bluuebunny/crossref_metadata_2025 huggingface dataset:
Romantic Relationship Dissolution, Microbiota, and Fibers
Authors: Chuang Jie-Yu
Published: April 2021

Microbiota inhabit nearly every part of our body with the gut microbiota representing the greatest density and absolute abundance. The gut-microbiota-brain axis facilitates bidirectional communication between gut microbiota and the brain. For instance, romantic relationship not only brings joy, it is also associated with increased gut microbiota diversity and health benefits whereas reduced microbiota diversity is related to obesity, cardiac disease, type 2 diabetes, and inflammatory disorders. Research has shown that dietary fibers may increase microbiota diversity and exert antidepressant effect. Among a plethora of life stressors, romantic relationship dissolution is a relatively common and painful experience that people encounter from time to time. Depressed mood, social isolation and poor intake are all associated with romantic relationship dissolution. In this article, it is hypothesized that romantic relationship dissolution is accompanied by decreased gut microbiota diversity which could be corrected with the ingestion of dietary fibers with an additional antidepressant benefit.
CXCR4 and CXCR7 Signaling Pathways: A Focus on the Cross-Talk Between Cancer Cells and Tumor Microenvironment
Authors: Santagata Sara , Ieranò Caterina , Trotta Anna Maria , Capiluongo Anna , Auletta Federica , Guardascione Giuseppe , Scala Stefania
Published: April 2021

The chemokine receptor 4 (CXCR4) and 7 (CXCR7) are G-protein-coupled receptors (GPCRs) activated through their shared ligand CXCL12 in multiple human cancers. They play a key role in the tumor/tumor microenvironment (TME) promoting tumor progression, targeting cell proliferation and migration, while orchestrating the recruitment of immune and stromal cells within the TME. CXCL12 excludes T cells from TME through a concentration gradient that inhibits immunoactive cells access and promotes tumor vascularization. Thus, dual CXCR4/CXCR7 inhibition will target different cancer components. CXCR4/CXCR7 antagonism should prevent the development of metastases by interfering with tumor cell growth, migration and chemotaxis and favoring the frequency of T cells in TME. Herein, we discuss the current understanding on the role of CXCL12/CXCR4/CXCR7 cross-talk in tumor progression and immune cells recruitment providing support for a combined CXCR4/CXCR7 targeting therapy. In addition, we consider emerging approaches that coordinately target both immune checkpoints and CXCL12/CXCR4/CXCR7 axis.
The Expression of Three Negative Co-Stimulatory B7 Family Molecules in Small Cell Lung Cancer and Their Effect on Prognosis
Authors: Qiu Meng-jun , Xia Qin , Chen Yao-bing , Fang Xie-fan , Li Qiu-ting , Zhu Li-sheng , Jiang Xin , Xiong Zhi-fan , Yang Sheng-li
Published: April 2021

Background

In recent years, immune checkpoint inhibitors have shown significant effects in a variety of solid tumors. However, due to the low incidence of small cell lung cancer (SCLC) and its unclear mechanism, immune checkpoints in SCLC have not been fully studied.

Methods

We evaluated the expression of PD-L1, B7-H3, and B7-H4 in 115 SCLC tissue specimens using immunohistochemistry. The clinical data of patients with SCLC were retrospectively reviewed to investigate three negative co-stimulatory B7 family molecules’ ability to affect the prognosis of SCLC.

Results

Among the SCLC patients with complete follow-up data (n = 107), sixty-nine (64.49%) expressed moderate to high B7-H3 levels, which correlated positively with tumor sizes (P < 0.001). Eighty (74.77%) patients expressed moderate to high B7-H4 levels, which correlated positively with metastases (P = 0.049). The positive expression of B7-H3 and B7-H4 correlated significantly with shortened overall survival (OS) (B7-H3, P = 0.006; B7-H4, P = 0.019). PD-L1 was positively expressed only in 13.08% of cancer tissues, and there was no significant correlation with prognosis. The Cox proportional hazards regression showed that B7-H3 was an independent prognostic indicator of OS (P = 0.028; HR = 2.125 [95% CI = 0.985-4.462]).

Conclusions

Our results suggest that B7-H3 has a negative predictive effect on SCLC. This outcome provides a theoretical basis for the subsequent research on immune checkpoint inhibitors targeting B7-H3.
Prediction Model of Tumor Regression Grade for Advanced Gastric Cancer After Preoperative Chemotherapy
Authors: Xu Wei , Ma Qianchen , Wang Lingquan , He Changyu , Lu Sheng , Ni Zhentian , Hua Zichen , Zhu Zhenglun , Yang Zhongyin , Zheng Yanan , Feng Runhua , Yan Chao , Li Chen , Yao Xuexin , Chen Mingmin , Liu Wentao , Yan Min , Zhu Zhenggang
Published: April 2021

Background

Preoperative chemotherapy (PCT) has been considered an important treatment for advanced gastric cancer (AGC). The tumor regression grade (TRG) system is an effective tool for the assessment of patient responses to PCT. Pathological complete response (TRG = 0) of the primary tumor is an excellent predictor of better prognosis. However, which patients could achieve pathological complete response (TRG = 0) after chemotherapy is still unknown. The study aimed to find predictors of TRG = 0 in AGC.

Methods

A total of 304 patients with advanced gastric cancer from July 2009 to November 2018 were enrolled retrospectively. All patients were randomly assigned (2:1) to training and internal validation groups. In addition, 124 AGC patients receiving PCT from December 2018 to June 2020 were included prospectively in the external validation cohort. A prediction model for TRG = 0 was established based on four predictors in the training group and was validated in the internal and external validation groups.

