bluuebunny/crossref_metadata_2025 huggingface dataset:
Mechanism of activation of porcine dendritic cells by an α-D-glucan nanoparticle adjuvant and a nanoparticle/poly(I:C) combination adjuvant
Authors: Hernandez-Franco Juan F. , Xie Shaojun , Thimmapuram Jyothi , Ragland Darryl , HogenEsch Harm
Published: September 2022

Recent studies have shown that corn-derived cationic α-D-glucan nanoparticles, known as Nano-11, significantly increase the immune response when used as a vaccine adjuvant in mice and in pigs. Furthermore, the nanoparticles can be formulated with other immunostimulators such as poly(I:C), which further enhances the immune response. The current experiments were aimed at elucidating the mechanism of action of Nano-11 alone and in combination with poly(I:C). The effect of these adjuvants on porcine monocyte-derived dendritic cells (Mo-DCs) was determined by RNA-sequencing, supplemented with flow cytometry, cytokine analysis, and Western blots. Adsorption of poly(I:C) to Nano-11 reduced its cytotoxicity for Mo-DCs. Exposure of Mo-DCs to Nano-11 and Nano-11/poly(I:C) induced differential expression of 979 and 2016 genes, respectively. Gene Ontology enrichment and KEGG pathway analysis revealed many changes in gene expression related to inflammation, innate immunity, immune response to infections, and metabolism. Nano-11 and Nano-11/poly(I:C) induced maturation of the Mo-DCs as indicated by increased expression of costimulatory molecules and MHC II. Increased expression of genes downstream of p38 MAPK activation revealed a role for this signaling pathway in the activation of Mo-DCs by the adjuvants. This was confirmed by Western blot and inhibition of TNF-secretion upon incubation with the p38 inhibitor SB203580. These experiments provide insights into the mechanism of action of the novel adjuvants Nano-11 and Nano-11/poly(I:C).
Reproductive potential of fall armyworm Spodoptera frugiperda (J.E. Smith) and effects of feeding on diverse maize genotypes under artificial infestation
Authors: Anyanda Geoffrey N. , Bruce Anani Y. , Makumbi Dan , Ahonsi Monday , Kahuthia-Gathu Ruth , Namikoye Samita E. , Beyene Yoseph , Prasanna B. M.
Published: September 2022

Fall armyworm (FAW) Spodoptera frugiperda (J.E. Smith) has become a major threat to maize production in Africa. In this study, six maize genotypes were assessed for their resistance to FAW under artificial infestation in both laboratory and net house conditions. These included two FAW-tolerant hybrids (CKHFAW180294 and CKH191221), two commercial hybrids (WE2115 and CKH10717), and two open-pollinated varieties (ZM523 and KDV4). Larval development time and reproductive potential were assessed on maize leaves in the laboratory and a life table for FAW was constructed. The maize genotypes were also artificially infested with three FAW neonates at two phenological stages (V5 and V7) and reproductive stage (R1) in the net house. Leaf and ear damage scores were recorded on a scale of 1–9. Larval development time varied significantly between maize genotypes with the highest on CKH191221 (16.4 days) and the lowest on KDV4 (13.7 days). The intrinsic rate of natural increase for life tables varied from 0.24 on CKH191221 to 0.41 on KDV4. Mean generation time of FAW ranged from 17.6 to 22.8 days on KDV4 and CKH191221, respectively. Foliar damage was the lowest on CKH191221, and the highest on KDV4 at V7 infestation stage in week 1. CKH191221 had the lowest ear damage score, whereas ZM523 had the highest scores at V5 infestation stage. The highest and lowest yield reductions were observed on ZM523 (64%) at V7 infestation stage and CKHFAW180294 (6%) at R1 infestation stage, respectively. The results indicated the potential for developing tropical mid-altitude maize germplasm with native genetic resistance to FAW.
Brewery by-products (yeast and spent grain) as protein sources in rainbow trout (Oncorhynchus mykiss) feeds
Authors: Estévez Alicia , Padrell Lluis , Iñarra Bruno , Orive Mikel , San Martin David
Published: September 2022

A trial was conducted to analyze the effect of the inclusion of yeast and spent grain obtained from breweries in feeds for rainbow trout (Oncorhynchus mykiss), taking into account the availability of these by-products, produced in large quantities in Europe. The ingredients were assayed in both dried and hydrolyzed format and compared with a commercial dried or hydrolyzed yeast. According to the results, the inclusion of 20% yeast and 15% spent grain in the feed, formulated with only 15% inclusion of fish meal, produced similar results in growth among all the groups, a food conversion significantly lower for the control and spent grain formulated feeds, and rainbow trout muscle composition similar to the fish fed with a control commercial feed and showed a protein digestibility of 87%–89% without differences with the commercial yeast. Hydrolysis of the ingredients had no effects on the protein digestibility of the feeds. Protein digestibility of the ingredients was lower for spent grain. An inclusion rate not higher than 15% for spent grain is recommended. These industrial by-products can be a good source to reduce the use of plant-based ingredients and increase the sustainability of both sectors, brewery industry, and aquaculture.
Berberine in fish nutrition: Impact on hepatoenteric health, antioxidative and immune status
Authors: Wang Lei , Sagada Gladstone , Wang Chenyang , Gao Chang , Wang Bin , Shao Qingjun , Yan Yunzhi
Published: September 2022

