bluuebunny/crossref_metadata_2025 huggingface dataset:
Post-treatment serum triglyceride: An effective biomarker for body fat mass and overall survival in esophageal squamous cell cancer patients treated with chemoradiotherapy
Authors: Lyu Jiahua , Yang Ningjing , Guan Wang , Xiao Ling , Nie Xinyu , Liang Long , Bai Hansong , Li Churong , Kuang Hao , Wang Xiao , Li Tao
Published: December 2022

Objectives

Although lipids have been assessed for their possible roles in cancer survival prediction, studies on the association between serum triglyceride (TG) levels and the prognosis of esophageal squamous cell carcinoma (ESCC) patients are limited. This study aimed to evaluate whether serum TG is associated with outcomes in patients with ESCC and investigate any interaction between serum TG and clinical parameters, especially body fat mass.

Materials and methods

We conducted a prospective case study on patients diagnosed with ESCC between March 2012 and November 2018. We measured patients’ serum TG levels before and after treatment. The association between serum TG and overall survival (OS) was evaluated using hazard ratios. We sought to determine a threshold point using optimal stratification. Survival analysis was performed using Kaplan–Meier curves and a Cox proportional hazards model.

Results

Of the 257 participants diagnosed with ESCC, 200 (77.8%) were men. Median follow-up time was 22.4 months (range 3.3–92.4 months). Using univariate Cox proportional hazard analysis and subsequent multivariate analysis, post-TG levels, Karnofsky performance scores, T stages, and chemotherapy cycles were shown to be independent prognostic factors for OS (p < 0.05). The post-TG cut-off point to best classify patients with respect to time to mortality was 1.47 mmol/L. A post-TG level of ≥ 1.47 mmol/L could independently predict a better OS (hazard ratio: 0.55, 95% confidence interval: 0.37–0.79). The associations were consistent across the subtypes of clinical parameters. Furthermore, the post-body mass index, post-subcutaneous adipose tissue area, post-visceral adipose tissue area, post-total adiposity tissue area, and post-total adipose density exhibited a strong positive association with post-TG levels.

Conclusion

Post-TG levels were found to be a significant positive prognostic biomarker for body fat mass and OS in ESCC patients.
Integrated bioinformatics and in silico approaches reveal the biological targets and molecular mechanisms of 1,25-dihydroxyvitamin D against COVID-19 and diabetes mellitus
Authors: Zeng Fanqiang , Xu Yongli , Tang Chaoling , Yan Zhigang , Wei Chaohe
Published: December 2022

Coronavirus disease 2019 (COVID-19) and diabetes mellitus (DM) are two major diseases threatening human health. The susceptibility of DM patients to COVID-19 and their worse outcomes have forced us to explore efficient routes to combat COVID-19/DM. As the most active form of Vitamin D, 1,25-dihydroxyvitamin D (1,25(OH)2D) has been shown a beneficial effect in the treatment of COVID-19/DM. However, the anti-COVID-19/DM mechanisms of 1,25(OH)2D remain unclear. In this study, an approach combining network pharmacology and molecular docking was performed to reveal the potential hub target genes and underlying mechanisms of 1,25(OH)2D in the treatment of COVID-19/DM. The hub targets and interaction pathways related to 1,25(OH)2D were identified by integrating the key 1,25(OH)2D-target-signaling pathway-COVID-19/DM networks. Fifteen hub targets of 1,25(OH)2D against COVID-19DM were determined, including EGFR, PIK3R1, PIK3CA, STAT3, MAPK1, ESR1, HSP90AA1, LCK, MTOR, IGF1, AR, NFKB1, PIK3CB, PTPN1, and MAPK14. An enrichment analysis of the hub targets further revealed that the effect of 1,25(OH)2D against COVID-19/DM involved multiple biological processes, cellular components, molecular functions and biological signaling pathways. Molecular docking disclosed that 1,25(OH)2D docked nicely with the hub target proteins, including EGFR, PIK3R1, and PIK3CA. These findings suggested that the potential mechanisms of 1,25(OH)2D against COVID-19/DM may be related to multiple biological targets and biological signaling pathways.
Dietary supplementation with Mexican foods, Opuntia ficus indica, Theobroma cacao, and Acheta domesticus: Improving obesogenic and microbiota features in obese mice
Authors: Rosas-Campos Rebeca , Meza-Rios Alejandra , Rodriguez-Sanabria J. Samael , Rosa-Bibiano Ricardo De la , Corona-Cervantes Karina , García-Mena Jaime , Santos Arturo , Sandoval-Rodriguez Ana , Armendariz-Borunda Juan
Published: December 2022

Introduction

An obesogenic diet, a diet high in saturated fats and sugars, is a risk factor for the development of multiple obesity-related diseases. In this study, our aim was to evaluate the effect of supplementation with a mixture of Mexican functional foods (MexMix), Opuntia ficus indica (nopal), Theobroma cacao, and Acheta domesticus (edible crickets), compared with a high-fat and fructose/sucrose diet on an obesogenic mice model.

Methods

For this study, 18 male C57BL/6J mice were used, which were divided into three groups: (1) control group: normal diet (ND), (2) HF/FS group: high-fat diet along with 4.2% fructose/sucrose and water (ad libitum access), and (3) therapeutic group (MexMix): HF/FS diet up to week 8, followed by HF/FS diet supplemented with 10% nopal, 10% cocoa, and 10% cricket for 8 weeks.

