lapo María , Beroiza Katherine , Grunert Klaus G.
Published: May 2022

Reciprocal family influences in the food domain have been little explored, particularly during the COVID-19 pandemic. To fill in this gap, this study explored actor and partner effects between parents’ food modeling and parents’ and their adolescent children’s diet quality and satisfaction with food-related life (SWFoL); and the mediating role of diet quality between modeling and SWFoL. This study used a cross-sectional design. A sample of 430 different-sex dual-earner parents and one adolescent child were recruited in Rancagua, Chile, between March and June 2020. Parents answered the modeling dimension of the Comprehensive Feeding Practices Questionnaire. Parents and adolescents answered the Adapted Healthy Eating Index (AHEI) and the SWFoL Scale. Analyses were conducted using the Actor-Partner Interdependence Model and structural equation modeling. Results showed that one parent’s modeling enhanced diet quality for themselves, their partner, and the adolescents. Parents’ modeling was associated with their own SWFoL, directly and via their own diet quality. There were positive associations between mothers’ modeling and adolescents’ SWFoL; between mothers’ diet quality and fathers’ SWFoL; and between mothers’ modeling and fathers’ SWFoL via the fathers’ diet quality. Parents’ modeling can improve the three family members’ diet quality, while mothers’ modeling and diet quality showed to improve fathers’ and adolescents’ SWFoL.
Physicochemical Characterization and Antioxidant and Hypolipidaemic Activities of a Polysaccharide From the Fruit of Kadsura coccinea (Lem.) A. C. Smith
Authors: Long Hairong , Xia Xianghua , Liao Suqi , Wu Tao , Wang Lijun , Chen Qianping , Wei Shugen , Gu Xiaoyu , Zhu Zhenjun
Published: May 2022

Kadsura coccinea fruit, a novel fruit resource, has attracted wide interest, but the physicochemical characteristics and biological activities of its polysaccharides remain unclear. This study investigated the physicochemical properties of a polysaccharide extracted from K. coccinea fruit polysaccharide (KCFP) and evaluated its antioxidant and hypolipidaemic activities in vitro and in vivo. KCFP is an amorphous, thermally stable pectin heteropolysaccharide with an average molecular weight of 204.6 kDa that is mainly composed of mannose, rhamnose, glucose, galactose, xylose, arabinose, galacturonic acid (molar percentage >70%) and glucuronic acid. 2,2-Diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) free radical scavenging assays and an iron reducing antioxidant power assay showed that KCFP has strong antioxidant capacity, while the bile acid binding assay showed that KCFP has hypolipidaemic potential in vitro. The antioxidant and hypolipidaemic activities of KCFP were further evaluated in high-fat diet-induced hyperlipidaemic mice. KCFP significantly increased the activities of superoxide dismutase, glutathione peroxidase and catalase, decreased the malondialdehyde content, significantly reduced the total cholesterol (TC), triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C) levels, and increased the amount of high-density lipoprotein cholesterol (HDL-C). These findings suggest that KCFP could be used as a functional food to remedy oxidative damage and hyperlipidaemia.
Prognostic Significance of the Stage at Which an MRD-Negative Status Is Achieved for Patients With Multiple Myeloma Who Received ASCT
Authors: Sun Qian , Li Xiaozhe , Gu Jingli , Huang Beihui , Liu Junru , Chen Meilan , Li Juan
Published: May 2022

Objective

To explore the prognostic significance of the stage at which a minimal residual disease (MRD)-negative status is achieved for patients with newly diagnosed multiple myeloma (NDMM) who received autologous hematopoietic stem cell transplantation (ASCT).

Cases and Methods

A retrospective analysis of 186 NDMM patients who received “induction therapy-ASCT-maintenance therapy” in our center and achieved an MRD-negative status was performed. Patients were divided into three groups, A (induction therapy), B (3 months after ASCT), and C (maintenance therapy), according to the stage at which an MRD-negative status was achieved.

Results

The median time to progression (TTP) of 186 patients was not reached; the median overall survival (OS) was 113.8 months. The median TTP of the patients in three groups was not reached (P=0.013), and the median OS of the patients in three groups was not reached, not reached, and 71.2 months, respectively (P=0.026). Among patients with standard-risk cytogenetics, the median TTP of those in all three groups was not reached (P=0.121), and the median OS of the patients in three groups was not reached, not reached, and 99.6 months, respectively (P=0.091). Among patients with high-risk cytogenetics, the median TTP of those in three groups was not reached, 53.9 months, and 35.8 months (P=0.060), and the median OS was not reached, 71.2 months, and 60.2 months, respectively (P=0.625). Among patients with R-ISS stage I-II, the median TTP of those in three groups was not reached (P=0.174), and the median OS of the patients in three groups was not reached, not reached, and 99.6 months, respectively (P=0.186). Among the 29 patients with R-ISS stage III, the median TTP of those in the 3 groups were unreached, unreached, and 35.1 months (P<0.001), and the median OS was unreached, unreached, and 48.5 months, respectively (P=0.020). In all enrolled patients, the stage of reaching MRD-negative was an independent prognostic factor for TTP, rather than a prognostic factor for OS. The stage of reaching MRD-negative in patients with R-ISS III was an independent prognostic factor for OS.