Berberine, an isoquinoline alkaloid found in some traditional medicinal plants, such as Berberis vulgaris and Coptis Chinensis, has been considered as an effective drug in treating obesity, hypertension, type-2 diabetes, hyperlipidemia, and gout in humans and animals. It currently has certain applications in fish nutrition and health, mainly because it has strong biological and pharmacological properties, such as antioxidative, anti-inflammation, antidiarrheal, analgesic, antimicrobial, anticancer, hepatoprotective, and lipid- and glucose-lowering properties. Recent studies revealed that berberine supplementation in different fish diets could alleviate liver pathological changes, intestinal histological and microbiota alterations caused by high lipid and carbohydrate diets, as well as improve growth performance, antioxidative and immune status, and stress resistance ability of fish. However, the beneficial effects of berberine vary with fish species, basal diet, feeding modes, supplementation level, and etc. This review highlights the bioavailability and toxicity of berberine, and its mechanisms in lipid and glucose metabolism, antioxidation, anti-inflammation, and protection of intestinal health, as well as the other findings on supplementing berberine in the fish diet. Moreover, this review provides future perspectives on berberine application in fish nutrition and health.
Large-scale effects of turbidity on coral bleaching in the Hawaiian islands
Authors: Carlson Rachel R. , Li Jiwei , Crowder Larry B. , Asner Gregory P.
Published: September 2022

Turbidity from land-based runoff has been identified as a possible driver of coral bleaching refugia, as particulate matter in turbid habitats may block excessive irradiance and alter the food supply to corals during ocean heatwaves. However, negative effects of turbidity have also been documented worldwide, and high-resolution data across reef regions are required to identify habitats where turbidity is harmful or helpful during heatwaves. We monitored turbidity across five Main Hawaiian Islands during a 2019 ocean heatwave using Planet Dove satellites (3.7 m spatial resolution, extracted at 100 m resolution) to examine relationships between turbidity and coral bleaching occurrence and severity. We also attributed turbidity to urban and non-urban land uses to determine how turbidity associated with different human activities affects coral bleaching. We found that, while turbidity had a negative relationship with coral bleaching severity, this effect weakened at higher temperatures, especially in rural areas. However, turbidity maintained a slightly negative effect on bleaching severity in urban settings. In addition, while thermal stress was the predominant driver of bleaching occurrence, interactions between temperature and local variables like turbidity and wave energy were the most significant drivers of bleaching severity. This study represents one of the first high-resolution analyses of turbid refugia at large spatial scales. We show how new data sources from remote sensing can provide scalable yet context-specific information to coastal managers addressing land-sea runoff.
Heavy metal pollution status and deposition history of mangrove sediments in Zhanjiang Bay, China
Authors: Tang Daobin , Luo Songying , Deng Suyan , Huang Rui , Chen Bishan , Deng Ziyi
Published: September 2022

Mangroves have high ecological service value and play an important role in achieving carbon neutrality. However, the ecological services provided by mangroves are gradually declining due to the threat of various pollutants, especially heavy metal (HM) pollution. Researching the status and history of heavy metals (HMs) in mangrove sediments improves understanding of how mangroves can be protected. We studied the Zhanjiang Bay mangroves, which is an important part of the Zhanjiang Mangrove National Nature Reserve, and is greatly affected by human activities, as an example. We analyzed the pollution levels and deposition process of HMs and their influencing factors. In the mangrove surface sediments of Zhanjiang Bay, Pb, Cr, and Co were slightly to moderate enriched and Cu was moderate-heavy enriched. Zn and Hg showed moderate-heavy enrichment and heavy enrichment, respectively. Cu, Zn, Hg, and Co were 1.5, 1.88, 2.66, and 1.27 times the local background, respectively. Cu, Zn, and Hg mainly originated from anthropogenic sources, and Co may have derived from natural sources. The HM data of mangrove sedimentary cores in Zhanjiang Bay were obtained for the first time; high HM content appeared in the deep layer of the cores but not in the mangrove surface sediments. Both cores were well documented for the effects of natural and anthropogenic factors on the deposition process of HMs. Among them, the high enrichment of Hg in 1909–1921 may be closely related to human activities rather than natural formation. Before 1954, dense mangroves favored the accumulation and gradual increase of HMs. The intense human activity in 1945–1963 during the period of economic construction and reclamation of the Nansan Island Engineering led to significant increases in Cu, Zn, Pb, Cr, and Co, which reached their highest values in more than one hundred years. After 1963, anthropic factors such as deforestation and conversion to aquaculture sharply reduced mangrove area. Reclamation engineering enhanced tidal erosion. Natural factors such as precipitation, storm surge, sea-level rise, and high tides have accelerated the erosion and dilution of mangrove sediments in Zhanjiang Bay. These factors have led to the gradual reduction of HM content in sedimentary cores.
Unraveling the mechanism of sulfur nutrition in pigeonpea inoculated with sulfur-oxidizing bacteria
Authors: Malviya Deepti , Varma Ajit , Singh Udai B. , Singh Shailendra , Saxena Anil K.
Published: September 2022