Results

Through univariate and multivariate analyses, we found that CA199, CA724, tumor differentiation and short axis of the largest regional lymph node (LNmax) were independent predictors of TRG = 0. Based on the four predictors, we established a prediction model for TRG = 0. The AUC values of the prediction model in the training, internal and external validation groups were 0.84, 0.73 and 0.82, respectively.

Conclusions

We found that CA199, CA724, tumor differentiation and LNmax were associated with pathological response in advanced gastric cancer. The prediction model could provide guidance for clinical work.
CHI3L2 Is a Novel Prognostic Biomarker and Correlated With Immune Infiltrates in Gliomas
Authors: Liu Liling , Yang Yuanzhong , Duan Hao , He Jiahua , Sun Lu , Hu Wanming , Zeng Jing
Published: April 2021

CHI3L2 (Chitinase-3-Like Protein 2) is a member of chitinase-like proteins (CLPs), which belong to the glycoside hydrolase 18 family. Its homologous gene, CHI3L1, has been extensively studied in various tumors and has been shown to be related to immune infiltration in breast cancer and glioblastoma. High CHI3L2 expression was reported to be associated with poor prognosis in breast cancer and renal cell carcinoma. However, the prognostic significance of CHI3L2 in glioma and its correlation between immune infiltration remains unclear. In this study, we examined 288 glioma samples by immunohistochemistry to find that CHI3L2 is expressed in tumor cells and macrophages in glioma tissues and highly expressed in glioblastoma and IDH wild-type gliomas. Relationships between CHI3L2 expression and clinical features (grade, age, Ki67 index, P53, PHH3 (mitotic figures), ATRX, TERTp, MGMTp, IDH, and 1p/19q co-deleted status) were evaluated. Kaplan-Meier survival was conducted to show high CHI3L2 expression in tumor cells (TC) and macrophage cells (MC) indicated poor prognosis in diffusely infiltrating glioma (DIG), lower-grade glioma (LGG), and IDH wild-type gliomas (IDH-wt). The overall survival time was higher in patients with dual-low CHI3L2 expression in TC and MC compared to those in patients with non-dual CHI3L2 expression and dual high expression in DIG and IDH wild-type gliomas. By univariate and multivariate analysis, we found that high CHI3L2 expression in tumor cells was an independent unfavorable prognostic factor in glioma patients. Moreover, we used two datasets (TCGA and CGGA) to verify the results of our study and explore the potential functional role of CHI3L2 by GO and KEGG analyses in gliomas. TIMER platform analysis indicated CHI3L2 expression was closely related to diverse marker genes of tumor immune infiltrating cells, including monocytes, TAMs, M1 macrophages, M2 macrophages, TGFβ1+ Treg and T cell exhaustion in GBM and LGG. Western Blot validated CHI3L2 is expressed in glioma cells and microglia cells. The results of flow cytometry showed that CHI3L2 induces the apoptosis of CD8+ T cells. In conclusion, these results demonstrate CHI3L2 is related to poor prognosis and immune infiltrates in gliomas, suggesting it may serve as a promising prognostic biomarker and represent a new target for glioma patients.
Autophagy Process in Trophoblast Cells Invasion and Differentiation: Similitude and Differences With Cancer Cells
Authors: Carvajal Lorena , Gutiérrez Jaime , Morselli Eugenia , Leiva Andrea
Published: April 2021

Early human placental development begins with blastocyst implantation, then the trophoblast differentiates and originates the cells required for a proper fetal nutrition and placental implantation. Among them, extravillous trophoblast corresponds to a non-proliferating trophoblast highly invasive that allows the vascular remodeling which is essential for appropriate placental perfusion and to maintain the adequate fetal growth. This process involves different placental cell types as well as molecules that allow cell growth, cellular adhesion, tissular remodeling, and immune tolerance. Remarkably, some of the cellular processes required for proper placentation are common between placental and cancer cells to finally support tumor growth. Indeed, as in placentation trophoblasts invade and migrate, cancer cells invade and migrate to promote tumor metastasis. However, while these processes respond to a controlled program in trophoblasts, in cancer cells this regulation is lost. Interestingly, it has been shown that autophagy, a process responsible for the degradation of damaged proteins and organelles to maintain cellular homeostasis, is required for invasion of trophoblast cells and for vascular remodeling during placentation. In cancer cells, autophagy has a dual role, as it has been shown both as tumor promoter and inhibitor, depending on the stage and tumor considered. In this review, we summarized the similarities and differences between trophoblast cell invasion and cancer cell metastasis specifically evaluating the role of autophagy in both processes.
Case Report: Dacomitinib May Not Benefit Patients Who Develop Rare Compound Mutations After Later-Line Osimertinib Treatment
Authors: Li Hong-Shuai , Yang Guang-Jian , Wang Yan
Published: April 2021

The acquired EGFR C797X mutation has been identified as the most notable resistance to osimertinib, and novel secondary mutations of EGFR L718 and L792 residues have also been demonstrated to confer osimertinib resistance, making the choice of medication after osimertinib treatment a quandary. Dacomitinib has been reported to have potential impact on patients acquiring rare compound mutations after osimertinib resistance; however, little evidence is available to date. In five lung adenocarcinoma patients resistant to later-line osimertinib, recurrent mutations at EGFR L792 and/or L718 were identified using targeted next-generation sequencing of tissue or cell-free DNA from plasma or pleural effusion. Dacomitinib was initiated after osimertinib resistance; however, all patients progressed within 2 months. Molecular structural simulation revealed that L792H + T790M and L718Q mutations could interfere with the binding of dacomitinib to EGFR and potentially cause primary drug resistance. Our case series study, to our knowledge, is the first to report the clinical efficacy of dacomitinib in patients harboring rare complex mutations after later-line osimertinib resistance.
Cancer in Africa: The Untold Story
Authors: Hamdi Yosr , Abdeljaoued-Tej Ines , Zatchi Afzal Ali , Abdelhak Sonia , Boubaker Samir , Brown Joel S. , Benkahla Alia
Published: April 2021