Conclusion

For the same patients who are MRD-negative, the prognoses of those who achieve an MRD-negative status at different groups are different. The stage at which an MRD-negative status is achieved can predict the prognosis of patients with R-ISS stage III.
Neuregulin 4 Boosts the Efficacy of Anti-ERBB2 Neutralizing Antibodies
Authors: Miano Carmen , Romaniello Donatella , Mazzeschi Martina , Morselli Alessandra , Da Pra Silvia , Sacchi Francesca , Bongiovanni Chiara , Sgarzi Michela , Pantano Elvira , Lauriola Mattia , D’Uva Gabriele
Published: May 2022

ERBB4 is a tyrosine kinase receptor reported to exert both oncogenic and tumor suppressor activities. These paradoxical effects were suggested to stem from different ERBB4 homo-/hetero-dimers and/or isoforms. By stratifying breast cancer patients for clinical and molecular subtypes and ERBB4 mRNA abundance, we here report that higher ERBB4 levels correlate with longer relapse-free survival in breast cancer patients of HER2-enriched and luminal A molecular subtypes, proposing a cancer-protecting role for this receptor in these specific subgroups. We also observed that HER2-enriched breast cancers express intermediate ERBB4 mRNA levels compared to luminal and triple-negative/basal-like subgroups, which displayed the highest and the lowest levels, respectively. Inspired by these clinical data, we tested the activation of ERBB4 by Neuregulins as a potential anticancer strategy for HER2+ breast cancers. To this end, we employed two HER2+ breast cancer cellular models (BT474 and SKBR3), which express intermediate/high and low ERBB4 levels, respectively. Cell proliferation and motility were evaluated on these cellular models following treatments with Neuregulin 1 (NRG1), which activates both ERBB3 and ERBB4, or Neuregulin 4 (NRG4), which specifically activates ERBB4. Both NRG1 and NRG4 were used alone or in combination with anti-ERBB2 neutralizing antibodies, namely trastuzumab and pertuzumab. In vitro treatment with NRG1 on BT474 cells restrained cell growth and reduced the anti-proliferative efficacy of trastuzumab. In contrast, treatment with NRG1 on SKBR3 cells increased cell proliferation and migration, and partially or completely impaired the anti-proliferative/anti-migratory action of trastuzumab and/or pertuzumab. Importantly, in both the cell lines, treatment with NRG4 robustly potentiated the anti-proliferative action of trastuzumab and pertuzumab. Collectively, our data in HER2+ breast cancer cells highlight that NRG1 may exert both pro- and anti-proliferative effects, and may reduce the efficacy of anti-HER2 agents, whereas NRG4 may boost the anti-proliferative effects of anti-ERBB2 agents. We propose a provocative paradigm shift in the field of growth factors in cancer progression, suggesting the administration of ERBB4 ligands, such as Neuregulin 4, as a strategy to improve the efficacy of anti-ERBB2 agents.
Prospective Medicinal Plants and Their Phytochemicals Shielding Autoimmune and Cancer Patients Against the SARS-CoV-2 Pandemic: A Special Focus on Matcha
Authors: Kiriacos Caroline Joseph , Khedr Monika Rafik , Tadros Miray , Youness Rana A.
Published: May 2022

Background

Being “positive” has been one of the most frustrating words anyone could hear since the end of 2019. This word had been overused globally due to the high infectious nature of SARS-CoV-2. All citizens are at risk of being infected with SARS-CoV-2, but a red warning sign has been directed towards cancer and immune-compromised patients in particular. These groups of patients are not only more prone to catch the virus but also more predisposed to its deadly consequences, something that urged the research community to seek other effective and safe solutions that could be used as a protective measurement for cancer and autoimmune patients during the pandemic.

Aim

The authors aimed to turn the spotlight on specific herbal remedies that showed potential anticancer activity, immuno-modulatory roles, and promising anti-SARS-CoV-2 actions.

Methodology

To attain the purpose of the review, the research was conducted at the States National Library of Medicine (PubMed). To search databases, the descriptors used were as follows: “COVID-19”/”SARS-CoV-2”, “Herbal Drugs”, “Autoimmune diseases”, “Rheumatoid Arthritis”, “Asthma”, “Multiple Sclerosis”, “Systemic Lupus Erythematosus” “Nutraceuticals”, “Matcha”, “EGCG”, “Quercetin”, “Cancer”, and key molecular pathways.

Results

This manuscript reviewed most of the herbal drugs that showed a triple action concerning anticancer, immunomodulation, and anti-SARS-CoV-2 activities. Special attention was directed towards “matcha” as a novel potential protective and therapeutic agent for cancer and immunocompromised patients during the SARS-CoV-2 pandemic.