An investigation was carried out to understand the mechanism(s) involved in the uptake of sulfur (S) as sulfate in pigeonpea following single inoculation of two sulfur-oxidizing bacteria (SOB),Stenotrophomonas maltophiliaandStenotrophomonas pavaniiin the treatments amended with either elemental sulfur (S0) or sulfate (S6). Colonization potential and biofilm formation were analyzed through confocal laser scanning microscope (CLSM) and scanning electron microscope (SEM). Furthermore, the effect of seed inoculation on root architecture, expression of genes involved in sulfur oxidation (sox) in bacterial inoculants, and genes involved in sulfate transport in pigeonpea (PpSULTR) were analyzed to correlate with the higher uptake of S in roots and shoots of pigeonpea. Both the SOB exhibited a good colonization potential and biofilm formation on the roots of pigeonpea. Among the 11soxgenes targeted in rhizosphere of pigeonpea, expression was achieved for seven genes, which showed 2-fold increase in treatments inoculated withS. maltophiliaand amended with either S6or S0. The inoculation ofS. maltophiliaand amendment of S0led to increased expression ofPpSULTRgenes by several folds in roots. The inoculation of SOB had a significant influence on non-enzymatic (osmolytes like proline) and enzymatic (PAL, peroxidase, superoxide dismutase, and catalase) levels. The results revealed a significant increase in sulfur uptake in roots and shoots in treatment inoculated withS. maltophiliaand amended with S6. The investigation showed that the SOB-mediated over-expression ofPpSULTRgenes in roots of pigeonpea andsoxgenes in the rhizosphere were acting synergistically in facilitating higher uptake and translocation of S in roots and shoots of pigeonpea plants.
A novel pyroptosis-regulated gene signature for predicting prognosis and immunotherapy response in hepatocellular carcinoma
Authors: Zhang Baozhu , Wang Zhan
Published: September 2022

Background: Pyroptosis, a newly discovered type of programmed cell death, has both anti-tumor and tumor-promoting effects on carcinogenesis. In hepatocellular carcinoma (HCC), however, the associations between pyroptosis-regulated genes and prognosis, immune microenvironment, and immunotherapy response remain unclear.

Samples and methods: Sequencing data were collected from The Cancer Genome Atlas database, The International Cancer Genome Consortium (ICGC), and The Integrative Molecular Database of Hepatocellular Carcinoma (HCCDB). First, we investigated the expression levels and copy number variations (CNVs) of 56 pyroptosis genes in HCC and pan-cancer. Next, we identified 614 genes related to 56 pyroptosis-associated genes at the expression, mutation, and CNVs levels. Pathway enrichment analysis of 614 genes in the Hallmark, KEGG, and Reactome databases yielded a total of 253 significant signaling pathways. The pyroptosis-regulated genes (PRGs) comprised 108 genes that were derived from the top 20 signaling pathways, of which 57 genes had prognostic value in HCC. The least absolute shrinkage and selection operator (LASSO) analysis was performed to screen for PRGs with prognostic values. Ultimately, we constructed a risk score model with seven PRGs to predict HCC prognosis and validated its predictive value in three independent HCC cohorts. Risk scores were used to illustrate receiver operating characteristic (ROC) curves predicting 1, 3, and 5-years overall survival (OS). Single-sample gene set enrichment analysis (ssGSEA), was performed to study 28 types of immune cells infiltrated in HCC. The relationship between the risk signature and six immune checkpoint genes and immunotherapy was analyzed.

Results: A total of seven PRGs were obtained following multiple screening steps. The risk score model containing seven PRGs was found to correlate significantly with the HCC prognosis of the training group. In addition, we validated the risk score model in two additional HCC cohorts. The risk score significantly correlated with infiltrating immune cells (i. e. CD4+ T cells, etc.), ICB key molecules (i. e. HAVCR2, etc.), and ICB response.

Conclusions: This study demonstrated a vital role of PRGs in predicting the prognosis and immunotherapy response of HCC patients. The risk model could pave the way for drugs targeting pyroptosis and immune checkpoints in HCC.
A non-synonymous single nucleotide polymorphism in SIRT6 predicts neurological severity in Friedreich ataxia
Authors: Rodden Layne N. , Rummey Christian , Dong Yi Na , Lagedrost Sarah , Regner Sean , Brocht Alicia , Bushara Khalaf , Delatycki Martin B. , Gomez Christopher M. , Mathews Katherine , Murray Sarah , Perlman Susan , Ravina Bernard , Subramony S. H. , Wilmot George , Zesiewicz Theresa , Bolotta Alessandra , Domissy Alain , Jespersen Christine , Ji Baohu , Soragni Elisabetta , Gottesfeld Joel M. , Lynch David R.
Published: September 2022

Introduction: Friedreich ataxia (FRDA) is a recessive neurodegenerative disease characterized by progressive ataxia, dyscoordination, and loss of vision. The variable length of the pathogenic GAA triplet repeat expansion in the FXN gene in part explains the interindividual variability in the severity of disease. The GAA repeat expansion leads to epigenetic silencing of FXN; therefore, variability in properties of epigenetic effector proteins could also regulate the severity of FRDA.

Methods: In an exploratory analysis, DNA from 88 individuals with FRDA was analyzed to determine if any of five non-synonymous SNPs in HDACs/SIRTs predicted FRDA disease severity. Results suggested the need for a full analysis at the rs352493 locus in SIRT6 (p.Asn46Ser). In a cohort of 569 subjects with FRDA, disease features were compared between subjects homozygous for the common thymine SIRT6 variant (TT) and those with the less common cytosine variant on one allele and thymine on the other (CT). The biochemical properties of both variants of SIRT6 were analyzed and compared.

