bluuebunny/crossref_metadata_2025 huggingface dataset:
Honeycomb-like Structured Film, a Novel Therapeutic Device, Suppresses Tumor Growth in an In Vivo Ovarian Cancer Model
Authors: Ohta Tsuyoshi , Tanaka Masaru , Taki Seitaro , Nakagawa Hiroyuki , Nagase Satoru
Published: January 2023

Ovarian cancer cell dissemination can lead to the mortality of patients with advanced ovarian cancer. Complete surgery for no gross residual disease contributes to a more favorable prognosis than that of patients with residual disease. HCFs have highly regular porous structures and their 3D porous structures act as scaffolds for cell adhesion. HCFs are fabricated from biodegradable polymers and have been widely used in tissue engineering. This study aimed to show that HCFs suppress tumor growth in an in vivo ovarian cancer model. The HCF pore sizes had a significant influence on tumor growth inhibition, and HCFs induced morphological changes that rounded out ovarian cancer cells. Furthermore, we identified gene ontology (GO) terms and clusters of genes downregulated by HCFs. qPCR analysis demonstrated that a honeycomb structure downregulated the expression of CXCL2, FOXC1, MMP14, and SNAI2, which are involved in cell proliferation, migration, invasion, angiogenesis, focal adhesion, extracellular matrix (ECM), and epithelial–mesenchymal transition (EMT). Collectively, HCFs induced abnormal focal adhesion and cell morphological changes, subsequently inhibiting the differentiation, proliferation and motility of ovarian cancer cells. Our data suggest that HCFs could be a novel device for inhibiting residual tumor growth after surgery, and could reduce surgical invasiveness and improve the prognosis for patients with advanced ovarian cancer.
Long-Term Outcomes of Endoscopic Submucosal Dissection for Colorectal Epithelial Neoplasms: A Systematic Review
Authors: Nishizawa Toshihiro , Ueda Takashi , Ebinuma Hirotoshi , Toyoshima Osamu , Suzuki Hidekazu
Published: January 2023

In this review, we summarize up-to-date reports with five-year observation after colorectal endoscopic submucosal dissection (ESD). Five-year cause-specific survival rates ranged from 98.6 to 100%. The local recurrence rates ranged from 1.1 to 2.2% in complete resection and 7.5 to 25.0% in incomplete resection. Incomplete resection was a risk factor for local recurrence. In non-curative ESD, five-year cause-specific survival rates ranged from 93.8 to 100% with additional surgery, and 92.7 to 99.1% without surgery. The choice of additional surgery should be based on the individual patient’s age, concomitant diseases, wishes, life expectancy, and the risk of lymph node metastasis. The metachronous cancer rates ranged from 0.22 to 1.1%. Both local recurrence and metachronous tumors should be checked with a follow-up colonoscopy after ESD.
MiRNAs and snoRNAs in Bone Metastasis: Functional Roles and Clinical Potential
Authors: Puppo Margherita , Jaafar Mariam , Diaz Jean-Jacques , Marcel Virginie , Clézardin Philippe
Published: January 2023

Bone is a frequent site of metastasis. Bone metastasis is associated with a short-term prognosis in cancer patients, and current treatments aim to slow its growth, but are rarely curative. Thus, revealing molecular mechanisms that explain why metastatic cells are attracted to the bone micro-environment, and how they successfully settle in the bone marrow—taking advantage over bone resident cells—and grow into macro-metastasis, is essential to propose new therapeutic approaches. MicroRNAs and snoRNAs are two classes of small non-coding RNAs that post-transcriptionally regulate gene expression. Recently, microRNAs and snoRNAs have been pointed out as important players in bone metastasis by (i) preparing the pre-metastatic niche, directly and indirectly affecting the activities of osteoclasts and osteoblasts, (ii) promoting metastatic properties within cancer cells, and (iii) acting as mediators within cells to support cancer cell growth in bone. This review aims to highlight the importance of microRNAs and snoRNAs in metastasis, specifically in bone, and how their roles can be linked together. We then discuss how microRNAs and snoRNAs are secreted by cancer cells and be found as extracellular vesicle cargo. Finally, we provide evidence of how microRNAs and snoRNAs can be potential therapeutic targets, at least in pre-clinical settings, and how their detection in liquid biopsies can be a useful diagnostic and/or prognostic biomarker to predict the risk of relapse in cancer patients.
Prognostic Role of Neutrophil-to-Lymphocyte Ratio (NLR), Lymphocyte-to-Monocyte Ratio (LMR), Platelet-to-Lymphocyte Ratio (PLR) and Lymphocyte-to-C Reactive Protein Ratio (LCR) in Patients with Hepatocellular Carcinoma (HCC) undergoing Chemoembolizations (TACE) of the Liver: The Unexplored Corner Linking Tumor Microenvironment, Biomarkers and Interventional Radiology
Authors: Minici Roberto , Siciliano Maria Anna , Ammendola Michele , Santoro Rita Carlotta , Barbieri Vito , Ranieri Girolamo , Laganà Domenico
Published: January 2023