Conclusion

This review sheds light on the pivotal role of “matcha” as a tri-acting herbal tea having a potent antitumorigenic effect, immunomodulatory role, and proven anti-SARS-CoV-2 activity, thus providing a powerful shield for high-risk patients such as cancer and autoimmune patients during the pandemic.
Deep Learning for Per-Fraction Automatic Segmentation of Gross Tumor Volume (GTV) and Organs at Risk (OARs) in Adaptive Radiotherapy of Cervical Cancer
Authors: Breto Adrian L. , Spieler Benjamin , Zavala-Romero Olmo , Alhusseini Mohammad , Patel Nirav V. , Asher David A. , Xu Isaac R. , Baikovitz Jacqueline B. , Mellon Eric A. , Ford John C. , Stoyanova Radka , Portelance Lorraine
Published: May 2022

Background/Hypothesis

MRI-guided online adaptive radiotherapy (MRI-g-OART) improves target coverage and organs-at-risk (OARs) sparing in radiation therapy (RT). For patients with locally advanced cervical cancer (LACC) undergoing RT, changes in bladder and rectal filling contribute to large inter-fraction target volume motion. We hypothesized that deep learning (DL) convolutional neural networks (CNN) can be trained to accurately segment gross tumor volume (GTV) and OARs both in planning and daily fractions’ MRI scans.

Materials/Methods

We utilized planning and daily treatment fraction setup (RT-Fr) MRIs from LACC patients, treated with stereotactic body RT to a dose of 45-54 Gy in 25 fractions. Nine structures were manually contoured. MASK R-CNN network was trained and tested under three scenarios: (i) Leave-one-out (LOO), using the planning images of N- 1 patients for training; (ii) the same network, tested on the RT-Fr MRIs of the “left-out” patient, (iii) including the planning MRI of the “left-out” patient as an additional training sample, and tested on RT-Fr MRIs. The network performance was evaluated using the Dice Similarity Coefficient (DSC) and Hausdorff distances. The association between the structures’ volume and corresponding DSCs was investigated using Pearson’s Correlation Coefficient, r.

Results

MRIs from fifteen LACC patients were analyzed. In the LOO scenario the DSC for Rectum, Femur, and Bladder was >0.8, followed by the GTV, Uterus, Mesorectum and Parametrium (0.6-0.7). The results for Vagina and Sigmoid were suboptimal. The performance of the network was similar for most organs when tested on RT-Fr MRI. Including the planning MRI in the training did not improve the segmentation of the RT-Fr MRI. There was a significant correlation between the average organ volume and the corresponding DSC (r = 0.759, p = 0.018).

Conclusion

We have established a robust workflow for training MASK R-CNN to automatically segment GTV and OARs in MRI-g-OART of LACC. Albeit the small number of patients in this pilot project, the network was trained to successfully identify several structures while challenges remain, especially in relatively small organs. With the increase of the LACC cases, the performance of the network will improve. A robust auto-contouring tool would improve workflow efficiency and patient tolerance of the OART process.
Solasonine Causes Redox Imbalance and Mitochondrial Oxidative Stress of Ferroptosis in Lung Adenocarcinoma
Authors: Zeng Yao-Ying , Luo Ying-Bin , Ju Xu-Dong , Zhang Bo , Cui Ya-Jing , Pan Yan-Bin , Tian Jian-Hui , Teng Wen-Jing , Wu Jianchun , Li Yan
Published: May 2022

Ferroptosis, a type of iron-dependent oxidative cell death caused by excessive lipid peroxidation, is emerging as a promising cancer therapeutic strategy. Solasonine has been reported as a potential compound in tumor suppression, which is closely linked to ferroptosis. However, ferroptosis caused by solasonine is insufficiently identified and elaborated in lung adenocarcinoma, a fatal disease with high morbidity and mortality rates. First, the biochemical and morphological changes in Calu-1 and A549 cells exposed to solasonine are observed using a cell death assay and a microscope. The cell viability assay is performed after determining the executive concentration of solasonine to assess the effects of solasonine on tumor growth in Calu-1 and A549 cells. The ferroptosis is then identified by using ferroptosis-related reagents on CCK-8, lipid peroxidation assessment, Fe2+, and ROS detection. Furthermore, the antioxidant system, which includes GSH, Cys, GPx4, SLC7A11, and mitochondrial function, is measured to identify the potential pathways. According to the results, solasonine precisely exerts antitumor ability in lung adenocarcinoma cells. Ferroptosis is involved in the solasonine-induced cell death, as well as the accumulation of lipid peroxide, Fe2+, and ROS. Moreover, the failures of antioxidant defense and mitochondrial damage are considered to make a significant contribution to the occurrence of ferroptosis caused by solasonine. The study describes the potential process of ferroptosis caused by solasonine when dealing with lung adenocarcinoma. This encouraging evidence suggests that solasonine may be useful in the treatment of lung cancer.
Resection of Noncontrast-Enhancing Regions Deteriorated the Immunotherapeutic Efficacy of HSPPC-96 Vaccination in Treating Glioblastoma
Authors: Chi Xiaohan , Wang Yi , Li Chunzhao , Huang Xijian , Gao Hua , Zhang Yang , Ji Nan
Published: May 2022