Results

MexMix mice showed significantly reduced body weight, liver weight, visceral fat, and epididymal fat compared with HF/FS mice. Levels of triglycerides, cholesterol, LDL cholesterol, insulin, glucose, GIP, leptin, PAI-1, and resistin were also significantly reduced. For identifying the gut microbiota in the model, 16S rRNA gene sequencing analysis was performed, and the results showed that MexMix supplementation increased the abundance of Lachnospira, Eubacterium coprostanoligenes, and Blautia, bacteria involved in multiple beneficial metabolic effects. It is noteworthy that the mice supplemented with MexMix showed improvements in cognitive parameters, as evaluated by the novel object recognition test.

Conclusion

Hence, supplementation with MexMix food might represent a potential strategy for the treatment of obesity and other diseases associated with excessive intake of fats and sugars.
Complex molecular profile of DNA repair genes in epithelial ovarian carcinoma patients with different sensitivity to platinum-based therapy
Authors: Seborova Karolina , Hlavac Viktor , Holy Petr , Bjørklund Sunniva S. , Fleischer Thomas , Rob Lukas , Hruda Martin , Bouda Jiri , Mrhalova Marcela , Allah Mohammad Moufaq Khatar Al Obeed , Vodicka Pavel , Fiala Ondrej , Soucek Pavel , Kristensen Vessela N. , Vodickova Ludmila , Vaclavikova Radka
Published: December 2022

Epithelial ovarian carcinoma (EOC) is known for high mortality due to diagnosis at advanced stages and frequent therapy resistance. Previous findings suggested that the DNA repair system is involved in the therapeutic response of cancer patients and DNA repair genes are promising targets for novel therapies. This study aimed to address complex inter-relations among gene expression levels, methylation profiles, and somatic mutations in DNA repair genes and EOC prognosis and therapy resistance status. We found significant associations of DUT expression with the presence of peritoneal metastases in EOC patients. The high-grade serous EOC subtype was enriched with TP53 mutations compared to other subtypes. Furthermore, somatic mutations in XPC and PRKDC were significantly associated with worse overall survival of EOC patients, and higher FAAP20 expression in platinum-resistant than platinum-sensitive patients was observed. We found higher methylation of RAD50 in platinum-resistant than in platinum-sensitive patients. Somatic mutations in BRCA1 and RAD9A were significantly associated with higher RBBP8 methylation in platinum-sensitive compared to platinum-resistant EOC patients. In conclusion, we discovered associations of several candidate genes from the DNA repair pathway with the prognosis and platinum resistance status of EOC patients, which deserve further validation as potential predictive biomarkers.
Long-term follow up of patients with hematological malignancies treated with total body irradiation using intensity modulated radiation therapy
Authors: Ladbury Colton , Hao Claire , Yang Dongyun , Hui Susanta , Han Chunhui , Liu An , Salhotra Amandeep , Nakamura Ryotaro , Rosenthal Joseph , Stein Anthony , Wong Jeffrey , Dandapani Savita
Published: December 2022

Background

With the advent of modern radiation treatment technologies such as intensity modulated radiation therapy (IMRT), there has been increasing interest in its use for total body irradiation (TBI) conditioning regimens for hematopoietic cell transplantation (HCT) to achieve lower doses to critical organs such as the lungs and kidneys. Although this has been reported on in early studies, long-term safety and efficacy data is limited.

Methods

We performed a single institution matched-pair retrospective analysis of patients treated with IMRT TBI and standard TBI between 2010 and 2020 to provide data on long-term outcomes. Patients with hematologic malignancies, who could not tolerate standing for traditional TBI or who received prior radiation received IMRT TBI. Patients were matched based on age, diagnosis, disease status, and year of transplant, and were matched 2:1 to the standard TBI and IMRT TBI cohorts. Patient and treatment characteristics, toxicity, graft-versus-host disease (GVHD), dosimetry, and outcomes were evaluated for each cohort.

Results

A total of 13 patients met inclusion criteria for the IMRT cohort, leading to 26 patients in the standard TBI cohort. There was no significant difference in relevant clinical factors between the cohorts. Reasons for using IMRT over conventional TBI included being unable to stand (n=5), prior radiation (n=5), and pediatric patient requiring anesthesia (n=3). Among living patients, median follow-up for all patients was 5.1 years in the IMRT TBI cohort and 5.5 years in the standard TBI cohort. The 5-yr estimate of OS was 68% in the IMRT TBI cohort and 60% in the standard TBI cohort (p=0.706). The 5-yr estimate of RFS was 54% in the IMRT TBI cohort and 60% in the standard TBI cohort (p=0.529). There was no clinically significant pneumonitis, nephritis, hypothyroidism, or cataracts reported in the IMRT TBI cohort. 41.7% of patients in the IMRT TBI cohort and 79.2% of patients in the standard TBI cohort experienced Grade II-IV acute GVHD (p=0.023).

Conclusions

IMRT TBI appears to lead to favorable long-term outcome and dosimetry, and therefore potentially improved long-term toxicity profile compared to conventional TBI. IMRT TBI warrants further investigation as part of larger prospective trials.
NK cells reduce anergic T cell development in early-stage tumors by promoting myeloid cell maturation
Authors: Lindsay Robin S. , Melssen Marit M. , Stasiak Katarzyna , Annis Jessica L. , Woods Amber N. , Rodriguez Anthony B. , Brown Michael G. , Engelhard Victor H.
Published: December 2022

Introduction

Studies of NK cells in tumors have primarily focused on their direct actions towards tumor cells. We evaluated the impact of NK cells on expression of homing receptor ligands on tumor vasculature, intratumoral T cell number and function, and T cell activation in tumor draining lymph node.

Methods

Using an implantable mouse model of melanoma, T cell responses and homing receptor ligand expression on the vasculature were evaluated with and without NK cells present during the early stages of the tumor response by flow cytometry.