TACE plays a pivotal role in hepatocellular carcinoma, from disease control to downstaging and bridging to liver transplant. Response to TACE is a surrogate marker of tumor aggressive biology, with manifold practical implications such as survival, the need for more aggressive treatments in the intermediate stage, the selection of patients on the transplant waiting list, the dropout rate from the transplant list and the post-transplant recurrence rate. Inflammation-based scores are biomarkers of the relationship between the tumor stromal microenvironment and the immune response. Investigating the connection among the tumor stromal microenvironment, biomarkers, and the response to TACE is crucial to recognize TACE refractoriness/failure, thus providing patients with tailored therapeutics. This review aims to provide a comprehensive overview of the prognostic roles of the neutrophil-to-lymphocyte ratio (NLR), the lymphocyte-to-monocyte ratio (LMR), the platelet-to-lymphocyte ratio (PLR), and the lymphocyte-to-C reactive protein ratio (LCR) in patients with HCC undergoing chemoembolization of the liver. Inflammation-based scores may be convenient, easily obtained, low-cost, and reliable biomarkers with prognostic significance for HCC undergoing TACE. Baseline cut-off values differ between various studies, thus increasing confusion about using of inflammation-based scores in clinical practice. Further investigations should be conducted to establish the optimal cut-off values for inflammation-based scores, consolidating their use in clinical practice.
Increasing Dosage of Leucovorin Results in Pharmacokinetic and Gene Expression Differences When Administered as Two-Hour Infusion or Bolus Injection to Patients with Colon Cancer
Authors: Taflin Helena , Odin Elisabeth , Carlsson Göran , Gustavsson Bengt , Wettergren Yvonne , Bexe Lindskog Elinor
Published: January 2023

The combination of 5-fluorouracil (5-FU) and leucovorin (LV) forms the chemotherapy backbone for patients with colorectal cancer. However, the LV administration is often standardized and not based on robust scientific data. To address these issues, a randomized pharmacokinetics study was performed in patients with colon cancer. Thirty patients were enrolled, receiving 60, 200 or 500 mg/m2 LV as a single two-hour infusion. Blood, tumor, mucosa, and resection margin biopsies were collected. Folate concentrations were analyzed with LC-MS/MS and gene expression with qPCR. Data from a previous study where patients received LV as bolus injections were used as comparison. Saturation of methylenetetrahydrofolate (MeTHF) and tetrahydrofolate (THF) levels was seen after two-hour infusion and polyglutamated MeTHF + THF levels in tumors decreased with increasing LV dosage. The decrease was associated with decreased FPGS and increased GGH expression, which was not observed after LV bolus injection. In the bolus group, results indicate activation of a metabolic switch possibly promoting TYMS inhibition in response to 5-FU. Different metabolic mechanisms appear to be induced when LV is administered as infusion and bolus injection. Since maximal inhibition of TYMS by the 5-FU metabolite 5-fluoro-2′-deoxyuridine 5′-monophosphate (FdUMP) requires excess polyglutamated MeTHF, the results point in favor of the bolus regimen.
Towards Novel Gene and Cell Therapy Approaches for Cervical Cancer
Authors: Polten Robert , Kutle Ivana , Hachenberg Jens , Klapdor Rüdiger , Morgan Michael , Schambach Axel
Published: January 2023

Cervical cancer is one of the most common malignancies in women, and the majority of cases are caused by infection with high-risk human papilloma virus (HPV) subtypes. Despite effective preventative measures, such as vaccinations against HPV, over 300,000 women die world-wide from cervical cancer each year. Once cervical cancer is diagnosed, treatment may consist of radial hysterectomy, or chemotherapy and radiotherapy, or a combination of therapies dependent upon the disease stage. Unfortunately, overall prognosis for patients with metastatic or recurrent disease remains poor. In these cases, immunotherapies may be useful based on promising preclinical work, some of which has been successfully translated to the clinic. For example, approaches using monoclonal antibodies directed against surface proteins important for control of immune checkpoints (i.e., immune checkpoint inhibitors) were shown to improve outcome in many cancer settings, including cervical cancer. Additionally, initial clinical studies showed that application of cytotoxic immune cells modified to express chimeric antigen receptors (CAR) or T cell receptors (TCR) for better recognition and elimination of tumor cells may be useful to control cervical cancer. This review explores these important topics, including strengths and limitations of standard and developing approaches, and how some novel treatment strategies may be optimally used to offer the best possible treatment for cervical cancer patients.
Barriers to Early Presentation amongst Rural Residents Experiencing Symptoms of Colorectal Cancer: A Qualitative Interview Study
Authors: Dobson Christina , Deane Jennifer , Macdonald Sara , Murchie Peter , Ellwood Christina , Angell Lorraine , Rubin Greg
Published: January 2023

Rural cancer inequalities are evident internationally, with rural cancer patients 5% less likely to survive than their urban counterparts. There is evidence to suggest that diagnostic delays prior to entry into secondary care may be contributing to these poorer rural cancer outcomes. This study explores the symptom appraisal and help-seeking decision-making of people experiencing symptoms of colorectal cancer in rural areas of England. Patients were randomly invited from 4 rural practices, serving diverse communities. Semi-structured interviews were undertaken with 40 people who had experienced symptoms of colorectal cancer in the preceding 8 weeks. Four key themes were identified as influential in participants’ willingness and timeliness of consultation: a desire to rule out cancer (facilitator of help-seeking); stoicism and self-reliance (barrier to help-seeking); time scarcity (barrier to help-seeking); and GP/patient relationship (barrier or facilitator, depending on perceived strength of the relationship). Self-employed, and “native” rural residents most commonly reported experiencing time scarcity and poor GP/patient relationships as a barrier to (re-)consultation. Targeted, active safety-netting approaches, and increased continuity of care, may be particularly beneficial to expedite timely diagnoses and minimise cancer inequalities for rural populations.
Tumor Microenvironment before and after Chemoradiation in Locally Advanced Rectal Cancer: Beyond PD-L1
Authors: Tayshetye Pritam , Friday Andrew J. , Omstead Ashten N. , Verma Tanvi , Miller Stacey , Zheng Ping , Jani Prashant , Zaidi Ali , Finley Gene
Published: January 2023