Surgical resection remains a first-line therapy for glioblastoma multiforme (GBM). Increased extent of resection (EOR) of noncontrast-enhancing regions in T2-weighted MRI images (T2-EOR) provides a survival benefit for GBM patients receiving standard radio/chemotherapy. However, whether it also improves immunotherapeutic outcomes remains unclear. We calculated the T2-EOR by comparing the preoperative and postoperative MRI T2 hyperintensity outside the enhancing tumour and correlated the T2-EOR with immunological and clinical outcomes from our published early-phase trial of heat shock protein peptide complex-96 (HSPPC-96) vaccination in treating a cohort of 19 patients with newly diagnosed GBMs (NCT02122822). Patients with higher T2-EOR exhibited shorter progression-free survival (PFS) (HR 11.29, p=0.002) and overall survival (OS) (HR 6.5, p=0.003) times than patients with lower T2-EOR. T2-EOR was negatively correlated with the levels of tumour specific immune response (TSIR) post-vaccination (R=-0.725, p<0.001) and absolute TSIR increase from pre- to post-vaccination (R=-0.679, p=0.001). Multivariate Cox regression models revealed that higher T2-EOR represented an independent risk factor for PFS (HR 19.85, p=0.0068) and OS (HR 21.24, p=0.0185) in this patient cohort. Taken together, increased T2-EOR deteriorated immunotherapeutic outcomes by suppressing TSIR, suggesting the potential of T2-EOR as an early biomarker for predicting the immunotherapeutic efficacy of HSPPC-96 vaccination.
Development of a Chemoresistant Risk Scoring Model for Prechemotherapy Osteosarcoma Using Single-Cell Sequencing
Authors: Zeng Ziliang , Li Wenpeng , Zhang Di , Zhang Chi , Jiang Xu , Guo Rui , Wang Zheyu , Yang Canchun , Yan Haolin , Zhang Zhilei , Wang Qiwei , Huang Renyuan , Zhao Qiancheng , Li Bo , Hu Xumin , Gao Liangbin
Published: May 2022

Background

Chemoresistance is one of the leading causes that severely limits the success of osteosarcoma treatment. Evaluating chemoresistance before chemotherapy poses a new challenge for researchers. We established an effective chemoresistance risk scoring model for prechemotherapy osteosarcoma using single-cell sequencing.

Methods

We comprehensively analyzed osteosarcoma data from the bulk mRNA sequencing dataset TARGET-OS and the single-cell RNA sequencing (scRNA-seq) dataset GSE162454. Chemoresistant tumor clusters were identified using enrichment analysis and AUCell scoring. Its differentiated trajectory was achieved with inferCNV and pseudotime analysis. Ligand–receptor interactions were annotated with iTALK. Furthermore, we established a chemoresistance risk scoring model using LASSO regression based on scRNA-seq-based markers of chemoresistant tumor clusters. The TARGET-OS dataset was used as the training group, and the bulk mRNA array dataset GSE33382 was used as the validation group. Finally, the performance was verified for its discriminatory ability and calibration.

Results

Using bulk RNA data, we found that osteogenic expression was upregulated in chemoresistant osteosarcoma as compared to chemosensitive osteosarcoma. Then, we transferred the bulk RNA findings to scRNA-seq and noticed osteosarcoma tumor clusters C14 and C25 showing osteogenic cancer stem cell expression patterns, which fit chemoresistant characteristics. C14 and C25 possessed bridge roles in interactions with other clusters. On the one hand, they received various growth factor stimulators and could potentially transform into a proliferative state. On the other hand, they promote local tumor angiogenesis, bone remodeling and immunosuppression. Next, we identified a ten-gene signature from the C14 and C25 markers and constructed a chemoresistant risk scoring model using LASSO regression model. Finally, we found that chemoresistant osteosarcoma had higher chemoresistance risk score and that the model showed good discriminatory ability and calibration in both the training and validation groups (AUCtrain = 0.82; AUCvalid = 0.84). Compared with that of the classic bulk RNA-based model, it showed more robust performance in validation environment (AUCvalid-scRNA = 0.84; AUCvalid-bulk DEGs = 0.54).

Conclusions

Our work provides insights into understanding chemoresistant osteosarcoma tumor cells and using single-cell sequencing to establish a chemoresistance risk scoring model. The model showed good discriminatory ability and calibration and provided us with a feasible way to evaluate chemoresistance in prechemotherapy osteosarcoma.
NDUFAF6-Related Leigh Syndrome Caused by Rare Pathogenic Variants: A Case Report and the Focused Review of Literature
Authors: Kim Jaewon , Lee Jaewoong , Jang Dae-Hyun
Published: May 2022

Leigh syndrome is a neurodegenerative disorder that presents with fluctuation and stepwise deterioration, such as neurodevelopmental delay and regression, dysarthria, dysphagia, hypotonia, dystonia, tremor, spasticity, epilepsy, and respiratory problems. The syndrome characteristically presents symmetric necrotizing lesions in the basal ganglia, brainstem, cerebellum, thalamus, and spinal cord on cranial magnetic resonance imaging. To date, more than 85 genes are known to be associated with Leigh syndrome. Here, we present a rare case of a child who developed Leigh syndrome due to pathogenic variants of NDUFAF6, which encodes an assembly factor of complex I, a respiratory chain subunit. A targeted next-generation sequencing analysis related to mitochondrial disease revealed a missense variant (NM_152416.4:c.371T > C; p.Ile124Thr) and a frameshift variant (NM_152416.4:c.233_242del; p.Leu78GInfs*10) inherited biparentally. The proband underwent physical therapy and nutrient cocktail therapy, but his physical impairment gradually worsened.
The SES-CD Could Be a Predictor of Short- and Long-Term Mucosal Healing After Exclusive Enteral Nutrition in Pediatric Crohn’s Disease Patients
Authors: Tang Wenjuan , Hu Wenhui , Shi Peng , Ye Ziqing , Wu Jie , Zhang Ye , Wang Yuhuan , Huang Ying
Published: May 2022