Results

NK cells in early-stage tumors are one source of IFNγ that augments homing receptor ligand expression. More significantly, NK cell depletion resulted in increased numbers of intratumoral T cells with an anergic phenotype. Anergic T cell development in tumor draining lymph node was associated with increased T-cell receptor signaling but decreased proliferation and effector cell activity, and an incomplete maturation phenotype of antigen presenting cells. These effects of NK depletion were similar to those of blocking CD40L stimulation.

Discussion

We conclude that an important function of NK cells is to drive proper APC maturationviaCD40L during responses to early-stage tumors, reducing development of anergic T cells. The reduced development of anergic T cells resulting in improved tumor control and T cell responses when NK cells were present.
The role of 18F-FDG PET/CT in patients with synchronous multiple primary malignant neoplasms occurring at the same time
Authors: Luo Zhe Huang , Qi Wan Ling , Jin Ai Fang , Liao Feng Xiang , Liu Qian , Zeng Qing Yun
Published: December 2022

Background

Synchronous multiple primary malignant neoplasms occurring at the same time (SMPMNS) are not currently uncommon in clinical oncological practice; however, the diagnostic performance of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) for SMPMNS needs further elucidation.

Purpose

This study aimed to evaluate the application of 18F-FDG PET/CT in patients with SMPMNS.

Materials and methods

The clinical and imaging data of 37 patients with SMPMNS who had undergone 18F-FDG PET/CT from October 2010 to December 2020 were retrospectively analyzed. The kappa consistency test was applied to evaluate the consistency of the diagnostic performance between PET/CT and conventional imaging (CI). The sensitivity, specificity, and accuracy of PET/CT and CI in the detection of metastatic lesions were compared.

Results

This retrospective diagnostic study included 74 lesions identified in 37 patients with SMPMNS, with 94.6% of patients having double primary tumors. Of the incidences of SMPMNS, 18.9% occurred in the same organ system, with respiratory tumors being the most common type of neoplasm (43.2%) and the lung being the most common primary site (40.5%). The overall survival of SMPMNS patients without metastases was longer than that of those with metastases (χ2 = 12.627, p = 0.000). The maximum standardized uptake value (SUVmax), the SUVmax ratio (larger SUVmax/smaller SUVmax), and the difference index of SUVmax (DISUVmax) [(larger SUVmax − smaller SUVmax)/larger SUVmax] of the primary lesions ranged from 0.9 to 41.7 (average = 12.3 ± 7.9), from 0.3 to 26.7 (average = 4.4 ± 6.9), and from 0.0% to 96.3% (average = 50.3% ± 29.3%), respectively. With regard to diagnostic accuracy, PET/CT and CI showed poor consistency (κ = 0.096, p = 0.173). For the diagnosis of primary lesions (diagnosed and misdiagnosed), PET/CT and CI also showed poor consistency (κ = 0.277, p = 0.000), but the diagnostic performance of PET/CT was better than that of CI. In the diagnosis of metastases, the patient-based sensitivity, specificity, and accuracy of PET/CT were 100.0%, 81.8%, and 89.2%, respectively, while those of CI were 73.3%, 100.0%, 89.2%, respectively. The sensitivity and specificity values were significantly different, with PET/CT having higher sensitivity (p = 0.02) and CI showing higher specificity (p = 0.02).

Conclusions

18F-FDG PET/CT improves the diagnostic performance for SMPMNS and is a good imaging modality for patients with SMPMNS.
Application of artificial intelligence in the diagnosis of subepithelial lesions using endoscopic ultrasonography: a systematic review and meta-analysis
Authors: Liu Xin-Yuan , Song Wen , Mao Tao , Zhang Qi , Zhang Cuiping , Li Xiao-Yu
Published: December 2022

Endoscopic ultrasonography (EUS) is the most common method for diagnosing gastrointestinal subepithelial lesions (SELs); however, it usually requires histopathological confirmation using invasive methods. Artificial intelligence (AI) algorithms have made significant progress in medical imaging diagnosis. The purpose of our research was to explore the application of AI in the diagnosis of SELs using EUS and to evaluate the diagnostic performance of AI-assisted EUS. Three databases, PubMed, EMBASE, and the Cochrane Library, were comprehensively searched for relevant literature. RevMan 5.4.1 and Stata 17.0, were used to calculate and analyze the combined sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and summary receiver-operating characteristic curve (SROC). Eight studies were selected from 380 potentially relevant studies for the meta-analysis of AI-aided EUS diagnosis of SELs. The combined sensitivity, specificity, and DOR of AI-aided EUS were 0.92 (95% CI, 0.85-0.96), 0.80 (95% CI, 0.70-0.87), and 46.27 (95% CI, 19.36-110.59), respectively). The area under the curve (AUC) was 0.92 (95% CI, 0.90-0.94). The AI model in differentiating GIST from leiomyoma had a pooled AUC of 0.95, sensitivity of 0.93, specificity of 0.88, PLR of 8.04, and NLR of 0.08. The combined sensitivity, specificity, and AUC of the AI-aided EUS diagnosis in the convolutional neural network (CNN) model were 0.93, 0.81, and 0.94, respectively. AI-aided EUS diagnosis using conventional brightness mode (B-mode) EUS images had a combined sensitivity of 0.92, specificity of 0.79, and AUC of 0.92. AI-aided EUS diagnosis based on patients had a combined sensitivity, specificity, and AUC of 0.95, 0.83, and 0.96, respectively. Additionally, AI-aided EUS was superior to EUS by experts in terms of sensitivity (0.93 vs. 0.71), specificity (0.81 vs. 0.69), and AUC (0.94 vs. 0.75). In conclusion, AI-assisted EUS is a promising and reliable method for distinguishing SELs, with excellent diagnostic performance. More multicenter cohort and prospective studies are expected to be conducted to further develop AI-assisted real-time diagnostic systems and validate the superiority of AI systems.