Background: In locally advanced rectal cancer treatment, neoadjuvant concurrent chemoradiation therapy (cCRT) is the standard of care. The tumor microenvironment (TME) is a complex entity comprising of tumor cells, immune cells and surrounding stroma and is closely associated with tumor growth and survival, response to antitumor therapies and also resistance to treatment. We aimed to assess the change in biomarkers associated with TME following standard neoadjuvant cCRT in rectal cancer. Methods: We accessed archival tissue from rectal cancer patients treated with neoadjuvant cCRT at Allegheny Health Network (AHN) facilities over the past 14 years. Pre-treatment and post-treatment biopsies were assayed for PD-L1, CD8+ T-cells, CXCL9, TIM-3, IDO-1, IFN-G, IL17RE, LAG-3, and OX40 in 41 patients. Results: We found statistically significant upregulation in multiple biomarkers namely CD8, IL17RE, LAG3 and OX40 post neoadjuvant cCRT and a trend towards upregulation, although not statistically significant, in biomarkers PD-L1, CXCL9, TIM-3, IDO-1 and IFN-G expression. Conclusions: This provides a glimpse into the TME before and after neoadjuvant cCRT. We suggest that the biomarkers noted to be upregulated could be used for designing appropriate clinical trials and development of therapeutic targeted drug therapy in an effort to achieve better response to neoadjuvant therapy, increasing clinical and pathological complete response rates and improved overall outcomes.
Differentiating Ductal Adenocarcinoma of the Pancreas from Benign Conditions Using Routine Health Records: A Prospective Case-Control Study
Authors: Zardab Mohamed , Balarajah Vickna , Banerjee Abhirup , Stasinos Konstantinos , Saad Amina , Imrali Ahmet , Hughes Christine , Roberts Rhiannon , Vajrala Ajith , Chelala Claude , Kocher Hemant M. , Dayem Ullah Abu Z. M.
Published: January 2023

The study aimed to develop a prediction model for differentiating suspected PDAC from benign conditions. We used a prospective cohort of patients with pancreatic disease (n = 762) enrolled at the Barts Pancreas Tissue Bank (2008-2021) and performed a case-control study examining the association of PDAC (n = 340) with predictor variables including demographics, comorbidities, lifestyle factors, presenting symptoms and commonly performed blood tests. Age (over 55), weight loss in hypertensive patients, recent symptoms of jaundice, high serum bilirubin, low serum creatinine, high serum alkaline phosphatase, low red blood cell count and low serum sodium were identified as the most important features. These predictors were then used for training several machine-learning-based risk-prediction models on 75% of the cohort. Models were assessed on the remaining 25%. A logistic regression-based model had the best overall performance in the validation cohort (area-under-the-curve = 0.90; Spiegelhalter’s z = −1·82, p = 0.07). Setting a probability threshold of 0.15 guided by the maximum F2-score of 0.855, 96.8% sensitivity was reached in the full cohort, which could lead to earlier detection of 84.7% of the PDAC patients. The prediction model has the potential to be applied in primary, secondary and emergency care settings for the early distinction of suspected PDAC patients and expedited referral to specialist hepato-pancreatico-biliary services.
Gene Expression Profiling Elucidates Cellular Responses to NCX4040 in Human Ovarian Tumor Cells: Implications in the Mechanisms of Action of NCX4040
Authors: Sinha Birandra K. , Tokar Erik J. , Li Jianying , Bushel Pierre R.
Published: January 2023

The nitric oxide donor, NCX4040 is a non-steroidal anti-inflammatory-NO donor and has been shown to be extremely cytotoxic to a number of human tumors, including ovarian tumors cells. We have found that NCX4040 is cytotoxic against both OVCAR-8 and its adriamycin-selected OVCAR-8 variant (NCI/ADR-RES) tumor cell lines. While the mechanism of action of NCX4040 is not entirely clear, we as well as others have shown that NCX4040 generates reactive oxygen species (ROS) and induces DNA damage in tumor cells. Recently, we have reported that NCX4040 treatment resulted in a significant depletion of cellular glutathione, and formation of both reactive oxygen and nitrogen species (ROS/RNS), resulting in oxidative stress in these tumor cells. Furthermore, our results indicated that more ROS/RNS were generated in OVCAR-8 cells than in NCI/ADR-RES cells due to increased activities of superoxide dismutase (SOD), glutathione peroxidase and transferases expressed in NCI/ADR-RES cells. Further studies suggested that NCX4040-induced cell death may be mediated by peroxynitrite formed from NCX4040 in cells. In this study we used microarray analysis following NCX4040 treatment of both OVCAR-8 and its ADR-resistant variant to identify various molecular pathways involved in NCX4040-induced cell death. Here, we report that NCX4040 treatment resulted in the differential induction of oxidative stress genes, inflammatory response genes (TNF, IL-1, IL-6 and COX2), DNA damage response and MAP kinase response genes. A mechanism of tumor cell death is proposed based on our findings where oxidative stress is induced by NCX4040 from simultaneous induction of NOX4, TNF-α and CHAC1 in tumor cell death.
Pathological Response Predicts Survival after Pancreatectomy following Neoadjuvant FOLFIRINOX for Pancreatic Cancer
Authors: Jeon Hyun Jeong , Jeong Hye Jeong , Lim Soo Yeun , Yoon So Jeong , Kim Hongbeom , Han In Woong , Heo Jin Seok , Shin Sang Hyun
Published: January 2023