Aims

To explore the predictors of mucosal healing (MH) for short- and long-term after exclusive enteral nutrition (EEN) in pediatric Crohn’s disease (CD) patients.

Methods

A retrospective analysis was performed for newly diagnosed active CD patients admitted to our center from January 2017 to 30 December 2020, who were treated with EEN for induction therapy with a minimum of 12 months of follow-up post-EEN. According to the simple endoscopic score for CD (SES-CD), at 1-year post-EEN, 17 patients with an SES-CD < 3 were classified into the sustained MH group (sMH), and 33 patients with an SES-CD ≥ 3 were classified into the sustained non-MH group (sNMH). Statistical methods were used to compare the differences between the two groups and explore the predictors of MH at the end of EEN and 1-year post-EEN.

Results

The SES-CD in the sMH group was lower than that in the sNMH group both at baseline and the end of EEN [sMH vs. sNMH: 8.7 ± 1.2 vs. 16.2 ± 1.0, respectively, p < 0.001 at baseline; 1.0 (3.5) vs. 4.0 (2.0), respectively, p < 0.01 at the end of EEN]. The weighted Pediatric Crohn’s Disease Activity Index and erythrocyte sedimentation rate in the sMH group were lower than those in the sNMH group at baseline (both p < 0.05), but showed no difference at the end of EEN. From baseline to 1-year post-EEN, compared with patients in the sNMH group, there were more patients classified with L1 in the sMH group at each time point (all p < 0.001) and fewer patients classified with L3 in the sMH group at baseline and 1-year post-EEN. After EEN, fewer patients received infliximab and had a longer exposure time to infliximab in the sMH group than in the sNMH group. Only the SES-CD at baseline was negatively associated with MH at the end of EEN (OR = 1.40 95% CI = 1.12–1.67, p = 0.00) and 1-year post-EEN (OR = 1.33, 95% CI = 1.12–1.58, p = 0.001), and the cut off value was 11.5.

Conclusion

The SES-CD could predict both short- and long-term MH for EEN. Patients with an SES-CD < 11.5 had a high probability of reaching MH by EEN-inducing therapy and maintaining sustained MH at 1-year post-EEN. Patients with an SES-CD greater than 11.5 at baseline should be treated more aggressively with biologics.
Aconiti Lateralis Radix Praeparata as Potential Anticancer Herb: Bioactive Compounds and Molecular Mechanisms
Authors: Zhang Wen , Lu Chaoying , Cai Shuhui , Feng Yaru , Shan Jinjun , Di Liuqing
Published: May 2022

Aconiti Lateralis Radix Praeparata (Fuzi in Chinese) is a traditional herbal medicine widely used in China and other Asian countries. In clinical practice, it is often used to treat heart failure, rheumatoid arthritis, and different kinds of pains. Fuzi extract and its active ingredients exert considerable anticancer, anti-inflammatory, and analgesic effects. The main chemical substances of Fuzi include alkaloids, polysaccharides, flavonoids, fatty acids, and sterols. Among of them, alkaloids and polysaccharides are responsible for the anticancer efficacy. Most bioactive alkaloids in Fuzi possess C19 diterpenoid mother nucleus and these natural products show great potential for cancer therapy. Moreover, polysaccharides exert extraordinary tumor-suppressive functions. This review comprehensively summarized the active ingredients, antineoplastic effects, and molecular mechanisms of Fuzi by searching PubMed, Web of Science, ScienceDirect, and CNKI. The anticancer effects are largely attributed to inducing apoptosis and autophagy, inhibiting proliferation, migration and invasion, regulating body immunity, affecting energy metabolism, as well as reversing multidrug resistance. Meanwhile, several signaling pathways and biological processes are mainly involved, such as NF-κB, EMT, HIF-1, p38 MAPK, PI3K/AKT/mTOR, and TCA cycle. Collectively, alkaloids and polysaccharides in Fuzi might serve as attractive therapeutic candidates for the development of anticancer drugs. This review would lay a foundation and provide a basis for further basic research and clinical application of Fuzi.
RETRACTED: Quercetin Inhibits Tumorigenesis of Colorectal Cancer Through Downregulation of hsa_circ_0006990
Authors: Chen Bin , Wu Linguangjin , Tang Xiaoxia , Wang Ting , Wang Shuyun , Yu Hongjie , Wan Guangsheng , Xie Manli , Zhang Ruijuan , Xiao Haijuan , Deng Wanli
Published: May 2022