Systematic Review Registration:

PROSPERO (https://www.crd.york.ac.uk/PROSPERO/), identifier CRD42022303990.
Durable complete response for oligometastatic renal cell carcinoma with immune checkpoint inhibition and cytoreductive nephrectomy in a Jehovah’s witness: A case report
Authors: Zhuang Tony Zibo , Harik Lara , Force Seth , Hadadi Agreen , Bilen Mehmet Asim , Brown Jacqueline T. , Carthon Bradley C. , Goldman Jamie , Kucuk Omer , Master Viraj A. , Nazha Bassel
Published: December 2022

The role of cytoreductive nephrectomy in patients with metastatic renal cell carcinoma is a subject of debate. We report a durable complete response in a 62-year-old man Jehovah’s Witness with metastatic clear cell renal cell carcinoma who received two cycles of nivolumab/ipilimumab followed by radical nephrectomy and metastasectomy of known pulmonary disease site, both without a clinical need for perioperative blood transfusions. The patient continues to be without evidence of disease and without additional need for systemic therapy over a year after his radical nephrectomy. The case highlights that cytoreductive nephrectomy continues to play a role in the era of immune checkpoint inhibitors.
Multi-modality radiomics nomogram based on DCE-MRI and ultrasound images for benign and malignant breast lesion classification
Authors: Liu Xinmiao , Zhang Ji , Zhou Jiejie , He Yun , Xu Yunyu , Zhang Zhenhua , Cao Guoquan , Miao Haiwei , Chen Zhongwei , Zhao Youfan , Jin Xiance , Wang Meihao
Published: December 2022

Objective

To develop a multi-modality radiomics nomogram based on DCE-MRI, B-mode ultrasound (BMUS) and strain elastography (SE) images for classifying benign and malignant breast lesions.

Material and Methods

In this retrospective study, 345 breast lesions from 305 patients who underwent DCE-MRI, BMUS and SE examinations were randomly divided into training (n = 241) and testing (n = 104) datasets. Radiomics features were extracted from manually contoured images. The inter-class correlation coefficient (ICC), Mann-Whitney U test and the least absolute shrinkage and selection operator (LASSO) regression were applied for feature selection and radiomics signature building. Multivariable logistic regression was used to develop a radiomics nomogram incorporating radiomics signature and clinical factors. The performance of the radiomics nomogram was evaluated by its discrimination, calibration, and clinical usefulness and was compared with BI-RADS classification evaluated by a senior breast radiologist.

Results

The All-Combination radiomics signature derived from the combination of DCE-MRI, BMUS and SE images showed better diagnostic performance than signatures derived from single modality alone, with area under the curves (AUCs) of 0.953 and 0.941 in training and testing datasets, respectively. The multi-modality radiomics nomogram incorporating the All-Combination radiomics signature and age showed excellent discrimination with the highest AUCs of 0.964 and 0.951 in two datasets, respectively, which outperformed all single modality radiomics signatures and BI-RADS classification. Furthermore, the specificity of radiomics nomogram was significantly higher than BI-RADS classification (both p < 0.04) with the same sensitivity in both datasets.

Conclusion

The proposed multi-modality radiomics nomogram based on DCE-MRI and ultrasound images has the potential to serve as a non-invasive tool for classifying benign and malignant breast lesions and reduce unnecessary biopsy.
WWOX-rs13338697 genotype predicts therapeutic efficacy of ADI-PEG 20 for patients with advanced hepatocellular carcinoma
Authors: Chu Yu-De , Liu Hui-Fen , Chen Yi-Chen , Chou Chun-Hung , Yeh Chau-Ting
Published: December 2022

Background

Previous studies have identified three single nucleotide polymorphisms (SNPs): GALNT14-rs9679162, WWOX-rs13338697 and rs6025211. Their genotypes are associated with therapeutic outcomes in hepatocellular carcinoma (HCC). Herein, we examined whether these SNP genotypes could predict the clinical outcome of HCC patients treated with ADI-PEG 20.

Methods

Totally 160 patients with advanced HCC, who had previously been enrolled in clinical trials, including 113 receiving ADI-PEG 20 monotherapy (cohort-1) and 47 receiving FOLFOX/ADI-PEG 20 combination treatment (cohort-2), were included retrospectively.

Results

The WWOX-rs13338697-GG genotype was associated with favorable overall survival in cohort-1 patients (P = 0.025), whereas the rs6025211-TT genotype was associated with unfavorable time-to-tumor progression in cohort-1 (P = 0.021) and cohort-1 plus 2 patients (P = 0.008). As ADI-PEG 20 can reduce plasma arginine levels, we examined its pretreatment levels in relation to the WWOX-rs13338697 genotypes. Pretreatment plasma arginine levels were found to be significantly higher in patients carrying the WWOX-rs13338697-GG genotype (P = 0.006). We next examined the association of the WWOX-rs13338697 genotypes with WWOX tissue protein levels in 214 paired (cancerous/noncancerous) surgically resected HCC tissues (cohort-3). The WWOX-rs13338697-GG genotype was associated with decreased tissue levels of WWOX and ASS1. Mechanistic studies showed that WWOX and ASS1 levels were downregulated in hypoxic HCC cells. Silencing WWOX to mimic low WWOX protein expression in HCC in patients with the WWOX-rs13338697-GG genotype, enhanced HIF1A increment under hypoxia, further decreased ASS1, and increased cell susceptibility to ADI-PEG 20.