Background: The clinical course of complete pathologic response (cPR) in pancreatic cancer after neoadjuvant chemotherapy is not well known. The aim of this study was to investigate the clinical course of patients according to pathological response, including cPR, who received only FOLIFIRNOX in advanced pancreatic cancer. Methods: Patients who underwent pancreatectomy after FOLFIRINOX for pancreatic ductal adenocarcinoma (PDAC) from 2017 to 2019 were retrospectively reviewed. cPR was defined as an absence of residual tumor on pathologic report. A nearly complete pathologic response (ncPR) was defined as a tumor confined to pancreas parenchyma, less than 1 cm without lymph-node metastasis. cPR and ncPR were assigned into a favorable pathologic response group (fPR). Kaplan–Meier method and Cox proportional hazard models were used for analysis. Results: Of a total 64 patients, 8 (12.5%) had a cPR and 8 (12.5%) had a ncPR. In the fPR group, median OS and DFS were superior to those of non-pathologic response group (more than 60 months vs. 38 months, p < 0.001; more than 42 months vs. 10 months, p < 0.001). On multivariable analyses, fPR and adjuvant therapy were independent prognostic factors for OS (HR: 0.12; 95% CI: 0.02–0.96, p = 0.05; HR: 0.26; 95% CI: 0.09–0.74, p = 0.01) and DFS (HR: 0.31; 95% CI: 0.12–0.86, p = 0.02; HR:0.31; 95% CI: 0.13–0.72, p = 0.01). Conclusions: pathologic response predicts survival after pancreatectomy following neoadjuvant FOLFIRINOX for pancreatic cancer, and adjuvant chemotherapy following neoadjuvant treatment might be beneficial for OS and DFS.
Catalytic Activation of Hydrogen Peroxide Using Highly Porous Hydrothermally Modified Manganese Catalysts for Removal of Azithromycin Antibiotic from Aqueous Solution
Authors: Hasanpour Fatemeh , Saien Javad , Norouzi Omid
Published: January 2023

Hydrogen peroxide catalytic activation holds great promise in the treatment of persistent pollutants. In this study, the novel Mn-Acacair/Al, Mn-Acacarg/Al and Mn-BTCarg/Al catalysts, supported on Al2O3, were applied for rapid hydrogen peroxide activation and azithromycin antibiotic removal. The catalysts were prepared by the calcination-hydrothermal method under air or argon atmosphere. The characterization confirmed that the modification of manganese with acetylacetonate and benzene-1,3,5-tricarboxylic acid (H3BTC) O-donor ligands highly improves the catalyst porosity, amorphousity, and abundance of coordinately unsaturated sites, which facilitate the generation of reactive oxygen species. The hydrogen peroxide activation and azithromycin removal reached 98.4% and 99.3% after 40 min using the Mn-BTCarg/Al catalyst with incredible stability and reusability. Only a 5.2% decrease in activity and less than 2% manganese releasing in solutions were detected after five regeneration cycles under the optimum operating conditions. The removal intermediates were identified by LC-MS/MS analysis, and the pathways were proposed. The hydroxylation and decarboxylation reactions play a key role in the degradation reaction.
Synthesis and Characterization of Ca-ALG/MgO/Ag Nanocomposite Beads for Catalytic Degradation of Direct Red Dye
Authors: Albalwi Hanan A.
Published: January 2023

Increased water pollution due to the tremendous increase of dye-containing effluent is still a serious problem which, in turn, adversely affects aquatic life and, consequently, the balance of our ecosystem. The aim of this research was to investigate whether Ca-ALG/MgO/Ag nanocomposite beads successfully prepared from calcium alginate hydrogels with MgO (Ca-ALG/MgO) doped with Ag nanoparticles (Ag NPs) caused effective degradation of Direct Red 83 dye. The formation of nanocomposite beads was confirmed by X-ray diffraction (XRD), Transmission Electron Microscope (TEM), Dynamic Light Scattering (DLS), and Energy Dispersive X-ray Analysis (EDX). The results from the EDX analysis proved that both MgO and Ag nanoparticles within the alginate beads network were present. This study also examines the effects of various operating parameters, such as the reducing agent, time of reaction, the concentration of the dye solution, and the catalyst dosage, which were examined and studied carefully to find the optimum degradation conditions. The kinetics and isothermal study revealed that the degradation process using Ca-ALG/MgO/Ag nanocomposite beads as a catalyst in the presence of sodium borohydride (NaBH4) as a reducing agent was the best fit for the pseudo-first-order model and the Temkin isotherm model. The results indicated that the optimum dosage of Ca-ALG/MgO/Ag was 0.3 g for a dye concentration of 50 mg/L, and equilibrium of the degradation process was attained at 340 min. Accordingly, it could be stated that the catalyst, Ca-ALG/MgO/Ag nanocomposite beads, is considered efficient for the degradation of Direct Red 83 dye. The degradation efficiency reached 95% approximately. Furthermore, after four runs of reuse, Ca-ALG/MgO/Ag nanocomposite beads exhibited excellent performance and long-term stability.
Microbial Lignocellulolytic Enzymes for the Effective Valorization of Lignocellulosic Biomass: A Review
Authors: Nargotra Parushi , Sharma Vishal , Lee Yi-Chen , Tsai Yung-Hsiang , Liu Yung-Chuan , Shieh Chwen-Jen , Tsai Mei-Ling , Dong Cheng-Di , Kuo Chia-Hung
Published: January 2023