Quercetin can significantly inhibit the progression of colorectal cancer (CRC). However, its specific mechanism remains largely unclear. In this study, we aimed to explore the correlation among quercetin, tumour-associated macrophages (TAMs) and circular RNAs (circRNAs) in the progression of CRC and to present a novel strategy for the treatment of CRC. In this study, we revealed that quercetin could suppress the autophagy of M2-TAMs and induced their differentiation into M1-TAMs, by which quercetin significantly reversed the inhibition of M2-TAMS on CRC cell apoptosis and the promotion of M2-TAMS on CRC cell proliferation. Moreover, quercetin could promote the expression of downregulated hsa_circ_0006990 in CRC cells co-cultured with M2-TAMs, and the overexpression of hsa_circ_0006990 significantly reversed the anti-tumour effect of quercetin on CRC. Furthermore, we found quercetin can notably suppress the progression of CRC via mediation of the hsa_circ_0006990/miR-132-3p/MUC13 axis. In conclusion, our results suggested that quercetin inhibits the tumorigenesis of CRC via inhibiting the polarisation of M2 macrophages and downregulating hsa_circ_0006990. Our study provides useful insights for those exploring new methods of treating CRC.
Comparative Efficacy of Pharmacological Treatments for Adults With Autosomal Dominant Polycystic Kidney Disease: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials
Authors: Tsukamoto Shunichiro , Urate Shingo , Yamada Takayuki , Azushima Kengo , Yamaji Takahiro , Kinguchi Sho , Uneda Kazushi , Kanaoka Tomohiko , Wakui Hiromichi , Tamura Kouichi
Published: May 2022

Background: Tolvaptan is the gold standard treatment for autosomal dominant polycystic kidney disease (ADPKD), while several other drugs have the potential to inhibit the progression of ADPKD. However, individual clinical trials may not show sufficient differences in clinical efficacy due to small sample sizes. Furthermore, the differences in therapeutic efficacy among drugs are unclear. Herein, we investigated the effect of the ADPKD treatments.

Methods: We systematically searched PubMed, Medline, EMBASE, and the Cochrane Library through January 2022 to identify randomized controlled trials in ADPKD patients that compared the effects of treatments with placebo or conventional therapy. A network meta-analysis was performed to compare the treatments indirectly. The primary outcomes were changes in kidney function and the rate of total kidney volume (TKV) growth.

Results: Sixteen studies were selected with a total of 4,391 patients. Tolvaptan significantly preserved kidney function and inhibited TKV growth compared to the placebo {standardized mean difference (SMD) [95% confidence interval (CI)]: 0.24 (0.16; 0.31) and MD: −2.70 (−3.10; −2.30), respectively}. Tyrosine kinase inhibitors and mammalian target of rapamycin (mTOR) inhibitors inhibited TKV growth compared to the placebo; somatostatin analogs significantly inhibited TKV growth compared to the placebo and tolvaptan [MD: −5.69 (−7.34; −4.03) and MD: −2.99 (−4.69; −1.29), respectively]. Metformin tended to preserve renal function, although it was not significant [SMD: 0.28 (−0.05; 0.61), p = 0.09].

Conclusion: The therapeutic effect of tolvaptan was reasonable as the gold standard for ADPKD treatment, while somatostatin analogs also showed notable efficacy in inhibiting TKV growth.

Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42022300814.
CNST is Characteristic of Leukemia Stem Cells and is Associated With Poor Prognosis in AML
Authors: Liu Haoyu , Zhang Xu , Zhao Ziyan , Zhu Hongying , Li Danyang , Yang Yang , Zhao Wenbo , Zhang Fei , Wang Yuefeng , Zhu Lina , Ding Zewen , Li Xiangzhi
Published: May 2022

Consortin (CNST) is a protein located on the trans-Golgi network that can target transmembrane proteins to the plasma membrane. Although CNST was discovered more than 10 years ago, there are still not enough studies on its function. During our search for possible new acute myeloid leukemia (AML) markers, we found that CNST was overexpressed in almost all patients with AML. By analyzing profiling data from public databases, we found that CNST expression inversely correlated with overall survival among AML patients. There was a great variation in CNST expression among different subtypes of AML, and the expression was the highest in the t(8,21) subtype, which was probably due to the direct regulation of CNST transcription by RUNX1-RUNX1T1. In addition, we analyzed the expression of CNST in different cells of the hematopoietic system. We found that CNST was associated with the low differentiation degrees of hematopoietic cells and had the highest expression level in leukemia stem cells (LSCs). Finally, we analyzed the CNST-related gene network and found that the genes negatively correlated with CNST are involved in various immune-related pathways, which indicates that CNST is likely related to immune evasion, LSC niche retention, and assembly of stress granules. In conclusion, our study suggests that CNST has the potential to be a diagnostic and prognostic biomarker for AML.
Title: Multi-Omics and Immune Landscape of Proliferative LncRNA Signatures: Implications for Risk Stratification and Immunotherapy in Hepatocellular Carcinoma
Authors: Liu Chi , Gao Jie , Yang Dongjing , Yu Qiwen , Zhang Shuijun
Published: May 2022

Background: Long noncoding RNAs (lncRNAs) are significantly implicated in tumor proliferation. Nevertheless, proliferation-derived lncRNAs and their latent clinical significance remain largely unrevealed in hepatocellular carcinoma (HCC).