Comclusion

In summary, the WWOX-rs13338697 and rs6025211 genotypes predicted treatment outcomes in ADI-PEG 20-treated advanced HCC patients. The WWOX-rs13338697-GG genotype was associated with lower tissue WWOX and ASS1 levels and higher pretreatment plasma arginine levels, resembling an arginine auxotrophic phenotype requires excessive extracellular arginine supply. Silencing WWOX to mimic HCC with the WWOX-rs13338697-GG genotype further stimulated HCC cell response to hypoxia through increased HIF1A expression, leading to further reduction of ASS1 and thus increased cell susceptibility to ADI-PEG 20.
Study on the relationship between intrapartum group B streptococcus prophylaxis and food allergy in children
Authors: Zhang Hong , Xu Kang , Liu Zhihui , Shi Yuanmei , Li Hui , Yin Xiaoping
Published: December 2022

Objective

To investigate the associations between intrapartum antibiotic prophylaxis of group B streptococcus (GBS) in pregnant women and the risk of food allergy in Chinese children

Design

Retrospective cohort study of 2,909 mother-child pairs.

Setting

Taixing People's Hospital in Eastern China.

Participants

Term infants born 2018–2019, followed longitudinally from birth to 3 years.

Exposures

The GBS-IAP was defined as therapy with intravenous penicillin G or ampicillin or cefazolin ≥4 h prior to delivery to the mother. Reference infants were defined as born without or with other intrapartum antibiotic exposure.

Methods

To investigate the incidence information of food allergy in children aged 18 months and three years old. Kaplan-Meier survival analysis and log-rank tests were used to evaluate the cumulative incidence in the group with GBS-IAP and the group without GBS-IAP. Cox proportional hazards models were conducted to determine the univariate and multivariate association between maternal GBS-IAP and incident food allergy after various covariates were adjusted.

Results

The cumulative incidence of food allergy in the group with GBS-IAP was higher than that in the group without GBS-IAP in children under 18 months old (8.1% vs. 4.5%, P = 0.005, log-rank test), but no significant differences were observed in children under three years old (9.2% vs. 7.0%, P = 0.146, log-rank test). The univariate cox proportional hazards model in children under 18 months old revealed that children in the GBS-IAP group had faster food allergy development when compared with children in the group without GBS-IAP (HR.: 1.887,95% CI: 1.207–2.950, P = 0.005), so was the multivariate model (HR.: 1.906,95% CI: 1.158–3.137, P = 0.011). However, both univariate (HR: 1.343, 95% CI: 0.891∼2.026, P = 0.159) and multivariate (HR: 1.253, 95%CI: 0.796∼1.972, P = 0.329) cox proportional hazards model in children under three years old showed no significant differences between children in the group with GBS-IAP and group without GBS-IAP.

Conclusion

Intrapartum antibiotic prophylaxis of group B streptococcus may increase the cumulative incidence and risk of food allergy in children under 18 months old, but it had no significant effect on children under three years old.
Cannabis sativa L. alleviates loperamide-induced constipation by modulating the composition of gut microbiota in mice
Authors: Li Rong , Li Min , Li Bei , Chen Wei‐Hua , Liu Zhi
Published: December 2022

MaZiRenWan (MZRW) is the most frequently used Traditional Chinese Medicine formula to treat chronic constipation, Cannabis sativa L. is regarded as a monarch drug in MZRW. However, the targets of Cannabis sativa L. that enhance colonic motility and improve constipation symptoms remain unknown. This study was designed to investigate the laxative effect and underlying mechanism of the water extract of Cannabis sativa L. (WECSL) using a loperamide-induced constipation mouse model. We found that WECSL treatment significantly improved intestinal motility and water-electrolyte metabolism, decreased inflammatory responses, prevented gut barrier damage, and relieved anxiety and depression in constipated mice. WECSL also structurally remodeled the composition of the gut microbiota and altered the abundance of bacteria related to inflammation, specifically Butyricicoccus and Parasutterella. Moreover, WECSL failed to relieve constipation symptoms following intestinal flora depletion, indicating that WECSL alleviates constipation symptoms depending on the gut microbiota. Our research provides a basis for WECSL to be further investigated in the treatment of constipation from the perspective of modern medicine.
Intranasal neuropeptide Y is most effective in some aspects of acute stress compared to melatonin, oxytocin and orexin
Authors: Zubkov Eugene , Abramova Olga , Zorkina Yana , Ochneva Aleksandra , Ushakova Valeria , Morozova Anna , Gurina Olga , Majouga Alexander , Chekhonin Vladimir
Published: December 2022

Objectives: In the current study, we compared the effects of a single intranasal administration of clomipramine with effects of four neuropeptides, melatonin, oxytocin, orexin, and neuropeptide Y, to compare them in an acute stress model.

Methods: The anti-stress effect was evaluated in the sucrose preference and forced swimming tests. Serum corticosterone level in rats was measured to evaluate the stress response.

Results: Neuropeptide Y reduced immobilization time in the Porsolt test and decreased corticosterone levels, but increased the anhedonia. Orexin had no positive effect on animal behavior, but decreased corticosterone levels. Oxytocin decreased immobilization time, maintained anhedonia at the level of control, but did not affect corticosterone levels. Melatonin demonstrated no positive effects in any of the tests.