Background

Despite rising incidence and mortality rates in Africa, cancer has been given low priority in the research field and in healthcare services. Indeed, 57% of all new cancer cases around the world occur in low income countries exacerbated by lack of awareness, lack of preventive strategies, and increased life expectancies. Despite recent efforts devoted to cancer epidemiology, statistics on cancer rates in Africa are often dispersed across different registries. In this study our goal included identifying the most promising prevention and treatment approaches available in Africa. To do this, we collated and analyzed the incidence and fatality rates for the 10 most common and fatal cancers in 56 African countries grouped into 5 different regions (North, West, East, Central and South) over 16-years (2002–2018). We examined temporal and regional trends by investigating the most important risk factors associated to each cancer type. Data were analyzed by cancer type, African region, gender, measures of socioeconomic status and the availability of medical devices.

Results

We observed that Northern and Southern Africa were most similar in their cancer incidences and fatality rates compared to other African regions. The most prevalent cancers are breast, bladder and liver cancers in Northern Africa; prostate, lung and colorectal cancers in Southern Africa; and esophageal and cervical cancer in East Africa. In Southern Africa, fatality rates from prostate cancer and cervical cancer have increased. In addition, these three cancers are less fatal in Northern and Southern Africa compared to other regions, which correlates with the Human Development Index and the availability of medical devices. With the exception of thyroid cancer, all other cancers have higher incidences in males than females.

Conclusion

Our results show that the African continent suffers from a shortage of medical equipment, research resources and epidemiological expertise. While recognizing that risk factors are interconnected, we focused on risk factors more or less specific to each cancer type. This helps identify specific preventive and therapeutic options in Africa. We see a need for implementing more accurate preventive strategies to tackle this disease as many cases are likely preventable. Opportunities exist for vaccination programs for cervical and liver cancer, genetic testing and use of new targeted therapies for breast and prostate cancer, and positive changes in lifestyle for lung, colorectal and bladder cancers. Such recommendations should be tailored for the different African regions depending on their disease profiles and specific needs.
Large Cell Neuro-Endocrine Carcinoma of the Lung: Current Treatment Options and Potential Future Opportunities
Authors: Ferrara Miriam Grazia , Stefani Alessio , Simbolo Michele , Pilotto Sara , Martini Maurizio , Lococo Filippo , Vita Emanuele , Chiappetta Marco , Cancellieri Alessandra , D’Argento Ettore , Trisolini Rocco , Rindi Guido , Scarpa Aldo , Margaritora Stefano , Milella Michele , Tortora Giampaolo , Bria Emilio
Published: April 2021

Large-cell neuroendocrine carcinomas of the lung (LCNECs) are rare tumors representing 1–3% of all primary lung cancers. Patients with LCNEC are predominantly male, older, and heavy smokers. Histologically, these tumors are characterized by large cells with abundant cytoplasm, high mitotic rate, and neuroendocrine immunohistochemistry-detected markers (chromogranin-A, synaptophysin, and CD56). In 2015 the World Health Organization classified LCNEC as a distinct subtype of pulmonary large-cell carcinoma and, therefore, as a subtype of non-small cell lung carcinoma (NSCLC). Because of the small-sized tissue samples and the likeness to other neuroendocrine tumors, the histological diagnosis of LCNEC remains difficult. Clinically, the prognosis of metastatic LCNECs is poor, with high rates of recurrence after surgery alone and overall survival of approximately 35% at 5 years, even for patients with early stage disease that is dramatically shorter compared with other NSCLC subtypes. First-line treatment options have been largely discussed but with limited data based on phase II studies with small sample sizes, and there are no second-line well defined treatments. To date, no standard treatment regimen has been developed, and how to treat LCNEC is still on debate. In the immunotherapy and targeted therapy era, in which NSCLC treatment strategies have been radically reshaped, a few data are available regarding these opportunities in LCNEC. Due to lack of knowledge in this field, many efforts have been done for a deeper understanding of the biological and molecular characteristics of LCNEC. Next generation sequencing analyses have identified subtypes of LCNEC that may be relevant for prognosis and response to therapy, but further studies are needed to better define the clinical impact of these results. Moreover, scarce data exist about PD-L1 expression in LCNEC and its predictive value in this histotype with regard to immunotherapy efficacy. In the literature some cases are reported concerning LCNEC metastatic patients carrying driver mutations, especially EGFR alterations, showing targeted therapy efficacy in this setting of disease. Due to the rarity and the challenging understanding of LCNEC, in this review we aim to summarize the management options currently available for treatment of LCNEC.
Avoiding Full Lymphadenectomies in Intermediate- and High-Risk Endometrial Cancer by Sentinel Lymph Node Biopsy Implementation
Authors: Pineda Virginia García , Zapardiel Ignacio , Gracia Myriam , Siegrist Jaime , Diestro María Dolores , Alonso María , Hernández Alicia
Published: April 2021

Objective

To evaluate the role of sentinel lymph node biopsy (SLNB) to avoid staging lymphadenectomies by detecting nodal metastasis in intermediate- and high-risk endometrial cancer (EC).