The urgent demand for alternative energy sources has been sparked by the tremendous burden on fossil fuels and the resulting acute energy crisis and climate change issues. Lignocellulosic biomass is a copious renewable and alternative bioresource for the generation of energy fuels and biochemicals in biorefineries. Different pretreatment strategies have been established to overcome biomass recalcitrance and face technological challenges, such as high energy consumption and operational costs and environmental hazards, among many. Biological pretreatment using microbial enzymes is an environmentally benign and low-cost method that holds promising features in the effective pretreatment of lignocellulosic biomass. Due to their versatility and eco-friendliness, cellulases, hemicellulases, and ligninolytic enzymes have been recognized as “green biocatalysts” with a myriad of industrial applications. The current review provides a detailed description of different types of lignocellulolytic enzymes, their mode of action, and their prospective applications in the valorization of lignocellulosic biomass. Solid state fermentation holds great promise in the microbial production of lignocellulolytic enzymes owing to its energy efficient, environment friendly, and higher product yielding features utilizing the lignocellulosic feedstocks. The recent trends in the application of enzyme immobilization strategies for improved enzymatic catalysis have been discussed. The major bottlenecks in the bioprocessing of lignocellulosic biomass using microbial enzymes and future prospects have also been summarized.
Novel Bifunctional Nitrogen Doped MoS2/COF-C4N Vertical Heterostructures for Electrocatalytic HER and OER
Authors: Zhang Nan , Yang Zhaodi , Liu Wenshan , Zhang Fengming , Yan Hong
Published: January 2023

Highly active and earth-abundant catalysts for hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) play vital roles in developing efficient water splitting to produce hydrogen fuels. Here, we reported an effective strategy to fabricate a completely new nitrogen-doped MoS2/COF-C4N vertical heterojunction (N-MoS2/COF-C4N) as precious-metal-free bifunctional electrocatalysts for both HER and OER. Compared with MoS2 and COF-C4N, the obtained vertical N-MoS2/COF-C4N catalyst showed enhanced HER with a low overpotential of 106 mV at 10 mA cm−2, which is six times lower than MoS2. The superior acidic HER activity, molecular mechanism, and charge transfer characteristic of this vertical N-MoS2/COF-C4N were investigated experimentally and theoretically in detail. Its basic OER activity is almost equal to that of COF-C4N with an overpotential of 349 mV at 10 mA cm−2, which showed that the in-situ growing method maintains the exposure of the C active sites to the greatest extent. The preparation and investigation for vertical N-MoS2/COF-C4N provide ideas and a research basis for us to further explore promising overall water-splitting electrocatalysts.
Delivery of CRISPR/Cas9 Plasmid DNA by Hyperbranched Polymeric Nanoparticles Enables Efficient Gene Editing
Authors: Xiu Kemao , Saunders Laura , Wen Luan , Ruan Jinxue , Dong Ruonan , Song Jun , Yang Dongshan , Zhang Jifeng , Xu Jie , Chen Y. Eugene , Ma Peter X.
Published: January 2023

Gene editing nucleases such as CRISPR/Cas9 have enabled efficient and precise gene editing in vitro and hold promise of eventually achieving in vivo gene editing based therapy. However, a major challenge for their use is the lack of a safe and effective virus-free system to deliver gene editing nuclease elements. Polymers are a promising class of delivery vehicle due to their higher safety compared to currently used viral vectors, but polymers suffer from lower transfection efficiency. Polymeric vectors have been used for small nucleotide delivery but have yet to be used successfully with plasmid DNA (pDNA), which is often several hundred times larger than small nucleotides, presenting an engineering challenge. To address this, we extended our previously reported hyperbranched polymer (HP) delivery system for pDNA delivery by synthesizing several variants of HPs: HP-800, HP-1.8K, HP-10K, HP-25K. We demonstrate that all HPs have low toxicity in various cultured cells, with HP-25K being the most efficient at packaging and delivering pDNA. Importantly, HP-25K mediated delivery of CRISPR/Cas9 pDNA resulted in higher gene-editing rates than all other HPs and Lipofectamine at several clinically significant loci in different cell types. Consistently, HP-25K also led to more robust base editing when delivering the CRISPR base editor “BE4-max” pDNA to cells compared with Lipofectamine. The present work demonstrates that HP nanoparticles represent a promising class of vehicle for the non-viral delivery of pDNA towards the clinical application of gene-editing therapy.
Reconstitution of Caruncle Placenta through the 20α-HSD/Casp-3 Apoptotic Pathway during Early Pregnancy in Bovines
Authors: Lee Ji-Hye , Oh Min-Gee , Kim Sang-Hwan
Published: January 2023

Trophoblast cells of endometrium during bovine pregnancy with different characteristics undergo dynamic changes during uterine remodeling, which can be observed as continuous changes, as P4 secreted by the mother is replaced by placental hormones. In this context, the present study analyzed tissues’ morphological changes through uterine apoptosis during early pregnancy. In addition, the expression pattern associated with apoptosis genes and 20α-HSD was determined in the endometrium and caruncle tissues. The localization of 20α-HSD, VEGF, Casp3, and mTOR protein was also determined in endometrium and caruncle during early pregnancy. From around 30 days, caruncle trophoblast cells with very high invasiveness expanded the villus section as the gestation period progressed. The surrounding cells detached and reorganized into new cells. In addition, an analysis of the effect of apoptosis on cell reorganization in the caruncle revealed that the expression of 20α-HSD/Casp-3 signals in the villus section gradually increased from 30 to 90 days. However, on the 30th day, glandular epithelial cells occurred sporadically in the trophoblast cell section. Moreover, the apoptosis of trophoblast cells increased at 90 days. Taken together, the results of the present study show that changes in the uterus during early pregnancy promote changes during later pregnancy by inducing the reorganization through the stimulation of 20α-HSD and Casp-3, promoting uterine and caruncle tissues, unlike cell development mediated by hormone signaling.
Metabolomic Changes as Key Factors of Green Plant Regeneration Efficiency of Triticale In Vitro Anther Culture
Authors: Orłowska Renata , Zebrowski Jacek , Dynkowska Wioletta Monika , Androsiuk Piotr , Bednarek Piotr Tomasz
Published: January 2023