Conclusion: The intranasal administered neuropeptide Y could be a promising compound for the treatment of stress disorders.
Loss-of-function N178T variant of the human P2Y4 receptor is associated with decreased severity of coronary artery disease and improved glucose homeostasis
Authors: Horckmans Michael , Diaz Villamil Esteban , Verdier Céline , Laurell Henrik , Ruidavets Jean-Bernard , De Roeck Lucas , Combes Guillaume , Martinez Laurent O. , Communi Didier
Published: December 2022

Human P2Y4 is a UTP receptor, while in mice it is activated by both ATP and UTP. P2Y4 knockout (KO) in mice protects against myocardial infarction and is characterized by increased adiponectin secretion by adipocytes, and decreased cardiac inflammation and permeability under ischemic conditions. The relevance of these data has, however, not been explored to date in humans. In a population study comprising 50 patients with coronary artery disease (CAD) and 50 age-matched control individuals, we analyzed P2RY4 mutations and their potential association with CAD severity and fasting plasma parameters. Among the mutations identified, we focused our attention on a coding region polymorphism (rs3745601) that results in replacement of the asparagine at residue 178 with threonine (N178T) located in the second extracellular loop of the P2Y4 receptor. The N178T variant is a loss-of-function mutation of the human P2Y4 receptor and is encountered less frequently in coronary patients than in control individuals. In coronary patients, carriers of the N178T variant had significantly reduced jeopardy and Gensini cardiac severity scores, as well as lower resting heart rates and plasma levels of N-terminal pro-brain natriuretic peptide (NT-proBNP). Regarding fasting plasma parameters, the N178T variant was associated with a lower concentration of glucose. Accordingly, P2Y4 KO mice had significantly improved glucose tolerance and insulin sensitivity compared with their WT littermate controls. The improvement of insulin sensitivity resulting from lack of the P2Y4 receptor was no longer observed in the absence of adiponectin. The present study identifies a frequent loss-of-function P2Y4 variant associated with less severe coronary artery atherosclerosis and lower fasting plasma glucose in coronary patients. The role of the P2Y4 receptor in glucose homeostasis was confirmed in mouse. P2Y4 antagonists could thus have therapeutic applications in the treatment of myocardial infarction and type 2 diabetes.
Effect of vitamin K on wound healing: A systematic review and meta-analysis based on preclinical studies
Authors: Tang Saiqing , Ruan Zhen , Ma Axue , Wang Dong , Kou Jiushe
Published: December 2022

Background: In recent years, many studies have found that vitamin K is beneficial to wound healing. However, some research results seem to be in conflict. The purpose of this study was to evaluate the effect of vitamin K on wound healing.

Methods: We systematically and comprehensively searched the PubMed, Web of Science, Embase, Cochrane library, China National Knowledge Infrastructure (CNKI), VIP and Wanfang eletronic databases. We applied revman5.3 software to calculate the weighted mean difference (WMD) of 95% confidence interval (CI) of animal and cell groups to evaluate the effect of vitamin K on wound healing. Two researchers independently selected studies and used the Cochrane Collaboration tool to assess the risk of bias in the included studies. The overall quality of evidence was assessed using the Recommendation, Assessment, Development and Evaluation (GRADE) working group approch.

Results: Among the 1081 articles searched, 6 articles (16 studies in total) met the inclusion criteria. The results of quantitative analysis showed that vitamin K was beneficial to increase the wound healing rate in animal models [rat model: WMD = 27.45 (95% CI: 13.46, 41.44); p = 0.0001], but the opposite result was obtained in cell experiments [WMD = −33.84 (95% CI: −56.90, −10.79); p = 0.004].

Conclusion: This meta-analysis hits that vitamin K could affect the process of wound healing, especially in animal models. While we could not know the clear role at present, which requires larger scale research. In addition, the concentration and safe dose of vitamin K also deserve further study.
Appraising the therapeutical potentials of Alchornea laxiflora (Benth.) Pax & K. Hoffm., an underexplored medicinal herb: A systematic review
Authors: Jain Nem Kumar , Tailang Mukul , Kumar Santosh , Chandrasekaran Balakumar , Alghazwani Yahia , Chandramoorthy Harish C. , Kumar Ashish , Deshpande Hemali , Wal Pranay , Balamurugan Manickam , Chidambaram Kumarappan
Published: December 2022

Ethnopharmacological relevance:Alchornea laxiflora (Benth.) Pax & K. Hoffm. (Euphorbiaceae) is an important traditional medicinal plant grown in tropical Africa. The stem, leaves, and root have been widely used in the folk medicine systems in Nigeria, Cameroon, South Africa, and Ghana to treat various ailments, including inflammatory, infectious, and central nervous system disorders, such as anxiety and epilepsy.

Material and methods: The scientific name of the plant was validated using the “The Plant List,” “Kew Royal Botanic Gardens,” and Tropicos Nomenclatural databases. The literature search on A. laxiflora was performed using electronic search engines and databases such as Google scholar, ScienceDirect, PubMed, AJOL, Scopus, and Mendeley.

Results: To the best of our knowledge, no specific and detailed review has been reported on A. laxiflora. Consequently, this review provides an up-to-date systematic presentation on ethnobotany, phytoconstituents, pharmacological activities, and toxicity profiles of A. laxiflora. Phytochemical investigations disclosed the presence of important compounds, such as alkaloids, flavonoids, phenolics, terpenoids, and fatty acids. Furthermore, various pharmacological activities and traditional uses reported for this botanical drug were discussed comprehensively.