Results: Linear regression in the exploratory cohort suggested that an SNP (rs352493) in SIRT6 correlated with neurological severity in FRDA. The follow-up analysis in a larger cohort agreed with the initial result that the genotype of SIRT6 at the locus rs352493 predicted the severity of disease features of FRDA. Those in the CT SIRT6 group performed better on measures of neurological and visual function over time than those in the more common TT SIRT6 group. The Asn to Ser amino acid change resulting from the SNP in SIRT6 did not alter the expression or enzymatic activity of SIRT6 or frataxin, but iPSC-derived neurons from people with FRDA in the CT SIRT6 group showed whole transcriptome differences compared to those in the TT SIRT6 group.

Conclusion: People with FRDA in the CT SIRT6 group have less severe neurological and visual dysfunction than those in the TT SIRT6 group. Biochemical analyses indicate that the benefit conferred by T to C SNP in SIRT6 does not come from altered expression or enzymatic activity of SIRT6 or frataxin but is associated with changes in the transcriptome.
A polymorphic transcriptional regulatory domain in the amyotrophic lateral sclerosis risk gene CFAP410 correlates with differential isoform expression
Authors: Marshall Jack N. G. , Fröhlich Alexander , Li Li , Pfaff Abigail L. , Middlehurst Ben , Spargo Thomas P. , Iacoangeli Alfredo , Lang Bing , Al-Chalabi Ammar , Koks Sulev , Bubb Vivien J. , Quinn John P.
Published: September 2022

We describe the characterisation of a variable number tandem repeat (VNTR) domain within intron 1 of the amyotrophic lateral sclerosis (ALS) risk gene CFAP410 (Cilia and flagella associated protein 410) (previously known as C21orf2), providing insight into how this domain could support differential gene expression and thus be a modulator of ALS progression or risk. We demonstrated the VNTR was functional in a reporter gene assay in the HEK293 cell line, exhibiting both the properties of an activator domain and a transcriptional start site, and that the differential expression was directed by distinct repeat number in the VNTR. These properties embedded in the VNTR demonstrated the potential for this VNTR to modulate CFAP410 expression. We extrapolated these findings in silico by utilisation of tagging SNPs for the two most common VNTR alleles to establish a correlation with endogenous gene expression. Consistent with in vitro data, CFAP410 isoform expression was found to be variable in the brain. Furthermore, although the number of matched controls was low, there was evidence for one specific isoform being correlated with lower expression in those with ALS. To address if the genotype of the VNTR was associated with ALS risk, we characterised the variation of the CFAP410 VNTR in ALS cases and matched controls by PCR analysis of the VNTR length, defining eight alleles of the VNTR. No significant difference was observed between cases and controls, we noted, however, the cohort was unlikely to contain sufficient power to enable any firm conclusion to be drawn from this analysis. This data demonstrated that the VNTR domain has the potential to modulate CFAP410 expression as a regulatory element that could play a role in its tissue-specific and stimulus-inducible regulation that could impact the mechanism by which CFAP410 is involved in ALS.
Extraction and characterization of a pectin from sea buckthorn peel
Authors: Zhu Yulian , Liu Keshan , Yuen Michael , Yuen Tina , Yuen Hywel , Peng Qiang
Published: September 2022

Sea buckthorn peel is the by-product of the sea buckthorn processing, which contains many bioactive compounds. In this paper, sea buckthorn high methoxyl pectin (SBHMP) was obtained, with a yield of 8% and a light-colored. The SBHMP was a high methoxyl with a degree of esterification of 57.75% and uronic acid content of 65.35%. The structural and morphological characterization of SBHMP were analyzed by high-performance liquid chromatography, Fourier-transform infrared spectroscopy, and scanning electron microscopy. Results showed that SBHMP presented a sheet and layered stacked morphological, and was mainly composed of galacturonic acid, arabinose, galactose, rhamnose, and mannose, which indicated that SBHMP mainly consisted of homogalacturonan (HG) and rhamnogalacturonan-I (RG-I) type pectin polysaccharides. In addition, SBHMP also presented significant gel, thickening, and emulsifying properties. The results exhibited that SBHMP could form jelly-like gels under acid and high sucrose conditions, presenting a shear-thinning behavior and increasing apparent viscosity with the enhancement of pectin and sucrose contents. Besides, SBHMP could form oil-in-water emulsions with pectin concentrations of 1.0–3.0%. When the SBHMP concentrations were 2.0 and 3.0%, the emulsions were stable during 7 days of storage. Findings in this paper demonstrated the potential of SBHMP to be a food thickener and emulsifier and support the in-depth utilization of sea buckthorn by-products.
Research progress on the mechanism of radiation enteritis
Authors: Fan Jinjia , Lin Binwei , Fan Mi , Niu Tintin , Gao Feng , Tan Bangxian , Du Xiaobo
Published: September 2022

Radiation enteritis (Re) is one of the most common complications of radiation therapy for abdominal tumors. The efficacy of cancer treatment by radiation is often limited by the side effects of Re. Re can be acute or chronic. Treatment of acute Re is essentially symptomatic. However, chronic Re usually requires surgical procedures. The underlying mechanisms of Re are complex and have not yet been elucidated. The purpose of this review is to provide an overview of the pathogenesis of Re. We reviewed the role of intestinal epithelial cells, intestinal stem cells (ISCs), vascular endothelial cells (ECs), intestinal microflora, and other mediators of Re, noting that a better understanding of the pathogenesis of Re may lead to better treatment modalities.
Cost-effectiveness analysis of adjuvant therapy with atezolizumab in Chinese patients with stage IB-IIIA resectable NSCLC after adjuvant chemotherapy
Authors: Chen Ping , Yang Qing , Li Yinfeng , Jing Xiaomei , Chen Jing
Published: September 2022

Background

Atezolizumab was first shown to significantly improve progression-free survival (PFS) after platinum-based chemotherapy in early-stage non-small cell lung cancer (NSCLC) in the IMpower010 Phase 3 trial. However, the cost-effectiveness and potential economic impact of atezolizumab treatment in Chinese patients are unknown.