Green plant regeneration efficiency (GPRE) via in vitro anther culture results from biochemical pathways and cycle dysfunctions that may affect DNA and histone methylation, with gene expression influencing whole cell functioning. The reprogramming from gametophytic to sporophytic fate is part of the phenomenon. While DNA methylation and sequence changes related to the GPRE have been described, little attention was paid to the biochemical aspects of the phenomenon. Furthermore, only a few theoretical models that describe the complex relationships between biochemical aspects of GPRE and the role of Cu(II) ions in the induction medium and as cofactors of enzymatic reactions have been developed. Still, none of these models are devoted directly to the biochemical level. Fourier transform infrared (FTIR) spectroscopy was used in the current study to analyze triticale regenerants derived under various in vitro tissue culture conditions, including different Cu(II) and Ag(I) ion concentrations in the induction medium and anther culture times. The FTIR spectra of S-adenosyl-L-methionine (SAM), glutathione, and pectins in parallel with the Cu(II) ions, as well as the evaluated GPRE values, were put into the structural equation model (SEM). The data demonstrate the relationships between SAM, glutathione, pectins, and Cu(II) in the induction medium and how they affect GPRE. The SEM reflects the cell functioning under in vitro conditions and varying Cu(II) concentrations. In the presented model, the players are the Krebs and Yang cycles, the transsulfuration pathway controlled by Cu(II) ions acting as cofactors of enzymatic reactions, and the pectins of the primary cell wall.
The Past and Present Lives of the Intraocular Transmembrane Protein CD36
Authors: Yang Rucui , Liu Qingping , Zhang Mingzhi
Published: January 2023

Cluster of differentiation 36 (CD36) belongs to the B2 receptors of the scavenger receptor class B family, which is comprised of single-chain secondary transmembrane glycoproteins. It is present in a variety of cell types, including monocytes, macrophages, microvascular endothelial cells, adipocytes, hepatocytes, platelets, skeletal muscle cells, kidney cells, cardiomyocytes, taste bud cells, and a variety of other cell types. CD36 can be localized on the cell surface, mitochondria, endoplasmic reticulum, and endosomes, playing a role in lipid accumulation, oxidative stress injury, apoptosis, and inflammatory signaling. Recent studies have found that CD36 is expressed in a variety of ocular cells, including retinal pigment epithelium (RPE), retinal microvascular endothelial cells, retinal ganglion cells (RGC), Müller cells, and photoreceptor cells, playing an important role in eye diseases, such as age-related macular degeneration (AMD), diabetic retinopathy (DR), and glaucoma. Therefore, a comprehensive understanding of CD36 function and downstream signaling pathways is of great significance for the prevention and treatment of eye diseases. This article reviews the molecular characteristics, distribution, and function of scavenger receptor CD36 and its role in ophthalmology in order to deepen the understanding of CD36 in eye diseases and provide new ideas for treatment strategies.
Effects of Microbeam Irradiation on Rodent Esophageal Smooth Muscle Contraction
Authors: Frerker Bernd , Fiedler Stefan , Kirschstein Timo , Lange Falko , Porath Katrin , Sellmann Tina , Kutzner Leonie , Wilde Fabian , Moosmann Julian , Köhling Rüdiger , Hildebrandt Guido , Schültke Elisabeth
Published: January 2023

Background: High-dose-rate radiotherapy has shown promising results with respect to normal tissue preservation. We developed an ex vivo model to study the physiological effects of experimental radiotherapy in the rodent esophageal smooth muscle. Methods: We assessed the physiological parameters of the esophageal function in ex vivo preparations of the proximal, middle, and distal segments in the organ bath. High-dose-rate synchrotron irradiation was conducted using both the microbeam irradiation (MBI) technique with peak doses greater than 200 Gy and broadbeam irradiation (BBI) with doses ranging between 3.5–4 Gy. Results: Neither MBI nor BBI affected the function of the contractile apparatus. While peak latency and maximal force change were not affected in the BBI group, and no changes were seen in the proximal esophagus segments after MBI, a significant increase in peak latency and a decrease in maximal force change was observed in the middle and distal esophageal segments. Conclusion: No severe changes in physiological parameters of esophageal contraction were determined after high-dose-rate radiotherapy in our model, but our results indicate a delayed esophageal function. From the clinical perspective, the observed increase in peak latency and decreased maximal force change may indicate delayed esophageal transit.
SESN2 Knockdown Increases Betulinic Acid-Induced Radiosensitivity of Hypoxic Breast Cancer Cells
Authors: Güttler Antje , Weinholdt Claus , Ruff Elisabeth , Reidt Judith , Darnstaedt Elisa , Wildemann Alicia , Petrenko Marina , Keßler Jacqueline , Kappler Matthias , Grosse Ivo , Vordermark Dirk , Bache Matthias
Published: January 2023