Methods

A single institutional retrospective study was performed including all patients with intermediate- and high-risk EC who underwent surgical nodal staging between January 2012 and December 2019. Patients with disseminated disease detected on imaging techniques or at the time of surgery were excluded. Patients were evaluable if they underwent nodal staging with SLNB and pelvic (PLD) and paraaortic (PALD) lymph node dissection. We analyzed the accuracy of the sentinel lymph node technique. Only patients with at least one sentinel lymph node (SLN) detected were included in the sensitivity and negative predictive value (NPV) analyses. The tracers used were technetium 99m, blue dye, and indocyanine green.

Results

Eighty-eight patients presented intermediate- and high-risk EC (51 patients and 37 patients respectively) and underwent SLNB with consecutive PLD and PALD. The median (range) number of sentinel nodes retrieved was 2.9 (0–11). The global detection rate of SLN was 96.6% with a bilateral detection of 80.7% when considering all tracers used. However, when combination of indocyanine green and technetium was used the bilateral detection rate was 90.3%. Nodal metastases were detected in 17 (19.3%) cases, 8 (47%) of them corresponded to low volume metastasis (LVM), 7 (87.5%) of them diagnosed at ultrastaging pathologic exam. Finally, we obtained a sensitivity of 90%, a NPV of 97.5%, and a false negative rate (FNR) of 10% in the intermediate-risk EC compared to sensitivity of 85.7%, NPV of 96.6%, and FNR of 14.3% in the high-risk EC group. The only patient with isolated paraaortic nodal metastasis was found at the high-risk group, 1.1%.

Conclusions

According to our results, full lymphadenectomy could be avoided by performing SLNB in patients with intermediate-risk EC because the only false negative case detected was at the beginning of ICG learning curve. For high-risk EC patients we did not find enough evidence to support the systematic avoidance of staging full lymph node dissection. Nevertheless, SLNB should be performed in all cases of EC as it improves LVM diagnosis substantially.
Research Progress of Circular RNA in Gastrointestinal Tumors
Authors: Fang Na , Ding Guo-Wen , Ding Hao , Li Juan , Liu Chao , Lv Lu , Shi Yi-Jun
Published: April 2021

circular RNA (circRNA) is a closed ring structure formed by cyclic covalent bonds connecting the 5’-end and 3’-end of pre-mRNA. circRNA is widely distributed in eukaryotic cells. Recent studies have shown that circRNA is involved in the pathogenesis and development of multiple types of diseases, including tumors. circRNA is specifically expressed in tissues. And the stability of circRNA is higher than that of linear RNA, which can play biological roles through sponge adsorption of miRNA, interaction with RNA binding protein, regulation of gene transcription, the mRNA and protein translation brake, and translation of protein and peptides. These characteristics render circRNAs as biomarkers and therapeutic targets of tumors. Gastrointestinal tumors are common malignancies worldwide, which seriously threaten human health. In this review, we summarize the generation and biological characteristics of circRNA, molecular regulation mechanism and related effects of circRNA in gastrointestinal tumors.
COVID-19 Pandemic: Different Associative Relationships of City Lockdown With Preterm Births in Three Cities – An Ecological Study
Authors: Cheung Po-Yin , Alshaikh Belal , Yang Chuanzhong
Published: April 2021

In 2020, the global spread of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection (also known as COVID-19) has led to pandemic health issues with significant changes in individual and community practices. Preterm birth could be one of the risks in pregnant mothers who are infected by the SARS-CoV-2. Preterm births contribute upto 10% of all births and incur significant impact on the child health and cost to the health care system. However, the association of city lockdown during COVID-19 pandemic with the rate of preterm births is unclear. In a cohort study, we examined the association of city lockdown during the COVID-19 pandemic with the births at different gestations in three different cities. Compared with the pre-pandemic epoch, the associative relationships ranged from a decrease in all births, all births across all preterm gestations and to preterm births in moderately and late preterm gestations. We concluded that there were variable associative relationships of city lockdown during COVID-19 pandemic with preterm births. This could be related to the differences in health, societal and cultural factors, which will inspire further studies in this area.
A Review of the Toxicity and Phytochemistry of Medicinal Plant Species Used by Herbalists in Treating People Living With HIV/AIDS in Uganda
Authors: Anywar G. , Kakudidi E. , Byamukama R. , Mukonzo J. , Schubert A. , Oryem-Origa H. , Jassoy C.
Published: April 2021

Introduction: Despite concerns about toxicity, potentially harmful effects and herb-drug interactions, the use of herbal medicines remains widely practiced by people living with HIV/AIDS (PLHIV) in Uganda.

Objective: The objective of the paper was to comprehensively review the literature on the toxicity and chemical composition of commonly used medicinal plant species in treating PLHIV in Uganda.

Methods: We reviewed relevant articles and books published over the last sixty years on ethnobotany, antiviral/anti-HIV activity, toxicity, phytochemistry of Vachellia hockii, Albizia coriaria, Bridelia micrantha, Cryptolepis sanguinolenta, Erythrina abyssinica, Gardenia ternifolia, Gymnosporia senegalensis, Psorospermum febrifugium, Securidaca longipendunculata, Warburgia ugandensis and Zanthoxylum chalybeum and their synonyms. We searched PubMed, Web of Science, Scopus, Science Direct and Google Scholar.