Conclusion: This systemic review presents the current status and perspectives of A. laxiflora as a potential therapeutic modality that would assist future researchers in exploring this African botanical drug as a source of novel drug candidates for varied diseases.
Autonomic imbalance and atrial ectopic activity—a pathophysiological and clinical view
Authors: Scridon Alina
Published: December 2022

The heart is one of the most richly innervated organs and the impact of the complex cardiac autonomic network on atrial electrophysiology and arrhythmogenesis, including on atrial ectopy, is widely recognized. The aim of this review is to discuss the main mechanisms involved in atrial ectopic activity. An overview of the anatomic and physiological aspects of the cardiac autonomic nervous system is provided as well as a discussion of the main pathophysiological pathways linking autonomic imbalance and atrial ectopic activity. The most relevant data on cardiac neuromodulation strategies are emphasized. Unanswered questions and hotspots for future research are also identified.
Critical periods in Drosophila neural network development: Importance to network tuning and therapeutic potential
Authors: Coulson Bramwell , Hunter Iain , Doran Sarah , Parkin Jill , Landgraf Matthias , Baines Richard A.
Published: December 2022

Critical periods are phases of heightened plasticity that occur during the development of neural networks. Beginning with pioneering work of Hubel and Wiesel, which identified a critical period for the formation of ocular dominance in mammalian visual network connectivity, critical periods have been identified for many circuits, both sensory and motor, and across phyla, suggesting a universal phenomenon. However, a key unanswered question remains why these forms of plasticity are restricted to specific developmental periods rather than being continuously present. The consequence of this temporal restriction is that activity perturbations during critical periods can have lasting and significant functional consequences for mature neural networks. From a developmental perspective, critical period plasticity might enable reproducibly robust network function to emerge from ensembles of cells, whose properties are necessarily variable and fluctuating. Critical periods also offer significant clinical opportunity. Imposed activity perturbation during these periods has shown remarkable beneficial outcomes in a range of animal models of neurological disease including epilepsy. In this review, we spotlight the recent identification of a locomotor critical period in Drosophila larva and describe how studying this model organism, because of its simplified nervous system and an almost complete wired connectome, offers an attractive prospect of understanding how activity during a critical period impacts a neuronal network.
Feasibility of plant-expression system for production of recombinant anti-human IgE: An alternative production platform for therapeutic monoclonal antibodies
Authors: Hanittinan Oranicha , Rattanapisit Kaewta , Malla Ashwini , Tharakhet Kittipan , Ketloy Chutitorn , Prompetchara Eakachai , Phoolcharoen Waranyoo
Published: December 2022

Omalizumab, the anti-immunoglobulin IgE antibody is the only approved and available monoclonal antibody as an auxiliary medicament for the severe respiratory allergic reactions. It forms small size immune complexes by binding to free IgE, thereby inhibiting the interaction of IgE with its receptors. Additionally, the anti-IgE can also differently shape the airflow by impeding the stimulation of IgE receptors present on structural cells in the respiratory tract. The present study aimed to use plants as an expression system for anti-human IgE antibody production, usingNicotiana benthamianaas hosts. RecombinantAgrobacterium tumefacienscontaining heavy chain (HC) and light chain (LC) domains of anti-human IgE were co-transformed inN. benthamiana. The assembling of the antibody and its expression was detected by SDS-PAGE and Western blot analysis. The functional ability of the anti-IgE antibody was determinedviaits binding capacity with target IgE by ELISA and the inhibition of basophil activation. The anti-human IgE mAb generated in plants was shown to be effective in binding to its target IgE and inhibit the IgE-crosslink in RS-ATL8 reporter cells. Although, antibody yield and purification process have to be further optimized, this study demonstrates the use of plant expression system as a promising platform for the production of Omalizumab which showed a comparablein vitrofunction to that of commercial Omalizumab (Xolair) in the inhibition of basophil activation.
Apple detection and instance segmentation in natural environments using an improved Mask Scoring R-CNN Model
Authors: Wang Dandan , He Dongjian
Published: December 2022

The accurate detection and segmentation of apples during growth stage is essential for yield estimation, timely harvesting, and retrieving growth information. However, factors such as the uncertain illumination, overlaps and occlusions of apples, homochromatic background and the gradual change in the ground color of apples from green to red, bring great challenges to the detection and segmentation of apples. To solve these problems, this study proposed an improved Mask Scoring region-based convolutional neural network (Mask Scoring R-CNN), known as MS-ADS, for accurate apple detection and instance segmentation in a natural environment. First, the ResNeSt, a variant of ResNet, combined with a feature pyramid network was used as backbone network to improve the feature extraction ability. Second, high-level architectures including R-CNN head and mask head were modified to improve the utilization of high-level features. Convolutional layers were added to the original R-CNN head to improve the accuracy of bounding box detection (bbox_mAP), and the Dual Attention Network was added to the original mask head to improve the accuracy of instance segmentation (mask_mAP). The experimental results showed that the proposed MS-ADS model effectively detected and segmented apples under various conditions, such as apples occluded by branches, leaves and other apples, apples with different ground colors and shadows, and apples divided into parts by branches and petioles. The recall, precision, false detection rate, and F1 score were 97.4%, 96.5%, 3.5%, and 96.9%, respectively. A bbox_mAP and mask_mAP of 0.932 and 0.920, respectively, were achieved on the test set, and the average run-time was 0.27 s per image. The experimental results indicated that the MS-ADS method detected and segmented apples in the orchard robustly and accurately with real-time performance. This study lays a foundation for follow-up work, such as yield estimation, harvesting, and automatic and long-term acquisition of apple growth information.
Identification of beneficial Lebanese Trichoderma spp. wheat endophytes
Authors: Matar Naeif , Macadré Catherine , Ammar Gamal A. G. , Peres Alexis , Collet Boris , Boustany Naim El , Rajjou Loïc , As-Sadi Falah , Dufresne Marie , Ratet Pascal
Published: December 2022