Betulinic acid (BA) is a natural compound well known for its anti-inflammatory, anti-viral, anti-bacterial, anti-malarial effects and anti-tumor properties. Its enhanced cytotoxicity in tumor cells and induction of cell death in various cancer entities qualifies BA as an interesting candidate for novel treatment concepts. Our analyses showed enhanced cytotoxicity and radiosensitization under hypoxic conditions in human breast cancer cells. So far, the underlying mechanisms are unknown. Therefore, we investigated the BA-treated human breast cancer cell lines MDA-MB-231 and MCF-7 under normoxic and hypoxic conditions based on microarray technology. Hypoxia and BA regulated a variety of genes in both breast cancer cell lines. KEGG pathway analysis identified an enrichment of the p53 pathway in MCF-7 cells (wtp53) under hypoxia. In MDA-MB-231 cells (mtp53) an additional BA incubation was required to activate the p53 signaling pathway. Fourteen down-regulated and up-regulated genes of the p53 pathway were selected for further validation via qRT-PCR in a panel of five breast cancer cell lines. The stress-induced gene Sestrin-2 (SESN2) was identified as one of the most strongly up-regulated genes after BA treatment. Knockdown of SESN2 enhanced BA-induced ROS production, DNA damage, radiosensitivity and reduced autophagy in breast cancer cells. Our results identified SESN2 as an important target to enhance the radiobiological and anti-tumor effects of BA on breast cancer cells.
Relationship between Mitochondrial Quality Control Markers, Lower Extremity Tissue Composition, and Physical Performance in Physically Inactive Older Adults
Authors: Picca Anna , Triolo Matthew , Wohlgemuth Stephanie E. , Martenson Matthew S. , Mankowski Robert T. , Anton Stephen D. , Marzetti Emanuele , Leeuwenburgh Christiaan , Hood David A.
Published: January 2023

Altered mitochondrial quality and function in muscle may be involved in age-related physical function decline. The role played by the autophagy–lysosome system, a major component of mitochondrial quality control (MQC), is incompletely understood. This study was undertaken to obtain initial indications on the relationship between autophagy, mitophagy, and lysosomal markers in muscle and measures of physical performance and lower extremity tissue composition in young and older adults. Twenty-three participants were enrolled, nine young (mean age: 24.3 ± 4.3 years) and 14 older adults (mean age: 77.9 ± 6.3 years). Lower extremity tissue composition was quantified volumetrically by magnetic resonance imaging and a tissue composition index was calculated as the ratio between muscle and intermuscular adipose tissue volume. Physical performance in older participants was assessed via the Short Physical Performance Battery (SPPB). Protein levels of the autophagy marker p62, the mitophagy mediator BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3), the lysosomal markers transcription factor EB, vacuolar-type ATPase, and lysosomal-associated membrane protein 1 were measured by Western immunoblotting in vastus lateralis muscle biopsies. Older adults had smaller muscle volume and lower tissue composition index than young participants. The protein content of p62 and BNIP3 was higher in older adults. A negative correlation was detected between p62 and BNIP3 and the tissue composition index. p62 and BNIP3 were also related to the performance on the 5-time sit-to-stand test of the SPPB. Our results suggest that an altered expression of markers of the autophagy/mitophagy–lysosomal system is related to deterioration of lower extremity tissue composition and muscle dysfunction. Additional studies are needed to clarify the role of defective MQC in human muscle aging and identify novel biological targets for drug development.
Probiotics Mechanism of Action on Immune Cells and Beneficial Effects on Human Health
Authors: Mazziotta Chiara , Tognon Mauro , Martini Fernanda , Torreggiani Elena , Rotondo John Charles
Published: January 2023

Immune cells and commensal microbes in the human intestine constantly communicate with and react to each other in a stable environment in order to maintain healthy immune activities. Immune system-microbiota cross-talk relies on a complex network of pathways that sustain the balance between immune tolerance and immunogenicity. Probiotic bacteria can interact and stimulate intestinal immune cells and commensal microflora to modulate specific immune functions and immune homeostasis. Growing evidence shows that probiotic bacteria present important health-promoting and immunomodulatory properties. Thus, the use of probiotics might represent a promising approach for improving immune system activities. So far, few studies have been reported on the beneficial immune modulatory effect of probiotics. However, many others, which are mainly focused on their metabolic/nutritional properties, have been published. Therefore, the mechanisms behind the interaction between host immune cells and probiotics have only been partially described. The present review aims to collect and summarize the most recent scientific results and the resulting implications of how probiotic bacteria and immune cells interact to improve immune functions. Hence, a description of the currently known immunomodulatory mechanisms of probiotic bacteria in improving the host immune system is provided.
Azilsartan Modulates HMGB1/NF-κB/p38/ERK1/2/JNK and Apoptosis Pathways during Renal Ischemia Reperfusion Injury
Authors: Alaaeldin Rania , Bakkar Sally M. , Mohyeldin Reham H. , Ali Fares E. M. , Abdel-Maqsoud Nehad M. Reda , Fathy Moustafa
Published: January 2023

Renal ischemia/reperfusion (IR) injury is characterized by an unexpected impairment of blood flow to the kidney. Azilsartan is an angiotensin receptor blocker that is approved for the management of hypertension. The present study aimed to investigate, on molecular basics, the nephroprotective activity of azilsartan on renal IR injury in rats. Rats were assigned into four groups: (1) Sham group, (2) Azilsartan group, (3) IR group, and (4) IR/Azilsartan-treated group. Histological examination and renal function were evaluated. Levels of KIM-1, HMGB1, caspase 3, GPX, SOD, NF-κB, and p53 proteins were investigated using ELISA. mRNA levels of IL-1β, IL6, IL10, TNF-α, NF-κB, p53, and bax were assessed by qRT-PCR. Expression of p38, JNK, and ERK1/2 proteins was investigated by Western blotting. IR injury resulted in tissue damage, elevation of creatinine, BUN, KIM-1, HMGB1, caspase 3, NF-κB, and p53 levels, decreasing GPX and SOD activities, and up-regulation of NF-κB, IL-1β, IL6, TNF-α, p53, and bax genes. Furthermore, it up-regulated the expression of phosphorylated/total ratio of p38, ERK1/2, and JNK proteins. Interestingly, treatment of the injured rats with azilsartan significantly alleviated IR injury-induced histopathological and biochemical changes. It reduced the creatinine, BUN, KIM-1, HMGB1, caspase-3, NF-κB, and p53 levels, elevated GPX and SOD activities, down-regulated the expression of NF-κB, IL-1β, IL6, TNF-α, p53, and bax genes, and up-regulated IL10 gene expression. Furthermore, it decreased the phosphorylated/total ratio of p38, ERK1/2, and JNK proteins. Azilsartan exhibited nephroprotective activity in IR-injured rats via its antioxidant effect, suppression of inflammation, attenuation of apoptosis, and inhibition of HMGB1/NF-κB/p38/ERK1/2/JNK signaling pathway.
Influences of Impurity Gases in Air on Room-Temperature Hydrogen-Sensitive Pt–SnO2 Composite Nanoceramics: A Case Study of H2S
Authors: Lu Xilai , Wu Menghan , Huang Yong , Song Jiannan , Liu Yong , Yan Zhiqiao , Chen Feng , Zhao Jieting , Chen Wanping
Published: January 2023