Discussion: Most of the plant species reviewed apart from P. febrifugium, S. longipedunculata and C. sanguinolenta lacked detailed phytochemical analyses as well as the quantification and characterization of their constituents. Crude plant extracts were the most commonly used. However, purified/single component extracts from different plant parts were also used in some studies. The U87 human glioblastoma was the most commonly used cell line. Water, ethanol, methanol and DMSO were the commonest solvents used. In some instances, isolated purified compounds/extracts such as Cryptolepine and Psorospermin were used.

Conclusion: Cytotoxicity varied with cell type, solvent and extract type used making it difficult for direct comparison of the plant species. Five of the eleven plant species namely, A. coriaria, C. sanguinolenta, G. ternifolia, P. febrifugium and Z. chalybeum had no cytotoxicity studies in animal models. For the remaining six plant species, the crude aqueous and ethanol extracts were mainly used in acute oral toxicity studies in mice. Herbalists reported only A. coriaria and W. ugandensis to cause toxic side effects in humans. However, selective cytotoxic plant extracts can potentially be beneficial as anticancer or anti-tumour drugs.
Pharmacokinetics of Anthraquinones from Medicinal Plants
Authors: Wang Dongpeng , Wang Xian-He , Yu Xiongjie , Cao Fengjun , Cai Xiaojun , Chen Ping , Li Minglun , Feng Yibin , Li Hongliang , Wang Xuanbin
Published: April 2021

Anthraquinones are bioactive natural products, some of which are active components in medicinal medicines, especially Chinese medicines. These compounds exert actions including purgation, anti-inflammation, immunoregulation, antihyperlipidemia, and anticancer effects. This study aimed to review the pharmacokinetics (PKs) of anthraquinones, which are importantly associated with their pharmacological and toxicological effects. Anthraquinones are absorbed mainly in intestines. The absorption rates of free anthraquinones are faster than those of their conjugated glycosides because of the higher liposolubility. A fluctuation in blood concentration and two absorption peaks of anthraquinones may result from the hepato-intestinal circulation, reabsorption, and transformation. Anthraquinones are widely distributed throughout the body, mainly in blood-flow rich organs and tissues, such as blood, intestines, stomach, liver, lung, kidney, and fat. The metabolic pathways of anthraquinones are hydrolysis, glycuronidation, sulfation, methylation/demethylation, hydroxylation/dehydroxylation, oxidation/reduction (hydrogenation), acetylation and esterification by intestinal flora and liver metabolic enzymes, among which hydrolysis, glycuronidation and sulfation are dominant. Of note, anthraquinones can be transformed into each other. The main excretion routes for anthraquinones are the kidney, recta, and gallbladder. Conclusion: Some anthraquinones and their glycosides, such as aloe-emodin, chrysophanol, emodin, physcion, rhein and sennosides, have attracted the most PK research interest due to their more biological activities and/or detectability. Anthraquinones are mainly absorbed in the intestines and are mostly distributed in blood flow-rich tissues and organs. Transformation into another anthraquinone may increase the blood concentration of the latter, leading to an increased pharmacological and/or toxicological effect. Drug-drug interactions influencing PK may provide insights into drug compatibility theory to enhance or reduce pharmacological/toxicological effects in Chinese medicine formulae and deserve deep investigation.
Ramulus Mori (Sangzhi) Alkaloids (SZ-A) Ameliorate Glucose Metabolism Accompanied by the Modulation of Gut Microbiota and Ileal Inflammatory Damage in Type 2 Diabetic KKAy Mice
Authors: Liu Quan , Liu Shuainan , Cao Hui , Ji Wenming , Li Caina , Huan Yi , Lei Lei , Fu Yaxin , Gao Xuefeng , Liu Yuling , Shen Zhufang
Published: April 2021

The novel Traditional Chinese Medicine Ramulus Mori (Sangzhi) alkaloid tablets (SZ-A) are approved by The China National Medical Products Administration for the treatment of type 2 diabetes mellitus (T2DM). However, the extensive pharmacological characteristics and the underlying mechanism are unknown. This study investigated the mechanisms by which SZ-A ameliorates glucose metabolism in KKAy mice, an animal model of T2DM. Diabetic KKAy mice were treated intragastrically with SZ-A once daily for 8 weeks, after which glucose levels, lipid metabolism, gut microbiome, systemic inflammatory factors, luminal concentrations of short-chain fatty acids (fecal samples), and ileal proteomic changes were evaluated. The ileum tissues were collected, and the effects of SZ-A on pathological inflammatory damage were evaluated by hematoxylin and eosin staining, immunofluorescence, and immunohistochemistry. The mRNA and protein expression levels of various inflammatory markers, including monocyte chemoattractant protein-1 and phosphorylated nuclear factor kappa B p65, were detected in the ileum tissues. SZ-A improved glucose metabolism with enhanced insulin response and elevated glucagon-like peptide 1 (GLP-1) nearly 2.7-fold during the glucose tolerance test in diabetic KKAy mice. Gut microbiota analysis demonstrated that SZ-A administration elevated the abundance of Bacteroidaceae and Verrucomicrobia, reduced the levels of Rikenellaceae and Desulfovibrionaceae; and increased the concentrations of fecal acetic and propionic acids compared to the diabetic model group. Additionally, SZ-A markedly improved ileal inflammatory injury and pro-inflammatory macrophage infiltration and improved intestinal mucosal barrier function in diabetic KKAy mice. SZ-A also attenuated the levels of circulating endotoxin, pro-inflammatory cytokines, and chemokines in the mice sera. Collectively, SZ-A ameliorated the overall metabolic profile including glucose and lipid metabolism in KKAy mice, which may be associated with an improvement in GLP-1 and insulin secretion, at least in part by modulating the gut microbiome and relieving the degree of ileal and systemic inflammation.
Multifocal Analysis of Acute Pain After Third Molar Removal
Authors: Weckwerth Giovana Maria , Dionísio Thiago José , Costa Yuri Martins , Zupelari-Gonçalves Paulo , Oliveira Gabriela Moraes , Torres Elza Araújo , Bonjardim Leonardo Rigoldi , Faria Flavio Augusto Cardoso , Calvo Adriana Maria , Moore Troy , Absher Devin Michael , Santos Carlos Ferreira
Published: April 2021