Methods

Markov models were constructed based on follow-up data from the IMpower010 trial and assessed separately in the programmed cell death receptor ligand-1 (PD-L1) tumor cells (TC) ≥ 1% stage II – IIIA group, all stage II – IIIA groups, and the intention-to-treat (ITT) group (stage IB–IIIA). Efficacy and safety data were obtained from the IMpower010 trial, and costs and utility values were derived from the literature and local surveys to estimate their incremental cost-effectiveness ratios (ICERs) compared with willingness-to-pay (WTP) thresholds in scenarios implementing patient assistance programs (PAP) or drug price negotiations. Univariate sensitivity analysis and probabilistic sensitivity analysis (PSA) were performed to investigate the stability of the model results.

Results

Compared with best supportive care (BSC), atezolizumab produced an additional 0.45 quality-adjusted life-years (QALYs), 0.04 QALYs, and -0.0028 QALYs in the PD-L1 TC ≥ 1% stage II – IIIA group, all stage II – IIIA groups, and the ITT group, and the ICERs were 108,825.37/QALY, 1,028,538.22/QALY, and -14,381,171.55/QALY, respectively. The ICERs all exceeded the WTP threshold of $27,354 per QALY (three times the per capita gross domestic product of China in 2022), and univariate sensitivity analysis showed that the price of atezolizumab played a crucial role in the model results. PSA showed that the probability of cost-effectiveness of atezolizumab in the PD-L1 TC ≥ 1% stage II – IIIA group, all stage II – IIIA groups, and the ITT group increased with the increasing WTP threshold.

Conclusion

From the perspective of China’s health care system, in the PD-L1 TC ≥ 1% stage II – IIIA group, all stage II – IIIA groups, and the ITT group, the use of atezolizumab in the adjuvant treatment of patients with early-stage NSCLC after platinum-based chemotherapy is unlikely to be cost-effective. The implementation of PAP or price reduction negotiations for atezolizumab might be among the most effective measures to improve its cost-effectiveness.
Immunotherapies of retinoblastoma: Effective methods for preserving vision in the future
Authors: Wang Ling , Li Shixu , Mei Jun , Ye Lin
Published: September 2022

Retinoblastoma is the most common intraocular tumor in children. Patients can be cured by enucleation, but it can lead to vision loss. Chemotherapy is the main method of treatment for RB currently. Unfortunately, chemoresistant and tumor metastasis often happen, resulting in a relatively poor prognosis. Therefore, immunotherapy becomes one of the optimal choices. Targeting not only tumor cells but also the active tumor microenvironment is a novel strategy for RB treatment. Here, we conclude several potential targets for RB immunotherapy, including gangliosides GD2, PD-1 and PD-L1, B7H3, EpCAM and SYK. We also review the techniques for CART, bispecific antibodies and genetically modified Dendritic cells according to the characteristics of different targets and discuss the feasibility of immunotherapy with different targets.
Efficacy and safety of neoadjuvant immunotherapy combined with chemotherapy in locally advanced esophageal cancer: A meta-analysis
Authors: Wang Jincheng , Zhang Kun , Liu Tianzhou , Song Ying , Hua Peiyan , Chen Shu , Li Jindong , Liu Yang , Zhao Yinghao
Published: September 2022

Objective

The progress of neoadjuvant therapy for resectable locally advanced esophageal cancer has been stagnant. There has been much progress in immunotherapy for advanced esophageal cancer, but the efficacy and safety of neoadjuvant immunotherapy for resectable locally advanced esophageal cancer have not yet been definitively demonstrated.

Methods

Original articles describing the safety and efficacy of neoadjuvant immunotherapy in resectable locally advanced esophagus published until July 2022 were retrieved from PubMed, Embase, and the Cochrane Library. The ratio (OR) and 95% confidence interval (CI) were calculated to conduct heterogeneity and subgroup analysis.

Results

In total, 759 patients from 21 studies were enrolled. The effectiveness of neoadjuvant immunotherapy in combination with chemotherapy was evaluated using the major pathologic response (MPR) and pathologic complete response (PCR). In the enrolled patients, 677 were treated surgically and 664 achieved R0 resection. Major pathological remission was achieved in 52.0% (95% CI: 0.44–0.57) of patients on neoadjuvant immunotherapy combined with chemotherapy and complete pathological remission in 29.5% (95% CI: 0.25–0.32) of patients. The safety was primarily assessed by the incidence of treatment-related adverse events (TRAEs) and surgical resection rates. The incidence of TRAEs and the surgical resection rate combined ORs were 0.15 (95% CI: 0.09–0.22) and 0.86 (95% CI: 0.83–0.89), respectively.