Wheat is one of the most important crops in the world. Its production can be influenced by a diversity of beneficial and pathogenic rhizospheric microbes, including fungi. Amongst them, beneficial Trichoderma spp. can be used as alternatives to chemical fertilizers, as they are cheap and harmless to the environment. Our study aimed to isolate, identify, and characterize Trichoderma spp. from Lebanon associated with wheat. Two Trichoderma strains belonging to T. afroharzianum, and T. guizhouense species, were isolated and found to be endophytes, enhancing root growth and producing Indole-3-acetic acid. Inoculation also improved seedling development, and increased plant growth and yield. Furthermore, the two strains inhibit Fusarium growth in vitro. These Trichoderma spp. have thus the capacity to be used as organic fertilizers for wheat.
Improving berry quality and antioxidant ability in ‘Ruidu Hongyu’ grapevine through preharvest exogenous 2,4-epibrassinolide, jasmonic acid and their signaling inhibitors by regulating endogenous phytohormones
Authors: Li Jiajia , Javed Hafiz Umer , Wu Zishu , Wang Lei , Han Jiayu , Zhang Ying , Ma Chao , Jiu Songtao , Zhang Caixi , Wang Shiping
Published: December 2022

Grape berries contain a variety of metabolites, such as anthocyanins, sugars, fatty acids, and antioxidants. Endogenous phytohormones strongly influence these metabolites, which regulate berry quality improvement. In this study, we evaluated the effects of 2,4-epibrassinolide (EBR, brassinolide (BR)-like growth regulator), jasmonic acid (JA), and their signaling inhibitors brassinazole (Brz), and sodium diethyldithiocarbamate (DIECA) on berry quality and antioxidant ability. Overall, the pre-harvest application of 0.5 mg L-1EBR and 100 μmol L-1JA significantly influences the quality of the grape berry. Results showed that EBR was superior to other treatments at enhancing the content of different metabolites, including anthocyanins, fructose, glucose, and a variety of fatty acids, in grapes. EBR and JA also enhanced the synthesis of gibberellin3(GA3), cytokinin (CTK), salicylic acid (SA), JA, methyl jasmonate (MeJA), BR, and abscisic acid (ABA), while inhibiting the synthesis of auxin (IAA). Most genes related to BR/JA and anthocyanins/sugars/fatty acids biosynthesis were up-regulated. The effects of Brz and DIECA on the grape berry quality were totally reversed throughout the study, as shown by EBR and JA. According to correlation analysis, EBR and JA have a beneficial positive interaction that promotes the formation of strong coherences in grape berries between ABA/IAA/ZT-fruit expansion, BR/JA/MeJA/GA3/ZR-biochemical characteristics development, JA/MeJA/ABA/GA3/SA/ZR-antioxidant capacity enhancement, and JA/MeJA/IAA/GA3/ZT/ZR-fatty acids accumulation. In this regard, we concluded that preharvest exogenous 0.5 mg L-1EBR and 100 μmol L-1JA is a successful way to improve grape berry quality.
Physiological responses and antibiotic-degradation capacity of duckweed (Lemna aequinoctialis) exposed to streptomycin
Authors: Huang Weijuan , Kong Rui , Chen Lijun , An Yuxing
Published: December 2022

Aquatic plants are constantly exposed to various water environmental pollutants. Few data on how antibiotics affect duckweed health and its removal ability. The aim of this study was to investigate the impact of streptomycin on the physiological change and uptake capability in duckweed (Lemna aequinoctialis) after exposure at different time points (0, 5, 10, 15 and 20 days). Duckweeds were exposed to streptomycin at a range of concentrations (0.1-10 mM). Results indicated that the high streptomycin concentrations (≥1 mM) resulted in a lower duckweed biomass (21.5-41.5%), RGR (0.258-0.336 g d−1), decrease in total Chl and increase in carotenoids. Antioxidative enzymes, including CAT (18-42.88 U mg protein-1), APX (0.41-0.76 U mg protein-1), and SOD (0.52-0.71 U mg protein-1) were found to accumulate in the streptomycin groups in comparison to the control group. The significant reduction (72-82%) in streptomycin content at 20 d compared to the control (40-55%) suggested that duckweed has a high ability in removing streptomycin. Transcriptome analysis showed that the secondary metabolic pathways including phenylpropanoid biosynthesis and flavonoid biosynthesis were significantly upregulated in the streptomycin setup compared to the control. Therefore, our findings suggested that duckweed can contribute to the streptomycin degradation, which should be highly recommended to the treatment of aquaculture wastewater and domestic sewage.
Climate-responsive DNA methylation is involved in the biosynthesis of lignin in birch
Authors: Chen Bowei , Guo Yile , Zhang Xu , Wang Lishan , Cao Lesheng , Zhang Tianxu , Zhang Zihui , Zhou Wei , Xie Linan , Wang Jiang , Sun Shanwen , Yang Chuanping , Zhang Qingzhu
Published: December 2022

Lignin is one of the most important secondary metabolites and essential to the formation of cell walls. Changes in lignin biosynthesis have been reported to be associated with environmental variations and can influence plant fitness and their adaptation to abiotic stresses. However, the molecular mechanisms underlying this association remain unclear. In this study, we evaluated the relations between the lignin biosynthesis and environmental factors and explored the role of epigenetic modification (DNA methylation) in contributing to these relations if any in natural birch. Significantly negative correlations were observed between the lignin content and temperature ranges. Analyzing the transcriptomes of birches in two habitats with different temperature ranges showed that the expressions of genes and transcription factors (TFs) involving lignin biosynthesis were significantly reduced at higher temperature ranges. Whole-genome bisulfite sequencing revealed that promoter DNA methylation of two NAC-domain TFs, BpNST1/2 and BpSND1, may be involved in the inhibition of these gene expressions, and thereby reduced the content of lignin. Based on these results we proposed a DNA methylation-mediated lignin biosynthesis model which responds to environmental factors. Overall, this study suggests the possibility of environmental signals to induce epigenetic variations that result in changes in lignin content, which can aid to develop resilient plants to combat ongoing climate changes or to manipulate secondary metabolite biosynthesis for agricultural, medicinal, or industrial values.