Background: To analyze the pain modulation capacity profile in a Brazilian population, the relationship between opioid receptor (OPRM1) and Catechol-O-methyltransferase (COMT) 1polymorphisms and pain modulation capacity was determined through preoperative pain modulation tests and acute postoperative pain control evaluation, swelling, and trismus in 200 volunteers undergoing lower third molar removal.

Methods: Psychologic and clinical parameters were measured. Patient DNA was sequenced for single nucleotide polymorphisms in OPRM1 and COMT, and the salivary concentration of interleukin (IL)-2 (IL)-6, interferon (IFN)-γ and tumor necrosis factor (TNF)-α was evaluated. Primary outcomes were the influence of all predictors on the fluctuation of pain intensity using a visual analogue scale (VAS), and swelling and trismus on the 2nd and 7th postoperative days. Preoperative pain modulation capacity (CPM), pain catastrophizing scale (PCS), body mass index (BMI), and surgery duration and difficulty were evaluated.

Results: Salivary concentration of IFN-γ and IL-2 as well as the duration of surgery influenced the fluctuation of postoperative pain in the VAS, and in the sum of the differences in pain intensity test at 8, 48, and 96 h. BMI influenced swelling, while both BMI and COMT haplotype influenced trismus on the 2nd postoperative day.

Conclusion: Polymorphisms in COMT, salivary concentrations of IL-2 and IFN-γ, BMI, and duration of surgery were predictors for pain fluctuation, swelling, and trismus on the 2nd day after lower third molar extraction. This therapy was effective in controlling inflammatory symptomatology after lower third molar extraction and ibuprofen was well tolerated by patients.

Clinical Trial Registration:www.ClinicalTrials.gov, identifier NCT03169127.
Random Fields in Physics, Biology and Data Science
Authors: Hernández-Lemus Enrique
Published: April 2021

A random field is the representation of the joint probability distribution for a set of random variables. Markov fields, in particular, have a long standing tradition as the theoretical foundation of many applications in statistical physics and probability. For strictly positive probability densities, a Markov random field is also a Gibbs field, i.e., a random field supplemented with a measure that implies the existence of a regular conditional distribution. Markov random fields have been used in statistical physics, dating back as far as the Ehrenfests. However, their measure theoretical foundations were developed much later by Dobruschin, Lanford and Ruelle, as well as by Hammersley and Clifford. Aside from its enormous theoretical relevance, due to its generality and simplicity, Markov random fields have been used in a broad range of applications in equilibrium and non-equilibrium statistical physics, in non-linear dynamics and ergodic theory. Also in computational molecular biology, ecology, structural biology, computer vision, control theory, complex networks and data science, to name but a few. Often these applications have been inspired by the original statistical physics approaches. Here, we will briefly present a modern introduction to the theory of random fields, later we will explore and discuss some of the recent applications of random fields in physics, biology and data science. Our aim is to highlight the relevance of this powerful theoretical aspect of statistical physics and its relation to the broad success of its many interdisciplinary applications.
Experimental Evidence of A2A–D2 Receptor–Receptor Interactions in the Rat and Human Carotid Body
Authors: Stocco Elena , Sfriso Maria Martina , Borile Giulia , Contran Martina , Barbon Silvia , Romanato Filippo , Macchi Veronica , Guidolin Diego , De Caro Raffaele , Porzionato Andrea
Published: April 2021

Adenosine A2A receptors (A2AR) and dopamine D2 receptors (D2R) are known to be involved in the physiological response to hypoxia, and their expression/activity may be modulated by chronic sustained or intermittent hypoxia. To date, A2AR and D2R can form transient physical receptor–receptor interactions (RRIs) giving rise to a dynamic equilibrium able to influence ligand binding and signaling, as demonstrated in different native tissues and transfected mammalian cell systems. Given the presence of A2AR and D2R in type I cells, type II cells, and afferent nerve terminals of the carotid body (CB), the aim of this work was to demonstrate here, for the first time, the existence of A2AR–D2R heterodimers by in situ proximity ligation assay (PLA). Our data by PLA analysis and tyrosine hydroxylase/S100 colocalization indicated the formation of A2AR–D2R heterodimers in type I and II cells of the CB; the presence of A2AR–D2R heterodimers also in afferent terminals is also suggested by PLA signal distribution. RRIs could play a role in CB dynamic modifications and plasticity in response to development/aging and environmental stimuli, including chronic intermittent/sustained hypoxia. Exploring other RRIs will allow for a broad comprehension of the regulative mechanisms these interactions preside over, with also possible clinical implications.
Effects of Non-directional Mechanical Trauma on Gastrointestinal Tract Injury in Rats
Authors: Liu Lihong , Wen Lianpu , Gao Chuanzhou , Piao Hua , Zhao Hui , Yu Deqin , Zhu Liang , Li Shuzhuang
Published: April 2021