Methods: This research enrolled 658 HCC patients from five independent cohorts. We retrieved 50 Hallmark gene sets from the MSigDB portal. Consensus clustering was applied to identify heterogeneous proliferative subtypes, and the nearest template prediction (NTP) was utilized to validate the subtypes. We introduced an integrative framework (termed “ProLnc”) to identify proliferation-derived lncRNAs. Moreover, a proliferation-related signature was developed and verified in four independent cohorts.

Results: In 50 Hallmarks, seven proliferation pathways were significantly upregulated and correlated with a worse prognosis. Subsequently, we deciphered two heterogeneous proliferative subtypes in TCGA-LIHC. Subtype 2 displayed enhanced proliferative activities and a worse prognosis, whereas subtype 1 was associated with hyperproliferative HCC and a favorable prognosis. The NTP further verified the robustness and reproducibility of two subtypes in four cohorts derived from different platforms. Combining the differentially expressed lncRNAs from two subtypes with proliferative lncRNA modulators from our ProLnc pipeline, we determined 230 proliferation-associated lncRNAs. Based on the bootstrapping channel and the verification of multiple cohorts, we further identified ten lncRNAs that stably correlated with prognosis. Subsequently, we developed and validated a proliferative lncRNA signature (ProLncS) that could independently and accurately assess the overall survival (OS) and relapse-free survival (RFS) of HCC patients in the four cohorts. Patients with high ProLncS score displayed significantly genomic alterations (e.g., TP53 mutation, 8p23-8p24 copy number variation) and higher abundances of immune cells and immune checkpoint molecules, which suggested immunotherapy was more suitable for patients with high ProLncS score.

Conclusion: Our work provided new insights into the heterogeneity of tumor proliferation, and ProLncS could be a prospective tool for tailoring the clinical decision and management of HCC.
Estimation of Eigenvalues for the ψ-Laplace Operator on Bi-Slant Submanifolds of Sasakian Space Forms
Authors: Alkhaldi Ali H. , Khan Meraj Ali , Aquib Mohd. , Alqahtani Lamia Saeed
Published: May 2022

This study attempts to establish new upper bounds on the mean curvature and constant sectional curvature of the first positive eigenvalue of the ψ − Laplacian operator on Riemannian manifolds. Various approaches are being used to find the first eigenvalue for the ψ − Laplacian operator on closed oriented bi-slant submanifolds in a Sasakian space form. We extend different Reilly-like inequalities to the ψ − Laplacian on bi-slant submanifolds in a unit sphere depending on our results for the Laplacian operator. The conclusion of this study considers some special cases as well.
Effects of Interval Training Under Hypoxia on Hematological Parameters, Hemodynamic Function, and Endurance Exercise Performance in Amateur Female Runners in Korea
Authors: Park Hun-Young , Jung Won-Sang , Kim Sung-Woo , Kim Jisu , Lim Kiwon
Published: May 2022

Interval training under hypoxia (IHT) is commonly used to enhance endurance exercise performance. However, previous studies examining hematologic changes related to the immune system that affect health and conditioning are lacking. This study aimed to evaluate the effects of IHT for 6-weeks on hematological parameters, hemodynamic function, and endurance exercise performance in amateur Korean female runners. Twenty healthy amateur Korean female runners (age: 24.85 ± 3.84 years) were equally assigned to normoxic training group (NTG) for interval training under normoxia (760 mmHg) and hypoxic training group (HTG) for interval training under hypobaric hypoxia (526 mmHg, 3000 m simulated altitude) according to their body composition and endurance exercise performance. All participants performed 120-min of training sessions, consisting of 20-min of warm-up, 60-min of interval training, and 20-min of cool-down. The training program was performed 3-days per week for 6-weeks. Warm-up and cool-down were performed for 20-min at 60% maximal heart rate (HRmax). The interval training sessions comprised 10 repetitions of interval exercise (5-min of exercise corresponding to 90–95% HRmax and 1-min of rest) on a treadmill. All participants underwent measurements of hematological parameters, hemodynamic function, and endurance exercise performance before and after training. Both groups showed a significant increase in erythropoietin (EPO) level and a decrease in monocyte abundance, with EPO showing a greater increase in the HTG than in the NTG. B cell abundance significantly increased in the NTG; hematocrit and neutrophil counts significantly increased, and lymphocyte counts significantly decreased in the HTG. The HTG showed a significant improvement in oxygen uptake, stroke volume index, and end-diastolic volume index compared to the NTG. In addition, both groups showed significant improvements in heart rate, end-systolic volume index, and cardiac output index. The maximal oxygen uptake and 3000 m time trial record were significantly improved in both groups, and the HTG showed a tendency to improve more than the NTG. In conclusion, the IHT was effective in enhancing endurance exercise performance through improved hemodynamic function. Furthermore, hematological parameters of immune system showed a normal range before and after training and were not negatively affected.
Dissecting the Genetic Architecture of Carbon Partitioning in Sorghum Using Multiscale Phenotypes
Authors: Boatwright J. Lucas , Sapkota Sirjan , Myers Matthew , Kumar Neeraj , Cox Alex , Jordan Kathleen E. , Kresovich Stephen
Published: May 2022