Conclusion

Neoadjuvant immunotherapy combined with chemotherapy in locally advanced resectable esophageal cancer is effective and safe.
Molecular characteristics, clinical significance, and cancer immune interactions of cuproptosis and ferroptosis-associated genes in colorectal cancer
Authors: Li Yang , Wang Ru-yao , Deng Yu-jiao , Wu Shao-hua , Sun Xinti , Mu Hong
Published: September 2022

Objective

To systematically analyze the expression of cuproptosis and ferroptosis genes and their impact on the development, prognosis, tumor microenvironment (TME), and treatment response in colorectal cancer (CRC) patients

Methods

We systematically evaluated 33 cuproptosis and ferroptosis-related genes and comprehensively identified the correlations between cuproptosis and ferroptosis-related genes and transcriptional patterns, prognosis, and clinical features. Three distinct subgroups were identified in CRC using the TCGA database and the GEO database. We next assessed the relationship between the molecular features, prognostic significance, and clinical indicators of the prognostic genes in the cuproptosis and ferroptosis-related gene clusters. In addition, a PAC_score, which accurately predicted the prognosis of CRC patients and the efficacy of immunomodulatory mAbs, was obtained.

Results

Patients in the low expression group (low expression of cuproptosis and ferroptosis-related genes) had a longer survival compared to the high expression group. We identified two distinct prognosis-associated molecular subtypes and observed an association between clinical information and prognosis. The enrichment analysis of differential genes associated with prognosis showed that the main enrichment was related to biological processes such as metastasis and metabolism. Next, the PCA_score for predicting overall survival (OS) was established and its reliable predictive value in CRC patients was confirmed. Furthermore, highly reliable nomogram was created to facilitate the clinical feasibility of the PCA_score. It was found that the immunomodulatory mAbs, PD-L1 and CTLA4 were highly expressed in the low PCA_score score group with statistically significance.

Conclusion

Overall, the PCA scores of prognostic differential genes in the cuproptosis and ferroptosis-related gene clusters were strongly associated with clinical characteristics, prognosis, and immunotherapy in CRC patients. This data may promote further exploration of more effective immunotherapy strategies for CRC.
OIT3 serves as a novel biomarker of hepatocellular carcinoma by mediating ferroptosis via regulating the arachidonic acid metabolism
Authors: Wen Jie , Aili Abudureyimujiang , Yan Yao Xue , Lai YuLin , Niu Shaoqing , He Shasha , Zhang Xiaokai , Zhang Guixiong , Li Jiaping
Published: September 2022

Background

Oncoprotein-Induced Transcript 3 Protein (OIT3) was identified as a liver-specific gene with abnormal expression in hepatocellular carcinoma (HCC). Herein, we aimed to examine the function and specific mechanism of OIT3 in HCC.

Methods

Bioinformatic analyses and tissue microarray via immunohistochemistry were used to validate the expression of OIT3 in HCC. The biofunctions of OIT3 in HCC were determined in vitro and in vivo. The mechanism was confirmed by RNA-Sequence and Western blotting. The uni- and multivariate analyses were used to identify the independent predictors for HCC.

Results

Low expression of OIT3 was observed in HCC and predicted a poor clinical outcome. Ectopic expression of OIT3 could inhibit the proliferation, migration, and invasion abilities of HCC cells. Mechanistically, OIT3 upregulated the expression of ALOX15 and CYP4F3, thus inducing arachidonic acid increase, ROS accumulation, and lipid peroxidation, and eventually causing ferroptosis. OIT3 was validated as a prognostic predictor for HCC patients.

Conclusions

Our findings revealed a novel role of OIT3 in the process of tumorigenesis of HCC. OIT3 inhibited reproliferation, migration, and invasion of HCC cells by triggering ferroptosis, which indicates that OIT3 could serve as a potential biomarker in HCC.
Evaluation of the potential of ultrasound-mediated drug delivery for the treatment of ovarian cancer through preclinical studies
Authors: Wang Yi-Chao , Tian Jing-Yan , Han Ying-Ying , Liu Yun-Fei , Chen Si-Yao , Guo Feng-Jun
Published: September 2022

Ovarian cancer (OC) has the greatest mortality rate among gynecological cancers, with a five-year survival rate of <50%. Contemporary adjuvant chemotherapy mostly fails in the case of OCs that are refractory, metastatic, recurrent, and drug-resistant. Emerging ultrasound (US)-mediated technologies show remarkable promise in overcoming these challenges. Absorption of US waves by the tissue results in the generation of heat due to its thermal effect causing increased diffusion of drugs from the carriers and triggering sonoporation by increasing the permeability of the cancer cells. Certain frequencies of US waves could also produce a cavitation effect on drug-filled microbubbles (MBs, phospholipid bilayers) thereby generating shear force and acoustic streaming that could assist drug release from the MBs, and promote the permeability of the cell membrane. A new class of nanoparticles that carry therapeutic agents and are guided by US contrast agents for precision delivery to the site of the ovarian tumor has been developed. Phase-shifting of nanoparticles by US sonication has also been engineered to enhance the drug delivery to the ovarian tumor site. These technologies have been used for targeting the ovarian cancer stem cells and protein moieties that are particularly elevated in OCs including luteinizing hormone-releasing hormone, folic acid receptor, and vascular endothelial growth factor. When compared to healthy ovarian tissue, the homeostatic parameters at the tissue microenvironment including pH, oxygen levels, and glucose metabolism differ significantly in ovarian tumors. US-based technologies have been developed to take advantage of these tumor-specific alterations for precision drug delivery. Preclinical efficacy of US-based targeting of currently used clinical chemotherapies presented in this review has the potential for rapid human translation, especially for formulations that use all substances that are deemed to be generally safe by the U.S. Food and Drug Administration.
Clinical course and role of embolization in patients with spontaneous rupture of hepatocellular carcinoma
Authors: Park Juil , Jeong Yun Soo , Suh Yun Seok , Kim Hyo-Cheol , Chung Jin Wook , Choi Jin Woo
Published: September 2022

Background

A diverse clinical course after the spontaneous rupture of hepatocellular carcinoma (HCC) renders nonstandardized treatment protocols.