Mechanical trauma can (MT) cause secondary injury, such as cardiomyocyte apoptosis and cardiac dysfunction has been reported. However, the effects of mechanical trauma on gastrointestinal tract is unclear. This study aims to observe the main location and time of gastrointestinal tract injury caused by non-directional trauma and explain the reason of the increase of LPS in blood caused by mechanical injury. Morphological changes in the stomach, ileum and cecum at different time points after MT were observed in this experiment. The results reveal that the injury to the cecal mucosa in the rats was more obvious than that in the ileum and the stomach. The cecal epithelial cell junction was significantly widened at 20 min after MT, and the plasma LPS and D-lactic acid concentrations increased significantly at the same time point. In addition, some bacterial structures in the widened intercellular space and near the capillary wall of the cecal mucosa were detected at 12 h after MT. This finding suggests that the main reason for the increase in LPS in plasma after MT is cecal mucosal injury. This study is important for the early intervention of the gastrointestinal tract to prevent secondary injury after MT.
The Use of Defatted Tenebrio molitor Larvae Meal as a Main Protein Source Is Supported in European Sea Bass (Dicentrarchus labrax) by Data on Growth Performance, Lipid Metabolism, and Flesh Quality
Authors: Basto Ana , Calduch-Giner Josep , Oliveira Beatriz , Petit Lisa , Sá Tiago , Maia Margarida R. G. , Fonseca Susana C. , Matos Elisabete , Pérez-Sánchez Jaume , Valente Luisa M. P.
Published: April 2021

Objective

This study aims to determine the maximal inclusion level of defatted (d-) Tenebrio molitor larvae meal (TM) able to replace dietary fishmeal (FM) without compromising growth performance, general metabolism, and flesh quality traits in European sea bass, and to evaluate the major underlying physiological mechanisms.

Materials and Methods

Fish (55 ± 2 g) were fed with diets containing increasing levels of dTM: 0, 40, 80 and 100% (CTRL, TM40, TM80, and TM100, respectively) to replace FM. After 10 weeks of feeding, the growth performance, nutrient and energy balance, intestinal integrity, plasma metabolites and the expression of genes related to growth and nutrient metabolism, in liver and muscle were determined. The fatty acids (FA) profile, textural properties and color were also evaluated in muscle.

Results

Protein and lipids digestibility remained unaltered up to 80% dTM inclusion. Growth performance parameters were similar among dietary treatments. The dTM inclusion increased the hepatosomatic index in fish fed TM100. Muscle eicosapentaenoic acid, docosahexaenoic acid and n-3 long-chain polyunsaturated FA levels were maintained up to 80% dTM inclusion, but total cholesterol and non-esterified FA increased with dietary dTM inclusion. In liver, the expression of elongation of very long-chain FA protein 6 (elovl6) and FA desaturase 2 (fads2) did not change in fish fed TM40 and TM80, but elovl6 decreased whilst fads2 increased in fish fed TM100 when compared to those fed CTRL. The expression of cholesterol 7 alpha-monooxygenase (cyp7a1) decreased with dietary dTM inclusion. In muscle, the expression of myoblast determination protein-2 (myod2) decreased in fish fed TM80 and TM100.

Conclusion

It is feasible to substitute dietary FM by dTM up to 80% in European sea bass without detrimental effects on nutrient digestibility, growth performance and associated genetic pathways, whilst assuring fillet nutritional value for human consumption.
Developing Climate-Resilient, Direct-Seeded, Adapted Multiple-Stress-Tolerant Rice Applying Genomics-Assisted Breeding
Authors: Sandhu Nitika , Yadav Shailesh , Catolos Margaret , Cruz Ma Teresa Sta , Kumar Arvind
Published: April 2021

There is an urgent need to breed dry direct-seeded adapted rice varieties in order to address the emerging scenario of water–labor shortage. The aim of this study was to develop high-yielding, direct-seeded adapted varieties utilizing biparental to multiparental crosses involving as many as six different parents in conventional breeding programs and 12 parents in genomics-assisted breeding programs. The rigorous single plant selections were followed from the F2 generation onwards utilizing phenotypic selection and quantitative trait locus (QTL)/gene-based/linked markers for tracking the presence of desirable alleles of targeted QTL/genes. In conventional breeding, multiparent lines had significantly higher yields (2,072–6,569 kg ha−1) than the biparental lines (1,493–6,326 kg ha−1). GAB lines derived from multiparent crosses had significantly higher (3,293–6,719 kg ha−1) yields than the multiparent lines from conventional breeding (2,072–6,569 kg ha−1). Eleven promising lines from genomics-assisted breeding carrying 7–11 QTL/genes and eight lines from conventional breeding with grain-yield improvement from 727 to 1,705 kg ha−1 and 68 to 902 kg ha−1, respectively, over the best check were selected. The developed lines may be released as varieties/parental lines to develop better rice varieties for direct-seeded situations or as novel breeding material to study genetic interactions.
Trichoderma asperellum Inoculation as a Tool for Attenuating Drought Stress in Sugarcane
Authors: Scudeletti Daniele , Crusciol Carlos Alexandre Costa , Bossolani João William , Moretti Luiz Gustavo , Momesso Letusa , Servaz Tubaña Brenda , de Castro Sérgio Gustavo Quassi , De Oliveira Elisa Fidêncio , Hungria Mariangela
Published: April 2021