Carbon partitioning in plants may be viewed as a dynamic process composed of the many interactions between sources and sinks. The accumulation and distribution of fixed carbon is not dictated simply by the sink strength and number but is dependent upon the source, pathways, and interactions of the system. As such, the study of carbon partitioning through perturbations to the system or through focus on individual traits may fail to produce actionable developments or a comprehensive understanding of the mechanisms underlying this complex process. Using the recently published sorghum carbon-partitioning panel, we collected both macroscale phenotypic characteristics such as plant height, above-ground biomass, and dry weight along with microscale compositional traits to deconvolute the carbon-partitioning pathways in this multipurpose crop. Multivariate analyses of traits resulted in the identification of numerous loci associated with several distinct carbon-partitioning traits, which putatively regulate sugar content, manganese homeostasis, and nitrate transportation. Using a multivariate adaptive shrinkage approach, we identified several loci associated with multiple traits suggesting that pleiotropic and/or interactive effects may positively influence multiple carbon-partitioning traits, or these overlaps may represent molecular switches mediating basal carbon allocating or partitioning networks. Conversely, we also identify a carbon tradeoff where reduced lignin content is associated with increased sugar content. The results presented here support previous studies demonstrating the convoluted nature of carbon partitioning in sorghum and emphasize the importance of taking a holistic approach to the study of carbon partitioning by utilizing multiscale phenotypes.
Germination Characteristics Associated With Glutathione S-Transferases Endowed Quizalofop-p-Ethyl Resistance in Polypogon fugax
Authors: Chen Wen , Peng Yajun , Lin Qiaojiao , Zhang Tianzhu , Yan Bei , Bai Lianyang , Pan Lang
Published: May 2022

Quantification of germination characteristics between herbicide-resistant and -susceptible weeds might provide methods to control resistant weeds and permit better prediction of evolution and persistence of herbicide resistance. This study aimed to compare the germination characteristics of Asian minor bluegrass (Polypogon fugax) populations that are resistant or susceptible to quizalofop-p-ethyl under controlled conditions, which the resistance mechanism is involved in glutathione S-transferases (GSTs) metabolism-based resistance. No major differences in seed germination were found at diverse temperatures, pH ranges, and light conditions. However, a significant difference that seed response to a gradient of osmotic and salt stress between the resistant and susceptible P. fugax populations were found. Two stress response genes (P5CS-1 and CDPK-2) in P. fugax were likely involved in germination rate as well as germination speed in response to these stresses. Subsequently, population verification demonstrated that P5CS-1 and CDPK-2 genes may be linked to the resistance mechanism. Additionally, the two genes play an important role in response to salt stress and osmotic stress as shown by transcript abundance after stress treatments. Our findings suggest that the variation of the germination characteristics in P. fugax associates with the presence of GST-endowed resistance mechanism.
Genomics Enabled Breeding Strategies for Major Biotic Stresses in Pea (Pisum sativum L.)
Authors: Parihar Ashok Kumar , Kumar Jitendra , Gupta Debjyoti Sen , Lamichaney Amrit , Naik SJ Satheesh , Singh Anil K. , Dixit Girish P. , Gupta Sanjeev , Toklu Faruk
Published: May 2022

Pea (Pisum sativumL.) is one of the most important and productive cool season pulse crops grown throughout the world. Biotic stresses are the crucial constraints in harnessing the potential productivity of pea and warrant dedicated research and developmental efforts to utilize omics resources and advanced breeding techniques to assist rapid and timely development of high-yielding multiple stress-tolerant–resistant varieties. Recently, the pea researcher’s community has made notable achievements in conventional and molecular breeding to accelerate its genetic gain. Several quantitative trait loci (QTLs) or markers associated with genes controlling resistance for fusarium wilt, fusarium root rot, powdery mildew, ascochyta blight, rust, common root rot, broomrape, pea enation, and pea seed borne mosaic virus are available for the marker-assisted breeding. The advanced genomic tools such as the availability of comprehensive genetic maps and linked reliable DNA markers hold great promise toward the introgression of resistance genes from different sources to speed up the genetic gain in pea. This review provides a brief account of the achievements made in the recent past regarding genetic and genomic resources’ development, inheritance of genes controlling various biotic stress responses and genes controlling pathogenesis in disease causing organisms, genes/QTLs mapping, and transcriptomic and proteomic advances. Moreover, the emerging new breeding approaches such as transgenics, genome editing, genomic selection, epigenetic breeding, and speed breeding hold great promise to transform pea breeding. Overall, the judicious amalgamation of conventional and modern omics-enabled breeding strategies will augment the genetic gain and could hasten the development of biotic stress-resistant cultivars to sustain pea production under changing climate. The present review encompasses at one platform the research accomplishment made so far in pea improvement with respect to major biotic stresses and the way forward to enhance pea productivity through advanced genomic tools and technologies.