Purpose

To evaluate clinical course and role of transcatheter arterial embolization (TAE) in patients with rupture of HCC.

Materials and methods

This retrospective study included 127 patients who were treated for ruptured HCC at single institution between 2005 and 2014. After multidisciplinary discussion, patients underwent medical management, TAE, emergency surgery or staged surgery. Patients were retrospectively divided into two groups based on the intent of treatment: curative and palliative. The rebleeding rate and 1-month and overall survival (OS) were compared between two groups. The incidence and survival of patients with intraperitoneal drop metastasis (IPDM) were also analyzed.

Results

The overall rebleeding rate in patients who underwent TAE was 3.1% (3/96). One-month mortality rate was 6.3% (8/127). The rebleeding and 1-month mortality rates were not significantly different between two groups. OS was significantly higher in the curative treatment group (median: 12.0 vs 2.2 months,p<0.001). Among 96 patients who initially received TAE, ten patients underwent staged operation (10.4%). The median OS for medical management, TAE, emergency surgery and staged surgery was 2.8, 8.7, 19.1 and 71.1 months, respectively. Of all patients, 15.2% developed IPDM mostly within 1 year and their survival was poorer than that of patients without IPDM (median: 6.3 vs. 15.1 months,p<0.001).

Conclusion

TAE provided effective immediate hemostasis with a low rebleeding rate and may serve as a bridge to elective surgery. IPDM frequently occurred within 1 year and manifested poor survival; thus, close surveillance should be considered for patients with spontaneous rupture of HCC.
Immunomodulatory and anti-inflammatory therapeutic potential of gingerols and their nanoformulations
Authors: Yücel Çiğdem , Karatoprak Gökçe Şeker , Açıkara Özlem Bahadır , Akkol Esra Küpeli , Barak Timur Hakan , Sobarzo-Sánchez Eduardo , Aschner Michael , Shirooie Samira
Published: September 2022

Ginger (Zingiber officinale Roscoe), a member of the Zingiberaceae family, is one of the most popular spices worldwide, known since ancient times, and used both as a spice and a medicinal plant. The phenolic compounds found in ginger are predominantly gingerols, shogaols, and paradols. Gingerols are the major phenolic compounds found in fresh ginger and contain mainly 6-gingerol as well as 4-, 5-, 8-, 10-, and 12-gingerols. Gingerols possess a wide array of bioactivities, such as antioxidant and anticancer, among others. Regarding the different array of biological activities and published data on the mechanisms underlying its action, the complex interaction between three key events, including inflammation, oxidative stress, and immunity, appears to contribute to a plethora of pharmacological activities of this compound. Among these, the immunomodulatory properties of these compounds, which attract attention due to their effects on the immune system, have been the focus of many studies. Gingerols can alleviate inflammation given their ability to inhibit the activation of protein kinase B (Akt) and nuclear factor kappa B (NF-κB) signaling pathways, causing a decrease in proinflammatory and an increase in anti-inflammatory cytokines. However, given their low bioavailability, it is necessary to develop new and more effective strategies for treatment with gingerols. In order to overcome this problem, recent studies have addressed new drug delivery systems containing gingerols. In this review, the immunomodulatory activities of gingerol and its underlying mechanisms of action combined with the contributions of developed nanodrug delivery systems to this activity will be examined.
Thyroid hormone-dependent oligodendroglial cell lineage genomic and non-genomic signaling through integrin receptors
Authors: Emamnejad Rahimeh , Dass Mary , Mahlis Michael , Bozkurt Salome , Ye Sining , Pagnin Maurice , Theotokis Paschalis , Grigoriadis Nikolaos , Petratos Steven
Published: September 2022

Multiple sclerosis (MS) is a heterogeneous autoimmune disease whereby the pathological sequelae evolve from oligodendrocytes (OLs) within the central nervous system and are targeted by the immune system, which causes widespread white matter pathology and results in neuronal dysfunction and neurological impairment. The progression of this disease is facilitated by a failure in remyelination following chronic demyelination. One mediator of remyelination is thyroid hormone (TH), whose reliance on monocarboxylate transporter 8 (MCT8) was recently defined. MCT8 facilitates the entry of THs into oligodendrocyte progenitor cell (OPC) and pre-myelinating oligodendrocytes (pre-OLs). Patients with MS may exhibit downregulated MCT8 near inflammatory lesions, which emphasizes an inhibition of TH signaling and subsequent downstream targeted pathways such as phosphoinositide 3-kinase (PI3K)-Akt. However, the role of the closely related mammalian target of rapamycin (mTOR) in pre-OLs during neuroinflammation may also be central to the remyelination process and is governed by various growth promoting signals. Recent research indicates that this may be reliant on TH-dependent signaling through β1-integrins. This review identifies genomic and non-genomic signaling that is regulated through mTOR in TH-responsive pre-OLs and mature OLs in mouse models of MS. This review critiques data that implicates non-genomic Akt and mTOR signaling in response to TH-dependent integrin receptor activation in pre-OLs. We have also examined whether this can drive remyelination in the context of neuroinflammation and associated sequelae. Importantly, we outline how novel therapeutic small molecules are being designed to target integrin receptors on oligodendroglial lineage cells and whether these are viable therapeutic options for future use in clinical trials for MS.
Apple pectin-based Zataria multiflora essential oil (ZEO) nanoemulsion: An approach to enhance ZEO DNA damage induction in breast cancer cells as in vitro and in silico studies reveal
Authors: Salehi Fahimeh , Behboudi Hossein , Salehi Elaheh , Ardestani Sussan K. , Piroozmand Firoozeh , Kavoosi Gholamreza
Published: September 2022