Drought stress is an important concern worldwide which reduces crop yield and quality. To alleviate this problem, Trichoderma asperellum has been used as a plant growth-promoting fungus capable of inducing plant tolerance to biotic and abiotic stresses. Here, we examined the effect of T. asperellum inoculation on sugarcane plant above and belowground development under drought stress and investigated the role of this fungus on inducing tolerance to drought at physiological and biochemical levels. The experiment was performed in pots under greenhouse conditions, with four treatments and four replicates. The treatments consisted of sugarcane plants inoculated or not with T. asperellum and grown under drought stress and adequate water availability. Drought-stressed sugarcane plants inoculated with T. asperellum changed the crop nutrition and chlorophyll and carotenoid concentrations, resulting in increased photosynthesis rate, stomatal conductance, and water use efficiency compared to the non-inoculated plants. In addition, the antioxidant metabolism also changed, increasing the superoxide dismutase and peroxidase enzyme activities, as well as the proline concentration and sugar portioning. These cascade effects enhanced the root and stalk development, demonstrating that T. asperellum inoculation is an important tool in alleviating the negative effects of drought stress in sugarcane. Future studies should be performed to elucidate if T. asperellum should be reapplied to the sugarcane ratoons.
Genetic and Management Effects on Barley Yield and Phenology in the Mediterranean Basin
Authors: Cammarano Davide , Ronga Domenico , Francia Enrico , Akar Taner , Al-Yassin Adnan , Benbelkacem Abdelkader , Grando Stefania , Romagosa Ignacio , Stanca Antonio Michele , Pecchioni Nicola
Published: April 2021

Heading time in barley is considered a key developmental stage controlling adaptation to the environment and it affects grain yield; with the combination of agronomy (planting dates) and genetics being some of the determinants of adaptation to environmental conditions in order to escape late frost, heat, and terminal drought stresses. The objectives of this study are (i) to apply a gene-based characterization of 118 barley doubled haploid recombinants for vernalization, photoperiod, and earliness per se; (ii) use such information to quantify the optimal combination of genotype/sowing date that escapes extreme weather events; and (iii) how water and nitrogen management impact on grain yield. The doubled haploid barley genotypes with different allelic combinations for vernalization, photoperiod, and earliness per se were grown in eight locations across the Mediterranean basin. This information was linked with the crop growth model parameters. The photoperiod and earliness per se alleles modify the length of the phenological cycle, and this is more evident in combination with the recessive allele of the vernalization gene VRN-H2. In hot environments such as Algeria, Syria, and Jordan, early sowing dates (October 30 and December15) would be chosen to minimize the risk of exposing barley to heat stress. To maintain higher yields in the Mediterranean basin, barley breeding activities should focus on allelic combinations that have recessive VRN-H2 and EPS2 genes, since the risk of cold stress is much lower than the one represented by heat stress.
Phrasal Learning Is a Horse Apiece: No Recognition Memory Advantages for Idioms in L1 and L2 Adult Learners
Authors: Beck Sara D. , Weber Andrea
Published: April 2021

Native (L1) and to some extent non-native (L2) speakers have shown processing advantages for idioms compared to novel literal phrases, and there is limited evidence that this advantage also extends to memory in L1 children. This study investigated whether these advantages generalize to recognition memory in adults. It employed a learning paradigm to test whether there is a recognition memory advantage for idioms compared to literal phrases in adult L1 and L2 learners considering both form and meaning recognition. Additionally, we asked whether the presence of unfamiliar vocabulary interferes with phrasal learning by looking at recall of such unfamiliar words. When encountering new idioms, L2 learners often must cope with both figurative meaning and unfamiliar vocabulary. While single word meaning need not interfere with idiomatic meaning, it is a building block for the meaning of literal phrases. In Experiment 1, L2 learners showed equal recall for the form and meaning of literal and idiomatic phrases in which either all words were highly familiar, or one word was unfamiliar. However, unfamiliar words decreased overall recognition and were also remembered significantly better in literal compared to idiomatic phrases. In Experiment 2, L1 speakers also showed no recall differences between phrase types, but they displayed a trending increase in recognition in the presence of unfamiliar words. We conclude that there is no inherent recognition memory advantage for idioms based on figurativeness alone, and word- and phrasal meaning interact differently in learner groups.
Arts in Education: A Systematic Review of Competency Outcomes in Quasi-Experimental and Experimental Studies
Authors: Schneider Verena , Rohmann Anette
Published: April 2021

Arts education in schools frequently experiences the pressure of being validated by demonstrating quantitative impact on academic outcomes. The quantitative evidence to date has been characterized by the application of largely correlational designs and frequently applies a narrow focus on instrumental outcomes such as academically relevant competencies. The present review aims to summarize quantitative evidence from quasi-experimental and experimental studies with pre-test post-test designs on the effects of school-based arts education on a broader range of competency outcomes, including intra- and interindividual competencies. A systematic literature search was conducted to identify relevant evaluation studies. Twenty-four articles reporting on 26 evaluation studies were eligible for inclusion, and their results were reviewed in terms of art domains and outcome categories. Whilst there is some evidence of beneficial effects on some competencies, for example of music education on arithmetic abilities, speech segmentation and processing speed, the evidence across arts domains and for different outcomes is limited due to small sample sizes, small number of studies, and a large range of effect sizes. The review highlights that sufficiently powered (quasi-)experimental studies with pre-test post-test designs evaluating arts education are sparse and that the “gold standard” of experimental research comes at the expense of a number of other study characteristics such as sample size, intervention and follow-up length. By summarizing the limitations of the current (quasi-)experimental research, the application of experimental designs is critically assessed and a combination with qualitative methods in mixed-method designs and choice of relevant outcomes discussed.