The slight but cumulative influence of impurity gases in air poses a great threat to the long-term stability of room-temperature gas sensors. Room-temperature hydrogen-sensitive Pt–SnO2 composite nanoceramics of 5 wt% Pt were prepared through pressing and sintering. The response of a sample was over 10,000 after being exposed to 500 ppm H2S–20% O2–N2 at room temperature, and the room-temperature hydrogen sensing capacity was seriously degraded even for samples that had aged dozens of days since H2S exposure. Mild heat treatments such as 160 °C for 10 min were found able to fully activate those H2S-exposed samples. As the peak of S 2p electron was clearly detected in H2S-exposed samples, it was proposed that for room-temperature hydrogen-sensitive Pt–SnO2 composite nanoceramics, H2S exposure induced degradation results from the poisoning of Pt by H2S deposited on it, which can be removed through a mild heat treatment. Periodic mild heat treatment should be a convenient and effective measure for room-temperature metal oxide gas sensors to achieve long-term stability through preventing the accumulation of impurity gases in air deposited on them.
Humidity and Temperature Sensing of Mixed Nickel–Magnesium Spinel Ferrites
Authors: Dojcinovic Milena P. , Vasiljevic Zorka Z. , Rakocevic Lazar , Pavlovic Vera P. , Ammar-Merah Souad , Vujancevic Jelena D. , Nikolic Maria Vesna
Published: January 2023

Temperature- and humidity-sensing properties were evaluated of NixMg1-x spinel ferrites (0 ≤ x ≤ 1) synthesized by a sol-gel combustion method using citric acid as fuel and nitrate ions as oxidizing agents. After the exothermic reaction, amorphous powders were calcined at 700 °C followed by characterization with XRD, FTIR, XPS, EDS and Raman spectroscopy and FESEM microscopy. Synthesized powders were tested as humidity- and temperature-sensing materials in the form of thick films on interdigitated electrodes on alumina substrate in a climatic chamber. The physicochemical investigation of synthesized materials revealed a cubic spinel Fd3¯m phase, nanosized but agglomerated particles with a partially to completely inverse spinel structure with increasing Ni content. Ni0.1Mg0.9Fe2O4 showed the highest material constant (B30,90) value of 3747 K and temperature sensitivity (α) of −4.08%/K compared to pure magnesium ferrite (B30,90 value of 3426 K and α of −3.73%/K) and the highest average sensitivity towards humidity of 922 kΩ/%RH in the relative humidity (RH) range of 40–90% at the working temperature of 25 °C.
Automated Multistep Lateral Flow Immunoassay Using a Smartphone for the Quantification of Foodborne Bacteria from Fresh Lettuce
Authors: Phangwipas Pattarapon , Thangavel Balamurugan , Shin Joong
Published: January 2023

Foodborne illnesses are one of the most severe and prevalent health problems in the world. Thus, achieving the rapid and accurate identification of foodborne pathogens is important. This study presents an automatic device to perform a multistep immunoassay on a lateral flow immunoassay strip to detect foodborne pathogens from fresh lettuce. The device is automatically operated using a smartphone application that we developed, which allows users to quantify the detection results. In this study, we characterize the device’s limit of detection and demonstrate the detection and quantification of Escherichia coli O157:H7 from contaminated lettuce. We then compare the quantified result to that calculated by counting colonies from agar plates. The device is capable of detecting contamination in lettuces that have as low as 5 × 104 Escherichia coli O157:H7 per 10 g.
Critical Thinking in Ethical and Neutral Settings in Gifted Children and Non-Gifted Children
Authors: Fabio Rosa Angela , Croce Alessandra , Calabrese Chiara
Published: January 2023

The present study examined the performance on five phases of critical thinking in gifted and nongifted children in two settings: ethical and neutral. Ninety-one children, 32 gifted (8–10 years old), 32 normally developing children matched for chronological age (8–10 years old) and 27 normally developing children matched for mental age (12–13 years old) completed critical thinking tasks. The findings confirmed that intellectually gifted children had higher critical thinking capacity than typically developing children. The results reveal that the basic factor determining best performances in critical thinking is mental age and not chronological age. However, critical thinking ability was the same in ethical and neutral settings. Analysis of the phases of critical thinking show that the first and the third phase, clarification and evaluation, specifically differentiates gifted from nongifted children. These phases refer to the ability to understand the type of problem rapidly and to assess the credibility of statements and to assess the logical strength of the actual or intended inferential relationships among statements, descriptions, questions or other forms of representation.