Zataria multiflora essential oil (ZEO) is a natural complex of compounds with a high apoptotic potential against breast cancer cells and minor toxicity toward normal cells; however, similar to many essential oils, ZEO utilization in pharmaceutical industries has limitations due to its labile and sensitive ingredients. Nanoemulsification based on natural polymers is one approach to overcome this issue. In this study, an apple pectin-ZEO nanoemulsion (AP-ZEONE) was prepared and its morphology, FTIR spectra, and physical properties were characterized. Furthermore, it was shown that AP-ZEONE substantially suppresses the viability of MDA-MB-231, T47D, and MCF-7 breast cancer cells. AP-ZEONE significantly induced apoptotic morphological alterations and DNA fragmentation as confirmed by fluorescent staining and TUNEL assay. Moreover, AP-ZEONE induced apoptosis in MDA-MB-231 cells by loss of mitochondrial membrane potential (ΔΨm) associated with the accumulation of reactive oxygen species (ROS), G2/M cell cycle arrest, and DNA strand breakage as flow cytometry, DNA oxidation, and comet assay analysis revealed, respectively. Spectroscopic and computational studies also confirmed that AP-ZEONE interacts with genomic DNA in a minor groove/partial intercalation binding mode. This study demonstrated the successful inhibitory effect of AP-ZEONE on metastatic breast cancer cells, which may be beneficial in the therapy process.
Regulatory mechanisms of tetramethylpyrazine on central nervous system diseases: A review
Authors: Liu Yue , Yang Guang , Cui Wenqiang , Zhang Yunling , Liang Xiao
Published: September 2022

Central nervous system (CNS) diseases can lead to motor, sensory, speech, cognitive dysfunction, and sometimes even death. These diseases are recognized to cause a substantial socio-economic impact on a global scale. Tetramethylpyrazine (TMP) is one of the main active ingredients extracted from the Chinese herbal medicine Ligusticum striatum DC. (Chuan Xiong). Many in vivo and in vitro studies have demonstrated that TMP has a certain role in the treatment of CNS diseases through inhibiting calcium ion overload and glutamate excitotoxicity, anti-oxidative/nitrification stress, mitigating inflammatory response, anti-apoptosis, protecting the integrity of the blood-brain barrier (BBB) and facilitating synaptic plasticity. In this review, we summarize the roles and mechanisms of action of TMP on ischemic cerebrovascular disease, spinal cord injury, Parkinson’s disease, Alzheimer’s disease, cognitive impairments, migraine, and depression. Our review will provide new insights into the clinical applications of TMP and the development of novel therapeutics.
Pancreatic injury following immune checkpoint inhibitors: A systematic review and meta-analysis
Authors: Zhang Tian , Wang Yi , Shi Chunhui , Liu Xiaochun , Lv Shangbin , Wang Xin , Li Weihong
Published: September 2022

Background: Pancreatic injury (pancreatitis, amylase/lipase elevation) is a rare adverse event of immune checkpoint inhibitors (ICIs). With the high number of clinical studies on ICIs, the incidence and characteristics of associated pancreatic injury (PI) need to be reevaluated.

Methods: A systematic review and meta-analysis was conducted to assess the incidence of PI in cancer patients who received ICIs in randomized controlled trials (RCTs). PubMed, Embase, the ASCO, ESMO, and AACR conference proceedings before 1 April 2022, were investigated for relevant research.

Results: 50 RCTs involving 35,223 patients were included. The incidence of ICIs-PI was 2.22% (95% CI = 1.94%–2.53%). The incidence of PI was 3.76% (95% CI = 1.84–7.67%) when combining two ICIs, which was higher than single ICIs [2.25% (95% CI = 1.91–2.65%)]. The ICIs were ranked from high to low based on PI incidence: PD-L1 inhibitors 3.01% (95% CI = 1.86–4.87%), CTLA-4 inhibitors 2.92% (95% CI = 0.99–8.65%) and PD-1 Inhibitor 2% (95% CI = 1.67–2.39%). The ICI with the highest rate of PI was pembrolizumab 7.23.% (95% CI = 1.69–30.89%). In addition, the incidence of severe ICIs-PI was 2.08% (95% CI = 1.76–2.46%); and the incidence of severe PI was 2.32% (95% CI = 1.76–3.06%) when combining two ICIs, which was higher than single ICI [1.95% (95% CI = 1.58–2.41%)]. The ICIs were ranked from high to low according to the incidence of severe PI: PD-L1 inhibitors 3.1% (95% CI = 1.7–5.64%), CTLA-4 inhibitors 2.69% (95% CI = 0.76–9.49%), PD-1 inhibitors 1.80% (95% CI = 1.41–2.29%).

Conclusion: Treatment with multiple ICIs result in a higher incidence of PI compared to single ICIs, irrespective of the grade of pancreatic injury. The incidence of PI caused by PD-L1 inhibitors is higher than that of CTLA-4 inhibitors and PD-1 Inhibitor, and Pembrolizumab has the highest rate of ICIs-PI. Although the incidence of ICIs-PI is not high, they are usually severe (≥ grade 3 events).